Page 264 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

238 Clodoveo Ferri, Dilia Giuggioli and Marco Sebastiani

sensitive to the small variations in daily steroid dosage of 1 to 2 mg, may also derive benefit
from dietary therapy.

Cyclophosphamide and rituximab are each first-line therapies for EMCs [1, 4, 17, 18].
Rituximab is first-choice treatment based on the results of observational and controlled
studies in seronegative and seropositive HCV patients with CV [1, 4, 17-19]. Traditional and
double-filtration PE can reduce the levels of circulating IC and cryoglobulins [1, 4, 17]. Oral
cyclophosphamide at the dose of 50 to 100 mg per day for 2 to 6 weeks during the tapering of
apheretic sessions reinforces the beneficial effects of PE. Moreover, the latter can also
potentiate the effect of cyclophosphamide [9], and is beneficial in the treatment of fulminant
manifestations of CV such as widespread vasculitis and active MPGN.

The treatment of CV should be tailored to individual patients according to the severity of
clinical symptoms, with the most severe vasculitic manifestations treated promptly with
combination corticosteroids, PE, and cyclophosphamide or rituximab [1, 4, 17]. Pilot studies
suggest that sequential or combined antiviral and immunosuppressive treatment is a useful
strategy [4, 20, 21] especially in those with major clinical manifestations and partial or
transitory remission after standard therapy. Clinically asymptomatic patients may be
monitored without treatment even in the presence of elevated cryocrit levels. Careful clinical
monitoring of the disease is mandatory in all cases with particular attention to neoplastic
transformation [1, 4].

Conclusion

Cryoglobulinemic vasculitis is an important model for the study of virally-mediated
autoimmune and lymphoproliferative diseases. Recent advancements in the understanding of
the underlying multifactorial and multistep processes in the etiopathogenesis of CV have
translated into effective therapy poised against eradication of HCV infection as both a
triggering factor and contributor to the self-perpetuating mechanism of autoimmune disease,
while targeting the variably severe consequences of LCV, systemic SVV, multiorgan
involvement the predeliction for malignancy. Future challenges in CV include improvements
in the differential diagnosis with some overlapping disorders, as well as the improvement in
therapeutic strategies.

References

[1] Ferri C. Mixed cryoglobulinemia. Orphanet J. Rare Dis. 2008; 3: 25. doi:
10.1186/1750-1172-3-25.

[2] Meltzer M, Franklin EC, Elias K, et al. Cryoglobulinemia. A clinical and laboratory
study. II. Cryoglobulins with rheumatoid factor activity. Am. J. Med. 1966; 40: 837-
856.

[3] Gorevic PD, Kassab HJ, Levo Y, et al. Mixed Cryoglobulinemia: clinical aspects and
long-term follow-up of 40 patients. Am. J. Med. 1980; 69: 287-308.

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