To the Editor: Dupilumab is a human monoclonal antibody approved to treat adult moderate-to-severe atopic dermatitis (AD). The treatment resistance of AD is defined as the lack of response to therapy despite compliance to the prescribed treatment, and potential diagnostic testing has been suggested to identify alternative or concomitant diagnoses in cases in which there is incomplete response to dupilumab.1Narla S. Silverberg J.I. Simpson E.I. Management of inadequate response and adverse effects to dupilumab in atopic dermatitis.J Am Acad Dermatol. 2022; 86: 628-636https://doi.org/10.1016/j.jaad.2021.06.017Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 2Ashbaugh A. Murase E.M. Raffi J. Botto N. Murase J.E. Characterization of residual facial dermatitis on dupilumab (RFDD): a retrospective chart review to delineate the potential role of expanded series patch testing.Dermatitis. 2022; 33: 51-61https://doi.org/10.1097/DER.0000000000000801Crossref PubMed Scopus (1) Google Scholar, 3Raffi J. Suresh R. Botto N. Murase J.E. The impact of dupilumab on patch testing and the prevalence of co-morbid allergic contact dermatitis in recalcitrant atopic dermatitis: a retrospective chart review.J Am Acad Dermatol. 2020; 82: 132-138https://doi.org/10.1016/j.jaad.2019.09.028Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 4Semaan S. Abel M.K. Raffi J. Murase J.E. A clinician’s guide to cutaneous T-cell lymphoma presenting as recalcitrant eczematous dermatitis in adults.Int J Womens Dermatol. 2021; 7: 422-427https://doi.org/10.1016/j.ijwd.2021.04.004Crossref PubMed Scopus (4) Google Scholar We reported the results of diagnostic testing in 50 patients with incomplete response to dupilumab who were prescribed dupilumab for a presumed diagnosis of AD and provided guidance for the management of eczematous dermatitis nonresponsive to dupilumab. This study involved retrospective data collection from medical records and was approved by the University of California, San Francisco, institutional review board. The inclusion criteria consisted of incomplete response to dupilumab, characterized by <80% patient-reported improvement of total body surface area during the first 3 to 6 months on dupilumab. A retrospective chart review of 233 patients on dupilumab was performed, wherein 50 patients were classified as incomplete responders to dupilumab. The following comorbid or alternative diagnoses were identified based on diagnostic testing: allergic contact dermatitis (n = 47), parapsoriasis or psoriasis (n = 3), polymorphous light eruption (n = 8), cutaneous lupus and mixed connective tissue disease (n = 4), lymphoma (n = 1), tinea (n = 1), scabies (n = 1), Netherton syndrome (n = 1), and diffuse urticarial and eczematous eruption associated with systemic inflammation (n = 1). Out of the 50 patients, 18 patients were diagnosed with comorbid allergic contact dermatitis and an additional alternative condition. Data on patient demographics, the necessity for further diagnostic testing, areas of residual dermatitis while on dupilumab, and the results of diagnostic testing are outlined in Table I. The details of patch test series and the test’s results are detailed in Supplementary Tables I and II5Marks J.G. Belsito D.V. DeLeo V.A. et al.North American Contact Dermatitis Group patch test results for the detection of delayed-type hypersensitivity to topical allergens.J Am Acad Dermatol. 1998; 38: 911-918https://doi.org/10.1016/s0190-9622(98)70587-0Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar (available via Mendeley at https://data.mendeley.com/datasets/dncpdjd4hz/1).Table ISummary of patient demographics, mean time on dupilumab, necessity for further diagnostic testing, mean time from dupilumab initiation to diagnostic testing, areas of residual dermatitis while on dupilumab, and results of diagnostic testingDiagnosis (n)Mean age (y)SexMean time on dupilumab (mo)Mean time from dupilumab initiation to diagnosis (mo)Side effectsNecessity for further diagnostic testingFemaleMaleAreas of dermatitis on dupilumab (%)Diagnostic testing (%)Biopsy (H & E) [% (number of positive tests/total number of patients tested)]Allergic contact dermatitis (n = 47)∗Patients with allergic contact dermatitis as the sole concomitant diagnosis with atopic dermatitis were included (29/47 patients); those with an additional alternative diagnosis were excluded so as not to confound the reporting of study results.46.169.0% (20/29)31.0% (9/29)23.814.9 (26/29)†Not all patient information was available to analyze the time from dupilumab initiation to diagnosis.Dry or pruritic eyes (4), dry skin (1), injection site reaction (2)Residual dermatitis on dupilumab or no response to dupilumabScalp6.9% (2/29)Patch testing (see Supplementary Table I)100.0% (29/29)Spongiotic dermatitisSpongiotic dermatitis with eosinophilsSpongiotic dermatitis with neutrophilsSpongiotic dermatitis with lymphocytesSpongiotic psoriasiform dermatitis26.7% (4/15)33.3% (5/15)6.7% (1/15)6.7% (1/15)26.7% (4/15)Face51.7% (15/29)Eyelids24.1% (7/29)Neck24.1% (7/29)Trunk37.9% (12/29)Hands13.8% (4/29)Upper extremities34.5% (10/29)Lower extremities31.0% (9/29)Genitals3.4% (1/29)Parapsoriasis/psoriasis (n = 3)49100% (3/3)0.0% (0/3)3.01.5 (2/3)†Not all patient information was available to analyze the time from dupilumab initiation to diagnosis.Dry eyes (2)Residual dermatitis (plaques) on dupilumabTrunk33.3% (1/3)Biopsy H & E100% (3/3)Psoriasiform dermatitis with eosinophilsSpongiotic dermatitis33.3% (1/3)66.7% (2/3)Hands33.3% (1/3)Foot66.7% (2/3)Polymorphous light eruption (n = 8)41.562.5% (5/8)37.5% (3/8)7.813.8 (4/8)†Not all patient information was available to analyze the time from dupilumab initiation to diagnosis.Dry eyes (2)Dermatitis in a photosensitive distribution on dupilumab, worsens with sun exposureFace75.0% (6/8)ANABiopsy with DIFAnti-dsDNA antibodyPhototesting(−) 100% (7/7)(−) 100% (3/3)(+) 100% (2/2)(−) 100% (2/2)Spongiotic dermatitisPsoriasiform dermatitis42.9% (3/7)57.1% (4/7)Neck50.0% (4/8)Hands37.5% (3/8)Upper trunk12.5% (1/8)Upper extremities12.5% (1/8)Cutaneous lupus and mixed connective tissue disease (n = 4)57100.0% (4/4)0.0% (0/4)24.01.4 (2/4)†Not all patient information was available to analyze the time from dupilumab initiation to diagnosis.Joint pain (2)Dermatitis in a photosensitive distribution on dupilumab, worsens with sun exposureFace75.0% (3/4)ANA (1:80 speckled, 1:320, 1:2560)Biopsy with DIFAnti-Smith RNP antibodyAnti-centromere antibodyAnti-SSA antibody(+) 100% (4/4)(+) 33.3% (1/3)(−) 66.7% (2/3)(+) 25.0% (1/4)(+) 25.0% (1/4)(+) 25.0% (1/4)Spongiotic dermatitisVacuolar interface and perivascular dermatitisDiscoid lupusAcantholytic dyskeratosisLichen simplex chronicus with eosinophils75.0% (3/4)50.0% (2/4)25.0% (1/4)25.0% (1/4)25.0% (1/4)Eyes25.0% (1/4)Neck50.0% (2/4)Trunk25.0% (2/4)Upper extremities75.0% (3/4)Lower extremities25.0% (1/4)Hands75.0% (1/4)Lymphoma (n = 1)740.0% (0/1)100.0% (1/1)5.04NoneNo response to dupilumab, atrophic plaquesFaceBodyBiopsy H & ET-cell receptor delta-expressing epidermotropic T-cell lymphomaSystemic contact dermatitis (n = 1)570.0% (0/1)100.0% (1/1)18.017NoneAppearance of dermatitis on dupilumab with supplement/medication exposure (high-dose vitamin B12 because of cobalt allergy)Upper trunkUpper extremitiesTrial off supplement or medicationN/ATinea pedis (n = 1)210.0% (0/1)100.0% (1/1)12.015NoneResidual dermatitis on dupilumabFeetKOH: hyphaeSpongiotic dermatitisScabies (n = 1)71100.0% (1/1)0.0% (0/1)2.04NoneNo response on dupilumabDaily pruritus and burrowsNipplesTrunkUpper extremitiesLower extremitiesKOH: scabiesSpongiotic dermatitisNetherton syndrome (n = 1)68100.0% (1/1)0% (0/1)9.0N/ANoneResidual dermatitis on dupilumab, geographic plaques with scale at margin of erythemaTrunkUpper extremitiesLower extremitiesKOHSPINK5(−)(+)Psoriasiform dermatitisSpongiotic dermatitis with eosinophilsPerivascular dermatitis with eosinophilsDiffuse urticarial and eczematous eruption associated with systemic inflammation (n = 1)22100% (1/1)0% (0/1)14.0N/ANoneNo response to dupilumab, diffuse eczematous and urticarial plaquesFaceNeckTrunkUpper extremitiesLower extremitiesCU indexIgECRPESRPeriodic fever syndrome panel38.417686338(−)Perivascular inflammation and rare intravascular neutrophilsSpongiotic dermatitisSpongiotic dermatitis with eosinophilsANA, Antinuclear antibody; CRP, C-reactive protein; CU, chronic urticaria; DIF, direct immunofluorescence; dsDNA, double-stranded DNA; ESR, erythrocyte sedimentation rate; H & E, hematoxylin and eosin; IgE, immunoglobulin E; KOH, potassium hydroxide; N/A, not applicable; RNP, ribonucleoprotein particle; SPINK5, serine peptidase inhibitor Kazal type 5.∗ Patients with allergic contact dermatitis as the sole concomitant diagnosis with atopic dermatitis were included (29/47 patients); those with an additional alternative diagnosis were excluded so as not to confound the reporting of study results.† Not all patient information was available to analyze the time from dupilumab initiation to diagnosis. Open table in a new tab ANA, Antinuclear antibody; CRP, C-reactive protein; CU, chronic urticaria; DIF, direct immunofluorescence; dsDNA, double-stranded DNA; ESR, erythrocyte sedimentation rate; H & E, hematoxylin and eosin; IgE, immunoglobulin E; KOH, potassium hydroxide; N/A, not applicable; RNP, ribonucleoprotein particle; SPINK5, serine peptidase inhibitor Kazal type 5. Patients who reported photosensitivity while on dupilumab were diagnosed with polymorphous light eruption, cutaneous lupus, or mixed connective tissue disease. All the patients reported at least some history of photosensitivity prior to the initiation of dupilumab. The patients continued to have photosensitivity after the medication was discontinued, and there were no patients in whom photosensitivity was directly attributed to dupilumab. Dupilumab does not appear to treat concomitant photosensitive dermatitis. Out of the 233 patients evaluated, the only 2 patients who experienced joint pain as a side effect of dupilumab were diagnosed with cutaneous lupus or mixed connective tissue disease. Upon evaluation of cases with incomplete or lack of response to dupilumab, the morphology and location of residual dermatitis and patient history played a significant role in determining appropriate diagnostic testing. All 50 patients with incomplete or lack of response to dupilumab had concomitant conditions or entirely different diagnoses, 38 of whom had a delay in this diagnosis by an average of 12.8 months. Interestingly, 94% of the patients had at least 1 contact allergen identified. Patients diagnosed with AD who fail to respond or respond incompletely to dupilumab should be evaluated for concomitant conditions that may be responsible for residual dermatoses. Early identification may improve clearance rate, resulting in faster resolution. We have provided the results of the evaluation of patients with residual dermatitis in Fig 1. The limitations of this study include its retrospective design and the subjectivity of patient-reported clearance. Dr Murase has participated in Advisory Boards for Genzyme/Sanofi, Eli Lilly, Dermira, LeoPharma, and UCB; participated in disease statement management talks for Regeneron and UCB; and provided dermatologic consulting services for UpToDate. Drs Ashbaugh and Botto and Author Bai have no conflicts of interest to declare.