Sarcoidosis in Adults

Background

• Sarcoidosis is a systemic disease of unknown cause characterized by the formation of immune granulomas in any organ, most commonly the lungs, intrathoracic lymph nodes, skin, and eyes.
• Sarcoidosis is found worldwide, but incidence, manifestations, and disease course varies with race, sex, and age.
• Genetic predisposition is postulated to lead to an exaggerated inflammatory response to certain environmental exposures including infection with mycobacteria or propionibacteria, or other organic and inorganic substances.
• Spontaneous remission occurs in about one-half of all patients and the likelihood of remission correlates with the disease stage.
• Important complications include heart failure, cardiac arrest, pulmonary fibrosis, pulmonary hypertension, and kidney involvement including kidney stones and nephrocalcinosis.

Evaluation

• The diagnosis of sarcoidosis is confirmed by compatible clinical and x-ray findings, biopsy evidence of noncaseating granuloma (from safest and most accessible organ), and the exclusion of other causes.
  • Clinical findings may include a persistent cough, shortness of breath, atypical chest pain, fatigue, weight loss, fever, night sweats, malaise, uveitis, skin papules, peripheral lymphadenopathy, erythema nodosum, elevated liver enzymes, and/or abnormal chest x-ray.
  • Sarcoidosis may be asymptomatic and only suspected by an incidental chest x-ray or computed tomography findings.
  • Two presentations may be diagnosed clinically without the need for biopsy.
    • Lofgren syndrome presents with acute erythema nodosum, arthritis or periarthritis (generally in ankle region), and bilateral hilar adenopathy.
    • Heerfordt syndrome presents with acute parotitis, fever, uveitis, and typically facial nerve palsy.
• The differential is broad due to diverse, the nonspecific presentation and a range of organ involvement and includes fungal and mycobacterial infections, occupational-, environmental-, or drug-induced granulomatosis, other types of interstitial lung disease, malignancy, immunodeficiency, and vasculitis.
• Patients with suspected sarcoidosis should have a complete evaluation to assess for multisystem disease, which should include pulmonary, cardiac, neurological, and ocular testing; the extent of testing depends mostly on the presence of signs and symptoms.
  • Blood tests may include complete blood count, serum calcium, creatinine, and liver enzymes. No reliable biomarker is currently available for diagnosis in routine clinical practice.
  • Bronchoalveolar lavage findings may be used to support a diagnosis of pulmonary sarcoidosis, but by itself is not diagnostic.
  • 12-lead electrocardiography should be part of the routine baseline assessment.
  • In patients with suspicion of cardiac involvement, further evaluation with cardiac magnetic resonance or 18F-fluorodeoxyglucose-positron emission tomography should be considered.

Management

• There is no cure for sarcoidosis. Treatment only impacts the granulomatous process and its clinical consequences, and control of the disease is achieved in about 70% of patients.
• 20%-70% of patients require systemic therapy. The decision to treat depends on the potential for severe dysfunction or permanent damage to major organs, the likelihood of mortality without treatment, and the presence of incapacitating constitutional symptoms.
• Oral corticosteroids are considered the first-line treatment.
  • The typical starting regimen is prednisone 20-40 mg/day for 6-12 weeks.
  • This is followed by a biweekly taper of 5 mg/day until 5-10 mg/day is reached for maintenance treatment.
• Other treatment options for patients with symptoms refractory to corticosteroids or for corticosteroid-sparing include immunosuppressive drugs (alone or in addition to corticosteroids), such as methotrexate or tumor necrosis factor antagonists, and immunomodulators such as hydroxychloroquine.
• Transplant of the heart, lung, liver, or kidney may be warranted for end-stage disease after all medical therapies have been tried.
• Due to a high rate of relapse following withdrawal or tapering of corticosteroids, follow-up testing including clinical exam, chest x-ray, pulmonary function testing, electrocardiogram, and blood tests should continue for a minimum of 3 years after end of the initial treatment period.