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Background: Sézary syndrome is a leukaemic variant of cutaneous T‐cell lymphoma with poor prognosis. With the exception of stem cell transplantation, current treatments for SS are not curative. Rather, they aim at reducing disease burden and improving quality of life. Yet, pruritus – the major cause for impaired quality of life in these patients – is notoriously difficult to treat. Thus, supportive treatments addressing agonizing pruritus are urgently needed. Objectives: To explore the clinical and immunological effects of type 2 cytokine blockade with dupilumab as supportive treatment in Sézary syndrome. Methods: A Sézary syndrome patient with stable disease but intractable pruritus was treated with dupilumab in combination with continued extracorporeal photopheresis. Close clinical and immunological monitoring on blood and skin samples from the patient was performed over 44 weeks. In vitro assays with patient's lymphoma cells were performed to address effects of dupilumab on Sézary cell's response to Th2 cytokines. Results: Clinically, dupilumab treatment induced rapid and sustained reduction in itch and improvement of skin and lymph node involvement. In both blood and skin, a reduction in Th2 bias was observed. Intriguingly, lymphocyte counts and Sézary cells in blood increased and later stabilized under dupilumab treatment. In vitro, dupilumab abrogated the anti‐apoptotic and activating effects of Th2 cytokines on Sézary cells. Conclusions: In this Sézary patient, inhibition of IL‐4 and IL‐13 signalling was associated with striking clinical benefit in terms of quality of life, pruritus and use of topical corticosteroids. While safety remains an important concern, our data support the future exploration of Th2 modulation for supportive care in Sézary Syndrome. [ABSTRACT FROM AUTHOR]

To the Editor Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease characterized by widespread follicular hyperkeratosis and erythrosquamous plaques with demarcated islands of sparing.1 Spontaneous remissions can occur, but PRP often shows a prolonged and therapy-resistant course.2 Although the pathogenesis remains incompletely understood, the Th17 axis is implicated in driving cutaneous inflammation in PRP.3 Accordingly, biologics inhibiting the Th17 pathway have been successfully used.4 Interestingly, figurate dermatoses resembling erythema gyratum repens (EGR) have been observed during the resolution phase of PRP.5-7 Yet, whether EGR-like eruptions may also occur under anti-IL-17 treatment remains unclear.7 Here, we describe two cases of severe PRP developing an EGR-like eruption under anti-IL-17 therapy. The sudden appearance of an EGR-like eruption in PRP patients receiving immunomodulatory treatment such as anti-IL-17 antibodies can cause concern, since EGR is regarded as a paraneoplastic dermatosis or may be interpreted as drug-induced skin reaction.6-9 Yet, our cases and the current literature argue against such concerns: first, EGR-like eruptions may occur during the resolving phase of PRP, in the absence of underlying malignancy.5 Second, growing evidence suggests that EGR-like eruptions may appear regardless of whether PRP resolves spontaneously or as a consequence of successful therapy. In summary, our cases raise awareness of EGR-like eruptions as a feature of resolving PRP under biologic therapy. [Extracted from the article]

Dear Editor, Neutrophilic dermatoses (NDs) comprise a group of autoinflammatory disorders characterized by a neutrophilic-rich infiltrate in the skin. Histology showed dermal oedema with an interstitial and perivascular neutrophilic infiltrate with some foci of diapedesis. [Extracted from the article]

Background Cutaneous ( CLP) and oral lichen planus ( OLP) as the main subtypes of lichen planus ( LP) present with different clinical manifestation and disease course, although their histopathologic features such as the band-like lymphocyte infiltrate and keratinocyte apoptosis are similar. So far, the underlying cellular and molecular mechanisms remain poorly understood. Objective The aim of this study was to characterize and compare the in situ cellular infiltrates, cytokine expression profiles and apoptosis markers in CLP and OLP. Methods Using immunofluorescence staining and laser scanning microscopy, we evaluated the cellular infiltrate ( CD1a, CD3, CD4, CD8, CD21, CD57, CD123), cytokine expression (interleukin ( IL)-1, IL-6, IL-9, IL-10, IL-17, IL-22, IL-23, tumour necrosis factor-α, transforming growth factor-β, interferon ( IFN)-γ), and apoptosis markers (Fas, Fas ligand, cleaved caspase-3, TUNEL) of 21 anonymized biopsy specimens of LP (11 CLP, 10 OLP). Results Among infiltrating cells mainly T cells and natural killer ( NK) cells as well as plasmacytoid dendritic cells ( DC) were observed. A predominance of CD8+ T cells was noted in OLP. In both CLP and OLP, T helper (Th)1, Th9, Th17, and Th22-type cytokines were expressed. The expression of IL-9, IFN-γ and IL-22 was higher in CLP compared to that of OLP ( P = 0.0165; P = 0.0016; P = 0.052 respectively). Expression of Fas and Fas ligand as well as cleaved caspase-3-positive cells was observed in the epithelium of all LP samples. Conclusions The cell and cytokine patterns of CLP and OLP were partially distinct and generally resembled those reported for autoimmune diseases. The presence of CD8+ and NK cells as well as Fas/Fas ligand expression suggested that various pathways involved in keratinocyte apoptosis are relevant for LP. These results might help to establish targeted therapies for LP. [ABSTRACT FROM AUTHOR]

To cite this article: Schlapbach C, Zawodniak A, Irla N, Adam J, Hunger RE, Yerly D, Pichler WJ, Yawalkar N. NKp46+ cells express granulysin in multiple cutaneous adverse drug reactions. Allergy 2011; 66: 1469-1476. Abstract Background: The spectrum of cutaneous adverse drug reactions (cADRs) ranges from benign presentations to severe life-threatening forms such as toxic epidermal necrolysis (TEN). In TEN, granulysin has been shown to be the key cytotoxic molecule. Still, little is known about the expression of granulysin in other cADRs. As an important source of granulysin, natural killer (NK) cells are of major interest in cADRs. Recently, NKp46 has been identified as the most selective NK-cell marker. However, the role of NKp46+ cells in cADRs and their contribution to granulysin expression remain to be elucidated. Methods: Immunohistochemical and immunofluorescence staining of tissue sections from multiple cADRs were quantitatively and qualitatively evaluated. Further, in vivo and in vitro drug-stimulation tests were performed. Results: Granulysin is expressed at different levels in multiple cADRs both by NKp46+ cells and by CD8+ T cells. Even in mild forms of cADRs, granulysin can be induced in vivo and in vitro in a drug-specific manner. NKp46+ cells were found to infiltrate the dermal/epidermal junction particularly in TEN. Conclusion: The impressive clinical differences of cADRs may not be uniquely explained by the expression of granulysin. Additional factors such as drug-specific activation and recruitment of NKp46+ cells to the epidermis may play a role in determining the severity of cADRs. Therefore, unraveling the effects of drugs on NK-cell activation and trafficking may help to better understand the cytotoxic mechanisms behind cADRs. [ABSTRACT FROM AUTHOR]

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT. The localized Psoriasis Area and Severity Index (locPASI) of the head, trunk, upper and lower extremities was analyzed over two years following the start of systemic non-/biologic treatment. A total of 316 female and 517 male patients were analyzed. Male patients had a higher baseline locPASI for legs, trunk and arms (p < 0.001), but not for the head (p = 0.961). The locPASI for the head in younger female patients (18-40 years) had a higher score than those aged 55 + (p = 0.022) and after two years, middle aged (41-54) showed a lower score compared to younger patients (p = 0.045). Younger male patients revealed a lower score after two years of therapy in the leg- and arm-area compared to older (p = 0.018 and p = 0.048, respectively). Female patients on non-biologics had a fast initial response, converging with male patients' scores over 24 months. Over 75% locPASI reduction was observed for female head-area (81.4%), male trunk (82.7%) and legs (76.1%). Absolute locPASI ≤ 2 was achieved 3-6 months for all locations with interleukin (IL)-17, IL-12/23 and IL-23-inhibitors, except for the legs of male patients on anti-IL-17 and female patients on anti-IL-12/23 and -IL-23. After two years, male patients did not achieve a locPASI ≤ 2 for any biologic-treatment in the legs, nor for the arms on anti-TNF-α. Significant disparities in localized PASI were observed between female and male patients. The age, sex and severity of distinct localizations should be considered to optimize treatment goals., (© 2024. The Author(s).)

Background: Biologics are among the most effective therapies for psoriasis. However, many patients are only introduced to them at advanced stages of the disease course., Objectives: Our aim was to identify predictors of initiating biologic therapy in patients with psoriasis and compare patients initiating biologics early versus late in their disease course., Methods: Kaplan-Meier curves visualized time to biologic initiation, while Cox regression models further explored variables as predictors of biologic initiation. Mann-Whitney U and chi-squared tests compared patients who started biologics early with those who began biologics later in the disease course., Results: Our primary analysis included 233 psoriasis patients. Cox regression showed that age at diagnosis (P = 0.007), general physical well-being (P = 0.02), and nail psoriasis severity (P = 0.02) were significantly associated with time to biologic initiation. Our secondary analysis, the comparisons between patients starting biologics early versus later in the disease course, included a total of 378 patients. The median (interquartile range [IQR]) age at diagnosis was 34.5 (25.0-51.2) years for patients initiating biologics within 5 years, compared to 22.0 (15.0-32.8) years for patients initiating biologics later (P < 0.0001). The median (IQR) age at initiation was 37.0 (27.0-53.2) and 45.0 (36.0-55.0) years for patients initiating biologics earlier versus later than 5 years (P = 0.04)., Conclusions: Age at diagnosis, general well-being, and severity of nail psoriasis significantly predicted future initiation of biologic treatment. Patients initiating biologics early in their disease course were generally older at diagnosis but younger at the time of biologic initiation compared to patients initiating biologics later in their disease course., (© 2024 the International Society of Dermatology.)

Background: Topical corticosteroid phobia (TOPICOP) is associated with poor treatment adherence and is common among patients with skin disease. Knowledge about corticosteroid phobia and treatment adherence among patients with chronic hand eczema (CHE) is limited., Objectives: To investigate patient-reported outcomes regarding topical corticosteroids (TCSs), and their impact on treatment adherence in patients with CHE., Methods: Patients with CHE from the Danish Skin Cohort answered a questionnaire including the TOPICOP scale and Medication Adherence Report Scale. Response rate was 69.2%., Results: Of 927 with CHE, 75.5% totally or almost agreed that TCS damage the skin, 48.9% totally or almost agreed that TCS would affect their future health and 36.3% reported some degree of fear of TCS although they were unaware of any TCS-associated risks. Most patients (77.9%) always or often stop treatment as soon as possible, whereas 54.8% always or often wait as long as possible before starting treatment. Overall, 38.8% reported that they had taken less medicine than prescribed and 54.0% had stopped treatment throughout a period. Treatment adherence decreased with increasing corticosteroid phobia (P = .004)., Limitations: TOPICOP has not been validated in patients with CHE., Conclusions: Corticosteroid phobia is common among patients with CHE and negatively associated with treatment adherence., Competing Interests: Conflicts of interest Dr Christensen has been a subinvestigator for LEO Pharma, with no relation to this manuscript. Dr Guttman-Yassky is an employee of Mount Sinai, has received research grants from Boehringer Ingelheim, LEO Pharma, Pfizer, Cara Therapeutics, UCB, Kyowa Kirin, RAPT, Amgen, GSK, Incyte, Sanofi, Bristol Meyers Squibb, Aslan, Regeneron, AnaptysBio, Concert, and Janssen, and is a consultant for AbbVie, Almirall, Amgen, AnaptysBio, Apogee Therapeutics, Apollo Therapeutics Limited, Artax Biopharma Inc, AstraZeneca, Bristol Meyers Squibb, Boehringer Ingelheim, Cara Therapeutics, Centrexion Therapeutics Corporation, Connect Biopharm, Eli Lilly, Enveda Biosciences, Escient Pharmaceuticals, Inc, Fairmount Funds Management LLC, FL2022-001, Inc, Galderma, Gate Bio, Google Ventures (GV), GSK Immunology, Horizon Therapeutics USA, Inc, Incyte, Inmagene, Janssen Biotech, Japan Tobacco, Jasper Therapeutics, Kyowa Kirin, LEO Pharma, Merck, Nektar Therapeutics, Novartis Pharmaceuticals Corporation, NUMAB Therapeutics AG, OrbiMed Advisors LLC, OTSUKA Pfizer, Pharmaxis Ltd, Pioneering Medicine VII, Inc, Proteologix US Inc, RAPT, Regeneron Pharmaceuticals, Ribon Therapeutics, Inc, Sanofi, SATO, Schrödinger, Inc, Sun Pharma Advanced Research Company (SPARC), Teva Branded Pharmaceutical Products R&D, Inc, and UCB, with no relation to this manuscript. Dr Ezzedine has been a consultant and speaker and has received funding from AbbVie, Incyte, Lilly, Pfizer, Pierre Fabre, L’Oreal, BMS, and MSD, with no relation to this manuscript. Dr Schlapbach has received honoraria as adviser or speaker for AbbVie, Almirall, BMS, Incyte, LEO Pharma, Lilly, Kiowa Kirin, Novartis, Pfizer, and Sanofi and has received research funding from PPM Services, with no relation to this manuscript. Dr Molin has received honoraria as consultant/adviser or speaker and/or grants from AbbVie, Almirall, Aralez, Arcutis, Basilea, Bausch and Lomb, Bristol Myer Squibb, Boehringer Ingelheim, Evidera, Galderma, GSK, Incyte, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi, Sun Pharma, and UCB, and is currently investigator for Novartis and LEO Pharma, with no relation to this manuscript. Dr Zhang has served on advisory boards and receives honorarium for Pfizer Investment Co, Ltd, Novartis Pharmaceuticals (China), Sanofi China, LEO Pharma (Shanghai) Co, Ltd, GSK (China) Investment Co, Ltd, Eli Lilly and Company (China), Xi’an Janssen Pharmaceutical Ltd, Bristol-Myers Squibb (China) Investment Co, Ltd, Beijing Wenfeng Tianji Pharma Ltd, Keymed Biosciences (Chengdu) Ltd, Akeso Biopharma Co, Ltd, Reistone Biopharma Co, Ltd, and Kintor Pharmaceutical Ltd, with no relation to this manuscript. Dr Zachariae has been a paid speaker for Eli Lilly, Novartis, CSL, and LEO Pharma, and has been a consultant or has served on advisory boards with AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, Takeda, Amgen, and CSL, with no relation to this manuscript. Dr Thomsen has been a speaker or has served on advisory boards for Sanofi, AbbVie, LEO Pharma, Pfizer, Eli Lilly, Novartis, UCB Pharma, Union Therapeutics, Almirall, and Janssen Pharmaceuticals, and has received research support from Sanofi, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals, with no relation to this manuscript. Dr Thyssen is an adviser for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, has a speaker for AbbVie, Almirall, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, received research grants from Pfizer, Regeneron, and Sanofi-Genzyme, and is a full time employee at LEO Pharma. Dr Egeberg has received research funding from Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, Boehringer Ingelheim, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation, has received honoraria as consultant and/or speaker from Amgen, AbbVie, Almirall, LEO Pharma, Zuellig Pharma Ltd, Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co, Ltd, Pfizer, Eli Lilly and Company, Novartis, Union Therapeutics, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, McNeil Consumer Healthcare, Horizon Therapeutics, Boehringer Ingelheim, and Janssen Pharmaceuticals, and is currently employed by LEO Pharma, with no relation to this manuscript. Authors Sieborg and Nymand have no conflicts of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Psoriatic arthritis (PsA) is a prevalent comorbidity among patients with psoriasis, heavily contributing to their burden of disease, usually diagnosed several years after the diagnosis of psoriasis., Objectives: To investigate the predictability of psoriatic arthritis in patients with psoriasis and to identify important predictors., Methods: Data from the Swiss Dermatology Network on Targeted Therapies (SDNTT) involving patients treated for psoriasis were utilized. A combination of gradient-boosted decision trees and mixed models was used to classify patients based on their diagnosis of PsA or its absence. The variables with the highest predictive power were identified. Time to PsA diagnosis was visualized with the Kaplan-Meier method and the relationship between severity of psoriasis and PsA was explored through quantile regression., Results: A diagnosis of psoriatic arthritis was registered at baseline of 407 (29.5%) treatment series. 516 patients had no registration of PsA, 257 patients had PsA at inclusion, and 91 patients were diagnosed with PsA after inclusion. The model's AUROCs was up to 73.7%, and variables with the highest discriminatory power were age, PASI, physical well-being, and severity of nail psoriasis. Among patients who developed PsA after inclusion, significantly more first treatment series were classified in the PsA-group, compared to those with no PsA registration. PASI was significantly correlated with the median burden/severity of PsA ( P = .01)., Conclusions: Distinguishing between patients with and without PsA based on clinical characteristics is feasible and even predicting future diagnoses of PsA is possible. Patients at higher risk can be identified using important predictors of PsA., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ms. Nielsen has nothing to declare Dr. Petersen has nothing to declare With no relation to the present manuscript Dr. LV Maul has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Eli Lilly, MSD, Novartis, Pierre Fabre, Roche, and Sanofi. Dr. Thomsen has been a speaker or advisor for Sanofi, AbbVie, LEO Pharma, Pfizer, Eli Lilly, Novartis, UCB Pharma, Almirall, and Janssen Pharmaceuticals, and received research support from Sanofi, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals, outside the submitted work. With no relation to the present manuscript, Dr. Schlapbach has received honoraria as adviser for Abbvie, BMS, LEO Pharma, Lilly, Kiowa Kirin, Novartis, and Pfizer and has received research funding from PPM Services. Prof. Kündig has intermittent, project focused consulting and/or advisory relationships with Leo Pharma, Janssen-Cilag, Eli Lilly, Pierre Fabre, Sanofi Genzyme, Abbvie, Biomed AG, Novartis, Almirall, Bristol-Myers Squibb, Galderma, L’Oréal/LaRoche-Posay, Merck-Sharp & Dohme, Zur Rose AG, Allergy Therapeutics AG, Derma2go AG, Oncobit AG, EVAX AG, Saiba Biotechnology AG, Saiba Animal Health AG, AltiBio Corp, Encoded Corp, Mabylon AG, MannKind Corp, XBiotech Corp. With no relation to the present manuscript, Dr. Wu is or has been an investigator, consultant, or speaker for AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Bausch Health, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Codex Labs, Dermavant, DermTech, Dr. Reddy’s Laboratories, Eli Lilly, EPI Health, Galderma, Incyte, Janssen, LEO Pharma, Mindera, Novartis, Pfizer, Regeneron, Samsung Bioepis, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, and Zerigo Health. Dr. Cozzio is or has been involved in advisory activities for AbbVie, Eli Lilly, Sanofi, Janssen-Cilag, Leo, Amgen. Dr. Conrad is or has been Scientific adviser and/or clinical study investigator for AbbVie, Actelion, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli-Lilly, Galderma, Incyte, Janssen, LEO pharma, MSD, Novartis, Pfizer, Samsung, Sanofi, and UCB With no relation to the present manuscript, Prof. Navarini declares being a consultant and advisor and/or receiving speaking fees and/or grants and/or served as an investigator in clinical trials for AbbVie, Almirall, Amgen, Biomed, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GSK, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre Pharma, Regeneron, Sandoz, Sanofi, and UCB. With no relation to the present manuscript Dr. Thyssen is a full time employee at LEO Pharma and is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, a speaker for AbbVie, Almirall, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, and received research grants from Pfizer, Regeneron, and Sanofi-Genzyme. Dr. Boehncke has received honoraria as a speaker and/or advisor from Abbvie, Almirall, Amgen, BMS, Leo, Lilly, Novartis, and UCB. With no relation to the present manuscript Dr. Kristensen reports speakers bureau: Pfizer, AbbVie, Amgen, UCB, Galapagos, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals & Consultancy for Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals. With no relation to the present manuscript Dr. Egeberg has received research funding from Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, Boehringer Ingelheim, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation, and honoraria as consultant and/or speaker from AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, McNeil Consumer Healthcare, Horizon Therapeutics, Boehringer Ingelheim, and Janssen Pharmaceuticals. With no relation to the present manuscript Dr. Maul has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, BMS, Celgene, Eli Lilly, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, UCB. With no relation to the present manuscript Dr. Yawalkar has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galderma, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Sanofi-Genzyme, UCB., (© The Author(s) 2023.)

Background: Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab-associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy., Methods: Tear fluids were collected from AD patients with DAOSD (ADwDAOSD), AD patients without DAOSD (ADw/oDAOSD), and non-AD patients before and during dupilumab therapy, and analyzed using a specialized proteomic approach quantifying inflammatory markers. The ocular surface microbiome was determined by next generation sequencing technology., Results: Upon dupilumab therapy, an upregulation of 31 inflammatory markers was observed in DAOSD tear fluids compared to baseline in AD patients. While IL-12B was upregulated in both ADwDAOSD and ADw/oDAOSD groups, the pattern of inflammatory markers significantly differed between groups and over time. In the ADwDAOSD group, a shift from a mixed Th2/Th17 pattern at baseline toward a Th1/Th17 profile under dupilumab was observed. Furthermore, an upregulation of remodeling and fibrosis markers was seen in DAOSD. Semantic map and hierarchical cluster analyses of baseline marker expression revealed four clusters distinguishing between AD and non-AD as well as ADwDAOSD and ADw/oDAOSD patient groups. In a pilot study, dupilumab therapy was associated with a decrease in richness of the ocular surface microbiome., Conclusions: DAOSD is characterized by a Th1/Th17 cytokine profile and an upregulation of markers known to promote remodeling and fibrosis. The expression pattern of inflammatory markers in tear fluids at baseline might serve as a prognostic factor for DAOSD., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)