Sharon Baum

Low-dose methotrexate treatment for moderate-to-severe atopic dermatitis in adults

Background  Atopic dermatitis (AD) is a common inflammatory skin disease. Methotrexate (MTX) was suggested as an effective treatment option in cases of moderate‐to‐severe atopic dermatitis. This study assessed the efficacy and safety of treatment with low weekly doses of methotrexate for moderate‐to‐severe AD in adults.

Diagnosis and classification of autoimmune blistering diseases

Blistering skin diseases are a group of autoimmune disorders that are characterized by autoantibodies against structural proteins of the epidermis or the dermal-epidermal junction and clinically by blisters and erosions on skin and/or mucous membranes. Since clinical criteria and histopathological characteristics are not sufficient for diagnosis, direct immunofluorescence microscopy of a biopsy specimen or serological tests are needed for exact diagnosis. The differentiation between the various disorders became more important since prognosis as well as different treatment options are nowadays available for the various diseases. Moreover, some bullous diseases may indicate the presence of an underlying malignancy. The detection of serum autoantibodies have been shown to correlate with disease activity and thus may be helpful in deciding treatment options for these patients.

Autoimmune bullous diseases: The spectrum of infectious agent antibodies and review of the literature

Pemphigus and bullous pemphigoid are two autoimmune diseases that have a similar pathogenesis. Both have a genetic predisposition which promotes the production of auto-antibodies targeted against different components of the epidermal desmosome and hemidesmosome. Environmental factors play an important role in the pathogenesis of this autoimmune disease. Among these, the role of infectious agents was debated as a causative factor. We sought to determine a possible connection between various infectious agents and autoimmune bullous disease (ABD). A cohort of 148 serum samples of patients with pemphigus, bullous pemphigoid and controls was screened for evidence of a prior infection with HBV, HCV, EBV, CMV, Helicobacter pylori, Toxoplasma gondii and Treponema pallidum, utilizing the Bio-Rad BioPlex 2200 system as well as ELISA assays to complete the panel. HBV, HCV, H. pylori, T. gondii and CMV were demonstrated to have significantly higher prevalence of antibodies in patients with pemphigus and bullous pemphigoid in comparison to controls. Among them, we found a novel association between H. pylori and ABD. Our study suggests a contributing role for HBV, HCV, H. pylori, T. gondii and CMV in inducing ABD in the genetically susceptible host.

The role of IVIg treatment in severe pemphigus vulgaris

Background  High‐dose intravenous immunoglobulin (IVIg) has become a part of the treatment armentarium in pemphigus vulgaris (PV). Some consider IVIg as an adjuvant steroid sparing agent in PV, while others as disease modifying that can be used as monotherapy.

Population-Specific Association between a Polymorphic Variant in ST18, Encoding a Pro-Apoptotic Molecule, and Pemphigus Vulgaris

Pemphigus vulgaris (PV) is a severe autoimmune blistering disease caused by anti-epithelial antibodies, leading to disruption of cell-cell adhesion. Although the disease is exceedingly rare worldwide, it is known to be relatively prevalent in Jewish populations. The low prevalence of the disease represents a significant obstacle to a genome-wide approach to the mapping of susceptibility genes. We reasoned that the study of a genetically homogeneous cohort characterized by a high prevalence of PV may help exposing associated signals while reducing spurious results due to population sub-structure. We performed a genome-wide association study using 300K single-nucleotide polymorphisms (SNPs) in a case-control study of 100 PV patients of Jewish descent and 397 matched control individuals, followed by replication of significantly associated SNPs in three additional cohorts of Jewish, Egyptian, and German origin. In addition to the major histocompatibility complex locus, a genomic segment on 8q11.23 that spans the ST18 gene was also found to be significantly associated with PV. This association was confirmed in the Jewish and Egyptian replication sets but not in the German sample, suggesting that ST18-associated variants may predispose to PV in a population-specific manner. ST18 regulates apoptosis and inflammation, two processes of direct relevance to the pathogenesis of PV. Further supporting the relevance of ST18 to PV, we found this gene to be overexpressed in the skin of PV patients as compared with healthy individuals.

Narrow band UVB: is it effective and safe for paediatric psoriasis and atopic dermatitis?

Background  Phototherapy has a time‐honoured place in the treatment of variety of skin diseases in adults. The use of this modality in children is limited mainly due to concerns about long‐term carcinogenic potential. Only a few clinical trials have been performed on the efficacy and safety of phototherapy in children.

Treatment of cutaneous leishmaniasis with intralesional sodium stibogluconate.

Background  Cutaneous leishmaniasis is endemic in Israel. Leishmania major is the most prevalent species that cause cutaneous leishmaniasis. Current treatment options are limited and there are few investigations in search of alternative ones.

Evidence for Methotrexate as a Useful Treatment for Steroid- dependent Chronic Urticaria

Chronic urticaria is a relatively common disorder that can be severe and may impair quality of life. The management of recalcitrant chronic urticaria that is not responding to histamine antagonists includes short-term systemic corticosteroids, anti-inflammatory drugs (colchicine, dapsone and sulfasalazine) and immunomodulatory agents, such as cyclosporine, methotrexate, plasmapheresis and intravenous immunoglobulin. We report here our retrospective experience with the use of methotrexate in 8 patients (2 males and 6 females) with recalcitrant chronic urticaria who were not responding to high-dose first- and second-generation antihistamines. The mean duration of the disease prior to methotrexate treatment was 12 ± 8 months. Patients were treated for a mean duration of 4.5 months with a mean dose of 15 mg methotrexate/week. A complete response was achieved in 7 out of 8 patients (87%). Five out of the 7 patients were disease-free during a period of 1-10 months follow-up after discontinuing methotrexate and prednisone therapy. No serious adverse effects were reported. Methotrexate is an effective and safe treatment for chronic urticaria in patients who are not responsive to conventional therapy.

UVB therapy of pityriasis lichenoides--our experience with 29 patients.

Background  Pityriasis lichenoides comprises a clinical and pathological spectrum of disorders. So far no highly effective treatment has been reported. Previous small studies have suggested that ultraviolet B (UVB) is a good alternative.

Identification of a Functional Risk Variant for Pemphigus Vulgaris in the ST18 Gene.

Pemphigus vulgaris (PV) is a life-threatening autoimmune mucocutaneous blistering disease caused by disruption of intercellular adhesion due to auto-antibodies directed against epithelial components. Treatment is limited to immunosuppressive agents, which are associated with serious adverse effects. The propensity to develop the disease is in part genetically determined. We therefore reasoned that the delineation of PV genetic basis may point to novel therapeutic strategies. Using a genome-wide association approach, we recently found that genetic variants in the vicinity of the ST18 gene confer a significant risk for the disease. Here, using targeted deep sequencing, we identified a PV-associated variant residing within the ST18 promoter region (p<0.0002; odds ratio = 2.03). This variant was found to drive increased gene transcription in a p53/p63-dependent manner, which may explain the fact that ST18 is up-regulated in the skin of PV patients. We then discovered that when overexpressed, ST18 stimulates PV serum-induced secretion of key inflammatory molecules and contributes to PV serum-induced disruption of keratinocyte cell-cell adhesion, two processes previously implicated in the pathogenesis of PV. Thus, the present findings indicate that ST18 may play a direct role in PV and consequently represents a potential target for the treatment of this disease.