A Case of Multiple Myeloma Complicated by Type I Cryoglobulinemia

Introduction/Background/Significance: Type I cryoglobulinemia develops in the setting of monoclonal gammopathies for about 10-15% of cases. Clinically patient's will present with severe cutaneous involvement which may include purpura, skin ulcerations, and/or glomerulonephritis.

Materials and Methods/Case Presentation/Objective: 54-year-old male with a past medical history of ESRD on peritoneal dialysis, multiple myeloma s/p chemotherapy in 2019, nephrotic syndrome, and hypertension who presented to the ED for cramping in the upper extremities and abdomen. CT Abd/Pelvis revealed large pericardial effusion, and a subsequent echo revealed a large pericardial effusion with no evidence of cardiac tamponade. CTS was following, and the patient underwent pericardial window and drain placement. In addition, given the patient's worsening uremia with chronic azotemia, the patient was transitioned to hemodialysis. During the hospital course, the patient was endorsing bilateral hand pain which initially was thought to be chemotherapy-induced peripheral neuropathy. However, the patient developed upper extremity lesions noted on fingertips, under the nail beds, splinter hemorrhage, and mottled toes, raising concern for calciphylaxis vs embolic disease given new-onset atrial fibrillation vs cryoglobulinemia. TEE was negative for embolic sources, CTA of the chest/upper extremity/abdominal aorta was unremarkable, and US arterial of the lower extremity was negative for occlusion.The patient was started on sodium thiosulfate while pending dermatology obtained punch biopsy results. Pathology of the biopsy suggested thrombotic vasculopathy with necrosis. Labs were positive for cryoglobulin analysis, low C4, elevated free kappa light chains, IgG kappa monoclonal band. Given findings for cryoglobulinemia, sodium thiosulfate was discontinued, and the patient was started on stress dose steroids. The patient was started on a seven day course of plasmapheresis with Hematology/Oncology following. The patient was discharged on prednisone, with plans for outpatient plasma exchange, Rituximab initiation, and close follow-up.

Results/Description/Main Outcome Measures: Type I cryoglobulinemia is a rare complication in patients with B cell lymphoproliferative disorders that can cause severe cutaneous involvement.

Conclusions: Cryoglobulinemia is classified into three types based on immunoglobulin composition with type 1 including the monoclonal immunoglobulins IgG, IgM, IgA. As in our case, patients with type 1 cryoglobulinemia often present with symptoms related to hyper-viscosity including Raynaud's, digital ischemia, and purpura. The pathogenesis of cryoglobulinemia results from precipitation at lower temperatures of immune complex formations which leads to vascular occlusion and inflammation. In addition, deposition of such cryoglobulins can lead to vasculitis particularly in small to medium sized vessels. Treatment is directed against the underlying disorder of the malignant B-cell lineage and reserved for symptomatic disease. For severe manifestations immunosuppressive therapy is the first line which includes corticosteroids, Rituximab, and plasmapheresis. Long-term management of type I cryoglobulinemia involves treating the underlying monoclonal gammopathy and monitoring recurrence. A study demonstrated that reported relapse rate of Type I non-infectious cryoglobulinemic vasculitis was 28%. It is important to have close follow-up with SPEP, immunofixation, and complement studies to detect early signs of recurrence. Further, patients should be educated to report symptoms like purpura, digit ischemia, or neuropathy as soon as symptoms begin as early detection can prevent severe complications.