That investigation, now published as a case report and literature review in BMC Pediatrics, describes how an isolated, initially mild but progressive rise in liver enzymes turned out to be the first visible signal of childhood-onset primary Sjögren’s syndrome, a rare autoimmune disease that most clinicians associate with dry eyes and dry mouth rather than hepatic inflammation. The report, authored by Kai Li, Chenling Zhang, Na Zeng, and Mingwu Chen and colleagues at Anhui Provincial Hospital and the University of Science and Technology of China, is a striking reminder that autoimmune diseases in children can announce themselves through organ systems that seem, on the surface, entirely unrelated to their usual targets.

The biochemical details of the case are worth unpacking, because they illustrate why the diagnosis was so elusive. For roughly the first twenty months of the boy’s illness, his alanine aminotransferase, or ALT, and his gamma-glutamyl transferase, or GGT, two of the standard enzymes clinicians use to gauge liver injury, hovered below twice the upper limit of normal. That is a level many guidelines classify as mild, and it is exactly the range in which clinicians often suspect fatty liver, residual viral infection, or simply laboratory noise. His creatine kinase, an enzyme that rises when muscle is damaged, was repeatedly normal, which helped rule out a muscular origin for the enzyme elevations. Abdominal ultrasound showed only mild hepatic steatosis, a fatty change in the liver that could plausibly have absorbed the blame.

The team worked systematically through the usual suspects. Infectious causes were excluded, as was any drug-related injury, and a panel of autoantibodies associated with autoimmune liver disease, including those linked to autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, came back negative. That negativity matters, because autoimmune liver diseases are the standard explanations for unexplained chronic enzyme elevation in a child, and their serological fingerprints were absent. What remained was a slowly smoldering process with no obvious address, the kind of clinical limbo in which patients can drift for years while the underlying disease advances unchecked.

The turning point came when the boy’s immune profile was tested more broadly. He proved strongly positive for anti-SSA, anti-SSB, and anti-Ro52 antibodies, a trio of autoantibodies that serve as hallmark markers of Sjögren’s syndrome, an autoimmune condition in which the body’s exocrine glands, particularly the salivary and lacrimal glands, come under lymphocytic attack. Critically, the boy had no sicca symptoms at all, no dry eyes, no dry mouth, none of the complaints that typically define the disease in adults. A salivary gland biopsy sealed the diagnosis, revealing focal lymphocytic sialadenitis with a focus score of at least one aggregate of immune cells per four square millimeters, the histological threshold used in international classification criteria for the disease.

Childhood-onset primary Sjögren’s syndrome is genuinely rare, and its presentation in children is notoriously heterogeneous. While adults usually present with the glandular dryness that gives the disease its name, children more often show non-specific or extraglandular features, including recurrent parotitis, arthritis, rash, or, as this case demonstrates, laboratory abnormalities in distant organs. Hepatic involvement in pediatric Sjögren’s has been reported only infrequently, and it is especially unusual for liver enzyme elevation to be the very first manifestation, preceding any glandular symptoms by years. The authors reviewed the existing literature to place their case in context, and the picture that emerges is one of a disease that pediatricians rarely have on their differential when the presenting complaint is an abnormal liver panel.

The report is also candid about the limits of what could be proven. Liver biopsy and magnetic resonance cholangiopancreatography, the imaging technique used to visualize the bile ducts, were not performed, which means the precise mechanism of the boy’s liver injury remains incompletely characterized. The authors explicitly note that a causal relationship between the Sjögren’s syndrome and the hepatic abnormalities could not be definitively established, and they recommend continued follow-up to reassess alternative or coexisting diagnoses. This kind of epistemic honesty is important in case reports, where the temptation to draw a clean narrative line between diagnosis and treatment response can outpace the evidence. The mild steatosis seen on ultrasound, for instance, raises the possibility that metabolic factors contributed to the enzyme elevations even if they did not tell the whole story.

Treatment, however, appeared to vindicate the autoimmune hypothesis. The boy received tofacitinib, a Janus kinase inhibitor that blocks intracellular signaling pathways used by immune cells to drive inflammation, along with hydroxychloroquine, an antimalarial drug with immunomodulatory effects that is a mainstay of systemic autoimmune disease therapy, and a short course of diammonium glycyrrhizinate, a licorice-derived compound with anti-inflammatory activity used in China for liver protection. The response was decisive. His liver biochemistry normalized and remained within reference ranges throughout eight months of follow-up, a sustained remission that, while not proof of causation, is difficult to dismiss as coincidence.

The choice of tofacitinib is itself noteworthy. Janus kinase inhibitors have become one of the most closely watched drug classes in immunology, praised for their oral convenience and broad anti-inflammatory reach, and their expanding use in pediatric rheumatology reflects growing confidence in targeted immune modulation. In this case, the combination of a JAK inhibitor with hydroxychloroquine addressed the systemic autoimmune process rather than treating the liver in isolation, a therapeutic philosophy that only becomes available once the correct diagnosis is in hand. Had the boy remained labeled as a fatty liver case, he might never have received immunosuppressive therapy at all.

For clinicians, the practical lesson is that isolated, persistent, slowly progressive liver enzyme elevation in a child, even when mild, deserves a diagnostic strategy that extends beyond hepatology. The authors suggest that when infectious, drug-related, and autoimmune liver causes have been excluded, and especially when the biochemical pattern evolves over months to years, clinicians should consider systemic autoimmune diseases, including Sjögren’s syndrome, even in the complete absence of sicca symptoms. Simple serological tests for anti-SSA, anti-SSB, and anti-Ro52 antibodies are widely available, and a positive result can redirect an entire diagnostic workup. For researchers, the case adds to the small but growing literature on extraglandular manifestations of pediatric Sjögren’s and underscores how much remains unknown about the disease’s hepatic dimension. For families, it is a reminder that a child’s body rarely reads the textbook, and that the answer to one organ’s quiet distress may lie in an immune system attacking somewhere no one thought to look.

Subject of Research: Childhood-onset primary Sjögren's syndrome presenting as isolated progressive liver enzyme elevation

Article Title: The diagnostic dilemma of isolated, initially mild but progressive liver enzyme elevation as an initial manifestation of childhood-onset primary Sjögren’s syndrome: a case report and literature review

Article References: Li, K., Zhang, C., Zeng, N., & Chen, M. (2026). The diagnostic dilemma of isolated, initially mild but progressive liver enzyme elevation as an initial manifestation of childhood-onset primary Sjögren’s syndrome: a case report and literature review. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07734-1

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07734-1

Keywords: Sjögren's syndrome, pediatrics, liver enzymes, autoimmune disease, hepatic involvement, anti-SSA antibodies, tofacitinib, case report, JAK inhibitor, childhood-onset, autoimmune hepatitis, liver biopsy