mycophenolic-acid and Synovitis

Disabling pansclerotic morphea of childhood (DPMC) is a rare subtype of juvenile localized scleroderma (JLS) characterized by pansclerosis mainly affecting children under the age of 14. This aggressive disease has a poor prognosis due to the rapid progression of deep musculoskeletal atrophy resulting in cutaneous ulceration and severe joint contractures. We describe the challenges in treating a previously well 5-year-old male who has refractory symptoms of DPMC. Over the 29 months, since his initial presentation, we trialed over ten therapies. There was subjective improvement with prednisolone and mycophenolate mofetil (MMF). However, other therapies including biologics and tyrosine kinase inhibitors (TKI) were ineffective. The patient has been referred for hematopoietic stem cell transplant given ongoing disease progression. We conducted a literature search focusing on English articles with keywords including DPMC. Publications with limited information or describing cases aged 20 and above were excluded. Thirty-seven case reports were identified and the reported treatments were evaluated. Methotrexate and corticosteroids have been the most commonly utilized. MMF has been anecdotally effective. Biologics, TKI, and Janus kinase inhibitors lack evidence in DPMC, but have had demonstrated efficacy in similar pathologies including systemic sclerosis, and, thus, have been used for DPMC. Phototherapy has been documented to be reducing skin thickness and stiffness of plaques. Eventually, most children require multi-modal and high-dose immunosuppressive therapies to reduce the inflammation inflicted by the disease. Long-term antibiotics and nutritional support are important in the ongoing care of these patients.

Topics: Antirheumatic Agents; Biological Products; Biopsy; Child, Preschool; Contracture; Edema; Hematopoietic Stem Cell Transplantation; Humans; Hydroxychloroquine; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Janus Kinase Inhibitors; Male; Methylprednisolone; Mycophenolic Acid; Prednisolone; Protein Kinase Inhibitors; Scleroderma, Localized; Scleroderma, Systemic; Skin; Synovitis; Treatment Failure; Treatment Outcome

To determine whether patients with juvenile systemic granulomatous disease (JSGD) (Blau syndrome) and uveitis have a characteristic ocular phenotype.. Clinical and imaging data were collected retrospectively from patients attending the Regional Combined Paediatric Rheumatology and Ocular Inflammatory Service, Bristol Eye Hospital. General demographic information, laterality of the uveitis, age at onset, anatomical classification and course of the uveitis, clinical phenotype and specific NOD2 mutation were recorded for each patient.. Seventeen eyes from nine patients (five males; four females) were included in the study. Mean age at the disease onset was 15 months, range 1-84 months. Eight patients had bilateral uveitis. Anterior uveitis was present in five eyes, intermediate uveitis in two eyes, and there were 10 eyes with panuveitis, manifesting as multifocal choroiditis. Appearance of optic disc included indistinct disc margins in six eyes, optic nerve head pallor in six eyes, optic disc vessel sheathing in four eyes, and there was peripapillary hypo/hyperpigmentation in 13 eyes accompanied with characteristic peripapillary nodular excrescences. Among NOD2 mutations, the p.R334W was the most commonly detected (n: four cases), and three patients carried novel variants, the p.E338D and p.D390V variants in one patient, and the p.H520Y and p.Q809K variants in two different patients.. Chronic bilateral panuveitis and a nodular peripapillary appearance in childhood onset uveitis are characteristic features of JSGD, which support the need for an appropriate genetic NOD2 analysis.

Topics: Age of Onset; Arthritis; Child, Preschool; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Infant; Male; Methotrexate; Mutation; Mycophenolic Acid; Nod2 Signaling Adaptor Protein; Optic Nerve; Phenotype; Prednisolone; Retina; Retrospective Studies; Sarcoidosis; Synovitis; Uveitis; Visual Acuity

Topics: Arthritis, Rheumatoid; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Mycophenolic Acid; Polymyositis; Quality of Life; Scleroderma, Systemic; Synovitis; Treatment Outcome