Sarcoidosis

Classic presentation

Etiology

Sarcoidosis is a systemic disorder characterized by widespread, immune-mediated formation of noncaseating granulomas.

General
- Inhalation of foreign antigen �?monocyte differentiation �?activation of interstitial dendritic cells and alveolar macrophages
- Interstitial dendritic cells migrate towards mediastinal lymph nodes and alveolar macrophages differentiate, serving as antigen-presenting cells to circulating T helper (Th) cells �?differentiation and clonal expansion of T cells
- T cell recruitment and �?B-cell activity �?local immune hyperactivity and inflammation �?formation of noncaseating granulomas in the lungs and the lymphatic system
Granuloma formation: Mature granulomas are composed of epithelioid cells and macrophages surrounded by lymphocytes and fibroblasts.
- Macrophages activate Th1 cells.
- Th1 cells stimulate the formation of epithelioid cells and multinucleated giant cells by releasing IFN-γ.
- Epithelioid cells produce angiotensin-converting enzyme (ACE) and release cytokines that recruit more immune cells.
- Asteroid bodies: star-shaped, eosinophilic inclusion bodies consisting of various lipids (e.g., from sarcoidosis, foreign body reactions)

Tip

Compared with TB, which has caseating granulomas.
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Fibrosis: Epithelioid cells secrete cytokines to recruit fibroblasts, leading to fibrosis �?damage of organs and tissue
Calcium dysregulation: activated pulmonary alveolar macrophages �?�?1-alpha hydroxylase expression and activity �?�?1,25-dihydroxyvitamin D (calcitriol) �?hypervitaminosis D �?hyperphosphatemia, hypercalcemia, and, possibly, renal failure

Lungs are the most commonly affected organ (90% of affected individuals).
Often asymptomatic in the early stages
Classic finding is hilar lymphadenopathy
Interstitial fibrosis
- Cough, exertional dyspnea, chest pain
- Mild rales on pulmonary auscultation

Erythema nodosum: most common nonspecific cutaneous manifestation
Lupus pernio
- A pathognomonic manifestation of sarcoidosis characterized by extensive, violaceous skin plaques (i.e., epithelioid granulomas of the dermis) on the nose, cheeks, chin, and/or ears

Cranial nerve palsy (unilateral or bilateral facial nerve palsy is the most common)
Diabetes insipidus

Sarcoid uveitis
- Most common ocular manifestation
- Manifests with pain, redness, and photophobia

Nephrolithiasis, nephrocalcinosis (calcium oxalate > calcium phosphate stones)
Bone pain, arthralgias, myalgias, fractures
- Because most of the calcium is released from bones
Constipation
- Increase in extracellular Ca²⁺ �?membrane potential outside is more positive �?more amount of depolarization is needed to initiate action potential �?decreased excitability of muscle and nerve tissue
Abdominal pain
Nausea and vomiting
Anorexia
Peptic ulcer disease
- hypercalcemia-induced increase of gastric acid secretion and gastrin levels.
Neuropsychiatric symptoms such as anxiety, depression, fatigue, and cognitive dysfunction
Diminished muscle excitability
- Cardiac arrhythmias
  - ECG: Shorten QT interval, see ECGs#QT interval
- Muscle weakness, paresis
Polyuria and dehydration
- Due to acquired renal ADH resistance. Although ADH is being secreted, the kidneys no longer respond to it adequately (nephrogenic diabetes insipidus).

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Tip

Increased ACE levels may be seen. However, they are not specific for sarcoidosis and should not be used in isolation for diagnosis or monitoring.

Chest x-ray
- Preferred initial test for all patients with suspected sarcoidosis
- Classic findings: bilateral hilar lymphadenopathy with or without pulmonary infiltrates (i.e., reticular and/or ground glass opacities)

Schaumann bodies: cellular inclusion bodies consisting of intracytoplasmic calcium and protein with laminar stratification (e.g., sarcoidosis, tuberculosis, Crohn disease, berylliosis)

Bronchoalveolar lavage (BAL):�?CD4:CD8 ratio
- CD4+ lymphocytes release interferon-gamma and TNF-alpha to drive macrophage activation and granuloma formation.