title: Pharmacotherapeutic management of pulmonary sarcoidosis.
abstract: Corticosteroids are the mainstay of treatment for sarcoidosis. Although the indications for medical therapy of sarcoidosis are controversial, standard therapy for symptomatic, progressive disease consists of corticosteroids. The British Thoracic Society concluded, with respect to systemic corticosteroids for the treatment of sarcoidosis, that some patients required no treatment, some required prednisone for control of symptoms, and others, with persistent disease, appeared to benefit from long-term corticosteroid therapy. Inhaled budesonide can be an effective treatment for lung sarcoidosis, with few adverse effects, when used in combination with oral systemic corticosteroids such as deflazacort administered in a tapered regimen for 6 months. A randomized controlled trial has also demonstrated the efficacy of 3 months of treatment with oral prednisolone in a tapered regimen followed by inhaled budesonide for 15 months in patients with early stage pulmonary sarcoidosis.Alternative drugs are required in chronic resistant sarcoidosis and/or in conditions where systemic corticosteroids are contraindicated. Immunosuppressive agents (chlorambucil, cyclophosphamide, methotrexate, cyclosporine, azathioprine), anticytokine agents (thalidomide, pentoxifylline), antimalarials (chloroquine, hydroxychloroquine), melatonin and monoclonal antibody (infliximab) have been used in such situations. Chlorambucil and cyclophosphamide have been used in anecdotal cases of pulmonary sarcoidosis as corticosteroid-sparing agents. However, their toxicity and neoplastic potential recommend prudence in patient selection. A comparison between combination therapy with cyclosporine and prednisone and prednisone alone has shown an increased prevalence of serious adverse effects with combined therapy with no between-group differences in treatment efficacy. The cost and toxicity of cyclosporine limit its use to patients in whom its efficacy has been proven. In patients with chronic or refractory disease, methotrexate, usually administered once a week as a single oral dose for at least 2 years, has resulted in a significant improvement in respiratory function, chest radiographs and extrapulmonary manifestations. In most patients, this treatment enabled discontinuation of corticosteroids. Azathioprine may be effective as a corticosteroid-sparing agent in the long-term treatment of sarcoidosis. The combination of prednisolone and azathioprine over a period of 2 years has induced long-lasting remission in patients with resistant sarcoidosis. Thalidomide at low doses is effective in selected cases of sarcoidosis with cutaneous and mild pulmonary involvement. Pentoxifylline alone or combined with low doses of corticosteroids has achieved significant improvement in respiratory function in patients with pulmonary sarcoidosis. Chloroquine and hydroxychloroquine have been shown to have a specific effect in cutaneous manifestations, neurological involvement and hypercalcemia associated with sarcoidosis. Infliximab has yielded good results in patients with chronic resistant pulmonary and extrapulmonary sarcoidosis resistant to corticosteroid and cytotoxic therapy. The effectiveness of melatonin in cutaneous and pulmonary sarcoidosis has also been confirmed in a single center.
authors.affiliation: Cardiac and Thoracic Department, Respiratory Pathophysiology Section, University of Pisa, Pisa, Italy. pfazzi@dcap.med.unipi.it
authors.forename: Piera
authors.initials: P
authors.lastname: Fazzi
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000962:Antimalarials / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D017565:Sarcoidosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000962:Antimalarials; D007166:Immunosuppressive Agents