TNF-alpha and IL-10 gene polymorphisms show a weak association with pemphigus vulgaris in the Slovak population.

BACKGROUND: Pemphigus vulgaris is a rare chronic autoimmune disease of skin and mucous membranes, with several cytokines participating in its development. The role of their gene polymorphisms in susceptibility to the disease is, however, not fully understood. OBJECTIVE: The aim of our case-control study was to investigate whether some of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes (IL-1alpha, IL-1beta, IL-1RI, IL-1Ra, IL-4Ralpha, IL-12, IFN-gamma, TGF-beta1, TNF-alpha, IL-2, IL-4, IL-6 and IL-10) are associated with pemphigus vulgaris in the Slovak population. METHODS: DNA samples were obtained from 34 pemphigus vulgaris patients and 140 healthy controls of Slovak origin. Cytokine gene SNPs were determined using the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. Results We found a weak association between pemphigus vulgaris and polymorphic variants in TNF-alpha and IL-10 genes only, with haplotypes TNF-alpha-308G/-238G and IL-10 -1082A/-819C/-592C being significantly overrepresented in pemphigus vulgaris patients (TNF-alpha GG: 94.12% vs. 82.86%, P = 0.0216; IL-10 ACC: 44.12% vs. 30.00%, P = 0.0309). CONCLUSIONS: Our preliminary results suggest that certain TNF-alpha and IL-10 gene polymorphisms might contribute to genetic susceptibility to pemphigus vulgaris; however, their overall impact on disease development will be rather limited.

Norwegian scabies in immunosuppressed patient misdiagnosed as an adverse drug reaction.

BACKGROUND: Norwegian or crusted scabies is considered a rare affection and presumably represents an abnormal host immune response to Sarcoptes scabiei. As the condition mimics a range of dermatoses, it can be easily misdiagnosed and mismanaged. CASE REPORT: A 85-year-old woman suffering from bullous pemphigoid was referred for evaluation with presumptive diagnosis of an adverse drug reaction to hydrochlorothiazide or lacipil. Systemic corticosteroid therapy as the mainstay in the control of the bullous skin disorder was increased, but the skin condition worsened. ELISA for the detection of antibodies against the drugs suspected of causing hypersensitivity was negative. Histological examination disclosed inflammatory cells in the upper dermis and parasites. Direct microscopy of the scraped material revealed numerous parasites of the Sarcoptes scabiei type. The patient was treated with topical keratolytics following traditional scabicides for twice as long in comparison with the standard protocol. CONCLUSION: Norwegian scabies may be misdiagnosed and mismanaged in immunosuppressed patients. The diagnosis of scabies should always be considered in immunosuppressed patients with pruritus.

Pemphigus vulgaris: a 11-year review.

BACKGROUND: Pemphigus vulgaris (PV) is a rare, chronic life-threatening autoimmune blistering disease of the skin and mucous membranes. METHODS: A retrospective analysis of 31 patients with the diagnosis of pemphigus vulgaris, admitted for hospitalization from January 1996 to December 2006. Descriptive statistics has been used for data evaluation. RESULTS: The average age at onset was 49.0 +/- 16.2 years, with female to male ratio 1.4/1. Diagnosis was confirmed histologically and by a direct immunofluorescence. Mucocutaneous form of PV was observed in 25 patients (80.%), mucous form in 3 patients (9.7%), cutaneuos form in 3 patients (9.7%). Factors preceding the onset of PV were most often viral (38.7%) and bacterial (35.5%) infections, dental focuses (25.8%), stress (16.1%), and contact with chemical substances (16.1%). 6 patients (19.4%) did not indicate any triggering factor. Corticosteroids alone were given to 18 patients, combined with azatioprin or cyclosporin to 13 patients, and 1 patient was treated with intravenous immunoglobulin. Adverse events were mostly osteopenia/osteoporosis (41.9%), hyperlipoproteinemia (41.9%), cataract (32.3%) and Cushing's syndrome (32.3%). Cutaneous and mucous infections were most often caused by Staphylococcus aureus and Candida albicans, respectively. 3 patients died (9.7%), and in 3 patients (9.7%) in a long term remission, the immunosuppressive treatment was discontinued. CONCLUSION: Pemphigus vulgaris is still a life-threatening disease. Although corticosteroids dramatically improved the mortality, and are still considered the first-choice therapy, significant morbidity of the disease and the corticosteroid treatment still exists. The combination of corticosteroids with corticosteroid-sparing agents delays the onset of adverse events (Fig. 2, Ref. 33).

Paraneoplastic vasculitis associated with hairy cell leukemia.

Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disease, accounting for about 2-3% of all leukemias in adults. The skin lesions were described in about 10-12% of patients. Vasculitis in lymphoproliferative disease is relatively uncommon and may predate the diagnosis of lymphoproliferative disease. A 54-year old female with one month history of general symptoms and sudden onset of maculopapular exanthema on the skin, suffered from anemia, leukopenia and thrombocytopenia. Examination of the skin biopsy revealed lymphocytic vasculitis. Immunophenotyping of the skin biopsy revealed cell population with CD45RO, and small groups with CD20, partly DBA44 positivity. Bone marrow trepanobiopsy showed 50% infiltration with medium-sized lymphoid cells with clear cytoplasm and immunophenotypic coexpression of CD20 and DBA-44 antigens. The diagnosis of HCL was confirmed by flow cytometry of the bone marrow and of the peripheral blood cells that revealed pathological cell population with expression of CD11c, CD19, CD25, CD103. The patient was successfully treated with a single dose of cladribrine. The patient with acute vasculitis should be screened and monitored for possible lymphoproliferative diseases. Skin manifestation of acute vasculitis accompanied with hairy cells may be the first manifestation of HCL. Purine nucleoside analogue cladribrine is considered as the first line of therapy for HCL and induces a total response in more than 80% of cases with HCL.

Dermatitis herpetiformis in siblings.

Two Caucasian sisters, XZ and YZ, suffered from DH. However, the clinical course of their diseases was different; patient XZ, contrary to her sister YZ, suffered besides dermatitis herpetiformis (DH) also from coeliac disease (CD) and an autoimmune thyroid disease. The sisters were ordered to adhere to gluten-free diet and dapsone was prescribed, however, patient XZ developed a hypersensitivity to dapsone. The HLA typing disclosed that they were homozygous and that they shared HLA alleles DQB1*0201. Our results confirm the known association of DH to other autoimmune disorders and its well established association the HLA-DQB1*0201 allele. Although DH is generally not regarded as a familial disease our case report suggests its familial character (Fig. 3, Ref. 10). Full Text (Free, PDF) www.bmj.sk.