CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.
"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.
Patrice Wendling/IMNG Medical Media
Dr. Lisa Christopher-Stine
Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.
Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.
"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.
The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.
Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.
"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."
The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.
There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.
Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.
A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).
Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).
Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.
The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).
Dr. Christopher-Stine reported having no relevant financial relationships.