Cryoglobulinemic vasculitis

Last updated: December 13, 2022

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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.

Cryoglobulinemia can cause cryoglobulinemic vasculitis, however, many patients are asymptomatic. [1][2]

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. [1][2]

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. [1]

The triad of arthralgia, palpable purpura, and fatigue is seen in ∼ 80% of patients with cryoglobulinemic vasculitis. [2]

General principles [1][2]

  • 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.

General principles [1][2][4]

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. [2][4]

Pharmacotherapy

Recommended pharmacotherapy for cryoglobulinemia based on disease severity [1][2][4]
Disease severity

Definition

Management
Mild disease
Moderate to severe disease
Life-threatening disease
  • Multiple or extensive cutaneous ulceration
  • RPGN
  • CNS involvement
  • GI ischemia
  • Alveolar hemorrhage

Plasmapheresis [2][4]

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

Management of the underlying cause [4]

Supportive care

  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

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