Clinical characteristics, radiological features and outcomes in pulmonary involvement of cryoglobulinemia

Abstract

Background: Cryoglobulinemia with pulmonary involvement is rare, and its characteristics, radiological findings, and outcomes are still poorly understood.

Methods: Ten patients with pulmonary involvement of 491 cryoglobulinemia patients at Peking Union Medical College Hospital were enrolled in this retrospective study. We analyzed the characteristics, radiological features and management of pulmonary involvement patients, and compared with those of non-pulmonary involvement with cryoglobulinemia.

Results: The 10 patients with pulmonary involvement (2 males; median age, 53 years) included three patients with type I cryoglobulinemia and seven patients with mixed cryoglobulinemia. All of 10 patients were IgM isotype cryoglobulinemia. All type I patients were secondary to B-cell non-Hodgkin lymphoma. Four mixed patients were essential, and the remaining patients were secondary to infections (n = 2) and systemic lupus erythematosus (n = 1), respectively. Six patients had additional affected organs, including skin (60%), kidney (50%), peripheral nerves (30%), joints (20%), and heart (20%). The pulmonary symptoms included dyspnea (50%), dry cough (30%), chest tightness (30%), and hemoptysis (10%). Chest computed tomography (CT) showed diffuse ground-glass opacity (80%), nodules (40%), pleural effusions (30%), and reticulation (20%). Two patients experienced life-threatening diffuse alveolar hemorrhage. Five patients received corticosteroid-based regimens, and four received rituximab-based regimens. All patients on rituximab-based regimens achieved clinical remission. The estimated two-year overall survival (OS) was 40%. Patients with pulmonary involvement had significantly worse OS and progression-free survival than non-pulmonary involvement patients of cryoglobulinemia (P < 0.0001).

Conclusions: A diagnosis of pulmonary involvement should be highly suspected for patients with cryoglobulinemia and chest CT-indicated infiltrates without other explanations. Patients with pulmonary involvement had a poor prognosis. Rituximab-based treatment may improve the outcome.

Keywords: Alveolar hemorrhage; Cryoglobulinemia; Diffuse ground-glass opacity; Rituximab.

Fig. 1

A-E, CT imaging findings associated with cryoglobulinemia and lung involvement. A, Diffuse, bilateral, patchy GGOs. B, Diffuse alveolar hemorrhage. C, Solitary large nodule in the right upper lobe. D, Diffuse, bilateral, multiple, small nodules. E, Bilateral pleural thickening. F, Bilateral pleural effusions

Fig. 2

CT scans during the treatment of patient #2. A-C, Bilateral multiple patchy and diffuse GGOs along with symptoms of acute dyspnea and hemoptysis. D-F, Remarkable improvement of pulmonary infiltrates after high-dose corticosteroids and rituximab for 4 courses. G-I, Stability of symptoms and infiltrates on repeat chest CT 6 months after the episode of hemoptysis (A)

Fig. 3

Comparison of survival among patients of cryoglobulinemia. (A) Overall survival (OS) and progression-free survival (PFS) of the whole cohort (n = 491). (B) OS of cryoglobulinemia patients with pulmonary involvement (n = 10) and those without pulmonary involvement (n = 481). (C) PFS of cryoglobulinemia patients with pulmonary involvement (n = 10) and those without pulmonary involvement (n = 481)