Juvenile-onset mixed connective tissue disease: A multicenter retrospective cohort study

Semin Arthritis Rheum. 2026 Feb:76:152889. doi: 10.1016/j.semarthrit.2025.152889. Epub 2025 Dec 11.

Abstract

Objectives: Juvenile-onset mixed connective tissue disease (jMCTD) accounts for 7-23 % of MCTD cases but remains poorly described. We aimed to characterize clinical features, treatments, and outcomes of patients with jMCTD, and compare them to adult-onset MCTD (aMCTD) patients.

Methods: We conducted a multicenter, retrospective, case-control study within the French MCTD cohort. Each jMCTD patient was compared to 3 matched aMCTD patients.

Results: Forty-seven jMCTD patients (93.6 % girls; median age at onset 14 [11-16] years) were included. Forty-four (93.6 %) jMCTD patients fulfilled either Sharp or Kasukawa diagnostic criteria. None of them met other diagnostic criteria without fulfilling Sharp or Kasukawa criteria. At diagnosis, jMCTD patients' main manifestations were Raynaud's phenomenon, arthralgia, and myalgia. jMCTD patients had less frequently puffy fingers than aMCTD (p < 0.0001). Cumulatively, jMCTD patients mainly received glucocorticoids (80.9 %), hydroxychloroquine (95.7 %) and immunosuppressants (93.6 %). They received a higher initial dose of glucocorticoids (30 [20-60] mg/day vs. 15 [10-35] mg/day, p = 0.02), and significantly more frequently methotrexate (Methotrexate) and rituximab (p = 0.01) over time compared to aMCTD. After a median follow-up of 9.8 [6.6-16.2] years, 29 (61.7 %) jMCTD patients were in remission (vs. 62 (44.0 %) aMCTD; p < 0.05), 36 % had progressed to another CTD (vs. 30.5 % aMCTD; p = 0.5), mainly systemic lupus erythematosus, 11 (23.4 %) had developed interstitial lung disease, 2 (4.3 %) pulmonary arterial hypertension, and 1 (2.1 %) died.

Conclusions: jMCTD share the same clinical characteristics as aMCTD patients, but less frequently have puffy fingers. Outcomes appear more favorable in jMCTD than aMCTD, with higher remission rates, albeit at the cost of more intensive treatment.

Keywords: Adult onset; Classification; Juvenile onset; Mixed connective tissue disease; Outcome; Prognosis; Sharp syndrome; Treatments.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Antirheumatic Agents / therapeutic use
  • Case-Control Studies
  • Child
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Mixed Connective Tissue Disease* / diagnosis
  • Mixed Connective Tissue Disease* / drug therapy
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Glucocorticoids
  • Immunosuppressive Agents
  • Antirheumatic Agents
  • Hydroxychloroquine