Tag Archives: pemphigus foliaceus

This study aimed to highlight the importance of routine screening for hyperglycemia and to develop a standardized, evidence-based approach for the management of pemphigus patients on prolonged systemic corticosteroid (CS) therapy. A cross-sectional study was conducted in two university-affiliated teaching hospitals using a referred sample of 200 patients with a confirmed diagnosis of pemphigus vulgaris, pemphigus foliaceus, or mucous membrane pemphigoid. All patients were receiving systemic CS therapy. A total of 150 patients responded to the survey. Six participants were excluded and 144 were included. The main outcome measure was blood glucose level to detect hyperglycemia. New-onset hyperglycemia was identified in 40% of patients who received CS therapy. None of the expected variables, including age, body mass index, family history of diabetes, corticosteroid dose, and duration of corticosteroid therapy, were independently associated with new-onset hyperglycemia. These findings indicate that the prevalence of CS-induced hyperglycemia in pemphigus patients is 40% and that in patients with pemphigus or MMP, CS therapy is associated with a markedly increased risk for hyperglycemia (odds ratio = 10.7, 95% confidence interval 1.38–83.50) compared with that of patients with the same diseases who do not receive CS therapy.

Full article available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-4632.2012.05470.x/abstract

Background  Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially fatal blistering diseases caused by autoantibodies targeting desmoglein (Dsg) adhesion proteins. Previous studies have shown an IgG4 > IgG1 predominance of anti-Dsg 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 patients with pemphigus.

Objectives  The primary aim of the study was to quantitate total and Dsg-specific IgG subclasses in patients with pemphigus.

Methods  IgG subclasses and Dsg-specific IgG1 and IgG4 were quantitated in patients with PV and PF, and in sera from age-matched controls using a subclass enzyme-linked immunosorbent assay. The effectiveness of IgG4 depletion in blocking IgG pathogenicity in PV was determined using a keratinocyte dissociation assay.

Results  Dsg-specific antibodies comprised a median of 7·1% and 4·2% of total IgG4 in patients with PV and PF, respectively, with eightfold and fourfold enrichment in IgG4 vs. IgG1. Total serum IgG4, but not other IgG subclasses, was enriched in patients with PV and PF compared with 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  Dsg-specific autoantibodies are significantly enriched in IgG4, which may explain the enrichment of total serum IgG4 in some patients with pemphigus. By preferentially targeting autoimmune rather than beneficial immune antibodies, IgG4-targeted therapies may offer safer treatment options for pemphigus.

Full article available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.2012.11144.x/abstract

We evaluated the effectiveness of mizoribine, a newly developed immunosuppressive agent, as an adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. Eleven pemphigus patients (eight pemphigus vulgaris and three pemphigus foliaceus) received the combination therapy of prednisolone and mizoribine. Complete remission was observed in three of the eight patients with pemphigus vulgaris and in one of the three patients with pemphigus foliaceus. The four patients with complete remission had a rapid clinical response and achieved remission at a median of 11.8 months. Partial remission was achieved in two of the three patients with pemphigus foliaceus. The median time to achieve partial remission was 16.0 months. Six (55.6%) of the 11 patients with pemphigus had complete or partial remission and were able to taper their prednisolone. The cumulative probability of having a complete remission was 64.3% at 19 months of follow-up using Kaplan–Meier analysis. The effectiveness of the additional mizoribine therapy could be attributed to its corticosteroid-sparing properties as well as its immunosuppressive effects. The serum concentration titer of mizoribine was around 1.0 μg/mL 2 hours after administration. Patients who were not improved by the additional mizoribine might require a continuously higher dose of mizoribine to achieve effective therapy.

Full Article available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1529-8019.2012.01469.x/abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Full article available at: http://www.medworm.com/index.php?rid=6328120&cid=c_297_49_f&fid=36647&url=http%3A%2F%2Fwww.ojrd.com%2Fcontent%2F7%2F1%2F49

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

Background -  Glucocorticoids as sole therapy for pemphigus foliaceus (PF) in cats are not always successful, and it is common to need additional immunomodulating agents to manage the disease. Hypothesis/Objectives -  This retrospective study evaluated the use of modified ciclosporin as an adjuvant or sole immunomodulating drug in cats with PF and compared their response to PF cats managed with chlorambucil. Animals -  Fifteen client-owned cats diagnosed with PF that received ciclosporin and/or chlorambucil as part of their treatment and had adequate follow-up to assess treatment response were evaluated. Methods -  Records were reviewed from feline PF patients presented between the years of 1999 and 2009. Cats were divided into two treatment groups: those treated with ciclosporin and those treated with chlorambucil. Most cats in both groups also received concurrent systemic glucocorticoids. Each group contained six patients. Three cats were treated with both medications and are discussed separately. Time to disease remission, remission-inducing glucocorticoid dose, maintenance or final glucocorticoid dose, disease response and adverse effects were assessed. Results -  There was no significant difference in remission times or disease response between groups. All six patients maintained with ciclosporin for PF management were weaned off systemic glucocorticoids, while glucocorticoid therapy was stopped in only one of the six cats receiving chlorambucil. Conclusions and clinical importance -  Modified ciclosporin is effective in the management of feline pemphigus foliaceus and is glucocorticoid sparing. PMID: 22731616 [PubMed – as supplied by publisher] (Source: Veterinary Dermatology)
http://www.ncbi.nlm.nih.gov/pubmed/22731616?dopt=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://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.2012.11144.x/abstract

Neuromyelitis optica (NMO, also eponymously known as Devic’s disease) is an immune‐mediated demyelinating disease of the central nervous system that can lead to significant disability. Pediatric NMO is a rare disorder often reported after an infection. The authors report a 16year-old female patient with pemphigus foliaceus who developed subacute optic neuritis followed by cervical transverse myelitis. Restricted distribution of the lesions in the optic nerve and spinal cord was confirmed by ophthalmological evaluation and magnetic resonance imaging of the brain and spinal cord. She was started on intravenous methylprednisolone and then given a maintenance oral prednisone. Subsequently, she was treated with a nonsteroidal immunosuppressant, mycophenolate mofetil, with a target dose of 1000mg twice a day. Over the course of months, patient noted significant recovery of previous deficits and resolution of the cervical cord enhancement, expansion and cystic dilatation that was previously seen. This case is noteworthy for being the first patient reported with neuromyelitis optica associated with pemphigus foliaceus.

 

Source: http://www.jns-journal.com/article/PIIS0022510X12002183/abstract

Herpes virus infections are well known infectious complications of pemphigus and bullous pemphigoid. We describe pathologic findings utilizing autopsy tissue from several organs from a patient affected by a new variant of endemic pemphigus in El Bagre, Colombia, South America.

We describe a patient by a new variant of endemic pemphigus foliaceus from El Bagre that was receiving high-dosage immunosuppressants when hospitalized and died suddenly following contact with a second patient affected by chicken pox.

We performed studies utilizing hematoxylin and eosin, immunohistochemistry, and direct immunofluorescence techniques on tissues from several organs.

We detected the presence of varicella zoster virus, as well as strong positivity for α-1 antitrypsin in the heart, kidneys, spleen, liver, skin, brain, lungs, pancreas, small and large intestines, and skeletal muscle. In regard to structural damage in the kidney and heart, we believe the observed damage is associated with the presence of autoantibodies to these organs, since both of them are rich in plakins and El Bagre-EPF patients present significant antibodies to plakin molecules.

In patients with endemic pemphigus foliaceus, we recommend complete isolation of the patient when receiving high dosages of systemic immunosuppressive agents. We further suggest the clinical possibility of a synergistic, fatal interaction between active pemphigus foliaceus, varicella zoster virus, herpes simplex virus, immunosuppressive agents, and a systemic activation of α-1 antitrypsin. Thus, we suggest adequate bed spacing, barrier nursing, and preventative testing for α-1 antitrypsin activation are warranted in these patients to address these complications.

 

Source: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-4632.2011.05296.x/abstract