Sarcoidosis is a multiorgan disease characterized by the formation of noncaseating epithelioid cell granulomas. Granulomatous lesions may resolve spontaneously, or they may continue to progress to a fibrotic state with resultant tissue damage. Currently, the cause of sarcoidosis remains unknown. This disorder is seen more frequently in African Americans, and females are afflicted twice as often as males.
Various organ systems can be involved but most commonly the lungs, eyes, and skin are affected. Clinical manifestations include cough, dyspnea, fatigue, weight loss, night sweats, fever, chest pain, sputum production, hemoptysis, erythema nodosum, uveitis, iritis, arthritis, conjunctivitis, Bells palsy, peripheral neuropathy, and pituitary dysfunction. Lofgren's syndrome refers to the acute presentation of sarcoidosis that is characterized by the triad of arthritis, erythema nodosum, and bilateral hilar adenopathy on CXR. Lupus pernio refers to indurated, lumpy, violaceous lesions of the nose, cheeks, lips or ears. Anterior uveitis is the most common ocular manifestation. Hypercalciuria, hypercalcemia and nephrolithiasis are common manifestations; therefore, once diagnosed, patients should be tested by determining a 24-hour urinary excretion of calcium and urinalysis plus imaging studies if appropriate.
Pulmonary disease can be staged according to abnormalities found on routine chest roentgenograms: stage 0--normal chest radiograph; stage 1--bilateral hilar adenopathy without pulmonary infiltrates; stage 2--bilateral hilar adenopathy with pulmonary infiltrates; stage 3--pulmonary infiltrates without the presence of hilar adenopathy; and stage 4--fibrotic bands, bullae, hilar retraction, bronchiectasis, and/or diaphragmatic tenting. Pulmonary impairment may manifest as restrictive lung disease with a decreased DLCO on pulmonary function testing, or as hypoxemia at rest or during exercise. Serial PFTs may be used to follow disease progression or response to therapy.
The diagnosis of sarcoidosis is made clinically based on symptoms, radiographic findings, and biopsy specimens with a lack of infectious etiology. Patients with Lofgren's syndrome need no further work up and can proceed to treatment or surveillance. In cases without Lofgren's syndrome, biopsy tissue should be obtained from affected organs. Biopsy of skin nodules, when present, are easily obtainable; however, biopsies should not be done on erythema nodosum or erythema multiforme because they do not contain granulomas. Transbronchial biopsy is the procedure of choice when skin lesions are not present; however, in stage 1 disease, mediastinoscopy may be necessary. Other potential biopsy sites include the conjunctival sac, parotid glands, lacrimal glands or , less commonly, the liver. If none of the above secondary sites show disease involvement and transbronchial biopsy is not diagnostic, mediastinoscopy, endoscopic guided intrathoracic lymph node biopsy or open lung biopsy should be considered. Cultures and special stains for mycobacterium and fungi should be performed on all biopsy specimens to exclude other causes for granulomatous disease. The diagnosis of sarcoidosis should not be made even if the pathology of biopsied tissues is consistent with noncaseating granulomas until other potential etiologies of granulomas has been excluded. The differential should include fungal diseases, mycobacterial infections, beryllium disease, Wegeners granulomatosis, primary biliary cirrhosis, rheumatoid arthritis, pulmonary abscess, bronchogenic cyst, amyloidosis, parasitic infections, and malignancy.
An elevated serum angiotensin-converting enzyme (ACE) is found in 60% of patients with sarcoid, ACE levels may imply disease activity but are not diagnostic, sensitive or specific. In fact, since many other conditions are associated with an elevated serum ACE level, this test is not helpful in the workup of this disorder. Other conditions associated with an elevation of the serum ACE are Gauchers disease, leprosy, lymphangiomyomatosis, diabetes mellitus with retinopathy, hepatic cirrhosis, hyperthyroidism, and silicosis.
The first step in treatment is to effectively determine which patients merit therapy. Treatment of patients with lung involvement remains a controversial issue as to which patients require therapy. Asymptomatic patients with stage 1 disease without extrapulmonary involvement do not warrant therapy. These patients should be followed with serial chest radiographs and pulmonary function testing. Worsening disease as evidenced by the above-mentioned parameters may necessitate therapy. Patients whose symptoms include only fever and joint pains may respond to treatment with NSAIDs. When there is doubt as to how best to proceed, involving a specialist trained in the treatment of sardcoid patients may be prudent. Steroids are considered highly effective. Other agents used include hydroxychloroquine, methotrexate, and azathioprine.