Classic presentation

• HiIar lymphadenopathy
• Cough, dyspnea
• Often asymptomatic, detected on routine chest x-ray

Etiology

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Pathophysiology

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.

• 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

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Clinical features

Pulmonary sarcoidosis

• 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

Extrapulmonary sarcoidosis

Cutaneous sarcoidosis

• 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

Butterfly rash as seen in systemic lupus erythematosus

Neurosarcoidosis

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

Ocular sarcoidosis

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

Symptoms of hypercalcemia

Clinical features

• 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).

Link to original

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Diagnostics

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.

Imaging

• 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)

Biopsy

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

Additional studies

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

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Treatment

• Steroids
• Other immunosuppressants

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