Systemic Involvement in Sarcoidosis 

Pulmonary

> 90%

Granulomas form in alveolar septa and bronchiolar and bronchial walls, causing diffuse pulmonary disease

Rarely pulmonary arteries and veins can also be involved, causing pulmonary hypertension

Often it is asymptomatic and detected incidentally on chest imaging (chest radiograph or CT scan)

Spontaneously resolves in many patients but can cause progressive pulmonary dysfunction, leading to limitations in physical function, cavitary lesions, respiratory failure, and death in a few

Constitutional

80%

Fatigue, chronic pain, and fibromyalgia

Dermatologic

25%

Erythema nodosum:

• Red or discolored, indurated, tender nodules on anterior legs

• More common among people of European, Puerto Rican, or Mexican descent

• Usually remits in 3–6 months but may recur

• Surrounding joints often arthritic (Löfgren syndrome)

• May be good prognostic sign

• Biopsy of erythema nodosum lesions is unnecessary because granulomas, characteristic of sarcoidosis, are absent

Common skin lesions:

• Plaques

• Macules and papules

• Subcutaneous nodules

• Hypopigmentation

• Hyperpigmentation

Lupus pernio:

• Violaceous plaques on the nose, cheeks, lips, and ears

• More common among Black American and Puerto Rican patients

• Often associated with lung fibrosis

• Poor prognostic sign

Lymph nodes

• Thoracic lymph nodes

• Extra-thoracic lymph nodes

Thoracic lymph nodes: 90%

Extrathoracic lymph nodes: 15%

Hilar or mediastinal involvement in most patients

Intra-abdominal or nontender to tender peripheral (neck, axilla or groin)l lymphadenopathy in few patients

Hepatic

12%

Usually asymptomatic

Manifests with mild elevations in liver function test results, hypolucent lesions on CT scans with contrast

Rarely, clinically significant cholestasis or cirrhosis

Unclear distinction between sarcoidosis and granulomatous hepatitis when sarcoidosis affects the liver only

Ocular

12%

Uveitis (most common), causing blurred vision, photophobia, and tearing

Can cause blindness

Spontaneously resolves in most patients

May manifest with conjunctivitis, iridocyclitis, chorioretinitis, dacryocystitis, lacrimal gland infiltration causing dry eyes, optic neuritis, glaucoma, or cataracts

Ocular involvement more common among Black American patients and patients of Japanese descent

Annual screening indicated for early disease detection

Psychiatric

10%

Depression (common), but uncertain whether it is a primary manifestation of sarcoidosis or a response to the prolonged course of disease and frequent recurrences

Splenic

10%

Usually asymptomatic

Manifests with left upper quadrant pain and thrombocytopenia or as an incidental finding on ultrasound or CT

Neurologic

< 10%

Cranial neuropathy, especially the 7th nerve (causing facial nerve palsy) or 8th nerve (causing hearing loss)

Optic and peripheral neuropathy (common)

May affect any cranial nerve

Central nervous system involvement, with nodular lesions or diffuse meningeal inflammation typically in the cerebellum and brain stem

Hypothalamic and pituitary stalk infiltration, possibly causing panhypopituitarism

Arginine vasopressin deficiency, polyphagia and obesity, and thermoregulatory and libidinal changes

Upper respiratory tract

< 10%

Acute and chronic granulomatous inflammation of nasal and sinus mucosa with symptoms indistinguishable from common allergic and infectious sinusitis; more common in patients with lupus pernio

Laryngeal involvement present as nodule over vocal cords and hoarseness

Tracheal involvement can lead to tracheal stenosis (rare)

Diagnosis confirmed by biopsy

Hematologic

< 5–30%

Lymphocytopenia

Anemia due to granulomatous infiltration of bone marrow, sometimes causing pancytopenia

Splenic sequestration causing thrombocytopenia

Leukopenia

Bone

5%

Osteolytic or cystic lesions, mostly asymptomatic

Osteopenia

Cardiac

< 5%

Conduction blocks and arrhythmias (most common), sometimes causing sudden death (cardiac sarcoidosis)

Heart failure due to restrictive cardiomyopathy (primary) or Class V pulmonary hypertension (multifactorial)

Transient papillary muscle dysfunction and pericarditis (rare)

More common among patients of Japanese ancestry, in whom cardiomyopathy is the most frequent cause of sarcoidosis-related death

Oral

< 5%

Asymptomatic parotid swelling (most common)

Parotitis with xerostomia

Heerfordt syndrome (uveoparotid fever), characterized by uveitis, bilateral parotid swelling, facial palsy, and chronic fever

Oral lupus pernio, which may disfigure the hard palate and may involve the cheek, tongue, and gums

Muscle

< 1%

Asymptomatic disease with or without enzyme elevations in most patients

Sometimes insidious or acute myopathy with muscle weakness

Joint

< 1%

Ankle, knee, wrist, and elbow arthritis (most common)

May cause chronic arthritis with Jaccoud deformities or dactylitis

Löfgren syndrome (triad of acute migratory polyarthritis, erythema nodosum, and hilar adenopathy)

Renal

< 1%

Asymptomatic hypercalciuria (most common)

Interstitial nephritis

Chronic kidney disease caused by nephrolithiasis and nephrocalcinosis due to chronic hypercalciuria and requiring renal replacement (dialysis or transplantation) in some patients

Gastrointestinal tract

Rare

Most common gastric involvement by granulomas (asymptomatic or gastritis not responding to PPI)

Oropharyngeal or esophageal dysphagia due to respective muscle involvement by granulomas

Rarely, appendicular, colon, or rectal involvement

Mesenteric lymphadenopathy that may cause abdominal pain

Endocrine

Rare

Hypothalamic and pituitary stalk infiltration, possibly causing panhypopituitarism

May cause thyroid infiltration without dysfunction

Secondary hypoparathyroidism due to hypercalcemia

Pleural

Rare

Causes lymphocytic exudative effusions, usually bilateral

Reproductive

Rare

Case reports of endometrial, ovarian, epididymal, and testicular involvement

No effect on fertility

May subside during pregnancy and relapse postpartum