Pulmonology · Interstitial Lung Disease
The facts most likely to be tested
Press 1–5 to rate · ↑↓ to navigate
Sarcoidosis is a systemic granulomatous disease characterized by non-caseating granulomas in affected organs.
The classic pulmonary presentation involves bilateral hilar lymphadenopathy and reticular opacities on chest imaging.
Löfgren syndrome is the acute form of sarcoidosis presenting with the triad of erythema nodosum, bilateral hilar lymphadenopathy, and polyarthralgia.
Laboratory findings frequently reveal hypercalcemia and hypercalciuria due to 1-alpha-hydroxylase activity in macrophages causing increased 1,25-dihydroxyvitamin D production.
Serum angiotensin-converting enzyme (ACE) levels are often elevated, though this test lacks sufficient sensitivity and specificity for definitive diagnosis.
The diagnosis is confirmed via tissue biopsy showing non-caseating granulomas after excluding infectious etiologies like tuberculosis and fungal infections.
Systemic corticosteroids are the first-line treatment for patients with symptomatic pulmonary disease, organ-threatening involvement, or persistent hypercalcemia.
Vignette unlocked
A 32-year-old African American woman presents to the clinic with a two-week history of painful, red nodules on her shins and bilateral ankle pain. Physical examination reveals tender, erythematous nodules on the anterior lower extremities and bilateral hilar lymphadenopathy on chest X-ray. Her serum calcium is 11.2 mg/dL, and her ACE level is elevated. She has no history of fever, night sweats, or weight loss.
What is the most likely diagnosis?
Löfgren syndrome (a form of Sarcoidosis)
The patient presents with the classic triad of Löfgren syndrome (erythema nodosum, bilateral hilar lymphadenopathy, and polyarthralgia), which is a specific, high-yield clinical presentation of sarcoidosis.
Full handout
High yield triage
Etiology / Epidemiology
Systemic granulomatous disease most common in African American females and Northern Europeans.
Clinical Manifestations
Presents with Löfgren syndrome, bilateral hilar lymphadenopathy, and erythema nodosum.
Diagnosis
Biopsy showing non-caseating granulomas is the gold standard; exclude TB/fungal infections.
Treatment
Oral corticosteroids are first-line for symptomatic disease; monitor for secondary infections.
Prognosis
Most cases resolve spontaneously; 20% develop permanent lung impairment or organ damage.
Full handout
Epidemiology & Etiology
Peak incidence occurs in patients aged 20–40 years. There is a notable predilection for African American women and individuals of Scandinavian descent. The etiology remains idiopathic, likely involving an exaggerated immune response to an unknown environmental antigen.
Pertinent Anatomy
The disease primarily affects the pulmonary system and intrathoracic lymph nodes. Extrapulmonary involvement frequently targets the skin, eyes, liver, and heart, which may lead to conduction blocks.
Pathophysiology
Characterized by an exaggerated T-cell response leading to the formation of non-caseating granulomas. These granulomas secrete 1-alpha-hydroxylase, causing increased conversion of vitamin D to its active form. This results in hypercalcemia and hypercalciuria due to increased intestinal calcium absorption.
Clinical Manifestations
Patients often present with dry cough, dyspnea, and chest pain. Löfgren syndrome is a classic triad of erythema nodosum, bilateral hilar lymphadenopathy, and polyarthralgias. Red flags include uveitis, parotid gland enlargement, and Heerfordt syndrome (uveoparotid fever).
Diagnosis
The gold standard is tissue biopsy demonstrating non-caseating granulomas. Chest X-ray typically shows bilateral hilar lymphadenopathy. Labs often reveal elevated ACE levels and hypercalcemia, though these lack high specificity.
Treatment
Oral corticosteroids (prednisone) are the first-line treatment for symptomatic pulmonary or extrapulmonary involvement. Contraindications include untreated latent tuberculosis. For refractory cases, methotrexate is the preferred second-line agent.
Prognosis
The majority of patients achieve spontaneous remission within 2 years. 20% of patients experience progressive disease leading to pulmonary fibrosis or end-organ failure. Annual ophthalmologic exams and ECGs are required to monitor for silent progression.
Differential Diagnosis
Tuberculosis: caseating granulomas and positive acid-fast bacilli
Berylliosis: indistinguishable histology; requires history of aerospace/electronics exposure
Lymphoma: systemic B-symptoms and abnormal lymph node architecture
Histoplasmosis: fungal etiology; common in Ohio/Mississippi River valleys
Hypersensitivity pneumonitis: associated with specific environmental triggers like bird droppings