BACKGROUND: Mycobacterium haemophilum is a rare, slow-growing nontuberculous mycobacterium known to cause infections primarily in immunocompromised individuals. M. haemophilum infections typically present as skin and soft tissue infections
however, infections may progress to disseminated disease involving multiple organ systems. Diagnosing M. haemophilum infections can be challenging due to its slow growth in conventional culture methods and its resemblance to other mycobacterial species. As a result, it may be misidentified or overlooked, leading to delays in diagnosis and appropriate treatment. The prognosis of M. haemophilum infections can vary depending on factors such as the extent of the disease, the timeliness of diagnosis, and the patient's underlying health condition. SUMMARY: In this case report, we provide a detailed clinical presentation, diagnostic workup, and treatment course of a heart transplant patient with M. haemophilum infection. Our patient presented with worsening generalized pain in multiple skin lesions. After extensive rheumatologic and infectious workup leading to nodule biopsies, the patient was diagnosed with M. haemophilum by Karius test and started on appropriate treatment. CONCLUSION: Early recognition and appropriate treatment are essential for improving outcomes and reducing morbidity and mortality associated M. haemophilum. This case underscores the clinical utility of the Karius test in identifying unusual pathogens in a heart transplant patient with a complex medical history, emphasizing the role of next generation sequencing tests in aiding in earlier diagnosis to guide treatment and improve patient outcomes in challenging infectious disease cases.