Contact Dermatitis

The Diagnosis: Cutaneous Mastocytosis

A shave skin biopsy from the right lateral breast and a punch skin biopsy from the right thigh showed similar histopathology. There were dermal predominantly perivascular aggregates of cells demonstrating basophilic granular cytoplasm and round to oval nuclei (Figure, A and B). These cells were highlighted by CD117 immunohistochemical stain (Figure, C), consistent with mastocytes. Additionally, occasional lymphocytes and rare eosinophils were noted. These histopathologic findings confirmed the diagnosis of cutaneous mastocytosis (CM). The patient’s complete blood cell count was within reference range, but serum tryptase was elevated at 15.7 μg/L (reference range, <11.0 μg/L), which prompted a bone marrow biopsy to rule out systemic mastocytosis (SM). The result showed normocellular bone marrow with no evidence of dysplasia or increased blasts, granuloma, lymphoproliferative disorder, or malignancy. Fluorescence in situ hybridization for PDGFRA (platelet-derived growth factor receptor alpha) and KIT mutation was negative. Because CM developed predominantly on the right breast where the patient previously had received radiation therapy, we concluded that this reaction was triggered by exposure to ionizing radiation.

Mastocytosis can be divided into 2 groups: CM and SM.¹ The histologic differential diagnosis of CM includes solitary mastocytoma, urticaria pigmentosa, telangiectasia macularis eruptiva perstans, and diffuse mastocytosis.² Clinicopathologic correlation is of crucial importance to render the final diagnosis in these disorders. Immunohistochemically, mast cells express CD177, CD5, CD68, tryptase, and chymase. Unlike normal mast cells, neoplastic cells express CD2 and/or CD25; CD25 is commonly expressed in cutaneous involvement by SM.²

Macdonald and Feiwel³ reported the first case of CM following ionizing radiation. Cutaneous mastocytosis is most common in female patients and presents with redbrown macules originating at the site of radiation therapy. Prior literature suggests that radiation-associated CM has a predilection for White patients⁴; however, our patient was Hispanic. It also is important to note that the presentation of this rash may differ in individuals with skin of color. In one case it spread beyond the radiation site.² Systemic mast call–mediated symptoms can occur in both CM and SM. The macules manifest as blanching with pressure.⁵ Typically these macules also are asymptomatic, though a positive Darier sign has been reported.^6,7 The interval between radiotherapy and CM has ranged from 3 to 24 months.²

Patients with CM should have a serum tryptase evaluation along with a complete blood cell count, serum biochemistry, and liver function tests. Elevated serum tryptase has a high positive predictive value for SM and should prompt a bone marrow biopsy. Our patient’s bone marrow biopsy results failed to establish SM; however, her serum tryptase levels will be carefully monitored going forward. At the time of publication, the skin macules were still persistent but not worsening or symptomatic.

Treatment is focused on symptomatic relief of cutaneous symptoms, if present; avoiding triggers of mast cell degranulation; and implementing the use of oral antihistamines and leukotriene antagonists as needed. Because our patient was completely asymptomatic, we did not recommend any topical or oral treatment. However, we do counsel patients on avoiding triggers of mast cell degranulation including nonsteroidal anti-inflammatory drugs, morphine and codeine derivatives, alcohol, certain anesthetics, and anticholinergic medications.⁸

Additional diagnoses were ruled out for the following reasons: Although lichen planus pigmentosus presents with ill-defined, oval, gray-brown macules, histopathology shows a bandlike lymphocytic infiltrate at the dermoepidermal junction. Solar lentiginosis is characterized by grouped tan macules in a sun-exposed distribution. A fixed drug eruption is a delayed hypersensitivity reaction, usually to an ingested medication, characterized by violaceous or hyperpigmented patches, with histopathology showing interface dermatitis with a lymphoeosinophilic infiltrate. Eruptive seborrheic keratoses can result from sunburn or dermatitis but does not show mastocytes on histopathology.⁸

In conclusion, dermatologists should be reminded of the rare possibility of CM when evaluating an atypical eruption in a prior radiation field.

The Diagnosis: Cutaneous Mastocytosis

A shave skin biopsy from the right lateral breast and a punch skin biopsy from the right thigh showed similar histopathology. There were dermal predominantly perivascular aggregates of cells demonstrating basophilic granular cytoplasm and round to oval nuclei (Figure, A and B). These cells were highlighted by CD117 immunohistochemical stain (Figure, C), consistent with mastocytes. Additionally, occasional lymphocytes and rare eosinophils were noted. These histopathologic findings confirmed the diagnosis of cutaneous mastocytosis (CM). The patient’s complete blood cell count was within reference range, but serum tryptase was elevated at 15.7 μg/L (reference range, <11.0 μg/L), which prompted a bone marrow biopsy to rule out systemic mastocytosis (SM). The result showed normocellular bone marrow with no evidence of dysplasia or increased blasts, granuloma, lymphoproliferative disorder, or malignancy. Fluorescence in situ hybridization for PDGFRA (platelet-derived growth factor receptor alpha) and KIT mutation was negative. Because CM developed predominantly on the right breast where the patient previously had received radiation therapy, we concluded that this reaction was triggered by exposure to ionizing radiation.

Mastocytosis can be divided into 2 groups: CM and SM.¹ The histologic differential diagnosis of CM includes solitary mastocytoma, urticaria pigmentosa, telangiectasia macularis eruptiva perstans, and diffuse mastocytosis.² Clinicopathologic correlation is of crucial importance to render the final diagnosis in these disorders. Immunohistochemically, mast cells express CD177, CD5, CD68, tryptase, and chymase. Unlike normal mast cells, neoplastic cells express CD2 and/or CD25; CD25 is commonly expressed in cutaneous involvement by SM.²

Macdonald and Feiwel³ reported the first case of CM following ionizing radiation. Cutaneous mastocytosis is most common in female patients and presents with redbrown macules originating at the site of radiation therapy. Prior literature suggests that radiation-associated CM has a predilection for White patients⁴; however, our patient was Hispanic. It also is important to note that the presentation of this rash may differ in individuals with skin of color. In one case it spread beyond the radiation site.² Systemic mast call–mediated symptoms can occur in both CM and SM. The macules manifest as blanching with pressure.⁵ Typically these macules also are asymptomatic, though a positive Darier sign has been reported.^6,7 The interval between radiotherapy and CM has ranged from 3 to 24 months.²

Patients with CM should have a serum tryptase evaluation along with a complete blood cell count, serum biochemistry, and liver function tests. Elevated serum tryptase has a high positive predictive value for SM and should prompt a bone marrow biopsy. Our patient’s bone marrow biopsy results failed to establish SM; however, her serum tryptase levels will be carefully monitored going forward. At the time of publication, the skin macules were still persistent but not worsening or symptomatic.

Treatment is focused on symptomatic relief of cutaneous symptoms, if present; avoiding triggers of mast cell degranulation; and implementing the use of oral antihistamines and leukotriene antagonists as needed. Because our patient was completely asymptomatic, we did not recommend any topical or oral treatment. However, we do counsel patients on avoiding triggers of mast cell degranulation including nonsteroidal anti-inflammatory drugs, morphine and codeine derivatives, alcohol, certain anesthetics, and anticholinergic medications.⁸

Additional diagnoses were ruled out for the following reasons: Although lichen planus pigmentosus presents with ill-defined, oval, gray-brown macules, histopathology shows a bandlike lymphocytic infiltrate at the dermoepidermal junction. Solar lentiginosis is characterized by grouped tan macules in a sun-exposed distribution. A fixed drug eruption is a delayed hypersensitivity reaction, usually to an ingested medication, characterized by violaceous or hyperpigmented patches, with histopathology showing interface dermatitis with a lymphoeosinophilic infiltrate. Eruptive seborrheic keratoses can result from sunburn or dermatitis but does not show mastocytes on histopathology.⁸

In conclusion, dermatologists should be reminded of the rare possibility of CM when evaluating an atypical eruption in a prior radiation field.

The Diagnosis: Cutaneous Mastocytosis

A shave skin biopsy from the right lateral breast and a punch skin biopsy from the right thigh showed similar histopathology. There were dermal predominantly perivascular aggregates of cells demonstrating basophilic granular cytoplasm and round to oval nuclei (Figure, A and B). These cells were highlighted by CD117 immunohistochemical stain (Figure, C), consistent with mastocytes. Additionally, occasional lymphocytes and rare eosinophils were noted. These histopathologic findings confirmed the diagnosis of cutaneous mastocytosis (CM). The patient’s complete blood cell count was within reference range, but serum tryptase was elevated at 15.7 μg/L (reference range, <11.0 μg/L), which prompted a bone marrow biopsy to rule out systemic mastocytosis (SM). The result showed normocellular bone marrow with no evidence of dysplasia or increased blasts, granuloma, lymphoproliferative disorder, or malignancy. Fluorescence in situ hybridization for PDGFRA (platelet-derived growth factor receptor alpha) and KIT mutation was negative. Because CM developed predominantly on the right breast where the patient previously had received radiation therapy, we concluded that this reaction was triggered by exposure to ionizing radiation.

Mastocytosis can be divided into 2 groups: CM and SM.¹ The histologic differential diagnosis of CM includes solitary mastocytoma, urticaria pigmentosa, telangiectasia macularis eruptiva perstans, and diffuse mastocytosis.² Clinicopathologic correlation is of crucial importance to render the final diagnosis in these disorders. Immunohistochemically, mast cells express CD177, CD5, CD68, tryptase, and chymase. Unlike normal mast cells, neoplastic cells express CD2 and/or CD25; CD25 is commonly expressed in cutaneous involvement by SM.²

Macdonald and Feiwel³ reported the first case of CM following ionizing radiation. Cutaneous mastocytosis is most common in female patients and presents with redbrown macules originating at the site of radiation therapy. Prior literature suggests that radiation-associated CM has a predilection for White patients⁴; however, our patient was Hispanic. It also is important to note that the presentation of this rash may differ in individuals with skin of color. In one case it spread beyond the radiation site.² Systemic mast call–mediated symptoms can occur in both CM and SM. The macules manifest as blanching with pressure.⁵ Typically these macules also are asymptomatic, though a positive Darier sign has been reported.^6,7 The interval between radiotherapy and CM has ranged from 3 to 24 months.²

Patients with CM should have a serum tryptase evaluation along with a complete blood cell count, serum biochemistry, and liver function tests. Elevated serum tryptase has a high positive predictive value for SM and should prompt a bone marrow biopsy. Our patient’s bone marrow biopsy results failed to establish SM; however, her serum tryptase levels will be carefully monitored going forward. At the time of publication, the skin macules were still persistent but not worsening or symptomatic.

Treatment is focused on symptomatic relief of cutaneous symptoms, if present; avoiding triggers of mast cell degranulation; and implementing the use of oral antihistamines and leukotriene antagonists as needed. Because our patient was completely asymptomatic, we did not recommend any topical or oral treatment. However, we do counsel patients on avoiding triggers of mast cell degranulation including nonsteroidal anti-inflammatory drugs, morphine and codeine derivatives, alcohol, certain anesthetics, and anticholinergic medications.⁸

Additional diagnoses were ruled out for the following reasons: Although lichen planus pigmentosus presents with ill-defined, oval, gray-brown macules, histopathology shows a bandlike lymphocytic infiltrate at the dermoepidermal junction. Solar lentiginosis is characterized by grouped tan macules in a sun-exposed distribution. A fixed drug eruption is a delayed hypersensitivity reaction, usually to an ingested medication, characterized by violaceous or hyperpigmented patches, with histopathology showing interface dermatitis with a lymphoeosinophilic infiltrate. Eruptive seborrheic keratoses can result from sunburn or dermatitis but does not show mastocytes on histopathology.⁸

In conclusion, dermatologists should be reminded of the rare possibility of CM when evaluating an atypical eruption in a prior radiation field.

Approximately 20% of the general population has a contact allergy.¹ Allergic contact dermatitis (ACD) is a delayed type IV hypersensitivity reaction mediated by T lymphocytes.² Axillary ACD presentation is variable but typically includes an eczematous eruption with erythematous scaly patches or plaques. Common products in contact with the axillae include deodorants, antiperspirants, razors, bodywash, and clothing.

Axillary skin is distinct from skin elsewhere on the body due to both anatomical characteristics and unique human self-care practices. Axillary skin has reduced barrier function, faster stratum corneum turnover, and altered lipid levels.^3-5 Moreover, the axillae often are subject to shaving or other hair removal practices that alter the local environment, as layers of stratum corneum and hair are mechanically removed, which causes irritation and predisposes the skin to enhanced sensitivity to topical exposures.^6,7 With the abundance of apocrine and eccrine glands, the axillae are prone to sweat, which also can accentuate contact allergy.^2,3 Other factors, such as occlusion and friction, contribute to axillary contact allergy.^8,9

Patch testing is the gold standard for the diagnosis of ACD and aids in identification of culprit allergens. A thorough patient history and examination of the rash distribution may provide further clues; for example, dermatitis due to a deodorant typically affects the vault, whereas textile dye dermatitis tends to spare the vault.^10,11 Baseline-limited patch testing detects up to two-thirds of clinically relevant allergens.¹² Therefore, patients may require subsequent testing with supplemental allergens.

The differential diagnosis for axillary lesions is broad—including inflammatory diseases such as irritant contact dermatitis and hidradenitis suppurativa, genetic disorders such as Hailey-Hailey disease, and infectious causes such as erythrasma—but may be narrowed with a thorough physical examination and patient history, histopathology, bedside diagnostic techniques (eg, scrapings and Wood lamp examination), and patch testing. Systemic contact dermatitis (SCD) or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) also may be suspected in cases of intertriginous dermatoses.

We review the potential allergens in products used on the axillae as well as the management of axillary ACD. We also discuss axillary dermatitis as a manifestation of SCD and SDRIFE.

Top Allergens in Products Used on the Axillae

Fragrance—A 1982 North American Contact Dermatitis Group study on cosmetic products identified fragrances as the most common cause of ACD,¹³ and this trend continues to hold true with more recent data.¹⁴ The incidence of fragrance allergy may be increasing, with positive patch tests to a fragrance chemical in 10% of patch test clinic populations.¹⁵ Fragrances are a ubiquitous ingredient in deodorants and antiperspirants, which are important sources implicated in the development and elicitation of fragrance ACD.¹⁶ One study found that fragrance was present in 97 of 107 (90%) deodorants available at Walgreens pharmacies.¹¹

In a study of patients with a history of an axillary rash caused by a deodorant spray, Johansen et al¹⁷ reported that the likelihood of fragrance allergy is increased by a factor of 2.4. This risk of developing a fragrance allergy may be exacerbated in those who shave; Edman¹⁸ reported that the odds ratio of developing a fragrance allergy among men who shave their beards was 2.9. Although there are no specific data on the effects of shaving on ACD, shaving in general can induce localized irritation and increase percutaneous absorption.¹⁹

The individual fragrance components in deodorants most likely to cause ACD include hydroxycitronellal, eugenol, and geraniol—all constituent ingredients in patch test formulations of fragrance mixture I.^11,20 Other common fragrance allergens associated with ACD include hydroxymethylpentylcyclohexenecarboxaldehyde, farnesol, and balsam of Peru.^21-27 Hydroperoxides of limonene and linalool, common fragrances in detergents and personal care products, are increasingly recognized as contact allergens and have been reported to cause axillary ACD from deodorants.^28-30

Dermatitis involving the bilateral axillary vaults wherever deodorant or antiperspirant was directly applied is the most common presentation of ACD due to fragrance (Figure 1).¹⁷ An eczematous eruption is common, though scale may be less apparent than in nonflexural regions. Axillary ACD secondary to fragrances also may result from use of fragranced laundry detergents, fabric softeners, soaps, and perfumes, and may spare the vaults.^10,29,31,32 Less common presentations of axillary ACD due to fragrance include pigmented dermatoses; for example, ACD from an antiperspirant containing hydroperoxide of limonene presented as hyperpigmented patches with minimal erythema and scaling in the edges of the axillary folds.^33,34

Diagnosis of a fragrance ACD typically is made with a standard patch test series including fragrance mixture I and balsam of Peru, which may detect 75% and 50% of fragrance sensitivities, respectively.³⁵ Patch testing may be followed with a repeated open application test of the product in question.³⁶ Additionally, it may be appropriate to test for other fragrance allergens including balsam of Tolu, fragrance mixture II, lichen acid mix, and hydroxyperoxides of linalool and limonene (among other botanicals) if standard patch testing is negative and suspicion of fragrance ACD remains elevated.¹¹

Propylene Glycol—Propylene glycol (PG)—a versatile substance that functions as a solvent, humectant, emulsifier, stabilizer, and antimicrobial—is the second most common contact allergen present in deodorants.¹¹ It is prevalent in both personal care and household products, including deodorants, cosmetics, foods, toothpaste, cleaning agents, and detergents.^11,37 Propylene glycol is both an allergen and an irritant. Among deodorants/antiperspirants, PG is both a common irritant and allergen, as its concentration may be particularly high (as much as 73%).³⁸ One commonly reported example of PG contact dermatitis is from the topical medicament minoxidil.^39,40

Patch testing data have demonstrated a positivity rate for PG ranging between 0.1% to 3.8%. The variability in these findings likely is due to differences in the tested concentrations of PG, as higher concentrations sometimes required to elicit an allergic reaction also may create a stronger irritation effect.⁴¹ Propylene glycol irritancy and the occlusive nature of the axillae may enhance sensitization to other allergens, as demonstrated by Agren-Jonsson and Magnusson,⁴² who reported sensitization to propantheline bromide and trichlorocarbanilide in patients who used a lotion with 90% PG. Many PG-containing products beyond deodorants/antiperspirants may be applied to the axillae, including steroid creams, lotions, shaving creams, and bodywashes.^38,43

The diagnosis of PG allergy via patch testing is challenging and at times controversial given its irritant nature. False-positive irritant reactions have been documented, characterized by a weak reaction at 48 hours that is absent by 96 hours (decrescendo reaction). A reaction may not appear until 96 hours (crescendo reaction), which typically indicates a true contact allergy but in the case of PG also may be the substance acting as a “late irritant.”⁴⁴ Fast (<24 hours) and well-demarcated reactions suggest irritation.⁴⁵ Regardless, reactions to PG on patch testing, even those regarded as weak, may be considered relevant in consideration of the clinical context.³⁷

Aluminum—Aluminum is the active ingredient in most antiperspirants, typically in the form of aluminum chloride, aluminum chlorohydrate, aluminum zirconium trichlorohydrex gly, or aluminum zirconium tetrachlorohydrex gly.⁴⁶ Aluminum mechanically obstructs the eccrine glands to reduce sweat.⁴⁷ Although aluminum is an uncommon allergen, a possible presentation of aluminum allergy is axillary vault dermatitis secondary to antiperspirant use.⁴⁶ Another potential manifestation is a ringlike reaction to the Finn Chambers (SmartPractice) used in patch testing.⁴⁶ In one case of aluminum-induced axillary dermatitis, a 28-year-old woman presented with eczema of the axillae, and subsequent patch testing revealed an allergy to aluminum chloride. The rash resolved upon cessation of use of an aluminum-containing deodorant.⁴⁸

Aluminum has been reported to cause granulomatous dermatitis in the axillae. This reaction typically presents as red-brown, pruritic papules limited to the area in which deodorant was applied, with histopathology revealing epithelioid granulomas.^49-51

Alum deodorants—considered a natural alternative—contain aluminum bound to potassium or ammonium in the form of a crystal or powder. Alum crystal deodorants have been reported to cause both a typical erythematous pruritic dermatitis as well as a granulomatous dermatitis with red-brown papules.^52,53 The granulomatous dermatitis caused by either form of aluminum resolves with avoidance and use of topical steroids or topical tacrolimus.^49,50,52,53

The diagnosis of aluminum ACD via patch testing may be identified with empty Finn Chambers, which are metallic aluminum, or with patch placement of aluminum chloride hexahydrate, though the former is only positive in patients with a strong allergy.^54,55 In 2022, aluminum was named Allergen of the Year by the American Contact Dermatitis Society, with recommendations to conduct patch testing with aluminum chloride hexahydrate 10% rather than the traditional 2% to increase diagnostic yield.⁵⁵ Additionally, it is recommended that aluminum be included in baseline patch testing for children due to the high prevalence of aluminum allergy in children and early exposure via childhood vaccines.^54-56 In patients with aluminum allergy, providers may suggest purchasing aluminum-free deodorants or provide recipes for homemade deodorant that includes ingredients such as arrowroot powder, cornstarch, and diatomaceous earth.⁴⁶

Nickel—Nickel is the most commonly identified contact allergen on patch testing yet an infrequent cause of axillary dermatitis. A case report from 2014 described axillary dermatitis in a woman that worsened during a positive patch test to nickel. Improvement was noted when the patient switched to titanium shaving razors.⁵⁷ Nickel allergy also may present in the form of SCD. In one report, a woman developed dermatitis of the flexural areas, including the axillae, 3 months after undergoing a sterilization procedure in which nickel-containing tubal implants were placed.⁵⁸ Patch testing revealed a positive reaction to nickel. The patient experienced complete resolution of the steroid-resistant dermatitis following removal of the implants via salpingectomy.⁵⁸

Textile Dye—In contrast to dermatitis caused by deodorants/antiperspirants, contact allergy to textile dyes presents as dermatitis involving the axillary borders but sparing the axillary vaults (Figures 2 and 3).¹⁰ Other potential presentations of textile dye dermatitis include erythema multiforme–like eruptions and erythematous wheal–type reactions.⁵⁹ Textile dyes are classified as disperse vs nondisperse, with the majority of contact dermatoses caused by disperse dyes, specifically Disperse Orange 1, blue 106, and blue 124.^60-62 Ryberg et al⁶¹ found that the axilla is one of the more common locations to be affected by textile dye allergy, particularly in women, which was further supported by Seidenari et al,⁶³ who found that skin folds were affected in 27% of study participants allergic to textile dyes (N=437), a finding that is likely due to friction, sweat, and occlusion.⁶² In one case report of a patient with dermatitis caused by reactive dyes, the garment required 3 washes before the patient experienced resolution of dermatitis.⁶⁴ For patients with textile dye dermatitis, mitigation strategies include washing clothing before wearing, especially for darkly dyed items; avoiding tight clothing; wearing garments made of cotton, wool, silk, or linen; and choosing light-colored garments.^9,64,65

Axillary Dermatitis as a Manifestation of SCD and SDRIFE

Systemic contact dermatitis occurs when an individual who was previously sensitized to a particular allergen develops ACD of the skin with systemic exposure to that allergen or immunochemically related allergens. Exposure may occur via ingestion, inhalation, intravenous, intramuscular, and transepidermal routes.⁶⁶ Systemic contact dermatitis manifests in a variety of ways, including focal flares at sites of prior contact dermatitis (recall reaction), vesicular hand dermatitis, intertriginous eruptions including axillary dermatitis, and generalized eruptions.⁶⁷

Systemic contact dermatitis rarely involves systemic symptoms, and onset typically is within days of exposure. The 3 most common groups of allergens causing SCD are metals, medications, and plants and herbals.⁶⁸ These allergens have all been reported to cause axillary dermatitis via SCD.^58,69,70 Foods containing balsam of Peru that may lead to SCD include citrus, chocolate, tomato, and certain alcohols.^70,71 Patients with a positive patch test to balsam of Peru may experience improvement of their dermatitis after reduction of balsam of Peru–rich foods from their diet.⁷⁰ Metals implicated in SCD include mercury, nickel, and gold.^72-74 Finally, PG ingestion also has been implicated in cases of SCD.³⁷

Symmetrical drug-related intertriginous and flexural exanthema is another condition that presents as intertriginous dermatitis and differs from SCD in that the eruption does not require presensitization; there may be no known prior exposure to the agent causing dermatitis. Historically, SDRIFE was described as baboon syndrome because of its frequent involvement of the buttocks with diffuse, well-demarcated, erythematous dermatitis resembling that of a baboon. This term is no longer used due to its insensitive nature and incomplete depiction of SDRIFE, which can affect body sites other than the buttocks.^68,75,76 Specific criteria to make this diagnosis include sharply demarcated and/or V-shaped erythema of the gluteal/perianal area, involvement of at least 1 other intertriginous or flexural region, symmetry of affected areas, and an absence of systemic symptoms.⁷⁶ There also may be papules, pustules, and vesicles present in affected areas. Symmetrical drug-related intertriginous and flexural exanthema most often is caused by β-lactam antibiotics, but other associated drugs include chemotherapeutic agents, such as mitomycin C.⁷⁶

Histopathology of both SCD and SDRIFE is variable and typically nonspecific, often revealing epidermal spongiosis and a perivascular mononuclear cell infiltrate with occasional neutrophils and eosinophils.⁷⁶ A case of SCD to mercury presenting as intertriginous dermatitis demonstrated a leukocytoclastic vasculitis pattern on biopsy.⁷⁷

Systemic contact dermatitis is diagnosed via a patch test, while SDRIFE typically has a negative patch test result and requires oral rechallenge testing, which reproduces the rash within hours.^78,79

Additional Allergens Causing Axillary ACD

Although fragrance is the most common allergen in deodorants, other ingredients have been shown to cause axillary ACD (Table).^80-90 In addition to these ingredients, allergens not previously mentioned that may be present in deodorants include lanolin, essential oils, and parabens.¹¹ Methylisothiazolinone in laundry detergent also has been found to instigate ACD.⁹¹ Fragrances and preservatives in laundry detergents also may contribute to dermatitis.⁹²

Other products that have caused axillary contact dermatitis include topical exposure to medicaments including clindamycin,⁹³ ethylenediamine in nystatin cream,⁹⁴ methylprednisolone acetate⁹⁵ and dipropylene glycol in a hydrocortisone lotion,⁹⁶ wood dusts from tropical hardwoods,⁹⁷ and tobacco.⁹⁸

Management of ACD

The most effective strategy in the management of patients with contact dermatitis is avoidance of the offending agent. Additionally, clinicians may recommend the use of topical steroids and/or calcineurin inhibitors to hasten resolution.²

For patients with contact dermatitis, a clinician may recommend product substitutions with few potential allergens to use prior to patch testing. Patients with a fragrance allergy should look for products specifically labeled as “fragrance free” rather than “hypoallergenic” or “unscented,” as the latter two may still contain minimal amounts of fragrance.³⁵ Patients should be educated on the functions of the allergens to which they are allergic so they may adequately avoid potential sources of contact.⁹⁹ For suspected textile dye dermatitis, instructing patients to wash clothing before wearing and to avoid synthetic fabrics, dark dyes, and tightly fitted clothing may help.^9,64,65

 

 

Differential Diagnosis

The differential diagnosis for axillary lesions is broad, including infectious, inflammatory, and autoimmune etiologies. Irritant contact dermatitis (ICD) presents similar to ACD, though it is more immediate in onsetand typically demonstrates symptoms of burning and stinging rather than pruritus. Although histopathology is not reliable in differentiating ICD and ACD, it has been shown that focal parakeratosis is associated with ACD, whereas necrotic epidermal keratinocytes are found in ICD.¹⁰⁰

Intertrigo presents as large, erythematous, opposing patches or plaques confined to inguinal, submammary, axillary, and/or abdominal folds. Findings of beefy red erythema and peripheral satellite pustules may implicate presence of Candida, which can be identified with potassium hydroxide preparations.

Inverse psoriasis presents as sharply demarcated, erythematous, moist, smooth plaques or patches with minimal scale. The most common area of involvement is the inguinal folds, followed by the axillae, inframammary folds, perianal area, umbilicus, and retroauricular areas. Involvement of the elbows and knees or a positive family history of psoriasis may be useful knowledge in establishing the diagnosis. A biopsy may show dermal eosinophils, epidermal spongiosis, and focal serum in the scale, in addition to features of typical psoriasis plaques.¹⁰¹

Seborrheic dermatitis typically is an erythematous eruption, often with yellowish greasy scale. Simultaneous involvement of the face and scalp may be noted. Although typically a clinical diagnosis, biopsy demonstrates shoulder parakeratosis with follicular plugging and lymphocytic exocytosis.

Hailey-Hailey disease (also called benign familial pemphigus) is an autosomal-dominant genetic condition presenting as moist, malodorous, painful, vegetative plaques, patches, or scaly pustules in flexural areas, frequently with flaccid blisters. Lesions are provoked by traumatic stimuli. Onset occurs in the second to fourth decades and may improve with age. The diagnosis is confirmed by biopsy, which demonstrates acantholysis of the epidermis. The moist superficial patches of Hailey-Hailey disease help distinguish it from comparably drier Darier disease, the other acantholytic disease of the axillae.

Granular parakeratosis (also called hyperkeratotic flexural erythema) is an uncommon dermatosis most often observed in middle-aged women. It presents as red-brown keratotic papules coalescing into plaques, often with overlying scale in intertriginous areas. This disorder may be related to exposure to aluminum, a key component of antiperspirants.¹⁰² Diagnosis with a skin biopsy demonstrates granular parakeratosis.

Infections most commonly include erythrasma, tinea, and candidiasis. Erythrasma caused by Corynebacterium minutissimum may present in the axillae and/or groin with sharply demarcated, red-brown patches. Wood lamp examination reveals coral red fluorescence. Tinea corporis, a dermatophyte infection, may present as scaly erythematous plaques with advancing borders and central clearing. Fungal cultures and potassium hydroxide preparations are useful to confirm the diagnosis.

Pseudofolliculitis barbae most often is thought of as a condition affecting the beard in Black men, but it also may present in individuals of all races who shave the axillary and inguinal regions. Typical features include pruritic inflammatory papules and pustules with surrounding erythema and hyperpigmentation.

Fox-Fordyce disease is a disorder of the apocrine sweat glands that presents as several flesh-colored, perifollicular, monomorphic papules in the axillae. It typically is a disease of young females and also can involve the areola and vulva. Histopathology may show hyperkeratosis, irregular acanthosis, and dilated sweat glands.

Hidradenitis suppurativa is a chronic inflammatory condition that presents with multiple cysts; nodules; abscesses; sinus tract formation; and suppuration of the axillary, anogenital, and sometimes inframammary areas, typically at the onset of puberty. The diagnosis is best supported by history and physical examination, which may be notable for recurrent abscesses, draining tracts, double comedones, and ropelike scarring.

Extramammary Paget disease is a rare malignancy affecting apocrine gland–bearing areas, including axillary and genital regions. It most commonly presents as a unilateral or asymmetric, scaly, erythematous plaque. Histopathology demonstrates Paget cells with abundant clear cytoplasm and pleomorphic nuclei, typically grouped in the lower portion of the epidermis.

Final Thoughts

Axillary dermatoses often can be challenging to diagnose given the range of pathologies that can present in intertriginous areas. Allergic contact dermatitis is a common culprit due to unique anatomical considerations and self-care practices, including shaving/hair removal; use of deodorants, antiperspirants, bodywashes, and clothing; and frictional and moisture influences. The most likely offender among contact allergens is fragrance, but other possibilities to consider include PG, preservatives, aluminum, nickel, and textile dyes. Albeit less common, systemic exposure to allergens may result in SCD and SDRIFE with a rash in intertriginous zones, including the axillae. Additionally, other infectious, inflammatory, and autoimmune etiologies should be considered and ruled out.

Patch testing is the most reliable method to diagnose suspected ACD. Once confirmed, management includes the use of topical steroids and avoidance of the causative agent. Additionally, patients should be informed of the American Contact Dermatitis Society Contact Allergen Management Program (https://www.contactderm.org/patient-support/camp-access), which provides patients with useful information on products that are safe to use based on their patch testing results.

Approximately 20% of the general population has a contact allergy.¹ Allergic contact dermatitis (ACD) is a delayed type IV hypersensitivity reaction mediated by T lymphocytes.² Axillary ACD presentation is variable but typically includes an eczematous eruption with erythematous scaly patches or plaques. Common products in contact with the axillae include deodorants, antiperspirants, razors, bodywash, and clothing.

Axillary skin is distinct from skin elsewhere on the body due to both anatomical characteristics and unique human self-care practices. Axillary skin has reduced barrier function, faster stratum corneum turnover, and altered lipid levels.^3-5 Moreover, the axillae often are subject to shaving or other hair removal practices that alter the local environment, as layers of stratum corneum and hair are mechanically removed, which causes irritation and predisposes the skin to enhanced sensitivity to topical exposures.^6,7 With the abundance of apocrine and eccrine glands, the axillae are prone to sweat, which also can accentuate contact allergy.^2,3 Other factors, such as occlusion and friction, contribute to axillary contact allergy.^8,9

Patch testing is the gold standard for the diagnosis of ACD and aids in identification of culprit allergens. A thorough patient history and examination of the rash distribution may provide further clues; for example, dermatitis due to a deodorant typically affects the vault, whereas textile dye dermatitis tends to spare the vault.^10,11 Baseline-limited patch testing detects up to two-thirds of clinically relevant allergens.¹² Therefore, patients may require subsequent testing with supplemental allergens.

The differential diagnosis for axillary lesions is broad—including inflammatory diseases such as irritant contact dermatitis and hidradenitis suppurativa, genetic disorders such as Hailey-Hailey disease, and infectious causes such as erythrasma—but may be narrowed with a thorough physical examination and patient history, histopathology, bedside diagnostic techniques (eg, scrapings and Wood lamp examination), and patch testing. Systemic contact dermatitis (SCD) or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) also may be suspected in cases of intertriginous dermatoses.

We review the potential allergens in products used on the axillae as well as the management of axillary ACD. We also discuss axillary dermatitis as a manifestation of SCD and SDRIFE.

Top Allergens in Products Used on the Axillae

Fragrance—A 1982 North American Contact Dermatitis Group study on cosmetic products identified fragrances as the most common cause of ACD,¹³ and this trend continues to hold true with more recent data.¹⁴ The incidence of fragrance allergy may be increasing, with positive patch tests to a fragrance chemical in 10% of patch test clinic populations.¹⁵ Fragrances are a ubiquitous ingredient in deodorants and antiperspirants, which are important sources implicated in the development and elicitation of fragrance ACD.¹⁶ One study found that fragrance was present in 97 of 107 (90%) deodorants available at Walgreens pharmacies.¹¹

In a study of patients with a history of an axillary rash caused by a deodorant spray, Johansen et al¹⁷ reported that the likelihood of fragrance allergy is increased by a factor of 2.4. This risk of developing a fragrance allergy may be exacerbated in those who shave; Edman¹⁸ reported that the odds ratio of developing a fragrance allergy among men who shave their beards was 2.9. Although there are no specific data on the effects of shaving on ACD, shaving in general can induce localized irritation and increase percutaneous absorption.¹⁹

The individual fragrance components in deodorants most likely to cause ACD include hydroxycitronellal, eugenol, and geraniol—all constituent ingredients in patch test formulations of fragrance mixture I.^11,20 Other common fragrance allergens associated with ACD include hydroxymethylpentylcyclohexenecarboxaldehyde, farnesol, and balsam of Peru.^21-27 Hydroperoxides of limonene and linalool, common fragrances in detergents and personal care products, are increasingly recognized as contact allergens and have been reported to cause axillary ACD from deodorants.^28-30

Dermatitis involving the bilateral axillary vaults wherever deodorant or antiperspirant was directly applied is the most common presentation of ACD due to fragrance (Figure 1).¹⁷ An eczematous eruption is common, though scale may be less apparent than in nonflexural regions. Axillary ACD secondary to fragrances also may result from use of fragranced laundry detergents, fabric softeners, soaps, and perfumes, and may spare the vaults.^10,29,31,32 Less common presentations of axillary ACD due to fragrance include pigmented dermatoses; for example, ACD from an antiperspirant containing hydroperoxide of limonene presented as hyperpigmented patches with minimal erythema and scaling in the edges of the axillary folds.^33,34

Diagnosis of a fragrance ACD typically is made with a standard patch test series including fragrance mixture I and balsam of Peru, which may detect 75% and 50% of fragrance sensitivities, respectively.³⁵ Patch testing may be followed with a repeated open application test of the product in question.³⁶ Additionally, it may be appropriate to test for other fragrance allergens including balsam of Tolu, fragrance mixture II, lichen acid mix, and hydroxyperoxides of linalool and limonene (among other botanicals) if standard patch testing is negative and suspicion of fragrance ACD remains elevated.¹¹

Propylene Glycol—Propylene glycol (PG)—a versatile substance that functions as a solvent, humectant, emulsifier, stabilizer, and antimicrobial—is the second most common contact allergen present in deodorants.¹¹ It is prevalent in both personal care and household products, including deodorants, cosmetics, foods, toothpaste, cleaning agents, and detergents.^11,37 Propylene glycol is both an allergen and an irritant. Among deodorants/antiperspirants, PG is both a common irritant and allergen, as its concentration may be particularly high (as much as 73%).³⁸ One commonly reported example of PG contact dermatitis is from the topical medicament minoxidil.^39,40

Patch testing data have demonstrated a positivity rate for PG ranging between 0.1% to 3.8%. The variability in these findings likely is due to differences in the tested concentrations of PG, as higher concentrations sometimes required to elicit an allergic reaction also may create a stronger irritation effect.⁴¹ Propylene glycol irritancy and the occlusive nature of the axillae may enhance sensitization to other allergens, as demonstrated by Agren-Jonsson and Magnusson,⁴² who reported sensitization to propantheline bromide and trichlorocarbanilide in patients who used a lotion with 90% PG. Many PG-containing products beyond deodorants/antiperspirants may be applied to the axillae, including steroid creams, lotions, shaving creams, and bodywashes.^38,43

The diagnosis of PG allergy via patch testing is challenging and at times controversial given its irritant nature. False-positive irritant reactions have been documented, characterized by a weak reaction at 48 hours that is absent by 96 hours (decrescendo reaction). A reaction may not appear until 96 hours (crescendo reaction), which typically indicates a true contact allergy but in the case of PG also may be the substance acting as a “late irritant.”⁴⁴ Fast (<24 hours) and well-demarcated reactions suggest irritation.⁴⁵ Regardless, reactions to PG on patch testing, even those regarded as weak, may be considered relevant in consideration of the clinical context.³⁷

Aluminum—Aluminum is the active ingredient in most antiperspirants, typically in the form of aluminum chloride, aluminum chlorohydrate, aluminum zirconium trichlorohydrex gly, or aluminum zirconium tetrachlorohydrex gly.⁴⁶ Aluminum mechanically obstructs the eccrine glands to reduce sweat.⁴⁷ Although aluminum is an uncommon allergen, a possible presentation of aluminum allergy is axillary vault dermatitis secondary to antiperspirant use.⁴⁶ Another potential manifestation is a ringlike reaction to the Finn Chambers (SmartPractice) used in patch testing.⁴⁶ In one case of aluminum-induced axillary dermatitis, a 28-year-old woman presented with eczema of the axillae, and subsequent patch testing revealed an allergy to aluminum chloride. The rash resolved upon cessation of use of an aluminum-containing deodorant.⁴⁸

Aluminum has been reported to cause granulomatous dermatitis in the axillae. This reaction typically presents as red-brown, pruritic papules limited to the area in which deodorant was applied, with histopathology revealing epithelioid granulomas.^49-51

Alum deodorants—considered a natural alternative—contain aluminum bound to potassium or ammonium in the form of a crystal or powder. Alum crystal deodorants have been reported to cause both a typical erythematous pruritic dermatitis as well as a granulomatous dermatitis with red-brown papules.^52,53 The granulomatous dermatitis caused by either form of aluminum resolves with avoidance and use of topical steroids or topical tacrolimus.^49,50,52,53

The diagnosis of aluminum ACD via patch testing may be identified with empty Finn Chambers, which are metallic aluminum, or with patch placement of aluminum chloride hexahydrate, though the former is only positive in patients with a strong allergy.^54,55 In 2022, aluminum was named Allergen of the Year by the American Contact Dermatitis Society, with recommendations to conduct patch testing with aluminum chloride hexahydrate 10% rather than the traditional 2% to increase diagnostic yield.⁵⁵ Additionally, it is recommended that aluminum be included in baseline patch testing for children due to the high prevalence of aluminum allergy in children and early exposure via childhood vaccines.^54-56 In patients with aluminum allergy, providers may suggest purchasing aluminum-free deodorants or provide recipes for homemade deodorant that includes ingredients such as arrowroot powder, cornstarch, and diatomaceous earth.⁴⁶

Nickel—Nickel is the most commonly identified contact allergen on patch testing yet an infrequent cause of axillary dermatitis. A case report from 2014 described axillary dermatitis in a woman that worsened during a positive patch test to nickel. Improvement was noted when the patient switched to titanium shaving razors.⁵⁷ Nickel allergy also may present in the form of SCD. In one report, a woman developed dermatitis of the flexural areas, including the axillae, 3 months after undergoing a sterilization procedure in which nickel-containing tubal implants were placed.⁵⁸ Patch testing revealed a positive reaction to nickel. The patient experienced complete resolution of the steroid-resistant dermatitis following removal of the implants via salpingectomy.⁵⁸

Textile Dye—In contrast to dermatitis caused by deodorants/antiperspirants, contact allergy to textile dyes presents as dermatitis involving the axillary borders but sparing the axillary vaults (Figures 2 and 3).¹⁰ Other potential presentations of textile dye dermatitis include erythema multiforme–like eruptions and erythematous wheal–type reactions.⁵⁹ Textile dyes are classified as disperse vs nondisperse, with the majority of contact dermatoses caused by disperse dyes, specifically Disperse Orange 1, blue 106, and blue 124.^60-62 Ryberg et al⁶¹ found that the axilla is one of the more common locations to be affected by textile dye allergy, particularly in women, which was further supported by Seidenari et al,⁶³ who found that skin folds were affected in 27% of study participants allergic to textile dyes (N=437), a finding that is likely due to friction, sweat, and occlusion.⁶² In one case report of a patient with dermatitis caused by reactive dyes, the garment required 3 washes before the patient experienced resolution of dermatitis.⁶⁴ For patients with textile dye dermatitis, mitigation strategies include washing clothing before wearing, especially for darkly dyed items; avoiding tight clothing; wearing garments made of cotton, wool, silk, or linen; and choosing light-colored garments.^9,64,65

Axillary Dermatitis as a Manifestation of SCD and SDRIFE

Systemic contact dermatitis occurs when an individual who was previously sensitized to a particular allergen develops ACD of the skin with systemic exposure to that allergen or immunochemically related allergens. Exposure may occur via ingestion, inhalation, intravenous, intramuscular, and transepidermal routes.⁶⁶ Systemic contact dermatitis manifests in a variety of ways, including focal flares at sites of prior contact dermatitis (recall reaction), vesicular hand dermatitis, intertriginous eruptions including axillary dermatitis, and generalized eruptions.⁶⁷

Systemic contact dermatitis rarely involves systemic symptoms, and onset typically is within days of exposure. The 3 most common groups of allergens causing SCD are metals, medications, and plants and herbals.⁶⁸ These allergens have all been reported to cause axillary dermatitis via SCD.^58,69,70 Foods containing balsam of Peru that may lead to SCD include citrus, chocolate, tomato, and certain alcohols.^70,71 Patients with a positive patch test to balsam of Peru may experience improvement of their dermatitis after reduction of balsam of Peru–rich foods from their diet.⁷⁰ Metals implicated in SCD include mercury, nickel, and gold.^72-74 Finally, PG ingestion also has been implicated in cases of SCD.³⁷

Symmetrical drug-related intertriginous and flexural exanthema is another condition that presents as intertriginous dermatitis and differs from SCD in that the eruption does not require presensitization; there may be no known prior exposure to the agent causing dermatitis. Historically, SDRIFE was described as baboon syndrome because of its frequent involvement of the buttocks with diffuse, well-demarcated, erythematous dermatitis resembling that of a baboon. This term is no longer used due to its insensitive nature and incomplete depiction of SDRIFE, which can affect body sites other than the buttocks.^68,75,76 Specific criteria to make this diagnosis include sharply demarcated and/or V-shaped erythema of the gluteal/perianal area, involvement of at least 1 other intertriginous or flexural region, symmetry of affected areas, and an absence of systemic symptoms.⁷⁶ There also may be papules, pustules, and vesicles present in affected areas. Symmetrical drug-related intertriginous and flexural exanthema most often is caused by β-lactam antibiotics, but other associated drugs include chemotherapeutic agents, such as mitomycin C.⁷⁶

Histopathology of both SCD and SDRIFE is variable and typically nonspecific, often revealing epidermal spongiosis and a perivascular mononuclear cell infiltrate with occasional neutrophils and eosinophils.⁷⁶ A case of SCD to mercury presenting as intertriginous dermatitis demonstrated a leukocytoclastic vasculitis pattern on biopsy.⁷⁷

Systemic contact dermatitis is diagnosed via a patch test, while SDRIFE typically has a negative patch test result and requires oral rechallenge testing, which reproduces the rash within hours.^78,79

Additional Allergens Causing Axillary ACD

Although fragrance is the most common allergen in deodorants, other ingredients have been shown to cause axillary ACD (Table).^80-90 In addition to these ingredients, allergens not previously mentioned that may be present in deodorants include lanolin, essential oils, and parabens.¹¹ Methylisothiazolinone in laundry detergent also has been found to instigate ACD.⁹¹ Fragrances and preservatives in laundry detergents also may contribute to dermatitis.⁹²

Other products that have caused axillary contact dermatitis include topical exposure to medicaments including clindamycin,⁹³ ethylenediamine in nystatin cream,⁹⁴ methylprednisolone acetate⁹⁵ and dipropylene glycol in a hydrocortisone lotion,⁹⁶ wood dusts from tropical hardwoods,⁹⁷ and tobacco.⁹⁸

Management of ACD

The most effective strategy in the management of patients with contact dermatitis is avoidance of the offending agent. Additionally, clinicians may recommend the use of topical steroids and/or calcineurin inhibitors to hasten resolution.²

For patients with contact dermatitis, a clinician may recommend product substitutions with few potential allergens to use prior to patch testing. Patients with a fragrance allergy should look for products specifically labeled as “fragrance free” rather than “hypoallergenic” or “unscented,” as the latter two may still contain minimal amounts of fragrance.³⁵ Patients should be educated on the functions of the allergens to which they are allergic so they may adequately avoid potential sources of contact.⁹⁹ For suspected textile dye dermatitis, instructing patients to wash clothing before wearing and to avoid synthetic fabrics, dark dyes, and tightly fitted clothing may help.^9,64,65

 

 

Differential Diagnosis

The differential diagnosis for axillary lesions is broad, including infectious, inflammatory, and autoimmune etiologies. Irritant contact dermatitis (ICD) presents similar to ACD, though it is more immediate in onsetand typically demonstrates symptoms of burning and stinging rather than pruritus. Although histopathology is not reliable in differentiating ICD and ACD, it has been shown that focal parakeratosis is associated with ACD, whereas necrotic epidermal keratinocytes are found in ICD.¹⁰⁰

Intertrigo presents as large, erythematous, opposing patches or plaques confined to inguinal, submammary, axillary, and/or abdominal folds. Findings of beefy red erythema and peripheral satellite pustules may implicate presence of Candida, which can be identified with potassium hydroxide preparations.

Inverse psoriasis presents as sharply demarcated, erythematous, moist, smooth plaques or patches with minimal scale. The most common area of involvement is the inguinal folds, followed by the axillae, inframammary folds, perianal area, umbilicus, and retroauricular areas. Involvement of the elbows and knees or a positive family history of psoriasis may be useful knowledge in establishing the diagnosis. A biopsy may show dermal eosinophils, epidermal spongiosis, and focal serum in the scale, in addition to features of typical psoriasis plaques.¹⁰¹

Seborrheic dermatitis typically is an erythematous eruption, often with yellowish greasy scale. Simultaneous involvement of the face and scalp may be noted. Although typically a clinical diagnosis, biopsy demonstrates shoulder parakeratosis with follicular plugging and lymphocytic exocytosis.

Hailey-Hailey disease (also called benign familial pemphigus) is an autosomal-dominant genetic condition presenting as moist, malodorous, painful, vegetative plaques, patches, or scaly pustules in flexural areas, frequently with flaccid blisters. Lesions are provoked by traumatic stimuli. Onset occurs in the second to fourth decades and may improve with age. The diagnosis is confirmed by biopsy, which demonstrates acantholysis of the epidermis. The moist superficial patches of Hailey-Hailey disease help distinguish it from comparably drier Darier disease, the other acantholytic disease of the axillae.

Granular parakeratosis (also called hyperkeratotic flexural erythema) is an uncommon dermatosis most often observed in middle-aged women. It presents as red-brown keratotic papules coalescing into plaques, often with overlying scale in intertriginous areas. This disorder may be related to exposure to aluminum, a key component of antiperspirants.¹⁰² Diagnosis with a skin biopsy demonstrates granular parakeratosis.

Infections most commonly include erythrasma, tinea, and candidiasis. Erythrasma caused by Corynebacterium minutissimum may present in the axillae and/or groin with sharply demarcated, red-brown patches. Wood lamp examination reveals coral red fluorescence. Tinea corporis, a dermatophyte infection, may present as scaly erythematous plaques with advancing borders and central clearing. Fungal cultures and potassium hydroxide preparations are useful to confirm the diagnosis.

Pseudofolliculitis barbae most often is thought of as a condition affecting the beard in Black men, but it also may present in individuals of all races who shave the axillary and inguinal regions. Typical features include pruritic inflammatory papules and pustules with surrounding erythema and hyperpigmentation.

Fox-Fordyce disease is a disorder of the apocrine sweat glands that presents as several flesh-colored, perifollicular, monomorphic papules in the axillae. It typically is a disease of young females and also can involve the areola and vulva. Histopathology may show hyperkeratosis, irregular acanthosis, and dilated sweat glands.

Hidradenitis suppurativa is a chronic inflammatory condition that presents with multiple cysts; nodules; abscesses; sinus tract formation; and suppuration of the axillary, anogenital, and sometimes inframammary areas, typically at the onset of puberty. The diagnosis is best supported by history and physical examination, which may be notable for recurrent abscesses, draining tracts, double comedones, and ropelike scarring.

Extramammary Paget disease is a rare malignancy affecting apocrine gland–bearing areas, including axillary and genital regions. It most commonly presents as a unilateral or asymmetric, scaly, erythematous plaque. Histopathology demonstrates Paget cells with abundant clear cytoplasm and pleomorphic nuclei, typically grouped in the lower portion of the epidermis.

Final Thoughts

Axillary dermatoses often can be challenging to diagnose given the range of pathologies that can present in intertriginous areas. Allergic contact dermatitis is a common culprit due to unique anatomical considerations and self-care practices, including shaving/hair removal; use of deodorants, antiperspirants, bodywashes, and clothing; and frictional and moisture influences. The most likely offender among contact allergens is fragrance, but other possibilities to consider include PG, preservatives, aluminum, nickel, and textile dyes. Albeit less common, systemic exposure to allergens may result in SCD and SDRIFE with a rash in intertriginous zones, including the axillae. Additionally, other infectious, inflammatory, and autoimmune etiologies should be considered and ruled out.

Patch testing is the most reliable method to diagnose suspected ACD. Once confirmed, management includes the use of topical steroids and avoidance of the causative agent. Additionally, patients should be informed of the American Contact Dermatitis Society Contact Allergen Management Program (https://www.contactderm.org/patient-support/camp-access), which provides patients with useful information on products that are safe to use based on their patch testing results.

Approximately 20% of the general population has a contact allergy.¹ Allergic contact dermatitis (ACD) is a delayed type IV hypersensitivity reaction mediated by T lymphocytes.² Axillary ACD presentation is variable but typically includes an eczematous eruption with erythematous scaly patches or plaques. Common products in contact with the axillae include deodorants, antiperspirants, razors, bodywash, and clothing.

Axillary skin is distinct from skin elsewhere on the body due to both anatomical characteristics and unique human self-care practices. Axillary skin has reduced barrier function, faster stratum corneum turnover, and altered lipid levels.^3-5 Moreover, the axillae often are subject to shaving or other hair removal practices that alter the local environment, as layers of stratum corneum and hair are mechanically removed, which causes irritation and predisposes the skin to enhanced sensitivity to topical exposures.^6,7 With the abundance of apocrine and eccrine glands, the axillae are prone to sweat, which also can accentuate contact allergy.^2,3 Other factors, such as occlusion and friction, contribute to axillary contact allergy.^8,9

Patch testing is the gold standard for the diagnosis of ACD and aids in identification of culprit allergens. A thorough patient history and examination of the rash distribution may provide further clues; for example, dermatitis due to a deodorant typically affects the vault, whereas textile dye dermatitis tends to spare the vault.^10,11 Baseline-limited patch testing detects up to two-thirds of clinically relevant allergens.¹² Therefore, patients may require subsequent testing with supplemental allergens.

The differential diagnosis for axillary lesions is broad—including inflammatory diseases such as irritant contact dermatitis and hidradenitis suppurativa, genetic disorders such as Hailey-Hailey disease, and infectious causes such as erythrasma—but may be narrowed with a thorough physical examination and patient history, histopathology, bedside diagnostic techniques (eg, scrapings and Wood lamp examination), and patch testing. Systemic contact dermatitis (SCD) or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) also may be suspected in cases of intertriginous dermatoses.

We review the potential allergens in products used on the axillae as well as the management of axillary ACD. We also discuss axillary dermatitis as a manifestation of SCD and SDRIFE.

Top Allergens in Products Used on the Axillae

Fragrance—A 1982 North American Contact Dermatitis Group study on cosmetic products identified fragrances as the most common cause of ACD,¹³ and this trend continues to hold true with more recent data.¹⁴ The incidence of fragrance allergy may be increasing, with positive patch tests to a fragrance chemical in 10% of patch test clinic populations.¹⁵ Fragrances are a ubiquitous ingredient in deodorants and antiperspirants, which are important sources implicated in the development and elicitation of fragrance ACD.¹⁶ One study found that fragrance was present in 97 of 107 (90%) deodorants available at Walgreens pharmacies.¹¹

In a study of patients with a history of an axillary rash caused by a deodorant spray, Johansen et al¹⁷ reported that the likelihood of fragrance allergy is increased by a factor of 2.4. This risk of developing a fragrance allergy may be exacerbated in those who shave; Edman¹⁸ reported that the odds ratio of developing a fragrance allergy among men who shave their beards was 2.9. Although there are no specific data on the effects of shaving on ACD, shaving in general can induce localized irritation and increase percutaneous absorption.¹⁹

The individual fragrance components in deodorants most likely to cause ACD include hydroxycitronellal, eugenol, and geraniol—all constituent ingredients in patch test formulations of fragrance mixture I.^11,20 Other common fragrance allergens associated with ACD include hydroxymethylpentylcyclohexenecarboxaldehyde, farnesol, and balsam of Peru.^21-27 Hydroperoxides of limonene and linalool, common fragrances in detergents and personal care products, are increasingly recognized as contact allergens and have been reported to cause axillary ACD from deodorants.^28-30

Dermatitis involving the bilateral axillary vaults wherever deodorant or antiperspirant was directly applied is the most common presentation of ACD due to fragrance (Figure 1).¹⁷ An eczematous eruption is common, though scale may be less apparent than in nonflexural regions. Axillary ACD secondary to fragrances also may result from use of fragranced laundry detergents, fabric softeners, soaps, and perfumes, and may spare the vaults.^10,29,31,32 Less common presentations of axillary ACD due to fragrance include pigmented dermatoses; for example, ACD from an antiperspirant containing hydroperoxide of limonene presented as hyperpigmented patches with minimal erythema and scaling in the edges of the axillary folds.^33,34

Diagnosis of a fragrance ACD typically is made with a standard patch test series including fragrance mixture I and balsam of Peru, which may detect 75% and 50% of fragrance sensitivities, respectively.³⁵ Patch testing may be followed with a repeated open application test of the product in question.³⁶ Additionally, it may be appropriate to test for other fragrance allergens including balsam of Tolu, fragrance mixture II, lichen acid mix, and hydroxyperoxides of linalool and limonene (among other botanicals) if standard patch testing is negative and suspicion of fragrance ACD remains elevated.¹¹

Propylene Glycol—Propylene glycol (PG)—a versatile substance that functions as a solvent, humectant, emulsifier, stabilizer, and antimicrobial—is the second most common contact allergen present in deodorants.¹¹ It is prevalent in both personal care and household products, including deodorants, cosmetics, foods, toothpaste, cleaning agents, and detergents.^11,37 Propylene glycol is both an allergen and an irritant. Among deodorants/antiperspirants, PG is both a common irritant and allergen, as its concentration may be particularly high (as much as 73%).³⁸ One commonly reported example of PG contact dermatitis is from the topical medicament minoxidil.^39,40

Patch testing data have demonstrated a positivity rate for PG ranging between 0.1% to 3.8%. The variability in these findings likely is due to differences in the tested concentrations of PG, as higher concentrations sometimes required to elicit an allergic reaction also may create a stronger irritation effect.⁴¹ Propylene glycol irritancy and the occlusive nature of the axillae may enhance sensitization to other allergens, as demonstrated by Agren-Jonsson and Magnusson,⁴² who reported sensitization to propantheline bromide and trichlorocarbanilide in patients who used a lotion with 90% PG. Many PG-containing products beyond deodorants/antiperspirants may be applied to the axillae, including steroid creams, lotions, shaving creams, and bodywashes.^38,43

The diagnosis of PG allergy via patch testing is challenging and at times controversial given its irritant nature. False-positive irritant reactions have been documented, characterized by a weak reaction at 48 hours that is absent by 96 hours (decrescendo reaction). A reaction may not appear until 96 hours (crescendo reaction), which typically indicates a true contact allergy but in the case of PG also may be the substance acting as a “late irritant.”⁴⁴ Fast (<24 hours) and well-demarcated reactions suggest irritation.⁴⁵ Regardless, reactions to PG on patch testing, even those regarded as weak, may be considered relevant in consideration of the clinical context.³⁷

Aluminum—Aluminum is the active ingredient in most antiperspirants, typically in the form of aluminum chloride, aluminum chlorohydrate, aluminum zirconium trichlorohydrex gly, or aluminum zirconium tetrachlorohydrex gly.⁴⁶ Aluminum mechanically obstructs the eccrine glands to reduce sweat.⁴⁷ Although aluminum is an uncommon allergen, a possible presentation of aluminum allergy is axillary vault dermatitis secondary to antiperspirant use.⁴⁶ Another potential manifestation is a ringlike reaction to the Finn Chambers (SmartPractice) used in patch testing.⁴⁶ In one case of aluminum-induced axillary dermatitis, a 28-year-old woman presented with eczema of the axillae, and subsequent patch testing revealed an allergy to aluminum chloride. The rash resolved upon cessation of use of an aluminum-containing deodorant.⁴⁸

Aluminum has been reported to cause granulomatous dermatitis in the axillae. This reaction typically presents as red-brown, pruritic papules limited to the area in which deodorant was applied, with histopathology revealing epithelioid granulomas.^49-51

Alum deodorants—considered a natural alternative—contain aluminum bound to potassium or ammonium in the form of a crystal or powder. Alum crystal deodorants have been reported to cause both a typical erythematous pruritic dermatitis as well as a granulomatous dermatitis with red-brown papules.^52,53 The granulomatous dermatitis caused by either form of aluminum resolves with avoidance and use of topical steroids or topical tacrolimus.^49,50,52,53

The diagnosis of aluminum ACD via patch testing may be identified with empty Finn Chambers, which are metallic aluminum, or with patch placement of aluminum chloride hexahydrate, though the former is only positive in patients with a strong allergy.^54,55 In 2022, aluminum was named Allergen of the Year by the American Contact Dermatitis Society, with recommendations to conduct patch testing with aluminum chloride hexahydrate 10% rather than the traditional 2% to increase diagnostic yield.⁵⁵ Additionally, it is recommended that aluminum be included in baseline patch testing for children due to the high prevalence of aluminum allergy in children and early exposure via childhood vaccines.^54-56 In patients with aluminum allergy, providers may suggest purchasing aluminum-free deodorants or provide recipes for homemade deodorant that includes ingredients such as arrowroot powder, cornstarch, and diatomaceous earth.⁴⁶

Nickel—Nickel is the most commonly identified contact allergen on patch testing yet an infrequent cause of axillary dermatitis. A case report from 2014 described axillary dermatitis in a woman that worsened during a positive patch test to nickel. Improvement was noted when the patient switched to titanium shaving razors.⁵⁷ Nickel allergy also may present in the form of SCD. In one report, a woman developed dermatitis of the flexural areas, including the axillae, 3 months after undergoing a sterilization procedure in which nickel-containing tubal implants were placed.⁵⁸ Patch testing revealed a positive reaction to nickel. The patient experienced complete resolution of the steroid-resistant dermatitis following removal of the implants via salpingectomy.⁵⁸

Textile Dye—In contrast to dermatitis caused by deodorants/antiperspirants, contact allergy to textile dyes presents as dermatitis involving the axillary borders but sparing the axillary vaults (Figures 2 and 3).¹⁰ Other potential presentations of textile dye dermatitis include erythema multiforme–like eruptions and erythematous wheal–type reactions.⁵⁹ Textile dyes are classified as disperse vs nondisperse, with the majority of contact dermatoses caused by disperse dyes, specifically Disperse Orange 1, blue 106, and blue 124.^60-62 Ryberg et al⁶¹ found that the axilla is one of the more common locations to be affected by textile dye allergy, particularly in women, which was further supported by Seidenari et al,⁶³ who found that skin folds were affected in 27% of study participants allergic to textile dyes (N=437), a finding that is likely due to friction, sweat, and occlusion.⁶² In one case report of a patient with dermatitis caused by reactive dyes, the garment required 3 washes before the patient experienced resolution of dermatitis.⁶⁴ For patients with textile dye dermatitis, mitigation strategies include washing clothing before wearing, especially for darkly dyed items; avoiding tight clothing; wearing garments made of cotton, wool, silk, or linen; and choosing light-colored garments.^9,64,65

Axillary Dermatitis as a Manifestation of SCD and SDRIFE

Systemic contact dermatitis occurs when an individual who was previously sensitized to a particular allergen develops ACD of the skin with systemic exposure to that allergen or immunochemically related allergens. Exposure may occur via ingestion, inhalation, intravenous, intramuscular, and transepidermal routes.⁶⁶ Systemic contact dermatitis manifests in a variety of ways, including focal flares at sites of prior contact dermatitis (recall reaction), vesicular hand dermatitis, intertriginous eruptions including axillary dermatitis, and generalized eruptions.⁶⁷

Systemic contact dermatitis rarely involves systemic symptoms, and onset typically is within days of exposure. The 3 most common groups of allergens causing SCD are metals, medications, and plants and herbals.⁶⁸ These allergens have all been reported to cause axillary dermatitis via SCD.^58,69,70 Foods containing balsam of Peru that may lead to SCD include citrus, chocolate, tomato, and certain alcohols.^70,71 Patients with a positive patch test to balsam of Peru may experience improvement of their dermatitis after reduction of balsam of Peru–rich foods from their diet.⁷⁰ Metals implicated in SCD include mercury, nickel, and gold.^72-74 Finally, PG ingestion also has been implicated in cases of SCD.³⁷

Symmetrical drug-related intertriginous and flexural exanthema is another condition that presents as intertriginous dermatitis and differs from SCD in that the eruption does not require presensitization; there may be no known prior exposure to the agent causing dermatitis. Historically, SDRIFE was described as baboon syndrome because of its frequent involvement of the buttocks with diffuse, well-demarcated, erythematous dermatitis resembling that of a baboon. This term is no longer used due to its insensitive nature and incomplete depiction of SDRIFE, which can affect body sites other than the buttocks.^68,75,76 Specific criteria to make this diagnosis include sharply demarcated and/or V-shaped erythema of the gluteal/perianal area, involvement of at least 1 other intertriginous or flexural region, symmetry of affected areas, and an absence of systemic symptoms.⁷⁶ There also may be papules, pustules, and vesicles present in affected areas. Symmetrical drug-related intertriginous and flexural exanthema most often is caused by β-lactam antibiotics, but other associated drugs include chemotherapeutic agents, such as mitomycin C.⁷⁶

Histopathology of both SCD and SDRIFE is variable and typically nonspecific, often revealing epidermal spongiosis and a perivascular mononuclear cell infiltrate with occasional neutrophils and eosinophils.⁷⁶ A case of SCD to mercury presenting as intertriginous dermatitis demonstrated a leukocytoclastic vasculitis pattern on biopsy.⁷⁷

Systemic contact dermatitis is diagnosed via a patch test, while SDRIFE typically has a negative patch test result and requires oral rechallenge testing, which reproduces the rash within hours.^78,79

Additional Allergens Causing Axillary ACD

Although fragrance is the most common allergen in deodorants, other ingredients have been shown to cause axillary ACD (Table).^80-90 In addition to these ingredients, allergens not previously mentioned that may be present in deodorants include lanolin, essential oils, and parabens.¹¹ Methylisothiazolinone in laundry detergent also has been found to instigate ACD.⁹¹ Fragrances and preservatives in laundry detergents also may contribute to dermatitis.⁹²

Other products that have caused axillary contact dermatitis include topical exposure to medicaments including clindamycin,⁹³ ethylenediamine in nystatin cream,⁹⁴ methylprednisolone acetate⁹⁵ and dipropylene glycol in a hydrocortisone lotion,⁹⁶ wood dusts from tropical hardwoods,⁹⁷ and tobacco.⁹⁸

Management of ACD

The most effective strategy in the management of patients with contact dermatitis is avoidance of the offending agent. Additionally, clinicians may recommend the use of topical steroids and/or calcineurin inhibitors to hasten resolution.²

For patients with contact dermatitis, a clinician may recommend product substitutions with few potential allergens to use prior to patch testing. Patients with a fragrance allergy should look for products specifically labeled as “fragrance free” rather than “hypoallergenic” or “unscented,” as the latter two may still contain minimal amounts of fragrance.³⁵ Patients should be educated on the functions of the allergens to which they are allergic so they may adequately avoid potential sources of contact.⁹⁹ For suspected textile dye dermatitis, instructing patients to wash clothing before wearing and to avoid synthetic fabrics, dark dyes, and tightly fitted clothing may help.^9,64,65

 

 

Differential Diagnosis

The differential diagnosis for axillary lesions is broad, including infectious, inflammatory, and autoimmune etiologies. Irritant contact dermatitis (ICD) presents similar to ACD, though it is more immediate in onsetand typically demonstrates symptoms of burning and stinging rather than pruritus. Although histopathology is not reliable in differentiating ICD and ACD, it has been shown that focal parakeratosis is associated with ACD, whereas necrotic epidermal keratinocytes are found in ICD.¹⁰⁰

Intertrigo presents as large, erythematous, opposing patches or plaques confined to inguinal, submammary, axillary, and/or abdominal folds. Findings of beefy red erythema and peripheral satellite pustules may implicate presence of Candida, which can be identified with potassium hydroxide preparations.

Inverse psoriasis presents as sharply demarcated, erythematous, moist, smooth plaques or patches with minimal scale. The most common area of involvement is the inguinal folds, followed by the axillae, inframammary folds, perianal area, umbilicus, and retroauricular areas. Involvement of the elbows and knees or a positive family history of psoriasis may be useful knowledge in establishing the diagnosis. A biopsy may show dermal eosinophils, epidermal spongiosis, and focal serum in the scale, in addition to features of typical psoriasis plaques.¹⁰¹

Seborrheic dermatitis typically is an erythematous eruption, often with yellowish greasy scale. Simultaneous involvement of the face and scalp may be noted. Although typically a clinical diagnosis, biopsy demonstrates shoulder parakeratosis with follicular plugging and lymphocytic exocytosis.

Hailey-Hailey disease (also called benign familial pemphigus) is an autosomal-dominant genetic condition presenting as moist, malodorous, painful, vegetative plaques, patches, or scaly pustules in flexural areas, frequently with flaccid blisters. Lesions are provoked by traumatic stimuli. Onset occurs in the second to fourth decades and may improve with age. The diagnosis is confirmed by biopsy, which demonstrates acantholysis of the epidermis. The moist superficial patches of Hailey-Hailey disease help distinguish it from comparably drier Darier disease, the other acantholytic disease of the axillae.

Granular parakeratosis (also called hyperkeratotic flexural erythema) is an uncommon dermatosis most often observed in middle-aged women. It presents as red-brown keratotic papules coalescing into plaques, often with overlying scale in intertriginous areas. This disorder may be related to exposure to aluminum, a key component of antiperspirants.¹⁰² Diagnosis with a skin biopsy demonstrates granular parakeratosis.

Infections most commonly include erythrasma, tinea, and candidiasis. Erythrasma caused by Corynebacterium minutissimum may present in the axillae and/or groin with sharply demarcated, red-brown patches. Wood lamp examination reveals coral red fluorescence. Tinea corporis, a dermatophyte infection, may present as scaly erythematous plaques with advancing borders and central clearing. Fungal cultures and potassium hydroxide preparations are useful to confirm the diagnosis.

Pseudofolliculitis barbae most often is thought of as a condition affecting the beard in Black men, but it also may present in individuals of all races who shave the axillary and inguinal regions. Typical features include pruritic inflammatory papules and pustules with surrounding erythema and hyperpigmentation.

Fox-Fordyce disease is a disorder of the apocrine sweat glands that presents as several flesh-colored, perifollicular, monomorphic papules in the axillae. It typically is a disease of young females and also can involve the areola and vulva. Histopathology may show hyperkeratosis, irregular acanthosis, and dilated sweat glands.

Hidradenitis suppurativa is a chronic inflammatory condition that presents with multiple cysts; nodules; abscesses; sinus tract formation; and suppuration of the axillary, anogenital, and sometimes inframammary areas, typically at the onset of puberty. The diagnosis is best supported by history and physical examination, which may be notable for recurrent abscesses, draining tracts, double comedones, and ropelike scarring.

Extramammary Paget disease is a rare malignancy affecting apocrine gland–bearing areas, including axillary and genital regions. It most commonly presents as a unilateral or asymmetric, scaly, erythematous plaque. Histopathology demonstrates Paget cells with abundant clear cytoplasm and pleomorphic nuclei, typically grouped in the lower portion of the epidermis.

Final Thoughts

Axillary dermatoses often can be challenging to diagnose given the range of pathologies that can present in intertriginous areas. Allergic contact dermatitis is a common culprit due to unique anatomical considerations and self-care practices, including shaving/hair removal; use of deodorants, antiperspirants, bodywashes, and clothing; and frictional and moisture influences. The most likely offender among contact allergens is fragrance, but other possibilities to consider include PG, preservatives, aluminum, nickel, and textile dyes. Albeit less common, systemic exposure to allergens may result in SCD and SDRIFE with a rash in intertriginous zones, including the axillae. Additionally, other infectious, inflammatory, and autoimmune etiologies should be considered and ruled out.

Patch testing is the most reliable method to diagnose suspected ACD. Once confirmed, management includes the use of topical steroids and avoidance of the causative agent. Additionally, patients should be informed of the American Contact Dermatitis Society Contact Allergen Management Program (https://www.contactderm.org/patient-support/camp-access), which provides patients with useful information on products that are safe to use based on their patch testing results.

Clinical Importance

Western poison ivy (Toxicodendron rydbergii) is responsible for many of the cases of Toxicodendron contact dermatitis (TCD) reported in the western and northern United States. Toxicodendron plants cause more cases of allergic contact dermatitis (ACD) in North America than any other allergen¹; 9 million Americans present to physician offices and 1.6 million present to emergency departments annually for ACD, emphasizing the notable medical burden of this condition.^2,3 Exposure to urushiol, a plant resin containing potent allergens, precipitates this form of ACD.

An estimated 50% to 75% of adults in the United States demonstrate clinical sensitivity and exhibit ACD following contact with T rydbergii.⁴ Campers, hikers, firefighters, and forest workers often risk increased exposure through physical contact or aerosolized allergens in smoke. According to the Centers for Disease Control and Prevention, the incidence of visits to US emergency departments for TCD nearly doubled from 2002 to 2012,⁵ which may be explained by atmospheric CO₂ levels that both promote increased growth of Toxicodendron species and augment their toxicity.⁶

Cutaneous Manifestations

The clinical presentation of T rydbergii contact dermatitis is similar to other allergenic members of the Toxicodendron genus. Patients sensitive to urushiol typically develop a pruritic erythematous rash within 1 to 2 days of exposure (range, 5 hours to 15 days).⁷ Erythematous and edematous streaks initially manifest on the extremities and often progress to bullae and oozing papulovesicles. In early disease, patients also may display black lesions on or near the rash⁸ (so-called black-dot dermatitis) caused by oxidized urushiol deposited on the skin—an uncommon yet classic presentation of TCD. Generally, symptoms resolve without complications and with few sequalae, though hyperpigmentation or a secondary infection can develop on or near affected areas.^9,10

Taxonomy

The Toxicodendron genus belongs to the Anacardiaceae family, which includes pistachios, mangos, and cashews, and causes more cases of ACD than every other plant combined.⁴ (Shelled pistachios and cashews do not possess cross-reacting allergens and should not worry consumers; mango skin does contain urushiol.)

Toxicodendron (formerly part of the Rhus genus) includes several species of poison oak, poison ivy, and poison sumac and can be found in shrubs (T rydbergii and Toxicodendron diversilobum), vines (Toxicodendron radicans and Toxicodendron pubescens), and trees (Toxicodendron vernix). In addition, Toxicodendron taxa can hybridize with other taxa in close geographic proximity to form morphologic intermediates. Some individual plants have features of multiple species.¹¹

Etymology

The common name of T rydbergii—western poison ivy—misleads the public; the plant contains no poison that can cause death and does not grow as ivy by wrapping around trees, as T radicans and English ivy (Hedera helix) do. Its formal genus, Toxicodendron, means “poison tree” in Greek and was given its generic name by the English botanist Phillip Miller in 1768,¹² which caused the renaming of Rhus rydbergii as T rydbergii. The species name honors Per Axel Rydberg, a 19th and 20th century Swedish-American botanist.

Distribution

Toxicodendron rydbergii grows in California and other states in the western half of the United States as well as the states bordering Canada and Mexico. In Canada, it reigns as the most dominant form of poison ivy.¹³ Hikers and campers find T rydbergii in a variety of areas, including roadsides, river bottoms, sandy shores, talus slopes, precipices, and floodplains.¹¹ This taxon grows under a variety of conditions and in distinct regions, and it thrives in both full sun or shade.

 

 

Identifying Features

Toxicodendron rydbergii turns red earlier than most plants; early red summer leaves should serve as a warning sign to hikers from a distance (Figure 1). It displays trifoliate ovate leaves (ie, each leaf contains 3 leaflets) on a dwarf nonclimbing shrub (Figure 2). Although the plant shares common features with its cousin T radicans (eastern poison ivy), T rydbergii is easily distinguished by its thicker stems, absence of aerial rootlets (abundant in T radicans), and short (approximately 1 meter) height.⁴

Photograph courtesy of Thomas W. McGovern, MD.

Curly hairs occupy the underside of T rydbergii leaflets and along the midrib; leaflet margins appear lobed or rounded. Lenticels appear as small holes in the bark that turn gray in the cold and become brighter come spring.¹³

Photograph courtesy of Thomas W. McGovern, MD.

The plant bears glabrous long petioles (leaf stems) and densely grouped clusters of yellow flowers. In autumn, the globose fruit—formed in clusters between each twig and leaf petiole (known as an axillary position)—change from yellow-green to tan (Figure 3). When urushiol exudes from damaged leaflets or other plant parts, it oxidizes on exposure to air and creates hardened black deposits on the plant. Even when grown in garden pots, T rydbergii maintains its distinguishing features.¹¹

“Western poison ivy” by Whitney Cranshaw is licensed under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/us/).

Dermatitis-Inducing Plant Parts

All parts of T rydbergii including leaves, stems, roots, and fruit contain the allergenic sap throughout the year.¹⁴ A person must damage or bruise the plant for urushiol to be released and produce its allergenic effects; softly brushing against undamaged plants typically does not induce dermatitis.⁴

Pathophysiology of Urushiol

Urushiol, a pale yellow, oily mixture of organic compounds conserved throughout all Toxicodendron species, contains highly allergenic alkyl catechols. These catechols possess hydroxyl groups at positions 1 and 2 on a benzene ring; the hydrocarbon side chain of poison ivies (typically 15–carbon atoms long) attaches at position 3.¹⁵ The catechols and the aliphatic side chain contribute to the plant’s antigenic and dermatitis-inducing properties.¹⁶

The high lipophilicity of urushiol allows for rapid and unforgiving absorption into the skin, notwithstanding attempts to wash it off. Upon direct contact, catechols of urushiol penetrate the epidermis and become oxidized to quinone intermediates that bind to antigen-presenting cells in the epidermis and dermis. Epidermal Langerhans cells and dermal macrophages internalize and present the antigen to CD4⁺ T cells in nearby lymph nodes. This sequence results in production of inflammatory mediators, clonal expansion of T-effector and T-memory cells specific to the allergenic catechols, and an ensuing cytotoxic response against epidermal cells and the dermal vasculature. Keratinocytes and monocytes mediate the inflammatory response by releasing other cytokines.^4,17

Sensitization to urushiol generally occurs at 8 to 14 years of age; therefore, infants have lower susceptibility to dermatitis upon contact with T rydbergii.¹⁸ Most animals do not experience sensitization upon contact; in fact, birds and forest animals consume the urushiol-rich fruit of T rydbergii without harm.³

Prevention and Treatment

Toxicodendron dermatitis typically lasts 1 to 3 weeks but can remain for as long as 6 weeks without treatment.¹⁹ Recognition and physical avoidance of the plant provides the most promising preventive strategy. Immediate rinsing with soap and water can prevent TCD by breaking down urushiol and its allergenic components; however, this is an option for only a short time, as the skin absorbs 50% of urushiol within 10 minutes after contact.²⁰ Nevertheless, patients must seize the earliest opportunity to wash off the affected area and remove any residual urushiol. Patients must be cautious when removing and washing clothing to prevent further contact.

Most health care providers treat TCD with a corticosteroid to reduce inflammation and intense pruritus. A high-potency topical corticosteroid (eg, clobetasol) may prove effective in providing early therapeutic relief in mild disease.²¹ A short course of a systemic steroid quickly and effectively quenches intense itching and should not be limited to what the clinician considers severe disease. Do not underestimate the patient’s symptoms with this eruption.

Prednisone dosing begins at 1 mg/kg daily and is then tapered slowly over 2 weeks (no shorter a time) for an optimal treatment course of 15 days.²² Prescribing an inadequate dosage and course of a corticosteroid leaves the patient susceptible to rebound dermatitis—and loss of trust in their provider.

Intramuscular injection of the long-acting corticosteroid triamcinolone acetonide with rapid-onset betamethasone provides rapid relief and fewer adverse effects than an oral corticosteroid.²² Despite the long-standing use of sedating oral antihistamines by clinicians, these drugs provide no benefit for pruritus or sleep because the histamine does not cause the itching of TCD, and antihistamines disrupt normal sleep architecture.^23-25

Patients can consider several over-the-counter products that have varying degrees of efficacy.^4,26 The few products for which prospective studies support their use include Tecnu (Tec Laboraties Inc), Zanfel (RhusTox), and the well-known soaps Dial (Henkel Corporation) and Goop (Critzas Industries, Inc).^27,28

Aside from treating the direct effects of TCD, clinicians also must take note of any look for signs of secondary infection and occasionally should consider supplementing treatment with an antibiotic.

Clinical Importance

Western poison ivy (Toxicodendron rydbergii) is responsible for many of the cases of Toxicodendron contact dermatitis (TCD) reported in the western and northern United States. Toxicodendron plants cause more cases of allergic contact dermatitis (ACD) in North America than any other allergen¹; 9 million Americans present to physician offices and 1.6 million present to emergency departments annually for ACD, emphasizing the notable medical burden of this condition.^2,3 Exposure to urushiol, a plant resin containing potent allergens, precipitates this form of ACD.

An estimated 50% to 75% of adults in the United States demonstrate clinical sensitivity and exhibit ACD following contact with T rydbergii.⁴ Campers, hikers, firefighters, and forest workers often risk increased exposure through physical contact or aerosolized allergens in smoke. According to the Centers for Disease Control and Prevention, the incidence of visits to US emergency departments for TCD nearly doubled from 2002 to 2012,⁵ which may be explained by atmospheric CO₂ levels that both promote increased growth of Toxicodendron species and augment their toxicity.⁶

Cutaneous Manifestations

The clinical presentation of T rydbergii contact dermatitis is similar to other allergenic members of the Toxicodendron genus. Patients sensitive to urushiol typically develop a pruritic erythematous rash within 1 to 2 days of exposure (range, 5 hours to 15 days).⁷ Erythematous and edematous streaks initially manifest on the extremities and often progress to bullae and oozing papulovesicles. In early disease, patients also may display black lesions on or near the rash⁸ (so-called black-dot dermatitis) caused by oxidized urushiol deposited on the skin—an uncommon yet classic presentation of TCD. Generally, symptoms resolve without complications and with few sequalae, though hyperpigmentation or a secondary infection can develop on or near affected areas.^9,10

Taxonomy

The Toxicodendron genus belongs to the Anacardiaceae family, which includes pistachios, mangos, and cashews, and causes more cases of ACD than every other plant combined.⁴ (Shelled pistachios and cashews do not possess cross-reacting allergens and should not worry consumers; mango skin does contain urushiol.)

Toxicodendron (formerly part of the Rhus genus) includes several species of poison oak, poison ivy, and poison sumac and can be found in shrubs (T rydbergii and Toxicodendron diversilobum), vines (Toxicodendron radicans and Toxicodendron pubescens), and trees (Toxicodendron vernix). In addition, Toxicodendron taxa can hybridize with other taxa in close geographic proximity to form morphologic intermediates. Some individual plants have features of multiple species.¹¹

Etymology

The common name of T rydbergii—western poison ivy—misleads the public; the plant contains no poison that can cause death and does not grow as ivy by wrapping around trees, as T radicans and English ivy (Hedera helix) do. Its formal genus, Toxicodendron, means “poison tree” in Greek and was given its generic name by the English botanist Phillip Miller in 1768,¹² which caused the renaming of Rhus rydbergii as T rydbergii. The species name honors Per Axel Rydberg, a 19th and 20th century Swedish-American botanist.

Distribution

Toxicodendron rydbergii grows in California and other states in the western half of the United States as well as the states bordering Canada and Mexico. In Canada, it reigns as the most dominant form of poison ivy.¹³ Hikers and campers find T rydbergii in a variety of areas, including roadsides, river bottoms, sandy shores, talus slopes, precipices, and floodplains.¹¹ This taxon grows under a variety of conditions and in distinct regions, and it thrives in both full sun or shade.

 

 

Identifying Features

Toxicodendron rydbergii turns red earlier than most plants; early red summer leaves should serve as a warning sign to hikers from a distance (Figure 1). It displays trifoliate ovate leaves (ie, each leaf contains 3 leaflets) on a dwarf nonclimbing shrub (Figure 2). Although the plant shares common features with its cousin T radicans (eastern poison ivy), T rydbergii is easily distinguished by its thicker stems, absence of aerial rootlets (abundant in T radicans), and short (approximately 1 meter) height.⁴

Photograph courtesy of Thomas W. McGovern, MD.

Curly hairs occupy the underside of T rydbergii leaflets and along the midrib; leaflet margins appear lobed or rounded. Lenticels appear as small holes in the bark that turn gray in the cold and become brighter come spring.¹³

Photograph courtesy of Thomas W. McGovern, MD.

The plant bears glabrous long petioles (leaf stems) and densely grouped clusters of yellow flowers. In autumn, the globose fruit—formed in clusters between each twig and leaf petiole (known as an axillary position)—change from yellow-green to tan (Figure 3). When urushiol exudes from damaged leaflets or other plant parts, it oxidizes on exposure to air and creates hardened black deposits on the plant. Even when grown in garden pots, T rydbergii maintains its distinguishing features.¹¹

“Western poison ivy” by Whitney Cranshaw is licensed under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/us/).

Dermatitis-Inducing Plant Parts

All parts of T rydbergii including leaves, stems, roots, and fruit contain the allergenic sap throughout the year.¹⁴ A person must damage or bruise the plant for urushiol to be released and produce its allergenic effects; softly brushing against undamaged plants typically does not induce dermatitis.⁴

Pathophysiology of Urushiol

Urushiol, a pale yellow, oily mixture of organic compounds conserved throughout all Toxicodendron species, contains highly allergenic alkyl catechols. These catechols possess hydroxyl groups at positions 1 and 2 on a benzene ring; the hydrocarbon side chain of poison ivies (typically 15–carbon atoms long) attaches at position 3.¹⁵ The catechols and the aliphatic side chain contribute to the plant’s antigenic and dermatitis-inducing properties.¹⁶

The high lipophilicity of urushiol allows for rapid and unforgiving absorption into the skin, notwithstanding attempts to wash it off. Upon direct contact, catechols of urushiol penetrate the epidermis and become oxidized to quinone intermediates that bind to antigen-presenting cells in the epidermis and dermis. Epidermal Langerhans cells and dermal macrophages internalize and present the antigen to CD4⁺ T cells in nearby lymph nodes. This sequence results in production of inflammatory mediators, clonal expansion of T-effector and T-memory cells specific to the allergenic catechols, and an ensuing cytotoxic response against epidermal cells and the dermal vasculature. Keratinocytes and monocytes mediate the inflammatory response by releasing other cytokines.^4,17

Sensitization to urushiol generally occurs at 8 to 14 years of age; therefore, infants have lower susceptibility to dermatitis upon contact with T rydbergii.¹⁸ Most animals do not experience sensitization upon contact; in fact, birds and forest animals consume the urushiol-rich fruit of T rydbergii without harm.³

Prevention and Treatment

Toxicodendron dermatitis typically lasts 1 to 3 weeks but can remain for as long as 6 weeks without treatment.¹⁹ Recognition and physical avoidance of the plant provides the most promising preventive strategy. Immediate rinsing with soap and water can prevent TCD by breaking down urushiol and its allergenic components; however, this is an option for only a short time, as the skin absorbs 50% of urushiol within 10 minutes after contact.²⁰ Nevertheless, patients must seize the earliest opportunity to wash off the affected area and remove any residual urushiol. Patients must be cautious when removing and washing clothing to prevent further contact.

Most health care providers treat TCD with a corticosteroid to reduce inflammation and intense pruritus. A high-potency topical corticosteroid (eg, clobetasol) may prove effective in providing early therapeutic relief in mild disease.²¹ A short course of a systemic steroid quickly and effectively quenches intense itching and should not be limited to what the clinician considers severe disease. Do not underestimate the patient’s symptoms with this eruption.

Prednisone dosing begins at 1 mg/kg daily and is then tapered slowly over 2 weeks (no shorter a time) for an optimal treatment course of 15 days.²² Prescribing an inadequate dosage and course of a corticosteroid leaves the patient susceptible to rebound dermatitis—and loss of trust in their provider.

Intramuscular injection of the long-acting corticosteroid triamcinolone acetonide with rapid-onset betamethasone provides rapid relief and fewer adverse effects than an oral corticosteroid.²² Despite the long-standing use of sedating oral antihistamines by clinicians, these drugs provide no benefit for pruritus or sleep because the histamine does not cause the itching of TCD, and antihistamines disrupt normal sleep architecture.^23-25

Patients can consider several over-the-counter products that have varying degrees of efficacy.^4,26 The few products for which prospective studies support their use include Tecnu (Tec Laboraties Inc), Zanfel (RhusTox), and the well-known soaps Dial (Henkel Corporation) and Goop (Critzas Industries, Inc).^27,28

Aside from treating the direct effects of TCD, clinicians also must take note of any look for signs of secondary infection and occasionally should consider supplementing treatment with an antibiotic.

Clinical Importance

Western poison ivy (Toxicodendron rydbergii) is responsible for many of the cases of Toxicodendron contact dermatitis (TCD) reported in the western and northern United States. Toxicodendron plants cause more cases of allergic contact dermatitis (ACD) in North America than any other allergen¹; 9 million Americans present to physician offices and 1.6 million present to emergency departments annually for ACD, emphasizing the notable medical burden of this condition.^2,3 Exposure to urushiol, a plant resin containing potent allergens, precipitates this form of ACD.

An estimated 50% to 75% of adults in the United States demonstrate clinical sensitivity and exhibit ACD following contact with T rydbergii.⁴ Campers, hikers, firefighters, and forest workers often risk increased exposure through physical contact or aerosolized allergens in smoke. According to the Centers for Disease Control and Prevention, the incidence of visits to US emergency departments for TCD nearly doubled from 2002 to 2012,⁵ which may be explained by atmospheric CO₂ levels that both promote increased growth of Toxicodendron species and augment their toxicity.⁶

Cutaneous Manifestations

The clinical presentation of T rydbergii contact dermatitis is similar to other allergenic members of the Toxicodendron genus. Patients sensitive to urushiol typically develop a pruritic erythematous rash within 1 to 2 days of exposure (range, 5 hours to 15 days).⁷ Erythematous and edematous streaks initially manifest on the extremities and often progress to bullae and oozing papulovesicles. In early disease, patients also may display black lesions on or near the rash⁸ (so-called black-dot dermatitis) caused by oxidized urushiol deposited on the skin—an uncommon yet classic presentation of TCD. Generally, symptoms resolve without complications and with few sequalae, though hyperpigmentation or a secondary infection can develop on or near affected areas.^9,10

Taxonomy

The Toxicodendron genus belongs to the Anacardiaceae family, which includes pistachios, mangos, and cashews, and causes more cases of ACD than every other plant combined.⁴ (Shelled pistachios and cashews do not possess cross-reacting allergens and should not worry consumers; mango skin does contain urushiol.)

Toxicodendron (formerly part of the Rhus genus) includes several species of poison oak, poison ivy, and poison sumac and can be found in shrubs (T rydbergii and Toxicodendron diversilobum), vines (Toxicodendron radicans and Toxicodendron pubescens), and trees (Toxicodendron vernix). In addition, Toxicodendron taxa can hybridize with other taxa in close geographic proximity to form morphologic intermediates. Some individual plants have features of multiple species.¹¹

Etymology

The common name of T rydbergii—western poison ivy—misleads the public; the plant contains no poison that can cause death and does not grow as ivy by wrapping around trees, as T radicans and English ivy (Hedera helix) do. Its formal genus, Toxicodendron, means “poison tree” in Greek and was given its generic name by the English botanist Phillip Miller in 1768,¹² which caused the renaming of Rhus rydbergii as T rydbergii. The species name honors Per Axel Rydberg, a 19th and 20th century Swedish-American botanist.

Distribution

Toxicodendron rydbergii grows in California and other states in the western half of the United States as well as the states bordering Canada and Mexico. In Canada, it reigns as the most dominant form of poison ivy.¹³ Hikers and campers find T rydbergii in a variety of areas, including roadsides, river bottoms, sandy shores, talus slopes, precipices, and floodplains.¹¹ This taxon grows under a variety of conditions and in distinct regions, and it thrives in both full sun or shade.

 

 

Identifying Features

Toxicodendron rydbergii turns red earlier than most plants; early red summer leaves should serve as a warning sign to hikers from a distance (Figure 1). It displays trifoliate ovate leaves (ie, each leaf contains 3 leaflets) on a dwarf nonclimbing shrub (Figure 2). Although the plant shares common features with its cousin T radicans (eastern poison ivy), T rydbergii is easily distinguished by its thicker stems, absence of aerial rootlets (abundant in T radicans), and short (approximately 1 meter) height.⁴

Photograph courtesy of Thomas W. McGovern, MD.

Curly hairs occupy the underside of T rydbergii leaflets and along the midrib; leaflet margins appear lobed or rounded. Lenticels appear as small holes in the bark that turn gray in the cold and become brighter come spring.¹³

Photograph courtesy of Thomas W. McGovern, MD.

The plant bears glabrous long petioles (leaf stems) and densely grouped clusters of yellow flowers. In autumn, the globose fruit—formed in clusters between each twig and leaf petiole (known as an axillary position)—change from yellow-green to tan (Figure 3). When urushiol exudes from damaged leaflets or other plant parts, it oxidizes on exposure to air and creates hardened black deposits on the plant. Even when grown in garden pots, T rydbergii maintains its distinguishing features.¹¹

“Western poison ivy” by Whitney Cranshaw is licensed under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/us/).

Dermatitis-Inducing Plant Parts

All parts of T rydbergii including leaves, stems, roots, and fruit contain the allergenic sap throughout the year.¹⁴ A person must damage or bruise the plant for urushiol to be released and produce its allergenic effects; softly brushing against undamaged plants typically does not induce dermatitis.⁴

Pathophysiology of Urushiol

Urushiol, a pale yellow, oily mixture of organic compounds conserved throughout all Toxicodendron species, contains highly allergenic alkyl catechols. These catechols possess hydroxyl groups at positions 1 and 2 on a benzene ring; the hydrocarbon side chain of poison ivies (typically 15–carbon atoms long) attaches at position 3.¹⁵ The catechols and the aliphatic side chain contribute to the plant’s antigenic and dermatitis-inducing properties.¹⁶

The high lipophilicity of urushiol allows for rapid and unforgiving absorption into the skin, notwithstanding attempts to wash it off. Upon direct contact, catechols of urushiol penetrate the epidermis and become oxidized to quinone intermediates that bind to antigen-presenting cells in the epidermis and dermis. Epidermal Langerhans cells and dermal macrophages internalize and present the antigen to CD4⁺ T cells in nearby lymph nodes. This sequence results in production of inflammatory mediators, clonal expansion of T-effector and T-memory cells specific to the allergenic catechols, and an ensuing cytotoxic response against epidermal cells and the dermal vasculature. Keratinocytes and monocytes mediate the inflammatory response by releasing other cytokines.^4,17

Sensitization to urushiol generally occurs at 8 to 14 years of age; therefore, infants have lower susceptibility to dermatitis upon contact with T rydbergii.¹⁸ Most animals do not experience sensitization upon contact; in fact, birds and forest animals consume the urushiol-rich fruit of T rydbergii without harm.³

Prevention and Treatment

Toxicodendron dermatitis typically lasts 1 to 3 weeks but can remain for as long as 6 weeks without treatment.¹⁹ Recognition and physical avoidance of the plant provides the most promising preventive strategy. Immediate rinsing with soap and water can prevent TCD by breaking down urushiol and its allergenic components; however, this is an option for only a short time, as the skin absorbs 50% of urushiol within 10 minutes after contact.²⁰ Nevertheless, patients must seize the earliest opportunity to wash off the affected area and remove any residual urushiol. Patients must be cautious when removing and washing clothing to prevent further contact.

Most health care providers treat TCD with a corticosteroid to reduce inflammation and intense pruritus. A high-potency topical corticosteroid (eg, clobetasol) may prove effective in providing early therapeutic relief in mild disease.²¹ A short course of a systemic steroid quickly and effectively quenches intense itching and should not be limited to what the clinician considers severe disease. Do not underestimate the patient’s symptoms with this eruption.

Prednisone dosing begins at 1 mg/kg daily and is then tapered slowly over 2 weeks (no shorter a time) for an optimal treatment course of 15 days.²² Prescribing an inadequate dosage and course of a corticosteroid leaves the patient susceptible to rebound dermatitis—and loss of trust in their provider.

Intramuscular injection of the long-acting corticosteroid triamcinolone acetonide with rapid-onset betamethasone provides rapid relief and fewer adverse effects than an oral corticosteroid.²² Despite the long-standing use of sedating oral antihistamines by clinicians, these drugs provide no benefit for pruritus or sleep because the histamine does not cause the itching of TCD, and antihistamines disrupt normal sleep architecture.^23-25

Patients can consider several over-the-counter products that have varying degrees of efficacy.^4,26 The few products for which prospective studies support their use include Tecnu (Tec Laboraties Inc), Zanfel (RhusTox), and the well-known soaps Dial (Henkel Corporation) and Goop (Critzas Industries, Inc).^27,28

Aside from treating the direct effects of TCD, clinicians also must take note of any look for signs of secondary infection and occasionally should consider supplementing treatment with an antibiotic.

Nasal tanning spray is a recent phenomenon that has been gaining popularity among consumers on TikTok and other social media platforms. The active ingredient in the tanning spray is melanotan II—a synthetic analog of α‒melanocyte-stimulating hormone,^1,2 a naturally occurring hormone responsible for skin pigmentation. α‒Melanocyte-stimulating hormone is a derivative of the precursor proopiomelanocortin, an agonist on the melanocortin-1 receptor that promotes formation of eumelanin.^1,3 Eumelanin then provides pigmentation to the skin.³ Apart from its use for tanning, melanotan II has been reported to increase sexual function and aid in weight loss.¹

Melanotan II is not approved by the US Food and Drug Administration; however, injectable formulations can be obtained illegally on the Internet as well as at some tanning salons and beauty parlors.⁴ Although injectable forms of melanotan II have been used for years to artificially increase skin pigmentation, the newly hyped nasal tanning sprays are drawing the attention of consumers. The synthetic chemical spray is inhaled into the nasal mucosae, where it is readily absorbed into the bloodstream to act on melanocortin receptors throughout the body, thus enhancing skin pigmentation.² Because melanotan II is not approved, there is no guarantee that the product purchased from those sources is pure; therefore, consumers risk inhaling or injecting contaminated chemicals.⁵

In a 2017 study, Kirk and Greenfield⁶ cited self-image as a common concern among participants who expressed a preference for appearing tanned.⁶ Societal influence and standards to which young adults, particularly young women, often are accustomed drive some to take steps to achieve tanned skin, which they view as more attractive and healthier than untanned skin.^7,8

Social media consumption is a significant risk factor for developing or exacerbating body dissatisfaction among impressionable teenagers and young adults, who may be less risk averse and therefore choose to embrace trends such as nasal tanning sprays to enhance their appearance, without considering possible consequences. Most young adults, and even teens, are aware of the risks associated with tanning beds, which may propel them to seek out what they perceive as a less-risky tanning alternative such as a tanner delivered via a nasal route, but it is unlikely that this group is fully informed about the possible dangers of nasal tanning sprays.

It is crucial for dermatologists and other clinicians to provide awareness and education about the potential harm of nasal tanning sprays. Along with the general risks of using an unregulated substance, common adverse effects include acne, facial flushing, gastrointestinal tract upset, and sensitivity to sunlight (Table).^1,9,10 Several case reports have linked melanotan II to cutaneous changes, including dysplastic nevi and even melanoma.¹ Less common complications, such as renal infarction and priapism, also have been observed with melanotan II use.^9,10

Even with the known risks involving tanning beds and skin cancer, an analysis by Kream et al¹¹ in 2020 showed that 90% (441/488) of tanning-related videos on TikTok promoted a positive view of tanning. Of these TikTok videos involving pro-tanning trends, 3% (12/441) were specifically about melanotan II nasal spray, injection, or both, which has only become more popular since this study was published.¹¹

Dermatologists should be aware of the impact that tanning trends, such as nasal tanning spray, can have on all patients and initiate discussions regarding the risks of using these products with patients as appropriate. Alternatives to nasal tanning sprays such as spray-on tans and self-tanning lotions are safer ways for patients to achieve a tanned look without the health risks associated with melanotan II.

Nasal tanning spray is a recent phenomenon that has been gaining popularity among consumers on TikTok and other social media platforms. The active ingredient in the tanning spray is melanotan II—a synthetic analog of α‒melanocyte-stimulating hormone,^1,2 a naturally occurring hormone responsible for skin pigmentation. α‒Melanocyte-stimulating hormone is a derivative of the precursor proopiomelanocortin, an agonist on the melanocortin-1 receptor that promotes formation of eumelanin.^1,3 Eumelanin then provides pigmentation to the skin.³ Apart from its use for tanning, melanotan II has been reported to increase sexual function and aid in weight loss.¹

Melanotan II is not approved by the US Food and Drug Administration; however, injectable formulations can be obtained illegally on the Internet as well as at some tanning salons and beauty parlors.⁴ Although injectable forms of melanotan II have been used for years to artificially increase skin pigmentation, the newly hyped nasal tanning sprays are drawing the attention of consumers. The synthetic chemical spray is inhaled into the nasal mucosae, where it is readily absorbed into the bloodstream to act on melanocortin receptors throughout the body, thus enhancing skin pigmentation.² Because melanotan II is not approved, there is no guarantee that the product purchased from those sources is pure; therefore, consumers risk inhaling or injecting contaminated chemicals.⁵

In a 2017 study, Kirk and Greenfield⁶ cited self-image as a common concern among participants who expressed a preference for appearing tanned.⁶ Societal influence and standards to which young adults, particularly young women, often are accustomed drive some to take steps to achieve tanned skin, which they view as more attractive and healthier than untanned skin.^7,8

Social media consumption is a significant risk factor for developing or exacerbating body dissatisfaction among impressionable teenagers and young adults, who may be less risk averse and therefore choose to embrace trends such as nasal tanning sprays to enhance their appearance, without considering possible consequences. Most young adults, and even teens, are aware of the risks associated with tanning beds, which may propel them to seek out what they perceive as a less-risky tanning alternative such as a tanner delivered via a nasal route, but it is unlikely that this group is fully informed about the possible dangers of nasal tanning sprays.

It is crucial for dermatologists and other clinicians to provide awareness and education about the potential harm of nasal tanning sprays. Along with the general risks of using an unregulated substance, common adverse effects include acne, facial flushing, gastrointestinal tract upset, and sensitivity to sunlight (Table).^1,9,10 Several case reports have linked melanotan II to cutaneous changes, including dysplastic nevi and even melanoma.¹ Less common complications, such as renal infarction and priapism, also have been observed with melanotan II use.^9,10

Even with the known risks involving tanning beds and skin cancer, an analysis by Kream et al¹¹ in 2020 showed that 90% (441/488) of tanning-related videos on TikTok promoted a positive view of tanning. Of these TikTok videos involving pro-tanning trends, 3% (12/441) were specifically about melanotan II nasal spray, injection, or both, which has only become more popular since this study was published.¹¹

Dermatologists should be aware of the impact that tanning trends, such as nasal tanning spray, can have on all patients and initiate discussions regarding the risks of using these products with patients as appropriate. Alternatives to nasal tanning sprays such as spray-on tans and self-tanning lotions are safer ways for patients to achieve a tanned look without the health risks associated with melanotan II.

Nasal tanning spray is a recent phenomenon that has been gaining popularity among consumers on TikTok and other social media platforms. The active ingredient in the tanning spray is melanotan II—a synthetic analog of α‒melanocyte-stimulating hormone,^1,2 a naturally occurring hormone responsible for skin pigmentation. α‒Melanocyte-stimulating hormone is a derivative of the precursor proopiomelanocortin, an agonist on the melanocortin-1 receptor that promotes formation of eumelanin.^1,3 Eumelanin then provides pigmentation to the skin.³ Apart from its use for tanning, melanotan II has been reported to increase sexual function and aid in weight loss.¹

Melanotan II is not approved by the US Food and Drug Administration; however, injectable formulations can be obtained illegally on the Internet as well as at some tanning salons and beauty parlors.⁴ Although injectable forms of melanotan II have been used for years to artificially increase skin pigmentation, the newly hyped nasal tanning sprays are drawing the attention of consumers. The synthetic chemical spray is inhaled into the nasal mucosae, where it is readily absorbed into the bloodstream to act on melanocortin receptors throughout the body, thus enhancing skin pigmentation.² Because melanotan II is not approved, there is no guarantee that the product purchased from those sources is pure; therefore, consumers risk inhaling or injecting contaminated chemicals.⁵

In a 2017 study, Kirk and Greenfield⁶ cited self-image as a common concern among participants who expressed a preference for appearing tanned.⁶ Societal influence and standards to which young adults, particularly young women, often are accustomed drive some to take steps to achieve tanned skin, which they view as more attractive and healthier than untanned skin.^7,8

Social media consumption is a significant risk factor for developing or exacerbating body dissatisfaction among impressionable teenagers and young adults, who may be less risk averse and therefore choose to embrace trends such as nasal tanning sprays to enhance their appearance, without considering possible consequences. Most young adults, and even teens, are aware of the risks associated with tanning beds, which may propel them to seek out what they perceive as a less-risky tanning alternative such as a tanner delivered via a nasal route, but it is unlikely that this group is fully informed about the possible dangers of nasal tanning sprays.

It is crucial for dermatologists and other clinicians to provide awareness and education about the potential harm of nasal tanning sprays. Along with the general risks of using an unregulated substance, common adverse effects include acne, facial flushing, gastrointestinal tract upset, and sensitivity to sunlight (Table).^1,9,10 Several case reports have linked melanotan II to cutaneous changes, including dysplastic nevi and even melanoma.¹ Less common complications, such as renal infarction and priapism, also have been observed with melanotan II use.^9,10

Even with the known risks involving tanning beds and skin cancer, an analysis by Kream et al¹¹ in 2020 showed that 90% (441/488) of tanning-related videos on TikTok promoted a positive view of tanning. Of these TikTok videos involving pro-tanning trends, 3% (12/441) were specifically about melanotan II nasal spray, injection, or both, which has only become more popular since this study was published.¹¹

Dermatologists should be aware of the impact that tanning trends, such as nasal tanning spray, can have on all patients and initiate discussions regarding the risks of using these products with patients as appropriate. Alternatives to nasal tanning sprays such as spray-on tans and self-tanning lotions are safer ways for patients to achieve a tanned look without the health risks associated with melanotan II.

Acrylates are a ubiquitous family of synthetic thermoplastic resins that are employed in a wide array of products. Since the discovery of acrylic acid in 1843 and its industrialization in the early 20th century, acrylates have been used by many different sectors of industry.¹ Today, acrylates can be found in diverse sources such as adhesives, coatings, electronics, nail cosmetics, dental materials, and medical devices. Although these versatile compounds have revolutionized numerous sectors, their potential to trigger allergic contact dermatitis (ACD) has garnered considerable attention in recent years. In 2012, acrylates as a group were named Allergen of the Year by the American Contact Dermatitis Society,² and one member—isobornyl acrylate—also was given the infamous award in 2020.³ In this article, we highlight the chemistry of acrylates, the growing prevalence of acrylate contact allergy, common sources of exposure, patch testing considerations, and management/prevention strategies.

Chemistry and Uses of Acrylates

Acrylates are widely used due to their pliable and resilient properties.⁴ They begin as liquid monomers of (meth)acrylic acid or cyanoacrylic acid that are molded to the desired application before being cured or hardened by one of several means: spontaneously, using chemical catalysts, or with heat, UV light, or a light-emitting diode. Once cured, the final polymers (ie, [meth]acrylates, cyanoacrylates) serve a myriad of different purposes. Table 1 includes some of the more clinically relevant sources of acrylate exposure. Although this list is not comprehensive, it offers a glimpse into the vast array of uses for acrylates.

Acrylate Contact Allergy

Acrylic monomers are potent contact allergens, but the polymerized final products are not considered allergenic, assuming they are completely cured; however, ACD can occur with incomplete curing.⁶ It is of clinical importance that once an individual becomes sensitized to one type of acrylate, they may develop cross-reactions to others contained in different products. Notably, cyanoacrylates generally do not cross-react with (meth)acrylates; this has important implications for choosing safe alternative products in sensitized patients, though independent sensitization to cyanoacrylates is possible.^7,8

Epidemiology and Risk Factors

The prevalence of acrylate allergy in the general population is unknown; however, there is a trend of increased patch test positivity in studies of patients referred for patch testing. A 2018 study by the European Environmental Contact Dermatitis Research Group reported positive patch tests to acrylates in 1.1% of 18,228 patients tested from 2013 to 2015.⁹ More recently, a multicenter European study (2019-2020) reported a 2.3% patch test positivity to 2-hydroxyethyl methacrylate (HEMA) among 7675 tested individuals,¹⁰ and even higher HEMA positivity was reported in Spain (3.7% of 1884 patients in 2019-2020).¹¹ In addition, the North American Contact Dermatitis Group (NACDG) reported positive patch test reactions to HEMA in 3.2% of 4111 patients tested from 2019 to 2020, a statistically significant increase compared with those tested in 2009 to 2018 (odds ratio, 1.25 [95% CI, 1.03-1.51]; P=.02).¹²

Historically, acrylate sensitization primarily stemmed from occupational exposure. A retrospective analysis of occupational dermatitis performed by the NACDG (2001-2016) showed that HEMA was among the top 10 most common occupational allergens (3.4% positivity [83/2461]) and had the fifth highest percentage of occupationally relevant reactions (73.5% [83/113]).¹³ High-risk occupations include dental providers and nail technicians. Dentistry utilizes many materials containing acrylates, including uncured plastic resins used in dental prostheses, dentin bonding materials, and glass ionomers.¹⁴ A retrospective analysis of 585 dental personnel who were patch tested by the NACDG (2001-2018) found that more than 20% of occupational ACD cases were related to acrylates.¹⁵ Nail technicians are another group routinely exposed to acrylates through a variety of modern nail cosmetics. In a 7-year study from Portugal evaluating acrylate ACD, 68% (25/37) of cases were attributed to occupation, 80% (20/25) of which were in nail technicians.¹⁶ Likewise, among 28 nail technicians in Sweden who were referred for patch testing, 57% (16/28) tested positive for at least 1 acrylate.¹⁷

Modern Sources of Acrylate Exposure

Once thought to be a predominantly occupational exposure, acrylates have rapidly made their way into everyday consumer products. Clinicians should be aware of several sources of clinically relevant acrylate exposure, including nail cosmetics, consumer electronics, and medical/surgical adhesives.

A 2016 study found a shift to nail cosmetics as the most common source of acrylate sensitization.¹⁸ Nail cosmetics that contain acrylates include traditional acrylic, gel (shellac), dipped, and press-on (false) nails.¹⁹ The NACDG found that the most common allergen in patients experiencing ACD associated with nail products (2001-2016) was HEMA (56.6% [273/482]), far ahead of the traditional nail polish allergen tosylamide (36.2% [273/755]). Over the study period, the frequency of positive patch tests statistically increased for HEMA (P=.0069) and decreased for tosylamide (P<.0001).²⁰ There is concern that the use of home gel nail kits, which can be purchased online at the click of a button, may be associated with a risk for acrylate sensitization.^21,22 A recent study surveyed a Facebook support group for individuals with self-reported reactions to nail cosmetics, finding that 78% of the 199 individuals had used at-home gel nail kits, and more than 80% of them first developed skin reactions after starting to use at-home kits.²³ The risks for sensitization are thought to be greater when self-applying nail acrylates compared to having them done professionally because individuals are more likely to spill allergenic monomers onto the skin at home; it also is possible that home techniques could lead to incomplete curing. Table 2 reviews the different types of acrylic nail cosmetics.

Medical adhesives and equipment are other important areas where acrylates can be encountered in abundance. A review by Spencer et al¹⁸ cautioned wound dressings as an up-and-coming source of sensitization, and this has been demonstrated in the literature as coming to fruition.²⁶ Another study identified acrylates in 15 of 16 (94%) tested medical adhesives; among 7 medical adhesives labeled as hypoallergenic, 100% still contained acrylates and/or abietic acid.²⁷ Multiple case reports have described ACD to adhesives of electrocardiogram electrodes containing acrylates.^28-31 Physicians providing care to patients with diabetes mellitus also must be aware of acrylates in glucose monitors and insulin pumps, either found in the adhesives or leaching from the inside of the device to reach the skin.³² Isobornyl acrylate in particular has made quite the name for itself in this sector, being crowned the 2020 Allergen of the Year owing to its key role in cases of ACD to diabetes devices.³

Cyanoacrylate-based tissue adhesives (eg, 2‐octyl cyanoacrylate) are now well documented to cause postoperative ACD.^33,34 Although robust prospective data are limited, studies suggest that 2% to 14% of patients develop postoperative skin reactions following 2-octyl cyanoacrylate application.^35-37 It has been shown that sensitization to tissue adhesives often occurs after the first application, followed by an eruption of ACD as long as a month later, which can create confusion about the nature of the rash for patients and health care providers alike, who may for instance attribute it to infection rather than allergy.³⁸ In the orthopedic literature, a woman with a known history of acrylic nail ACD had knee arthroplasty failure attributed to acrylic bone cement with resolution of the joint symptoms after changing to a cementless device.³⁹

Awareness of the common use of acrylates is important to identify the cause of reactions from products that would otherwise seem nonallergenic. A case of occupational ACD to isobornyl acrylate in UV-cured phone screen protectors has been reported⁴⁰; several cases of ACD to acrylates in headphones^41,42 as well as one related to a wearable fitness device also have been reported.⁴³ Given all these possible sources of exposure, ACD to acrylates should be on your radar.

When to Consider Acrylate ACD

When working up a patient with dermatitis, it is essential to ask about occupational history and hobbies to get a sense of potential contact allergen exposures. The typical presentation of occupational acrylate-associated ACD is hand eczema, specifically involving the fingertips.^5,24,25,44 Acrylate ACD should be considered in patients with nail dystrophy and a history of wearing acrylic nails.⁴⁵ There can even be involvement of the face and eyelids secondary to airborne contact or ectopic spread from the hands.²⁴ Spreading vesicular eruptions associated with adhesives also should raise concern. The Figure depicts several possible presentations of ACD to acrylates. In a time of abundant access to products containing acrylates, dermatologists should consider this allergy in their differential diagnosis and consider patch testing.

Photographs courtesy of Brandon L. Adler, MD.

Patch Testing to Acrylates

The gold standard for ACD diagnosis is patch testing. It should be noted that no acrylates are included in the thin-layer rapid use epicutaneous (T.R.U.E.) test series. Several acrylates are tested in expanded patch test series including the American Contact Dermatitis Society Core Allergen series and North American 80 Comprehensive Series. 2-Hydroxyethyl methacrylate is thought to be the most important screening allergen to test. Ramos et al¹⁶ reported a positive patch test to HEMA in 81% (30/37) of patients who had any type of acrylate allergy.

If initial testing to a limited number of acrylates is negative but clinical suspicion remains high, expanded acrylates/plastics and glue series also are available from commercial patch test suppliers. Testing to an expanded panel of acrylates is especially pertinent to consider in suspected occupational cases given the risk of workplace absenteeism and even disability that come with continued exposure to the allergen. Of note, isobornyl acrylate is not included in the baseline patch test series and must be tested separately, particularly because it usually does not cross-react with other acrylates, and therefore allergy could be missed if not tested on its own.

Acrylates are volatile substances that have been shown to degrade at room temperature and to a lesser degree when refrigerated. Ideally, they should be stored in a freezer and not used beyond their expiration date. Furthermore, it is advised that acrylate patch tests be prepared immediately prior to placement on the patient and to discard the initial extrusion from the syringe, as the concentration at the tip may be decreased.^46,47

With regard to tissue adhesives, the actual product should be tested as-is because these are not commercially available patch test substances.⁴⁸ Occasionally, patients who are sensitized to the tissue adhesive will not react when patch tested on intact skin. If clinical suspicion remains high, scratch patch testing may confirm contact allergy in cases of negative testing on intact skin.⁴⁹

Management and Prevention

Once a diagnosis of ACD secondary to acrylates has been established, counseling patients on allergen avoidance strategies is essential. For (meth)acrylate-allergic patients who want to continue using modern nail products, cyanoacrylate-based options (eg, dipped, press-on nails) can be considered as an alternative, as they do not cross-react, though independent sensitization is still possible. However, traditional nail polish is the safest option to recommend.

The concern with acrylate sensitization extends beyond the immediate issue that brought the patient into your clinic. Dermatologists must counsel patients who are sensitized to acrylates on the possible sequelae of acrylate-containing dental or orthopedic procedures. Oral lichenoid lesions, denture stomatitis, burning mouth syndrome, or even acute facial swelling have been reported following dental work in patients with acrylate allergy.^50-53 Dentists of patients with acrylate ACD should be informed of the diagnosis so acrylates can be avoided during dental work; if unavoidable, all possible steps should be taken to ensure complete curing of the monomers. In the surgical setting, patients sensitized to cyanoacrylate-based tissue adhesives should be offered wound closure alternatives such as sutures or staples.³⁴

In patients with diabetes mellitus who develop ACD to their glucose monitor or insulin pump, ideally they should be switched to a device that does not contain acrylates. Problematically, these devices are constantly being reformulated, and manufacturers do not always divulge their components, which can make it challenging to determine safe alternative options.^32,54 Various barrier products may help on a case-by-case basis.⁵⁵Preventative measures should be implemented in workplaces that utilize acrylates, including dental practices and nail salons. Acrylic monomers have been shown to penetrate most gloves within minutes of exposure.^56,57 Double gloving with nitrile gloves affords some protection for no longer than 60 minutes.⁶ 4H gloves have been shown to provide true protection but result in a loss of dexterity.⁵⁸ The fingerstall technique involves removing the fingers from a 4H glove, inserting them on the fingers, and applying a more flexible glove on top to hold them in place; this offers a hybrid between protection and finger dexterity.⁵⁹

Final Interpretation

In a world characterized by technological advancements and increasing accessibility to acrylate-containing products, we hope this brief review serves as a resource and reminder to dermatologists to consider acrylates as a potential cause of ACD with diverse presentations and important future implications for affected individuals. The rising trend of acrylate allergy necessitates comprehensive assessment and shared decision-making between physicians and patients. As we navigate the ever-changing landscape of materials and technologies, clinicians must remain vigilant to avoid some potentially sticky situations for patients.

Acrylates are a ubiquitous family of synthetic thermoplastic resins that are employed in a wide array of products. Since the discovery of acrylic acid in 1843 and its industrialization in the early 20th century, acrylates have been used by many different sectors of industry.¹ Today, acrylates can be found in diverse sources such as adhesives, coatings, electronics, nail cosmetics, dental materials, and medical devices. Although these versatile compounds have revolutionized numerous sectors, their potential to trigger allergic contact dermatitis (ACD) has garnered considerable attention in recent years. In 2012, acrylates as a group were named Allergen of the Year by the American Contact Dermatitis Society,² and one member—isobornyl acrylate—also was given the infamous award in 2020.³ In this article, we highlight the chemistry of acrylates, the growing prevalence of acrylate contact allergy, common sources of exposure, patch testing considerations, and management/prevention strategies.

Chemistry and Uses of Acrylates

Acrylates are widely used due to their pliable and resilient properties.⁴ They begin as liquid monomers of (meth)acrylic acid or cyanoacrylic acid that are molded to the desired application before being cured or hardened by one of several means: spontaneously, using chemical catalysts, or with heat, UV light, or a light-emitting diode. Once cured, the final polymers (ie, [meth]acrylates, cyanoacrylates) serve a myriad of different purposes. Table 1 includes some of the more clinically relevant sources of acrylate exposure. Although this list is not comprehensive, it offers a glimpse into the vast array of uses for acrylates.

Acrylate Contact Allergy

Acrylic monomers are potent contact allergens, but the polymerized final products are not considered allergenic, assuming they are completely cured; however, ACD can occur with incomplete curing.⁶ It is of clinical importance that once an individual becomes sensitized to one type of acrylate, they may develop cross-reactions to others contained in different products. Notably, cyanoacrylates generally do not cross-react with (meth)acrylates; this has important implications for choosing safe alternative products in sensitized patients, though independent sensitization to cyanoacrylates is possible.^7,8

Epidemiology and Risk Factors

The prevalence of acrylate allergy in the general population is unknown; however, there is a trend of increased patch test positivity in studies of patients referred for patch testing. A 2018 study by the European Environmental Contact Dermatitis Research Group reported positive patch tests to acrylates in 1.1% of 18,228 patients tested from 2013 to 2015.⁹ More recently, a multicenter European study (2019-2020) reported a 2.3% patch test positivity to 2-hydroxyethyl methacrylate (HEMA) among 7675 tested individuals,¹⁰ and even higher HEMA positivity was reported in Spain (3.7% of 1884 patients in 2019-2020).¹¹ In addition, the North American Contact Dermatitis Group (NACDG) reported positive patch test reactions to HEMA in 3.2% of 4111 patients tested from 2019 to 2020, a statistically significant increase compared with those tested in 2009 to 2018 (odds ratio, 1.25 [95% CI, 1.03-1.51]; P=.02).¹²

Historically, acrylate sensitization primarily stemmed from occupational exposure. A retrospective analysis of occupational dermatitis performed by the NACDG (2001-2016) showed that HEMA was among the top 10 most common occupational allergens (3.4% positivity [83/2461]) and had the fifth highest percentage of occupationally relevant reactions (73.5% [83/113]).¹³ High-risk occupations include dental providers and nail technicians. Dentistry utilizes many materials containing acrylates, including uncured plastic resins used in dental prostheses, dentin bonding materials, and glass ionomers.¹⁴ A retrospective analysis of 585 dental personnel who were patch tested by the NACDG (2001-2018) found that more than 20% of occupational ACD cases were related to acrylates.¹⁵ Nail technicians are another group routinely exposed to acrylates through a variety of modern nail cosmetics. In a 7-year study from Portugal evaluating acrylate ACD, 68% (25/37) of cases were attributed to occupation, 80% (20/25) of which were in nail technicians.¹⁶ Likewise, among 28 nail technicians in Sweden who were referred for patch testing, 57% (16/28) tested positive for at least 1 acrylate.¹⁷

Modern Sources of Acrylate Exposure

Once thought to be a predominantly occupational exposure, acrylates have rapidly made their way into everyday consumer products. Clinicians should be aware of several sources of clinically relevant acrylate exposure, including nail cosmetics, consumer electronics, and medical/surgical adhesives.

A 2016 study found a shift to nail cosmetics as the most common source of acrylate sensitization.¹⁸ Nail cosmetics that contain acrylates include traditional acrylic, gel (shellac), dipped, and press-on (false) nails.¹⁹ The NACDG found that the most common allergen in patients experiencing ACD associated with nail products (2001-2016) was HEMA (56.6% [273/482]), far ahead of the traditional nail polish allergen tosylamide (36.2% [273/755]). Over the study period, the frequency of positive patch tests statistically increased for HEMA (P=.0069) and decreased for tosylamide (P<.0001).²⁰ There is concern that the use of home gel nail kits, which can be purchased online at the click of a button, may be associated with a risk for acrylate sensitization.^21,22 A recent study surveyed a Facebook support group for individuals with self-reported reactions to nail cosmetics, finding that 78% of the 199 individuals had used at-home gel nail kits, and more than 80% of them first developed skin reactions after starting to use at-home kits.²³ The risks for sensitization are thought to be greater when self-applying nail acrylates compared to having them done professionally because individuals are more likely to spill allergenic monomers onto the skin at home; it also is possible that home techniques could lead to incomplete curing. Table 2 reviews the different types of acrylic nail cosmetics.

Medical adhesives and equipment are other important areas where acrylates can be encountered in abundance. A review by Spencer et al¹⁸ cautioned wound dressings as an up-and-coming source of sensitization, and this has been demonstrated in the literature as coming to fruition.²⁶ Another study identified acrylates in 15 of 16 (94%) tested medical adhesives; among 7 medical adhesives labeled as hypoallergenic, 100% still contained acrylates and/or abietic acid.²⁷ Multiple case reports have described ACD to adhesives of electrocardiogram electrodes containing acrylates.^28-31 Physicians providing care to patients with diabetes mellitus also must be aware of acrylates in glucose monitors and insulin pumps, either found in the adhesives or leaching from the inside of the device to reach the skin.³² Isobornyl acrylate in particular has made quite the name for itself in this sector, being crowned the 2020 Allergen of the Year owing to its key role in cases of ACD to diabetes devices.³

Cyanoacrylate-based tissue adhesives (eg, 2‐octyl cyanoacrylate) are now well documented to cause postoperative ACD.^33,34 Although robust prospective data are limited, studies suggest that 2% to 14% of patients develop postoperative skin reactions following 2-octyl cyanoacrylate application.^35-37 It has been shown that sensitization to tissue adhesives often occurs after the first application, followed by an eruption of ACD as long as a month later, which can create confusion about the nature of the rash for patients and health care providers alike, who may for instance attribute it to infection rather than allergy.³⁸ In the orthopedic literature, a woman with a known history of acrylic nail ACD had knee arthroplasty failure attributed to acrylic bone cement with resolution of the joint symptoms after changing to a cementless device.³⁹

Awareness of the common use of acrylates is important to identify the cause of reactions from products that would otherwise seem nonallergenic. A case of occupational ACD to isobornyl acrylate in UV-cured phone screen protectors has been reported⁴⁰; several cases of ACD to acrylates in headphones^41,42 as well as one related to a wearable fitness device also have been reported.⁴³ Given all these possible sources of exposure, ACD to acrylates should be on your radar.

When to Consider Acrylate ACD

When working up a patient with dermatitis, it is essential to ask about occupational history and hobbies to get a sense of potential contact allergen exposures. The typical presentation of occupational acrylate-associated ACD is hand eczema, specifically involving the fingertips.^5,24,25,44 Acrylate ACD should be considered in patients with nail dystrophy and a history of wearing acrylic nails.⁴⁵ There can even be involvement of the face and eyelids secondary to airborne contact or ectopic spread from the hands.²⁴ Spreading vesicular eruptions associated with adhesives also should raise concern. The Figure depicts several possible presentations of ACD to acrylates. In a time of abundant access to products containing acrylates, dermatologists should consider this allergy in their differential diagnosis and consider patch testing.

Photographs courtesy of Brandon L. Adler, MD.

Patch Testing to Acrylates

The gold standard for ACD diagnosis is patch testing. It should be noted that no acrylates are included in the thin-layer rapid use epicutaneous (T.R.U.E.) test series. Several acrylates are tested in expanded patch test series including the American Contact Dermatitis Society Core Allergen series and North American 80 Comprehensive Series. 2-Hydroxyethyl methacrylate is thought to be the most important screening allergen to test. Ramos et al¹⁶ reported a positive patch test to HEMA in 81% (30/37) of patients who had any type of acrylate allergy.

If initial testing to a limited number of acrylates is negative but clinical suspicion remains high, expanded acrylates/plastics and glue series also are available from commercial patch test suppliers. Testing to an expanded panel of acrylates is especially pertinent to consider in suspected occupational cases given the risk of workplace absenteeism and even disability that come with continued exposure to the allergen. Of note, isobornyl acrylate is not included in the baseline patch test series and must be tested separately, particularly because it usually does not cross-react with other acrylates, and therefore allergy could be missed if not tested on its own.

Acrylates are volatile substances that have been shown to degrade at room temperature and to a lesser degree when refrigerated. Ideally, they should be stored in a freezer and not used beyond their expiration date. Furthermore, it is advised that acrylate patch tests be prepared immediately prior to placement on the patient and to discard the initial extrusion from the syringe, as the concentration at the tip may be decreased.^46,47

With regard to tissue adhesives, the actual product should be tested as-is because these are not commercially available patch test substances.⁴⁸ Occasionally, patients who are sensitized to the tissue adhesive will not react when patch tested on intact skin. If clinical suspicion remains high, scratch patch testing may confirm contact allergy in cases of negative testing on intact skin.⁴⁹

Management and Prevention

Once a diagnosis of ACD secondary to acrylates has been established, counseling patients on allergen avoidance strategies is essential. For (meth)acrylate-allergic patients who want to continue using modern nail products, cyanoacrylate-based options (eg, dipped, press-on nails) can be considered as an alternative, as they do not cross-react, though independent sensitization is still possible. However, traditional nail polish is the safest option to recommend.

The concern with acrylate sensitization extends beyond the immediate issue that brought the patient into your clinic. Dermatologists must counsel patients who are sensitized to acrylates on the possible sequelae of acrylate-containing dental or orthopedic procedures. Oral lichenoid lesions, denture stomatitis, burning mouth syndrome, or even acute facial swelling have been reported following dental work in patients with acrylate allergy.^50-53 Dentists of patients with acrylate ACD should be informed of the diagnosis so acrylates can be avoided during dental work; if unavoidable, all possible steps should be taken to ensure complete curing of the monomers. In the surgical setting, patients sensitized to cyanoacrylate-based tissue adhesives should be offered wound closure alternatives such as sutures or staples.³⁴

In patients with diabetes mellitus who develop ACD to their glucose monitor or insulin pump, ideally they should be switched to a device that does not contain acrylates. Problematically, these devices are constantly being reformulated, and manufacturers do not always divulge their components, which can make it challenging to determine safe alternative options.^32,54 Various barrier products may help on a case-by-case basis.⁵⁵Preventative measures should be implemented in workplaces that utilize acrylates, including dental practices and nail salons. Acrylic monomers have been shown to penetrate most gloves within minutes of exposure.^56,57 Double gloving with nitrile gloves affords some protection for no longer than 60 minutes.⁶ 4H gloves have been shown to provide true protection but result in a loss of dexterity.⁵⁸ The fingerstall technique involves removing the fingers from a 4H glove, inserting them on the fingers, and applying a more flexible glove on top to hold them in place; this offers a hybrid between protection and finger dexterity.⁵⁹

Final Interpretation

In a world characterized by technological advancements and increasing accessibility to acrylate-containing products, we hope this brief review serves as a resource and reminder to dermatologists to consider acrylates as a potential cause of ACD with diverse presentations and important future implications for affected individuals. The rising trend of acrylate allergy necessitates comprehensive assessment and shared decision-making between physicians and patients. As we navigate the ever-changing landscape of materials and technologies, clinicians must remain vigilant to avoid some potentially sticky situations for patients.

Acrylates are a ubiquitous family of synthetic thermoplastic resins that are employed in a wide array of products. Since the discovery of acrylic acid in 1843 and its industrialization in the early 20th century, acrylates have been used by many different sectors of industry.¹ Today, acrylates can be found in diverse sources such as adhesives, coatings, electronics, nail cosmetics, dental materials, and medical devices. Although these versatile compounds have revolutionized numerous sectors, their potential to trigger allergic contact dermatitis (ACD) has garnered considerable attention in recent years. In 2012, acrylates as a group were named Allergen of the Year by the American Contact Dermatitis Society,² and one member—isobornyl acrylate—also was given the infamous award in 2020.³ In this article, we highlight the chemistry of acrylates, the growing prevalence of acrylate contact allergy, common sources of exposure, patch testing considerations, and management/prevention strategies.

Chemistry and Uses of Acrylates

Acrylates are widely used due to their pliable and resilient properties.⁴ They begin as liquid monomers of (meth)acrylic acid or cyanoacrylic acid that are molded to the desired application before being cured or hardened by one of several means: spontaneously, using chemical catalysts, or with heat, UV light, or a light-emitting diode. Once cured, the final polymers (ie, [meth]acrylates, cyanoacrylates) serve a myriad of different purposes. Table 1 includes some of the more clinically relevant sources of acrylate exposure. Although this list is not comprehensive, it offers a glimpse into the vast array of uses for acrylates.

Acrylate Contact Allergy

Acrylic monomers are potent contact allergens, but the polymerized final products are not considered allergenic, assuming they are completely cured; however, ACD can occur with incomplete curing.⁶ It is of clinical importance that once an individual becomes sensitized to one type of acrylate, they may develop cross-reactions to others contained in different products. Notably, cyanoacrylates generally do not cross-react with (meth)acrylates; this has important implications for choosing safe alternative products in sensitized patients, though independent sensitization to cyanoacrylates is possible.^7,8

Epidemiology and Risk Factors

The prevalence of acrylate allergy in the general population is unknown; however, there is a trend of increased patch test positivity in studies of patients referred for patch testing. A 2018 study by the European Environmental Contact Dermatitis Research Group reported positive patch tests to acrylates in 1.1% of 18,228 patients tested from 2013 to 2015.⁹ More recently, a multicenter European study (2019-2020) reported a 2.3% patch test positivity to 2-hydroxyethyl methacrylate (HEMA) among 7675 tested individuals,¹⁰ and even higher HEMA positivity was reported in Spain (3.7% of 1884 patients in 2019-2020).¹¹ In addition, the North American Contact Dermatitis Group (NACDG) reported positive patch test reactions to HEMA in 3.2% of 4111 patients tested from 2019 to 2020, a statistically significant increase compared with those tested in 2009 to 2018 (odds ratio, 1.25 [95% CI, 1.03-1.51]; P=.02).¹²

Historically, acrylate sensitization primarily stemmed from occupational exposure. A retrospective analysis of occupational dermatitis performed by the NACDG (2001-2016) showed that HEMA was among the top 10 most common occupational allergens (3.4% positivity [83/2461]) and had the fifth highest percentage of occupationally relevant reactions (73.5% [83/113]).¹³ High-risk occupations include dental providers and nail technicians. Dentistry utilizes many materials containing acrylates, including uncured plastic resins used in dental prostheses, dentin bonding materials, and glass ionomers.¹⁴ A retrospective analysis of 585 dental personnel who were patch tested by the NACDG (2001-2018) found that more than 20% of occupational ACD cases were related to acrylates.¹⁵ Nail technicians are another group routinely exposed to acrylates through a variety of modern nail cosmetics. In a 7-year study from Portugal evaluating acrylate ACD, 68% (25/37) of cases were attributed to occupation, 80% (20/25) of which were in nail technicians.¹⁶ Likewise, among 28 nail technicians in Sweden who were referred for patch testing, 57% (16/28) tested positive for at least 1 acrylate.¹⁷

Modern Sources of Acrylate Exposure

Once thought to be a predominantly occupational exposure, acrylates have rapidly made their way into everyday consumer products. Clinicians should be aware of several sources of clinically relevant acrylate exposure, including nail cosmetics, consumer electronics, and medical/surgical adhesives.

A 2016 study found a shift to nail cosmetics as the most common source of acrylate sensitization.¹⁸ Nail cosmetics that contain acrylates include traditional acrylic, gel (shellac), dipped, and press-on (false) nails.¹⁹ The NACDG found that the most common allergen in patients experiencing ACD associated with nail products (2001-2016) was HEMA (56.6% [273/482]), far ahead of the traditional nail polish allergen tosylamide (36.2% [273/755]). Over the study period, the frequency of positive patch tests statistically increased for HEMA (P=.0069) and decreased for tosylamide (P<.0001).²⁰ There is concern that the use of home gel nail kits, which can be purchased online at the click of a button, may be associated with a risk for acrylate sensitization.^21,22 A recent study surveyed a Facebook support group for individuals with self-reported reactions to nail cosmetics, finding that 78% of the 199 individuals had used at-home gel nail kits, and more than 80% of them first developed skin reactions after starting to use at-home kits.²³ The risks for sensitization are thought to be greater when self-applying nail acrylates compared to having them done professionally because individuals are more likely to spill allergenic monomers onto the skin at home; it also is possible that home techniques could lead to incomplete curing. Table 2 reviews the different types of acrylic nail cosmetics.

Medical adhesives and equipment are other important areas where acrylates can be encountered in abundance. A review by Spencer et al¹⁸ cautioned wound dressings as an up-and-coming source of sensitization, and this has been demonstrated in the literature as coming to fruition.²⁶ Another study identified acrylates in 15 of 16 (94%) tested medical adhesives; among 7 medical adhesives labeled as hypoallergenic, 100% still contained acrylates and/or abietic acid.²⁷ Multiple case reports have described ACD to adhesives of electrocardiogram electrodes containing acrylates.^28-31 Physicians providing care to patients with diabetes mellitus also must be aware of acrylates in glucose monitors and insulin pumps, either found in the adhesives or leaching from the inside of the device to reach the skin.³² Isobornyl acrylate in particular has made quite the name for itself in this sector, being crowned the 2020 Allergen of the Year owing to its key role in cases of ACD to diabetes devices.³

Cyanoacrylate-based tissue adhesives (eg, 2‐octyl cyanoacrylate) are now well documented to cause postoperative ACD.^33,34 Although robust prospective data are limited, studies suggest that 2% to 14% of patients develop postoperative skin reactions following 2-octyl cyanoacrylate application.^35-37 It has been shown that sensitization to tissue adhesives often occurs after the first application, followed by an eruption of ACD as long as a month later, which can create confusion about the nature of the rash for patients and health care providers alike, who may for instance attribute it to infection rather than allergy.³⁸ In the orthopedic literature, a woman with a known history of acrylic nail ACD had knee arthroplasty failure attributed to acrylic bone cement with resolution of the joint symptoms after changing to a cementless device.³⁹

Awareness of the common use of acrylates is important to identify the cause of reactions from products that would otherwise seem nonallergenic. A case of occupational ACD to isobornyl acrylate in UV-cured phone screen protectors has been reported⁴⁰; several cases of ACD to acrylates in headphones^41,42 as well as one related to a wearable fitness device also have been reported.⁴³ Given all these possible sources of exposure, ACD to acrylates should be on your radar.

When to Consider Acrylate ACD

When working up a patient with dermatitis, it is essential to ask about occupational history and hobbies to get a sense of potential contact allergen exposures. The typical presentation of occupational acrylate-associated ACD is hand eczema, specifically involving the fingertips.^5,24,25,44 Acrylate ACD should be considered in patients with nail dystrophy and a history of wearing acrylic nails.⁴⁵ There can even be involvement of the face and eyelids secondary to airborne contact or ectopic spread from the hands.²⁴ Spreading vesicular eruptions associated with adhesives also should raise concern. The Figure depicts several possible presentations of ACD to acrylates. In a time of abundant access to products containing acrylates, dermatologists should consider this allergy in their differential diagnosis and consider patch testing.

Photographs courtesy of Brandon L. Adler, MD.

Patch Testing to Acrylates

The gold standard for ACD diagnosis is patch testing. It should be noted that no acrylates are included in the thin-layer rapid use epicutaneous (T.R.U.E.) test series. Several acrylates are tested in expanded patch test series including the American Contact Dermatitis Society Core Allergen series and North American 80 Comprehensive Series. 2-Hydroxyethyl methacrylate is thought to be the most important screening allergen to test. Ramos et al¹⁶ reported a positive patch test to HEMA in 81% (30/37) of patients who had any type of acrylate allergy.

If initial testing to a limited number of acrylates is negative but clinical suspicion remains high, expanded acrylates/plastics and glue series also are available from commercial patch test suppliers. Testing to an expanded panel of acrylates is especially pertinent to consider in suspected occupational cases given the risk of workplace absenteeism and even disability that come with continued exposure to the allergen. Of note, isobornyl acrylate is not included in the baseline patch test series and must be tested separately, particularly because it usually does not cross-react with other acrylates, and therefore allergy could be missed if not tested on its own.

Acrylates are volatile substances that have been shown to degrade at room temperature and to a lesser degree when refrigerated. Ideally, they should be stored in a freezer and not used beyond their expiration date. Furthermore, it is advised that acrylate patch tests be prepared immediately prior to placement on the patient and to discard the initial extrusion from the syringe, as the concentration at the tip may be decreased.^46,47

With regard to tissue adhesives, the actual product should be tested as-is because these are not commercially available patch test substances.⁴⁸ Occasionally, patients who are sensitized to the tissue adhesive will not react when patch tested on intact skin. If clinical suspicion remains high, scratch patch testing may confirm contact allergy in cases of negative testing on intact skin.⁴⁹

Management and Prevention

Once a diagnosis of ACD secondary to acrylates has been established, counseling patients on allergen avoidance strategies is essential. For (meth)acrylate-allergic patients who want to continue using modern nail products, cyanoacrylate-based options (eg, dipped, press-on nails) can be considered as an alternative, as they do not cross-react, though independent sensitization is still possible. However, traditional nail polish is the safest option to recommend.

The concern with acrylate sensitization extends beyond the immediate issue that brought the patient into your clinic. Dermatologists must counsel patients who are sensitized to acrylates on the possible sequelae of acrylate-containing dental or orthopedic procedures. Oral lichenoid lesions, denture stomatitis, burning mouth syndrome, or even acute facial swelling have been reported following dental work in patients with acrylate allergy.^50-53 Dentists of patients with acrylate ACD should be informed of the diagnosis so acrylates can be avoided during dental work; if unavoidable, all possible steps should be taken to ensure complete curing of the monomers. In the surgical setting, patients sensitized to cyanoacrylate-based tissue adhesives should be offered wound closure alternatives such as sutures or staples.³⁴

In patients with diabetes mellitus who develop ACD to their glucose monitor or insulin pump, ideally they should be switched to a device that does not contain acrylates. Problematically, these devices are constantly being reformulated, and manufacturers do not always divulge their components, which can make it challenging to determine safe alternative options.^32,54 Various barrier products may help on a case-by-case basis.⁵⁵Preventative measures should be implemented in workplaces that utilize acrylates, including dental practices and nail salons. Acrylic monomers have been shown to penetrate most gloves within minutes of exposure.^56,57 Double gloving with nitrile gloves affords some protection for no longer than 60 minutes.⁶ 4H gloves have been shown to provide true protection but result in a loss of dexterity.⁵⁸ The fingerstall technique involves removing the fingers from a 4H glove, inserting them on the fingers, and applying a more flexible glove on top to hold them in place; this offers a hybrid between protection and finger dexterity.⁵⁹

Final Interpretation

In a world characterized by technological advancements and increasing accessibility to acrylate-containing products, we hope this brief review serves as a resource and reminder to dermatologists to consider acrylates as a potential cause of ACD with diverse presentations and important future implications for affected individuals. The rising trend of acrylate allergy necessitates comprehensive assessment and shared decision-making between physicians and patients. As we navigate the ever-changing landscape of materials and technologies, clinicians must remain vigilant to avoid some potentially sticky situations for patients.

Prurigo nodularis (PN), a condition that historically has been a challenge to treat, now has a US Food and Drug Administration (FDA)–approved therapy—dupilumab—with other agents in the pipeline. As clinicians, we recognize PN as typically symmetric, keratotic, papular and nodular lesions presenting in older adults with chronic pruritus; patients with atopic dermatitis make up roughly half of patients with PN, but a workup for pruritus is indicated in other settings.¹ In the United States, Black patients are 3.4-times more likely than White patients to have PN.² The differential diagnosis includes conditions such nodular scabies, pemphigoid nodularis, acquired perforating disorders, and hypertrophic lichen planus, which also should be considered, especially in cases that are refractory to first-line therapies. Recent breakthroughs in therapy have come from substantial progress in our understanding of the pathogenesis of PN as driven by disorders of cytokine expression and/or neurocutaneous aberrations. We review progress in the treatment of PN over the last 3 years.

Treatment Guidelines

In 2020, an expert panel published consensus treatment guidelines for PN.¹ The panel, which proposed a 4-tiered approach targeting both neural and immunologic mechanisms in the pathogenesis of PN, emphasized the importance of tailoring treatment to the individual patient. Topical therapies remained the mainstay of treatment, with agents such as topical capsaicin, ketamine, lidocaine, and amitriptyline targeting the neural component and topical corticosteroids, calcineurin inhibitors, and calcipotriol and intralesional corticosteroids targeting the immunologic component. Phototherapy, methotrexate, cyclosporine, antidepressants, and gabapentinoids used with varying degrees of success were noted to have acceptable tolerability.¹

FDA-Approved Therapy

In September 2022, the FDA approved dupilumab for the treatment of PN. An antagonist of the IL-4 receptor, dupilumab was found to reduce both pruritus and skin lesions over a 24-week period in 2 phase 3 clinical trials.³ Results also demonstrated progressive improvements in measures assessing quality of life and pruritus over the study period, suggesting that continued treatment could lead to even further improvements in these measures. Adverse events were minimal and similar between the dupilumab- and placebo-treated groups.³

The FDA approval of dupilumab is a promising step in decreasing the disease burden of widespread or refractory PN, both for patients and the health care system. The treatment of patients with PN has been more challenging due to comorbidities, including mental health conditions, endocrine disorders, cardiovascular conditions, renal conditions, malignancy, and HIV.^4,5 These comorbidities can complicate the use of traditional systemic and immunosuppressive agents. Dupilumab has virtually no contraindications and has demonstrated safety in almost all patient populations.⁶

Consistent insurance coverage for patients who respond to dupilumab remains to be determined. A review investigating the use of dupilumab in patients with atopic dermatitis at the University of Pittsburgh Medical Center (Pittsburgh, Pennsylvania) found that of 179 patients, 67 (37.4%) did not start dupilumab, mainly due to insurance denial (34/179 [19%]) or copay (20/179 [11%]). Medicare patients were less likely to receive treatment compared to those on private insurance or Medicaid.⁷ In a recent review of 701 patients with PN, the mean age was 64.8 years,⁵ highlighting the concern about obtaining insurance coverage for dupilumab in this population given the higher likelihood that these patients will be on Medicare. Prescribers should be aware that coverage denials are likely and should be prepared to advocate for their patients by citing recent studies to hopefully obtain coverage for dupilumab in the treatment of PN. Resources such as the Dupixent MyWay program (https://www.dupixent.com/support-savings/dupixent-my-way) can provide useful recommendations for pursuing insurance approval for this agent.

Investigation of Janus Kinase Inhibitors

Emerging data suggest that Janus kinase (JAK) inhibitors may be beneficial in the treatment of PN. Patients with refractory PN have been treated off label with the JAK inhibitor tofacitinib at a dosage of 5 mg twice daily with improvement in symptoms and minimal side effects.^8,9 Similarly, a case report showed that off-label use of the JAK inhibitor baricitinib resulted in marked improvement in pruritus and clearance of lesions at a dosage of 4 mg daily, with reduction in pruritus seen as early as 1 week after treatment initiation.¹⁰ Although most patients are able to tolerate JAK inhibitors, known side effects include acne, viral infections, gastrointestinal tract upset, and the potential increased risk for malignancy.¹¹ The use of topical JAK inhibitors such as ruxolitinib has not yet been studied in PN, though cost may limit use to localized disease.

Other New Therapies

Recent case reports and case series have found the vitamin A derivative alitretinoin to be an effective treatment for recalcitrant PN, typically at a dosage of 30 mg daily.^12,13 Sustained remission was noted even after discontinuation of the medication.¹² Alitretinoin, which has been demonstrated to be effective in treating dermatitis,¹⁴ was well tolerated. Similar to JAK inhibitors, there are minimal data investigating the use of topical retinoids in the treatment of localized PN.

Topical cannabinoids have shown benefit in the treatment of pruritus¹⁵ and may be beneficial for the treatment of PN, though there currently are limited data in the literature. With the use of both medical and legal recreational marijuana on the rise, there is an increased interest in cannabinoids, particularly as many patients consider these agents to be more “natural”—and therefore preferable—treatment options. As the use of cannabis derivatives become more commonplace in both traditional and complementary medicine, providers should be prepared to field questions from patients about their potential for PN.

Finally, the IL-31RA inhibitor nemolizumab also has shown promise in the treatment of PN. A recent study suggested that nemolizumab helps modulate inflammatory and neural signaling in PN.¹⁶ Nemolizumab has been granted breakthrough therapy designation for the treatment of pruritus in PN based on a phase 2 study that demonstrated improvement in pruritus and skin lesions in a group of 70 patients with moderate to severe PN.¹⁷ Nemolizumab, which is used to treat pruritus in atopic dermatitis, has minimal side effects including upper respiratory tract infections and peripheral edema.¹⁸

Final Thoughts

Prurigo nodularis historically has been considered difficult to treat, particularly in those with widespread lesions. Dupilumab—the first FDA-approved treatment of PN—is now an exciting option, not just for patients with underlying atopic dermatitis. Not all patients will respond to the medication, and the ease of obtaining insurance approval has yet to be established; therefore, having other treatment options will be imperative. In patients with recalcitrant disease, several other treatment options have shown promise in the treatment of PN; in particular, JAK inhibitors, alitretinoin, and nemolizumab should be considered in patients with widespread refractory PN who are willing to try alternative agents. Ongoing research should be focused on these medications as well as on the development of other novel treatments aimed at relieving affected patients.

Prurigo nodularis (PN), a condition that historically has been a challenge to treat, now has a US Food and Drug Administration (FDA)–approved therapy—dupilumab—with other agents in the pipeline. As clinicians, we recognize PN as typically symmetric, keratotic, papular and nodular lesions presenting in older adults with chronic pruritus; patients with atopic dermatitis make up roughly half of patients with PN, but a workup for pruritus is indicated in other settings.¹ In the United States, Black patients are 3.4-times more likely than White patients to have PN.² The differential diagnosis includes conditions such nodular scabies, pemphigoid nodularis, acquired perforating disorders, and hypertrophic lichen planus, which also should be considered, especially in cases that are refractory to first-line therapies. Recent breakthroughs in therapy have come from substantial progress in our understanding of the pathogenesis of PN as driven by disorders of cytokine expression and/or neurocutaneous aberrations. We review progress in the treatment of PN over the last 3 years.

Treatment Guidelines

In 2020, an expert panel published consensus treatment guidelines for PN.¹ The panel, which proposed a 4-tiered approach targeting both neural and immunologic mechanisms in the pathogenesis of PN, emphasized the importance of tailoring treatment to the individual patient. Topical therapies remained the mainstay of treatment, with agents such as topical capsaicin, ketamine, lidocaine, and amitriptyline targeting the neural component and topical corticosteroids, calcineurin inhibitors, and calcipotriol and intralesional corticosteroids targeting the immunologic component. Phototherapy, methotrexate, cyclosporine, antidepressants, and gabapentinoids used with varying degrees of success were noted to have acceptable tolerability.¹

FDA-Approved Therapy

In September 2022, the FDA approved dupilumab for the treatment of PN. An antagonist of the IL-4 receptor, dupilumab was found to reduce both pruritus and skin lesions over a 24-week period in 2 phase 3 clinical trials.³ Results also demonstrated progressive improvements in measures assessing quality of life and pruritus over the study period, suggesting that continued treatment could lead to even further improvements in these measures. Adverse events were minimal and similar between the dupilumab- and placebo-treated groups.³

The FDA approval of dupilumab is a promising step in decreasing the disease burden of widespread or refractory PN, both for patients and the health care system. The treatment of patients with PN has been more challenging due to comorbidities, including mental health conditions, endocrine disorders, cardiovascular conditions, renal conditions, malignancy, and HIV.^4,5 These comorbidities can complicate the use of traditional systemic and immunosuppressive agents. Dupilumab has virtually no contraindications and has demonstrated safety in almost all patient populations.⁶

Consistent insurance coverage for patients who respond to dupilumab remains to be determined. A review investigating the use of dupilumab in patients with atopic dermatitis at the University of Pittsburgh Medical Center (Pittsburgh, Pennsylvania) found that of 179 patients, 67 (37.4%) did not start dupilumab, mainly due to insurance denial (34/179 [19%]) or copay (20/179 [11%]). Medicare patients were less likely to receive treatment compared to those on private insurance or Medicaid.⁷ In a recent review of 701 patients with PN, the mean age was 64.8 years,⁵ highlighting the concern about obtaining insurance coverage for dupilumab in this population given the higher likelihood that these patients will be on Medicare. Prescribers should be aware that coverage denials are likely and should be prepared to advocate for their patients by citing recent studies to hopefully obtain coverage for dupilumab in the treatment of PN. Resources such as the Dupixent MyWay program (https://www.dupixent.com/support-savings/dupixent-my-way) can provide useful recommendations for pursuing insurance approval for this agent.

Investigation of Janus Kinase Inhibitors

Emerging data suggest that Janus kinase (JAK) inhibitors may be beneficial in the treatment of PN. Patients with refractory PN have been treated off label with the JAK inhibitor tofacitinib at a dosage of 5 mg twice daily with improvement in symptoms and minimal side effects.^8,9 Similarly, a case report showed that off-label use of the JAK inhibitor baricitinib resulted in marked improvement in pruritus and clearance of lesions at a dosage of 4 mg daily, with reduction in pruritus seen as early as 1 week after treatment initiation.¹⁰ Although most patients are able to tolerate JAK inhibitors, known side effects include acne, viral infections, gastrointestinal tract upset, and the potential increased risk for malignancy.¹¹ The use of topical JAK inhibitors such as ruxolitinib has not yet been studied in PN, though cost may limit use to localized disease.

Other New Therapies

Recent case reports and case series have found the vitamin A derivative alitretinoin to be an effective treatment for recalcitrant PN, typically at a dosage of 30 mg daily.^12,13 Sustained remission was noted even after discontinuation of the medication.¹² Alitretinoin, which has been demonstrated to be effective in treating dermatitis,¹⁴ was well tolerated. Similar to JAK inhibitors, there are minimal data investigating the use of topical retinoids in the treatment of localized PN.

Topical cannabinoids have shown benefit in the treatment of pruritus¹⁵ and may be beneficial for the treatment of PN, though there currently are limited data in the literature. With the use of both medical and legal recreational marijuana on the rise, there is an increased interest in cannabinoids, particularly as many patients consider these agents to be more “natural”—and therefore preferable—treatment options. As the use of cannabis derivatives become more commonplace in both traditional and complementary medicine, providers should be prepared to field questions from patients about their potential for PN.

Finally, the IL-31RA inhibitor nemolizumab also has shown promise in the treatment of PN. A recent study suggested that nemolizumab helps modulate inflammatory and neural signaling in PN.¹⁶ Nemolizumab has been granted breakthrough therapy designation for the treatment of pruritus in PN based on a phase 2 study that demonstrated improvement in pruritus and skin lesions in a group of 70 patients with moderate to severe PN.¹⁷ Nemolizumab, which is used to treat pruritus in atopic dermatitis, has minimal side effects including upper respiratory tract infections and peripheral edema.¹⁸

Final Thoughts

Prurigo nodularis historically has been considered difficult to treat, particularly in those with widespread lesions. Dupilumab—the first FDA-approved treatment of PN—is now an exciting option, not just for patients with underlying atopic dermatitis. Not all patients will respond to the medication, and the ease of obtaining insurance approval has yet to be established; therefore, having other treatment options will be imperative. In patients with recalcitrant disease, several other treatment options have shown promise in the treatment of PN; in particular, JAK inhibitors, alitretinoin, and nemolizumab should be considered in patients with widespread refractory PN who are willing to try alternative agents. Ongoing research should be focused on these medications as well as on the development of other novel treatments aimed at relieving affected patients.

Prurigo nodularis (PN), a condition that historically has been a challenge to treat, now has a US Food and Drug Administration (FDA)–approved therapy—dupilumab—with other agents in the pipeline. As clinicians, we recognize PN as typically symmetric, keratotic, papular and nodular lesions presenting in older adults with chronic pruritus; patients with atopic dermatitis make up roughly half of patients with PN, but a workup for pruritus is indicated in other settings.¹ In the United States, Black patients are 3.4-times more likely than White patients to have PN.² The differential diagnosis includes conditions such nodular scabies, pemphigoid nodularis, acquired perforating disorders, and hypertrophic lichen planus, which also should be considered, especially in cases that are refractory to first-line therapies. Recent breakthroughs in therapy have come from substantial progress in our understanding of the pathogenesis of PN as driven by disorders of cytokine expression and/or neurocutaneous aberrations. We review progress in the treatment of PN over the last 3 years.

Treatment Guidelines

In 2020, an expert panel published consensus treatment guidelines for PN.¹ The panel, which proposed a 4-tiered approach targeting both neural and immunologic mechanisms in the pathogenesis of PN, emphasized the importance of tailoring treatment to the individual patient. Topical therapies remained the mainstay of treatment, with agents such as topical capsaicin, ketamine, lidocaine, and amitriptyline targeting the neural component and topical corticosteroids, calcineurin inhibitors, and calcipotriol and intralesional corticosteroids targeting the immunologic component. Phototherapy, methotrexate, cyclosporine, antidepressants, and gabapentinoids used with varying degrees of success were noted to have acceptable tolerability.¹

FDA-Approved Therapy

In September 2022, the FDA approved dupilumab for the treatment of PN. An antagonist of the IL-4 receptor, dupilumab was found to reduce both pruritus and skin lesions over a 24-week period in 2 phase 3 clinical trials.³ Results also demonstrated progressive improvements in measures assessing quality of life and pruritus over the study period, suggesting that continued treatment could lead to even further improvements in these measures. Adverse events were minimal and similar between the dupilumab- and placebo-treated groups.³

The FDA approval of dupilumab is a promising step in decreasing the disease burden of widespread or refractory PN, both for patients and the health care system. The treatment of patients with PN has been more challenging due to comorbidities, including mental health conditions, endocrine disorders, cardiovascular conditions, renal conditions, malignancy, and HIV.^4,5 These comorbidities can complicate the use of traditional systemic and immunosuppressive agents. Dupilumab has virtually no contraindications and has demonstrated safety in almost all patient populations.⁶

Consistent insurance coverage for patients who respond to dupilumab remains to be determined. A review investigating the use of dupilumab in patients with atopic dermatitis at the University of Pittsburgh Medical Center (Pittsburgh, Pennsylvania) found that of 179 patients, 67 (37.4%) did not start dupilumab, mainly due to insurance denial (34/179 [19%]) or copay (20/179 [11%]). Medicare patients were less likely to receive treatment compared to those on private insurance or Medicaid.⁷ In a recent review of 701 patients with PN, the mean age was 64.8 years,⁵ highlighting the concern about obtaining insurance coverage for dupilumab in this population given the higher likelihood that these patients will be on Medicare. Prescribers should be aware that coverage denials are likely and should be prepared to advocate for their patients by citing recent studies to hopefully obtain coverage for dupilumab in the treatment of PN. Resources such as the Dupixent MyWay program (https://www.dupixent.com/support-savings/dupixent-my-way) can provide useful recommendations for pursuing insurance approval for this agent.

Investigation of Janus Kinase Inhibitors

Emerging data suggest that Janus kinase (JAK) inhibitors may be beneficial in the treatment of PN. Patients with refractory PN have been treated off label with the JAK inhibitor tofacitinib at a dosage of 5 mg twice daily with improvement in symptoms and minimal side effects.^8,9 Similarly, a case report showed that off-label use of the JAK inhibitor baricitinib resulted in marked improvement in pruritus and clearance of lesions at a dosage of 4 mg daily, with reduction in pruritus seen as early as 1 week after treatment initiation.¹⁰ Although most patients are able to tolerate JAK inhibitors, known side effects include acne, viral infections, gastrointestinal tract upset, and the potential increased risk for malignancy.¹¹ The use of topical JAK inhibitors such as ruxolitinib has not yet been studied in PN, though cost may limit use to localized disease.

Other New Therapies

Recent case reports and case series have found the vitamin A derivative alitretinoin to be an effective treatment for recalcitrant PN, typically at a dosage of 30 mg daily.^12,13 Sustained remission was noted even after discontinuation of the medication.¹² Alitretinoin, which has been demonstrated to be effective in treating dermatitis,¹⁴ was well tolerated. Similar to JAK inhibitors, there are minimal data investigating the use of topical retinoids in the treatment of localized PN.

Topical cannabinoids have shown benefit in the treatment of pruritus¹⁵ and may be beneficial for the treatment of PN, though there currently are limited data in the literature. With the use of both medical and legal recreational marijuana on the rise, there is an increased interest in cannabinoids, particularly as many patients consider these agents to be more “natural”—and therefore preferable—treatment options. As the use of cannabis derivatives become more commonplace in both traditional and complementary medicine, providers should be prepared to field questions from patients about their potential for PN.

Finally, the IL-31RA inhibitor nemolizumab also has shown promise in the treatment of PN. A recent study suggested that nemolizumab helps modulate inflammatory and neural signaling in PN.¹⁶ Nemolizumab has been granted breakthrough therapy designation for the treatment of pruritus in PN based on a phase 2 study that demonstrated improvement in pruritus and skin lesions in a group of 70 patients with moderate to severe PN.¹⁷ Nemolizumab, which is used to treat pruritus in atopic dermatitis, has minimal side effects including upper respiratory tract infections and peripheral edema.¹⁸

Final Thoughts

Prurigo nodularis historically has been considered difficult to treat, particularly in those with widespread lesions. Dupilumab—the first FDA-approved treatment of PN—is now an exciting option, not just for patients with underlying atopic dermatitis. Not all patients will respond to the medication, and the ease of obtaining insurance approval has yet to be established; therefore, having other treatment options will be imperative. In patients with recalcitrant disease, several other treatment options have shown promise in the treatment of PN; in particular, JAK inhibitors, alitretinoin, and nemolizumab should be considered in patients with widespread refractory PN who are willing to try alternative agents. Ongoing research should be focused on these medications as well as on the development of other novel treatments aimed at relieving affected patients.

Clinical Importance

Dendrocnide moroides is arguably the most brutal of stinging plants, even leading to death in dogs, horses, and humans in rare cases.^1-3 Commonly called gympie-gympie (based on its discovery by gold miners near the town of Gympie in Queensland, Australia), D moroides also has been referred to as the mulberrylike stinging tree or stinger.^2,4-6

Family and Nomenclature

The Australian stinging tree belongs to the family Urticaceae (known as the nettle family) within the order Rosales.^1,2,3,5 Urticaceae is derived from the Latin term urere (to burn)—an apt description of the clinical experience of patients with D moroides–induced urticaria.

Urticaceae includes 54 genera, comprising herbs, shrubs, small trees, and vines found predominantly in tropical regions. Dendrocnide comprises approximately 40 species, all commonly known in Australia as stinging trees.^2,7,8

Distribution

Dendrocnide moroides is found in the rainforests of Australia and Southeast Asia.² Because the plant has a strong need for sunlight and wind protection, it typically is found in light-filled gaps within the rainforest, in moist ravines, along the edges of creeks, and on land bordering the rainforest.^3,6

Appearance

Although D moroides is referred to as a tree, it is an understory shrub that typically grows to 3 m, with heart-shaped, serrated, dark green leaves that are 50-cm wide (Figure 1).⁶ The leaves are produced consistently through the year, with variable growth depending on the season.⁹

Reprinted with permission from Hurley.&lt;sup&gt;6&lt;/sup&gt;

The plant is covered in what appears to be soft downy fur made up of trichomes (or plant hairs).^1,6 The density of the hairs on leaves decreases as they age.^2,9 The fruit, which is actually edible (if one is careful to avoid hairs), appears similar to red to dark purple raspberries growing on long stems.^5,6

Cutaneous Manifestations

Symptoms of contact with the stems and leaves of D moroides range from slight irritation to serious neurologic disorders, including neuropathy. The severity of the reaction depends on the person, how much skin was contacted, and how one came into contact with the plant.^1,5 Upon touch, there is an immediate reaction, with burning, urticaria, and edema. Pain increases, peaking 30 minutes later; then the pain slowly subsides.¹ Tachycardia and throbbing regional lymphadenopathy can occur for 1 to 4 hours.^1,6

Cutaneous Findings—Examination reveals immediate piloerection, erythema due to arteriolar dilation, and local swelling.² These findings may disappear after 1 hour or last as long as 24 hours.¹ Although objective signs may fade, subjective pain, pruritus, and burning can persist for months.³

Dermatitis-Inducing Plant Parts

After contact with the stems or leaves, the sharp trichomes become embedded in the skin, making them difficult to remove.¹ The toxins are contained in siliceous hairs that the human body cannot break down.³ Symptoms can be experienced for as long as 1 year after contact, especially when the skin is pressed firmly or washed with hot or cold water.^3,6 Because the plant’s hairs are shed continuously, being in close proximity to D moroides for longer than 20 minutes can lead to extreme sneezing, nosebleeds, and major respiratory damage from inhaling hairs.^1,6,9

The stinging hairs of D moroides differ from irritant hairs on other plants because they contain physiologically active substances. Stinging hairs are classified as either a hypodermic syringe, which expels liquid only, or as a tragia-type syringe, in which liquid and sharp crystals are injected.

The Australian stinging tree falls into the first of these 2 groups (Figure 2)¹; the sharp tip of the hair breaks on contact, leading to expulsion of the toxin into skin.^1,4 The hairs function as a defense against mammalian herbivores but typically have no impact on pests.¹ Nocturnal beetles and on occasion possums and red-legged pademelons dare to eat D moroides.^3,6

Republished under the Creative Commons Attribution (CC-BY 4.0).&lt;i&gt;1&lt;/i&gt;

The Irritant

Initially, formic acid was proposed as the irritant chemical in D moroides¹; other candidates have included neurotransmitters, such as histamine, acetylcholine, and serotonin, as well as inorganic ions, such as potassium. These compounds may play a role but none explain the persistent sensory effects and years-long stable nature of the toxin.^1,4

The most likely culprit irritant is a member of a newly discovered family of neurotoxins, the gympietides. These knot-shaped chemicals, found in D moroides and some spider venoms, have the ability to activate voltage-gated sodium channels of cutaneous neurons and cause local cutaneous vasodilation by stimulating neurotransmitter release.⁴ These neurotoxins not only generate pain but also suppress the mechanism used to interrupt those pain signals.¹⁰ Synthesized gympietides can replicate the effects of natural contact, indicating that they are the primary active toxins. These toxins are ultrastable, thus producing lasting effects.¹

Although much is understood about the evolution and distribution of D moroides and the ecological role that it plays, there is still more to learn about the plant’s toxicology.

 

 

Prevention and Treatment

Prevention—Dendrocnide moroides dermatitis is best prevented by avoiding contact with the plant and related species, as well as wearing upper body clothing with long sleeves, pants, and boots, though plant hairs can still penetrate garments and sting.^2,3

Therapy—There is no reversal therapy of D moroides dermatitis but symptoms can be managed.⁴ For pain, analgesics, such as opioids, have been used; on occasion, however, pain is so intense that even morphine does not help.^4,10

Systemic or topical corticosteroids are the main therapy for many forms of plant-induced dermatitis because they are able to decrease cytokine production and stop lymphocyte production. Adding an oral antihistamine can alleviate histamine-mediated pruritus but not pruritus that is mediated by other chemicals.¹¹

Other methods of relieving symptoms of D moroides dermatitis have been proposed or reported anecdotally. Diluted hydrochloric acid can be applied to the skin to denature remaining toxin.⁴ The sap of Alocasia brisbanensis (the cunjevoi plant) can be rubbed on affected areas to provide a cooling effect, but do not allow A brisbanensis sap to enter the mouth, as it contains calcium oxalate, a toxic irritant found in dumb cane (Dieffenbachia species). The roots of the Australian stinging tree also can be ground and made into a paste, which is applied to the skin.³ However, given the stability of the toxin, we do not recommend these remedies.

Instead, heavy-duty masking tape or hot wax can be applied to remove plant hairs from the skin. The most successful method of removing plant hair is hair removal wax strips, which are considered an essential component of a first aid kit where D moroides is found.³

Clinical Importance

Dendrocnide moroides is arguably the most brutal of stinging plants, even leading to death in dogs, horses, and humans in rare cases.^1-3 Commonly called gympie-gympie (based on its discovery by gold miners near the town of Gympie in Queensland, Australia), D moroides also has been referred to as the mulberrylike stinging tree or stinger.^2,4-6

Family and Nomenclature

The Australian stinging tree belongs to the family Urticaceae (known as the nettle family) within the order Rosales.^1,2,3,5 Urticaceae is derived from the Latin term urere (to burn)—an apt description of the clinical experience of patients with D moroides–induced urticaria.

Urticaceae includes 54 genera, comprising herbs, shrubs, small trees, and vines found predominantly in tropical regions. Dendrocnide comprises approximately 40 species, all commonly known in Australia as stinging trees.^2,7,8

Distribution

Dendrocnide moroides is found in the rainforests of Australia and Southeast Asia.² Because the plant has a strong need for sunlight and wind protection, it typically is found in light-filled gaps within the rainforest, in moist ravines, along the edges of creeks, and on land bordering the rainforest.^3,6

Appearance

Although D moroides is referred to as a tree, it is an understory shrub that typically grows to 3 m, with heart-shaped, serrated, dark green leaves that are 50-cm wide (Figure 1).⁶ The leaves are produced consistently through the year, with variable growth depending on the season.⁹

Reprinted with permission from Hurley.&lt;sup&gt;6&lt;/sup&gt;

The plant is covered in what appears to be soft downy fur made up of trichomes (or plant hairs).^1,6 The density of the hairs on leaves decreases as they age.^2,9 The fruit, which is actually edible (if one is careful to avoid hairs), appears similar to red to dark purple raspberries growing on long stems.^5,6

Cutaneous Manifestations

Symptoms of contact with the stems and leaves of D moroides range from slight irritation to serious neurologic disorders, including neuropathy. The severity of the reaction depends on the person, how much skin was contacted, and how one came into contact with the plant.^1,5 Upon touch, there is an immediate reaction, with burning, urticaria, and edema. Pain increases, peaking 30 minutes later; then the pain slowly subsides.¹ Tachycardia and throbbing regional lymphadenopathy can occur for 1 to 4 hours.^1,6

Cutaneous Findings—Examination reveals immediate piloerection, erythema due to arteriolar dilation, and local swelling.² These findings may disappear after 1 hour or last as long as 24 hours.¹ Although objective signs may fade, subjective pain, pruritus, and burning can persist for months.³

Dermatitis-Inducing Plant Parts

After contact with the stems or leaves, the sharp trichomes become embedded in the skin, making them difficult to remove.¹ The toxins are contained in siliceous hairs that the human body cannot break down.³ Symptoms can be experienced for as long as 1 year after contact, especially when the skin is pressed firmly or washed with hot or cold water.^3,6 Because the plant’s hairs are shed continuously, being in close proximity to D moroides for longer than 20 minutes can lead to extreme sneezing, nosebleeds, and major respiratory damage from inhaling hairs.^1,6,9

The stinging hairs of D moroides differ from irritant hairs on other plants because they contain physiologically active substances. Stinging hairs are classified as either a hypodermic syringe, which expels liquid only, or as a tragia-type syringe, in which liquid and sharp crystals are injected.

The Australian stinging tree falls into the first of these 2 groups (Figure 2)¹; the sharp tip of the hair breaks on contact, leading to expulsion of the toxin into skin.^1,4 The hairs function as a defense against mammalian herbivores but typically have no impact on pests.¹ Nocturnal beetles and on occasion possums and red-legged pademelons dare to eat D moroides.^3,6

Republished under the Creative Commons Attribution (CC-BY 4.0).&lt;i&gt;1&lt;/i&gt;

The Irritant

Initially, formic acid was proposed as the irritant chemical in D moroides¹; other candidates have included neurotransmitters, such as histamine, acetylcholine, and serotonin, as well as inorganic ions, such as potassium. These compounds may play a role but none explain the persistent sensory effects and years-long stable nature of the toxin.^1,4

The most likely culprit irritant is a member of a newly discovered family of neurotoxins, the gympietides. These knot-shaped chemicals, found in D moroides and some spider venoms, have the ability to activate voltage-gated sodium channels of cutaneous neurons and cause local cutaneous vasodilation by stimulating neurotransmitter release.⁴ These neurotoxins not only generate pain but also suppress the mechanism used to interrupt those pain signals.¹⁰ Synthesized gympietides can replicate the effects of natural contact, indicating that they are the primary active toxins. These toxins are ultrastable, thus producing lasting effects.¹

Although much is understood about the evolution and distribution of D moroides and the ecological role that it plays, there is still more to learn about the plant’s toxicology.

 

 

Prevention and Treatment

Prevention—Dendrocnide moroides dermatitis is best prevented by avoiding contact with the plant and related species, as well as wearing upper body clothing with long sleeves, pants, and boots, though plant hairs can still penetrate garments and sting.^2,3

Therapy—There is no reversal therapy of D moroides dermatitis but symptoms can be managed.⁴ For pain, analgesics, such as opioids, have been used; on occasion, however, pain is so intense that even morphine does not help.^4,10

Systemic or topical corticosteroids are the main therapy for many forms of plant-induced dermatitis because they are able to decrease cytokine production and stop lymphocyte production. Adding an oral antihistamine can alleviate histamine-mediated pruritus but not pruritus that is mediated by other chemicals.¹¹

Other methods of relieving symptoms of D moroides dermatitis have been proposed or reported anecdotally. Diluted hydrochloric acid can be applied to the skin to denature remaining toxin.⁴ The sap of Alocasia brisbanensis (the cunjevoi plant) can be rubbed on affected areas to provide a cooling effect, but do not allow A brisbanensis sap to enter the mouth, as it contains calcium oxalate, a toxic irritant found in dumb cane (Dieffenbachia species). The roots of the Australian stinging tree also can be ground and made into a paste, which is applied to the skin.³ However, given the stability of the toxin, we do not recommend these remedies.

Instead, heavy-duty masking tape or hot wax can be applied to remove plant hairs from the skin. The most successful method of removing plant hair is hair removal wax strips, which are considered an essential component of a first aid kit where D moroides is found.³

Clinical Importance

Dendrocnide moroides is arguably the most brutal of stinging plants, even leading to death in dogs, horses, and humans in rare cases.^1-3 Commonly called gympie-gympie (based on its discovery by gold miners near the town of Gympie in Queensland, Australia), D moroides also has been referred to as the mulberrylike stinging tree or stinger.^2,4-6

Family and Nomenclature

The Australian stinging tree belongs to the family Urticaceae (known as the nettle family) within the order Rosales.^1,2,3,5 Urticaceae is derived from the Latin term urere (to burn)—an apt description of the clinical experience of patients with D moroides–induced urticaria.

Urticaceae includes 54 genera, comprising herbs, shrubs, small trees, and vines found predominantly in tropical regions. Dendrocnide comprises approximately 40 species, all commonly known in Australia as stinging trees.^2,7,8

Distribution

Dendrocnide moroides is found in the rainforests of Australia and Southeast Asia.² Because the plant has a strong need for sunlight and wind protection, it typically is found in light-filled gaps within the rainforest, in moist ravines, along the edges of creeks, and on land bordering the rainforest.^3,6

Appearance

Although D moroides is referred to as a tree, it is an understory shrub that typically grows to 3 m, with heart-shaped, serrated, dark green leaves that are 50-cm wide (Figure 1).⁶ The leaves are produced consistently through the year, with variable growth depending on the season.⁹

Reprinted with permission from Hurley.&lt;sup&gt;6&lt;/sup&gt;

The plant is covered in what appears to be soft downy fur made up of trichomes (or plant hairs).^1,6 The density of the hairs on leaves decreases as they age.^2,9 The fruit, which is actually edible (if one is careful to avoid hairs), appears similar to red to dark purple raspberries growing on long stems.^5,6

Cutaneous Manifestations

Symptoms of contact with the stems and leaves of D moroides range from slight irritation to serious neurologic disorders, including neuropathy. The severity of the reaction depends on the person, how much skin was contacted, and how one came into contact with the plant.^1,5 Upon touch, there is an immediate reaction, with burning, urticaria, and edema. Pain increases, peaking 30 minutes later; then the pain slowly subsides.¹ Tachycardia and throbbing regional lymphadenopathy can occur for 1 to 4 hours.^1,6

Cutaneous Findings—Examination reveals immediate piloerection, erythema due to arteriolar dilation, and local swelling.² These findings may disappear after 1 hour or last as long as 24 hours.¹ Although objective signs may fade, subjective pain, pruritus, and burning can persist for months.³

Dermatitis-Inducing Plant Parts

After contact with the stems or leaves, the sharp trichomes become embedded in the skin, making them difficult to remove.¹ The toxins are contained in siliceous hairs that the human body cannot break down.³ Symptoms can be experienced for as long as 1 year after contact, especially when the skin is pressed firmly or washed with hot or cold water.^3,6 Because the plant’s hairs are shed continuously, being in close proximity to D moroides for longer than 20 minutes can lead to extreme sneezing, nosebleeds, and major respiratory damage from inhaling hairs.^1,6,9

The stinging hairs of D moroides differ from irritant hairs on other plants because they contain physiologically active substances. Stinging hairs are classified as either a hypodermic syringe, which expels liquid only, or as a tragia-type syringe, in which liquid and sharp crystals are injected.

The Australian stinging tree falls into the first of these 2 groups (Figure 2)¹; the sharp tip of the hair breaks on contact, leading to expulsion of the toxin into skin.^1,4 The hairs function as a defense against mammalian herbivores but typically have no impact on pests.¹ Nocturnal beetles and on occasion possums and red-legged pademelons dare to eat D moroides.^3,6

Republished under the Creative Commons Attribution (CC-BY 4.0).&lt;i&gt;1&lt;/i&gt;

The Irritant

Initially, formic acid was proposed as the irritant chemical in D moroides¹; other candidates have included neurotransmitters, such as histamine, acetylcholine, and serotonin, as well as inorganic ions, such as potassium. These compounds may play a role but none explain the persistent sensory effects and years-long stable nature of the toxin.^1,4

The most likely culprit irritant is a member of a newly discovered family of neurotoxins, the gympietides. These knot-shaped chemicals, found in D moroides and some spider venoms, have the ability to activate voltage-gated sodium channels of cutaneous neurons and cause local cutaneous vasodilation by stimulating neurotransmitter release.⁴ These neurotoxins not only generate pain but also suppress the mechanism used to interrupt those pain signals.¹⁰ Synthesized gympietides can replicate the effects of natural contact, indicating that they are the primary active toxins. These toxins are ultrastable, thus producing lasting effects.¹

Although much is understood about the evolution and distribution of D moroides and the ecological role that it plays, there is still more to learn about the plant’s toxicology.

 

 

Prevention and Treatment

Prevention—Dendrocnide moroides dermatitis is best prevented by avoiding contact with the plant and related species, as well as wearing upper body clothing with long sleeves, pants, and boots, though plant hairs can still penetrate garments and sting.^2,3

Therapy—There is no reversal therapy of D moroides dermatitis but symptoms can be managed.⁴ For pain, analgesics, such as opioids, have been used; on occasion, however, pain is so intense that even morphine does not help.^4,10

Systemic or topical corticosteroids are the main therapy for many forms of plant-induced dermatitis because they are able to decrease cytokine production and stop lymphocyte production. Adding an oral antihistamine can alleviate histamine-mediated pruritus but not pruritus that is mediated by other chemicals.¹¹

Other methods of relieving symptoms of D moroides dermatitis have been proposed or reported anecdotally. Diluted hydrochloric acid can be applied to the skin to denature remaining toxin.⁴ The sap of Alocasia brisbanensis (the cunjevoi plant) can be rubbed on affected areas to provide a cooling effect, but do not allow A brisbanensis sap to enter the mouth, as it contains calcium oxalate, a toxic irritant found in dumb cane (Dieffenbachia species). The roots of the Australian stinging tree also can be ground and made into a paste, which is applied to the skin.³ However, given the stability of the toxin, we do not recommend these remedies.

Instead, heavy-duty masking tape or hot wax can be applied to remove plant hairs from the skin. The most successful method of removing plant hair is hair removal wax strips, which are considered an essential component of a first aid kit where D moroides is found.³

Children with atopic dermatitis (AD) were significantly more likely to have positive patch test results than were children without AD, according to a study of over 900 children evaluated for allergic contact dermatitis (ACD) with patch testing, a finding that investigators say underscores the value of considering ACD in patients with AD and referring more children for testing.

ACD is underdetected in children with AD. In some cases, it may be misconstrued to be AD, and patch testing, the gold standard for diagnosing ACD, is often not performed, said senior author JiaDe Yu, MD, MS, a pediatric dermatologist and director of contact and occupational dermatology at Massachusetts General Hospital, Boston, and his co-authors, in the study published in the Journal of the American Academy of Dermatology.

Dr. JiaDe Yu

UCHealth

Top allergens

The top 10 allergens between children with and without AD were largely similar, the authors of the study report. Nickel was the most common allergen identified in both groups, and cobalt was in the top five for both groups. Fragrances (including hydroperoxides of linalool), preservatives (including methylisothiazolinone [MI]), and neomycin ranked in the top 10 in both groups, though prevalence differed.

MI, a preservative frequently used in personal care products and in other products like school glue and paint, was the second most common allergen identified in children with AD. Allergy to MI has “recently become an epidemic in the United States, with rapidly increasing prevalence and importance as a source of ACD among both children and adults,” the authors note.

Children with AD were significantly more likely, however, to have ACD to bacitracin (OR, 3.23; P = .030) and to cocamidopropyl betaine (OR, 3.69; P = .0007), the latter of which is a popular surfactant used in “baby” and “gentle” skincare products. This is unsurprising, given that children with AD are “more often exposed to a myriad of topical treatments,” Dr. Yu and his colleagues write.

Although not a top 10 allergen for either group, ACD to “carba mix,” a combination of three chemicals used to make medical adhesives and other rubber products (such as pacifiers, toys, school supplies, and rubber gloves) was significantly more common in children with AD than in those without (OR, 3.36; P = .025).

Among other findings from the study: Children with AD were more likely to have a longer history of dermatitis (4.1 vs. 1.6 years, P < .0001) prior to patch testing. Testing occurred at a mean age of 11 and 12.3 years for children with and without AD, respectively.

The number of allergens tested and the patch testing series chosen per patient were “not statistically different” between the children with and without AD, the researchers report.

Patch testing availability

Clinicians may be hesitant to subject a child to patch testing, but the process is well tolerated in most children, Dr. Perryman said. She uses a modified panel for children that omits less relevant allergens and usually limits patch testing to age 2 years or older due to a young child’s smaller surface area.

Dr. Yu, who developed an interest in patch testing during his residency at the Medical College of Wisconsin, Milwaukee, where he worked with a patch-testing expert, will test children as young as 3-4 months with a “small selection of patches.”

The challenge with a call for more patch testing is a shortage of trained physicians. “In all of Boston, where we have hundreds of dermatologists, there are only about four of us who really do patch testing. My wait time is about 6 months,” said Dr. Yu, who is also an assistant professor at Harvard Medical School, Boston.

Allergists at Massachusetts General Hospital do “some patch testing ... but they refer a lot of the most complicated cases to me,” he said, noting that patch testing and management of ACD involves detailed counseling for patients about avoidance of allergens. “Overall dermatologists represent the largest group of doctors who have proficiency in patch testing, and there just aren’t many of us.”

Dr. Perryman also said that patch testing is often performed by dermatologists who specialize in treating ACD and AD, though there seems to be “regional variance” in the level of involvement of dermatologists and allergists in patch testing.

Not all residency programs have hands-on patch testing opportunities, Dr. Yu said. A study published in Dermatitis, which he co-authored, showed that in 2020, 47.5% of dermatology residency programs had formal patch testing rotations. This represented improvement but is still not enough, he said.

The American Contact Dermatitis Society offers patch-testing mentorship programs, and the American Academy of Dermatology has recently begun offered a patch testing workshop at its annual meetings, said Dr. Yu, who received 4 weeks of training in the Society’s mentorship program and is now involved in the American Academy of Dermatology’s workshops and as a trainer/lecturer at the Contact Dermatitis Institute.

The study was supported by the Dermatology Foundation. Dr. Yu and his co-investigators reported no conflicts of interest. Dr. Perryman had no disclosures.

A version of this article first appeared on Medscape.com.

Children with atopic dermatitis (AD) were significantly more likely to have positive patch test results than were children without AD, according to a study of over 900 children evaluated for allergic contact dermatitis (ACD) with patch testing, a finding that investigators say underscores the value of considering ACD in patients with AD and referring more children for testing.

ACD is underdetected in children with AD. In some cases, it may be misconstrued to be AD, and patch testing, the gold standard for diagnosing ACD, is often not performed, said senior author JiaDe Yu, MD, MS, a pediatric dermatologist and director of contact and occupational dermatology at Massachusetts General Hospital, Boston, and his co-authors, in the study published in the Journal of the American Academy of Dermatology.

Dr. JiaDe Yu

UCHealth

Top allergens

The top 10 allergens between children with and without AD were largely similar, the authors of the study report. Nickel was the most common allergen identified in both groups, and cobalt was in the top five for both groups. Fragrances (including hydroperoxides of linalool), preservatives (including methylisothiazolinone [MI]), and neomycin ranked in the top 10 in both groups, though prevalence differed.

MI, a preservative frequently used in personal care products and in other products like school glue and paint, was the second most common allergen identified in children with AD. Allergy to MI has “recently become an epidemic in the United States, with rapidly increasing prevalence and importance as a source of ACD among both children and adults,” the authors note.

Children with AD were significantly more likely, however, to have ACD to bacitracin (OR, 3.23; P = .030) and to cocamidopropyl betaine (OR, 3.69; P = .0007), the latter of which is a popular surfactant used in “baby” and “gentle” skincare products. This is unsurprising, given that children with AD are “more often exposed to a myriad of topical treatments,” Dr. Yu and his colleagues write.

Although not a top 10 allergen for either group, ACD to “carba mix,” a combination of three chemicals used to make medical adhesives and other rubber products (such as pacifiers, toys, school supplies, and rubber gloves) was significantly more common in children with AD than in those without (OR, 3.36; P = .025).

Among other findings from the study: Children with AD were more likely to have a longer history of dermatitis (4.1 vs. 1.6 years, P < .0001) prior to patch testing. Testing occurred at a mean age of 11 and 12.3 years for children with and without AD, respectively.

The number of allergens tested and the patch testing series chosen per patient were “not statistically different” between the children with and without AD, the researchers report.

Patch testing availability

Clinicians may be hesitant to subject a child to patch testing, but the process is well tolerated in most children, Dr. Perryman said. She uses a modified panel for children that omits less relevant allergens and usually limits patch testing to age 2 years or older due to a young child’s smaller surface area.

Dr. Yu, who developed an interest in patch testing during his residency at the Medical College of Wisconsin, Milwaukee, where he worked with a patch-testing expert, will test children as young as 3-4 months with a “small selection of patches.”

The challenge with a call for more patch testing is a shortage of trained physicians. “In all of Boston, where we have hundreds of dermatologists, there are only about four of us who really do patch testing. My wait time is about 6 months,” said Dr. Yu, who is also an assistant professor at Harvard Medical School, Boston.

Allergists at Massachusetts General Hospital do “some patch testing ... but they refer a lot of the most complicated cases to me,” he said, noting that patch testing and management of ACD involves detailed counseling for patients about avoidance of allergens. “Overall dermatologists represent the largest group of doctors who have proficiency in patch testing, and there just aren’t many of us.”

Dr. Perryman also said that patch testing is often performed by dermatologists who specialize in treating ACD and AD, though there seems to be “regional variance” in the level of involvement of dermatologists and allergists in patch testing.

Not all residency programs have hands-on patch testing opportunities, Dr. Yu said. A study published in Dermatitis, which he co-authored, showed that in 2020, 47.5% of dermatology residency programs had formal patch testing rotations. This represented improvement but is still not enough, he said.

The American Contact Dermatitis Society offers patch-testing mentorship programs, and the American Academy of Dermatology has recently begun offered a patch testing workshop at its annual meetings, said Dr. Yu, who received 4 weeks of training in the Society’s mentorship program and is now involved in the American Academy of Dermatology’s workshops and as a trainer/lecturer at the Contact Dermatitis Institute.

The study was supported by the Dermatology Foundation. Dr. Yu and his co-investigators reported no conflicts of interest. Dr. Perryman had no disclosures.

A version of this article first appeared on Medscape.com.

Children with atopic dermatitis (AD) were significantly more likely to have positive patch test results than were children without AD, according to a study of over 900 children evaluated for allergic contact dermatitis (ACD) with patch testing, a finding that investigators say underscores the value of considering ACD in patients with AD and referring more children for testing.

ACD is underdetected in children with AD. In some cases, it may be misconstrued to be AD, and patch testing, the gold standard for diagnosing ACD, is often not performed, said senior author JiaDe Yu, MD, MS, a pediatric dermatologist and director of contact and occupational dermatology at Massachusetts General Hospital, Boston, and his co-authors, in the study published in the Journal of the American Academy of Dermatology.

Dr. JiaDe Yu

UCHealth

Top allergens

The top 10 allergens between children with and without AD were largely similar, the authors of the study report. Nickel was the most common allergen identified in both groups, and cobalt was in the top five for both groups. Fragrances (including hydroperoxides of linalool), preservatives (including methylisothiazolinone [MI]), and neomycin ranked in the top 10 in both groups, though prevalence differed.

MI, a preservative frequently used in personal care products and in other products like school glue and paint, was the second most common allergen identified in children with AD. Allergy to MI has “recently become an epidemic in the United States, with rapidly increasing prevalence and importance as a source of ACD among both children and adults,” the authors note.

Children with AD were significantly more likely, however, to have ACD to bacitracin (OR, 3.23; P = .030) and to cocamidopropyl betaine (OR, 3.69; P = .0007), the latter of which is a popular surfactant used in “baby” and “gentle” skincare products. This is unsurprising, given that children with AD are “more often exposed to a myriad of topical treatments,” Dr. Yu and his colleagues write.

Although not a top 10 allergen for either group, ACD to “carba mix,” a combination of three chemicals used to make medical adhesives and other rubber products (such as pacifiers, toys, school supplies, and rubber gloves) was significantly more common in children with AD than in those without (OR, 3.36; P = .025).

Among other findings from the study: Children with AD were more likely to have a longer history of dermatitis (4.1 vs. 1.6 years, P < .0001) prior to patch testing. Testing occurred at a mean age of 11 and 12.3 years for children with and without AD, respectively.

The number of allergens tested and the patch testing series chosen per patient were “not statistically different” between the children with and without AD, the researchers report.

Patch testing availability

Clinicians may be hesitant to subject a child to patch testing, but the process is well tolerated in most children, Dr. Perryman said. She uses a modified panel for children that omits less relevant allergens and usually limits patch testing to age 2 years or older due to a young child’s smaller surface area.

Dr. Yu, who developed an interest in patch testing during his residency at the Medical College of Wisconsin, Milwaukee, where he worked with a patch-testing expert, will test children as young as 3-4 months with a “small selection of patches.”

The challenge with a call for more patch testing is a shortage of trained physicians. “In all of Boston, where we have hundreds of dermatologists, there are only about four of us who really do patch testing. My wait time is about 6 months,” said Dr. Yu, who is also an assistant professor at Harvard Medical School, Boston.

Allergists at Massachusetts General Hospital do “some patch testing ... but they refer a lot of the most complicated cases to me,” he said, noting that patch testing and management of ACD involves detailed counseling for patients about avoidance of allergens. “Overall dermatologists represent the largest group of doctors who have proficiency in patch testing, and there just aren’t many of us.”

Dr. Perryman also said that patch testing is often performed by dermatologists who specialize in treating ACD and AD, though there seems to be “regional variance” in the level of involvement of dermatologists and allergists in patch testing.

Not all residency programs have hands-on patch testing opportunities, Dr. Yu said. A study published in Dermatitis, which he co-authored, showed that in 2020, 47.5% of dermatology residency programs had formal patch testing rotations. This represented improvement but is still not enough, he said.

The American Contact Dermatitis Society offers patch-testing mentorship programs, and the American Academy of Dermatology has recently begun offered a patch testing workshop at its annual meetings, said Dr. Yu, who received 4 weeks of training in the Society’s mentorship program and is now involved in the American Academy of Dermatology’s workshops and as a trainer/lecturer at the Contact Dermatitis Institute.

The study was supported by the Dermatology Foundation. Dr. Yu and his co-investigators reported no conflicts of interest. Dr. Perryman had no disclosures.

A version of this article first appeared on Medscape.com.

The tropical rat mite (Ornithonyssus bacoti) belongs to the family Macronyssidae. Theses mites are commonly mistaken for red bird mites or Nordic bird mites because they belong to the same family and have similar characteristics.¹ Although O bacoti is called the tropical rat mite, it also can be found in moderate climates.^2,3

Characteristics

The life cycle of a tropical rat mite lasts 11 to 13 days and includes 5 stages: egg, larva, protonymph, deutonymph, and adult.^1,2 The length of the mite (0.3–0.7 mm) varies with the stage of development.¹ Adults can reach 0.75 to 1.40 mm, with females larger than males and possibly visible with the naked eye.^1,2

Two or 3 days after a blood meal, the female mite lays approximately 100 eggs in its nest but not on the surface of a host. The eggs hatch into larvae after 1 to 4 days and go on to complete their life cyle.¹ During developmental stages, mites occupy their hosts for blood meals. Mites search for their hosts at night and prefer wild or pet rodents for blood meals but are not host specific and can be found on many mammals including birds, cats, racoons, and squirrels.⁴

Although tropical rat mites prefer rodent hosts, they can infest humans when their preferred host is unavailable. In the United States, the first case of human dermatitis due to a tropical rate mite occurred in 1923. In Europe, rat mite dermatitis was first reported in a human in 1931, possibly due to contamination of sailing vessels.⁴

Infestation and Transmission

Tropical rat mites prefer wild and pet rodents as hosts because the mites are able to feed on their blood over long periods.⁴ During the day, the mite spends most of its time hiding in dark dry spaces; it is most active during the night, traveling to find a host for meals.^3-5 If a preferred host is not present, the mite may choose to infest a human.⁵

Human infestation occurs most often upon close bodily contact with an infected animal or pet rodent that was sold without parasites having been eliminated.^3-5 Mites are able to survive without a host for as long as 6 months; they may travel after a meal.^1,2 Therefore, individuals who do not have a pet rodent can be infested if an infected wild rodent has infested their living space.^1,3-5

Clinical Presentation of Infestation

Patients infested with tropical rat mites present with pruritic cutaneous lesions, most often on unclothed parts of the body that are easily exposed to mites; lesions rarely occur on the scalp.⁵ People of any age or gender can be infested. Rat mite bites can present as single or grouped, pruritic, erythematous papules ranging in size from 4 to 10 mm in diameter.^5-7 Excoriations may be present due to excessive scratching. Although rare, vesicles or nodules have been reported.^5,7

Diagnosis of the underlying cause of the cutaneous manifestations often is difficult because mites are not visible during the day, as they are less active then.² Lesions often are misdiagnosed as an allergic response, a bacterial infection, or various forms of dermatitis.¹ A parasitic cause often is not considered unless the physician or patient detects a mite or many trials of therapies fail to provide relief.^1,3-5 Eliciting a thorough history may disclose that the patient has had close contact with rodents or lives in a community center, shelter, or shared space. If any of the patient’s close contacts have a similar presentation, infestation with mites should be considered.

 

 

Treatment and Prevention

Patients should be educated about treatment options and measures that need to be taken to prevent reinfection. It has been reported that tropical rat mites can survive without a blood meal for as long as 6 months; therefore, meticulous inspection and decontamination of all living spaces is required.^1,4 Once identified, physicians may prescribe an antiparasitic such as permethrin or pyriproxyfen to prevent further infestation and eliminate mites on the host.⁵ Lindane and benzyl benzoate previously were reported to be effective but should be prescribed only in correctly diagnosed cases due to the potential adverse effects of both therapies.^4,7-10 For effective treatment, physicians should thoroughly review the proper application of topical treatments with patients. Topical creams should be massaged into the skin from the head to the soles of the feet, covering all creases of the skin and between the fingers and toes. Antiparasitic creams should be left on the skin for 8 to 14 hours, and all members of the household should be examined and treated, if necessary, by a physician. A thorough bath removes tropical rat mites, but preventive measures should be taken to prevent reinfestation.⁴ Antihistamines or glucocorticoids also can be used as symptomatic treatment.^6,8

Avoiding Reinfestation—Preventive measures should be taken to prevent reinfestation, including evaluation by an exterminator for any wild rodents to remove nests and treat the living space with an acaricide.⁵ Insecticides administered by exterminators, including malathion, methyl carbamate, and lindane, also have been reported to be effective for preventing reinfestation.^5,7-9 A veterinarian should be consulted if the patient owns any pets to ensure proper identification of any potential tropical rat mites and treatments that may be necessary for any household pets.¹

Case Report

A 68-year-old man presented to the dermatology outpatient clinic with diffuse pruritus of the skin and scalp. He reported no other symptoms and had never had a total-body skin examination. His primary care physician recently prescribed a dose pack of methylprednisolone 4-mg tablets, which relieved the symptoms except for a mild scalp itch. His wife did not experience itching, and he denied noticing mites or fleas on his pet dog. Physical examination did not reveal any contributory findings, such as erythema or rash. Ketoconazole shampoo 2% and fluocinolone solution 0.01% were prescribed for scalp pruritus; however, he could not afford those medications and therefore did not take them.

Two weeks later, the patient presented with diffuse itching that involved the scalp, trunk, and extremities. He denied groin pruritus. He reported that the itching was worse at night. His wife continued to be asymptomatic. The patient reported that his health screening was up-to-date, and he had no interval health changes. A complete blood cell count, thyroid studies, and a comprehensive metabolic panel performed recently were within reference range. He denied recent travel or taking new medications. Physical examination revealed a somewhat linear distribution of erythematous urticarial papules on the right side of the abdomen. Red dermatographic excoriations were noted on the back. No burrows were visualized. He was given intramuscular triamcinolone 60 mg and was advised to have his house evaluated for bed bugs and his pet dog evaluated by a veterinarian for mites. During the triamcinolone injection, the medical assistant observed a 1- to 2-mm red insect, which fell into his clothing and could not be further evaluated.

After 1 month, the patient had no improvement of the pruritus; instead, it became worse. During this time, his wife developed intermittent urticarial-like eruptions. He was taking oral diphenhydramine nightly and applying triamcinolone cream 0.5% that he had at home from an earlier skin problem as needed. Physical examination findings correlated with worsening symptoms. He had multiple erythematous urticarial papules—many of which were excoriated—across the chest, abdomen, buttocks, and back. The arms had multiple excoriations. The urticarial papules coalesced in the anterior axillary folds, yet no burrows were visualized. In the left anterior axillary fold adjacent to one of the urticarial papules, a 1-mm mobile mite was identified on dermoscopy. Further evaluation by microscopy showed morphologic characteristics of a tropical rat mite (Figure). The patient admitted that his house had a mouse infestation that he was struggling to eliminate. Permethrin cream 5% was prescribed. Because the patient could not afford the prescription, he was advised to use the triamcinolone cream 0.5%and oral diphenhydramine that he had at home nightly for symptomatic relief. He was advised to hire an exterminator to eradicate the mouse and mite infestation to prevent reinfestation.

Identification of Rate Mite Dermatitis

The characteristics of tropical rat mite dermatitis can be confused with many other conditions, such as infection. Even when a mite is identified, it can be difficult to classify it as a tropical rat mite. To confirm the diagnosis of tropical rat mite dermatitis, the parasite needs to be identified. Skin scrapings can be collected from pruritic lesions and examined microscopically in the hope of revealing the rat mites. The recommendation is to collect skin scrapings from the dorsal aspect of the hands or from the neck.⁵ Patients may report finding mites in their living space or on their bedding or clothing.

Although the tropical rat mite was reported as a vector for endemic typhus between humans, no other cases of transmission between humans have been reported since.^11,12 Studies reporting non–human subject research and case reports have shown that O bacoti is a vector for Rickettsia akari, Coxiella burnetii, Francisella tularensis, Yersinia pestis, Eastern equine encephalitis virus (Alphavirus), Enterovirus (Picornaviridae), Langat virus (Flavivirus), and Hantaan orthohantavirus.^5,11-17 However, no cases of these infectious diseases being transmitted naturally have been reported.⁵

Confirmation of O bacoti as a vector for human pathogens is difficult because it relies on identification of the mite in the clinic.⁵ The epidemiologic importance of the mite in transmitting infectious disease is unknown; reports of human cases of mite infestation are rare. We present this information to increase awareness and help dermatologists and other health care providers identify O bacoti.

The tropical rat mite (Ornithonyssus bacoti) belongs to the family Macronyssidae. Theses mites are commonly mistaken for red bird mites or Nordic bird mites because they belong to the same family and have similar characteristics.¹ Although O bacoti is called the tropical rat mite, it also can be found in moderate climates.^2,3

Characteristics

The life cycle of a tropical rat mite lasts 11 to 13 days and includes 5 stages: egg, larva, protonymph, deutonymph, and adult.^1,2 The length of the mite (0.3–0.7 mm) varies with the stage of development.¹ Adults can reach 0.75 to 1.40 mm, with females larger than males and possibly visible with the naked eye.^1,2

Two or 3 days after a blood meal, the female mite lays approximately 100 eggs in its nest but not on the surface of a host. The eggs hatch into larvae after 1 to 4 days and go on to complete their life cyle.¹ During developmental stages, mites occupy their hosts for blood meals. Mites search for their hosts at night and prefer wild or pet rodents for blood meals but are not host specific and can be found on many mammals including birds, cats, racoons, and squirrels.⁴

Although tropical rat mites prefer rodent hosts, they can infest humans when their preferred host is unavailable. In the United States, the first case of human dermatitis due to a tropical rate mite occurred in 1923. In Europe, rat mite dermatitis was first reported in a human in 1931, possibly due to contamination of sailing vessels.⁴

Infestation and Transmission

Tropical rat mites prefer wild and pet rodents as hosts because the mites are able to feed on their blood over long periods.⁴ During the day, the mite spends most of its time hiding in dark dry spaces; it is most active during the night, traveling to find a host for meals.^3-5 If a preferred host is not present, the mite may choose to infest a human.⁵

Human infestation occurs most often upon close bodily contact with an infected animal or pet rodent that was sold without parasites having been eliminated.^3-5 Mites are able to survive without a host for as long as 6 months; they may travel after a meal.^1,2 Therefore, individuals who do not have a pet rodent can be infested if an infected wild rodent has infested their living space.^1,3-5

Clinical Presentation of Infestation

Patients infested with tropical rat mites present with pruritic cutaneous lesions, most often on unclothed parts of the body that are easily exposed to mites; lesions rarely occur on the scalp.⁵ People of any age or gender can be infested. Rat mite bites can present as single or grouped, pruritic, erythematous papules ranging in size from 4 to 10 mm in diameter.^5-7 Excoriations may be present due to excessive scratching. Although rare, vesicles or nodules have been reported.^5,7

Diagnosis of the underlying cause of the cutaneous manifestations often is difficult because mites are not visible during the day, as they are less active then.² Lesions often are misdiagnosed as an allergic response, a bacterial infection, or various forms of dermatitis.¹ A parasitic cause often is not considered unless the physician or patient detects a mite or many trials of therapies fail to provide relief.^1,3-5 Eliciting a thorough history may disclose that the patient has had close contact with rodents or lives in a community center, shelter, or shared space. If any of the patient’s close contacts have a similar presentation, infestation with mites should be considered.

 

 

Treatment and Prevention

Patients should be educated about treatment options and measures that need to be taken to prevent reinfection. It has been reported that tropical rat mites can survive without a blood meal for as long as 6 months; therefore, meticulous inspection and decontamination of all living spaces is required.^1,4 Once identified, physicians may prescribe an antiparasitic such as permethrin or pyriproxyfen to prevent further infestation and eliminate mites on the host.⁵ Lindane and benzyl benzoate previously were reported to be effective but should be prescribed only in correctly diagnosed cases due to the potential adverse effects of both therapies.^4,7-10 For effective treatment, physicians should thoroughly review the proper application of topical treatments with patients. Topical creams should be massaged into the skin from the head to the soles of the feet, covering all creases of the skin and between the fingers and toes. Antiparasitic creams should be left on the skin for 8 to 14 hours, and all members of the household should be examined and treated, if necessary, by a physician. A thorough bath removes tropical rat mites, but preventive measures should be taken to prevent reinfestation.⁴ Antihistamines or glucocorticoids also can be used as symptomatic treatment.^6,8

Avoiding Reinfestation—Preventive measures should be taken to prevent reinfestation, including evaluation by an exterminator for any wild rodents to remove nests and treat the living space with an acaricide.⁵ Insecticides administered by exterminators, including malathion, methyl carbamate, and lindane, also have been reported to be effective for preventing reinfestation.^5,7-9 A veterinarian should be consulted if the patient owns any pets to ensure proper identification of any potential tropical rat mites and treatments that may be necessary for any household pets.¹

Case Report

A 68-year-old man presented to the dermatology outpatient clinic with diffuse pruritus of the skin and scalp. He reported no other symptoms and had never had a total-body skin examination. His primary care physician recently prescribed a dose pack of methylprednisolone 4-mg tablets, which relieved the symptoms except for a mild scalp itch. His wife did not experience itching, and he denied noticing mites or fleas on his pet dog. Physical examination did not reveal any contributory findings, such as erythema or rash. Ketoconazole shampoo 2% and fluocinolone solution 0.01% were prescribed for scalp pruritus; however, he could not afford those medications and therefore did not take them.

Two weeks later, the patient presented with diffuse itching that involved the scalp, trunk, and extremities. He denied groin pruritus. He reported that the itching was worse at night. His wife continued to be asymptomatic. The patient reported that his health screening was up-to-date, and he had no interval health changes. A complete blood cell count, thyroid studies, and a comprehensive metabolic panel performed recently were within reference range. He denied recent travel or taking new medications. Physical examination revealed a somewhat linear distribution of erythematous urticarial papules on the right side of the abdomen. Red dermatographic excoriations were noted on the back. No burrows were visualized. He was given intramuscular triamcinolone 60 mg and was advised to have his house evaluated for bed bugs and his pet dog evaluated by a veterinarian for mites. During the triamcinolone injection, the medical assistant observed a 1- to 2-mm red insect, which fell into his clothing and could not be further evaluated.

After 1 month, the patient had no improvement of the pruritus; instead, it became worse. During this time, his wife developed intermittent urticarial-like eruptions. He was taking oral diphenhydramine nightly and applying triamcinolone cream 0.5% that he had at home from an earlier skin problem as needed. Physical examination findings correlated with worsening symptoms. He had multiple erythematous urticarial papules—many of which were excoriated—across the chest, abdomen, buttocks, and back. The arms had multiple excoriations. The urticarial papules coalesced in the anterior axillary folds, yet no burrows were visualized. In the left anterior axillary fold adjacent to one of the urticarial papules, a 1-mm mobile mite was identified on dermoscopy. Further evaluation by microscopy showed morphologic characteristics of a tropical rat mite (Figure). The patient admitted that his house had a mouse infestation that he was struggling to eliminate. Permethrin cream 5% was prescribed. Because the patient could not afford the prescription, he was advised to use the triamcinolone cream 0.5%and oral diphenhydramine that he had at home nightly for symptomatic relief. He was advised to hire an exterminator to eradicate the mouse and mite infestation to prevent reinfestation.

Identification of Rate Mite Dermatitis

The characteristics of tropical rat mite dermatitis can be confused with many other conditions, such as infection. Even when a mite is identified, it can be difficult to classify it as a tropical rat mite. To confirm the diagnosis of tropical rat mite dermatitis, the parasite needs to be identified. Skin scrapings can be collected from pruritic lesions and examined microscopically in the hope of revealing the rat mites. The recommendation is to collect skin scrapings from the dorsal aspect of the hands or from the neck.⁵ Patients may report finding mites in their living space or on their bedding or clothing.

Although the tropical rat mite was reported as a vector for endemic typhus between humans, no other cases of transmission between humans have been reported since.^11,12 Studies reporting non–human subject research and case reports have shown that O bacoti is a vector for Rickettsia akari, Coxiella burnetii, Francisella tularensis, Yersinia pestis, Eastern equine encephalitis virus (Alphavirus), Enterovirus (Picornaviridae), Langat virus (Flavivirus), and Hantaan orthohantavirus.^5,11-17 However, no cases of these infectious diseases being transmitted naturally have been reported.⁵

Confirmation of O bacoti as a vector for human pathogens is difficult because it relies on identification of the mite in the clinic.⁵ The epidemiologic importance of the mite in transmitting infectious disease is unknown; reports of human cases of mite infestation are rare. We present this information to increase awareness and help dermatologists and other health care providers identify O bacoti.

The tropical rat mite (Ornithonyssus bacoti) belongs to the family Macronyssidae. Theses mites are commonly mistaken for red bird mites or Nordic bird mites because they belong to the same family and have similar characteristics.¹ Although O bacoti is called the tropical rat mite, it also can be found in moderate climates.^2,3

Characteristics

The life cycle of a tropical rat mite lasts 11 to 13 days and includes 5 stages: egg, larva, protonymph, deutonymph, and adult.^1,2 The length of the mite (0.3–0.7 mm) varies with the stage of development.¹ Adults can reach 0.75 to 1.40 mm, with females larger than males and possibly visible with the naked eye.^1,2

Two or 3 days after a blood meal, the female mite lays approximately 100 eggs in its nest but not on the surface of a host. The eggs hatch into larvae after 1 to 4 days and go on to complete their life cyle.¹ During developmental stages, mites occupy their hosts for blood meals. Mites search for their hosts at night and prefer wild or pet rodents for blood meals but are not host specific and can be found on many mammals including birds, cats, racoons, and squirrels.⁴

Although tropical rat mites prefer rodent hosts, they can infest humans when their preferred host is unavailable. In the United States, the first case of human dermatitis due to a tropical rate mite occurred in 1923. In Europe, rat mite dermatitis was first reported in a human in 1931, possibly due to contamination of sailing vessels.⁴

Infestation and Transmission

Tropical rat mites prefer wild and pet rodents as hosts because the mites are able to feed on their blood over long periods.⁴ During the day, the mite spends most of its time hiding in dark dry spaces; it is most active during the night, traveling to find a host for meals.^3-5 If a preferred host is not present, the mite may choose to infest a human.⁵

Human infestation occurs most often upon close bodily contact with an infected animal or pet rodent that was sold without parasites having been eliminated.^3-5 Mites are able to survive without a host for as long as 6 months; they may travel after a meal.^1,2 Therefore, individuals who do not have a pet rodent can be infested if an infected wild rodent has infested their living space.^1,3-5

Clinical Presentation of Infestation

Patients infested with tropical rat mites present with pruritic cutaneous lesions, most often on unclothed parts of the body that are easily exposed to mites; lesions rarely occur on the scalp.⁵ People of any age or gender can be infested. Rat mite bites can present as single or grouped, pruritic, erythematous papules ranging in size from 4 to 10 mm in diameter.^5-7 Excoriations may be present due to excessive scratching. Although rare, vesicles or nodules have been reported.^5,7

Diagnosis of the underlying cause of the cutaneous manifestations often is difficult because mites are not visible during the day, as they are less active then.² Lesions often are misdiagnosed as an allergic response, a bacterial infection, or various forms of dermatitis.¹ A parasitic cause often is not considered unless the physician or patient detects a mite or many trials of therapies fail to provide relief.^1,3-5 Eliciting a thorough history may disclose that the patient has had close contact with rodents or lives in a community center, shelter, or shared space. If any of the patient’s close contacts have a similar presentation, infestation with mites should be considered.

 

 

Treatment and Prevention

Patients should be educated about treatment options and measures that need to be taken to prevent reinfection. It has been reported that tropical rat mites can survive without a blood meal for as long as 6 months; therefore, meticulous inspection and decontamination of all living spaces is required.^1,4 Once identified, physicians may prescribe an antiparasitic such as permethrin or pyriproxyfen to prevent further infestation and eliminate mites on the host.⁵ Lindane and benzyl benzoate previously were reported to be effective but should be prescribed only in correctly diagnosed cases due to the potential adverse effects of both therapies.^4,7-10 For effective treatment, physicians should thoroughly review the proper application of topical treatments with patients. Topical creams should be massaged into the skin from the head to the soles of the feet, covering all creases of the skin and between the fingers and toes. Antiparasitic creams should be left on the skin for 8 to 14 hours, and all members of the household should be examined and treated, if necessary, by a physician. A thorough bath removes tropical rat mites, but preventive measures should be taken to prevent reinfestation.⁴ Antihistamines or glucocorticoids also can be used as symptomatic treatment.^6,8

Avoiding Reinfestation—Preventive measures should be taken to prevent reinfestation, including evaluation by an exterminator for any wild rodents to remove nests and treat the living space with an acaricide.⁵ Insecticides administered by exterminators, including malathion, methyl carbamate, and lindane, also have been reported to be effective for preventing reinfestation.^5,7-9 A veterinarian should be consulted if the patient owns any pets to ensure proper identification of any potential tropical rat mites and treatments that may be necessary for any household pets.¹

Case Report

A 68-year-old man presented to the dermatology outpatient clinic with diffuse pruritus of the skin and scalp. He reported no other symptoms and had never had a total-body skin examination. His primary care physician recently prescribed a dose pack of methylprednisolone 4-mg tablets, which relieved the symptoms except for a mild scalp itch. His wife did not experience itching, and he denied noticing mites or fleas on his pet dog. Physical examination did not reveal any contributory findings, such as erythema or rash. Ketoconazole shampoo 2% and fluocinolone solution 0.01% were prescribed for scalp pruritus; however, he could not afford those medications and therefore did not take them.

Two weeks later, the patient presented with diffuse itching that involved the scalp, trunk, and extremities. He denied groin pruritus. He reported that the itching was worse at night. His wife continued to be asymptomatic. The patient reported that his health screening was up-to-date, and he had no interval health changes. A complete blood cell count, thyroid studies, and a comprehensive metabolic panel performed recently were within reference range. He denied recent travel or taking new medications. Physical examination revealed a somewhat linear distribution of erythematous urticarial papules on the right side of the abdomen. Red dermatographic excoriations were noted on the back. No burrows were visualized. He was given intramuscular triamcinolone 60 mg and was advised to have his house evaluated for bed bugs and his pet dog evaluated by a veterinarian for mites. During the triamcinolone injection, the medical assistant observed a 1- to 2-mm red insect, which fell into his clothing and could not be further evaluated.

After 1 month, the patient had no improvement of the pruritus; instead, it became worse. During this time, his wife developed intermittent urticarial-like eruptions. He was taking oral diphenhydramine nightly and applying triamcinolone cream 0.5% that he had at home from an earlier skin problem as needed. Physical examination findings correlated with worsening symptoms. He had multiple erythematous urticarial papules—many of which were excoriated—across the chest, abdomen, buttocks, and back. The arms had multiple excoriations. The urticarial papules coalesced in the anterior axillary folds, yet no burrows were visualized. In the left anterior axillary fold adjacent to one of the urticarial papules, a 1-mm mobile mite was identified on dermoscopy. Further evaluation by microscopy showed morphologic characteristics of a tropical rat mite (Figure). The patient admitted that his house had a mouse infestation that he was struggling to eliminate. Permethrin cream 5% was prescribed. Because the patient could not afford the prescription, he was advised to use the triamcinolone cream 0.5%and oral diphenhydramine that he had at home nightly for symptomatic relief. He was advised to hire an exterminator to eradicate the mouse and mite infestation to prevent reinfestation.

Identification of Rate Mite Dermatitis

The characteristics of tropical rat mite dermatitis can be confused with many other conditions, such as infection. Even when a mite is identified, it can be difficult to classify it as a tropical rat mite. To confirm the diagnosis of tropical rat mite dermatitis, the parasite needs to be identified. Skin scrapings can be collected from pruritic lesions and examined microscopically in the hope of revealing the rat mites. The recommendation is to collect skin scrapings from the dorsal aspect of the hands or from the neck.⁵ Patients may report finding mites in their living space or on their bedding or clothing.

Although the tropical rat mite was reported as a vector for endemic typhus between humans, no other cases of transmission between humans have been reported since.^11,12 Studies reporting non–human subject research and case reports have shown that O bacoti is a vector for Rickettsia akari, Coxiella burnetii, Francisella tularensis, Yersinia pestis, Eastern equine encephalitis virus (Alphavirus), Enterovirus (Picornaviridae), Langat virus (Flavivirus), and Hantaan orthohantavirus.^5,11-17 However, no cases of these infectious diseases being transmitted naturally have been reported.⁵

Confirmation of O bacoti as a vector for human pathogens is difficult because it relies on identification of the mite in the clinic.⁵ The epidemiologic importance of the mite in transmitting infectious disease is unknown; reports of human cases of mite infestation are rare. We present this information to increase awareness and help dermatologists and other health care providers identify O bacoti.

The Diagnosis: Flagellate Dermatitis

Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.

Flagellate dermatitis usually appears on the torso as linear whiplike streaks.¹ The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.²

Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.³ Flagellate dermatitis also is seen in some patients with dermatomyositis.⁴ A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.

Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),^5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.⁶ Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.⁶

In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.

The Diagnosis: Flagellate Dermatitis

Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.

Flagellate dermatitis usually appears on the torso as linear whiplike streaks.¹ The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.²

Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.³ Flagellate dermatitis also is seen in some patients with dermatomyositis.⁴ A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.

Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),^5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.⁶ Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.⁶

In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.

The Diagnosis: Flagellate Dermatitis

Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.

Flagellate dermatitis usually appears on the torso as linear whiplike streaks.¹ The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.²

Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.³ Flagellate dermatitis also is seen in some patients with dermatomyositis.⁴ A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.

Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),^5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.⁶ Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.⁶

In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.