Abstract Introduction MDA5-positive dermatomyositis is frequently complicated by rapidly progressive interstitial lung disease(RP-ILD). We report a case of concurrent RP-ILD and Pneumocystis Jirovecii pneumonia(PJP), highlighting diagnostic and therapeutic challenges carried by the elevated risk of opportunistic infection. Description A 57-year-old woman presented to clinic with a two-month history of violaceous papules on multiple Metacarpophalangeal(MCP) and Proximal Interphalangeal(PIP) joints, violaceous erythema on proximal extremities, subtle periocular erythema and edema, and ulcerations overlying elbow erythema. Skin biopsy supported the diagnosis of dermatomyositis and serology revealed elevated MDA5 antibody titers(142 U; normal 20). Baseline chest computed tomography(CT) demonstrated ground-glass opacities(GGOs), concerning for interstitial lung disease(ILD). She was started on methotrexate and prednisone 50mg daily, tapered by 10mg weekly to 20mg. She was also diagnosed with Tuberculosis infection(TBI) and started on Rifapentine/INH for 12 weeks. Subsequently, she developed worsening cough and dyspnea, prompting hospital admission. On admission, chest CT showed rapid progression of GGOs. Empiric antibiotics and trimethoprim-sulfamethoxazole were initiated for possible pneumonia and PJP, however she developed worsening hypoxemia requiring ICU and high-flow nasal cannula. Induced sputum PCR confirmed PJP. Despite therapy, a repeat chest CT showed worsening GGOs. Given concern for concurrent RP-ILD, she received pulse-dose steroids, one dose of intravenous cyclophosphamide, and IVIG for four days. A third immunosuppressive agent was deferred due to pancytopenia. She showed gradual pulmonary improvement and was discharged on prednisone 60mg daily with PJP therapy. At follow-up, tofacitinib was initiated and subsequently daratumumab for refractory cutaneous disease. Discussion This case highlights the challenges of managing MDA5-positive dermatomyositis complicated by RP-ILD and an opportunistic infection. Anti-MDA5 antibodies are strongly associated with aggressive ILD, often the major cause of morbidity and mortality. However, treatment requires potent immunosuppression that increases infection risk. Distinguishing ILD progression from infection is difficult, as both manifest with GGOs and hypoxemia. In this patient, the coexistence of RP-ILD and PJP complicated management and required a balance between antimicrobial therapy and immunosuppression. The presence of TBI further added to the challenge given the risk of reactivation under immunosuppression. Current guidelines recommend prophylaxis in patients receiving prolonged high-dose corticosteroids, as well as patients with MDA5-positive Dermatomyositis as it is an independent risk factor for PJP. This case emphasizes the importance of infection prevention to avoid preventable complications. Outcomes in MDA5-positive dermatomyositis with RP-ILD remain poor, and currently no standardized diagnostic or treatment protocols exist. Optimal management of this disease necessitates a multidisciplinary approach, careful surveillance, and urgent formulation of unified guidelines. This abstract is funded by: none
Surya et al. (Fri,) studied this question.