Israel Medical Association Journal

The DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), also known as DIHS (drug-induced hypersensitivity syndrome), presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, producing damage in several systems, especially kidney, heart, lungs, and pancreas. The pathogenesis is related to specific drugs (especially the aromatic anticonvulsants), altered immune response, sequential reactivation of herpes virus, and association with some HLA alleles. Glucocorticoids are the basis for the treatment of the syndrome, which may be given with intravenous immunoglobulin and, in selected cases, ganciclovir. This article reviews current concepts regarding the interaction of drugs, viruses and immune responses during this complex adverse-drug reaction.
 

Background: Anti-lipoprotein lipase antibodies have been described in rare cases of patients with hypertriglyceridemia. However, no systematic study evaluating these antibodies in patients with this lipid abnormality has been undertaken.

Objectives: To analyze the correlation of anti-lipoprotein lipase (anti-LPL) antibodies with other laboratory findings in patients with hypertriglyceridemia but no autoimmune disease.

Methods: We evaluated 44 hypertriglyceridemic patients without autoimmune disease. Clinical and laboratory evaluations included analyses of co-morbidities, fasting lipid profile and anti-LPL antibodies.

Results: Mean patient age was 55 ± 10 years; 46% of the patients were female and 64% were Caucasian. The mean disease duration was 94.4 months and mean body mass index 28.7 ± 3.6 kg/m²; 34.0% were diabetic, 25.0% were obese, 72.7% had systemic arterial hypertension, 75% were sedentary, 15.9% were smokers, 56.8% had a family history of dyslipidemia, 45.5% had a family history of coronary insufficiency, 20.5% had acute myocardial infarction, 9.0% had undergone revascularization and 11.0% angioplasty, 79.5% were being treated with statins and 43.2% were taking fibrates. Median triglyceride levels were 254 mg/dl (range 100-3781 mg/dl), and total cholesterol level was 233 ± 111 mg/dl. High-density lipoprotein was 42.6 ± 15.4 mg/dl, low-density lipoprotein 110.7 ± 42.4 mg/dl and very low-density lipoprotein 48 ± 15 mg/dl. Anti-LPL antibodies were identified in 2 patients (4.5%), both of whom had a family history of dyslipidemia, coronary insufficiency and acute myocardial infarction; one had undergone myocardial revascularization and percutaneous transluminal coronary angioplasty, and both were using fibrates and had normal triglyceride levels.

Conclusions: Our findings demonstrate a correlation between the immune response and dyslipoproteinemia in hypertriglyceridemic patients, suggesting that autoimmune disease contributes to the dyslipidemia process.
 

Primary biliary cirrhosis is considered a model autoimmune disease because of the similarities between patients, their relative homogeneous presentation and natural history, and the presence of the signature autoantibody, the anti-mitochondrial antibodies. PBC[1] also illustrates the potential role of genetic and environmental influence and is unique in having several well-defined animal models that recapitulate distinct features of the disease. The pathogenesis of the disease includes genetic predisposition, the production of both innate and adaptive immune responses, and cholangiocyte-specific biology that addresses the specificity of disease. In this review we highlight these features of PBC in comparison to other autoimmune diseases.

Background: Epidemiological data show significant associations of vitamin D deficiency and autoimmune diseases. Vitamin D may prevent autoimmunity by stimulating naturally occurring regulatory T cells.

Objectives: To elucidate whether vitamin D supplementation increases Tregs[1] frequency (%Tregs) of circulating CD4+ T cells.

Methods: We performed an uncontrolled vitamin D supplementation trial among 50 apparently healthy subjects including supplementation of 140,000 IU at baseline and after 4 weeks (visit 1). The final follow-up visit was performed 8 weeks after the baseline examination (visit 2). Blood was drawn at each study visit to determine 25-hydroxyvitamin D levels and %Tregs. Tregs were characterized as CD4+CD25++ T cells with expression of the transcription factor forkhead box P3 and low or absent expression of CD127.

Results: Forty-six study participants (65% females, mean age ± SD 31 ± 8 years) completed the trial. 25(OH)D[2] levels increased from 23.9 ± 12.9 ng/ml at baseline to 45.9 ± 14.0 ng/ml at visit 1 and 58.0 ± 15.1 ng/ml at visit 2. %Tregs at baseline were 4.8 ± 1.4. Compared to baseline levels we noticed a significant increase of %Tregs at study visit 1 (5.9 ± 1.7, P < 0.001) and 2 (5.6 ± 1.6, P < 0.001).

Conclusions: Vitamin D supplementation was associated with significantly increased %Tregs in apparently healthy individuals. This immunomodulatory effect of vitamin D might underlie the associations of vitamin D deficiency and autoimmune diseases. Hence, our finding provides a rationale for further studies to investigate vitamin D effects on autoimmunological processes.