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 35-year-old African-American female presents to the emergency room complaining of chest pain. She also complains of recent onset arthritis and increased photosensitivity. Physical examination reveals bilateral facial rash. Which of the following is most likely to be observed in this patient?

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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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