What is cryoglobulinaemia?


Cryoglobulins are antibodies directed against other immunoglobulins, forming immune complexes that precipitate in the cold (e.g. at 4° C). They can lead to type III hypersensitivity reactions, with typical clinical manifestations including purpuric rash, often of the lower extremities, arthralgia and peripheral neuropathy. They dissolve when warmed to 37°C that's why testing for cryoglobulins requires the transport of a serum specimen to the laboratory at 37°C. Presence of such abnormal immunoglobulin in the blood is known as cryoglobulinaemia. 

Types of cryoglobulinaemia: It is of 3 types 

types of cryoglobulins
[Types of cryoglobulins]

Features  of cryoglobulinaemia:

▪︎ Raynaud's only seen in type I (in severe cases they can cause acronecrosis)
▪︎ Cutaneous: vascular purpura, ulcerations 
▪︎ Arthralgia (Non-erosive polyarthralgia associates with hepatitis C)
▪︎ Polyneuropathy, Mononeuritis multiplex
▪︎ Renal involvement (diffuse or Membranoproliferative glomerulonephritis)
▪︎ Hepatosplenomegaly

Meltzer's triad
[Meltzer's triad]

Investigations for cryoglobulinaemia:

▪︎ High ESR
▪︎ Positive RF
▪︎ Hypocomplementaemia (Especially C4)
▪︎ Presence of cryoglobulins in the serum 
▪︎ Skin biopsy (if purpura present)
▪︎ Serology for hepatitis C infection
▪︎ Active urine sediments due to glomerulonephritis ( e.g. blood ++, proteins ++)

Treatment of cryoglobulinaemia:

▪︎Plasmapheresis: In case of acute cryoglobulinaemia causing severe renal impairment or acronecrosis
▪︎Drugs: Steroid (prednisolone), cyclophosphamide and chlorambucil are in less acute situations 
▪︎HCV treatment: When cryoglobulinaemia is secondary to HCV infection, the treatment of choice includes the combination of pegylated interferon-a interferon-alpha and ribavirin

In RA, RF is positive in 80% of patients, whereas, in Sjogren’s syndrome and cryoglobulinaemia, it is prevalent in up to 90% of cases.


  • Step Up to MRCP Review Notes for P1 & P2 By Dr Khaled El Magraby 1st ed 2015; page: 724
  • Davidsons Principles and Practice of Medicine 23 edition; page: 84

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