P2.209: From Arthritis to Enigma: Unraveling a 15-Month-Old’s Hidden Hyaline Fibromatosis Syndrome, A Case Report and Review of the Literature

Introduction: Hyaline Fibromatosis Syndrome (HFS) is a rare syndrome characterized by hyaline deposits in the papillary dermis and other tissues. The disease classically presents with joint contractures, decreased skin elasticity, hyperpigmented lesions over extensor surfaces of joints, perianal masses, failure to thrive, protein losing enteropathy, and gingival hypertrophy.

Case Description: A 15-month-old Hispanic male with previously diagnosed polyarticular juvenile idiopathic arthritis (JIA) presented to a pediatric rheumatology clinic due to clinical worsening despite treatment with prednisone and methotrexate. His symptoms initially started at 4 months of age with swelling and stiffness of bilateral knees. His fingers started to swell at 7 months old and he developed a "claw position" of his hands with overlying joint erythema. The patient was previously diagnosed with polyarticular JIA in Mexico based on positive ANA ( < 1:80), elevated inflammatory markers, and ultrasound findings of symmetrical active polyarticular synovitis involving shoulders, elbows, wrists, knees, ankles, and metatarsophalangeal. On assessment, the patient had clinical evidence of contractures of the wrists, shoulders, fingers, elbows and ankles in addition to palpable joint enlargement. He was also noted to have a perianal mass and hyperpigmented macules over bony prominences of multiple joints. He was admitted and underwent a whole-body magnetic resonance imaging (MRI) that showed T2 bright and T1 dark signal involving the juxta-articular soft tissues surrounding both shoulders, elbows and wrists with signal abnormality also noted within the subcutaneous fat. Prior genetic testing in Mexico demonstrated heterozygous ANTXR2 gene variant. Genetics and Dermatology were consulted to perform genetic testing and a skin biopsy that confirmed a diagnosis of ANTXR2-related HFS. Prednisone and methotrexate were discontinued while inpatient. The patient received both inpatient physical and occupational therapy with a plan to continue outpatient at discharge.

Discussion: HFS is a rare, autosomal recessive disorder with less than 100 documented cases worldwide. It has two subtypes, the more severe form is called Infantile Systemic Hyalinosis (ISH) while the milder phenotype is called Juvenile Hyaline Fibromatosis (JHF). ISH has significant morbidity and mortality in early childhood, while patients with JHF can survive into adulthood. Diagnosis is based on characteristic clinical features and variants in ANTXR2 gene. Treatment targets symptoms and includes nutritional support for failure to thrive such as a nasogastric tube, gastrostomy tube, or parenteral nutrition. Patients with protein-losing enteropathy may require albumin infusions. Physical therapy is recommended for joint contractures, and pain is managed with nonsteroidal anti-inflammatory drugs, opiates, or gabapentin. Skin lesions may require surgical resection. Families should undergo genetic counseling if they desire future pregnancies.

Conclusion: Although rare in children, HFS should be considered as a differential for patients with concern for JIA who also display multiple extra-articular signs and symptoms. Early diagnosis is imperative to improve quality of life and morbidity.