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A “missed” cryoglobulin: the importance of in vitro calcium concentration
  1. MARC ANDRÉ,
  2. HAKIM MAHAMMEDI,
  3. OLIVIER AUMAITRE
  1. ARLETTE TRIDON
  1. JEAN-DANIEL TISSOT
  1. JEAN-CHARLES PIETTE
  1. Department of Internal Medicine, Gabriel Montpied Hospital, CHU of Clermont-Ferrand, BP 69, 63003 Clermont-Ferrand Cedex 1, France
  2. Laboratory of Immunology, University of Medicine and Pharmacy, BP 38, 63001 Clermont-Ferrand Cedex 1, France
  3. Fondation Centre de Transfusion Sanguine (SRTS VD), 27 rue du Bugnon, CH-1005 Lausanne, Switzerland
  4. Department of Internal Medicine, Pitié-Salpêtrière Hospital, 75651 Paris Cedex 13, France
  1. Dr Aumaitre

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Cryoglobulins are immunoglobulins which precipitate at reduced temperature and that redissolve by warming the serum sample to 37 °C. Mixed cryoglobulinaemia may manifest clinically as skin, articular, renal, and peripheral nerve complications.1 To ensure optimal detection, blood samples must be obtained and preserved at 37 °C. We report on a patient whose clinical presentation was suggestive of cryoglobulinaemia. Because cryoglobulins had been either undetectable or found at very low levels for several years despite repeated careful blood sample examinations with conventional assays, we initially thought he had Henoch-Schönlein purpura. The recent use of a modified assay finally led us to diagnose mixed cryoglobulinaemia. Included below is a description of the method used for cryoglobulin detection, emphasising the importance of in vitro calcium concentration.

Case report

A 52 year old man with multiple lipoma had a 20 year history of polyarthralgias affecting elbows, wrists, hands, knees, and feet, a 10 year history of Raynaud's disease affecting the hands and feet, and a seven year history of palpable purpura. His sister had coeliac disease. In June 1996 he developed attacks of abdominal pain concomitantly with arthralgias and palpable purpura of both legs. Serum creatinine was 95 μmol/l. Gammaglobulins were low (4.2 g/l) on serum protein electrophoresis. Serum concentrations of immunoglobulins were 4.49 g/l for IgG (normal range 6.42–11.92), 1.84 g/l for IgM (normal range 0.52–1.47), and 2.51 g/l for IgA (normal range 1.05–3.36). Tests for rheumatoid factors, including the Rose-Waaler test (Sanofi Pasteur, Marnes La Coquette, France), were positive (table 1), but other serum autoantibodies remained negative, including antinuclear, anti-DNA, and antineutrophil cytoplasmic antibodies. Complement concentrations were notably down, both …

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