see also:

• hypothermia
• Raynaud's phenomenon
• frostbite

• cryoglobulinemia is a rare condition in which those who have cryoglobulins (these immunoglobulin complexes typically precipitate at temperatures below 37degC and will dissolve again if the blood is heated) may develop serious complications when exposed to the cold.
• NB. not to be confused with cold agglutinin disease which is agglutination of red blood cells in response to cold

• rare, affecting 1 in 100,000 people
• mainly affects women aged 40-60yrs (women: men ratio is 3:1)
• usually has an underlying condition - but if not is called essential or idiopathic cryoglobulinemia
  • 90% of cases in the Mediterranean are in those with hepatitis C virus ¹⁾ and 40-65% of patients with hepatitis C virus have cryoglobulins²⁾
• it seems that the clinical effects may be exacerbated by certain infections or vaccinations in those who have underlying conditions such as hepatitis B virus or hepatitis C virus
  • examples include Covid-19 mRNA vaccines ³⁾ and Covid-19 infection
• very rarely it may be precipitated by vaccinations in those without pre-existing underlying conditions
  • vaccination with influenza and pneumococcal vaccines ⁴⁾

• may be asymptomatic unless acute features are precipitated by an immune event such as infection or vaccination

• Raynaud's like cyanosis / blue toe syndrome
• arterial thrombosis and gangrene may occur in extremities, ear and kidneys
• retinal haemorrhage may occur
• hyperviscosity syndrome may cause:
  • headache, confusion, blurry or loss of vision, hearing loss, and epistaxis

• arthralgia / arthritis of MCP and PIPjts of hands and feet but also may involve knees and ankles
• myalgias
• fatigue
• some may develop fever
• 80% have palpable purpura
• those with type 3 mat develop livedoid vasculopathy and/or cold induced urticaria
• up to 20% may develop ischaemic necrosis
• immune complex disease may cause renal injury and glomerulonephritis (GN)
• peripheral neuropathy
• vasculitis of the skin (cryoglobulinaemic vasculitis)

• lung injury causing cough, SOB
• hepatomegaly
• splenomegaly
• GIT bleeding

• Rheumatoid factor is 80-90% sensitive for cryoglobulinaemia
• low C4 complement level
• further Ix:
  • cryocrit estimation ⁶⁾
    • serum is centrifuged and then refrigerated to allow precipitation of cryoglobulin
    • Type I cryoglobulinemia presents as a precipitate within 24 hours with a 3 to 5-day window.
    • Type II/III present with precipitation approximately 5 to 7 days after initial refrigeration
    • a cryocrit greater than 0.5 to 1% or concentration over 50 mcg/mL is significant
    • type II, cryocrit is between 2 to 7%
    • type III cryocrit is usually 1 to 3%
  • immunoelectrophoresis and immunofixation to detect and quantify the presence of monoclonal IgG, IgM, IgA, κ light chain, or λ light chain immunoglobins.