Tag Archives: pemphigus vulgaris

There are a limited number of reports indicating the role of human leukocyte antigen (HLA) class I alleles in pemphigus vulgaris. This study was designed to highlight the association of HLA class I alleles with pemphigus vulgaris in Iran. Fifty patients with pemphigus vulgaris, diagnosed based on clinical, histological and direct immunofluorescence findings were enrolled into this study. The control group consisted of 50 healthy, age- and sex-matched individuals. HLA typing of class I (A, B and C alleles) was carried out using polymerase chain reaction based on the sequence-specific primer method. This study showed the higher frequency of HLA-B*44:02 (= 0.007), -C*04:01 (< 0.001), -C*15:02 (< 0.001) and -C*16:01 (= 0.027) in the patient group, compared to the controls, while the frequency of HLA-C*06:02 (< 0.001) and -C*18:01 (= 0.008) in the patients with pemphigus vulgaris was significantly lower than the controls. Regarding the linkage disequilibrium between HLA class I alleles, the HLA-A*03:01, -B*51:01, -C*16:02 haplotype (4% vs 0%,= 0.04) is suggested to be a predisposing factor, whereas HLA-A*26:01, -B*38, -C*12:03 haplotype (0% vs 6%, = 0.01) is suggested to be a protective factor. In conclusion, it is suggested that HLA-B*44:02, -C*04:01, -C*15:02 alleles and HLA-A*03:01, -B*51:01, -C*16:02 haplotype are susceptibility factors for development of pemphigus vulgaris in the Iranian population, while HLA-C*06:02, -C*18:01 alleles and HLA-A*26:01, -B*38, -C*12:03 haplotype may be considered as protective alleles.

Full article available here: http://onlinelibrary.wiley.com/doi/10.1111/1346-8138.12071/abstract;jsessionid=B90D811159F2CE1C4C357306A37A9D15.d04t04

Human epidermis shows a non-neuronal cholinergic system including keratinocyte (kc) acetylcholine (Ach) axis which is composed by enzymes and two families of Ach receptors (muscarinic and nicotinic receptors). The activity of these two receptors can regulate the interkeratinocytes and kcs-extracellular matrix adhesion modifying the regulation of intercellular adhesion molecules like cadherins and integrins. Some authors demonstrate that acantholysis in pemphigus depends not only on anti desmogleins antibodies (abs) (mostly IgG) but even on other abs directed against kc membrane antigens (e.g. anti Ach receptors Abs). In the early phase of pemphigus pathogenesis, anti Ach receptors Abs block Ach signaling essential for cell shape and intercellular adhesion and increase the phosphorylation of adhesion molecules. Combined with the action of abs antidesmogleins, anti Ach receptors Abs cause the acantholytic phenomenon. In vitro experiments show that high doses of Ach in acantholytic kcs can rapidly reverse this pathologic event. In vivo experiments using neonatal mice model of Pemphigus have demonstrated that cholinergic agonists reduce these lesions. Therapy with pyridostigmine bromide and Nicotinamide per os or pilocarpine used topically, drugs that present cholinomimetic effects, has lead to encouraging results in patients affected by Pemphigus disease. Cholinergic agents could have a strategic role in the therapy of pemphigus since they could be responsible for the early stage of acantholytic diseases.

Full article available at: http://www.ingentaconnect.com/content/ben/aiaamc/2012/00000011/00000003/art00008

Pemphigus vulgaris (PV) is an autoimmune mucocutaneous disease presenting clinically with blisters or erosions of the skin and mucous membrane. The main histopathologic characteristic of this disease is suprabasal vesicles due to loss of cell–cell adhesion between keratinocytes named acantholysis. Studies have shown that apoptosis is increased in PV. The purpose of this study is to investigate the role of apoptosis in blister formation in PV.

Methods

This cross-sectional study was conducted on 25 specimens of oral PV. The presence of apoptosis was evaluated using the TUNEL technique in the normal perilesional region, vesicle area, and acantholytic cells. Also, the expression of Bax pro-apoptotic marker was assessed by the biotin–streptavidin immunohistochemical method. SPSS software was used for Wilcoxon test analysis. P values <0.05 were considered significant.

Results

The percentage and intensity staining of TUNEL-positive cells were noteworthy. There were statistically significant differences between basal and parabasal) = 0.05 (, tombstone with vesicle roof (= 0.038) and basal with tombstone (= 0.038). However, the expression and staining intensity of pro-apoptotic marker Bax were weak, and no statistically significant differences were observed between the various areas.

Conclusion

The results obtained in the present study suggest that the process of apoptosis occurs early in PV because it was observed in the perilesional normal appearing tissue. Also, the process of apoptosis may cause exacerbation or speeding of the bulla formation. In other words, inhibition of apoptosis in the patients could reduce the severity of the lesions.

Full article available here: http://www.medworm.com/index.php?rid=6781830&cid=c_297_32_f&fid=28436&url=http%3A%2F%2Fonlinelibrary.wiley.com%2Fresolve%2Fdoi%3FDOI%3D10.1111%252Fjop.12022

Introduction: Though oral aphthosis is common, it has a significant impact on the quality of life in the patients. It is the most common oral ulcerative condition encountered in clinical practice. This study describes the characteristics and patterns of oral aphthosis seen at a tertiary dermatological centre in Singapore, with emphasis in evaluating the management gaps and in identifying underlying systemic diseases and nutritional deficiencies. Materials and Methods: This is a retrospective review of medical records over a 10-year period between June 2000 and June 2010. Two hundred and thirteen patients were identified using the search terms ‘oral ulcers’, ‘aphthous ulcers’, ‘oral aphthosis’, and ‘Behcet’s disease’. Patients with Behcet’s disease without oral ulcers and other diagnoses such as pemphigus vulgaris, lichen planus and herpes simplex were excluded. The remaining patients were evaluated with regard to demographic characteristics, characteristics of oral ulcers, associated connective tissue disorders and nutritional deficiencies, diagnostic tests results, treatment response as well as follow-up duration. Results: One hundred and seventy-five patients were included in this study. One hundred and one patients had recurrent oral aphthosis, with 77 having simple aphthosis and 24 having complex aphthosis. Fourteen patients (8%) fulfilled the International Study Criteria (ISG) for Behcet’s disease, of which, 85.71% had complex aphthosis. The therapeutic ladder for such patients ranged from topical steroids and colchicine through to oral corticosteroids and/or dapsone therapy. Conclusion: Recurrent oral aphthosis is a niche condition in which dermatologists are well-poised to manage. This study demonstrates that a more definitive management and therapeutic algorithm for oral aphthosis are needed for better management patients in the future. In particular, complex aphthosis needs to be monitored for progression onto Behcet’s disease.

From: http://www.ncbi.nlm.nih.gov/pubmed/23138144?dopt=Abstract

Pemphigus is a rare vesiculobullous autoimmune disease that exhibits blistering of the skin and oral cavity. It is caused by autoantibodies directed against antigens on the surface of keratinocytes. All forms of pemphigus are associated with the presence of circulating and skin-fixed autoantibodies. Pemphigus vegetans is a rare clinical variant of pemphigus vulgaris and comprises up to 5 percent of all pemphigus cases. In the following we present the oral presentation of pemphigus vegetans. We describe a 33-year-old man who was referred to our clinic complaining about mouth sores, tooth pain, and multiple pustules. During clinical exam we were able to recognize multiple pustules, ulcerated areas on the gingiva, and whitish mucosal plaques. Clinical, histopathological, and direct immunofluorescence findings were compatible with pemphigus vegetans.

Full article available at: http://www.ncbi.nlm.nih.gov/pubmed/23122017?dopt=Abstract

The clinical and epidemiological features of pemphigus vulgaris (PV) are well documented but there remain few reports of oesophageal involvement of PV. Although previously considered to be rare, recent reports have suggested that up to 87% of patients with PV may have symptoms, or endoscopic features, of oesophageal disease that may be poorly responsive to conventional corticosteroid-sparing immunosuppression.

The present report details the clinical and immunological features of a 53 year old Asian female who developed symptoms and signs of oesophageal PV during therapy with azathioprine and decreasing prednisolone dosage. Oesophageal involvement occurred during stable oral disease.

Oesophageal involvement can occur without significant oro-cutaneous lesions and immunological evidence of PV. This suggests that immunological targets for oesophageal disease may differ from those of other mucocutaneous areas, and that conventional first-line systemic therapy may not be effective for oesophageal lesions.

Full article available at: http://www.ingentaconnect.com/content/ubpl/wlmj/2012/00000004/00000002/art00001

Background.  Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune vesicobullous disorders with IgG autoantibodies directed against desmoglein (Dsg)1 and 3, which lead to intraepidermal acantholysis.

Aim.  To characterize the clinical and immunological profile of patients with PF or PV with umbilical involvement.

Methods.  In total, 10 patients (7 women, 3 men; age range 24–70 years, disease duration 3–16 years) diagnosed with either PV (n = 5) or mucocutaneous PF (n = 5) were assessed according to their clinical features, histopathology and immunological findings .

Results.  Erythema, erosions, crusts and vegetating skin lesions were the main clinical features of the umbilical region. DIF of the umbilical region gave positive results for intercellular epidermal IgG and C3 deposits in eight patients and for IgG alone in the other two. Indirect immunofluorescence with IgG conjugate showing the typical pemphigus pattern was positive in all 10 patients, with titres varying from 1 : 160 to 1 : 2560. ELISA with recombinant Dsg1 gave scores of 24–266 in PF and 0–270 in PV. Reactivity to recombinant Dsg3 was positive in all five patients with PV (ELISA 22–98) and was negative in all PF sera.

Conclusions.  All 10 patients with pemphigus with umbilical presentation had the clinical and immunopathological features of either PF or PV. This peculiar presentation, not yet completely elucidated, has rarely been reported in the literature. A possible explanation for this unique presentation may be the presence of either novel epitopes or an association with embryonic or scar tissue located in the umbilical-cord region.

Full article available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2230.2012.04468.x/abstract

The molecular basis of disease heterogeneity in autoimmune conditions such as Pemphigus vulgaris is poorly understood. Although desmoglein 3 (Dsg3) has been well established as a primary target of immunoglobulin (Ig) autoantibodies in PV, there remain several questions regarding the overall distribution of anti-Dsg3 Ig subtypes among patient subsets and considerable controversy regarding whether an isotype switch can be observed between phases of disease activity. To systematically address the outstanding questions related to Ig-isotype specificity in PV, we analyzed IgA, IgM, IgG1, 2, 3 and 4 anti-Dsg3 levels by ELISA in 202 serum samples obtained from 92 patients with distinct clinical profiles based on a set of defined variable (activity, morphology, age, duration) and constant (HLA-type, gender, age of onset) clinical parameters, and 47 serum samples from HLA-matched and -unmatched controls. Our findings provide support for earlier studies identifying IgG4 and IgG1 as the predominant antibodies in PV with significantly higher levels in active than remittent patients. We do not see evidence for an isotype switch between phases of disease activity and remission, and both IgG4 and IgG1 subtypes remain elevated in remittent patients relative to controls. We do, however, find IgG4 to be the sole subtype that further distinguishes PV patient subgroups based on different disease morphologies, disease duration, and HLA-types. These data provide further insight into the immune mechanisms responsible for phenotypic expression of disease, and contribute to the broader effort to establish comprehensive immunoprofiles underlying disease heterogeneity to facilitate increasingly specific and individualized therapeutic interventions.

Full article available at: http://www.ncbi.nlm.nih.gov/pubmed/22779708

Pemphigus is a chronic, muco-cutaneous autoimmune blistering disorder; two main variants being pemphigus vulgaris (PV) and pemphigus foliaceus (PF). PV is the most common subtype, varying between 75 to 92% of total pemphigus patients. Although no community based studies are undertaken to estimate the incidence of pemphigus in India, it is relatively common. A questionnaire based survey in Thrissur district of south India estimated pemphigus incidence to be 4.4 per million population. Mortality due to pemphigus has decreased remarkably with the aggressive and widespread use of corticosteroids, prior to which it was as high as 90%. High dose corticosteroids were once used in combination with other immunosuppressants with good improvement, but such high doses of corticosteroids were often associated with severe side effects, and were responsible for the death of nearly 10% of the patients. With the aim of reducing the adverse effects of long term, high dose steroid administration dexamethasone cyclophosphamide pulse (DCP) therapy was introduced in 1984. Since then DCP or oral corticosteroids with or without adjuvant immunosuppressants (azathioprine, cyclophosphamide, mycophenolatemofetil, and cyclosporine) have been the corner-stone of therapy for these disorders in India. Despite the benefits associated with DCP therapy compared to high dose oral steroids, it cannot be denied that even DCP therapy with or without adjuvants can lead to numerous adverse events, which account for majority of deaths in pemphigus. Moreover there are few patients who fail to improve with these conventional treatments or have contraindications for their usage. Thus there has been a constant search for newer therapeutic modalities in pemphigus. Rituximab (Reditux. Dr. Reddy’s, Hyderabad, India and MabThera TM , Roche, Basel, Switzerland), a monoclonal chimeric IgG1 antibody targeting the B cell specific cell-surface antigen CD20, is one such newer novel therapy for pemphigus (an off-label indication for its use. It has so far been approved by FDA for use only in CD 20+ B cell non-Hodgkin’s lymphoma, treatment resistant rheumatoid arthritis, Wegener’s granulomatosis and microscopic polyangiitis).

There is currently no consensus on the optimal dosage and schedule of rituximab in treatment of pemphigus. The various treatment protocols followed include:

  1. Lymphoma protocol- Most commonly followed protocol. Rituximab is administered at a dose of 375mg/m 2 body surface area weekly for four weeks.
  2. Rheumatoid arthritis protocol- Two doses of rituximab 1g is administered at an interval of 15 days. Increasingly used by dermatologists and is the protocol currently followed in our institute. Advantage over the lymphoma protocol include less cost and fewer infusions.
  3. Combination therapy- Rituximab has been used in combination with IVIG, immunoadsorption and dexamethasone pulse therapy
  4. Long-term rituximab treatment with regular infusions every 4 or 12 weeks following an induction cycle of infusions every week

Full article can be viewed at: http://www.ijdvl.com/article.asp?issn=0378-6323;year=2012;volume=78;issue=6;spage=671;epage=676;aulast=Kanwar

Background  The classic treatment for pemphigus vulgaris is prednisolone. Immunosuppressive drugs can be used in association.

Objective  To compare the efficacy of Azathioprine in reducing the Disease Activity Index (DAI).

Patients and methods  A double blind randomized controlled study was conducted on 56 new patients, assigned to two therapeutic groups: (i) prednisolone plus placebo; (ii) prednisolone plus Azathioprine. Patients were checked regularly for 1 year. ‘Complete remission’ was defined as healing of all lesions after 12 months, and prednisolone <7.5 mg daily, (DAI ≤ 1). Analysis was done by ‘Intention To Treat’ (ITT) and ‘Treatment Completed Analysis’ (TCA).

Results  Both groups were similar in age, gender, disease duration, and DAI. Primary endpoint: By ITT and TCA, the mean DAI improved in both groups with no significant difference between them. The difference became significant for the last trimester (3 months; ITT:P = 0.033, TCA: P = 0.045). Secondary endpoint: The total steroid dose decreased significantly in both groups, with no significant difference between them, except for the last trimester (ITT: P = 0.011, TCA: P = 0.035). The mean daily steroid dose decreased gradually in both groups becoming statistically significant in favour of azathioprine, in the last trimester, especially at 12th months (ITT: P = 0.002, TCA:P = 0.005). Complete remission was significant at 12 months only for TCA (AZA/Control: 53.6%/39.9%, P = 0.043).

Limitations  Sample size was rather small to demonstrate all differences. Other limitations include the choice of primary and secondary endpoints and the unavailability to measure thiopurine methyltransferase activity.

Conclusion  Azathioprine helps to reduce prednisolone dose in long-run.

Full article available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1468-3083.2012.04717.x/abstract;jsessionid=4F8C646E8902BB54AC0026B542EF91FD.d03t01