Cutis

The Diagnosis: Erythema Ab Igne

Given the patient's reticulated hyperpigmented lesions in the setting of recent space heater use with heater closer to the more affected leg, erythema ab igne was diagnosed. Patient education was provided and moving the heater away from the lower extremities was advised.

Erythema ab igne first was described by German dermatologist Abraham Buschke as hitze melanose, meaning melanosis induced by heat. The classic skin findings were first observed on the lower legs of patients who worked in front of open fires or coal stoves.¹ Over the years, new causes of erythema ab igne secondary to prolonged thermal radiation exposure have been reported.¹ In the elderly, hospitalized, and chronic pain patients, erythema ab igne has been observed in areas treated with heating pads and blankets.² Other triggers such as frequent hot bathing, furniture, steam radiators, space heaters, and laptops also have been reported.^3-6 Laptop-induced erythema ab igne is a diagnosis that has been reported in the last decade and its incidence likely will increase in the future.⁶

The clinical manifestations of erythema ab igne correlate with the frequency and duration of heat exposure. Acutely, a mild and transient erythema develops in the affected area. With chronic heat exposure, these areas subsequently develop a permanent reticulated hyperpigmented pattern and may eventually become atrophic.^2,6 All body surfaces are at risk, but erythema ab igne classically involves the legs, lower back, and/or abdomen. Lesions typically are asymptomatic; however, burning and pruritus can be present.^2,6 Bullous erythema ab igne, though rare, has been reported,⁷ suggesting a potential transition from erythema ab igne to burns.⁶

Biopsy is not recommended for diagnosis; however, the histopathologic changes of erythema ab igne include hyperkeratosis, interface dermatitis, epidermal atrophy with apoptotic keratinocytes, and melanin incontinence. Although this condition typically is benign, histologic findings could resemble actinic keratosis, suggesting that chronic changes induced by infrared thermal radiation may lead to squamous cell carcinoma or rarely Merkel cell carcinoma. The latency for developing carcinoma appears to extend 30 years, with a 30% tendency for recurrence or metastasis. Given the possibility of an increase in erythema ab igne in the pediatric population in the upcoming years, as displayed by our patient, and increasing laptop and electronic use in children and adolescents, it is important to be aware of this skin condition and the potential complications of it going undiagnosed.^2,6

No specific therapy for erythema ab igne exists. Treatment is centered on eliminating exposure to the heat source. With appropriate removal, the reticulated hyperpigmented lesions will resolve, sometimes taking several months.

Differential diagnosis includes livedo reticularis, livedoid vasculopathy, and cutis marmorata. The reticulated purpuric lesions of livedo reticularis involving the extremities often mimic erythema ab igne's cutaneous morphology; however, livedo reticularis frequently is associated with conditions such as drug reactions, infections, thrombosis, and vasculitides,² as opposed to erythema ab igne, which frequently is associated with conditions causing pain or decreased body temperature, thus necessitating use of heating devices, as seen in our patient. Livedoid vasculopathy is characterized by purpuric macules involving the lower legs and feet that progress to recurrent leg ulcers. Our patient's asymptomatic lesions and absence of ulcers excluded this diagnosis.⁸ Lastly, cutis marmorata, a congenital condition, is characterized by blue-violet vascular networks that often display ulceration and atrophy of the involved skin as well as hypertrophy or atrophy of the involved limb⁹; these clinical findings were not present in our patient and this diagnosis would not explain the relationship between the cutaneous lesions and heat exposure. 

The Diagnosis: Erythema Ab Igne

Given the patient's reticulated hyperpigmented lesions in the setting of recent space heater use with heater closer to the more affected leg, erythema ab igne was diagnosed. Patient education was provided and moving the heater away from the lower extremities was advised.

Erythema ab igne first was described by German dermatologist Abraham Buschke as hitze melanose, meaning melanosis induced by heat. The classic skin findings were first observed on the lower legs of patients who worked in front of open fires or coal stoves.¹ Over the years, new causes of erythema ab igne secondary to prolonged thermal radiation exposure have been reported.¹ In the elderly, hospitalized, and chronic pain patients, erythema ab igne has been observed in areas treated with heating pads and blankets.² Other triggers such as frequent hot bathing, furniture, steam radiators, space heaters, and laptops also have been reported.^3-6 Laptop-induced erythema ab igne is a diagnosis that has been reported in the last decade and its incidence likely will increase in the future.⁶

The clinical manifestations of erythema ab igne correlate with the frequency and duration of heat exposure. Acutely, a mild and transient erythema develops in the affected area. With chronic heat exposure, these areas subsequently develop a permanent reticulated hyperpigmented pattern and may eventually become atrophic.^2,6 All body surfaces are at risk, but erythema ab igne classically involves the legs, lower back, and/or abdomen. Lesions typically are asymptomatic; however, burning and pruritus can be present.^2,6 Bullous erythema ab igne, though rare, has been reported,⁷ suggesting a potential transition from erythema ab igne to burns.⁶

Biopsy is not recommended for diagnosis; however, the histopathologic changes of erythema ab igne include hyperkeratosis, interface dermatitis, epidermal atrophy with apoptotic keratinocytes, and melanin incontinence. Although this condition typically is benign, histologic findings could resemble actinic keratosis, suggesting that chronic changes induced by infrared thermal radiation may lead to squamous cell carcinoma or rarely Merkel cell carcinoma. The latency for developing carcinoma appears to extend 30 years, with a 30% tendency for recurrence or metastasis. Given the possibility of an increase in erythema ab igne in the pediatric population in the upcoming years, as displayed by our patient, and increasing laptop and electronic use in children and adolescents, it is important to be aware of this skin condition and the potential complications of it going undiagnosed.^2,6

No specific therapy for erythema ab igne exists. Treatment is centered on eliminating exposure to the heat source. With appropriate removal, the reticulated hyperpigmented lesions will resolve, sometimes taking several months.

Differential diagnosis includes livedo reticularis, livedoid vasculopathy, and cutis marmorata. The reticulated purpuric lesions of livedo reticularis involving the extremities often mimic erythema ab igne's cutaneous morphology; however, livedo reticularis frequently is associated with conditions such as drug reactions, infections, thrombosis, and vasculitides,² as opposed to erythema ab igne, which frequently is associated with conditions causing pain or decreased body temperature, thus necessitating use of heating devices, as seen in our patient. Livedoid vasculopathy is characterized by purpuric macules involving the lower legs and feet that progress to recurrent leg ulcers. Our patient's asymptomatic lesions and absence of ulcers excluded this diagnosis.⁸ Lastly, cutis marmorata, a congenital condition, is characterized by blue-violet vascular networks that often display ulceration and atrophy of the involved skin as well as hypertrophy or atrophy of the involved limb⁹; these clinical findings were not present in our patient and this diagnosis would not explain the relationship between the cutaneous lesions and heat exposure. 

The Diagnosis: Erythema Ab Igne

Given the patient's reticulated hyperpigmented lesions in the setting of recent space heater use with heater closer to the more affected leg, erythema ab igne was diagnosed. Patient education was provided and moving the heater away from the lower extremities was advised.

Erythema ab igne first was described by German dermatologist Abraham Buschke as hitze melanose, meaning melanosis induced by heat. The classic skin findings were first observed on the lower legs of patients who worked in front of open fires or coal stoves.¹ Over the years, new causes of erythema ab igne secondary to prolonged thermal radiation exposure have been reported.¹ In the elderly, hospitalized, and chronic pain patients, erythema ab igne has been observed in areas treated with heating pads and blankets.² Other triggers such as frequent hot bathing, furniture, steam radiators, space heaters, and laptops also have been reported.^3-6 Laptop-induced erythema ab igne is a diagnosis that has been reported in the last decade and its incidence likely will increase in the future.⁶

The clinical manifestations of erythema ab igne correlate with the frequency and duration of heat exposure. Acutely, a mild and transient erythema develops in the affected area. With chronic heat exposure, these areas subsequently develop a permanent reticulated hyperpigmented pattern and may eventually become atrophic.^2,6 All body surfaces are at risk, but erythema ab igne classically involves the legs, lower back, and/or abdomen. Lesions typically are asymptomatic; however, burning and pruritus can be present.^2,6 Bullous erythema ab igne, though rare, has been reported,⁷ suggesting a potential transition from erythema ab igne to burns.⁶

Biopsy is not recommended for diagnosis; however, the histopathologic changes of erythema ab igne include hyperkeratosis, interface dermatitis, epidermal atrophy with apoptotic keratinocytes, and melanin incontinence. Although this condition typically is benign, histologic findings could resemble actinic keratosis, suggesting that chronic changes induced by infrared thermal radiation may lead to squamous cell carcinoma or rarely Merkel cell carcinoma. The latency for developing carcinoma appears to extend 30 years, with a 30% tendency for recurrence or metastasis. Given the possibility of an increase in erythema ab igne in the pediatric population in the upcoming years, as displayed by our patient, and increasing laptop and electronic use in children and adolescents, it is important to be aware of this skin condition and the potential complications of it going undiagnosed.^2,6

No specific therapy for erythema ab igne exists. Treatment is centered on eliminating exposure to the heat source. With appropriate removal, the reticulated hyperpigmented lesions will resolve, sometimes taking several months.

Differential diagnosis includes livedo reticularis, livedoid vasculopathy, and cutis marmorata. The reticulated purpuric lesions of livedo reticularis involving the extremities often mimic erythema ab igne's cutaneous morphology; however, livedo reticularis frequently is associated with conditions such as drug reactions, infections, thrombosis, and vasculitides,² as opposed to erythema ab igne, which frequently is associated with conditions causing pain or decreased body temperature, thus necessitating use of heating devices, as seen in our patient. Livedoid vasculopathy is characterized by purpuric macules involving the lower legs and feet that progress to recurrent leg ulcers. Our patient's asymptomatic lesions and absence of ulcers excluded this diagnosis.⁸ Lastly, cutis marmorata, a congenital condition, is characterized by blue-violet vascular networks that often display ulceration and atrophy of the involved skin as well as hypertrophy or atrophy of the involved limb⁹; these clinical findings were not present in our patient and this diagnosis would not explain the relationship between the cutaneous lesions and heat exposure. 

When I am in clinic, I often get at least 3 to 4 inquiries each day from patients about the necessity for dietary restrictions or alterations as well as the benefits of these changes in limiting their dermatological disease processes. I usually am restricted in my response because the research rarely indicates benefits of one diet versus another; however, this discussion has recently become a heavily researched area as patients have come to value natural nonpharmaceutical approaches to their holistic care. In this article, a few dietary restrictions and supplements are reviewed that may have a beneficial effect in managing patients with acne vulgaris and atopic dermatitis.

Acne Vulgaris

In 1969 Fulton et al¹ conducted one of the first few trials on acne and diet management. In this crossover, patient-blinded, interventional study, patients were divided into 2 subgroups (N=65): 1 adolescent patient with moderate acne was compared to 1 male prisoner given a chocolate bar for 4 weeks or a control bar with equivalent caloric index. The results indicated no change in acne vulgaris lesions based on either intervention; however, there were obvious deficiencies in the study including small sample size, inappropriate grouping of an adolescent patient versus a prisoner, and limited study period.¹

Since then, multiple studies have been conducted with parallel participants, large sample sizes, and at least a 12-week study period. In 2005, Adebamowo et al² studied 47,355 women using a validated food frequency questionnaire that determined the amount of dairy consumed, specifically skim milk. The study showed a positive link between increased dairy consumption and acne formation; however, again due to the retrospective analysis and recall bias, it is difficult to determine if a link can truly be noted between acne and dairy in this study.²

More recently, LaRosa et al³ conducted a study that included 225 participants aged 14 to 19 years. Excluding participants with lactose intolerance and current use of oral contraceptives and isotretinoin, the study placed 120 participants in the test group versus 105 participants in the control group. The study was conducted using 3 telephone interviews and a 24-hour diet recall technique. The results supported a link between acne and skim milk consumption. Again, although the studied relied on participant self-reports of diet and followed a case-control design, a possible association was suspected but not validated.³ A longitudinal, questionnaire-based population study performed by Ulvestad et al⁴ included 2489 patients. This study further evaluated recall of dairy product consumption at 15 to 16 years of age and then 3 years later acne severity was self-assessed and reported at 18 to 19 years of age. Overall, this evaluation indicated that a high intake of dairy products and acne in adolescence have been positively associated. However, it was another retrospective study with recall bias.⁴ In 2009 Melnick and Schmitz⁵ concluded that milk causes the body to elevate both insulin and insulinlike growth factor 1 levels. In another study by Melnick⁶ in 2011, a definitive link between increased insulin and insulinlike growth factor 1 signaling in promoting comedogenesis was reported. Given the few studies that show the potential link between dairy products and acne, this dairy-free diet can be considered as a diet recommendation for acne patients.

Atopic Dermatitis

A Cochrane review conducted in 2012 regarding dietary supplements as a treatment of atopic dermatitis evaluated randomized controlled trials (N=596). Supplementation with vitamin D, fish oil, olive oil, zinc sulfate, selenium, vitamin E, pyridoxine, sea buckthorn seed oil, hempseed oil, sunflower oil (linoleic acid), and docosahexaenoic acid were evaluated among all the studies reviewed for atopic dermatitis.⁷ Bronsnick et al⁸ conducted a review of evidence supporting vitamin supplementation and atopic dermatitis, and for the most part determined that the studies had insufficient evidence. The only positive correlation was noted with prebiotics and probiotics in another Cochrane review in 2013, which evaluated 4 studies with 1428 infants showing prebiotic supplementation reduced atopic dermatitis.⁹ In 2014 Panduru et al¹⁰ evaluated 16 studies in a meta-analysis that showed how probiotics were possibly beneficial in both general and high-risk atopic populations. Specifically, a subgroup analysis showed that Lactobacillus and Lactobacillus with Bifidobacterium also can be protective against atopic dermatitis.¹⁰ Lastly, diet avoidance in pregnancy or during lactation in infants up to 18 months of age did not have any effect on improving the infant’s atopic dermatitis based on a 2012 Cochrane review that included 952 participants.¹¹

Conclusion

Overall, there are some benefits to dietary restrictions and supplementation as indicated by the studies reviewed here; however, the extent to which these changes contribute to disease manifestation has only been linked, not definitively proven. Randomized controlled trials with large sample sizes, double-blind studies, and appropriately controlled studies with comparative patient populations are difficult to obtain, as diet cannot be completely restrictive for every patient. Patients should be provided with the latest data supporting a possible link between dairy consumption and acne production as well as prebiotics or probiotics during pregnancy and at infancy to reduce the risk for atopic dermatitis with the caveat of association. That said, future studies might prove that dietary and environmental alterations may prevent disease progression or appearance far more than previously assumed.

When I am in clinic, I often get at least 3 to 4 inquiries each day from patients about the necessity for dietary restrictions or alterations as well as the benefits of these changes in limiting their dermatological disease processes. I usually am restricted in my response because the research rarely indicates benefits of one diet versus another; however, this discussion has recently become a heavily researched area as patients have come to value natural nonpharmaceutical approaches to their holistic care. In this article, a few dietary restrictions and supplements are reviewed that may have a beneficial effect in managing patients with acne vulgaris and atopic dermatitis.

Acne Vulgaris

In 1969 Fulton et al¹ conducted one of the first few trials on acne and diet management. In this crossover, patient-blinded, interventional study, patients were divided into 2 subgroups (N=65): 1 adolescent patient with moderate acne was compared to 1 male prisoner given a chocolate bar for 4 weeks or a control bar with equivalent caloric index. The results indicated no change in acne vulgaris lesions based on either intervention; however, there were obvious deficiencies in the study including small sample size, inappropriate grouping of an adolescent patient versus a prisoner, and limited study period.¹

Since then, multiple studies have been conducted with parallel participants, large sample sizes, and at least a 12-week study period. In 2005, Adebamowo et al² studied 47,355 women using a validated food frequency questionnaire that determined the amount of dairy consumed, specifically skim milk. The study showed a positive link between increased dairy consumption and acne formation; however, again due to the retrospective analysis and recall bias, it is difficult to determine if a link can truly be noted between acne and dairy in this study.²

More recently, LaRosa et al³ conducted a study that included 225 participants aged 14 to 19 years. Excluding participants with lactose intolerance and current use of oral contraceptives and isotretinoin, the study placed 120 participants in the test group versus 105 participants in the control group. The study was conducted using 3 telephone interviews and a 24-hour diet recall technique. The results supported a link between acne and skim milk consumption. Again, although the studied relied on participant self-reports of diet and followed a case-control design, a possible association was suspected but not validated.³ A longitudinal, questionnaire-based population study performed by Ulvestad et al⁴ included 2489 patients. This study further evaluated recall of dairy product consumption at 15 to 16 years of age and then 3 years later acne severity was self-assessed and reported at 18 to 19 years of age. Overall, this evaluation indicated that a high intake of dairy products and acne in adolescence have been positively associated. However, it was another retrospective study with recall bias.⁴ In 2009 Melnick and Schmitz⁵ concluded that milk causes the body to elevate both insulin and insulinlike growth factor 1 levels. In another study by Melnick⁶ in 2011, a definitive link between increased insulin and insulinlike growth factor 1 signaling in promoting comedogenesis was reported. Given the few studies that show the potential link between dairy products and acne, this dairy-free diet can be considered as a diet recommendation for acne patients.

Atopic Dermatitis

A Cochrane review conducted in 2012 regarding dietary supplements as a treatment of atopic dermatitis evaluated randomized controlled trials (N=596). Supplementation with vitamin D, fish oil, olive oil, zinc sulfate, selenium, vitamin E, pyridoxine, sea buckthorn seed oil, hempseed oil, sunflower oil (linoleic acid), and docosahexaenoic acid were evaluated among all the studies reviewed for atopic dermatitis.⁷ Bronsnick et al⁸ conducted a review of evidence supporting vitamin supplementation and atopic dermatitis, and for the most part determined that the studies had insufficient evidence. The only positive correlation was noted with prebiotics and probiotics in another Cochrane review in 2013, which evaluated 4 studies with 1428 infants showing prebiotic supplementation reduced atopic dermatitis.⁹ In 2014 Panduru et al¹⁰ evaluated 16 studies in a meta-analysis that showed how probiotics were possibly beneficial in both general and high-risk atopic populations. Specifically, a subgroup analysis showed that Lactobacillus and Lactobacillus with Bifidobacterium also can be protective against atopic dermatitis.¹⁰ Lastly, diet avoidance in pregnancy or during lactation in infants up to 18 months of age did not have any effect on improving the infant’s atopic dermatitis based on a 2012 Cochrane review that included 952 participants.¹¹

Conclusion

Overall, there are some benefits to dietary restrictions and supplementation as indicated by the studies reviewed here; however, the extent to which these changes contribute to disease manifestation has only been linked, not definitively proven. Randomized controlled trials with large sample sizes, double-blind studies, and appropriately controlled studies with comparative patient populations are difficult to obtain, as diet cannot be completely restrictive for every patient. Patients should be provided with the latest data supporting a possible link between dairy consumption and acne production as well as prebiotics or probiotics during pregnancy and at infancy to reduce the risk for atopic dermatitis with the caveat of association. That said, future studies might prove that dietary and environmental alterations may prevent disease progression or appearance far more than previously assumed.

When I am in clinic, I often get at least 3 to 4 inquiries each day from patients about the necessity for dietary restrictions or alterations as well as the benefits of these changes in limiting their dermatological disease processes. I usually am restricted in my response because the research rarely indicates benefits of one diet versus another; however, this discussion has recently become a heavily researched area as patients have come to value natural nonpharmaceutical approaches to their holistic care. In this article, a few dietary restrictions and supplements are reviewed that may have a beneficial effect in managing patients with acne vulgaris and atopic dermatitis.

Acne Vulgaris

In 1969 Fulton et al¹ conducted one of the first few trials on acne and diet management. In this crossover, patient-blinded, interventional study, patients were divided into 2 subgroups (N=65): 1 adolescent patient with moderate acne was compared to 1 male prisoner given a chocolate bar for 4 weeks or a control bar with equivalent caloric index. The results indicated no change in acne vulgaris lesions based on either intervention; however, there were obvious deficiencies in the study including small sample size, inappropriate grouping of an adolescent patient versus a prisoner, and limited study period.¹

Since then, multiple studies have been conducted with parallel participants, large sample sizes, and at least a 12-week study period. In 2005, Adebamowo et al² studied 47,355 women using a validated food frequency questionnaire that determined the amount of dairy consumed, specifically skim milk. The study showed a positive link between increased dairy consumption and acne formation; however, again due to the retrospective analysis and recall bias, it is difficult to determine if a link can truly be noted between acne and dairy in this study.²

More recently, LaRosa et al³ conducted a study that included 225 participants aged 14 to 19 years. Excluding participants with lactose intolerance and current use of oral contraceptives and isotretinoin, the study placed 120 participants in the test group versus 105 participants in the control group. The study was conducted using 3 telephone interviews and a 24-hour diet recall technique. The results supported a link between acne and skim milk consumption. Again, although the studied relied on participant self-reports of diet and followed a case-control design, a possible association was suspected but not validated.³ A longitudinal, questionnaire-based population study performed by Ulvestad et al⁴ included 2489 patients. This study further evaluated recall of dairy product consumption at 15 to 16 years of age and then 3 years later acne severity was self-assessed and reported at 18 to 19 years of age. Overall, this evaluation indicated that a high intake of dairy products and acne in adolescence have been positively associated. However, it was another retrospective study with recall bias.⁴ In 2009 Melnick and Schmitz⁵ concluded that milk causes the body to elevate both insulin and insulinlike growth factor 1 levels. In another study by Melnick⁶ in 2011, a definitive link between increased insulin and insulinlike growth factor 1 signaling in promoting comedogenesis was reported. Given the few studies that show the potential link between dairy products and acne, this dairy-free diet can be considered as a diet recommendation for acne patients.

Atopic Dermatitis

A Cochrane review conducted in 2012 regarding dietary supplements as a treatment of atopic dermatitis evaluated randomized controlled trials (N=596). Supplementation with vitamin D, fish oil, olive oil, zinc sulfate, selenium, vitamin E, pyridoxine, sea buckthorn seed oil, hempseed oil, sunflower oil (linoleic acid), and docosahexaenoic acid were evaluated among all the studies reviewed for atopic dermatitis.⁷ Bronsnick et al⁸ conducted a review of evidence supporting vitamin supplementation and atopic dermatitis, and for the most part determined that the studies had insufficient evidence. The only positive correlation was noted with prebiotics and probiotics in another Cochrane review in 2013, which evaluated 4 studies with 1428 infants showing prebiotic supplementation reduced atopic dermatitis.⁹ In 2014 Panduru et al¹⁰ evaluated 16 studies in a meta-analysis that showed how probiotics were possibly beneficial in both general and high-risk atopic populations. Specifically, a subgroup analysis showed that Lactobacillus and Lactobacillus with Bifidobacterium also can be protective against atopic dermatitis.¹⁰ Lastly, diet avoidance in pregnancy or during lactation in infants up to 18 months of age did not have any effect on improving the infant’s atopic dermatitis based on a 2012 Cochrane review that included 952 participants.¹¹

Conclusion

Overall, there are some benefits to dietary restrictions and supplementation as indicated by the studies reviewed here; however, the extent to which these changes contribute to disease manifestation has only been linked, not definitively proven. Randomized controlled trials with large sample sizes, double-blind studies, and appropriately controlled studies with comparative patient populations are difficult to obtain, as diet cannot be completely restrictive for every patient. Patients should be provided with the latest data supporting a possible link between dairy consumption and acne production as well as prebiotics or probiotics during pregnancy and at infancy to reduce the risk for atopic dermatitis with the caveat of association. That said, future studies might prove that dietary and environmental alterations may prevent disease progression or appearance far more than previously assumed.

Review the PDF of the fact sheet on Direct Immunofluorescence Staining Patterns in Blistering Disorders with board-relevant, easy-to-review material. This fact sheet reviews the dermatologic conditions that typically have positive immunofluorescence staining patterns.

Practice Questions

1. Which autoimmune blistering disease shows deposition of immunoglobulin on the floor of salt-split skin?

a. BP
b. dermatitis herpetiformis
c. epidermolysis bullosa acquisita
d. paraneoplastic pemphigus
e. PV

2. What medicine is commonly implicated in drug-induced pemphigus?

a. acetaminophen
b. amoxicillin
c. naproxen
d. penicillamine
e. penicillin

3. Which autoimmune blistering disease predominantly shows deposition of IgG on DIF?

a. dermatitis herpetiformis
b. IgA pemphigus
c. linear IgA bullous dermatosis
d. paraneoplastic pemphigus
e. porphyria cutanea tarda

4. Which of the following diseases has a negative direct immunofluorescence?

a. dermatitis herpetiformis
b. herpes gestationis
c. pemphigus vulgaris
d. porphyria cutanea tarda
e. transient acantholytic dermatosis

5. Which of the following diseases shows a linear deposition of IgG and C3 along the dermoepidermal junction?

a. CP
b. IgA pemphigus
c. PF
d. porphyria cutanea tarda
e. PV

Answers to practice questions provided on next page

Practice Question Answers

1. Which autoimmune blistering disease shows deposition of immunoglobulin on the floor of salt-split skin?
a. BP
b. dermatitis herpetiformis
c. epidermolysis bullosa acquisita
d. paraneoplastic pemphigus
e. PV

2. What medicine is commonly implicated in drug-induced pemphigus?
a. acetaminophen
b. amoxicillin
c. naproxen
d. penicillamine
e. penicillin

3. Which autoimmune blistering disease predominantly shows deposition of IgG on DIF?
a. dermatitis herpetiformis
b. IgA pemphigus
c. linear IgA bullous dermatosis
d. paraneoplastic pemphigus
e. porphyria cutanea tarda

4. Which of the following diseases has a negative direct immunofluorescence?
a. dermatitis herpetiformis
b. herpes gestationis
c. pemphigus vulgaris
d. porphyria cutanea tarda
e. transient acantholytic dermatosis

5. Which of the following diseases shows a linear deposition of IgG and C3 along the dermoepidermal junction?
a. CP
b. IgA pemphigus
c. PF
d. porphyria cutanea tarda
e. PV

Review the PDF of the fact sheet on Direct Immunofluorescence Staining Patterns in Blistering Disorders with board-relevant, easy-to-review material. This fact sheet reviews the dermatologic conditions that typically have positive immunofluorescence staining patterns.

Practice Questions

1. Which autoimmune blistering disease shows deposition of immunoglobulin on the floor of salt-split skin?

a. BP
b. dermatitis herpetiformis
c. epidermolysis bullosa acquisita
d. paraneoplastic pemphigus
e. PV

2. What medicine is commonly implicated in drug-induced pemphigus?

a. acetaminophen
b. amoxicillin
c. naproxen
d. penicillamine
e. penicillin

3. Which autoimmune blistering disease predominantly shows deposition of IgG on DIF?

a. dermatitis herpetiformis
b. IgA pemphigus
c. linear IgA bullous dermatosis
d. paraneoplastic pemphigus
e. porphyria cutanea tarda

4. Which of the following diseases has a negative direct immunofluorescence?

a. dermatitis herpetiformis
b. herpes gestationis
c. pemphigus vulgaris
d. porphyria cutanea tarda
e. transient acantholytic dermatosis

5. Which of the following diseases shows a linear deposition of IgG and C3 along the dermoepidermal junction?

a. CP
b. IgA pemphigus
c. PF
d. porphyria cutanea tarda
e. PV

Answers to practice questions provided on next page

Practice Question Answers

1. Which autoimmune blistering disease shows deposition of immunoglobulin on the floor of salt-split skin?
a. BP
b. dermatitis herpetiformis
c. epidermolysis bullosa acquisita
d. paraneoplastic pemphigus
e. PV

2. What medicine is commonly implicated in drug-induced pemphigus?
a. acetaminophen
b. amoxicillin
c. naproxen
d. penicillamine
e. penicillin

3. Which autoimmune blistering disease predominantly shows deposition of IgG on DIF?
a. dermatitis herpetiformis
b. IgA pemphigus
c. linear IgA bullous dermatosis
d. paraneoplastic pemphigus
e. porphyria cutanea tarda

4. Which of the following diseases has a negative direct immunofluorescence?
a. dermatitis herpetiformis
b. herpes gestationis
c. pemphigus vulgaris
d. porphyria cutanea tarda
e. transient acantholytic dermatosis

5. Which of the following diseases shows a linear deposition of IgG and C3 along the dermoepidermal junction?
a. CP
b. IgA pemphigus
c. PF
d. porphyria cutanea tarda
e. PV

Review the PDF of the fact sheet on Direct Immunofluorescence Staining Patterns in Blistering Disorders with board-relevant, easy-to-review material. This fact sheet reviews the dermatologic conditions that typically have positive immunofluorescence staining patterns.

Practice Questions

1. Which autoimmune blistering disease shows deposition of immunoglobulin on the floor of salt-split skin?

a. BP
b. dermatitis herpetiformis
c. epidermolysis bullosa acquisita
d. paraneoplastic pemphigus
e. PV

2. What medicine is commonly implicated in drug-induced pemphigus?

a. acetaminophen
b. amoxicillin
c. naproxen
d. penicillamine
e. penicillin

3. Which autoimmune blistering disease predominantly shows deposition of IgG on DIF?

a. dermatitis herpetiformis
b. IgA pemphigus
c. linear IgA bullous dermatosis
d. paraneoplastic pemphigus
e. porphyria cutanea tarda

4. Which of the following diseases has a negative direct immunofluorescence?

a. dermatitis herpetiformis
b. herpes gestationis
c. pemphigus vulgaris
d. porphyria cutanea tarda
e. transient acantholytic dermatosis

5. Which of the following diseases shows a linear deposition of IgG and C3 along the dermoepidermal junction?

a. CP
b. IgA pemphigus
c. PF
d. porphyria cutanea tarda
e. PV

Answers to practice questions provided on next page

Practice Question Answers

1. Which autoimmune blistering disease shows deposition of immunoglobulin on the floor of salt-split skin?
a. BP
b. dermatitis herpetiformis
c. epidermolysis bullosa acquisita
d. paraneoplastic pemphigus
e. PV

2. What medicine is commonly implicated in drug-induced pemphigus?
a. acetaminophen
b. amoxicillin
c. naproxen
d. penicillamine
e. penicillin

3. Which autoimmune blistering disease predominantly shows deposition of IgG on DIF?
a. dermatitis herpetiformis
b. IgA pemphigus
c. linear IgA bullous dermatosis
d. paraneoplastic pemphigus
e. porphyria cutanea tarda

4. Which of the following diseases has a negative direct immunofluorescence?
a. dermatitis herpetiformis
b. herpes gestationis
c. pemphigus vulgaris
d. porphyria cutanea tarda
e. transient acantholytic dermatosis

5. Which of the following diseases shows a linear deposition of IgG and C3 along the dermoepidermal junction?
a. CP
b. IgA pemphigus
c. PF
d. porphyria cutanea tarda
e. PV

To the Editor:

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder that causes subepithelial damage and scarring of mucosal surfaces with or without skin involvement.¹ The clinical presentation is highly variable. The oropharynx is the most common site of initial presentation, followed by ocular, nasopharyngeal, anogenital, skin, laryngeal, and esophageal involvement.² Patients often present to a variety of specialists depending on initial symptoms, and due to the diverse clinical manifestations, MMP often is misdiagnosed. Our patient presented an even greater challenge because the disease progressed to tracheal and bronchial involvement.

A 37-year-old man presented to his primary care physician with a chief concern of a sore throat and oral ulcers. The patient was treated with a course of antibiotics followed by a nystatin oral solution. He continued to develop ulcerative lesions on the soft palate, posterior pharynx, and nasal mucosae. He sought treatment from 2 otolaryngologists (ENTs) and a gastroenterologist, and continued to be treated with multiple oral antibiotics, fluconazole, and topical nystatin. Despite treatment, the patient developed pansinusitis and laryngitis and presented to the ENT department at our institution with severe hoarseness and dyspnea on exertion. Examination by the ENT department revealed ulcerative lesions of the nares with stenosis and ulcers along the soft palate. Videolaryngostroboscopy showed remarkable supraglottic edema with thick endolaryngeal mucus. The patient worked as a funeral director and had notable formaldehyde exposure. He also hunted wild game and performed taxidermy regularly.

The patient was admitted and treated with intravenous dexamethasone for a compromised airway. Subsequently, he was taken to the operating room and had biopsies performed of the posterior pharynx. Given his exposure history, the infectious disease department was consulted and he was evaluated for multiple viral, bacterial, and fungal suspects including leishmania and tularemia. Age-appropriate screening, physical examination, and review of systems were negative for an underlying neoplasm. Histopathologic examination revealed a subepithelial vesicular mucositis with a mixed infiltrate of lymphocytes and histiocytes. Direct immunofluorescence microscopy demonstrated strong linear fluorescence along the epithelial-subepithelial junction with IgG and C3. Based on these findings, the diagnosis of MMP was made.

Further testing for bullous pemphigoid antigen 1 (BP230) and bullous pemphigoid antigen 2 (BP180) were negative. On one occasion the patient tested positive for anti-BP230 IgG, but it was at a level judged to be insignificant (7.5 [reference range, <9]). The patient also was negative for autoantibodies against desmoglein 1 and 3. Indirect immunofluorescence using rat bladder epithelium was not performed.

The patient was started on methotrexate and oral prednisone by the rheumatology department, but after 1 week, he presented in respiratory distress and was taken for an emergency tracheostomy. The patient eventually was referred to the dermatology department where methotrexate was discontinued and the patient was started on titrating doses of prednisone and mycophenolate mofetil. Eight weeks later, the patient became completely aphonic and was taken by ENT for dilation of the supraglottic, glottic, and subglottic stenosis with mucosal triamcinolone injections. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily was initiated in addition to mycophenolate mofetil 3 g and prednisone 80 mg, but again the patient developed near-complete tracheal stenosis just proximal to the tracheostomy entry site. At 16 weeks, balloon dilation was repeated with dexamethasone injections and topical mitomycin C. Subsequently, the patient regained some use of his voice. Although the next several laryngoscopes showed improvement in the patient’s epiglottis and glottis, the trachea continued to require debridement and dilation.

Despite maximal medical therapy and surgical interventions, the patient had little improvement in his voice and large clots of blood obstructed his tracheostomy daily. He was unable to sleep in his preferred position on the stomach (prone) due to dyspnea but had less distress sleeping on his back (supine). The patient was referred to the pulmonology department for an endotracheobronchoscopy to further evaluate the airway. It was discovered that the mucosa of the trachea from the level of the tracheostomy to the carina was friable with active erosions and thick bloody secretions (Figure 1). Lesions extended as far as the scope was able to visualize to the left upper lobe takeoff and the right mainstem bronchus (Figure 2). Biopsies of the carinal mucosa showed 3+/3+ linear fluorescence with IgG along the dermoepidermal junction. Salt-split studies were performed, but because the specimen was fragmented, it was not possible to assess if the fluorescence was present at the floor or at the roof of the split.

Given the severity of disease and failure to respond to other aggressive immunosuppressive therapies as well as having been with a tracheostomy for 22 months, the patient was started on 2 doses of intravenous rituximab 1 g 2 weeks apart along with trimethoprim-sulfamethoxazole (3 times weekly) for pneumocystis pneumonia prophylaxis. No complications were observed during infusions. After 2 rituximab infusions, he was weaned off of prednisone and a repeat bronchoscopy showed no airway ulcers beyond the distal trachea or endobronchial obstruction. However, the subglottic space and area above the tracheostomy showed remarkable stenosis with a cobblestone pattern and granulation tissue with continued narrowing of the subglottic area. The ENT performed further dilation and after 34 months, the tracheostomy was removed and a T-tube was placed. The patient required cleaning out of the T-tube approximately every 3 months, and after 2 years the original T-tube was replaced with a new one. At the time of this report, the ENT recommended removing the T-tube, but the patient was reluctant to do so; therefore, a second T-tube replacement is planned. He continues to do well without relapse and has been off all medical therapy for nearly 4 years.

Mucous membrane pemphigoid is an acquired autoimmune subepithelial blistering disease that predominantly affects mucous membranes with or without skin involvement. This condition has been referred to as cicatricial pemphigoid, oral pemphigoid, and ocular cicatricial pemphigoid, among other names. It is characterized by linear deposition of IgG, IgA, or C3 along the epithelial basement membrane zone. According to the international consensus on MMP, the target antigens identified in the epithelial basement membrane zone include bullous pemphigoid antigen 1 (BP230), bullous pemphigoid antigen 2 (BP180), laminin 5 (α3, β3, γ2 chains), laminin 6 (α3 chain), type VII collagen, and integrin β4 subunit.³ Not all patients with MMP will have circulating autoantibodies to the above components, and although our patient did have detectable anti-BP230 IgG, it was not considered clinically significant. Furthermore, the type of autoantibody does not impact decisions regarding therapy selection.³

Although rare, MMP is well-known to dermatologists and ophthalmologists who manage a large majority of MMP patients depending on which mucosa is involved. Mucous membrane pemphigoid is extremely rare in the lower respiratory tract, and when these lesions are discovered, it often is in the face of life-threatening respiratory distress. Mucous membrane pemphigoid is a challenging disease to treat, even more so when the primary specialty physician is unable to visualize the affected areas. Our patient’s disease was limited primarily to the pharynx, larynx, trachea, and bronchi with few oral lesions. According to a PubMed search of articles indexed for MEDLINE using the terms mucous membrane pemphigus, cicatricial pemphigoid, trachea, bronchus, and fatal, 8 reports (7 case reports and 1 prospective study) of MMP involving the lower respiratory tract have been published.^4-11 Of the case reports, each patient also presented with involvement of the eyes or skin.^4,5,7-11 Four of these cases were fatal secondary to cardiopulmonary arrest.^5,7,9,10 In the prospective study, 110 consecutive patients with clinical, histologic, and immunologic criteria of MMP were examined with a flexible nasopharyngolaryngoscope.⁶ Thirty-eight patients had nose or throat symptoms but only 10 had laryngeal involvement and 5 had acute dyspnea. The nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 patients, which was fatal in 3.⁶

Medical treatment should be based on the following factors of the patient’s disease: site, severity, and rapidity of progression.³ High-risk patients can be defined as those who have lesions at any of the following sites: ocular, genital, nasopharyngeal, esophageal, and laryngeal mucosae. As our patient had involvement at several high-risk sites, in particular sites only visualized by various scoping procedures, a team of physicians including dermatologists, ENT physicians, pulmonologists, and oncologists was necessary to facilitate his care. Scarring is the hallmark of MMP and prevention of scarring is the most important aspect of treatment of MMP. Surgical repair of the previously involved mucosa is difficult, as the tissue is prone to re-scarring and difficult to heal. Over the last several years, there has been increasing evidence for the use of rituximab in autoimmune bullous skin diseases including pemphigus vulgaris, epidermolysis bullosa acquisita, and MMP.^12-14 After 2 infusions of rituximab, our patient had clearance of his disease and currently is doing well with a T-tube.

Acknowledgments

We thank Kim Yancey, MD (Dallas, Texas), for providing access to the patient’s diagnostic laboratory immunology and reviewing biopsy specimens; Luis Angel, MD (San Antonio, Texas), for providing bronchoscopy photographs; and C. Blake Simpson, MD (San Antonio, Texas), for co-managing this challenging case.

To the Editor:

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder that causes subepithelial damage and scarring of mucosal surfaces with or without skin involvement.¹ The clinical presentation is highly variable. The oropharynx is the most common site of initial presentation, followed by ocular, nasopharyngeal, anogenital, skin, laryngeal, and esophageal involvement.² Patients often present to a variety of specialists depending on initial symptoms, and due to the diverse clinical manifestations, MMP often is misdiagnosed. Our patient presented an even greater challenge because the disease progressed to tracheal and bronchial involvement.

A 37-year-old man presented to his primary care physician with a chief concern of a sore throat and oral ulcers. The patient was treated with a course of antibiotics followed by a nystatin oral solution. He continued to develop ulcerative lesions on the soft palate, posterior pharynx, and nasal mucosae. He sought treatment from 2 otolaryngologists (ENTs) and a gastroenterologist, and continued to be treated with multiple oral antibiotics, fluconazole, and topical nystatin. Despite treatment, the patient developed pansinusitis and laryngitis and presented to the ENT department at our institution with severe hoarseness and dyspnea on exertion. Examination by the ENT department revealed ulcerative lesions of the nares with stenosis and ulcers along the soft palate. Videolaryngostroboscopy showed remarkable supraglottic edema with thick endolaryngeal mucus. The patient worked as a funeral director and had notable formaldehyde exposure. He also hunted wild game and performed taxidermy regularly.

The patient was admitted and treated with intravenous dexamethasone for a compromised airway. Subsequently, he was taken to the operating room and had biopsies performed of the posterior pharynx. Given his exposure history, the infectious disease department was consulted and he was evaluated for multiple viral, bacterial, and fungal suspects including leishmania and tularemia. Age-appropriate screening, physical examination, and review of systems were negative for an underlying neoplasm. Histopathologic examination revealed a subepithelial vesicular mucositis with a mixed infiltrate of lymphocytes and histiocytes. Direct immunofluorescence microscopy demonstrated strong linear fluorescence along the epithelial-subepithelial junction with IgG and C3. Based on these findings, the diagnosis of MMP was made.

Further testing for bullous pemphigoid antigen 1 (BP230) and bullous pemphigoid antigen 2 (BP180) were negative. On one occasion the patient tested positive for anti-BP230 IgG, but it was at a level judged to be insignificant (7.5 [reference range, <9]). The patient also was negative for autoantibodies against desmoglein 1 and 3. Indirect immunofluorescence using rat bladder epithelium was not performed.

The patient was started on methotrexate and oral prednisone by the rheumatology department, but after 1 week, he presented in respiratory distress and was taken for an emergency tracheostomy. The patient eventually was referred to the dermatology department where methotrexate was discontinued and the patient was started on titrating doses of prednisone and mycophenolate mofetil. Eight weeks later, the patient became completely aphonic and was taken by ENT for dilation of the supraglottic, glottic, and subglottic stenosis with mucosal triamcinolone injections. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily was initiated in addition to mycophenolate mofetil 3 g and prednisone 80 mg, but again the patient developed near-complete tracheal stenosis just proximal to the tracheostomy entry site. At 16 weeks, balloon dilation was repeated with dexamethasone injections and topical mitomycin C. Subsequently, the patient regained some use of his voice. Although the next several laryngoscopes showed improvement in the patient’s epiglottis and glottis, the trachea continued to require debridement and dilation.

Despite maximal medical therapy and surgical interventions, the patient had little improvement in his voice and large clots of blood obstructed his tracheostomy daily. He was unable to sleep in his preferred position on the stomach (prone) due to dyspnea but had less distress sleeping on his back (supine). The patient was referred to the pulmonology department for an endotracheobronchoscopy to further evaluate the airway. It was discovered that the mucosa of the trachea from the level of the tracheostomy to the carina was friable with active erosions and thick bloody secretions (Figure 1). Lesions extended as far as the scope was able to visualize to the left upper lobe takeoff and the right mainstem bronchus (Figure 2). Biopsies of the carinal mucosa showed 3+/3+ linear fluorescence with IgG along the dermoepidermal junction. Salt-split studies were performed, but because the specimen was fragmented, it was not possible to assess if the fluorescence was present at the floor or at the roof of the split.

Given the severity of disease and failure to respond to other aggressive immunosuppressive therapies as well as having been with a tracheostomy for 22 months, the patient was started on 2 doses of intravenous rituximab 1 g 2 weeks apart along with trimethoprim-sulfamethoxazole (3 times weekly) for pneumocystis pneumonia prophylaxis. No complications were observed during infusions. After 2 rituximab infusions, he was weaned off of prednisone and a repeat bronchoscopy showed no airway ulcers beyond the distal trachea or endobronchial obstruction. However, the subglottic space and area above the tracheostomy showed remarkable stenosis with a cobblestone pattern and granulation tissue with continued narrowing of the subglottic area. The ENT performed further dilation and after 34 months, the tracheostomy was removed and a T-tube was placed. The patient required cleaning out of the T-tube approximately every 3 months, and after 2 years the original T-tube was replaced with a new one. At the time of this report, the ENT recommended removing the T-tube, but the patient was reluctant to do so; therefore, a second T-tube replacement is planned. He continues to do well without relapse and has been off all medical therapy for nearly 4 years.

Mucous membrane pemphigoid is an acquired autoimmune subepithelial blistering disease that predominantly affects mucous membranes with or without skin involvement. This condition has been referred to as cicatricial pemphigoid, oral pemphigoid, and ocular cicatricial pemphigoid, among other names. It is characterized by linear deposition of IgG, IgA, or C3 along the epithelial basement membrane zone. According to the international consensus on MMP, the target antigens identified in the epithelial basement membrane zone include bullous pemphigoid antigen 1 (BP230), bullous pemphigoid antigen 2 (BP180), laminin 5 (α3, β3, γ2 chains), laminin 6 (α3 chain), type VII collagen, and integrin β4 subunit.³ Not all patients with MMP will have circulating autoantibodies to the above components, and although our patient did have detectable anti-BP230 IgG, it was not considered clinically significant. Furthermore, the type of autoantibody does not impact decisions regarding therapy selection.³

Although rare, MMP is well-known to dermatologists and ophthalmologists who manage a large majority of MMP patients depending on which mucosa is involved. Mucous membrane pemphigoid is extremely rare in the lower respiratory tract, and when these lesions are discovered, it often is in the face of life-threatening respiratory distress. Mucous membrane pemphigoid is a challenging disease to treat, even more so when the primary specialty physician is unable to visualize the affected areas. Our patient’s disease was limited primarily to the pharynx, larynx, trachea, and bronchi with few oral lesions. According to a PubMed search of articles indexed for MEDLINE using the terms mucous membrane pemphigus, cicatricial pemphigoid, trachea, bronchus, and fatal, 8 reports (7 case reports and 1 prospective study) of MMP involving the lower respiratory tract have been published.^4-11 Of the case reports, each patient also presented with involvement of the eyes or skin.^4,5,7-11 Four of these cases were fatal secondary to cardiopulmonary arrest.^5,7,9,10 In the prospective study, 110 consecutive patients with clinical, histologic, and immunologic criteria of MMP were examined with a flexible nasopharyngolaryngoscope.⁶ Thirty-eight patients had nose or throat symptoms but only 10 had laryngeal involvement and 5 had acute dyspnea. The nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 patients, which was fatal in 3.⁶

Medical treatment should be based on the following factors of the patient’s disease: site, severity, and rapidity of progression.³ High-risk patients can be defined as those who have lesions at any of the following sites: ocular, genital, nasopharyngeal, esophageal, and laryngeal mucosae. As our patient had involvement at several high-risk sites, in particular sites only visualized by various scoping procedures, a team of physicians including dermatologists, ENT physicians, pulmonologists, and oncologists was necessary to facilitate his care. Scarring is the hallmark of MMP and prevention of scarring is the most important aspect of treatment of MMP. Surgical repair of the previously involved mucosa is difficult, as the tissue is prone to re-scarring and difficult to heal. Over the last several years, there has been increasing evidence for the use of rituximab in autoimmune bullous skin diseases including pemphigus vulgaris, epidermolysis bullosa acquisita, and MMP.^12-14 After 2 infusions of rituximab, our patient had clearance of his disease and currently is doing well with a T-tube.

Acknowledgments

We thank Kim Yancey, MD (Dallas, Texas), for providing access to the patient’s diagnostic laboratory immunology and reviewing biopsy specimens; Luis Angel, MD (San Antonio, Texas), for providing bronchoscopy photographs; and C. Blake Simpson, MD (San Antonio, Texas), for co-managing this challenging case.

To the Editor:

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder that causes subepithelial damage and scarring of mucosal surfaces with or without skin involvement.¹ The clinical presentation is highly variable. The oropharynx is the most common site of initial presentation, followed by ocular, nasopharyngeal, anogenital, skin, laryngeal, and esophageal involvement.² Patients often present to a variety of specialists depending on initial symptoms, and due to the diverse clinical manifestations, MMP often is misdiagnosed. Our patient presented an even greater challenge because the disease progressed to tracheal and bronchial involvement.

A 37-year-old man presented to his primary care physician with a chief concern of a sore throat and oral ulcers. The patient was treated with a course of antibiotics followed by a nystatin oral solution. He continued to develop ulcerative lesions on the soft palate, posterior pharynx, and nasal mucosae. He sought treatment from 2 otolaryngologists (ENTs) and a gastroenterologist, and continued to be treated with multiple oral antibiotics, fluconazole, and topical nystatin. Despite treatment, the patient developed pansinusitis and laryngitis and presented to the ENT department at our institution with severe hoarseness and dyspnea on exertion. Examination by the ENT department revealed ulcerative lesions of the nares with stenosis and ulcers along the soft palate. Videolaryngostroboscopy showed remarkable supraglottic edema with thick endolaryngeal mucus. The patient worked as a funeral director and had notable formaldehyde exposure. He also hunted wild game and performed taxidermy regularly.

The patient was admitted and treated with intravenous dexamethasone for a compromised airway. Subsequently, he was taken to the operating room and had biopsies performed of the posterior pharynx. Given his exposure history, the infectious disease department was consulted and he was evaluated for multiple viral, bacterial, and fungal suspects including leishmania and tularemia. Age-appropriate screening, physical examination, and review of systems were negative for an underlying neoplasm. Histopathologic examination revealed a subepithelial vesicular mucositis with a mixed infiltrate of lymphocytes and histiocytes. Direct immunofluorescence microscopy demonstrated strong linear fluorescence along the epithelial-subepithelial junction with IgG and C3. Based on these findings, the diagnosis of MMP was made.

Further testing for bullous pemphigoid antigen 1 (BP230) and bullous pemphigoid antigen 2 (BP180) were negative. On one occasion the patient tested positive for anti-BP230 IgG, but it was at a level judged to be insignificant (7.5 [reference range, <9]). The patient also was negative for autoantibodies against desmoglein 1 and 3. Indirect immunofluorescence using rat bladder epithelium was not performed.

The patient was started on methotrexate and oral prednisone by the rheumatology department, but after 1 week, he presented in respiratory distress and was taken for an emergency tracheostomy. The patient eventually was referred to the dermatology department where methotrexate was discontinued and the patient was started on titrating doses of prednisone and mycophenolate mofetil. Eight weeks later, the patient became completely aphonic and was taken by ENT for dilation of the supraglottic, glottic, and subglottic stenosis with mucosal triamcinolone injections. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily was initiated in addition to mycophenolate mofetil 3 g and prednisone 80 mg, but again the patient developed near-complete tracheal stenosis just proximal to the tracheostomy entry site. At 16 weeks, balloon dilation was repeated with dexamethasone injections and topical mitomycin C. Subsequently, the patient regained some use of his voice. Although the next several laryngoscopes showed improvement in the patient’s epiglottis and glottis, the trachea continued to require debridement and dilation.

Despite maximal medical therapy and surgical interventions, the patient had little improvement in his voice and large clots of blood obstructed his tracheostomy daily. He was unable to sleep in his preferred position on the stomach (prone) due to dyspnea but had less distress sleeping on his back (supine). The patient was referred to the pulmonology department for an endotracheobronchoscopy to further evaluate the airway. It was discovered that the mucosa of the trachea from the level of the tracheostomy to the carina was friable with active erosions and thick bloody secretions (Figure 1). Lesions extended as far as the scope was able to visualize to the left upper lobe takeoff and the right mainstem bronchus (Figure 2). Biopsies of the carinal mucosa showed 3+/3+ linear fluorescence with IgG along the dermoepidermal junction. Salt-split studies were performed, but because the specimen was fragmented, it was not possible to assess if the fluorescence was present at the floor or at the roof of the split.

Given the severity of disease and failure to respond to other aggressive immunosuppressive therapies as well as having been with a tracheostomy for 22 months, the patient was started on 2 doses of intravenous rituximab 1 g 2 weeks apart along with trimethoprim-sulfamethoxazole (3 times weekly) for pneumocystis pneumonia prophylaxis. No complications were observed during infusions. After 2 rituximab infusions, he was weaned off of prednisone and a repeat bronchoscopy showed no airway ulcers beyond the distal trachea or endobronchial obstruction. However, the subglottic space and area above the tracheostomy showed remarkable stenosis with a cobblestone pattern and granulation tissue with continued narrowing of the subglottic area. The ENT performed further dilation and after 34 months, the tracheostomy was removed and a T-tube was placed. The patient required cleaning out of the T-tube approximately every 3 months, and after 2 years the original T-tube was replaced with a new one. At the time of this report, the ENT recommended removing the T-tube, but the patient was reluctant to do so; therefore, a second T-tube replacement is planned. He continues to do well without relapse and has been off all medical therapy for nearly 4 years.

Mucous membrane pemphigoid is an acquired autoimmune subepithelial blistering disease that predominantly affects mucous membranes with or without skin involvement. This condition has been referred to as cicatricial pemphigoid, oral pemphigoid, and ocular cicatricial pemphigoid, among other names. It is characterized by linear deposition of IgG, IgA, or C3 along the epithelial basement membrane zone. According to the international consensus on MMP, the target antigens identified in the epithelial basement membrane zone include bullous pemphigoid antigen 1 (BP230), bullous pemphigoid antigen 2 (BP180), laminin 5 (α3, β3, γ2 chains), laminin 6 (α3 chain), type VII collagen, and integrin β4 subunit.³ Not all patients with MMP will have circulating autoantibodies to the above components, and although our patient did have detectable anti-BP230 IgG, it was not considered clinically significant. Furthermore, the type of autoantibody does not impact decisions regarding therapy selection.³

Although rare, MMP is well-known to dermatologists and ophthalmologists who manage a large majority of MMP patients depending on which mucosa is involved. Mucous membrane pemphigoid is extremely rare in the lower respiratory tract, and when these lesions are discovered, it often is in the face of life-threatening respiratory distress. Mucous membrane pemphigoid is a challenging disease to treat, even more so when the primary specialty physician is unable to visualize the affected areas. Our patient’s disease was limited primarily to the pharynx, larynx, trachea, and bronchi with few oral lesions. According to a PubMed search of articles indexed for MEDLINE using the terms mucous membrane pemphigus, cicatricial pemphigoid, trachea, bronchus, and fatal, 8 reports (7 case reports and 1 prospective study) of MMP involving the lower respiratory tract have been published.^4-11 Of the case reports, each patient also presented with involvement of the eyes or skin.^4,5,7-11 Four of these cases were fatal secondary to cardiopulmonary arrest.^5,7,9,10 In the prospective study, 110 consecutive patients with clinical, histologic, and immunologic criteria of MMP were examined with a flexible nasopharyngolaryngoscope.⁶ Thirty-eight patients had nose or throat symptoms but only 10 had laryngeal involvement and 5 had acute dyspnea. The nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 patients, which was fatal in 3.⁶

Medical treatment should be based on the following factors of the patient’s disease: site, severity, and rapidity of progression.³ High-risk patients can be defined as those who have lesions at any of the following sites: ocular, genital, nasopharyngeal, esophageal, and laryngeal mucosae. As our patient had involvement at several high-risk sites, in particular sites only visualized by various scoping procedures, a team of physicians including dermatologists, ENT physicians, pulmonologists, and oncologists was necessary to facilitate his care. Scarring is the hallmark of MMP and prevention of scarring is the most important aspect of treatment of MMP. Surgical repair of the previously involved mucosa is difficult, as the tissue is prone to re-scarring and difficult to heal. Over the last several years, there has been increasing evidence for the use of rituximab in autoimmune bullous skin diseases including pemphigus vulgaris, epidermolysis bullosa acquisita, and MMP.^12-14 After 2 infusions of rituximab, our patient had clearance of his disease and currently is doing well with a T-tube.

Acknowledgments

We thank Kim Yancey, MD (Dallas, Texas), for providing access to the patient’s diagnostic laboratory immunology and reviewing biopsy specimens; Luis Angel, MD (San Antonio, Texas), for providing bronchoscopy photographs; and C. Blake Simpson, MD (San Antonio, Texas), for co-managing this challenging case.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease.¹ The majority of BP cases are idiopathic and occur in patients older than 60 years. The disease is characterized by the development of circulating IgG autoantibodies reacting with the BP180 antigen of the basement membrane zone.¹ Psoriasis vulgaris (PV) is a common, chronic, immune-mediated disease affecting approximately 2% of the world’s population including children and adults.² Both entities may coexist with internal disorders such as hypertension, diabetes mellitus, coronary heart disease, congestive heart failure, hyperlipidemia, and cerebrovascular accident. It has been postulated that BP more often coexists with neurological disorders, such as stroke and Parkinson disease,³ whereas PV usually is associated with cardiovascular disorders and diabetes mellitus.² We report the case of a 35-year-old man with chronic PV and metabolic syndrome who developed BP that was successfully treated with methotrexate (MTX).

Case Report

A 35-year-old man with a 15-year history of PV, class 3 obesity (body mass index, 69.2), and thrombosis of the left leg was referred to the dermatology department due to a sudden extensive erythematous and bullous eruption located on the trunk, arms, and legs with involvement of the oral mucosa that had started 4 weeks prior. The skin lesions were accompanied by severe pruritus. On admission to the hospital, the patient presented with stable psoriatic plaques located on the trunk, arms, and proximal part of the lower legs with a psoriasis area severity index score of 11.8 (Figure 1A). He also had disseminated tense blisters and erosions partially arranged in an annular pattern located on the border of the psoriatic plaques as well as on an erythematous base or within unaffected skin (Figure 1B). Additionally, a few small erosions were present on the oral mucosa.

The patient’s father had a history of PV, but there was no family history of obesity or autoimmune blistering disorders. On physical examination, central obesity was noted with a waist circumference of 180 cm and a body mass index of 69.2; his blood pressure was 220/150 mm Hg. Laboratory tests revealed leukocytosis (20.06×10⁹/L [reference range, 4.5–11.0×10⁹/L]) with neutrophilia (16.2×10⁹/L [reference range, 1.6–7.6×10⁹/L]; 80.9% [reference range, 40.0%–70.0%]), eosinophilia (1.01×10⁹/L [reference range, 0–0.5×10⁹/L]), elevated C-reactive protein levels (49.4 mg/L [reference range, 0.0–9.0 mg/L]), elevated erythrocyte sedimentation rate (35 mm/h [reference range, 0–12 mm/h]), elevated γ-glutamyltransferase (66 U/L [reference range, 0–55 U/L]), decreased high-density lipoprotein levels (38 mg/dL [reference range, ≥40 mg/dL]), elevated fasting plasma glucose (116 mg/dL or 6.4 mmol/L [reference range, 70–99 mg/dL or 3.9–5.5 mmol/L]), elevated total IgE (1540 µg/L [reference range, 0–1000 µg/L]), elevated D-dimer (3.21 µg/mL [reference range, <0.5 µg/mL]), and low free triiodothyronine levels (130 pg/dL [reference range, 171–371 pg/dL]). The total protein level was 6.5 g/dL (reference range, 6.0–8.0 g/dL) and albumin level was 3.2 g/dL (reference range, 4.02–4.76 g/dL). A chest radiograph showed no abnormalities.

Based on the physical examination and laboratory testing, it was determined that the patient fulfilled 4 of 5 criteria for metabolic syndrome described by the International Diabetes Federation in 2006 (Table).⁴ Direct immunofluorescence performed on normal-appearing perilesional skin demonstrated linear IgG and C3 deposits along the basement membrane zone. Indirect immunofluorescence detected circulating IgG autoantibodies at a titer of 1:80. Serum studies using biochip mosaics⁵ revealed the reactivity of circulating IgG antibodies to the epidermal side of salt-split skin and with antigen dots of tetrameric BP180-NC16a, which prompted the diagnosis of BP (Figure 2).

Oral treatment with MTX 12.5 mg once weekly with clobetasol propionate cream applied to affected skin was initiated for 4 weeks. The PV resolved completely and blister formation stopped. A few weeks later BP reappeared, even though the patient was still taking MTX. The treatment failure may have been related to the patient’s class 3 obesity; therefore, the dose was increased to 20 mg once weekly for 8 weeks, which led to rapid healing of BP erosions. The patient was monitored for 2 months with no symptoms of recurrence.

Comment

Psoriasis Comorbidities

The correlation between PV and cardiovascular disorders such as myocardial infarction, cerebrovascular accident, and pulmonary embolism has been well established and is widely accepted.² It also has been documented that the risk for metabolic syndrome with components such as diabetes mellitus, hypertension, lipid abnormalities, obesity, and arteriosclerosis is notably increased in PV patients.⁶ Moreover, associated internal disorders are responsible for a 3- to 4-year reduction in life expectancy in patients with moderate to severe PV.⁷

Correlation of PV and BP

Psoriasis also may coexist with autoimmune disorders such as rheumatoid arthritis, lupus erythematosus, and blistering disorders.⁸ There are more than 60 known cases reporting PV in association with various types of subepidermal blistering diseases, including pemphigus vulgaris, epidermolysis bullosa acquisita, anti-p200 pemphigoid, and BP.^8,9 The pathogenetic relationship between BP and PV remains obscure. In most published cases, PV preceded BP by 5 to 30 years, possibly ascribable to patients being diagnosed with PV at a younger age.⁹ In general, patients with BP and PV are younger than patients with BP only, with a mean age of 62 years.⁹ Because our patient was in his mid-30s when he developed BP, in such cases physicians should take under consideration any triggering factors (eg, drugs). Physical examination and detailed laboratory findings allowed us to make the patient aware of the potential for development of metabolic syndrome. This condition in combination with PV could be a predisposing factor for BP development. According to more recent research, PV is considered a generalized inflammatory process rather than a disorder limited to the skin and joints.¹⁰ The chronic inflammatory process in psoriatic skin results in exposure of autoantigens, leading to an immune response and the production of BP antibodies. The neutrophil elastase enzyme present in psoriatic lesions also may take part in dermoepidermal junction degradation and blister formation of BP.¹¹ According to other observations, some antipsoriatic therapies (eg, psoralen plus UVA, UVB, dithranol, coal tar) could be associated with development of BP.¹² Moreover, it was shown that psoralen plus UVA therapy, which is widely used in PV treatment, alters the cytokine profile from helper T cells T_H1 to T_H2.¹² T_H2-dependent cytokines predominate the sera and erosions in BP patients and seem to be notably relevant to the pathophysiology of the disease.¹³ The history of our patient’s psoriatic treatment included only topical corticosteroids, keratolytic agents, and occasionally dithranol and coal tar; however, UV phototherapy or any other systemic therapies had never been utilized. Three previously reported cases of patients with PV and BP also revealed no history of UV phototherapy,^8,9 which suggests that mechanisms responsible for coexistence of PV and BP are more complex. It has been proven that proinflammatory cytokines secreted by T_H1 and T_H17 cells, in particular tumor necrosis factor α, IL-17, IL-22, and IL-23, play an important role in the development of psoriatic lesions.¹⁰ On the other hand, these cytokines are known to contribute to vascular inflammation, leading to development of arteriosclerosis, as well as to regulate adipogenesis and obesity.^14,15 Arakawa et al¹⁶ reported increased expression of IL-17 in lesional skin in BP. They concluded that IL-17 may contribute to the recruitment of eosinophils and neutrophils and tissue damage in BP. Therefore, it is highly likely that IL-17 might be a common factor underlying the coexistence of BP with PV and metabolic syndrome. More such reports are required for better understanding this association.

BP Treatment

Selecting a therapy for BP with coexistent PV is challenging, especially in patients with extreme obesity and metabolic syndrome. It is well established that obesity correlates with a higher incidence of PV and more severe disease. On the other hand, obesity also influences response to therapy. Systemic corticosteroids are contraindicated in psoriasis patients because of severe side effects, such as rebound phenomenon of psoriatic lesions and risk for development of generalized pustular PV. Although systemic corticosteroids are effective in BP, high-dose therapy may potentially be life-threatening, particularly in these obese patients with conditions such as hypertension and diabetes mellitus, among others,¹ as was observed in our case. Taking into consideration the above mentioned conditions and our experience on such cases, the current patient had received MTX (12.5 mg once weekly) and clobetasol propionate cream, which led to the rapid healing of the psoriatic plaques, whereas BP was more resistant to this therapy. This response may be explained by our patient’s class 3 obesity (body mass index, 69.2). Therefore, the dose of MTX was increased to 20 mg once weekly and was successful. The decision to use MTX was supported by evidence that this medicine may reduce the risk for arteriosclerosis and cardiovascular disorders.¹⁷

There are some alternative therapeutic options for patients with coexisting BP and PV, such as cyclosporine,¹⁸ combination low-dose cyclosporine and low-dose systemic corticosteroids,¹⁹ dapsone,²⁰ azathioprine,²¹ mycophenolate mofetil,²² and acitretin.²³ It also has been shown that biologics (eg, ustekinumab) may be a successful solution in patients with PV and antilaminin-γ1 pemphigoid.²⁴ However, these alternative therapeutic regimens could not be considered in our patient because of serious coexisting internal disorders.

Conclusion

We present a case of concomitant BP and PV in a patient with metabolic syndrome. Although the pathogenic role of this unique coexistence is not fully understood, MTX proved suitable and effective in this single case. Further studies should be performed to elucidate the pathogenic relationship and therapeutic solutions for cases with coexisting PV, BP, and metabolic syndrome.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease.¹ The majority of BP cases are idiopathic and occur in patients older than 60 years. The disease is characterized by the development of circulating IgG autoantibodies reacting with the BP180 antigen of the basement membrane zone.¹ Psoriasis vulgaris (PV) is a common, chronic, immune-mediated disease affecting approximately 2% of the world’s population including children and adults.² Both entities may coexist with internal disorders such as hypertension, diabetes mellitus, coronary heart disease, congestive heart failure, hyperlipidemia, and cerebrovascular accident. It has been postulated that BP more often coexists with neurological disorders, such as stroke and Parkinson disease,³ whereas PV usually is associated with cardiovascular disorders and diabetes mellitus.² We report the case of a 35-year-old man with chronic PV and metabolic syndrome who developed BP that was successfully treated with methotrexate (MTX).

Case Report

A 35-year-old man with a 15-year history of PV, class 3 obesity (body mass index, 69.2), and thrombosis of the left leg was referred to the dermatology department due to a sudden extensive erythematous and bullous eruption located on the trunk, arms, and legs with involvement of the oral mucosa that had started 4 weeks prior. The skin lesions were accompanied by severe pruritus. On admission to the hospital, the patient presented with stable psoriatic plaques located on the trunk, arms, and proximal part of the lower legs with a psoriasis area severity index score of 11.8 (Figure 1A). He also had disseminated tense blisters and erosions partially arranged in an annular pattern located on the border of the psoriatic plaques as well as on an erythematous base or within unaffected skin (Figure 1B). Additionally, a few small erosions were present on the oral mucosa.

The patient’s father had a history of PV, but there was no family history of obesity or autoimmune blistering disorders. On physical examination, central obesity was noted with a waist circumference of 180 cm and a body mass index of 69.2; his blood pressure was 220/150 mm Hg. Laboratory tests revealed leukocytosis (20.06×10⁹/L [reference range, 4.5–11.0×10⁹/L]) with neutrophilia (16.2×10⁹/L [reference range, 1.6–7.6×10⁹/L]; 80.9% [reference range, 40.0%–70.0%]), eosinophilia (1.01×10⁹/L [reference range, 0–0.5×10⁹/L]), elevated C-reactive protein levels (49.4 mg/L [reference range, 0.0–9.0 mg/L]), elevated erythrocyte sedimentation rate (35 mm/h [reference range, 0–12 mm/h]), elevated γ-glutamyltransferase (66 U/L [reference range, 0–55 U/L]), decreased high-density lipoprotein levels (38 mg/dL [reference range, ≥40 mg/dL]), elevated fasting plasma glucose (116 mg/dL or 6.4 mmol/L [reference range, 70–99 mg/dL or 3.9–5.5 mmol/L]), elevated total IgE (1540 µg/L [reference range, 0–1000 µg/L]), elevated D-dimer (3.21 µg/mL [reference range, <0.5 µg/mL]), and low free triiodothyronine levels (130 pg/dL [reference range, 171–371 pg/dL]). The total protein level was 6.5 g/dL (reference range, 6.0–8.0 g/dL) and albumin level was 3.2 g/dL (reference range, 4.02–4.76 g/dL). A chest radiograph showed no abnormalities.

Based on the physical examination and laboratory testing, it was determined that the patient fulfilled 4 of 5 criteria for metabolic syndrome described by the International Diabetes Federation in 2006 (Table).⁴ Direct immunofluorescence performed on normal-appearing perilesional skin demonstrated linear IgG and C3 deposits along the basement membrane zone. Indirect immunofluorescence detected circulating IgG autoantibodies at a titer of 1:80. Serum studies using biochip mosaics⁵ revealed the reactivity of circulating IgG antibodies to the epidermal side of salt-split skin and with antigen dots of tetrameric BP180-NC16a, which prompted the diagnosis of BP (Figure 2).

Oral treatment with MTX 12.5 mg once weekly with clobetasol propionate cream applied to affected skin was initiated for 4 weeks. The PV resolved completely and blister formation stopped. A few weeks later BP reappeared, even though the patient was still taking MTX. The treatment failure may have been related to the patient’s class 3 obesity; therefore, the dose was increased to 20 mg once weekly for 8 weeks, which led to rapid healing of BP erosions. The patient was monitored for 2 months with no symptoms of recurrence.

Comment

Psoriasis Comorbidities

The correlation between PV and cardiovascular disorders such as myocardial infarction, cerebrovascular accident, and pulmonary embolism has been well established and is widely accepted.² It also has been documented that the risk for metabolic syndrome with components such as diabetes mellitus, hypertension, lipid abnormalities, obesity, and arteriosclerosis is notably increased in PV patients.⁶ Moreover, associated internal disorders are responsible for a 3- to 4-year reduction in life expectancy in patients with moderate to severe PV.⁷

Correlation of PV and BP

Psoriasis also may coexist with autoimmune disorders such as rheumatoid arthritis, lupus erythematosus, and blistering disorders.⁸ There are more than 60 known cases reporting PV in association with various types of subepidermal blistering diseases, including pemphigus vulgaris, epidermolysis bullosa acquisita, anti-p200 pemphigoid, and BP.^8,9 The pathogenetic relationship between BP and PV remains obscure. In most published cases, PV preceded BP by 5 to 30 years, possibly ascribable to patients being diagnosed with PV at a younger age.⁹ In general, patients with BP and PV are younger than patients with BP only, with a mean age of 62 years.⁹ Because our patient was in his mid-30s when he developed BP, in such cases physicians should take under consideration any triggering factors (eg, drugs). Physical examination and detailed laboratory findings allowed us to make the patient aware of the potential for development of metabolic syndrome. This condition in combination with PV could be a predisposing factor for BP development. According to more recent research, PV is considered a generalized inflammatory process rather than a disorder limited to the skin and joints.¹⁰ The chronic inflammatory process in psoriatic skin results in exposure of autoantigens, leading to an immune response and the production of BP antibodies. The neutrophil elastase enzyme present in psoriatic lesions also may take part in dermoepidermal junction degradation and blister formation of BP.¹¹ According to other observations, some antipsoriatic therapies (eg, psoralen plus UVA, UVB, dithranol, coal tar) could be associated with development of BP.¹² Moreover, it was shown that psoralen plus UVA therapy, which is widely used in PV treatment, alters the cytokine profile from helper T cells T_H1 to T_H2.¹² T_H2-dependent cytokines predominate the sera and erosions in BP patients and seem to be notably relevant to the pathophysiology of the disease.¹³ The history of our patient’s psoriatic treatment included only topical corticosteroids, keratolytic agents, and occasionally dithranol and coal tar; however, UV phototherapy or any other systemic therapies had never been utilized. Three previously reported cases of patients with PV and BP also revealed no history of UV phototherapy,^8,9 which suggests that mechanisms responsible for coexistence of PV and BP are more complex. It has been proven that proinflammatory cytokines secreted by T_H1 and T_H17 cells, in particular tumor necrosis factor α, IL-17, IL-22, and IL-23, play an important role in the development of psoriatic lesions.¹⁰ On the other hand, these cytokines are known to contribute to vascular inflammation, leading to development of arteriosclerosis, as well as to regulate adipogenesis and obesity.^14,15 Arakawa et al¹⁶ reported increased expression of IL-17 in lesional skin in BP. They concluded that IL-17 may contribute to the recruitment of eosinophils and neutrophils and tissue damage in BP. Therefore, it is highly likely that IL-17 might be a common factor underlying the coexistence of BP with PV and metabolic syndrome. More such reports are required for better understanding this association.

BP Treatment

Selecting a therapy for BP with coexistent PV is challenging, especially in patients with extreme obesity and metabolic syndrome. It is well established that obesity correlates with a higher incidence of PV and more severe disease. On the other hand, obesity also influences response to therapy. Systemic corticosteroids are contraindicated in psoriasis patients because of severe side effects, such as rebound phenomenon of psoriatic lesions and risk for development of generalized pustular PV. Although systemic corticosteroids are effective in BP, high-dose therapy may potentially be life-threatening, particularly in these obese patients with conditions such as hypertension and diabetes mellitus, among others,¹ as was observed in our case. Taking into consideration the above mentioned conditions and our experience on such cases, the current patient had received MTX (12.5 mg once weekly) and clobetasol propionate cream, which led to the rapid healing of the psoriatic plaques, whereas BP was more resistant to this therapy. This response may be explained by our patient’s class 3 obesity (body mass index, 69.2). Therefore, the dose of MTX was increased to 20 mg once weekly and was successful. The decision to use MTX was supported by evidence that this medicine may reduce the risk for arteriosclerosis and cardiovascular disorders.¹⁷

There are some alternative therapeutic options for patients with coexisting BP and PV, such as cyclosporine,¹⁸ combination low-dose cyclosporine and low-dose systemic corticosteroids,¹⁹ dapsone,²⁰ azathioprine,²¹ mycophenolate mofetil,²² and acitretin.²³ It also has been shown that biologics (eg, ustekinumab) may be a successful solution in patients with PV and antilaminin-γ1 pemphigoid.²⁴ However, these alternative therapeutic regimens could not be considered in our patient because of serious coexisting internal disorders.

Conclusion

We present a case of concomitant BP and PV in a patient with metabolic syndrome. Although the pathogenic role of this unique coexistence is not fully understood, MTX proved suitable and effective in this single case. Further studies should be performed to elucidate the pathogenic relationship and therapeutic solutions for cases with coexisting PV, BP, and metabolic syndrome.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease.¹ The majority of BP cases are idiopathic and occur in patients older than 60 years. The disease is characterized by the development of circulating IgG autoantibodies reacting with the BP180 antigen of the basement membrane zone.¹ Psoriasis vulgaris (PV) is a common, chronic, immune-mediated disease affecting approximately 2% of the world’s population including children and adults.² Both entities may coexist with internal disorders such as hypertension, diabetes mellitus, coronary heart disease, congestive heart failure, hyperlipidemia, and cerebrovascular accident. It has been postulated that BP more often coexists with neurological disorders, such as stroke and Parkinson disease,³ whereas PV usually is associated with cardiovascular disorders and diabetes mellitus.² We report the case of a 35-year-old man with chronic PV and metabolic syndrome who developed BP that was successfully treated with methotrexate (MTX).

Case Report

A 35-year-old man with a 15-year history of PV, class 3 obesity (body mass index, 69.2), and thrombosis of the left leg was referred to the dermatology department due to a sudden extensive erythematous and bullous eruption located on the trunk, arms, and legs with involvement of the oral mucosa that had started 4 weeks prior. The skin lesions were accompanied by severe pruritus. On admission to the hospital, the patient presented with stable psoriatic plaques located on the trunk, arms, and proximal part of the lower legs with a psoriasis area severity index score of 11.8 (Figure 1A). He also had disseminated tense blisters and erosions partially arranged in an annular pattern located on the border of the psoriatic plaques as well as on an erythematous base or within unaffected skin (Figure 1B). Additionally, a few small erosions were present on the oral mucosa.

The patient’s father had a history of PV, but there was no family history of obesity or autoimmune blistering disorders. On physical examination, central obesity was noted with a waist circumference of 180 cm and a body mass index of 69.2; his blood pressure was 220/150 mm Hg. Laboratory tests revealed leukocytosis (20.06×10⁹/L [reference range, 4.5–11.0×10⁹/L]) with neutrophilia (16.2×10⁹/L [reference range, 1.6–7.6×10⁹/L]; 80.9% [reference range, 40.0%–70.0%]), eosinophilia (1.01×10⁹/L [reference range, 0–0.5×10⁹/L]), elevated C-reactive protein levels (49.4 mg/L [reference range, 0.0–9.0 mg/L]), elevated erythrocyte sedimentation rate (35 mm/h [reference range, 0–12 mm/h]), elevated γ-glutamyltransferase (66 U/L [reference range, 0–55 U/L]), decreased high-density lipoprotein levels (38 mg/dL [reference range, ≥40 mg/dL]), elevated fasting plasma glucose (116 mg/dL or 6.4 mmol/L [reference range, 70–99 mg/dL or 3.9–5.5 mmol/L]), elevated total IgE (1540 µg/L [reference range, 0–1000 µg/L]), elevated D-dimer (3.21 µg/mL [reference range, <0.5 µg/mL]), and low free triiodothyronine levels (130 pg/dL [reference range, 171–371 pg/dL]). The total protein level was 6.5 g/dL (reference range, 6.0–8.0 g/dL) and albumin level was 3.2 g/dL (reference range, 4.02–4.76 g/dL). A chest radiograph showed no abnormalities.

Based on the physical examination and laboratory testing, it was determined that the patient fulfilled 4 of 5 criteria for metabolic syndrome described by the International Diabetes Federation in 2006 (Table).⁴ Direct immunofluorescence performed on normal-appearing perilesional skin demonstrated linear IgG and C3 deposits along the basement membrane zone. Indirect immunofluorescence detected circulating IgG autoantibodies at a titer of 1:80. Serum studies using biochip mosaics⁵ revealed the reactivity of circulating IgG antibodies to the epidermal side of salt-split skin and with antigen dots of tetrameric BP180-NC16a, which prompted the diagnosis of BP (Figure 2).

Oral treatment with MTX 12.5 mg once weekly with clobetasol propionate cream applied to affected skin was initiated for 4 weeks. The PV resolved completely and blister formation stopped. A few weeks later BP reappeared, even though the patient was still taking MTX. The treatment failure may have been related to the patient’s class 3 obesity; therefore, the dose was increased to 20 mg once weekly for 8 weeks, which led to rapid healing of BP erosions. The patient was monitored for 2 months with no symptoms of recurrence.

Comment

Psoriasis Comorbidities

The correlation between PV and cardiovascular disorders such as myocardial infarction, cerebrovascular accident, and pulmonary embolism has been well established and is widely accepted.² It also has been documented that the risk for metabolic syndrome with components such as diabetes mellitus, hypertension, lipid abnormalities, obesity, and arteriosclerosis is notably increased in PV patients.⁶ Moreover, associated internal disorders are responsible for a 3- to 4-year reduction in life expectancy in patients with moderate to severe PV.⁷

Correlation of PV and BP

Psoriasis also may coexist with autoimmune disorders such as rheumatoid arthritis, lupus erythematosus, and blistering disorders.⁸ There are more than 60 known cases reporting PV in association with various types of subepidermal blistering diseases, including pemphigus vulgaris, epidermolysis bullosa acquisita, anti-p200 pemphigoid, and BP.^8,9 The pathogenetic relationship between BP and PV remains obscure. In most published cases, PV preceded BP by 5 to 30 years, possibly ascribable to patients being diagnosed with PV at a younger age.⁹ In general, patients with BP and PV are younger than patients with BP only, with a mean age of 62 years.⁹ Because our patient was in his mid-30s when he developed BP, in such cases physicians should take under consideration any triggering factors (eg, drugs). Physical examination and detailed laboratory findings allowed us to make the patient aware of the potential for development of metabolic syndrome. This condition in combination with PV could be a predisposing factor for BP development. According to more recent research, PV is considered a generalized inflammatory process rather than a disorder limited to the skin and joints.¹⁰ The chronic inflammatory process in psoriatic skin results in exposure of autoantigens, leading to an immune response and the production of BP antibodies. The neutrophil elastase enzyme present in psoriatic lesions also may take part in dermoepidermal junction degradation and blister formation of BP.¹¹ According to other observations, some antipsoriatic therapies (eg, psoralen plus UVA, UVB, dithranol, coal tar) could be associated with development of BP.¹² Moreover, it was shown that psoralen plus UVA therapy, which is widely used in PV treatment, alters the cytokine profile from helper T cells T_H1 to T_H2.¹² T_H2-dependent cytokines predominate the sera and erosions in BP patients and seem to be notably relevant to the pathophysiology of the disease.¹³ The history of our patient’s psoriatic treatment included only topical corticosteroids, keratolytic agents, and occasionally dithranol and coal tar; however, UV phototherapy or any other systemic therapies had never been utilized. Three previously reported cases of patients with PV and BP also revealed no history of UV phototherapy,^8,9 which suggests that mechanisms responsible for coexistence of PV and BP are more complex. It has been proven that proinflammatory cytokines secreted by T_H1 and T_H17 cells, in particular tumor necrosis factor α, IL-17, IL-22, and IL-23, play an important role in the development of psoriatic lesions.¹⁰ On the other hand, these cytokines are known to contribute to vascular inflammation, leading to development of arteriosclerosis, as well as to regulate adipogenesis and obesity.^14,15 Arakawa et al¹⁶ reported increased expression of IL-17 in lesional skin in BP. They concluded that IL-17 may contribute to the recruitment of eosinophils and neutrophils and tissue damage in BP. Therefore, it is highly likely that IL-17 might be a common factor underlying the coexistence of BP with PV and metabolic syndrome. More such reports are required for better understanding this association.

BP Treatment

Selecting a therapy for BP with coexistent PV is challenging, especially in patients with extreme obesity and metabolic syndrome. It is well established that obesity correlates with a higher incidence of PV and more severe disease. On the other hand, obesity also influences response to therapy. Systemic corticosteroids are contraindicated in psoriasis patients because of severe side effects, such as rebound phenomenon of psoriatic lesions and risk for development of generalized pustular PV. Although systemic corticosteroids are effective in BP, high-dose therapy may potentially be life-threatening, particularly in these obese patients with conditions such as hypertension and diabetes mellitus, among others,¹ as was observed in our case. Taking into consideration the above mentioned conditions and our experience on such cases, the current patient had received MTX (12.5 mg once weekly) and clobetasol propionate cream, which led to the rapid healing of the psoriatic plaques, whereas BP was more resistant to this therapy. This response may be explained by our patient’s class 3 obesity (body mass index, 69.2). Therefore, the dose of MTX was increased to 20 mg once weekly and was successful. The decision to use MTX was supported by evidence that this medicine may reduce the risk for arteriosclerosis and cardiovascular disorders.¹⁷

There are some alternative therapeutic options for patients with coexisting BP and PV, such as cyclosporine,¹⁸ combination low-dose cyclosporine and low-dose systemic corticosteroids,¹⁹ dapsone,²⁰ azathioprine,²¹ mycophenolate mofetil,²² and acitretin.²³ It also has been shown that biologics (eg, ustekinumab) may be a successful solution in patients with PV and antilaminin-γ1 pemphigoid.²⁴ However, these alternative therapeutic regimens could not be considered in our patient because of serious coexisting internal disorders.

Conclusion

We present a case of concomitant BP and PV in a patient with metabolic syndrome. Although the pathogenic role of this unique coexistence is not fully understood, MTX proved suitable and effective in this single case. Further studies should be performed to elucidate the pathogenic relationship and therapeutic solutions for cases with coexisting PV, BP, and metabolic syndrome.

To the Editor:

Dyschromatosis symmetrica hereditaria (DSH)(Online Mendelian Inheritance in Man 127400), also called reticulate acropigmentation of Dohi, is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes on the dorsal aspects of the hands and feet. Linkage analysis has revealed that the DSH gene locus resides on chromosome 1q11-q21,¹ and the adenosine deaminase RNA specific gene, ADAR1 (also called DSRAD), in this region has been identified as being responsible for the development of DSH.² We report a sporadic case of severe DSH with the ADAR1 gene detected in a mutation analysis.

A 6-year-old girl presented with a mixture of hyperpigmented and hypopigmented macules on the dorsal aspects of the hands and feet and the curved side of the wrists, heels, and knees, as well as scattered frecklelike and depigmented spots on the face, ears, neck, arms, and upper back (Figure 1). Her parents noted that hyperpigmented and hypopigmented macules on the dorsal aspects of the hands developed at 5 months of age. Exacerbation after exposure to sunlight resulted in the eruption becoming remarkable in summer and fainter in winter. The skin lesions gradually became more progressive. Physical examination revealed that the patient generally was healthy.

After obtaining informed consent, we performed a mutation analysis of the ADAR1 gene in our patient and her parents. We used a kit to extract genomic DNA from peripheral blood, which was then used to amplify the exons of the ADAR1 gene with intronic flanking sequences by polymerase chain reaction with the primer.³ After amplification, polymerase chain reaction products were purified. We sequenced the ADAR1 gene. Sequence comparisons and analysis found that the patient (proband) carried a heterozygous insertional mutation c.2253insG in exon 6 of the ADAR1 gene. This mutation was not detected in the proband’s healthy parents and 100 normal individuals (Figure 2).

Dyschromatosis symmetrica hereditaria is acquired by autosomal-dominant inheritance and is mainly reported in Asians, especially in Japan and China. Oyama et al⁴ reviewed 185 cases of DSH in Japan and found the onset of this disease usually was during infancy or childhood; 73% of patients developed the skin lesions before 6 years of age. Suzuki et al⁵ reported 10 unrelated Japanese patients and found the onset of disease ranged from 1 year of age to childhood. Zhang et al^1,6 investigated 78 Chinese patients with DSH including 8 multigenerational families and 2 sporadic patients and found the age of disease onset ranged from 6 months to 15 years of age. The age of onset in our patient (5 months) was younger than these prior reports.

Patients with DSH have a characteristic appearance including a mixture of hyperpigmented and hypopigmented macules of various sizes on the dorsal aspects of the hands and feet. Few patients have similar lesions on the knees and elbows. Many patients have frecklelike macules on the face and arms.^1-6 One patient has been described with scattered depigmented spots on the face and chest.¹ Our patient had a characteristic appearance as well as some special manifestations including skin lesions on the curved side of the wrist, ears, neck, and upper back.

The human ADAR1 gene spans 30 kilobase and contains 15 exons. It encodes RNA-specific adenosine deaminase composed of 1226 amino acid residues. This enzyme is important for various functions such as site-specific RNA editing and nuclear translation. This enzyme has 2 Z-alpha domains, 3 double-stranded RNA–binding domains, and the putative deaminase domain corresponding to exon 2, exons 2 to 7, and exons 9 to 14 of ADAR1, respectively.⁶

Mutation analysis of the ADAR1 gene in this case showed heterozygous insertion mutation c.2253insG in exon 6 of the ADAR1 gene, which changed the reading frame, and 475 amino acid residues in C-terminus are replaced by 90 amino acid residues (TSSRAQVRLPSKSWGSLVPSRLRTQQEA RQAGSSRCGSPCLDWGEREGRTHGFHRG NPSDRGQSQKNYAPPLKVPRSTAKT DTPSHWQHLP). This mutation was not detected in the proband’s healthy parents and the 100 control individuals, which indicated that it was a de novo mutation and the pathogenic mutation of DSH rather than a common polymorphism.

In conclusion, we report a novel mutation of the ADAR1 gene with a heavy clinical phenotype in DSH. This study expands the spectrum of clinical manifestations and demonstrates the ADAR1 mutation in DSH.

Acknowledgments
We are most grateful to the patient and her family for taking part in our study.

To the Editor:

Dyschromatosis symmetrica hereditaria (DSH)(Online Mendelian Inheritance in Man 127400), also called reticulate acropigmentation of Dohi, is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes on the dorsal aspects of the hands and feet. Linkage analysis has revealed that the DSH gene locus resides on chromosome 1q11-q21,¹ and the adenosine deaminase RNA specific gene, ADAR1 (also called DSRAD), in this region has been identified as being responsible for the development of DSH.² We report a sporadic case of severe DSH with the ADAR1 gene detected in a mutation analysis.

A 6-year-old girl presented with a mixture of hyperpigmented and hypopigmented macules on the dorsal aspects of the hands and feet and the curved side of the wrists, heels, and knees, as well as scattered frecklelike and depigmented spots on the face, ears, neck, arms, and upper back (Figure 1). Her parents noted that hyperpigmented and hypopigmented macules on the dorsal aspects of the hands developed at 5 months of age. Exacerbation after exposure to sunlight resulted in the eruption becoming remarkable in summer and fainter in winter. The skin lesions gradually became more progressive. Physical examination revealed that the patient generally was healthy.

After obtaining informed consent, we performed a mutation analysis of the ADAR1 gene in our patient and her parents. We used a kit to extract genomic DNA from peripheral blood, which was then used to amplify the exons of the ADAR1 gene with intronic flanking sequences by polymerase chain reaction with the primer.³ After amplification, polymerase chain reaction products were purified. We sequenced the ADAR1 gene. Sequence comparisons and analysis found that the patient (proband) carried a heterozygous insertional mutation c.2253insG in exon 6 of the ADAR1 gene. This mutation was not detected in the proband’s healthy parents and 100 normal individuals (Figure 2).

Dyschromatosis symmetrica hereditaria is acquired by autosomal-dominant inheritance and is mainly reported in Asians, especially in Japan and China. Oyama et al⁴ reviewed 185 cases of DSH in Japan and found the onset of this disease usually was during infancy or childhood; 73% of patients developed the skin lesions before 6 years of age. Suzuki et al⁵ reported 10 unrelated Japanese patients and found the onset of disease ranged from 1 year of age to childhood. Zhang et al^1,6 investigated 78 Chinese patients with DSH including 8 multigenerational families and 2 sporadic patients and found the age of disease onset ranged from 6 months to 15 years of age. The age of onset in our patient (5 months) was younger than these prior reports.

Patients with DSH have a characteristic appearance including a mixture of hyperpigmented and hypopigmented macules of various sizes on the dorsal aspects of the hands and feet. Few patients have similar lesions on the knees and elbows. Many patients have frecklelike macules on the face and arms.^1-6 One patient has been described with scattered depigmented spots on the face and chest.¹ Our patient had a characteristic appearance as well as some special manifestations including skin lesions on the curved side of the wrist, ears, neck, and upper back.

The human ADAR1 gene spans 30 kilobase and contains 15 exons. It encodes RNA-specific adenosine deaminase composed of 1226 amino acid residues. This enzyme is important for various functions such as site-specific RNA editing and nuclear translation. This enzyme has 2 Z-alpha domains, 3 double-stranded RNA–binding domains, and the putative deaminase domain corresponding to exon 2, exons 2 to 7, and exons 9 to 14 of ADAR1, respectively.⁶

Mutation analysis of the ADAR1 gene in this case showed heterozygous insertion mutation c.2253insG in exon 6 of the ADAR1 gene, which changed the reading frame, and 475 amino acid residues in C-terminus are replaced by 90 amino acid residues (TSSRAQVRLPSKSWGSLVPSRLRTQQEA RQAGSSRCGSPCLDWGEREGRTHGFHRG NPSDRGQSQKNYAPPLKVPRSTAKT DTPSHWQHLP). This mutation was not detected in the proband’s healthy parents and the 100 control individuals, which indicated that it was a de novo mutation and the pathogenic mutation of DSH rather than a common polymorphism.

In conclusion, we report a novel mutation of the ADAR1 gene with a heavy clinical phenotype in DSH. This study expands the spectrum of clinical manifestations and demonstrates the ADAR1 mutation in DSH.

Acknowledgments
We are most grateful to the patient and her family for taking part in our study.

To the Editor:

Dyschromatosis symmetrica hereditaria (DSH)(Online Mendelian Inheritance in Man 127400), also called reticulate acropigmentation of Dohi, is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes on the dorsal aspects of the hands and feet. Linkage analysis has revealed that the DSH gene locus resides on chromosome 1q11-q21,¹ and the adenosine deaminase RNA specific gene, ADAR1 (also called DSRAD), in this region has been identified as being responsible for the development of DSH.² We report a sporadic case of severe DSH with the ADAR1 gene detected in a mutation analysis.

A 6-year-old girl presented with a mixture of hyperpigmented and hypopigmented macules on the dorsal aspects of the hands and feet and the curved side of the wrists, heels, and knees, as well as scattered frecklelike and depigmented spots on the face, ears, neck, arms, and upper back (Figure 1). Her parents noted that hyperpigmented and hypopigmented macules on the dorsal aspects of the hands developed at 5 months of age. Exacerbation after exposure to sunlight resulted in the eruption becoming remarkable in summer and fainter in winter. The skin lesions gradually became more progressive. Physical examination revealed that the patient generally was healthy.

After obtaining informed consent, we performed a mutation analysis of the ADAR1 gene in our patient and her parents. We used a kit to extract genomic DNA from peripheral blood, which was then used to amplify the exons of the ADAR1 gene with intronic flanking sequences by polymerase chain reaction with the primer.³ After amplification, polymerase chain reaction products were purified. We sequenced the ADAR1 gene. Sequence comparisons and analysis found that the patient (proband) carried a heterozygous insertional mutation c.2253insG in exon 6 of the ADAR1 gene. This mutation was not detected in the proband’s healthy parents and 100 normal individuals (Figure 2).

Dyschromatosis symmetrica hereditaria is acquired by autosomal-dominant inheritance and is mainly reported in Asians, especially in Japan and China. Oyama et al⁴ reviewed 185 cases of DSH in Japan and found the onset of this disease usually was during infancy or childhood; 73% of patients developed the skin lesions before 6 years of age. Suzuki et al⁵ reported 10 unrelated Japanese patients and found the onset of disease ranged from 1 year of age to childhood. Zhang et al^1,6 investigated 78 Chinese patients with DSH including 8 multigenerational families and 2 sporadic patients and found the age of disease onset ranged from 6 months to 15 years of age. The age of onset in our patient (5 months) was younger than these prior reports.

Patients with DSH have a characteristic appearance including a mixture of hyperpigmented and hypopigmented macules of various sizes on the dorsal aspects of the hands and feet. Few patients have similar lesions on the knees and elbows. Many patients have frecklelike macules on the face and arms.^1-6 One patient has been described with scattered depigmented spots on the face and chest.¹ Our patient had a characteristic appearance as well as some special manifestations including skin lesions on the curved side of the wrist, ears, neck, and upper back.

The human ADAR1 gene spans 30 kilobase and contains 15 exons. It encodes RNA-specific adenosine deaminase composed of 1226 amino acid residues. This enzyme is important for various functions such as site-specific RNA editing and nuclear translation. This enzyme has 2 Z-alpha domains, 3 double-stranded RNA–binding domains, and the putative deaminase domain corresponding to exon 2, exons 2 to 7, and exons 9 to 14 of ADAR1, respectively.⁶

Mutation analysis of the ADAR1 gene in this case showed heterozygous insertion mutation c.2253insG in exon 6 of the ADAR1 gene, which changed the reading frame, and 475 amino acid residues in C-terminus are replaced by 90 amino acid residues (TSSRAQVRLPSKSWGSLVPSRLRTQQEA RQAGSSRCGSPCLDWGEREGRTHGFHRG NPSDRGQSQKNYAPPLKVPRSTAKT DTPSHWQHLP). This mutation was not detected in the proband’s healthy parents and the 100 control individuals, which indicated that it was a de novo mutation and the pathogenic mutation of DSH rather than a common polymorphism.

In conclusion, we report a novel mutation of the ADAR1 gene with a heavy clinical phenotype in DSH. This study expands the spectrum of clinical manifestations and demonstrates the ADAR1 mutation in DSH.

Acknowledgments
We are most grateful to the patient and her family for taking part in our study.

Metastatic Crohn disease (MCD) is defined by the presence of cutaneous noncaseating granulomatous lesions that are noncontiguous with the gastrointestinal (GI) tract or fistulae.¹ The clinical presentation of MCD is so variable that its diagnosis requires a high index of suspicion.^1,2 In particular, the presence of erythematous tender nodules on the legs is easily mistaken for erythema nodosum (EN). Skin biopsy has an important role in confirming the diagnosis, as histopathological examination would reveal a noncaseating granuloma similar to those in the involved GI tract.² Herein, we report a case of MCD on the right leg that was clinically reminiscent of unilateral EN.

Case Report

A 21-year-old woman presented to the dermatology department with 2 painful erythematous nodules on the lower right leg of 2 weeks’ duration. She also reported abdominal pain, diarrhea, and bloody stool. She had been diagnosed with Crohn disease (CD) 6 years prior that had been well controlled with systemic low-dose steroids (5–15 mg/d), metronidazole (750 mg/d), and intermittent mesalamine and antidiarrheal drugs. However, she had not taken her medication for several weeks on her own authority. Subsequently, the patient developed skin lesions, which were characterized by ill-defined erythematous nodules with tenderness on the right lower leg along with GI symptoms (Figure 1). Laboratory studies revealed anemia (hemoglobin, 9.9 g/dL [reference range, 12.0–16.0 g/dL]) and an elevated C-reactive protein level (4.3 mg/dL [reference range, 0–0.3 mg/dL]). Other routine laboratory findings were normal.

Histopathologically, a skin biopsy from the right ankle showed vague, ill-defined, noncaseating granulomas scattered in the deep dermis and lobules of the subcutis (Figure 2). The granulomas were composed of epithelioid cells and Langerhans-type giant cells. Lymphocytes and neutrophils also were present, but eosinophils were absent. Immunohistochemical staining revealed that the infiltrating cells were mostly CD4⁺ helper/inducer T cells intermixed with CD8⁺ suppressor/cytotoxic T cells. The CD4:CD8 ratio was approximately 2:1. Counts of CD20⁺ B cells were low. Epithelioid cells and giant cells were positive for CD68.

A colonoscopy was performed to evaluate the aggravation of CD. Multiple longitudinal ulcers were observed in the ileocecal valve area and from the transverse colon to the sigmoid colon (Figure 3A). Histopathologic findings from the colon showed mucosal ulceration and noncaseating granulomas with heavy infiltration of lymphocytes and plasma cells (Figure 3B). Staining for infectious microorganisms (eg, Ziehl-Neelsen, periodic acid–Schiff, Gram) was negative. A polymerase chain reaction performed on sections cut from the paraffin block of the skin biopsy was negative for Mycobacterium tuberculosis DNA.

Based on the clinical and histopathologic findings, the patient was diagnosed with MCD that was clinically reminiscent of unilateral EN. Four weeks after the initiation of therapy with systemic corticosteroids (25 mg/d), oral metronidazole (750 mg/d), and mesalamine (1200 mg/d) for CD, the skin lesions were completely resolved and the patient’s GI symptoms improved simultaneously.

Comment

Crohn disease is a chronic inflammatory granulomatous disease of the GI tract that often is associated with reactive cutaneous lesions including EN, pyoderma gangrenosum, necrotizing vasculitis, and epidermolysis bullosa acquisita. Of these, EN is the most common to appear in CD patients and has been reported to occur in 1% to 15% of patients.^3-5 In particular, skin lesions on the leg presenting as tender erythematous nodules and patches are often diagnosed as EN, which is relatively common. In our case, we initially suspected EN due to the rare presentation of MCD and lack of specific clinical features; however, the skin biopsy revealed noncaseating granulomas in the mid to deep dermis and subcutis consistent with MCD.

Metastatic Crohn disease is a rare disease entity and is characterized by the presence of noncaseating granulomas of the skin at sites separated from the GI tract by normal tissue.¹ Although its pathogenesis is unclear, it has been suggested that immune complexes deposited in the skin could be responsible for the granulomatous reactions.⁴ A T lymphocyte–mediated type IV hypersensitivity reaction also could be responsible.^6,7 Because antimicrobial therapy can be curative for infection-related MCD, special histologic stains and/or tissue cultures can help to exclude an infectious etiology.⁸

Clinical presentations of MCD vary greatly, with observations such as single or multiple erythematous swellings, papules, plaques, nodules, abscesses, and ulcers.^1,2 The relationship between these clinical presentations and the intestinal activity of CD still is unknown; in some cases, however, the metastatic granulomatous lesions and the bowel disease show comparable severity.^2,9,10 In a review of the literature, MCD was generally reported to present in the genital area in children. In adults, lesions most frequently present in the genital area, followed by ulcers on the arms and legs.^1,2 These variations in clinical features and location resemble benign or infectious disease and can lead to delays in diagnosis.

Histopathologically, MCD lesions usually are ill-defined noncaseating granulomas with numerous multinucleated giant cells and lymphomononuclear cells located mostly in the dermis and occasionally extending into the subcutis. The cutaneous granulomata are similar to those present in the affected GI tract. Lymphocytes and plasma cells also are commonly present and eosinophils can be prominent.^1,2,11 In some cases of MCD, granulomatous vasculitis of small- to medium-sized vessels can be found and is associated with dermal and subcutaneous granulomatous inflammation.^8,11,12 Misago and Narisawa¹³ suggested that granulomatous vasculitis and panniculitis associated with CD is considered to be a rare subtype of MCD. Few cases of MCD presenting as granulomatous panniculitis have been described in the literature.^14-16 Our patient presented with lesions that clinically resembled EN; however, the biopsy was more consistent with MCD. The Table summarizes the distinguishing clinical and histopathological features of MCD in our case and classic EN.

Although some authors believe that MCD is not related to CD activity, others assert that MCD lesions may parallel GI activity.^1,2 Our patient was treated with systemic corticosteroids, oral metronidazole, and mesalamine to control the GI symptoms associated with CD. Four weeks after treatment, the GI symptoms and skin lesions improved simultaneously without any additional dermatologic treatment. We believe that MCD has the potential to serve as an early marker of the recurrence of CD and can help with the early diagnosis of CD aggravation, though an association between MCD and CD activity has not been confirmed.

Conclusion

We reported a case of MCD that was clinically reminiscent of unilateral EN and associated with GI disease activity. Physicians should be aware of the possibility of skin manifestations in CD, especially when erythematous nodular lesions are present on the leg.

Metastatic Crohn disease (MCD) is defined by the presence of cutaneous noncaseating granulomatous lesions that are noncontiguous with the gastrointestinal (GI) tract or fistulae.¹ The clinical presentation of MCD is so variable that its diagnosis requires a high index of suspicion.^1,2 In particular, the presence of erythematous tender nodules on the legs is easily mistaken for erythema nodosum (EN). Skin biopsy has an important role in confirming the diagnosis, as histopathological examination would reveal a noncaseating granuloma similar to those in the involved GI tract.² Herein, we report a case of MCD on the right leg that was clinically reminiscent of unilateral EN.

Case Report

A 21-year-old woman presented to the dermatology department with 2 painful erythematous nodules on the lower right leg of 2 weeks’ duration. She also reported abdominal pain, diarrhea, and bloody stool. She had been diagnosed with Crohn disease (CD) 6 years prior that had been well controlled with systemic low-dose steroids (5–15 mg/d), metronidazole (750 mg/d), and intermittent mesalamine and antidiarrheal drugs. However, she had not taken her medication for several weeks on her own authority. Subsequently, the patient developed skin lesions, which were characterized by ill-defined erythematous nodules with tenderness on the right lower leg along with GI symptoms (Figure 1). Laboratory studies revealed anemia (hemoglobin, 9.9 g/dL [reference range, 12.0–16.0 g/dL]) and an elevated C-reactive protein level (4.3 mg/dL [reference range, 0–0.3 mg/dL]). Other routine laboratory findings were normal.

Histopathologically, a skin biopsy from the right ankle showed vague, ill-defined, noncaseating granulomas scattered in the deep dermis and lobules of the subcutis (Figure 2). The granulomas were composed of epithelioid cells and Langerhans-type giant cells. Lymphocytes and neutrophils also were present, but eosinophils were absent. Immunohistochemical staining revealed that the infiltrating cells were mostly CD4⁺ helper/inducer T cells intermixed with CD8⁺ suppressor/cytotoxic T cells. The CD4:CD8 ratio was approximately 2:1. Counts of CD20⁺ B cells were low. Epithelioid cells and giant cells were positive for CD68.

A colonoscopy was performed to evaluate the aggravation of CD. Multiple longitudinal ulcers were observed in the ileocecal valve area and from the transverse colon to the sigmoid colon (Figure 3A). Histopathologic findings from the colon showed mucosal ulceration and noncaseating granulomas with heavy infiltration of lymphocytes and plasma cells (Figure 3B). Staining for infectious microorganisms (eg, Ziehl-Neelsen, periodic acid–Schiff, Gram) was negative. A polymerase chain reaction performed on sections cut from the paraffin block of the skin biopsy was negative for Mycobacterium tuberculosis DNA.

Based on the clinical and histopathologic findings, the patient was diagnosed with MCD that was clinically reminiscent of unilateral EN. Four weeks after the initiation of therapy with systemic corticosteroids (25 mg/d), oral metronidazole (750 mg/d), and mesalamine (1200 mg/d) for CD, the skin lesions were completely resolved and the patient’s GI symptoms improved simultaneously.

Comment

Crohn disease is a chronic inflammatory granulomatous disease of the GI tract that often is associated with reactive cutaneous lesions including EN, pyoderma gangrenosum, necrotizing vasculitis, and epidermolysis bullosa acquisita. Of these, EN is the most common to appear in CD patients and has been reported to occur in 1% to 15% of patients.^3-5 In particular, skin lesions on the leg presenting as tender erythematous nodules and patches are often diagnosed as EN, which is relatively common. In our case, we initially suspected EN due to the rare presentation of MCD and lack of specific clinical features; however, the skin biopsy revealed noncaseating granulomas in the mid to deep dermis and subcutis consistent with MCD.

Metastatic Crohn disease is a rare disease entity and is characterized by the presence of noncaseating granulomas of the skin at sites separated from the GI tract by normal tissue.¹ Although its pathogenesis is unclear, it has been suggested that immune complexes deposited in the skin could be responsible for the granulomatous reactions.⁴ A T lymphocyte–mediated type IV hypersensitivity reaction also could be responsible.^6,7 Because antimicrobial therapy can be curative for infection-related MCD, special histologic stains and/or tissue cultures can help to exclude an infectious etiology.⁸

Clinical presentations of MCD vary greatly, with observations such as single or multiple erythematous swellings, papules, plaques, nodules, abscesses, and ulcers.^1,2 The relationship between these clinical presentations and the intestinal activity of CD still is unknown; in some cases, however, the metastatic granulomatous lesions and the bowel disease show comparable severity.^2,9,10 In a review of the literature, MCD was generally reported to present in the genital area in children. In adults, lesions most frequently present in the genital area, followed by ulcers on the arms and legs.^1,2 These variations in clinical features and location resemble benign or infectious disease and can lead to delays in diagnosis.

Histopathologically, MCD lesions usually are ill-defined noncaseating granulomas with numerous multinucleated giant cells and lymphomononuclear cells located mostly in the dermis and occasionally extending into the subcutis. The cutaneous granulomata are similar to those present in the affected GI tract. Lymphocytes and plasma cells also are commonly present and eosinophils can be prominent.^1,2,11 In some cases of MCD, granulomatous vasculitis of small- to medium-sized vessels can be found and is associated with dermal and subcutaneous granulomatous inflammation.^8,11,12 Misago and Narisawa¹³ suggested that granulomatous vasculitis and panniculitis associated with CD is considered to be a rare subtype of MCD. Few cases of MCD presenting as granulomatous panniculitis have been described in the literature.^14-16 Our patient presented with lesions that clinically resembled EN; however, the biopsy was more consistent with MCD. The Table summarizes the distinguishing clinical and histopathological features of MCD in our case and classic EN.

Although some authors believe that MCD is not related to CD activity, others assert that MCD lesions may parallel GI activity.^1,2 Our patient was treated with systemic corticosteroids, oral metronidazole, and mesalamine to control the GI symptoms associated with CD. Four weeks after treatment, the GI symptoms and skin lesions improved simultaneously without any additional dermatologic treatment. We believe that MCD has the potential to serve as an early marker of the recurrence of CD and can help with the early diagnosis of CD aggravation, though an association between MCD and CD activity has not been confirmed.

Conclusion

We reported a case of MCD that was clinically reminiscent of unilateral EN and associated with GI disease activity. Physicians should be aware of the possibility of skin manifestations in CD, especially when erythematous nodular lesions are present on the leg.

Metastatic Crohn disease (MCD) is defined by the presence of cutaneous noncaseating granulomatous lesions that are noncontiguous with the gastrointestinal (GI) tract or fistulae.¹ The clinical presentation of MCD is so variable that its diagnosis requires a high index of suspicion.^1,2 In particular, the presence of erythematous tender nodules on the legs is easily mistaken for erythema nodosum (EN). Skin biopsy has an important role in confirming the diagnosis, as histopathological examination would reveal a noncaseating granuloma similar to those in the involved GI tract.² Herein, we report a case of MCD on the right leg that was clinically reminiscent of unilateral EN.

Case Report

A 21-year-old woman presented to the dermatology department with 2 painful erythematous nodules on the lower right leg of 2 weeks’ duration. She also reported abdominal pain, diarrhea, and bloody stool. She had been diagnosed with Crohn disease (CD) 6 years prior that had been well controlled with systemic low-dose steroids (5–15 mg/d), metronidazole (750 mg/d), and intermittent mesalamine and antidiarrheal drugs. However, she had not taken her medication for several weeks on her own authority. Subsequently, the patient developed skin lesions, which were characterized by ill-defined erythematous nodules with tenderness on the right lower leg along with GI symptoms (Figure 1). Laboratory studies revealed anemia (hemoglobin, 9.9 g/dL [reference range, 12.0–16.0 g/dL]) and an elevated C-reactive protein level (4.3 mg/dL [reference range, 0–0.3 mg/dL]). Other routine laboratory findings were normal.

Histopathologically, a skin biopsy from the right ankle showed vague, ill-defined, noncaseating granulomas scattered in the deep dermis and lobules of the subcutis (Figure 2). The granulomas were composed of epithelioid cells and Langerhans-type giant cells. Lymphocytes and neutrophils also were present, but eosinophils were absent. Immunohistochemical staining revealed that the infiltrating cells were mostly CD4⁺ helper/inducer T cells intermixed with CD8⁺ suppressor/cytotoxic T cells. The CD4:CD8 ratio was approximately 2:1. Counts of CD20⁺ B cells were low. Epithelioid cells and giant cells were positive for CD68.

A colonoscopy was performed to evaluate the aggravation of CD. Multiple longitudinal ulcers were observed in the ileocecal valve area and from the transverse colon to the sigmoid colon (Figure 3A). Histopathologic findings from the colon showed mucosal ulceration and noncaseating granulomas with heavy infiltration of lymphocytes and plasma cells (Figure 3B). Staining for infectious microorganisms (eg, Ziehl-Neelsen, periodic acid–Schiff, Gram) was negative. A polymerase chain reaction performed on sections cut from the paraffin block of the skin biopsy was negative for Mycobacterium tuberculosis DNA.

Based on the clinical and histopathologic findings, the patient was diagnosed with MCD that was clinically reminiscent of unilateral EN. Four weeks after the initiation of therapy with systemic corticosteroids (25 mg/d), oral metronidazole (750 mg/d), and mesalamine (1200 mg/d) for CD, the skin lesions were completely resolved and the patient’s GI symptoms improved simultaneously.

Comment

Crohn disease is a chronic inflammatory granulomatous disease of the GI tract that often is associated with reactive cutaneous lesions including EN, pyoderma gangrenosum, necrotizing vasculitis, and epidermolysis bullosa acquisita. Of these, EN is the most common to appear in CD patients and has been reported to occur in 1% to 15% of patients.^3-5 In particular, skin lesions on the leg presenting as tender erythematous nodules and patches are often diagnosed as EN, which is relatively common. In our case, we initially suspected EN due to the rare presentation of MCD and lack of specific clinical features; however, the skin biopsy revealed noncaseating granulomas in the mid to deep dermis and subcutis consistent with MCD.

Metastatic Crohn disease is a rare disease entity and is characterized by the presence of noncaseating granulomas of the skin at sites separated from the GI tract by normal tissue.¹ Although its pathogenesis is unclear, it has been suggested that immune complexes deposited in the skin could be responsible for the granulomatous reactions.⁴ A T lymphocyte–mediated type IV hypersensitivity reaction also could be responsible.^6,7 Because antimicrobial therapy can be curative for infection-related MCD, special histologic stains and/or tissue cultures can help to exclude an infectious etiology.⁸

Clinical presentations of MCD vary greatly, with observations such as single or multiple erythematous swellings, papules, plaques, nodules, abscesses, and ulcers.^1,2 The relationship between these clinical presentations and the intestinal activity of CD still is unknown; in some cases, however, the metastatic granulomatous lesions and the bowel disease show comparable severity.^2,9,10 In a review of the literature, MCD was generally reported to present in the genital area in children. In adults, lesions most frequently present in the genital area, followed by ulcers on the arms and legs.^1,2 These variations in clinical features and location resemble benign or infectious disease and can lead to delays in diagnosis.

Histopathologically, MCD lesions usually are ill-defined noncaseating granulomas with numerous multinucleated giant cells and lymphomononuclear cells located mostly in the dermis and occasionally extending into the subcutis. The cutaneous granulomata are similar to those present in the affected GI tract. Lymphocytes and plasma cells also are commonly present and eosinophils can be prominent.^1,2,11 In some cases of MCD, granulomatous vasculitis of small- to medium-sized vessels can be found and is associated with dermal and subcutaneous granulomatous inflammation.^8,11,12 Misago and Narisawa¹³ suggested that granulomatous vasculitis and panniculitis associated with CD is considered to be a rare subtype of MCD. Few cases of MCD presenting as granulomatous panniculitis have been described in the literature.^14-16 Our patient presented with lesions that clinically resembled EN; however, the biopsy was more consistent with MCD. The Table summarizes the distinguishing clinical and histopathological features of MCD in our case and classic EN.

Although some authors believe that MCD is not related to CD activity, others assert that MCD lesions may parallel GI activity.^1,2 Our patient was treated with systemic corticosteroids, oral metronidazole, and mesalamine to control the GI symptoms associated with CD. Four weeks after treatment, the GI symptoms and skin lesions improved simultaneously without any additional dermatologic treatment. We believe that MCD has the potential to serve as an early marker of the recurrence of CD and can help with the early diagnosis of CD aggravation, though an association between MCD and CD activity has not been confirmed.

Conclusion

We reported a case of MCD that was clinically reminiscent of unilateral EN and associated with GI disease activity. Physicians should be aware of the possibility of skin manifestations in CD, especially when erythematous nodular lesions are present on the leg.

When using biologic therapies for psoriasis, it is important to evaluate long-term efficacy (>4 years of follow-up). Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Prior studies have yielded inconsistent results.

Vilarrasa et al (J Am Acad Dermatol. 2016;74:1066-1072) conducted an observational retrospective study called ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis) to determine drug survival (the mean length of time patients remain on a drug) in a cohort of 427 patients (63.5% male; mean age, 50.2 years) with moderate to severe psoriasis vulgaris (mean baseline psoriasis area and severity index [PASI], 16.4). In addition to determining mean drug survival times for etanercept, infliximab, adalimumab, and ustekinumab, investigators searched for variables that positively or negatively affected drug survival times. Data were extracted from clinical records of patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression.

The investigators evaluated 703 treatment courses. The overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months; 95% CI, 17.4-28.6) than in patients with body mass index less than 30 (37.3 months; 95% CI, 29.4-45.1; P=.001). Drug survival was significantly higher for ustekinumab than for any other biologic agent (log-rank test, P<.001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment and PASI 75 and PASI 90 responses at week 16 prolonged drug survival. Data were collected retrospectively.

What’s the issue?

These results should help to educate patients and to manage expectations about drug efficacy. They should also give guidance to physicians. Patients who respond rapidly to biologics—PASI 70 or PASI 90 clearance during the induction phase—are more likely to enjoy long-term remission. In contrast, those with a high body mass index should be advised that their psoriasis may take longer to respond to treatment and may need combination therapy for optimal clearance.

We want to know your views! Tell us what you think.

When using biologic therapies for psoriasis, it is important to evaluate long-term efficacy (>4 years of follow-up). Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Prior studies have yielded inconsistent results.

Vilarrasa et al (J Am Acad Dermatol. 2016;74:1066-1072) conducted an observational retrospective study called ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis) to determine drug survival (the mean length of time patients remain on a drug) in a cohort of 427 patients (63.5% male; mean age, 50.2 years) with moderate to severe psoriasis vulgaris (mean baseline psoriasis area and severity index [PASI], 16.4). In addition to determining mean drug survival times for etanercept, infliximab, adalimumab, and ustekinumab, investigators searched for variables that positively or negatively affected drug survival times. Data were extracted from clinical records of patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression.

The investigators evaluated 703 treatment courses. The overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months; 95% CI, 17.4-28.6) than in patients with body mass index less than 30 (37.3 months; 95% CI, 29.4-45.1; P=.001). Drug survival was significantly higher for ustekinumab than for any other biologic agent (log-rank test, P<.001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment and PASI 75 and PASI 90 responses at week 16 prolonged drug survival. Data were collected retrospectively.

What’s the issue?

These results should help to educate patients and to manage expectations about drug efficacy. They should also give guidance to physicians. Patients who respond rapidly to biologics—PASI 70 or PASI 90 clearance during the induction phase—are more likely to enjoy long-term remission. In contrast, those with a high body mass index should be advised that their psoriasis may take longer to respond to treatment and may need combination therapy for optimal clearance.

We want to know your views! Tell us what you think.

When using biologic therapies for psoriasis, it is important to evaluate long-term efficacy (>4 years of follow-up). Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Prior studies have yielded inconsistent results.

Vilarrasa et al (J Am Acad Dermatol. 2016;74:1066-1072) conducted an observational retrospective study called ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis) to determine drug survival (the mean length of time patients remain on a drug) in a cohort of 427 patients (63.5% male; mean age, 50.2 years) with moderate to severe psoriasis vulgaris (mean baseline psoriasis area and severity index [PASI], 16.4). In addition to determining mean drug survival times for etanercept, infliximab, adalimumab, and ustekinumab, investigators searched for variables that positively or negatively affected drug survival times. Data were extracted from clinical records of patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression.

The investigators evaluated 703 treatment courses. The overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months; 95% CI, 17.4-28.6) than in patients with body mass index less than 30 (37.3 months; 95% CI, 29.4-45.1; P=.001). Drug survival was significantly higher for ustekinumab than for any other biologic agent (log-rank test, P<.001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment and PASI 75 and PASI 90 responses at week 16 prolonged drug survival. Data were collected retrospectively.

What’s the issue?

These results should help to educate patients and to manage expectations about drug efficacy. They should also give guidance to physicians. Patients who respond rapidly to biologics—PASI 70 or PASI 90 clearance during the induction phase—are more likely to enjoy long-term remission. In contrast, those with a high body mass index should be advised that their psoriasis may take longer to respond to treatment and may need combination therapy for optimal clearance.

We want to know your views! Tell us what you think.

Myth: Psoriasis Is Infectious The precise cause of psoriasis is unknown, but researchers believe the immune system and genetics play major roles in its development, according to the National Psoriasis Foundation. The skin cells in patients with psoriasis grow at an abnormally fast rate, which causes the buildup of psoriasis lesions. Usually, something triggers psoriasis to flare.

A common misconception among patients is that psoriasis is caused by an infection. Psoriasis is not contagious and psoriasis lesions are not infectious.

However, psoriasis patients are more prone to infections than those without psoriasis. Risk factors for serious infections in psoriasis patients include immune dysregulation, systemic immunosuppressive medications, and comorbid health conditions such as diabetes mellitus or obesity. A 2016 study revealed an increased incidence of serious infections (eg, cellulitis, herpes simplex virus infection, any fungal infection, infectious arthritis, methicillin-resistant Staphylococcus aureus) in hospitalized patients with psoriasis. Higher rates were seen among nonwhite and non-privately insured patients.

In a 2011 study, the likelihood of infectious diseases in patients with psoriasis was twice as high as the reference population. The risk was highest in patients with more severe psoriasis but was not associated with recent systemic antipsoriatic drug dispensing. Respiratory tract, abdominal, and skin infections occurred most frequently in patients with psoriasis.

Poor access to adequate dermatologic care may contribute to higher rates of infections. Dermatologists must closely monitor patients with psoriasis for infection. More research is needed to develop interventions for prevention.

Expert Commentary Psoriasis patients have long faced discrimination because of an  irrational fear that their disease was somehow contagious. In fact this is completely false. This highlights the need for education of the public, so that they understand the true causes and nature of the disease.
—Jeffrey M. Weinberg, MD (New York, New York)

Myth: Psoriasis Is Infectious The precise cause of psoriasis is unknown, but researchers believe the immune system and genetics play major roles in its development, according to the National Psoriasis Foundation. The skin cells in patients with psoriasis grow at an abnormally fast rate, which causes the buildup of psoriasis lesions. Usually, something triggers psoriasis to flare.

A common misconception among patients is that psoriasis is caused by an infection. Psoriasis is not contagious and psoriasis lesions are not infectious.

However, psoriasis patients are more prone to infections than those without psoriasis. Risk factors for serious infections in psoriasis patients include immune dysregulation, systemic immunosuppressive medications, and comorbid health conditions such as diabetes mellitus or obesity. A 2016 study revealed an increased incidence of serious infections (eg, cellulitis, herpes simplex virus infection, any fungal infection, infectious arthritis, methicillin-resistant Staphylococcus aureus) in hospitalized patients with psoriasis. Higher rates were seen among nonwhite and non-privately insured patients.

In a 2011 study, the likelihood of infectious diseases in patients with psoriasis was twice as high as the reference population. The risk was highest in patients with more severe psoriasis but was not associated with recent systemic antipsoriatic drug dispensing. Respiratory tract, abdominal, and skin infections occurred most frequently in patients with psoriasis.

Poor access to adequate dermatologic care may contribute to higher rates of infections. Dermatologists must closely monitor patients with psoriasis for infection. More research is needed to develop interventions for prevention.

Expert Commentary Psoriasis patients have long faced discrimination because of an  irrational fear that their disease was somehow contagious. In fact this is completely false. This highlights the need for education of the public, so that they understand the true causes and nature of the disease.
—Jeffrey M. Weinberg, MD (New York, New York)

Myth: Psoriasis Is Infectious The precise cause of psoriasis is unknown, but researchers believe the immune system and genetics play major roles in its development, according to the National Psoriasis Foundation. The skin cells in patients with psoriasis grow at an abnormally fast rate, which causes the buildup of psoriasis lesions. Usually, something triggers psoriasis to flare.

A common misconception among patients is that psoriasis is caused by an infection. Psoriasis is not contagious and psoriasis lesions are not infectious.

However, psoriasis patients are more prone to infections than those without psoriasis. Risk factors for serious infections in psoriasis patients include immune dysregulation, systemic immunosuppressive medications, and comorbid health conditions such as diabetes mellitus or obesity. A 2016 study revealed an increased incidence of serious infections (eg, cellulitis, herpes simplex virus infection, any fungal infection, infectious arthritis, methicillin-resistant Staphylococcus aureus) in hospitalized patients with psoriasis. Higher rates were seen among nonwhite and non-privately insured patients.

In a 2011 study, the likelihood of infectious diseases in patients with psoriasis was twice as high as the reference population. The risk was highest in patients with more severe psoriasis but was not associated with recent systemic antipsoriatic drug dispensing. Respiratory tract, abdominal, and skin infections occurred most frequently in patients with psoriasis.

Poor access to adequate dermatologic care may contribute to higher rates of infections. Dermatologists must closely monitor patients with psoriasis for infection. More research is needed to develop interventions for prevention.

Expert Commentary Psoriasis patients have long faced discrimination because of an  irrational fear that their disease was somehow contagious. In fact this is completely false. This highlights the need for education of the public, so that they understand the true causes and nature of the disease.
—Jeffrey M. Weinberg, MD (New York, New York)