- Email: [email protected]
IgA pemphigus in a child
Volume 25 Number 2, Part 2 August 1991
24. Jimbow K, Fitzpatrick TB, Szabo G, et aI. Congenital circumscribed hypomelanosis; a characterization based on electron microscopic study of tuberous sclerosis, nevus depigmentosus, and piebaldism. J Invest Dermatol 1975; 64:50-62. 25. Tibbles lA, Cohen MM Jr. The Proteus syndrome: the Elephant Man diagnosed. Br Med J Clin Res 1986;293: 683-5. 26. Bialer MG, Riedy MJ, Wilson WG. Proteus syndrome versus Bannayan Zonana syndrome: a problem in differential diagnosis. Eur J Pediatr 1988;148:122-5.
Proteus syndrome 27. NanneyLB, Stoscheck CM, Magid M, et aI. Altered [l2sI] epidermal growth factor binding and receptor distribution in psoriasis. J Invest DermatolI986;86:26Q-S. 28. Rothe M, Falanga V. Growth factors. Their biology and promise in dermatologic diseases and tissue repair. Arch Dermatol1989jI25:1390-8. 29. Happle R. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J AM ACAD DERMATOL 1987;16:899-906. 30. Happle R. Cutaneous manifestation of lethal genes. Hum Genet 1986;72:280.
IgA pemphigus in a child Ruggero Caputo, MD, Grazia Pistritto, MD, Enrica Gianni, MD, Guido Canninati, MD, Anna Crupi, MD, Emilio Berti, MD, Carlo Gelmetti, MD, and Simona Croci, MD
Milan, Italy The authors describe the first case of 19A pemphigus reported in a child. (1 AM ACAD DERMATOL 1991;25:383-6.)
The term IgA pemphigus has been suggested by Beutner et al. l to designate a rare type of pemphigus characterized by a vesicular-bullous eruption that simulates subcorneal pustular dermatosis or pemphigus foliaceus, subcorneal or intraepidermal acantholysis, and intercellular IgA antibodies in the upper epidermis. Eleven cases in adults have been reported. l - ID We report the first case of IgA pemphigus in a child. CASE REPORT
An ll-year-old girl had a blistering eruption for 15 days that was initially diagnosed as streptococcal impetigo and treated unsuccessfully with erythromycin. Her eruption involved mainly the upper trunk (Fig. 1), the neck, and retroauricular areas (Fig. 2). The abdomen and buttocks were also affected. Mucous membranes, palms, and soles were spared. The eruption consisted of irregular, erythematous areas covered with small blisters, crusts, and scales, and some isolated bullae. These lesions tended to coalesce to form ringlike or serpiginous patFrom the First Department of Dermatology and Pediatric Dermatology. University of Milan. Reprint requests: Prof. Ruggero Caputo, Clinica Dermatologica r, Via Pace. 9, 20122 Milano, ITALY. 16/4/24616
Fig. 1. Vesicular, scaling lesions on trunk and arms.
383
Journal of the American Academy of Dermatology
384 Caputo et al.
Fig. 2. Typical lesions in retroauricular region.
Fig. 3. Direct immunofluorescence of lesional skin: IgA deposits in papillary dermis.
terns. A few blisters were present at the periphery ofthese areas. Nikolsky sign was not found. Cultures of blister fluid grew no organisms. For immunologic study, the biopsy specimen oflesional skin WlolS immediately frozen in liquid nitrogen and stored at·~ 20 0 C until use. For direct immunofluorescence, frozen sections were dried for 4 hours and then rinsed in phosphate-buffered saline solution (PBS), O.lmol/L, pH 7.2, for 15 minutes. They were incubated with fluorescein-conjugatedF(ab'h fragments of rabbit IgG to human 19G, 19A 19M (Dako, Glostrup, Denmark) and fluorescein-Conjugated rabbit IgG to human C3 diluted 1:30 in PBS, rinsed again for 15 minutes in PBS, and finally mounted in 50% glycerol in PBS. Indirect immunofluorescence was performed on nor-
mal monkey esophagus sections, incubated subsequently with patient serum diluted 1:2, 1: 10, or 1:40 in PBS, rinsed in PBS for 30 minutes, incubated with fluoresceinconjugated F(ab'h fragments of rabbit IgG to human IgG or IgA for 1 hour, rinsed twice in PBS for 10 minutes and mounted in 50% glycerol in PBS. Histopathologic examination revealed a subcorneal bulla with some acantholytic cells, spongiosis of the malpighian layer, and marked edema in the papillary dermis, with infiltration of mononuclear and polymorphous cells. Direct immunofluorescence of the lesional skin revealed intercellular IgA deposits in the upper epidermis (Fig. 3). All other immunoreactants were negative. Indirect immunofluorescence on both rabbit esophagus and guinea pig lip was negative. When monkey esophagus was used
Volume 25 Number 2, Part 2 August 1991
IgA pemphigus in a child 385
as a substrate, a low titer of IgA antibodies specific for epithelial intercellular spaces was revealed (Fig. 4). The patient was treated for 3months with dapsone (50 mg/day) and methylprednisolone (4 mg/day), and the lesions gradually disappeared. One month after the withdrawal of therapy, the eruptkm recurred and the patient was treated with etretinate (1 mg/kg/day) for 4 months. Two months after cessation of treatment, the eruption has not recurred. DISCUSSION
Our patient's condition has the clinical, histo.pathologic, and immunologic features that characterize IgA pemphigus, I a rare condition that has been described previously only in adults. l - IO In 1987 Saurat et a1. ll reported a vesicula-pustular dermatosis in a 10-year-old girl that showed pemphiguslike IgA deposits. We consider this case to be different from our case and from other cases of IgA pemphigus because of the presence ofblood and tissue eosinophilia, the absence of acantholysis, the different distribution of IgA deposits, and the absence of serum IgA antibodies to epidermal antigens. In children, the main clinical differential diagnoses are impetigo contagiosa, linear IgA dermatosis, subcorneal pustular dermatosis, and pemphigus foliaceus. Impetigo is readily distinguished from IgA pemphigus by the results of culture of blister fluid and by the rapid response to antibiotic treatment. Linear IgA dermatosis is ruled out clinically by the larger and deeper bullae. Blister formation is at the dermoepidermal junction and IgA is deposited along the basement membrane zone. Subcorneal pustular dermatosis, a rare disease in children,12 differs from IgA pemphigus clinically by the presence of extremely superficial pustules. The pustules are subcorneal with only single acantholytic cells. No immune deposits are formed. Pemphigus foliaceus is characterized by large, flaccid bullae and scaling. The cleavage is subcorneal and there are acantholytic cells. IgG deposition is always found in the intercellular spaces. Our case shows that, in children, we can distinguish two rare forms of pemphigus immunologically: a well-known IgG type and a newly recognized IgA type. The IgG type often requires high-dose corticosteroid therapy and has a poor prognosis. IgA pemphigus seems to be more benign and is easily controlled by the combination of low-dose cortico-
Fig. 4. Indirect immunofluorescence with monkey esophagus: IgA antibodies specific for the intercellular space. steroid and dapsone therapy. It also seems to respond well to etretinate therapy. REFERENCES 1. Beutner EH, Chorzelski P, McDonough Wilson R, et al. IgA pemphigus foliaceus. Report oftwo cases and a review of the literature. J AM ACAD DERMATOL 1989;20:89-97. 2. Wallach D, Cottenot F, Pelbois G, et al. Subcorneal pustular dermatosis and monoclonal IgA. Br J Dermatol 1982;107:229-34. 3. TagamiH, Iwatsuki K, Iwase Y,eta1.Subcorneal pustular dermatosis with vesiculo-bullous eruption. Demonstration of subcorneal IgA deposits and a leukocyte chemotactic factor. Br J DermatoI1983;109:581-7. 4. Burrows D, Bingham EA. Subcorneal pustular dermatosis and IgA gammopathy. Br J Dermatol 1984;111:91-3. 5. Huff lC, Golitz LE, Kunke KS. Intraepidermal neutrophilic IgA dermatosis. N Engl J Med 1985;313:643-5. 6. Hashimoto T, Inamoto N, Nakamura K, et al. Intercellular IgA dermatosis with clinical features of subcorneal pustular dermatosis. Arch DermatoI1987;123:1062-S. 7. Nishikawa T, Shimizo H, Hashimoto T. Role oflgA intercellular antibodies: report of clinically and immunopathologically atypical cases [Abstract]. Seventeenth World Congress of Dermatology 1987;(Part 1):73.
Caputo et aJ. 8, ()ol1nick H, Thies W, Taud W, et al. Intra-epidennale l1~u~rophileund eosinophile IgA-Dennatose, In: Gollnick ~,$tadler R,eds. Dia-Klinik. Stuttgart: Schattauer, :~~67:68-70.
9.'pjetteW, IlurkenRR, Ray TL. Intraepidermal neutrophilic 19A dermatosis: presence of circulating pemphiguslike 19A antibody specific for monkey epithelium [Abstract]. J Invest DermatoI1987;88:512.
Journal of the American Academy of Dermatology 10. Stolz W, Bieber T, Meurer M. Is the atypical neutrophilic dennatosis with subcorneal IgA deposits a variant ofpemphigus foliaceus? Br J DermatoI1989;121:276-9. 11. Saurat J-H, Merot Y, Salomon D, et al. Pemphigus-like IgA deposits and vesiculo-pustular dermatosis in a 10year-old girl. Dermatologica 1987;175:96-100. 12. Johnson SAM, Cripps DJ. Subcorneal pustular dermatosis in children. Arch DermatoI1974;109:73-7.
Erythema multifonne after contact dermatitis in response to an epoxy sealant Margot J. Whitfe1d, MBBS, and Jason K. Rivers, MD, FRCPC Camperdown, New South Wales, Australia A case of erythema multiforme associated with an allergic contact dermatitis in response to an epoxy-based compound is presented. Patch tests revealed a positive reaction to both the epoxy resin and the hardener. Chemicals applied directly to the skin should be considered as a potential cause of erythema multiforme. (J AM ACAD DERMATOL 1991;25:386-8.)
Epoxy resins cause more instances of occupational dermatitis than any other group ofchemicals. I Although erythema multifonne (EM) has occasionally been reported in conjunction with allergic contact dermatitis in response to various allergens,2-27 this association has been documented only once before in the case of epoxy resins. 2 We report another case of EM that developed in association with a contact dermatitis to an epoxy resin and hardener. CASE REPORT
A 46-year-old swimming pool attendant had an intensely pruritic papular eruption of 24 hours' duration on her upper limbs. For the preceding 10 days, she had been engaged in repairing and repainting the swimming pool. Although she had attempted to protect her arms, paint had splashed onto her arms daily. The "paint" was actually a swimming pool sealant that contained 55% epoxy resin (molecular weight 380) and an epoxy hardener, isophoronediamine. From the Department of Dermatology, The University of Sydney, Royal Prince Alfred Hospital. Reprint requests: J. Rivers, MD, Division of Dermatology, Faculty of Medicine, The University of British Columbia, 855 W. Tenth Ave., Vancouver, B.C., Canada V5Z 1L7.
16/4/24613
386
The patient's medical history was unremarkable aside from previous eczematous reactions to several perfumes and cosmetics. There was no personal or family history of atopy. Physical examination revealed an erythematous papulovesicular and bullous eruption confined to the middle part of the upper extremities (Fig. 1). A clinical diagnosis of acute allergic contact dermatitis was made, and the epoxy sealant was considered the causative agent. The patient was treated with Burow's solution compresses and betamethasone valerate 0.05% cream three times daily. She avoided the workplace, and her condition improved considerably over the next 5 days. Nine days after the onset of the dermatitis, a new eruption developed on the patient's forearms and quickly spread to the hands. When seen 3 days after the onset of the new eruption, her arms and hands were covered with erythematous papules and plaques, some with a targetlike appearance (Fig. 2). The oral and ocular mucosae were uninvolved, and the results of the remainder of the physical examination were normal. A diagnosis of EM was made, The eruption resolved during the next 2 weeks and has not recurred. Patch tests with the TRUE Test standard series showed positive reactions at 48 and 96 hours to epoxy resin and fragrance mix, and a positive response to balsam of Peru at 96 hours only. Further patch testing with the epoxy resin (2% in petrolatum and I %in acetone) and the
24. Jimbow K, Fitzpatrick TB, Szabo G, et aI. Congenital circumscribed hypomelanosis; a characterization based on electron microscopic study of tuberous sclerosis, nevus depigmentosus, and piebaldism. J Invest Dermatol 1975; 64:50-62. 25. Tibbles lA, Cohen MM Jr. The Proteus syndrome: the Elephant Man diagnosed. Br Med J Clin Res 1986;293: 683-5. 26. Bialer MG, Riedy MJ, Wilson WG. Proteus syndrome versus Bannayan Zonana syndrome: a problem in differential diagnosis. Eur J Pediatr 1988;148:122-5.
Proteus syndrome 27. NanneyLB, Stoscheck CM, Magid M, et aI. Altered [l2sI] epidermal growth factor binding and receptor distribution in psoriasis. J Invest DermatolI986;86:26Q-S. 28. Rothe M, Falanga V. Growth factors. Their biology and promise in dermatologic diseases and tissue repair. Arch Dermatol1989jI25:1390-8. 29. Happle R. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J AM ACAD DERMATOL 1987;16:899-906. 30. Happle R. Cutaneous manifestation of lethal genes. Hum Genet 1986;72:280.
IgA pemphigus in a child Ruggero Caputo, MD, Grazia Pistritto, MD, Enrica Gianni, MD, Guido Canninati, MD, Anna Crupi, MD, Emilio Berti, MD, Carlo Gelmetti, MD, and Simona Croci, MD
Milan, Italy The authors describe the first case of 19A pemphigus reported in a child. (1 AM ACAD DERMATOL 1991;25:383-6.)
The term IgA pemphigus has been suggested by Beutner et al. l to designate a rare type of pemphigus characterized by a vesicular-bullous eruption that simulates subcorneal pustular dermatosis or pemphigus foliaceus, subcorneal or intraepidermal acantholysis, and intercellular IgA antibodies in the upper epidermis. Eleven cases in adults have been reported. l - ID We report the first case of IgA pemphigus in a child. CASE REPORT
An ll-year-old girl had a blistering eruption for 15 days that was initially diagnosed as streptococcal impetigo and treated unsuccessfully with erythromycin. Her eruption involved mainly the upper trunk (Fig. 1), the neck, and retroauricular areas (Fig. 2). The abdomen and buttocks were also affected. Mucous membranes, palms, and soles were spared. The eruption consisted of irregular, erythematous areas covered with small blisters, crusts, and scales, and some isolated bullae. These lesions tended to coalesce to form ringlike or serpiginous patFrom the First Department of Dermatology and Pediatric Dermatology. University of Milan. Reprint requests: Prof. Ruggero Caputo, Clinica Dermatologica r, Via Pace. 9, 20122 Milano, ITALY. 16/4/24616
Fig. 1. Vesicular, scaling lesions on trunk and arms.
383
Journal of the American Academy of Dermatology
384 Caputo et al.
Fig. 2. Typical lesions in retroauricular region.
Fig. 3. Direct immunofluorescence of lesional skin: IgA deposits in papillary dermis.
terns. A few blisters were present at the periphery ofthese areas. Nikolsky sign was not found. Cultures of blister fluid grew no organisms. For immunologic study, the biopsy specimen oflesional skin WlolS immediately frozen in liquid nitrogen and stored at·~ 20 0 C until use. For direct immunofluorescence, frozen sections were dried for 4 hours and then rinsed in phosphate-buffered saline solution (PBS), O.lmol/L, pH 7.2, for 15 minutes. They were incubated with fluorescein-conjugatedF(ab'h fragments of rabbit IgG to human 19G, 19A 19M (Dako, Glostrup, Denmark) and fluorescein-Conjugated rabbit IgG to human C3 diluted 1:30 in PBS, rinsed again for 15 minutes in PBS, and finally mounted in 50% glycerol in PBS. Indirect immunofluorescence was performed on nor-
mal monkey esophagus sections, incubated subsequently with patient serum diluted 1:2, 1: 10, or 1:40 in PBS, rinsed in PBS for 30 minutes, incubated with fluoresceinconjugated F(ab'h fragments of rabbit IgG to human IgG or IgA for 1 hour, rinsed twice in PBS for 10 minutes and mounted in 50% glycerol in PBS. Histopathologic examination revealed a subcorneal bulla with some acantholytic cells, spongiosis of the malpighian layer, and marked edema in the papillary dermis, with infiltration of mononuclear and polymorphous cells. Direct immunofluorescence of the lesional skin revealed intercellular IgA deposits in the upper epidermis (Fig. 3). All other immunoreactants were negative. Indirect immunofluorescence on both rabbit esophagus and guinea pig lip was negative. When monkey esophagus was used
Volume 25 Number 2, Part 2 August 1991
IgA pemphigus in a child 385
as a substrate, a low titer of IgA antibodies specific for epithelial intercellular spaces was revealed (Fig. 4). The patient was treated for 3months with dapsone (50 mg/day) and methylprednisolone (4 mg/day), and the lesions gradually disappeared. One month after the withdrawal of therapy, the eruptkm recurred and the patient was treated with etretinate (1 mg/kg/day) for 4 months. Two months after cessation of treatment, the eruption has not recurred. DISCUSSION
Our patient's condition has the clinical, histo.pathologic, and immunologic features that characterize IgA pemphigus, I a rare condition that has been described previously only in adults. l - IO In 1987 Saurat et a1. ll reported a vesicula-pustular dermatosis in a 10-year-old girl that showed pemphiguslike IgA deposits. We consider this case to be different from our case and from other cases of IgA pemphigus because of the presence ofblood and tissue eosinophilia, the absence of acantholysis, the different distribution of IgA deposits, and the absence of serum IgA antibodies to epidermal antigens. In children, the main clinical differential diagnoses are impetigo contagiosa, linear IgA dermatosis, subcorneal pustular dermatosis, and pemphigus foliaceus. Impetigo is readily distinguished from IgA pemphigus by the results of culture of blister fluid and by the rapid response to antibiotic treatment. Linear IgA dermatosis is ruled out clinically by the larger and deeper bullae. Blister formation is at the dermoepidermal junction and IgA is deposited along the basement membrane zone. Subcorneal pustular dermatosis, a rare disease in children,12 differs from IgA pemphigus clinically by the presence of extremely superficial pustules. The pustules are subcorneal with only single acantholytic cells. No immune deposits are formed. Pemphigus foliaceus is characterized by large, flaccid bullae and scaling. The cleavage is subcorneal and there are acantholytic cells. IgG deposition is always found in the intercellular spaces. Our case shows that, in children, we can distinguish two rare forms of pemphigus immunologically: a well-known IgG type and a newly recognized IgA type. The IgG type often requires high-dose corticosteroid therapy and has a poor prognosis. IgA pemphigus seems to be more benign and is easily controlled by the combination of low-dose cortico-
Fig. 4. Indirect immunofluorescence with monkey esophagus: IgA antibodies specific for the intercellular space. steroid and dapsone therapy. It also seems to respond well to etretinate therapy. REFERENCES 1. Beutner EH, Chorzelski P, McDonough Wilson R, et al. IgA pemphigus foliaceus. Report oftwo cases and a review of the literature. J AM ACAD DERMATOL 1989;20:89-97. 2. Wallach D, Cottenot F, Pelbois G, et al. Subcorneal pustular dermatosis and monoclonal IgA. Br J Dermatol 1982;107:229-34. 3. TagamiH, Iwatsuki K, Iwase Y,eta1.Subcorneal pustular dermatosis with vesiculo-bullous eruption. Demonstration of subcorneal IgA deposits and a leukocyte chemotactic factor. Br J DermatoI1983;109:581-7. 4. Burrows D, Bingham EA. Subcorneal pustular dermatosis and IgA gammopathy. Br J Dermatol 1984;111:91-3. 5. Huff lC, Golitz LE, Kunke KS. Intraepidermal neutrophilic IgA dermatosis. N Engl J Med 1985;313:643-5. 6. Hashimoto T, Inamoto N, Nakamura K, et al. Intercellular IgA dermatosis with clinical features of subcorneal pustular dermatosis. Arch DermatoI1987;123:1062-S. 7. Nishikawa T, Shimizo H, Hashimoto T. Role oflgA intercellular antibodies: report of clinically and immunopathologically atypical cases [Abstract]. Seventeenth World Congress of Dermatology 1987;(Part 1):73.
Caputo et aJ. 8, ()ol1nick H, Thies W, Taud W, et al. Intra-epidennale l1~u~rophileund eosinophile IgA-Dennatose, In: Gollnick ~,$tadler R,eds. Dia-Klinik. Stuttgart: Schattauer, :~~67:68-70.
9.'pjetteW, IlurkenRR, Ray TL. Intraepidermal neutrophilic 19A dermatosis: presence of circulating pemphiguslike 19A antibody specific for monkey epithelium [Abstract]. J Invest DermatoI1987;88:512.
Journal of the American Academy of Dermatology 10. Stolz W, Bieber T, Meurer M. Is the atypical neutrophilic dennatosis with subcorneal IgA deposits a variant ofpemphigus foliaceus? Br J DermatoI1989;121:276-9. 11. Saurat J-H, Merot Y, Salomon D, et al. Pemphigus-like IgA deposits and vesiculo-pustular dermatosis in a 10year-old girl. Dermatologica 1987;175:96-100. 12. Johnson SAM, Cripps DJ. Subcorneal pustular dermatosis in children. Arch DermatoI1974;109:73-7.
Erythema multifonne after contact dermatitis in response to an epoxy sealant Margot J. Whitfe1d, MBBS, and Jason K. Rivers, MD, FRCPC Camperdown, New South Wales, Australia A case of erythema multiforme associated with an allergic contact dermatitis in response to an epoxy-based compound is presented. Patch tests revealed a positive reaction to both the epoxy resin and the hardener. Chemicals applied directly to the skin should be considered as a potential cause of erythema multiforme. (J AM ACAD DERMATOL 1991;25:386-8.)
Epoxy resins cause more instances of occupational dermatitis than any other group ofchemicals. I Although erythema multifonne (EM) has occasionally been reported in conjunction with allergic contact dermatitis in response to various allergens,2-27 this association has been documented only once before in the case of epoxy resins. 2 We report another case of EM that developed in association with a contact dermatitis to an epoxy resin and hardener. CASE REPORT
A 46-year-old swimming pool attendant had an intensely pruritic papular eruption of 24 hours' duration on her upper limbs. For the preceding 10 days, she had been engaged in repairing and repainting the swimming pool. Although she had attempted to protect her arms, paint had splashed onto her arms daily. The "paint" was actually a swimming pool sealant that contained 55% epoxy resin (molecular weight 380) and an epoxy hardener, isophoronediamine. From the Department of Dermatology, The University of Sydney, Royal Prince Alfred Hospital. Reprint requests: J. Rivers, MD, Division of Dermatology, Faculty of Medicine, The University of British Columbia, 855 W. Tenth Ave., Vancouver, B.C., Canada V5Z 1L7.
16/4/24613
386
The patient's medical history was unremarkable aside from previous eczematous reactions to several perfumes and cosmetics. There was no personal or family history of atopy. Physical examination revealed an erythematous papulovesicular and bullous eruption confined to the middle part of the upper extremities (Fig. 1). A clinical diagnosis of acute allergic contact dermatitis was made, and the epoxy sealant was considered the causative agent. The patient was treated with Burow's solution compresses and betamethasone valerate 0.05% cream three times daily. She avoided the workplace, and her condition improved considerably over the next 5 days. Nine days after the onset of the dermatitis, a new eruption developed on the patient's forearms and quickly spread to the hands. When seen 3 days after the onset of the new eruption, her arms and hands were covered with erythematous papules and plaques, some with a targetlike appearance (Fig. 2). The oral and ocular mucosae were uninvolved, and the results of the remainder of the physical examination were normal. A diagnosis of EM was made, The eruption resolved during the next 2 weeks and has not recurred. Patch tests with the TRUE Test standard series showed positive reactions at 48 and 96 hours to epoxy resin and fragrance mix, and a positive response to balsam of Peru at 96 hours only. Further patch testing with the epoxy resin (2% in petrolatum and I %in acetone) and the