warfarin and Dermatomyositis

Calcinosis cutis constitutes a heterogeneous group of chronic disorder. It can be associated with disturbance of calcium and/or phosphate metabolism (metastatic, tumor calcinosis, calciphylaxis) but may also develop without any metabolic disorder, in particular during the course of connective tissue diseases. Among these, the most common are dermatomyositis and the limited form of systemic sclerosis. The physiopathology of calcinosis cutis is poorly known. It can cause pain, chronic ulcerations, infections, which are sources of sometimes major disability. Treatment of calcinosis is challenging because no drug has been shown to be reliably effective in stopping the progression or decreasing dystrophic calcifications in controlled trials. Calcium blocker and colchicine are generally prescribed as the first line systemic therapy. In the localized forms of small lesions, surgical excision is often effective and sometimes preceded by local treatments (laser therapy, extracorporeal shock wave lithotripsy, topical sodium thiosulfate, etc.) or systemic treatment (minocycline, warfarine). When calcinosis is disseminated, it may require additional treatments (aluminium hydroxyde, bisphosphonates) possibly associated with surgery in case of large lesions. Time to response may be prolonged from weeks to months. The calcinosis cutis can lead to secondary infection, pain and functional disability that have to be prevented.

Topics: Calcinosis; Calcium Channel Blockers; Colchicine; Dermatomyositis; Humans; Minocycline; Scleroderma, Systemic; Warfarin

Patients with calcinosis universalis secondary to dermatomyositis or systemic sclerosis have increased levels of the calcium-binding amino acid, gamma-carboxyglutamic acid. The enzyme that effects gamma carboxylation of glutamic acid is warfarin-sensitive. Four patients with calcinosis universalis were treated with 1 mg per day of warfarin for 18 months in a non-blind initial study. Two patients had both decreased gamma-carboxyglutamic acid urinary concentration and decreased extra-skeletal uptake on technetium 99m-diphosphonate whole-body nuclear scanning. In a subsequent double-blind placebo study, two thirds of the patients receiving 1 mg per day of warfarin had decreases in extra-skeletal nuclear tracer uptake after 18 months, compared with none of the four patients receiving placebo. No patient had a change in clinical assessment, bleeding complication, or baseline normal prothrombin time. This low-dose warfarin regimen appears to have no demonstrable adverse effects, and these results suggest a beneficial effect on the progression of calcinosis in these rheumatic diseases.

Topics: Bone and Bones; Calcinosis; Dermatomyositis; Double-Blind Method; Drug Evaluation; Humans; Radiography; Radionuclide Imaging; Random Allocation; Scleroderma, Systemic; Skin Diseases; Time Factors; Warfarin

A 27-year-old male patient with calcinosis universalis resulting from dermatomyositis was successfully treated with low-dose warfarin. On his trunk and extremities, there were many subcutaneous calcified nodules, and knee flexion was difficult. After oral warfarin therapy for three years, the calcified nodules became smaller, and the knee mobility improved. His serum vitamin K level was abnormally high, decreased just after starting warfarin therapy, and then remained within the normal range. Since vitamin K has been known to play an important role in the Ca2+ binding process in bones or tissues, we suggest that this therapy is effective in reducing subcutaneous calcification through the vitamin K cycle.

Topics: Administration, Oral; Adult; Calcinosis; Dermatomyositis; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Male; Radiography; Treatment Outcome; Warfarin

Topics: Calcinosis; Dermatomyositis; Humans; Warfarin

Topics: Adolescent; Adult; Calcinosis; Child; Dermatomyositis; Female; Humans; Male; Scleroderma, Systemic; Tomography, X-Ray Computed; Warfarin

The effect of warfarin sodium on excretion of calcium, phosphorus, and 4-carboxy-L-glutamic acid (Gla) was studied in 5 patients with ectopic calcification (2 with scleroderma, 1 with dermatomyositis, and 2 with myositis ossificans progressiva). Warfarin reduced urinary excretion of Gla in all patients, but no changes in calcium and phosphorus excretion or in objective parameters of calcinosis were observed during 6-36 months of treatment. Two patients experienced hemorrhagic complications during therapy, emphasizing a hazard of long-term anticoagulation treatment. Since ectopic calcium deposits contain Gla-rich protein, suppression of Gla synthesis by warfarin sodium over a longer period may prevent deposition and allow removal of existing calcinosis deposits.

Topics: Adult; Bone and Bones; Calcium; Carbon Radioisotopes; Chromatography, High Pressure Liquid; Cyclic AMP; Dermatomyositis; Female; Follow-Up Studies; Glutamates; Hemorrhage; Humans; Male; Middle Aged; Myositis Ossificans; Phosphorus; Radiography; Radionuclide Imaging; Scleroderma, Systemic; Warfarin