Development of morphea in patients receiving biologic therapies: A systematic review

To the Editor: An infrequently reported cutaneous complication of biologic treatment is onset localized scleroderma or morphea. Given increasing use therapy worldwide, it essential for health care providers to anticipate and manage potential adverse effects. This review aims summarize reports morphea development in patients receiving therapies targeting inflammatory pathways implicated psoriasis. EMBASE MEDLINE search was conducted on May 8, 2020, accordance with PRISMA guidelines, using key words “biologic” specific psoriasis AND “morphea” (Supplemental Tables I II available via Mendeley at 10.17632/bjgghsp5gn.2). Of 262 records identified, 9 studies met inclusion criteria a total mean age 45.5 years were added (Table I, Fig 1). Men accounted 44% cases (n = 4) women 56% 5). Overall, while tumor necrosis factor α inhibitors 7 (adalimumab, n 4; etanercept, 2; golimumab, 1) interleukin (IL) 12 23 antagonists 2 (ustekinumab, 2). these patients, 6 had plaque, 1 pansclerotic, linear morphea, not reported. Their location included legs, upper extremities, chest, abdomen, trunk, back.Table ISummary biologicsStudy characteristics demographic informationBiologic informationPatient characteristicsCharacteristics morpheaMorphea resolutionSourcesAge (y)/sexDrugBiologic mechanismDose frequencyIndicationComorbiditiesOther medications (dose frequency)Latency period (months)Morphea typeNo. lesionsMorphea present injection siteLocationTreatment (dose, frequency)Postdiagnosis follow-up (months)Complete (CR) partial (PR) resolutionMorphea course (months)Potential reason resolution145/MEtanerceptTNF-α inhibitor50 mg twice weekly 3 mo, followed by once-weekly moPsoriasisNRNR18PlaqueMultipleYesRight lower aspect thighs, flanks, backIntralesional corticosteroids3PRNRNR254/MEtanerceptTNF-α inhibitor25 weeklyRheumatoid arthritisNRSulphasalazine (2 g daily)36PlaqueMultipleNRLumbar areaTopical corticosteroid, vitamin E oil preparation sulphasalazine daily mo; methylprednisolone, 100 every wk; rituximab, 1000 wk14PR14Resolved after etanercept stopped337/MAdalimumabTNF-α inhibitorNRAnkylosing spondylitisNRNR12PlaqueMultipleNoLeft right legsTopical corticosteroids, dose frequency NR18PR18Resolved adalimumab stopped417/FAdalimumabTNF-α inhibitor40 14 dCrohn's diseaseTuberculosisIsoniazid (300 mg/d)2.8PlaqueSingleYesAbdomenTopical NR12CR2NR542/FAdalimumabTNF-α inhibitorNR, moPsoriasisLichen planus, neutrocytopenia, hypothyroidismPrednisolone (20 mg, daily) discharge6PanscleroticMultipleNoLimbs trunknarrowband ultraviolet B NR, ≥3 mo) calcipotriol mo)NRPR3Resolved tx6NR/MMean 16.4 ± 3.2AdalimumabTNF-α inhibitorNRCrohn's diseaseNRNRNRNRNRNRNRNRNRNRNRNR758/FGolimumabTNF-α inhibitorsNRAnkylosing spondylitis4 episodes uveitisSystemic methotrexate, anti-inflammatory drugs, leflunomide23LinearMultipleNoLower limbsNRNRNRNRNR863/FUstekinumabIL-12/IL-23 antagonistNRPsoriasisNRPhototherapy6PlaqueMultipleNoLeft legsPhototherapy, NRNRNRNRResolved ustekinumab stopped948/FUstekinumabIL-12/IL-23 antagonistNRUlcerative colitisPresumed psoriasisAntibiotics, tofacitinib, mesalamine12PlaqueMultipleNoBack, bilateral extremitiesNonmodified cyclosporine, 200 daily12CR2Resolved tx1. Stewart FA et al. New side effect TNF-alpha inhibitors: Skinmed. 2013;11(1):59–60.2. Chimenti MS Resolution rituximab occurring during patient rheumatoid arthritis. Eur J Dermatol. 2013;23(2):273–4.3. Ramírez Morphea associated adalimumab: case report literature. Mod Rheumatol. 2012;22(4):602–4.4. Mattozzi C Morphea, an unusual anti-TNF-alpha treatment. 2010;20(3):400–1.5. Inoue-Nishimoto T Possible association anti-tumor factor-α antibody scleroderma-like changes lichen planus. 2015;25(5):513–5.6. Civitelli F CO32 folliculitis pediatric Crohn’s disease: series. Digest Liver Dis. 2011;43:S409.7. Torrente-Segarra V Linear golimumab spondyloarthritis. Reumatol Clin. 2020;16(4):303-305.8. Escalas Onset psoriatic under ustekinumab: Coexistence effect? Am Acad 2017;76(6S1):AB184.9. Steuer AB undergoing ustekinumab. JAAD Case Rep. 2019;5(7):590–592.CR, Complete resolution; F, female patient; IL, interleukin; M, male reported; PR, TNF, factor; tx, treatment; y, years. Open table new tab 1. 2013;11(1):59–60. 2. 2013;23(2):273–4. 3. 2012;22(4):602–4. 4. 2010;20(3):400–1. 5. 2015;25(5):513–5. 6. 2011;43:S409. 7. 2020;16(4):303-305. 8. 2017;76(6S1):AB184. 9. 2019;5(7):590–592. CR, The latency between initiation ranged from 2.8 36 months (mean 14.5 months). Specifically, 16.3 (adalimumab 6.9 months, 27 months), whereas IL-12 -23 (ie, ustekinumab) months. 5 who resolution periods, remission 18 7.8 In 33% 3), attributed discontinuation biologics, 20% 2) experienced treatment, which narrowband cyclosporine Our identified occurred inhibitors. These have secondary effects transforming growth β, may cause fibroblast proliferation, extracellular matrix protein synthesis, ultimately skin thickening characteristic morphea.1Border W.A. Noble N.A. Transforming beta tissue fibrosis.N Engl Med. 1994; 331: 1286-1292Crossref PubMed Scopus (2940) Google Scholar However, our analysis greater proportion developing 44.4%) be reflection prescription rates compared other biologics.2Sator P. Safety tolerability psoriasis: summarizing 15 real-life experience.Ther Adv Chronic 2018; 9: 147-158Crossref (21) Although manifestations inhibition rarely been reported,3Otani I.M. Levin A.S. Banerji A. Cutaneous reactions biologics.Curr Allergy Asthma 18: 12Crossref (3) this group biologics cases. classic pathway activates T-helper 17 cells, release proinflammatory cytokines such as IL-17A; animal illustrated elevated levels IL-23, IL-17A peripheral blood fibrotic sites systemic sclerosis.4Ichihara Jinnin M. Ihn H. Treatment improved tightening sclerosis.Clin Exp 2017; 35: 208-210PubMed Also, trauma contributing developed site. Limitations include small sample size, making difficult generalize findings. Additionally, causal relationship cannot elucidated because observational nature studies. No causality assessment published criteria, thus indicating publication bias. Further are required confirm