Children diagnosed with Sjögren's disease may exhibit two distinct patterns that persist into adulthood—one characterized by high disease activity and symptom burden, the other by low activity and symptoms. Further, 13% of these patients developed lymphoma over time, according to a retrospective-prospective cohort study that followed 30 patients for up to 25 years.
The study, conducted at University College London Hospital's adolescent and young adult rheumatology service, represents the first long-term evaluation of childhood-onset Sjögren's disease with trajectory analysis that followed patients into adulthood. Between March 1, 2020, and June 30, 2024, researchers identified patients who were a mean age of 13 years at onset and were diagnosed with childhood-onset Sjögren's disease based on expert opinion.
Latent class growth analysis revealed two European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) trajectories: high activity (mean of approximately 4, n = 12) vs low activity (mean of about 1, n = 18). "These trajectories were not characterized by differences in sex, age, disease duration, length of follow-up, autoantibodies or medications," wrote lead study author Coziana Ciurtin, PhD, of the Centre for Adolescent Rheumatology, University College London, and colleagues. "This finding suggests possible underlying distinct molecular mechanisms driving the two phenotypes."
Among 22 patients with sufficient data, researchers also identified distinct symptom trajectories using the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI): high symptom burden (mean of approximately 6, n = 15) vs low symptom burden (mean of about 3, n = 7). Notably, only 6 patients (27%) showed concordance between high disease activity and high symptom burden. Nine patients (41%) had low activity but high symptoms, which highlighted a disconnect between objective disease measures and subjective symptom impact—a challenge similar to that in adult Sjögren's disease. At last assessment, the median ESSDAI score was 2 and the ESSPRI score was 5. Damage accrual (defined as Sjögren's Syndrome Disease Damage Index [SSDDI] score greater than or equal to 1) occurred in 17 patients (57%) and was predominantly glandular, reflecting objective decreases in saliva or tear secretion. Three patients (18% of those with damage) already experienced tooth loss by early adulthood.
The lymphoma rate proved particularly striking. Four patients (13%) developed lymphoma during follow-up: 3 with mucosa-associated lymphoid tissue (MALT) lymphoma and 1 with peripheral T-cell non-Hodgkin lymphoma. Three patients achieved full recovery following radiotherapy or chemotherapy, while one was undergoing treatment at last assessment.
Diagnostic delay emerged as a significant factor. All 9 children diagnosed more than 3 years after symptom onset reported dryness, compared with only 38% (8/21) who were diagnosed within 3 years. This result suggested that dryness develops gradually over time, and early diagnosis may precede classic sicca symptoms.
The cohort's demographic composition included 28 females (93%) and two males (7%). Ethnicity breakdown showed 17 White (57%), 7 Black (23%), and 6 Asian (20%) patients. The most common manifestations at onset were fatigue (22 patients, 73%), arthralgia (21, 70%), dryness (17, 57%), and glandular swelling (15, 50%). Overlap syndromes occurred in 7 patients (23%) with childhood-onset systemic lupus erythematosus and 2 (7%) with juvenile idiopathic arthritis.
Ultrasound examination proved diagnostically valuable and essential. It supported diagnosis in 27 patients (90%) based on Outcome Measures in Rheumatology (OMERACT) scoring. This high reliance on ultrasound may explain why only 12 patients (40%) had diagnostic minor salivary gland biopsies with focus scores greater than or equal to 1: ultrasound findings reduced the need for invasive biopsy in many cases. At diagnosis, 20 patients (74% of those with ultrasounds) had OMERACT score 1, 4 (15%) had score 2, and 3 (11%) had score 3.
Classification criteria performance showed limitations, primarily because many children had not yet developed objective dryness at diagnosis. At diagnosis, only 12 patients (40%) fulfilled 2016 American College of Rheumatology (ACR)-EULAR criteria, 9 (30%) met pediatric diagnostic criteria, and 12 (40%) achieved definite or probable diagnosis by established standards. These proportions increased at last assessment to 20 (67%), 14 (47%), and 19 (63%), respectively, mainly due to development of objective dryness over time.
Treatment strategies reflected expert opinion in the absence of approved therapies. At last assessment, 25 patients (83%) had received hydroxychloroquine, 11 (37%) received azathioprine, 8 (27%) had mycophenolate mofetil, and 7 (23%) received methotrexate. Seven patients received rituximab for severe manifestations including transverse myelitis, optic neuritis, nephritis, refractory glandular disease, and vasculitis. "Treatment with belimumab (for a concomitant diagnosis of childhood-onset SLE with musculoskeletal and mucocutaneous manifestations) or adalimumab or baricitinib (for a concomitant diagnosis of juvenile idiopathic arthritis) was used in one [patient] each (3%)," the researchers noted.
Serological profiles showed 29 patients (97%) were antinuclear antibody positive, 25 (83%) were anti-Ro positive, 12 (40%) were anti-La positive, and 13 (43%) were rheumatoid factor positive. Eight patients (27%) had serum IgG concentrations that exceeded 20 g/L at diagnosis, while 10 (33%) had abnormally elevated IgG based on age-specific reference ranges.
The researchers identified important limitations including small sample size, partial retrospective data collection, single-center design, and incomplete ESSPRI data for 8 patients. They emphasized that damage accrual did not differ significantly based on activity and symptom trajectory.
"This preliminary evaluation of long-term outcomes of childhood-onset Sjögren's disease in adulthood showed distinct patterns of disease and symptom trajectories and that a high proportion of children and young people develop damage in early adulthood," concluded Dr. Ciurtin and colleagues. "These findings highlight the need for improved research quality and evidence-based management strategies for better outcomes in this population." Specifically, the researchers emphasized validation in larger, ethnically and geographically diverse cohorts and called for research into the molecular mechanisms that drive distinct disease phenotypes to enable early, tailored interventions.
Disclosures: Dr. Ciurtin reported a research grant from GSK and speaker honoraria from Novartis. Mr. Wilson reported speaker honoraria from Novartis, and support for attending the 2025 British Society for Rheumatology annual meeting from Medac. All other authors declared no competing interests.
Source: The Lancet Rheumatology