The Journal of Dermatology Vol. 19: 626-628, 1992
Short repor
Subcorneal Pustular Dermatosis and IgA Multiple Myeloma Lajos Bolcskei, Sandor Husz, Janos Hunyadi, Gyula Varga* and Attila Dobozy Abstract
A case of subcomeal pustular dermatosis associated with IgA multiple myeloma is described, The significance of the combination of the two diseases is not yet known, but the association is certainly more than coincidence.
Key words:
Sneddon-Wilkinson disease
Introduction Subcorneal pustular dermatosis is a rare, chronic, recurrent disease usually seen in women after the fourth decade. The cutaneous lesions are typically found on the trunk and in the flexures and form circinate patterns. The pustules are sterile, but secondary infection often occurs. There are no characteristic immunopathological changes, although in some cases .immunofluorescence staining has been observed. This report presents a case of subcorneal pustular dermatosis associated with IgA multiple myeloma.
Case Report The patient, D.H., a 76-year-old man, had a 6 to 7-year history of skin disease in the form of red, inflamed, itchy spots, first on the upper arm and then all over the body. Thin-walled, quickly erupting pustules occurred in the spots. Hospitalization was necessitated by non-healing exacerbations all over the body, which started 6 months prior to clinical treatment. On admission, there were numerous erosions covered with brown scars 1 cm in size, often Received October 7, 1991; accepted for publication July 3,1992. Albert Szent-Gyorgyi Medical University Department of Dermatology (Head: Prof. Attila Dobozy) and *the 2nd Department of Internal Medicine (Head: Prof. Miklos Csanady), Szeged, Hungary. Reprint requests to: Lajos Bolcskei, Department of Dermatology, Albert Szent-Gyorgyi Medical University, H-6701 Szeged, P.o. Box 480, Hungary.
Fig. 1. General aspects of lesions. coalescing to cover large areas on the trunk and limbs (Fig. 1), as well as similar-sized pustules with thin walls and cloudy content (Fig. 2). Laboratory results: Erythrocyte sedimentation rate: 100 mm/hour; hematocrit: 39%; hemoglobin: 13.3 g/dl; urine: gravity: 1.010; protein: opalescing; pus: -l-: serum alkalinephosphatase: 190 U/L; serum uric acid: 396 f.lmol/L; serum total protein: 8.76 g/dl; albumin: 4.25 g/dl; beta-I globulin: 1.46 g/dl; beta-2
Subcorneal Pustular Dermatosis
Fig. 2.
Lesions on the trunk.
globulin: 1.8 g/dl; gamma globulin: 0.44 giL; albumin-globulin ratio: 0.94; electrophoresis revealed an "M" component; IgG: 0.565 gl dl; IgA: 1.036 g/dl; IgM: 0.014 g/dl; immunoelectrophoresis: IgA kappa-type paraprotein. Streptococcus faecalis, Pseudomonas aeruginosa and Micrococcus were cultured from the pustules. Sternum puncture: Bone marrow biopsy showed diffuse 40-50% immature plasma cells, with smaller homogeneous plasma cell foci in some places. Radiology: X-ray examination ofthe skull revealed small areas of rarefaction in the os occipitale, with no characteristic edges. Other X-ray examinations '(chest, pelvis, gastric, and scintigraphia ofthe skeleton) did not reveal any pathological changes. Histology: This revealed the formation of subcorneal pustules. Marked edematous exocytosis could be seen on the epithelium beneath the pustules. The infiltrate had a miscellaneous composition. Mononuclear cell infiltration could be observed in the edematous dermis, mainly around the blood vessels (Fig. 3). Immunohistological examination revealed no pathological changes, with anti human IgA-, IgG-, IgM-, and C3-FITC conjugates, The results of the examinations led to a diagnosis of subcorneal pustular dermatosis associated with mUltiple myeloma. During treatment (diaminodiphenylsulphon, Carmustine, Vinblastin, Endoxan, Alkeran, Prednisolon), the dermatologic symptoms improved, but the general state of the patient deteriorated. Uremia and pneumonia developed, and the patient died. The autopsy results confirmed the clinical diagnosis.
627
Fig. 3. Histology of a subcorneal pustule. H.E. x140.
Discussion
Our case was typical of the disease originally described by Sneddon and Wilkinson in 1956 (12). The cause of the disease is not known, but it has been described in association with other diseases, including IgG cryoglobulinemia (13), IgA paraproteinemia (1, 4, 6, 9,14,17,18,20, 22), IgA (2, 5,10,16) or IgG (3, 7) myeloma, and pyoderma gangrenosum (5, 17, 22). In five cases, immunofluorescence revealed C3, C4, and IgA deposits (1,5, 13, 18,20) in the areas of the dermoepidermal junction and the epidermis (in the subcorneal region). The connection between myeloproliferative diseases and neutrophilic dermatoses (dermatitis herpetiformis, pyoderma gangrenosum and Sweet's syndrome) is known. It seems that such a connection also exists between gammopathies and subcorneal pustular dermatosis. Various authors presume a pathogenetic connection between the IgA dysfunction and neutrophilic dermatoses (8, 11, 19), but we can not exclude the possibility that chronic inflammation stimulates the production of monoclonal immunoglobulin, because the dermatologic symptoms preceded the occurrence of myeloma by several years (4-27 years) in all known cases (3, 8, 10, 16, 21). The main therapeutic drug in this disease is Dapsone. Etretinate in combination with Dapsone has been reported to have beneficial effects (4, 14, 15). Good results have been obtained with Psoralen administered locally and with ultraviolet radiation (15). Chemo-
G2R
B6lcskei et al
therapy of the myeloma has also resulted in an improvement in the symptoms (7,10). References 1) Burrows D, Bingham EA: Subcorneal pustular dermatosis and IgA gammopathy, BrJ Dermatol, 111: (suppl 26): 91-93, 1984. 2) Cream lJ, Grimes SM, Roberts PD: Subcorneal pustulosis and IgA myelomatosis, BrJ Dermatol, 1: 550, 1977. 3) Dahlouk MY, Krouha MS, Colonna P, Marill FG: Association de pustulose sous-cornee e SneddonWilkinson et de myelomatose, Bull Soc Fr Dermatol Syp~ 82: 273-274, 1975. 4) Kasha EE, Epinette WW: Subcorneal pustular dermatosis in association with a monoclonal IgA gammopathy: A report and review of the literature,] Am Acad Dermatol, 19: 854-858, 1988. 5) Marsden JR, Millard LG: Pyoderma gangrenosum, subcorneal pustular dermatosis and IgA paraproteinaemia, BrJ Dermatol, 114: 125-129, 1986. 6) Peterson WC, ~artansson S, Fusaro RM: Subcornea1 pustular dermatosis. An immunoelectrophoretic study, Acta Derm Venereol (Stockh), 45: 203-206, 1965. 7) Roda J, Canellas da Silva F: Erupcao pustulosa num caso de mieloma multiplo, Trab Soc Port Dermatol Venereo~ 23: 235-242, 1965. 8) Russel J: Cutaneous manifestations of paraproteinaemia Part II, BrJ Dermatol, 104: 209-220, 1981. 9) Ryatt KS; Dodman BA, Cotterill JA: Subcorneal pustular dermatosis and IgA gammopathy, &ta Derm Venereol (Stockh), 61: 560-561, 1981. 10) Schnitzler JL, Verret B, Schubert A, Pouplard A, Simon L: Pustulose sous-cornee de Sneddon-Wilkinson avec acantholyse et myelome a IgA, Ann Dermatol Venereol, 104: 170-172, 1977. 11) Schroder L, Szperalski B, Koh q, Christophers E: IgA associated inhibition of polymorphonuclear
12) 13) 14)
15)
16)
17)
18)
19)
20)
21)
22)
leucocyte chemotaxis in neutrophilic dermatoses, ] Invest Dermatol, 77: 464-468, 1981. Sneddon IB, Wilkinson DS: Subcorneal pustular dermatosis, BrJ Dermatol, 68: 385-394, 1956. Sneddon IB, Wilkinson DS: Subcorneal pustular dermatosis, BrJ Dermatol, 100: 61-68, 1979. Souteyrand P, Baron O,Janin A, Gilard AM, Mosser C: Pustulose sous-cornee de Sneddon-Wilkinson et dysglobulinemie monoclonale a IgA: effect favorable du Tygason, Ann Dermatol Venereol, 110: 769-770, 1983. Tagami H, Iwatsuki K, Iwase Y, Yamada M: Subcorneal pustular dermatosis with vesiculo-bullous eruption. Demonstration of subcorneal IgA deposits and a leucocyte chemotactic factor, BrJ Dermatol, 109: 581-587,1973. Tio RD, Di Vito F, Salvi F: Subcorneal pustular dermatosis and IgA myeloma, Dermatologica, 170: 240-243, 1985. Venning VA, Ryan TJ: Subcornea1 pustular dermatosis followed by pyoderma gangrenosum, BrJ Med, 115: 117-118,1986. Wallach D, Cottenot F, Pelbois G, Cavelier B, Didierjean L, SauratJ: Subcorneal pustular dermatosis and monoclonal IgA, BrJ Dermatol, 107: 229-234, 1982. Wallach D,Janssen F, Vignon-Pennamen M, Lemarchand-Venencie F, Cottenot F: Atypical neutrophilic dermatosis with subcorneal IgA deposits, Arch Dermatol, 123: 790-795, 1987. Wallach D, Foldes C, Cottenot F: Pustulose souscornee, acantholyse superficielle et 19A monoclonale, Ann Dermatol Venereol, 109: 959-963, 1982. Wallach D: Pustulose sous-cornees et gammapathies monoclonales, Ann Med Interne (Paris), 135: 672-676, 1984. Wolff K: Subkorneale pustulose Dermatose (Sneddon-Wilkinson); Pyoderma gangrenosum mit IgAParaproteineamie, Dermatol Monatsschr, 157: 842, 1971.
Short repor
Subcorneal Pustular Dermatosis and IgA Multiple Myeloma Lajos Bolcskei, Sandor Husz, Janos Hunyadi, Gyula Varga* and Attila Dobozy Abstract
A case of subcomeal pustular dermatosis associated with IgA multiple myeloma is described, The significance of the combination of the two diseases is not yet known, but the association is certainly more than coincidence.
Key words:
Sneddon-Wilkinson disease
Introduction Subcorneal pustular dermatosis is a rare, chronic, recurrent disease usually seen in women after the fourth decade. The cutaneous lesions are typically found on the trunk and in the flexures and form circinate patterns. The pustules are sterile, but secondary infection often occurs. There are no characteristic immunopathological changes, although in some cases .immunofluorescence staining has been observed. This report presents a case of subcorneal pustular dermatosis associated with IgA multiple myeloma.
Case Report The patient, D.H., a 76-year-old man, had a 6 to 7-year history of skin disease in the form of red, inflamed, itchy spots, first on the upper arm and then all over the body. Thin-walled, quickly erupting pustules occurred in the spots. Hospitalization was necessitated by non-healing exacerbations all over the body, which started 6 months prior to clinical treatment. On admission, there were numerous erosions covered with brown scars 1 cm in size, often Received October 7, 1991; accepted for publication July 3,1992. Albert Szent-Gyorgyi Medical University Department of Dermatology (Head: Prof. Attila Dobozy) and *the 2nd Department of Internal Medicine (Head: Prof. Miklos Csanady), Szeged, Hungary. Reprint requests to: Lajos Bolcskei, Department of Dermatology, Albert Szent-Gyorgyi Medical University, H-6701 Szeged, P.o. Box 480, Hungary.
Fig. 1. General aspects of lesions. coalescing to cover large areas on the trunk and limbs (Fig. 1), as well as similar-sized pustules with thin walls and cloudy content (Fig. 2). Laboratory results: Erythrocyte sedimentation rate: 100 mm/hour; hematocrit: 39%; hemoglobin: 13.3 g/dl; urine: gravity: 1.010; protein: opalescing; pus: -l-: serum alkalinephosphatase: 190 U/L; serum uric acid: 396 f.lmol/L; serum total protein: 8.76 g/dl; albumin: 4.25 g/dl; beta-I globulin: 1.46 g/dl; beta-2
Subcorneal Pustular Dermatosis
Fig. 2.
Lesions on the trunk.
globulin: 1.8 g/dl; gamma globulin: 0.44 giL; albumin-globulin ratio: 0.94; electrophoresis revealed an "M" component; IgG: 0.565 gl dl; IgA: 1.036 g/dl; IgM: 0.014 g/dl; immunoelectrophoresis: IgA kappa-type paraprotein. Streptococcus faecalis, Pseudomonas aeruginosa and Micrococcus were cultured from the pustules. Sternum puncture: Bone marrow biopsy showed diffuse 40-50% immature plasma cells, with smaller homogeneous plasma cell foci in some places. Radiology: X-ray examination ofthe skull revealed small areas of rarefaction in the os occipitale, with no characteristic edges. Other X-ray examinations '(chest, pelvis, gastric, and scintigraphia ofthe skeleton) did not reveal any pathological changes. Histology: This revealed the formation of subcorneal pustules. Marked edematous exocytosis could be seen on the epithelium beneath the pustules. The infiltrate had a miscellaneous composition. Mononuclear cell infiltration could be observed in the edematous dermis, mainly around the blood vessels (Fig. 3). Immunohistological examination revealed no pathological changes, with anti human IgA-, IgG-, IgM-, and C3-FITC conjugates, The results of the examinations led to a diagnosis of subcorneal pustular dermatosis associated with mUltiple myeloma. During treatment (diaminodiphenylsulphon, Carmustine, Vinblastin, Endoxan, Alkeran, Prednisolon), the dermatologic symptoms improved, but the general state of the patient deteriorated. Uremia and pneumonia developed, and the patient died. The autopsy results confirmed the clinical diagnosis.
627
Fig. 3. Histology of a subcorneal pustule. H.E. x140.
Discussion
Our case was typical of the disease originally described by Sneddon and Wilkinson in 1956 (12). The cause of the disease is not known, but it has been described in association with other diseases, including IgG cryoglobulinemia (13), IgA paraproteinemia (1, 4, 6, 9,14,17,18,20, 22), IgA (2, 5,10,16) or IgG (3, 7) myeloma, and pyoderma gangrenosum (5, 17, 22). In five cases, immunofluorescence revealed C3, C4, and IgA deposits (1,5, 13, 18,20) in the areas of the dermoepidermal junction and the epidermis (in the subcorneal region). The connection between myeloproliferative diseases and neutrophilic dermatoses (dermatitis herpetiformis, pyoderma gangrenosum and Sweet's syndrome) is known. It seems that such a connection also exists between gammopathies and subcorneal pustular dermatosis. Various authors presume a pathogenetic connection between the IgA dysfunction and neutrophilic dermatoses (8, 11, 19), but we can not exclude the possibility that chronic inflammation stimulates the production of monoclonal immunoglobulin, because the dermatologic symptoms preceded the occurrence of myeloma by several years (4-27 years) in all known cases (3, 8, 10, 16, 21). The main therapeutic drug in this disease is Dapsone. Etretinate in combination with Dapsone has been reported to have beneficial effects (4, 14, 15). Good results have been obtained with Psoralen administered locally and with ultraviolet radiation (15). Chemo-
G2R
B6lcskei et al
therapy of the myeloma has also resulted in an improvement in the symptoms (7,10). References 1) Burrows D, Bingham EA: Subcorneal pustular dermatosis and IgA gammopathy, BrJ Dermatol, 111: (suppl 26): 91-93, 1984. 2) Cream lJ, Grimes SM, Roberts PD: Subcorneal pustulosis and IgA myelomatosis, BrJ Dermatol, 1: 550, 1977. 3) Dahlouk MY, Krouha MS, Colonna P, Marill FG: Association de pustulose sous-cornee e SneddonWilkinson et de myelomatose, Bull Soc Fr Dermatol Syp~ 82: 273-274, 1975. 4) Kasha EE, Epinette WW: Subcorneal pustular dermatosis in association with a monoclonal IgA gammopathy: A report and review of the literature,] Am Acad Dermatol, 19: 854-858, 1988. 5) Marsden JR, Millard LG: Pyoderma gangrenosum, subcorneal pustular dermatosis and IgA paraproteinaemia, BrJ Dermatol, 114: 125-129, 1986. 6) Peterson WC, ~artansson S, Fusaro RM: Subcornea1 pustular dermatosis. An immunoelectrophoretic study, Acta Derm Venereol (Stockh), 45: 203-206, 1965. 7) Roda J, Canellas da Silva F: Erupcao pustulosa num caso de mieloma multiplo, Trab Soc Port Dermatol Venereo~ 23: 235-242, 1965. 8) Russel J: Cutaneous manifestations of paraproteinaemia Part II, BrJ Dermatol, 104: 209-220, 1981. 9) Ryatt KS; Dodman BA, Cotterill JA: Subcorneal pustular dermatosis and IgA gammopathy, &ta Derm Venereol (Stockh), 61: 560-561, 1981. 10) Schnitzler JL, Verret B, Schubert A, Pouplard A, Simon L: Pustulose sous-cornee de Sneddon-Wilkinson avec acantholyse et myelome a IgA, Ann Dermatol Venereol, 104: 170-172, 1977. 11) Schroder L, Szperalski B, Koh q, Christophers E: IgA associated inhibition of polymorphonuclear
12) 13) 14)
15)
16)
17)
18)
19)
20)
21)
22)
leucocyte chemotaxis in neutrophilic dermatoses, ] Invest Dermatol, 77: 464-468, 1981. Sneddon IB, Wilkinson DS: Subcorneal pustular dermatosis, BrJ Dermatol, 68: 385-394, 1956. Sneddon IB, Wilkinson DS: Subcorneal pustular dermatosis, BrJ Dermatol, 100: 61-68, 1979. Souteyrand P, Baron O,Janin A, Gilard AM, Mosser C: Pustulose sous-cornee de Sneddon-Wilkinson et dysglobulinemie monoclonale a IgA: effect favorable du Tygason, Ann Dermatol Venereol, 110: 769-770, 1983. Tagami H, Iwatsuki K, Iwase Y, Yamada M: Subcorneal pustular dermatosis with vesiculo-bullous eruption. Demonstration of subcorneal IgA deposits and a leucocyte chemotactic factor, BrJ Dermatol, 109: 581-587,1973. Tio RD, Di Vito F, Salvi F: Subcorneal pustular dermatosis and IgA myeloma, Dermatologica, 170: 240-243, 1985. Venning VA, Ryan TJ: Subcornea1 pustular dermatosis followed by pyoderma gangrenosum, BrJ Med, 115: 117-118,1986. Wallach D, Cottenot F, Pelbois G, Cavelier B, Didierjean L, SauratJ: Subcorneal pustular dermatosis and monoclonal IgA, BrJ Dermatol, 107: 229-234, 1982. Wallach D,Janssen F, Vignon-Pennamen M, Lemarchand-Venencie F, Cottenot F: Atypical neutrophilic dermatosis with subcorneal IgA deposits, Arch Dermatol, 123: 790-795, 1987. Wallach D, Foldes C, Cottenot F: Pustulose souscornee, acantholyse superficielle et 19A monoclonale, Ann Dermatol Venereol, 109: 959-963, 1982. Wallach D: Pustulose sous-cornees et gammapathies monoclonales, Ann Med Interne (Paris), 135: 672-676, 1984. Wolff K: Subkorneale pustulose Dermatose (Sneddon-Wilkinson); Pyoderma gangrenosum mit IgAParaproteineamie, Dermatol Monatsschr, 157: 842, 1971.
