To identify the manifestations of sarcoidosis, the American Thoracic Society (ATS) is recommending four key lab tests to screen for renal sarcoidosis, abnormal calcium metabolism, hepatic sarcoidosis, and hematological abnormalities.

Sarcoidosis often involves the lungs or chest lymph nodes, “but otherwise has unpredictable clinical features. The management of sarcoidosis is not well established,” Elliott Crouser, MD, director of the Sarcoidosis Specialty Clinic at The Ohio State University Wexner Medical Center and lead co-author of the guidelines, told CLN Stat. It’s a diagnosis by exclusion, requiring lab tests such as histopathology specimens, tissue cultures, and serology tests. Diagnosis is based on three major criteria: a compatible clinical presentation, finding non-necrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease.

The ATS clinical practice guideline calls for testing approaches such as imaging and lab tests (calcium, creatinine, alkaline phosphatase (ALP), and complete blood count) to detect organ involvement, Crouser said. He and his colleagues conducted systematic reviews and meta-analyses to arrive at their recommendations. Among these, 10 questions addressed diagnostic testing.

One question tackled the matter of screening sarcoidosis patients with no renal symptoms. Guideline authors suggested that clinicians use a baseline serum creatinine test to screen for renal sarcoidosis in patients without symptoms or established renal sarcoidosis. “We felt that renal involvement in sarcoidosis is often asymptomatic at the time of sarcoidosis diagnosis and is a potentially serious condition that is treatable,” Crouser explained.

For patients with sarcoidosis with neither hepatic symptoms nor established hepatic sarcoidosis, the guideline recommends baseline serum ALP testing to screen for hepatic sarcoidosis. Due to insufficient evidence, the panelists held off on any recommendation for baseline serum transaminase testing in this population. “We opted to provide a recommendation based on low-quality evidence because it is important to identify sarcoidosis involving the liver due to the risk of developing cirrhosis, and because many of the treatments commonly used to treat sarcoidosis can adversely affect the liver,” Crouser said. Published evidence showed that liver function tests (LFTs) are often abnormal, leading to a change in therapy.

Among the LFTs, ALP was most often abnormal. The panelists concluded that adding transaminase testing would not further improve case detection.

Calcium metabolism is abnormal in approximately 16% of sarcoidosis patients. If untreated, it can lead to complications such as kidney stones or acute or chronic renal disease. “Thus, screening for calcium metabolism was highly recommended,” Crouser said. The panel suggested baseline serum calcium testing to screen for abnormal calcium metabolism in patients with no signs of hypercalcemia. He noted that 24-hour urine calcium testing is the most accurate approach, but also more expensive, time consuming, less convenient, and less reproducible. “Serum calcium is easily obtained in most clinical laboratories, and most of the data upon which the guideline recommendations are based were derived from studies that used serum calcium as the screening tool,” added Crouser.

If a patient needs a vitamin D metabolism assessment, clinicians should measure both 25-hydroxyvitamin D and 1,25 dihydroxyvitamin D levels to determine the necessity of vitamin D replacement.

The panelists also suggested that clinicians use baseline complete blood cell count (CBC) testing to screen for hematological abnormalities. Anemia is common in sarcoidosis, often reflecting granulomatous bone marrow involvement. It can also contribute to dyspnea symptoms, Crouser said. Leukopenia and particularly lymphopenia are also common and reflect active sarcoidosis. In rare instances, thrombocytopenia can occur in sarcoidosis. “Thus, CBC testing detects the two most common disease-relevant hematological findings, anemia and leukopenia, and is useful for clinical purposes including the assessment of dyspnea, disease activity, and to screen for bone marrow involvement,” he said.

Most of the recommendations were based on poor-quality evidence, underscoring a need to improve research efforts to guide clinicians. “Thus, clinicians are encouraged to apply the recommendations within the clinical context of each individual patient,” the authors suggested.