Erythema annulare-like acantholytic dermatosis (EAAD): nonbullous pemphigus or a new entity?

This article describes a case of unusual annular erythema-like dermatosis, with histological features of pemphigus foliaceus (subcorneal acantholysis) and IgG antibodies in circulation and bound in vivo to the keratinocyte surface. The reactivity of the antibodies, restricted to human squamous epithelium, was unique, differing from that of all known forms of pemphigus. This also was confirmed by immunoprecipitation. The problem is that these circulating antibodies could be missed if not determined on human substrate. It is to be established whether such cases present a new type of pemphigus or a unknown dermatosis with an autoimmune response of a pemphigus type.

IgA pemphigus foliaceus with a clinical presentation of pemphigus herpetiformis.

A patient with clinical features of herpetiform pemphigus of the foliaceus type had histologic findings consistent with pemphigus. Intercellular IgA deposits in a pattern like that of IgG in pemphigus were present. Circulating pemphigus-type IgA-class antibodies reacted first only with guinea pig and later in the disease also with monkey esophagus sections. IgG-class pemphigus antibodies were blocked by the IgA-class antibodies of this patient. In addition, the IgA-class pemphigus antibodies in this patient were blocked by the IgG-class pemphigus antibodies in tests on guinea pig and monkey esophagus. This indicates that the IgA-class antibodies in this patient were directed either to the same antigen as the IgG-class pemphigus foliaceus antibodies or to one that is close enough to it to give steric hindrance. The skin lesions responded poorly to systemic corticosteroid therapy. Dapsone therapy initially produced dramatic improvement, but the condition flared to the point that plasmapheresis, in addition to high doses of corticosteroids and cyclophosphamide, had to be used to control it.

Is pemphigus herpetiformis an entity?

Clinical, histologic, and immunofluorescence studies were performed in 15 patients with pemphigus herpetiformis. The initial diagnosis was dermatitis herpetiformis, IgA linear bullous dermatosis or bullous pemphigoid. The histology varied depending on the character of skin lesions, and showed eosinophilic spongiosis or slight acantholysis and/or polymorphonuclear papillary microabscesses. Direct immunofluorescence showed invariably intercellular IgG staining, and indirect immunofluorescence on monkey esophagus substrate was positive, at some periods, in five cases. About half of the patients responded to therapy with sulfones and prednisone, and only one patient responded to sulfones alone. Half of the patients required combined therapy with prednisone and cyclophosphamide or with higher doses of prednisone. In consecutive relapses, nine patients retained the pattern of pemphigus herpetiformis: in the others, lesions were mostly of pemphigus seborrheicus-foliaceus type.

IgA endomysium antibody in children with dermatitis herpetiformis treated with gluten-free diet.

The IgA antibody to endomysium of smooth muscle (IgA-EmA) was measured in 32 children with confirmed dermatitis herpetiformis who were eating gluten-free diets. One patient had IgA-EmA before treatment but had a negative test one month later while on the diet. Two so treated for less than one year still had antibody, but of seven children treated for more than one year with gluten-free diet, none had detectable antibody. It was present in 13 of 20 children not adhering to the prescribed diet. The antibody was absent in 4 children with linear IgA bullous dermatosis and 43 children with various skin and intestinal diseases. These findings correspond to those in adults with dermatitis herpetiformis and indicate that IgA-EmA is also a marker for gluten-sensitive enteropathy in children.

Stripping of the stratum corneum in patients with psoriasis: production of prepinpoint papules and psoriatic lesions.

In patients with psoriasis, partial stripping of the stratum corneum induced minute erythematous and edematous, nonscaling papules six hours to seven days later. These "prepinpoint papules" PPPs) comparable to spontaneous PPPs, which we described earlier, appeared in 75 of 159 patients with active psoriasis but in none of 27 controls; 73% to 91% of these PPPs, depending on the activity of the disease, transformed into pinpoint papules. Histological and histochemical examinations of the PPPs showed infiltrates containing numerous polymorphonuclear leukocytes around the vessels and penetrating into the epidermis, partly destroying it. The earliest change in the epidermis was thinning of the granular layer without other features of psoriasis. Immunoglobulin G and complement deposits on stratum corneum (SC) antigen sites were found in the PPPs initially in about one third, and later in two thirds of the papules, whereas they were present in virtually all of the psoriatic pinpoint papules. Papules induced by stripping, similar to spontaneous PPPs, play a central role in the etiology of at least some forms of psoriasis. Polymorphonuclear leukocyte infiltrates and SC antibody binding are key features of the conversion of PPP to pinpoint psoriatic lesions.

Dermatitis herpetiformis: IgA deposits in gingiva, buccal mucosa, and skin.

Fourteen patients who had dermatitis herpetiformis of the skin with no gingival lesions were studied. In each patient biopsy specimens of normal gingiva, buccal mucosa, and perilesional skin were examined for IgA and IgG deposits. Depending on the method of handling biopsy specimens for immunofluorescence, IgA deposits were detected in 21 to 25 percent of gingival specimens, 27 to 46 percent of buccal mucosal specimens, and 64 to 76 percent of skin specimens. The occurrence of IgA deposits in the gingival papillae, a site where lesions of DH have not been reported in the past or observed in this study, suggests that these IgA deposits alone may not play a primary role in the pathogenesis of this disease. Similar immunofluorescent findings of IgA deposits were observed in both quick-frozen biopsy specimens and those placed in holding solution, indicating the suitability of the holding solution for transporting suggested DH biopsy material.

[Is psoriasis an autoimmunologic disease?]. / Ist die Psoriasis eine autoimmunologische Erkrankung?

DThe defective function of T-lymphocytes, which is a finding in active psoriasis, is transitional and reversible, whereas the immunological mechanism is mainly related to the formation of immune complexes consisting of stratum corneum antibodies and stratum corneum antigen, which through binding of complement and activation of chemotactic complement components is responsible for the phenomenon of "squirting papillae". The earliest lesions preceding pin point papules, called pre-pin-point papules, were induced by stripping or developed spontaneously in a marked field closely observed for several days. In the changes preceding earliest psoriatic lesions. Abundant polymorphonuclear infiltrates are present, and polymorphs seem to play an important role in a selfperpetuating of disease process. The therapeutic implications of the immunologic studies in psoriasis are: either depletion of activated polymorphs (eg. continuous peritoneal dialysis) and/or removal of the factors responsible for their activation (eg. treatment of focal infections) or external use of the drugs affecting the antigenicity of stratum corneum (tars), or inhibition of exocytosis (a probable mechanism of puva).

Autoimmunity in psoriasis. Relation of disease activity and forms of psoriasis to immunofluorescence findings.

Immunofluorescence (IF) studies using the test providing information on the reactivity of stratum corneum (SC) antibodies and their in vivo binding have been performed in 193 cases of psoriasis and 89 cases with other dermatoses. It has been shown that: 1. Essentially all fully developed, active psoriatic lesions had IgG deposits in the stratum corneum at the sites of the SC antigen, presumably due to in vivo binding of SC antibodies. 2. In various forms of psoriasis SC antigen sites appeared to be completely or almost completely satured with in vivo deposits of IgG as seen in tests with SC antibodies. 3. In most but not all lesions complement components C3 and/or C4 was found in a comparable pattern in the SC, especially when multiple specimens of single cases were studied. Partial or complete saturation of the SC antigen could be observed by the performance of complement indirect IF tests for SC antibodies in such specimens. 4. In lesions with typical histology of psoriasis the above-mentioned immunologic characteristics appeared to be a constant finding. However, in specimens of recent lesions which had not yet developed typical histology a proportion (2 of 17) were negative both for IgG and complement deposits. In receding lesions weak deposits of IgG were present only in a few specimens and complement deposits were as a rule negative. 5. In a group of 89 control specimens of other dermatoses only occasional cases gave the psoriasiform IF pattern, but about 30% of the specimens gave positive reactions in the SC though these were usually of a different pattern.

Autoimmune phenomena in psoriasis.

The striatum corneum (SC) antibodies are present in all human sera as seen by indirect immunofluorescent (IF) staining. They appear to bind in vivo to the stratum corneum of psoriatic lesions. They fix complement in vitro in a two step complement IF test system using either anti C4 or anti C3 conjugates as indicators. IF tests with proper controls showed that the SC antigen in psoriatic scales is coated not only with IgG but in a majority of the lesions also with complement. These observations afford indirect evidence for the participation of SC antibodies and the ensuing fixation of complement in the development of psoriatic lesions.

Studies on the Koebner phenomenon.

The examination of induced Koebner reactions in 71 patients by the IF methods and by histology at selected times after scratching, show, that immunologically specific but non-disease specific reactions of stratum corneum (SC) antibodies occur adjacent to the crusts in both control subjects and psoriasis patients. In lesions induced by scratching in patients with psoriasis there develop progressively additional foci of apparent in viveo binding of SC antibodies. IF deposits may appear before histologic or clinical changes. The widespread immune deposits in the SC with typical histologic changes of psoriasis seem to be a sign of impending clinical psoriasis while single foci of in vivo bound SC antibodies may be cleared by the body without the development of psoriasis.

Immunologic phenomena in herpes gestationis.

Immunofluorescence studies were performed in 12 cases of herpes gestations. Direct IF staining (performed in 10 of them) revealed a highly characteristic pattern, notably 1) Constantly BMZ deposits of complement component C3, 2) In most biopsy specimens also C4 and C5, 3) Deposits of C4, C5, properdin and IgG variable in different specimens of given patients. About half of the specimens examined contained properdin and about one third stained for IgG, 4) Findings of IgM, IgA, IgD and IgE were consistently negative, 5) Serum findings of BMZ antibodies in given cases were variable. In two cases circulating BMZ antibodies were detected in one of the samples examined. On the base of these findings it seems that HG is related to BP.