Cutis

The Diagnosis: Recurrent Cutaneous T-Cell Lymphoma

The skin biopsy revealed alternating orthokeratosis and parakeratosis with mild to moderate spongiosis and intraepidermal vesiculation as well as individual and nested atypical mononuclear cells with moderately enlarged hyperchromatic nuclei in the epidermis. There was a superficial interstitial lymphocytic infiltrate with occasional enlarged cells (Figure, A and B), and atypical cells in the epidermis and dermis stained with antibodies against CD3 and CD4 (Figure, C and D) but not against CD20 or CD8. These histopathologic findings were consistent with cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) type. Additional application of bexarotene gel on days the patient received narrowband UVB was recommended with noted improvement of the skin.

Cutaneous T-cell lymphomas are a heterogenous group of diseases with monoclonal proliferation of T lymphocytes that largely are confined to the skin at the time of diagnosis.¹ The incidence of CTCL rose steadily for more than 25 years, with an annual age-adjusted incidence of 6.4 to 9.6 cases per million individuals in the United States from 1973 to 2002.² Mycosis fungoides is the most common classification of CTCL. It usually is characterized by patches or plaques of scaly erythema or poikiloderma; however, it also can present with annular, arcuate, concentrative, annular and linear morphologies. Mycosis fungoides tumor cells typically express a mature memory T helper cell phenotype of CD3+, CD4+, and CD8−, but there are different variants that have been discovered.³ Mycosis fungoides distributed in a spiral pattern is a distinctly unusual manifestation. Mechanisms of such dynamic morphologies are unknown but may represent an interplay between malignant cell proliferation and lost immune responses in temporospatial relationships.

The presence of keratotic gyrate lesions on acral surfaces should raise the possibility of pagetoid reticulosis. However, our patient had a history of MF involving areas of the body beyond the extremities, making this diagnosis less likely. Pagetoid reticulosis is categorized as an MF variant under the current World Health Organization– European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas.⁴ Pagetoid reticulosis clinically presents as a solitary psoriasiform or hyperkeratotic patch or plaque that affects the distal extremities. Variable immunophenotypes have been shown in pagetoid reticulosis, such as CD4−/CD8+ and CD4−/CD8−, while classic MF typically shows CD4+/CD8−, as in our case.⁵

Tinea pedis is a superficial fungal infection usually caused by anthropophilic dermatophytes, with Trichophyton rubrum being the most common organism. Four common clinical presentations of tinea pedis have been identified: interdigital, moccasin, vesicular, and acute ulcerative. Clinical presentation ranges from macerations, ulcerations, and erosions in the toe web spaces to dry hyperkeratotic scaling and fissures on the plantar foot.⁶ Tinea pedis primarily affects the plantar and interdigital spaces, sparing the dorsal foot and ankle. Treatment is recommended to alleviate symptoms and limit the spread of infection; topical antifungals for 4 weeks is the treatment of choice. However, recurrence is common, and maintenance therapy often is indicated. Oral antifungals or a combination of both topical and oral medications may be needed in certain cases.⁷

Erythema annulare centrifugum (EAC) is a rare dermatologic disease described as erythematous or urticarial papules that can enlarge centrifugally to form annular lesions that clear centrally. Thought to be a hypersensitivity reaction to an underlying condition, EAC has been associated with fungal infections, various cutaneous diseases, and even internal malignancies. Clinically, EAC can be divided into 2 forms: deep and superficial. Deep gyrate erythema is characterized by a firm indurated border with rare scaling and pruritus that histologically shows perivascular lymphocytic infiltration in the upper and deep dermis. Superficial gyrate erythema has minimally elevated lesions with an indistinct border and trailing scales and pruritus; histopathologic findings present a dense, perivascular, lymphocytic infiltration restricted to the upper dermis.⁸ Therapy for EAC is directed at relieving symptoms and treating the underlying condition if there is one associated.

Granuloma annulare (GA) is a common skin disorder classically characterized by ringed erythematous plaques, though many variants have been identified. Localized GA is the most common variant and presents with pink-red, nonscaly, annular patches or plaques, typically affecting the hands and feet. Generalized GA is characterized as diffuse annular patches or plaques classically affecting the trunk and extremities. Histology is notable for mucin with a palisading or interstitial pattern of granulomatous inflammation, which was not evident in our patient.⁹ Topical or intralesional corticosteroids are the first-line treatment of localized GA; however, localized GA generally is self-limited, and treatment often is not necessary. Treatment with cryosurgery, laser therapy, and topical dapsone and tacrolimus also has been described, but evidence of the efficacy of these agents is limited. For generalized GA, phototherapy currently is the most reliable therapy. Systemic therapies include antimalarials, fumaric acid esters, biologics, antimicrobials, and isotretinoin.¹⁰

Erythema gyratum repens (EGR) is a rare dermatologic disease described as erythematous concentric bands arranged in parallel rings that can be annular, figurate, or gyrate, with a fine scale trailing the leading edge. Histopathologic features of EGR are nonspecific but are characterized by a perivascular, superficial, mononuclear dermatitis. Diagnosis is based on its characteristic clinical presentation. Although EGR commonly is associated with internal malignancies such as bronchial carcinoma, it also may be associated with benign conditions.¹¹ Improvement often is seen with successful therapy of the underlying associated malignancy.¹²

Treatment of MF is based on tumor-node-metastasisblood classification, prognostic factors, and clinical stage at the time of diagnosis. Early-stage MF (IA–IIA) commonly is treated with skin-directed therapies such as topical corticosteroids, topical mechlorethamine, topical retinoids, UV phototherapy, and localized radiotherapy. In late stages (IIB–IV), systemic therapy is indicated and includes systemic retinoids, interferon alfa, chemotherapy, monoclonal antibodies, and psoralen plus UVA.¹³ In many cases, patients may require combination therapy to achieve remission or better control of their condition, as in our patient.

The Diagnosis: Recurrent Cutaneous T-Cell Lymphoma

The skin biopsy revealed alternating orthokeratosis and parakeratosis with mild to moderate spongiosis and intraepidermal vesiculation as well as individual and nested atypical mononuclear cells with moderately enlarged hyperchromatic nuclei in the epidermis. There was a superficial interstitial lymphocytic infiltrate with occasional enlarged cells (Figure, A and B), and atypical cells in the epidermis and dermis stained with antibodies against CD3 and CD4 (Figure, C and D) but not against CD20 or CD8. These histopathologic findings were consistent with cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) type. Additional application of bexarotene gel on days the patient received narrowband UVB was recommended with noted improvement of the skin.

Cutaneous T-cell lymphomas are a heterogenous group of diseases with monoclonal proliferation of T lymphocytes that largely are confined to the skin at the time of diagnosis.¹ The incidence of CTCL rose steadily for more than 25 years, with an annual age-adjusted incidence of 6.4 to 9.6 cases per million individuals in the United States from 1973 to 2002.² Mycosis fungoides is the most common classification of CTCL. It usually is characterized by patches or plaques of scaly erythema or poikiloderma; however, it also can present with annular, arcuate, concentrative, annular and linear morphologies. Mycosis fungoides tumor cells typically express a mature memory T helper cell phenotype of CD3+, CD4+, and CD8−, but there are different variants that have been discovered.³ Mycosis fungoides distributed in a spiral pattern is a distinctly unusual manifestation. Mechanisms of such dynamic morphologies are unknown but may represent an interplay between malignant cell proliferation and lost immune responses in temporospatial relationships.

The presence of keratotic gyrate lesions on acral surfaces should raise the possibility of pagetoid reticulosis. However, our patient had a history of MF involving areas of the body beyond the extremities, making this diagnosis less likely. Pagetoid reticulosis is categorized as an MF variant under the current World Health Organization– European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas.⁴ Pagetoid reticulosis clinically presents as a solitary psoriasiform or hyperkeratotic patch or plaque that affects the distal extremities. Variable immunophenotypes have been shown in pagetoid reticulosis, such as CD4−/CD8+ and CD4−/CD8−, while classic MF typically shows CD4+/CD8−, as in our case.⁵

Tinea pedis is a superficial fungal infection usually caused by anthropophilic dermatophytes, with Trichophyton rubrum being the most common organism. Four common clinical presentations of tinea pedis have been identified: interdigital, moccasin, vesicular, and acute ulcerative. Clinical presentation ranges from macerations, ulcerations, and erosions in the toe web spaces to dry hyperkeratotic scaling and fissures on the plantar foot.⁶ Tinea pedis primarily affects the plantar and interdigital spaces, sparing the dorsal foot and ankle. Treatment is recommended to alleviate symptoms and limit the spread of infection; topical antifungals for 4 weeks is the treatment of choice. However, recurrence is common, and maintenance therapy often is indicated. Oral antifungals or a combination of both topical and oral medications may be needed in certain cases.⁷

Erythema annulare centrifugum (EAC) is a rare dermatologic disease described as erythematous or urticarial papules that can enlarge centrifugally to form annular lesions that clear centrally. Thought to be a hypersensitivity reaction to an underlying condition, EAC has been associated with fungal infections, various cutaneous diseases, and even internal malignancies. Clinically, EAC can be divided into 2 forms: deep and superficial. Deep gyrate erythema is characterized by a firm indurated border with rare scaling and pruritus that histologically shows perivascular lymphocytic infiltration in the upper and deep dermis. Superficial gyrate erythema has minimally elevated lesions with an indistinct border and trailing scales and pruritus; histopathologic findings present a dense, perivascular, lymphocytic infiltration restricted to the upper dermis.⁸ Therapy for EAC is directed at relieving symptoms and treating the underlying condition if there is one associated.

Granuloma annulare (GA) is a common skin disorder classically characterized by ringed erythematous plaques, though many variants have been identified. Localized GA is the most common variant and presents with pink-red, nonscaly, annular patches or plaques, typically affecting the hands and feet. Generalized GA is characterized as diffuse annular patches or plaques classically affecting the trunk and extremities. Histology is notable for mucin with a palisading or interstitial pattern of granulomatous inflammation, which was not evident in our patient.⁹ Topical or intralesional corticosteroids are the first-line treatment of localized GA; however, localized GA generally is self-limited, and treatment often is not necessary. Treatment with cryosurgery, laser therapy, and topical dapsone and tacrolimus also has been described, but evidence of the efficacy of these agents is limited. For generalized GA, phototherapy currently is the most reliable therapy. Systemic therapies include antimalarials, fumaric acid esters, biologics, antimicrobials, and isotretinoin.¹⁰

Erythema gyratum repens (EGR) is a rare dermatologic disease described as erythematous concentric bands arranged in parallel rings that can be annular, figurate, or gyrate, with a fine scale trailing the leading edge. Histopathologic features of EGR are nonspecific but are characterized by a perivascular, superficial, mononuclear dermatitis. Diagnosis is based on its characteristic clinical presentation. Although EGR commonly is associated with internal malignancies such as bronchial carcinoma, it also may be associated with benign conditions.¹¹ Improvement often is seen with successful therapy of the underlying associated malignancy.¹²

Treatment of MF is based on tumor-node-metastasisblood classification, prognostic factors, and clinical stage at the time of diagnosis. Early-stage MF (IA–IIA) commonly is treated with skin-directed therapies such as topical corticosteroids, topical mechlorethamine, topical retinoids, UV phototherapy, and localized radiotherapy. In late stages (IIB–IV), systemic therapy is indicated and includes systemic retinoids, interferon alfa, chemotherapy, monoclonal antibodies, and psoralen plus UVA.¹³ In many cases, patients may require combination therapy to achieve remission or better control of their condition, as in our patient.

The Diagnosis: Recurrent Cutaneous T-Cell Lymphoma

The skin biopsy revealed alternating orthokeratosis and parakeratosis with mild to moderate spongiosis and intraepidermal vesiculation as well as individual and nested atypical mononuclear cells with moderately enlarged hyperchromatic nuclei in the epidermis. There was a superficial interstitial lymphocytic infiltrate with occasional enlarged cells (Figure, A and B), and atypical cells in the epidermis and dermis stained with antibodies against CD3 and CD4 (Figure, C and D) but not against CD20 or CD8. These histopathologic findings were consistent with cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) type. Additional application of bexarotene gel on days the patient received narrowband UVB was recommended with noted improvement of the skin.

Cutaneous T-cell lymphomas are a heterogenous group of diseases with monoclonal proliferation of T lymphocytes that largely are confined to the skin at the time of diagnosis.¹ The incidence of CTCL rose steadily for more than 25 years, with an annual age-adjusted incidence of 6.4 to 9.6 cases per million individuals in the United States from 1973 to 2002.² Mycosis fungoides is the most common classification of CTCL. It usually is characterized by patches or plaques of scaly erythema or poikiloderma; however, it also can present with annular, arcuate, concentrative, annular and linear morphologies. Mycosis fungoides tumor cells typically express a mature memory T helper cell phenotype of CD3+, CD4+, and CD8−, but there are different variants that have been discovered.³ Mycosis fungoides distributed in a spiral pattern is a distinctly unusual manifestation. Mechanisms of such dynamic morphologies are unknown but may represent an interplay between malignant cell proliferation and lost immune responses in temporospatial relationships.

The presence of keratotic gyrate lesions on acral surfaces should raise the possibility of pagetoid reticulosis. However, our patient had a history of MF involving areas of the body beyond the extremities, making this diagnosis less likely. Pagetoid reticulosis is categorized as an MF variant under the current World Health Organization– European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas.⁴ Pagetoid reticulosis clinically presents as a solitary psoriasiform or hyperkeratotic patch or plaque that affects the distal extremities. Variable immunophenotypes have been shown in pagetoid reticulosis, such as CD4−/CD8+ and CD4−/CD8−, while classic MF typically shows CD4+/CD8−, as in our case.⁵

Tinea pedis is a superficial fungal infection usually caused by anthropophilic dermatophytes, with Trichophyton rubrum being the most common organism. Four common clinical presentations of tinea pedis have been identified: interdigital, moccasin, vesicular, and acute ulcerative. Clinical presentation ranges from macerations, ulcerations, and erosions in the toe web spaces to dry hyperkeratotic scaling and fissures on the plantar foot.⁶ Tinea pedis primarily affects the plantar and interdigital spaces, sparing the dorsal foot and ankle. Treatment is recommended to alleviate symptoms and limit the spread of infection; topical antifungals for 4 weeks is the treatment of choice. However, recurrence is common, and maintenance therapy often is indicated. Oral antifungals or a combination of both topical and oral medications may be needed in certain cases.⁷

Erythema annulare centrifugum (EAC) is a rare dermatologic disease described as erythematous or urticarial papules that can enlarge centrifugally to form annular lesions that clear centrally. Thought to be a hypersensitivity reaction to an underlying condition, EAC has been associated with fungal infections, various cutaneous diseases, and even internal malignancies. Clinically, EAC can be divided into 2 forms: deep and superficial. Deep gyrate erythema is characterized by a firm indurated border with rare scaling and pruritus that histologically shows perivascular lymphocytic infiltration in the upper and deep dermis. Superficial gyrate erythema has minimally elevated lesions with an indistinct border and trailing scales and pruritus; histopathologic findings present a dense, perivascular, lymphocytic infiltration restricted to the upper dermis.⁸ Therapy for EAC is directed at relieving symptoms and treating the underlying condition if there is one associated.

Granuloma annulare (GA) is a common skin disorder classically characterized by ringed erythematous plaques, though many variants have been identified. Localized GA is the most common variant and presents with pink-red, nonscaly, annular patches or plaques, typically affecting the hands and feet. Generalized GA is characterized as diffuse annular patches or plaques classically affecting the trunk and extremities. Histology is notable for mucin with a palisading or interstitial pattern of granulomatous inflammation, which was not evident in our patient.⁹ Topical or intralesional corticosteroids are the first-line treatment of localized GA; however, localized GA generally is self-limited, and treatment often is not necessary. Treatment with cryosurgery, laser therapy, and topical dapsone and tacrolimus also has been described, but evidence of the efficacy of these agents is limited. For generalized GA, phototherapy currently is the most reliable therapy. Systemic therapies include antimalarials, fumaric acid esters, biologics, antimicrobials, and isotretinoin.¹⁰

Erythema gyratum repens (EGR) is a rare dermatologic disease described as erythematous concentric bands arranged in parallel rings that can be annular, figurate, or gyrate, with a fine scale trailing the leading edge. Histopathologic features of EGR are nonspecific but are characterized by a perivascular, superficial, mononuclear dermatitis. Diagnosis is based on its characteristic clinical presentation. Although EGR commonly is associated with internal malignancies such as bronchial carcinoma, it also may be associated with benign conditions.¹¹ Improvement often is seen with successful therapy of the underlying associated malignancy.¹²

Treatment of MF is based on tumor-node-metastasisblood classification, prognostic factors, and clinical stage at the time of diagnosis. Early-stage MF (IA–IIA) commonly is treated with skin-directed therapies such as topical corticosteroids, topical mechlorethamine, topical retinoids, UV phototherapy, and localized radiotherapy. In late stages (IIB–IV), systemic therapy is indicated and includes systemic retinoids, interferon alfa, chemotherapy, monoclonal antibodies, and psoralen plus UVA.¹³ In many cases, patients may require combination therapy to achieve remission or better control of their condition, as in our patient.

Insurers Target Modifier -25

Modifier -25 allows reporting of both a minor procedure (ie, one with a 0- or 10-day global period) and a separate and distinct evaluation and management (E/M) service on the same date of service.¹ Because of the multicomplaint nature of dermatology, the ability to report a same-day procedure and an E/M service is critical for efficient, cost-effective, and patient-centered dermatologic care. However, it is well known that the use of modifier -25 has been under notable insurer scrutiny and is a common reason for medical record audits.^2,3 Some insurers have responded to increased utilization of modifier -25 by cutting reimbursement for claims that include both a procedure and an E/M service or by denying one of the services altogether.^4-6 The Centers for Medicare and Medicaid Services also have expressed concern about this coding combination with proposed cuts to reimbursement.⁷ Moreover, the Office of Inspector General has announced a work plan to investigate the frequent utilization of E/M codes and minor procedures by dermatologists.⁸ Clearly, modifier -25 is a continued target by insurers and regulators; therefore, dermatologists will want to make sure their coding and documentation meet all requirements and are updated for the new E/M codes for 2021.

The American Medical Association’s Current Procedural Terminology indicates that modifier -25 allows reporting of a “significant, separately identifiable evaluation and management service by the same physician or other qualified health care professional on the same day of a procedure or other service.”¹ Given that dermatology patients typically present with multiple concerns, dermatologists commonly evaluate and treat numerous conditions during one visit. Understanding what constitutes a separately identifiable E/M service is critical to bill accurately and to pass insurer audits.

Global Surgical Package

To appropriately bill both a procedure and an E/M service, the physician must indicate that the patient’s condition required an E/M service above and beyond the usual work of the procedure. The compilation of evaluation and work included in the payment for a procedure is called the global surgical package.⁹ In general, the global surgical package includes local or topical anesthesia; the surgical service/procedure itself; immediate postoperative care, including dictating the operative note; meeting/discussing the patient’s procedure with family and other physicians; and writing orders for the patient. For minor procedures (ie, those with either 0- or 10-day global periods), the surgical package also includes same-day E/M services associated with the decision to perform surgery. An appropriate history and physical examination as well as a discussion of the differential diagnosis, treatment options, and risk and benefits of treatment are all included in the payment of a minor procedure itself. Therefore, an evaluation to discuss a patient’s condition or change in condition, alternatives to treatment, or next steps after a diagnosis related to a treatment or diagnostic procedure should not be separately reported. Moreover, the fact that the patient is new to the physician is not in itself sufficient to allow reporting of an E/M service with these minor procedures. For major procedures (ie, those with 90-day postoperative periods), the decision for surgery is excluded from the global surgical package.

2021 E/M Codes Simplify Documentation

The biggest coding change of 2021 was the new E/M codes.¹⁰ Prior to this year, the descriptors of E/M services recognized 7 components to define the levels of E/M services¹¹: history and nature of the presenting problem; physical examination; medical decision-making (MDM); counseling; coordination of care; and time. Furthermore, history, physical examination, and MDM were all broken down into more granular elements that were summed to determine the level for each component; for example, the history of the presenting problem was defined as a chronological description of the development of the patient’s present illness, including the following elements: location, quality, severity, duration, timing, context, modifying factors, and associated signs and symptoms. Each of these categories would constitute bullet points to be summed to determine the level of history. Physical examination and MDM bullet points also would be summed to determine a proper coding level.¹¹ Understandably, this coding scheme was complicated and burdensome to medical providers.

The redefinition of the E/M codes for 2021 substantially simplified the determination of coding level and documentation.¹⁰ The revisions to the E/M office visit code descriptors and documentation standards are now centered around how physicians think and take care of patients and not on mandatory standards and checking boxes. The main changes involve MDM as the prime determinant of the coding level. Elements of MDM affecting coding for an outpatient or office visit now include only 3 components: the number and complexity of problems addressed in the encounter, the amount or complexity of data to be reviewed and analyzed, and the risk of complications or morbidity of patient management. Gone are the requirements from the earlier criteria requiring so many bullet points for the history, physical examination, and MDM.

Dermatologists may ask, “How does the new E/M coding structure affect reporting and documenting an E/M and a procedure on the same day?” The answer is that the determination of separate and distinct is basically unchanged with the new E/M codes; however, the documentation requirements for modifier -25 using the new E/M codes are simplified.

As always, the key to determining whether a separate and distinct E/M service was provided and subsequently documented is to deconstruct the medical note. All evaluation services associated with the procedure—making a clinical diagnosis or differential diagnosis, decision to perform surgery, and discussion of alternative treatments—should be removed from one’s documentation as shown in the example below. If a complete E/M service still exists, then an E/M may be billed in addition to the procedure. Physical examination of the treatment area is included in the surgical package. With the prior E/M criteria, physical examination of the procedural area could not be used again as a bullet point to count for the E/M level. However, with the new 2021 coding requirements, the documentation of a separate MDM will be sufficient to meet criteria because documentation of physical examination is not a requirement.

Modifier -25 Examples

Let’s examine a typical dermatologist medical note. An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. The patient also complains of a growing tender lesion on the left elbow of 2 months’ duration. Physical examination reveals a linear vesicular eruption on the left wrist and a tender hyperkeratotic papule on the left elbow. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed. The decision is made to perform a tangential biopsy of the lesion on the left elbow because of the suspicion for malignancy. The biopsy is performed the same day.

This case clearly illustrates performance of an E/M service in the treatment of rhus dermatitis, which is separate and distinct from the biopsy procedure; however, in evaluating whether the case meets the documentation requirements for modifier -25, the information in the medical note inclusive to the procedure’s global surgical package, including history associated with establishing the diagnosis, physical examination of the procedure area(s), and discussion of treatment options, is eliminated, leaving the following notes: An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed.

Because the physical examination of the body part (left arm) is included in the procedure’s global surgical package, the examination of the left wrist cannot be used as coding support for the E/M service. This makes a difference for coding level in the prior E/M coding requirements, which required examination bullet points. However, with the 2021 E/M codes, documentation of physical examination bullet points is irrelevant to the coding level. Therefore, qualifying for a modifier -25 claim is more straightforward in this case with the new code set. Because bullet points are not integral to the 2021 E/M codes, qualifying and properly documenting for a higher level of service will likely be more common in dermatology.

Final Thoughts

Frequent use of modifier -25 is a critical part of a high-quality and cost-effective dermatology practice. Same-day performance of minor procedures and E/M services allows for more rapid and efficient diagnosis and treatment of various conditions as well as minimizing unnecessary office visits. The new E/M codes for 2021 actually make the documentation of a separate and distinct E/M service less complicated because the bullet point requirements associated with the old E/M codes have been eliminated. Understanding how the new E/M code descriptors affect modifier -25 reporting and clear documentation of separate, distinct, and medically necessary E/M services will be needed due to increased insurer scrutiny and audits.

Insurers Target Modifier -25

Modifier -25 allows reporting of both a minor procedure (ie, one with a 0- or 10-day global period) and a separate and distinct evaluation and management (E/M) service on the same date of service.¹ Because of the multicomplaint nature of dermatology, the ability to report a same-day procedure and an E/M service is critical for efficient, cost-effective, and patient-centered dermatologic care. However, it is well known that the use of modifier -25 has been under notable insurer scrutiny and is a common reason for medical record audits.^2,3 Some insurers have responded to increased utilization of modifier -25 by cutting reimbursement for claims that include both a procedure and an E/M service or by denying one of the services altogether.^4-6 The Centers for Medicare and Medicaid Services also have expressed concern about this coding combination with proposed cuts to reimbursement.⁷ Moreover, the Office of Inspector General has announced a work plan to investigate the frequent utilization of E/M codes and minor procedures by dermatologists.⁸ Clearly, modifier -25 is a continued target by insurers and regulators; therefore, dermatologists will want to make sure their coding and documentation meet all requirements and are updated for the new E/M codes for 2021.

The American Medical Association’s Current Procedural Terminology indicates that modifier -25 allows reporting of a “significant, separately identifiable evaluation and management service by the same physician or other qualified health care professional on the same day of a procedure or other service.”¹ Given that dermatology patients typically present with multiple concerns, dermatologists commonly evaluate and treat numerous conditions during one visit. Understanding what constitutes a separately identifiable E/M service is critical to bill accurately and to pass insurer audits.

Global Surgical Package

To appropriately bill both a procedure and an E/M service, the physician must indicate that the patient’s condition required an E/M service above and beyond the usual work of the procedure. The compilation of evaluation and work included in the payment for a procedure is called the global surgical package.⁹ In general, the global surgical package includes local or topical anesthesia; the surgical service/procedure itself; immediate postoperative care, including dictating the operative note; meeting/discussing the patient’s procedure with family and other physicians; and writing orders for the patient. For minor procedures (ie, those with either 0- or 10-day global periods), the surgical package also includes same-day E/M services associated with the decision to perform surgery. An appropriate history and physical examination as well as a discussion of the differential diagnosis, treatment options, and risk and benefits of treatment are all included in the payment of a minor procedure itself. Therefore, an evaluation to discuss a patient’s condition or change in condition, alternatives to treatment, or next steps after a diagnosis related to a treatment or diagnostic procedure should not be separately reported. Moreover, the fact that the patient is new to the physician is not in itself sufficient to allow reporting of an E/M service with these minor procedures. For major procedures (ie, those with 90-day postoperative periods), the decision for surgery is excluded from the global surgical package.

2021 E/M Codes Simplify Documentation

The biggest coding change of 2021 was the new E/M codes.¹⁰ Prior to this year, the descriptors of E/M services recognized 7 components to define the levels of E/M services¹¹: history and nature of the presenting problem; physical examination; medical decision-making (MDM); counseling; coordination of care; and time. Furthermore, history, physical examination, and MDM were all broken down into more granular elements that were summed to determine the level for each component; for example, the history of the presenting problem was defined as a chronological description of the development of the patient’s present illness, including the following elements: location, quality, severity, duration, timing, context, modifying factors, and associated signs and symptoms. Each of these categories would constitute bullet points to be summed to determine the level of history. Physical examination and MDM bullet points also would be summed to determine a proper coding level.¹¹ Understandably, this coding scheme was complicated and burdensome to medical providers.

The redefinition of the E/M codes for 2021 substantially simplified the determination of coding level and documentation.¹⁰ The revisions to the E/M office visit code descriptors and documentation standards are now centered around how physicians think and take care of patients and not on mandatory standards and checking boxes. The main changes involve MDM as the prime determinant of the coding level. Elements of MDM affecting coding for an outpatient or office visit now include only 3 components: the number and complexity of problems addressed in the encounter, the amount or complexity of data to be reviewed and analyzed, and the risk of complications or morbidity of patient management. Gone are the requirements from the earlier criteria requiring so many bullet points for the history, physical examination, and MDM.

Dermatologists may ask, “How does the new E/M coding structure affect reporting and documenting an E/M and a procedure on the same day?” The answer is that the determination of separate and distinct is basically unchanged with the new E/M codes; however, the documentation requirements for modifier -25 using the new E/M codes are simplified.

As always, the key to determining whether a separate and distinct E/M service was provided and subsequently documented is to deconstruct the medical note. All evaluation services associated with the procedure—making a clinical diagnosis or differential diagnosis, decision to perform surgery, and discussion of alternative treatments—should be removed from one’s documentation as shown in the example below. If a complete E/M service still exists, then an E/M may be billed in addition to the procedure. Physical examination of the treatment area is included in the surgical package. With the prior E/M criteria, physical examination of the procedural area could not be used again as a bullet point to count for the E/M level. However, with the new 2021 coding requirements, the documentation of a separate MDM will be sufficient to meet criteria because documentation of physical examination is not a requirement.

Modifier -25 Examples

Let’s examine a typical dermatologist medical note. An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. The patient also complains of a growing tender lesion on the left elbow of 2 months’ duration. Physical examination reveals a linear vesicular eruption on the left wrist and a tender hyperkeratotic papule on the left elbow. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed. The decision is made to perform a tangential biopsy of the lesion on the left elbow because of the suspicion for malignancy. The biopsy is performed the same day.

This case clearly illustrates performance of an E/M service in the treatment of rhus dermatitis, which is separate and distinct from the biopsy procedure; however, in evaluating whether the case meets the documentation requirements for modifier -25, the information in the medical note inclusive to the procedure’s global surgical package, including history associated with establishing the diagnosis, physical examination of the procedure area(s), and discussion of treatment options, is eliminated, leaving the following notes: An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed.

Because the physical examination of the body part (left arm) is included in the procedure’s global surgical package, the examination of the left wrist cannot be used as coding support for the E/M service. This makes a difference for coding level in the prior E/M coding requirements, which required examination bullet points. However, with the 2021 E/M codes, documentation of physical examination bullet points is irrelevant to the coding level. Therefore, qualifying for a modifier -25 claim is more straightforward in this case with the new code set. Because bullet points are not integral to the 2021 E/M codes, qualifying and properly documenting for a higher level of service will likely be more common in dermatology.

Final Thoughts

Frequent use of modifier -25 is a critical part of a high-quality and cost-effective dermatology practice. Same-day performance of minor procedures and E/M services allows for more rapid and efficient diagnosis and treatment of various conditions as well as minimizing unnecessary office visits. The new E/M codes for 2021 actually make the documentation of a separate and distinct E/M service less complicated because the bullet point requirements associated with the old E/M codes have been eliminated. Understanding how the new E/M code descriptors affect modifier -25 reporting and clear documentation of separate, distinct, and medically necessary E/M services will be needed due to increased insurer scrutiny and audits.

Insurers Target Modifier -25

Modifier -25 allows reporting of both a minor procedure (ie, one with a 0- or 10-day global period) and a separate and distinct evaluation and management (E/M) service on the same date of service.¹ Because of the multicomplaint nature of dermatology, the ability to report a same-day procedure and an E/M service is critical for efficient, cost-effective, and patient-centered dermatologic care. However, it is well known that the use of modifier -25 has been under notable insurer scrutiny and is a common reason for medical record audits.^2,3 Some insurers have responded to increased utilization of modifier -25 by cutting reimbursement for claims that include both a procedure and an E/M service or by denying one of the services altogether.^4-6 The Centers for Medicare and Medicaid Services also have expressed concern about this coding combination with proposed cuts to reimbursement.⁷ Moreover, the Office of Inspector General has announced a work plan to investigate the frequent utilization of E/M codes and minor procedures by dermatologists.⁸ Clearly, modifier -25 is a continued target by insurers and regulators; therefore, dermatologists will want to make sure their coding and documentation meet all requirements and are updated for the new E/M codes for 2021.

The American Medical Association’s Current Procedural Terminology indicates that modifier -25 allows reporting of a “significant, separately identifiable evaluation and management service by the same physician or other qualified health care professional on the same day of a procedure or other service.”¹ Given that dermatology patients typically present with multiple concerns, dermatologists commonly evaluate and treat numerous conditions during one visit. Understanding what constitutes a separately identifiable E/M service is critical to bill accurately and to pass insurer audits.

Global Surgical Package

To appropriately bill both a procedure and an E/M service, the physician must indicate that the patient’s condition required an E/M service above and beyond the usual work of the procedure. The compilation of evaluation and work included in the payment for a procedure is called the global surgical package.⁹ In general, the global surgical package includes local or topical anesthesia; the surgical service/procedure itself; immediate postoperative care, including dictating the operative note; meeting/discussing the patient’s procedure with family and other physicians; and writing orders for the patient. For minor procedures (ie, those with either 0- or 10-day global periods), the surgical package also includes same-day E/M services associated with the decision to perform surgery. An appropriate history and physical examination as well as a discussion of the differential diagnosis, treatment options, and risk and benefits of treatment are all included in the payment of a minor procedure itself. Therefore, an evaluation to discuss a patient’s condition or change in condition, alternatives to treatment, or next steps after a diagnosis related to a treatment or diagnostic procedure should not be separately reported. Moreover, the fact that the patient is new to the physician is not in itself sufficient to allow reporting of an E/M service with these minor procedures. For major procedures (ie, those with 90-day postoperative periods), the decision for surgery is excluded from the global surgical package.

2021 E/M Codes Simplify Documentation

The biggest coding change of 2021 was the new E/M codes.¹⁰ Prior to this year, the descriptors of E/M services recognized 7 components to define the levels of E/M services¹¹: history and nature of the presenting problem; physical examination; medical decision-making (MDM); counseling; coordination of care; and time. Furthermore, history, physical examination, and MDM were all broken down into more granular elements that were summed to determine the level for each component; for example, the history of the presenting problem was defined as a chronological description of the development of the patient’s present illness, including the following elements: location, quality, severity, duration, timing, context, modifying factors, and associated signs and symptoms. Each of these categories would constitute bullet points to be summed to determine the level of history. Physical examination and MDM bullet points also would be summed to determine a proper coding level.¹¹ Understandably, this coding scheme was complicated and burdensome to medical providers.

The redefinition of the E/M codes for 2021 substantially simplified the determination of coding level and documentation.¹⁰ The revisions to the E/M office visit code descriptors and documentation standards are now centered around how physicians think and take care of patients and not on mandatory standards and checking boxes. The main changes involve MDM as the prime determinant of the coding level. Elements of MDM affecting coding for an outpatient or office visit now include only 3 components: the number and complexity of problems addressed in the encounter, the amount or complexity of data to be reviewed and analyzed, and the risk of complications or morbidity of patient management. Gone are the requirements from the earlier criteria requiring so many bullet points for the history, physical examination, and MDM.

Dermatologists may ask, “How does the new E/M coding structure affect reporting and documenting an E/M and a procedure on the same day?” The answer is that the determination of separate and distinct is basically unchanged with the new E/M codes; however, the documentation requirements for modifier -25 using the new E/M codes are simplified.

As always, the key to determining whether a separate and distinct E/M service was provided and subsequently documented is to deconstruct the medical note. All evaluation services associated with the procedure—making a clinical diagnosis or differential diagnosis, decision to perform surgery, and discussion of alternative treatments—should be removed from one’s documentation as shown in the example below. If a complete E/M service still exists, then an E/M may be billed in addition to the procedure. Physical examination of the treatment area is included in the surgical package. With the prior E/M criteria, physical examination of the procedural area could not be used again as a bullet point to count for the E/M level. However, with the new 2021 coding requirements, the documentation of a separate MDM will be sufficient to meet criteria because documentation of physical examination is not a requirement.

Modifier -25 Examples

Let’s examine a typical dermatologist medical note. An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. The patient also complains of a growing tender lesion on the left elbow of 2 months’ duration. Physical examination reveals a linear vesicular eruption on the left wrist and a tender hyperkeratotic papule on the left elbow. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed. The decision is made to perform a tangential biopsy of the lesion on the left elbow because of the suspicion for malignancy. The biopsy is performed the same day.

This case clearly illustrates performance of an E/M service in the treatment of rhus dermatitis, which is separate and distinct from the biopsy procedure; however, in evaluating whether the case meets the documentation requirements for modifier -25, the information in the medical note inclusive to the procedure’s global surgical package, including history associated with establishing the diagnosis, physical examination of the procedure area(s), and discussion of treatment options, is eliminated, leaving the following notes: An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed.

Because the physical examination of the body part (left arm) is included in the procedure’s global surgical package, the examination of the left wrist cannot be used as coding support for the E/M service. This makes a difference for coding level in the prior E/M coding requirements, which required examination bullet points. However, with the 2021 E/M codes, documentation of physical examination bullet points is irrelevant to the coding level. Therefore, qualifying for a modifier -25 claim is more straightforward in this case with the new code set. Because bullet points are not integral to the 2021 E/M codes, qualifying and properly documenting for a higher level of service will likely be more common in dermatology.

Final Thoughts

Frequent use of modifier -25 is a critical part of a high-quality and cost-effective dermatology practice. Same-day performance of minor procedures and E/M services allows for more rapid and efficient diagnosis and treatment of various conditions as well as minimizing unnecessary office visits. The new E/M codes for 2021 actually make the documentation of a separate and distinct E/M service less complicated because the bullet point requirements associated with the old E/M codes have been eliminated. Understanding how the new E/M code descriptors affect modifier -25 reporting and clear documentation of separate, distinct, and medically necessary E/M services will be needed due to increased insurer scrutiny and audits.

The US population is becoming more diverse. By 2044, it is predicted that there will be a majority minority population in the United States.¹ Therefore, it is imperative to continue to develop educational mechanisms for all dermatologists to increase and maintain competency in skin of color dermatology, which will contribute to the achievement of health equity for patients with all skin tones and hair types.

Not only is clinical skin of color education necessary, but diversity, equity, and inclusion (DEI) education for dermatologists also is critical. Clinical examination,² diagnosis, and treatment of skin and hair disorders across the skin of color spectrum with cultural humility is essential to achieve health equity. If trainees, dermatologists, other specialists, and primary care clinicians are not frequently exposed to patients with darker skin tones and coily hair, the nuances in diagnosing and treating these patients must be learned in alternate ways.

To ready the nation’s physicians and clinicians to care for the growing diverse population, exposure to more images of dermatologic diseases in those with darker skin tones in journal articles, textbooks, conference lectures, and online dermatology image libraries is necessary to help close the skin of color training and practice gap.^3,4 The following initiatives demonstrate how Cutis has sought to address these educational gaps and remains committed to improving DEI education in dermatology.

Collaboration With the Skin of Color Society

The Skin of Color Society (SOCS), which was founded in 2004 by Dr. Susan C. Taylor, is a dermatologic organization with more than 800 members representing 32 countries. Its mission includes promoting awareness and excellence within skin of color dermatology through research, education, and mentorship. The SOCS has utilized strategic partnerships with national and international dermatologists, as well as professional medical organizations and community, industry, and corporate groups, to ultimately ensure that patients with skin of color receive the expert care they deserve.⁵ In 2017, Cutis published the inaugural article in its collaboration with the SOCS,⁶ and more articles, which undergo regular peer review, continue to be published quarterly (https://www.mdedge.com/dermatology/skin-color).

Increase Number of Journal Articles on Skin of Color Topics

Increasing the number of journal articles on skin of color–related topics needs to be intentional, as it is a tool that has been identified as a necessary part of enhancing awareness and subsequently improving patient care. Wilson et al⁷ used stringent criteria to review all articles published from January 2018 to October 2020 in 52 dermatology journals for inclusion of topics on skin of color, hair in patients with skin of color, diversity and inclusion, and socioeconomic and health care disparities in the skin of color population. The journals they reviewed included publications based on continents with majority skin of color populations, such as Asia, as well as those with minority skin of color populations, such as Europe. During the study period, the percentage of articles covering skin of color ranged from 2.04% to 61.8%, with an average of 16.8%.⁷

The total number of Cutis articles published during the study period was 709, with 132 (18.62%) meeting the investigators’ criteria for articles on skin of color; these included case reports in which at least 1 patient with skin of color was featured.⁷ Overall, Cutis ranked 16th of the 52 journals for inclusion of skin of color content. Cutis was one of only a few journals based in North America, a non–skin-of-color–predominant continent, to make the top 16 in this study.⁷

Some of the 132 skin of color articles published in Cutis were the result of the journal’s collaboration with the SOCS. Through this collaboration, articles were published on a variety of skin of color topics, including DEI (6), alopecia and hair care (5), dermoscopy/optical coherence tomography imaging (1), atopic dermatitis (1), cosmetics (1), hidradenitis suppurativa (1), pigmentation (1), rosacea (1), and skin cancer (2). These articles also resulted in a number of podcast discussions (https://www.mdedge.com/podcasts/dermatology-weekly), including one on dealing with DEI, one on pigmentation, and one on dermoscopy/optical coherence tomography imaging. The latter featured the SOCS Scientific Symposium poster winners in 2020.

The number of articles published specifically through Cutis’s collaboration with the SOCS accounted for only a small part of the journal’s 132 skin of color articles identified in the study by Wilson et al.⁷ We speculate that Cutis’s display of intentional commitment to supporting the inclusion of skin of color articles in the journal may in turn encourage its broader readership to submit more skin of color–focused articles for peer review.

Wilson et al⁷ specifically remarked that “Cutis’s [Skin of Color] section in each issue is a promising idea.” They also highlighted Clinics in Dermatology for committing an entire issue to skin of color; however, despite this initiative, Clinics in Dermatology still ranked 35th of 52 journals with regard to the overall percentage of skin of color articles published.⁷ This suggests that a journal publishing one special issue on skin of color annually is a helpful addition to the literature, but increasing the number of articles related to skin of color in each journal issue, similar to Cutis, will ultimately result in a higher overall number of skin of color articles in the dermatology literature.

Both Amuzie et al⁴ and Wilson et al⁷ concluded that the higher a journal’s impact factor, the lower the number of skin of color articles published.However, skin of color articles published in high-impact journals received a higher number of citations than those in other lower-impact journals.⁴ High-impact journals may use Cutis as a model for increasing the number of skin of color articles they publish, which will have a notable impact on increasing skin of color knowledge and educating dermatologists.

Coverage of Diversity, Equity, and Inclusion

In another study, Bray et al⁸ conducted a PubMed search of articles indexed for MEDLINE from January 2008 to July 2019 to quantify the number of articles specifically focused on DEI in a variety of medical specialties. The field of dermatology had the highest number of articles published on DEI (25) compared to the other specialties, including family medicine (23), orthopedic surgery (12), internal medicine (9), general surgery (7), radiology (6), ophthalmology (2), and anesthesiology (2).⁸ However, Wilson et al⁷ found that, out of all the categories of skin of color articles published in dermatology journals during their study period, those focused on DEI made up less than 1% of the total number of articles. Dermatology is off to a great start compared to other specialties, but there is still more work to do in dermatology for DEI. Cutis’s collaboration with the SOCS has resulted in 6 DEI articles published since 2017.

Think Beyond Dermatology Education

The collaboration between Cutis and the SOCS was established to create a series of articles dedicated to increasing the skin of color dermatology knowledge base of the Cutis readership and beyond; however, increased readership and more citations are needed to amplify the reach of the articles published by these skin of color experts. Cutis’s collaboration with SOCS is one mechanism to increase the skin of color literature, but skin of color and DEI articles outside of this collaboration should continue to be published in each issue of Cutis.

The collaboration between SOCS and Cutis was and continues to be a forward-thinking step toward improving skin of color dermatology education, but there is still work to be done across the medical literature with regard to increasing intentional publication of skin of color articles. Nondermatologist clinicians in the Cutis readership benefit from knowledge of skin of color, as all specialties and primary care will see increased patient diversity in their examination rooms.

To further ensure that primary care is not left behind, Cutis has partnered with The Journal of Family Practice to produce a new column called Dx Across the Skin of Color Spectrum (https://www.mdedge.com/dermatology/dx-across-skin-color-spectrum), which is co-published in both journals.^9,10 These one-page fact sheets highlight images of dermatologic conditions in skin of color as well as images of the same condition in lighter skin, a concept suggested by Cutis Associate Editor, Dr. Candrice R. Heath. The goal of this new column is to increase the accurate diagnosis of dermatologic conditions in skin of color and to highlight health disparities related to a particular condition in an easy-to-understand format. Uniquely, Dr. Heath co-authors this content with family physician Dr. Richard P. Usatine.

Final Thoughts

The entire community of medical journals should continue to develop creative ways to educate their readership. Medical professionals stay up-to-date on best practices through journal articles, textbooks, conferences, and even podcasts. Therefore, it is best to incorporate skin of color knowledge throughout all educational programming, particularly through enduring materials such as journal articles. Wilson et al⁷ suggested that a minimum of 16.8% of a dermatology journal’s articles in each issue should focus on skin of color in addition to special focus issues, as this will work toward more equitable dermatologic care.

Knowledge is only part of the equation; compassionate care with cultural humility is the other part. Publishing scientific facts about biology and structure, diagnosis, and treatment selection in skin of color, as well as committing to lifelong learning about the differences in our patients despite the absence of shared life or cultural experiences, may be the key to truly impacting health equity.¹¹ We believe that together we will get there one journal article and one citation at a time.

The US population is becoming more diverse. By 2044, it is predicted that there will be a majority minority population in the United States.¹ Therefore, it is imperative to continue to develop educational mechanisms for all dermatologists to increase and maintain competency in skin of color dermatology, which will contribute to the achievement of health equity for patients with all skin tones and hair types.

Not only is clinical skin of color education necessary, but diversity, equity, and inclusion (DEI) education for dermatologists also is critical. Clinical examination,² diagnosis, and treatment of skin and hair disorders across the skin of color spectrum with cultural humility is essential to achieve health equity. If trainees, dermatologists, other specialists, and primary care clinicians are not frequently exposed to patients with darker skin tones and coily hair, the nuances in diagnosing and treating these patients must be learned in alternate ways.

To ready the nation’s physicians and clinicians to care for the growing diverse population, exposure to more images of dermatologic diseases in those with darker skin tones in journal articles, textbooks, conference lectures, and online dermatology image libraries is necessary to help close the skin of color training and practice gap.^3,4 The following initiatives demonstrate how Cutis has sought to address these educational gaps and remains committed to improving DEI education in dermatology.

Collaboration With the Skin of Color Society

The Skin of Color Society (SOCS), which was founded in 2004 by Dr. Susan C. Taylor, is a dermatologic organization with more than 800 members representing 32 countries. Its mission includes promoting awareness and excellence within skin of color dermatology through research, education, and mentorship. The SOCS has utilized strategic partnerships with national and international dermatologists, as well as professional medical organizations and community, industry, and corporate groups, to ultimately ensure that patients with skin of color receive the expert care they deserve.⁵ In 2017, Cutis published the inaugural article in its collaboration with the SOCS,⁶ and more articles, which undergo regular peer review, continue to be published quarterly (https://www.mdedge.com/dermatology/skin-color).

Increase Number of Journal Articles on Skin of Color Topics

Increasing the number of journal articles on skin of color–related topics needs to be intentional, as it is a tool that has been identified as a necessary part of enhancing awareness and subsequently improving patient care. Wilson et al⁷ used stringent criteria to review all articles published from January 2018 to October 2020 in 52 dermatology journals for inclusion of topics on skin of color, hair in patients with skin of color, diversity and inclusion, and socioeconomic and health care disparities in the skin of color population. The journals they reviewed included publications based on continents with majority skin of color populations, such as Asia, as well as those with minority skin of color populations, such as Europe. During the study period, the percentage of articles covering skin of color ranged from 2.04% to 61.8%, with an average of 16.8%.⁷

The total number of Cutis articles published during the study period was 709, with 132 (18.62%) meeting the investigators’ criteria for articles on skin of color; these included case reports in which at least 1 patient with skin of color was featured.⁷ Overall, Cutis ranked 16th of the 52 journals for inclusion of skin of color content. Cutis was one of only a few journals based in North America, a non–skin-of-color–predominant continent, to make the top 16 in this study.⁷

Some of the 132 skin of color articles published in Cutis were the result of the journal’s collaboration with the SOCS. Through this collaboration, articles were published on a variety of skin of color topics, including DEI (6), alopecia and hair care (5), dermoscopy/optical coherence tomography imaging (1), atopic dermatitis (1), cosmetics (1), hidradenitis suppurativa (1), pigmentation (1), rosacea (1), and skin cancer (2). These articles also resulted in a number of podcast discussions (https://www.mdedge.com/podcasts/dermatology-weekly), including one on dealing with DEI, one on pigmentation, and one on dermoscopy/optical coherence tomography imaging. The latter featured the SOCS Scientific Symposium poster winners in 2020.

The number of articles published specifically through Cutis’s collaboration with the SOCS accounted for only a small part of the journal’s 132 skin of color articles identified in the study by Wilson et al.⁷ We speculate that Cutis’s display of intentional commitment to supporting the inclusion of skin of color articles in the journal may in turn encourage its broader readership to submit more skin of color–focused articles for peer review.

Wilson et al⁷ specifically remarked that “Cutis’s [Skin of Color] section in each issue is a promising idea.” They also highlighted Clinics in Dermatology for committing an entire issue to skin of color; however, despite this initiative, Clinics in Dermatology still ranked 35th of 52 journals with regard to the overall percentage of skin of color articles published.⁷ This suggests that a journal publishing one special issue on skin of color annually is a helpful addition to the literature, but increasing the number of articles related to skin of color in each journal issue, similar to Cutis, will ultimately result in a higher overall number of skin of color articles in the dermatology literature.

Both Amuzie et al⁴ and Wilson et al⁷ concluded that the higher a journal’s impact factor, the lower the number of skin of color articles published.However, skin of color articles published in high-impact journals received a higher number of citations than those in other lower-impact journals.⁴ High-impact journals may use Cutis as a model for increasing the number of skin of color articles they publish, which will have a notable impact on increasing skin of color knowledge and educating dermatologists.

Coverage of Diversity, Equity, and Inclusion

In another study, Bray et al⁸ conducted a PubMed search of articles indexed for MEDLINE from January 2008 to July 2019 to quantify the number of articles specifically focused on DEI in a variety of medical specialties. The field of dermatology had the highest number of articles published on DEI (25) compared to the other specialties, including family medicine (23), orthopedic surgery (12), internal medicine (9), general surgery (7), radiology (6), ophthalmology (2), and anesthesiology (2).⁸ However, Wilson et al⁷ found that, out of all the categories of skin of color articles published in dermatology journals during their study period, those focused on DEI made up less than 1% of the total number of articles. Dermatology is off to a great start compared to other specialties, but there is still more work to do in dermatology for DEI. Cutis’s collaboration with the SOCS has resulted in 6 DEI articles published since 2017.

Think Beyond Dermatology Education

The collaboration between Cutis and the SOCS was established to create a series of articles dedicated to increasing the skin of color dermatology knowledge base of the Cutis readership and beyond; however, increased readership and more citations are needed to amplify the reach of the articles published by these skin of color experts. Cutis’s collaboration with SOCS is one mechanism to increase the skin of color literature, but skin of color and DEI articles outside of this collaboration should continue to be published in each issue of Cutis.

The collaboration between SOCS and Cutis was and continues to be a forward-thinking step toward improving skin of color dermatology education, but there is still work to be done across the medical literature with regard to increasing intentional publication of skin of color articles. Nondermatologist clinicians in the Cutis readership benefit from knowledge of skin of color, as all specialties and primary care will see increased patient diversity in their examination rooms.

To further ensure that primary care is not left behind, Cutis has partnered with The Journal of Family Practice to produce a new column called Dx Across the Skin of Color Spectrum (https://www.mdedge.com/dermatology/dx-across-skin-color-spectrum), which is co-published in both journals.^9,10 These one-page fact sheets highlight images of dermatologic conditions in skin of color as well as images of the same condition in lighter skin, a concept suggested by Cutis Associate Editor, Dr. Candrice R. Heath. The goal of this new column is to increase the accurate diagnosis of dermatologic conditions in skin of color and to highlight health disparities related to a particular condition in an easy-to-understand format. Uniquely, Dr. Heath co-authors this content with family physician Dr. Richard P. Usatine.

Final Thoughts

The entire community of medical journals should continue to develop creative ways to educate their readership. Medical professionals stay up-to-date on best practices through journal articles, textbooks, conferences, and even podcasts. Therefore, it is best to incorporate skin of color knowledge throughout all educational programming, particularly through enduring materials such as journal articles. Wilson et al⁷ suggested that a minimum of 16.8% of a dermatology journal’s articles in each issue should focus on skin of color in addition to special focus issues, as this will work toward more equitable dermatologic care.

Knowledge is only part of the equation; compassionate care with cultural humility is the other part. Publishing scientific facts about biology and structure, diagnosis, and treatment selection in skin of color, as well as committing to lifelong learning about the differences in our patients despite the absence of shared life or cultural experiences, may be the key to truly impacting health equity.¹¹ We believe that together we will get there one journal article and one citation at a time.

The US population is becoming more diverse. By 2044, it is predicted that there will be a majority minority population in the United States.¹ Therefore, it is imperative to continue to develop educational mechanisms for all dermatologists to increase and maintain competency in skin of color dermatology, which will contribute to the achievement of health equity for patients with all skin tones and hair types.

Not only is clinical skin of color education necessary, but diversity, equity, and inclusion (DEI) education for dermatologists also is critical. Clinical examination,² diagnosis, and treatment of skin and hair disorders across the skin of color spectrum with cultural humility is essential to achieve health equity. If trainees, dermatologists, other specialists, and primary care clinicians are not frequently exposed to patients with darker skin tones and coily hair, the nuances in diagnosing and treating these patients must be learned in alternate ways.

To ready the nation’s physicians and clinicians to care for the growing diverse population, exposure to more images of dermatologic diseases in those with darker skin tones in journal articles, textbooks, conference lectures, and online dermatology image libraries is necessary to help close the skin of color training and practice gap.^3,4 The following initiatives demonstrate how Cutis has sought to address these educational gaps and remains committed to improving DEI education in dermatology.

Collaboration With the Skin of Color Society

The Skin of Color Society (SOCS), which was founded in 2004 by Dr. Susan C. Taylor, is a dermatologic organization with more than 800 members representing 32 countries. Its mission includes promoting awareness and excellence within skin of color dermatology through research, education, and mentorship. The SOCS has utilized strategic partnerships with national and international dermatologists, as well as professional medical organizations and community, industry, and corporate groups, to ultimately ensure that patients with skin of color receive the expert care they deserve.⁵ In 2017, Cutis published the inaugural article in its collaboration with the SOCS,⁶ and more articles, which undergo regular peer review, continue to be published quarterly (https://www.mdedge.com/dermatology/skin-color).

Increase Number of Journal Articles on Skin of Color Topics

Increasing the number of journal articles on skin of color–related topics needs to be intentional, as it is a tool that has been identified as a necessary part of enhancing awareness and subsequently improving patient care. Wilson et al⁷ used stringent criteria to review all articles published from January 2018 to October 2020 in 52 dermatology journals for inclusion of topics on skin of color, hair in patients with skin of color, diversity and inclusion, and socioeconomic and health care disparities in the skin of color population. The journals they reviewed included publications based on continents with majority skin of color populations, such as Asia, as well as those with minority skin of color populations, such as Europe. During the study period, the percentage of articles covering skin of color ranged from 2.04% to 61.8%, with an average of 16.8%.⁷

The total number of Cutis articles published during the study period was 709, with 132 (18.62%) meeting the investigators’ criteria for articles on skin of color; these included case reports in which at least 1 patient with skin of color was featured.⁷ Overall, Cutis ranked 16th of the 52 journals for inclusion of skin of color content. Cutis was one of only a few journals based in North America, a non–skin-of-color–predominant continent, to make the top 16 in this study.⁷

Some of the 132 skin of color articles published in Cutis were the result of the journal’s collaboration with the SOCS. Through this collaboration, articles were published on a variety of skin of color topics, including DEI (6), alopecia and hair care (5), dermoscopy/optical coherence tomography imaging (1), atopic dermatitis (1), cosmetics (1), hidradenitis suppurativa (1), pigmentation (1), rosacea (1), and skin cancer (2). These articles also resulted in a number of podcast discussions (https://www.mdedge.com/podcasts/dermatology-weekly), including one on dealing with DEI, one on pigmentation, and one on dermoscopy/optical coherence tomography imaging. The latter featured the SOCS Scientific Symposium poster winners in 2020.

The number of articles published specifically through Cutis’s collaboration with the SOCS accounted for only a small part of the journal’s 132 skin of color articles identified in the study by Wilson et al.⁷ We speculate that Cutis’s display of intentional commitment to supporting the inclusion of skin of color articles in the journal may in turn encourage its broader readership to submit more skin of color–focused articles for peer review.

Wilson et al⁷ specifically remarked that “Cutis’s [Skin of Color] section in each issue is a promising idea.” They also highlighted Clinics in Dermatology for committing an entire issue to skin of color; however, despite this initiative, Clinics in Dermatology still ranked 35th of 52 journals with regard to the overall percentage of skin of color articles published.⁷ This suggests that a journal publishing one special issue on skin of color annually is a helpful addition to the literature, but increasing the number of articles related to skin of color in each journal issue, similar to Cutis, will ultimately result in a higher overall number of skin of color articles in the dermatology literature.

Both Amuzie et al⁴ and Wilson et al⁷ concluded that the higher a journal’s impact factor, the lower the number of skin of color articles published.However, skin of color articles published in high-impact journals received a higher number of citations than those in other lower-impact journals.⁴ High-impact journals may use Cutis as a model for increasing the number of skin of color articles they publish, which will have a notable impact on increasing skin of color knowledge and educating dermatologists.

Coverage of Diversity, Equity, and Inclusion

In another study, Bray et al⁸ conducted a PubMed search of articles indexed for MEDLINE from January 2008 to July 2019 to quantify the number of articles specifically focused on DEI in a variety of medical specialties. The field of dermatology had the highest number of articles published on DEI (25) compared to the other specialties, including family medicine (23), orthopedic surgery (12), internal medicine (9), general surgery (7), radiology (6), ophthalmology (2), and anesthesiology (2).⁸ However, Wilson et al⁷ found that, out of all the categories of skin of color articles published in dermatology journals during their study period, those focused on DEI made up less than 1% of the total number of articles. Dermatology is off to a great start compared to other specialties, but there is still more work to do in dermatology for DEI. Cutis’s collaboration with the SOCS has resulted in 6 DEI articles published since 2017.

Think Beyond Dermatology Education

The collaboration between Cutis and the SOCS was established to create a series of articles dedicated to increasing the skin of color dermatology knowledge base of the Cutis readership and beyond; however, increased readership and more citations are needed to amplify the reach of the articles published by these skin of color experts. Cutis’s collaboration with SOCS is one mechanism to increase the skin of color literature, but skin of color and DEI articles outside of this collaboration should continue to be published in each issue of Cutis.

The collaboration between SOCS and Cutis was and continues to be a forward-thinking step toward improving skin of color dermatology education, but there is still work to be done across the medical literature with regard to increasing intentional publication of skin of color articles. Nondermatologist clinicians in the Cutis readership benefit from knowledge of skin of color, as all specialties and primary care will see increased patient diversity in their examination rooms.

To further ensure that primary care is not left behind, Cutis has partnered with The Journal of Family Practice to produce a new column called Dx Across the Skin of Color Spectrum (https://www.mdedge.com/dermatology/dx-across-skin-color-spectrum), which is co-published in both journals.^9,10 These one-page fact sheets highlight images of dermatologic conditions in skin of color as well as images of the same condition in lighter skin, a concept suggested by Cutis Associate Editor, Dr. Candrice R. Heath. The goal of this new column is to increase the accurate diagnosis of dermatologic conditions in skin of color and to highlight health disparities related to a particular condition in an easy-to-understand format. Uniquely, Dr. Heath co-authors this content with family physician Dr. Richard P. Usatine.

Final Thoughts

The entire community of medical journals should continue to develop creative ways to educate their readership. Medical professionals stay up-to-date on best practices through journal articles, textbooks, conferences, and even podcasts. Therefore, it is best to incorporate skin of color knowledge throughout all educational programming, particularly through enduring materials such as journal articles. Wilson et al⁷ suggested that a minimum of 16.8% of a dermatology journal’s articles in each issue should focus on skin of color in addition to special focus issues, as this will work toward more equitable dermatologic care.

Knowledge is only part of the equation; compassionate care with cultural humility is the other part. Publishing scientific facts about biology and structure, diagnosis, and treatment selection in skin of color, as well as committing to lifelong learning about the differences in our patients despite the absence of shared life or cultural experiences, may be the key to truly impacting health equity.¹¹ We believe that together we will get there one journal article and one citation at a time.

Practice Gap

Onychocryptosis, colloquially known as an ingrown nail, most commonly affects the lateral folds of the toenails. It also can affect the fingernails and the distal aspect of the nail unit, though these presentations are not as well described in the literature. In onychocryptosis, the nail plate grows downward into the periungual skin, resulting in chronic pain and inflammation. Risk factors include overtrimming the nails with rounded edges, local trauma, nail surgery, wearing tight footwear, obesity, and onychomycosis.¹

Although surgical intervention might be required for severe or refractory disease, conservative treatment options are first line and often curative. A variety of techniques have been designed to separate the ingrown portion of the nail plate from underlying skin, including placement of an intervening piece of dental floss, cotton, or plastic tubing.²

Anchor taping is another effective method of treating onychocryptosis; a strip of tape is used to gently pull and secure the affected nail fold away from the overlying nail plate. This technique has been well described for the treatment of onychocryptosis of the lateral toenail.^3-5 In 2017, Arai and Haneke⁵ presented a modified technique for the treatment of distal disease.

We present a simplified method that was used successfully in a case of distal onychocryptosis of the thumbnail that occurred approximately 4 months after complete nail avulsion with a nail matrix biopsy (Figure 1).

The Technique

A strongly adhesive, soft cotton, elastic tape that is 1-inch wide, such as Elastikon Elastic Tape (Johnson & Johnson), is used to pull and secure the hyponychium away from the overlying nail plate. When this technique is used for lateral onychocryptosis, a single strip of tape is secured to the affected lateral nail fold, pulled obliquely and proximally, and secured to the base of the digit.^3-5 In the Arai and Haneke⁵ method for the treatment of distal disease, a piece of tape is first placed at the distal nail fold, pulled proximally, and secured to the ventral aspect of the digit. Then, 1 or 2 additional strips of tape are applied to the lateral nail folds, pulled obliquely, and adhered to the base of the digit, as in the classic technique for lateral onychocryptosis.⁵

In our modification for the treatment of distal disease, only 2 strips of tape are required, each approximately 5-cm long. The first strip of tape is applied to the hyponychium parallel to the long axis of the finger, pulled away from the distal edge of the nail plate, and secured obliquely and proximally to the base of the finger on one side. The second strip of tape is applied to the hyponychium in the same manner, directly overlying the first strip, but is then pulled obliquely in the opposite direction and secured to the other side of the proximal finger (Figure 2). The 2 strips of tape are applied directly overlying each other at the distal nail fold but with opposing tension vectors to optimize pull on the distal nail fold. This modification eliminates the need to apply an initial strip of tape along the long axis of the digit, as described by Arai and Haneke.⁵

Practice Implications

Anchor taping is a common and effective treatment of onychocryptosis. Most techniques described in the literature are for lateral toenail cases, which often are managed by podiatry. A modification for the treatment of distal onychocryptosis has been previously described.⁵ We describe a similar modification using 2 tape strips pulled in opposite directions, which successfully resolved a case of distal onychocryptosis of the fingernail that developed following a nail procedure.

Because nail dystrophy is a relatively common complication of nail surgery, dermatologic surgeons should be aware of this simple, cost-effective, and noninvasive technique for the treatment of distal onychocryptosis.

Practice Gap

Onychocryptosis, colloquially known as an ingrown nail, most commonly affects the lateral folds of the toenails. It also can affect the fingernails and the distal aspect of the nail unit, though these presentations are not as well described in the literature. In onychocryptosis, the nail plate grows downward into the periungual skin, resulting in chronic pain and inflammation. Risk factors include overtrimming the nails with rounded edges, local trauma, nail surgery, wearing tight footwear, obesity, and onychomycosis.¹

Although surgical intervention might be required for severe or refractory disease, conservative treatment options are first line and often curative. A variety of techniques have been designed to separate the ingrown portion of the nail plate from underlying skin, including placement of an intervening piece of dental floss, cotton, or plastic tubing.²

Anchor taping is another effective method of treating onychocryptosis; a strip of tape is used to gently pull and secure the affected nail fold away from the overlying nail plate. This technique has been well described for the treatment of onychocryptosis of the lateral toenail.^3-5 In 2017, Arai and Haneke⁵ presented a modified technique for the treatment of distal disease.

We present a simplified method that was used successfully in a case of distal onychocryptosis of the thumbnail that occurred approximately 4 months after complete nail avulsion with a nail matrix biopsy (Figure 1).

The Technique

A strongly adhesive, soft cotton, elastic tape that is 1-inch wide, such as Elastikon Elastic Tape (Johnson & Johnson), is used to pull and secure the hyponychium away from the overlying nail plate. When this technique is used for lateral onychocryptosis, a single strip of tape is secured to the affected lateral nail fold, pulled obliquely and proximally, and secured to the base of the digit.^3-5 In the Arai and Haneke⁵ method for the treatment of distal disease, a piece of tape is first placed at the distal nail fold, pulled proximally, and secured to the ventral aspect of the digit. Then, 1 or 2 additional strips of tape are applied to the lateral nail folds, pulled obliquely, and adhered to the base of the digit, as in the classic technique for lateral onychocryptosis.⁵

In our modification for the treatment of distal disease, only 2 strips of tape are required, each approximately 5-cm long. The first strip of tape is applied to the hyponychium parallel to the long axis of the finger, pulled away from the distal edge of the nail plate, and secured obliquely and proximally to the base of the finger on one side. The second strip of tape is applied to the hyponychium in the same manner, directly overlying the first strip, but is then pulled obliquely in the opposite direction and secured to the other side of the proximal finger (Figure 2). The 2 strips of tape are applied directly overlying each other at the distal nail fold but with opposing tension vectors to optimize pull on the distal nail fold. This modification eliminates the need to apply an initial strip of tape along the long axis of the digit, as described by Arai and Haneke.⁵

Practice Implications

Anchor taping is a common and effective treatment of onychocryptosis. Most techniques described in the literature are for lateral toenail cases, which often are managed by podiatry. A modification for the treatment of distal onychocryptosis has been previously described.⁵ We describe a similar modification using 2 tape strips pulled in opposite directions, which successfully resolved a case of distal onychocryptosis of the fingernail that developed following a nail procedure.

Because nail dystrophy is a relatively common complication of nail surgery, dermatologic surgeons should be aware of this simple, cost-effective, and noninvasive technique for the treatment of distal onychocryptosis.

Practice Gap

Onychocryptosis, colloquially known as an ingrown nail, most commonly affects the lateral folds of the toenails. It also can affect the fingernails and the distal aspect of the nail unit, though these presentations are not as well described in the literature. In onychocryptosis, the nail plate grows downward into the periungual skin, resulting in chronic pain and inflammation. Risk factors include overtrimming the nails with rounded edges, local trauma, nail surgery, wearing tight footwear, obesity, and onychomycosis.¹

Although surgical intervention might be required for severe or refractory disease, conservative treatment options are first line and often curative. A variety of techniques have been designed to separate the ingrown portion of the nail plate from underlying skin, including placement of an intervening piece of dental floss, cotton, or plastic tubing.²

Anchor taping is another effective method of treating onychocryptosis; a strip of tape is used to gently pull and secure the affected nail fold away from the overlying nail plate. This technique has been well described for the treatment of onychocryptosis of the lateral toenail.^3-5 In 2017, Arai and Haneke⁵ presented a modified technique for the treatment of distal disease.

We present a simplified method that was used successfully in a case of distal onychocryptosis of the thumbnail that occurred approximately 4 months after complete nail avulsion with a nail matrix biopsy (Figure 1).

The Technique

A strongly adhesive, soft cotton, elastic tape that is 1-inch wide, such as Elastikon Elastic Tape (Johnson & Johnson), is used to pull and secure the hyponychium away from the overlying nail plate. When this technique is used for lateral onychocryptosis, a single strip of tape is secured to the affected lateral nail fold, pulled obliquely and proximally, and secured to the base of the digit.^3-5 In the Arai and Haneke⁵ method for the treatment of distal disease, a piece of tape is first placed at the distal nail fold, pulled proximally, and secured to the ventral aspect of the digit. Then, 1 or 2 additional strips of tape are applied to the lateral nail folds, pulled obliquely, and adhered to the base of the digit, as in the classic technique for lateral onychocryptosis.⁵

In our modification for the treatment of distal disease, only 2 strips of tape are required, each approximately 5-cm long. The first strip of tape is applied to the hyponychium parallel to the long axis of the finger, pulled away from the distal edge of the nail plate, and secured obliquely and proximally to the base of the finger on one side. The second strip of tape is applied to the hyponychium in the same manner, directly overlying the first strip, but is then pulled obliquely in the opposite direction and secured to the other side of the proximal finger (Figure 2). The 2 strips of tape are applied directly overlying each other at the distal nail fold but with opposing tension vectors to optimize pull on the distal nail fold. This modification eliminates the need to apply an initial strip of tape along the long axis of the digit, as described by Arai and Haneke.⁵

Practice Implications

Anchor taping is a common and effective treatment of onychocryptosis. Most techniques described in the literature are for lateral toenail cases, which often are managed by podiatry. A modification for the treatment of distal onychocryptosis has been previously described.⁵ We describe a similar modification using 2 tape strips pulled in opposite directions, which successfully resolved a case of distal onychocryptosis of the fingernail that developed following a nail procedure.

Because nail dystrophy is a relatively common complication of nail surgery, dermatologic surgeons should be aware of this simple, cost-effective, and noninvasive technique for the treatment of distal onychocryptosis.

Autoeczematization (AE), or id reaction, is a disseminated eczematous reaction that occurs days or weeks after exposure to a primary stimulus, resulting from a release of antigen(s). Whitfield¹ first described AE in 1921, when he postulated that the id reaction was due to sensitization of the skin after a primary stimulus. He called it “a form of auto-intoxication derived from changes in the patient’s own tissues.”¹ The exact prevalence of id reactions is unknown; one study showed that 17% of patients with dermatophyte infections developed an id reaction, typically tinea pedis linked with vesicles on the palms.² Tinea capitis is one of the most common causes of AE in children, which is frequently misdiagnosed as a drug reaction. Approximately 37% of patients diagnosed with stasis dermatitis develop an id reaction (Figure 1). A history of contact dermatitis is common in patients presenting with AE.^2-6

Pathophysiology of Id Reactions

An abnormal immune response against autologous skin antigens may be responsible for the development of AE. Shelley⁵ postulated that hair follicles play an important role in id reactions, as Sharquie et al⁶ recently emphasized for many skin disorders. The pathogenesis of AE is uncertain, but circulating T lymphocytes play a role in this reaction. Normally, T cells are activated by a release of antigens after a primary exposure to a stimulus. However, overactivation of these T cells induces autoimmune reactions such as AE.⁷ Activated T lymphocytes express HLA-DR and IL-2 receptor, markers elevated in the peripheral blood of patients undergoing id reactions. After treatment, the levels of activated T lymphocytes decline. An increase in the number of CD25⁺ T cells and a decrease in the number of suppressor T cells in the blood may occur during an id reaction.^7-9 Keratinocytes produce proinflammatory cytokines, such as thymic stromal erythropoietin, IL-25, and IL-33, that activate T cells.^10-12 Therefore, the most likely pathogenesis of an id reaction is that T lymphocytes are activated at the primary reaction site due to proinflammatory cytokines released by keratinocytes. These activated T cells then travel systemically via hematogenous dissemination. The spread of activated T lymphocytes produces an eczematous reaction at secondary locations distant to the primary site.⁹

Clinical and Histopathological Features of Id Reactions

Clinically, AE is first evident as a vesicular dissemination that groups to form papules or nummular patches and usually is present on the legs, feet, arms, and/or trunk (Figure 2). The primary dermatitis is localized to the area that was the site of contact to the offending stimuli. This localized eczematous eruption begins with an acute or subacute onset. It has the appearance of small crusted vesicles with erythema (Figure 1). The first sign of AE is vesicles presenting near the primary site on flexural surfaces or on the hands and feet. A classic example is tinea pedis linked with vesicles on the palms and sides of the fingers, resembling dyshidrotic eczema. Sites of prior cutaneous trauma, such as dermatoses, scars, and burns, are common locations for early AE. In later stages, vesicles disseminate to the legs, arms, and trunk, where they group to form papules and nummular patches in a symmetrical pattern.^5,13-15 These lesions may be extremely pruritic. The pruritus may be so intense that it interrupts daily activities and disrupts the ability to fall or stay asleep.¹⁶

Histologically, biopsy specimens show psoriasiform spongiotic dermatitis with mononuclear cells contained in the vesicles. Interstitial edema and perivascular lymphohistiocytic infiltrates are evident. Eosinophils also may be present. This pattern is not unique toid reactions.^17-19 Although AE is a reaction pattern that may be due to a fungal or bacterial infection, the etiologic agent is not evident microscopically within the eczema itself.

Etiology of Id Reactions

Id reactions most commonly occur from either stasis dermatitis or tinea pedis, although a wide variety of other causes should be considered. Evaluation of the primary site rather than the id reaction may identify an infectious or parasitic agent. Sometimes the AE reaction is specifically named: dermatophytid with dermatophytosis, bacterid with a bacterial infectious process, and tuberculid with tuberculosis. Similarly, there may be reactions to underlying candidiasis, sporotrichosis, histoplasmosis, and other fungal infections that can cause a cutaneous id reaction.^18,20-22Mycobacterium species, Pseudomonas, Staphylococcus, and Streptococcus are bacterial causes of AE.^15,23-26 Viral infections that can cause an id reaction are herpes simplex virus and molluscum contagiosum.^27-29 Scabies, leishmaniasis, and pediculosis capitis are parasitic infections that may be etiologic.^14,30,31 In addition, noninfectious stimuli besides stasis dermatitis that can produce id reactions include medications, topical creams, tattoo ink, sutures, radiotherapy, and dyshidrotic eczema. The primary reaction to these agents is a localized dermatitis followed by the immunological response that induces a secondary reaction distant from the primary site.^17,18,32-38

Differential Diagnoses

Differential diagnoses include other types of eczema and some vesicular eruptions. Irritant contact dermatitis is another dermatosis that presents as a widespread vesicular eruption due to repetitive exposure to toxic irritants. The rash is erythematous with pustules, blisters, and crusts. It is only found in areas directly exposed to irritants, as opposed to AE, which spreads to areas distant to the primary reaction site. Irritant contact dermatitis presents with more of a burning sensation, whereas AE is more pruritic.^39,40 Allergic contact dermatitis presents with erythematous vesicles and papules and sometimes with bullae. There is edema and crust formation, which often can spread past the point of contact in later stages. Similar to AE, there is intense pruritus. However, allergic contact dermatitis most commonly is caused by exposure to metals, cosmetics, and fragrances, whereas infectious agents and stasis dermatitis are the most common causes of AE.^40,41 It may be challenging to distinguish AE from other causes of widespread eczematous dissemination. Vesicular eruptions sometimes require distinction from AE, including herpetic infections, insect bite reactions, and drug eruptions.^18,42

Treatment

The underlying condition should be treated to mitigate the inflammatory response causing the id reaction. If not skillfully orchestrated, the id reaction can reoccur. For infectious causes of AE, an antifungal, antibacterial, antiviral, or antiparasitic should be given. If stasis dermatitis is responsible for the id reaction, compression stockings and leg elevation are indicated. The id reaction itself is treated with systemic or topical corticosteroids and wet compresses if acute. The goal of these treatments is to reduce patient discomfort caused by the inflammation and pruritus.^18,43

Conclusion

Id reactions are an unusual phenomenon that commonly occurs after fungal skin infections and stasis dermatitis. T lymphocytes and keratinocytes may play a key role in this reaction, with newer research further delineating the process and possibly providing enhanced treatment options. Therapy focuses on treating the underlying condition, supplemented with corticosteroids for the autoeczema.

Autoeczematization (AE), or id reaction, is a disseminated eczematous reaction that occurs days or weeks after exposure to a primary stimulus, resulting from a release of antigen(s). Whitfield¹ first described AE in 1921, when he postulated that the id reaction was due to sensitization of the skin after a primary stimulus. He called it “a form of auto-intoxication derived from changes in the patient’s own tissues.”¹ The exact prevalence of id reactions is unknown; one study showed that 17% of patients with dermatophyte infections developed an id reaction, typically tinea pedis linked with vesicles on the palms.² Tinea capitis is one of the most common causes of AE in children, which is frequently misdiagnosed as a drug reaction. Approximately 37% of patients diagnosed with stasis dermatitis develop an id reaction (Figure 1). A history of contact dermatitis is common in patients presenting with AE.^2-6

Pathophysiology of Id Reactions

An abnormal immune response against autologous skin antigens may be responsible for the development of AE. Shelley⁵ postulated that hair follicles play an important role in id reactions, as Sharquie et al⁶ recently emphasized for many skin disorders. The pathogenesis of AE is uncertain, but circulating T lymphocytes play a role in this reaction. Normally, T cells are activated by a release of antigens after a primary exposure to a stimulus. However, overactivation of these T cells induces autoimmune reactions such as AE.⁷ Activated T lymphocytes express HLA-DR and IL-2 receptor, markers elevated in the peripheral blood of patients undergoing id reactions. After treatment, the levels of activated T lymphocytes decline. An increase in the number of CD25⁺ T cells and a decrease in the number of suppressor T cells in the blood may occur during an id reaction.^7-9 Keratinocytes produce proinflammatory cytokines, such as thymic stromal erythropoietin, IL-25, and IL-33, that activate T cells.^10-12 Therefore, the most likely pathogenesis of an id reaction is that T lymphocytes are activated at the primary reaction site due to proinflammatory cytokines released by keratinocytes. These activated T cells then travel systemically via hematogenous dissemination. The spread of activated T lymphocytes produces an eczematous reaction at secondary locations distant to the primary site.⁹

Clinical and Histopathological Features of Id Reactions

Clinically, AE is first evident as a vesicular dissemination that groups to form papules or nummular patches and usually is present on the legs, feet, arms, and/or trunk (Figure 2). The primary dermatitis is localized to the area that was the site of contact to the offending stimuli. This localized eczematous eruption begins with an acute or subacute onset. It has the appearance of small crusted vesicles with erythema (Figure 1). The first sign of AE is vesicles presenting near the primary site on flexural surfaces or on the hands and feet. A classic example is tinea pedis linked with vesicles on the palms and sides of the fingers, resembling dyshidrotic eczema. Sites of prior cutaneous trauma, such as dermatoses, scars, and burns, are common locations for early AE. In later stages, vesicles disseminate to the legs, arms, and trunk, where they group to form papules and nummular patches in a symmetrical pattern.^5,13-15 These lesions may be extremely pruritic. The pruritus may be so intense that it interrupts daily activities and disrupts the ability to fall or stay asleep.¹⁶

Histologically, biopsy specimens show psoriasiform spongiotic dermatitis with mononuclear cells contained in the vesicles. Interstitial edema and perivascular lymphohistiocytic infiltrates are evident. Eosinophils also may be present. This pattern is not unique toid reactions.^17-19 Although AE is a reaction pattern that may be due to a fungal or bacterial infection, the etiologic agent is not evident microscopically within the eczema itself.

Etiology of Id Reactions

Id reactions most commonly occur from either stasis dermatitis or tinea pedis, although a wide variety of other causes should be considered. Evaluation of the primary site rather than the id reaction may identify an infectious or parasitic agent. Sometimes the AE reaction is specifically named: dermatophytid with dermatophytosis, bacterid with a bacterial infectious process, and tuberculid with tuberculosis. Similarly, there may be reactions to underlying candidiasis, sporotrichosis, histoplasmosis, and other fungal infections that can cause a cutaneous id reaction.^18,20-22Mycobacterium species, Pseudomonas, Staphylococcus, and Streptococcus are bacterial causes of AE.^15,23-26 Viral infections that can cause an id reaction are herpes simplex virus and molluscum contagiosum.^27-29 Scabies, leishmaniasis, and pediculosis capitis are parasitic infections that may be etiologic.^14,30,31 In addition, noninfectious stimuli besides stasis dermatitis that can produce id reactions include medications, topical creams, tattoo ink, sutures, radiotherapy, and dyshidrotic eczema. The primary reaction to these agents is a localized dermatitis followed by the immunological response that induces a secondary reaction distant from the primary site.^17,18,32-38

Differential Diagnoses

Differential diagnoses include other types of eczema and some vesicular eruptions. Irritant contact dermatitis is another dermatosis that presents as a widespread vesicular eruption due to repetitive exposure to toxic irritants. The rash is erythematous with pustules, blisters, and crusts. It is only found in areas directly exposed to irritants, as opposed to AE, which spreads to areas distant to the primary reaction site. Irritant contact dermatitis presents with more of a burning sensation, whereas AE is more pruritic.^39,40 Allergic contact dermatitis presents with erythematous vesicles and papules and sometimes with bullae. There is edema and crust formation, which often can spread past the point of contact in later stages. Similar to AE, there is intense pruritus. However, allergic contact dermatitis most commonly is caused by exposure to metals, cosmetics, and fragrances, whereas infectious agents and stasis dermatitis are the most common causes of AE.^40,41 It may be challenging to distinguish AE from other causes of widespread eczematous dissemination. Vesicular eruptions sometimes require distinction from AE, including herpetic infections, insect bite reactions, and drug eruptions.^18,42

Treatment

The underlying condition should be treated to mitigate the inflammatory response causing the id reaction. If not skillfully orchestrated, the id reaction can reoccur. For infectious causes of AE, an antifungal, antibacterial, antiviral, or antiparasitic should be given. If stasis dermatitis is responsible for the id reaction, compression stockings and leg elevation are indicated. The id reaction itself is treated with systemic or topical corticosteroids and wet compresses if acute. The goal of these treatments is to reduce patient discomfort caused by the inflammation and pruritus.^18,43

Conclusion

Id reactions are an unusual phenomenon that commonly occurs after fungal skin infections and stasis dermatitis. T lymphocytes and keratinocytes may play a key role in this reaction, with newer research further delineating the process and possibly providing enhanced treatment options. Therapy focuses on treating the underlying condition, supplemented with corticosteroids for the autoeczema.

Autoeczematization (AE), or id reaction, is a disseminated eczematous reaction that occurs days or weeks after exposure to a primary stimulus, resulting from a release of antigen(s). Whitfield¹ first described AE in 1921, when he postulated that the id reaction was due to sensitization of the skin after a primary stimulus. He called it “a form of auto-intoxication derived from changes in the patient’s own tissues.”¹ The exact prevalence of id reactions is unknown; one study showed that 17% of patients with dermatophyte infections developed an id reaction, typically tinea pedis linked with vesicles on the palms.² Tinea capitis is one of the most common causes of AE in children, which is frequently misdiagnosed as a drug reaction. Approximately 37% of patients diagnosed with stasis dermatitis develop an id reaction (Figure 1). A history of contact dermatitis is common in patients presenting with AE.^2-6

Pathophysiology of Id Reactions

An abnormal immune response against autologous skin antigens may be responsible for the development of AE. Shelley⁵ postulated that hair follicles play an important role in id reactions, as Sharquie et al⁶ recently emphasized for many skin disorders. The pathogenesis of AE is uncertain, but circulating T lymphocytes play a role in this reaction. Normally, T cells are activated by a release of antigens after a primary exposure to a stimulus. However, overactivation of these T cells induces autoimmune reactions such as AE.⁷ Activated T lymphocytes express HLA-DR and IL-2 receptor, markers elevated in the peripheral blood of patients undergoing id reactions. After treatment, the levels of activated T lymphocytes decline. An increase in the number of CD25⁺ T cells and a decrease in the number of suppressor T cells in the blood may occur during an id reaction.^7-9 Keratinocytes produce proinflammatory cytokines, such as thymic stromal erythropoietin, IL-25, and IL-33, that activate T cells.^10-12 Therefore, the most likely pathogenesis of an id reaction is that T lymphocytes are activated at the primary reaction site due to proinflammatory cytokines released by keratinocytes. These activated T cells then travel systemically via hematogenous dissemination. The spread of activated T lymphocytes produces an eczematous reaction at secondary locations distant to the primary site.⁹

Clinical and Histopathological Features of Id Reactions

Clinically, AE is first evident as a vesicular dissemination that groups to form papules or nummular patches and usually is present on the legs, feet, arms, and/or trunk (Figure 2). The primary dermatitis is localized to the area that was the site of contact to the offending stimuli. This localized eczematous eruption begins with an acute or subacute onset. It has the appearance of small crusted vesicles with erythema (Figure 1). The first sign of AE is vesicles presenting near the primary site on flexural surfaces or on the hands and feet. A classic example is tinea pedis linked with vesicles on the palms and sides of the fingers, resembling dyshidrotic eczema. Sites of prior cutaneous trauma, such as dermatoses, scars, and burns, are common locations for early AE. In later stages, vesicles disseminate to the legs, arms, and trunk, where they group to form papules and nummular patches in a symmetrical pattern.^5,13-15 These lesions may be extremely pruritic. The pruritus may be so intense that it interrupts daily activities and disrupts the ability to fall or stay asleep.¹⁶

Histologically, biopsy specimens show psoriasiform spongiotic dermatitis with mononuclear cells contained in the vesicles. Interstitial edema and perivascular lymphohistiocytic infiltrates are evident. Eosinophils also may be present. This pattern is not unique toid reactions.^17-19 Although AE is a reaction pattern that may be due to a fungal or bacterial infection, the etiologic agent is not evident microscopically within the eczema itself.

Etiology of Id Reactions

Id reactions most commonly occur from either stasis dermatitis or tinea pedis, although a wide variety of other causes should be considered. Evaluation of the primary site rather than the id reaction may identify an infectious or parasitic agent. Sometimes the AE reaction is specifically named: dermatophytid with dermatophytosis, bacterid with a bacterial infectious process, and tuberculid with tuberculosis. Similarly, there may be reactions to underlying candidiasis, sporotrichosis, histoplasmosis, and other fungal infections that can cause a cutaneous id reaction.^18,20-22Mycobacterium species, Pseudomonas, Staphylococcus, and Streptococcus are bacterial causes of AE.^15,23-26 Viral infections that can cause an id reaction are herpes simplex virus and molluscum contagiosum.^27-29 Scabies, leishmaniasis, and pediculosis capitis are parasitic infections that may be etiologic.^14,30,31 In addition, noninfectious stimuli besides stasis dermatitis that can produce id reactions include medications, topical creams, tattoo ink, sutures, radiotherapy, and dyshidrotic eczema. The primary reaction to these agents is a localized dermatitis followed by the immunological response that induces a secondary reaction distant from the primary site.^17,18,32-38

Differential Diagnoses

Differential diagnoses include other types of eczema and some vesicular eruptions. Irritant contact dermatitis is another dermatosis that presents as a widespread vesicular eruption due to repetitive exposure to toxic irritants. The rash is erythematous with pustules, blisters, and crusts. It is only found in areas directly exposed to irritants, as opposed to AE, which spreads to areas distant to the primary reaction site. Irritant contact dermatitis presents with more of a burning sensation, whereas AE is more pruritic.^39,40 Allergic contact dermatitis presents with erythematous vesicles and papules and sometimes with bullae. There is edema and crust formation, which often can spread past the point of contact in later stages. Similar to AE, there is intense pruritus. However, allergic contact dermatitis most commonly is caused by exposure to metals, cosmetics, and fragrances, whereas infectious agents and stasis dermatitis are the most common causes of AE.^40,41 It may be challenging to distinguish AE from other causes of widespread eczematous dissemination. Vesicular eruptions sometimes require distinction from AE, including herpetic infections, insect bite reactions, and drug eruptions.^18,42

Treatment

The underlying condition should be treated to mitigate the inflammatory response causing the id reaction. If not skillfully orchestrated, the id reaction can reoccur. For infectious causes of AE, an antifungal, antibacterial, antiviral, or antiparasitic should be given. If stasis dermatitis is responsible for the id reaction, compression stockings and leg elevation are indicated. The id reaction itself is treated with systemic or topical corticosteroids and wet compresses if acute. The goal of these treatments is to reduce patient discomfort caused by the inflammation and pruritus.^18,43

Conclusion

Id reactions are an unusual phenomenon that commonly occurs after fungal skin infections and stasis dermatitis. T lymphocytes and keratinocytes may play a key role in this reaction, with newer research further delineating the process and possibly providing enhanced treatment options. Therapy focuses on treating the underlying condition, supplemented with corticosteroids for the autoeczema.

To the Editor:

Oral immunosuppressive therapies are prescribed for moderate to severe atopic dermatitis. Patients often consult YouTube to make informed decisions about these therapies. In the United States, most health-related online searches are initiated through a search engine, which frequently leads to social media sites such as YouTube. Recent studies have examined the reasons why users turn to the Internet for health-related information, indicating that users typically seek specific information regarding health concerns.^1,2 Furthermore, social media platforms such as YouTube are a popular means of sharing health information with the public.^3-5 Currently, YouTube has more than 1 billion registered users, and 30 million health-related videos are watched each day.⁶ Almost one-third of US consumers use YouTube, Facebook, and Twitter to obtain medical information.⁷ YouTube is a versatile tool because of its video-discovery mechanisms such as a keyword-based search engine, video-recommendation system, highlight feature for videos on home pages, and the capacity to embed YouTube videos on various web pages.⁸ Searchers use videos that are short, fast paced, emotion evoking, from credible sources, recently uploaded, and relevant to the searcher for aiding in health decisions.⁹ Furthermore, studies have demonstrated YouTube’s capacity to support a change in attitude and increase users’ knowledge. In fact, YouTube had higher impact on recall, attitudes, and behaviors when compared with written materials on other social media platforms, such as Facebook and Twitter.⁹ We conducted a cross-sectional study to examine the quality of YouTube videos on oral therapies for atopic dermatitis, such as cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil.

On April 23, 2020, we performed 8 searches using a private browser with default filters on YouTube (Figure). Injectables were not included in the analysis, as the YouTube experience on dupilumab previously has been investigated.¹⁰ The top 40 videos from each search were screened by 3 researchers. Duplicates, non–English-language videos, and videos that did not discuss atopic dermatitis or oral therapies were excluded, resulting in 73 videos included in this analysis. Testimonials generated by patients made up 39 of 73 (53.4%) videos. Health care professionals created 23 of 73 (31.5%) videos, and educators with financial interest created 11 of 73 (15.1%) videos. The dates of production for the videos spanned from 2008 to 2020.

Importantly, this analysis is limited by its lack of quality-assessment tools for video-based resources such as JAMA score and DISCERN score.^14,15 However, these metrics have limited ability to evaluate audiovisual elements, indicating the need for novel tools to score their validity.

To the Editor:

Oral immunosuppressive therapies are prescribed for moderate to severe atopic dermatitis. Patients often consult YouTube to make informed decisions about these therapies. In the United States, most health-related online searches are initiated through a search engine, which frequently leads to social media sites such as YouTube. Recent studies have examined the reasons why users turn to the Internet for health-related information, indicating that users typically seek specific information regarding health concerns.^1,2 Furthermore, social media platforms such as YouTube are a popular means of sharing health information with the public.^3-5 Currently, YouTube has more than 1 billion registered users, and 30 million health-related videos are watched each day.⁶ Almost one-third of US consumers use YouTube, Facebook, and Twitter to obtain medical information.⁷ YouTube is a versatile tool because of its video-discovery mechanisms such as a keyword-based search engine, video-recommendation system, highlight feature for videos on home pages, and the capacity to embed YouTube videos on various web pages.⁸ Searchers use videos that are short, fast paced, emotion evoking, from credible sources, recently uploaded, and relevant to the searcher for aiding in health decisions.⁹ Furthermore, studies have demonstrated YouTube’s capacity to support a change in attitude and increase users’ knowledge. In fact, YouTube had higher impact on recall, attitudes, and behaviors when compared with written materials on other social media platforms, such as Facebook and Twitter.⁹ We conducted a cross-sectional study to examine the quality of YouTube videos on oral therapies for atopic dermatitis, such as cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil.

On April 23, 2020, we performed 8 searches using a private browser with default filters on YouTube (Figure). Injectables were not included in the analysis, as the YouTube experience on dupilumab previously has been investigated.¹⁰ The top 40 videos from each search were screened by 3 researchers. Duplicates, non–English-language videos, and videos that did not discuss atopic dermatitis or oral therapies were excluded, resulting in 73 videos included in this analysis. Testimonials generated by patients made up 39 of 73 (53.4%) videos. Health care professionals created 23 of 73 (31.5%) videos, and educators with financial interest created 11 of 73 (15.1%) videos. The dates of production for the videos spanned from 2008 to 2020.

Importantly, this analysis is limited by its lack of quality-assessment tools for video-based resources such as JAMA score and DISCERN score.^14,15 However, these metrics have limited ability to evaluate audiovisual elements, indicating the need for novel tools to score their validity.

To the Editor:

Oral immunosuppressive therapies are prescribed for moderate to severe atopic dermatitis. Patients often consult YouTube to make informed decisions about these therapies. In the United States, most health-related online searches are initiated through a search engine, which frequently leads to social media sites such as YouTube. Recent studies have examined the reasons why users turn to the Internet for health-related information, indicating that users typically seek specific information regarding health concerns.^1,2 Furthermore, social media platforms such as YouTube are a popular means of sharing health information with the public.^3-5 Currently, YouTube has more than 1 billion registered users, and 30 million health-related videos are watched each day.⁶ Almost one-third of US consumers use YouTube, Facebook, and Twitter to obtain medical information.⁷ YouTube is a versatile tool because of its video-discovery mechanisms such as a keyword-based search engine, video-recommendation system, highlight feature for videos on home pages, and the capacity to embed YouTube videos on various web pages.⁸ Searchers use videos that are short, fast paced, emotion evoking, from credible sources, recently uploaded, and relevant to the searcher for aiding in health decisions.⁹ Furthermore, studies have demonstrated YouTube’s capacity to support a change in attitude and increase users’ knowledge. In fact, YouTube had higher impact on recall, attitudes, and behaviors when compared with written materials on other social media platforms, such as Facebook and Twitter.⁹ We conducted a cross-sectional study to examine the quality of YouTube videos on oral therapies for atopic dermatitis, such as cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil.

On April 23, 2020, we performed 8 searches using a private browser with default filters on YouTube (Figure). Injectables were not included in the analysis, as the YouTube experience on dupilumab previously has been investigated.¹⁰ The top 40 videos from each search were screened by 3 researchers. Duplicates, non–English-language videos, and videos that did not discuss atopic dermatitis or oral therapies were excluded, resulting in 73 videos included in this analysis. Testimonials generated by patients made up 39 of 73 (53.4%) videos. Health care professionals created 23 of 73 (31.5%) videos, and educators with financial interest created 11 of 73 (15.1%) videos. The dates of production for the videos spanned from 2008 to 2020.

Importantly, this analysis is limited by its lack of quality-assessment tools for video-based resources such as JAMA score and DISCERN score.^14,15 However, these metrics have limited ability to evaluate audiovisual elements, indicating the need for novel tools to score their validity.

To the Editor:

Atopic dermatitis (eczema) affects approximately 20% of children worldwide.¹ In atopic dermatitis management, patient education is crucial for optimal outcomes.² The COVID-19 pandemic has impacted patient-physician interactions. To ensure safety of patients and physicians, visits may have been canceled, postponed, or conducted virtually, leaving less time for discussion and questions.³ As a consequence, patients may seek information about atopic dermatitis from alternative sources, including YouTube videos. We performed a cross-sectional study to analyze YouTube videos about topical treatments for atopic dermatitis.

During the week of July 16, 2020, we performed 4 private browser YouTube searches with default filters using the following terms: eczema topicals, eczema topical treatments, atopic dermatitis topicals, and atopic dermatitis topical treatments. For video selection, we defined topical treatments as topical corticosteroids, topical calcineurin inhibitors, crisaborole, emollients, wet wraps, and any prospective treatment topically administered. For each of the 4 searches, 2 researchers (A.M. and A.T.) independently examined the top 75 videos, yielding a total of 300 videos. Of them, 98 videos were duplicates, 19 videos were not about atopic dermatitis, and 91 videos were not about topical treatments, leaving a total of 92 videos for analysis (Figure 1).

Although less popular, professional source videos had a significantly higher DISCERN overall quality rating score (question 16) compared to those categorized as nonprofessional source (3.92 vs 1.53; P<.001). In contrast, nonprofessional source videos scored significantly higher on the quality-of-life question (question 13) compared to professional source videos (3.90 vs 2.56; P<.001)(eTable). (Three professional source videos were removed from YouTube before DISCERN scores could be assigned.)

To the Editor:

Atopic dermatitis (eczema) affects approximately 20% of children worldwide.¹ In atopic dermatitis management, patient education is crucial for optimal outcomes.² The COVID-19 pandemic has impacted patient-physician interactions. To ensure safety of patients and physicians, visits may have been canceled, postponed, or conducted virtually, leaving less time for discussion and questions.³ As a consequence, patients may seek information about atopic dermatitis from alternative sources, including YouTube videos. We performed a cross-sectional study to analyze YouTube videos about topical treatments for atopic dermatitis.

During the week of July 16, 2020, we performed 4 private browser YouTube searches with default filters using the following terms: eczema topicals, eczema topical treatments, atopic dermatitis topicals, and atopic dermatitis topical treatments. For video selection, we defined topical treatments as topical corticosteroids, topical calcineurin inhibitors, crisaborole, emollients, wet wraps, and any prospective treatment topically administered. For each of the 4 searches, 2 researchers (A.M. and A.T.) independently examined the top 75 videos, yielding a total of 300 videos. Of them, 98 videos were duplicates, 19 videos were not about atopic dermatitis, and 91 videos were not about topical treatments, leaving a total of 92 videos for analysis (Figure 1).

Although less popular, professional source videos had a significantly higher DISCERN overall quality rating score (question 16) compared to those categorized as nonprofessional source (3.92 vs 1.53; P<.001). In contrast, nonprofessional source videos scored significantly higher on the quality-of-life question (question 13) compared to professional source videos (3.90 vs 2.56; P<.001)(eTable). (Three professional source videos were removed from YouTube before DISCERN scores could be assigned.)

To the Editor:

Atopic dermatitis (eczema) affects approximately 20% of children worldwide.¹ In atopic dermatitis management, patient education is crucial for optimal outcomes.² The COVID-19 pandemic has impacted patient-physician interactions. To ensure safety of patients and physicians, visits may have been canceled, postponed, or conducted virtually, leaving less time for discussion and questions.³ As a consequence, patients may seek information about atopic dermatitis from alternative sources, including YouTube videos. We performed a cross-sectional study to analyze YouTube videos about topical treatments for atopic dermatitis.

During the week of July 16, 2020, we performed 4 private browser YouTube searches with default filters using the following terms: eczema topicals, eczema topical treatments, atopic dermatitis topicals, and atopic dermatitis topical treatments. For video selection, we defined topical treatments as topical corticosteroids, topical calcineurin inhibitors, crisaborole, emollients, wet wraps, and any prospective treatment topically administered. For each of the 4 searches, 2 researchers (A.M. and A.T.) independently examined the top 75 videos, yielding a total of 300 videos. Of them, 98 videos were duplicates, 19 videos were not about atopic dermatitis, and 91 videos were not about topical treatments, leaving a total of 92 videos for analysis (Figure 1).

Although less popular, professional source videos had a significantly higher DISCERN overall quality rating score (question 16) compared to those categorized as nonprofessional source (3.92 vs 1.53; P<.001). In contrast, nonprofessional source videos scored significantly higher on the quality-of-life question (question 13) compared to professional source videos (3.90 vs 2.56; P<.001)(eTable). (Three professional source videos were removed from YouTube before DISCERN scores could be assigned.)

Plants can contribute to a variety of dermatoses. The Toxicodendron genus, which includes poison ivy, poison oak, and poison sumac, is a well-known and common cause of allergic contact dermatitis (ACD), but many other plants can cause direct or airborne contact dermatitis, especially in gardeners, florists, and farmers. This article provides an overview of different plant-related dermatoses and culprit plants as well as how these dermatoses should be diagnosed and treated.

Epidemiology

Plant dermatoses affect more than 50 million individuals each year.^1,2 In the United States, the Toxicodendron genus causes ACD in more than 70% of exposed individuals, leading to medical visits.³ An urgent care visit for a plant-related dermatitis is estimated to cost $168, while an emergency department visit can cost 3 times as much.⁴ Although less common, Compositae plants are another important culprit of plant dermatitis, particularly in gardeners, florists, and farmers. Data from the 2017-2018 North American Contact Dermatitis Group screening series (N=4947) showed sesquiterpene lactones and Compositae to be positive in 0.5% of patch-tested patients.⁵

Plant Dermatitis Classifications

Plant dermatitis can be classified into 5 main categories: ACD, mechanical irritant contact dermatitis, chemical irritant contact dermatitis, light-mediated dermatitis, and pseudophytodermatitis.⁶

Allergic contact dermatitis is an immune-mediated type IV delayed hypersensitivity reaction. The common molecular allergens in plants include phenols, α-methylene-γ-butyrolactones, quinones, terpenes, disulfides, isothiocyanates, and polyacetylenic derivatives.⁶

Plant contact dermatitis due to mechanical and chemical irritants is precipitated by multiple mechanisms, including disruption of the epidermal barrier and subsequent cytokine release from keratinocytes.⁷ Nonimmunologic contact urticaria from plants is thought to be a type of irritant reaction precipitated by mechanical or chemical trauma.⁸

Light-mediated dermatitis includes phytophotodermatitis and photoallergic contact dermatitis. Phytophotodermatitis is a phototoxic reaction triggered by exposure to both plant-derived furanocoumarin and UVA light.⁹ By contrast, photoallergic contact dermatitis is a delayed hypersensitivity reaction from prior sensitization to a light-activated antigen.¹⁰

Pseudophytodermatitis, as its name implies, is not truly mediated by an allergen or irritant intrinsic to the plant but rather by dyes, waxes, insecticides, or arthropods that inhabit the plant or are secondarily applied.⁶

Common Plant Allergens

Anacardiaceae Family
Most of the allergenic plants within the Anacardiaceae family belong to the Toxicodendron genus, which encompasses poison ivy (Toxicodendron radicans), poison oak (Toxicodendron pubescens,Toxicodendron quercifolium, Toxicodendron diversiloum), and poison sumac (Toxicodendron vernix). Poison ivy is the celebrity of the Anacardiaceae family and contributes to most cases of plant-related ACD. It is found in every state in the continental United States. Poison oak is another common culprit found in the western and southeastern United States.¹¹ Plants within the Anacardiaceae family contain an oleoresin called urushiol, which is the primary sensitizing substance. Although poison ivy and poison oak grow well in full sun to partial shade, poison sumac typically is found in damp swampy areas east of the Rocky Mountains. Most cases of ACD related to Anacardiaceae species are due to direct contact with urushiol from a Toxicodendron plant, but burning of brush containing Toxicodendron can cause airborne exposure when urushiol oil is carried by smoke particles.¹² Sensitization to Toxicodendron can cause ACD to other Anacardiaceae species such as the Japanese lacquer tree (Toxicodendron vernicifluum), mango tree (Mangifera indica), cashew tree (Anacardium occidentale), and Indian marking nut tree (Semecarpus anacardium).⁶ Cross-reactions to components of the ginkgo tree (Ginkgo biloba) also are possible.

Toxicodendron plants can be more easily identified and avoided with knowledge of their characteristic leaf patterns. The most dependable way to identify poison ivy and poison oak species is to look for plants with 3 leaves, giving rise to the common saying, “Leaves of three, leave them be.” Poison sumac plants have groups of 7 to 13 leaves arranged as pairs along a central rib. Another helpful finding is a black deposit that Toxicodendron species leave behind following trauma to the leaves. Urushiol oxidizes when exposed to air and turns into a black deposit that can be seen on damaged leaves themselves or can be demonstrated in a black spot test to verify if a plant is a Toxicodendron species. The test is performed by gathering (carefully, without direct contact) a few leaves in a paper towel and crushing them to release sap. Within minutes, the sap will turn black if the plant is indeed a Toxicodendron species.¹³Pruritic, edematous, erythematous papules, plaques, and eventual vesicles in a linear distribution are suspicious for Toxicodendron exposure. Although your pet will not develop Toxicodendron ACD, oleoresin-contaminated pets can transfer the oils to their owners after coming into contact with these plants. Toxicodendron dermatitis also can be acquired from oleoresin-contaminated fomites such as clothing and shoes worn in the garden or when hiking. Toxicodendron dermatitis can appear at different sites on the body at different times depending on the amount of oleoresin exposure as well as epidermal thickness. For example, the oleoresin can be transferred from the hands to body areas with a thinner stratum corneum (eg, genitalia) and cause subsequent dermatitis.¹

Compositae Family
The Compositae family (also known as Asteraceae) is a large plant family with more than 20,000 species, including numerous weeds, wildflowers, and vegetables. The flowers, leaves, stems, and pollens of the Compositae family are coated by cyclic esters called sesquiterpene lactones. Mitchell and Dupuis¹⁴ showed that sesquiterpene lactones are the allergens responsible for ACD to various Compositae plants, including ragweed (Ambrosia), sneezeweed (Helenium), and chrysanthemums (Chrysanthemum). Common Compositae vegetables such as lettuce (Lactuca sativa) have been reported to cause ACD in chefs, grocery store produce handlers, gardeners, and even owners of lettuce-eating pet guinea pigs and turtles.¹⁵ Similarly, artichokes (Cynara scolymus) can cause ACD in gardeners.¹⁶ Exposure to Compositae species also has been implicated in photoallergic reactions, and studies have demonstrated that some patients with chronic actinic dermatitis also have positive patch test reactions to Compositae species and/or sesquiterpene lactones.^17,18

In addition to direct contact with Compositae plants, airborne exposure to sesquiterpene lactones can cause ACD.¹⁴ The pattern of airborne contact dermatitis typically involves exposed areas such as the eyelids, central face, and/or neck. The beak sign also can be a clue to airborne contact dermatitis, which involves dermatitis of the face that spares the nasal tip and/or nasal ridge. It is thought that the beak sign may result from increased sebaceous gland concentration on the nose, which prevents penetration of allergens and irritants.¹⁹ Unlike photoallergic contact dermatitis, which also can involve the face, airborne ACD frequently involves photoprotected areas such as the submandibular chin and the upper lip. Davies and Kersey²⁰ reported the case of a groundsman who was cutting grass with dandelions (Taraxacum officinale) and was found to have associated airborne ACD of the face, neck, and forearms due to Compositae allergy. In a different setting, the aromas of chamomile (Matricaria chamomilla) have been reported to cause airborne ACD in a tea drinker.²¹ Paulsen²² found that ingestion of chamomile tea can induce systemic ACD in sensitized individuals.

Alstroemeriaceae, Liliaceae, and Primulaceae
Florists are exposed to many plant species and have a high prevalence of ACD. Thiboutot et al²³ found that 15 of 57 (26%) floral workers experienced hand dermatitis that cleared with time away from work. The Peruvian lily (Alstroemeria, Alstroemeriaceae family), which contains tuliposide A, was found to be the leading cause of sensitization.²³ Tulips (Tulipa, Liliaceae family), as the flower name suggests, also contain tuliposide A, which along with mechanical irritation from the course tecta fibers on the bulbs lead to a dermatitis known as tulip fingers.^24,25 Poison primrose (Primula obconica, Primulaceae family), cultivated for its highly colorful flowers, contains the contact allergen primin.⁶ A common clinical presentation of ACD for any of these culprit flowers is localized dermatitis of the thumb and index finger in a florist or gardener.

Plants That Cause Irritant Reactions

Cactuses
Although the long spines of the Cactaceae family of cactuses is a warning for passersby, it is the small and nearly invisible barbed hairs (glochids) that inflict a more dramatic cutaneous reaction. The prickly pear cactus (Opuntia species) is a good example of such a plant, as its glochids cause mechanical irritation but also can become embedded in the skin and result in subcutaneous granulomas known as sabra dermatitis.²⁶

Stinging Nettle
The dermatologic term urticaria owes its namesake to the stinging nettle plant, which comes from the family Urticaceae. The stinging nettle has small hairs on its leaves, referred to as stinging trichomes, which have needlelike tips that pierce the skin and inject a mix of histamine, formic acid, and acetylcholine, causing a pruritic dermatitis that may last up to 12 hours.²⁷ The plant is found worldwide and is a common weed in North America.

Phytophotodermatitis

Lemons and limes (Rutaceae family) are common culprits of phytophotodermatitis, often causing what is known as a margarita burn after outdoor consumption or preparation of this tasty citrus beverage.²⁸ An accidental spray of lime juice on the skin while adding it to a beer, guacamole, salsa, or any other food or beverage also can cause phytophotodermatitis.^29-31 Although the juice of lemons and limes contains psoralens, the rind can contain a 6- to 186-fold increased concentration.³² Psoralen is the photoactive agent in Rutaceae plants that intercalates in double-stranded DNA and promotes intrastrand cross-links when exposed to UVA light, which ultimately leads to dermatitis.⁹ Phytophotodermatitis commonly causes erythema, edema, and painful bullae on sun-exposed areas and classically heals with hyperpigmentation.

Pseudophytodermatitis can occur in grain farmers and harvesters who handle wheat and/or barley and incidentally come in contact with insects and chemicals on the plant material. Pseudophytodermatitis from mites in the wheat and/or barley plant can occur at harvest time when contact with the plant material is high. Insects such as the North American itch mite (Pediculoides ventricosus) can cause petechiae, wheals, and pustules. In addition, insecticides such as malathion and arsenical sprays that are applied to plant leaves can cause pseudophytodermatitis, which may be initially diagnosed as dermatitis to the plant itself.⁶

Patch Testing to Plants

When a patient presents with recurrent or persistent dermatitis and a plant contact allergen is suspected, patch testing is indicated. Most comprehensive patch test series contain various plant allergens, such as sesquiterpene lactones, Compositae mix, and limonene hydroperoxides, and patch testing to a specialized plant series may be necessary. Poison ivy/oak/sumac allergens typically are not included in patch test series because of the high prevalence of allergic reactions to these chemicals and the likelihood of sensitization when patch testing with urushiol. Compositae contact sensitization can be difficult to diagnose because neither sesquiterpene lactone mix 0.1% nor parthenolide 0.1% are sensitive enough to pick up all Compositae allergies.^33,34 Paulsen and Andersen³⁴ proposed that if Compositae sensitization is suspected, testing should include sesquiterpene lactone, parthenolide, and Compositae mix II 2.5%, as well as other potential Compositae allergens based on the patient’s history.³⁴

Because plants can have geographic variability and contain potentially unknown allergens,³⁵ testing to plant components may increase the diagnostic yield of patch testing. Dividing the plant into component parts (ie, stem, bulb, leaf, flower) is helpful, as different components have different allergen concentrations. It is important to consult expert resources before proceeding with plant component patch testing because irritant reactions are frequent and may confound the testing.³⁶

Prevention and Treatment

For all plant dermatoses, the mainstay of prevention is to avoid contact with the offending plant material. Gloves can be an important protective tool for plant dermatitis prevention; the correct material depends on the plant species being handled. Rubber gloves should not be worn to protect against Toxicodendron plants since the catechols in urushiol are soluble in rubber; vinyl gloves should be worn instead.⁶ Marks³⁷ found that tuliposide A, the allergen in the Peruvian lily (Alstroemeria), penetrates both vinyl and latex gloves; it does not penetrate nitrile gloves. If exposed, the risk of dermatitis can be decreased if the allergen is washed away with soap and water as soon as possible. Some allergens such as Toxicodendron are absorbed quickly and need to be washed off within 10 minutes of exposure.⁶ Importantly, exposed gardening gloves may continue to perpetuate ACD if the allergen is not also washed off the gloves themselves.

For light-mediated dermatoses, sun avoidance or use of an effective sunscreen can reduce symptoms in an individual who has already been exposed.¹⁰ UVA light activates psoralen-mediated dermatitis but not until 30 to 120 minutes after absorption into the skin.³⁸

Barrier creams are thought to be protective against plant ACD through a variety of mechanisms. The cream itself is meant to reduce skin contact to an allergen or irritant. Additionally, barrier creams contain active ingredients such as silicone, hydrocarbons, and aluminum chlorohydrate, which are thought to trap or transform offending agents before contacting the skin. When contact with a Toxicodendron species is anticipated, Marks et al³⁹ found that dermatitis was absent or significantly reduced when 144 patients were pretreated with quaternium-18 bentonite lotion 5% (P<.0001).

Although allergen avoidance and use of gloves and barrier creams are the mainstays of preventing plant dermatoses, treatment often is required to control postexposure symptoms. For all plant dermatoses, topical corticosteroids can be used to reduce inflammation and pruritus. In some cases, systemic steroids may be necessary. To prevent rebound of dermatitis, patients often require a 3-week or longer course of oral steroids to quell the reaction, particularly if the dermatitis is vigorous or an id reaction is present.⁴⁰ Antihistamines and cold compresses also can provide symptomatic relief.

Final Interpretation

Plants can cause a variety of dermatoses. Although Toxicodendron plants are the most frequent cause of ACD, it is important to keep in mind that florists, gardeners, and farmers are exposed to a large variety of allergens, irritants, and phototoxic agents that cause dermatoses as well. Confirmation of plant-induced ACD involves patch testing against suspected species. Prevention involves use of appropriate barriers and avoidance of implicated plants. Treatment includes topical steroids, antihistamines, and prednisone.

Plants can contribute to a variety of dermatoses. The Toxicodendron genus, which includes poison ivy, poison oak, and poison sumac, is a well-known and common cause of allergic contact dermatitis (ACD), but many other plants can cause direct or airborne contact dermatitis, especially in gardeners, florists, and farmers. This article provides an overview of different plant-related dermatoses and culprit plants as well as how these dermatoses should be diagnosed and treated.

Epidemiology

Plant dermatoses affect more than 50 million individuals each year.^1,2 In the United States, the Toxicodendron genus causes ACD in more than 70% of exposed individuals, leading to medical visits.³ An urgent care visit for a plant-related dermatitis is estimated to cost $168, while an emergency department visit can cost 3 times as much.⁴ Although less common, Compositae plants are another important culprit of plant dermatitis, particularly in gardeners, florists, and farmers. Data from the 2017-2018 North American Contact Dermatitis Group screening series (N=4947) showed sesquiterpene lactones and Compositae to be positive in 0.5% of patch-tested patients.⁵

Plant Dermatitis Classifications

Plant dermatitis can be classified into 5 main categories: ACD, mechanical irritant contact dermatitis, chemical irritant contact dermatitis, light-mediated dermatitis, and pseudophytodermatitis.⁶

Allergic contact dermatitis is an immune-mediated type IV delayed hypersensitivity reaction. The common molecular allergens in plants include phenols, α-methylene-γ-butyrolactones, quinones, terpenes, disulfides, isothiocyanates, and polyacetylenic derivatives.⁶

Plant contact dermatitis due to mechanical and chemical irritants is precipitated by multiple mechanisms, including disruption of the epidermal barrier and subsequent cytokine release from keratinocytes.⁷ Nonimmunologic contact urticaria from plants is thought to be a type of irritant reaction precipitated by mechanical or chemical trauma.⁸

Light-mediated dermatitis includes phytophotodermatitis and photoallergic contact dermatitis. Phytophotodermatitis is a phototoxic reaction triggered by exposure to both plant-derived furanocoumarin and UVA light.⁹ By contrast, photoallergic contact dermatitis is a delayed hypersensitivity reaction from prior sensitization to a light-activated antigen.¹⁰

Pseudophytodermatitis, as its name implies, is not truly mediated by an allergen or irritant intrinsic to the plant but rather by dyes, waxes, insecticides, or arthropods that inhabit the plant or are secondarily applied.⁶

Common Plant Allergens

Anacardiaceae Family
Most of the allergenic plants within the Anacardiaceae family belong to the Toxicodendron genus, which encompasses poison ivy (Toxicodendron radicans), poison oak (Toxicodendron pubescens,Toxicodendron quercifolium, Toxicodendron diversiloum), and poison sumac (Toxicodendron vernix). Poison ivy is the celebrity of the Anacardiaceae family and contributes to most cases of plant-related ACD. It is found in every state in the continental United States. Poison oak is another common culprit found in the western and southeastern United States.¹¹ Plants within the Anacardiaceae family contain an oleoresin called urushiol, which is the primary sensitizing substance. Although poison ivy and poison oak grow well in full sun to partial shade, poison sumac typically is found in damp swampy areas east of the Rocky Mountains. Most cases of ACD related to Anacardiaceae species are due to direct contact with urushiol from a Toxicodendron plant, but burning of brush containing Toxicodendron can cause airborne exposure when urushiol oil is carried by smoke particles.¹² Sensitization to Toxicodendron can cause ACD to other Anacardiaceae species such as the Japanese lacquer tree (Toxicodendron vernicifluum), mango tree (Mangifera indica), cashew tree (Anacardium occidentale), and Indian marking nut tree (Semecarpus anacardium).⁶ Cross-reactions to components of the ginkgo tree (Ginkgo biloba) also are possible.

Toxicodendron plants can be more easily identified and avoided with knowledge of their characteristic leaf patterns. The most dependable way to identify poison ivy and poison oak species is to look for plants with 3 leaves, giving rise to the common saying, “Leaves of three, leave them be.” Poison sumac plants have groups of 7 to 13 leaves arranged as pairs along a central rib. Another helpful finding is a black deposit that Toxicodendron species leave behind following trauma to the leaves. Urushiol oxidizes when exposed to air and turns into a black deposit that can be seen on damaged leaves themselves or can be demonstrated in a black spot test to verify if a plant is a Toxicodendron species. The test is performed by gathering (carefully, without direct contact) a few leaves in a paper towel and crushing them to release sap. Within minutes, the sap will turn black if the plant is indeed a Toxicodendron species.¹³Pruritic, edematous, erythematous papules, plaques, and eventual vesicles in a linear distribution are suspicious for Toxicodendron exposure. Although your pet will not develop Toxicodendron ACD, oleoresin-contaminated pets can transfer the oils to their owners after coming into contact with these plants. Toxicodendron dermatitis also can be acquired from oleoresin-contaminated fomites such as clothing and shoes worn in the garden or when hiking. Toxicodendron dermatitis can appear at different sites on the body at different times depending on the amount of oleoresin exposure as well as epidermal thickness. For example, the oleoresin can be transferred from the hands to body areas with a thinner stratum corneum (eg, genitalia) and cause subsequent dermatitis.¹

Compositae Family
The Compositae family (also known as Asteraceae) is a large plant family with more than 20,000 species, including numerous weeds, wildflowers, and vegetables. The flowers, leaves, stems, and pollens of the Compositae family are coated by cyclic esters called sesquiterpene lactones. Mitchell and Dupuis¹⁴ showed that sesquiterpene lactones are the allergens responsible for ACD to various Compositae plants, including ragweed (Ambrosia), sneezeweed (Helenium), and chrysanthemums (Chrysanthemum). Common Compositae vegetables such as lettuce (Lactuca sativa) have been reported to cause ACD in chefs, grocery store produce handlers, gardeners, and even owners of lettuce-eating pet guinea pigs and turtles.¹⁵ Similarly, artichokes (Cynara scolymus) can cause ACD in gardeners.¹⁶ Exposure to Compositae species also has been implicated in photoallergic reactions, and studies have demonstrated that some patients with chronic actinic dermatitis also have positive patch test reactions to Compositae species and/or sesquiterpene lactones.^17,18

In addition to direct contact with Compositae plants, airborne exposure to sesquiterpene lactones can cause ACD.¹⁴ The pattern of airborne contact dermatitis typically involves exposed areas such as the eyelids, central face, and/or neck. The beak sign also can be a clue to airborne contact dermatitis, which involves dermatitis of the face that spares the nasal tip and/or nasal ridge. It is thought that the beak sign may result from increased sebaceous gland concentration on the nose, which prevents penetration of allergens and irritants.¹⁹ Unlike photoallergic contact dermatitis, which also can involve the face, airborne ACD frequently involves photoprotected areas such as the submandibular chin and the upper lip. Davies and Kersey²⁰ reported the case of a groundsman who was cutting grass with dandelions (Taraxacum officinale) and was found to have associated airborne ACD of the face, neck, and forearms due to Compositae allergy. In a different setting, the aromas of chamomile (Matricaria chamomilla) have been reported to cause airborne ACD in a tea drinker.²¹ Paulsen²² found that ingestion of chamomile tea can induce systemic ACD in sensitized individuals.

Alstroemeriaceae, Liliaceae, and Primulaceae
Florists are exposed to many plant species and have a high prevalence of ACD. Thiboutot et al²³ found that 15 of 57 (26%) floral workers experienced hand dermatitis that cleared with time away from work. The Peruvian lily (Alstroemeria, Alstroemeriaceae family), which contains tuliposide A, was found to be the leading cause of sensitization.²³ Tulips (Tulipa, Liliaceae family), as the flower name suggests, also contain tuliposide A, which along with mechanical irritation from the course tecta fibers on the bulbs lead to a dermatitis known as tulip fingers.^24,25 Poison primrose (Primula obconica, Primulaceae family), cultivated for its highly colorful flowers, contains the contact allergen primin.⁶ A common clinical presentation of ACD for any of these culprit flowers is localized dermatitis of the thumb and index finger in a florist or gardener.

Plants That Cause Irritant Reactions

Cactuses
Although the long spines of the Cactaceae family of cactuses is a warning for passersby, it is the small and nearly invisible barbed hairs (glochids) that inflict a more dramatic cutaneous reaction. The prickly pear cactus (Opuntia species) is a good example of such a plant, as its glochids cause mechanical irritation but also can become embedded in the skin and result in subcutaneous granulomas known as sabra dermatitis.²⁶

Stinging Nettle
The dermatologic term urticaria owes its namesake to the stinging nettle plant, which comes from the family Urticaceae. The stinging nettle has small hairs on its leaves, referred to as stinging trichomes, which have needlelike tips that pierce the skin and inject a mix of histamine, formic acid, and acetylcholine, causing a pruritic dermatitis that may last up to 12 hours.²⁷ The plant is found worldwide and is a common weed in North America.

Phytophotodermatitis

Lemons and limes (Rutaceae family) are common culprits of phytophotodermatitis, often causing what is known as a margarita burn after outdoor consumption or preparation of this tasty citrus beverage.²⁸ An accidental spray of lime juice on the skin while adding it to a beer, guacamole, salsa, or any other food or beverage also can cause phytophotodermatitis.^29-31 Although the juice of lemons and limes contains psoralens, the rind can contain a 6- to 186-fold increased concentration.³² Psoralen is the photoactive agent in Rutaceae plants that intercalates in double-stranded DNA and promotes intrastrand cross-links when exposed to UVA light, which ultimately leads to dermatitis.⁹ Phytophotodermatitis commonly causes erythema, edema, and painful bullae on sun-exposed areas and classically heals with hyperpigmentation.

Pseudophytodermatitis can occur in grain farmers and harvesters who handle wheat and/or barley and incidentally come in contact with insects and chemicals on the plant material. Pseudophytodermatitis from mites in the wheat and/or barley plant can occur at harvest time when contact with the plant material is high. Insects such as the North American itch mite (Pediculoides ventricosus) can cause petechiae, wheals, and pustules. In addition, insecticides such as malathion and arsenical sprays that are applied to plant leaves can cause pseudophytodermatitis, which may be initially diagnosed as dermatitis to the plant itself.⁶

Patch Testing to Plants

When a patient presents with recurrent or persistent dermatitis and a plant contact allergen is suspected, patch testing is indicated. Most comprehensive patch test series contain various plant allergens, such as sesquiterpene lactones, Compositae mix, and limonene hydroperoxides, and patch testing to a specialized plant series may be necessary. Poison ivy/oak/sumac allergens typically are not included in patch test series because of the high prevalence of allergic reactions to these chemicals and the likelihood of sensitization when patch testing with urushiol. Compositae contact sensitization can be difficult to diagnose because neither sesquiterpene lactone mix 0.1% nor parthenolide 0.1% are sensitive enough to pick up all Compositae allergies.^33,34 Paulsen and Andersen³⁴ proposed that if Compositae sensitization is suspected, testing should include sesquiterpene lactone, parthenolide, and Compositae mix II 2.5%, as well as other potential Compositae allergens based on the patient’s history.³⁴

Because plants can have geographic variability and contain potentially unknown allergens,³⁵ testing to plant components may increase the diagnostic yield of patch testing. Dividing the plant into component parts (ie, stem, bulb, leaf, flower) is helpful, as different components have different allergen concentrations. It is important to consult expert resources before proceeding with plant component patch testing because irritant reactions are frequent and may confound the testing.³⁶

Prevention and Treatment

For all plant dermatoses, the mainstay of prevention is to avoid contact with the offending plant material. Gloves can be an important protective tool for plant dermatitis prevention; the correct material depends on the plant species being handled. Rubber gloves should not be worn to protect against Toxicodendron plants since the catechols in urushiol are soluble in rubber; vinyl gloves should be worn instead.⁶ Marks³⁷ found that tuliposide A, the allergen in the Peruvian lily (Alstroemeria), penetrates both vinyl and latex gloves; it does not penetrate nitrile gloves. If exposed, the risk of dermatitis can be decreased if the allergen is washed away with soap and water as soon as possible. Some allergens such as Toxicodendron are absorbed quickly and need to be washed off within 10 minutes of exposure.⁶ Importantly, exposed gardening gloves may continue to perpetuate ACD if the allergen is not also washed off the gloves themselves.

For light-mediated dermatoses, sun avoidance or use of an effective sunscreen can reduce symptoms in an individual who has already been exposed.¹⁰ UVA light activates psoralen-mediated dermatitis but not until 30 to 120 minutes after absorption into the skin.³⁸

Barrier creams are thought to be protective against plant ACD through a variety of mechanisms. The cream itself is meant to reduce skin contact to an allergen or irritant. Additionally, barrier creams contain active ingredients such as silicone, hydrocarbons, and aluminum chlorohydrate, which are thought to trap or transform offending agents before contacting the skin. When contact with a Toxicodendron species is anticipated, Marks et al³⁹ found that dermatitis was absent or significantly reduced when 144 patients were pretreated with quaternium-18 bentonite lotion 5% (P<.0001).

Although allergen avoidance and use of gloves and barrier creams are the mainstays of preventing plant dermatoses, treatment often is required to control postexposure symptoms. For all plant dermatoses, topical corticosteroids can be used to reduce inflammation and pruritus. In some cases, systemic steroids may be necessary. To prevent rebound of dermatitis, patients often require a 3-week or longer course of oral steroids to quell the reaction, particularly if the dermatitis is vigorous or an id reaction is present.⁴⁰ Antihistamines and cold compresses also can provide symptomatic relief.

Final Interpretation

Plants can cause a variety of dermatoses. Although Toxicodendron plants are the most frequent cause of ACD, it is important to keep in mind that florists, gardeners, and farmers are exposed to a large variety of allergens, irritants, and phototoxic agents that cause dermatoses as well. Confirmation of plant-induced ACD involves patch testing against suspected species. Prevention involves use of appropriate barriers and avoidance of implicated plants. Treatment includes topical steroids, antihistamines, and prednisone.

Plants can contribute to a variety of dermatoses. The Toxicodendron genus, which includes poison ivy, poison oak, and poison sumac, is a well-known and common cause of allergic contact dermatitis (ACD), but many other plants can cause direct or airborne contact dermatitis, especially in gardeners, florists, and farmers. This article provides an overview of different plant-related dermatoses and culprit plants as well as how these dermatoses should be diagnosed and treated.

Epidemiology

Plant dermatoses affect more than 50 million individuals each year.^1,2 In the United States, the Toxicodendron genus causes ACD in more than 70% of exposed individuals, leading to medical visits.³ An urgent care visit for a plant-related dermatitis is estimated to cost $168, while an emergency department visit can cost 3 times as much.⁴ Although less common, Compositae plants are another important culprit of plant dermatitis, particularly in gardeners, florists, and farmers. Data from the 2017-2018 North American Contact Dermatitis Group screening series (N=4947) showed sesquiterpene lactones and Compositae to be positive in 0.5% of patch-tested patients.⁵

Plant Dermatitis Classifications

Plant dermatitis can be classified into 5 main categories: ACD, mechanical irritant contact dermatitis, chemical irritant contact dermatitis, light-mediated dermatitis, and pseudophytodermatitis.⁶

Allergic contact dermatitis is an immune-mediated type IV delayed hypersensitivity reaction. The common molecular allergens in plants include phenols, α-methylene-γ-butyrolactones, quinones, terpenes, disulfides, isothiocyanates, and polyacetylenic derivatives.⁶

Plant contact dermatitis due to mechanical and chemical irritants is precipitated by multiple mechanisms, including disruption of the epidermal barrier and subsequent cytokine release from keratinocytes.⁷ Nonimmunologic contact urticaria from plants is thought to be a type of irritant reaction precipitated by mechanical or chemical trauma.⁸

Light-mediated dermatitis includes phytophotodermatitis and photoallergic contact dermatitis. Phytophotodermatitis is a phototoxic reaction triggered by exposure to both plant-derived furanocoumarin and UVA light.⁹ By contrast, photoallergic contact dermatitis is a delayed hypersensitivity reaction from prior sensitization to a light-activated antigen.¹⁰

Pseudophytodermatitis, as its name implies, is not truly mediated by an allergen or irritant intrinsic to the plant but rather by dyes, waxes, insecticides, or arthropods that inhabit the plant or are secondarily applied.⁶

Common Plant Allergens

Anacardiaceae Family
Most of the allergenic plants within the Anacardiaceae family belong to the Toxicodendron genus, which encompasses poison ivy (Toxicodendron radicans), poison oak (Toxicodendron pubescens,Toxicodendron quercifolium, Toxicodendron diversiloum), and poison sumac (Toxicodendron vernix). Poison ivy is the celebrity of the Anacardiaceae family and contributes to most cases of plant-related ACD. It is found in every state in the continental United States. Poison oak is another common culprit found in the western and southeastern United States.¹¹ Plants within the Anacardiaceae family contain an oleoresin called urushiol, which is the primary sensitizing substance. Although poison ivy and poison oak grow well in full sun to partial shade, poison sumac typically is found in damp swampy areas east of the Rocky Mountains. Most cases of ACD related to Anacardiaceae species are due to direct contact with urushiol from a Toxicodendron plant, but burning of brush containing Toxicodendron can cause airborne exposure when urushiol oil is carried by smoke particles.¹² Sensitization to Toxicodendron can cause ACD to other Anacardiaceae species such as the Japanese lacquer tree (Toxicodendron vernicifluum), mango tree (Mangifera indica), cashew tree (Anacardium occidentale), and Indian marking nut tree (Semecarpus anacardium).⁶ Cross-reactions to components of the ginkgo tree (Ginkgo biloba) also are possible.

Toxicodendron plants can be more easily identified and avoided with knowledge of their characteristic leaf patterns. The most dependable way to identify poison ivy and poison oak species is to look for plants with 3 leaves, giving rise to the common saying, “Leaves of three, leave them be.” Poison sumac plants have groups of 7 to 13 leaves arranged as pairs along a central rib. Another helpful finding is a black deposit that Toxicodendron species leave behind following trauma to the leaves. Urushiol oxidizes when exposed to air and turns into a black deposit that can be seen on damaged leaves themselves or can be demonstrated in a black spot test to verify if a plant is a Toxicodendron species. The test is performed by gathering (carefully, without direct contact) a few leaves in a paper towel and crushing them to release sap. Within minutes, the sap will turn black if the plant is indeed a Toxicodendron species.¹³Pruritic, edematous, erythematous papules, plaques, and eventual vesicles in a linear distribution are suspicious for Toxicodendron exposure. Although your pet will not develop Toxicodendron ACD, oleoresin-contaminated pets can transfer the oils to their owners after coming into contact with these plants. Toxicodendron dermatitis also can be acquired from oleoresin-contaminated fomites such as clothing and shoes worn in the garden or when hiking. Toxicodendron dermatitis can appear at different sites on the body at different times depending on the amount of oleoresin exposure as well as epidermal thickness. For example, the oleoresin can be transferred from the hands to body areas with a thinner stratum corneum (eg, genitalia) and cause subsequent dermatitis.¹

Compositae Family
The Compositae family (also known as Asteraceae) is a large plant family with more than 20,000 species, including numerous weeds, wildflowers, and vegetables. The flowers, leaves, stems, and pollens of the Compositae family are coated by cyclic esters called sesquiterpene lactones. Mitchell and Dupuis¹⁴ showed that sesquiterpene lactones are the allergens responsible for ACD to various Compositae plants, including ragweed (Ambrosia), sneezeweed (Helenium), and chrysanthemums (Chrysanthemum). Common Compositae vegetables such as lettuce (Lactuca sativa) have been reported to cause ACD in chefs, grocery store produce handlers, gardeners, and even owners of lettuce-eating pet guinea pigs and turtles.¹⁵ Similarly, artichokes (Cynara scolymus) can cause ACD in gardeners.¹⁶ Exposure to Compositae species also has been implicated in photoallergic reactions, and studies have demonstrated that some patients with chronic actinic dermatitis also have positive patch test reactions to Compositae species and/or sesquiterpene lactones.^17,18

In addition to direct contact with Compositae plants, airborne exposure to sesquiterpene lactones can cause ACD.¹⁴ The pattern of airborne contact dermatitis typically involves exposed areas such as the eyelids, central face, and/or neck. The beak sign also can be a clue to airborne contact dermatitis, which involves dermatitis of the face that spares the nasal tip and/or nasal ridge. It is thought that the beak sign may result from increased sebaceous gland concentration on the nose, which prevents penetration of allergens and irritants.¹⁹ Unlike photoallergic contact dermatitis, which also can involve the face, airborne ACD frequently involves photoprotected areas such as the submandibular chin and the upper lip. Davies and Kersey²⁰ reported the case of a groundsman who was cutting grass with dandelions (Taraxacum officinale) and was found to have associated airborne ACD of the face, neck, and forearms due to Compositae allergy. In a different setting, the aromas of chamomile (Matricaria chamomilla) have been reported to cause airborne ACD in a tea drinker.²¹ Paulsen²² found that ingestion of chamomile tea can induce systemic ACD in sensitized individuals.

Alstroemeriaceae, Liliaceae, and Primulaceae
Florists are exposed to many plant species and have a high prevalence of ACD. Thiboutot et al²³ found that 15 of 57 (26%) floral workers experienced hand dermatitis that cleared with time away from work. The Peruvian lily (Alstroemeria, Alstroemeriaceae family), which contains tuliposide A, was found to be the leading cause of sensitization.²³ Tulips (Tulipa, Liliaceae family), as the flower name suggests, also contain tuliposide A, which along with mechanical irritation from the course tecta fibers on the bulbs lead to a dermatitis known as tulip fingers.^24,25 Poison primrose (Primula obconica, Primulaceae family), cultivated for its highly colorful flowers, contains the contact allergen primin.⁶ A common clinical presentation of ACD for any of these culprit flowers is localized dermatitis of the thumb and index finger in a florist or gardener.

Plants That Cause Irritant Reactions

Cactuses
Although the long spines of the Cactaceae family of cactuses is a warning for passersby, it is the small and nearly invisible barbed hairs (glochids) that inflict a more dramatic cutaneous reaction. The prickly pear cactus (Opuntia species) is a good example of such a plant, as its glochids cause mechanical irritation but also can become embedded in the skin and result in subcutaneous granulomas known as sabra dermatitis.²⁶

Stinging Nettle
The dermatologic term urticaria owes its namesake to the stinging nettle plant, which comes from the family Urticaceae. The stinging nettle has small hairs on its leaves, referred to as stinging trichomes, which have needlelike tips that pierce the skin and inject a mix of histamine, formic acid, and acetylcholine, causing a pruritic dermatitis that may last up to 12 hours.²⁷ The plant is found worldwide and is a common weed in North America.

Phytophotodermatitis

Lemons and limes (Rutaceae family) are common culprits of phytophotodermatitis, often causing what is known as a margarita burn after outdoor consumption or preparation of this tasty citrus beverage.²⁸ An accidental spray of lime juice on the skin while adding it to a beer, guacamole, salsa, or any other food or beverage also can cause phytophotodermatitis.^29-31 Although the juice of lemons and limes contains psoralens, the rind can contain a 6- to 186-fold increased concentration.³² Psoralen is the photoactive agent in Rutaceae plants that intercalates in double-stranded DNA and promotes intrastrand cross-links when exposed to UVA light, which ultimately leads to dermatitis.⁹ Phytophotodermatitis commonly causes erythema, edema, and painful bullae on sun-exposed areas and classically heals with hyperpigmentation.

Pseudophytodermatitis can occur in grain farmers and harvesters who handle wheat and/or barley and incidentally come in contact with insects and chemicals on the plant material. Pseudophytodermatitis from mites in the wheat and/or barley plant can occur at harvest time when contact with the plant material is high. Insects such as the North American itch mite (Pediculoides ventricosus) can cause petechiae, wheals, and pustules. In addition, insecticides such as malathion and arsenical sprays that are applied to plant leaves can cause pseudophytodermatitis, which may be initially diagnosed as dermatitis to the plant itself.⁶

Patch Testing to Plants

When a patient presents with recurrent or persistent dermatitis and a plant contact allergen is suspected, patch testing is indicated. Most comprehensive patch test series contain various plant allergens, such as sesquiterpene lactones, Compositae mix, and limonene hydroperoxides, and patch testing to a specialized plant series may be necessary. Poison ivy/oak/sumac allergens typically are not included in patch test series because of the high prevalence of allergic reactions to these chemicals and the likelihood of sensitization when patch testing with urushiol. Compositae contact sensitization can be difficult to diagnose because neither sesquiterpene lactone mix 0.1% nor parthenolide 0.1% are sensitive enough to pick up all Compositae allergies.^33,34 Paulsen and Andersen³⁴ proposed that if Compositae sensitization is suspected, testing should include sesquiterpene lactone, parthenolide, and Compositae mix II 2.5%, as well as other potential Compositae allergens based on the patient’s history.³⁴

Because plants can have geographic variability and contain potentially unknown allergens,³⁵ testing to plant components may increase the diagnostic yield of patch testing. Dividing the plant into component parts (ie, stem, bulb, leaf, flower) is helpful, as different components have different allergen concentrations. It is important to consult expert resources before proceeding with plant component patch testing because irritant reactions are frequent and may confound the testing.³⁶

Prevention and Treatment

For all plant dermatoses, the mainstay of prevention is to avoid contact with the offending plant material. Gloves can be an important protective tool for plant dermatitis prevention; the correct material depends on the plant species being handled. Rubber gloves should not be worn to protect against Toxicodendron plants since the catechols in urushiol are soluble in rubber; vinyl gloves should be worn instead.⁶ Marks³⁷ found that tuliposide A, the allergen in the Peruvian lily (Alstroemeria), penetrates both vinyl and latex gloves; it does not penetrate nitrile gloves. If exposed, the risk of dermatitis can be decreased if the allergen is washed away with soap and water as soon as possible. Some allergens such as Toxicodendron are absorbed quickly and need to be washed off within 10 minutes of exposure.⁶ Importantly, exposed gardening gloves may continue to perpetuate ACD if the allergen is not also washed off the gloves themselves.

For light-mediated dermatoses, sun avoidance or use of an effective sunscreen can reduce symptoms in an individual who has already been exposed.¹⁰ UVA light activates psoralen-mediated dermatitis but not until 30 to 120 minutes after absorption into the skin.³⁸

Barrier creams are thought to be protective against plant ACD through a variety of mechanisms. The cream itself is meant to reduce skin contact to an allergen or irritant. Additionally, barrier creams contain active ingredients such as silicone, hydrocarbons, and aluminum chlorohydrate, which are thought to trap or transform offending agents before contacting the skin. When contact with a Toxicodendron species is anticipated, Marks et al³⁹ found that dermatitis was absent or significantly reduced when 144 patients were pretreated with quaternium-18 bentonite lotion 5% (P<.0001).

Although allergen avoidance and use of gloves and barrier creams are the mainstays of preventing plant dermatoses, treatment often is required to control postexposure symptoms. For all plant dermatoses, topical corticosteroids can be used to reduce inflammation and pruritus. In some cases, systemic steroids may be necessary. To prevent rebound of dermatitis, patients often require a 3-week or longer course of oral steroids to quell the reaction, particularly if the dermatitis is vigorous or an id reaction is present.⁴⁰ Antihistamines and cold compresses also can provide symptomatic relief.

Final Interpretation

Plants can cause a variety of dermatoses. Although Toxicodendron plants are the most frequent cause of ACD, it is important to keep in mind that florists, gardeners, and farmers are exposed to a large variety of allergens, irritants, and phototoxic agents that cause dermatoses as well. Confirmation of plant-induced ACD involves patch testing against suspected species. Prevention involves use of appropriate barriers and avoidance of implicated plants. Treatment includes topical steroids, antihistamines, and prednisone.

Atopic dermatitis (AD) is an incredibly common chronic skin disease, affecting up to 25% of children and 7% of adults in the United States.^1,2 Despite the prevalence of this disease and its impact on patient quality of life, research and scholarly work in AD has been limited until recent years. A PubMed search of articles indexed for MEDLINE using the term atopic dermatitis showed that there were fewer than 500 articles published in 2000 and 965 in 2010; with our more recent acceleration in research, there were 2168 articles published in 2020 and more than 1300 published in just the first half of 2021 (through June). This new research includes insights into the pathogenesis of AD and study of the disease impact and comorbidities as well as an extensive amount of drug development and clinical trial work for new topical and systemic therapies.

New Agents to Treat AD

The 2016 approval of crisaborole,³ a phosphodiesterase 4 inhibitor, followed by the approval of dupilumab, an IL-4 and IL-13 pathway inhibitor and the first biologic agent approved for AD,⁴ ushered in a new age of therapy. We currently are awaiting the incorporation of a new set of topical nonsteroidal agents, oral Janus kinase (JAK) inhibitors, and new biologic agents for AD, several of which have completed phase 3 trials and extended safety evaluations. How these new drugs will impact our standard treatment across the spectrum of care for AD is not yet known.

The emergence of new systemic therapies is timely, as the most used systemic medications previously were oral corticosteroids, despite their use being advised against in standard practice guidelines. Other agents such as methotrexate, cyclosporine, azathioprine, and mycophenolate are discussed in the literature and AD treatment guidelines as being potentially useful, though absence of US Food and Drug Administration (FDA) approval and the need for frequent laboratory monitoring, as well as drug-specific side effects and an increased risk of infection, limit their use in the United States, especially in pediatric and adolescent populations.⁵

The approval of dupilumab as a systemic therapy—initially for adults and subsequently for teenagers (12–17 years of age) and then children (6–11 years of age)—has markedly influenced the standard of care for moderate to severe AD. This agent has been shown to have a considerable impact on disease severity and quality of life, with a good safety profile and the added benefit of not requiring continuous (or any) laboratory monitoring.^6-8 Ongoing studies of dupilumab in children (ClinicalTrials.gov identifiers NCT02612454, NCT03346434), including those younger than 1 year,⁹ raise the question of how commonly this medication might be incorporated into care across the entire age spectrum of patients with AD. What standards will there be for assessment of severity, disease impact, and persistence to warrant use in younger ages? Will early treatment with novel systemic agents change the overall course of the disease and minimize the development of comorbidities? The answers to these questions remain to be seen.

JAK Inhibitors for AD
Additional novel therapeutics currently are undergoing studies for treatment of AD, most notably the oral JAK inhibitors upadacitinib,¹⁰ baricitinib,¹¹ and abrocitinib.¹² Each of these agents has completed phase 3 trials for AD. Two of these agents—upadacitinib and baricitinib—have prior FDA approval for use in other disease states. Of note, baricitinib is already approved for treatment of moderate to severe AD in adults in more than 40 countries¹³; however, the use of these agents in other diseases brings about concerns of malignancy, severe infection, and thrombosis. In the clinical trials for AD, many of these events have not been seen, but the number of patients treated is limited, and longer-term safety assessment is important.^10,11

How will the oral JAK inhibitors be incorporated into care compared to biologic agents such as dupilumab? Tolerance and more serious potential adverse events are concerns, with nausea, headaches, and acneform eruptions being associated with some of the medications, in addition to potential issues with herpes simplex and zoster infections. However, oral JAK inhibitors have the benefit of not requiring injections, something that many patients may prefer, and data show that these drugs generally are associated with a rapid reduction in pruritus and, depending on the drug, very quick and profound effects on objective signs of AD.^10-12 Two head-to-head studies have been completed comparing dupilumab to oral JAK inhibitors in adults: the JADE COMPARE trial examining dupilumab vs abrocitinib¹² and the Heads UP trial comparing dupilumab vs upadacitinib.¹⁴ Compared to dupilumab, higher-dose abrocitinib showed more rapid responses, superiority in itch response, and similarity or superiority in other outcomes depending on the time point of the evaluation. Adverse event profiles differed; for example, abrocitinib was associated with more nausea, acneform eruptions, and herpes zoster, while dupilumab had higher rates of conjunctivitis.¹² Upadacitinib, which was only studied at higher dosing (30 mg daily), showed superiority to dupilumab in itch response and in improvement in AD severity in multiple outcome measures; however, there were increases in serious infections, eczema herpeticum, herpes zoster, and laboratory-related adverse events.¹⁴ Dupilumab has the advantage of studies of extended use along with real-world experience, generally with excellent safety and tolerance other than injection-site reactions and conjunctivitis.⁸ Biologics targeting IL-13—tralokinumab and lebrikizumab—also are to be added to our armamentarium.^15,16 The addition of these agents and JAK inhibitors as new systemic treatment options points to the quickly evolving future of AD treatment for patients with extensive disease.

New topical therapies in development provide even more treatment options. New nonsteroidal topicals include topical JAK inhibitors such as ruxolitinib¹⁷; tapinarof,¹⁸ an aryl hydrocarbon receptor modulator; and phosphodiesterase 4 inhibitors. These agents may be useful either as monotherapy, as studied, potentially without the regional limitations associated with stronger topical corticosteroids, but also should be useful in clinical practice as part of therapeutic regimens with other topical steroid and nonsteroidal agents.

The Microbiome and AD

In addition, research looking at topical microbes as specific interventions that may mediate the microbiome and inflammation of AD are intriguing. A recent phase 1 trial from the University of California San Diego¹⁹ indicated that topical bacteriotherapy directed at decreasing Staphylococcus aureus may provide an impact in AD. Observations by Kong et al²⁰ showed that gram-negative microbiome differences are seen in AD patients compared to unaffected individuals, which has fueled studies showing that Roseomonas mucosa, a gram-negative skin commensal, when applied as a topical live biotherapeutic agent has improved disease severity in children and adults with AD.²¹ Although further studies are underway, these initial data suggest a role for microbiome-modifying therapies as AD treatment.

Chronic Hand Eczema

Chronic hand eczema (CHE), which has considerable overlap with AD in many patients, especially children and adolescents,^22-24 is another area of interesting research. This high-prevalence condition is associated with allergic and irritant contact dermatitis^24-26—conditions that are both considered alternative diagnoses for and exacerbators of AD²⁷—and is a disease process currently being targeted for new therapies. Delgocitinib (NCT04872101, NCT04871711), the novel JAK inhibitor ARQ-252 (NCT04378569), among other topical agents, as well as systemic therapeutics such as gusacitinib (NCT03728504), are in active trials for CHE. Given CHE’s impact on quality of life²⁸ and its overlap with AD, investigation into this disorder can help drive future AD research as well as lead to better knowledge and treatment of CHE.

Final Thoughts

Despite the promising results of these myriad new therapies in AD, there are many factors that influence how and when we use these drugs, including their approval status, FDA labeling, and the ability of patients to access and afford treatment. Additionally, continued study is needed to evaluate the long-term safety and extended efficacy of newer drugs, such as the oral JAK inhibitors. Despite these hurdles, the current landscape of research and development is rapidly evolving. Compared to the many years when only one main group of therapies was a reasonable option for patients, the future of AD treatment looks bright.

Atopic dermatitis (AD) is an incredibly common chronic skin disease, affecting up to 25% of children and 7% of adults in the United States.^1,2 Despite the prevalence of this disease and its impact on patient quality of life, research and scholarly work in AD has been limited until recent years. A PubMed search of articles indexed for MEDLINE using the term atopic dermatitis showed that there were fewer than 500 articles published in 2000 and 965 in 2010; with our more recent acceleration in research, there were 2168 articles published in 2020 and more than 1300 published in just the first half of 2021 (through June). This new research includes insights into the pathogenesis of AD and study of the disease impact and comorbidities as well as an extensive amount of drug development and clinical trial work for new topical and systemic therapies.

New Agents to Treat AD

The 2016 approval of crisaborole,³ a phosphodiesterase 4 inhibitor, followed by the approval of dupilumab, an IL-4 and IL-13 pathway inhibitor and the first biologic agent approved for AD,⁴ ushered in a new age of therapy. We currently are awaiting the incorporation of a new set of topical nonsteroidal agents, oral Janus kinase (JAK) inhibitors, and new biologic agents for AD, several of which have completed phase 3 trials and extended safety evaluations. How these new drugs will impact our standard treatment across the spectrum of care for AD is not yet known.

The emergence of new systemic therapies is timely, as the most used systemic medications previously were oral corticosteroids, despite their use being advised against in standard practice guidelines. Other agents such as methotrexate, cyclosporine, azathioprine, and mycophenolate are discussed in the literature and AD treatment guidelines as being potentially useful, though absence of US Food and Drug Administration (FDA) approval and the need for frequent laboratory monitoring, as well as drug-specific side effects and an increased risk of infection, limit their use in the United States, especially in pediatric and adolescent populations.⁵

The approval of dupilumab as a systemic therapy—initially for adults and subsequently for teenagers (12–17 years of age) and then children (6–11 years of age)—has markedly influenced the standard of care for moderate to severe AD. This agent has been shown to have a considerable impact on disease severity and quality of life, with a good safety profile and the added benefit of not requiring continuous (or any) laboratory monitoring.^6-8 Ongoing studies of dupilumab in children (ClinicalTrials.gov identifiers NCT02612454, NCT03346434), including those younger than 1 year,⁹ raise the question of how commonly this medication might be incorporated into care across the entire age spectrum of patients with AD. What standards will there be for assessment of severity, disease impact, and persistence to warrant use in younger ages? Will early treatment with novel systemic agents change the overall course of the disease and minimize the development of comorbidities? The answers to these questions remain to be seen.

JAK Inhibitors for AD
Additional novel therapeutics currently are undergoing studies for treatment of AD, most notably the oral JAK inhibitors upadacitinib,¹⁰ baricitinib,¹¹ and abrocitinib.¹² Each of these agents has completed phase 3 trials for AD. Two of these agents—upadacitinib and baricitinib—have prior FDA approval for use in other disease states. Of note, baricitinib is already approved for treatment of moderate to severe AD in adults in more than 40 countries¹³; however, the use of these agents in other diseases brings about concerns of malignancy, severe infection, and thrombosis. In the clinical trials for AD, many of these events have not been seen, but the number of patients treated is limited, and longer-term safety assessment is important.^10,11

How will the oral JAK inhibitors be incorporated into care compared to biologic agents such as dupilumab? Tolerance and more serious potential adverse events are concerns, with nausea, headaches, and acneform eruptions being associated with some of the medications, in addition to potential issues with herpes simplex and zoster infections. However, oral JAK inhibitors have the benefit of not requiring injections, something that many patients may prefer, and data show that these drugs generally are associated with a rapid reduction in pruritus and, depending on the drug, very quick and profound effects on objective signs of AD.^10-12 Two head-to-head studies have been completed comparing dupilumab to oral JAK inhibitors in adults: the JADE COMPARE trial examining dupilumab vs abrocitinib¹² and the Heads UP trial comparing dupilumab vs upadacitinib.¹⁴ Compared to dupilumab, higher-dose abrocitinib showed more rapid responses, superiority in itch response, and similarity or superiority in other outcomes depending on the time point of the evaluation. Adverse event profiles differed; for example, abrocitinib was associated with more nausea, acneform eruptions, and herpes zoster, while dupilumab had higher rates of conjunctivitis.¹² Upadacitinib, which was only studied at higher dosing (30 mg daily), showed superiority to dupilumab in itch response and in improvement in AD severity in multiple outcome measures; however, there were increases in serious infections, eczema herpeticum, herpes zoster, and laboratory-related adverse events.¹⁴ Dupilumab has the advantage of studies of extended use along with real-world experience, generally with excellent safety and tolerance other than injection-site reactions and conjunctivitis.⁸ Biologics targeting IL-13—tralokinumab and lebrikizumab—also are to be added to our armamentarium.^15,16 The addition of these agents and JAK inhibitors as new systemic treatment options points to the quickly evolving future of AD treatment for patients with extensive disease.

New topical therapies in development provide even more treatment options. New nonsteroidal topicals include topical JAK inhibitors such as ruxolitinib¹⁷; tapinarof,¹⁸ an aryl hydrocarbon receptor modulator; and phosphodiesterase 4 inhibitors. These agents may be useful either as monotherapy, as studied, potentially without the regional limitations associated with stronger topical corticosteroids, but also should be useful in clinical practice as part of therapeutic regimens with other topical steroid and nonsteroidal agents.

The Microbiome and AD

In addition, research looking at topical microbes as specific interventions that may mediate the microbiome and inflammation of AD are intriguing. A recent phase 1 trial from the University of California San Diego¹⁹ indicated that topical bacteriotherapy directed at decreasing Staphylococcus aureus may provide an impact in AD. Observations by Kong et al²⁰ showed that gram-negative microbiome differences are seen in AD patients compared to unaffected individuals, which has fueled studies showing that Roseomonas mucosa, a gram-negative skin commensal, when applied as a topical live biotherapeutic agent has improved disease severity in children and adults with AD.²¹ Although further studies are underway, these initial data suggest a role for microbiome-modifying therapies as AD treatment.

Chronic Hand Eczema

Chronic hand eczema (CHE), which has considerable overlap with AD in many patients, especially children and adolescents,^22-24 is another area of interesting research. This high-prevalence condition is associated with allergic and irritant contact dermatitis^24-26—conditions that are both considered alternative diagnoses for and exacerbators of AD²⁷—and is a disease process currently being targeted for new therapies. Delgocitinib (NCT04872101, NCT04871711), the novel JAK inhibitor ARQ-252 (NCT04378569), among other topical agents, as well as systemic therapeutics such as gusacitinib (NCT03728504), are in active trials for CHE. Given CHE’s impact on quality of life²⁸ and its overlap with AD, investigation into this disorder can help drive future AD research as well as lead to better knowledge and treatment of CHE.

Final Thoughts

Despite the promising results of these myriad new therapies in AD, there are many factors that influence how and when we use these drugs, including their approval status, FDA labeling, and the ability of patients to access and afford treatment. Additionally, continued study is needed to evaluate the long-term safety and extended efficacy of newer drugs, such as the oral JAK inhibitors. Despite these hurdles, the current landscape of research and development is rapidly evolving. Compared to the many years when only one main group of therapies was a reasonable option for patients, the future of AD treatment looks bright.

Atopic dermatitis (AD) is an incredibly common chronic skin disease, affecting up to 25% of children and 7% of adults in the United States.^1,2 Despite the prevalence of this disease and its impact on patient quality of life, research and scholarly work in AD has been limited until recent years. A PubMed search of articles indexed for MEDLINE using the term atopic dermatitis showed that there were fewer than 500 articles published in 2000 and 965 in 2010; with our more recent acceleration in research, there were 2168 articles published in 2020 and more than 1300 published in just the first half of 2021 (through June). This new research includes insights into the pathogenesis of AD and study of the disease impact and comorbidities as well as an extensive amount of drug development and clinical trial work for new topical and systemic therapies.

New Agents to Treat AD

The 2016 approval of crisaborole,³ a phosphodiesterase 4 inhibitor, followed by the approval of dupilumab, an IL-4 and IL-13 pathway inhibitor and the first biologic agent approved for AD,⁴ ushered in a new age of therapy. We currently are awaiting the incorporation of a new set of topical nonsteroidal agents, oral Janus kinase (JAK) inhibitors, and new biologic agents for AD, several of which have completed phase 3 trials and extended safety evaluations. How these new drugs will impact our standard treatment across the spectrum of care for AD is not yet known.

The emergence of new systemic therapies is timely, as the most used systemic medications previously were oral corticosteroids, despite their use being advised against in standard practice guidelines. Other agents such as methotrexate, cyclosporine, azathioprine, and mycophenolate are discussed in the literature and AD treatment guidelines as being potentially useful, though absence of US Food and Drug Administration (FDA) approval and the need for frequent laboratory monitoring, as well as drug-specific side effects and an increased risk of infection, limit their use in the United States, especially in pediatric and adolescent populations.⁵

The approval of dupilumab as a systemic therapy—initially for adults and subsequently for teenagers (12–17 years of age) and then children (6–11 years of age)—has markedly influenced the standard of care for moderate to severe AD. This agent has been shown to have a considerable impact on disease severity and quality of life, with a good safety profile and the added benefit of not requiring continuous (or any) laboratory monitoring.^6-8 Ongoing studies of dupilumab in children (ClinicalTrials.gov identifiers NCT02612454, NCT03346434), including those younger than 1 year,⁹ raise the question of how commonly this medication might be incorporated into care across the entire age spectrum of patients with AD. What standards will there be for assessment of severity, disease impact, and persistence to warrant use in younger ages? Will early treatment with novel systemic agents change the overall course of the disease and minimize the development of comorbidities? The answers to these questions remain to be seen.

JAK Inhibitors for AD
Additional novel therapeutics currently are undergoing studies for treatment of AD, most notably the oral JAK inhibitors upadacitinib,¹⁰ baricitinib,¹¹ and abrocitinib.¹² Each of these agents has completed phase 3 trials for AD. Two of these agents—upadacitinib and baricitinib—have prior FDA approval for use in other disease states. Of note, baricitinib is already approved for treatment of moderate to severe AD in adults in more than 40 countries¹³; however, the use of these agents in other diseases brings about concerns of malignancy, severe infection, and thrombosis. In the clinical trials for AD, many of these events have not been seen, but the number of patients treated is limited, and longer-term safety assessment is important.^10,11

How will the oral JAK inhibitors be incorporated into care compared to biologic agents such as dupilumab? Tolerance and more serious potential adverse events are concerns, with nausea, headaches, and acneform eruptions being associated with some of the medications, in addition to potential issues with herpes simplex and zoster infections. However, oral JAK inhibitors have the benefit of not requiring injections, something that many patients may prefer, and data show that these drugs generally are associated with a rapid reduction in pruritus and, depending on the drug, very quick and profound effects on objective signs of AD.^10-12 Two head-to-head studies have been completed comparing dupilumab to oral JAK inhibitors in adults: the JADE COMPARE trial examining dupilumab vs abrocitinib¹² and the Heads UP trial comparing dupilumab vs upadacitinib.¹⁴ Compared to dupilumab, higher-dose abrocitinib showed more rapid responses, superiority in itch response, and similarity or superiority in other outcomes depending on the time point of the evaluation. Adverse event profiles differed; for example, abrocitinib was associated with more nausea, acneform eruptions, and herpes zoster, while dupilumab had higher rates of conjunctivitis.¹² Upadacitinib, which was only studied at higher dosing (30 mg daily), showed superiority to dupilumab in itch response and in improvement in AD severity in multiple outcome measures; however, there were increases in serious infections, eczema herpeticum, herpes zoster, and laboratory-related adverse events.¹⁴ Dupilumab has the advantage of studies of extended use along with real-world experience, generally with excellent safety and tolerance other than injection-site reactions and conjunctivitis.⁸ Biologics targeting IL-13—tralokinumab and lebrikizumab—also are to be added to our armamentarium.^15,16 The addition of these agents and JAK inhibitors as new systemic treatment options points to the quickly evolving future of AD treatment for patients with extensive disease.

New topical therapies in development provide even more treatment options. New nonsteroidal topicals include topical JAK inhibitors such as ruxolitinib¹⁷; tapinarof,¹⁸ an aryl hydrocarbon receptor modulator; and phosphodiesterase 4 inhibitors. These agents may be useful either as monotherapy, as studied, potentially without the regional limitations associated with stronger topical corticosteroids, but also should be useful in clinical practice as part of therapeutic regimens with other topical steroid and nonsteroidal agents.

The Microbiome and AD

In addition, research looking at topical microbes as specific interventions that may mediate the microbiome and inflammation of AD are intriguing. A recent phase 1 trial from the University of California San Diego¹⁹ indicated that topical bacteriotherapy directed at decreasing Staphylococcus aureus may provide an impact in AD. Observations by Kong et al²⁰ showed that gram-negative microbiome differences are seen in AD patients compared to unaffected individuals, which has fueled studies showing that Roseomonas mucosa, a gram-negative skin commensal, when applied as a topical live biotherapeutic agent has improved disease severity in children and adults with AD.²¹ Although further studies are underway, these initial data suggest a role for microbiome-modifying therapies as AD treatment.

Chronic Hand Eczema

Chronic hand eczema (CHE), which has considerable overlap with AD in many patients, especially children and adolescents,^22-24 is another area of interesting research. This high-prevalence condition is associated with allergic and irritant contact dermatitis^24-26—conditions that are both considered alternative diagnoses for and exacerbators of AD²⁷—and is a disease process currently being targeted for new therapies. Delgocitinib (NCT04872101, NCT04871711), the novel JAK inhibitor ARQ-252 (NCT04378569), among other topical agents, as well as systemic therapeutics such as gusacitinib (NCT03728504), are in active trials for CHE. Given CHE’s impact on quality of life²⁸ and its overlap with AD, investigation into this disorder can help drive future AD research as well as lead to better knowledge and treatment of CHE.

Final Thoughts

Despite the promising results of these myriad new therapies in AD, there are many factors that influence how and when we use these drugs, including their approval status, FDA labeling, and the ability of patients to access and afford treatment. Additionally, continued study is needed to evaluate the long-term safety and extended efficacy of newer drugs, such as the oral JAK inhibitors. Despite these hurdles, the current landscape of research and development is rapidly evolving. Compared to the many years when only one main group of therapies was a reasonable option for patients, the future of AD treatment looks bright.