DIRECT IMMUNOFLUORESCENT STUDY OF THE SKIN ON OCCURRENCE OF COMPLEMENT IN PEMPHIGUS

In 6 cases of pemphigus (4 pemphigus vulgaris, 1 pemphigus vegetans and 1 pemphigus erythematosus) the direct immunofluorescent method (DIF) revealed various complement factors, as there are Cl_q, C4 (β₁E), β1 A and α₂D, localized in the intercellular spaces of the epidermis of the skin or mucosa immediately next to the bulla. Immunoglobulin and complement were shown together in the prickle cell layer of the epidermis, while complement staining alone usually could be shown in the intercellular spaces of basal cell layers and in the junctional zone. The possibility that antibody-mediated complement deposition and/or alternate pathway activation may play a role in the underlying mechanism in pemphigus is discussed.     

Distinct types of IgG and IgA anti-intercellular autoantibodies from patients with pemphigus and vesiculopustular dermatosis

The pattern of binding of two different types of IgA class pemphigus-like antibodies was compared with that of the true IgG class pemphigus antibody. The IgG antibodies from pemphigus vulgaris (PV) and pemphigus foliaceus (PF) sera bound to the intercellular spaces in normal human epidermis, whereas only the PV antibody reacted with monolayers of keratinocytes derived from human foreskin. Both IgG and IgA antibodies from a patient with PF were found in the intercellular spaces of the epidermis and only the IgA antibody reacted with the cultured keratinocytes. The IgA antibody from a patient with a vesiculopustular eruption and whose serum contained IgA intercellular space antibody alone, bound to the upper epidermis but not to the monolayers of keratinocytes. These findings indicate that PV but not PF antigens can be expressed by monolayers of cultured human keratinocytes and that there are at least two distinct types of IgA intercellular antibodies.     

Pemphigus vegetans of the Hallopeau type. Detection of pemphigus antibodies with direct and indirect immunofluorescence

We report the case of a 25-year-old woman with bullous lesions diagnosed as the rare pustular type of pemphigus described by Hallopeau. Direct immunofluorescence studies revealed deposits of IgG and C3 in the intercellular spaces of the epidermis; the indirect immunofluorescence technique revealed circulating antiepithelial IgG antibodies. The skin lesions cleared completely following treatment with systemic corticosteroids and azathioprine. These findings indicate the disease first described by Hallopeau as "pyodermite végétante" does indeed belong to the pemphigus group, being a rare type of pemphigus vegetans.     

IgA pemphigus foliaceus. Report of two cases and a review of the literature

The cases of two patients with vesiculobullous lesions were diagnosed clinically and histopathologically as pemphigus foliaceus; unexpectedly, both revealed intercellular IgA, but not IgG, in the upper epidermis by direct immunofluorescence. Such histologic and immunofluorescence findings have been reported in eight other cases. In our cases no circulating IgA or IgG intercellular antibodies could be detected; in four of eight other reported cases IgA antibodies showed intercellular staining like that of pemphigus antibodies. Subcorneal acantholytic lesions occurred in both our cases; of the other cases reported, five had essentially identical histopathologic findings. The clinical and histopathologic features of pemphigus, as well as the recent findings of circulating IgA intercellular antibodies alone or with IgG antibodies, appear to place this disease into the spectrum of pemphigus. The 10 IgA pemphigus cases reported to date fall into one of two groups, the IgA pemphigus foliaceus (including our two cases) and IgA pemphigus of the intraepidermal neutrophilic type, which seems to be less common.     

Complement and antibody deposition in Brazilian pemphigus foliaceus and correlation of disease activity with circulating antibodies

Brazilian pemphigus foliaceus is a blistering skin disease endemic to central and southern areas of South America. In this study of skin biopsy specimens from 14 patients we present evidence that complement and immunoglobulins were present by direct immunofluorescence in the epidermal intercellular spaces in all patients. Eight of 14 patients had granular deposits of C3 in the basement membrane zone. By indirect immunofluorescence, serum samples from all 19 patients tested demonstrated the presence of circulating IgG autoantibody. Autoantibodies deposited in the intercellular spaces in titers ranging from 1:10 to more than 1:1280, and the titers drastically decreased during treatment. This is the first study to demonstrate complement deposition in the skin in Brazilian pemphigus foliaceus.     

The occurrence of IgA pemphigus foliaceus without neutrophilic infiltration

A 70-year-old woman with pemphigus foliaceus is reported. Direct immunofluoscence performed on perilesional skin revealed deposits of IgA, C3 and lambda chains in the intercellular substance of the upper stratum spinosum. indirect immunofluorescence demonstrated serum antibodies of the IgA class against the intercellular region of the upper epidermis at an initial titre of 1:2560. Histological studies, performed together with immunofluorescence revealed an absence of a district neutrophil infiltrate either in the epidermis or dermis, contrary to the findings in cases with intra-epidermal IgA deposits reported previously.     

Intercellular complement C3 binding in normal skin of patients without pemphigus

We report here direct immunofluorescence studies of normal skin biopsies that exhibited only complement C3 staining in intercellular areas of epithelium with a view toward evaluating the significance of such findings. During a 5-year period, 11,000 skin biopsy specimens were examined for in vivo binding of immunoglobulins, fibrin, and complement C3 by means of defined direct immunofluorescence methods. Four of ten patients demonstrating intercellular C3 deposits alone had drug-related reactions or erythema multiforme, and four were subsequently shown to have a connective tissue disease. Pemphigus was ruled out in all ten cases in these retrospective studies. These observations indicate that the finding of intercellular C3 deposits in the absence of IgG in normal skin is not a sign of pemphigus but, rather, a sign either of an unusual type of drug reaction or, possibly, of some connective tissue disease. However, the finding of intercellular C3 plus IgG (with or without other immunoglobulins) is a sign of pemphigus. The mechanism of C3 deposition without immunoglobulins is not clear.     

THE EFFECT OF VARIOUS DETERGENTS ON HUMAN EPIDERMIS

Summary.— The authors describe a case of pemphigus, confirmed histologically (acantholysis) and by immunofluorescence studies (circulating pemphigus autoantibodies in the titre of 1:1280, and in vivo bound immunoglobulins IgG, and complement in the intercellular substance of the epidermis). The symptoms developed 10 months after a burn which refused to heal and involved the site of the burn and other skin areas.
The possible connection between the development of pemphigus and the burn is discussed in the light of reports of pemphigus-like antibodies in burns, which normally appear temporarily in some patients and are never bound in vivo .     

HERPETIFORM PEMPHIGUS, A VARIABLE PATTERN OF PEMPHIGUS

ABSTRACT: A patient with the clinical features of dermatitis herpetiformis and the histological features of pemphigus, subcorneal dermatosis and dermatitis herpetiformis did not respond to treatment with pyridine or sulfones. Systemic steroids and azothioprine were effective. Immunofluorescence studies demonstrated circulating pemphigus antibodies and IgG bound in vivo in the intercellular spaces of the epidermis.     

副肿瘤性天疱疮1例

报告1例副肿瘤性天疱疮。患者女性，48岁，因多形皮肤粘膜损害1月伴发非霍奇金淋巴瘤2年余入院。皮肤病理活检示棘刺松解性大疱，直接免疫荧光棘细胞间及基底膜区免疫反应物沉积。其免疫组化示T细胞侵入表皮现象。     

IMMUNOPATHOLOGICAL INVESTIGATIONS IN THE SENEARUSHER SYNDROME (COEXISTENCE OF PEMPHIGUS AND LUPUS ERYTHEMATOSUS)

SUMMARY.— In 5 of 6 cases of the Senear-Usher syndrome, in skin specimens from erythematous facial lesions, the immunofluorescence method demonstrated immunoglobulins and in vivo -fixed complement in the dermoepidermal junction, which is a finding characteristic of lupus erythematosus.
Antibodies against nuclei were also present in all but one case, and in one there was coexistent systemic lupus erythematosus with positive LE phenomenon.
In all 6 cases of the SU syndrome the presence of IgG as well as C'3a, C'4 was demonstrated in the intercellular spaces of the epidermis; this is a finding characteristic of pemphigus.
In 6 cases of pemphigus vulgaris, which served as controls, neither immuno-globulins nor in vivo -fixed complement could be demonstrated in the dermoepidermal junction.
These investigations suggest that the SU syndrome could, at least in the vast majority of cases, result from the coexistence of pemphigus and lupus erythematosus.     

用红斑型天疱疮患者血清IgG诱导新生小鼠天疱疮的实验研究

本文系用红斑型天疱疮血清IgG,被动转移给BaIb/c新生小鼠,诱导新生小鼠天疱疮的实验研究.2例患者血清天疱疮抗体的滴度均为1:128.患者血清IgG按每日每克体重5 mg经腹腔接射给生后4及8小时的Balb/c小鼠,注射后24小时及48小时5只小鼠有3只皮肤见到小水疱,直接免疫荧光检查表皮细胞间有IgG沉着,常规组织病理检查见到表皮内水疱及棘细胞松解.本实验证明:天疱疮自身抗体在人类红斑型天疱疮发病中的作用,这种执体可被动转给新生小鼠.     

用免疫荧光技术观察表皮与血清中天疱疮自身抗体

对11名落叶型(PF),8名寻常型天疱疮(PV)进行了免疫荧光法检查.全部PF与PV表皮ICS在DIF检查中均出现IgG与C₃沉积,其中84.6%患者血清中天疱疮抗体(PAb)阳性,多数滴度为1:40-1:1280,45.4%PF患者在DIF染色中其IgG主要或仅只沉积在表皮浅层ICS部位,而PV则否.著者在讨论中提出:(1)在DIF检查中表皮ICS有IgG沉积即可确诊为天疱疮;(2)若此沉积在表皮浅层之强度较深层伪强,超过一个“+”时可确定为PF;(3)在大疱性皮肤病患者血清中,若PAb滴度较高时(>1:40),可以确定为天疱疮的诊断.     

Subcorneal pustular dermatosis-type IgA pemphigus induced by thiol drugs

We report a case of subcorneal pustular dermatosis (SPD)-type IgA pemphigus arising in a 49 year-old woman with rheumatoid arthritis who had been treated with chrysotherapy. Scaly erythemic plaques containing vesicles and pustules occurred on her chest and abdomen during the course of anti-rheumatic treatments using prednisolone at 11 mg/day and thiol compounds (bucillamine and gold sodium thiomalate). Histological investigations revealed subcorneal pustules containing many neutrophils and a few acantholytic cells, and intercellular IgA deposits at the upper epidermis of the eruptions without any other immunoglobulins and complement component C3. Circulating IgA antibodies directed against intercellular spaces of the epidermis were found by prolonged incubation of normal skin specimens in medium containing 20% patient's serum in an explant culture, although standard indirect immunofluorescence for IgA antibodies was negative. The eruptions were treated successfully with prednisolone, 30 mg/day, dapsone, 50 mg/day, and discontinuance of the thiol compound. In addition to the coexistent rheumatoid arthritis, both thiol compounds might have been responsible for the development of the eruptions.     

Neonatal Pemphigus Vulgaris: Trsmtel Transmission of Antibodies

A male infant with skin lesions was born to a 28-year-old mother who was under treatment for pemphigus vulgaris (PV), diagnosed eight years earlier. Circulating IgG class pemphigus antibody was found in the infant's blood, and deposition of IgG in the intercellular spaces of the epidermis was seen. The infant's lesions resolved within three weeks, and pemphigus antibody titer became negative by seven weeks. The pathogenetic role of PV antibodies and the risk for a fetus of a mother suffering from PV are discussed.     

ULTRASTRUCTURAL LOCALIZATION OF PEMPHIGUS ANTIBODIES WITHIN THE EPIDERMIS

Ultrastructural localization of pemphigus autoantibodies has been studied, using the periodatelysine-paraformaldehyde fixation method of McLean et al. The deposition of pemphigus autoantibodies was always found in the intercellular spaces of the epidermis, but not observed between the basal surface of basal cells and the basal lamina. Within desmosomes, a linear deposition of antibodies was also found, coresponding to the intermediate dense layer of Odland.     

Immunoglobulin A pemphigus associated with immunoglobulin A gammopathy and lung cancer

Immunoglobulin (Ig)A pemphigus is a rare disease marked by a vesiculopustular eruption characterized by intercellular IgA deposition in the epidermis. It has clinical and histopathological heterogeneity and encompasses two subgroups: subcorneal pustular dermatosis type and intraepidermal neutrophilic IgA dermatosis type. IgA pemphigus has been rarely associated with monoclonal IgA paraprotein, myeloma and B-cell lymphoma in the past. We report the first case, to our knowledge, of a 47-year-old male patient with a subcorneal pustular dermatosis type of IgA pemphigus associated with IgA gammopathy and lung cancer.     

Immunolocalization of target autoantigens in IgA pemphigus

IgA pemphigus is a rare autoimmune bullous disease characterized by IgA deposition at keratinocyte cell surfaces. Clinically and histologically, IgA pemphigus is divided into two major subtypes: subcorneal pustular dermatosis (SPD) type and intraepidermal neutrophilic IgA dermatosis (IEN) type. Using cDNA transfection and living cell immunofluorescence, we previously showed that desmocollin 1, one of the desmosomal cadherins, is the autoantigen in SPD-type IgA pemphigus, but the autoantigen in IEN type is still unclear. In the present study we investigated antigen localization by postembedding immunoelectron microscopy. We examined three sera each of SPD-type and IEN-type IgA pemphigus. In SPD-type, gold particles were observed predominantly in the extracellular spaces between keratinocytes at desmosomes, although a few particles were observed in the intracellular domain at the desmosomal attachment plaques. In IEN type, the gold particles were observed mainly in the intercellular spaces in nondesmosomal areas. These results provide evidence that the IgA in the sera of SPD-type IgA pemphigus reacts with the extracellular domain of desmocollins. In contrast, the autoantigen for IEN type may in fact not be a component of desmosomes. IEN-type IgA pemphigus may be the first member of the pemphigus group of autoimmune bullous dermatoses that reacts with a nondesmosomal transmembranous protein.     

Two Brazilian cases of IgA pemphigus

IgA pemphigus is a rare, neutrophilic, acantholytic skin disorder with approximately 70 cases described in the literature. We report two patients with the subcorneal pustular dermatosis (SPD) type of IgA pemphigus. Initially, both patients were misdiagnosed as subcorneal pustular dermatosis of Sneddon and Wilkinson. The correct diagnosis was only made after detecting intercellular IgA depositions in the epidermis by direct immunofluorescence. Immunoblotting (IB) of normal human epidermal extracts, performed on both sera, was negative for Dsg 1, Dsg 3, BP 230, BP 180, 210 kDa envoplakin, and 190 kDa periplakin. ELISA for desmogleins (Dsg 1 and Dsg 3) showed that neither of the cases had IgA antibodies to Dsg. The c-DNA transfection test for desmocollins (Dsc) revealed that the IgA antibodies of both patients reacted with desmocollin 1. This result supports the hypothesis that the autoantigen in SPD type IgA pemphigus is desmocollin 1.     

A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of pemphigus

OBJECTIVE: To investigate the safety and efficacy of oral methylprednisolone combined with azathioprine sodium or mycophenolate mofetil for the treatment of pemphigus. DESIGN: A prospective, multicenter, randomized, nonblinded clinical trial to compare 2 parallel groups of patients with pemphigus (pemphigus vulgaris and pemphigus foliaceus) treated with oral methylprednisolone plus azathioprine or oral methylprednisolone plus mycophenolate mofetil. Settings Thirteen departments of dermatology in Germany. Patients We included patients with pemphigus vulgaris (n = 33) or pemphigus foliaceus (n = 7) evidenced by clinical lesions suggestive of pemphigus, intraepidermal blistering on histological analysis of skin biopsy specimens, intercellular deposition of IgG within the epidermis, and immunoblot analysis findings for antidesmoglein 3 and/or antidesmoglein 1 autoantibodies. MAIN OUTCOME MEASURES: The cumulative total methylprednisolone doses and rate of remission. Secondary outcome measures were safety profiles and duration of remission. RESULTS: In 13 (72%) of 18 patients with pemphigus receiving oral methylprednisolone and azathioprine, complete remission was achieved after a mean +/- SD of 74 +/- 127 days compared with 20 (95%) of 21 patients receiving oral methylprednisolone and mycophenolate mofetil in whom complete remission occurred after a mean +/- SD of 91 +/- 113 days. The total median cumulative methylprednisolone dose used was 8916 mg (SD, +/-29 844 mg) in the azathioprine group compared with 9334 mg (SD, +/-13 280 mg) in the mycophenolate group. In 6 (33%) of 18 patients treated with azathioprine, grade 3 or 4 adverse effects were documented in contrast to 4 (19%) of 21 patients who received mycophenolate mofetil. Conclusion Mycophenolate mofetil and azathioprine demonstrate similar efficacy, corticosteroid-sparing effects, and safety profiles as adjuvants during treatment of pemphigus vulgaris and pemphigus foliaceus.