**5. Precautions**

Certain precautions should be observed to reduce side effects of drugs used. CyP dose should be adjusted for renal function and age.

**6. Conclusion**

**Author details**

Christina G. Katsiari1

ssaly, Larissa, Greece

183-200.

379: 348-360.

**References**

Small vessel vasculitis may be a manifestation of systemic vasculitis or may be confined to the skin. Therefore, biopsy of skin lesion with immunofluorescence and careful search for systemic disease are mandatory for the correct diagnosis. The treatment of cryoglobulinae‐ mic vasculitis is based on the underlining aetiology. In HCV positive patients with severe vasculitic manifestations, immunosuppressives with plasmapheresis is the modality of choice. Anti-HCV treatment is administered after the control of inflammatory manifesta‐ tions. In HCV-associated cryoglobulinaemic vasculitis with mild disease, anti-HCV treat‐ ment may suffice. HSP is usually a self limited disease. In patients with HSP complications, corticosteroids remain the main treatment. In severe refractory cases, plasmapheresis in con‐ junction with immunosuppressives have been tried. Idiopathic cutaneous leukocytoclastic vasculitis is most of the time a mild disease and does not require toxic medications. Rituxi‐

mab is a promising new treatment for systemic or refractory small vessel vasculitis.

1 Rheumatology Clinic, School of Medicine, Faculty of Health Sciences, University of The‐

[1] Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis and Rheumatism 1994; 37: 187-192

[2] Tedeschi A, Barate C, Minola E, Morra E. Cryoglobulinemia. Blood Review 2007; 21:

[3] Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet 2012;

[4] Misiani R, Bellavita P, Fenili D, Vicari O, Marchesi D, Sironi PL, Zilio P, Vernocchi A, Massazza M, Vendramin G. Interferon alfa-2a therapy in cryoglobulinemia associat‐ ed with hepatitis C virus. The New England Journal of Medicine 1994; 330: 751-756.

and Lazaros I. Sakkas1,2\*

Treatment of ANCA-Negative Small Vessel Vasculitis

http://dx.doi.org/10.5772/54272

231

, Theodora Simopoulou1

2 Center of Molecular Medicine,Old Dominion University, Norfolk, VA, USA

\*Address all correspondence to: lsakkas@med.uth.gr

Patients should be checked for tuberculosis with chest x-rays and PPD skin test, and patients with latent tuberculosis should receive prophylaxis with isoniazid plus vitamin B6. Patients on IV pulse CyP, receive antiemetic drug (ondaserton) immediately prior to and 8 hours af‐ ter the CyP pulse. On the day of IV CyP pulse, patients receive oral or IV hydration with 2-3 liters of fluid. They also receive IV 2-mercaptoethanesulfonate (mesna) (20% of CyP dose) immediately before and at 2, 4 and 8 hours after the CyP pulse to reduce irritation of urinary bladder. The dose of next IV CyP pulse is adjusted to keep nadir white blood cell (WBC) count (12-14 days after the IV pulse) >3,000/μL. The rate of leucopenia, infections, and gona‐ dal toxicity is reduced in the IV pulse CyP compared to oral CyP regimen [83,84]. Oral mes‐ na is also beneficial for patients on oral CyP.

According to a recent study ever-tobacco smoking and previous episode of hemorrhagic cystitis were strong predictors for the development of cancer in the urinary tract. Thus pa‐ tients with these characteristics need close surveillance with urine cytology tests.

All patients receiving CyP are advised to take prophylaxis against Pneumocystis jiroveci with trimethoprime/sulphamethoxazole (800/160 mg thrice weekly).

Gonadal failure is a common side effect in patients treated with CyP, where the risk increas‐ es in parallel with the increase of the cumulative dose received. No standard care to pre‐ serve gonadal function has been proposed for patients with small vessel vasculitis under CyP. For similar issues encountered in female patients with systemic lupus erythematosus (SLE) two protocols exist: administration of leuprolide acetate with or without transdermal estrogen and depo-progesterone for contraception. Leuprolide should be administered 10-14 days prior to each CyP infusion. In men with SLE, administration of intramuscular monthly injections of testosterone has been proposed. Analogous approaches should probably be adopted for young patients with small vessel vasculitis at risk.

Patients on immunosuppression should not be vaccinated with live attenuated vaccines. They can and should be vaccinated with dead pathogens. Patients with granulomatosis with polyangiitis(Wegener's granulomatosis) exhibit adequate antibody [85] and cell-mediated immune response to influenza vaccines [86].

INFα may cause hepatic dysfunction and extreme caution is advised in patients with cirrho‐ sis. PEG-INFα and ribavirin are contraindicated in renal impairment (creatinine clearance [ClCr] <50ml). Ribavirin can cause haemolytic anaemia.

Colchicine can induce gastrointestinal upset (diarrhoea, vomiting) and rarely cytopenia. Dapsone can cause granulopenia and severe haemolysis in patients with glucose-6-phos‐ phate dehydrogenase (G6PD) deficiency. Therefore, before initiation of dapsone, G6PD should be measured, and then full blood count regularly. Side effects of HCQ are rare and include retinopathy and cytopenias.

### **6. Conclusion**

**5. Precautions**

should be adjusted for renal function and age.

230 Updates in the Diagnosis and Treatment of Vasculitis

na is also beneficial for patients on oral CyP.

Certain precautions should be observed to reduce side effects of drugs used. CyP dose

Patients should be checked for tuberculosis with chest x-rays and PPD skin test, and patients with latent tuberculosis should receive prophylaxis with isoniazid plus vitamin B6. Patients on IV pulse CyP, receive antiemetic drug (ondaserton) immediately prior to and 8 hours af‐ ter the CyP pulse. On the day of IV CyP pulse, patients receive oral or IV hydration with 2-3 liters of fluid. They also receive IV 2-mercaptoethanesulfonate (mesna) (20% of CyP dose) immediately before and at 2, 4 and 8 hours after the CyP pulse to reduce irritation of urinary bladder. The dose of next IV CyP pulse is adjusted to keep nadir white blood cell (WBC) count (12-14 days after the IV pulse) >3,000/μL. The rate of leucopenia, infections, and gona‐ dal toxicity is reduced in the IV pulse CyP compared to oral CyP regimen [83,84]. Oral mes‐

According to a recent study ever-tobacco smoking and previous episode of hemorrhagic cystitis were strong predictors for the development of cancer in the urinary tract. Thus pa‐

All patients receiving CyP are advised to take prophylaxis against Pneumocystis jiroveci

Gonadal failure is a common side effect in patients treated with CyP, where the risk increas‐ es in parallel with the increase of the cumulative dose received. No standard care to pre‐ serve gonadal function has been proposed for patients with small vessel vasculitis under CyP. For similar issues encountered in female patients with systemic lupus erythematosus (SLE) two protocols exist: administration of leuprolide acetate with or without transdermal estrogen and depo-progesterone for contraception. Leuprolide should be administered 10-14 days prior to each CyP infusion. In men with SLE, administration of intramuscular monthly injections of testosterone has been proposed. Analogous approaches should probably be

Patients on immunosuppression should not be vaccinated with live attenuated vaccines. They can and should be vaccinated with dead pathogens. Patients with granulomatosis with polyangiitis(Wegener's granulomatosis) exhibit adequate antibody [85] and cell-mediated

INFα may cause hepatic dysfunction and extreme caution is advised in patients with cirrho‐ sis. PEG-INFα and ribavirin are contraindicated in renal impairment (creatinine clearance

Colchicine can induce gastrointestinal upset (diarrhoea, vomiting) and rarely cytopenia. Dapsone can cause granulopenia and severe haemolysis in patients with glucose-6-phos‐ phate dehydrogenase (G6PD) deficiency. Therefore, before initiation of dapsone, G6PD should be measured, and then full blood count regularly. Side effects of HCQ are rare and

tients with these characteristics need close surveillance with urine cytology tests.

with trimethoprime/sulphamethoxazole (800/160 mg thrice weekly).

adopted for young patients with small vessel vasculitis at risk.

immune response to influenza vaccines [86].

include retinopathy and cytopenias.

[ClCr] <50ml). Ribavirin can cause haemolytic anaemia.

Small vessel vasculitis may be a manifestation of systemic vasculitis or may be confined to the skin. Therefore, biopsy of skin lesion with immunofluorescence and careful search for systemic disease are mandatory for the correct diagnosis. The treatment of cryoglobulinae‐ mic vasculitis is based on the underlining aetiology. In HCV positive patients with severe vasculitic manifestations, immunosuppressives with plasmapheresis is the modality of choice. Anti-HCV treatment is administered after the control of inflammatory manifesta‐ tions. In HCV-associated cryoglobulinaemic vasculitis with mild disease, anti-HCV treat‐ ment may suffice. HSP is usually a self limited disease. In patients with HSP complications, corticosteroids remain the main treatment. In severe refractory cases, plasmapheresis in con‐ junction with immunosuppressives have been tried. Idiopathic cutaneous leukocytoclastic vasculitis is most of the time a mild disease and does not require toxic medications. Rituxi‐ mab is a promising new treatment for systemic or refractory small vessel vasculitis.
