Clinical features of cryoglobulinaemia and cryoglobulinaemic vasculitis

Galli, 2019

A spectrum of disease may occur. Cryoglobulinaemia may be asymptomatic. Clinical features of cryoglobulinaemia, in order of severity, include:

  • benign purpuric rash on the lower limbs, skin ulcers
  • arthralgias
  • peripheral neuropathy
  • cryoglobulinaemic organ dysfunction
    • about 50% of people have liver disease
    • about one-third of people have kidney disease.

Cryoglobulinaemic vasculitis is an inflammatory syndrome that can cause minor skin manifestations to life-threatening vasculitis (of small and medium-sized vessels) and organ damage. About one-third of patients have kidney disease (glomerulonephritis).

The clinical symptoms and signs result from cryoglobulins aggregating and lodging in blood vessels causing local ischaemia. These cryoglobulin aggregates also activate local inflammatory cascades, typically through the complement system. Severe disease is associated with Raynaud phenomenon, digital ischaemia and gangrene, and organ damage associated with vasculitis affecting the kidneys, gastrointestinal system, lungs, cardiovascular system or central nervous system (CNS).

Common organ-threatening features include:

  • kidney disease—most frequently glomerulonephritis; subsequent nephritis or nephrotic syndrome, chronic kidney failure
  • gastrointestinal disease—intestinal ischaemia, cholecystitis, pancreatitis, peritoneal vasculitis
  • lung disease—alveolitis, pulmonary haemorrhage, interstitial lung disease (pulmonary fibrosis), infections
  • cardiovascular disease—cardiomyopathy, accelerated atherosclerosis
  • CNS disease—ischaemic stroke and transient ischaemic attack, cerebral vasculitis, encephalopathy.