Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (Drs. Gupta, Patel, and Parth Rali); Department of Family Medicine, Barbara and Zucker School of Medicine at Hofstra/ Northwell – South Shore University Hospital, NY (Drs. Caceres and Mayur Rali) rohit.gupta@tuhs.temple.edu
The authors reported no potential conflict of interest relevant to this article.
Management includes ruling out alternate diagnoses, identifying occult/overt organ involvement, determining treatment, and recognizing worrisome features.
› Consider biopsy to aid in diagnosing sarcoidosis; it may be avoided with a high clinical suspicion for sarcoidosis (eg, Löfgren syndrome, lupus pernio, or Heerfordt syndrome). C
› Rule out alternative diagnoses such as infection, malignancy, collagen vascular disease, and vasculitis. C
› Identify extra-pulmonary organ involvement, as clinically indicated, by screening with a baseline eye examination; complete blood count; creatinine, alkaline phosphatase, and calcium levels; electrocardiogram, and other organ-specific studies. C
› Make a patient-centered decision whether to begin antiinflammatory treatment based on symptomatology and risk of organ failure or death. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence B Inconsistent or limited-quality patient-oriented evidence C Consensus, usual practice, opinion, disease-oriented evidence, case series
References
Sarcoidosis is a multisystem inflammatory disease of unclear etiology that primarily affects the lungs. It can occur at any age but usually develops before the age of 50 years, with an initial peak incidence at 20 to 29 years and a second peak incidence after 50 years of age, especially among women in Scandinavia and Japan.1Sarcoidosis affects men and women of all racial and ethnic groups throughout the world, but differences based on race, sex, and geography are noted.1
The highest rates are reported in northern European and African-American individuals, particularly in women.1,2 The adjusted annual incidence of sarcoidosis among African Americans is approximately 3 times that among White Americans3 and is more likely to be chronic and fatal in African Americans.3 The disease can be familial with a possible recessive inheritance mode with incomplete penetrance.4 Risk of sarcoidosis in monozygotic twins appears to be 80 times greater than that in the general population, which supports genetic factors accounting for two-thirds of disease susceptibility.5
Likely factors in the development of sarcoidosis
The exact cause of sarcoidosis is unknown, but we have insights into its pathogenesis and potential triggers.1,6-9 Genes involved are being identified: class I and II human leukocyte antigen (HLA) molecules are most consistently associated with risk of sarcoidosis. Environmental exposures can activate the innate immune system and precondition a susceptible individual to react to potential causative antigens in a highly polarized, antigen-specific Th1 immune response. The epithelioid granulomatous response involves local proinflammatory cytokine production and enhanced T-cell immunity at sites of inflammation.10 Granulomas generally form to confine pathogens, restrict inflammation, and protect surrounding tissue.11-13
Sarcoidosis is a diagnosis of exclusion; one must rule out infections, occupational or environmental exposures, malignancies, and other disorders that cause granulomatous inflammation.
ACCESS (A Case Control Etiologic Study of Sarcoidosis) identified several environmental exposures such as chemicals used in the agriculture industry, mold or mildew, and musty odors at work.14 Tobacco use was not associated with sarcoidosis.14 Recent studies have shown positive associations with service in the US Navy,15 metal working,16 firefighting,17 the handling of building supplies,18 and onsite exposure while assisting in rescue efforts at the World Trade Center disaster.19 Other data support the likelihood that specific environmental exposures associated with microbe-rich environments modestly increase the risk of sarcoidosis.14 Mycobacterial and propionibacterial DNA and RNA are potentially associated with sarcoidosis.20
Clinical manifestations are nonspecific
The diagnosis of sarcoidosis can be difficult and delayed due to diverse organ involvement and nonspecific presentations. TABLE 121-31 shows the diverse manifestations in a patient with suspected sarcoidosis. Around 50% of the patients are asymptomatic.23,24 Sarcoidosis is a diagnosis of exclusion, starting with a detailed history to rule out infections, occupational or environmental exposures, malignancies, and other possible disorders (TABLE 2).22
Diagnostic work-up
The primary objective of a diagnostic evaluation in most suspected cases of sarcoidosis is to corroborate the clinical and radiologic features with pathologic evidence of non-necrotizing granulomas and to exclude other causes of granulomatous inflammation.22
Radiologic studies
Chest x-ray (CXR) provides diagnostic and prognostic informationin the evaluation of sarcoidosis using the Scadding classification system (FIGURE 1).21,25,32,33 Interobserver variability, especially between stages II and III and III and IV is the major limitation of this system.32 At presentation, radiographs are abnormal in approximately 90% of patients.34 Lymphadenopathy is the most common radiographic abnormality, occurring in more than two-thirds of cases, and pulmonary opacities (nodules and reticulation) with a middle to upper lobe predilection are present in 20% to 50% of patients.1,31,35 The nodules vary in size and can coalesce and cause alveolar collapse, thus producing consolidation.36 Linear opacities radiating laterally from the hilum into the middle and upper zones are characteristic in fibrotic disease.
