minocycline and Calcinosis

Calcinosis, insoluble calcium compounds deposited in skin and other tissues, is a crippling sequela of dermatomyositis. Prolonged disease associated with ongoing inflammation, ischemia, repetitive trauma, and certain autoantibodies are associated with calcinosis. Herein, we describe potential pathogenic mechanisms including the role of mitochondrial calcification. There are no widely effective treatments for calcinosis. We review available pharmacologic therapies for calcinosis including those targeting calcium and phosphorus metabolism; immunosuppressive/anti-inflammatory therapies; and vasodilators. Mounting evidence supports the use of various formulations of sodium thiosulfate in the treatment of calcinosis. Although the early institution of aggressive immunosuppression may prevent calcinosis in juvenile dermatomyositis, only limited data support improvement once it has developed. Minocycline can be useful particularly for lesions associated with surrounding inflammation. Powerful vasodilators, such as prostacyclin analogs, may have promise in the treatment of calcinosis, but further studies are necessary. Surgical removal of lesions when amenable is our treatment of choice.

Topics: Anti-Inflammatory Agents; Autoantibodies; Calcinosis; Calcium; Dermatomyositis; Humans; Inflammation; Minocycline; Phosphorus; Prostaglandins I; Vasodilator Agents

The aim of this study was to provide updated information on the prevalence, pathogenesis, diagnostics and therapeutics of calcinosis cutis associated with systemic sclerosis (SSc).. Observational studies show ethnic and geographical differences in the prevalence of calcinosis. In addition to clinical and serological associations, biochemical studies and in-vivo models have attempted to explain theories behind its pathogenesis, including prolonged state of inflammation, mechanical stress, hypoxia and dysregulation in bone and phosphate metabolism. Long-term use of proton pump inhibitors may increase the risk for calcinosis in SSc. Few single-centre observational studies have shown mild benefit with minocycline and topical sodium thiosulfate.. Calcinosis cutis is the deposition of insoluble calcium in the skin and subcutaneous tissues. It affects up to 40% of SSc patients and causes significant morbidity. Long disease duration, features of vascular dysfunction and osteoporosis have been associated with calcinosis. Altered levels of inorganic pyrophosphate and fibroblast growth factor-23 have been implicated in dysregulated phosphate metabolism that may lead to calcinosis in SSc. Plain radiography can help with diagnosis and quantifying the calcinosis burden. Surgical treatment remains the most effective therapy when feasible. At present, no medical therapies have proven efficacy in large randomized controlled trials.

Topics: Calcinosis; Calcium; Diphosphates; Humans; Minocycline; Proton Pump Inhibitors; Scleroderma, Systemic

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

Because calcinosis cutis is a rare syndrome, there is a notable lack of controlled clinical trials on its treatment. The efficacy of calcinosis treatment has only been reported in single cases or small case series. No treatment has been generally accepted as standard therapy, although various treatments have been reported to be beneficial, including warfarin, bisphosphonates, minocycline, ceftriaxone, diltiazem, aluminium hydroxide, probenecid, intralesional corticosteroids, intravenous immunoglobulin, curettage, surgical excision, carbon dioxide laser, and extracorporeal shock wave lithotripsy.

Topics: Biopsy, Needle; Calcinosis; Ceftriaxone; Combined Modality Therapy; Drug Therapy, Combination; Education, Medical, Continuing; Evidence-Based Medicine; Female; Humans; Immunoglobulins, Intravenous; Immunohistochemistry; Laser Therapy; Lasers, Gas; Male; Minocycline; Prognosis; Recurrence; Risk Assessment; Severity of Illness Index; Skin Diseases; Treatment Outcome; Warfarin

The endodontic regenerative procedure (ERP), which is an alternative to calcium hydroxide-induced apexification, involves the use of a triple antibiotic paste (TAP) as a dressing material. The aim of this study was to evaluate the response of rat subcutaneous tissue to implanted polyethylene tubes that were filled with TAP or calcium hydroxide.. Thirty rats received 2 individual implants of polyethylene tubes filled with TAP or calcium hydroxide paste (CHP) and another empty tube as a control. Thirty additional rats received 2 individual implants consisting of polyethylene tubes filled with dressing material carriers (macrogol and propylene glycol) and a sham procedure. After 7, 15, 30, 60, and 90 days, 12 animals were euthanized, and the tubes and surrounding tissue were removed and processed for histology by using glycol methacrylate and stained with hematoxylin and eosin. The histological score ranged from 0 to 3 depending on the content of inflammatory cells; the fibrous capsule was considered thin or thick, and necrosis and calcification were recorded as present or absent. The results were analyzed using the Kruskal-Wallis test.. Both dressing materials induced moderate reactions at 7 and 15 days. These reactions were similar to the control (P > .05) and reduced in intensity (to mild) from day 30 onward (P > .05). The carriers did not interfere with the reaction of the dressing materials.. TAP and CHP were biocompatible over the different experimental periods examined.

Topics: Animals; Anti-Bacterial Agents; Apexification; Biocompatible Materials; Calcinosis; Calcium Hydroxide; Ciprofloxacin; Drug Carriers; Drug Combinations; Fibrosis; Lymphocytes; Macrophages; Male; Materials Testing; Metronidazole; Minocycline; Necrosis; Polyethylene Glycols; Rats; Rats, Wistar; Regeneration; Root Canal Filling Materials; Subcutaneous Tissue; Time Factors; Tooth, Nonvital

To evaluate the effect of minocycline as treatment for cutaneous calcinosis in limited cutaneous systemic sclerosis (lcSSc).. Patients with lcSSc who had cutaneous calcinosis causing pain or ulceration, or both, were prescribed minocycline 50 or 100 mg daily regularly in an open label manner between November 1994 and April 2000. At routine clinical follow up the appearance of the calcinosis deposits was assessed clinically and radiographically, and the patients' assessment of the degree of discomfort, size, and frequency of ulceration was recorded. Demographic data, including disease duration, clinical features, and antinuclear antibody (ANA) titres, were also recorded.. Nine patients have been treated to date. Eight of the nine patients were ANA positive, five of whom were positive for anticentromere antibodies. Eight patients have shown definite improvement and seven patients continue to receive treatment. The frequency of ulceration and inflammation associated with the calcinosis deposits decreased with treatment. The size of the calcinosis deposits also decreased but was less dramatic than expected. Improvement occurred at the earliest after one month of treatment with a mean (SD) of 4.8 (3.8) months. The mean (SD) length of treatment was 3.5 (1.9) years. An unexpected effect was the darkening of the calcinosis deposits to a blue/black colour.. Minocycline may be effective in the control of calcinosis in systemic sclerosis. A low dose only is required and appears to be generally well tolerated. The mechanism of action may be mainly through inhibition of matrix metalloproteinases and anti-inflammatory effects. Calcium binding properties and antibacterial actions may also have a role.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibodies, Antinuclear; Calcinosis; Female; Hand; Humans; Middle Aged; Minocycline; Scleroderma, Systemic; Skin Diseases, Metabolic