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• W3213369522 abstract "To the Editor: Pemphigus encompasses a group of autoimmune blistering skin conditions caused by the loss of intraepidermal adhesions.1Fuertes I. Guilabert A. Mascaró Jr., J.M. Iranzo P. Rituximab in childhood pemphigus vulgaris: a long-term follow-up case and review of the literature.Dermatology. 2010; 221: 13-16Google Scholar Although it is proposed that 1.4% to 2.9% of all pemphigus vulgaris cases present in pediatric patients, there is a lack of synthesized data regarding the use of rituximab in this population.1Fuertes I. Guilabert A. Mascaró Jr., J.M. Iranzo P. Rituximab in childhood pemphigus vulgaris: a long-term follow-up case and review of the literature.Dermatology. 2010; 221: 13-16Google Scholar We performed a systematic review examining the safety and efficacy of rituximab in pediatric patients with pemphigus. We searched EMBASE, PubMed, Web of Science, and Google Scholar databases using the terms “pemphigus AND rituximab” from database inception to May 2, 2021. Two reviewers independently performed title and abstract screening followed by full-text review using the Covidence systematic review software. Original studies utilizing rituximab for the treatment of a pemphigus condition in a pediatric (≤17 years) patient were included. Study and patient characteristics, as well as preceding and concomitant treatments are detailed in Table I.1Fuertes I. Guilabert A. Mascaró Jr., J.M. Iranzo P. Rituximab in childhood pemphigus vulgaris: a long-term follow-up case and review of the literature.Dermatology. 2010; 221: 13-16Google Scholar, 2Bilgic-Temel A. Özgen Z. Harman M. Kapıcıoğlu Y. Uzun S. Rituximab therapy in pediatric pemphigus patients: a retrospective analysis of five Turkish patients and review of the literature.Pediatr Dermatol. 2019; 36: 646-650Google Scholar, 3Connelly E.A. Aber C. Kleiner G. Nousari C. Charles C. Schachner L.A. Generalized erythrodermic pemphigus foliaceus in a child and its successful response to rituximab treatment.Pediatr Dermatol. 2007; 24: 172-176Google Scholar, 4Didona D. Paolino G. Donati M. Caposeina D. Calvieri S. Didona B. Resolution of a case of pediatric pemphigus vulgaris treated with rituximab.Acta Dermatovenerol Croat. 2014; 22: 288-290Google Scholar, 5Kanwar A.J. Sawatkar G.U. Vinay K. Hashimoto T. Childhood pemphigus vulgaris successfully treated with rituximab.Indian J Dermatol Venereol Leprol. 2012; 78: 632-634Google Scholar, 6Kanwar A.J. Tsuruta D. Vinay K. et al.Efficacy and safety of rituximab treatment in Indian pemphigus patients.J Eur Acad Dermatol Venereol. 2013; 27: e17-e23Google Scholar, 7Kianfar N. Dasdar S. Mahmoudi H. Tavakolpour S. Balighi K. Daneshpazhooh M. Rituximab in childhood and juvenile autoimmune bullous diseases as first-line and second-line treatment: a case series of 13 patients.J Dermatolog Treat. 2020; : 1-6Google Scholar, 8Kincaid L. Weinstein M. Rituximab therapy for childhood pemphigus vulgaris.Pediatr Dermatol. 2016; 33: e61-e64Google Scholar, 9Kong H.H. Prose N.S. Ware R.E. Hall III, R.P. Successful treatment of refractory childhood pemphgus vulgaris with anti-CD20 monoclonal antibody (rituximab).Pediatr Dermatol. 2005; 22: 461-464Google Scholar, 10Kong Y.L. Lim Y.L. Chandran N.S. Retrospective study on autoimmune blistering disease in paediatric patients.Pediatr Dermatol. 2015; 32: 845-852Google Scholar, 11Loh T.Y. Paravar T. Rituximab in the management of juvenile pemphigus foliaceus.Dermatol Online J. 2017; 23 (13030/qt0415n1r5)Google Scholar, 12Mamelak A.J. Eid M.P. Cohen B.A. Anhalt G.J. Rituximab therapy in severe juvenile pemphigus vulgaris.Cutis. 2007; 80: 335-340Google Scholar, 13Reguiai Z. Tabary T. Maizières M. Bernard P. Rituximab treatment of severe pemphigus: long-term results including immunologic follow-up.J Am Acad Dermatol. 2012; 67: 623-629Google Scholar, 14Sakhiya J. Sakhiya D. Khambhati R. et al.Modified rheumatoid arthritis protocol for rituximab in pemphigus: a retrospective case series.J Clin Aesthet Dermatol. 2020; 13: 47-52Google Scholar, 15Schmidt E. Herzog S. Bröcker E.B. Zillikens D. Goebeler M. Long-standing remission of recalcitrant juvenile pemphigus vulgaris after adjuvant therapy with rituximab.Br J Dermatol. 2005; 153: 449-451Google Scholar, 16Vinay K. Kanwar A.J. Sawatkar G.U. Dogra S. Ishii N. Hashimoto T. Successful use of rituximab in the treatment of childhood and juvenile pemphigus.J Am Acad Dermatol. 2014; 71: 669-675Google Scholar Sixteen studies containing 43 patients (36 with pemphigus vulgaris and 7 with pemphigus foliaceous) were included. The patients were aged from 1.75 to 17 years, with a mean duration of disease of 2 years. Complete resolution was reported in 77% of patients, 21% experienced partial resolution, and 1 patient died of sepsis-related complications without response assessment. The most common adverse events were infusion reaction (fever, dyspnea, rigor, tachycardia, and chills; 18%), angioedema (7%), reduction in peripheral B-cell counts (5%), and the onset of sepsis (5%).Table ICharacteristics of the studies and patientsStudy type/No. of patients/CountryPatientRituximabOutcomeAge/sexDuration (years)Preceding systemic treatmentsConcomitant systemic CCSDoseFrequencyNo. of infusionsCumulative doseAdverse eventsTreatment assessmentTime of treatment assessment (months)Follow-up period (months)Retrospective cohort study/5/Turkey2Bilgic-Temel A. Özgen Z. Harman M. Kapıcıoğlu Y. Uzun S. Rituximab therapy in pediatric pemphigus patients: a retrospective analysis of five Turkish patients and review of the literature.Pediatr Dermatol. 2019; 36: 646-650Google Scholar16/M1MP, AZAYes1000 mgEvery 15 days22000 mgNoneCR126014/M3MP, AZA, dapsone, MMF, IVIGNo1000 mgEvery 15 days22000 mgNonePR124913/M4MMF, MP, AZA, dapsoneNo1000 mgEvery 15 days22000 mgNonePR12609/F4MP, AZA, IVIG, dapsoneYes500 mgEvery 15 days21000 mgNoneCR122510/F1MP, IVIGYes375 mg/m2WeeklyNRNRNoneCR1219Case report/1∗Diagnosed with pemphigus foliaceous./United States3Connelly E.A. Aber C. Kleiner G. Nousari C. Charles C. Schachner L.A. Generalized erythrodermic pemphigus foliaceus in a child and its successful response to rituximab treatment.Pediatr Dermatol. 2007; 24: 172-176Google Scholar1.75/F∗Diagnosed with pemphigus foliaceous.NRMP, IVIGYes375 mg/m2Weekly124500 mg/m2NoneCR33Case report/1/Italy4Didona D. Paolino G. Donati M. Caposeina D. Calvieri S. Didona B. Resolution of a case of pediatric pemphigus vulgaris treated with rituximab.Acta Dermatovenerol Croat. 2014; 22: 288-290Google Scholar11/M0.8PRED, IVIGNo375 mg/m218 days apart2750 mg/m2NonePR1010Case report/1/Spain1Fuertes I. Guilabert A. Mascaró Jr., J.M. Iranzo P. Rituximab in childhood pemphigus vulgaris: a long-term follow-up case and review of the literature.Dermatology. 2010; 221: 13-16Google Scholar14M9MP, PRED, cyclosporine, AZA, dapsone, oral goldYes375 mg/m2Weekly41500 mg/m2NoneCR112Case report/1/India and Japan5Kanwar A.J. Sawatkar G.U. Vinay K. Hashimoto T. Childhood pemphigus vulgaris successfully treated with rituximab.Indian J Dermatol Venereol Leprol. 2012; 78: 632-634Google Scholar11/M0.3DP, PSL, AZAYes375 mg/m2Every 15 days2750 mg/m2NoneCR88Prospective cohort study/2/India and Japan6Kanwar A.J. Tsuruta D. Vinay K. et al.Efficacy and safety of rituximab treatment in Indian pemphigus patients.J Eur Acad Dermatol Venereol. 2013; 27: e17-e23Google Scholar9/M0.5DP, AZA, PSLYes375 mg/m2Every 15 days2750 mg/m2Angioedema during infusionCR2.2511.517/M0.75DCP, CP, PSLYes1000 mgEvery 15 days22000 mgSepsisDied due to sepsis-related complicationsNRNRCase series/12/Iran7Kianfar N. Dasdar S. Mahmoudi H. Tavakolpour S. Balighi K. Daneshpazhooh M. Rituximab in childhood and juvenile autoimmune bullous diseases as first-line and second-line treatment: a case series of 13 patients.J Dermatolog Treat. 2020; : 1-6Google Scholar14/M3.08PSL, AZA, MMFNo500 mgEvery 15 days42000 mgNoneCR1610314/F2.5PSL, AZANo500 mgEvery 15 days42000 mgChills and feverCR151814/F0NoneYes500 mgEvery 15 days42000 mgNonePR1528.516/F0NoneYes500 mgEvery 15 days42000 mgFeverCR155817/M0.08NoneYes500 mgEvery 15 days42000 mgDyspneaCR565716/F1.3PSL, AZANo500 mgEvery 15 days42000 mgDyspnea, rigor, tachycardiaPR335116/F0.6PSL, AZA, MMFNo500 mgEvery 15 days42000 mgNoneCR2710217/F0.08NoneYes500 mgEvery 15 days42000 mgNoneCR2951.516/F0.8PSLNo500 mgEvery 15 days42000 mgDyspneaCR24511/M0.3PSL, AZAYes500 mgEvery 15 days21000 mgFever, infectionCR39714/F∗Diagnosed with pemphigus foliaceous.0.08NoneYes500 mgEvery 15 days42000 mgNonePR162516/M∗Diagnosed with pemphigus foliaceous.0.08NoneYes500 mgEvery 15 days42000 mgHeadacheCR555Case report/1/Canada8Kincaid L. Weinstein M. Rituximab therapy for childhood pemphigus vulgaris.Pediatr Dermatol. 2016; 33: e61-e64Google Scholar4/F0.16PRED, IVIG, AZAYes, and AZA375 mg/m2Every 15 days2750 mg/m2Infusion reaction (urticaria and low-grade fever)CR212Case report/1/United States9Kong H.H. Prose N.S. Ware R.E. Hall III, R.P. Successful treatment of refractory childhood pemphgus vulgaris with anti-CD20 monoclonal antibody (rituximab).Pediatr Dermatol. 2005; 22: 461-464Google Scholar17/F7AZA, PRED, MP, MMF, IVIG, PPYes375 mg/m2Every 15 days41500 mg/m2Five days after the first infusion, CD20 B cells decreased from 3.2% to 0.2% and CD19 B cells decreased from 3.7% to undetectable. After 4 infusions, CD20 B cells remained at 0.2% and CD19 B cells were 0.1%CR1717Retrospective cohort study/1/Singapore10Kong Y.L. Lim Y.L. Chandran N.S. Retrospective study on autoimmune blistering disease in paediatric patients.Pediatr Dermatol. 2015; 32: 845-852Google Scholar9/MNRMMF, AZA, PSL, MTXNR700 mg/m2Every 2 weeks21400 mg/m2Neutropenic sepsisCR2525Case report/1/United States11Loh T.Y. Paravar T. Rituximab in the management of juvenile pemphigus foliaceus.Dermatol Online J. 2017; 23 (13030/qt0415n1r5)Google Scholar17/M∗Diagnosed with pemphigus foliaceous.0.83AZA, doxycycline, PREDYes375 mg/m2Every 15 days2750 mg/m2NonePR33Case series/2/United States12Mamelak A.J. Eid M.P. Cohen B.A. Anhalt G.J. Rituximab therapy in severe juvenile pemphigus vulgaris.Cutis. 2007; 80: 335-340Google Scholar16/FNRIMC, PRED, MMF, AZA, IVIGNo, and PP375 mg/m2Weekly83000 mg/m2NoneCR6616/F2PRED, MMF, PPNo, IVIG added after375 mg/m2Weekly41500 mg/m2NonePR33Retrospective cohort study/2/France13Reguiai Z. Tabary T. Maizières M. Bernard P. Rituximab treatment of severe pemphigus: long-term results including immunologic follow-up.J Am Acad Dermatol. 2012; 67: 623-629Google Scholar14/FNRSCS, IVIGYes375 mg/m2Weekly2750 mg/m2NoneCR62624/M∗Diagnosed with pemphigus foliaceous.NRSCS, dapsoneYes375 mg/m2Weekly1375 mg/m2NoneCR2323Retrospective cohort study/1/India14Sakhiya J. Sakhiya D. Khambhati R. et al.Modified rheumatoid arthritis protocol for rituximab in pemphigus: a retrospective case series.J Clin Aesthet Dermatol. 2020; 13: 47-52Google Scholar17/M6PRED, AZAYes1000 mgEvery 15 days33000 mgFatigueCR1240Case report/1/Germany15Schmidt E. Herzog S. Bröcker E.B. Zillikens D. Goebeler M. Long-standing remission of recalcitrant juvenile pemphigus vulgaris after adjuvant therapy with rituximab.Br J Dermatol. 2005; 153: 449-451Google Scholar14/M2.5PSL, AZA, dapsone, SPAIP, MMF, CP, MP, IVIGYes, and MMF, IVIG375 mg/m2Weekly31125 mg/m2Circulating B cells became undetectable within 2 weeks after the first infusionCR924Retrospective cohort study/10/India and Japan16Vinay K. Kanwar A.J. Sawatkar G.U. Dogra S. Ishii N. Hashimoto T. Successful use of rituximab in the treatment of childhood and juvenile pemphigus.J Am Acad Dermatol. 2014; 71: 669-675Google Scholar9/M0.5AZA, SCS, DPYes375 mg/m2Weekly2750 mg/m2AngioedemaCR4.53611/M1AZA, SCS, DPYes375 mg/m2Weekly2750 mg/m2Infusion reactionCR4.5816/M3AZA, SCS, DP, MTXYes500 mgWeekly21000 mgNoneCR62017/M1AZA, SCS, DP, MMFYes500 mgWeekly21000 mgNoneCR41917/M7SCSYes500 mgWeekly21000 mgInfusion reactionCR41817/F3SCSYes500 mgWeekly21000 mgNoneCR5.51713/M∗Diagnosed with pemphigus foliaceous.3AZA, SCS, DPYes500 mgWeekly21000 mgNoneCR71513/F1AZA, SCSYes500 mgWeekly21000 mgURTICR51412/M2.5AZA, SCSYes500 mgWeekly21000 mgAngioedemaCR21212/M∗Diagnosed with pemphigus foliaceous.3SCSYes500 mgWeekly21000 mgNonePR3.58AZA, Azathioprine; CCS, corticosteroid; CP, cyclophosphamide; CR, complete resolution; DCP, dexamethasone cyclophosphamide pulse; DP, dexamethasone pulse; IMC, intramuscular corticosteroids; IVIG, intravenous immunoglobulin; MMF, mycophenolate mofetil; MP, methylprednisolone; MTX, methotrexate; NR, not reported; PP, plasmapheresis; PR, partial resolution; PRED, prednisone; PSL, prednisolone; SCS, systemic corticosteroids; SPAIP, Staphylococcal protein A immunoadsorptions in combination with prednisolone; URTI, upper respiratory tract infection.∗ Diagnosed with pemphigus foliaceous. Open table in a new tab AZA, Azathioprine; CCS, corticosteroid; CP, cyclophosphamide; CR, complete resolution; DCP, dexamethasone cyclophosphamide pulse; DP, dexamethasone pulse; IMC, intramuscular corticosteroids; IVIG, intravenous immunoglobulin; MMF, mycophenolate mofetil; MP, methylprednisolone; MTX, methotrexate; NR, not reported; PP, plasmapheresis; PR, partial resolution; PRED, prednisone; PSL, prednisolone; SCS, systemic corticosteroids; SPAIP, Staphylococcal protein A immunoadsorptions in combination with prednisolone; URTI, upper respiratory tract infection. We found evidence to support the efficacy of rituximab for the treatment of pediatric pemphigus. All but 1 patient experienced disease improvement, and the majority achieved complete resolution. Most adverse events were mild and did not require treatment discontinuation. Two patients developed B-cell depletion. However, neither experienced subsequent infection or sepsis. There is limited evidence to suggest that the long-term absence of B cells in patients with rheumatoid arthritis treated with rituximab increases the risk of malignancy or infection.17Chen D.R. Cohen P.L. Living life without B cells: is repeated B-cell depletion a safe and effective long-term treatment plan for rheumatoid arthritis?.Int J Clin Rheumtol. 2012; 7: 159-166Google Scholar Children also appear to be at increased risk of hypogammaglobulinemia with rituximab compared with adults.18Khojah A.M. Miller M.L. Klein-Gitelman M.S. et al.Rituximab-associated hypogammaglobulinemia in pediatric patients with autoimmune diseases.Pediatr Rheumatol Online J. 2019; 17: 61Google Scholar Two patients developed sepsis, which is one of the most common causes of death in pemphigus patients. One patient on concomitant immunosuppressant therapy developed neutropenic sepsis but recovered following the administration of subcutaneous granulocyte-macrophage colony-stimulating factor.10Kong Y.L. Lim Y.L. Chandran N.S. Retrospective study on autoimmune blistering disease in paediatric patients.Pediatr Dermatol. 2015; 32: 845-852Google Scholar Another patient died of Staphylococcus aureus–positive sepsis 1 week after drug initiation (concomitant immunosuppression was not reported).6Kanwar A.J. Tsuruta D. Vinay K. et al.Efficacy and safety of rituximab treatment in Indian pemphigus patients.J Eur Acad Dermatol Venereol. 2013; 27: e17-e23Google Scholar The management of pemphigus vulgaris with rituximab in adults typically follows either the rheumatoid arthritis protocol (two 1000-mg infusions at 2-week intervals) or the lymphoma protocol (4 weekly infusions of 375 mg/m2). Our review demonstrates considerable heterogeneity in rituximab dosing regimens when prescribed for pediatric patients. This heterogeneity precluded our ability to perform a meta-analysis and to provide data in selecting the most effective dosing schedules for pediatric patients. Limitations of this review include the small number of patients and incomplete data reporting in some studies, as well as the potential for bias. Through its targeting of autoreactive B cells in pemphigus, rituximab appears to be a promising new therapy for pediatric pemphigus. However, long-term clinical follow-up is needed to conclude the safety of rituximab in the pediatric population reasonably and to determine the optimal dosage and frequency of rituximab cycles and the length of maintenance therapy. None disclosed." @default.
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• W3213369522 title "Efficacy of rituximab in pediatric pemphigus: A literature review" @default.
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