Case Report Dermatology 1992;185:311-313
Unit of Occupational and Environmental Dermatology, Louvain University, Brussels, Belgium
Key Words Intraepidermal neutrophilic dermatosis Pemphigus IgA
Intraepidermal Neutrophilic IgA Dermatosis: Pemphigus-Like IgA Deposits Abstract A case of intraepidermal neutrophilic IgA dermatosis with intercellular IgA deposit in the upper epidermis is reported. Indirect immunofluorescence was negative but immunoelectrophoresis showed a slight increase of IgA. The chemotactic activity of neutrophils was normal. Colchicine controlled the lesions.
Case Report A man. aged 60. with no familial or personal history of skin dis ease. complained of a I month history of cutaneous lesions. At the first dermatological out-patient visit, we were impressed by the pres ence of numerous erythematous plaques covered by small pustules, crusts and scales (fig. 1). Some of the lesions tended to coalesce, form ing circulate patterns with scaly margins (fig. 2). The lesions were widespread all over the trunk; there was no involvement of the limbs or the mucous membranes. Subjective symptoms, such as pruritus or painful sensations, were not prominent. General examination of the patient was devoid of any particularities. Routine blood examination provided results within the range of normal values. A slight increase of polyclonal IgA was formed on immunoelectrophoresis. The chemotactic activity of neutrophils was normal. Two skin biopsies were taken from pustular lesions. Both biopsy specimens showed the following lesions: intraepidermal bullae and/or pustules filled with neutrophils and eosinophils (fig. 3). There was a dermal perivascular infiltrate con taining mononuclear cells, neutrophils and a few eosinophils. Exocytosis of inflammatory cells to epidermis was common. Serial sections showed that some pustules were more superficial (i.c. subcorneal) whereas others were deeply inserted in the lower epidermis. On one of the biopsies, a few acantholytic cells were present (fig.4). Direct immunofluorescence of normal skin adjacent to lesions obtained on two different occasions always showed IgA deposits in the intercellular spaces of the upper epidermis (fig.5). In the first spec imen concurrent deposition of IgG and C3 was also demonstrated. Indirect immunofluorescence is consistently negative. Cultures from the lesions yield no organisms. Immunoblotting was performed on the serum of the patient by Dr. Bernard in the Department of Prof. Saurat from Geneva with an anti genic extract of bovine tongue 11] and revealed circulating antibodies
of the IgG class reacting strongly with a 130-kD protein, a most impor tant epitope of the antigen of pemphigus vulgaris. IgA reacting slightly with the same antigen was also observed with this technique. Skin lesions did not respond to diaminodiphenylsulfonc (given for 3 weeks at a dose of 100 mg/day). The treatment strategy was therefore reevaluated and colchicine was prescribed at a dose of I mg/day. A rapid improvement of the skin lesions was noticed; all skin lesions dis appeared 2 weeks after the onset of the treatment. The patient now entirely free of an)' skin lesions although the drug was stopped 2 years ago.
Discussion This patient clinically demonstrates a chronic pustular eruption of the trunk. These lesions tend to coalesce, form ing circulate patterns. The histopathological picture with the formation of pus tules in the subcorneal areas is that of a subcorneal pustular dermatosis of Sneddon and Wilkinson (SPD) associated with some features of a transient and persistent acantholyt ic dermatosis (or Grover’s disease), a benign familial pem phigus (or Hailey-Hailey) and/or a pemphigus herpetifor mis. These features [2] arc considered to be identical to those of intraepidermal neutrophilic IgA dermatosis. Since its first description by Sneddon and Wilkinson in 1956, about 150 cases have been reported in the literature. Twelve of them were associated with a monoclonal gammopathy (benign IgA or other cases associated with a lym-
Dr. P. Gengoux Unit of Occupational and Environmental Dermatology Louvain University. 30. Clos Chapelle-aux-Champs IJCL 3030. B-1200 Brussels (Belgium)
© 1992 Karger AG. Basel 1018-xS665AJ2/1854-0311 $ 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 1:04:48 AM
P. Gengoux D. Tennstedt J.M. Lachapelle
Fig. 3. Intraepidermal pustule filled with neutrophils and eosin ophils. HE. x 190.
Fig. 1. Wide spread eruption of erythematous plaques covered by pustules, crusts and scales.
Fig. 4. A few acantholytic cells are present in a pustule. HE. x 190.
Fig. 2. Some of the lesions tend to coalesce, forming circulate patterns with scaly margins.
312
Fig. 5. Granular intercellular IgA deposits arc seen in the upper portion of the epidermis: immunofluorescence technique, x 190.
Gcngoux/Tennstedt/Laehapelle
Intraepidermal Neutrophilic IgA Dermatosis
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 1:04:48 AM
phoma or a myeloma). Lesions associated with benign IgA relapsed under treatment with diaminodiphenylsulfone. In 1982. Wallach et al. ]3] reported a case of SPD that showed IgA deposition in the upper epidermis of lesional skin and also circulation autoantibodies against the same area of the epidermis. However, in their case, the staining pattern was diffuse rather than intercellular. Tagami et al. [4) and Huff et al. [5] reported cases resembling SPD with in vivo bound IgA in the intercellular spaces of the epider mis, but without demonstrable circulating IgA antibodies.
Wallach [6] did not agree with Huff concerning the sepa ration of subcorneal pustular dermatosis from intraepidcrmal neutrophilic IgA dermatosis. In his view, intraepidermal neutrophilic IgA dermatosis may be considered as a subgroup of pustular eruptions, characterized by intraepidermal IgA deposits and. at times, by additional immuno logic abnormalities, among which IgA gammopathy is noteworthy. Hashimoto et al. [7], Saurai et al. [8] and Piette et al. [9] presented cases in which IgA bound in vivo to the intercel lular spaces of the epidermis and circulating IgA antibodies were found. Immuno-electrophoresis does not always reveal an alteration of IgA level. Tagami pointed out that IgA in SPD serum is an autoantibody belonging mainly to the IgA, subclass [4]. This is consistent with the well-known fact that most circulating IgA, belongs to the subclass of IgA [10], To be exhaustive the check-up of intraepidermal neu trophilic IgA dermatosis should include a study of the neu trophil function. In fact. Schroder reported that serum IgA in 'neutrophilic dermatoses' inhibits in vitro chemotaxis of the polymorphonuclear leukocytes [11|. but it seems that inhibitory fractions are seen in patients with long-standing neutrophil-related diseases [12], This observation has not been reported until now in SPD. Tagami demonstrated a chcmotactic factor in lcsional horny tissues [4], The concurrent deposition of IgG. IgM and C3 in the first specimen of our case and in the other observations from the literature may not disqualify IgA in
the pathogenesis of the lesions; indeed, for example, the localization of neutrophils in upper epidermis, mid-epider mis or under the stratum corneum depends on the age and the clinical appearance of the lesions. Pemphigus herpetiformis can be excluded by the ab sence of eosinophilia in many occasions. Despite the few reports on intraepidermal IgA deposits, heterogeneity of the group had led Beutner et al. [13] to classify the observations from the literature following the linear pattern in the cornea or the intercellular pattern of IgA deposition. Zillikens et al. [14] have proposed a classification of der matoses with intraepidermal IgA deposits into three sub groups following the localization of IgA deposits and pus tules in the epidermis. It seems that our case should be included in the group of IgA pemphigus of the intraepidermal type because of inter cellular staining with IgA and intraepidermal localization of the pustules. Based on intercellular deposits of IgG and C3 in the epidermis by immunofluorescence and antibodies reacting with the antigen of pemphigus vulgaris by immunoblotting. our case could be considered as a pemphigus vulgaris. Nevertheless the participation of IgA and conse quently of neutrophils, make the clinical picture, the treat ment and the follow-up quite different from what is found in classical pemphigus vulgaris. So we are inclined to think that IgA pemphigus is not a ‘true’ pemphigus with IgA but a completely different entity, the denomination of which ought to be different from the term 'pemphigus’.
References 6 Wallach D: Letter to the Editor: Intraepider mal neutrophilic IgA dermatosis. N Engl J Med 1986:315:66. 7 Hashimoto Z. Nobuko I. Kinvyo X. Takeji N: Intercellular IgA with clinical features of sub corneal pustular dermatosis. Arch Dermatol 1987:123:1062-1065. 8 Saurat JH. Merot D. Salomon D. Didicrjcan I.: Pemphigus-like IgA deposits and vcsiculopustular dermatosis in a 10-ycar-old girl. Der matológica 1987:175:96-100. 9 Piette W. Russel R. Burken R. Ray TL: Intra epidermal neutrophilic IgA dermatosis: Pres ence of circulating pemphigus-like IgA anti body specific for monkey epithelium. J Invest Dermatol 1987:88:512. 10 Kett K. Brandtzag P. Radi .1: Different sub class distribution of IgA-producing cells in human lymphoid organs and various secretory tissues. .1 Immunol 1986:136:3631-3635.
11 Schröder JM. Szperalski R. Koch CJ. Chris tophers E: IgA associated inhibition of poly morphonuclear leukocyte chemotaxis in neu trophilic dermatoses. .1 Invest Dermatol 1981; 77:464-468. 12 Christophers E. Schröder JM: Neutrophil granulocyte chemotaxis and psoriasis. Haut arzt 1981:32:558-568. 13 Beutner EH. Chorzelski TS. Donough WR. Kumar V. Michel B. Helm F. Jablonska S: IgA pemphigus foliaceus. J Am Acad Dermatol 1989:20:89-87. 14 Zillikens D. Miller K. Hartmann AA, Burg G: IgA pemphigus foliaceus: A case report. Der matológica 1990; 181:304-307.
313
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 1:04:48 AM
1 Prost C. Intrador L. Roujeau JC. Bernard P. Rcvuz J. Dubertrel L: An antigenic extract of bovine tongue for analysis of both pemphigus vulgaris and bullous pemphigoid antibodies by immunoblotting. .1 Invest Dermatol 1989; 92:502. 2 Sneddon IB. Wilkinson DS: Subcorneal pustu lar dermatosis. Br J Dermatol 1979; 100:61-68. 3 Wallach D. Cottenot F. Pclbois G. Cavelier B. Didierjean L. Saurat J11 : Subcorneal pustular dermatosis and monoclonal IgA. Br J Derma tol 1982:107:229-234. 4 Tagami H. Iwatsuki K. Iwasc Y. Yamada M: Subcorneal pustular dermatosis with vcsiculobullous eruptions: Demonstration of subcor neal IgA deposits and leucocyte chcmotactic factor. Br J Dermatol 1983:109:581-587. 5 Huff JC. Golitz I.F.. Kunker KS: Intraepider mal neutrophilic IgA dermatosis. N Engl .1 Med 1985:313:1643-1645.
Unit of Occupational and Environmental Dermatology, Louvain University, Brussels, Belgium
Key Words Intraepidermal neutrophilic dermatosis Pemphigus IgA
Intraepidermal Neutrophilic IgA Dermatosis: Pemphigus-Like IgA Deposits Abstract A case of intraepidermal neutrophilic IgA dermatosis with intercellular IgA deposit in the upper epidermis is reported. Indirect immunofluorescence was negative but immunoelectrophoresis showed a slight increase of IgA. The chemotactic activity of neutrophils was normal. Colchicine controlled the lesions.
Case Report A man. aged 60. with no familial or personal history of skin dis ease. complained of a I month history of cutaneous lesions. At the first dermatological out-patient visit, we were impressed by the pres ence of numerous erythematous plaques covered by small pustules, crusts and scales (fig. 1). Some of the lesions tended to coalesce, form ing circulate patterns with scaly margins (fig. 2). The lesions were widespread all over the trunk; there was no involvement of the limbs or the mucous membranes. Subjective symptoms, such as pruritus or painful sensations, were not prominent. General examination of the patient was devoid of any particularities. Routine blood examination provided results within the range of normal values. A slight increase of polyclonal IgA was formed on immunoelectrophoresis. The chemotactic activity of neutrophils was normal. Two skin biopsies were taken from pustular lesions. Both biopsy specimens showed the following lesions: intraepidermal bullae and/or pustules filled with neutrophils and eosinophils (fig. 3). There was a dermal perivascular infiltrate con taining mononuclear cells, neutrophils and a few eosinophils. Exocytosis of inflammatory cells to epidermis was common. Serial sections showed that some pustules were more superficial (i.c. subcorneal) whereas others were deeply inserted in the lower epidermis. On one of the biopsies, a few acantholytic cells were present (fig.4). Direct immunofluorescence of normal skin adjacent to lesions obtained on two different occasions always showed IgA deposits in the intercellular spaces of the upper epidermis (fig.5). In the first spec imen concurrent deposition of IgG and C3 was also demonstrated. Indirect immunofluorescence is consistently negative. Cultures from the lesions yield no organisms. Immunoblotting was performed on the serum of the patient by Dr. Bernard in the Department of Prof. Saurat from Geneva with an anti genic extract of bovine tongue 11] and revealed circulating antibodies
of the IgG class reacting strongly with a 130-kD protein, a most impor tant epitope of the antigen of pemphigus vulgaris. IgA reacting slightly with the same antigen was also observed with this technique. Skin lesions did not respond to diaminodiphenylsulfonc (given for 3 weeks at a dose of 100 mg/day). The treatment strategy was therefore reevaluated and colchicine was prescribed at a dose of I mg/day. A rapid improvement of the skin lesions was noticed; all skin lesions dis appeared 2 weeks after the onset of the treatment. The patient now entirely free of an)' skin lesions although the drug was stopped 2 years ago.
Discussion This patient clinically demonstrates a chronic pustular eruption of the trunk. These lesions tend to coalesce, form ing circulate patterns. The histopathological picture with the formation of pus tules in the subcorneal areas is that of a subcorneal pustular dermatosis of Sneddon and Wilkinson (SPD) associated with some features of a transient and persistent acantholyt ic dermatosis (or Grover’s disease), a benign familial pem phigus (or Hailey-Hailey) and/or a pemphigus herpetifor mis. These features [2] arc considered to be identical to those of intraepidermal neutrophilic IgA dermatosis. Since its first description by Sneddon and Wilkinson in 1956, about 150 cases have been reported in the literature. Twelve of them were associated with a monoclonal gammopathy (benign IgA or other cases associated with a lym-
Dr. P. Gengoux Unit of Occupational and Environmental Dermatology Louvain University. 30. Clos Chapelle-aux-Champs IJCL 3030. B-1200 Brussels (Belgium)
© 1992 Karger AG. Basel 1018-xS665AJ2/1854-0311 $ 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 1:04:48 AM
P. Gengoux D. Tennstedt J.M. Lachapelle
Fig. 3. Intraepidermal pustule filled with neutrophils and eosin ophils. HE. x 190.
Fig. 1. Wide spread eruption of erythematous plaques covered by pustules, crusts and scales.
Fig. 4. A few acantholytic cells are present in a pustule. HE. x 190.
Fig. 2. Some of the lesions tend to coalesce, forming circulate patterns with scaly margins.
312
Fig. 5. Granular intercellular IgA deposits arc seen in the upper portion of the epidermis: immunofluorescence technique, x 190.
Gcngoux/Tennstedt/Laehapelle
Intraepidermal Neutrophilic IgA Dermatosis
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 1:04:48 AM
phoma or a myeloma). Lesions associated with benign IgA relapsed under treatment with diaminodiphenylsulfone. In 1982. Wallach et al. ]3] reported a case of SPD that showed IgA deposition in the upper epidermis of lesional skin and also circulation autoantibodies against the same area of the epidermis. However, in their case, the staining pattern was diffuse rather than intercellular. Tagami et al. [4) and Huff et al. [5] reported cases resembling SPD with in vivo bound IgA in the intercellular spaces of the epider mis, but without demonstrable circulating IgA antibodies.
Wallach [6] did not agree with Huff concerning the sepa ration of subcorneal pustular dermatosis from intraepidcrmal neutrophilic IgA dermatosis. In his view, intraepidermal neutrophilic IgA dermatosis may be considered as a subgroup of pustular eruptions, characterized by intraepidermal IgA deposits and. at times, by additional immuno logic abnormalities, among which IgA gammopathy is noteworthy. Hashimoto et al. [7], Saurai et al. [8] and Piette et al. [9] presented cases in which IgA bound in vivo to the intercel lular spaces of the epidermis and circulating IgA antibodies were found. Immuno-electrophoresis does not always reveal an alteration of IgA level. Tagami pointed out that IgA in SPD serum is an autoantibody belonging mainly to the IgA, subclass [4]. This is consistent with the well-known fact that most circulating IgA, belongs to the subclass of IgA [10], To be exhaustive the check-up of intraepidermal neu trophilic IgA dermatosis should include a study of the neu trophil function. In fact. Schroder reported that serum IgA in 'neutrophilic dermatoses' inhibits in vitro chemotaxis of the polymorphonuclear leukocytes [11|. but it seems that inhibitory fractions are seen in patients with long-standing neutrophil-related diseases [12], This observation has not been reported until now in SPD. Tagami demonstrated a chcmotactic factor in lcsional horny tissues [4], The concurrent deposition of IgG. IgM and C3 in the first specimen of our case and in the other observations from the literature may not disqualify IgA in
the pathogenesis of the lesions; indeed, for example, the localization of neutrophils in upper epidermis, mid-epider mis or under the stratum corneum depends on the age and the clinical appearance of the lesions. Pemphigus herpetiformis can be excluded by the ab sence of eosinophilia in many occasions. Despite the few reports on intraepidermal IgA deposits, heterogeneity of the group had led Beutner et al. [13] to classify the observations from the literature following the linear pattern in the cornea or the intercellular pattern of IgA deposition. Zillikens et al. [14] have proposed a classification of der matoses with intraepidermal IgA deposits into three sub groups following the localization of IgA deposits and pus tules in the epidermis. It seems that our case should be included in the group of IgA pemphigus of the intraepidermal type because of inter cellular staining with IgA and intraepidermal localization of the pustules. Based on intercellular deposits of IgG and C3 in the epidermis by immunofluorescence and antibodies reacting with the antigen of pemphigus vulgaris by immunoblotting. our case could be considered as a pemphigus vulgaris. Nevertheless the participation of IgA and conse quently of neutrophils, make the clinical picture, the treat ment and the follow-up quite different from what is found in classical pemphigus vulgaris. So we are inclined to think that IgA pemphigus is not a ‘true’ pemphigus with IgA but a completely different entity, the denomination of which ought to be different from the term 'pemphigus’.
References 6 Wallach D: Letter to the Editor: Intraepider mal neutrophilic IgA dermatosis. N Engl J Med 1986:315:66. 7 Hashimoto Z. Nobuko I. Kinvyo X. Takeji N: Intercellular IgA with clinical features of sub corneal pustular dermatosis. Arch Dermatol 1987:123:1062-1065. 8 Saurat JH. Merot D. Salomon D. Didicrjcan I.: Pemphigus-like IgA deposits and vcsiculopustular dermatosis in a 10-ycar-old girl. Der matológica 1987:175:96-100. 9 Piette W. Russel R. Burken R. Ray TL: Intra epidermal neutrophilic IgA dermatosis: Pres ence of circulating pemphigus-like IgA anti body specific for monkey epithelium. J Invest Dermatol 1987:88:512. 10 Kett K. Brandtzag P. Radi .1: Different sub class distribution of IgA-producing cells in human lymphoid organs and various secretory tissues. .1 Immunol 1986:136:3631-3635.
11 Schröder JM. Szperalski R. Koch CJ. Chris tophers E: IgA associated inhibition of poly morphonuclear leukocyte chemotaxis in neu trophilic dermatoses. .1 Invest Dermatol 1981; 77:464-468. 12 Christophers E. Schröder JM: Neutrophil granulocyte chemotaxis and psoriasis. Haut arzt 1981:32:558-568. 13 Beutner EH. Chorzelski TS. Donough WR. Kumar V. Michel B. Helm F. Jablonska S: IgA pemphigus foliaceus. J Am Acad Dermatol 1989:20:89-87. 14 Zillikens D. Miller K. Hartmann AA, Burg G: IgA pemphigus foliaceus: A case report. Der matológica 1990; 181:304-307.
313
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 1:04:48 AM
1 Prost C. Intrador L. Roujeau JC. Bernard P. Rcvuz J. Dubertrel L: An antigenic extract of bovine tongue for analysis of both pemphigus vulgaris and bullous pemphigoid antibodies by immunoblotting. .1 Invest Dermatol 1989; 92:502. 2 Sneddon IB. Wilkinson DS: Subcorneal pustu lar dermatosis. Br J Dermatol 1979; 100:61-68. 3 Wallach D. Cottenot F. Pclbois G. Cavelier B. Didierjean L. Saurat J11 : Subcorneal pustular dermatosis and monoclonal IgA. Br J Derma tol 1982:107:229-234. 4 Tagami H. Iwatsuki K. Iwasc Y. Yamada M: Subcorneal pustular dermatosis with vcsiculobullous eruptions: Demonstration of subcor neal IgA deposits and leucocyte chcmotactic factor. Br J Dermatol 1983:109:581-587. 5 Huff JC. Golitz I.F.. Kunker KS: Intraepider mal neutrophilic IgA dermatosis. N Engl .1 Med 1985:313:1643-1645.
