IgG4-Related Skin Disease in a 9-Year-Old Patient: Remission Under Mycophenolate Mofetil After Rituximab Failure

Background IgG4 related disease (IgG4-RD) is a systemic immune-mediated disease characterized by inflammation and fibrosis of nearly any organ.[1] This condition is rarely reported in children and especially with cutaneous involvement. We report the case of IgG4 related disease in a young girl with an initial orbital presentation, which evolved with an isolated multicentric skin presentation. Remission was not achieved with rituximab therapy, but patient remains disease free after 2 years of mycophenolate mofetil (MMF) monotherapy.

Case Report A 9-year-old girl was referred to our Tertiary Center for painless unilateral swollen upper eyelids, progressing for 5 months. Personal history was negative. Imagery confirmed a well-defined heterogeneous mass of the upper orbit. Initial workup showed elevated inflammatory markers, normal IgG4, absence of antinuclear and slightly positive p-ANCA antibodies (MPO). Histopathological examination of the orbital biopsy revealed IgG4-positive plasma cell infiltration, confirming the diagnosis of IgG4-RD. Remission was rapidly achieved with oral steroids (initially 1 mg/kg/day) with a 5 month-tapering. Few months later, the patient presented with subcutaneous asymptomatic lesions on her left thigh, initially diagnosed as post-traumatic hematoma. Persistence and the emergence of a second lesion on the thorax raise the suspicion of infiltrative tumor. On 18F-FDG PET/CT, 2 other lesions on the right thigh and the right buttock were revealed. Skin biopsy confirmed IgG4-RD relapse. Complementary workup showed serological positivity of IgG4 (3.15 g/L). Rituximab was started with initial remission during the first year. Relapses occurred with recurrent skin infiltration following each viral episode, even with a second cure of rituximab. Given the lack of response to rituximab, treatment was switched to MMF (2000 mg/m²/day) with a complete remission (and negative PET/CT).

Conclusion This case highlights the importance of considering atypical forms of IgG4-RD, especially in pediatric populations, which can lead to misdiagnosis. As far as we know, this case is the fifth one describing cutaneous involvement in pediatric patients. The treatment remains challenging. Corticosteroids and B cell-targeted therapies are the cornerstones of treatment.[1] Rituximab has been considered a first-line therapy in IgG4-RD, particularly for patients with severe or refractory disease. However, for some patients, alternative therapies are sometimes needed.[2] MMF is an alternative effective steroid sparing agent with more positive evidence for the latter.[3]

References [1.] Stone J. Rheumatology 2025;64:i24-i27. [2.] Sapountzi E. Children 2025;12:213. [3.] Karim F. Pediatric Rheumatology 2016;14:18.