Cryoglobulins are Igs that precipitate at low temperatures.
1. Type I cryoglobulinaemia:
• Type I: monoclonal IgG or IgM (25% of cases).
• The cryoglobulins obstruct vessels (occlusive vasculopathy), causing RBC
extravasation without inflammation (no vasculitis).
• Associations: chronic lymphatic leukaemia, multiple myeloma, Waldenström
macroglobulinaemia.
What should I look for?
• Patients are sensitive to cold and complain of raynaud phenomenon.
• Mottling of the skin or blotchy cyanosis of the helix of the ears, as well as fingers and
toes.
• Initially, cold-induced lesions may be urticarial but then become purpuric and blister or
ulcerate.
2. Type II and type III mixed cryoglobulinaemia
• Type II: monoclonal and polyclonal Igs (25% of cases).
• Type III: polyclonal Igs (50% of cases).
• Immune complexes precipitated in vessel walls induce a small-vessel vasculitis that can
affect many organs.
• Associations: connective tissue diseases, e.g. RA or SLE; infections, especially HCV
infection in type II mixed cryoglobulinaemia. HCV infection triggers B-cell clonal
expansions that may be associated with monoclonal gammopathy or, rarely, non-Hodgkin
B-cell lymphoma.
What should I look for?
• Palpable purpura: the first sign in most patients.
• Arthralgia (70%).
• Sensorimotor neuropathy (60%).
• Raynaud phenomenon (30%).
• Renal involvement (20–30%).
• Chronic leg ulcers (15%), usually above the malleoli, surrounded by purpura, but
without signs of venous stasis.