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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

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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.

http://www.ncbi.nlm.nih.gov/pubmed/21996575?dopt=Abstract

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

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vulgaris may not occur immediately after birth.

http://onlinelibrary.wiley.com/doi/10.1111/j.1525-1470.2012.01828.x/abstract;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: http://www.e-ijd.org/text.asp?2012/57/5/411/100513

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.

http://www.ncbi.nlm.nih.gov/pubmed/22892774?dopt=Abstract

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 .
http://onlinelibrary.wiley.com/doi/10.1111/bjd.12012/abstract

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.
http://www.ncbi.nlm.nih.gov/pubmed/22803659?dopt=Abstract
Authors: Asahina A, Koga H, Suzuki Y, Hashimoto T Abstract IgA pemphigus includes subcorneal pustular dermatosis (SPD)-type and intraepidermal neutrophilic IgA dermatosis (IEN)-type. Cases of IgG/IgA pemphigus have recently been documented(1) . Nonetheless, individual reports of IgA pemphigus indicate considerable heterogeneity. PMID: 22757612 [PubMed – as supplied by publisher] (Source: The British Journal of Dermatology)
http://www.ncbi.nlm.nih.gov/pubmed/22757612?dopt=Abstract
Background:  Pemphigus vulgaris (PV) is an autoimmune blistering skin disorder characterized by the presence of suprabasal acantholysis and autoantibodies against desmoglein 3. There are two different clinical forms: mucocutaneous (MCPV) or mucosal (MPV). However, it is not clear how PV lesions in oral, ear, nose and throat (OENT) areas produced by the very dynamic of the anatomical structures involved in the functions of the aerodigestive tract. Objectives:  To investigate the pattern of OENT manifestations in PV, and their relationship with physiological traumatic mechanisms in stratified squamous epithelium structures. Patients:  A prospective analysis of 40 patients diagnosed with MCPV (22 patients) or MPV (18 patients) was carried out in the University Clinic of Navarra. OENT manifestations were evaluated in all patients endoscopically. OENT involvement was divided into anatomical areas. Results:  The most frequent symptom was pain, mainly on oral mucosa (87,5%). Buccal mucosa (90%), posterior wall of pharynx (67.5%), upper edge of epiglottis (85%) and nasal vestibule (70%) were the areas most frequently affected in the OENT mucosa. These localizations were related to physiological traumatic mechanisms in polystratified squamous epithelium structures. Conclusions:  OENT endoscopy should be included in the examination of all PV patients. To know the most frequent localizations of active lesions on OENT mucosa in PV will help us to interpreter more efficiently the findings from OENT endoscopy. Also, information related to traumatic physiological mechanisms on OENT areas must be offered to patients in order to avoid the appearance of new active PV lesions.
PMID: 22716123 [PubMed – as supplied by publisher] (Source: The British Journal of Dermatology)
from MedWorm: Pemphigus http://www.medworm.com/index.php?rid=6310669&cid=c_297_12_f&fid=37668&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2FPubMed%2F22716123%3Fdopt%3DAbstract

Bullous pemphigoid (BP) is an autoimmune blistering skin disease. Autoantibodies to BP180 and BP230 can be detected by indirect immunofluorescence (IIF) on different substrates (oesophagus, salt-split-skin, BP180-antigen dots, BP230-transfected cells) and ELISA. Here, we compared test characteristics of these test systems. We analysed sera from BP patients (n=60) in whom the clinical diagnosis had been confirmed histopathologically. The control cohort comprised sera from patients with other autoimmune-associated (n=22) or inflammatory (n=35) skin diseases. All samples were tested by IIF (EUROIMMUN™ Dermatology Mosaic) and ELISA (EUROIMMUN and MBL). Anti-BP180 is best detected with BP180-antigen dots by IIF (sensitivity: 88%; specificity: 97%). As

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compared to IIF, the differences with both BP180 ELISA techniques are small though. Likelihood ratios (LRs) for positive and negative test results are >10 and between 0.1 and 0.2, respectively, for all test systems. Detection of anti-BP230 is highly variable (sensitivity range 38-60%; specificity range 83-98%). Only the IIF test reveals a LR for positive test results >10. Since the LRs for a negative test are all ~0.5, negative test results for anti-BP230 antibodies do not help to exclude BP. In conclusion, the multi-parameter IIF test reveals a good diagnostic performance in BP. Since this test simultaneously allows for the detection of anti-Dsg1 and anti-Dsg3 antibodies, involved in pemphigus foliaceus and vulgaris, a single test-incubation may be sufficient to differentiate between the most frequent autoimmune blistering diseases.

In conclusion, the multi-parameter IIF test reveals a good diagnostic performance in BP. Since this test simultaneously allows for the detection of anti-Dsg1 and anti-Dsg3 antibodies, involved in pemphigus foliaceus and vulgaris, a single test-incubation may be sufficient to differentiate between the most frequent autoimmune blistering diseases. PMID: 22580378 [PubMed – in process] (Source: Journal of Immunological Methods)
from MedWorm: Pemphigus http://www.medworm.com/index.php?rid=6304089&cid=c_297_3_f&fid=33859&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2FPubMed%2F22580378%3Fdopt%3DAbstract

Abstract

BACKGROUND:

Systematic reviews and meta-analysis are essential tools to accurately and reliably summarize evidence, and can be used as a starting point for developing practice guidelines for the diagnosis and treatment of patients.

AIM:

To estimate the diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) to detect anti-BP180 and anti-desmoglein 3 (Dsg3) autoantibodies in the diagnosis of autoimmune blistering skin diseases.

METHODS:

A Medline search of English written articles, published between 1994 and 2011, reporting data on the sensitivity and specificity of diagnostic tests was conducted using the following search terms: “BP180 autoantibodies”, “Dsg3 autoantibodies”, and “enzyme linked immunosorbent assay”. The selected articles have been evaluated according to the quality of the statistical methods used to calculate diagnostic accuracy (definition of cutoff value, use of ROC curves, and selection of control cases). The meta-analysis was performed using a summary ROC (SROC) curve and a random-effect model to independently combine sensitivity and specificity across studies.

RESULTS:

The search yielded 69 publications on BP180 autoantibodies and 178 on Dsg3 autoantibodies. A total of 30 studies met the inclusion criteria: 17 provided data on the assays to detect autoantibodies to BP180 in a sample of 583 patients with bullous pemphigoid (BP), while 13 studies provided data on the assays to search for anti-Dsg3 autoantibodies in a sample of 1058 patients with pemphigus vulgaris (PV). The 17 studies on BP180 autoantibodies yielded a pooled sensitivity of 0.87 (95% confidence interval (CI) 0.85 to 0.89) and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The area under the curve (AUC) for the SROC curve was 0.988, and the summary diagnostic odds ratio was 374.91 (CI, 249.97 to 562.30). The 13 studies on Dsg3 autoantibodies which met the inclusion criteria, yielded a pooled sensitivity of 0.97 (CI, 0.95 to 0.98), and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The AUC for the SROC curve was 0.995 and the summary diagnostic odds ratio was 1466.11 (95% CI, 750.36 to 2864.61).

CONCLUSIONS:

Results of the meta-analysis demonstrated that ELISA tests for anti-BP180 and anti-Dsg3 autoantibodies have high sensitivity and specificity for BP and PV, respectively, and can be used in daily laboratory practice for the initial diagnosis of autoimmune blistering skin diseases.
PMID: 22781589 [PubMed – as supplied by publisher] (Source: Autoimmunity Reviews)

from MedWorm: Pemphigus http://www.medworm.com/index.php?rid=6303276&cid=c_297_3_f&fid=34528&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2FPubMed%2F22781589%3Fdopt%3DAbstract