- Email: [email protected]
A painful eruption in a woman with Darier disease
J AM ACAD DERMATOL VOLUME 67, NUMBER 5
dyshidrosiform pemphigoid, antibodies to the hemidesmosomes of the basement membrane predominate; in BrunstingePerry cicatricial pemphigoid, the anchoring filament component laminin 332 is also reported. Localized, nonscarring bullous pemphigoid has been described to arise spontaneously and at areas of trauma. Nontraumatic bullae most commonly arise in the pretibial area and either remain localized or precede more generalized bullous pemphigoid. No localizing mechanism has been described, although speculation regarding vascular disease in the lower extremities has been proposed. Localized traumatic bullous pemphigoid has also been described as arising secondary to physical trauma and remaining limited to the site of injury, such as surgical sites, poorly healing wounds, amputation sites, and even as an isomorphic response in patients with chronic pruritus. Treatment of dyshidrosiform pemphigoid, like that of bullous pemphigoid, focuses on immunosuppressive therapy. Topical corticosteroids are regarded as the first-line therapy, with the addition of systemic corticosteroids, dapsone, mycophenolate mofetil, or azathioprine combination therapy as indicated. No clinical, laboratory, or histopathologic findings have been shown to be predictive of either the duration or extent of involvement in patients with localized or generalized bullous pemphigoid. Although half of patients with generalized bullous pemphigoid in 1 hospital series experienced clinical remission after 3 years, no similar studies regarding dyshidrosiform pemphigoid exist. In our patient’s case, a high potency topical corticosteroid applied twice daily was sufficient to obtain a clinical remission after 4 months of therapy. For this series, the recommended choices are: 1, b; 2, a; 3, c; 4, b. BIBLIOGRAPHY Chang Y, Liu H, Wong C. Bullous pemphigoid—a report of 86 cases from Taiwan. Clin Exp Dermatol 1996;21:20-2. Forschner A, Fierlbeck G. Localized pemphigoid on the soles of both feet. Int J Dermatol 2005;44:312-4. Gammon W, Fine J, Forbes M, Briggaman R. Immunofluorescence on split skin for the detection and differentiation of basement membrane zone autoantibodies. J Am Acad Dermatol 1992; 27:79-87. Ishii N, Hamada T, Dainichi T, Karashima T, Nakama T, Yasumoto S, et al. Epidermolysis bulosa acquisita: what’s new? J Dermatol 2010;37:220-30. Kim Y, Kim M, Kim H, Park Y. Dyshidrosiform bullous pemphigoid. Acta Derm Venereol 2004;84:253-4. Martin JM, Pinazo I, Molina I, Monteaguda C, Villalon G, Reig I, et al. Cicatricial pemphigoid of the Brunsting-Perry type. Int J Dermatol 2009;48:293-4. Patrizi A, Rizzoli L, Benassi L, Neri I. Another case of dyshidrosiform pemphigoid. J Eur Acad Dermatol Venereol 2003;17:370.
JAAD grand rounds 1089
Person JR, Rogers RS 3rd, Perry HO. Localized pemphigoid. Br J Dermatol 1976;95:531-4. Ujiie H, Shibaki A, Nishie W, Shimizu H. What’s new in bullous pemphigoid. J Dermatol 2010;37:194-204. Venning V, Wojnarowska F. Lack of predictive factors for the clinical course of bullous pemphigoid. J Am Acad Dermatol 1992;26:585-9.
A painful eruption in a woman with Darier disease Daniel Walker, BS, Rachael L. Cayce, MD, and Travis Vandergriff, MD Dallas, Texas A 48-year-old white woman with a history of Darier disease presented with an acute painful and burning eruption on her chest. She had been treated for previous flares of her disease with topical triamcinolone and drying powders, but stated that this eruption was not responding to these usual treatments. Days before her presentation, she had been given narcotics and minocycline for presumed impetiginization without an improvement in the rash or her level of pain. The physical examination revealed numerous pink papules coalescing into reticulate plaques across the anterior surface of her chest and inframammary regions (Fig 5). Many of these papules had monomorphous punched out erosions and ulcers with either a glistening pink base or an adherent yellow crust. Along the hairline were numerous erythematous plaques with thick, greasy scale. There were also yellow-brown keratotic papules on her ventral forearms, abdomen, lower back, and shins. 5. What is the most likely diagnosis? a. Pemphigus vulgaris b. Kaposi varicelliform eruption c. Ecthyma d. Bullous impetigo e. Allergic contact dermatitis 6. Which of the following viruses is most commonly implicated in this condition? a. Coxsackie virus b. Vaccinia virus c. Herpes simplex virus d. Cytomegalovirus e. Human papillomavirus 7. Darier disease is thought to be caused by what molecular alteration? a. Abnormal keratinocyte calcium signaling b. Impaired communication by gap junctions c. Deficiency in collagen synthesis d. Alteration in basement membrane structural proteins e. DNA mismatch repair genes
1090 JAAD grand rounds
8. Which of the following skin diseases may also be associated with Kaposi varicelliform eruption? a. Atopic dermatitis b. Psoriasis c. Epidermolysis bullosa d. Cutaneous lupus erythematosus e. Morphea (localized scleroderma) Discussion Darier disease is a rare chronic dermatosis inherited in an autosomal dominant pattern. The disease leads to altered keratinization of the epidermis, nails, and mucous membranes. Mutations in ATP2A2 lead to Darier disease. The gene encodes a calcium pump present in the sarcoplasmic reticulum, which normally maintains a low level of calcium in the cytoplasm. Clinically, patients with Darier disease present with persistent firm, greasy, crusted papules that are skin-colored or yellow-brown. These papules commonly coalesce into irregular warty plaques on the seborrheic areas of the upper trunk and scalp margins. The disease typically appears in adolescence and is exacerbated by heat, sweating, and ultraviolet light. Kaposi varicelliform eruption (KVE) is a viral infection most often caused by herpes simplex virus (HSV), but other reported causes include vaccinia and Coxsackie viruses. KVE has been reported as a complication in a number of dermatoses, including ichthyosis vulgaris, atopic dermatitis, bullous pemphigoid, seborrheic dermatitis, and Darier disease. KVE is often observed during exacerbations of the underlying skin disease. KVE typically presents as closely grouped clusters of monomorphic, disseminated vesiculopustules that may be accompanied by fever, chills, malaise, and regional lymphadenopathy. These lesions often progress to painful hemorrhagic, crusted, punchedout erosions that may coalesce to larger plaques. The head, neck, and upper body are most commonly affected. Involvement of the eye is considered an ophthalmologic emergency, and in these cases an ophthalmology consultation should be made.
J AM ACAD DERMATOL
NOVEMBER 2012
Early treatment of KVE is important to avoid scarring and other sequelae. There is a potential for systemic viremia that may lead to multiorgan failure and death. Facial and eyelid involvement may lead to herpetic keratitis or blepharoconjunctivitis, which can result in blindness. In children, disseminated HSV may lead to bone marrow suppression, disseminated intravascular coagulopathy, or death caused by viremia. The most commonly used antiviral treatment for severe KVE is highdose intravenous acyclovir. Valacyclovir is also an effective treatment and provides better oral availability and a more convenient dosing schedule. Oral antivirals should be reserved for patients with milder disease who do not require hospital admission. The underlying mechanism for KVE occurrence in Darier disease remains unknown. It has been hypothesized to result from a defect in cell-mediated immunity; however, no specific abnormality in immune function has been shown. Perhaps a defect in the barrier function of skin predisposes these patients to a secondary viral infection, because KVE typically occurs in areas where the skin barrier is disrupted. In our patient, a viral culture was obtained and she was immediately started on oral valacyclovir given the high degree of clinical suspicion. HSV type 1 was identified in the culture, and she had immediate improvement within 1 day of starting treatment. Complete resolution of the eruption was achieved in 1 week with oral antivirals and local wound care. For this series, the recommended choices are: 5, b; 6, c; 7, a; 8, a. BIBLIOGRAPHY Burge S. Darier’s disease—the clinical features and pathogenesis. Clin Exp Dermatol 1994;19:193-205. Carney JF, Caroline NL, Nankervis GA, Pomeranz JR. Eczema vaccinatum and eczema herpeticum in Darier disease. Arch Dermatol 1973;107:613-4. Demis D. In: Clinical dermatology, vol. 14-3. Philidelphia (PA): Lippincott; 1990. Doeglas HM, Moolhuysen TM. Kaposi’s varicelliform eruption. Two cases caused by herpesvirus hominis infection complicating Darier’s disease. Arch Dermatol 1969;100:592-5. Loeffel ED, Meyer JS. Eczema vaccinatum in Darier’s disease. Arch Dermatol 1970;102:451-6. Morganroth GS, Glick SA, Perez MI, Castiglione FM Jr, Bolognia JL. Kaposi’s varicelliform eruption complicating irritant contact dermatitis. J Am Acad Dermatol 1992;27:1030-1. Sais G, Jucgla A, Curc o N, Peyrı J. Kaposi’s varicelliform eruption with ocular involvement. Arch Dermatol 1994; 130:1209-10. Sanderson IR, Brueton LA, Savage MO, Harper JI. Eczema herpeticum: a potentially fatal disease. Br Med J (Clin Res Ed) 1987; 294:693-4.
dyshidrosiform pemphigoid, antibodies to the hemidesmosomes of the basement membrane predominate; in BrunstingePerry cicatricial pemphigoid, the anchoring filament component laminin 332 is also reported. Localized, nonscarring bullous pemphigoid has been described to arise spontaneously and at areas of trauma. Nontraumatic bullae most commonly arise in the pretibial area and either remain localized or precede more generalized bullous pemphigoid. No localizing mechanism has been described, although speculation regarding vascular disease in the lower extremities has been proposed. Localized traumatic bullous pemphigoid has also been described as arising secondary to physical trauma and remaining limited to the site of injury, such as surgical sites, poorly healing wounds, amputation sites, and even as an isomorphic response in patients with chronic pruritus. Treatment of dyshidrosiform pemphigoid, like that of bullous pemphigoid, focuses on immunosuppressive therapy. Topical corticosteroids are regarded as the first-line therapy, with the addition of systemic corticosteroids, dapsone, mycophenolate mofetil, or azathioprine combination therapy as indicated. No clinical, laboratory, or histopathologic findings have been shown to be predictive of either the duration or extent of involvement in patients with localized or generalized bullous pemphigoid. Although half of patients with generalized bullous pemphigoid in 1 hospital series experienced clinical remission after 3 years, no similar studies regarding dyshidrosiform pemphigoid exist. In our patient’s case, a high potency topical corticosteroid applied twice daily was sufficient to obtain a clinical remission after 4 months of therapy. For this series, the recommended choices are: 1, b; 2, a; 3, c; 4, b. BIBLIOGRAPHY Chang Y, Liu H, Wong C. Bullous pemphigoid—a report of 86 cases from Taiwan. Clin Exp Dermatol 1996;21:20-2. Forschner A, Fierlbeck G. Localized pemphigoid on the soles of both feet. Int J Dermatol 2005;44:312-4. Gammon W, Fine J, Forbes M, Briggaman R. Immunofluorescence on split skin for the detection and differentiation of basement membrane zone autoantibodies. J Am Acad Dermatol 1992; 27:79-87. Ishii N, Hamada T, Dainichi T, Karashima T, Nakama T, Yasumoto S, et al. Epidermolysis bulosa acquisita: what’s new? J Dermatol 2010;37:220-30. Kim Y, Kim M, Kim H, Park Y. Dyshidrosiform bullous pemphigoid. Acta Derm Venereol 2004;84:253-4. Martin JM, Pinazo I, Molina I, Monteaguda C, Villalon G, Reig I, et al. Cicatricial pemphigoid of the Brunsting-Perry type. Int J Dermatol 2009;48:293-4. Patrizi A, Rizzoli L, Benassi L, Neri I. Another case of dyshidrosiform pemphigoid. J Eur Acad Dermatol Venereol 2003;17:370.
JAAD grand rounds 1089
Person JR, Rogers RS 3rd, Perry HO. Localized pemphigoid. Br J Dermatol 1976;95:531-4. Ujiie H, Shibaki A, Nishie W, Shimizu H. What’s new in bullous pemphigoid. J Dermatol 2010;37:194-204. Venning V, Wojnarowska F. Lack of predictive factors for the clinical course of bullous pemphigoid. J Am Acad Dermatol 1992;26:585-9.
A painful eruption in a woman with Darier disease Daniel Walker, BS, Rachael L. Cayce, MD, and Travis Vandergriff, MD Dallas, Texas A 48-year-old white woman with a history of Darier disease presented with an acute painful and burning eruption on her chest. She had been treated for previous flares of her disease with topical triamcinolone and drying powders, but stated that this eruption was not responding to these usual treatments. Days before her presentation, she had been given narcotics and minocycline for presumed impetiginization without an improvement in the rash or her level of pain. The physical examination revealed numerous pink papules coalescing into reticulate plaques across the anterior surface of her chest and inframammary regions (Fig 5). Many of these papules had monomorphous punched out erosions and ulcers with either a glistening pink base or an adherent yellow crust. Along the hairline were numerous erythematous plaques with thick, greasy scale. There were also yellow-brown keratotic papules on her ventral forearms, abdomen, lower back, and shins. 5. What is the most likely diagnosis? a. Pemphigus vulgaris b. Kaposi varicelliform eruption c. Ecthyma d. Bullous impetigo e. Allergic contact dermatitis 6. Which of the following viruses is most commonly implicated in this condition? a. Coxsackie virus b. Vaccinia virus c. Herpes simplex virus d. Cytomegalovirus e. Human papillomavirus 7. Darier disease is thought to be caused by what molecular alteration? a. Abnormal keratinocyte calcium signaling b. Impaired communication by gap junctions c. Deficiency in collagen synthesis d. Alteration in basement membrane structural proteins e. DNA mismatch repair genes
1090 JAAD grand rounds
8. Which of the following skin diseases may also be associated with Kaposi varicelliform eruption? a. Atopic dermatitis b. Psoriasis c. Epidermolysis bullosa d. Cutaneous lupus erythematosus e. Morphea (localized scleroderma) Discussion Darier disease is a rare chronic dermatosis inherited in an autosomal dominant pattern. The disease leads to altered keratinization of the epidermis, nails, and mucous membranes. Mutations in ATP2A2 lead to Darier disease. The gene encodes a calcium pump present in the sarcoplasmic reticulum, which normally maintains a low level of calcium in the cytoplasm. Clinically, patients with Darier disease present with persistent firm, greasy, crusted papules that are skin-colored or yellow-brown. These papules commonly coalesce into irregular warty plaques on the seborrheic areas of the upper trunk and scalp margins. The disease typically appears in adolescence and is exacerbated by heat, sweating, and ultraviolet light. Kaposi varicelliform eruption (KVE) is a viral infection most often caused by herpes simplex virus (HSV), but other reported causes include vaccinia and Coxsackie viruses. KVE has been reported as a complication in a number of dermatoses, including ichthyosis vulgaris, atopic dermatitis, bullous pemphigoid, seborrheic dermatitis, and Darier disease. KVE is often observed during exacerbations of the underlying skin disease. KVE typically presents as closely grouped clusters of monomorphic, disseminated vesiculopustules that may be accompanied by fever, chills, malaise, and regional lymphadenopathy. These lesions often progress to painful hemorrhagic, crusted, punchedout erosions that may coalesce to larger plaques. The head, neck, and upper body are most commonly affected. Involvement of the eye is considered an ophthalmologic emergency, and in these cases an ophthalmology consultation should be made.
J AM ACAD DERMATOL
NOVEMBER 2012
Early treatment of KVE is important to avoid scarring and other sequelae. There is a potential for systemic viremia that may lead to multiorgan failure and death. Facial and eyelid involvement may lead to herpetic keratitis or blepharoconjunctivitis, which can result in blindness. In children, disseminated HSV may lead to bone marrow suppression, disseminated intravascular coagulopathy, or death caused by viremia. The most commonly used antiviral treatment for severe KVE is highdose intravenous acyclovir. Valacyclovir is also an effective treatment and provides better oral availability and a more convenient dosing schedule. Oral antivirals should be reserved for patients with milder disease who do not require hospital admission. The underlying mechanism for KVE occurrence in Darier disease remains unknown. It has been hypothesized to result from a defect in cell-mediated immunity; however, no specific abnormality in immune function has been shown. Perhaps a defect in the barrier function of skin predisposes these patients to a secondary viral infection, because KVE typically occurs in areas where the skin barrier is disrupted. In our patient, a viral culture was obtained and she was immediately started on oral valacyclovir given the high degree of clinical suspicion. HSV type 1 was identified in the culture, and she had immediate improvement within 1 day of starting treatment. Complete resolution of the eruption was achieved in 1 week with oral antivirals and local wound care. For this series, the recommended choices are: 5, b; 6, c; 7, a; 8, a. BIBLIOGRAPHY Burge S. Darier’s disease—the clinical features and pathogenesis. Clin Exp Dermatol 1994;19:193-205. Carney JF, Caroline NL, Nankervis GA, Pomeranz JR. Eczema vaccinatum and eczema herpeticum in Darier disease. Arch Dermatol 1973;107:613-4. Demis D. In: Clinical dermatology, vol. 14-3. Philidelphia (PA): Lippincott; 1990. Doeglas HM, Moolhuysen TM. Kaposi’s varicelliform eruption. Two cases caused by herpesvirus hominis infection complicating Darier’s disease. Arch Dermatol 1969;100:592-5. Loeffel ED, Meyer JS. Eczema vaccinatum in Darier’s disease. Arch Dermatol 1970;102:451-6. Morganroth GS, Glick SA, Perez MI, Castiglione FM Jr, Bolognia JL. Kaposi’s varicelliform eruption complicating irritant contact dermatitis. J Am Acad Dermatol 1992;27:1030-1. Sais G, Jucgla A, Curc o N, Peyrı J. Kaposi’s varicelliform eruption with ocular involvement. Arch Dermatol 1994; 130:1209-10. Sanderson IR, Brueton LA, Savage MO, Harper JI. Eczema herpeticum: a potentially fatal disease. Br Med J (Clin Res Ed) 1987; 294:693-4.