Extrathoracic clinical manifestations of sarcoidosis
The most common extrathoracic manifestations are cutaneous and ocular involvement. Skin rash occurs in up to 33% of patients and may be manifest as erythema nodosum in acute sarcoidosis or as subcutaneous nodules, papules, plaques, tattoo/scar sarcoidosis, and lupus pernio in chronic disease. Eye involvement (25%–50%) is frequently bilateral and can be the initial manifestation or occur anytime during the disease. Any area of the eye may be involved but anterior uveitis is the most common. Since uveitis can be subclinical, all patients with sarcoidosis should undergo a baseline slit-lamp examination. Sarcoidosis of the lacrimal glands is also common, causing eye dryness and keratoconjunctivitis. Granulomatous involvement of the orbit can present as proptosis. Arthralgias are present in the majority of patients, but inflammatory arthritis occurs in up to 25% and is classified as acute or chronic. The acute form is more common and often occurs with Lofgren syndrome. The arthritis is usually oligoarticular or polyarticular involving large joints, with the ankles being most common. The joint swelling may be due to a periarthritis rather than true synovitis. Osseous sarcoidosis is found in up to 13% but is frequently asymptomatic. There is a predilection for the phalanges of the hands and feet, but any bone can be affected. The incidence of skeletal muscle involvement is highly variable because most of the patients are asymptomatic. Muscle involvement with noncaseating granulomas on biopsy may be found in 50% to 80% of all patients with sarcoidosis, but symptomatic myositis is only reported in <3%. Hepatosplenomegaly (5%–20%) or elevated alkaline phosphatase (20%–30%) is a common finding but rarely cause significant organ injury. Bilateral parotid enlargement is seen in approximately 4% and can be associated with xerostomia. Neurologic findings are observed in 5% and may be the presenting manifestation of sarcoidosis. Unilateral facial nerve palsy is most common, but any region of the brain and spinal cord can be involved. Encephalopathy, mass lesions, aseptic meningitis, peripheral neuropathy, and small fiber neuropathy can also occur. Heart involvement (approximately 5%) due to granulomatous inflammation of the myocardium and/or the conduction system presents with ventricular arrhythmias, conduction abnormalities, and heart failure. However, many patients are asymptomatic. Up to 25% of patients with sarcoidosis have evidence of cardiac involvement on autopsy. Isolated sarcoidosis affecting the heart has been reported. Hematologic manifestations include anemia and leukopenia. Anemia of chronic disease is most common, but bone marrow involvement may be found in up to 27% of anemic patients. Leukopenia may be due to sequestration of lymphocytes to sites of inflammation or hypersplenism. The hypothalamic–pituitary axis may be involved and classically presents as diabetes insipidus. Kidney and gastrointestinal organs are rarely affected. Vasculitis of any size vessel has been described. Fatigue is common (over 50%) and can be disabling.
