Prostatic malakoplakia is an uncommon chronic inflammatory disorder, tumor-like but non-cancerous, the diagnosis of which pivots crucially on the identification of characteristic Michaelis-Gutmann bodies within the pathological tissue. We hereby present an inaugural case report of prostatic malakoplakia concurrent with sepsis caused by multidrug-resistant Escherichia coli, verified through blood culture and metagenomic next-generation sequencing (mNGS). The pathogenesis might be associated with infections by Escherichia coli, immune system irregularities, or lysosomal dysfunction. Although the patient had no chronic underlying diseases, he presented early with sepsis and multi-organ dysfunction. This case emphasizes the imperative to further investigate the association between malakoplakia and Escherichia coli, the necessity for prompt diagnosis, and the supportive role of mNGS, and the treatment strategy focuses on rapid control of infection and systemic inflammatory response.

Rationale: Anti-phospholipase A2 receptor (PLA2R) antibody is a highly specific serological marker for primary membranous nephropathy, with a detection rate of <2% in minimal change disease (MCD). This case represents the first report of PLA2R-positive adult MCD complicated by active pulmonary tuberculosis (TB) and systemic osteoarthropathy, highlighting the potential for chronic infection to induce PLA2R antibodies through inflammatory activation or molecular mimicry. Patient concerns: A 73-year-old male with 7-year steroid-dependent nephrotic syndrome developed pulmonary TB and systemic osteoarthropathy during immunosuppressive therapy. Diagnoses: Serial renal biopsies confirmed MCD/focal segmental glomerulosclerosis (FSGS) without membranous nephropathy features. PLA2R antibody was transiently positive (16.6 RU/mL) during active TB but turned negative after anti-TB treatment. TB was confirmed by next-generation sequencing. Interventions: A multidisciplinary strategy was implemented: rifapentine replaced rifampicin to maintain tacrolimus levels; rituximab was administered for refractory proteinuria; and TB was treated with a 9-month regimen. Osteoarthropathy was managed with Tripterygium glycosides and joint injections. Outcomes: Following rituximab administration, 24-hour urinary protein decreased from 6.32 g to 1.5 g. TB was controlled with sputum conversion within 2 months. PLA2R antibody became negative post anti-TB therapy, supporting the hypothesis of infection-induced seropositivity. No renal function decline or TB dissemination occurred. Lessons: This case suggests that chronic infections like TB may transiently induce PLA2R antibodies via inflammatory activation, highlighting the need for dynamic serologic and histopathologic correlation to avoid misdiagnosis in PLA2R-positive non-MN patients. Multidisciplinary management is critical to balance immunosuppression and infection control.