Effect of dupilumab on allergic contact dermatitis and patch testing

To the Editor: Although pathogenesis of allergic contact dermatitis (ACD) has been classically thought to be driven predominantly by Th1, its complex pathophysiology is now accepted include Th2, Th17, and Th22 pathways.1Dhingra N. Shemer A. Da Rosa J.C. et al.Molecular profiling skin identifies allergen-dependent differences in immune response.J Allergy Clin Immunol. 2014; 134: 362-372Abstract Full Text PDF PubMed Scopus (147) Google Scholar Due involvement Th2 pathway concomitant ACD diagnosis many patients with atopic (AD), numerous reports have recently described use dupilumab ACD.2Boonstra M. Rustemeyer T. Middelkamp-Hup M.A. Both children adult difficult-to-treat high prevalences are frequently polysensitized.J Eur Acad Dermatol Venereol. 2018; 32: 1554-1561Crossref (7) A systematic review was conducted better understand effect on patch testing results. This registered PROSPERO (CRD42020193449) followed PRISMA guidelines.3Liberati Altman D.G. Tetzlaff J. al.The statement for reporting reviews meta-analyses studies that evaluate healthcare interventions: explanation elaboration.BMJ. 2009; 62: e1-e34Google We searched Medline EMBASE databases June 20, 2020 using following terms: “dermatitis,” “allergic dermatitis,” “hand “facial “patch testing,” AND “dupilumab” (Supplemental Table I; available via Mendeley at https://doi.org/10.17632/b74xk7fzgy.1). The search yielded 1099 studies, which 1024 were excluded after title/abstract screening 56 full-text reasons: no history prior (n = 42), study not evaluating ACD/patch 7), nonprimary research article 4), or non-English 3). Original reported least 1 patient treatment included. From 19 72 (mean age, 54.34 years) included (Table I). Of patients, 44 clinical effects ACD, 25 testing, 3 both. 47 results, resulted clearance 9 partial improvement 31, 4, worsening 3. who achieved clearance, 6 had miscellaneous personal care products 2 fragrances as main clinically relevant allergens testing. Notably, 18 hand involvement, 17 improved use.Table IStudies treatmentStudyAge, SexPresentation ACDClinically PT results initiation∗The relevance an allergen determined appearance dermatitis.Efficacy ACD1[1]83 yo F[2]69 F[1]Trunk extremities[2]Abdomen, buttocks, all extremities[2] Propylene glycol[1]6 Mo–IGA 1, BSA 5%[2]4 2%2[1]90 M[2]70 FNRNR–Which ones relevant[1]13-Week follow up–90% improvement, <1%[2]Week 1: <1%; mo–development repeated flares342 FWorsening eczema hands armsColophonium24 Hours first injection–recall site4[1]20 F[2]52 F[3]53 F[1]BSA >80% generalized[2]BSA 40% affecting torso, extremities[3]Hands > face, back, extremities[1]Rubber accelerators, dyes/formaldehyde resin, cosmetic/preservatives/adhesives[2]Rubber dyes[3]Hairdresser/dyes, cosmetic/preservatives/adhesives, fragrancesAll >90% improvement[1]Within weeks–dramatic 13 mo–clear[2]3-4 Weeks–improvement; mo–near clear[3]Near clear since start53M, 2F mean age: 53[1]BSA 60%, mainly hands[2]Generalized dermatitis, accentuation legs[3]Face eyelid[4]BSA 65%–generalized[5]BSA 45%–eyelids, neck, arms, trunk[1-4]Balsam Peru, fragrances[5]Nickel[1]4 Weeks–90% improvement[2]4 Weeks–clear[3]85% Improvement starting dupilumab[4]6 Weeks–80% face recalcitrant[5]7 Days–50% reduction pruritus score; mo–80% resolved; mo–90% itch[2-5]Discontinued AA644 M2-4 Weeks post stent insertion–generalized eczemaNickel8 Weeks–significant (despite inability avoid allergen)712 F3 mo–Severe eczematous scalp, neckRosin dust piecesCouple weeks–significant limited ability allergen)86M, 9F age 52.6Mean 48%11/15–Hand involvementCocamidopropyl betaine (40%), nickel (33%), oleamidopropyl dimethylamine (27%), myroxylon pereirae (20%), fragrance mix (20%)Mean 85% (range 70%-100%)950 FChronic eczema, HECSI score 244/360NR–Which relevantWeek 4–HESCI 115/360Week 16–almost (HESCI 11/360)1063 F5 yr–worsening eczemaFormaldehydeNR1140 yr–Papulovesicular feetNickel sulfate, bronopol, methylisothiazolinone, compositae mix, hydroperoxides linaloolNR1223 patientsNRNR–which relevantNR13[1]65 F[2]51 M[1]Sudden widespread hands[2]Face, forearms, handsSesquiterpene lactones[1]2 Weeks–clear arms; initial facial then a slight within mo[2]1 Mo–Improvement eczema143M, 3F 55.3Overlapping AD ACD–BSA <15%Miscellaneous products: hair 3), emollients and/or 2)Within 2-4 mo–All experienced major improvement; 4 complete clearance; flared exposure allergen; completely discontinued AA15[1]52 F[2]54 F[3]54 FOverlapping ACD:[1]Body, face[2]Chest, bodyACD only:[3]FD generalized pruritus[3]Sweet Baby Shampoo[1]Few mo–Dramatic but residual face. 2.5 mo–after additional AA–75% improvement[2]1 mo–Significant FD; AA–clear[3]2 mo–clear1654 MGeneralized photodistributed eruptionsNR–Which relevantPartial response17[1]66 F[2]28 relevant[1]7 d–Developed severe periocular exacerbation perioral AD[2]5.5 mo–AD flare hands, first-time dermatitis1862 M2 yr–anal genital pruritusPropylene glycol, patient's toothpaste, deodorant, shaving cream1 mo–clear1954 mo–hand feetMI, MCI/MI, 2-n-octyl-4-isothiazolin-3-one, 4,4-dithiodimorpholineWithin improvementBold text notes associated treatment. AA, Allergen avoidance; dermatitis; AD, BSA, body surface area; d, day; F, female; FD, HECSI, severity index; HEMA, hydroxythylmethacrylate; IGA, investigator's global assessment; M, male; mo, month; methylchloroisothiazolinone/methylisothiazolinone; NR, reported; PT, testing; yo, years old; yr, year.∗ dermatitis. Open table new tab Bold year. Between 28 same tested to, while on, 144 occasions. pairs, lost 8 newly positive, 71 persistent (48 unknown; II). Dupilumab-induced inhibition resulting polarization may explain inconsistent results.4Yamane M.L.M. Belsito D.V. Glass L.R.D. Two differing presentations side dermatitis.Orbit. 2019; 38: 390-394Crossref (12) Therefore, depending response pathway, certain responses lost, unaffected, worsened. For example, through subsequent genomic data analysis from biopsies, Dhingra al1Dhingra found Th1/Th17 demonstrated strong Th2/Th22 polarization. In alignment these findings, balsam Peru positivity initiation (Study 3; Moreover, also 7 5, 8, 18; I).Table IIPatch pre-versus initiationStudyPositive pre dupilumabPositive initiationComparison pre/post test result1FormaldehydeMethylisothiazolinone, dimethylaminopropylamine 1% aqueous∗Limited comparison tested.L: Formaldehyde2Multiple allergens, including sulfate (2+), bronopol methylisothiazolinone (3+), (1+), linalool (2+)Previously positive tested: (2+) (3+)P: Bronopol, methylisothiazolinoneL: Nickel linalool3125 (fragrances, preservatives, emulsifiers surfactants, hairdressing, sunscreen, topical therapy, metals, adhesives, varnishes, textile dyes)Same testedP: Fragrances (19), preservatives (12), surfactants (11), hairdressing (2), therapy (5), metals adhesives varnishes dyes (2) [64 allergies]L: emulsifier/surfactant (propylene glycol 10%, 100% amerchol L101, dimethylaminopropylamine) (4), (balsam 1) sunscreens (sulisobenzone phenylbenzimidazole-5-sulfonic acid) (vanadium [III] chloride phenyl mercuric acetate) preservative (iodopropynyl butyl carbamate) (1), medicament (Bacitracin) resin (tosylamide formaldehyde) (1) [13 allergies]4[1]Neomycin bacitracin, ethyl acrylate, glutaraldehyde, ammonium persulfate[2]Budesonide, alclometasone-17, 21 dipropionate[1]Amerchol lanolin alcohol, wool alcohols ointment, kanamycin neomycin eugenol, lyral, citral, MX-25 Fragrance Mix II, linalool, hydroperoxide limonene, perfume mix[2]Budesonide, dipropionate, propylene stearyl trace benzyl (6 different allergens)[1]∗Limited tested.P: Neomycin sulfateN: citral[2]∗Limited Budesonide, dipropionateN: Amerchol glycol5Nickel methylchloroisothiazolinone/methylisothiazolinone, 4,4-dithiodimorpholineRepeat only methylisothiazolinone: bothP: methylisothiazolinoneL, Lost; N, new; P, persistent.∗ Limited tested. L, persistent. It important note primary management identify remove them, especially keeping mind cost this time. However, demonstrates potential recalcitrant ACD. Responses vary, allergen, noted our study. Limitations reliance case series, small number nonstandardized data, overlapping conditions, isolated quality assessment established tool reports/series showed majority did discuss alternative causes results.5Murad M.H. Sultan S. Haffar Bazerbachi F. Methodological synthesis series reports.BMJ Evid Based Med. 23: 60-63Crossref (586) Larger standardized trials needed delineate whether suited based patterns allergen-specific dupilumab. Dr Pratt consultant AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Leo, Novartis, Pfizer, Sanofi Genzyme, UBC, Valeant. Yeung speaker, consultant, investigator Allergan, Astellas, Boehringer Ingelheim, Centocor, Coherus, Dermira, Forward, Galderma, GSK, MedImmune, Merck, Regeneron, Roche, Takeda, UCB, Valeant, Xenon. Mufti authors Jo Sachdeva conflicts interest declare.