Lymphopaenia may indicate sarcoidosis in uveitis

Lymphopaenia can help non-invasively diagnose sarcoidosis-associated uveitis, researchers say.

In a retrospective analysis, the researchers, from Erasmus University in the Netherlands, found a strong association between lymphopaenia and sarcoidosis in patients with first uveitis attacks.

They published the findings in the British Journal of Ophthalmology.

Sarcoidosis often involves the eyes, usually manifesting as uveitis. The gold standard of diagnosis, ocular histology, is difficult, and uveitis may precede extraocular manifestations of sarcoidosis.

Chest radiography and serum biomarkers, such as angiotensin-converting enzyme (ACE) and lysozyme, meet the Workshop on Ocular Sarcoidosis criteria. But they have limited positive predictive value.

T-lymphocytes in sarcoidosis skew from the peripheral blood to the affected tissue, causing a relative lymphopaenia.

Soluble interleukin 2 receptor (sIL-2R) reflects activation of T-lymphocytes, and earlier studies suggested its diagnostic value is comparable to ACE.

To investigate the utility of lymphopaenia as a biomarker, the researchers studied 191 patients with new onset of uveitis at Erasmus University Medical Center from January 2011 to 2017.

They originally identified 244 patients with a first episode of uveitis, but excluded 53 with known causes for lymphopaenia, such as immunosuppressive medication, infectious disease or systemic disease.

Two thirds of the patients were white, and two thirds were women. Their mean age at the onset of uveitis was 46.8 years.

Thirty-two patients were diagnosed with sarcoidosis-associated uveitis. Their ages, age at onset of uveitis, gender and ethnicity did not differ significantly from those not diagnosed with sarcoidosis.

However panuveitis was diagnosed in 75% of those with sarcoidosis, compared with 44% of those without. And 81% of those with sarcoidosis had bilateral involvement, compared with 48% of those without.

The researchers calculated that lymphopaenia as a test for sarcoidosis in these patients had a sensitivity (true positive rate) of 75% (95% confidence interval (CI) 60.0-90.0) and a specificity (true negative rate) of 76% (95% CI 70.2-83.3).

By contrast, chest radiography has a sensitivity of 64% and specificity of 91%. SIL-2R has a sensitivity of 81% and a specificity of 64%. ACE has a sensitivity of 30% and a specificity of 85%. Therefore lymphopaenia performs better than normal ACE levels do in ruling out sarcoidosis in the uveitis population.

The negative predictive value for lymphopaenia was 0.938 and the positive predictive value was 0.393. Of the other tests, only chest radiology had a higher positive predictive value: 0.47. And negative predictive values were similar of lower for all of the other tests compared to lymphopaenia. But chest radiology is more invasive and expensive, the researchers pointed out.

For lymphopaenia, the researchers calculated a C-statistic (the area under the receiver operating characteristic (ROC) curve) of 0.792 (0.710-0.874), and a Youden’s index (sensitivity+ specifity−1) of 0.517.

While the researchers used a lymphocyte count cutoff for diagnosis of lymphopaenia of 1.5 x109/L, the cutoff that corresponded to the highest Youden index was 1.47x109/L, with an associated sensitivity of 75% and specificity of 79%.

This differs from a cut-off proposed by earlier researchers of <1.0 x109/L. However this earlier research included patients with second or further episodes of uveitis, while the current study only looked at patients with new onset uveitis, the Erasmus University researchers wrote.

Concluding that lymphopaenia is useful in diagnosing sarcoidosis in uveitis, they reason that combining various tests, including lymphopaenia, sIL-2R and chest radiology is worth investigating.

Likewise, they reason that future research should look at the value of combining these laboratory tests and imaging with features, such as panuveitis and bilateral involvement.