Juvenile eosinophilic fasciitis: a single center case series

There were six patients within our juvenile EF cohort (Table 1). The majority were female (83%). Patients identified as non-Hispanic white (50%), Hispanic white (33%), and non-Hispanic black (17%). The median age at initial presentation was 13 years (range 4–16 years). Patient 6 had a mild preceding COVID-19 infection. Otherwise, no specific triggers, such as direct injury, intense exercise, other infections, associated medications, or neoplasms, were identified.

The median duration of symptoms before diagnosis was nine months (range 1–12 months). Most patients presented with bilateral, progressive painful swelling, induration, and thickening of the skin, leading to severe joint limitation. Patient 6 had unilateral involvement. All patients presented with a positive prayer sign (Fig. 1). The groove sign, a linear depression overlying veins with an elevated extremity, was not observed in any patients. Peau d’orange was noted in patient 1.

Common laboratory features included elevated peripheral eosinophilia (100%), immunoglobulin G (IgG) (83%), aldolase (67%), and ESR (67%). All patients had an anti-nuclear antibody (ANA) panel available at diagnosis; four patients had a positive ANA (titers range: 1:80–1:1280) without any extractable nuclear antigen antibodies. Five out of the six patients had rheumatoid factor evaluated and tested negative. Patient 6 with acquired hemophilia A had normal prothrombin time, elevated partial thromboplastin time (82.3 s, reference: 23.1–36.3 s), decreased factor 8 level (< 1, reference: 50–150%), and presence of factor 8 inhibitor. All the patients had an MRI consistent with fasciitis (Fig. 2).

H & E sections revealed inflammation that preferentially involved the fascia extending to the perimysium and fascial thickening (Fig. 3). In one case, there was focal destruction of myofibers. The intensity of inflammation ranged from mild to severe. Inflammatory infiltrates were composed of lymphocytes, plasma cells, and macrophages. Eosinophils were identified in four cases.

All patients received systemic corticosteroids and methotrexate. Other immunomodulatory medications were administered depending on the patient’s course, including hydroxychloroquine (n = 4), intravenous immunoglobulin (IVIG) (n = 3), tocilizumab (n = 2), rituximab (n = 2), and mycophenolate mofetil (n = 1).

Patient 1 was diagnosed at age 14 years and whose treatment included a course of IV steroids, methotrexate and hydroxychloroquine. His treatment was interrupted by periods of nonadherence, and approximately two years after his EF diagnosis, he had new generalized LS lesions. Oral methotrexate 25 mg weekly and hydroxychloroquine 400 mg daily were continued. Given the stability of his condition, he was transitioned to adult care and medications were discontinued. Throughout his pediatric rheumatology care, there was no recurrence of EF.

Patient 2 was diagnosed at the age of four years with a morphea and relapsing and remitting course of EF requiring intermittent corticosteroids (IV methylprednisolone), methotrexate (15 mg/m²/weekly subcutaneous (SQ) injections), hydroxychloroquine (3 mg/kg/day), and IVIG (2 g/kg monthly). She had remission of both morphea and EF leading to a gradual taper of medications. At age 13, she developed JIA, involving bilateral shoulder and temporomandibular joints; MRI without and with contrast showed chronic inflammatory arthritis, with erosive changes. After starting tocilizumab 162 mg SQ injections every 28 days, she achieved clinical remission. Notably, she has significant damage features of LS and EF (Fig. 4 A-B).

Patient 3 was diagnosed at age 10 years with extensive bilateral wrist/hand tenosynovitis, myofasciitis, and bilateral lower extremity fasciitis (Fig. 2 A). She was concurrently diagnosed with active linear LS of her right lower extremity (Fig. 4 C). She was treated with hydroxychloroquine (3 mg/kg/day), methylprednisolone (30 mg/kg IV for three days, then weekly for 12 weeks), IVIG (2 g/kg monthly), and methotrexate (15 mg/m²/weekly SQ injections). Given only a partial response, rituximab (750 mg/m²/dose two weeks apart for two doses) was added. Despite initial clinical improvement, her LS and EF relapsed, leading to the addition of tocilizumab (162 mg/dose IV every two weeks). For the past three years, she has maintained remission as confirmed by clinical examination and MRI. Subsequently, she has tapered off prednisone, methotrexate, and tocilizumab. Currently, she is on hydroxychloroquine with only LS damage features present (Fig. 4 D).

Patient 4 had a history of 22q11.23 deletion and epilepsy. EF was diagnosed at 12 years of age with extensive symmetric fasciitis (Fig. 2 B-C). She had limited and painful range of motion of her shoulders, elbows, wrists, fingers, hips, knees, and ankles. She was treated with prednisone (maximum dose of 40 mg daily, 1 mg/kg/day), IV methylprednisolone (30 mg/kg pulses weekly for four doses), and methotrexate (15 mg/m²/weekly SQ injections). This regimen led to a significant improvement in her joint limitation. While weaning corticosteroids, she developed skin changes and mild elevation of aldolase and lactate dehydrogenase, so mycophenolate mofetil (600 mg/m²/dose twice daily) was added leading to normalization of her labs, clinical features, and MRI. She tolerated a prednisone wean without issues. She remains in remission and is undergoing a gradual tapering of methotrexate.

Patient 5 had a history of Hashimoto thyroiditis, environmental allergies requiring immunotherapy, food allergies, and inherited mild factor XI deficiency. EF was diagnosed within three weeks of symptoms, including generalized edema, limitation of her bilateral shoulders, fingers, wrists, and decreased ability to squat. MRI of her bilateral thighs exhibited circumferential, uniform thickness edema-like signal along the intermuscular fascial planes diffusely about the pelvis and thighs. She was treated with IV methylprednisolone (1000 mg total for one dose), prednisone (maximum dose of 40 mg daily, approximately 1 mg/kg/day), IVIG (2 g/kg monthly for six doses), methotrexate (15 mg/m²/weekly oral), and hydroxychloroquine 200 mg daily (4 mg/kg/day). Within a month of treatment, her clinical symptoms and laboratory markers normalized. After six months of treatment, a repeat MRI showed interval resolution. She remains in remission on hydroxychloroquine and a slow wean of methotrexate.

Patient 6 was diagnosed with unilateral EF involving her left forearm, wrist, fingers, and lower extremity. Initially, she presented with left calf pain and swelling with negative DVT evaluation. She was misdiagnosed with a soft tissue infection. Her symptoms progressed over a month to include circumferential swelling of her left wrist, forearm, fingers, and lower extremity with associated limited range of motion. She also had scattered ecchymoses. MRI of her left upper and lower extremity demonstrated diffuse myositis and fasciitis. Given her diagnoses of EF and acquired hemophilia A, she was started on corticosteroids, rituximab, and methotrexate (25 mg weekly SQ injections). She was lost to specialty follow up care and received a truncated course of IV methylprednisolone (1000 mg weekly dose for two doses), prednisone (maximum: 40 mg daily), and rituximab (800 mg and then 1000 mg two weeks later) with improvement of her musculoskeletal symptoms and improvement of her factor 8 level. Fourteen months later, she presented with four days of acute onset bilateral upper and lower extremity swelling and was found to have peripheral eosinophilia and elevated CK, consistent with a flare of EF. She had no abnormal bruising and normal coagulation markers. She was given a three-day course of 1000 mg IV methylprednisolone, followed by prednisone taper, and started on methotrexate 25 mg SQ injections with notable improvement of her symptoms.