Sarcoidosis

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Pathophysiology - Granulomas Gone Wild

  • Trigger: Unknown inhaled antigen in genetically susceptible individuals.
  • Core Defect: Exaggerated, cell-mediated immune response driven by CD4+ Th1 cells.
  • Mechanism: Antigen-presenting cells (APCs) activate CD4+ T-cells, leading to a cytokine cascade (↑ IL-2, ↑ IFN-γ, ↑ TNF-α).
    • This recruits and activates macrophages, which differentiate into epithelioid cells and multinucleated giant cells, forming the hallmark non-caseating granulomas.

Asteroid body in multinucleated giant cell in sarcoidosis

High-Yield: Bronchoalveolar lavage (BAL) fluid characteristically shows a CD4/CD8 ratio > 3.5, reflecting the intense T-helper cell activity in the lungs.

Clinical Features - The Great Masquerader

  • General: Often asymptomatic (incidental CXR finding). Can present with fever, weight loss, fatigue.
  • Pulmonary (~90%): Dry cough, dyspnea, chest pain. The most common presentation.
    • Classic finding: Bilateral hilar lymphadenopathy (BHL).

Chest X-ray: Bilateral hilar lymphadenopathy in sarcoidosis

  • Skin (25%):
    • Erythema Nodosum: Painful red nodules on shins; associated with acute disease & good prognosis.
    • Lupus Pernio: Violaceous plaques on nose, cheeks, ears; specific for chronic sarcoidosis.
    • Papules, nodules, plaques.
  • Ocular (~25%): Anterior uveitis is most common; posterior uveitis, conjunctivitis, dry eyes.
  • Cardiac: Arrhythmias (heart block), cardiomyopathy, sudden death.
  • Neurologic: Cranial nerve palsies (esp. CN VII), aseptic meningitis.

Löfgren's Syndrome: An acute, high-prognosis triad of fever, bilateral hilar lymphadenopathy, and erythema nodosum/polyarthritis.

Diagnostics - Cracking the Case

  • Initial Labs:

    • ↑ Serum Angiotensin-Converting Enzyme (ACE) levels (in >75% of patients)
    • ↑ Serum calcium (hypercalcemia) due to granulomatous production of $1,25-(OH)_2D_3$
    • Pancytopenia on CBC
  • Imaging:

    • Chest X-Ray: The cornerstone. Bilateral hilar lymphadenopathy is the classic finding.
    • Gallium-67 Scan: Panda sign (lacrimal/salivary glands) & Lambda sign (hilar/paratracheal nodes).
  • Definitive Diagnosis:

    • Biopsy: Transbronchial biopsy is the preferred method. Shows non-caseating granulomas.

Löfgren's Syndrome: An acute, highly specific form of sarcoidosis presenting with fever, bilateral hilar lymphadenopathy, and erythema nodosum. Excellent prognosis.

Management - Taming Inflammation

  • Asymptomatic/Stage I: Observation; high rate of spontaneous remission.
  • Symptomatic Disease: Oral corticosteroids are first-line.
    • Indicated for worsening respiratory symptoms, cardiac, neuro, or ocular disease, or severe hypercalcemia.
    • Start prednisone 20-40 mg/day for 4-6 weeks, then slow taper.
  • Steroid-Sparing Agents: For refractory cases or to limit steroid toxicity.
    • Methotrexate (most common), azathioprine, leflunomide.

⭐ Infliximab, a TNF-α inhibitor, is reserved for severe, refractory sarcoidosis, especially neurosarcoidosis.

High-Yield Points - ⚡ Biggest Takeaways

  • Non-caseating granulomas are the pathognomonic finding on biopsy, essential for diagnosis.
  • Classic chest imaging reveals bilateral hilar lymphadenopathy and pulmonary reticular opacities.
  • Expect elevated serum ACE levels and hypercalcemia from extra-renal vitamin D activation by macrophages.
  • Key extrapulmonary signs include erythema nodosum, lupus pernio, and anterior uveitis.
  • Asymptomatic patients are often monitored; systemic corticosteroids are first-line for symptomatic disease.

Practice Questions: Sarcoidosis

Test your understanding with these related questions

A 47-year-old woman comes to the physician because of a 3-week history of a dry cough. She does not smoke or use illicit drugs. Physical examination shows mild conjunctival hyperemia. Chest auscultation shows fine crackles in both lung fields. Laboratory studies show a total calcium concentration of 10.8 mg/dL. The results of spirometry are shown (dashed loop shows normal for comparison). Further evaluation of this patient is most likely to show an increase in which of the following?

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Flashcards: Sarcoidosis

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What is the treatment for sarcoidosis? _____

TAP TO REVEAL ANSWER

What is the treatment for sarcoidosis? _____

Steroids (if symptomatic)

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