The clinical management of sarcoidosis - A 50-year experience at the Johns Hopkins Hospital

Sarcoidosis is an enigmatic disease with extremely variable manifestations in pattern, severity, and course. Since Longcope and Freiman's descriptive monograph in 1952 (50) summarizing the clinical findings of the first half of this century, new dimensions of assessing the disease and treatment have been added. The impact of corticosteroids is central. The present review extends the studies to the second half of this century. Earlier diagnosis is facilitated and treatment often reverses many of the disease manifestations and improves the quality and extent of life for the patient. The management issues and guidelines outlined in this paper for both intrathoracic and extrathoracic disease are based on several longitudinal studies of the sarcoidosis patients summarized here, and 50 years of clinical experience by the senior author (CJJ) at Johns Hopkins Hospital, a tertiary referral center with an active Sarcoid Clinic. Case reports are presented in the Appendix. It is clear that corticosteroids are the most effective therapeutic agent for sarcoidosis, usually with impressive and prompt response. This represents the dramatic difference in this disease after 1950. No more specific or effective immunosuppressive or antiinflammatory agents have been identified. Undesirable side effects are minimal if excessive doses are avoided. The effectiveness of 'steroid-sparing agents' such as methotrexate is uncertain. Although irreversible tissue damage from the disease may limit the effectiveness of treatment, benefits of corticosteroids greatly exceed the negative side effects. Since spontaneous remissions without treatment do occur, a period of observation of 2 years or more is warranted if the patient is relatively asymptomatic. Gradual radiographic progression for 2 or more years, even without major symptoms or reduction in pulmonary function, indicates the need for a trial of corticosteroid treatment, especially in white patients where symptoms may lag behind the radiographic changes. Relapses as treatment is withdrawn are frequent; especially in African-American patients, who tend to have more severe and more prolonged disease than white patients. A minimum of 1 year of treatment is recommended unless no improvement is noted after 3 months. Continued low- dose prednisone at daily doses of 10-15 mg is helpful in preventing relapses and further progression of disease. Periodic attempts at tapering are justified. Repeated relapses may indicate the need for lifelong treatment. When irreversible changes are present, especially in the presence of chronic fibrotic disease, changing goals of treatment to provide optimal supportive care may represent better management than having unrealistic expectations from increased corticosteroid dosage or the addition of other potentially toxic immunosuppressive agents. Many issues related to sarcoidosis require further research. The most important question facing sarcoid researchers today is the etiology. It is difficult to design specific therapy when the fundamental causes and disease mechanisms are not established. Rather than being a single disease with a single cause, it is possible that a number of genetic factors and environmental or infectious agents may result in an immune response that is manifested as sarcoidosis. Understanding basic causal mechanisms may help explain the varied disease manifestations and aid in designing curative treatments. Such etiologic questions should be explored from both a basic science and an epidemiologic approach. Therapeutic trials of new drugs such as pentoxyfylline and possibly thalidomide are needed to address their potential as well as limitations of steroid therapy. Finally, for patients who have progressed to organ failure, the problems of sarcoid recurrence in transplanted tissue, increased allograft rejection, and long- term prognosis of solid organ transplants have yet to be resolved. Researchers in the current National Institutes of Health multicenter epidemiologic study, A Case-Controlled Etiologic Study of Sarcoidosis (ACCESS), are looking for sarcoidosis risk factors, genetic markers, and potential infections agents and noting the course of the disease. They will generate hypotheses for further study, and develop defined methods for recording the course of disease. This model of several clinical centers forming the Sarcoid Research Group can facilitate future cooperative studies, some of which should be international.