Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (385 page)

   
Type II
(
essential mixed cryoglobulinemia
): monoclonal immunoglobulin mixed with at least one other type of polyclonal immunoglobulin, typically IgM or IgA and polyclonal IgG; always associated with rheumatoid factor (RF).

   Causes 40–60% of cases.

   Associated most often with chronic HCV or HIV infection; less often with HBV, EBV, bacterial and parasitic infections, autoimmune diseases, Sjögren syndrome, and syndrome of essential mixed cryoglobulinemia, immune complex nephritis.

   High-titer RF without definite rheumatic disease.

   C4 levels are decreased.

   
Type III:
mixed polyclonal immunoglobulin, most commonly IgM–IgG, occasionally IgA–IgG combinations, usually with RF. Types II and III generally produce 1–5 mg/dL CG.

   Causes 40–50% of cases.

   Most commonly associated with connective tissue disorders (SLE, Sjögren syndrome), persistent infections (HIV, HCV), and rarely with lymphoproliferative disorders.

   In types II and III, the skin, peripheral nervous system, and kidneys are predominantly involved.

   Who Should Be Suspected of CG?

Patients with cutaneous manifestations (erythematous macules, purpuric papules of the lower extremities, ulcers), the hyperviscosity syndrome, vasculitis, sensitivity to cold including Raynaud phenomenon, and the Meltzer triad: arthralgia, purpura, and weakness.

   Laboratory Findings

   CG are tested on serum (to distinguish from cryofibrinogen, which is tested on plasma [below]). The blood is obtained in test tubes without anticoagulant, prewarmed at 37°C, and let to clot at the same temperature. Serum is incubated at 4°C to detect turbidity or precipitate after 24–72 hours. That is compared with an aliquot of the same patient’s serum kept at 37°C, which should have no precipitate.