Pulmonary sarcoidosis treatment

The early impression that interferon alfa, alone or in combination with ribavirin, could reactivate or cause new subcutaneous sarcoid nodules and pulmonary or generalized sarcoidosis, has been confirmed by several reports, with prompt recovery after interferon alfa withdrawal (SED-13, 1097) (SEDA-20, 330) (SEDA-22, 404). The incidence may have been underestimated in one series, 3 patients out of 60 who received interferon alfa alone or combined with ribavirin developed pulmonary sarcoidosis (351). In a review of 27 cases, the time to onset was 15 days to 30 months, and there were dermatological signs in 50% (352). Five patients had also taken ribavirin, but an enhanced T cell immune reaction from the combination of interferon alfa plus ribavirin is speculative. However, the association of cutaneous or systemic sarcoidosis with interferon alfa, alone or in association with ribavirin, has been exemplified by various reports (353,354), including one patient whose sarcoidosis resolved with prednisone despite continued interferon alfa treatment (355). 

The use of AZA for IPF was first reported in an open-label trial by Winterbauer et al. (144). A subsequent double-blind, randomized trial demonstrated benefit versus placebo in approximately half of the patients treated (145). Demerits et al. demonstrated a higher response rate when AZA was given concomitantly with A-acetyl cysteine compared with AZA alone (146). AZA has also been used in the treatment of scleroderma-associated pulmonary fibrosis (147). Although not all investigators have reported benefit with the drug (148), the drug has also been useful in treating chronic pulmonary sarcoidosis (7). 

Pietinalho A, Lindhohn A, Haahtela T, et al. Inhaled budesonide for treatment of pulmonary sarcoidosis. Results of a double-blind, placebo-controlled, multicentre study. Eur Respir J 1996 9(suppl 23) 406s. 

Lewis SJ, Ainslie GM, Bateman ED. Efficacy of azathioprine as second-line treatment in pulmonary sarcoidosis. Sarcoidosis Vase Diffuse Lung Dis 1999 16 87-92. 

Wyser CP, van Schalkwyk EM, AUieit B, et al. Treatment of progressive pulmonary sarcoidosis with cyclosporin A a randomized controlled trial. Am J Respir Crit Care Med 1997 156 1371-1376. 

Carlesimo M, Giustini S, Rossi A, et al. Treatment of cutaneous and pulmonary sarcoidosis with thalidomide. J Am Acad Dermatol 1995 32 866-869. 

Treatment of sarcoidosis remains controversial. CSs are the cornerstone of therapy for severe or progressive sarcoidosis (pulmonary or extrapulmonary), and often produce dramatic resolution of disease (28,157). The long-term benefit of CS therapy has not been established, as relapses may occur upon taper or cessation of therapy (5,22,28,157). Early prospective, randomized smdies found no long-term benefit with CSs among patients with pulmonary sarcoidosis (158-161). However, these studies included patients with normal or near normal... 

Zic JA, Horowitz DH, Arzubiaga C, et al. Treatment of cutaneous sarcoidosis with chloroquine. Review of the hterature. Arch Dermatol 1991 127(7) 1034—1040. Tong Z, Dai H, Chen B, et al. Inhibition of cytokine release from alveolar macrophages in pulmonary sarcoidosis by pentoxifylhne comparison with dex-amethasone. Chest 2003 124(4) 1526-1532. 

Respiratory - pulmonary sarcoidosis Although numerous cases of IFNa-associated sarcoidosis have been reported (see above) [53 ], a case of pulmonary sarcoidosis in a 30-year-old woman being treated for multiple sclerosis with IFN(3 appears to be the first case of the involvement of this cytokine in this disorder. The patient presented with persistent bilateral areas of lung consolidation on serial radiographs 5 months after the initiation of treatment [57 ]. 

Bjortuft 0, Foerster A, Boe J, Geiran O (1994) Single lung transplantation as treatment for end-stage pulmonary sarcoidosis recurrence of sarcoidosis in two different lung allografts in one patient. J Heart Lung Transplant 13 24-29... 

In case series, CP has been useful in the treatment of scleroderma-associated pulmonary fibrosis (183-186). This benefit was confirmed in two large randomized, placebo-controlled trials of either oral (187) or intermittent, IV CP (147). CP has also been used in IPF (4,188), nonspecific interstitial lung disease (189,190), and to treat refractory sarcoidosis (usually neurologic disease) (191-193). 

TNF-a inhibitors have also been utilized to treat pulmonary fibrosis. In one study, IFF patients stabilized while receiving etanercept compared with progressive disease seen in the placebo-treated patients (250). In another report of symptomatic scleroderma patient with pulmonary fibrosis, quality of life improved while treated with infliximab, but the treatment did not affect the progression of pulmonary fibrosis or pulmonary hypertension (251). Case series suggest infliximab can improve RA-associated pulmonary fibrosis (252-254). However, other studies suggest that both infliximab (255,256) and etanercept (257) can be associated with development or progression of pulmonary fibrosis. Additionally, both drugs have been associated with the subsequent development of sarcoidosis (258-262). 

Gluskowski J, Hawrylkiewicz I, Zych D, et al. Effects of corticosteroid treatment on pulmonary haemodynamics in patients with sarcoidosis. Eur Respir J 1990 3(4) 403 07. 

Fisher KA, Serlin DM, Wilson KC, et al. Sarcoidosis-associated pulmonary hypertension outcome with long-term epopiostenol treatment. Chest 2006 130(5) 1481-1488. 

Pietinalho A, Tukiainen P, Haahtela T, et al. Early treatment of stage II sarcoidosis improves 5-year pulmonary function. Chest 2002 121(1) 24—31. 

Indications for treatment include (i) severe symptoms, such as debilitating cough or dyspnea (ii) abnormal gas exchange, diminished exercise tolerance, or abnormal pulmonary physiology (iii) progressive decline in these tests of impairment or (iv) evidence of pulmonary hypertension or cor pulmonale. Initial corticosteroid therapy should be similar to that used in sarcoidosis oral prednisone... 

Respiratory TNFa antagonists may be of benefit in the treatment of advanced or refractory sarcoidosis, a multisystem granulomatous inflammatory disease of unknown aetiology but, paradoxically, a sarcoidosis-like reaction may sometimes occur with TNFa blockade. A sarcoid-like reaction with pulmonary symptoms occurred in a patient with psoriatic arthritis soon after the initiation of adalimumab. lATthdrawal of the mAb and antiinflammatory therapy with corticosteroids resulted in resolution of the pulmonary symptoms [75 ]. 

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