Identification of clinical and immunological factors associated with clinical relapse of pemphigus vulgaris in remission.

BACKGROUND: Pemphigus vulgaris is a potentially fatal autoimmune epidermal blistering disease with a chronic and relapsing course. It is difficult to predict clinical relapse. Identification of clinical and immunological factors that are associated with early clinical relapse in a prospective study design may help in planning treatment for better maintenance of clinical remission. AIM: The aim of our study was to identify clinical and immunological factors associated with clinical relapse within 9 months of study inclusion in patients with pemphigus vulgaris in clinical remission. METHODS: Forty consecutive consenting patients who had been diagnosed to have pemphigus vulgaris and were in clinical remission on minimal therapy or off therapy were included. The patients were followed up every 3 months until 9 months. Clinical factors considered relevant were recorded at the beginning of the study. Immunological factors such as CD19+ B-cell count and CD19+CD27+ memory B cells/plasma cell count in peripheral blood were assessed at baseline [anti-desmoglein (Dsg) 1 and 3 titers were first assessed at 3 months, not at baseline] and repeated every 3 months, until 9 months or clinical relapse whichever was earlier. Direct immunofluorescence (DIF) of skin biopsy specimen was performed at study initiation and again at the time of clinical relapse or study completion, whichever occurred earlier. All patients completed the study. RESULTS: Of 40 patients, 11 (27.5%) experienced relapse as per definition, while 29 (72.5%) remained in complete remission. Clinical relapse during study duration was significantly more common in those who had onset of disease in oral mucosa [odds ratio (OR), 10.71; 95% confidence interval (CI) 1.21-94.86, P = 0.02], pruritus (OR 8.4; 95% CI 1.76-40.02, P = 0.01), and extensive cutaneous involvement during previous disease activity (OR 7.36; 95% CI 1.34-40.55, P = 0.03) and also pruritus during remission (P = 0.004). Immunological factors found to be significantly associated with early clinical relapse were raised CD19+ B-cell count at baseline (OR 7.84; 95% CI 1.39 - 53.41, P = 0.01), immunoglobulin G (OR 4.85; 95% CI 1.09-23.44, P = 0.04), and C3 (OR 20.33; 95% CI 3.02-199.5, P < 0.001) positivity in the intercellular space of the epidermis on DIF at study onset and rising anti-Dsg 3 antibody titers (OR 19.96; 95% CI 1.85- 310.9, P = 0.03). LIMITATIONS: Limited sample size, short follow-up duration, and inability to perform anti-Dsg enzyme linked immunosorbent assay for all the patients at all the time points of assessment are limitations of this study. CONCLUSION: Immunological relapse can be determined before clinical relapse, so that treatment can be restarted/modified and clinical remission can be maintained.

Paraneoplastic autoimmune multiorgan syndrome (paraneoplastic pemphigus) with unusual manifestations and without detectable autoantibodies.

We describe a patient with paraneoplastic autoimmune multiorgan syndrome (PAMS) secondary to a lymphoblastic T- cell lymphoma who presented with a lichenoid dermatitis and vitiligo, later developing bronchiolitis obliterans and autoimmune hepatitis. Notably, he had no detectable autoantibodies. The development of vitiligo and autoimmune hepatic involvement probably indicate a role for cytotoxic T- cell lymphocytes in the pathogenesis of this syndrome.

Comparison of enzyme-linked immunosorbent assay test with immunoblot assay in the diagnosis of pemphigus in Indian patients.

BACKGROUND: The diagnosis of pemphigus vulgaris (PV) and pemphigus foliaceous (PF) rests upon clinical, histological and immunofluorescence features. Enzyme-linked immunosorbent assay (ELISA) test and immunoblot (IB) assay have shown variable sensitivity and specificity. AIMS: We compared the utility of ELISA and IB in pemphigus patients. METHODS: Sixty-six pemphigus cases (PV-54, PF-12) and 72 controls (other vesicobullous disorders and healthy controls) were inducted. ELISA for anti-Dsg 3 and 1 antibodies and IB assay were performed. RESULTS: On ELISA, both mean anti-Dsg 1 and 3 titers were raised in PV and PF. Mean anti-Dsg 1 in mucocutaneous PV was significantly higher than in mucosal PV and mean anti-Dsg 3 was significantly raised in PV than in PF. Anti-Dsg 1 and 3 in the control group were negative. Sensitivity and specificity of ELISA in PV was 98.14% and 90.5% while in PF it was 91.6% and 61.1%, respectively.On IB in PV, 36 cases (66.67%) showed the 130 kDa and 160 kDa antigen bands, 12 (22.2%) only the 130 kDa and six (11.1%) only the 160 kDa band. Eight of the nine pure mucosal cases (88.8%) showed only the 130 kDa. In PF, only the 160 kDa antigen was detected. These antigens were not identified in the control group. Sensitivity and specificity of IB in PV was 88.9% and 100% and in PF it was 100% and 95.2%, respectively. CONCLUSION: Both tests could differentiate pemphigus from other dermatoses, including other blistering disorders. ELISA could not make a distinction between PV and PF or between the various clinical phenotypes of PV. IB differentiated between PV and PF and the different clinical variants of PV.

Imunofluorescencia direta na pele aparentemente sã, lesada e perilesional e indireta no penfigo foliaceo endemico (Fogo selvagem) / Direct immunofluorescence on the apparently healthy, injured and perilesional and indirect skin in endemic foliaceous pemphigus (Wildfire)

As imunofluorescencias direta e indireta constituem importante diagnostico nos penfigos. Foram estudados o soro e a pele aparentemente sa, lesada, eperilesional de 47 doentes de penfigo foliaceo endemico, sendo 15 doentes nao tratados e 32 em tratamento com prednisona. Quanto a forma clinica, 29 possuiam a forma localizada e 18 a generalizada da doenca. Atraves da imunofluorescencia direta analisou-se a frequencia de deposicao de IgA, IgM, IgG e suas subclasses (IgG1, IgG2, IgG3 e IgG4) e a fracao C3 do complemento nos espacos intercelulares da epiderme nas tres peles. A imunofluorescencia indireta, analisou-se frequencia de positividade dos titulos sorologicos da IgG e suas subclasses (IgG1, IgG2, IgG3 e IgG4), assim como as medias dos titulos nos dois grupos