Clinical features and pathogenesis of macroglobulinaemia.

Abstract

Serum protein abnormalities may be classified into dysproteinaemias -quantitative alterations in normal serum components-and paraproteinaemias, in which serum globulins normally absent or present in only minimal concentration (myeloma globulins, cryoglobu lins, and macroglobulins) are found in greatly increased amount. Macroglobulins are globulins of high mole cular weight (over one million) whose presence is associated with a definite syndrome, macroglobulin aemia, which requires ultracentrifugal analysis of the serum for conclusive diagnosis (Waldenstrom, 1944, 1948). This paper describes three new cases of macro globulinaemia and refers briefly to one (Case 4) previously reported (Mackay, 1956). The condition cannot be regarded as rare in Australia, for these four cases came under notice in Melbourne in a period of eight months. Patients are elderly, and males exceed females. The outstanding symptoms are lethargy and a bleeding tendency (epistaxis, oral bleeding, and easy bruising). There may be a history of vague ill-health for several years, with recurrent infections, often of the respiratory tract. Examination discloses slight painless enlargement of the liver, spleen, and lymph nodes in most cases, but bulky lymphoid hyperplasia seldom occurs (Mackay, 1956; Jahnke et al., 1956). Peripheral blood examination reveals some degree of anaemia, and usually pancytopenia. Despite the pro nounced bleeding tendency, no consistent coagulation defect is observed (Jahnke et al., 1956). A skeletal survey shows, at most, osteoporosis, but no focal translucencies. Many of the laboratory findings depend on the hyper globulinaemia, which ranges from 4 to 8 g. per 100 ml.: these include rouleaux formation in blood smears, a high erythrocyte sedimentation rate, a positive formol-gel test, and a myeloma-like protein component on filter-paper electrophoresis of serum. The serum viscosity increases with a fall in temperature, often with the formation of a gel which redissolves on warming ; this gel represents one type of cryoglobulin. The Sia test (a dense white pre cipitate on adding a drop of serum to distilled water) is a useful screening test, although false positives may occur, notably in multiple myeloma.