Relapse in Sarcoidosis: Are Steroids at Fault?
ABSTRACT & COMMENTARY
Synopsis: Among patients with sarcoidosis who relapsed, corticosteroid treatment itself, rather than the need for treatment, contributed to the propensity to relapse.
Source: Gottlieb JE, et al. Chest 1997;111:623-631.
In a large observational study of 337 patients with sarcoidosis, spontaneous remission, steroid-induced remission, and non-responsiveness were equally common outcomes. However, relapse was more common in those who had a steroid-induced remission and those with musculoskeletal and hepatic involvement at presentation. Relapses usually occurred within 2-6 months after discontinuance of corticosteroids. The authors suggest that steroid treatment contributes to prolonged resolution and relapse of sarcoidosis. Sarcoidosis continues to perplex both physicians and patients. There remains as much controversy about the etiology of this multisystem granulomatous illness as there is about diagnostic and treatment pathways.1 While it occurs in all races and age groups, sarcoidosis is significantly more prevalent in blacks and in individuals less than 40 years old (90%). Although treatment has been traditionally based on suppression of granulomatous inflammation using corticosteroids, the value of this approach has been questioned, and the effect of steroids on long-term outcome is uncertain. This large observational database study from Philadelphia by Gottlieb et al will not still this controversy.
Table
Indications for treatment with oral and inhaled corticosteroids
A. Indications for treatment with oral corticosteroids
• Severe pulmonary symptoms or
• Impaired lung function
• Progressive radiographic changes with worsening of:
• interstitial opacities
• fibrosis with honeycombing
• pulmonary hypertension
• Extrapulmonary sarcoidosis
• fever
• weakness
• fatigue
• arthralgia
• neuropathy or central nervous system diseases
• skin disease
• hepatic insufficiency
• cardiac diseases
• uveitis
• hypercalcemia
B. Indications for treatment with inhaled corticosteroids
• severe cough or airway hyperreactivity
• mild pulmonary symptoms
• mildly impaired lung function abnormalities
• alternative to oral prednisone for patients who require long-term low-dose prednisone < 10 mg/d
The authors examined a registry of all patients with documented sarcoidosis who were examined in their clinics (Thomas Jefferson University Hospital) and recorded clinical laboratory and radiologic information. The decision to initiate corticosteroid therapy (20 mg/d) was made by one of the investigators based on symptomatic rather than laboratory evidence of deterioration. Of the 337 patients enrolled, 118 had spontaneous remission, and 103 had steroid-induced remission (steroid treatment was more common in blacks [~3/4] compared to whites [~2/5]). The remainder were classified as "recalcitrant." Relapse was dramatically increased in the induced (74%) compared to the spontaneous remission group (8%). Pulmonary complaints were the most common presenting manifestations (~1/3) followed by uveitis, chest radiographic abnormalities, and skin lesions including erythema nodosum. Patients who relapsed were more likely to have musculoskeletal complaints or liver involvement at the time of presentation when compared to those with chest radiographic abnormalities alone. Patients with higher radiographic stages (II, III) at presentation were more likely to relapse than those with stage I (71%, 80% compared to 66%). Serum angiotensin converting enzyme measurement (ACE) paralleled the clinical course of disease. Following cessation of therapy, relapse was most common during the first six months. Because relapse was more common in those with steroid-treated remissions compared to those with spontaneous remission, the authors suggest that "corticosteroid treatment itself, rather than the need for treatment, contributed to the propensity to relapse." In three previous randomized treatment trials, relapse has been more common in steroid-treated patients.2-4
COMMENT BY ALAN M. FEIN, MD
There are many important "pearls" in this study, and its strength is the treasure of clinical epidemiology contained within this large database. Relapse in sarcoidosis is clearly a common clinical outcome, being observed in three-quarters of those who received initial adequate treatment with corticosteroids. It is also evident that relapse is no more common in black patients despite the high prevalence of sarcoidosis in this group and their more frequent receipt of steroid treatment. Musculoskeletal complaints or evidence of liver dysfunction were more common in relapsed patients, while those presenting with an abnormal chest radiograph alone were less likely to relapse. Because of the uncontrolled nature of the study, it is difficult to prove the authors’ hypothesis that steroid treatment of symptomatic deterioration predisposes to eventual relapses and prolongation of the total duration of the disease. In fact, I suspect that such treatment merely identified a group with more severe disease and thus more likely to relapse. However, their analysis of three controlled trials suggests that this theory is worth testing.
This paper only adds further controversy to the use of corticosteroids for progressive sarcoidosis. Currently, I continue to advise the use of steroids to suppress severe extrapulmonary manifestations of the disease (cardiac, CNS involvement, hypercalcemia, etc.). The use of oral corticosteroids in pulmonary sarcoidosis should be reserved for that group of symptomatic patients who do not spontaneously go into remission. As the authors suggest, unnecessary therapy could potentially prolong the severity and duration of the disease, and clinically significant long-term benefit of steroid treatment remains unproven. In addition, inhaled corticosteroids may be of value for early or mild sarcoidosis or where cough with airway reactivity is particularly troublesome. (See Table.)
References
1. Sharma OP. Pulmonary sarcoidosis. Am Rev Respir Dis 1993;147:1598.
2. Eule H, et al. The possible influence of corticosteroid therapy on the natural course of pulmonary sarcoidosis. Ann NY Acad Sci 1986;465:695-701.
3. Izumi T. Are corticosteroids harmful to sarcoidosis? Sarcoidosis 1994;11:119-122.
4. Gibson GJ, et al. British Society: Sarcoidosis study: Effects of long-term corticosteroid treatment. Thorax 1996;51:238-247.
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