Childhood-Onset Ocular Mucous Membrane Pemphigoid Presenting with Peripheral Ulcerative Keratitis: A Case Report and Review of the Literature

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Ramos-Dávila, Raul E. Ruiz-Lozano, Alejandro Rodriguez-Garcia, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4457273/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 May, 2025 Read the published version in Journal of Ophthalmic Inflammation and Infection → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose The purpose of this study was to describe the case of a pediatric patient diagnosed with mucous membrane pemphigoid (MMP) with exclusive ocular involvement presenting at diagnosis with peripheral ulcerative keratitis and provide a review of the literature. Methods A 12-year-old girl presented with cicatricial conjunctivitis and peripheral ulcerative keratitis (PUK). A conjunctival biopsy and direct immunofluorescence revealed linear deposits of IgG, IgM, and C3 at the basement membrane zone, confirming a diagnosis of ocular MMP. Results The patient was initially treated with dapsone 25 mg/day and prednisone 40 mg/day along with topical treatment including cyclosporine 0.05%, loteprednol etabonate 0.05%, and sodium hyaluronate 0.15% and trehalose 3%. Inflammation persisted as an increase in the extension of symblepharon was documented. Subsequently, dapsone was switched to oral methotrexate 15 mg/week and prednisone was successfully tapered to 5 mg/day. After three years of follow-up, disease activity remained quiescent. Conclusions Pediatric mucous membrane pemphigoid with ocular involvement is a rare condition of which few reports have been published, resulting in scarce information regarding its clinical course and response to treatment. We report the first case observed in a Hispanic patient, opening with peripheral ulcerative keratitis, and responding successfully to methotrexate. Figures Figure 1 Figure 2 Introduction Mucous membrane pemphigoid (MMP) is a rare systemic cicatrizing autoimmune disease that primarily affects the skin but more commonly involves mucous membranes, such as the conjunctiva, nasal cavity, oropharynx, esophagus, trachea, skin, and genitalia [ 1 ]. It has an estimated annual incidence of 2 cases per million, exhibiting a pronounced predilection for females, Caucasians, and elderly patients with a mean age at onset of 60–65 years [ 1 , 2 ]. Ocular involvement is observed in up to 70% of patients, leading to vision loss in nearly 50% of cases. This outcome is attributed to chronic progressive sub-epithelial fibrosis, tissue remodeling, and neovascularization [ 2 ]. Regrettably, preventable progressive fibrosis develops in nearly 40% of patients as the diagnosis is frequently delayed due to the non-specific nature of early clinical symptoms and signs and the limited sensitivity of immunopathological studies [ 3 ]. Previous reports indicate that only 50% of patients with ocular MMP present a positive direct immunofluorescence (DIF) result and that 26% exhibit false negative results, requiring multiple biopsies [ 4 ]. Prompt and aggressive treatment with immunosuppressive therapy is advocated; however, severe cases may progress and cause substantial morbidity despite intervention [ 1 ]. Based on the available information, only five pediatric cases have been documented in which MMP manifested exclusively ocular symptoms. These cases pose not only a diagnostic challenge but also a therapeutic dilemma since immunosuppressive drugs carry a considerable number of adverse effects, which is a matter of particular concern in children. We report the case of a 12-year-old girl diagnosed with ocular MMP and provide a review of previously reported cases of the disease appearing early in life. Case Report An otherwise healthy twelve-year-old female was referred to the Ophthalmology Department at Tecnologico de Monterrey, presenting with subacute redness in the left eye. The parents reported a 5-year history of chronic blepharitis and allergic conjunctivitis. Upon ophthalmic examination, a best corrected visual acuity (BCVA) of 20/25 and 20/40 was found in the right (OD) and left (OS) eye, respectively. A slit lamp exam revealed mild meibomian gland, dysfunction, and diffuse superficial punctate keratitis in both eyes (OU) accompanied by moderate conjunctival hyperemia in OS. Additionally, sub-epithelial fibrosis and symblepharon were observed in the nasal and temporal quadrants of the lower conjunctiva OU. (Figs. 1 A and 1 B). Notably, no papillary or follicular reactions were observed. The anterior segment, intraocular pressure, and fundoscopy yielded unremarkable findings. The patient denied symptoms of dry mouth or dysphagia, and no dermatologic lesions were observed. Loteprednol etabonate 0.5% four times daily, sodium hyaluronate 0.15% and trehalose 3% every 6 hours, lid hygiene, and topical azithromycin 15mg/g solution once a day were prescribed as initial treatment. The patient returned two weeks later with severe pain and decreased BCVA of 20/400 in OS. A temporal corneal stromal thinning was observed in the same eye (Fig. 1 C), establishing the diagnosis of peripheral ulcerative keratitis (PUK). Treatment was adjusted to include prednisone 20 mg/day and combined moxifloxacin 0.5%/ dexamethasone 0.1% eyedrops every 4 hours. After one week under this therapeutic regimen, the symptoms and vision improved to 20/50 in the left eye. Laboratory tests including a complete blood count, antineutrophil cytoplasmic antibodies (ANCA), antinuclear antibodies (ANA), rheumatoid factor, Anti-Ro/SSA and Anti-La/SSB antibodies, blood levels of complement components C3 and C4, C-reactive protein, and erythrocyte sedimentation rate were ordered, and biopsy from the superior and temporal bulbar conjunctiva in OS was performed. Results from laboratory tests were unremarkable except for decreased levels of serum complement fraction C4 at 4.0 IU/ml. The biopsy results from the upper bulbar conjunctiva revealed a non-keratinized stratified squamous epithelium with areas of acantholysis and scant chronic vascular inflammatory infiltrates (Fig. 2 A). Linear deposits of IgG, IgM, and C3 were detected with DIF in the basement membrane zone (BMZ), consistent with the diagnosis of ocular MMP (Fig. 2 B). Topical cyclosporine 0.05% twice a day was included in the treatment regimen [ 5 ]. Following the confirmation of blood levels of glucose-6-phosphate dehydrogenase within range, dapsone 50 mg/day was initiated. However, inflammation persisted for the following three months and an increase in the extension of symblepharon in OS was documented, warranting the decision to switch from dapsone to oral methotrexate at 15 mg/week and increase oral prednisone to 40 mg/day (Fig. 1 C, 1 D, 1 E). Remarkable clinical improvement was noted two months following the treatment modification, leading to the successful taper of oral prednisone. (Fig. 1 F, 1 G, 1 H). At the last follow-up visit, twenty-eight months after the initial consultation, ocular inflammation remained quiescent and discomfort subsided; however, severe meibomian gland dysfunction persisted. The patient remains on a treatment regimen that includes oral methotrexate 15 mg/week with folic acid supplementation, topical cyclosporine 0.05% twice a day, loteprednol etabonate 0.05% once a day, sodium hyaluronate 0.15% and trehalose 3% every 6 hours, dexpanthenol 5% every night, and prednisone 5 mg/day. Discussion Childhood-onset MMP is a rare condition, documented in only 28 patients reported in the literature, including mostly females (n=19, 68%) with a median age at diagnosis ranging from 1 to 17 years [6]. However, an estimated delay in diagnosis of 2 months to 5 years has been recorded among children with the disease. The most frequently affected sites in pediatric patients included the oral cavity (n=18, 64%), followed by the conjunctiva (n=11, 39%), the genital mucosa (n=10, 35%), the skin (n=6, 21%), and the upper respiratory pathway (n=5, 62.5%) [7–9]. Notably, only five patients presented isolated ocular disease [10–13]. Moreover, all patients with skin affection also presented ocular manifestations [6–9, 14–16]. Two patients with oral mucous, skin, and ocular affection died; the cause of death was not available for one while the other patient died from tracheal stenosis associated with the disease [15, 16]. General characteristics of previously reported cases of childhood-onset MMP are displayed in Table 1 and Table 2. Likewise, tissue involvement in adults presents most commonly in the oral cavity (85%), followed by the conjunctiva (65%), nasopharynx (20-40%), skin (20-35%), genitalia (20%), and more rarely the esophagus and trachea (5-15%) [17]. The prevalence of affected sites and features appears to be comparable to that of pediatric patients; however, genital involvement in children seems to be more prevalent than in adults. Table 1. Previously reported cases of childhood-onset MMP with ocular involvement. Reference Age (years)/sex Systemic findings Delay in diagnosis Treatment Commentary Jolliffe et al, 1977 13/girl Oral, genital, skin 3-months Tetracosactid Depot 1mg IM twice a week + Prednisolone 90 mg/day None Rosenbaum et al, 1984 6/boy Oral, genital, skin 1-year Methylprednisolone IV + Dapsone 2mg/kg/day Response to first-line treatment Iglesias L et al, 1992 12/boy None 5-years Dapsone None Kanwar et al, 2006 14/girl Nasal, oral, laryngeal 6-months Prednisolone 30mg/day + Dapsone 100mg/day Coeliac disease Gamm D et al, 2006 17/girl Oral, tracheal, skin 1-year Prednisone + dapsone Deceased from tracheal stenosis Iovine A et al, 2008 9/boy Oral, genital, laryngeal, skin 5-years Prednisolone 25 mg/day + Cyclosporine Bilateral corneal perforation Reconstructive surgery Deceased Kharfi M et al, 2010 1/boy Oral, nasal, skin 10-months Prednisone 2mg/kg/day + Dapsone 25mg/day for 3 years + topical cyclosporine every 6 hours for 3 years Bilateral corneal opacities Levallee A et al, 2013 12/girl None 2-years Dapsone 100 mg/day PUK episode Relapse after withdrawal Flores-Climente et al, 2019 2/boy None 6-months 1.Topical cyclosporine 2. Prednisolone 1mg/kg/day + MMF 15mg/kg/day + cyclosporine 4mg/kg/day 3. Dapsone 2mg/kg/day 4. Rituximab 375 mg/m2 at 2‐week intervals Responded to biologic therapy Pattnaik M et al, 2019 14/girl Oral, genital, nasal, skin 6-months 1. Prednisolone 1 mg/kg/day + Dapsone 2 mg/kg/day 2. Azathioprine 100mg/day Responded to second line treatment Ollero et al, 2022 1/boy None 5-months 1. Topical cyclosporine + botulinum toxin 2. Prednisolone steaglate + MMF 3. Cyclosporine 4. Dapsone 5. Rituximab Responded to biologic therapy Required reconstructive surgery Jitender MS et al, 2024 13/girl None 1-year 1. Prednisolone 0.5 mg/kg/day + dexamethasone 0.1% eyedrops 2. Azathioprine 50mg/day Well-controlled Jitender MS et al, 2024 16/girl Oral 2-years Prednisolone 0.5 mg/kg/day + dexamethasone 0.1% eyedrops and azathioprine 50mg/day Residual corneal scarring Ramos-Dávila et al, 2024 12/girl None 4-years 1. Prednisone 20 mg/day + topical cyclosporine + dapsone 25 mg/day 2. Prednisone 40 mg/day + Methotrexate 20mg/week + topical cyclosporine Responded to methotrexate *MMF, mycophenolate mofetil; mg, milligrams; kg, kilograms; m 2 , square meters; IM, intramuscular; IV; intravenous; PUK, peripheral ulcerative keratitis. Table 2. Previously reported cases of pediatric mucous membrane pemphigoid without ocular involvement Reference Age (years) / Sex Affected sites Delay in diagnosis Treatment Response Rogers et al, 1981 4/girl Genitalia 8-months NA NA Barnett et al, 1981 13/boy Gingivitis 9-months Non-specific steroids Yes Moy et al, 1986 9/girl Gingivitis 4-years Prednisone 40mg/day Yes Laskaris et al, 1988 14/girl Gingivitis 2-years Topical 0.1% triamcinolone paste Yes Sklavounou et al, 1990 13/boy Gingivitis 1-year Topical 1.0 mg betamethasone/day Yes Roche C et al, 2009 14/girl Gingivitis 4-month Mouth rinse with triamcinolone and chlortetracycline + miconazole oral gel Yes Farrell et al, 1999 14/girl Genitalia 9-months Topical clobetasol propionate cream Yes Farrell et al, 1999 8/girl Genitalia and gingivitis NA Prednisolone + dapsone + sulphapyridine Yes Cheng et al, 2001 8/girl Gingivitis 6-months Mouth rinse with 0.05% fluocinonide + 0.2% chlorhexidine Yes Schoeffler et al, 2004 9/girl Genitalia 4-months Clobetasol propionate cream + dapsone 1.5 mg/kg/day Yes Hoque et al, 2005 7/girl Genitalia 9-months Clobetasol propionate cream Yes Lourenco et al, 2006 4/girl Gingivitis 2-years Dapsone 50 mg/day for 20 months Yes Musa et al, 2002 9/girl Gingivitis 8-months Topical 0.05% fluocinonide gel switched to topical betamethasone. Poor compliance. Poor Lebeau et al, 2004 8/girl Genitalia 5-years Topical tacrolimus 0.1% for 9 months Yes Mostafa et al, 2009 6/boy Gingivitis 1-year Betamethasone cream and 0.2% chlorhexidine wash switched to 0.05% fluocinonide Yes *NA, not available; mg, milligrams; kg, kilograms The diagnosis is challenging, compounded by the very low prevalence of the disease in pediatric patients. In this population, reaching diagnosis could be hampered by alternative etiologies for cicatricial conjunctivitis such as hemorrhagic adenoviral conjunctivitis with membrane formation, chlamydial /trachoma keratoconjunctivitis, severe vernal keratoconjunctivitis, and pediatric blepharokeratoconjunctivitis, among others [18]. Moreover, patients may present with a long history of using diverse and multiple topical eye drops and potentially be misdiagnosed as drug-induced conjunctivitis. Proper diagnosis requires concordance between clinical signs and the detection of anti-basement zone autoantibodies. These autoantibodies are tissue-bound, detected by DIF microscopy, or circulating when detected by indirect immunofluorescence (IIF) [17]. DIF showing linear IgG, IgA, and/or C3 deposits at the subepithelial BMZ and/or dermal-epidermal junction is strongly recommended as the major single diagnostic test for MMP [17, 19]. Nonetheless, inaccurate tissue management or collection, along with initially negative results during the early stages of the disease, can result in false-negative outcomes, thereby impeding the timely and accurate diagnosis [3, 11, 17]. Likewise, a previously reported case of ocular MMP in a 12-year-old girl presented a negative DIF result at the initial presentation, subsequently turning positive two years later [11]. The mentioned case was the only patient who manifested an episode of PUK, as in our report. Autoimmune diseases are responsible for nearly half of the non-infectious etiologies of PUK, with rheumatoid arthritis and granulomatosis with polyangiitis being the most frequently underlying diagnoses [20, 21]. Moreover, PUK has only been documented in two additional patients with MMP; the before-stated pediatric patient and an older adult woman developing PUK following cataract surgery [11, 22]. After diagnosis has been properly established, prompt treatment should be initiated. Dapsone (1.0-1.5 mg/kg/day) combined with oral cyclophosphamide (2 mg/kg/day), or corticosteroids (0.5-1.5 mg/kg/day) are the recommended treatment options in adults diagnosed with ocular MMP [5, 17]. Cyclophosphamide has been particularly associated with a prompt response and prolonged remission in patients with ocular involvement [17]. Other alternatives include azathioprine (1.5-2.0 mg/kg/day), methotrexate (7-15 mg/week), mycophenolate mofetil (2 g/day), or sodium mycophenolic acid (1,440 mg/day) [17, 23]. Biologic therapy, such as rituximab (375 mg/m 2 weekly for 4 weeks or 1,000mg twice every 2 weeks) is usually reserved for refractory cases of severe MMP [17, 24]. Treatment in children is hindered by the extensive side effects of the drugs mentioned above and the lack of standardized regimens for MMP in this demographic. Prior cases of pediatric MMP included cyclosporine (4 mg/kg/day) in the treatment regimen; however, two out of three patients receiving this drug were unresponsive and required switching to another agent [12, 13, 15]. Interestingly, none of the prior cases were treated with methotrexate, an antimetabolite extensively studied in the pediatric population for other immune-mediated diseases, rendering an acceptable safety profile [23, 25–27]. The patient in our report presents the first case of pediatric ocular MMP successfully treated with methotrexate (15 mg/week). Pediatric MMP with ocular involvement is a rare condition that seems to share clinical features with the adult counterpart, albeit with a relatively more indolent evolution. Timely diagnosis and treatment are warranted but remain challenging. Declarations Literature search The authors conducted an extensive literature search using the National Library of Medicine’s PubMed and Google Scholar databases for all articles published until October 2023. The following search terms were used: “mucous membrane pemphigoid”, “ocular cicatricial pemphigoid,” “pemphigoid”, “pediatric”, “childhood”, “child”, “boy”, “girl”, “infant,” “”. Case reports, case series, letters to the editor, review articles, and original articles were included. Relevant references within articles found were also included. Ethics approval and consent to participate: Ethics approval for this study was waived by the Ethics Committee of the Instituto Tecnologico de Monterrey as it does not meet the criteria for research and was approved as a quality assurance study. This study was conducted in accordance with the Declaration of Helsinki. Consent for publication: Consent for publication was obtained from the patient’s guardian. Availability of data and material: Not applicable Competing interests: The authors declare that they have no competing interests. Funding: None to declare Authors' contributions: EMRD and RERL participated in the writing and data collection of the manuscript. ARG and CAG have substantively revised the work. All authors have approved the submitted version of this manuscript. References Taurone S, Spoletini M, Ralli M, Gobbi P, Artico M, Imre L, Czakò C, Kovàcs I, Greco A, Micera A (2019) Ocular mucous membrane pemphigoid: a review. Immunol Res 67:280–289. https://doi.org/10.1007/s12026-019-09087-7 Chan LS, Ahmed AR, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ, Fine J-D, Foster CS, Ghohestani R, Hashimoto T, Hoang-Xuan T, Kirtschig G, Korman NJ, Lightman S, Lozada-Nur F, Marinkovich MP, Mondino BJ, Prost-Squarcioni C III, Setterfield RSR, West JF, Wojnarowska DP, Woodley F, Yancey DT, Zillikens KB, Zone D JJ (2002) The First International Consensus on Mucous Membrane Pemphigoid: Definition, Diagnostic Criteria, Pathogenic Factors, Medical Treatment, and Prognostic Indicators. Arch Dermatol 138:370–379. https://doi.org/10.1001/archderm.138.3.370 Margolis T (2018) Evidence-Based Insights into the Utility of Conjunctival Biopsy in Mucous Membrane Pemphigoid. Ophthalmology 125:474–475. https://doi.org/10.1016/j.ophtha.2018.01.014 Ong HS, Setterfield JF, Minassian DC, Dart JK, 2009–2014 MMPSG, Booth D, Reid E, Carnt N, Gugliemetti S, Shanmuganathan V, Watson M, Saw V, Wilkins M, McCudden V, Ahmad S, Calder V, Waseem N, Scott B, Bunce C, Gage W, Gleeson M, Lund V, Sandhu G (2018) Mucous Membrane Pemphigoid with Ocular Involvement The Clinical Phenotype and Its Relationship to Direct Immunofluorescence Findings. Ophthalmology 125:496–504. https://doi.org/10.1016/j.ophtha.2017.10.004 Schmidt E, Rashid H, Marzano AV, Lamberts A, Zenzo GD, Diercks GFH, Alberti-Violetti S, Barry RJ, Borradori L, Caproni M, Carey B, Carrozzo M, Cianchini G, Corrà A, Dikkers FG, Feliciani C, Geerling G, Genovese G, Hertl M, Joly P, Meijer JM, Mercadante V, Murrell DF, Ormond M, Pas HH, Patsatsi A, Rauz S, Rhijn BD, Roth M, Setterfield J, Zillikens D, C.Prost, Zambruno G, Horváth B, Caux F (2021) European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part II. J Eur Acad Dermatol Venereol 35:1926–1948. https://doi.org/10.1111/jdv.17395 Jinagal J, Gupta B, Hanumanthu V, Chatterjee D, Limbu S, Malhotra C, Gupta A, Jain AK, Yangzes S, Mahajan R, Handa S, Pandav SS, De D (2024) Ocular Cicatricial Pemphigoid in Young Patients. Cornea. https://doi.org/10.1097/ico.0000000000003547 Rosenbaum MM, Esterly NB, Greenwald MJ, Gerson CR (1984) Cicatricial Pemphigoid in a 6-Year‐Old Child: Report of a Case and Review of the Literature. Pediatr Dermatol 2:13–22. https://doi.org/10.1111/j.1525-1470.1984.tb00435.x Kharfi M, Khaled A, Anane R, Fazaa B, Kamoun MR (2010) Early Onset Childhood Cicatricial Pemphigoid: A Case Report and Review of the Literature. Pediatr Dermatol 27:119–124. https://doi.org/10.1111/j.1525-1470.2009.01079.x Pattnaik M, Panda M, Dash M, Raj C (2019) A rare case of childhood mucous membrane pemphigoid involving both skin and mucosa. Indian J Paediatr Dermatol 20:160. https://doi.org/10.4103/ijpd.ijpd_71_18 Iglesias LS, Quismorio FP, McDonnell PJ, Barnes C (1992) Ocular Cicatricial Pemphigoid in a Twelve-Year-Old Boy. Cornea 11:365–367. https://doi.org/10.1097/00003226-199207000-00018 Lavallée A, Bourret-Massicotte D, Laughrea PA (2013) Childhood Mucous Membrane Pemphigoid. Cornea 32:1399–1401. https://doi.org/10.1097/ico.0b013e3182a0ce6e Flores-Climente V, Rozas‐Muñoz E, Martínez‐Grau A, Aucouturier F, Luna S, Baselga E (2019) Childhood ocular mucous membrane pemphigoid successfully treated with rituximab. Pediatr Dermatol 36:984–985. https://doi.org/10.1111/pde.13971 Ollero R, Soldevila A, Paz MF, de la, Martínez-Grau A (2022) Surgical Management of Ocular Cicatricial Pemphigoid in a Pediatric Patient. Cornea 41:911–913. https://doi.org/10.1097/ico.0000000000002932 JOLLIFFE DS, SIM-DAVIS D (1977) Clinical meeting of the St John’s Hospital Dermatological Society: 4 November 1976 Cicatricial pemphigoid in a young girl: report of a case. Clin Exp Dermatol 2:281–284. https://doi.org/10.1111/j.1365-2230.1977.tb02570.x Iovine A, Fimiani F, Vassallo P, Alessio M, Magli A (2008) Ocular Manifestations in a Case of Childhood Cicatricial Pemphigoid. Eur J Ophthalmol 18:636–638. https://doi.org/10.1177/112067210801800424 Gamm DM, Harris A, Mehran RJ, Wood M, Foster CS, Mootha VV (2006) Mucous Membrane Pemphigoid With Fatal Bronchial Involvement in a Seventeen-Year-Old Girl. Cornea 25:474–478. https://doi.org/10.1097/01.ico.0000178730.34564.c7 Du G, Patzelt S, van Beek N, Schmidt E (2022) Mucous membrane pemphigoid. Autoimmun Rev 21:103036. https://doi.org/10.1016/j.autrev.2022.103036 Vazirani J, Donthineni PR, Goel S, Sane SS, Mahuvakar S, Narang P, Shanbhag SS, Basu S (2020) Chronic cicatrizing conjunctivitis: A review of the differential diagnosis and an algorithmic approach to management. Indian J Ophthalmol 68:2349–2355. https://doi.org/10.4103/ijo.ijo_604_20 Jain N, Jakati S, Shanbhag SS, Basu S (2023) Direct Immunofluorescence Findings and Factors Affecting Conjunctival Biopsy Positivity in Ocular Mucous Membrane Pemphigoid. https://doi.org/10.1097/ico.0000000000003382 . Cornea Hassanpour K, ElSheikh RH, Arabi A, Frank CR, Elhusseiny AM, Eleiwa TK, Arami S, Djalilian AR, Kheirkhah A (2022) Peripheral Ulcerative Keratitis: A Review. J Ophthalmic Vis Res (JOVR) 17:252–275. https://doi.org/10.18502/jovr.v17i2.10797 Ruiz-Lozano RE, Ramos-Davila EM, Garza-Garza LA, Gutierrez-Juarez K, Hernandez-Camarena JC, Rodriguez-Garcia A (2023) Rheumatoid arthritis-associated peripheral ulcerative keratitis outcomes after early immunosuppressive therapy. Br J Ophthalmol 107:1246–1252. https://doi.org/10.1136/bjophthalmol-2022-321132 Kiire CA, Srinivasan S, Inglis A (2011) Peripheral Ulcerative Keratitis After Cataract Surgery in a Patient With Ocular Cicatricial Pemphigoid. Cornea 30:1176–1178. https://doi.org/10.1097/ico.0b013e3182141baa You C, Ma L, Anesi SD, Foster CS (2017) Long-term remission of ocular cicatricial pemphigoid off immunomodulatory therapy. Eur J Ophthalmol 28:157–162. https://doi.org/10.5301/ejo.5001050 Foster CS, Chang PY, Ahmed AR (2010) Combination of Rituximab and Intravenous Immunoglobulin for Recalcitrant Ocular Cicatricial Pemphigoid A Preliminary Report. Ophthalmology 117:861–869. https://doi.org/10.1016/j.ophtha.2009.09.049 McCluskey P, Chang JH, Singh R, Wakefield D (2004) Methotrexate therapy for ocular cicatricial pemphigoid. Ophthalmology 111:796–801. https://doi.org/10.1016/j.ophtha.2003.07.010 Ferrara G, Mastrangelo G, Barone P, Torre FL, Martino S, Pappagallo G, Ravelli A, Taddio A, Zulian F, Cimaz R, Group O behalf of the RIS (2018) Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting. Pediatr Rheumatol 16:46. https://doi.org/10.1186/s12969-018-0255-8 Gutiérrez-Suárez R, Burgos-Vargas R (2010) The use of methotrexate in children with rheumatic diseases. Clin Exp Rheumatol 28:S122–S127 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 29 May, 2025 Read the published version in Journal of Ophthalmic Inflammation and Infection → Version 1 posted Editorial decision: Revision requested 24 Dec, 2024 Reviews received at journal 30 Aug, 2024 Reviewers agreed at journal 21 Aug, 2024 Reviewers invited by journal 17 Jun, 2024 Submission checks completed at journal 22 May, 2024 Editor assigned by journal 22 May, 2024 First submitted to journal 21 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4457273","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":309550016,"identity":"521576a9-e82b-4c46-83ee-72c860d5958e","order_by":0,"name":"Eugenia M. Ramos-Dávila","email":"","orcid":"","institution":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey","correspondingAuthor":false,"prefix":"","firstName":"Eugenia","middleName":"M.","lastName":"Ramos-Dávila","suffix":""},{"id":309550017,"identity":"c3f46d73-ecbe-4e6c-bcc4-69f03879f9a8","order_by":1,"name":"Raul E. Ruiz-Lozano","email":"","orcid":"","institution":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey","correspondingAuthor":false,"prefix":"","firstName":"Raul","middleName":"E.","lastName":"Ruiz-Lozano","suffix":""},{"id":309550018,"identity":"07b8f61f-f596-4a8d-b1f6-ae24ef7eadb0","order_by":2,"name":"Alejandro Rodriguez-Garcia","email":"","orcid":"","institution":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey","correspondingAuthor":false,"prefix":"","firstName":"Alejandro","middleName":"","lastName":"Rodriguez-Garcia","suffix":""},{"id":309550019,"identity":"772a7cf5-8a0c-4235-93c4-b217ac56ac62","order_by":3,"name":"Carlos Alvarez-Guzman","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIie2PsUrEQBCGJwRyzZ7byYhFXmGPgFjEy6tsWIitYGOZKjZ3pL3gI9gIC6lXrrAx2EZsUqUTAjYpUrg5iCDkonYH7lcMM8t+/DMABsNhYqm+Hg0j7Qu/mnZ2ijNMJ3GvsL8obDdOKPS2qFTTgeugqBvdLOXLfdhUDFx6rEYVfL5kj1kCiwQjL9sQEHn5LlEvtsju+KjCIILtPAYrIcqzCYI4K4uHXuHsbY9Ca9iSDoKEPH3YHQPhbQrZTiqoU4gDYTJbeTZwWDK6zidTsKxB34JCK9fWSiHHcp6fc4Z7b6FpZFVN51+k9kxC2/kBTQv52t74Lj0dV4awryaMkX97+ZkAqPr9b4PBYPgXfALcglnijgS1dgAAAABJRU5ErkJggg==","orcid":"","institution":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey","correspondingAuthor":true,"prefix":"","firstName":"Carlos","middleName":"","lastName":"Alvarez-Guzman","suffix":""}],"badges":[],"createdAt":"2024-05-21 23:08:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4457273/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4457273/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12348-025-00480-y","type":"published","date":"2025-05-29T15:57:34+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":58078168,"identity":"b61d0454-3bfe-4420-90a1-d7dcbacca4a5","added_by":"auto","created_at":"2024-06-10 22:55:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2449562,"visible":true,"origin":"","legend":"\u003cp\u003eClinical images illustrating the progression observed from the initial presentation.\u003c/p\u003e\n\u003cp\u003e(A, B,) Subepithelial fibrosis, symblephara, and lissamine green staining in the bulbar and palpebral conjunctiva at first presentation. (C) Peripheral ulcerative keratitis on the left eye presenting two weeks after initial treatment. (D, G, F) Worsening of lissamine green staining, symblephara, and punctate epithelial keratitis. (G, H, I) Inflammation subsides in both the conjunctiva and cornea after treatment with methotrexate.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4457273/v1/c113942e2eac0d1bc20ed0cf.jpg"},{"id":58078167,"identity":"d1cc779f-d42c-411f-a532-6611a0b367f9","added_by":"auto","created_at":"2024-06-10 22:55:23","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":609628,"visible":true,"origin":"","legend":"\u003cp\u003eFindings from the histopathological and immunohistochemical examination of the conjunctival biopsy.\u003c/p\u003e\n\u003cp\u003e(A). Histopathological results of the conjunctival biopsy demonstrate non-keratinized stratified squamous epithelium with areas of acantholysis and scant chronic vascular inflammatory infiltrate. (B) Direct immunofluorescence displays a linear pattern of IgG, IgM, and C3 deposits on the basal lamina.\u003c/p\u003e","description":"","filename":"Figure2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4457273/v1/2655627b18dd68ebf101f60e.jpeg"},{"id":83784061,"identity":"b3c9c965-08fa-413f-88c5-b88098d5069e","added_by":"auto","created_at":"2025-06-02 16:19:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3879884,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4457273/v1/c6f58087-8d8b-4caa-9853-22ff17c2e543.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Childhood-Onset Ocular Mucous Membrane Pemphigoid Presenting with Peripheral Ulcerative Keratitis: A Case Report and Review of the Literature","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMucous membrane pemphigoid (MMP) is a rare systemic cicatrizing autoimmune disease that primarily affects the skin but more commonly involves mucous membranes, such as the conjunctiva, nasal cavity, oropharynx, esophagus, trachea, skin, and genitalia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It has an estimated annual incidence of 2 cases per million, exhibiting a pronounced predilection for females, Caucasians, and elderly patients with a mean age at onset of 60\u0026ndash;65 years [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOcular involvement is observed in up to 70% of patients, leading to vision loss in nearly 50% of cases. This outcome is attributed to chronic progressive sub-epithelial fibrosis, tissue remodeling, and neovascularization [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Regrettably, preventable progressive fibrosis develops in nearly 40% of patients as the diagnosis is frequently delayed due to the non-specific nature of early clinical symptoms and signs and the limited sensitivity of immunopathological studies [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Previous reports indicate that only 50% of patients with ocular MMP present a positive direct immunofluorescence (DIF) result and that 26% exhibit false negative results, requiring multiple biopsies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Prompt and aggressive treatment with immunosuppressive therapy is advocated; however, severe cases may progress and cause substantial morbidity despite intervention [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBased on the available information, only five pediatric cases have been documented in which MMP manifested exclusively ocular symptoms. These cases pose not only a diagnostic challenge but also a therapeutic dilemma since immunosuppressive drugs carry a considerable number of adverse effects, which is a matter of particular concern in children. We report the case of a 12-year-old girl diagnosed with ocular MMP and provide a review of previously reported cases of the disease appearing early in life.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eAn otherwise healthy twelve-year-old female was referred to the Ophthalmology Department at Tecnologico de Monterrey, presenting with subacute redness in the left eye. The parents reported a 5-year history of chronic blepharitis and allergic conjunctivitis. Upon ophthalmic examination, a best corrected visual acuity (BCVA) of 20/25 and 20/40 was found in the right (OD) and left (OS) eye, respectively. A slit lamp exam revealed mild meibomian gland, dysfunction, and diffuse superficial punctate keratitis in both eyes (OU) accompanied by moderate conjunctival hyperemia in OS. Additionally, sub-epithelial fibrosis and symblepharon were observed in the nasal and temporal quadrants of the lower conjunctiva OU. (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Notably, no papillary or follicular reactions were observed. The anterior segment, intraocular pressure, and fundoscopy yielded unremarkable findings. The patient denied symptoms of dry mouth or dysphagia, and no dermatologic lesions were observed. Loteprednol etabonate 0.5% four times daily, sodium hyaluronate 0.15% and trehalose 3% every 6 hours, lid hygiene, and topical azithromycin 15mg/g solution once a day were prescribed as initial treatment. The patient returned two weeks later with severe pain and decreased BCVA of 20/400 in OS. A temporal corneal stromal thinning was observed in the same eye (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC), establishing the diagnosis of peripheral ulcerative keratitis (PUK). Treatment was adjusted to include prednisone 20 mg/day and combined moxifloxacin 0.5%/ dexamethasone 0.1% eyedrops every 4 hours. After one week under this therapeutic regimen, the symptoms and vision improved to 20/50 in the left eye. Laboratory tests including a complete blood count, antineutrophil cytoplasmic antibodies (ANCA), antinuclear antibodies (ANA), rheumatoid factor, Anti-Ro/SSA and Anti-La/SSB antibodies, blood levels of complement components C3 and C4, C-reactive protein, and erythrocyte sedimentation rate were ordered, and biopsy from the superior and temporal bulbar conjunctiva in OS was performed. Results from laboratory tests were unremarkable except for decreased levels of serum complement fraction C4 at 4.0 IU/ml. The biopsy results from the upper bulbar conjunctiva revealed a non-keratinized stratified squamous epithelium with areas of acantholysis and scant chronic vascular inflammatory infiltrates (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Linear deposits of IgG, IgM, and C3 were detected with DIF in the basement membrane zone (BMZ), consistent with the diagnosis of ocular MMP (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Topical cyclosporine 0.05% twice a day was included in the treatment regimen [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Following the confirmation of blood levels of glucose-6-phosphate dehydrogenase within range, dapsone 50 mg/day was initiated. However, inflammation persisted for the following three months and an increase in the extension of symblepharon in OS was documented, warranting the decision to switch from dapsone to oral methotrexate at 15 mg/week and increase oral prednisone to 40 mg/day (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE). Remarkable clinical improvement was noted two months following the treatment modification, leading to the successful taper of oral prednisone. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eG, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eH).\u003c/p\u003e \u003cp\u003eAt the last follow-up visit, twenty-eight months after the initial consultation, ocular inflammation remained quiescent and discomfort subsided; however, severe meibomian gland dysfunction persisted. The patient remains on a treatment regimen that includes oral methotrexate 15 mg/week with folic acid supplementation, topical cyclosporine 0.05% twice a day, loteprednol etabonate 0.05% once a day, sodium hyaluronate 0.15% and trehalose 3% every 6 hours, dexpanthenol 5% every night, and prednisone 5 mg/day.\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eChildhood-onset MMP is a rare condition, documented in only 28 patients reported in the literature, including mostly females (n=19, 68%) with a median age at diagnosis ranging from 1 to 17 years [6]. However, an estimated delay in diagnosis of 2 months to 5 years has been recorded among children with the disease. The most frequently affected sites in pediatric patients included the oral cavity (n=18, 64%), followed by the conjunctiva (n=11, 39%), the genital mucosa (n=10, 35%), the skin (n=6, 21%), and the upper respiratory pathway (n=5, 62.5%) [7\u0026ndash;9]. Notably, only five patients presented isolated ocular disease [10\u0026ndash;13]. Moreover, all patients with skin affection also presented ocular manifestations [6\u0026ndash;9, 14\u0026ndash;16]. Two patients with oral mucous, skin, and ocular affection died; the cause of death was not available for one while the other patient died from tracheal stenosis associated with the disease [15, 16]. General characteristics of previously reported cases of childhood-onset MMP are displayed in Table 1 and Table 2. Likewise, tissue involvement in adults presents most commonly in the oral cavity (85%), followed by the conjunctiva (65%), nasopharynx (20-40%), skin (20-35%), genitalia (20%), and more rarely the esophagus and trachea (5-15%) [17]. \u0026nbsp;The prevalence of affected sites and features appears to be comparable to that of pediatric patients; however, genital involvement in children seems to be more prevalent than in adults.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Previously reported cases of childhood-onset MMP with ocular involvement.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"702\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eReference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)/sex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSystemic findings\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelay in diagnosis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCommentary\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJolliffe et al, 1977\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e13/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eOral, genital, skin\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e3-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e\n \u003cp\u003eTetracosactid Depot 1mg IM twice a week + Prednisolone 90 mg/day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRosenbaum et al, 1984\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e6/boy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eOral, genital, skin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e1-year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e\n \u003cp\u003eMethylprednisolone IV + Dapsone 2mg/kg/day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eResponse to first-line treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIglesias L et al, 1992\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e12/boy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e5-years\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e\n \u003cp\u003eDapsone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKanwar et al, 2006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e14/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eNasal, oral, laryngeal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e6-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e\n \u003cp\u003ePrednisolone 30mg/day + Dapsone 100mg/day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eCoeliac disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGamm D et al, 2006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e17/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eOral, tracheal, skin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e1-year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e\n \u003cp\u003ePrednisone + dapsone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eDeceased from tracheal stenosis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIovine A et al, 2008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e9/boy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eOral, genital, laryngeal, skin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e5-years\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e\n \u003cp\u003ePrednisolone 25 mg/day + Cyclosporine\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eBilateral corneal perforation\u003c/p\u003e\n \u003cp\u003eReconstructive surgery\u003c/p\u003e\n \u003cp\u003eDeceased\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKharfi M et al, 2010\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e1/boy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eOral, nasal, skin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e10-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e\n \u003cp\u003ePrednisone 2mg/kg/day + Dapsone 25mg/day for 3 years + topical cyclosporine every 6 hours for 3 years\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eBilateral corneal opacities\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLevallee A et al, 2013\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e12/girl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e2-years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e\n \u003cp\u003eDapsone 100 mg/day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003ePUK episode\u003c/p\u003e\n \u003cp\u003eRelapse after withdrawal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFlores-Climente et al, 2019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e2/boy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e6-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e1.Topical cyclosporine\u003cbr\u003e2. Prednisolone 1mg/kg/day + MMF 15mg/kg/day + cyclosporine 4mg/kg/day\u003cbr\u003e3. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Dapsone 2mg/kg/day\u003cbr\u003e4. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Rituximab 375 mg/m2 at 2‐week intervals\u0026nbsp;\u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eResponded to biologic therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePattnaik M et al, 2019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e14/girl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eOral, genital, nasal, skin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e6-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e1. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Prednisolone 1 mg/kg/day + Dapsone 2 mg/kg/day\u003cbr\u003e2. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Azathioprine 100mg/day\u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eResponded to second line treatment\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOllero et al, 2022\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e1/boy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e5-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e1. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Topical cyclosporine + botulinum toxin\u003cbr\u003e2. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Prednisolone steaglate + MMF\u003cbr\u003e3. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Cyclosporine\u0026nbsp;\u003cbr\u003e4. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Dapsone\u0026nbsp;\u003cbr\u003e5. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Rituximab\u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eResponded to biologic therapy\u003c/p\u003e\n \u003cp\u003eRequired reconstructive surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJitender MS et al, 2024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e13/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e1-year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e1. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Prednisolone 0.5 mg/kg/day + dexamethasone 0.1% eyedrops\u0026nbsp;\u003cbr\u003e2. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Azathioprine 50mg/day\u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eWell-controlled \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJitender MS et al, 2024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e16/girl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eOral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e2-years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e\n \u003cp\u003ePrednisolone 0.5 mg/kg/day + dexamethasone 0.1% eyedrops and azathioprine 50mg/day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eResidual corneal scarring\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.68091168091168%\" valign=\"top\" style=\"width: 11.7986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRamos-D\u0026aacute;vila et al, 2024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.695156695156695%\" valign=\"top\" style=\"width: 10.6475%;\"\u003e\n \u003cp\u003e12/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.965811965811966%\" valign=\"top\" style=\"width: 11.5108%;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.262108262108262%\" valign=\"top\" style=\"width: 9.7842%;\"\u003e\n \u003cp\u003e4-years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\" style=\"width: 35.3957%;\"\u003e1. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Prednisone 20 mg/day + topical cyclosporine + dapsone 25 mg/day\u003cbr\u003e2. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Prednisone 40 mg/day + Methotrexate 20mg/week + topical cyclosporine\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"22.507122507122507%\" valign=\"top\" style=\"width: 20.8633%;\"\u003e\n \u003cp\u003eResponded to methotrexate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*MMF, mycophenolate mofetil; mg, milligrams; kg, kilograms; m\u003csup\u003e2\u003c/sup\u003e, square meters; IM, intramuscular; IV; intravenous; PUK, peripheral ulcerative keratitis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003ePreviously reported cases of pediatric mucous membrane pemphigoid without ocular involvement\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"625\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eReference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years) / Sex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAffected sites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelay in diagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResponse\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRogers et al, 1981\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e4/girl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGenitalia\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e8-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBarnett et al, 1981\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e\u0026nbsp;13/boy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGingivitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e9-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eNon-specific steroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMoy et al, 1986\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e9/girl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGingivitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e4-years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003ePrednisone 40mg/day\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLaskaris et al, 1988\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e14/girl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGingivitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e2-years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eTopical 0.1% triamcinolone paste\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSklavounou et al, 1990\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e13/boy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGingivitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e1-year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eTopical 1.0 mg betamethasone/day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRoche C et al, 2009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e14/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGingivitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e4-month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eMouth rinse with triamcinolone and chlortetracycline + miconazole oral gel\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFarrell et al, 1999\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e14/girl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGenitalia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e9-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eTopical clobetasol propionate cream\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFarrell et al, 1999\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e8/girl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGenitalia and gingivitis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003ePrednisolone + dapsone + sulphapyridine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCheng et al, 2001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e8/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGingivitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e6-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eMouth rinse with 0.05% fluocinonide + 0.2% chlorhexidine\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSchoeffler et al, 2004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e9/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGenitalia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e4-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eClobetasol propionate cream + dapsone 1.5 mg/kg/day\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHoque et al, 2005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e7/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGenitalia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e9-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eClobetasol propionate cream\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLourenco et al, 2006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e4/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGingivitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e2-years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eDapsone 50 mg/day for 20 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMusa et al, 2002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e9/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGingivitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e8-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eTopical 0.05% fluocinonide gel switched to topical betamethasone. Poor compliance.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003ePoor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLebeau et al, 2004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e8/girl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGenitalia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e5-years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eTopical tacrolimus 0.1% for 9 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.64%\" valign=\"top\" style=\"width: 20.5502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMostafa et al, 2009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.96%\" valign=\"top\" style=\"width: 9.0615%;\"\u003e\n \u003cp\u003e6/boy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.96%\" valign=\"top\" style=\"width: 12.945%;\"\u003e\n \u003cp\u003eGingivitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.24%\" valign=\"top\" style=\"width: 10.356%;\"\u003e\n \u003cp\u003e1-year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.68%\" valign=\"top\" style=\"width: 35.4369%;\"\u003e\n \u003cp\u003eBetamethasone cream and 0.2% chlorhexidine wash switched to 0.05% fluocinonide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.52%\" valign=\"top\" style=\"width: 11.6505%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*NA, not available; mg, milligrams; kg, kilograms\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe diagnosis is challenging, compounded by the very low prevalence of the disease in pediatric patients. In this population, reaching diagnosis could be hampered by alternative etiologies for cicatricial conjunctivitis such as hemorrhagic adenoviral conjunctivitis with membrane formation, chlamydial /trachoma keratoconjunctivitis, severe vernal keratoconjunctivitis, and pediatric blepharokeratoconjunctivitis, among others [18]. Moreover, patients may present with a long history of using diverse and multiple topical eye drops and potentially be misdiagnosed as drug-induced conjunctivitis. Proper diagnosis requires concordance between clinical signs and the detection of anti-basement zone autoantibodies. These autoantibodies are tissue-bound, detected by DIF microscopy, or circulating when detected by indirect immunofluorescence (IIF) [17]. DIF showing linear IgG, IgA, and/or C3 deposits at the subepithelial BMZ and/or dermal-epidermal junction is strongly recommended as the major single diagnostic test for MMP [17, 19]. Nonetheless, inaccurate tissue management or collection, along with initially negative results during the early stages of the disease, can result in false-negative outcomes, thereby impeding the timely and accurate diagnosis [3, 11, 17]. Likewise, a previously reported case of ocular MMP in a 12-year-old girl presented a negative DIF result at the initial presentation, subsequently turning positive two years later [11]. The mentioned case was the only patient who manifested an episode of PUK, as in our report. Autoimmune diseases are responsible for nearly half of the non-infectious etiologies of PUK, with rheumatoid arthritis and granulomatosis with polyangiitis being the most frequently underlying diagnoses [20, 21]. Moreover, PUK has only been documented in two additional patients with MMP; the before-stated pediatric patient and an older adult woman developing PUK following cataract surgery [11, 22].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter diagnosis has been properly established, prompt treatment should be initiated. Dapsone (1.0-1.5 mg/kg/day) combined with oral cyclophosphamide (2 mg/kg/day), or corticosteroids (0.5-1.5 mg/kg/day) are the recommended treatment options in adults diagnosed with ocular MMP [5, 17]. Cyclophosphamide has been particularly associated with a prompt response and prolonged remission in patients with ocular involvement [17]. Other alternatives include azathioprine (1.5-2.0 mg/kg/day), methotrexate (7-15 mg/week), mycophenolate mofetil (2 g/day), or sodium mycophenolic acid (1,440 mg/day) [17, 23]. Biologic therapy, such as rituximab (375 mg/m\u003csup\u003e2\u003c/sup\u003e weekly for 4 weeks or 1,000mg twice every 2 weeks) is usually reserved for refractory cases of severe MMP [17, 24]. Treatment in children is hindered by the extensive side effects of the drugs mentioned above and the lack of standardized regimens for MMP in this demographic. Prior cases of pediatric MMP included cyclosporine (4 mg/kg/day) in the treatment regimen; however, two out of three patients receiving this drug were unresponsive and required switching to another agent [12, 13, 15]. Interestingly, none of the prior cases were treated with methotrexate, an antimetabolite extensively studied in the pediatric population for other immune-mediated diseases, rendering an acceptable safety profile [23, 25\u0026ndash;27]. The patient in our report presents the first case of pediatric ocular MMP successfully treated with methotrexate (15 mg/week). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePediatric MMP with ocular involvement is a rare condition that seems to share clinical features with the adult counterpart, albeit with a relatively more indolent evolution. Timely diagnosis and treatment are warranted but remain challenging. \u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eLiterature search\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors conducted an extensive literature search using the National Library of Medicine\u0026rsquo;s PubMed and Google Scholar databases for all articles published until October 2023. The following search terms were used: \u0026ldquo;mucous membrane pemphigoid\u0026rdquo;, \u0026ldquo;ocular cicatricial pemphigoid,\u0026rdquo; \u0026ldquo;pemphigoid\u0026rdquo;, \u0026ldquo;pediatric\u0026rdquo;, \u0026ldquo;childhood\u0026rdquo;, \u0026ldquo;child\u0026rdquo;, \u0026ldquo;boy\u0026rdquo;, \u0026ldquo;girl\u0026rdquo;, \u0026ldquo;infant,\u0026rdquo; \u0026ldquo;\u0026rdquo;. Case reports, case series, letters to the editor, review articles, and original articles were included. Relevant references within articles found were also included.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e Ethics approval for this study was waived by the Ethics Committee of the Instituto Tecnologico de Monterrey as it does not meet the criteria for research and was approved as a quality assurance study. This study was conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eConsent for publication was obtained from the patient\u0026rsquo;s guardian.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u0026nbsp;\u003c/strong\u003eNot applicable\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNone to declare\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003eEMRD and RERL participated in the writing and data collection of the manuscript. ARG and CAG have substantively revised the work. All authors have approved the submitted version of this manuscript.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTaurone S, Spoletini M, Ralli M, Gobbi P, Artico M, Imre L, Czak\u0026ograve; C, Kov\u0026agrave;cs I, Greco A, Micera A (2019) Ocular mucous membrane pemphigoid: a review. Immunol Res 67:280\u0026ndash;289. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s12026-019-09087-7\u003c/span\u003e\u003cspan address=\"10.1007/s12026-019-09087-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan LS, Ahmed AR, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ, Fine J-D, Foster CS, Ghohestani R, Hashimoto T, Hoang-Xuan T, Kirtschig G, Korman NJ, Lightman S, Lozada-Nur F, Marinkovich MP, Mondino BJ, Prost-Squarcioni C III, Setterfield RSR, West JF, Wojnarowska DP, Woodley F, Yancey DT, Zillikens KB, Zone D JJ (2002) The First International Consensus on Mucous Membrane Pemphigoid: Definition, Diagnostic Criteria, Pathogenic Factors, Medical Treatment, and Prognostic Indicators. Arch Dermatol 138:370\u0026ndash;379. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/archderm.138.3.370\u003c/span\u003e\u003cspan address=\"10.1001/archderm.138.3.370\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMargolis T (2018) Evidence-Based Insights into the Utility of Conjunctival Biopsy in Mucous Membrane Pemphigoid. Ophthalmology 125:474\u0026ndash;475. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ophtha.2018.01.014\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2018.01.014\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOng HS, Setterfield JF, Minassian DC, Dart JK, 2009\u0026ndash;2014 MMPSG, Booth D, Reid E, Carnt N, Gugliemetti S, Shanmuganathan V, Watson M, Saw V, Wilkins M, McCudden V, Ahmad S, Calder V, Waseem N, Scott B, Bunce C, Gage W, Gleeson M, Lund V, Sandhu G (2018) Mucous Membrane Pemphigoid with Ocular Involvement The Clinical Phenotype and Its Relationship to Direct Immunofluorescence Findings. Ophthalmology 125:496\u0026ndash;504. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ophtha.2017.10.004\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2017.10.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmidt E, Rashid H, Marzano AV, Lamberts A, Zenzo GD, Diercks GFH, Alberti-Violetti S, Barry RJ, Borradori L, Caproni M, Carey B, Carrozzo M, Cianchini G, Corr\u0026agrave; A, Dikkers FG, Feliciani C, Geerling G, Genovese G, Hertl M, Joly P, Meijer JM, Mercadante V, Murrell DF, Ormond M, Pas HH, Patsatsi A, Rauz S, Rhijn BD, Roth M, Setterfield J, Zillikens D, C.Prost, Zambruno G, Horv\u0026aacute;th B, Caux F (2021) European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology \u0026ndash; Part II. J Eur Acad Dermatol Venereol 35:1926\u0026ndash;1948. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jdv.17395\u003c/span\u003e\u003cspan address=\"10.1111/jdv.17395\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJinagal J, Gupta B, Hanumanthu V, Chatterjee D, Limbu S, Malhotra C, Gupta A, Jain AK, Yangzes S, Mahajan R, Handa S, Pandav SS, De D (2024) Ocular Cicatricial Pemphigoid in Young Patients. Cornea. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/ico.0000000000003547\u003c/span\u003e\u003cspan address=\"10.1097/ico.0000000000003547\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRosenbaum MM, Esterly NB, Greenwald MJ, Gerson CR (1984) Cicatricial Pemphigoid in a 6-Year‐Old Child: Report of a Case and Review of the Literature. Pediatr Dermatol 2:13\u0026ndash;22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1525-1470.1984.tb00435.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1525-1470.1984.tb00435.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKharfi M, Khaled A, Anane R, Fazaa B, Kamoun MR (2010) Early Onset Childhood Cicatricial Pemphigoid: A Case Report and Review of the Literature. Pediatr Dermatol 27:119\u0026ndash;124. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1525-1470.2009.01079.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1525-1470.2009.01079.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePattnaik M, Panda M, Dash M, Raj C (2019) A rare case of childhood mucous membrane pemphigoid involving both skin and mucosa. Indian J Paediatr Dermatol 20:160. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4103/ijpd.ijpd_71_18\u003c/span\u003e\u003cspan address=\"10.4103/ijpd.ijpd_71_18\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIglesias LS, Quismorio FP, McDonnell PJ, Barnes C (1992) Ocular Cicatricial Pemphigoid in a Twelve-Year-Old Boy. Cornea 11:365\u0026ndash;367. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/00003226-199207000-00018\u003c/span\u003e\u003cspan address=\"10.1097/00003226-199207000-00018\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLavall\u0026eacute;e A, Bourret-Massicotte D, Laughrea PA (2013) Childhood Mucous Membrane Pemphigoid. Cornea 32:1399\u0026ndash;1401. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/ico.0b013e3182a0ce6e\u003c/span\u003e\u003cspan address=\"10.1097/ico.0b013e3182a0ce6e\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlores-Climente V, Rozas‐Mu\u0026ntilde;oz E, Mart\u0026iacute;nez‐Grau A, Aucouturier F, Luna S, Baselga E (2019) Childhood ocular mucous membrane pemphigoid successfully treated with rituximab. Pediatr Dermatol 36:984\u0026ndash;985. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/pde.13971\u003c/span\u003e\u003cspan address=\"10.1111/pde.13971\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOllero R, Soldevila A, Paz MF, de la, Mart\u0026iacute;nez-Grau A (2022) Surgical Management of Ocular Cicatricial Pemphigoid in a Pediatric Patient. Cornea 41:911\u0026ndash;913. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/ico.0000000000002932\u003c/span\u003e\u003cspan address=\"10.1097/ico.0000000000002932\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJOLLIFFE DS, SIM-DAVIS D (1977) Clinical meeting of the St John\u0026rsquo;s Hospital Dermatological Society: 4 November 1976 Cicatricial pemphigoid in a young girl: report of a case. Clin Exp Dermatol 2:281\u0026ndash;284. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1365-2230.1977.tb02570.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1365-2230.1977.tb02570.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIovine A, Fimiani F, Vassallo P, Alessio M, Magli A (2008) Ocular Manifestations in a Case of Childhood Cicatricial Pemphigoid. Eur J Ophthalmol 18:636\u0026ndash;638. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1177/112067210801800424\u003c/span\u003e\u003cspan address=\"10.1177/112067210801800424\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGamm DM, Harris A, Mehran RJ, Wood M, Foster CS, Mootha VV (2006) Mucous Membrane Pemphigoid With Fatal Bronchial Involvement in a Seventeen-Year-Old Girl. Cornea 25:474\u0026ndash;478. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/01.ico.0000178730.34564.c7\u003c/span\u003e\u003cspan address=\"10.1097/01.ico.0000178730.34564.c7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDu G, Patzelt S, van Beek N, Schmidt E (2022) Mucous membrane pemphigoid. Autoimmun Rev 21:103036. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.autrev.2022.103036\u003c/span\u003e\u003cspan address=\"10.1016/j.autrev.2022.103036\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVazirani J, Donthineni PR, Goel S, Sane SS, Mahuvakar S, Narang P, Shanbhag SS, Basu S (2020) Chronic cicatrizing conjunctivitis: A review of the differential diagnosis and an algorithmic approach to management. Indian J Ophthalmol 68:2349\u0026ndash;2355. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4103/ijo.ijo_604_20\u003c/span\u003e\u003cspan address=\"10.4103/ijo.ijo_604_20\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJain N, Jakati S, Shanbhag SS, Basu S (2023) Direct Immunofluorescence Findings and Factors Affecting Conjunctival Biopsy Positivity in Ocular Mucous Membrane Pemphigoid. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/ico.0000000000003382\u003c/span\u003e\u003cspan address=\"10.1097/ico.0000000000003382\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Cornea\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHassanpour K, ElSheikh RH, Arabi A, Frank CR, Elhusseiny AM, Eleiwa TK, Arami S, Djalilian AR, Kheirkhah A (2022) Peripheral Ulcerative Keratitis: A Review. J Ophthalmic Vis Res (JOVR) 17:252\u0026ndash;275. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.18502/jovr.v17i2.10797\u003c/span\u003e\u003cspan address=\"10.18502/jovr.v17i2.10797\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRuiz-Lozano RE, Ramos-Davila EM, Garza-Garza LA, Gutierrez-Juarez K, Hernandez-Camarena JC, Rodriguez-Garcia A (2023) Rheumatoid arthritis-associated peripheral ulcerative keratitis outcomes after early immunosuppressive therapy. Br J Ophthalmol 107:1246\u0026ndash;1252. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/bjophthalmol-2022-321132\u003c/span\u003e\u003cspan address=\"10.1136/bjophthalmol-2022-321132\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKiire CA, Srinivasan S, Inglis A (2011) Peripheral Ulcerative Keratitis After Cataract Surgery in a Patient With Ocular Cicatricial Pemphigoid. Cornea 30:1176\u0026ndash;1178. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/ico.0b013e3182141baa\u003c/span\u003e\u003cspan address=\"10.1097/ico.0b013e3182141baa\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYou C, Ma L, Anesi SD, Foster CS (2017) Long-term remission of ocular cicatricial pemphigoid off immunomodulatory therapy. Eur J Ophthalmol 28:157\u0026ndash;162. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5301/ejo.5001050\u003c/span\u003e\u003cspan address=\"10.5301/ejo.5001050\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFoster CS, Chang PY, Ahmed AR (2010) Combination of Rituximab and Intravenous Immunoglobulin for Recalcitrant Ocular Cicatricial Pemphigoid A Preliminary Report. Ophthalmology 117:861\u0026ndash;869. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ophtha.2009.09.049\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2009.09.049\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCluskey P, Chang JH, Singh R, Wakefield D (2004) Methotrexate therapy for ocular cicatricial pemphigoid. Ophthalmology 111:796\u0026ndash;801. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ophtha.2003.07.010\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2003.07.010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerrara G, Mastrangelo G, Barone P, Torre FL, Martino S, Pappagallo G, Ravelli A, Taddio A, Zulian F, Cimaz R, Group O behalf of the RIS (2018) Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting. Pediatr Rheumatol 16:46. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12969-018-0255-8\u003c/span\u003e\u003cspan address=\"10.1186/s12969-018-0255-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuti\u0026eacute;rrez-Su\u0026aacute;rez R, Burgos-Vargas R (2010) The use of methotrexate in children with rheumatic diseases. Clin Exp Rheumatol 28:S122\u0026ndash;S127\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-ophthalmic-inflammation-and-infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joii","sideBox":"Learn more about [Journal of Ophthalmic Inflammation and Infection](http://joii-journal.springeropen.com)","snPcode":"12348","submissionUrl":"https://submission.nature.com/new-submission/12348/3","title":"Journal of Ophthalmic Inflammation and Infection","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4457273/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4457273/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe purpose of this study was to describe the case of a pediatric patient diagnosed with mucous membrane pemphigoid (MMP) with exclusive ocular involvement presenting at diagnosis with peripheral ulcerative keratitis and provide a review of the literature.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA 12-year-old girl presented with cicatricial conjunctivitis and peripheral ulcerative keratitis (PUK). A conjunctival biopsy and direct immunofluorescence revealed linear deposits of IgG, IgM, and C3 at the basement membrane zone, confirming a diagnosis of ocular MMP.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe patient was initially treated with dapsone 25 mg/day and prednisone 40 mg/day along with topical treatment including cyclosporine 0.05%, loteprednol etabonate 0.05%, and sodium hyaluronate 0.15% and trehalose 3%. Inflammation persisted as an increase in the extension of symblepharon was documented. Subsequently, dapsone was switched to oral methotrexate 15 mg/week and prednisone was successfully tapered to 5 mg/day. After three years of follow-up, disease activity remained quiescent.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePediatric mucous membrane pemphigoid with ocular involvement is a rare condition of which few reports have been published, resulting in scarce information regarding its clinical course and response to treatment. We report the first case observed in a Hispanic patient, opening with peripheral ulcerative keratitis, and responding successfully to methotrexate.\u003c/p\u003e","manuscriptTitle":"Childhood-Onset Ocular Mucous Membrane Pemphigoid Presenting with Peripheral Ulcerative Keratitis: A Case Report and Review of the Literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-10 22:55:18","doi":"10.21203/rs.3.rs-4457273/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-24T19:34:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-31T01:38:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"175992739536275312557507875263158395817","date":"2024-08-21T11:15:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-17T17:44:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-22T07:33:56+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-22T07:33:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Ophthalmic Inflammation and Infection","date":"2024-05-21T23:04:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ophthalmic-inflammation-and-infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joii","sideBox":"Learn more about [Journal of Ophthalmic Inflammation and Infection](http://joii-journal.springeropen.com)","snPcode":"12348","submissionUrl":"https://submission.nature.com/new-submission/12348/3","title":"Journal of Ophthalmic Inflammation and Infection","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"37aea4f6-cccd-459a-804e-6f48f5039f2e","owner":[],"postedDate":"June 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-02T16:08:40+00:00","versionOfRecord":{"articleIdentity":"rs-4457273","link":"https://doi.org/10.1186/s12348-025-00480-y","journal":{"identity":"journal-of-ophthalmic-inflammation-and-infection","isVorOnly":false,"title":"Journal of Ophthalmic Inflammation and Infection"},"publishedOn":"2025-05-29 15:57:34","publishedOnDateReadable":"May 29th, 2025"},"versionCreatedAt":"2024-06-10 22:55:18","video":"","vorDoi":"10.1186/s12348-025-00480-y","vorDoiUrl":"https://doi.org/10.1186/s12348-025-00480-y","workflowStages":[]},"version":"v1","identity":"rs-4457273","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4457273","identity":"rs-4457273","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}