Refractory idiopathic peripheral ulcerative keratitis in a pediatric patient

Dear Editor, Peripheral ulcerative keratitis (PUK) is a rare, potentially vision-threatening inflammatory disorder of the cornea characterized by progressive peripheral thinning with an epithelial defect and adjacent inflammation.[1] It carries a significant risk for corneal perforation and scarring, leading to profound visual loss. While PUK is well recognized in adults with systemic vasculitides such as rheumatoid arthritis, pediatric cases are exceedingly uncommon, and etiologies often remain idiopathic. Moreover, aggressive immunomodulatory therapy (IMT) or surgical interventions may be required, which present unique challenges in this age group. We report a case of refractory pediatric PUK with negative infectious and autoimmune workup, ultimately controlled with a combination of IMT and surgical management. A healthy 16-year-old male presented with 3 months of intermittent foreign-body sensation, photophobia, and redness in his right eye. He had no relevant medical or family history. Initial examination showed best-corrected visual acuity (BCVA) of 20/20 and no epithelial defect or corneal thinning. Symptoms briefly improved with topical corticosteroid, antihistamine, and lubricants. Six weeks later, he returned with worsening pain and redness. BCVA was 20/40, with nasal nonnecrotizing anterior scleritis and adjacent 50% corneal thinning, consistent with PUK [Figure 1a]. The anterior chamber was quiet. Laboratory and imaging workup, including autoimmune markers (antinuclear antibody, rheumatoid factor, anti-neutrophil cytoplasmic antibody, and anti-cyclic citrullinated peptide), infectious serologies (Hepatitis B/C, syphilis, lyme, and tuberculosis), and chest X-ray, was unremarkable.Figure 1: External photos of a severe refractory case of peripheral ulcerative keratitis in a pediatric patient. (a) Significant (50%) corneal thinning encompassing the nasal limbus before initiation of systemic prednisone (b) Relentless corneal thinning extending onto the paracentral cornea despite treatment with oral prednisone 1 mg/kg daily, subcutaneous methotrexate 25 mg weekly, and subcutaneous adalimumab 40 mg biweeklyOral prednisone (1 mg/kg/day) was initiated alongside doxycycline and Vitamin C. Subcutaneous methotrexate (25 mg weekly) and adalimumab (40 mg biweekly) were added sequentially. Despite these, progressive circumferential corneal thinning developed [Figure 1b]. Adalimumab was replaced by mycophenolate mofetil (1 g twice daily) and rituximab (960 mg IV × 2 doses, 2 weeks apart). Due to concern of impending perforation, 360° conjunctival recession, human amniotic membrane transplantation, and temporary tarsorrhaphy were performed. Inflammation resolved over 2 months, but diffuse stromal scarring and limbal stem cell deficiency reduced BCVA to 20/200 [Figure 2]. After 1 year, the patient remained quiescent off prednisone, maintained on methotrexate and mycophenolate (reduced to 750 mg BID for leukopenia). He remains stable under rheumatology care and is being evaluated for limbal stem cell transplantation.Figure 2: Remission of peripheral ulcerative keratitis in a pediatric patient with conjunctival recession, rituximab, and mycophenolate mofetil. (a) External photos showing diffuse corneal scarring and vascularization (b) Central anterior segment-optical coherence tomography (AS-OCT) scan of the affected eye showing hyperreflectivity of the stroma and central thinning (c) Central AS-OCT of the normal eye demonstrating baseline thickness and reflectivityThis case highlights a severe, refractory form of PUK in an adolescent without systemic disease, underscoring diagnostic and therapeutic challenges in pediatric patients. Review of the literature revealed 9 cases of PUK in pediatric patients that highlight similarities with the presented case but also the diversity of presentations [Table 1]. Most children present with nonspecific ocular surface symptoms over months before corneal thinning is recognized, and delayed diagnosis can result in corneal perforation.[2,5,9]Table 1: Summary of reported cases of pediatric peripheral ulcerative keratitisOur patient received early surgical intervention before perforation in contrast to other pediatric cases, where surgical intervention is performed after perforation.[2,5,8,9] Conjunctival recession has been shown in adult PUK to reduce inflammatory mediator influx and may have a benefit when combined with aggressive systemic therapy.[1] In our case, the patient trialed 4 different IMT agents before achieving remission with rituximab, mycophenolate, and methotrexate. Rituximab has demonstrated efficacy in refractory adult PUK, but pediatric use is scarcely reported.[10] To our knowledge, this represents the first case reporting the successful use of rituximab to control PUK in a pediatric patient. Although idiopathic cases such as this may be termed “Mooren ulcer,” distinctions exist.[1] Mooren ulcer in younger patients typically presents bilaterally and without scleritis.[11] Continued systemic follow-up remains essential, as PUK can precede the development of systemic autoimmune disease. This case demonstrates the importance of early recognition, thorough systemic workup, and aggressive treatment in pediatric PUK. Specifically, this case highlights that early intervention with conjunctival recession and amniotic membrane transplant may help prevent corneal perforation, and that rituximab may be an effective treatment option for refractory disease. Declaration of patient consent This study was performed in accordance with and conforming to the Declaration of Helsinki. The authors certify that they have obtained appropriate consent forms from the legal guardians of the patient. In the form, the guardians have given the consent for the images and other clinical information of the patient to be reported in the journal. The guardians understand that the names and initials of the patient will not be published, and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed. Data availability statement Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Financial support and sponsorship Nil. Conflicts of interest The authors declare that there are no conflicts of interest in this paper.