Excessive Immunosuppression: Pulmonary Granulomas Due to Mycoplasma in a Transplant Recipient

Introduction: Immunosuppression (IS) for kidney transplantation requires a delicate balance between preventing rejection and avoiding consequence. We report the first case of a kidney transplant recipient diagnosed with pulmonary caseating granulomas secondary to Mycoplasma pneumoniae (Mp). Case Description: A 2-year-old female received a living-related donor kidney transplant from her biologic father (CMV -/- and EBV +/-) for end stage kidney disease due to congenital nephrotic syndrome. EBV reactivation occurred 3 months post-transplant demonstrated by PCR showing >800,000 copies/mL. Low EBV copy numbers persisted for 14 years despite converting maintenance IS from tacrolimus and mycophenolate to sirolimus and azathioprine. Frequently, trough sirolimus levels were >10 ng/mL. At age 16 she presented with three days of non-productive cough and fever, and was treated with azithromycin without improvement. She presented to a local ED febrile, tachypneic, and ill-appearing. Chest x-ray confirmed multifocal pneumonia. Tests for COVID-19, influenza A & B, and RSV were negative. Immune flow cytometry revealed absolute CD4 count 339/mcL, CD8 1314/mcL and CD4:8 ratio of 0.26 (ref 1.09-4.26). EBV PCR was positive to 324 copies/mL, and serologies confirmed absence of EBV nuclear antibodies. Azathioprine was held and sirolimus dose reduced while IV broad-spectrum antibiotics were empirically started. Additional testing was negative for legionella, cryptococcus, aspergillus, tuberculosis, HIV, and histoplasmosis. A CT scan of the chest demonstrated multi-lobar pneumonia with near complete collapse of the right middle lobe. A bronchoalveolar lavage was performed and was negative for pneumocystis, acid-fast bacilli, fungal, viral and bacterial antigens. An interval CT scan had features concerning for PTLD. Endobronchial biopsy was performed, demonstrating caseating granulomas with adjacent cells containing EBV-positive nuclei. PTLD workup was negative. Advanced testing of the granulomatous specimen confirmed Mp by PCR. Discussion: Mycoplasma is typically self-limited. We hypothesize that over IS facilitated T-cell hypersensitivity and chronic active EBV, which created an inflammatory milieu that activated Mp-infected alveolar macrophages to form granulomas. To our knowledge this is the first report of pulmonary granulomas secondary to Mp diagnosed in a transplant patient.