Tag Archives: pemphigus foliaceus

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

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

Pemphigus foliaceus, the most common autoimmune skin condition in dogs and cats, is characterized by pustules, erosions, and crusts. In this article, we focus on the diagnosis and treatment of pemphigus foliaceus in dogs and cats.

The signs of an attack on keratinocyte adhesion structures are clinically evident. When the tight bonds between superficial keratinocytes are affected, it manifests as vesicles and pustules. When the tight bonds between basilar keratinocytes and the skin’s basement membrane are affected, it manifests as bullae (large blisters) and ulcers.

In pemphigus foliaceus in people, the most common target of autoantibodies is the desmoglein 1 (DSG1) glycoprotein in the desmosome. The autoantibody response primarily involves IgG (IgG4 subclass). Initial studies in dogs with pemphigus foliaceus only rarely detected an IgG autoantibody response, but more recent work using different substrates in indirect immunofluorescence testing confirms that IgG autoantibodies are important in canine pemphigus foliaceus. However, DSG1 is not commonly targeted in pemphigus foliaceus in dogs ; it is not yet known which part of the desmosome is targeted in most canine pemphigus foliaceus cases. Early immunoblotting studies revealed that the target was a 148 kDa or 160 kDa protein. Immunoelectron microscopy shows that the site of autoantibody binding is in the extracellular region of the desmosome.

Genetic factors can influence the development of pemphigus foliaceus. In dogs, it is more frequently diagnosed in two breeds with closely related genotypes, Akitas and chows. Pemphigus foliaceus has also been reported in littermates. No breed disposition has been noted in feline pemphigus foliaceus. Sex and age appear to be unrelated to the development of pemphigus foliaceus in dogs and cats. The age of onset is variable and ranges from 1 to 16 years in dogs and less than 1 year of age4 to up to 17 years of age in cats.

Background  Pemphigus foliaceus (PF) is a chronic cutaneous autoimmune blistering disease that is characterized by superficial blistering of the skin, and according to the current perspective is caused by autoantibodies directed against desmoglein (Dsg) 1.

Objectives  To examine early acantholysis in the skin of patients with PF at an ultrastructural level.

Methods  Two Nikolsky-negative (N−), five Nikolsky-positive (N+) and two lesional skin biopsies from immunoserologically defined patients with PF were studied by light and electron microscopy.

Results  We found no abnormalities in N− PF skin, whereas all the N+ skin biopsies displayed intercellular widening between desmosomes, a decreased number of desmosomes and hypoplastic desmosomes in the lower epidermal layers. Acantholysis was present in two of five N+ biopsies, but only in the upper epidermal layers. The lesional skin biopsies displayed acantholysis in the higher epidermal layers. Hypoplastic desmosomes were partially (pseudo-half-desmosomes) or completely torn off from the opposing cell.

Conclusion  We propose the following mechanism for acantholysis in PF: initially PF IgG causes a depletion of nonjunctional Dsg1, leading to intercellular widening between desmosomes starting in the lower layers and spreading upwards. Depletion of nonjunctional Dsg1 impairs the assembly of desmosomes, resulting in hypoplastic desmosomes and a decreased number of desmosomes. In addition, antibodies might promote disassembly of desmosomes. In the upper layers of the epidermis, where Dsg3 is not expressed and cannot compensate for Dsg1 loss, ongoing depletion of Dsg1 will finally result in a total disappearance of desmosomes and subsequent acantholysis.

Full article available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.2012.11173.x/abstract;jsessionid=624E75DA95767387AA80E95C275F4100.d02t01

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


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.

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.


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)