OUP user menu

Waldenstrom's syndromes

D. Geraint James
DOI: http://dx.doi.org/10.1093/qjmed/hcp061 67-68 First published online: 17 December 2009

Jan Gosta Waldenstrom (17 April 1906–1 December 1996) had a very medical background. His great grandfather was a general practitioner in North Sweden, grandfather Johan was Professor of Medicine in Uppsala and his father, Henning, was Professor of Orthopaedic Surgery in Stockholm. Three of Jan's sons, Johan, Anders and Erik represent a fifth generation in medicine. Jan studied medicine in Uppsala and Cambridge and also studied organic chemistry in the laboratory of the pyrrol chemist and Nobel Prize winner Hans Fisher in Munich, a background which equipped him for his approach to biochemical and metabolic aspects of medicine. He graduated in 1937 and eventually became Professor and Chairman of the Department of Medicine to the University of Lund (1950–72).

He was one of the world's great professors of medicine, one of the finest bedside clinicians and an outstanding editor of Acta Medica Scandinavica. He was elected to foreign membership of the US National Academy of Sciences, the French Academy of Sciences, Fellow of the Royal College of Physicians (1966) and Honorary Member of the Royal Society of Medicine, London. He received honorary doctorates from the Universities of Oslo, Dublin, Mainz and Oxford.

Jan was a knowledgeable botanist, multilingual, well read in literature and well versed in classical music. He maintained international contacts world wide and visited most of them.

Waldenstrom's uveoparotitis: Sarcoidosis

When Waldenstrom was a Lecturer in Medicine in Uppsale, he was quick to observe a group of patients with uveoparotitis attending the medical, surgical and ophthalmic clinics. He described five patients with bilateral parotid gland enlargement and bilateral uveitis. Four of them were women and they were all over 30 years of age. The disease process was clearly multisystem for one or other of these patients had evidence of involvement of the neurological system, lungs, lymph nodes or skin, as well as fever or hyperglobulinaemia. Sarcoid tissue was clearly demonstrable in the parotid gland tissue of one patient. Waldenstrom drew particular attention to bizarre neurological manifestations of sarcoidosis, which included right-sided facial palsy, hypoglossal nerve palsy or bilateral optic neuritis.

Waldenstrom's autoimmune chronic active hepatitis

In 1950, Jan Waldenstrom addressed a meeting on Digestion and Metabolic Diseases at Bad Kissingen in the Black Forest. The title of the paper was ‘Leber, Blutproteine and Nahrungseiweiss’. In this lecture, he referred to a particularly interesting group of young people, predominantly girls during or shortly after puberty, suffering from a form of chronic liver disease. The general features were moderate jaundice with intermittent bilirubinuria and, in the latter stage, with ascites and oesophageal varices. In almost all cases, there were spider naevi and acne. Amenorrhoea, which was anovulatory, was typical. Erythrocyte sedimentation was increased. Flocculation tests were positive. It has since received many names including lupoid hepatitis, active juvenile cirrhosis and plasma cell hepatitis.

Waldenstrom's macroglobulinaemia

The development of the ultracentrifuge in 1923 by T. Svedberg and K.O. Pedersen, and the electrophoresis apparatus in 1937 by A. Tiselius made it possible for Waldenstrom to make perhaps his most important contribution to medicine. These were his studies of γ-globulins in different clinical conditions. In 1943 Waldenstrom, in collaboration with K.O. Pedersen, demonstrated the presence of large quantities of a high-molecular weight globulin (macroglobulin) in plasma of a group of patients. The protein had a molecular weight of 1 000 000 and was designed IgM or γM. Pedersen studied the physico-chemical and chemical properties of the protein while Waldenstrom described the associated clinical features of the macroglobulinaema. The syndrome which now bears his name was published in 1944 when he described the hallmarks of incipent myelomatosis or essential hyperglobulinaemia with fibrinogenopenia. Waldenstrom subsequently suggested that disorders with unusual concentrations of immunoglobulins should be termed gammopathies. He differentiated the electrophoretic patterns of monoclonal and polyclonal gammopathies. The pattern of γ-globulin in a chronic viral disease was very broad (polyclonal) whereas in that of myeloma it was sharp with a narrow spike (monoclonal).

Waldenstrom's porphyria

He coined the term porphyria, identified porphobilinogen, established the dominant heredity of acute intermittent porphyria, and pointed out the disastrous role of barbiturates and other synthetic drugs in producing lethal porphyric attacks. He felt that acute intermittent porphyria was commonly inherited in northern Sweden.

Iron deficiency

He described ‘sideropenia sine anaemia’, iron deficiency in the absence of anaemia and the oesophageal web in some iron deficient patients. He regarded it as another epithelial change, similar to spooning of the nails (koilonychias) that results from iron deficiency.

Waldenstrom's carcinoid syndrome

He combined his clinical acumen and biochemical knowledge to provide a clear profile of the carcinoid syndrome. He provided a clear basis of information on the diarrhoea, flushing, skin changes, oedema and valvular heart disease upon which other scientists described the large quantities of 5-hydroxytryptamine (5HT) associated with this syndrome.

Conflict of interest: none declared.

Reference