Clinical Pearls & Morning Reports
Published September 8, 2021
The development of sarcoidosis requires both a genetic predisposition and environmental and sometimes occupational exposure to unknown substances or microbial antigens. It is generally accepted that a dysregulated immune response against one or more disease-promoting antigens results in an inflammatory process to eliminate the offending antigen. The disorder can affect virtually any organ in the body — predominantly the lungs, lymphatic system, skin, or eyes or a combination of these sites — and is characterized by the formation of noncaseating granulomas. Read the NEJM Review Article here.
Q: What age groups are most affected by sarcoidosis?
A: Sarcoidosis occurs throughout the world, affecting all races and ethnic groups and both sexes, with a slight predominance among women. It can affect people of all ages but mostly develops in young and middle-aged adults. The incidence has been reported to peak at 30 to 50 years of age in men and at 50 to 60 years of age in women. Some data suggest that the age at onset is increasing.
Q: How often does sarcoidosis become chronic in affected patients?
A: Although most patients with sarcoidosis are asymptomatic or have acute symptoms with spontaneous resolution, chronic disease develops in approximately one third of patients, waxing and waning or relentlessly progressing (if untreated) over an extended period. Less than 10% of patients die from sarcoidosis; most fatal cases are due to advanced lung disease, followed by cardiac complications.
A: The clinical diversity of sarcoidosis, as well as its resemblance to other, more common disorders, often leads to diagnostic uncertainty and treatment delays. Ultimately, the diagnosis of sarcoidosis is based on three major criteria: compatible clinical characteristics, identification of nonnecrotizing granulomas in one or more tissue samples, and the ruling out of other causes of granulomatous disease. Management of sarcoidosis is a major clinical challenge because of the highly variable disease manifestations. The decision of whether (and, if so, when) to treat an individual patient who has sarcoidosis depends on two major factors: the risk of organ failure or death and the extent to which the patient’s quality of life is impaired. The decision is complex and cannot be standardized. For patients with severe disease, timely treatment can mitigate disease manifestations and prevent long-term complications. Current treatment standards are based on low-quality evidence, but experts agree that therapeutic goals should focus on suppression of inflammation-induced organ dysfunction, assessed on the basis of objective metrics (e.g., lung function), and on the avoidance of toxic effects of drugs.
A: A consensus statement from sarcoidosis experts endorses glucocorticoids as the primary treatment for sarcoidosis, on the basis of their efficacy and ease of use. For patients requiring long-term suppression of inflammation to prevent irreversible organ damage or intolerable symptoms, early institution of glucocorticoid-sparing antisarcoidosis agents is generally recommended, either alone as first-line treatment or with a rapid reduction in glucocorticoid doses. Commonly used glucocorticoid-sparing agents for second-line treatment include methotrexate (the agent studied and prescribed most often), azathioprine, leflunomide, and mycophenolate. An alternative in this category is the antimalaria agent hydroxychloroquine, which has proved particularly useful for cutaneous disease, hypercalcemia, and some cases of neurosarcoidosis. If nonglucocorticoid antisarcoidosis agents, administered alone or in combination with glucocorticoids, are toxic or ineffective or if the disease is severe and progressive, third-line treatment with biologic agents or advanced immunomodulating agents may be considered. Infliximab and adalimumab (both TNF-α inhibitors) are effective options.