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Background/aims: Pemphigus vulgaris (PV) is an autoimmune disorder that has an etiology impacted by genetic and exogenous factors. Viral infections, in particular herpesvirus infections, have been identified as possible PV triggers which in addition cause serious complications in these patients. This study investigates the frequency of herpesvirus infections in patients with PV lesions., Methods: Polymerase chain reaction and DNA sequence analyses were used to determine the presence of herpes simplex virus (HSV)-1/2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus types 6, 7, and 8 (HHV-6, HHV-7, and HHV-8) DNA in 105 mucosal and/or skin swabs harvested from 23 patients presenting with PV lesions., Results: Thirty-six samples collected from 17 patients were positive for at least 1 virus; 3 were positive for HSV-1, 2 for HSV-2, 2 for CMV, and 7 each for HHV-6 and HHV-7. Coinfections were observed in 15 samples. Infections with VZV, EBV, HHV-6A, and HHV-8 were not detected. Herpesvirus infections were detected in 21% (13/62) of reactivated lesions, 54.5% (18/33) in persistent lesions, 40% (2/5) in exacerbated lesions, and 60% (3/5) in lesions in remission., Conclusion: PV lesions which do not show improvement following administration of adequate immunosuppressive therapy should be screened for the presence of herpesvirus infections., (Copyright © 2013 S. Karger AG, Basel.)

Acquired factor VIII (FVIII) inhibitor induces a bleeding disorder caused by specific antibodies to FVIII. The cause of approximately one fifth of cases can be attributed to autoimmune disorders, such as pemphigus. Here, we describe a case of refractory acquired FVIII inhibitor in a patient with primary pemphigus and its successful treatment with low-dose rituximab. Coagulation studies revealed a prolonged activated partial thromboplastin time, which could not be corrected with the mixing test. At the same time, the FVIII activity level was significantly reduced, and the FVIII inhibitor titer was elevated. A treatment regimen with prednisolone/cyclophosphamide followed by prednisolone/cyclosporine was used. The patient temporarily responded but then became resistant to these medicines. However, subsequent treatment with low-dose rituximab achieved considerable clinical and laboratory improvement in the same patient. Follow-up at 6 months revealed a low level of residual FVIII inhibitor activity with normal coagulation functions. No drug-related side effects were detected. In conclusion, our results indicate that low-dose rituximab might be an effective and safe treatment for patients with acquired FVIII inhibitor., (Copyright © 2011 S. Karger AG, Basel.)

Background: Pemphigus and systemic lupus erythematosus (SLE) have previously been reported to coexist in the same patient. However, the relationship between the 2 diseases has not been elucidated., Objective: This review was conducted to examine the relationship between pemphigus and SLE when they occur together in the same patient., Methods: We conducted a retrospective review of the literature to identify previously reported cases of pemphigus and SLE coexisting in the same patient. The temporal relationship, clinical course, response to therapy and effects of 1 disease on the other were examined., Results: Eight patients with a dual diagnosis of pemphigus and SLE have been previously reported. Most were female and non-Caucasian, with a mean age of 41 years. In the 8 patients reviewed here clinical outcomes, organ system involvement and demographic profiles are more typical of SLE. Seven of these 8 patients had pemphigus vulgaris, and 1 had pemphigus erythematosus. The limited follow-up did not permit studying issues of disease interaction. An additional 17 patients with pemphigus have been reported who have features suggestive of SLE. Organ system involvement in these patients was less typical of SLE., Conclusion: It appears that a true dual diagnosis of pemphigus and SLE is less common than suggested by the literature. Comparing patients with only pemphigus or only SLE to those with both may provide insights into genetic predisposition and pathogenesis, and provide an opportunity to study the effects of drugs that influence their course., (Copyright (c) 2007 S. Karger AG, Basel.)

A 70-year-old Caucasian man with chronic lymphocytic leukemia suffered from widespread, histologically proven cutaneous lichen planus responding to topical corticosteroids. 2 years later, he presented with painful erosive stomatitis and increasing dyspnea. Histology, direct and indirect immunofluorescence were diagnostic for paraneoplastic pemphigus. A full diagnostic workup could not disclose the cause of the progressive respiratory insufficiency. Despite aggressive treatment of the lymphocytic leukemia and the paraneoplastic pemphigus, the patient died 3 months after diagnosis. Paraneoplastic pemphigus may lead to pulmonary failure which is refractory to treatment and has a fatal outcome., (Copyright 2004 S. Karger AG, Basel)

Involvement of the nails in pemphigus vulgaris (PV) is rare and is usually seen when the disease is severe. The most common clinical manifestations are chronic paronychia and onychomadesis. Finger nails are more frequently involved than toe nails. We report a case of severe and persistent PV in which an exacerbation was preceded by an erosive and destructive lesion of the right hallux nail unit. A nail bed biopsy was performed to rule out a subungual tumour. The image of suprabasal acantholysis yielded the diagnosis of PV. This localisation and clinical manifestation of PV have only been reported once., (Copyright 2003 S. Karger AG, Basel)

Background: The simultaneous presence of features of pemphigus vulgaris (PV) in patients with bullous pemphigoid (BP) has previously been reported in the literature., Objective: The purpose of this retrospective study is to present 13 patients with an initial diagnosis of BP, who subsequently demonstrated coexistent serological features of both BP and PV., Methods: The following information on each patient was documented, at the time of initial diagnosis: clinical profile on presentation, histology, direct immunofluorescence, indirect immunofluorescence (IIF) using monkey esophagus as substrate, salt-split skin (SSS) and an immunoblot assay. Since all 13 patients failed to respond to conventional systemic therapy, intravenous immunoglobulin (IVIg) was used as an alternative treatment modality. Prior to initiating IVIg therapy, in all 13 patients, serological studies were performed. In addition to IIF using monkey esophagus, an immunoblot assay and SSS, an enzyme-linked immunosorbent assay (ELISA) was performed to detect antibodies to desmogleins. These different assays were done to identify pathological autoantibodies typical of BP and PV. A control group of 25 healthy normal individuals, 37 patients with BP, 17 patients with PV and 12 patients with pemphigus foliaceus were used for comparison of serological studies., Results: At the time of initial presentation, histological and immunopathological studies confirmed the diagnosis of BP in all 13 patients. Prior to the initiation of IVIg therapy, results of IIF using monkey esophagus as substrate demonstrated high levels of anti-intercellular cement substance (anti-ICS) or antikeratinocyte cell surface antibody. Sera of all 13 patients on SSS bound to the epidermal side of the split. In an immunoblot, using bovine gingival lysate as substrate, sera of 6 patients bound to both a 230-kD (BP Ag1) and 180-kD protein (BP Ag2), while 7 sera bound to only a 230-kD protein. All 13 patients had high levels of antibodies to desmoglein 3 on ELISA. In a pilot experiment, the anti-ICS antibody in sera from 6 random patients was found to be predominantly of the IgG4 subclass. Use of IVIg resulted in an effective clinical response and the maintenance of a prolonged clinical remission., Conclusion: In patients with BP, who are nonresponsive to conventional therapy, the presence of two autoimmune diseases or a dual diagnosis should be considered., (Copyright 2002 S. Karger AG, Basel)

An 80-year-old man, with a solid abdominal tumor and multiple skin lesions, was admitted to the hospital because of a perforated right cornea and an impending perforation of the left. The clinical, histological, immunohistological and immunoprecipitation findings of the skin lesions were consistent with Anhalt's criteria for paraneoplastic pemphigus (PNP). The underlying malignancy proved to be an incurable peripheral neuronal shaft tumor. Both conjunctivae appeared normal. The right eye revealed a flat anterior chamber, due to a spontaneous, central corneal perforation. The central part of the left cornea had severely thinned, resulting in a descemetocele, which eventually perforated. Multiple surgical interventions were needed to restore the anterior chamber in both eyes. Although a causative association between PNP and corneal perforation could not be demonstrated, we think that corneal melting should be added to the list of ocular complications in patients with PNP., (Copyright 2001 S. Karger AG, Basel.)

A 76-year-old woman, with a history of thymoma, presented with a painful extensive stomatitis, painful paronychia, lichenoid papules on the hands and superficial erosions on the neck and the trunk. Histological examination showed lichenoid changes, acantholytic blister formation and apoptotic keratinocytes. Direct immunofluorescence was positive for IgG both in the epidermal intercellular spaces and along the basement membrane zone. Indirect immunofluorescence was similarly positive in a pemphigus vulgaris pattern. There was only a partial response to intravenous corticoids. These findings allowed the diagnosis of paraneoplastic pemphigus. The diagnostic characteristics, histopathology and the differential diagnosis of this disease are discussed., (Copyright 2001 S. Karger AG, Basel.)

Background: Pemphigus and pemphigoid are two distinct groups of autoimmune blistering diseases. There are many reports of the simultaneous presence of clinical and serological features of both diseases in the same patient., Objective: This study is a retrospective review of the present literature on reports of patients with features of both pemphigus and pemphigoid. We recommend that these patients be considered as having a dual diagnosis., Methods: A review of the English language, peer-reviewed literature was conducted on patients described with features of pemphigus and pemphigoid. Available data on clinical profile, histology, immunopathology, treatment, follow-up and outcome were studied in 30 patients. They were divided into three groups: (1) bullous pemphigoid and pemphigus vulgaris, (2) mucous membrane or cicatricial pemphigoid and pemphigus vulgaris and (3) bullous pemphigoid and pemphigus foliaceus., Results: In all three groups, most patients had a clinical phenotype resembling both diseases. In 17 patients with bullous pemphigoid and pemphigus vulgaris, 83% had a skin biopsy consistent with bullous pemphigoid, 70% had direct immunofluorescence studies typical of bullous pemphigoid and sera of 83% had antibodies typical of pemphigus vulgaris on indirect immunofluorescence. In 10 patients with mucous membrane or cicatricial pemphigoid and pemphigus vulgaris, a histology of mucous membrane pemphigoid was reported in 60% of the patients, direct immunofluorescence studies typical of mucous membrane pemphigoid were reported in 70% of the patients and in 80%, autoantibodies characteristic of pemphigus vulgaris were observed. In 3 patients with bullous pemphigoid and pemphigus foliaceus, the histologies were consistent with bullous pemphigoid, direct immunofluorescence was typical of pemphigus foliaceus and their sera had both autoantibodies. The majority of the 30 patients required long-term high-dose corticosteroids and immunosuppressive agents to control their disease. Three patients with bullous pemphigoid and pemphigus vulgaris (18%) died due to effects of prolonged immunosuppression., Conclusion: We characterize a group of patients who have clinical, histological and immunopathological features of bullous or mucous membrane or cicatricial pemphigoid with serological features of pemphigus. These patients did not achieve a prolonged clinical remission by conventional therapy. It is possible that early identification of these patients may improve their prognosis., (Copyright 2001 S. Karger AG, Basel)

A 35-year-old man presented with a generalized bullous eruption and oral ulceration. He had been diagnosed as having systemic lupus erythematosus and pelvic Castleman disease (hyaline-vascular type) in the past. Histologic, direct and indirect immunofluorescence and immunoprecipitation studies confirmed a diagnosis of paraneoplastic pemphigus (PNP). Initially several medical treatments were tried unsuccessfully. The pelvic tumor was surgically removed and the mucocutaneous lesions slowly regressed. Four years after presentation, he developed polymyositis which was completely controlled with short courses of corticosteroids. There was no evidence of relapse of PNP or lupus erythematosus at that time. At the 6-year follow-up he showed no clinical evidence of PNP, lupus erythematosus or polymyositis without requiring immunosuppressive therapy. This case emphasizes the fact that patients with benign-neoplasm-associated PNP may undergo complete remission of the autoimmune disease upon complete excision of the tumor. This case also stresses the possible association of PNP with other autoimmune diseases such as lupus erythematosus and polymyositis.

A 63-year-old male patient spontaneously developed severe erosive orogenital mucositis, palmoplantar and gluteal inflammatory lesions resistant to therapy. The skin lesions clinically and histologically resembled lichen-planus-like graft-versus-host disease. Investigation for an underlying autoimmune or malignant disorder revealed a centrocytic-centroblastic low-grade non-Hodgkin's lymphoma (according to the Kiel classification) in the bone marrow, mesenterial and iliacal lymphoma. Serological titers were intermittently positive for ANA, anti-Sm/U1RNP, anti-Ro and anti-dsDNA. Immunoprecipitation of lysates from radiolabeled human keratinocytes with the patient's serum revealed circulating antibodies against 210-kD (desmoplakin II), 190- and 170-kD antigens but none against the 230-kD antigen or 250-kD desmoplakin I. Under cytostatic chemotherapy the lymphomas showed complete and long-lasting remission, whereas the mucocutaneous lesions persisted. Six years after diagnosis, the mucocutaneous lesions are sufficiently controlled by immunosuppressive therapy. In the presented case, several features of lymphoma-associated dysimmunoreactivity are assumed that bring about the intrinsic production of various autoantibodies typical of paraneoplastic pemphigus and systemic lupus erythematosus.

We report a case who was clinically and histopathologically diagnosed as herpetiform pemphigus (HP) and associated with autoimmune hemolytic anemia (AIHA). However, immunofluorescence studies demonstrated concurrent anti-cell-surface and anti-basement-membrane-zone antibodies in the patient's serum. Immunochemical studies showed that the patient's serum reacted with both the pemphigus foliaceus antigen and the two bullous pemphigoid antigens. Subsequently, the patient developed AIHA. Both anemia and skin lesions were successfully treated with oral prednisolone. We believe that this is the first case with HP in association with AIHA. The presence of autoantibodies against multiple antigens suggests an abnormal immunologic tolerance in the antibody production system in this patient.

Patients with pemphigus are occasionally associated with neoplasms. We report a case of pemphigus with carcinoid. To our knowledge, this is the first case of coexistence of pemphigus and carcinoid.

To evaluate the significance of the association of malignancy with autoimmune blistering diseases, we studied the incidence of internal malignancies in 496 pemphigus and 1,113 bullous pemphigoid (BP) patients in Japan. Statistical analysis showed that an association ratio of internal malignancies with pemphigus was 5.0% and that with BP was 5.8%. These ratios were significantly higher than that of the controls aged over 70 years (0.61%). Our results indicate that detailed examination for internal malignancy is essential for patients with pemphigus or BP.

A 67-year-old housewife had polymorphous eruptions with tense bullae on the extremities and upper trunk. Erosions were noted on the oral and esophageal mucosa. A skin biopsy showed subepidermal blistering with linear deposition of IgG and C3 at the basement membrane zone. In addition, intercellular deposition was observed at the lower part of the epidermis. On the basis of clinical and histological features, a diagnosis of bullous pemphigoid (BP) was made. After she was treated with prednisolone, the whole-skin lesions soon disappeared. An esophageal biopsy showed intercellular deposition of IgG and C3. Indirect immunofluorescence testing using esophageal mucosa of guinea pigs showed the same deposition at the titer of 1:20. Immunoblottings with this patient's serum revealed no reactions with either BP or pemphigus antigens. Her serum reacted strongly with a 190-kD protein, the nature of which was unknown. A treatment with ciclosporin was added to this steroid therapy, and the mucosal lesions improved gradually.

A case is reported of a 60-year-old woman with acantholytic vesiculopustular dermatosis and IgA-lambda monoclonal gammopathy. The histopathology of vesiculopustular lesions showed intraepidermal acantholytic and neutrophilic blisters. Direct immunofluorescence revealed intercellular (IC) IgD deposition with concurrent deposits of IgA and C3. Indirect immunofluorescence and immunoblotting studies revealed that the patient had circulating IgG and IgA anti-IC antibodies both of which recognized the 150-kD desmoglein that was pemphigus foliaceus antigen in a bovine desmosome preparation.

A patient is described who developed hyperkeratotic, hyperpigmented plaques, similar to acanthosis nigricans in re-epithelializing erosions of pemphigus foliaceus. The lesions regressed completely after a few months. This phenomenon can be attributed to a Köbner phenomenon after epidermal damage or can be a result of systemic corticosteroid therapy.

A 53-year-old female patient with pemphigus vulgaris under continuous immunosuppressive therapy for about 2 years presented a superficial spreading malignant melanoma on a pre-existing melanocytic naevus. After surgical removal of the inguinal lymph node group, a diffuse low-grade polymorphous immunocytoma was proved both histologically and immunocytochemically. The possible induction mechanisms are discussed.

We report the case of a patient with pemphigus who presented Nocardia asteroides septicemia. The infection was controlled with an original association of trimethoprim-sulfamethoxazole and amikacin.

An unusual vesculobullous disease and myasthenia gravis occurred concurrently with a malignant thymoma in a Japanese male. The bullous dermatosis had combined clinical and histological features of both dermatitis herpetiformis and pemphigus. Serum showed striated muscle antibodies and intercellular epithelial autoantibodies; the latter had been demonstrated even prior to the development of the skin lesions. Thus, immunologically, this dermatosis was confirmed to be a variety of pemphigus.

The occurrence of a Kaposi sarcoma during the course of a therapy for a pemphigus vulgaris is reported. Only five such associations have been previously described in the literature. On the other hand, several works have reported simultaneous occurrence of a Kaposi sarcoma with anomalies of the immune or lymphoïd systems (lymphoma, Hodgkin disease, Waldenström disease, mycosis fongoïdes. Hypothesis concerning the Kaposi sarcoma genesis can be suggested on the basis of these observations and remain to be confirmed.

A 74-year-old male patient with rheumatoid arthritis and Sjögren's syndrome developed pemphigus foliaceus. Clinically healthy skin tissue revealed a fluorescent band of IgM along the basal membrane and an intercellular deposit of C3 and IgG in the deepest areas of the epidermis. Similar investigations of diseased skin revealed no deposits of IgM, and C3 and IgG were spread over a large area of the epidermis, though following the same pattern. In sero-positive rheumatoid patients with and without vasculitis, C3 and IgM are frequently found in small dermal vessels immediately below the epidermis in apparently normal skin. The fluorescent band of IgM along the basal membrane is thought to be an expression of the patient's rheumatoid arthritis, in spite of the fact that this IgM site is not typically associated with rheumatoid arthritis. The change in the pattern of deposition is thought to be due to pemphigus foliaceus.

In the skin organ culture model of pemphigus, fibronectin concentrations of 300 and 500 micrograms/ml inhibited pemphigus plasma-induced acantholysis and intraepidermal binding of the pemphigus antibodies examined by direct immunofluorescence. A direct interaction of fibronectin with pemphigus antibodies could not be demonstrated by chromatography of pemphigus plasma on immobilized fibronectin or by incubation with fibronectin and subsequent precipitation with antifibronectin. We then measured fibronectin concentrations in the plasma of 15 patients suffering from various types of pemphigus and presenting different activities of their disease. Immunoreactive fibronectin levels in untreated patients with active disease were generally in the low normal or even clearly in the subnormal range. They had the tendency to decrease when the disease subsided during therapy with high doses of glucocorticoids, sometimes in combination with azathioprine. The fibronectin concentration in the blister fluid of a patient with acute, untreated pemphigus vulgaris was similar to that in a plasma sample taken at the same time. Skin biopsies of pemphigus patients exhibited an essentially normal fibronectin pattern in direct immunofluorescence. We discuss a possible protective role of fibronectin in pemphigus e.g., by reducing the permeability for pemphigus antibodies in the dermal-epidermal junction zone.

Although patients with disseminated pemphigus vulgaris may have involvement of the uterine cervix, such involvement is often detected only after vaginal discharge or bleeding. When a cervical smear is obtained, distinctive cytologic abnormalities may be observed; these may be attributed to the changes of pemphigus or to an associated reparative/inflammatory reaction. This study documents the first two cases of microinvasive squamous-cell carcinoma of the uterine cervix developing in association with uterine cervical pemphigus. The gross pathologic, cytologic and histologic features of these lesions are illustrated. The cytologic criteria that may be helpful in distinguishing between cells derived from microinvasive squamous-cell carcinoma and pemphigus of the uterine cervix are described.

A case is described with features both of Hailey-Hailey and Darier's disease in a male patient who presented skin lesions since he was 8 years old. The present case is discussed in relation to data obtained from the literature, and a differential diagnosis from Grover's disease is made.