Primary chronic cold agglutinin disease: a population based clinical study of 86 patients.
OBJECTIVE
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.


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%).


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.
Department of Medicine, Haugesund Hospital, Haugesund, Norway. s.beren@online.no
Sigbjørn
S
Berentsen
Elling
E
Ulvestad
Ruth
R
Langholm
Klaus
K
Beiske
Henrik
H
Hjorth-Hansen
Waleed
W
Ghanima
Jon Hjalmar
JH
Sørbø
Geir E
GE
Tjønnfjord
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000744:Anemia, Hemolytic, Autoimmune / Q000453:epidemiology* / Q000473:pathology / Q000628:therapy; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders; D009664:Norway / Q000453:epidemiology; D012189:Retrospective Studies