Early blood parameters for detecting sarcoidosis

Most people with sarcoidosis have probably experienced fatigue, joint pain, chest pain or shortness of breath among their early symptoms.

Your doctor first referred you for laboratory blood tests, and then the long search for the correct diagnosis began.

In addition to an elevated C-reactive protein (CRP), caused by the inflammatory process, other abnormal parameters may also appear.

An elevated CRP is a liver acute-phase protein released in response to inflammatory cytokines. However, it is nonspecific because it may indicate infections, tumours, rheumatism, inflammation and other conditions.

Let us assume that the more acute the condition, the higher the CRP value is likely to be.

In sarcoidosis, abnormalities may be found in creatinine, alkaline phosphatase and calcium. Significant changes in liver-function tests are an indication for specialist assessment.

After these basic tests, further serological and histopathological analyses may follow, together with X-ray, CT, MRI and biopsies (of lymph nodes, skin, bone marrow and other tissue). After diagnosis, ACE, 24-hour urinary calcium (the normal blood-calcium range is 8.6–10.3 mg/dL), CRP, liver values and TNF-α are often monitored, together with pulmonary testing such as DLCO, an ophthalmology examination and other assessments depending on the type of sarcoidosis.

Read the article about the key tests for the initial diagnosis of sarcoidosis.

Dino-Josip Ključarić

Key Tests for the Diagnosis and Management of Sarcoidosis

Guideline focus: a quartet of laboratory tests important for detecting kidney, liver and haematological involvement and for assessing calcium metabolism.

To identify manifestations of sarcoidosis, the American Thoracic Society (ATS) recommends four key laboratory tests to screen for renal sarcoidosis, abnormal calcium metabolism, hepatic sarcoidosis and haematological abnormalities.

Sarcoidosis often affects the lungs or intrathoracic lymph nodes, “but otherwise has unpredictable clinical features. Sarcoidosis treatment is not well established,” Elliott Crouser, MD, director of the specialised sarcoidosis clinic at The Ohio State University Wexner Medical Center and lead co-author of the guideline, told CLN Stat. Sarcoidosis is a diagnosis of exclusion and requires laboratory tests such as histopathological samples, tissue cultures and serological tests. The diagnosis is based on three main criteria: a compatible clinical presentation, non-necrotising granulomatous inflammation in one or more tissue samples, and exclusion of alternative causes of granulomatous disease.

The ATS clinical-practice guideline calls for imaging and laboratory testing—calcium, creatinine, alkaline phosphatase (ALP) and a complete blood count (CBC)—to detect organ involvement, Crouser said. He and his colleagues conducted systematic reviews and meta-analyses to develop their recommendations. Ten of the questions concerned diagnostic testing.

One question addressed screening patients with sarcoidosis who have no renal symptoms. The guideline authors suggest that clinicians use a basic serum-creatinine test to screen for renal sarcoidosis in patients without symptoms or established renal sarcoidosis. “We considered kidney involvement in sarcoidosis to be frequently asymptomatic at the time of diagnosis and potentially serious but treatable,” Crouser explained.

For patients with sarcoidosis who have no liver symptoms or established hepatic sarcoidosis, the guideline recommends basic serum ALP testing to screen for hepatic sarcoidosis. Because of insufficient evidence, the panel made no recommendation for routine serum-transaminase testing in this population. “We decided to provide a recommendation based on low-quality evidence because it is important to identify sarcoidosis involving the liver, given the risk of cirrhosis and because many treatments commonly used for sarcoidosis can adversely affect the liver,” Crouser said. Published evidence shows that liver-function tests (LFTs) are often abnormal, leading to treatment changes.

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

Calcium metabolism is abnormal in approximately 16% of patients with sarcoidosis. If untreated, this can lead to complications such as kidney stones or acute or chronic kidney disease. “Therefore, screening for calcium metabolism is strongly recommended,” Crouser said. The panel suggested basic serum-calcium testing to screen for abnormal calcium metabolism in patients without signs of hypercalcaemia. He noted that 24-hour urinary-calcium testing is the most accurate approach, but it is also more expensive, time-consuming, inconvenient and less reproducible. “Serum calcium is readily available in most clinical laboratories, and most of the data underlying the guideline recommendations came from studies using serum calcium as a screening tool,” Crouser added.

The panel also suggested that clinicians use a basic complete blood count (CBC) to detect haematological abnormalities. Anaemia is common in sarcoidosis and often reflects granulomatous involvement of the bone marrow. It can also contribute to dyspnoea, Crouser said. Leukopenia, and especially lymphopenia, are also common and reflect active sarcoidosis. In rare cases, thrombocytopenia can occur. “Thus, CBC testing identifies the two most common haematological findings relevant to the disease—anaemia and leukopenia—and is useful for clinical purposes, including assessment of dyspnoea, disease activity and screening for bone-marrow involvement,” he said.

Most recommendations were based on low-quality evidence, highlighting the need for stronger research to guide clinicians. “Clinicians are therefore encouraged to apply the recommendations within the clinical context of each individual patient,” the authors suggest.

Source: https://www.aacc.org/cln/cln-stat/2020/may/21/key-tests-for-sarcoidosis-diagnosis-and-management

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