Pemphigus: associations and management guidelines: facts and controversies

Abstract

Pemphigus, a prototypical organ-specific human autoimmune disease, may be associated with other immunity-related disorders, viral infections, and different types of tumors. Coexistence with immune diseases is fairly frequent and, for some of them (eg, myasthenia gravis, Basedow's disease, rheumatoid arthritis, or lupus erythematosus), common pathogenic mechanisms can be considered. The association with viral infections (mainly herpesvirus infections) raises the question of whether the virus triggers the outbreak of the disease or simply complicates its clinical course. Neoplastic proliferations coexisting with pemphigus have a different histogenesis and the pathogenic link may vary according to the associated tumor (thymoma, lymphoma, carcinoma, or sarcoma). A subset of pemphigus-neoplasia association is represented by Anhalt's paraneoplastic pemphigus, with peculiar clinical, histologic, and immunologic features characterizing it. Coexistence of pemphigus with Kaposi's sarcoma, albeit not frequent, offers an intriguing speculative interest. The cornerstone of management in pemphigus is the combination of systemic corticosteroids and immunosuppressants. The conventional treatment used in most cases is based on oral administration of deflazacort and azathioprine. In selected cases, mycophenolate mofetil is preferred to azathioprine. Severe forms of pemphigus require intravenous pulse therapy with dexamethasone (or methylprednisolone) and cyclophosphamide. In the recent years, the use of high-dose intravenous immunoglobulin therapy has gained several consents. Rituximab, a monoclonal anti-CD 20 antibody, which affects both the humoral and cell-mediated responses, has proved to give a good clinical response, often paralleled by decrease of pathogenic autoantibodies. The combination with intravenous immunoglobulin offers the double advantage of better clinical results and a reduced incidence of infection. Interventional treatments, such as plasmapheresis and extracorporeal immunoadsorption, are aimed at patients with life-threatening forms of pemphigus and high levels of circulating autoantibodies, a circumstance where the medical therapy alone risks failing. Second-line treatments include gold salts (which we do not favor because of the acantholytic potential inherent in thiol structure) and the association of oral tetracyclines with nicotinamide, which is rather safe. Local treatments, supplementary to the systemic therapy, are aimed at preventing infections and stimulating reepithelialization of eroded areas. Innovative topical treatments are epidermal growth factor, nicotinamide gel, pimecrolimus, and a proteomics-derived desmoglein peptide. Pemphigus patients should be warned against over-indulging in unnecessary drug intake, prolonged exposure to ultraviolet rays, intense emotional stress, and too spiced or too hot foods. Cigarette smoking is not contraindicated in pemphigus patients because of the nicotine anti-acantholytic properties.