Acute Digital Gangrene with Concurrent Sjogren’s Syndrome and Marginal Zone Lymphoma

Summary: BACKGROUND Digital gangrene poses a significant diagnostic challenge due to its diverse etiologies, including systemic autoimmune diseases, atherosclerosis, infections, drugs, vasculitis, and less commonly, malignancies. Malignancies can induce paraneoplastic syndromes, which may present with rheumatic manifestations such as Raynaud’s phenomenon or digital ischemia. Raynaud’s syndrome, acrocyanosis, and digital ischemia is less frequently seen in hematologic malignancies. Paraneoplastic vasculitis may rarely arise in malignancies such as Hodgkin’s disease or Multiple Myeloma. CASE PRESENTATION A 42-year-old male with Sjogren's Syndrome and Marginal Cell Lymphoma presented with right fourth digit swelling and discoloration. He also had pain and decreased flexion of the finger, fevers, night sweats, Raynaud’s phenomenon, parotid swelling, and sicca symptoms. The patient was previously on Methotrexate, Azathioprine, and Hydroxychloroquine, which were discontinued when he was diagnosed with Marginal Cell Lymphoma and was initiated on rituximab. The patient received the tenth cycle of rituximab two days prior to admission. Upon presentation to the hospital, vital signs were stable. Physical examination revealed a discoloration of the right fourth digit, a cutaneous ulcer on right second digit, reticulated pattern of legs, parotid gland swelling, and axillary lymphadenopathy. Laboratory workup revealed leukopenia, microcytic anemia, thrombocytopenia, elevated sedimentation rate (32 mm/hr) and C-reactive protein (112 mg/L), hypoalbuminemia, and negative Hepatitis C, RPR, and HIV. Arterial doppler of upper and lower extremities revealed no evidence of occlusive abnormalities. Right upper extremity CT showed soft tissue swelling of the right hand. Right hand MRI showed an early abscess on the lateral aspect of the fourth digit. He was initiated on IV Piperacillin-Tazobactam and Vancomycin. He underwent incision and drainage of the right fourth digit. Tissue culture grew MSSA and Enterococcus faecalis. The patient was transitioned to oral minocycline and Co-Amoxiclav. CT chest was negative for a source of septic emboli but showed increased size of pulmonary nodules, new hepatic lesions, and enlarged axillary, mediastinal, and abdominopelvic lymphadenopathy. CT-guided core liver biopsy with flow cytometry revealed monoclonal B cells with monoclonal plasma cells. Serum IFE, kappa/lambda ratio, and electrophoresis showed hypogammaglobulinemia but no monoclonal paraprotein. Necrosis of the digit progressed. Vasculitis workup including rheumatoid factor, cryoglobulins, ANCA, immunoglobulin subclasses, Scl-70, and anti-centromere were negative. Parotid ultrasound showed heterogeneous bilateral parotid glands with hypoechoic foci. Transthoracic echocardiogram (echo) was negative for valvular lesions, but it could not visualize the right ventricle. Transesophageal echo showed no vegetations of intra-cardiac thrombus. Debridement, irrigation, and partial amputation through the middle phalanx were performed. Surgical pathology showed skin and soft tissue necrosis and inflammation with abscess formation. Liver biopsy revealed clusters of B cells consistent with a history of lymphoma. He was discharged for outpatient oncology follow-up with his Rituximab schedule. DISCUSSION In this case, the differential diagnosis for digital necrosis included infection, malignancy, cryoglobulinemia, and vasculitis. He received antibiotics upon admission, and despite treatment, the gangrene progressed. While vasculitis and cryoglobulinemia were considered, the absence of multiorgan involvement and recent rituximab therapy favored an infectious or malignant cause. The patient’s neutropenia, lymphopenia, and hypoglobulinemia, suggested adequate immunosuppression from rituximab. Imaging and liver biopsy suggested a lymphoma flare as the primary pathology. The complex medical history and immunocompromised state of the patient posed challenges in diagnosis and management. CONCLUSION The objective of this case is to illuminate the intricacies involved in diagnosing the underlying cause of digital gangrene, especially in individuals with underlying autoimmune conditions and malignancies. Timely recognition of the underlying pathology is essential for appropriate treatment and prevention of complications.