PO:30:151 | Clinical characteristics and evolution of juvenile undifferentiated connective tissue diseases: results of a single-center study

Nicoletta D'Angelo^1|2, Stefania Costi³, Achille Marino³, Francesco Baldo³, Cecilia Beatrice Chighizola^1|3, Roberto Felice Caporali^1|2|3. | ¹Università degli Studi di Milano, Dipartimento di Scienze Cliniche e di Comunità, Milano, Italy; ²ASST G. Pini-CTO, UOC di Clinica Reumatologica, Milano, Italy; ³ASST G. Pini-CTO, UOC di Clinica Reumatologica Pediatrica, Milano, Italy

Background. Juvenile undifferentiated connective tissue diseases (UCTD) represent a heterogeneous clinical entity characterized by symptoms suggestive of connective tissue disease without meeting the classification criteria. Currently, epidemiological and prognostic knowledge about the pediatric population is limited, with implications for clinical and therapeutic management. The aim of our work is to describe the clinical and serological characteristics of a single-center cohort of patients with juvenile UCTD, evaluating the clinical course and potential evolution toward defined connective tissue diseases.

Materials and Methods. We conducted a retrospective study on 33 patients diagnosed with juvenile UCTD who were followed at our center from 2006 to 2025. Inclusion criteria: age 16 years or less at onset, disease duration of at least 12 months, at least one clinical sign suggestive of connective tissue disease, and positivity in at least two ANA or ENA tests. Demographic, clinical, serological, capillaroscopic, and therapeutic data were collected.

Results. The demographic and clinical characteristics are shown in Table 1. All patients tested positive for ANA. In 7 patients, ANA negativity was observed at a mean follow-up of 12 months, associated with lower ESR values (p<0.01) and a reduced presence of other antibodies (ENA, aPL, anti-dsDNA) (p=0.003). 3 of these patients had a scleroderma pattern at baseline; In one case, the pattern remained stable, in another it regressed to a borderline pattern, and in the third to non-specific abnormalities. During a median follow-up of 36 months (18-49 months), 5 patients (15.2%) progressed to defined connective tissue disease: 2 cases of SS, 1 case of SLE, 1 case of Sjögren's syndrome, and 1 case of anti-Jo1+ myositis. These patients had an earlier onset age (12 years vs 14.5 years), were positive for ENA, anti-dsDNA, or aPL in 4 out of 5 cases, and showed capillaroscopy alterations in 3 cases (2 scleroderma patterns and 1 non-specific abnormalities). Hydroxychloroquine was used in 22 patients, with all showing at least a 50% improvement in symptoms, and only one experiencing a mild side effect (headache). Other therapies used were: corticosteroids (8 patients), methotrexate (6), calcium channel blockers (5), and topical vasodilators (8).

Conclusions. We observed a high prevalence of skin manifestations, Raynaud's phenomenon, and inflammatory arthralgia. 15.2% of cases developed a defined connective tissue disease, confirming the risk of progression. Capillaroscopic anomalies, a young age of onset, and the presence of other antibodies beside ANA could be associated with a higher risk of progression. Patients with isolated ANA positivity showed a generally favorable course, higher rates of negativity, and improvements in capillaroscopy in most cases. Hydroxychloroquine has been shown to be well-tolerated and potentially useful. Prospective studies are needed to validate these results and identify patients at risk of progression early on.