Sarcoidosis

Overview

Sarcoidosis is a multi-system disease of unclear etiology characterized by the presence of non-caseating granulomas in multiple organs. Although any tissue can be involved, the primary clinical consequences are a result of lung involvement and the prototypical finding is that of bilateral hilar lymphadenopathy. Because granulomas are a feature of many disease processes, the diagnosis of sarcoidosis is one of exclusion and requires an extensive workup to rule out mycobacterial or fungal etiologies.

Etiology and Pathogenesis

The etiology and pathogenesis of sarcoidosis remain cryptic although it is thought that the root cause is immune dysfunction. Current thinking suggests that disease arises from a deranged inflammatory response to an infectious or non-infectious trigger in a genetically susceptible host.

Epidemiology

Sarcoidosis is found worldwide with the highest rates among Scandinavians. In the US, African Americans are at several fold higher risk than whites. In general, sarcoidosis is a disease of early-to-middle adulthood in an otherwise healthy individual, with onset typically between ages 20-40. The disease is largely sporadic with family history representing a mild risk factor. Interestingly, cigarette smoking is mildly protective.

Pathology

The key feature of sarcoidosis is the presence of non-caseating granulomas characterized by a central area of epitheloid macrophages, often fusing to form giant cells, surrounded by ring of CD4+ T-cells. Fibroblasts form a rim around this structure and over time generate a progressively expanding shell of fibrosis that ultimately replaces the entire granuloma with scar. As befits a non-caseating granuloma, central caseous necrosis is absent. Although these non-caseating granulomas can be found in any organ, they are most commonly observed in the hilar and paratracheal lymph nodes as well as pulmonary interstitium.

Clinical Consequences

Sarcoidosis may be completely asymptomatic and detected only upon chest radiography. When patients do seek medical attention pulmonary complaints are the most frequent reason followed by ocular and cutaneous symptoms. Whatever the presentation, constitutional symptoms, including fever, night sweats, and weight loss, are frequently encountered. Sarcoidosis often charts a relapsing-remiting course and happily completely resolves in most patients with few residual deficits. In a small subset, sarcoisis does lead to progressive organ dysfunction and death, usually via damage to the lungs. We discuss specific features of particular organs below.

The lungs are involved in over 90% of patients. Lymphadenopathy of the hilar and paratracheal lymph nodes, detectable by chest radiography, represents the most common starting point of a diagnostic workup. The pulmonary parenchyma is also affected in the vast majority of patients, with granuloma formation primarily in the pulmonary interstitium. In a minority of patients this leads to progressive interstitial fibrosis and honeycombing. For these patients this leads to a restrictive lung disease or generates increasing pulmonary hypertension and ultimately cor pulmonale.

While non-caseating granulomas can develop in the skin, the most common cutaneous finding in sarcoidosis is erythema nodosum, characterized by the development of deep tender red nodules typically on the shins.

Ocular pathology develops in a subset of patients and can manifest as inflammation of both the anterior eye, including anterior uveitis, or posterior eye, including retinitis. If left unchecked, blindness can occur.

Macrophages with granulomas tend to synthesize large amounts of Vitamin D and can result in hypercalcemia and hypercalcuria in a subset of patients.

As mentioned, sarcoidosis can affect virtually any organ and involvement of the heart, liver, spleen, bone marrow, muscles, bones, and central/peripheral nervous system are not uncommonly encountered with attendant clinical consequences.

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