mycophenolic-acid and Calcinosis

We present two cases of Nodular Regenerative Hyperplasia (NRH) associated with Juvenile Dermatomyositis (JDM).. Case 1: A nine-year-old Caucasian male with refractory JDM and anti-NXP2 autoantibodies was diagnosed at age two. Over seven years, he developed arthritis, dysphagia, dysphonia, severe calcinosis, and colitis. Complications included recurrent cellulitis, infections, and hepatosplenomegaly. Multiple medications were chronically used, including prednisone, methotrexate, azathioprine, cyclophosphamide, mycophenolate mofetil, rituximab, tacrolimus, etanercept, abatacept, infliximab, and tocilizumab. Case 2: A 19-year-old Asian female with chronically active JDM and anti-MDA5 autoantibodies was diagnosed at age 15. Symptomatology included ulcerative skin lesions, Raynaud's phenomenon with digital ulcers, arthritis, interstitial lung disease with pulmonary hypertension, and calcinosis. Medications included chronic use of prednisone, methotrexate, abatacept, cyclophosphamide, mycophenolate mofetil, rituximab, tofacitinib, and sildenafil. In both patients, clinical symptomatology was not suggestive of liver disease or portal hypertension, but laboratory studies revealed elevated serum transaminases with progressive thrombocytopenia and no active liver-associated infections. The first patient's liver ultrasound showed coarse hepatic texture with mild echogenicity, splenomegaly, and portal hypertension. The second patient's liver ultrasound was normal, but elastography indicated increased stiffness. Liver biopsy confirmed NRH in both patients.. It is difficult to recognize NRH in JDM, as it often presents with elevated transaminases which may be mistaken for JDM muscle flare, corticosteroid-related fatty liver, or medication-related transaminitis. NRH has been associated with several medications used to treat JDM, including methotrexate, azathioprine, and cyclophosphamide, which should be discontinued if NRH develops. Providers should consider NRH in JDM patients with severe, refractory disease who have persistently elevated transaminases and persistent thrombocytopenia.

Topics: Abatacept; Adolescent; Arthritis; Autoantibodies; Azathioprine; Calcinosis; Child; Cyclophosphamide; Dermatomyositis; Female; Humans; Hyperplasia; Hypertension, Portal; Liver; Male; Methotrexate; Mycophenolic Acid; Prednisone; Rituximab; Splenomegaly; Thrombocytopenia; Transaminases; Young Adult

Çakan M, Karadağ ŞG, Aktay Ayaz N. Complete and sustained resolution of calcinosis universalis in a juvenile dermatomyositis case with mycophenolate mofetil. Turk J Pediatr 2019; 61: 771-775. Juvenile dermatomyositis (JDM) is a rare, multisystemic, idiopathic vasculopathy mainly affecting the muscles and the skin. Gastrointestinal system, lungs, joints and heart may also be involved. Characteristic skin findings are heliotrope rash and Gottron papules but extensive skin involvement as large necrotic lesions are rarely reported. Calcinosis is one of the major issues in the long term. Delay in diagnosis, inadequate therapy at the initial phase, prolonged persistent disease activity are considered as major risk factors for the development of calcinosis. Treatment of calcinosis is also a major issue because no single treatment modality has been found to reproducibly stop or reverse calcification. A 5-year-old girl was admitted to our clinic with typical signs and symptoms of JDM. She was initially treated with high-dose corticosteroids, methotrexate and intravenous immunoglobulin (IVIG). Soon after, she developed necrotic ulcerative skin lesions and cyclosporine was added to her treatment regimen. By this treatment all muscle and skin manifestations were controlled but on the first year of follow-up she developed superficial calcification plaques on the upper extremities and calcinosis universalis like calcifications on the lower extremities. Calcifications did not respond to bisphosphonate (pamidronate) and IVIG treatment but mycophenolate mofetil resulted in rapid and sustained resolution of all calcification plaques.

Topics: Calcinosis; Child, Preschool; Dermatomyositis; Enzyme Inhibitors; Female; Humans; Mycophenolic Acid

Dermatomyositis is an inflammatory myopathy and commonly presents with progressive, symmetric proximal muscle weakness and cutaneous findings. Calcinosis is a severe manifestation that can be debilitating. The cutaneous manifestations of dermatomyositis may also develop in the absence of detectable muscle disease, and can persist after the successful treatment of myositis. The author reports a 30-year-old woman with biopsy-proven dermatomyositis who had failed previous trials of azathioprine and methotrexate. Her muscle weakness was controlled with mycophenolate mofetil and prednisone; however, she had recurrent attacks of painful calcinosis. The patient responded to intravenous immune globulin (IVIG) along with intravenous methylprednisone, followed by IVIG for 2 consecutive days each month. This regimen has been effective in preventing recurrence of her calcinosis. This case illustrates the cutaneous manifestation of dermatomyositis, which is often more refractory to treat as compared to the muscle involvement and require additional approaches such as IVIG.

Topics: Adult; Anti-Inflammatory Agents; Calcinosis; Dermatomyositis; Female; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Methylprednisolone; Muscle Weakness; Mycophenolic Acid; Prednisone; Secondary Prevention

Topics: Calcinosis; Child; Drug-Related Side Effects and Adverse Reactions; Humans; Immunosuppressive Agents; Kidney Transplantation; Lung Diseases; Mycophenolic Acid

We describe a case of chronic mineralizing pulmonary elastosis in a seven-yr-old boy following DD renal transplantation for Wilms tumour. Fourteen months post-transplantation he developed respiratory symptoms with lung biopsy demonstrating chronic mineralizing pulmonary elastosis thought to be secondary to immunosuppression with MMF. Symptomatic resolution occurred following MMF cessation.

Topics: Calcinosis; Chronic Disease; Humans; Immunosuppressive Agents; Infant; Kidney; Kidney Neoplasms; Kidney Transplantation; Male; Mycophenolic Acid; Nephrectomy; Pulmonary Fibrosis; Remission Induction; Renal Dialysis; Tomography, X-Ray Computed; Wilms Tumor

A 39-year-old woman presented with multiple branch retinal artery occlusions almost three years before developing a mass lesion containing calcium in the left frontal lobe. Brain biopsy revealed a small vessel vasculitis and ischemic necrosis of brain with dystrophic calcification. We believe this to be the first case of primary CNS vasculitis with branch retinal artery occlusions and brain calcification.

Topics: Adult; Brain; Calcinosis; Cyclophosphamide; Diagnostic Techniques, Ophthalmological; Female; Humans; Immunosuppressive Agents; Mycophenolic Acid; Prednisone; Retinal Artery Occlusion; Tomography, X-Ray Computed; Treatment Outcome; Vasculitis, Central Nervous System