Immune mediated necrotizing Myositis due to Malarone (Atovaquone/Proguanil)
Qutab Shah, Patricia Harkins, Deniz Demirdal, Aine Gorman, Angela Camon, Ausaf Mohammad, Killian O’Rourke
Department of Rheumatology Midland regional Hospital Tullamore
Immune-mediated necrotizing myopathy (IMNM) is a type of autoimmune myopathy characterized by relatively severe proximal weakness, myofiber necrosis with minimal inflammatory cell infiltrate on muscle biopsy, and infrequent extra-muscular involvement. We describe a case of a 44 old male who was referred to us with a four month history of grade 4/5 weakness of proximal upper and lower limbs. The patient was on anti malarial prophylaxis Malarone (Atovaquone/proguanil combination). Lab investigations revealed raised CK, LDH, Liver transaminases, and Aldolase. He had normal ESR, CRP, urate, renal profile, C3,C4, immunoglobulins and negative ENA, ANA, ANCA, Hepatitis B and C serology, TB Quantiferon, Mysositis specific antibody screen(MI-2,MI02 beta, TIF-1-gamma, MDAS, NXP2, SAE1, KU, PL-SCL 100, PM-SCL 75, JO-1, SRP, PL-7, PL-12, EJ, OJ, RO-52). HMGCOAR auto antibody was positive. CT thorax, abdomen, and pelvis showed mild sigmoid diverticulosis only. Whole body MRI showed no convincing evidence of muscle abnormality (However, patient was on steroids at the time of imaging). EMG findings were consistent with proximal myopathy suggestive of polymyositis.
Muscle biopsy of right thigh showed myopathic features with diagnostic possibilities including drug associated necrotizing myopathy. Ultrasound liver completed for deranged liver function showed possibility of fatty liver. Subsequent liver biopsy was normal. The patient had no cardiopulmonary, gastrointestinal symptoms. There was no history of DVT,PE, parotid swelling, lymphadenopathy, skin lesions, raynauds phenomenon, dysphagia or epilepsy. Chest X-ray, Pulmonary function test, and echocardiogram showed no abnormalities. The patient was treated with prednisolone 60 mg od reducing dose followed by Rituximab infusions 1g IV two weeks apart and also received IVIG (0.4g/kg) monthly and responded very well to treatment with improvement in muscle strength,4+/5 at quadriceps and 5/5 everywhere else. There has been marked improvement seen in his CK, AST,ALT and LDH reduced from peak values. He is currently maintained at 10 mg of prednisolone once daily and will be continuing with monthly IVIG IV infusions with repeat Rituximab infusions every six to nine months. IMNM associated with Malarone has only been reported in the literature once previously. Further details of this rare case will be discussed.