Localized Kaposi''s sarcoma in a patient with pemphigus vulgaris

We report the case of a patient with a 13-year history of pemphigus vulgaris (PV) treated with immunosuppressive agents, prednisone and mycophenolate mofetil who had developed lesions of Kaposi's sarcoma (KS) on a sole plaque of PV that had been previously treated with intralesional injections of steroids. The lesions were surgically removed and polymerase chain reaction (PCR) demonstrated human herpesvirus-8 (HHV-8) DNA. There were neither recurrences nor later dissemination of KS following gradual decrease of the immunosuppressive therapy. We suggest that the treatment with intralesional steroids may have influenced the local reactivation of a latent infection of the virus, determining the appearance of this localized KS.     

A mild form of captopril-induced pemphigus

We describe a mild form of drug-induced pemphigus in a woman with essential arterial hypertension treated with captopril. Complete recovery was observed three weeks after the therapy had been discontinued.     

Effects of chimeric molecule of recombinant Dsg3EC1-2 with toxin PE40 on T and B lymphocytes in Pemphigus Vulgaris

Objective:To observe the effects of the recombinant chimeric toxin Dsg3EC1-2PE40 on T and B lymphocytes isolated from Pemphigus Vulgaris (PV) patients to further study its biological therapeutic function for PV. Methods :Recombinant chimeric toxin Dsg3EC1-2PE40 was first identified, expressed and purified, and then its effects on T and B lymphocytes of PV patients in vitro were detected and quantified by ELISPOT assay and MTT assay. Results :The purity of the expressed protein Dsg3EC1-2PE40 was up to 80%. In ELISPOT assay, with Dsg3EC1-2PE40, the overall number of B cells that produce anti-Dsg3 antibodies among PV patients was only about 60% of the comparable number with Dsg3EC1-2. The proliferation of T cells of PV patients was inhibited markedly by Dsg3EC1-2PE40. There was significant difference between the different groups with Dsg3EC1-2PE40 and Dsg3EC1-2. Conclusion:The recombinant chimeric toxin Dsg3EC1-2PE40 decrease the number of B cells that produce anti-Dsg3 antibodies in PV patients and can inhibit or kill T cells of PV patients in vitro.     

A case of pemphigus vulgaris possibly triggered by quinolones

Pemphigus vulgaris is an autoimmune blistering disorder in which both genetic and environmental factors, mainly drugs, are thought to play a part in its aetiopathogenesis. Although some drugs that contain thiol groups, such as D-penicillamine and captopril, and non-thiol drugs, such as cephalosporin, have been reported to trigger or induce pemphigus, there are no previous reports regarding the influence of quinolones in triggering this disease. Here we present a case of pemphigus possibly triggered by quinolones.     

Pemphigus Vulgaris Associated with Autoimmune Hemolytic Anemia and Elevated TNFα

A 76-year-old female was admitted with many bullae and erythema on her trunk and extremities. A biopsy specimen showed significant intercellular edema in the lower epidermis and eosinophilic infiltration into the dermis and the epidermis. Immunofluorescent staining revealed the deposition of IgG in the intercellular area of her prickle cells. From these histologic findings and the typical clinical features, we diagnosed her as having pemphigus vulgaris. Examination of her blood revealed that she also suffered from autoimmune hemolytic anemia. Despite intensive treatment with prednisolone, she finally died. This case is of interest because of its rarity and the TNFα detected significantly in the blister fluid of this patient.     

Accelerating effects of epidermal growth factor on skin lesions of pemphigus vulgaris: a double-blind, randomized, controlled trial

BACKGROUND: Pemphigus vulgaris (PV) is a severe blistering disease involving the skin and mucous membranes. The most common causes of death in these patients are adverse effects of drugs, and infection. Skin lesions are one of the important sources of infection. Thus, any local treatment that could reduce healing time of lesions and consequently reduce the total dosage of drugs needed to treat is favourable. OBJECTIVE: To evaluate the efficacy of epidermal growth factor (EGF) in reducing healing time of lesions in patients with pemphigus vulgaris. METHODS: In this randomized, double-blind, within-patient, left/right, controlled trial, 20 hospitalized patients with pathologial and immunohistologial (direct and indirect immunoflourecence) proven pemphigus vulgaris (PV) were chosen. In addition, all patients had at least one appropriate pemphigus lesion on each side of the body that had not healed after 2-week systemic therapy and sterile saline washing. EGF (10 microg/g) in 0.1% silver sulfadiazine cream vs. 0.1% silver sulfadiazine cream alone was applied randomly on one side of the body. RESULTS: Kaplan-Meier survival analysis suggested that median time to heal with application of EGF plus silver sulfadiazine cream was 9 days, in comparison with 15 days for silver sulfadiazine cream alone (log-rank test, P=0.0003). No intervention-related adverse effect was observed during the study. CONCLUSIONS: EGF can significantly reduce healing time of skin lesions in patients with pemphigus vulgaris, at least when this cream base is applied (Cochrane skin group identifier: CSG20).     

Minocycline is a useful adjuvant therapy for pemphigus

Pemphigus is an autoimmune blistering disease with high mortality if untreated. The cases of 10 patients who had minocycline 100 mg daily added as adjuvant therapy are reported. Prior to the use of minocycline, all patients had active disease, nine were on prednisolone (10–40 mg) and five were on azathioprine (100–200 mg). The response was assessed on clinical improvement and reduction of immunosuppressive (IS) drugs. It was graded into four categories: major, minor, equivocal and no significant response. A major response was seen in four patients, minor in two, equivocal in one and no improvement in three patients. The prednisolone dose in the six responders was reduced to 0–6 mg (0 mg in three patients), with an average decrease of 21 mg. The average time to respond was 8 months. Of the six responders, three were on azathioprine, which was ceased in two patients and reduced by two-thirds in the other patient. No patient ceased minocycline because of side effects. In conclusion, minocycline 100 mg daily is a simple, safe and well tolerated treatment that should be tried in patients with pemphigus to reduce disease activity and/or the dose of potent IS agents.     

Pemphigus Vulgaris Autoantibody Response is Linked to HLA-DQB10503 in Pakistani Patients

ABSTRACT: Pemphigus vulgaris (PV) is an autoimmune disease of the skin and mucous membranes characterized by an autoantibody response against an epidermal cadherin. We performed high resolution HLA class II typing in 19 patients with PV from Rawalpindi, Pakistan and 19 non-Jewish European PV patients from Boston by sequence-specific oligonucleotide probe hybridization. The results were compared with two separate ethnically matched control populations. We found that PV patients from Pakistan had significantly increased frequencies of DRB1*1404 ( p = 0.01), DQA1*0101 ( p = 0.02), and DQB1*0503 ( p = 0.01). Among the patients of non-Jewish European ancestry, DRB1*1401 ( p < 10⁻⁶), DQA1*0101 ( p < 10⁻⁵) and DQB1*0503 ( p < 10⁻⁶), were increased in PV patients. Formal linkage analysis between the major histocompatibility complex and the PV antibody was performed in 67 relatives of the 19 Pakistani patients. The results showed strong evidence for linkage of HLA-DRB1*1404, DQA1*0101, DQB1*0503, with the presence of PV antibody in relatives’ families with a significant logarithm of the odds score of 6.06. Based on the three dimensional structure of class II molecules, we propose that HLA-DQA1*0101 and DQB1*0503, encode a negatively charged P9 peptide binding pocket of the DQ molecule and are significantly associated with susceptibility to PV in non-Jewish populations.     

Pemphigus vulgaris: the role of IL-1 and IL-1 receptor antagonist in pathogenesis and effects of intravenous immunoglobulin on their production

Intravenous immunoglobulin (IVIG) is increasingly being used for the treatment of autoimmune diseases. In the present report, the role of IVIG on in vivo and in vitro production of IL-1 and IL-1 receptor antagonist (Ra) was studied in patients with pemphigus vulgaris (PV). Serum samples from 20 untreated patients with active PV prior to initiation of systemic therapy, 20 patients receiving IVIG treatment, 20 patients in clinical remission after conventional therapy, and 20 normal human controls were studied to determine the serum levels of IL-1alpha, IL-1beta, and IL-1Ra. The in vitro production of these cytokines was measured in the culture supernatant of peripheral blood mononuclear cells (PBMC) from 10 PV patients immediately before and after IVIG therapy and from age and sex-matched 10 healthy donors simultaneously. Elevated levels of IL-1alpha and IL-1beta were detected (i) in the serum of untreated PV patients with active disease prior to systemic therapy and (ii) before IVIG infusions in patients receiving IVIG therapy. These increased levels are statistically significant when compared to the levels in healthy controls (P < 0.01). A marked reduction of IL-1alpha and IL-1beta was detected (i) in the serum of patients in prolonged clinical remission and (ii) immediately after IVIG infusion in those patients on IVIG therapy. Increased level of IL-1Ra was detected in PV patients in prolonged clinical remission and after IVIG infusion in those receiving IVIG therapy. These differences were statistically significant when compared to the levels in normal controls and to the levels in the sera of patients with active disease (P < 0.01) or just before the beginning of IVIG infusion (P < 0.01). Similar differences in the levels of IL-1alpha, IL-1beta, and IL-1Ra were found in the culture supernatant of PBMC isolated from the PV patients pre and post IVIG therapy. These observations suggests that, compared to normal controls, patients with active PV have reversed levels of IL-1alpha, IL-1beta, and IL-1Ra. IVIG therapy may down-regulate production of IL-1alpha and IL-1beta and enhance production of IL-1Ra, in vivo and in vitro. This might be one of the important mechanisms by which IVIG produces its early therapeutic effects in pemphigus vulgaris.