Spontaneous Pneumomediastinum due to Anti-Melanoma Differentiation-Associated Protein 5 Requiring a Bilateral Lung Transplant

Anti-melanoma differentiation-associated protein 5 (anti-MDA5) is a subset of dermatomyositis associated with respiratory complications, in which rapidly progressive interstitial lung disease (RPILD) is commonly cited, and spontaneous pneumomediastinum (SPM) is a rare complication. In medical literature, aggressive immunosuppressive therapy has been the mainstay of anti-MDA5-associated SPM management. Here, we report the first MDA5 case with SPM which was successfully treated with a double-lung transplant. We present a 48-year-old male who presented with multiple constitutional symptoms such as fevers, weight loss, malaise, and arthralgias, in association with erythroderma over the ears and fingers. Imaging of the chest demonstrated peripheral airspace disease, and myositis-specific serology returned positive for anti-Jo1 (medium-positive), anti-Ro52 (high-positive), and anti-MDA5 (weak-positive) autoantibodies. Therefore, the patient was begun on immunosuppressive therapy as the leading diagnosis included autoimmune myositis, possibly antisynthetase syndrome with interstitial lung disease (ILD). A year later, the patient presented with progressive shortness of breath, widespread macular erythematous facial rash, and new erythematous ulcerations over the fingertips. Imaging demonstrated a new SPM at this juncture. As the patient’s respiratory status continued to decline despite the use of immunosuppressive agents, a double-lung transplant was performed. Therefore, we propose that lung transplantation should be considered early in MDA5-SPM.

Hypercalcemia in a Patient Treated With Abaloparatide

Introduction: The antifracture efficacy of newer agents like PTHrP analogues is promising but knowledge about the mechanism of action and safety profile is needed in order to use these agents effectively. The reported incidence of hypercalcemia defined as albumin-adjusted serum calcium ≥10.7mg/dL was 3.4% in Abaloparitide. Case Presentation: A 59 year-old female with past medical history significant for diabetes mellitus type 2, hypothyroidism, necrotizing autoimmune myositis, osteoporosis and renal stones presented with complaints of generalized body aches and pains with swelling and redness of the left leg. The patient was diagnosed with osteoporosis based on atraumatic L4 compressive injury involving superior end plate. Her only DXA scan was 8 years ago which showed osteopenia, with the lowest T score of -1.2 at lumbar spine. Subsequent evaluation with DXA scan was unable to be performed due to physical disabilities. She was intolerant to oral bisphosphonates and was started on abaloparatide subcutaneous injections 2 weeks prior to her current admission. Her physical examination was positive for obesity, proximal muscle weakness and bilateral leg edema with bruises and left leg erythema. Laboratory findings showed hypercalcemia with corrected calcium levels of 12.48 mg/dl, suppressed intact PTH 4 pg/ml. Evaluations for secondary causes of hypercalcemia were negative. Her last dose of abaloparatide injection was the morning prior to her presentation to the emergency room. The patient was treated with IV fluids and her calcium level improved within 24 hours with normalization of intact PTH level in 72hrs. Abaloparatide injection was suspended on admission. Hypercalcemia with suppressed PTH was most likely secondary to abaloparatide given the timing of the hypercalcemia after the injection and resolution of hypercalcemia and normalization of PTH. Conclusions: Abaloparatide is a peptide that selectively binds to the RG conformation of the parathyroid hormone type 1 receptor. Abaloparatide is increasingly used following the results from the ACTIVE and ACTIVExtend trials which demonstrate significant increase in bone mineral density and risk reduction of vertebral, nonvertebral, clinical, and major osteoporotic fractures. Hypercalcemia was reported as a side effect, but there is no guidance on further evaluation or management of these patients. The incidence of hypercalcemia defined as albumin-adjusted serum calcium ≥10.7mg/dL is 3.4 % and risk is increased in patients with renal impairment. As in our case, transient hypercalcemia and PTH suppression may be associated with abaloparatide. Efficacy of abaloparatide and impact on bone density with delay or interrupted treatment are not available. Further studies are needed to guide monitoring and treatment of clinically symptomatic transient hypercalcemia in patients taking abaloparatide.

Statin related musculoskeletal complications; Necrotizing Autoimmune Myositis… more than Myalgia.

Statins are widely prescribed and well tolerated with most side effects now considered a nocebo effect. Occasionally, statins can be associated with immune mediated necrotizing myositis that is both difficult to diagnose and treat. Aggressive immunosuppressive therapy is the best recognized method of treatment of this complication.

COVID-19 IgG-related autoimmune inflammatory necrotizing myositis

The COVID-19 pandemic caused by the SARS-CoV-2 virus has affected millions of people around the globe. The most common presentation of COVID-19 is fever and upper and lower respiratory tract infection. Myalgia is fairly common in the prodromal phase of the viral illness which self-resolves. There is very scant literature on autoimmune myositis triggered by COVID-19 infection. We report a case of SARS-CoV-2 infection, who presented with progressive muscle weakness with rhabdomyolysis and necrotizing autoimmune myopathy on muscle biopsy. This case report imposes awareness of musculoskeletal autoimmune processes triggered by COVID-19 which requires clinical suspicion for early diagnosis and initiation of treatment.

Myasthenia gravis, myositis, myocarditis and anti-titin antibodies after Nivolumab/Ipilimumab: response with plasmapheresis

Context: Severe neurological manifestations following use of immune checkpoint inhibitors (ICIs) occur in 0.93% of patients, and together with cardiac toxicity have the higher lethality. Myasthenia gravis (MG) and polymyositis (PM) are rare, and treatment includes discontinuation of the immunotherapy, corticosteroids, and intravenous immunoglobulin (IVIG), with occasional use of plasmapheresis (PLEX). Biomarkers are not consistently reported. We report the case of a patient with MG, PM and myocarditis after ICI, with positive anti-titin antibodies and response to plasmapheresis. Case report: 81-year-old male developed ascending, subacute, progressive tetraparesis, dysphagia, ophthalmoparesis, and respiratory failure 2 weeks after second cycle of nivolumab/ipilimumab for metastatic melanoma. Physical examination showed: globally reduced strength, hypoactive reflexes, bilateral sixth nerve palsy and bilateral semi-ptosis. Prostigmine test was positive and electroneuromyography was compatible with myopathy. Labs revealed CPK 4000 U/L, troponin 9000U/L, autoimmune myositis panel negative, anti-titin antibodies (described in paraneoplastic MG and associated with severity) positive and cardiac MRI without fibrosis. Clinical picture was compatible with MG and PM with cardiac involvement. He received methylprednisolone and six PLEX sessions, with complete recovery. Four months after treatment, he developed cognitive impairment and large B-cell lymphoma (ICI complication). Conclusions: PM and MG may occur after ICI, especially in the first cycles, and anti-titin may be a biomarker of severity in these patients. Although guidelines recommend adding IVIG or PLEX in refractory or severe cases, PLEX may be first choice, especially if multiple ICI are present.