Related Experiment Video
Updated: Aug 9, 2026
An Immunohistopathologic Study to Profile the Folate Receptor Beta Macrophage and Vascular Immune Microenvironment in Giant Cell Arteritis
Published on: February 8, 2019
Primary chronic cold agglutinin disease: a population based clinical study of 86 patients
Sigbjørn Berentsen1, Elling Ulvestad, Ruth Langholm
1Department of Medicine, Haugesund Hospital, Haugesund, Norway. s.beren@online.no
Insights
Chronic cold agglutinin disease (CAD) is a lymphoproliferative disorder. This study details its epidemiology, clinical features, and treatment, finding Rituximab effective despite the disease not being indolent.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Chronic cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia with incompletely understood characteristics.
- Understanding the epidemiology and clinical spectrum of primary CAD is crucial for patient management.
Purpose of the Study:
- To comprehensively assess the epidemiology, clinical and pathological features, disease course, and therapeutic responses in primary CAD.
- To provide precise data on a poorly understood hematological disorder.
Main Methods:
- A population-based, retrospective follow-up study was conducted in Norway.
- Data were collected from 86 patients diagnosed with primary CAD.
Main Results:
- The prevalence of primary CAD was 16 cases per million, with a median age of onset at 67 years.
- Common manifestations include cold-induced circulatory symptoms (91%) and exacerbation of hemolytic anemia during febrile illness (74%).
- Rituximab demonstrated acceptable response rates (60%), while 90% had monoclonal IgM and 76% showed signs of lymphoma.
Conclusions:
- Primary CAD is a spectrum of clonal lymphoproliferative disorders, often presenting with lymphoma characteristics.
- Despite a generally favorable survival prognosis, CAD exhibits significant clinical activity and manifestations.
Background And Objectives:
Our knowledge of primary chronic cold agglutinin disease (CAD) is incomplete. The aim of this study was to collect comprehensive and precise data the on epidemiology, clinical and pathological features, course, and therapy of CAD.
Design And Methods:
We performed a population-based retrospective follow-up study of as many as possible of all CAD patients in Norway. Eighty-six patients were studied.
Results:
The prevalence of primary CAD was 16 cases per million inhabitants. The incidence rate was 1 per million per year. The median age at onset was 67 years (range, 30-92) and the male to female ratio was 0.55. The median survival was 12.5 years from onset. Autoimmune diseases other than CAD were reported in 8% of patients, cold-induced circulatory symptoms in 91%, and exacerbation of hemolytic anemia during febrile illness in 74%. At least 51% had received red blood cell transfusions. The mean initial hemoglobin level was 9.2 g/dL (range, 4.5-15.6) and the median monoclonal immunoglobulin level 4.0 g/L (range, 0.0-47.3). Most laboratory findings did not change significantly during a median follow-up of 5 years. Monoclonal IgM was detected in 90%; IgG and IgA in 3.5% each; with kappa light chains in 94%. An abnormal kappa/lambda ratio in bone marrow was found in 90%, lymphoma in 76%, and lymphoplasmacytic lymphoma in 50%. Transformation to aggressive lymphoma occurred in 3.5% during 10 years. Rituximab therapy was the only treatment showing acceptable response rates (60%).
Interpretation And Conclusions:
Primary CAD represents a spectrum of clonal lymphoproliferative bone marrow disorders, in most cases with morphological signs of lymphoma. Despite a favorable prognosis for survival, the disease is not indolent in terms of clinical manifestations.