Multisystem non-caseating granulomatous disease most commonly involving lungs and lymph nodes.
Also known as: sarcoid, sarcoidosis, noncaseating granuloma, Löfgren syndrome, Heerfordt syndrome
Overview
Idiopathic multisystem disorder characterized by formation of non-caseating epithelioid granulomas in affected organs — most commonly lung and intrathoracic lymph nodes, but virtually any organ can be involved.
Epidemiology
Incidence varies by race: highest in African Americans (35-80 per 100,000) and northern Europeans. Female predominance. Peak onset ages 20-40, with second peak in women 50-60. African American patients more often present with severe/multiorgan disease.
Try two board-style Sarcoidosis questions
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
Question 1PulmonaryMedium
A 35-year-old man undergoes a chest radiograph for a pre-employment physical that reveals asymptomatic bilateral hilar lymphadenopathy. He reports no fever, weight loss, or cough. Serum angiotensin-converting enzyme (ACE) is mildly elevated, and spirometry is normal. Which of the following is the most appropriate management?
AInitiate inhaled corticosteroid therapy
BInitiate systemic corticosteroid therapy
CObservation with follow-up in 3-6 months
DBronchoscopy with bronchoalveolar lavage
ECT chest and transbronchial lymph node biopsy
Reveal answer & full explanation
Correct answer: C — Observation with follow-up in 3-6 months
AInitiate inhaled corticosteroid therapy
BInitiate systemic corticosteroid therapy
CObservation with follow-up in 3-6 months✓
DBronchoscopy with bronchoalveolar lavage
ECT chest and transbronchial lymph node biopsy
Why observation with follow-up in 3-6 months is correct
The picture is asymptomatic Stage I sarcoidosis: symmetric bilateral hilar lymphadenopathy without infiltrates, normal spirometry, a mildly elevated ACE, and no constitutional symptoms
Asymptomatic Stage I disease remits spontaneously in the large majority of patients, so the standard of care is serial observation rather than treatment or invasive testing
Short-interval clinical and radiographic follow-up catches the minority who progress and need further evaluation
Why the others are wrong
Initiate systemic corticosteroid therapy — systemic steroids are reserved for significant symptoms, declining pulmonary function, hypercalcemia, or cardiac/neuro/ocular involvement, none of which are present; treating an asymptomatic patient is right-diagnosis-wrong-step
CT chest and transbronchial lymph node biopsy — tissue sampling is reserved for atypical or progressive presentations; pursuing it in a classic asymptomatic case is premature closure on an aggressive workup
Bronchoscopy with bronchoalveolar lavage — a lymphocyte-predominant lavage with an elevated CD4:CD8 ratio is supportive but not diagnostic, and confirming a classic asymptomatic Stage I picture would not change the plan of serial observation (over-testing an incidental finding)
Initiate inhaled corticosteroid therapy — an inhaled steroid can seem like a gentler compromise for mild lung involvement, but inhaled corticosteroids have no consistent evidence of benefit in pulmonary sarcoidosis, and an asymptomatic Stage I patient with normal spirometry needs no treatment at all (right-diagnosis-wrong-step)
Question 2PulmonaryMedium
A 44-year-old African American woman presents with bilateral hilar lymphadenopathy on CXR, mild dyspnea, and erythema nodosum on her shins. She has an elevated serum angiotensin-converting enzyme (ACE) level. Biopsy of a hilar lymph node shows noncaseating granulomas. Which of the following is the most appropriate initial treatment?
AMethotrexate
BObservation
CHydroxychloroquine
DPrednisone
EInfliximab
Reveal answer & full explanation
Correct answer: B — Observation
AMethotrexate
BObservation✓
CHydroxychloroquine
DPrednisone
EInfliximab
Why Observation is correct
This patient has stage I sarcoidosis: bilateral hilar lymphadenopathy without parenchymal infiltrates, with mild symptoms
Stage I sarcoidosis remits spontaneously in 60–70% of cases
With only mild dyspnea and erythema nodosum, observation is appropriate
Why the others are wrong
Prednisone — prednisone is first-line when treatment is required; indications include progressive pulmonary dysfunction, hypercalcemia, cardiac or neurologic disease, or uveitis — none of which are present here
Hydroxychloroquine — not a standard treatment for pulmonary sarcoidosis at this stage
Methotrexate — methotrexate is a second-line steroid-sparing agent, used when systemic treatment is required and steroids are not tolerated or insufficient
Infliximab — infliximab is a recognized option in sarcoidosis, but anti-TNF therapy is a third-line agent reserved for severe or refractory disease that persists despite glucocorticoids and second-line agents such as methotrexate; it has no role in mild stage I disease that is expected to remit on its own.
That's 2. Get 7,700+ more.
Unlock the full FirstPassPA bank: 7,700+ board-style questions, flashcards, and an AI tutor that explains every answer. Your 7-day free trial includes everything, and there's no credit card required.
You've read your 2 free diagnosis previews. Create your free account to unlock the full Sarcoidosis outline — plus all 514 diagnoses, 7,700+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Hypothesized antigen-driven T-helper 1 / Th17 response leading to non-caseating granuloma formation with epithelioid macrophages and CD4+ T cells. Activated macrophages produce 1-alpha-hydroxylase → 1,25-dihydroxyvitamin D → hypercalcemia in some patients. Exact triggering antigen unknown.
Clinical presentation
Symptoms
Pulmonary: dry cough, dyspnea, chest discomfort (~90% have lung involvement at some point)
Constitutional: fatigue, fever, weight loss, night sweats
Skin lesions (erythema nodosum on shins, lupus pernio on face/nose)
Lymphadenopathy (cervical, supraclavicular)
Hepatosplenomegaly
Eye exam: uveitis, conjunctival nodules
Classic findings
Bilateral hilar lymphadenopathy on CXR in young African American or northern European patient; Löfgren triad; lupus pernio; bell's-like facial palsy.
Differential diagnosis
Tuberculosis — Caseating granulomas (sarcoid is non-caseating), positive AFB, upper-lobe cavitation, exposure history
Lymphoma — B symptoms, bulky asymmetric lymphadenopathy, biopsy required
Hypersensitivity pneumonitis — Exposure history (birds, mold), upper-lobe centrilobular nodules, BAL with lymphocytosis (CD4:CD8 <1, opposite of sarcoid)
Berylliosis — Indistinguishable histology — requires beryllium exposure history and BeLPT (lymphocyte proliferation test)
Clinical/radiographic presentation + biopsy showing non-caseating granulomas + exclusion of alternative causes. Löfgren syndrome and asymptomatic Stage I CXR in a young patient may be diagnosed clinically without biopsy.
Labs
ACE level — elevated in ~60%, neither sensitive nor specific (poor diagnostic value)
Cardiac sarcoid: corticosteroids + immunosuppressant; ICD for sustained VT, cardiac arrest, or LVEF ≤35% despite treatment; when pacing is needed for high-grade AV block, an ICD (rather than a pacemaker alone) is reasonable because of the sudden-death risk (HRS 2014)
Pulmonary hypertension complicating sarcoid — referral to specialist; phosphodiesterase-5 inhibitors or endothelin antagonists in select cases
Lung transplantation for end-stage Stage IV fibrotic disease
Avoid vitamin D and calcium supplements in patients with hypercalcemia, hypercalciuria, or elevated 1,25-OH vitamin D (worsens hypercalcemia); check both 25-OH and 1,25-OH vitamin D before any vitamin D replacement (ATS 2020); sun exposure precautions
Complications
Pulmonary fibrosis (Scadding stage IV), pulmonary hypertension, aspergilloma in old cavities
Sudden cardiac death from arrhythmia or heart block (cardiac sarcoid)
Steroid-related adverse effects from chronic therapy
PANCE pearls
Löfgren syndrome (erythema nodosum + bilateral hilar adenopathy + arthralgia ± fever) carries an excellent prognosis with spontaneous remission in most patients.
Advanced pulmonary fibrosis (often with pulmonary hypertension) and cardiac sarcoid (heart block, VT, sudden death) are the leading causes of sarcoid mortality — low threshold for cardiac MRI/PET when symptoms suggest involvement.
Hypercalcemia in sarcoid is mediated by granuloma alpha-hydroxylase converting 25-OH-D to 1,25-OH-D — treat with steroids and AVOID vitamin D supplementation.
ACE level is too insensitive and nonspecific to diagnose or monitor sarcoid — do not rely on it.
Biopsy is essential to confirm non-caseating granulomas and exclude TB, fungi, and lymphoma before committing to immunosuppression.
References
ATS 2020 — Diagnosis and Detection of Sarcoidosis: An Official ATS Clinical Practice Guideline (Crouser et al., Am J Respir Crit Care Med 2020)
ERS 2021 — ERS Clinical Practice Guidelines on Treatment of Sarcoidosis (Baughman et al., Eur Respir J 2021)
HRS 2014 — HRS Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated with Cardiac Sarcoidosis (Birnie et al., Heart Rhythm 2014;11:1305-1323)
ACCESS Study — Clinical Characteristics of Patients in a Case Control Study of Sarcoidosis (Baughman et al., Am J Respir Crit Care Med 2001)
Practice Pulmonary questions on FirstPassPA
Turn this outline into retention. 7,700+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.