Contact Dermatitis

The world is an increasingly diverse place, which has particular relevance for the dermatologist. Skin color plays a significant role in diagnostic approach, as there are important differences in how cutaneous disease presents in patients with skin of color (SOC). Therefore, education about these differences is imperative. In this review, we focus on allergic contact dermatitis (ACD) and patch testing in patients with SOC. We discuss allergens common to this demographic and challenges encountered in patch testing patients with SOC. We also identify key health care disparities in the evaluation and management of ACD in this population.

Has contact allergy in SOC populations been studied in North America?

Over the last 2 decades, there have been only a handful of North American studies that address contact allergy in SOC populations. Patch test results from 114 Black patients and 877 White patients at the Cleveland Clinic from 1988 to 1991 showed that overall allergy frequency was relatively similar (43.0% vs 43.6%). There were notable differences in allergen sensitization. Paraphenylenediamine (PPD), which is used in hair dye, had more positive patch test reactions in Black patients (10.6% vs 4.5%), and both PPD (21.2% vs 4.2%) and imidazolidinyl urea, a formaldehyde-releasing preservative (9.1% vs 2.6%), were more frequently allergenic in Black men compared to White men.¹ Patch test results from the North American Contact Dermatitis Group from 1992 to 1998 described similar results, with minimal variation in the prevalence of ACD among 1014 Black and 8610 White patients (47%–49% vs 46%–49%).² Positive patch test reactions to PPD were higher in Black patients for 2 of 3 test cycles (13.5% vs 5.8% [1994-1996] and 10.3% vs 5.3% [1996-1998]). Positive patch test reactions were higher in White patients for dimethylol dimethyl hydantoin, a formaldehyde-releasing preservative, also for 2 of 3 test cycles (1.8% vs 0% [1992-1994] and 2.8% vs 0.3% [1994-1996]). Finally, positive patch test reactions to thioureas (rubber accelerators) had a mixed picture: 2 test cycles were higher in Black patients (1.9% vs 1.0% [1992-1994] and 1.3% vs 0.7% [1994-1996]), but the third cycle (1996-1998) was lower (0.7% vs 1.4%). Positive patch test reactions to the metal cobalt chloride were higher in Black patients in just 1 test cycle (9.2% vs 6.6% [1992-1994]). The authors suggested that the use of darker hair dyes in the Black community may lead to more sensitization to PPD. They also theorized that this population’s more frequent use of ointment-based skin care products may make them less susceptible to sensitization to preservatives such as formaldehyde, which more commonly are found in water-based products such as creams. They concluded that differences in sensitization patterns likely were driven by cultural practices affecting exposures.²

In 2016, the North American Contact Dermatitis Group reported patch test results in 434 Black and 6634 White patients (1998-2006).³ Again, ACD prevalence was about the same in both groups (45.9% vs 43.6%). However, they reported several allergens with different reaction patterns. Black patients had higher risk ratios (RRs) for 3 rubber accelerators: mercaptobenzothiazole (RR, 2.10), mercapto mix (RR, 2.27), and thiuram mix (RR, 1.44). They also reacted to PPD (RR, 1.56) and the antibiotic bacitracin (RR, 1.34) at higher frequencies than White patients, who more frequently reacted to formaldehyde (RR, 0.58); the formaldehyde-releasing preservatives quaternium-15 (RR, 0.63) and diazolidinyl urea (in petrolatum: RR, 0.44; aqueous: RR, 0.47); the clothing finish ethylene urea melamine formalin resin (RR, 0.45); and the fragrances fragrance mix 1 (RR, 0.65) and balsam of Peru (RR, 0.55).³

Patch testing of 139 African American or Black patients at the Cleveland Clinic (2003-2012) revealed that this population most commonly had positive reactions to nickel (27.5%), fragrance mix (18.1%), bacitracin (13.0%), balsam of Peru (12.3%), and PPD (10.9%). The authors highlighted unique features of physical examination in patients with darker skin types, including lichenification and/or hyperpigmentation in those with ACD and the potential for lack of erythema and/or a papular reaction with patch test readings.⁴ Recently, data was presented at the American Contact Dermatitis Society Annual Meeting (March 2021) on patterns of ACD in Black and White patch tested patients in Philadelphia (2009-2019).⁵ Using the North American 80 comprehensive series, the researchers documented statistically significant differences in allergen sensitivity between the 2 groups. Black patients reacted to disperse blue dye (P=.019) and textile dye mix (P=.001) at higher frequencies. There was a nonsignificant trend of more frequent positive reactions to PPD in Black patients (11% vs 6%).⁵

Notably, all of these studies examined only 1 or 2 racial groups with a focus on Black patients. Some authors commented that this was due to low numbers of Hispanic, Asian and Pacific Islander, and Native American patients in tested populations.^2,3,5 With approximately 13% of the US population self-identifying as Black,⁶ these patients and other minority races typically are underrepresented in large patch test studies. More data on patch test results for these groups is necessary for a complete understanding of patch testing in patients with SOC.

What are the challenges in patch testing SOC populations?

Patch testing in patients with SOC requires additional skills and experience. Darker skin does not reveal erythema as strikingly as lighter skin, making it more difficult to appreciate subtle color changes. Moreover, multiple studies have shown that ACD can have different presentations in Black patients.^4,7,8 Lichenification and hyperpigmentation may be early signs of ACD in comparison to bright erythema and vesicles that can be seen in lighter skin types. It also has been reported that scalp ACD can be mistaken for seborrheic dermatitis due to lack of erythema.⁷ Without a high degree of clinical suspicion, a diagnosis of ACD can be missed in this patient population.

Patch test interpretation also can be challenging in patients with SOC. An early papular or follicular eruption with minimal erythema can signal a positive reaction.^4,7 Because of these potentially subtle changes, patch testers should exercise care and attention when reading results for SOC populations. We recommend ample side lighting, palpation for adequate identification of positive reactions, and double-checking for positives that may have been overlooked on the initial review of findings.^4,7

What health care disparities impact the evaluation and management of ACD?

There are many factors at play in this dialogue. The challenges we identified in diagnosing ACD in darker skin types are important to consider. Lack of familiarity with these unique features can lead to a delay in diagnosis and ultimately a delay in referral for patch testing. This is where dermatology training can help fill in the gap, but are the majority of programs equipped to do so? Inadequate education and exposure to patients with SOC is an issue for many dermatology residency programs. Surveys of residents and program directors in geographically less diverse regions may not receive adequate education or exposure to patients with SOC.⁹ Further, there is a lack of representation of SOC images for general dermatologic conditions in textbooks,^10,11 which has a profound impact on the dermatologist’s ability to recognize common diseases in darker skin types. A 2019 survey of more than 5000 images from 2 dermatology textbooks showed SOC images comprised 22% to 32% of the total images.¹¹ However, SOC images are overrepresented in textbooks for sexually transmitted infections, constituting 47% to 58% of the images; they made up 28% of images for nonvenereal infections.¹¹ Why is that? In this article, we have shown the prevalence of ACD to be nearly equivalent in Black and White patients, yet a perusal of ACD images in dermatology textbooks will tell a different story. This trend deserves our attention; perhaps it is highlighting patterns of systemic racism seen in medicine. If our primary teaching materials are perpetuating stereotypes, we must consider the impact this can have on our personal implicit biases and the health care disparities that can ensue.

Additional factors impact time to diagnosis of ACD and referral for patch testing. A retrospective study examining distance to a North Carolina patch test referral clinic showed that patients living further from the clinic experienced a longer duration of dermatitis prior to patch test consultation and tended to live in areas with a higher county poverty rate.¹² Specifically, a 17.9% increase (P<.001) in the median duration of dermatitis was observed for every 50-mile increase in distance to the patch test clinic. County poverty rate was measured by the percentage of residents living below the poverty threshold; for every 5% increase in county poverty rate, a 16.3% increase (P<.032) in duration of dermatitis was found.¹²

These data highlight a relationship with which many dermatologists are familiar and underscore a need for dermatologists to practice in areas that are more geographically accessible. The recently increased utilization of telehealth modalities can potentially help to bridge this gap by decreasing delays in diagnosis and providing more affordable options for evaluation by a dermatologist for patients with socioeconomic obstacles.

Final Interpretation

The prevalence of ACD among Black and White patients is similar; however, there are important differences in patch test reaction frequencies that may be related to the diverse exposure patterns for each group. Additionally, patients with SOC may have unique clinical presentations of ACD, such as lichenification and hyperpigmentation. Darker skin types also may require specialized techniques for accurate patch test readings. It is imperative that dermatologists are trained to recognize all of these features. Health care disparities come in many forms and, in this setting, can result in delayed referral for patch testing. Additional studies are needed to further examine these health care disparities and identify potential solutions.

The world is an increasingly diverse place, which has particular relevance for the dermatologist. Skin color plays a significant role in diagnostic approach, as there are important differences in how cutaneous disease presents in patients with skin of color (SOC). Therefore, education about these differences is imperative. In this review, we focus on allergic contact dermatitis (ACD) and patch testing in patients with SOC. We discuss allergens common to this demographic and challenges encountered in patch testing patients with SOC. We also identify key health care disparities in the evaluation and management of ACD in this population.

Has contact allergy in SOC populations been studied in North America?

Over the last 2 decades, there have been only a handful of North American studies that address contact allergy in SOC populations. Patch test results from 114 Black patients and 877 White patients at the Cleveland Clinic from 1988 to 1991 showed that overall allergy frequency was relatively similar (43.0% vs 43.6%). There were notable differences in allergen sensitization. Paraphenylenediamine (PPD), which is used in hair dye, had more positive patch test reactions in Black patients (10.6% vs 4.5%), and both PPD (21.2% vs 4.2%) and imidazolidinyl urea, a formaldehyde-releasing preservative (9.1% vs 2.6%), were more frequently allergenic in Black men compared to White men.¹ Patch test results from the North American Contact Dermatitis Group from 1992 to 1998 described similar results, with minimal variation in the prevalence of ACD among 1014 Black and 8610 White patients (47%–49% vs 46%–49%).² Positive patch test reactions to PPD were higher in Black patients for 2 of 3 test cycles (13.5% vs 5.8% [1994-1996] and 10.3% vs 5.3% [1996-1998]). Positive patch test reactions were higher in White patients for dimethylol dimethyl hydantoin, a formaldehyde-releasing preservative, also for 2 of 3 test cycles (1.8% vs 0% [1992-1994] and 2.8% vs 0.3% [1994-1996]). Finally, positive patch test reactions to thioureas (rubber accelerators) had a mixed picture: 2 test cycles were higher in Black patients (1.9% vs 1.0% [1992-1994] and 1.3% vs 0.7% [1994-1996]), but the third cycle (1996-1998) was lower (0.7% vs 1.4%). Positive patch test reactions to the metal cobalt chloride were higher in Black patients in just 1 test cycle (9.2% vs 6.6% [1992-1994]). The authors suggested that the use of darker hair dyes in the Black community may lead to more sensitization to PPD. They also theorized that this population’s more frequent use of ointment-based skin care products may make them less susceptible to sensitization to preservatives such as formaldehyde, which more commonly are found in water-based products such as creams. They concluded that differences in sensitization patterns likely were driven by cultural practices affecting exposures.²

In 2016, the North American Contact Dermatitis Group reported patch test results in 434 Black and 6634 White patients (1998-2006).³ Again, ACD prevalence was about the same in both groups (45.9% vs 43.6%). However, they reported several allergens with different reaction patterns. Black patients had higher risk ratios (RRs) for 3 rubber accelerators: mercaptobenzothiazole (RR, 2.10), mercapto mix (RR, 2.27), and thiuram mix (RR, 1.44). They also reacted to PPD (RR, 1.56) and the antibiotic bacitracin (RR, 1.34) at higher frequencies than White patients, who more frequently reacted to formaldehyde (RR, 0.58); the formaldehyde-releasing preservatives quaternium-15 (RR, 0.63) and diazolidinyl urea (in petrolatum: RR, 0.44; aqueous: RR, 0.47); the clothing finish ethylene urea melamine formalin resin (RR, 0.45); and the fragrances fragrance mix 1 (RR, 0.65) and balsam of Peru (RR, 0.55).³

Patch testing of 139 African American or Black patients at the Cleveland Clinic (2003-2012) revealed that this population most commonly had positive reactions to nickel (27.5%), fragrance mix (18.1%), bacitracin (13.0%), balsam of Peru (12.3%), and PPD (10.9%). The authors highlighted unique features of physical examination in patients with darker skin types, including lichenification and/or hyperpigmentation in those with ACD and the potential for lack of erythema and/or a papular reaction with patch test readings.⁴ Recently, data was presented at the American Contact Dermatitis Society Annual Meeting (March 2021) on patterns of ACD in Black and White patch tested patients in Philadelphia (2009-2019).⁵ Using the North American 80 comprehensive series, the researchers documented statistically significant differences in allergen sensitivity between the 2 groups. Black patients reacted to disperse blue dye (P=.019) and textile dye mix (P=.001) at higher frequencies. There was a nonsignificant trend of more frequent positive reactions to PPD in Black patients (11% vs 6%).⁵

Notably, all of these studies examined only 1 or 2 racial groups with a focus on Black patients. Some authors commented that this was due to low numbers of Hispanic, Asian and Pacific Islander, and Native American patients in tested populations.^2,3,5 With approximately 13% of the US population self-identifying as Black,⁶ these patients and other minority races typically are underrepresented in large patch test studies. More data on patch test results for these groups is necessary for a complete understanding of patch testing in patients with SOC.

What are the challenges in patch testing SOC populations?

Patch testing in patients with SOC requires additional skills and experience. Darker skin does not reveal erythema as strikingly as lighter skin, making it more difficult to appreciate subtle color changes. Moreover, multiple studies have shown that ACD can have different presentations in Black patients.^4,7,8 Lichenification and hyperpigmentation may be early signs of ACD in comparison to bright erythema and vesicles that can be seen in lighter skin types. It also has been reported that scalp ACD can be mistaken for seborrheic dermatitis due to lack of erythema.⁷ Without a high degree of clinical suspicion, a diagnosis of ACD can be missed in this patient population.

Patch test interpretation also can be challenging in patients with SOC. An early papular or follicular eruption with minimal erythema can signal a positive reaction.^4,7 Because of these potentially subtle changes, patch testers should exercise care and attention when reading results for SOC populations. We recommend ample side lighting, palpation for adequate identification of positive reactions, and double-checking for positives that may have been overlooked on the initial review of findings.^4,7

What health care disparities impact the evaluation and management of ACD?

There are many factors at play in this dialogue. The challenges we identified in diagnosing ACD in darker skin types are important to consider. Lack of familiarity with these unique features can lead to a delay in diagnosis and ultimately a delay in referral for patch testing. This is where dermatology training can help fill in the gap, but are the majority of programs equipped to do so? Inadequate education and exposure to patients with SOC is an issue for many dermatology residency programs. Surveys of residents and program directors in geographically less diverse regions may not receive adequate education or exposure to patients with SOC.⁹ Further, there is a lack of representation of SOC images for general dermatologic conditions in textbooks,^10,11 which has a profound impact on the dermatologist’s ability to recognize common diseases in darker skin types. A 2019 survey of more than 5000 images from 2 dermatology textbooks showed SOC images comprised 22% to 32% of the total images.¹¹ However, SOC images are overrepresented in textbooks for sexually transmitted infections, constituting 47% to 58% of the images; they made up 28% of images for nonvenereal infections.¹¹ Why is that? In this article, we have shown the prevalence of ACD to be nearly equivalent in Black and White patients, yet a perusal of ACD images in dermatology textbooks will tell a different story. This trend deserves our attention; perhaps it is highlighting patterns of systemic racism seen in medicine. If our primary teaching materials are perpetuating stereotypes, we must consider the impact this can have on our personal implicit biases and the health care disparities that can ensue.

Additional factors impact time to diagnosis of ACD and referral for patch testing. A retrospective study examining distance to a North Carolina patch test referral clinic showed that patients living further from the clinic experienced a longer duration of dermatitis prior to patch test consultation and tended to live in areas with a higher county poverty rate.¹² Specifically, a 17.9% increase (P<.001) in the median duration of dermatitis was observed for every 50-mile increase in distance to the patch test clinic. County poverty rate was measured by the percentage of residents living below the poverty threshold; for every 5% increase in county poverty rate, a 16.3% increase (P<.032) in duration of dermatitis was found.¹²

These data highlight a relationship with which many dermatologists are familiar and underscore a need for dermatologists to practice in areas that are more geographically accessible. The recently increased utilization of telehealth modalities can potentially help to bridge this gap by decreasing delays in diagnosis and providing more affordable options for evaluation by a dermatologist for patients with socioeconomic obstacles.

Final Interpretation

The prevalence of ACD among Black and White patients is similar; however, there are important differences in patch test reaction frequencies that may be related to the diverse exposure patterns for each group. Additionally, patients with SOC may have unique clinical presentations of ACD, such as lichenification and hyperpigmentation. Darker skin types also may require specialized techniques for accurate patch test readings. It is imperative that dermatologists are trained to recognize all of these features. Health care disparities come in many forms and, in this setting, can result in delayed referral for patch testing. Additional studies are needed to further examine these health care disparities and identify potential solutions.

The world is an increasingly diverse place, which has particular relevance for the dermatologist. Skin color plays a significant role in diagnostic approach, as there are important differences in how cutaneous disease presents in patients with skin of color (SOC). Therefore, education about these differences is imperative. In this review, we focus on allergic contact dermatitis (ACD) and patch testing in patients with SOC. We discuss allergens common to this demographic and challenges encountered in patch testing patients with SOC. We also identify key health care disparities in the evaluation and management of ACD in this population.

Has contact allergy in SOC populations been studied in North America?

Over the last 2 decades, there have been only a handful of North American studies that address contact allergy in SOC populations. Patch test results from 114 Black patients and 877 White patients at the Cleveland Clinic from 1988 to 1991 showed that overall allergy frequency was relatively similar (43.0% vs 43.6%). There were notable differences in allergen sensitization. Paraphenylenediamine (PPD), which is used in hair dye, had more positive patch test reactions in Black patients (10.6% vs 4.5%), and both PPD (21.2% vs 4.2%) and imidazolidinyl urea, a formaldehyde-releasing preservative (9.1% vs 2.6%), were more frequently allergenic in Black men compared to White men.¹ Patch test results from the North American Contact Dermatitis Group from 1992 to 1998 described similar results, with minimal variation in the prevalence of ACD among 1014 Black and 8610 White patients (47%–49% vs 46%–49%).² Positive patch test reactions to PPD were higher in Black patients for 2 of 3 test cycles (13.5% vs 5.8% [1994-1996] and 10.3% vs 5.3% [1996-1998]). Positive patch test reactions were higher in White patients for dimethylol dimethyl hydantoin, a formaldehyde-releasing preservative, also for 2 of 3 test cycles (1.8% vs 0% [1992-1994] and 2.8% vs 0.3% [1994-1996]). Finally, positive patch test reactions to thioureas (rubber accelerators) had a mixed picture: 2 test cycles were higher in Black patients (1.9% vs 1.0% [1992-1994] and 1.3% vs 0.7% [1994-1996]), but the third cycle (1996-1998) was lower (0.7% vs 1.4%). Positive patch test reactions to the metal cobalt chloride were higher in Black patients in just 1 test cycle (9.2% vs 6.6% [1992-1994]). The authors suggested that the use of darker hair dyes in the Black community may lead to more sensitization to PPD. They also theorized that this population’s more frequent use of ointment-based skin care products may make them less susceptible to sensitization to preservatives such as formaldehyde, which more commonly are found in water-based products such as creams. They concluded that differences in sensitization patterns likely were driven by cultural practices affecting exposures.²

In 2016, the North American Contact Dermatitis Group reported patch test results in 434 Black and 6634 White patients (1998-2006).³ Again, ACD prevalence was about the same in both groups (45.9% vs 43.6%). However, they reported several allergens with different reaction patterns. Black patients had higher risk ratios (RRs) for 3 rubber accelerators: mercaptobenzothiazole (RR, 2.10), mercapto mix (RR, 2.27), and thiuram mix (RR, 1.44). They also reacted to PPD (RR, 1.56) and the antibiotic bacitracin (RR, 1.34) at higher frequencies than White patients, who more frequently reacted to formaldehyde (RR, 0.58); the formaldehyde-releasing preservatives quaternium-15 (RR, 0.63) and diazolidinyl urea (in petrolatum: RR, 0.44; aqueous: RR, 0.47); the clothing finish ethylene urea melamine formalin resin (RR, 0.45); and the fragrances fragrance mix 1 (RR, 0.65) and balsam of Peru (RR, 0.55).³

Patch testing of 139 African American or Black patients at the Cleveland Clinic (2003-2012) revealed that this population most commonly had positive reactions to nickel (27.5%), fragrance mix (18.1%), bacitracin (13.0%), balsam of Peru (12.3%), and PPD (10.9%). The authors highlighted unique features of physical examination in patients with darker skin types, including lichenification and/or hyperpigmentation in those with ACD and the potential for lack of erythema and/or a papular reaction with patch test readings.⁴ Recently, data was presented at the American Contact Dermatitis Society Annual Meeting (March 2021) on patterns of ACD in Black and White patch tested patients in Philadelphia (2009-2019).⁵ Using the North American 80 comprehensive series, the researchers documented statistically significant differences in allergen sensitivity between the 2 groups. Black patients reacted to disperse blue dye (P=.019) and textile dye mix (P=.001) at higher frequencies. There was a nonsignificant trend of more frequent positive reactions to PPD in Black patients (11% vs 6%).⁵

Notably, all of these studies examined only 1 or 2 racial groups with a focus on Black patients. Some authors commented that this was due to low numbers of Hispanic, Asian and Pacific Islander, and Native American patients in tested populations.^2,3,5 With approximately 13% of the US population self-identifying as Black,⁶ these patients and other minority races typically are underrepresented in large patch test studies. More data on patch test results for these groups is necessary for a complete understanding of patch testing in patients with SOC.

What are the challenges in patch testing SOC populations?

Patch testing in patients with SOC requires additional skills and experience. Darker skin does not reveal erythema as strikingly as lighter skin, making it more difficult to appreciate subtle color changes. Moreover, multiple studies have shown that ACD can have different presentations in Black patients.^4,7,8 Lichenification and hyperpigmentation may be early signs of ACD in comparison to bright erythema and vesicles that can be seen in lighter skin types. It also has been reported that scalp ACD can be mistaken for seborrheic dermatitis due to lack of erythema.⁷ Without a high degree of clinical suspicion, a diagnosis of ACD can be missed in this patient population.

Patch test interpretation also can be challenging in patients with SOC. An early papular or follicular eruption with minimal erythema can signal a positive reaction.^4,7 Because of these potentially subtle changes, patch testers should exercise care and attention when reading results for SOC populations. We recommend ample side lighting, palpation for adequate identification of positive reactions, and double-checking for positives that may have been overlooked on the initial review of findings.^4,7

What health care disparities impact the evaluation and management of ACD?

There are many factors at play in this dialogue. The challenges we identified in diagnosing ACD in darker skin types are important to consider. Lack of familiarity with these unique features can lead to a delay in diagnosis and ultimately a delay in referral for patch testing. This is where dermatology training can help fill in the gap, but are the majority of programs equipped to do so? Inadequate education and exposure to patients with SOC is an issue for many dermatology residency programs. Surveys of residents and program directors in geographically less diverse regions may not receive adequate education or exposure to patients with SOC.⁹ Further, there is a lack of representation of SOC images for general dermatologic conditions in textbooks,^10,11 which has a profound impact on the dermatologist’s ability to recognize common diseases in darker skin types. A 2019 survey of more than 5000 images from 2 dermatology textbooks showed SOC images comprised 22% to 32% of the total images.¹¹ However, SOC images are overrepresented in textbooks for sexually transmitted infections, constituting 47% to 58% of the images; they made up 28% of images for nonvenereal infections.¹¹ Why is that? In this article, we have shown the prevalence of ACD to be nearly equivalent in Black and White patients, yet a perusal of ACD images in dermatology textbooks will tell a different story. This trend deserves our attention; perhaps it is highlighting patterns of systemic racism seen in medicine. If our primary teaching materials are perpetuating stereotypes, we must consider the impact this can have on our personal implicit biases and the health care disparities that can ensue.

Additional factors impact time to diagnosis of ACD and referral for patch testing. A retrospective study examining distance to a North Carolina patch test referral clinic showed that patients living further from the clinic experienced a longer duration of dermatitis prior to patch test consultation and tended to live in areas with a higher county poverty rate.¹² Specifically, a 17.9% increase (P<.001) in the median duration of dermatitis was observed for every 50-mile increase in distance to the patch test clinic. County poverty rate was measured by the percentage of residents living below the poverty threshold; for every 5% increase in county poverty rate, a 16.3% increase (P<.032) in duration of dermatitis was found.¹²

These data highlight a relationship with which many dermatologists are familiar and underscore a need for dermatologists to practice in areas that are more geographically accessible. The recently increased utilization of telehealth modalities can potentially help to bridge this gap by decreasing delays in diagnosis and providing more affordable options for evaluation by a dermatologist for patients with socioeconomic obstacles.

Final Interpretation

The prevalence of ACD among Black and White patients is similar; however, there are important differences in patch test reaction frequencies that may be related to the diverse exposure patterns for each group. Additionally, patients with SOC may have unique clinical presentations of ACD, such as lichenification and hyperpigmentation. Darker skin types also may require specialized techniques for accurate patch test readings. It is imperative that dermatologists are trained to recognize all of these features. Health care disparities come in many forms and, in this setting, can result in delayed referral for patch testing. Additional studies are needed to further examine these health care disparities and identify potential solutions.

To the Editor:

Patients with psychocutaneous disorders present unique challenges to physicians. We illustrate the critical role that dermoscopy may play to illuminate exogenous skin pathology.

A 50-year-old woman with a reported medical history of systemic lupus erythematosus, chronic pain, and nonhealing leg ulcers presented to the emergency department with severe pain of the left lower leg and redness that was concerning for cellulitis. She sought treatment at an outside hospital for cellulitis 2 weeks prior but left against medical advice. Symptomatic review revealed chest pain, shortness of breath, nausea, vomiting, and diarrhea. The primary team started her on intravenous clindamycin and vancomycin for the presumed infection and scheduled narcotic medications due to concerns of intractable pain in the left leg. The dermatology department was consulted after failure to improve with 1 week of systemic antibiotics.

Physical examination revealed a geometric, atrophic, purple plaque on the left anterior shin from a prior leg ulcer as well as a diffuse red-pink patch extending from the knee to the ankle. Notably, the cellulitis spared the left posterior calf resting against the sheet and had a sharp line of demarcation at the distal shin. The leg was cool to the touch while the patient was distractible. She later reported that the leg was extremely tender to palpation. Dermoscopy revealed linear red pigments within skin furrows that accentuated skin lines (Figure). These findings raised suspicions of an external manipulation. The skin was wiped with an alcohol pad that removed a shimmering pink substance consistent in appearance to a cosmetic product. The skin beneath the cellulitis appeared normal.

Dermoscopy is not a standard method to diagnose cellulitis of the skin; however, when patients present with an atypical response to appropriate care, the presumed diagnosis must be challenged. This patient had dramatized symptoms, false medical history, and numerous hospitalizations that were suspicious for factitious disorder.¹ Furthermore, the physical examination was inconsistent with the classic course of cellulitis. In this case, dermoscopy had advantages over biopsies because it was noninvasive, gave immediate feedback, and provided a macroscopic view of the morphology. Via dermoscopy, we had an objective lens to distinguish cellulitis from cosmetic product and to obtain the correct diagnosis.

To the Editor:

Patients with psychocutaneous disorders present unique challenges to physicians. We illustrate the critical role that dermoscopy may play to illuminate exogenous skin pathology.

A 50-year-old woman with a reported medical history of systemic lupus erythematosus, chronic pain, and nonhealing leg ulcers presented to the emergency department with severe pain of the left lower leg and redness that was concerning for cellulitis. She sought treatment at an outside hospital for cellulitis 2 weeks prior but left against medical advice. Symptomatic review revealed chest pain, shortness of breath, nausea, vomiting, and diarrhea. The primary team started her on intravenous clindamycin and vancomycin for the presumed infection and scheduled narcotic medications due to concerns of intractable pain in the left leg. The dermatology department was consulted after failure to improve with 1 week of systemic antibiotics.

Physical examination revealed a geometric, atrophic, purple plaque on the left anterior shin from a prior leg ulcer as well as a diffuse red-pink patch extending from the knee to the ankle. Notably, the cellulitis spared the left posterior calf resting against the sheet and had a sharp line of demarcation at the distal shin. The leg was cool to the touch while the patient was distractible. She later reported that the leg was extremely tender to palpation. Dermoscopy revealed linear red pigments within skin furrows that accentuated skin lines (Figure). These findings raised suspicions of an external manipulation. The skin was wiped with an alcohol pad that removed a shimmering pink substance consistent in appearance to a cosmetic product. The skin beneath the cellulitis appeared normal.

Dermoscopy is not a standard method to diagnose cellulitis of the skin; however, when patients present with an atypical response to appropriate care, the presumed diagnosis must be challenged. This patient had dramatized symptoms, false medical history, and numerous hospitalizations that were suspicious for factitious disorder.¹ Furthermore, the physical examination was inconsistent with the classic course of cellulitis. In this case, dermoscopy had advantages over biopsies because it was noninvasive, gave immediate feedback, and provided a macroscopic view of the morphology. Via dermoscopy, we had an objective lens to distinguish cellulitis from cosmetic product and to obtain the correct diagnosis.

To the Editor:

Patients with psychocutaneous disorders present unique challenges to physicians. We illustrate the critical role that dermoscopy may play to illuminate exogenous skin pathology.

A 50-year-old woman with a reported medical history of systemic lupus erythematosus, chronic pain, and nonhealing leg ulcers presented to the emergency department with severe pain of the left lower leg and redness that was concerning for cellulitis. She sought treatment at an outside hospital for cellulitis 2 weeks prior but left against medical advice. Symptomatic review revealed chest pain, shortness of breath, nausea, vomiting, and diarrhea. The primary team started her on intravenous clindamycin and vancomycin for the presumed infection and scheduled narcotic medications due to concerns of intractable pain in the left leg. The dermatology department was consulted after failure to improve with 1 week of systemic antibiotics.

Physical examination revealed a geometric, atrophic, purple plaque on the left anterior shin from a prior leg ulcer as well as a diffuse red-pink patch extending from the knee to the ankle. Notably, the cellulitis spared the left posterior calf resting against the sheet and had a sharp line of demarcation at the distal shin. The leg was cool to the touch while the patient was distractible. She later reported that the leg was extremely tender to palpation. Dermoscopy revealed linear red pigments within skin furrows that accentuated skin lines (Figure). These findings raised suspicions of an external manipulation. The skin was wiped with an alcohol pad that removed a shimmering pink substance consistent in appearance to a cosmetic product. The skin beneath the cellulitis appeared normal.

Dermoscopy is not a standard method to diagnose cellulitis of the skin; however, when patients present with an atypical response to appropriate care, the presumed diagnosis must be challenged. This patient had dramatized symptoms, false medical history, and numerous hospitalizations that were suspicious for factitious disorder.¹ Furthermore, the physical examination was inconsistent with the classic course of cellulitis. In this case, dermoscopy had advantages over biopsies because it was noninvasive, gave immediate feedback, and provided a macroscopic view of the morphology. Via dermoscopy, we had an objective lens to distinguish cellulitis from cosmetic product and to obtain the correct diagnosis.

It’s time for the American Contact Dermatitis Society (ACDS) Allergen of the Year! For 2021, the esteemed award goes to acetophenone azine (AA). If you have never heard of this chemical, you are not alone. Acetophenone azine has been identified in foam materials made of the copolymer ethyl-vinyl acetate (EVA). Contact allergy to AA initially was reported in 2016.¹ There are only a few European and Canadian case reports and one case series of AA contact allergy in the literature, all of which are associated with foam shin pads or shin guards, shoe insoles, and/or flip-flops.^2-6 Acetophenone azine is an important emerging allergen, and in this column, we will introduce you to AA and the sneaky places it can lurk and cause allergic contact dermatitis (ACD). We also highlight diagnosis, management, and patch testing for AA contact allergy.

AA Contact Allergy in the Literature

The first case of AA contact allergy was reported in Europe in 2016 when a 13-year-old male soccer player developed severe lower leg dermatitis and later generalized dermatitis associated with wearing foam shin guards.¹ Patch testing to standard and supplemental trays was negative or not relevant; however, the patient exhibited strong reactions when patch tested directly to a piece of the shin guard soaked in acetone, water, and ethanol. Additional testing with AA diluted in acetone, water, and petrolatum resulted in positive patch test reactions to acetone dilutions of 1%, 0.1%, 0.01%, and 0.001% and aqueous solutions of 1% and 0.1%. Chromatographic analyses with high-performance liquid chromatography (HPLC) of shin guard extracts confirmed the culprit allergen to be AA.¹

In the following months, the same clinic saw 2 more cases of AA contact allergy.² An 11-year-old male soccer player developed lower leg dermatitis and later generalized dermatitis from wearing shin guards. Months later, he also developed dermatitis on the soles of the feet, which was attributed to wearing flip-flops. Patch tests to pieces of the shin guards and flip-flops were positive; AA in acetone 0.1% and 0.01% also was positive. As you might expect, HPLC again confirmed the presence of AA in the shin guards and flip-flops. The third patient was a 12-year-old boy with dermatitis on the soles of both feet; later he also developed a generalized dermatitis. Patch testing to pieces of the insoles of his sneakers and AA in acetone 0.1% and 0.01% was positive. Again, HPLC was positive for the presence of AA in the insoles of his sneakers.²

Several more cases of AA contact allergy have been reported in the literature. A 29-year-old European male hockey player demonstrated contact allergy to the gray foam of his shin pads as well as localized leg dermatitis followed by generalized dermatitis (are you noticing a trend yet?), and later dermatitis on the soles of the feet with positive patch-test reactions to pieces of his shin pads and shoe insoles as well as AA 0.1% and 0.01% in acetone.³ A 6-year-old Canadian male soccer player presented with leg dermatitis and later generalized dermatitis and dermatitis on the soles of the feet with positive reactions to pieces of his shin pads and shoe insoles as well as to AA 1% and 0.1% in petrolatum.⁴ A 17-year-old British male (another trend, all males so far!) hockey player developed dermatitis localized to the legs and positive patch tests to the worn foam inner lining of his shin pads as well as to AA 0.1%, 0.01%, and 0.001% in acetone.⁵Finally, Darrigade et al⁶ published a case series of 6 European children with AA contact allergy associated with shin pads and shoes; all had localized leg dermatitis, and some had generalized dermatitis. Patch testing to pieces of shin pads and shoe parts as well as to AA 0.1% in petrolatum and/or acetone showed with positive reactions to the foam pieces and AA in all 6 patients.

What’s the Deal With AA?

Acetophenone azine (also known as methylphenylketazine or bis[1-phenylethylidene]hydrazine) is composed of 2 acetophenone structures and a hydrazine moiety. It has been identified in EVA foam, which can be found in sports equipment such as shin pads or shin guards, shoes, and flip-flops. Raison-Peyron et al¹ confirmed the presence of AA in EVA foam but reported that they did not know the exact reason for its presence. The authors theorized that AA might be a catalyst during EVA polymerization and also noted that it has antimicrobial and antihelminthic activity.¹ Several authors noted that AA could be a by-product of EVA synthesis and that sports equipment manufacturers might not be aware of its presence in EVA.^2,4-6 Some noted that AA concentration was higher in shin guards than in shoe insoles; they thought this explained why patients reacted first to their shin guards and were perhaps even initially sensitized to the shin guards, as well as why shoe insole contact allergy commonly was reported later or only after allergy to shin guards had already developed.^4,6

Differential Diagnosis of Shin Pad or Shin Guard Dermatitis

We would be remiss if we did not mention the appropriate differential diagnosis when shin pad or shin guard dermatitis is identified. In fact, in most cases, shin guard dermatitis results from irritant contact dermatitis from friction, heat, and/or perspiration. Acetophenone azine contact allergy is not the most likely diagnosis when your sports-savvy, shin guard–wearing patient presents with anterior lower leg dermatitis. However, when conservative therapy (eg, barrier between the shin guard and the skin, control or management of perspiration, topical corticosteroid therapy) fails, patch testing to evaluate for ACD is indicated.

Management of AA Contact Allergy

As astute readers of this column are already aware, treatment of ACD requires strict allergen avoidance. You will find that we have the same recommendations for AA contact allergy. Given that there are only a handful of cases in the literature, there are limited recommendations on practical allergen avoidance other than “don’t wear the problem shin guards, shoe insoles, or flip-flops.” However, Darrigade et al⁶ recommended wearing polyurethane shin guards and leather insoles as alternatives when AA contact allergy is suspected or confirmed. They also made it clear that thick socks worn between shin guards and the skin often are not good enough to avoid ACD because the relevant allergens may achieve skin contact despite the barrier.⁶

Patch Testing for AA Contact Allergy

Historically, ACD to shin guards or shin pads, insoles of shoes, and even flip-flops has been associated with rubber-related chemicals such as mercapto mix, thiuram mix, N-isopropyl-N’-phenyl-p-phenylenediamine, thioureas, and carbamates, as well as dyes, benzoyl peroxide, and urea formaldehyde or phenol formaldehyde resins.¹ Most of these chemicals can be tested with standard screening series or supplemental series. Patients with contact allergy to AA may have negative patch testing to screening series and/or supplemental series and may have strong positive reactions to pieces of suspected foam shin pads or shin guards, shoes, and/or flip-flops. Although Koumaki et al⁵ recommended patch testing for AA contact allergy with AA 0.1% in acetone, Besner Morin et al⁴ mentioned that petrolatum may be a more desirable vehicle because it could maintain stability for a longer period of time. In fact, a 2021 article highlighting the American Contact Dermatitis Society Allergen of the Year recommends testing with either AA 0.1% in acetone or AA 0.1% in petrolatum.⁷ Unfortunately, AA is not commercially available for purchase at the time of publication. We are hopeful that this will change in the near future.

Final Interpretation

Acetophenone azine is an emerging allergen commonly identified in EVA foam and attributed to contact allergy to shin guards or pads, soles of shoes, and flip-flops. Most cases have been reported in Europe and Canada and have been identified in young male athletes. In addition to standard patch testing, athletes with lower leg dermatitis and/or dermatitis of the soles of the feet should undergo patch testing with AA 0.1% in acetone or petrolatum and pieces of the equipment and/or footwear.

It’s time for the American Contact Dermatitis Society (ACDS) Allergen of the Year! For 2021, the esteemed award goes to acetophenone azine (AA). If you have never heard of this chemical, you are not alone. Acetophenone azine has been identified in foam materials made of the copolymer ethyl-vinyl acetate (EVA). Contact allergy to AA initially was reported in 2016.¹ There are only a few European and Canadian case reports and one case series of AA contact allergy in the literature, all of which are associated with foam shin pads or shin guards, shoe insoles, and/or flip-flops.^2-6 Acetophenone azine is an important emerging allergen, and in this column, we will introduce you to AA and the sneaky places it can lurk and cause allergic contact dermatitis (ACD). We also highlight diagnosis, management, and patch testing for AA contact allergy.

AA Contact Allergy in the Literature

The first case of AA contact allergy was reported in Europe in 2016 when a 13-year-old male soccer player developed severe lower leg dermatitis and later generalized dermatitis associated with wearing foam shin guards.¹ Patch testing to standard and supplemental trays was negative or not relevant; however, the patient exhibited strong reactions when patch tested directly to a piece of the shin guard soaked in acetone, water, and ethanol. Additional testing with AA diluted in acetone, water, and petrolatum resulted in positive patch test reactions to acetone dilutions of 1%, 0.1%, 0.01%, and 0.001% and aqueous solutions of 1% and 0.1%. Chromatographic analyses with high-performance liquid chromatography (HPLC) of shin guard extracts confirmed the culprit allergen to be AA.¹

In the following months, the same clinic saw 2 more cases of AA contact allergy.² An 11-year-old male soccer player developed lower leg dermatitis and later generalized dermatitis from wearing shin guards. Months later, he also developed dermatitis on the soles of the feet, which was attributed to wearing flip-flops. Patch tests to pieces of the shin guards and flip-flops were positive; AA in acetone 0.1% and 0.01% also was positive. As you might expect, HPLC again confirmed the presence of AA in the shin guards and flip-flops. The third patient was a 12-year-old boy with dermatitis on the soles of both feet; later he also developed a generalized dermatitis. Patch testing to pieces of the insoles of his sneakers and AA in acetone 0.1% and 0.01% was positive. Again, HPLC was positive for the presence of AA in the insoles of his sneakers.²

Several more cases of AA contact allergy have been reported in the literature. A 29-year-old European male hockey player demonstrated contact allergy to the gray foam of his shin pads as well as localized leg dermatitis followed by generalized dermatitis (are you noticing a trend yet?), and later dermatitis on the soles of the feet with positive patch-test reactions to pieces of his shin pads and shoe insoles as well as AA 0.1% and 0.01% in acetone.³ A 6-year-old Canadian male soccer player presented with leg dermatitis and later generalized dermatitis and dermatitis on the soles of the feet with positive reactions to pieces of his shin pads and shoe insoles as well as to AA 1% and 0.1% in petrolatum.⁴ A 17-year-old British male (another trend, all males so far!) hockey player developed dermatitis localized to the legs and positive patch tests to the worn foam inner lining of his shin pads as well as to AA 0.1%, 0.01%, and 0.001% in acetone.⁵Finally, Darrigade et al⁶ published a case series of 6 European children with AA contact allergy associated with shin pads and shoes; all had localized leg dermatitis, and some had generalized dermatitis. Patch testing to pieces of shin pads and shoe parts as well as to AA 0.1% in petrolatum and/or acetone showed with positive reactions to the foam pieces and AA in all 6 patients.

What’s the Deal With AA?

Acetophenone azine (also known as methylphenylketazine or bis[1-phenylethylidene]hydrazine) is composed of 2 acetophenone structures and a hydrazine moiety. It has been identified in EVA foam, which can be found in sports equipment such as shin pads or shin guards, shoes, and flip-flops. Raison-Peyron et al¹ confirmed the presence of AA in EVA foam but reported that they did not know the exact reason for its presence. The authors theorized that AA might be a catalyst during EVA polymerization and also noted that it has antimicrobial and antihelminthic activity.¹ Several authors noted that AA could be a by-product of EVA synthesis and that sports equipment manufacturers might not be aware of its presence in EVA.^2,4-6 Some noted that AA concentration was higher in shin guards than in shoe insoles; they thought this explained why patients reacted first to their shin guards and were perhaps even initially sensitized to the shin guards, as well as why shoe insole contact allergy commonly was reported later or only after allergy to shin guards had already developed.^4,6

Differential Diagnosis of Shin Pad or Shin Guard Dermatitis

We would be remiss if we did not mention the appropriate differential diagnosis when shin pad or shin guard dermatitis is identified. In fact, in most cases, shin guard dermatitis results from irritant contact dermatitis from friction, heat, and/or perspiration. Acetophenone azine contact allergy is not the most likely diagnosis when your sports-savvy, shin guard–wearing patient presents with anterior lower leg dermatitis. However, when conservative therapy (eg, barrier between the shin guard and the skin, control or management of perspiration, topical corticosteroid therapy) fails, patch testing to evaluate for ACD is indicated.

Management of AA Contact Allergy

As astute readers of this column are already aware, treatment of ACD requires strict allergen avoidance. You will find that we have the same recommendations for AA contact allergy. Given that there are only a handful of cases in the literature, there are limited recommendations on practical allergen avoidance other than “don’t wear the problem shin guards, shoe insoles, or flip-flops.” However, Darrigade et al⁶ recommended wearing polyurethane shin guards and leather insoles as alternatives when AA contact allergy is suspected or confirmed. They also made it clear that thick socks worn between shin guards and the skin often are not good enough to avoid ACD because the relevant allergens may achieve skin contact despite the barrier.⁶

Patch Testing for AA Contact Allergy

Historically, ACD to shin guards or shin pads, insoles of shoes, and even flip-flops has been associated with rubber-related chemicals such as mercapto mix, thiuram mix, N-isopropyl-N’-phenyl-p-phenylenediamine, thioureas, and carbamates, as well as dyes, benzoyl peroxide, and urea formaldehyde or phenol formaldehyde resins.¹ Most of these chemicals can be tested with standard screening series or supplemental series. Patients with contact allergy to AA may have negative patch testing to screening series and/or supplemental series and may have strong positive reactions to pieces of suspected foam shin pads or shin guards, shoes, and/or flip-flops. Although Koumaki et al⁵ recommended patch testing for AA contact allergy with AA 0.1% in acetone, Besner Morin et al⁴ mentioned that petrolatum may be a more desirable vehicle because it could maintain stability for a longer period of time. In fact, a 2021 article highlighting the American Contact Dermatitis Society Allergen of the Year recommends testing with either AA 0.1% in acetone or AA 0.1% in petrolatum.⁷ Unfortunately, AA is not commercially available for purchase at the time of publication. We are hopeful that this will change in the near future.

Final Interpretation

Acetophenone azine is an emerging allergen commonly identified in EVA foam and attributed to contact allergy to shin guards or pads, soles of shoes, and flip-flops. Most cases have been reported in Europe and Canada and have been identified in young male athletes. In addition to standard patch testing, athletes with lower leg dermatitis and/or dermatitis of the soles of the feet should undergo patch testing with AA 0.1% in acetone or petrolatum and pieces of the equipment and/or footwear.

It’s time for the American Contact Dermatitis Society (ACDS) Allergen of the Year! For 2021, the esteemed award goes to acetophenone azine (AA). If you have never heard of this chemical, you are not alone. Acetophenone azine has been identified in foam materials made of the copolymer ethyl-vinyl acetate (EVA). Contact allergy to AA initially was reported in 2016.¹ There are only a few European and Canadian case reports and one case series of AA contact allergy in the literature, all of which are associated with foam shin pads or shin guards, shoe insoles, and/or flip-flops.^2-6 Acetophenone azine is an important emerging allergen, and in this column, we will introduce you to AA and the sneaky places it can lurk and cause allergic contact dermatitis (ACD). We also highlight diagnosis, management, and patch testing for AA contact allergy.

AA Contact Allergy in the Literature

The first case of AA contact allergy was reported in Europe in 2016 when a 13-year-old male soccer player developed severe lower leg dermatitis and later generalized dermatitis associated with wearing foam shin guards.¹ Patch testing to standard and supplemental trays was negative or not relevant; however, the patient exhibited strong reactions when patch tested directly to a piece of the shin guard soaked in acetone, water, and ethanol. Additional testing with AA diluted in acetone, water, and petrolatum resulted in positive patch test reactions to acetone dilutions of 1%, 0.1%, 0.01%, and 0.001% and aqueous solutions of 1% and 0.1%. Chromatographic analyses with high-performance liquid chromatography (HPLC) of shin guard extracts confirmed the culprit allergen to be AA.¹

In the following months, the same clinic saw 2 more cases of AA contact allergy.² An 11-year-old male soccer player developed lower leg dermatitis and later generalized dermatitis from wearing shin guards. Months later, he also developed dermatitis on the soles of the feet, which was attributed to wearing flip-flops. Patch tests to pieces of the shin guards and flip-flops were positive; AA in acetone 0.1% and 0.01% also was positive. As you might expect, HPLC again confirmed the presence of AA in the shin guards and flip-flops. The third patient was a 12-year-old boy with dermatitis on the soles of both feet; later he also developed a generalized dermatitis. Patch testing to pieces of the insoles of his sneakers and AA in acetone 0.1% and 0.01% was positive. Again, HPLC was positive for the presence of AA in the insoles of his sneakers.²

Several more cases of AA contact allergy have been reported in the literature. A 29-year-old European male hockey player demonstrated contact allergy to the gray foam of his shin pads as well as localized leg dermatitis followed by generalized dermatitis (are you noticing a trend yet?), and later dermatitis on the soles of the feet with positive patch-test reactions to pieces of his shin pads and shoe insoles as well as AA 0.1% and 0.01% in acetone.³ A 6-year-old Canadian male soccer player presented with leg dermatitis and later generalized dermatitis and dermatitis on the soles of the feet with positive reactions to pieces of his shin pads and shoe insoles as well as to AA 1% and 0.1% in petrolatum.⁴ A 17-year-old British male (another trend, all males so far!) hockey player developed dermatitis localized to the legs and positive patch tests to the worn foam inner lining of his shin pads as well as to AA 0.1%, 0.01%, and 0.001% in acetone.⁵Finally, Darrigade et al⁶ published a case series of 6 European children with AA contact allergy associated with shin pads and shoes; all had localized leg dermatitis, and some had generalized dermatitis. Patch testing to pieces of shin pads and shoe parts as well as to AA 0.1% in petrolatum and/or acetone showed with positive reactions to the foam pieces and AA in all 6 patients.

What’s the Deal With AA?

Acetophenone azine (also known as methylphenylketazine or bis[1-phenylethylidene]hydrazine) is composed of 2 acetophenone structures and a hydrazine moiety. It has been identified in EVA foam, which can be found in sports equipment such as shin pads or shin guards, shoes, and flip-flops. Raison-Peyron et al¹ confirmed the presence of AA in EVA foam but reported that they did not know the exact reason for its presence. The authors theorized that AA might be a catalyst during EVA polymerization and also noted that it has antimicrobial and antihelminthic activity.¹ Several authors noted that AA could be a by-product of EVA synthesis and that sports equipment manufacturers might not be aware of its presence in EVA.^2,4-6 Some noted that AA concentration was higher in shin guards than in shoe insoles; they thought this explained why patients reacted first to their shin guards and were perhaps even initially sensitized to the shin guards, as well as why shoe insole contact allergy commonly was reported later or only after allergy to shin guards had already developed.^4,6

Differential Diagnosis of Shin Pad or Shin Guard Dermatitis

We would be remiss if we did not mention the appropriate differential diagnosis when shin pad or shin guard dermatitis is identified. In fact, in most cases, shin guard dermatitis results from irritant contact dermatitis from friction, heat, and/or perspiration. Acetophenone azine contact allergy is not the most likely diagnosis when your sports-savvy, shin guard–wearing patient presents with anterior lower leg dermatitis. However, when conservative therapy (eg, barrier between the shin guard and the skin, control or management of perspiration, topical corticosteroid therapy) fails, patch testing to evaluate for ACD is indicated.

Management of AA Contact Allergy

As astute readers of this column are already aware, treatment of ACD requires strict allergen avoidance. You will find that we have the same recommendations for AA contact allergy. Given that there are only a handful of cases in the literature, there are limited recommendations on practical allergen avoidance other than “don’t wear the problem shin guards, shoe insoles, or flip-flops.” However, Darrigade et al⁶ recommended wearing polyurethane shin guards and leather insoles as alternatives when AA contact allergy is suspected or confirmed. They also made it clear that thick socks worn between shin guards and the skin often are not good enough to avoid ACD because the relevant allergens may achieve skin contact despite the barrier.⁶

Patch Testing for AA Contact Allergy

Historically, ACD to shin guards or shin pads, insoles of shoes, and even flip-flops has been associated with rubber-related chemicals such as mercapto mix, thiuram mix, N-isopropyl-N’-phenyl-p-phenylenediamine, thioureas, and carbamates, as well as dyes, benzoyl peroxide, and urea formaldehyde or phenol formaldehyde resins.¹ Most of these chemicals can be tested with standard screening series or supplemental series. Patients with contact allergy to AA may have negative patch testing to screening series and/or supplemental series and may have strong positive reactions to pieces of suspected foam shin pads or shin guards, shoes, and/or flip-flops. Although Koumaki et al⁵ recommended patch testing for AA contact allergy with AA 0.1% in acetone, Besner Morin et al⁴ mentioned that petrolatum may be a more desirable vehicle because it could maintain stability for a longer period of time. In fact, a 2021 article highlighting the American Contact Dermatitis Society Allergen of the Year recommends testing with either AA 0.1% in acetone or AA 0.1% in petrolatum.⁷ Unfortunately, AA is not commercially available for purchase at the time of publication. We are hopeful that this will change in the near future.

Final Interpretation

Acetophenone azine is an emerging allergen commonly identified in EVA foam and attributed to contact allergy to shin guards or pads, soles of shoes, and flip-flops. Most cases have been reported in Europe and Canada and have been identified in young male athletes. In addition to standard patch testing, athletes with lower leg dermatitis and/or dermatitis of the soles of the feet should undergo patch testing with AA 0.1% in acetone or petrolatum and pieces of the equipment and/or footwear.

To the Editor:

Melanocytic nevi are ubiquitous, and although they are benign, patients often desire to have them removed. We report a patient who presented to our clinic after attempting home removal of a concerning mole on the back with frankincense, a remedy that she found online.

A 43-year-old woman presented with a worrisome mole on the back. She had no personal history of skin cancer, but her father had a history of melanoma in situ in his 60s. The patient reported that she had the mole for years, but approximately 1 month prior to her visit she noticed that it began to bleed and crust, causing concern for melanoma. She read online that the lesion could be removed with topical application of the essential oil frankincense; she applied it directly to the lesion on the back. Within hours she developed a burn where it was applied with associated blistering.

Clinically, the lesion appeared as a darkly pigmented, well-circumscribed papule with hemorrhagic crust overlying a well-demarcated pink plaque (Figure 1). Dermatoscopically, the lesion lacked a pigment network and demonstrated 2 distinct pink papules with peripheral telangiectasia and a pink background with white streaks (Figure 2). A shave biopsy of the lesion demonstrated a nodular basal cell carcinoma extending to the base and margin.

Approximately 6 million individuals in the United States search the internet for health information daily, and as many as 41% of those do so to learn about alternative medicine.^5,6 Although information gleaned from search engines can be useful, it is unregulated and often can be inaccurate. Clinicians generally are unaware of the erroneous material presented online and, therefore, cannot appropriately combat patient misinformation. Our case demonstrates the need to maintain an awareness of common online fallacies to better answer patient questions and guide them to more accurate sources of dermatologic information and appropriate treatment.

To the Editor:

Melanocytic nevi are ubiquitous, and although they are benign, patients often desire to have them removed. We report a patient who presented to our clinic after attempting home removal of a concerning mole on the back with frankincense, a remedy that she found online.

A 43-year-old woman presented with a worrisome mole on the back. She had no personal history of skin cancer, but her father had a history of melanoma in situ in his 60s. The patient reported that she had the mole for years, but approximately 1 month prior to her visit she noticed that it began to bleed and crust, causing concern for melanoma. She read online that the lesion could be removed with topical application of the essential oil frankincense; she applied it directly to the lesion on the back. Within hours she developed a burn where it was applied with associated blistering.

Clinically, the lesion appeared as a darkly pigmented, well-circumscribed papule with hemorrhagic crust overlying a well-demarcated pink plaque (Figure 1). Dermatoscopically, the lesion lacked a pigment network and demonstrated 2 distinct pink papules with peripheral telangiectasia and a pink background with white streaks (Figure 2). A shave biopsy of the lesion demonstrated a nodular basal cell carcinoma extending to the base and margin.

Approximately 6 million individuals in the United States search the internet for health information daily, and as many as 41% of those do so to learn about alternative medicine.^5,6 Although information gleaned from search engines can be useful, it is unregulated and often can be inaccurate. Clinicians generally are unaware of the erroneous material presented online and, therefore, cannot appropriately combat patient misinformation. Our case demonstrates the need to maintain an awareness of common online fallacies to better answer patient questions and guide them to more accurate sources of dermatologic information and appropriate treatment.

To the Editor:

Melanocytic nevi are ubiquitous, and although they are benign, patients often desire to have them removed. We report a patient who presented to our clinic after attempting home removal of a concerning mole on the back with frankincense, a remedy that she found online.

A 43-year-old woman presented with a worrisome mole on the back. She had no personal history of skin cancer, but her father had a history of melanoma in situ in his 60s. The patient reported that she had the mole for years, but approximately 1 month prior to her visit she noticed that it began to bleed and crust, causing concern for melanoma. She read online that the lesion could be removed with topical application of the essential oil frankincense; she applied it directly to the lesion on the back. Within hours she developed a burn where it was applied with associated blistering.

Clinically, the lesion appeared as a darkly pigmented, well-circumscribed papule with hemorrhagic crust overlying a well-demarcated pink plaque (Figure 1). Dermatoscopically, the lesion lacked a pigment network and demonstrated 2 distinct pink papules with peripheral telangiectasia and a pink background with white streaks (Figure 2). A shave biopsy of the lesion demonstrated a nodular basal cell carcinoma extending to the base and margin.

Approximately 6 million individuals in the United States search the internet for health information daily, and as many as 41% of those do so to learn about alternative medicine.^5,6 Although information gleaned from search engines can be useful, it is unregulated and often can be inaccurate. Clinicians generally are unaware of the erroneous material presented online and, therefore, cannot appropriately combat patient misinformation. Our case demonstrates the need to maintain an awareness of common online fallacies to better answer patient questions and guide them to more accurate sources of dermatologic information and appropriate treatment.

To the Editor:

Psoriasis vulgaris is a chronic autoimmune inflammatory disease and biologic agents, such as anti–tumor necrosis factor α (TNF-α), are alternative drugs in case of resistance or adverse events to conventional ones.¹ The limitation of these agents is immunosuppression that may cause infections such as tuberculosis (TB). Prophylaxis is indicated to latent TB diseases if the purified protein derivative (tuberculin) skin test is higher than 5 mm before starting these treatments. The challenge in TB treatment is adverse drug reactions (ADRs) that are reported in 4% to 6% of cases.^2,3

Erythema multiforme–like dermatitis is a rare skin rash that develops due to isoniazid (INH). The clinical presentation includes erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH. Skin biopsy and patch tests are the supportive diagnostic methods. Isoniazid-associated skin rashes rarely are reported and generally are not severe enough to terminate the drug. We present a patient with psoriasis who received TB prophylaxis before anti–TNF-α use. He presented with erythema multiforme–like dermatitis due to INH. Withdrawal of the drug and treatment of the lesions were the first steps of intolerance, followed by a patch test with the culprit drug after recovery. We discuss the diagnostic drug allergy evaluation and treatment approach.

A 37-year-old man presented with a 15-year history of severe psoriasis with frequent flares. He was treated with various topical and systemic agents including acitretin and methotrexate at 4-year intervals. Despite the addition of phototherapy, he underwent a new treatment with anti–TNF-α, as the disease control with other treatments was insufficient. Before starting anti–TNF-α, preventive treatment against TB with INH (300 mg/d) was indicated with 20 mm of purified protein derivative. On approximately the 20th day of treatment, he developed pruritic erythema with desquamation and exfoliation localized to the hands and feet (Figure 1). Isoniazid was discontinued and a topical steroid was initiated. After 3 weeks, the skin lesions were completely improved and INH was reinitiated at the same dose with antihistamine prophylaxis (oral levocetirizine 5 mg/d). Seven days later, similar skin lesions presented that were more extensive on the arms and legs (Figure 2). Complete blood cell counts, renal and hepatic function tests, and hepatitis markers were within reference range in consultation with the allergy division. To distinguish the lesions from a psoriasis attack, a punch biopsy of the eruptive dermatitis showed erythema multiforme–like dermatitis including dermal edema and perivascular lymphocytic infiltration with no relation to psoriasis but consistent with a drug eruption. Isoniazid was discontinued, and the skin lesions resolved after 4 weeks of topical steroid and oral antihistamine use (Figure 3). There was no other drug use except INH, and a skin patch test with INH was positive at 72 hours (Figure 4). Skin tests with INH were done to 5 healthy lesions that were negative. Finally, TB prophylaxis was performed with rifampicin (10 mg/kg/d [600 mg/d]) for 4 months with no ADRs. The patient’s psoriasis lesions improved with anti–TNF-α that was initiated 1 month after starting TB prevention with rifampicin.

This case of erythema multiforme–like dermatitis was diagnosed with acral involvement, a positive patch test to INH, and lymphocytic inflammation in a skin biopsy. It was a drug-induced reaction, as skin lesions developed during INH intake and improved after drug withdrawal.

Isoniazid, also known as isonicotinylhydrazide, is an oral antibiotic used for the treatment of TB and other mycobacteria. Protective treatment against latent TB primarily is done with daily INH for 6 or 9 months; alternatively, INH may be taken weekly with rifapentine for 3 months or daily with rifampicin for 4 months. Daily rifampicin alone for 4 months also is an option. In general, these regimens have similar efficacy; however, in terms of safety, the rifampicin and rifapentine combination regimens have fewer hepatotoxicity events compared to the INH alone regimen, but there are more cutaneous and flulike reactions and gastrointestinal intolerance.⁴ Cutaneous ADRs to TB treatment such as mild itchiness and cutaneous eruptions usually are observed within 2 months of drug initiation. Pyrazinamide was reported as the most common drug associated with cutaneous ADRs, and INH was the rarest offending drug.⁵

The frequency of ADRs to INH is approximately 5.4%, and the most prevalent ADRs include asymptomatic elevation of serum liver enzyme concentrations, peripheral neuropathy, and hepatotoxicity, and skin lesions are less common.² Our patient’s laboratory test results excluded vitamin B deficiency, hepatic and renal dysfunction, and neuropathy.

Previously reported skin reactions related to INH were late-type reactions such as maculopapular rash, dermatitis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis.^5,6 The concerning prediagnosis of psoriatic exacerbation in our patient was ruled out by the absence of typical skin lesions such as well-defined, erythematous plaques and pustules and atypical localization such as the dorsal hands and feet rather than the knees, elbows, lumbosacral region, scalp, and abdomen, which is typical of psoriasis. DRESS syndrome was unlikely with the absence of fever, lymphadenopathy, hypereosinophilia, leukocytosis, and renal and hepatic dysfunction.⁷ There were no widespread blisters, epidermal detachment, or mucosal involvement on the trunk or face typically associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.^7,8 A possible diagnosis of contact dermatitis was suspected with likely skin lesions as exfoliation and chapping, typical localization on the hands and feet, and positive patch test that supported sensitization to the drug. However, the patient’s skin lesions were not eczematous (characterized by erythema, vesiculation, exudation, or bullous edema in the acute phase), and were not localized to areas of irritant exposure.³ In our patient, erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH was compatible with erythema multiforme, whereas the absence of target appearance, positive patch test, and late appearance were incompatible with erythema multiforme.⁸

Because the clinical picture did not fit contact dermatitis or erythema multiforme, a diagnosis of erythema multiforme–like noneczematous dermatitis was suggested. Noneczematous dermatitis has subtypes that include purpuric, lichenoid, pustular, lymphomatoid, dyshidrosiform, and pigmented, as well as erythema multiforme–like contact eruptions.⁹ These clinical entities are not associated with contact exposure, but are related to systemic exposure, as seen in our patient.¹⁰ The patch test positivity and skin biopsy report also supported the diagnosis of erythema multiforme–like dermatitis. Erythema multiforme–like dermatitis is thought to be caused by medications or infections inducing immunocomplexes and lymphocytic infiltration in the dermis and subepidermis. Nevertheless, the prognosis was self-limiting in both.⁸ The clinical polymorphism caused by INH in this patient was suggested to be related with individual susceptibility, variability of contact-activating modalities, and the targeted cutaneous structures. Furthermore, among the risk factors for cutaneous ADRs—HIV, polypharmacy, older age, and preexisting renal and liver impairment—the only notable factor in this patient was psoriasis as an autoimmune disorder.

Patients with skin diseases such as psoriasis should be followed up by closer monitoring during INH use. Withdrawal of the drug and symptomatic treatment of the lesions with corticosteroid and antihistamine are the first steps of drug intolerance. After complete recovery and termination of antiallergic drugs, diagnostic tests are recommended if the drug reaction was not life-threatening. Skin prick and intradermal tests are useful in early-type drug reactions, whereas patch testing and late evaluation of an intradermal test may be helpful in the diagnosis of delayed-type reactions. The full dose of INH is avoided in an intradermal test against irritation. A patch test with INH was performed by diluting a 100-mg tablet with 1 mL of distilled water, and used as 1/100, 1/10, and 1/1 dilutions.⁸ Patch testing with INH also was done in 5 healthy control patients to exclude the irritation effect in this case. The rechallenge of INH was done in a controlled manner in our patient to rule out psoriasis activation since it was a localized skin reaction with no serious ADR. An oral provocation test with the culprit drug is the gold standard of drug allergy diagnosis that should be done in a tertiary hospital with an intensive care unit.

This case of erythema multiforme–like dermatitis due to INH is interesting due to systemic intake of INH, which resulted in dermatitis with localized involvement similar to erythema multiforme but with no immunologic processes or prior sensitization. With the increasing use of anti–TNF-α treatment, INH use will be more prevalent than in the past for the treatment of latent TB. Even though the skin-restricted ADRs of INH are rare and minor, particular attention should be paid to patients with dermatologic diseases. In our case, diagnostic drug allergy evaluation was performed to optimize the second-line treatment of TB infection, in addition to early withdrawal of the culprit drug.

To the Editor:

Psoriasis vulgaris is a chronic autoimmune inflammatory disease and biologic agents, such as anti–tumor necrosis factor α (TNF-α), are alternative drugs in case of resistance or adverse events to conventional ones.¹ The limitation of these agents is immunosuppression that may cause infections such as tuberculosis (TB). Prophylaxis is indicated to latent TB diseases if the purified protein derivative (tuberculin) skin test is higher than 5 mm before starting these treatments. The challenge in TB treatment is adverse drug reactions (ADRs) that are reported in 4% to 6% of cases.^2,3

Erythema multiforme–like dermatitis is a rare skin rash that develops due to isoniazid (INH). The clinical presentation includes erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH. Skin biopsy and patch tests are the supportive diagnostic methods. Isoniazid-associated skin rashes rarely are reported and generally are not severe enough to terminate the drug. We present a patient with psoriasis who received TB prophylaxis before anti–TNF-α use. He presented with erythema multiforme–like dermatitis due to INH. Withdrawal of the drug and treatment of the lesions were the first steps of intolerance, followed by a patch test with the culprit drug after recovery. We discuss the diagnostic drug allergy evaluation and treatment approach.

A 37-year-old man presented with a 15-year history of severe psoriasis with frequent flares. He was treated with various topical and systemic agents including acitretin and methotrexate at 4-year intervals. Despite the addition of phototherapy, he underwent a new treatment with anti–TNF-α, as the disease control with other treatments was insufficient. Before starting anti–TNF-α, preventive treatment against TB with INH (300 mg/d) was indicated with 20 mm of purified protein derivative. On approximately the 20th day of treatment, he developed pruritic erythema with desquamation and exfoliation localized to the hands and feet (Figure 1). Isoniazid was discontinued and a topical steroid was initiated. After 3 weeks, the skin lesions were completely improved and INH was reinitiated at the same dose with antihistamine prophylaxis (oral levocetirizine 5 mg/d). Seven days later, similar skin lesions presented that were more extensive on the arms and legs (Figure 2). Complete blood cell counts, renal and hepatic function tests, and hepatitis markers were within reference range in consultation with the allergy division. To distinguish the lesions from a psoriasis attack, a punch biopsy of the eruptive dermatitis showed erythema multiforme–like dermatitis including dermal edema and perivascular lymphocytic infiltration with no relation to psoriasis but consistent with a drug eruption. Isoniazid was discontinued, and the skin lesions resolved after 4 weeks of topical steroid and oral antihistamine use (Figure 3). There was no other drug use except INH, and a skin patch test with INH was positive at 72 hours (Figure 4). Skin tests with INH were done to 5 healthy lesions that were negative. Finally, TB prophylaxis was performed with rifampicin (10 mg/kg/d [600 mg/d]) for 4 months with no ADRs. The patient’s psoriasis lesions improved with anti–TNF-α that was initiated 1 month after starting TB prevention with rifampicin.

This case of erythema multiforme–like dermatitis was diagnosed with acral involvement, a positive patch test to INH, and lymphocytic inflammation in a skin biopsy. It was a drug-induced reaction, as skin lesions developed during INH intake and improved after drug withdrawal.

Isoniazid, also known as isonicotinylhydrazide, is an oral antibiotic used for the treatment of TB and other mycobacteria. Protective treatment against latent TB primarily is done with daily INH for 6 or 9 months; alternatively, INH may be taken weekly with rifapentine for 3 months or daily with rifampicin for 4 months. Daily rifampicin alone for 4 months also is an option. In general, these regimens have similar efficacy; however, in terms of safety, the rifampicin and rifapentine combination regimens have fewer hepatotoxicity events compared to the INH alone regimen, but there are more cutaneous and flulike reactions and gastrointestinal intolerance.⁴ Cutaneous ADRs to TB treatment such as mild itchiness and cutaneous eruptions usually are observed within 2 months of drug initiation. Pyrazinamide was reported as the most common drug associated with cutaneous ADRs, and INH was the rarest offending drug.⁵

The frequency of ADRs to INH is approximately 5.4%, and the most prevalent ADRs include asymptomatic elevation of serum liver enzyme concentrations, peripheral neuropathy, and hepatotoxicity, and skin lesions are less common.² Our patient’s laboratory test results excluded vitamin B deficiency, hepatic and renal dysfunction, and neuropathy.

Previously reported skin reactions related to INH were late-type reactions such as maculopapular rash, dermatitis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis.^5,6 The concerning prediagnosis of psoriatic exacerbation in our patient was ruled out by the absence of typical skin lesions such as well-defined, erythematous plaques and pustules and atypical localization such as the dorsal hands and feet rather than the knees, elbows, lumbosacral region, scalp, and abdomen, which is typical of psoriasis. DRESS syndrome was unlikely with the absence of fever, lymphadenopathy, hypereosinophilia, leukocytosis, and renal and hepatic dysfunction.⁷ There were no widespread blisters, epidermal detachment, or mucosal involvement on the trunk or face typically associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.^7,8 A possible diagnosis of contact dermatitis was suspected with likely skin lesions as exfoliation and chapping, typical localization on the hands and feet, and positive patch test that supported sensitization to the drug. However, the patient’s skin lesions were not eczematous (characterized by erythema, vesiculation, exudation, or bullous edema in the acute phase), and were not localized to areas of irritant exposure.³ In our patient, erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH was compatible with erythema multiforme, whereas the absence of target appearance, positive patch test, and late appearance were incompatible with erythema multiforme.⁸

Because the clinical picture did not fit contact dermatitis or erythema multiforme, a diagnosis of erythema multiforme–like noneczematous dermatitis was suggested. Noneczematous dermatitis has subtypes that include purpuric, lichenoid, pustular, lymphomatoid, dyshidrosiform, and pigmented, as well as erythema multiforme–like contact eruptions.⁹ These clinical entities are not associated with contact exposure, but are related to systemic exposure, as seen in our patient.¹⁰ The patch test positivity and skin biopsy report also supported the diagnosis of erythema multiforme–like dermatitis. Erythema multiforme–like dermatitis is thought to be caused by medications or infections inducing immunocomplexes and lymphocytic infiltration in the dermis and subepidermis. Nevertheless, the prognosis was self-limiting in both.⁸ The clinical polymorphism caused by INH in this patient was suggested to be related with individual susceptibility, variability of contact-activating modalities, and the targeted cutaneous structures. Furthermore, among the risk factors for cutaneous ADRs—HIV, polypharmacy, older age, and preexisting renal and liver impairment—the only notable factor in this patient was psoriasis as an autoimmune disorder.

Patients with skin diseases such as psoriasis should be followed up by closer monitoring during INH use. Withdrawal of the drug and symptomatic treatment of the lesions with corticosteroid and antihistamine are the first steps of drug intolerance. After complete recovery and termination of antiallergic drugs, diagnostic tests are recommended if the drug reaction was not life-threatening. Skin prick and intradermal tests are useful in early-type drug reactions, whereas patch testing and late evaluation of an intradermal test may be helpful in the diagnosis of delayed-type reactions. The full dose of INH is avoided in an intradermal test against irritation. A patch test with INH was performed by diluting a 100-mg tablet with 1 mL of distilled water, and used as 1/100, 1/10, and 1/1 dilutions.⁸ Patch testing with INH also was done in 5 healthy control patients to exclude the irritation effect in this case. The rechallenge of INH was done in a controlled manner in our patient to rule out psoriasis activation since it was a localized skin reaction with no serious ADR. An oral provocation test with the culprit drug is the gold standard of drug allergy diagnosis that should be done in a tertiary hospital with an intensive care unit.

This case of erythema multiforme–like dermatitis due to INH is interesting due to systemic intake of INH, which resulted in dermatitis with localized involvement similar to erythema multiforme but with no immunologic processes or prior sensitization. With the increasing use of anti–TNF-α treatment, INH use will be more prevalent than in the past for the treatment of latent TB. Even though the skin-restricted ADRs of INH are rare and minor, particular attention should be paid to patients with dermatologic diseases. In our case, diagnostic drug allergy evaluation was performed to optimize the second-line treatment of TB infection, in addition to early withdrawal of the culprit drug.

To the Editor:

Psoriasis vulgaris is a chronic autoimmune inflammatory disease and biologic agents, such as anti–tumor necrosis factor α (TNF-α), are alternative drugs in case of resistance or adverse events to conventional ones.¹ The limitation of these agents is immunosuppression that may cause infections such as tuberculosis (TB). Prophylaxis is indicated to latent TB diseases if the purified protein derivative (tuberculin) skin test is higher than 5 mm before starting these treatments. The challenge in TB treatment is adverse drug reactions (ADRs) that are reported in 4% to 6% of cases.^2,3

Erythema multiforme–like dermatitis is a rare skin rash that develops due to isoniazid (INH). The clinical presentation includes erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH. Skin biopsy and patch tests are the supportive diagnostic methods. Isoniazid-associated skin rashes rarely are reported and generally are not severe enough to terminate the drug. We present a patient with psoriasis who received TB prophylaxis before anti–TNF-α use. He presented with erythema multiforme–like dermatitis due to INH. Withdrawal of the drug and treatment of the lesions were the first steps of intolerance, followed by a patch test with the culprit drug after recovery. We discuss the diagnostic drug allergy evaluation and treatment approach.

A 37-year-old man presented with a 15-year history of severe psoriasis with frequent flares. He was treated with various topical and systemic agents including acitretin and methotrexate at 4-year intervals. Despite the addition of phototherapy, he underwent a new treatment with anti–TNF-α, as the disease control with other treatments was insufficient. Before starting anti–TNF-α, preventive treatment against TB with INH (300 mg/d) was indicated with 20 mm of purified protein derivative. On approximately the 20th day of treatment, he developed pruritic erythema with desquamation and exfoliation localized to the hands and feet (Figure 1). Isoniazid was discontinued and a topical steroid was initiated. After 3 weeks, the skin lesions were completely improved and INH was reinitiated at the same dose with antihistamine prophylaxis (oral levocetirizine 5 mg/d). Seven days later, similar skin lesions presented that were more extensive on the arms and legs (Figure 2). Complete blood cell counts, renal and hepatic function tests, and hepatitis markers were within reference range in consultation with the allergy division. To distinguish the lesions from a psoriasis attack, a punch biopsy of the eruptive dermatitis showed erythema multiforme–like dermatitis including dermal edema and perivascular lymphocytic infiltration with no relation to psoriasis but consistent with a drug eruption. Isoniazid was discontinued, and the skin lesions resolved after 4 weeks of topical steroid and oral antihistamine use (Figure 3). There was no other drug use except INH, and a skin patch test with INH was positive at 72 hours (Figure 4). Skin tests with INH were done to 5 healthy lesions that were negative. Finally, TB prophylaxis was performed with rifampicin (10 mg/kg/d [600 mg/d]) for 4 months with no ADRs. The patient’s psoriasis lesions improved with anti–TNF-α that was initiated 1 month after starting TB prevention with rifampicin.

This case of erythema multiforme–like dermatitis was diagnosed with acral involvement, a positive patch test to INH, and lymphocytic inflammation in a skin biopsy. It was a drug-induced reaction, as skin lesions developed during INH intake and improved after drug withdrawal.

Isoniazid, also known as isonicotinylhydrazide, is an oral antibiotic used for the treatment of TB and other mycobacteria. Protective treatment against latent TB primarily is done with daily INH for 6 or 9 months; alternatively, INH may be taken weekly with rifapentine for 3 months or daily with rifampicin for 4 months. Daily rifampicin alone for 4 months also is an option. In general, these regimens have similar efficacy; however, in terms of safety, the rifampicin and rifapentine combination regimens have fewer hepatotoxicity events compared to the INH alone regimen, but there are more cutaneous and flulike reactions and gastrointestinal intolerance.⁴ Cutaneous ADRs to TB treatment such as mild itchiness and cutaneous eruptions usually are observed within 2 months of drug initiation. Pyrazinamide was reported as the most common drug associated with cutaneous ADRs, and INH was the rarest offending drug.⁵

The frequency of ADRs to INH is approximately 5.4%, and the most prevalent ADRs include asymptomatic elevation of serum liver enzyme concentrations, peripheral neuropathy, and hepatotoxicity, and skin lesions are less common.² Our patient’s laboratory test results excluded vitamin B deficiency, hepatic and renal dysfunction, and neuropathy.

Previously reported skin reactions related to INH were late-type reactions such as maculopapular rash, dermatitis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis.^5,6 The concerning prediagnosis of psoriatic exacerbation in our patient was ruled out by the absence of typical skin lesions such as well-defined, erythematous plaques and pustules and atypical localization such as the dorsal hands and feet rather than the knees, elbows, lumbosacral region, scalp, and abdomen, which is typical of psoriasis. DRESS syndrome was unlikely with the absence of fever, lymphadenopathy, hypereosinophilia, leukocytosis, and renal and hepatic dysfunction.⁷ There were no widespread blisters, epidermal detachment, or mucosal involvement on the trunk or face typically associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.^7,8 A possible diagnosis of contact dermatitis was suspected with likely skin lesions as exfoliation and chapping, typical localization on the hands and feet, and positive patch test that supported sensitization to the drug. However, the patient’s skin lesions were not eczematous (characterized by erythema, vesiculation, exudation, or bullous edema in the acute phase), and were not localized to areas of irritant exposure.³ In our patient, erythematoedematous lesions in an acral distribution with no mucosal involvement and systemic exposure to INH was compatible with erythema multiforme, whereas the absence of target appearance, positive patch test, and late appearance were incompatible with erythema multiforme.⁸

Because the clinical picture did not fit contact dermatitis or erythema multiforme, a diagnosis of erythema multiforme–like noneczematous dermatitis was suggested. Noneczematous dermatitis has subtypes that include purpuric, lichenoid, pustular, lymphomatoid, dyshidrosiform, and pigmented, as well as erythema multiforme–like contact eruptions.⁹ These clinical entities are not associated with contact exposure, but are related to systemic exposure, as seen in our patient.¹⁰ The patch test positivity and skin biopsy report also supported the diagnosis of erythema multiforme–like dermatitis. Erythema multiforme–like dermatitis is thought to be caused by medications or infections inducing immunocomplexes and lymphocytic infiltration in the dermis and subepidermis. Nevertheless, the prognosis was self-limiting in both.⁸ The clinical polymorphism caused by INH in this patient was suggested to be related with individual susceptibility, variability of contact-activating modalities, and the targeted cutaneous structures. Furthermore, among the risk factors for cutaneous ADRs—HIV, polypharmacy, older age, and preexisting renal and liver impairment—the only notable factor in this patient was psoriasis as an autoimmune disorder.

Patients with skin diseases such as psoriasis should be followed up by closer monitoring during INH use. Withdrawal of the drug and symptomatic treatment of the lesions with corticosteroid and antihistamine are the first steps of drug intolerance. After complete recovery and termination of antiallergic drugs, diagnostic tests are recommended if the drug reaction was not life-threatening. Skin prick and intradermal tests are useful in early-type drug reactions, whereas patch testing and late evaluation of an intradermal test may be helpful in the diagnosis of delayed-type reactions. The full dose of INH is avoided in an intradermal test against irritation. A patch test with INH was performed by diluting a 100-mg tablet with 1 mL of distilled water, and used as 1/100, 1/10, and 1/1 dilutions.⁸ Patch testing with INH also was done in 5 healthy control patients to exclude the irritation effect in this case. The rechallenge of INH was done in a controlled manner in our patient to rule out psoriasis activation since it was a localized skin reaction with no serious ADR. An oral provocation test with the culprit drug is the gold standard of drug allergy diagnosis that should be done in a tertiary hospital with an intensive care unit.

This case of erythema multiforme–like dermatitis due to INH is interesting due to systemic intake of INH, which resulted in dermatitis with localized involvement similar to erythema multiforme but with no immunologic processes or prior sensitization. With the increasing use of anti–TNF-α treatment, INH use will be more prevalent than in the past for the treatment of latent TB. Even though the skin-restricted ADRs of INH are rare and minor, particular attention should be paid to patients with dermatologic diseases. In our case, diagnostic drug allergy evaluation was performed to optimize the second-line treatment of TB infection, in addition to early withdrawal of the culprit drug.

Phytophotodermatitis (PPD) is a nonallergic contact dermatitis and thus is independent of the immune system, so prior sensitization is not required.^1-3 It sometimes is known by colorful names such as margarita photodermatitis, in which a slice of lime in a refreshing summer drink may be etiologic,^4,5 or berloque dermatitis, caused by exposure to perfumes containing bergapten (5-methoxypsoralen).^6,7 Phytophotodermatitis may develop when phototoxic agents such as furocoumarins, which protect plants from fungal pathogens, and psoralens are applied to the skin followed by exposure to UV light, more specifically in the UVA range of 320 to 400 nm. Thus, these chemicals produce a phototoxic rather than photoallergic reaction, leading to cellular damage. Furocoumarins and psoralens often are found in plants such as celery and figs as well as in citrus fruits such as limes, lemons, and grapefruits. Exposure may be cryptic, as the patient may not consider or mention the eruption as possibly caused by activities such as soaking one’s feet in a folk remedy containing fig leaves.^7,8 Once these phototoxic agents come in contact with the skin, the symptoms of PPD may arise within 24 hours of exposure, beginning as an acute dermatitis with erythema, edema, vesicles, or bullae accompanied by pain and itching.

Etiology

Phytophotodermatitis is caused by exposure to several different types of plants, including Ficus carica (common fig), the genus Citrus (eg, lime, lemon), or Pastina sativa (wild parsnip). Each of these contain furocoumarins and psoralens—phototoxic agents that cause cellular damage with epidermal necrosis and resultant pain when the skin is exposed to UVA light.^1-4 There are 2 types of photochemical reactions in PPD: type I reactions occur in the absence of oxygen, whereas oxygen is present in type II reactions. Both damage cell membranes and DNA, which then results in DNA interstrand cross-linking between the psoralen furan ring and the thymine or cytosine of DNA, activating arachidonic acid metabolic pathways to produce cell death.¹

Epidemiology

The incidence of PPD is unknown due to the high variability of reactions in individuals spanning from children to the elderly. It can be caused by many different wild and domestic plants in many areas of the world and can affect any individual regardless of age, race, gender, or ethnicity. Some individuals may be affected by hyperpigmentation without prominent inflammation.⁸ Diagnosis of PPD can be challenging, and an occupation and recreational history of exposure or recent travel with possible contact with plants may be required.

Occupational Dermatitis

Phytophotodermatitis also may be an occupational disease.^9-12 Occupational exposure may occur in soldiers during military drills and other activities, farm workers, chefs, gardeners, groundskeepers, food processors, bartenders, and florists. Wearing protective gloves when handling plants such as limes, lemons, grapefruit, celery, or parsnips may prevent occupational exposure. Exposure to hogweed, an invasive species originally introduced as an ornamental plant in Europe and the United States, can produce a dramatic acute photodermatitis from exposure to its sap, which contains the psoralens 5-methoxypsoralen and 8-methylpsoralen.^9-11

Recreational Dermatitis

Phytophotodermatitis may be caused by exposure to phototoxic agents during leisure activities. Recreational exposure can occur almost anywhere, including in the kitchen, backyard, park, or woods, as well as at the beach. One notable culprit in recreational PPD is cooking with limes, parsley, or parsnips—plants that often are employed as garnishes in dishes, allowing early exposure of juices on the hands. Individuals who garden recreationally should be aware of ornamental plants such as hogweed and figs, which are notorious for causing PPD.¹³ Children’s camp counselors should have knowledge of PPD, as children have considerable curiosity and may touch or play with attractive plants such as hogweed. Children enjoying sports in parks can accidentally fall onto or be exposed to wild parsnip or hogweed growing nearby and wake up the next day with erythema and burning.¹⁴ Photoprotection is important, but sunscreens containing carrot extract can produce PPD.¹⁵ Widespread PPD over 80% of the body surface area due to sunbathing after applying fig leaf tea as a tanning agent has been described.¹⁶ Eating figs does not cause photosensitization unless the juice is smeared onto the skin. Margarita dermatitis and “Mexican beer dermatitis” can occur due to limes and other citrus fruits being used as ingredients in summer drinks.⁵ Similarly, preparing sangria may produce PPD from lime and lemon juices.¹⁷ In one report, hiking in Corsica resulted in PPD following incidental contact with the endemic plant Peucedanum paniculatum.¹⁸

Perfume (Berloque) Dermatitis

Perfume dermatitis, or berloque dermatitis, is a type of PPD for which the name is derived from the German word berlock or the French word berloque meaning trinket or charm; it was first described in 1925 by Rosenthal⁷ with regard to pendantlike streaks of pigmentation on the neck, face, arms, or trunk. The dermatitis develops due to bergapten, a component of bergamot oil, which is derived from the rind of Citrus bergamia. Many perfumes contain bergamot oil, but the incidence of this condition has been diminished due to use of artificial bergamot oil.⁶

Clinical Manifestation

Phytophotodermatitis is first evident as erythematous patches that appear within 24 hours of initial exposure to a phototoxic agent and UVA light, sometimes with a burning sensation. Solar exposure within 48 hours of sufficient plant exposure is required. Perfuse sweating may enhance the reaction.¹⁹ Rarely, it first may be seen with the sudden appearance of asymptomatic hyperpigmentation. One may see the pattern of splash marks from lime or lemon juice (Figure 1). The acute dermatitis may be associated with adjacent cutaneous edema near the reaction site or along with the erythema and blister formation. Its severity is related to the intensity of sun exposure and amount of furocoumarins.² The most common etiologic plants are citrus fruits such as limes and lemons, but it also can be caused by celery, figs, parsley, parsnips, and even mustard.^1-3,12 Wild parsley may grow in grass, producing a bizarre pattern on the back in children who lay in the grass and then spend time in the sun. Phytophotodermatitis usually is followed by postinflammatory hyperpigmentation, which may be the principal or only finding in some individuals.⁸

Differential Diagnosis

Phytophotodermatitis may resemble other types of dermatitis, particularly other forms of contact dermatitis such poison ivy, and occasionally other environmental simulants such as jellyfish stings.^1-6,20,21 Photosensitizing disorders including porphyria cutanea tarda, pseudoporphyria, and lupus erythematosus must be distinguished from PPD.^22-24 Photosensitizing medications such tetracyclines, thiazide diuretics, sulfonamides, griseofulvin, and sulfonylureas should be considered. Airborne contact dermatitis may resemble PPD, as when poison ivy is burned and is exposed to the skin in sites of airborne contact.²⁰ Excessive solar exposure is popular, particularly among adolescents, so sunburn and sunburnlike reactions can be noteworthy.^25,26

Treatment

Phytophotodermatitis can be treated with topical steroids, sometimes adding an oral antihistamine, and occasionally oral steroids.^2-4 Localized pain or a burning sensation should respond to therapy. Alternatively, a cold compress applied to the skin can relieve the pain and pruritus, and the burn can be debrided and dressed daily with silver sulfadiazine plus an oral nonsteroidal anti-inflammatory drug. This eruption should be self-limited as long as it is recognized early and the cause avoided. Management of acute exposure includes prompt application of soap and water and avoidance of UV light exposure for 48 to 72 hours to prevent psoralen photoactivation.

Because PPD is essentially a chemical burn, a burn protocol and possible referral to a burn center may be needed, whether the reaction is acute or widespread.^{11,12,14,27,28} Surgical debridement and skin grafting rarely may be mandated.¹⁴ Postinflammatory hyperpigmentation may ensue as the dermatitis resolves but is not common.

The best approach for PPD is prevention (Figure 2). Individuals who are at risk should be aware of their surroundings and potential plants of concern and employ personal protective equipment to shield the skin from plant sap, which should be promptly removed if it comes in contact with the skin.

Phytophotodermatitis (PPD) is a nonallergic contact dermatitis and thus is independent of the immune system, so prior sensitization is not required.^1-3 It sometimes is known by colorful names such as margarita photodermatitis, in which a slice of lime in a refreshing summer drink may be etiologic,^4,5 or berloque dermatitis, caused by exposure to perfumes containing bergapten (5-methoxypsoralen).^6,7 Phytophotodermatitis may develop when phototoxic agents such as furocoumarins, which protect plants from fungal pathogens, and psoralens are applied to the skin followed by exposure to UV light, more specifically in the UVA range of 320 to 400 nm. Thus, these chemicals produce a phototoxic rather than photoallergic reaction, leading to cellular damage. Furocoumarins and psoralens often are found in plants such as celery and figs as well as in citrus fruits such as limes, lemons, and grapefruits. Exposure may be cryptic, as the patient may not consider or mention the eruption as possibly caused by activities such as soaking one’s feet in a folk remedy containing fig leaves.^7,8 Once these phototoxic agents come in contact with the skin, the symptoms of PPD may arise within 24 hours of exposure, beginning as an acute dermatitis with erythema, edema, vesicles, or bullae accompanied by pain and itching.

Etiology

Phytophotodermatitis is caused by exposure to several different types of plants, including Ficus carica (common fig), the genus Citrus (eg, lime, lemon), or Pastina sativa (wild parsnip). Each of these contain furocoumarins and psoralens—phototoxic agents that cause cellular damage with epidermal necrosis and resultant pain when the skin is exposed to UVA light.^1-4 There are 2 types of photochemical reactions in PPD: type I reactions occur in the absence of oxygen, whereas oxygen is present in type II reactions. Both damage cell membranes and DNA, which then results in DNA interstrand cross-linking between the psoralen furan ring and the thymine or cytosine of DNA, activating arachidonic acid metabolic pathways to produce cell death.¹

Epidemiology

The incidence of PPD is unknown due to the high variability of reactions in individuals spanning from children to the elderly. It can be caused by many different wild and domestic plants in many areas of the world and can affect any individual regardless of age, race, gender, or ethnicity. Some individuals may be affected by hyperpigmentation without prominent inflammation.⁸ Diagnosis of PPD can be challenging, and an occupation and recreational history of exposure or recent travel with possible contact with plants may be required.

Occupational Dermatitis

Phytophotodermatitis also may be an occupational disease.^9-12 Occupational exposure may occur in soldiers during military drills and other activities, farm workers, chefs, gardeners, groundskeepers, food processors, bartenders, and florists. Wearing protective gloves when handling plants such as limes, lemons, grapefruit, celery, or parsnips may prevent occupational exposure. Exposure to hogweed, an invasive species originally introduced as an ornamental plant in Europe and the United States, can produce a dramatic acute photodermatitis from exposure to its sap, which contains the psoralens 5-methoxypsoralen and 8-methylpsoralen.^9-11

Recreational Dermatitis

Phytophotodermatitis may be caused by exposure to phototoxic agents during leisure activities. Recreational exposure can occur almost anywhere, including in the kitchen, backyard, park, or woods, as well as at the beach. One notable culprit in recreational PPD is cooking with limes, parsley, or parsnips—plants that often are employed as garnishes in dishes, allowing early exposure of juices on the hands. Individuals who garden recreationally should be aware of ornamental plants such as hogweed and figs, which are notorious for causing PPD.¹³ Children’s camp counselors should have knowledge of PPD, as children have considerable curiosity and may touch or play with attractive plants such as hogweed. Children enjoying sports in parks can accidentally fall onto or be exposed to wild parsnip or hogweed growing nearby and wake up the next day with erythema and burning.¹⁴ Photoprotection is important, but sunscreens containing carrot extract can produce PPD.¹⁵ Widespread PPD over 80% of the body surface area due to sunbathing after applying fig leaf tea as a tanning agent has been described.¹⁶ Eating figs does not cause photosensitization unless the juice is smeared onto the skin. Margarita dermatitis and “Mexican beer dermatitis” can occur due to limes and other citrus fruits being used as ingredients in summer drinks.⁵ Similarly, preparing sangria may produce PPD from lime and lemon juices.¹⁷ In one report, hiking in Corsica resulted in PPD following incidental contact with the endemic plant Peucedanum paniculatum.¹⁸

Perfume (Berloque) Dermatitis

Perfume dermatitis, or berloque dermatitis, is a type of PPD for which the name is derived from the German word berlock or the French word berloque meaning trinket or charm; it was first described in 1925 by Rosenthal⁷ with regard to pendantlike streaks of pigmentation on the neck, face, arms, or trunk. The dermatitis develops due to bergapten, a component of bergamot oil, which is derived from the rind of Citrus bergamia. Many perfumes contain bergamot oil, but the incidence of this condition has been diminished due to use of artificial bergamot oil.⁶

Clinical Manifestation

Phytophotodermatitis is first evident as erythematous patches that appear within 24 hours of initial exposure to a phototoxic agent and UVA light, sometimes with a burning sensation. Solar exposure within 48 hours of sufficient plant exposure is required. Perfuse sweating may enhance the reaction.¹⁹ Rarely, it first may be seen with the sudden appearance of asymptomatic hyperpigmentation. One may see the pattern of splash marks from lime or lemon juice (Figure 1). The acute dermatitis may be associated with adjacent cutaneous edema near the reaction site or along with the erythema and blister formation. Its severity is related to the intensity of sun exposure and amount of furocoumarins.² The most common etiologic plants are citrus fruits such as limes and lemons, but it also can be caused by celery, figs, parsley, parsnips, and even mustard.^1-3,12 Wild parsley may grow in grass, producing a bizarre pattern on the back in children who lay in the grass and then spend time in the sun. Phytophotodermatitis usually is followed by postinflammatory hyperpigmentation, which may be the principal or only finding in some individuals.⁸

Differential Diagnosis

Phytophotodermatitis may resemble other types of dermatitis, particularly other forms of contact dermatitis such poison ivy, and occasionally other environmental simulants such as jellyfish stings.^1-6,20,21 Photosensitizing disorders including porphyria cutanea tarda, pseudoporphyria, and lupus erythematosus must be distinguished from PPD.^22-24 Photosensitizing medications such tetracyclines, thiazide diuretics, sulfonamides, griseofulvin, and sulfonylureas should be considered. Airborne contact dermatitis may resemble PPD, as when poison ivy is burned and is exposed to the skin in sites of airborne contact.²⁰ Excessive solar exposure is popular, particularly among adolescents, so sunburn and sunburnlike reactions can be noteworthy.^25,26

Treatment

Phytophotodermatitis can be treated with topical steroids, sometimes adding an oral antihistamine, and occasionally oral steroids.^2-4 Localized pain or a burning sensation should respond to therapy. Alternatively, a cold compress applied to the skin can relieve the pain and pruritus, and the burn can be debrided and dressed daily with silver sulfadiazine plus an oral nonsteroidal anti-inflammatory drug. This eruption should be self-limited as long as it is recognized early and the cause avoided. Management of acute exposure includes prompt application of soap and water and avoidance of UV light exposure for 48 to 72 hours to prevent psoralen photoactivation.

Because PPD is essentially a chemical burn, a burn protocol and possible referral to a burn center may be needed, whether the reaction is acute or widespread.^{11,12,14,27,28} Surgical debridement and skin grafting rarely may be mandated.¹⁴ Postinflammatory hyperpigmentation may ensue as the dermatitis resolves but is not common.

The best approach for PPD is prevention (Figure 2). Individuals who are at risk should be aware of their surroundings and potential plants of concern and employ personal protective equipment to shield the skin from plant sap, which should be promptly removed if it comes in contact with the skin.

Phytophotodermatitis (PPD) is a nonallergic contact dermatitis and thus is independent of the immune system, so prior sensitization is not required.^1-3 It sometimes is known by colorful names such as margarita photodermatitis, in which a slice of lime in a refreshing summer drink may be etiologic,^4,5 or berloque dermatitis, caused by exposure to perfumes containing bergapten (5-methoxypsoralen).^6,7 Phytophotodermatitis may develop when phototoxic agents such as furocoumarins, which protect plants from fungal pathogens, and psoralens are applied to the skin followed by exposure to UV light, more specifically in the UVA range of 320 to 400 nm. Thus, these chemicals produce a phototoxic rather than photoallergic reaction, leading to cellular damage. Furocoumarins and psoralens often are found in plants such as celery and figs as well as in citrus fruits such as limes, lemons, and grapefruits. Exposure may be cryptic, as the patient may not consider or mention the eruption as possibly caused by activities such as soaking one’s feet in a folk remedy containing fig leaves.^7,8 Once these phototoxic agents come in contact with the skin, the symptoms of PPD may arise within 24 hours of exposure, beginning as an acute dermatitis with erythema, edema, vesicles, or bullae accompanied by pain and itching.

Etiology

Phytophotodermatitis is caused by exposure to several different types of plants, including Ficus carica (common fig), the genus Citrus (eg, lime, lemon), or Pastina sativa (wild parsnip). Each of these contain furocoumarins and psoralens—phototoxic agents that cause cellular damage with epidermal necrosis and resultant pain when the skin is exposed to UVA light.^1-4 There are 2 types of photochemical reactions in PPD: type I reactions occur in the absence of oxygen, whereas oxygen is present in type II reactions. Both damage cell membranes and DNA, which then results in DNA interstrand cross-linking between the psoralen furan ring and the thymine or cytosine of DNA, activating arachidonic acid metabolic pathways to produce cell death.¹

Epidemiology

The incidence of PPD is unknown due to the high variability of reactions in individuals spanning from children to the elderly. It can be caused by many different wild and domestic plants in many areas of the world and can affect any individual regardless of age, race, gender, or ethnicity. Some individuals may be affected by hyperpigmentation without prominent inflammation.⁸ Diagnosis of PPD can be challenging, and an occupation and recreational history of exposure or recent travel with possible contact with plants may be required.

Occupational Dermatitis

Phytophotodermatitis also may be an occupational disease.^9-12 Occupational exposure may occur in soldiers during military drills and other activities, farm workers, chefs, gardeners, groundskeepers, food processors, bartenders, and florists. Wearing protective gloves when handling plants such as limes, lemons, grapefruit, celery, or parsnips may prevent occupational exposure. Exposure to hogweed, an invasive species originally introduced as an ornamental plant in Europe and the United States, can produce a dramatic acute photodermatitis from exposure to its sap, which contains the psoralens 5-methoxypsoralen and 8-methylpsoralen.^9-11

Recreational Dermatitis

Phytophotodermatitis may be caused by exposure to phototoxic agents during leisure activities. Recreational exposure can occur almost anywhere, including in the kitchen, backyard, park, or woods, as well as at the beach. One notable culprit in recreational PPD is cooking with limes, parsley, or parsnips—plants that often are employed as garnishes in dishes, allowing early exposure of juices on the hands. Individuals who garden recreationally should be aware of ornamental plants such as hogweed and figs, which are notorious for causing PPD.¹³ Children’s camp counselors should have knowledge of PPD, as children have considerable curiosity and may touch or play with attractive plants such as hogweed. Children enjoying sports in parks can accidentally fall onto or be exposed to wild parsnip or hogweed growing nearby and wake up the next day with erythema and burning.¹⁴ Photoprotection is important, but sunscreens containing carrot extract can produce PPD.¹⁵ Widespread PPD over 80% of the body surface area due to sunbathing after applying fig leaf tea as a tanning agent has been described.¹⁶ Eating figs does not cause photosensitization unless the juice is smeared onto the skin. Margarita dermatitis and “Mexican beer dermatitis” can occur due to limes and other citrus fruits being used as ingredients in summer drinks.⁵ Similarly, preparing sangria may produce PPD from lime and lemon juices.¹⁷ In one report, hiking in Corsica resulted in PPD following incidental contact with the endemic plant Peucedanum paniculatum.¹⁸

Perfume (Berloque) Dermatitis

Perfume dermatitis, or berloque dermatitis, is a type of PPD for which the name is derived from the German word berlock or the French word berloque meaning trinket or charm; it was first described in 1925 by Rosenthal⁷ with regard to pendantlike streaks of pigmentation on the neck, face, arms, or trunk. The dermatitis develops due to bergapten, a component of bergamot oil, which is derived from the rind of Citrus bergamia. Many perfumes contain bergamot oil, but the incidence of this condition has been diminished due to use of artificial bergamot oil.⁶

Clinical Manifestation

Phytophotodermatitis is first evident as erythematous patches that appear within 24 hours of initial exposure to a phototoxic agent and UVA light, sometimes with a burning sensation. Solar exposure within 48 hours of sufficient plant exposure is required. Perfuse sweating may enhance the reaction.¹⁹ Rarely, it first may be seen with the sudden appearance of asymptomatic hyperpigmentation. One may see the pattern of splash marks from lime or lemon juice (Figure 1). The acute dermatitis may be associated with adjacent cutaneous edema near the reaction site or along with the erythema and blister formation. Its severity is related to the intensity of sun exposure and amount of furocoumarins.² The most common etiologic plants are citrus fruits such as limes and lemons, but it also can be caused by celery, figs, parsley, parsnips, and even mustard.^1-3,12 Wild parsley may grow in grass, producing a bizarre pattern on the back in children who lay in the grass and then spend time in the sun. Phytophotodermatitis usually is followed by postinflammatory hyperpigmentation, which may be the principal or only finding in some individuals.⁸

Differential Diagnosis

Phytophotodermatitis may resemble other types of dermatitis, particularly other forms of contact dermatitis such poison ivy, and occasionally other environmental simulants such as jellyfish stings.^1-6,20,21 Photosensitizing disorders including porphyria cutanea tarda, pseudoporphyria, and lupus erythematosus must be distinguished from PPD.^22-24 Photosensitizing medications such tetracyclines, thiazide diuretics, sulfonamides, griseofulvin, and sulfonylureas should be considered. Airborne contact dermatitis may resemble PPD, as when poison ivy is burned and is exposed to the skin in sites of airborne contact.²⁰ Excessive solar exposure is popular, particularly among adolescents, so sunburn and sunburnlike reactions can be noteworthy.^25,26

Treatment

Phytophotodermatitis can be treated with topical steroids, sometimes adding an oral antihistamine, and occasionally oral steroids.^2-4 Localized pain or a burning sensation should respond to therapy. Alternatively, a cold compress applied to the skin can relieve the pain and pruritus, and the burn can be debrided and dressed daily with silver sulfadiazine plus an oral nonsteroidal anti-inflammatory drug. This eruption should be self-limited as long as it is recognized early and the cause avoided. Management of acute exposure includes prompt application of soap and water and avoidance of UV light exposure for 48 to 72 hours to prevent psoralen photoactivation.

Because PPD is essentially a chemical burn, a burn protocol and possible referral to a burn center may be needed, whether the reaction is acute or widespread.^{11,12,14,27,28} Surgical debridement and skin grafting rarely may be mandated.¹⁴ Postinflammatory hyperpigmentation may ensue as the dermatitis resolves but is not common.

The best approach for PPD is prevention (Figure 2). Individuals who are at risk should be aware of their surroundings and potential plants of concern and employ personal protective equipment to shield the skin from plant sap, which should be promptly removed if it comes in contact with the skin.

Evidence of human exposure to mercury dates as far back as the Egyptians in 1500 bc . ¹ The ancient Chinese believed mercury could prolong life, heal bones, and maintain vitality. ² Western medicine has utilized mercury in diuretics, laxatives, antibacterial agents, and antiseptics. ³ Health effects caused by chronic mercury exposure became increasingly apparent in the 1800s after hat makers who had inhaled mercuric nitrate vapors began to present with a host of neurologic symptoms, which is where the p hrase "mad as a hatter" was derived. ^4,5 In 1889, French neurologist Jean-Martin Charcot attributed rapid tremors to mercury poisoning. ⁶ By 1940, Kinnier Wilson ⁷ further characterized the effects of mercury, describing mercury-induced cognitive impairments. In the 1960s, Japanese researchers correlated elevated urinary mercury levels with an outbreak of Minamata disease, a condition characterized by tremors, sensory loss, ataxia, and visual constrictions. ⁸ The World Health Organization considers mercury to be one of the top 10 chemicals of major public health concern. ⁹

Mercury release in the environment primarily is a function of human activity, including coal-fired power plants, residential heating, and mining.^9,10 Mercury from these sources is commonly found in the sediment of lakes and bays, where it is enzymatically converted to methylmercury by aquatic microorganisms; subsequent food chain biomagnification results in elevated mercury levels in apex predators. Substantial release of mercury into the environment also can be attributed to health care facilities from their use of thermometers containing 0.5 to 3 g of elemental mercury,¹¹ blood pressure monitors, and medical waste incinerators.⁵

Mercury has been reported as the second most common cause of heavy metal poisoning after lead.¹² Standards from the US Food and Drug Administration dictate that methylmercury levels in fish and wheat products must not exceed 1 ppm.¹³ Most plant and animal food sources contain methylmercury at levels between 0.0001 and 0.01 ppm; mercury concentrations are especially high in tuna, averaging 0.4 ppm, while larger predatory fish contain levels in excess of 1 ppm.¹⁴ The use of mercury-containing cosmetic products also presents a substantial exposure risk to consumers.^5,10 In one study, 3.3% of skin-lightening creams and soaps purchased within the United States contained concentrations of mercury exceeding 1000 ppm.¹⁵

We describe a case of mercury toxicity resulting from intentional injection of liquid mercury into the right antecubital fossa in a suicide attempt.

Case Report

A 31-year-old woman presented to the family practice center for evaluation of a firm stained area on the skin of the right arm. She reported increasing anxiety, depression, tremors, irritability, and difficulty concentrating over the last 6 months. She denied headache and joint or muscle pain. Four years earlier, she had broken apart a thermometer and injected approximately 0.7 mL of its contents into the right arm in a suicide attempt. She intended to inject the thermometer’s contents directly into a vein, but the material instead entered the surrounding tissue. She denied notable pain or itching overlying the injection site. Her medications included aripiprazole and buspirone. She noted that she smoked half a pack of cigarettes per day and had a history of methamphetamine abuse. She was homeless and unemployed. Physical examination revealed an anxious tremulous woman with an erythematous to bluish gray, firm plaque on the right antecubital fossa (Figure 1). There were no notable tremors and no gait disturbance.

Her blood mercury level was greater than 100 µg/L and urine mercury was 477 µg/g (reference ranges, 1–8 μg/L and 4–5 μg/L, respectively). A radiograph of the right elbow area revealed scattered punctate foci of increased density within or overlying the anterolateral elbow soft tissues. She was diagnosed with mercury granuloma causing chronic mercury elevation. She underwent excision of the granuloma (Figure 2) with endovascular surgery via an elliptical incision. The patient was subsequently lost to follow-up.

Comment

Elemental mercury is a silver liquid at room temperature that spontaneously evaporates to form mercury vapor, an invisible, odorless, toxic gas. Accidental cutaneous exposure typically is safely managed by washing exposed skin with soap and water,¹⁶ though there is a potential risk for systemic absorption, especially when the skin is inflamed. When metallic mercury is subcutaneously injected, it is advised to promptly excise all subcutaneous areas containing mercury, regardless of any symptoms of systemic toxicity. Patients should subsequently be monitored for signs of both central nervous system (CNS) and renal deficits, undergo chelation therapy when systemic effects are apparent, and finally receive psychiatric consultation and treatment when necessary.¹⁷

Inorganic mercury compounds are formed when elemental mercury combines with sulfur or oxygen and often take the form of mercury salts, which appear as white crystals.¹⁶ These salts occur naturally in the environment and are used in pesticides, antiseptics, and skin-lightening creams and soaps.¹⁸

Methylmercury is a highly toxic, organic compound that is capable of crossing the placental and blood-brain barriers. It is the most common organic mercury compound found in the environment.¹⁶ Most humans have trace amounts of methylmercury in their bodies, typically as a result of consuming seafood.⁵

Exposure to mercury most commonly occurs through chronic consumption of methylmercury in seafood or acute inhalation of elemental mercury vapors.⁹ Iatrogenic cases of mercury exposure via injection also have been reported in the literature, including a case resulting in acute poisoning due to peritoneal lavage with mercury bichloride.¹⁹ Acute mercury-induced pulmonary damage typically resolves completely. However, there have been reported cases of exposure progressing to interstitial emphysema, pneumatocele, pneumothorax, pneumomediastinum, interstitial fibrosis, and chronic respiratory insufficiency, with examples of fatal acute respiratory distress syndrome being reported.^5,16,20 Although individuals who inhale mercury vapors initially may be unaware of exposure due to little upper airway irritation, symptoms following an initial acute exposure may include ptyalism, a metallic taste, dysphagia, enteritis, diarrhea, nausea, renal damage, and CNS effects.¹⁶ Additionally, exposure may lead to confusion with signs and symptoms of metal fume fever, including shortness of breath, pleuritic chest pain, stomatitis, lethargy, and vomiting.²⁰

Chronic exposure to mercury vapor can result in accumulation of mercury in the body, leading to neuropsychiatric, dermatologic, oropharyngeal, and renal manifestations. Sore throat, fever, headache, fatigue, dyspnea, chest pain, and pneumonitis are common.¹⁶ Typically, low-level exposure to elemental mercury does not lead to long-lasting health effects. However, individuals exposed to high-level elemental mercury vapors may require hospitalization. Treatment of acute mercury poisoning consists of removing the source of exposure, followed by cardiopulmonary support.¹⁶

Specific assays for mercury levels in blood and urine are useful to assess the level of exposure and risk to the patient. Blood mercury concentrations of 20 µg/L or below are considered within reference range; however, once blood and urine concentrations of mercury exceed 100 µg/L, clinical signs of acute mercury poisoning typically manifest.²¹ Chest radiographs can reveal pulmonary damage, while complete blood cell count, metabolic panel, and urinalysis can assess damage to other organs. Neuropsychiatric testing and nerve conduction studies may provide objective evidence of CNS toxicity. Assays for N-acetyl-β-D-glucosaminidase can provide an indication of early renal tubular dysfunction.¹⁶

Elemental mercury is not absorbed from the gastrointestinal tract, posing minimal risk for acute toxicity from ingestion. Generally, less than 10% of ingested inorganic mercury is absorbed from the gut, while elemental mercury is nonabsorbable.¹⁰ If an individual ingests a large amount of mercury, it may persist in the gastrointestinal tract for an extended period. Mercury is radiopaque, and abdominal radiographs should be obtained in all cases of ingestion.¹⁶

Mercury is toxic to the CNS and peripheral nervous system, resulting in erethism mercurialis, a constellation of neuropsychologic signs and symptoms including restlessness, irritability, insomnia, emotional lability, difficulty concentrating, and impaired memory. In severe cases, delirium and psychosis may develop. Other CNS effects include tremors, paresthesia, dysarthria, neuromuscular changes, headaches, polyneuropathy, and cerebellar ataxia, as well as ophthalmologic and audiologic impairment.^5,16

Upon inhalation exposure, patients with respiratory concerns should be given oxygen. Bronchospasms are treated with bronchodilators; however, if multiple chemical exposures are suspected, bronchial-sensitizing agents may pose additional risks. Corticosteroids and antibiotics have been recommended for treatment of chemical pneumonitis, but their efficacy has not been substantiated.¹⁶

Skin reactions associated with skin contact to elemental mercury are rare. However, hives and dermatitis have been observed following accidental contact with inorganic mercury compounds.⁵ Manifestation in children chronically exposed to mercury includes a nonallergic hypersensitivity (acrodynia),^5,17 which is characterized by pain and dusky pink discoloration in the hands and feet, most often seen in children chronically exposed to mercury absorbed from vapor inhalation or cutaneous exposure.¹⁶

Renal conditions associated with acute inhalation of elemental mercury vapor include proteinuria, nephrotic syndrome, temporary tubular dysfunction, acute tubular necrosis, and oliguric renal failure.¹⁶ Chronic exposure to inorganic mercury compounds also has been reported to cause renal damage.⁵ Chelation therapy should be performed for any symptomatic patient with a clear history of acute elemental mercury exposure.¹⁶ The most frequently used chelation agent in cases of acute inorganic mercury exposures is dimercaprol. In rare cases of mercury intoxication, hemodialysis is required in the treatment of renal failure and to expedite removal of dimercaprol-mercury complexes.¹⁶

Cardiovascular symptoms associated with acute inhalation of high levels of elemental mercury include tachycardia and hypertension.¹⁶ Increases in blood pressure, palpitations, and heart rate also have been observed in instances of acute elemental mercury exposure. Studies show that exposure to mercury increases both the risk for acute myocardial infarction as well as death from coronary heart and cardiovascular diseases.⁵

Conclusion

Mercury poisoning presents with varied neuropsychologic signs and symptoms. Our case provides insight into a unique route of exposure for mercury toxicity. In addition to the unusual presentation of a mercury granuloma, our case illustrates how surgical techniques can aid in removal of cutaneous reservoirs in the setting of percutaneous exposure.

Evidence of human exposure to mercury dates as far back as the Egyptians in 1500 bc . ¹ The ancient Chinese believed mercury could prolong life, heal bones, and maintain vitality. ² Western medicine has utilized mercury in diuretics, laxatives, antibacterial agents, and antiseptics. ³ Health effects caused by chronic mercury exposure became increasingly apparent in the 1800s after hat makers who had inhaled mercuric nitrate vapors began to present with a host of neurologic symptoms, which is where the p hrase "mad as a hatter" was derived. ^4,5 In 1889, French neurologist Jean-Martin Charcot attributed rapid tremors to mercury poisoning. ⁶ By 1940, Kinnier Wilson ⁷ further characterized the effects of mercury, describing mercury-induced cognitive impairments. In the 1960s, Japanese researchers correlated elevated urinary mercury levels with an outbreak of Minamata disease, a condition characterized by tremors, sensory loss, ataxia, and visual constrictions. ⁸ The World Health Organization considers mercury to be one of the top 10 chemicals of major public health concern. ⁹

Mercury release in the environment primarily is a function of human activity, including coal-fired power plants, residential heating, and mining.^9,10 Mercury from these sources is commonly found in the sediment of lakes and bays, where it is enzymatically converted to methylmercury by aquatic microorganisms; subsequent food chain biomagnification results in elevated mercury levels in apex predators. Substantial release of mercury into the environment also can be attributed to health care facilities from their use of thermometers containing 0.5 to 3 g of elemental mercury,¹¹ blood pressure monitors, and medical waste incinerators.⁵

Mercury has been reported as the second most common cause of heavy metal poisoning after lead.¹² Standards from the US Food and Drug Administration dictate that methylmercury levels in fish and wheat products must not exceed 1 ppm.¹³ Most plant and animal food sources contain methylmercury at levels between 0.0001 and 0.01 ppm; mercury concentrations are especially high in tuna, averaging 0.4 ppm, while larger predatory fish contain levels in excess of 1 ppm.¹⁴ The use of mercury-containing cosmetic products also presents a substantial exposure risk to consumers.^5,10 In one study, 3.3% of skin-lightening creams and soaps purchased within the United States contained concentrations of mercury exceeding 1000 ppm.¹⁵

We describe a case of mercury toxicity resulting from intentional injection of liquid mercury into the right antecubital fossa in a suicide attempt.

Case Report

A 31-year-old woman presented to the family practice center for evaluation of a firm stained area on the skin of the right arm. She reported increasing anxiety, depression, tremors, irritability, and difficulty concentrating over the last 6 months. She denied headache and joint or muscle pain. Four years earlier, she had broken apart a thermometer and injected approximately 0.7 mL of its contents into the right arm in a suicide attempt. She intended to inject the thermometer’s contents directly into a vein, but the material instead entered the surrounding tissue. She denied notable pain or itching overlying the injection site. Her medications included aripiprazole and buspirone. She noted that she smoked half a pack of cigarettes per day and had a history of methamphetamine abuse. She was homeless and unemployed. Physical examination revealed an anxious tremulous woman with an erythematous to bluish gray, firm plaque on the right antecubital fossa (Figure 1). There were no notable tremors and no gait disturbance.

Her blood mercury level was greater than 100 µg/L and urine mercury was 477 µg/g (reference ranges, 1–8 μg/L and 4–5 μg/L, respectively). A radiograph of the right elbow area revealed scattered punctate foci of increased density within or overlying the anterolateral elbow soft tissues. She was diagnosed with mercury granuloma causing chronic mercury elevation. She underwent excision of the granuloma (Figure 2) with endovascular surgery via an elliptical incision. The patient was subsequently lost to follow-up.

Comment

Elemental mercury is a silver liquid at room temperature that spontaneously evaporates to form mercury vapor, an invisible, odorless, toxic gas. Accidental cutaneous exposure typically is safely managed by washing exposed skin with soap and water,¹⁶ though there is a potential risk for systemic absorption, especially when the skin is inflamed. When metallic mercury is subcutaneously injected, it is advised to promptly excise all subcutaneous areas containing mercury, regardless of any symptoms of systemic toxicity. Patients should subsequently be monitored for signs of both central nervous system (CNS) and renal deficits, undergo chelation therapy when systemic effects are apparent, and finally receive psychiatric consultation and treatment when necessary.¹⁷

Inorganic mercury compounds are formed when elemental mercury combines with sulfur or oxygen and often take the form of mercury salts, which appear as white crystals.¹⁶ These salts occur naturally in the environment and are used in pesticides, antiseptics, and skin-lightening creams and soaps.¹⁸

Methylmercury is a highly toxic, organic compound that is capable of crossing the placental and blood-brain barriers. It is the most common organic mercury compound found in the environment.¹⁶ Most humans have trace amounts of methylmercury in their bodies, typically as a result of consuming seafood.⁵

Exposure to mercury most commonly occurs through chronic consumption of methylmercury in seafood or acute inhalation of elemental mercury vapors.⁹ Iatrogenic cases of mercury exposure via injection also have been reported in the literature, including a case resulting in acute poisoning due to peritoneal lavage with mercury bichloride.¹⁹ Acute mercury-induced pulmonary damage typically resolves completely. However, there have been reported cases of exposure progressing to interstitial emphysema, pneumatocele, pneumothorax, pneumomediastinum, interstitial fibrosis, and chronic respiratory insufficiency, with examples of fatal acute respiratory distress syndrome being reported.^5,16,20 Although individuals who inhale mercury vapors initially may be unaware of exposure due to little upper airway irritation, symptoms following an initial acute exposure may include ptyalism, a metallic taste, dysphagia, enteritis, diarrhea, nausea, renal damage, and CNS effects.¹⁶ Additionally, exposure may lead to confusion with signs and symptoms of metal fume fever, including shortness of breath, pleuritic chest pain, stomatitis, lethargy, and vomiting.²⁰

Chronic exposure to mercury vapor can result in accumulation of mercury in the body, leading to neuropsychiatric, dermatologic, oropharyngeal, and renal manifestations. Sore throat, fever, headache, fatigue, dyspnea, chest pain, and pneumonitis are common.¹⁶ Typically, low-level exposure to elemental mercury does not lead to long-lasting health effects. However, individuals exposed to high-level elemental mercury vapors may require hospitalization. Treatment of acute mercury poisoning consists of removing the source of exposure, followed by cardiopulmonary support.¹⁶

Specific assays for mercury levels in blood and urine are useful to assess the level of exposure and risk to the patient. Blood mercury concentrations of 20 µg/L or below are considered within reference range; however, once blood and urine concentrations of mercury exceed 100 µg/L, clinical signs of acute mercury poisoning typically manifest.²¹ Chest radiographs can reveal pulmonary damage, while complete blood cell count, metabolic panel, and urinalysis can assess damage to other organs. Neuropsychiatric testing and nerve conduction studies may provide objective evidence of CNS toxicity. Assays for N-acetyl-β-D-glucosaminidase can provide an indication of early renal tubular dysfunction.¹⁶

Elemental mercury is not absorbed from the gastrointestinal tract, posing minimal risk for acute toxicity from ingestion. Generally, less than 10% of ingested inorganic mercury is absorbed from the gut, while elemental mercury is nonabsorbable.¹⁰ If an individual ingests a large amount of mercury, it may persist in the gastrointestinal tract for an extended period. Mercury is radiopaque, and abdominal radiographs should be obtained in all cases of ingestion.¹⁶

Mercury is toxic to the CNS and peripheral nervous system, resulting in erethism mercurialis, a constellation of neuropsychologic signs and symptoms including restlessness, irritability, insomnia, emotional lability, difficulty concentrating, and impaired memory. In severe cases, delirium and psychosis may develop. Other CNS effects include tremors, paresthesia, dysarthria, neuromuscular changes, headaches, polyneuropathy, and cerebellar ataxia, as well as ophthalmologic and audiologic impairment.^5,16

Upon inhalation exposure, patients with respiratory concerns should be given oxygen. Bronchospasms are treated with bronchodilators; however, if multiple chemical exposures are suspected, bronchial-sensitizing agents may pose additional risks. Corticosteroids and antibiotics have been recommended for treatment of chemical pneumonitis, but their efficacy has not been substantiated.¹⁶

Skin reactions associated with skin contact to elemental mercury are rare. However, hives and dermatitis have been observed following accidental contact with inorganic mercury compounds.⁵ Manifestation in children chronically exposed to mercury includes a nonallergic hypersensitivity (acrodynia),^5,17 which is characterized by pain and dusky pink discoloration in the hands and feet, most often seen in children chronically exposed to mercury absorbed from vapor inhalation or cutaneous exposure.¹⁶

Renal conditions associated with acute inhalation of elemental mercury vapor include proteinuria, nephrotic syndrome, temporary tubular dysfunction, acute tubular necrosis, and oliguric renal failure.¹⁶ Chronic exposure to inorganic mercury compounds also has been reported to cause renal damage.⁵ Chelation therapy should be performed for any symptomatic patient with a clear history of acute elemental mercury exposure.¹⁶ The most frequently used chelation agent in cases of acute inorganic mercury exposures is dimercaprol. In rare cases of mercury intoxication, hemodialysis is required in the treatment of renal failure and to expedite removal of dimercaprol-mercury complexes.¹⁶

Cardiovascular symptoms associated with acute inhalation of high levels of elemental mercury include tachycardia and hypertension.¹⁶ Increases in blood pressure, palpitations, and heart rate also have been observed in instances of acute elemental mercury exposure. Studies show that exposure to mercury increases both the risk for acute myocardial infarction as well as death from coronary heart and cardiovascular diseases.⁵

Conclusion

Mercury poisoning presents with varied neuropsychologic signs and symptoms. Our case provides insight into a unique route of exposure for mercury toxicity. In addition to the unusual presentation of a mercury granuloma, our case illustrates how surgical techniques can aid in removal of cutaneous reservoirs in the setting of percutaneous exposure.

Evidence of human exposure to mercury dates as far back as the Egyptians in 1500 bc . ¹ The ancient Chinese believed mercury could prolong life, heal bones, and maintain vitality. ² Western medicine has utilized mercury in diuretics, laxatives, antibacterial agents, and antiseptics. ³ Health effects caused by chronic mercury exposure became increasingly apparent in the 1800s after hat makers who had inhaled mercuric nitrate vapors began to present with a host of neurologic symptoms, which is where the p hrase "mad as a hatter" was derived. ^4,5 In 1889, French neurologist Jean-Martin Charcot attributed rapid tremors to mercury poisoning. ⁶ By 1940, Kinnier Wilson ⁷ further characterized the effects of mercury, describing mercury-induced cognitive impairments. In the 1960s, Japanese researchers correlated elevated urinary mercury levels with an outbreak of Minamata disease, a condition characterized by tremors, sensory loss, ataxia, and visual constrictions. ⁸ The World Health Organization considers mercury to be one of the top 10 chemicals of major public health concern. ⁹

Mercury release in the environment primarily is a function of human activity, including coal-fired power plants, residential heating, and mining.^9,10 Mercury from these sources is commonly found in the sediment of lakes and bays, where it is enzymatically converted to methylmercury by aquatic microorganisms; subsequent food chain biomagnification results in elevated mercury levels in apex predators. Substantial release of mercury into the environment also can be attributed to health care facilities from their use of thermometers containing 0.5 to 3 g of elemental mercury,¹¹ blood pressure monitors, and medical waste incinerators.⁵

Mercury has been reported as the second most common cause of heavy metal poisoning after lead.¹² Standards from the US Food and Drug Administration dictate that methylmercury levels in fish and wheat products must not exceed 1 ppm.¹³ Most plant and animal food sources contain methylmercury at levels between 0.0001 and 0.01 ppm; mercury concentrations are especially high in tuna, averaging 0.4 ppm, while larger predatory fish contain levels in excess of 1 ppm.¹⁴ The use of mercury-containing cosmetic products also presents a substantial exposure risk to consumers.^5,10 In one study, 3.3% of skin-lightening creams and soaps purchased within the United States contained concentrations of mercury exceeding 1000 ppm.¹⁵

We describe a case of mercury toxicity resulting from intentional injection of liquid mercury into the right antecubital fossa in a suicide attempt.

Case Report

A 31-year-old woman presented to the family practice center for evaluation of a firm stained area on the skin of the right arm. She reported increasing anxiety, depression, tremors, irritability, and difficulty concentrating over the last 6 months. She denied headache and joint or muscle pain. Four years earlier, she had broken apart a thermometer and injected approximately 0.7 mL of its contents into the right arm in a suicide attempt. She intended to inject the thermometer’s contents directly into a vein, but the material instead entered the surrounding tissue. She denied notable pain or itching overlying the injection site. Her medications included aripiprazole and buspirone. She noted that she smoked half a pack of cigarettes per day and had a history of methamphetamine abuse. She was homeless and unemployed. Physical examination revealed an anxious tremulous woman with an erythematous to bluish gray, firm plaque on the right antecubital fossa (Figure 1). There were no notable tremors and no gait disturbance.

Her blood mercury level was greater than 100 µg/L and urine mercury was 477 µg/g (reference ranges, 1–8 μg/L and 4–5 μg/L, respectively). A radiograph of the right elbow area revealed scattered punctate foci of increased density within or overlying the anterolateral elbow soft tissues. She was diagnosed with mercury granuloma causing chronic mercury elevation. She underwent excision of the granuloma (Figure 2) with endovascular surgery via an elliptical incision. The patient was subsequently lost to follow-up.

Comment

Elemental mercury is a silver liquid at room temperature that spontaneously evaporates to form mercury vapor, an invisible, odorless, toxic gas. Accidental cutaneous exposure typically is safely managed by washing exposed skin with soap and water,¹⁶ though there is a potential risk for systemic absorption, especially when the skin is inflamed. When metallic mercury is subcutaneously injected, it is advised to promptly excise all subcutaneous areas containing mercury, regardless of any symptoms of systemic toxicity. Patients should subsequently be monitored for signs of both central nervous system (CNS) and renal deficits, undergo chelation therapy when systemic effects are apparent, and finally receive psychiatric consultation and treatment when necessary.¹⁷

Inorganic mercury compounds are formed when elemental mercury combines with sulfur or oxygen and often take the form of mercury salts, which appear as white crystals.¹⁶ These salts occur naturally in the environment and are used in pesticides, antiseptics, and skin-lightening creams and soaps.¹⁸

Methylmercury is a highly toxic, organic compound that is capable of crossing the placental and blood-brain barriers. It is the most common organic mercury compound found in the environment.¹⁶ Most humans have trace amounts of methylmercury in their bodies, typically as a result of consuming seafood.⁵

Exposure to mercury most commonly occurs through chronic consumption of methylmercury in seafood or acute inhalation of elemental mercury vapors.⁹ Iatrogenic cases of mercury exposure via injection also have been reported in the literature, including a case resulting in acute poisoning due to peritoneal lavage with mercury bichloride.¹⁹ Acute mercury-induced pulmonary damage typically resolves completely. However, there have been reported cases of exposure progressing to interstitial emphysema, pneumatocele, pneumothorax, pneumomediastinum, interstitial fibrosis, and chronic respiratory insufficiency, with examples of fatal acute respiratory distress syndrome being reported.^5,16,20 Although individuals who inhale mercury vapors initially may be unaware of exposure due to little upper airway irritation, symptoms following an initial acute exposure may include ptyalism, a metallic taste, dysphagia, enteritis, diarrhea, nausea, renal damage, and CNS effects.¹⁶ Additionally, exposure may lead to confusion with signs and symptoms of metal fume fever, including shortness of breath, pleuritic chest pain, stomatitis, lethargy, and vomiting.²⁰

Chronic exposure to mercury vapor can result in accumulation of mercury in the body, leading to neuropsychiatric, dermatologic, oropharyngeal, and renal manifestations. Sore throat, fever, headache, fatigue, dyspnea, chest pain, and pneumonitis are common.¹⁶ Typically, low-level exposure to elemental mercury does not lead to long-lasting health effects. However, individuals exposed to high-level elemental mercury vapors may require hospitalization. Treatment of acute mercury poisoning consists of removing the source of exposure, followed by cardiopulmonary support.¹⁶

Specific assays for mercury levels in blood and urine are useful to assess the level of exposure and risk to the patient. Blood mercury concentrations of 20 µg/L or below are considered within reference range; however, once blood and urine concentrations of mercury exceed 100 µg/L, clinical signs of acute mercury poisoning typically manifest.²¹ Chest radiographs can reveal pulmonary damage, while complete blood cell count, metabolic panel, and urinalysis can assess damage to other organs. Neuropsychiatric testing and nerve conduction studies may provide objective evidence of CNS toxicity. Assays for N-acetyl-β-D-glucosaminidase can provide an indication of early renal tubular dysfunction.¹⁶

Elemental mercury is not absorbed from the gastrointestinal tract, posing minimal risk for acute toxicity from ingestion. Generally, less than 10% of ingested inorganic mercury is absorbed from the gut, while elemental mercury is nonabsorbable.¹⁰ If an individual ingests a large amount of mercury, it may persist in the gastrointestinal tract for an extended period. Mercury is radiopaque, and abdominal radiographs should be obtained in all cases of ingestion.¹⁶

Mercury is toxic to the CNS and peripheral nervous system, resulting in erethism mercurialis, a constellation of neuropsychologic signs and symptoms including restlessness, irritability, insomnia, emotional lability, difficulty concentrating, and impaired memory. In severe cases, delirium and psychosis may develop. Other CNS effects include tremors, paresthesia, dysarthria, neuromuscular changes, headaches, polyneuropathy, and cerebellar ataxia, as well as ophthalmologic and audiologic impairment.^5,16

Upon inhalation exposure, patients with respiratory concerns should be given oxygen. Bronchospasms are treated with bronchodilators; however, if multiple chemical exposures are suspected, bronchial-sensitizing agents may pose additional risks. Corticosteroids and antibiotics have been recommended for treatment of chemical pneumonitis, but their efficacy has not been substantiated.¹⁶

Skin reactions associated with skin contact to elemental mercury are rare. However, hives and dermatitis have been observed following accidental contact with inorganic mercury compounds.⁵ Manifestation in children chronically exposed to mercury includes a nonallergic hypersensitivity (acrodynia),^5,17 which is characterized by pain and dusky pink discoloration in the hands and feet, most often seen in children chronically exposed to mercury absorbed from vapor inhalation or cutaneous exposure.¹⁶

Renal conditions associated with acute inhalation of elemental mercury vapor include proteinuria, nephrotic syndrome, temporary tubular dysfunction, acute tubular necrosis, and oliguric renal failure.¹⁶ Chronic exposure to inorganic mercury compounds also has been reported to cause renal damage.⁵ Chelation therapy should be performed for any symptomatic patient with a clear history of acute elemental mercury exposure.¹⁶ The most frequently used chelation agent in cases of acute inorganic mercury exposures is dimercaprol. In rare cases of mercury intoxication, hemodialysis is required in the treatment of renal failure and to expedite removal of dimercaprol-mercury complexes.¹⁶

Cardiovascular symptoms associated with acute inhalation of high levels of elemental mercury include tachycardia and hypertension.¹⁶ Increases in blood pressure, palpitations, and heart rate also have been observed in instances of acute elemental mercury exposure. Studies show that exposure to mercury increases both the risk for acute myocardial infarction as well as death from coronary heart and cardiovascular diseases.⁵

Conclusion

Mercury poisoning presents with varied neuropsychologic signs and symptoms. Our case provides insight into a unique route of exposure for mercury toxicity. In addition to the unusual presentation of a mercury granuloma, our case illustrates how surgical techniques can aid in removal of cutaneous reservoirs in the setting of percutaneous exposure.

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.

The American Contact Dermatitis Society has selected acetophenone azine, linked to reactions associated with shins pads and footwear, as the “Contact Allergen of the Year” for 2021.

©Jody Dingle/Fotolia.com

The announcement was made by Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, during a presentation at the annual meeting of the American Contact Dermatitis Society, held virtually this year. In his opinion, he said, the most exciting selections occur when international cooperation results in the identification of a new allergen that could become problematic, and acetophenone azine falls into this category.

The chemical formula of acetophenone azine is C₁₆H₁₆N₂.

Acetophenone azine was highlighted as a contact allergen in a recent report in Dermatitis. The authors, Nadia Raison-Peyron, MD, from the department of dermatology at the University of Montpelier (France), and Denis Sasseville, MD, from the division of dermatology at McGill University Health Center, Quebec, described publications and reports of about 12 cases of severe allergic contact dermatitis secondary to shin pads or footwear, mainly in children and teens in Europe (one case was in Canada).

A common feature of these cases was the presence of a foam used for cushioning, made of ethyl vinyl acetate (EVA) used in the relevant products.

In one case, a 13-year-old boy who wore shin pads for soccer developed contact dermatitis on both shins that spread, and was described as severe. Patch testing revealed the EVA foam in the shin pads as the only positive reaction. Similar cases have been reported after exposure to EVA-containing products, including shin pads, sneakers, flip-flops, ski boots, insoles, swimming goggles, and bicycle seats, according to the authors.

In some reports, cases related to footwear presented as dyshidrosiform, vesiculobullous eczema, with or without palmar lesions, or presented as plantar hyperkeratotic dermatitis, they wrote. In other cases, patients experienced scarring and postinflammatory hypopigmentation.

The compound is likely not added to EVA intentionally, they added, but instead is thought to result from reactions between additives during the manufacturing process. The presence of acetophenone azine is not well explained, but the current theory is that it results from a combination of “the degradation of the initiator dicumylperoxide and hydrazine from the foaming agent azodicarbonamide,” the authors said.

In the paper, Dr. Raison-Peyron and Dr. Sasseville recommended a patch testing concentration of 0.1% in acetone or petrolatum, as acetophenone azine is not currently available from path test suppliers, although it can be obtained from chemical product distributors.

“Given the recent discovery of this allergen, it is presumed that cases of allergic contact dermatitis would have been missed and labeled irritant contact dermatitis or dyshidrosis,” they noted. To avoid missing more cases, acetophenone azine should be added to the patch testing shoe series, as well as plastics and glues series, they emphasized.

Although no cases of allergic reactions to acetophenone azine have been reported in the United States to date, it is an emerging allergen that should be on the radar for U.S. dermatologists, Amber Atwater, MD, outgoing ACDS president, said in an interview. The lack of reported cases may be in part attributed to the fact that acetophenone azine is not yet available to purchase for testing in the United States, and the allergen could be present in shin guards and other products identified in reported cases, added Dr. Atwater, associate professor of dermatology, Duke University, Durham, N.C.

The American Contact Dermatitis Society has selected acetophenone azine, linked to reactions associated with shins pads and footwear, as the “Contact Allergen of the Year” for 2021.

©Jody Dingle/Fotolia.com

The announcement was made by Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, during a presentation at the annual meeting of the American Contact Dermatitis Society, held virtually this year. In his opinion, he said, the most exciting selections occur when international cooperation results in the identification of a new allergen that could become problematic, and acetophenone azine falls into this category.

The chemical formula of acetophenone azine is C₁₆H₁₆N₂.

Acetophenone azine was highlighted as a contact allergen in a recent report in Dermatitis. The authors, Nadia Raison-Peyron, MD, from the department of dermatology at the University of Montpelier (France), and Denis Sasseville, MD, from the division of dermatology at McGill University Health Center, Quebec, described publications and reports of about 12 cases of severe allergic contact dermatitis secondary to shin pads or footwear, mainly in children and teens in Europe (one case was in Canada).

A common feature of these cases was the presence of a foam used for cushioning, made of ethyl vinyl acetate (EVA) used in the relevant products.

In one case, a 13-year-old boy who wore shin pads for soccer developed contact dermatitis on both shins that spread, and was described as severe. Patch testing revealed the EVA foam in the shin pads as the only positive reaction. Similar cases have been reported after exposure to EVA-containing products, including shin pads, sneakers, flip-flops, ski boots, insoles, swimming goggles, and bicycle seats, according to the authors.

In some reports, cases related to footwear presented as dyshidrosiform, vesiculobullous eczema, with or without palmar lesions, or presented as plantar hyperkeratotic dermatitis, they wrote. In other cases, patients experienced scarring and postinflammatory hypopigmentation.

The compound is likely not added to EVA intentionally, they added, but instead is thought to result from reactions between additives during the manufacturing process. The presence of acetophenone azine is not well explained, but the current theory is that it results from a combination of “the degradation of the initiator dicumylperoxide and hydrazine from the foaming agent azodicarbonamide,” the authors said.

In the paper, Dr. Raison-Peyron and Dr. Sasseville recommended a patch testing concentration of 0.1% in acetone or petrolatum, as acetophenone azine is not currently available from path test suppliers, although it can be obtained from chemical product distributors.

“Given the recent discovery of this allergen, it is presumed that cases of allergic contact dermatitis would have been missed and labeled irritant contact dermatitis or dyshidrosis,” they noted. To avoid missing more cases, acetophenone azine should be added to the patch testing shoe series, as well as plastics and glues series, they emphasized.

Although no cases of allergic reactions to acetophenone azine have been reported in the United States to date, it is an emerging allergen that should be on the radar for U.S. dermatologists, Amber Atwater, MD, outgoing ACDS president, said in an interview. The lack of reported cases may be in part attributed to the fact that acetophenone azine is not yet available to purchase for testing in the United States, and the allergen could be present in shin guards and other products identified in reported cases, added Dr. Atwater, associate professor of dermatology, Duke University, Durham, N.C.

The American Contact Dermatitis Society has selected acetophenone azine, linked to reactions associated with shins pads and footwear, as the “Contact Allergen of the Year” for 2021.

©Jody Dingle/Fotolia.com

The announcement was made by Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, during a presentation at the annual meeting of the American Contact Dermatitis Society, held virtually this year. In his opinion, he said, the most exciting selections occur when international cooperation results in the identification of a new allergen that could become problematic, and acetophenone azine falls into this category.

The chemical formula of acetophenone azine is C₁₆H₁₆N₂.

Acetophenone azine was highlighted as a contact allergen in a recent report in Dermatitis. The authors, Nadia Raison-Peyron, MD, from the department of dermatology at the University of Montpelier (France), and Denis Sasseville, MD, from the division of dermatology at McGill University Health Center, Quebec, described publications and reports of about 12 cases of severe allergic contact dermatitis secondary to shin pads or footwear, mainly in children and teens in Europe (one case was in Canada).

A common feature of these cases was the presence of a foam used for cushioning, made of ethyl vinyl acetate (EVA) used in the relevant products.

In one case, a 13-year-old boy who wore shin pads for soccer developed contact dermatitis on both shins that spread, and was described as severe. Patch testing revealed the EVA foam in the shin pads as the only positive reaction. Similar cases have been reported after exposure to EVA-containing products, including shin pads, sneakers, flip-flops, ski boots, insoles, swimming goggles, and bicycle seats, according to the authors.

In some reports, cases related to footwear presented as dyshidrosiform, vesiculobullous eczema, with or without palmar lesions, or presented as plantar hyperkeratotic dermatitis, they wrote. In other cases, patients experienced scarring and postinflammatory hypopigmentation.

The compound is likely not added to EVA intentionally, they added, but instead is thought to result from reactions between additives during the manufacturing process. The presence of acetophenone azine is not well explained, but the current theory is that it results from a combination of “the degradation of the initiator dicumylperoxide and hydrazine from the foaming agent azodicarbonamide,” the authors said.

In the paper, Dr. Raison-Peyron and Dr. Sasseville recommended a patch testing concentration of 0.1% in acetone or petrolatum, as acetophenone azine is not currently available from path test suppliers, although it can be obtained from chemical product distributors.

“Given the recent discovery of this allergen, it is presumed that cases of allergic contact dermatitis would have been missed and labeled irritant contact dermatitis or dyshidrosis,” they noted. To avoid missing more cases, acetophenone azine should be added to the patch testing shoe series, as well as plastics and glues series, they emphasized.

Although no cases of allergic reactions to acetophenone azine have been reported in the United States to date, it is an emerging allergen that should be on the radar for U.S. dermatologists, Amber Atwater, MD, outgoing ACDS president, said in an interview. The lack of reported cases may be in part attributed to the fact that acetophenone azine is not yet available to purchase for testing in the United States, and the allergen could be present in shin guards and other products identified in reported cases, added Dr. Atwater, associate professor of dermatology, Duke University, Durham, N.C.