[Show abstract][Hide abstract] ABSTRACT: Vitamin D is critical for calcium homeostasis. Following cutaneous synthesis or ingestion, vitamin D is metabolized to 25(OH)D and then to the active form 1,25(OH)2D. Low serum vitamin D levels are common in the general population and cause a decline in calcium absorption, leading to low serum levels of ionized calcium, which in turn trigger the release of parathyroid hormone, promoting skeletal resorption and, eventually, bone loss or osteomalacia. Vitamin D deficiency is generally defined as a serum 25(OH)D concentration <25-37 nmol/l (<10-15 ng/ml), but the definition of the milder state of vitamin D insufficiency is controversial. Three recent meta-analyses concluded that vitamin D must be administered in combination with calcium in order to substantially reduce the risk of nonvertebral fracture in adults over the age of 50 years. Fracture protection is optimal when patient adherence to medication exceeds 80% and vitamin D doses exceed 700 IU/day. In addition to disordered calcium homeostasis, low vitamin D levels might have effects on cell proliferation and differentiation and immune function. Randomized, double-blind, placebo-controlled trials are needed to clarify whether vitamin D supplementation is beneficial in cancer, autoimmune disease and infection. This Review focuses on the pathophysiology, clinical correlates, evaluation and treatment of hypovitaminosis D.
Preview · Article · Oct 2008 · Nature Clinical Practice Rheumatology
[Show abstract][Hide abstract] ABSTRACT: C4 is encoded by 2 distinct but closely linked loci within the major histocompatibility complex locus on human chromosome 6. C4A deficiencies have been associated with autoimmune disease and C4B with increased frequency of infection. C4 deficiencies have rarely been associated with juvenile idiopathic arthritis (JIA). Our aim was to investigate the prevalence of deficiencies in C4 allotypes in JIA patients.
We evaluated 61 patients [35 JIA patients, 15 systemic lupus erythematosus patients, 9 rheumatoid arthritis patients, and 2 mixed connective tissue disease (CTD) patients] for C4 deficiency. Genomic DNA was isolated from whole blood and subjected to polymerase chain reaction using sequence-specific primers for C4 allotypes.
We found 5 JIA patients with C4 deficiencies. Two IgM rheumatoid factor-positive JIA polyarthritis patients had C4 deficiencies, one with complete C4A deficiency and another with partial C4A and complete C4B deficiency. Two oligoarthritis patients displayed partial C4B deficiencies, and complete C4B deficiency was revealed in 1 IgM rheumatoid factor-negative polyarthritis patient. Three patients had histories of recurrent infections and 2 demonstrated a more severe disease course. Disease controls showed 8 systemic lupus erythematosus patients had partial C4 deficiencies, whereas no deficiencies were revealed in the rheumatoid arthritis or mixed CTD patients.
Defects in the complement system have been implicated in the pathogenesis of CTD. However, the specific role of C4 in JIA is not clear. We demonstrate partial C4 deficiencies in 5 JIA patients. Our findings suggest an association between C4 deficiency and another CTD, JIA, as well as with disease severity and recurrent infections.
No preview · Article · Nov 2007 · JCR Journal of Clinical Rheumatology
[Show abstract][Hide abstract] ABSTRACT: Kawasaki Disease is a small-to-medium-vessel vasculitis that preferentially affects children. Kawasaki Disease can occur in adults, but the presentation may differ from that observed in children. Typical findings in both adults and children include fever, conjunctivitis, pharyngitis, and skin erythema progressing to a desquamating rash on the palms and soles. Adults more frequently present with cervical adenopathy (93% of adults vs. 15% of children), hepatitis (65% vs. 10%), and arthralgia (61% vs. 24-38%). In contrast, adults are less frequently affected by meningitis (10% vs. 34%), thrombocytosis (55% vs. 100%), and coronary artery aneurysms (5% vs. 18-25%). We report a case of acute Kawasaki Disease in a 24-year-old man who presented with rash, fever, and arthritis. He was successfully treated with high-dose aspirin and intravenous immunoglobulin (IVIG). Our case highlights the importance of considering Kawasaki Disease in adults presenting with symptoms commonly encountered in a general medical practice.
Preview · Article · Jun 2007 · Journal of General Internal Medicine