Treatment of CSVV is sometimes unnecessary as the disease is usually self-limiting. When possible, identification and removal of causative agents (e.g., infection, drug, chemicals, food) should be accomplished. Removal of an inciting agent is occasionally followed by rapid resolution of the lesions and no other treatment is indicated; otherwise local and systemic therapies are recommended (Sams, 1980; Soter and Wolff, 1987; Jorizzo et al., 1988; Lynch, 1988; Schifferli et al.,
1989; Chan et al., 1990; Habif, 1990; Braun-Falco et al., 1991; Ryan, 1992; Campanile and Lotti, 1995; Lotti et al., 1996; Comacchi et al., 1998a).
Local therapies are aimed at improving lower extremity circulation and relieve symptomatic complaints. Topical treatment (corticosteroid creams, calcineurin inhibitors, and antibiotic ointments) may be helpful in some patients however, there is no data to support their use (Barham et al., 2004). Gradient support stockings may also be useful as stasis changes often times compound the issue (Braun-Falco et al., 1991; Burge, 1991; Lotti et al., 1996; Comacchi et al., 1998a).
Systemic treatment is advised for patients with CSVV with significant systemic manifestations or those with significant cutaneous ulceration however almost no double-blind, placebo-controlled prospective trials exist (Lotti et al., 1998). Table 8 describes a therapeutic ladder for patients with CSVV (Barham et al., 2004).
Oral corticosteroids, prednisone at a dosage of 30-80 mg/day, tapered over 3-6 weeks often give effective symptom control. No controlled trials have been carried out to support the use in isolated CSVV, however, case series have shown benefit in cases with painful progressive cutaneous lesion.
Therapeutic ladder for patients with CSVV (Modified from Lotti et al., 1998; Barham K.L. et al., 2004)
Skin lesions alone Supportive therapya Antihistaminesa
Non-steroidal anti-inflammatory drugsb
Ulcerative skin lesions alone Thalidomidea
Low-dose weekly methotrexatea Prednisoneb
Systemic disease Prednisoneb Azathioprineb Cyclophosphamideb Mycophenolate mofetila Cyclosporinea
Interferon-a (if hepatitis C-associated)c Intravenous gammaglobulina Extracorporeal immunomodulationa
Biologic agents - infliximab, etanercept (TNF-a inhibitors)a a Case reports. b Case series. c Double-blind studies.
Rebound is a serious problem with rapid reduction of dose; therefore, a slow taper should be instituted. The risks of prednisone are well known and long-term use is rarely warranted (Lotti et al., 1998).
The neutrophil Chemotaxis inhibitor colchicine failed to show benefit in a randomized controlled trial (Sais et al., 1995). Despite this recent study anecdotal evidence and open label studies have demonstrated effectiveness. The recommended dose is 0.6 mg tid. Gastrointestinal symptoms are the usual limiting factor. Benefits may be seen as early as 2 weeks after initiating therapy (Hazen and Michel, 1979; Callen, 1985; Plotnick et al., 1989; Lotti et al., 1998).
Similarly, dapsone in doses of 50-200 mg/day has anecdotally been reported to be effective in isolated cases of CSVV. Response may take several weeks and may be more advantageous when used in combination with colchicine (Lotti et al., 1998).
Nonsteroidal anti-inflammatory drugs such as acetylsalicylic acid and indomethacin in addition to antihistamines can be used to alleviate symptoms more than improving the actual lesions (Lotti et al., 1998).
Immunosuppressive agents, such as azathioprine (50-200 mg/day), cyclophosphamide (2mg/kg/day or as monthly intravenous pulse), methotrexate (10-25 mg/week), and cyclosporine (3-5mg/kg/ day) have anecdotal evidence showing effectiveness in patients with a rapidly progressing course and systemic involvement that is controlled with cor-ticosteroids (Jorizzo et al., 1988; Lynch, 1988; Habif, 1990; Lotti, 1991; Stadler and Ruszczak, 1995; Lotti et al., 1996; Comacchi et al., 1998a).
The mode of action of immunoglobulin is complex involving modulation of the expression and function of Fc receptors, interference with the activation of complement and the cytokine network, provision of anti-idiotypic antibodies, and effects on the activation, differentiation, and effector functions of T- cells and B- cells. Currently only case reports are available to support its use in severe and refractory cases of CSVV (Mathieson et al., 1990; Ong and Benson, 2000).
The potential use of TNF-a inhibitors in systemic vasculitides is currently at the forefront of new treatment options available. TNF-a is known to play a crucial role in the establishment and maintenance of inflammation in multiple autoimmune and nonautoimmune disorders. A number of large placebo-controlled trials have shown TNF-a blockers as effective and well-tolerated treatment options in patients with Crohn's disease, rheumatoid and psoriatic arthritis, and psoriasis. So far, most case reports and case series have suggested favorable results with TNF-a inhibitor therapy in systemic lupus erythematosus (SLE), dermato- and polymyositis, giant cell arteritis, Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis (Lamprecht, 2005). Results of randomized, placebo-controlled trials are eagerly awaited for several connective tissue diseases and systemic vasculitides.
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