Cryoglobulinemia (CG) is the presence of serum immunoglobulin (precipitates at low temperature and redissolves at 37°C) complexed with other immunoglobulins or proteins. Associated clinical findings include purpura in cold-exposed sites, Raynaud’s phenomenon, cold urticaria, acral hemorrhagic necrosis, bleeding disorders, vasculitis, arthralgia, neurologic manifestations, hepatosplenomegaly, and glomerulonephritis.
Causes of Cryoglobulinemia
Precipitation of cryoglobulins (when present in large amounts) causes vessel occlusion, also associated with hyperviscosity (type I); immune complex deposition followed by complement activation and inflammation; platelet aggregation/consumption of clotting factors by cryoglobulins, causing coagulation disorder; small vessel thromboses and vasculitis produced by immune complexes (types II and III).
Symptoms of Cryoglobulinemia
Symptoms and signs may include:
- Purple/red spots on the extremities
- Skin ulcers and gangrene
- Fever
- Weakness
- Numbness, tingling, or weakness in the hands or feet
- Weight loss
Diagnosis
Clinical suspicion confirmed by detection of cryoglobulins.
Treatment
Treatment based on severity of symptoms and morbidity and mortality of underlying disease.
NSAIDs For mild dermatologic and articular symptoms.
Glucocorticoids For severe visceral involvement.
Cytotoxic Agents (cyclophosphamide, melphalan, chlorambucil) For renal disease; often combined with prednisone.
Plasmapheresis at 37°C For rapidly progressive disease.
Cryofiltration For patients refractory to other therapies.
Interferon α For patients with hepatitis C-associated CG.
References