Digital Necrosis Associated with Chronic Cold Haemagglutinin Disease.

A 48-year-old man noticed dark urine for the first time 3 years before the current presentation. He had also noticed that his fingers and ears became pale in winter. These signs disappeared when his body became warmer. Three years later, he moved to a colder region for a new job as an agricultural worker. On one winter day, he had to scrub farm tools outdoors, when the temperature was 0·6°C. On the following day, his fingers were painful and black (onset, day 1). He was transferred to our hospital from the local clinic on day 10. The clinical course prompted us to suspect chronic cold haemagglutinin disease. As expected, a cold agglutinin was detected, at a titre of 1:8192. A direct antiglobulin test was positive for C3d but negative for immunoglobulin (Ig)G. Serum immunoelectrophoresis demonstrated an IgM κ gammopathy with an IgM level of 5·2 g/l. Serum tests for cryoglobulins and hepatitis B and C viruses were all negative. Bone marrow examination identified aggregates of small lymphoid cells with surface expression of CD20. Immunohistochemistry and flow cytometry showed κ light chain restriction. He was thus diagnosed with chronic cold haemagglutinin disease associated with macroglobulinaemia. Plasmapheresis, but not heparin or a prostaglandin analogue, improved his peripheral circulation (day 11). However, his distal fingers showed dry necrosis (image, day 16). He received rituximab monotherapy followed by amputation of the fingers. Serum levels of IgM decreased in association with clearance of lymphoid aggregates from the bone marrow. He relocated to a warmer region and was lost to follow-up.