Monthly Archives: September 2012

MADAM, Autoantibodies in pemphigus target preferentially desmoglein 1 (Dsg1) and Dsg3, and rarely desmocollins 1-3 (Dsc1-3). Pemphigus herpetiformis (PH) is one of pemphigus subtypes and characterized by pruritic annular erythemas with vesicles in the periphery, rarity of mucosal involvement and histopathological change of eosinophilic spongiosis. Recently, IgG anti-Dsc3 autoantibodies were suggested to cause skin lesion in a case of pemphigus vulgaris. In this study, we report the first case of concurrent bullous pemphigoid (BP) and PH with IgG antibodies to both Dsgs and Dscs.


Background  Promoter polymorphisms of the macrophage migration inhibitory factor gene are associated with increased production of macrophage migration inhibitory factor. Elevated levels of macrophage migration inhibitory factor have been observed in the sera of patients with pemphigus vulgaris. More than this, macrophage migration inhibitory factor promoter gene polymorphism has been found to confer increased risk of susceptibility to chronic inflammatory diseases.

Objective  We investigated whether there is an association between promoter polymorphism of the macrophage migration inhibitory factor gene and pemphigus vulgaris.

Methods  One hundred and six patients with pemphigus vulgaris, and a control panel of one hundred healthy volunteers were genotyped for a single nucleotide polymorphism identified in the 5′-flanking region at the position −173 of the gene, using polymerase chain reaction–restriction fragment length analysis.

Results  We found a notably high prevalence of C/C genotype in our nation but no significant difference was observed between patients and controls.

Conclusion  The result of this study using a large and well documented trial of patients showed that macrophage migration inhibitory factor −173G-C polymorphism is not associated with pemphigus vulgaris; but as the role of macrophage migration inhibitory factor in the inflammatory process has not been delineated in detail and the prevalence of C/C genotype is notably higher in our nation, this finding merits more consideration.

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Various antigen-specific immunoassays are available for the serological diagnosis of autoimmune bullous diseases. However, a spectrum of different tissue-based and monovalent antigen-specific assays is required to establish the diagnosis. BIOCHIP mosaics consisting of different antigen substrates allow polyvalent immunofluorescence (IF) tests and provide antibody profiles in a single incubation.


Slides for indirect IF were prepared, containing BIOCHIPS with the following test substrates in each reaction field: monkey esophagus, primate salt-split skin, antigen dots of tetrameric BP180-NC16A as well as desmoglein 1-, desmoglein 3-, and BP230gC-expressing human HEK293 cells. This BIOCHIP mosaic was probed using a large panel of sera from patients with pemphigus vulgaris (PV, n equals 65), pemphigus foliaceus (PF, n equals 50), bullous pemphigoid (BP, n equals 42), and non-inflammatory skin diseases (n equals 97) as well as from healthy blood donors (n equals 100). Furthermore, to evaluate the usability in routine diagnostics, 454 consecutive sera from patients with suspected immunobullous disorders were prospectively analyzed in parallel using a) the IF BIOCHIP mosaic and b) a panel of single antibody assays as commonly used by specialized centers.


Using the BIOCHIP mosaic, sensitivities of the desmoglein 1-, desmoglein 3-, and NC16A-specific substrates were 90 percent, 98.5 percent and 100 percent, respectively. BP230 was recognized by 54 percent of the BP sera. Specificities ranged from 98.2 percent to 100 percent for all substrates. In the prospective study, a high agreement was found between the results obtained by the BIOCHIP mosaic and the single test panel for the diagnosis of BP, PV, PF, and sera without serum autoantibodies (Cohen’s kappa between 0.88 and 0.97).


The BIOCHIP mosaic contains sensitive and specific substrates for the indirect IF diagnosis of BP, PF, and PV. Its diagnostic accuracy is comparable with the conventional multi-step approach. The highly standardized and practical BIOCHIP mosaic will facilitate the serological diagnosis of autoimmune blistering diseases.

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Pemphigus is a potentially fatal autoimmune epidermal bullous disorder. Rituximab is a novel therapy for the treatment of refractory pemphigus. However, there is limited clinical data on safety and efficacy of rituximab in pediatric age group. Herein, we report an 11-year-old boy of childhood pemphigus vulgaris who failed to respond to dexamethasone pulse therapy and was subsequently treated with rituximab and achieved complete remission.;year=2012;volume=78;issue=5;spage=632;epage=634;aulast=Kanwar

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.

Dichorionic diamniotic twins were born at 37 weeks of gestation by cesarean section to a 34-year-old primigravid Japanese woman because the first twin was in breech presentation. The mother had been diagnosed with pemphigus vulgaris prior to her pregnancy. In addition to a high antidesmoglein 3 autoantibody titer, flaccid bullae and erosions on both of the twins’ lips and in their oral cavities at 13 days of age led to the diagnosis of neonatal pemphigus vulgaris. This case highlights the need for awareness that pemphigus vulgaris may not occur immediately after birth.;jsessionid

Associations between blood groups and several diseases are observed in the literature. Some of these have scientific support suggesting a rationale, statistical relation. The association between ABO groups with several malignancies, hypercholesterolemia, thrombosis, myocardial infarction, duodenal ulcer, infections, and autoimmune diseases is reported.  Pemphigus vulgaris (PV), a rare autoimmune, blistering disease, related to autoantibodies mainly directed to desmogleins, which lead to loss of keratinocyte adhesion.  The association between ABO groups and pemphigus has been proposed but not fully demonstrated. Shahkar et al., concluded the non-existent relationship between blood groups and the development of PV. The authors carried out a case-control study that showed there is no real association between blood groups and PV, in contrast to the work of Grob and Inderbitzin  and Altobella.  The authors determined that the presence of a particular blood group, in patients with the disease, does not vary significantly with “healthy” population distribution, which is very important because the relationship between blood groups and skin diseases has been controversial and not yet fully elucidated or explained clearly.

In 2007, Valikhani et al.,  showed not only that the ABO and Rhesus blood groups not have a particular distribution in the PV, other than the population, but no such relationship with any of the known variants of pemphigus, at least in Iran, suggesting the authors to conduct a study involving other areas of global demographic.

In Mexico, we conducted a similar study in a tertiary referral center for specialized dermatology consultation. We obtained the ABO and Rhesus blood groups of patients with PV in a period between January 2002 and October 2009, being our hospital a center that collects patients from different parts of Mexico and even South America.

We selected 70 charts of patients with PV. No differences in the presence of a particular blood group in patients with the disease were found (P=0.65). We sought to evaluate if any ABO group correlates with the clinical outcome (body surface area affected) of the patients studied. There were no positive or negative correlation between ABO groups and clinical outcome in PV (P=0.752)

We conclude, there is no association between ABO and Rhesus blood groups with PV, demonstrated by observing no differences between the presentations of a specific blood group in the disease. Moreover, there is no association between any ABO groups with the clinical outcome in PV.

Tirado-Sánchez A, Ponce-Olivera RM. Lack of relationship between blood groups and clinical outcome (body surface area affected) in patients with pemphigus vulgaris. Indian J Dermatol [serial online] 2012 [cited 2012 Sep 12];57:411-2. Available from:

A focused and commented review on the impact of dermatologic diseases and interventions in the solidary act of donating blood is presented to dermatologists to better advise their patients. This is a review of current Brazilian technical regulations on hemotherapeutic procedures as determined by Ministerial Directive #1353/2011 by the Ministry of Health and current internal regulations of the Hemotherapy Center of Ribeirão Preto, a regional reference center in hemotherapeutic procedures. Criteria for permanent inaptitude: autoimmune diseases (>1 organ involved), personal history of cancer other than basal cell carcinoma, severe atopic dermatitis or psoriasis, pemphigus foliaceus, porphyrias, filariasis, leprosy, extra pulmonary tuberculosis or paracoccidioidomycosis, and previous use of etretinate. Drugs that impose temporary ineligibility: other systemic retinoids, systemic corticosteroids, 5-alpha-reductase inhibitors, vaccines, methotrexate, beta-blockers, minoxidil, anti-epileptic, and anti-psychotic drugs. Other conditions that impose temporary ineligibility: occupational accident with biologic material, piercing, tattoo, sexually transmitted diseases, herpes, and bacterial infections, among others. Discussion: Thalidomide is currently missing in the teratogenic drugs list. Although finasteride was previously considered a drug that imposed permanent inaptitude, according to its short halflife current restriction of 1 month is still too long. Dermatologists should be able to advise their patients about proper timing to donate blood, and discuss the impact of drug withdrawal on treatment outcomes and to respect the designated washout periods.

We read with interest the study by Koga H et al1 and we believe that in light of recent observations including our data (Table 1) the “desmoglein compensation theory” as a explanation for localization of blisters should be revisited 2,3,4. Although the disruption of desmoglein-dependent cell adhesion by autoantibodies is the basic pathophysiology underlying blister formation in pemphigus 2−4, the clinical spectrum does not always mirror this pathogenic process. Three clinical types of pemphigus have been described, the mucosal dominant, cutaneous and mucocutaneous type 2,,3,4 .

Background:  Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially fatal blistering diseases caused by autoantibodies targeting desmoglein adhesion proteins. Previous studies have shown an IgG4>IgG1 predominance of anti-desmoglein antibodies in pemphigus; however, no studies have examined total serum IgG4 levels in pemphigus. IgG4 is induced by chronic antigen stimulation, which could occur with persistent skin blistering and potentially elevate the total serum IgG4 relative to other IgG subclasses in pemphigus patients. Objectives:  The primary aim of the study was to quantitate total and desmoglein-specific IgG subclasses in pemphigus patients. Methods:  IgG subclasses and desmoglein-specific IgG1 and IgG4 were quantitated in PV, PF, and age-matched normal sera using a subclass ELISA. The effectiveness of IgG4 depletion in blocking PV IgG pathogenicity was determined using a keratinocyte dissociation assay. Results:  Desmoglein-specific antibodies comprised a median of 7.1% and 4.2% of total IgG4 in PV and PF patients, with 8-fold and 4-fold enrichment in IgG4 versus IgG1. Total serum IgG4, but not other IgG subclasses, was enriched in PV and PF patients compared to age-matched controls (p=0.004 and p=0.005, respectively). IgG4 depletion of PV sera reduced pathogenicity in a keratinocyte dissociation assay and showed that affinity-purified IgG4 is more pathogenic than other serum IgG fractions. Conclusions:  Desmoglein-specific autoantibodies are significantly enriched in IgG4, which may explain the enrichment of total serum IgG4 in some pemphigus patients. By preferentially targeting autoimmune rather than beneficial immune antibodies, IgG4-targeted therapies may offer safer treatment options for pemphigus.