Case Report Suggests Disease Hallmarks for Diagnosing Early-onset Sarcoidosis

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by Magdalena Kegel |

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Diagnosing early-onset sarcoidosis

Researchers examining an infant born with a rare mutation that causes early-onset sarcoidosis demonstrated that a skin rash and persistent fever are typical disease features that could help in making an early diagnosis of the condition.

Based on an analyses of the infant’s immune responses, the team also suggested that low levels of the cytokine interleukin-1beta (IL-1beta) may be an additional feature.

Since physicians had missed the presence of granulomas in a skin biopsy during earlier examinations, the research team also urged physicians to more strongly consider the possibility that a skin rash in infants may be caused by early-onset sarcoidosis.

The study, “Early diagnosis of early-onset sarcoidosis: a case report with functional analysis and review of the literature,” was published in the journal Clinical Rheumatology.

The 9-month-old girl came to the attention of physicians at the Shinshu University School of Medicine in Japan because of prolonged fever and a skin rash, which she started developing five months earlier.

Doctors had tried to lower her fever with a variety of treatments, but unfortunately without success. Extensive tests did not find signs of infection and a chest scan was normal, although she had clear signs of inflammation.

Although physicians at another hospital had reported that a skin biopsy of the child was normal, an analysis of a larger skin lesion revealed granulomas of the type seen in sarcoidosis. Re-assessing the tissue examined earlier revealed that so-called non-caseating granulomas were indeed present in the tissue, but had been missed by the physicians.

Since early-onset sarcoidosis is identical to a disease caused by mutations in the NOD2 gene, physicians started genetic testing. They found a rare mutation in both copies of the gene (the M513T mutation), supporting the diagnosis of early-onset sarcoidosis.

But to better understand the disease processes and identify factors that may be used to support an early diagnosis in similar cases, the team did an extensive analysis, examining the production of cytokines and inflammatory pathways.

They found that the baby’s levels of IL-1beta were lower than normal. In addition, researchers found that NF-kappaB — a factor that activates a broad range of inflammatory processes — was abnormally active.

The team then searched scientific articles published between 1981 and 2016 in search of further clues of characteristic features that may aid a diagnosis.

Earlier studies showed that the skin rash was present in all children previously described with a diagnosis of early-onset sarcoidosis, and half of them also had a persistent fever. Eye problems were also found to be common in patients with this condition.

The team concluded that “skin rash with granuloma formation in infants with persistent inflammation represents a possible hallmark for the early diagnosis of EOS [early-onset sarcoidosis]. Greater understanding of the influence of the M513T mutation will contribute to improved diagnosis and treatments for EOS.”