Pathophysiology
Summary
Sarcoidosis is a multisystem disorder predominantly affecting the lungs, characterized by the formation of non-caseating granulomas—aggregates of macrophages devoid of central necrosis. Activation of CD4+ helper T-cells is a key immunological feature, leading to a disrupted immune response such as anergy to common skin antigens and polyclonal hypergammaglobulinemia. Bronchoalveolar lavage often reveals an elevated CD4+ to CD8+ ratio (>2:1). These granulomas may contain multinucleated giant cells and unique inclusions like asteroid bodies and Schaumann bodies, the latter of which show up as purple spots on histology and contain laminated calcium and protein. Clinical manifestations range from pulmonary symptoms like gradual onset of dyspnea on exertion & dry cough, to systemic symptoms including malaise, weight loss, & fever. The disease can also manifest with skin conditions such as erythema nodosum and lupus pernio, as well as ocular involvement like anterior uveitis. Retinal and optic nerve involvement can results in vision loss while lacrimal and salivary gland involvement can cause dry eyes & dry mouth. Sarcoidosis in the liver causes granulomatous hepatitis.
Sarcoidosis can also induce hypercalcemia and hypercalciuria, attributed to excess 1-α-hydroxylase enzyme activity in the granulomas, converting Vitamin D to its active form. This may lead to calcium kidney stones. Elevated levels of angiotensin-converting enzyme (ACE) are also commonly observed. Sarcoidosis often resolves spontaneously, while progressive cases can be treated with glucocorticoids.
Sarcoidosis can mimic berylliosis, another granulomatous disease commonly found in workers in the nuclear and aerospace industries. Both conditions feature non-caseating granulomas and can lead to interstitial fibrosis, but the fibrosis in berylliosis may be more prominent in the upper lobes.
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FAQs
Sarcoidosis typically manifests with a gradual onset of exertional dyspnea and a dry cough. Constitutional symptoms such as malaise, fever, anorexia, and weight loss are also common. Skin and ocular symptoms may include erythema nodosum, subcutaneous nodules, lupus pernio, and anterior uveitis. Other organ involvement can lead to granulomatous hepatitis and restrictive cardiomyopathy. Hypercalcemia may also occur due to increased 1-α-hydroxylase activity in activated macrophages.
Non-caseating granulomas are clusters of macrophages without central necrosis. In sarcoidosis, these granulomas are primarily found in the lung interstitium and can extend to hilar and paratracheal lymph nodes, resulting in hilar lymphadenopathy. Over time, these pulmonary granulomas may evolve into diffuse interstitial fibrosis.
Sarcoidosis and berylliosis both feature non-caseating granulomas; however, berylliosis is specifically linked to exposure to beryllium dust, commonly found in nuclear and aerospace industries. While sarcoidosis can affect multiple organ systems, berylliosis primarily involves the lungs, with interstitial fibrosis more prominent in the upper lobes.
An elevated CD4+ to CD8+ ratio (> 2:1) in bronchoalveolar lavage is suggestive of sarcoidosis. The disease may also cause anergy to common skin antigens that typically trigger type-IV (delayed) immune reactions. Elevated levels of angiotensin-converting enzyme (ACE), produced in the granulomas, along with hypercalcemia and polyclonal hypergammaglobulinemia, are other diagnostic markers.
Progressive sarcoidosis is mainly managed with glucocorticoids. Additional treatments may be tailored based on the affected organ system. For instance, hypercalcemia may necessitate specific interventions to lower calcium levels, and cardiac involvement could require management for restrictive cardiomyopathy.
