Type II cryoglobulinemia in a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma and Sjögren's disease

Abstract

Type II cryoglobulinemia is a rare disorder characterized by abnormal immunoglobulins (Igs) precipitating in the blood at low temperatures and redissolving upon warming. Sjogren's disease (SjD) is an autoimmune disorder involving secretory gland malfunction that leads to persistent dryness of the mouth and eyes. Here, we report the case of a 61-year-old woman with a 7-year history of SjD who was diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). However, her complicated clinical features could not be sufficiently explained by this disease alone. Immunofixation electrophoresis revealed monoclonal IgM-κ and polyclonal IgG-κ. The presence of precipitated cryoglobulin and elevated rheumatoid factor levels confirmed a diagnosis of type II cryoglobulinemia for this patient. To the best of our knowledge, this case represents the first report of a patient with CLL/SLL, SjD, and type II cryoglobulinemia, which increased our understanding of immune system-related disorders. Because certain similar mechanisms are involved in the pathogenesis of these three diseases, a combination treatment of rituximab, ibrutinib, and dexamethasone resulted in a favorable prognosis for this patient.

Keywords: Cryoglobulinemia; Sjögren’s disease; chronic lymphocytic leukemia; cryoglobulin; dexamethasone; ibrutinib; rituximab; small lymphocytic lymphoma.

Figure 1.

The clinical features of the patient. (a) Ulceration, scabs, hyperpigmentation, and inflammation occurred simultaneously on her right lower leg. (b) The lung computed tomography (CT) scan showed interstitial changes and pleural effusion in both lungs. (c) 18F-fluoreodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) revealed multiple highly metabolically active lymph nodes and skin on the right lower leg. (d) The results of immunofixation electrophoresis analysis of the serum. A small cluster of monoclonal bands can be seen in the far-left lane. The lanes labeled as G, M, and κ demonstrated a monoclonal IgM-κ band and polyclonal IgG-κ band, respectively. The lambda anti-sera were performing normally and the tests were conducted using serum and urine separately, with equivalent results observed and (e) the cryoglobulin testing showed positive results and the cryocrit was approximately 65%. Specifically, 20 mL of blood was drawn into collection tubes that were prewarmed to 37°C without anticoagulants. After clotting at 37°C for 30 minutes, the serum was separated by centrifugation at 37°C, placed into a graduated tube, and refrigerated at 4°C to allow cryoglobulin precipitation after 24 hours.

Figure 2.

The diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was made through pathological and flow cytometry analyses. (a) Flow cytometry analysis of P3 of the blood revealed CD5+, CD19+, CD20+, CD23±, FMC7−, CD22±, CD79b−, and slg− in 8.4% of all lymphocytes and 0.7% of the total cells. P2 was lymphocytes; 8.3% of the total cells. P4 was granulocytes; 86.0% of the total cells. P6 was monocytes; 4.3% of the total cells. (b) Immunophenotyping analysis of the lymph node revealed CD20+, Ki-67(1%+), CD10−, CD5+, CD19+, CD3(partial+), CD23+, Bcl2+, Bcl6−, and CyclinD1−. (c) Inguinal lymph node biopsy indicated SLL (hematoxylin and eosin [H&E] stain, 40×) and (d) skin biopsy indicated sclerosing panniculitis with SLL/CLL cell infiltration (H&E stain, 100× and 400×).

Figure 3.

Patient improvement after treatment. (a) The pulmonary inflammatory exudate was significantly alleviated after two cycles of therapy and (b) the skin ulcers and cyanosis on the patient’s right lower leg were improved.