Adult-Onset Dermatomyositis Complicated by Calcinosis Cutis

Presentation A 25-year-old African American woman with a four-year history of dermatomyositis (DM) presented with an ulcer in the right popliteal fossa of five weeks duration. Initially, the patient was diagnosed with DM based on typical heliotrope rash, photosensitivity, high creatinine kinase (CK), and interstitial lung disease. Her serology for other connective tissue diseases was negative. She was initially treated with oral prednisone 1mg/Kg/d. After normalization of CK levels, prednisone was tapered to 10mg/d but never discontinued. Two years later, she developed calcium deposits on the hips bilaterally. Over the past year, she developed dystrophic calcinosis cutis complicated by chronic skin ulcers. The patient’s past medical history is significant for bronchiolitis obliterance organizing pneumonia, gastroesophageal reflux disease, small joint polyarthritis, septic arthritis status/post arthroscopy, and chronic skin ulcers. Her medications include prednisone 10mg/day, a calcium supplement, mycophenolate, alendronate sodium, celecoxib, and famotidine. Physical Examination Physical examination revealed a young, healthy, African American woman with periorbital heliotrope discoloration and hyperpigmented patches on her malar prominences. There were numerous hypopigmented scars on all extremities at sites of healed ulcers. Several interphalangeal joints were minimally inflamed with Gottron’s papules present on the dorsa of the metacarpophalangeal and proximal interphalangeal joints bilaterally. She had normal muscle power. There was a shallow, round 9mm x 8mm ulcer in the right popliteal fossa (Figure 1). The bed of the ulcer had a white exudate containing calcium particles. The surrounding skin was moderately indurated. Diagnosis The patient was diagnosed with DM with ulcerating calcinosis cutis. Discussion DM is an idiopathic autoimmune-mediated inflammatory process affecting the striated muscles and skin. It is characterized by violaceous (heliotrope) discoloration of the eyelids, flat-topped, violaceous papules over the knuckles (Gottron’s papules), proximal muscle weakness, and occasionally interstitial pneumonitis, vasculitis, or myocardial involvement. It is believed to be triggered by drugs, malignancy, or infection in genetically predisposed individuals. The bimodal peaks of incidence in DM are 2–16 years in children and 40–60 years in adults. The median age of adult onset is 50 years and is associated with underlying malignancy in 10–50 percent of cases. Juvenile-onset DM has a median age of 6–7 years and is often complicated by calcinosis (Table 1).^1,2 DM can occur in association with other connective tissue disorders. Childhood sclerodermatomyositis is an overlap syndrome presenting with cutaneous changes of systemic sclerosis and DM, myositis, and a homogenous nuclear pattern of an antinuclear antibody, anti-PM/Scl Ab.³ Drugs, such as hydroxyurea, penicillamine, tryptophan, diclofenac, nonsteroidal anti-inflammatory drugs (NSAIDs), and lipid-lowering medications, can induce skin findings of DM. DM can simultaneously accompany or follow the detection of malignancy. The most common primary tumors associated with adult-onset DM are lung, breast, testicular, colon, stomach, and ovarian carcinomas. Neoplasia is not associated with juvenile DM. Clinical features of DM. DM is manifested by clinical signs and symptoms related to inflammation involving skin and striated muscles. The myositis is characterized with proximal muscle weakness that can precede, present simultaneously with, or follow skin manifestations. As muscle cells degenerate, the level of muscle enzymes in serum elevate in proportion to the degree and progression of the inflammatory process. If left untreated, it can progress to affect more distal muscles. Cardiac muscle involvement can also occur. Once treatment is initiated, CK levels in addition to clinical findings can be guides to follow up. Skin findings. Skin findings in DM include the following:⁴ 1. Gottron’s papules: Gottron’s papules are flat-topped, violaceous papules that are located on the dorsal aspects of the proximal and distal interphalangeal and metacarpophalangeal joints. They can become atrophic. 2. Gottron’s sign: Gottron’s sign presents as symmetric, confluent, violaceous-to-erythematous macules, located on the dorsa of the hands, patellae, medial malleoli, and olecranon process. 3. Heliotrope rash: Heliotrope rash is a periorbital, confluent, violaceous erythema with or without associated eyelid edema. 4. Shawl sign: Shawl sign presents as intensely pruritic, symmetrical, confluent, violaceous, erythematous macules, which are photodistributed on the forehead, scalp, cheeks, neck, and upper chest. Sparing may occur in photoprotected areas. 5. Periungual telangiectasia: Periungual telangiectasia is erythema and thrombosis of capillary loops with dystrophic cuticles. 6. Mechanic’s hand: Mechanic’s hand presents as a nonpruritic, bilateral, symmetric, confluent, hyperkeratotic eruption with scaling, fissuring, and hyperpigmentation located on the ulnar aspect of the thumb and radial aspect of the fingers with occasional extension to the palm. Mucinous plaques on palm creases and fingers have also been seen. Calcinosis in DM. Calcinosis is a major complication of DM that mainly affects children. It presents as firm dermal papules and nodules over bony prominences and tends to occur later in the course of juvenile-onset DM. If untreated, it can become widespread (calcinosis universalis), resulting in severe immobility. Osteoporosis and pathological fracture are complications of calcinosis. The nucleus of calcinosis consists of hydroxyapetite. Large subcutaneous deposits can contain a liquid suspension of calcium crystals called milk of calcium. The presence of macrophages, interleukin 6 (IL6), IL1, and tumor necrosis factor (TNF) in the milk of calcium and detectable levels of IL1 in the serum suggest a major role for activated macrophages in the process of calcinosis.⁵ Increased bone resorption markers and indices of calcium metabolism point to increased bone turnover in patients with extensive calcinosis.⁶ Some suggest that release of calcium from the mitochondria of the damaged muscle cells is the source for calcium deposition. Risk factors for developing calcinosis are young age, delay in diagnosis or therapy, and inconsistent or less aggressive treatments. The incidence of calcinosis is inversely proportional to the CK levels (Table 2).⁷Extramuscular systemic features associated with DM/amyopathic DM. Any soft tissue can be involved in the inflammatory process of DM. The most commonly involved organs are the heart and lungs. For unknown reasons, patients with DM who show less myositis with low serum CK levels have a higher tendency to develop interstitial pulmonary involvement (15–30%). Cardiac involvement, or myocarditis, usually presents as conduction defects. Pericarditis usually occurs in patients with overlap syndrome. Esophageal involvement is manifested as proximal and distal dysphagia. Proximal dysphagia correlates to myositis and responds to corticosteroid therapy. Distal dysphagia occurs more commonly in patients with overlap connective tissue disease. In general, dysphagia portends a poor prognosis. Vascular involvement in DM usually presents as small vessel vasculitis.^1,8 Treatment Treatment of DM. DM usually responds well to treatment with systemic steroids. This is usually combined with a steroid-sparing agent, as steroid-induced myopathy can occur after four to six weeks of therapy (Table 3). Current treatment for skin disease is less satisfactory, with many patients experiencing persistent cutaneous symptoms once muscle disease is in remission. Treatment of calcinosis. Evidence-based data show that aggressive initial immunosuppression can prevent or ameliorate the process of calcium deposition. Methylprednisone and methotrexate. A study on 12 subjects has shown that early initiation of aggressive treatment with intravenous methylprednisone and methotrexate (MTX) in patients with juvenile-onset DM is a useful combination for early treatment initiation, which prevented the development of calcinosis in a patient who received it within six weeks of diagnosis.⁹Warfarin. Vitamin K has been known to play a role in the calcium-binding process in bones and in abnormal calcium deposition in soft tissues. Warfarin was reported to reduce the amount of subcutaneous calcinosis and to improve mobility in a 27-year-old male with DM, calcinosis universalis, and very high serum vitamin K levels.¹⁰Diltiazem. Diltiazem in high dosage of 360mg/d was shown by body scanning to significantly reduce the mineral content of calcified tissues in a wheelchair-bound patient with DM.¹¹Aledronate. Aledronate is speculated to exert a two-fold action by 1) inhibiting bone resorption followed by reducing calcium turnover and 2) inhibiting calcium accretion in existing calcifications. Bisphosphonates. Bisphosphonates can inhibit macrophage pro-inflammatory cytokine production, such as IL1, IL6, and TNF.¹²Probenecid. Probenecid may be effective by increasing renal phosphate clearance.¹³Surgical removal. If conservative medical management fails to resolve calcinosis, surgical removal may be indicated if the patient’s mobility is compromised. Peripheral blood stem cell autograft. Peripheral blood stem cell autograft in a bedridden teenage girl with DM, arthritis, myalgia, skin ulcers, and diffuse calcinosis resulted in total disappearance of calcinosis and remission of her disease activity.¹⁴ Management In the case of this young, active woman, the authors consulted the dermatologic surgery team to discuss the advantages and disadvantages of surgical removal of the most extensive areas of calcinosis surrounding the wound. Because her disease did not compromise her normal activity and her wound was healing, the authors selected conservative management with simple moisture retentive dressings.