From the Guidelines
The workup for sarcoidosis should begin with a thorough history and physical examination, followed by chest imaging and pulmonary function tests, and definitive diagnosis requires histopathological confirmation of non-caseating granulomas, as recommended by the European Respiratory Society guidelines 1. The diagnosis of sarcoidosis is based on a compatible clinical presentation, radiographic findings, and histologic confirmation of noncaseating granulomatous inflammation.
Key Components of the Workup
- Chest imaging such as chest X-ray or high-resolution CT scan to assess for bilateral hilar lymphadenopathy or pulmonary infiltrates
- Pulmonary function tests to evaluate lung function
- Laboratory tests including complete blood count, comprehensive metabolic panel, serum calcium, angiotensin-converting enzyme (ACE) levels, and inflammatory markers like erythrocyte sedimentation rate
- Histopathological confirmation of non-caseating granulomas through bronchoscopy with transbronchial biopsy, mediastinoscopy, or biopsy of accessible affected organs
- Additional specialized testing such as bronchoalveolar lavage, gallium-67 scan, or PET scan to assess disease activity and distribution
- Ophthalmologic examination to detect ocular involvement
- Cardiac evaluation with ECG and echocardiogram if cardiac sarcoidosis is suspected Some key findings in sarcoidosis include:
- Non-caseating granulomas on histopathology
- Elevated ACE levels in 60-80% of patients
- Hypercalcemia or hypercalciuria in 10-20%
- Organ-specific manifestations such as erythema nodosum, uveitis, peripheral lymphadenopathy, or neurological symptoms depending on the organs involved The workup should be tailored to the patient's presenting symptoms and suspected organ involvement, as outlined in the American Thoracic Society clinical practice guideline 1.
Specialized Testing
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive modality that can be used for the diagnosis of sarcoidosis, with a pooled diagnostic accuracy of 79.1% 1. The use of EBUS-TBNA is recommended for diagnosis in patients with suspected sarcoidosis with mediastinal and/or hilar adenopathy, and conventional bronchoscopic techniques such as transbronchial lung biopsy (TBLB) and endobronchial biopsy (EBB) can enhance the yield of EBUS-TBNA in selected patients.
From the Research
Work-up and Findings Associated with Sarcoidosis
- Sarcoidosis is a systemic granulomatous disease with heterogeneous clinical manifestations, requiring a multidisciplinary approach for diagnosis and management 2.
- The diagnosis of sarcoidosis is most secure when supported by a tissue biopsy exhibiting noncaseating epithelioid granulomas with absence of known granulomagenic agents in a patient with multi-organ disease 3.
- A diagnosis of sarcoidosis should be suspected in any young or middle-aged adult presenting with unexplained cough, shortness of breath, or constitutional symptoms, especially among blacks or Scandinavians 4.
- Diagnosis relies on three criteria:
- a compatible clinical and radiologic presentation
- pathologic evidence of noncaseating granulomas
- exclusion of other diseases with similar findings, such as infections or malignancy 4
- Cutaneous involvement in sarcoidosis is classified as specific, when biopsy reveals non-caseating granulomas, and non-specific, typically erythema nodosum, with granulomatous skin lesions occurring in 9% to 37% of patients 5.
- Sarcoidosis usually presents with persistent dry cough, eye and skin manifestations, weight loss, fatigue, night sweats, and erythema nodosum, with diagnosis difficult due to nonspecific symptoms and only verified following histopathological examination 6.
Diagnostic Biopsy Sites
- The choice for biopsy is influenced by the presenting clinical constellation of organ involvement and the ease and safety of the biopsy procedure 3.
- Seven hundred and seventy-six diagnostic biopsies were performed, with 567 being intrathoracic and 198 extrathoracic, and 23 different organs yielded diagnostic biopsies 3.
- When cutaneous sarcoidosis or an enlarged extrathoracic lymph node is present, skin or lymph node biopsy is the preferred procedure 3.
Prognosis and Treatment
- Prognosis is variable and depends on epidemiologic factors, mode of onset, initial clinical course, and specific organ involvement 4.
- The optimal treatment for sarcoidosis remains unclear, but corticosteroid therapy has been the mainstay of therapy for those with significantly symptomatic or progressive pulmonary disease or serious extrapulmonary disease 4.
- Refractory or complex cases may require immunosuppressive therapy, and despite aggressive treatment, some patients may develop life-threatening pulmonary, cardiac, or neurologic complications from severe, progressive disease 4.