Prognostic Factors in Sarcoidosis

Sarcoidosis is a multisystem disorder of unknown etiology. Inflammation mediated by lymphocytes of Th1 phenotype leads to formation of non-caseating granulomas, consisting of epithelioid and multinucleated giant cells. In the majority of patients it affects intrathoracic lymph nodes and lungs, but all organs may be involved (ATS, ERS, WASOG Statement on Sarcoidosis). The overall prognosis is good, and in about 60 % of all cases the disease regresses spontaneously. In the rest of patients, sarcoidosis is a chronic disease, sometimes showing up with relapses, which often follow withdrawal or dose reduction of steroids (Gottlieb et al., 1997; Neville et al., 1983; Scadding, 1961). In about 10-15 % it slowly progresses to lung fibrosis, which is the major cause of death, affecting less than 1 % of patients in Europe and up to 5% in North America. The immunopathological concepts on sarcoidosis describe mechanisms leading to induction of granuloma formation, mechanisms responsible for prolongation and sustaining of inflammation, and mechanisms responsible for fibrosis (the latter are the worse recognized). Although the etiology of sarcoidosis is unknown, it is generally acknowledged that the disease develops in genetically predisposed subjects who were exposed to unidentified (presumably inhaled) antigen(s). This unidentified “sarcoid factor” has the ability to persist in the intracellular milieu of macrophages, which results in the production of cytokines responsible for transformation of Th0 to Th1 cells. In response, lymphocytes produce a variety of cytokines which conversely stimulate macrophages and induce their transformation to granuloma cells. There is premise to speculate that the ability to eliminate the antigen from the intracellular environment is sine qua non of complete and definitive remission (Grunewald, 2002). Although mechanisms regulating these processes are not known, this knowledge seems to be critical for understanding the pathogenesis of persistent and progressive sarcoidosis. Selection of patients at higher risk of lung fibrosis or other unfavorable outcomes at the early stages of disease is a hard task for a physician. There are no objective tests which would be helpful in this matter. Some prognostic factors important for a certain ethnic group may be useless in another. The most important question is whom to treat, and how to treat to achieve the best final cost/effect ratio. Statement on Sarcoidosis, a document published by ATS, ERS and WASOG in 1999, lists a number of clinical factors of prognostic significance. These factors include: lupus pernio, chronic uveitis, age of onset >40 yr, chronic hypercalcemia, nephrocalcinosis, black race, progressive pulmonary sarcoidosis, nasal mucosal involvement, cystic bone lesions, neurosarcoidosis, myocardial involvement and chronic respiratory insufficiency. Different prognostic factors of real or potential clinical relevance will be discussed in this chapter.