MS2 Sarcoidosis

• -onset <50 years, peak incidence is 20-40
• -Worldwide: Northern European has highest incidence
• -African Americans 3x > Caucasian Americans
•      -African Americans peak later (40-50); worse prognosis
• -Female predominance
• -Low income/poor socioeconomic status → more severe sarcoidosis
• -Treatment required in ~60% of patients

• Sarcoid in children:
• -children<adults (0.06 cases per 100,000)
• -Present: skin lesions, uveitis, arthritis, stage 1 changes in CXR
• -Ddx: familial juvenile systemic granulomatosis (Blau's syndrome)

• Exposure to irritants - wood-burning stoves, tree pollen, mold
• Exposure to inorganic particles - insecticides
• Association with US Navy, metalworking, firefighting
• PCR assessment of granulomas show: mycobacterial and propiobacterial DNA and RNA

Pathologic immune response triggered by exposure/inhalation of various environmental antigens

• Familial sarcoidosis is rare
• Greater concordance in monozygotic twins compared to dizygotic twins
• Patient with sarcoid 5x more likely to have family member with sarcoid
• *pattern of organ involvement might also be inherited
• Phenotype: Class I HLA-B8 antigens associated with acute sarcoidosis
• Susceptibility: Class II HLA antigens...

• -Granulomas are centrally organized macrophages & epithelioid cells encircled by lymphocytes
• -Granulomas confine pathogens
• -(Macrophages + chronic cytokine stimulation → differentiation to epithelioid cells)
• Multinucleated giant cells

• -CD4 T cells and APC initiate and maintain granulomas
• → Activated CD4+ cells differentiate Th1-like
• -Secrete IL-2, IFN-γ
• -Augment macrophage TNF-α production

• Macrophages
• CD4+ T cells
• Th1 cells
• IL-2, IFN-γ

• Granulomas of sarcoidosis
• -tight granulomas
• -giant cells

• Most detected incidentally on CXR
• Systemic symptoms (fatigue, night sweats, wt loss) are common
• 2/3 experience remission within 10yrs of Dx (50% in 3 years)
• 1/3 have unrelenting disease
• Recurrence is rare (<5%)
• Mortality: <5%, typically from pulmonary fibrosis

Granulomas may completely resolve BUT...

• -Pulmonary fibrosis occurs in ~1/4 patients
• -Shift from Th1 cells (IL-2) to Th2 (IL-4, -10, -13) maybe important to fibrosis

• Acute sarcoid (~20% of cases)
• -Fever
• -Arthritis (ankles in men)
• -Erythema nodosum (>women)
• -Bilateral hilar adenopathy
• -90% spontaneous resolution within 2 years
• -Scandinavian, Irish, African, & Puerto Rican women
• -Strong HLA-DQB1 association

• Diagnosis of exclusion
• -clinical and radiograph findings in 90%
• -must have histological evidence of noncaseating granulomas (absence of organisms or particles)
• -Bx (not needed in Löfgren's syndrome)
• -Bronchoscopy often required
•      -Transbronchial biopsy: 85% diagnostic yield

Bronch shows cobble stone, bumpy appearance - can be used to make dx without biopsy in 85% of cases

• ACE levels are elevated in 60% of pts with sarcoidosis
• Granulomas make angiotensin converting enzyme

• Symptoms:
• -Dry cough
• -Dyspnea
• -Chest pain/tightness and wheezing

• Stage 1-4: stage is a description, not a progression
• 1. Bilateral hilar lymphadenopathy (no infiltrates)
• 2. bilateral hilar lymphadenopathy (with infiltrates)
• 3. infiltrates (no nodes)
• 4. Nonspecfic scarring/injury (fibrotic bands, bullae, hilar retraction, bronchiectasis, diaphragmatic tenting)

sarcoid stage 1

• Stage I Lymphadenopathy:
• DDx:
• -Primary TB
• -Endemic Fungal (esp.) Histoplasmosis
• -Lymphoma
• -Small cell lung cancer with nodal metastases

Sarcoid stage 3

Sarcoid stage 2: lymphadenopathy + infiltrates

Sarcoid stage 4

• Nodular pattern:
• -Silicosis/pneumoconiosis: centrilobular and subpleural nodular
• -miliary TB: random nodules

• Fibrotic pattern:
• -Usual interstitial pneumonia (UIP): base and peripheral fibrosis, honeycombing
• -Chronic Hypersensitivity pneumonitis: mid zone fibrosis with mosaic pattern
• -Tuberculosis (more unilateral)

• 65% have abnormal PFTs
• -majority restricted, but mixed obstructive/restrictive is common
• -may respond to bronchodilators
• -80% will have normalized within 2 years

• Pulmonary hypertension relatively common:
• -14% at rest
• ->40% at exercise
• -loss of pulmonary vasculature
• -occasionally mimics small vessel disease (PAH) with granulomatous narrowing of small pulmonary arteries

• common: ~30%
• May be cosmetically/emotionally significant
• Lesions highly variable:
• Macules, papules, plaques, single lesions or crops
• Location: nape of neck, upper back, extremities & trunk; may appear in scars and tattoos

• Lupus pernio:
• -indurated, lumpy, violaceous lesions
• -nose, cheeks, lips, ears
• -often eroding into cartilage and bone
• -Women>Men
• -Associated with chronic disease & extrapulmonary disease
• -Remission is rare

• Erythema nodosum:
• -~10% of sarcoidosis
• -painful raised nodules
• -occur in allergy and inflammatory disease
• -lasts for weeks
• -Bx: nonspecific septal panniculitis (not useful for dx)

• 5% have clinically apparent cardiac involvement:
• 25% have cardiac granulmoa at autopsy
• -Cardiomyopathy
• -Arrhythmia: commonly bradyarrhythmias (block)

• Screening with 12 lead ECG
• Endomyocardial biopsy has low diagnostic value

• Eye is involved in 80% of sarcoid patients:
• ->20 ophthalmologic sx on presentation

• Slit lamp & fundoscopic exam mandatory:
• -multifocal chorioditis
• -swelling of the optic nerve
• -65% anterior uveitis → insidious cataract, glaucoma, vision loss

• 10% of sarcoid patients have neurologic symptoms
• 25% have evidence on autopsy

• -CN palsy > headache > ataxia > cognitive dysfunction > weakness > seizures
• -~13% with neuro sarcoidosis have NO OTHER organ involved
• -CSF is non-specific
• -MRI with gadolinium is sensitive for CNS disease
• -Tx: aggressive corticosteroids (immunosuppressives)

• 10% (elevated LFTs); however usually asymptomatic
• more common in African Americans vs. Caucasian Americans
• Liver and spleen granuloma seen 10% of the time on CT
• 60% with hypatic sarcoid have systemic symptoms: fever, night sweats, anorexia, wt loss

• Asymptomatic bone lesions are common
• May cause pain
• Chronic arthralgias are more common than acute arthritis

• Hypercalciuria is common, 40%
• Hypercalcemia in 10%
• Nephrolthiasis in 10%
• *Granulomatous macrophages convert Vit D to a more active metabolite
• Renal failure from granulomatous interstitial nephritis is rare (<1%)

• -Most pts do not require treatment; reserved for signficant symptoms
• -Prednisone is mainstay of therapy (20-40mg/day)

• Lack of response:
• -irreversible fibrotic disease
• -medication noncompliance
• -inadequate prednisone dose

• -Methotrexate is used as steroid sparring agent
• -Hydroxychloroquine used for hypercalcemia, CNS and skin disease
• -Future: TNF-α blockers (?)

• 3% of lung transplants are for sarcoidosis
• <1% of heart and liver transplants for sarcoidosis
• survival rates for lung and liver are the same as non-sarcoid patients
• Survival rates for heart transplant are better for short and intermediate-term survival
• **Sarcoidosis can recur in lung allograft (but does not affect survival)