Cryoglobulinemic vasculitis

Last updated: June 9, 2023

CME information and disclosurestoggle arrow icon

To see contributor disclosures related to this article, hover over this reference: [1]

Physicians may earn CME/MOC credit by reading information in this article to address a clinical question, and then completing a brief evaluation, in which they will identify their question and report the impact of any information learned on their clinical practice.

AMBOSS designates this Internet point-of-care activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should claim only credit commensurate with the extent of their participation in the activity.

For answers to questions about AMBOSS CME, including how to redeem CME/MOC credit, see "Tips and Links" at the bottom of this article.

Summarytoggle arrow icon

Cryoglobulinemic vasculitis is a type of small-vessel vasculitis characterized by the deposition of cryoglobulins. It is most commonly caused by type II and III cryoglobulinemia. Patients typically present with fatigue and other constitutional symptoms, along with palpable purpura, arthralgia, myalgias, and glomerulonephritis. Diagnosis is based on clinical features and laboratory findings, e.g., cryoglobulinemia; additional studies should be requested based on suspected organ involvement (e.g., kidney biopsy) and the underlying etiology (e.g., hepatitis C diagnostics). Management includes specific treatment of the underlying etiology (e.g., direct-acting antivirals for HCV infection), in addition to management of cryoglobulinemic vasculitis, which usually involves immunosuppressive agents (e.g., glucocorticoids plus rituximab) and is guided by disease severity. Plasmapheresis may also be considered in patients with life-threatening disease.

Definitiontoggle arrow icon

Etiologytoggle arrow icon

Cryoglobulinemia can cause cryoglobulinemic vasculitis, however, many patients are asymptomatic. [2][3]

Cryoglobulinemic vasculitis is more commonly associated with type II and III cryoglobulinemia than with type I cryoglobulinemia. Type I cryoglobulinemia typically manifests as a hyperviscosity syndrome. [2][3]

Cryoglobulinemia is caused by Cold-precipitable immunoglobulins and is commonly associated with the hepatitis C virus.

Most patients with cryoglobulinemia are asymptomatic; the prevalence of symptomatic cases varies widely (2–50%) across different populations. [2]

Clinical featurestoggle arrow icon

The triad of arthralgia, palpable purpura, and fatigue is seen in ∼ 80% of patients with cryoglobulinemic vasculitis. [3]

Diagnosticstoggle arrow icon

General principles [2][3]

  • Diagnosis is based on the presence of typical clinical features and laboratory findings.
  • Additional diagnostics (e.g., ANAs, CT scan) should be requested based on the suspected underlying cause.
  • A biopsy may be required to confirm organ involvement.

Laboratory studies

Cutaneous or renal biopsy

A biopsy should be performed in patients with suspected renal involvement.

Treatmenttoggle arrow icon

General principles [2][3][5]

Patients with rapidly progressive glomerulonephritis, CNS involvement, GI ischemia, or alveolar hemorrhage should receive prompt treatment with a combination of glucocorticoid pulses, rituximab, and plasmapheresis. [3][5]


Recommended pharmacotherapy for cryoglobulinemia based on disease severity [2][3][5]
Disease severity


Mild disease
Moderate to severe disease
Life-threatening disease

Plasmapheresis [3][5]

Patients receiving plasmapheresis to remove circulating cryoglobulins still always require treatment with immunosuppresants to prevent formation of new cryoglobulins.

Management of the underlying cause [5]

Supportive care

Referencestoggle arrow icon

  1. Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet. 2012; 379 (9813): p.348-60.doi: 10.1016/S0140-6736(11)60242-0 . | Open in Read by QxMD
  2. Roccatello D, Saadoun D, Ramos-Casals M, et al. Cryoglobulinaemia. Nat Rev Dis Primers. 2018; 4 (1): p.11.doi: 10.1038/s41572-018-0009-4 . | Open in Read by QxMD
  3. Braun GS, Horster S, Wagner KS, Ihrler S, Schmid H. Cryoglobulinaemic vasculitis: classification and clinical and therapeutic aspects. Postgrad Med J. 2007; 83 (976): p.87-94.doi: 10.1136/pgmj.2006.046078 . | Open in Read by QxMD
  4. Muchtar E, Magen H, Gertz MA. How I treat cryoglobulinemia. Blood. 2017; 129 (3): p.289-298.doi: 10.1182/blood-2016-09-719773 . | Open in Read by QxMD
  5. $Contributor Disclosures - Cryoglobulinemic vasculitis. All of the relevant financial relationships listed for the following individuals have been mitigated: Alexandra Willis (copyeditor, was previously employed by OPEN Health Communications). None of the other individuals in control of the content for this article reported relevant financial relationships with ineligible companies. For details, please review our full conflict of interest (COI) policy:.

Icon of a lock3 free articles remaining

You have 3 free member-only articles left this month. Sign up and get unlimited access.
 Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer