What are the diagnostic criteria for sarcoidosis (a systemic granulomatous disease)?

From the Guidelines

Diagnosing sarcoidosis requires a comprehensive approach involving multiple tests, including clinical evaluation, chest X-ray, pulmonary function tests, and histological confirmation through tissue biopsy showing non-caseating granulomas, as recommended by the American Thoracic Society clinical practice guideline 1. The diagnosis typically begins with a thorough clinical evaluation to assess symptoms and physical findings, followed by imaging tests such as chest X-ray and high-resolution CT scans to evaluate lung involvement, which occurs in over 90% of cases.

• A definitive diagnosis requires histological confirmation through tissue biopsy showing non-caseating granulomas, most commonly obtained from the lungs, lymph nodes, or skin lesions.
• Laboratory tests including complete blood count, comprehensive metabolic panel, serum calcium, and angiotensin-converting enzyme (ACE) levels can support the diagnosis, though elevated ACE is not specific to sarcoidosis 1.
• Additional testing may include bronchoscopy with bronchoalveolar lavage showing lymphocytosis with elevated CD4/CD8 ratio, and specialized tests like gallium-67 scans or PET scans to identify active inflammation sites.
• Ophthalmologic examination, cardiac testing, and neurological evaluation may be necessary depending on suspected organ involvement, as sarcoidosis can affect multiple organs and systems 1. The diagnosis ultimately requires excluding other granulomatous diseases such as tuberculosis, fungal infections, and malignancies, making it essentially a diagnosis of exclusion that combines clinical presentation, radiographic findings, and histopathological evidence while ruling out alternative causes 1.
• The European Respiratory Society clinical practice guidelines on treatment of sarcoidosis also emphasize the importance of a comprehensive diagnostic approach, including the use of cardiac MRI or positron emission tomography with fluorodeoxyglucose imaging to diagnose cardiac sarcoidosis or follow response to therapy 1.
• The guidelines also recommend considering the risk for death or organ failure and impairment of quality of life when deciding who and when to treat an individual sarcoidosis patient 1.
• Recent studies have identified features associated with increased risk for death from pulmonary disease, including pulmonary hypertension, reduced lung function, and pulmonary fibrosis, highlighting the need for early and accurate diagnosis and treatment 1.

From the Research

Diagnosing Sarcoidosis

• The diagnosis of sarcoidosis is made by the combination of clinical features and biopsy results, as stated in the study 2.
• Clinical features of sarcoidosis can be quite variable, but certain features such as multiorgan involvement can enhance diagnostic certainty 2.
• A Sarcoidosis Diagnostic Score (SDS) has been developed to summarize the clinical features of patients with possible sarcoidosis, with a sensitivity of 90.6% and specificity of 88.5% for an SDS clinical score ≥ 3 2.

Clinical Presentation

• Sarcoidosis is a multi-system disease that can affect any organ, with intrathoracic involvement occurring in 90% of patients 3.
• Common clinical features include respiratory symptoms, fatigue, skin lesions, uveitis, liver or splenic involvement, and peripheral arthritis 3.
• Certain clinical features, such as Löfgren's syndrome, lupus pernio, and Heerfordt's syndrome, are considered highly specific for the disease and do not require histological confirmation 3, 4.

Diagnostic Approach

• There is no gold standard diagnostic test or algorithm for sarcoidosis, and the diagnosis is based on a compatible clinical presentation, histologic findings, exclusion of alternative diseases, and evidence of systemic involvement 5.
• Histological confirmation is typically required, but may not be needed for certain clinical features such as Löfgren's or Heerfordt's syndrome 4.
• Diagnostic tests such as serum angiotensin-converting enzyme (ACE) levels, 67gallium scans, chest x-ray films, and pulmonary function tests may be used to support the diagnosis and monitor disease progression 6.

Diagnostic Criteria

• The diagnosis of sarcoidosis requires a compatible clinical and/or radiological presentation, histological evidence of non-necrotizing granulomatous inflammation, and exclusion of alternative causes of granulomatous disease 3, 5.
• Specific clinical criteria have been developed for the diagnosis of cardiac, neurological, and ocular sarcoidosis 3.