Successful treatment of dermatomyositis and associated calcinosis with adalimumab

Calcinosis cutis is the deposition of solid calcium salts in skin and subcutaneous tissue. The dystrophic form is seen with connective tissue diseases and is caused by tissue damage; patients have normal serum calcium and phosphate levels. A 24-year-old white woman presented with a 3month history of eyelid swelling and a 1-year history of a nonpruritic erythematous rash affecting her chest, face and arms, associated with migraines and with wrist and phalangeal joint pains. Physical examination revealed periorbital oedema, heliotrope rash (Fig. 1a), poikilodermatous rash over the neck (Fig. 1b), livedoid rash on the proximal limbs (Fig. 1c), Gottron papules and swollen metacarpophalangeal joints (Fig. 1d), flexor tenosynovitis and dilated nail-fold capillaries. Systems examination and laboratory tests, including antinuclear antibody, extractable nuclear antigen, double-stranded DNA, creatinine kinase and C-reactive protein, were normal. An expanded myositis-specific antibody screen demonstrated small ubiquitin-like modifier activating enzyme (SAE) antibodies. Baseline pulmonary function tests were normal. Histological examination of a skin biopsy revealed patchy lichenoid change, mild superficial dermal perivascular chronic inflammatory infiltrate and marked infiltrate in the mid and deep dermis, including prominent plasma cells, consistent with dermatomyositis (DM). Direct immunofluorescence was negative. SAE antibodies are associated with amyopathic DM and a late-onset myositis; therefore, the patient was monitored very carefully for this complication. One year after presentation, she developed myositis, which was confirmed by magnetic resonance imaging (MRI) of the upper arms, with equivocal thigh MRI scans. Creatinine kinase levels was 65 IU/L at the time of myositis, reaching a highest level of 96 IU/L, and always remaining within the normal range (24– 170 IU/L). Muscle biopsy did not demonstrate any myositis. Eight months after diagnosis, the patient developed extensive calcinosis in subcutaneous tissues and muscles, with large sheets of calcinosis in the upper arms (Figs 1e and 2a) and upper legs (Fig. 2c). The diffuse lacy reticular pattern is unusual in adults, occurring more commonly in juvenile DM. This may have been triggered by a miscarriage a month previously. She proceeded to have three further miscarriages and two successful pregnancies (Table 1). Multiple medications (Table 1) were tried without improvement. Reports of response of calcinosis (in juvenile DM) to anti-tumour necrosis factor (TNF)-a therapy, led us to try a course of infliximab infusions, but a severe allergic infusion reaction after the second dose precluded further use. Therapy with adalimumab, a fully humanized monoclonal anti-TNF-a drug, was then started. This produced an excellent response within 6 months of treatment, with a reduction in symptoms, skin rash, clearing of Gottron papules, increase in muscle bulk and strength, and softening and improvement of calcinosis (Figs 1f and 2b,d). This was switched to etanercept during the patient’s second pregnancy, then switched back to adalimumab. Her calcinosis continued to resolve and the treatment was withdrawn after 30 months, with the patient remaining in remission 3 years after stopping adalimumab. Calcinosis can lead to pain, limited mobility, weakness, joint contractures, muscle atrophy, skin ulcers and secondary infection. Dystrophic calcinosis cutis is believed to result from the intracellular accumulation of calcium, triggered by trauma, chronic inflammation or vascular hypoxia. Proinflammatory cytokines, such Correspondence: Dr Fangyi Xie, Department of Dermatology, Heavitree Hospital, Royal Devon and Exeter NHS Foundation Trust, Gladstone Road, Exeter, EX1 2ED, UK Email: fxie@nhs.net