Conjunctivitis is more prevalent in patients with atopic dermatitis (AD) than the general population, and is the most common adverse event during dupilumab treatment for AD. We aimed to characterize conjunctivitis diagnosed during AD dupilumab treatment and to assess effectiveness of ophthalmic treatments.

This prospective observational study enrolled adults with AD who received the approved dupilumab regimen in a real-world setting for at least 8 weeks prior to enrollment. At baseline, we compared ophthalmic signs and symptoms in two cohorts of patients who had received dupilumab for similar duration: one with conjunctivitis (group 1) and one with no conjunctivitis (group 2). All patients continued treatment with dupilumab, and group 1 patients received treatment for conjunctivitis at the discretion of the investigator. We assessed effectiveness of prescribed treatments and the outcomes of conjunctivitis up to Week 60. All analyses were descriptive.

A total of 35 patients were assessed in group 1 and 11 in group 2. Mean AD duration was 22.9 ± 15.2 years (group 1) and 13.1 ± 16.9 years (group 2). In group 1, 91% of patients reported a history of facial lesions during AD flares and 54% had current AD facial lesions, compared with 64% and 9%, respectively, in group 2. Ongoing facial contact dermatitis and rosacea were only reported in group 1 (11% and 9%, respectively). Common physical findings at baseline in group 1 compared with group 2 included periocular eczematous rash (65% vs. 18%) and/or lichenification (47% vs. 27%), posterior blepharitis with meibomian gland dysfunction (83% vs. 55%), bulbar hyperemia (89% vs. 46%) and conjunctival papillary pattern (69% vs. 27%); 24% of patients in group 1 and none in group 2 had corneal neovascularization, mostly in a single peripheral quadrant. There was no evidence of tear volume insufficiency. One patient in group 1 (3%) and two in group 2 (18%) had eyelash mites. Three patients (9%) in group 1 and one in group 2 (9%) had Staphylococcus aureus-positive conjunctival swabs. Most patients (88%) received multiple ophthalmic treatments for the qualifying conjunctivitis event. Investigators assessed topical corticosteroids and topical calcineurin inhibitors administered either as eye drops or ointment as the most effective treatments. Most conjunctivitis events recovered/resolved (84%) or were resolving/recovering (12%) at study end. Mean ± SD time to recovery from the initial visit was 171.9 ± 54.6 days. No participants discontinued treatment with dupilumab.

Prolonged history of AD and facial and/or eyelid AD lesions increased the likelihood of a conjunctivitis diagnosis during AD dupilumab treatment. Treatment of conjunctivitis with topical corticosteroids and/or calcineurin inhibitors resolved or controlled the event in most patients without need to discontinue dupilumab.

GOV: ClinicalTrial.gov Identifier: NCT04287608.

To evaluate and rank the comparative effectiveness of topical treatments for different types of ocular allergies through a systematic review and network meta-analysis.

A systematic search of electronic databases identified between January 2000 and December 2024 from PubMed, Cochrane CENTRAL, Google Scholar, and Scopus databases. Study Selection; randomized controlled trials assessing topical treatments for ocular allergy, including antihistamines, corticosteroids, immunomodulators, and combination therapies. Data Extraction and Synthesis; data were independently extracted and analyzed following PRISMA guidelines. Direct and indirect comparisons were evaluated using network meta-analysis, and SUCRA rankings assessed relative efficacy. Main Outcomes and Measures; reduction in ocular itching, redness, and inflammation. PROSPERO Registration number: CRD42025634572.

Olopatadine 0.1 % demonstrated highest efficacy in seasonal and perennial allergic conjunctivitis (SUCRA 0.88 and 0.85, respectively), while Tacrolimus 0.1 % showed superior effectiveness in vernal and atopic keratoconjunctivitis (SUCRA 0.92 and 0.89, respectively). Overall treatment effect was significant (OR = 6.95, 95 % CI: 6.24-7.75) with moderate heterogeneity (I2 = 50.8 %). Subgroup analysis revealed consistent efficacy across different types of allergic conjunctivitis, with seasonal allergic conjunctivitis showing the highest cumulative ranking probability (89.0 %).

This network meta-analysis provides strong evidence supporting condition-specific treatment approaches in ocular allergies. Newer antihistamines, particularly Olopatadine, are most effective for mild-moderate conditions, while immunomodulators, especially Tacrolimus, show superior efficacy in severe cases. These findings provide clear evidence-based hierarchies for clinical decision-making in the management of different types of allergic conjunctivitis.

Dupilumab-associated ocular surface disease (DAOSD) is a common side effect in paediatric atopic dermatitis (AD) patients treated with dupilumab. However, long-term real-world safety data is limited. Therefore, this study investigates the incidence of DAOSD in paediatric AD patients treated with dupilumab and identifies associated risk factors.

This prospective study included paediatric AD patients (aged 3-17 years) treated with dupilumab. Ocular symptoms were assessed every 4-12 weeks. DAOSD was initially treated with lubricating eye drops, antihistamine eye drops, and/or tacrolimus ointment for the external eyelids. Persistent symptoms were treated with ocular anti-inflammatory therapy. Ophthalmological examination was performed in patients with DAOSD requiring ocular anti-inflammatory therapy. Univariable and multivariable regression analyses were conducted to identify predictors for developing DAOSD.

A total of 104 patients (11.7 ± 4.0 years) with a median follow-up of 70.5 weeks were included. Overall, 34.6% (36/104) of patients developed DAOSD, of which 30.6% (11/36) required ocular anti-inflammatory therapy. The development of DAOSD was not age-dependent, nor was it associated with pre-existing allergic conjunctivitis. The most common ocular symptoms were pruritus (75.0%), redness (72.2%), and tearing (58.3%). Ophthalmological examination revealed tarsal conjunctivitis in all patients with DAOSD requiring ocular anti-inflammatory therapy. Baseline serum IgE levels of ≥ 3000 kU/L were independently associated with the development of DAOSD (OR 4.65; 95% CI 1.43-15.11, p = 0.011). DAOSD led to dupilumab discontinuation in 3.8% (4/104) of patients.

This prospective, long-term, real-world study shows that 34.6% of paediatric AD patients treated with dupilumab develop DAOSD. Elevated baseline serum IgE (≥ 3000 kU/L) may predict the development of DAOSD. The high incidence of DAOSD underscores the importance of awareness of ocular symptoms during dupilumab treatment, especially in (young) paediatric patients, where reporting ocular symptoms can be challenging and may lead to delayed diagnosis.

In clinical trials of patients with atopic dermatitis (AD), conjunctivitis and keratitis occurred more frequently with dupilumab than placebo. Studies using real-world data have also shown a higher incidence with dupilumab but did not use validated algorithms to identify the population and outcomes. The objective of this study was to investigate the incidence of conjunctivitis and keratitis among patients with moderate-to-severe AD treated with dupilumab relative to dupilumab-naïve patients in a real-world setting using validated algorithms.

A retrospective observational cohort study was conducted in an insurance claims database using validated algorithms for moderate-to-severe AD and ocular outcomes. Initiators of dupilumab were identified and propensity score (PS) matched with dupilumab-naïve patients with moderate-to-severe AD. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for conjunctivitis and keratitis during follow-up were estimated using Poisson regression.

Among 13,790 patients in the moderate-to-severe AD study population, 2175 dupilumab initiators and 2189 dupilumab-naïve patients were included in the analysis. Dupilumab was associated with an increased risk of conjunctivitis (IRR = 1.86 [95% CI 1.51-2.30]) and keratitis (IRR = 4.06 [95% CI 1.70-9.68]) compared to patients with moderate-to-severe AD not receiving dupilumab. The cumulative 1-year risk of conjunctivitis was 15.8% and 8.4% in the dupilumab and dupilumab-naïve cohorts, respectively; the cumulative 1-year risk of keratitis was 1.3% and 0.2%, respectively.

Study findings are consistent with safety data from clinical trials and existing literature. However, a few keratitis events were observed, and post hoc analyses suggested residual confounding might be present. The known benefit-risk profile for dupilumab remains unchanged.

Background: Ocular comorbidity in atopic dermatitis (AD) is known, but ocular surface disease (OSD) symptoms do not always result in a physiciańs diagnosis. Objective: To investigate the occurrence of OSD symptoms and self-reported vision and health in a general population and explore their association with AD. Methods: A cross-sectional questionnaire study using the nationwide population-based FOREVER cohort of Danish adults. The occurrence of OSD symptoms, self-reported vision and health, and their association with AD were investigated using logistic regression models. Results: A total of 57,464 (85%) out of 67,178 participants completed the questionnaire. 1,298 had current AD, 5,198 had a history of AD, and 50,968 never had AD. The occurrence of one or more OSD symptoms was associated with both current (adjusted odds ratio, 1.19; 95% confidence interval, 1.05-1.34; P = 0.006) and previous AD (1.16; 1.09-1.23; P < 0.001), compared to those who never had AD, after adjusting for age, sex, smoking status, and atopic comorbidities (asthma and rhinitis). Participants with current and previous AD also rated their overall health "worse" (1.29; 1.16-1.43; P < 0.001) (1.12; 1.06-1.18; P < 0.001), compared to those who never had AD. Conclusions: The occurrence of OSD symptoms and worse self-rated vision and health are associated with AD in a general population.

The arrival of biologics and small-molecule therapies (eg Janus kinase inhibitors) changed atopic dermatitis treatment, but older systemic treatments continue to be prescribed.

To provide real-world effectiveness, safety, and adherence data for dupilumab, cyclosporine, and methotrexate.

PEDIatric STudy in Atopic Dermatitis (NCT03687359) is a real-world, prospective, observational, 10-year study of children (<12 years) with inadequately controlled moderate-to-severe atopic dermatitis. We report 2-year interim results.

Median treatment durations were 8.1, 13.0, and 10.7 months for dupilumab (n = 144), methotrexate (n = 114), and cyclosporine (n = 121), respectively. Dupilumab had numerically greater within-group improvements than methotrexate and cyclosporine in Eczema Area and Severity Index (-12.4∗ vs -5.7∗ and -3.3); body surface area affected (-19.9%∗ vs -11.8%∗ and -8.8%∗); itching (night-time: -2.1∗ vs -0.4 and + 0.1; daytime: -1.5∗ vs +0.1 and + 0.2; ≥6 years); itching/scratching (-3.6∗ vs -1.4∗ and -0.2; <6 years); and Patient-Oriented Eczema Measure (-7.0∗ vs -4.7∗ and -1.5) (∗P < .05 within-group improvements from baseline). Dupilumab had less discontinuations (8.3% vs 28.9% and 43.0%) and adverse event(s) (18.1% vs 29.8% and 31.4%).

No randomization, placebo, or specified dosages.

Dupilumab was associated with numerically greater outcomes and higher adherence than cyclosporine or methotrexate.

Background: As the available treatments for moderate-to-severe atopic dermatitis (AD) expand, understanding patient and physician preferences becomes crucial for informed decision-making.

Objective: To quantify patient and physician preferences for biologics and oral systemic AD treatment attributes.

Materials and methods: We conducted a cross-sectional, online discrete choice experiment (DCE) involving 306 AD patients and 206 physicians throughout the United Kingdom and Germany. Qualitative interviews identified the key attributes for inclusion in the DCE. Each choice task comprised two hypothetical patient profiles. Data were analyzed using a random-parameters logit model.

Results: Results indicated a significant emphasis on efficacy, with reducing sleep disturbance and itch ranking first and second among patients, and the reverse for physicians. Time to itch relief was the third most important efficacy attribute for both groups, but relatively more important for patients than for physicians. For both groups, the risk of eye problems was the most important safety concern of those included. Mode of administration was not of great importance compared to efficacy and safety attributes.

Conclusions: Our findings suggest patients prioritize sleep disturbance, an attribute not captured in prior preference studies in AD, time to itch relief and itch. These findings emphasize the importance of addressing sleep-related issues, whilst also targeting fast itch control, to enhance patients' well-being.

To investigate the causal association between gut microbiota and allergic conjunctivitis.

A two-sample Mendelian randomization (MR) analysis was performed using the summary statistics of gut microbiota (18,340) from MiBio-Gen consortium and allergic conjunctivitis data (n = 218,792) obtained from the IEU Open GWAS project. F-statistics and sensitivity analyses were used to address potential biases and ensure the reliability of our findings. Reverse MR analysis was conducted to assess the possible of reverse causal relationships.

The inverse variance weighted estimates revealed the protective potential of the phylum Euryarchaeota against allergic conjunctivitis (OR = 0.87, p = 6.17 × 10-4). On the other hand, the genus Christensenellaceae R.7 group (OR = 0.75, p = 2.89 × 10-3), family Peptostreptococcaceae (OR = 0.83, p = 6.22 × 10-3), genus Lachnospiraceae FCS020 group (OR = 0.82, p = 0.02) all showed a suggestive protective association with allergic conjunctivitis. Additionally, sensitivity analysis confirmed the robustness of the above associations. In the reverse MR analysis, no significant causal association was found between gut microbiota and allergic conjunctivitis.

This study has revealed a potential causal correlation between the phylum Euryarchaeota and allergic conjunctivitis, offering new insights to improve prevention and treatment of this condition.

Ocular surface disorders have been reported among patients with various medical conditions, including atopic dermatitis (AD). Nonetheless, validated algorithms to identify conjunctivitis and keratitis in claims data are lacking.

Develop validated, claims-based algorithms for conjunctivitis and keratitis among patients with AD using medical records.

Patients with AD were identified in a claims database between March 2017 and November 2019. Among these patients, candidate algorithms were developed that included diagnosis codes for conjunctivitis or keratitis, alone and in combination with ophthalmic treatments. Among patients who met ≥ 1 candidate algorithms, a subset was randomly selected for medical record review. Additionally, records from a random sample of patients with AD were reviewed to assess sensitivity. Overall, 341 records were sought and 262 adjudicated by an expert ophthalmologist. The positive predictive value (PPV) of each algorithm was calculated and compared to a pre-specified threshold of ≥ 70%.

For conjunctivitis, the final algorithm was ≥ 1 conjunctivitis diagnosis (PPV = 81%, 95% confidence interval [CI]: 73%-87%). For keratitis, the final algorithm combined the following 2 candidate algorithms: ≥ 1 keratitis diagnosis and ≥ 1 dispensing of a topical antibiotic or antibiotic-steroid combination (PPV = 91%); and ≥ 1 keratitis diagnosis and ≥ 1 dispensing of an ophthalmic corticosteroid, topical immune-modulator, or topical NSAID (PPV = 68%) for an overall PPV of 80% (95% CI: 55%-93%).

The first claims-based algorithms to identify conjunctivitis and keratitis among AD patients were developed and validated. They are available for use in future studies, particularly to better understand conjunctivitis and keratitis occurrence among patients with AD.

The relationship between keratoconus and various allergic diseases has been a subject of controversy.

In the present study, a systematic review and meta-analysis was conducted to investigate the association between allergic rhinitis (AR) and keratoconus.

Relevant and eligible studies from PubMed, Web of Science, and the Cochrane Library were systematically reviewed to evaluate the association between AR and keratoconus. Observational studies that reported the number of patients with and without keratoconus, as well as the number of patients with keratoconus diagnosed with or without AR, were included. Two reviewers independently screened eligible studies and extracted data. A bivariate meta-analysis was conducted to calculate the pooled odds ratio of keratoconus in patients with versus without AR. A sensitivity analysis was performed using the adjusted odds ratio reported in the included studies to validate the findings.

Seven studies involving 775,574 participants were included in the meta-analysis. Among them, 29,082 patients had keratoconus. The pooled odds ratio of keratoconus in patients with AR was 1.71 (95% confidence interval [CI]: 1.36-2.15; P < .001; I2 = 96%), and the pooled adjusted odds ratio was 1.72 (95% CI: 1.23-2.40; P = .001; I2 = 97%).

Patients with AR have significantly higher odds of keratoconus than those without AR. Future studies are warranted to investigate the causal relationship and evaluate the cost-effectiveness of early screening, using methods such as corneal topography, and referral for keratoconus in patients with AR.

Although many studies have indicated that atopic dermatitis (AD) could contribute to the risk of keratoconus (KC), the causality between AD and KC remains controversial. This study aimed to explore the potential causal associations between AD and KC.

Instrumental variables for both exposures and outcomes were obtained from large-scale genome-wide association study summary statistics from previous meta-analyses. Mendelian randomization (MR) was applied to infer causal associations between AD and KC. Our main analyses were conducted by inverse-variance weighted (IVW) method multiplicative random effect model, complemented with additional five models and sensitivity analyses. Reverse MR analysis was applied to determine the direction of the causal association between AD and KC.

Both IVW and weighted median methods revealed a causal effect of AD on KC (IVW odds ratio [OR], 1.475; P = 4.16 × 10-4; weighted median OR, 1.351; P = 7.65 × 10-3). The weighted mode, simple mode, and MR Egger methods demonstrated consistent direction of causality. Evidence from all sensitivity analyses further supported these associations. Reverse MR analyses did not suggest causal effects of KC on AD.

This study supported a significant causal effect of AD on KC, and reverse MR analysis proved that the causal association was unilateral.

This study provides valid evidence that regular ophthalmic examinations are recommended for patients with AD to detect and prevent KC at an early stage.

Eyelid dermatitis (ED) affects a cosmetically significant area and leads to patients' distress. Despite ongoing and recent research efforts, ED remains a multidisciplinary problem that needs further characterization. We aimed to evaluate the atopic eyelid dermatitis (AED) frequency in ED patients and to perform their clinical profiling. PubMed databases were searched from 01.01.1980 till 01.02.2024 to PRISMA guidelines using a search strategy: (eyelid OR periorbital OR periocular) AND (dermatitis or eczema). Studies with patch-tested ED patients were included. Proportional meta-analysis was performed using JBI SUMARI software. We included 65 studies across Europe, North America, Asia and Australia, with a total of 21,793 patch-tested ED patients. AED was reported in 27.5% (95% CI 0.177, 0.384) of patch-tested ED patients. Isolated ED was noted in 51.6% (95% CI 0.408, 0.623) of 8453 ED patients with reported lesion distribution, including 430 patients with isolated AED. Our meta-analysis demonstrated that the AED frequency in patch-tested ED patients exceeded the previous estimate of 10%. Isolated AED was noted in adult patients, attending contact allergy clinics. Future studies are needed to elucidate the global prevalence and natural history of isolated AED in adults.

Cendakimab selectively targets interleukin (IL)-13, a type 2 cytokine implicated in atopic dermatitis (AD) pathogenesis, by inhibiting binding to its receptors (IL13R-α1 and IL13R-α2). Proof-of-concept work in AD supports using cendakimab for type 2 inflammatory diseases.

To evaluate the efficacy and safety of cendakimab compared with placebo in patients with moderate to severe AD.

This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging clinical trial was conducted from May 2021 to November 2022. Adult patients with moderate to severe AD and inadequate response to topical medications were enrolled at 69 sites in 5 countries (US [n = 26], Japan [n = 17], Canada [n = 9], Poland [n = 9], and Czech Republic [n = 8]). Data were analyzed between April 25, 2023, and October 16, 2023.

Patients were randomized (1:1:1:1) to receive subcutaneous cendakimab, 360 mg, every 2 weeks; 720 mg, every 2 weeks; 720 mg, once weekly; or placebo.

Mean percentage change in Eczema Area and Severity Index scores from baseline to week 16. Hierarchical testing with multiplicity adjustment was performed for 720 mg, once weekly vs placebo, then 720 mg, every 2 weeks vs placebo, and then 360 mg, every 2 weeks vs placebo.

Overall, 221 patients were randomized, and 220 received study drug (95 women [43%]; mean [SD] age, 37.7 [13.9] years; 720 mg, once weekly [54 (24%)]; 720 mg, every 2 weeks [55 (25%)]; 360 mg, every 2 weeks [55 (25%)]; placebo [56 (26%)]). The primary efficacy end point was met for cendakimab, 720 mg, once weekly vs placebo (-84.4 vs -62.7; P = .003) but missed statistical significance for 720 mg, every 2 weeks (-76.0 vs -62.7; P = .06). The treatment effect for 360 mg, every 2 weeks (-16.3; nominal P = .03 vs placebo) was comparable with 720 mg, once weekly (-21.8); however, significance was not claimed because the hierarchical testing sequence was interrupted. Of patients with treatment-emergent adverse events leading to discontinuation, 4 (7.4%) received 720 mg, once weekly; 2 (3.6%) 720 mg, every 2 weeks; 1 (1.8%) 360 mg, every 2 weeks; and 2 (3.6%) placebo.

The results of this randomized clinical trial indicated that cendakimab was effective, generally safe, and well-tolerated in patients with moderate to severe AD. The primary end point was met with a significant reduction in Eczema Area and Severity Index scores with 720 mg, once weekly at week 16. Cendakimab demonstrated progressive AD improvement at all doses during 16 weeks of treatment.

ClinicalTrials.gov Identifier: NCT04800315.

This comprehensive review offers a detailed look at atopic dermatitis (AD) treatment in Italy, focusing primarily on the use of biologics and small molecules. In response to advancing knowledge of AD's causes and treatments, there's a global need for updated guidelines to provide physicians with a more comprehensive clinical perspective, facilitating personalized treatment strategies. Dupilumab, a groundbreaking biologic, gained approval as a significant milestone. Clinical trials demonstrated its ability to significantly reduce AD severity scores, with an impressive 37% of patients achieving clear or nearly clear skin within just 16 weeks of treatment. Real-world studies further support its efficacy across various age groups, including the elderly, with a safety profile akin to that of younger adults. Tralokinumab, a more recent approval, shows promise in clinical trials, particularly among younger populations. However, its real-world application, especially in older individuals, lacks comprehensive data. Janus Kinases inhibitors like Upadacitinib, Baricitinib, and Abrocitinib hold substantial potential for AD treatment. Nevertheless, data remains limited for patients over 75, with older adults perceived to carry a higher risk profile. Integrated safety analyses revealed individuals aged 60 and above experiencing major adverse cardiovascular events and malignancies, underscoring the need for cautious consideration. While these therapies offer promise, especially among younger patients, further research is essential to determine their safety and efficacy in various populations, including pediatric, geriatric, and those with comorbidities. Biologics and small molecules are improving AD treatment, as shown in this review.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a bipolar age distribution in childhood, adolescence and middle adulthood. Up to 50% of AD patients show ocular involvement, which can be potentially sight threatening. Clinically, the majority of cases present with atopic blepharo(kerato)conjunctivitis or atopic keratoconjunctivitis (AKC); other clinical variants from this group of inflammatory ocular surface diseases are keratoconjunctivitis vernalis in childhood and adolescence and allergic conjunctivitis. In addition to the aforementioned blepharitis, keratitis and conjunctivitis, AD is also associated with eyelid involvement with subsequent eyelid malposition, limbal insufficiency with the development of pseudopterygia, (chronic) cicatrizing conjunctivitis with symblephara formation and fornix shortening, as well as ocular surface malignancies such as conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma. In addition, an association with AD or AKC has been described for keratoconus. Whereas the therapy of AD in dermatology has made revolutionary advances in recent years through the use of biologicals, the primary use of these biologicals in ophthalmological complications is still very hesitant. Treatment here is often provided using topical steroids and calcineurin inhibitors. The following article summarises recent developments in basic and clinical dermatological research and discusses them in the context of current concepts for ophthalmological therapy.

Atopic dermatitis (AD) is a chronic inflammatory skin disease for which new targeted therapies are currently available. Due to the increased rates of ocular surface disease (OSD) reported during treatment with these new targeted treatments, more insight into the occurrence and pathomechanism of OSD in moderate-to-severe AD patients is needed. Therefore, this review's first part highlights that most patients with moderate-to-severe AD already have characteristics of OSD before starting targeted treatment. Remarkably, not all AD patients with OSD report ocular symptoms. OSD in AD is associated with less conjunctival goblet cells (GC) compared to healthy controls. In addition, OSD severity in AD patients is associated with high AD activity, the presence of eyelid and/or facial eczema, and high levels of AD-related severity biomarkers in tear fluid. The second part of this review highlights that pre-existing ocular pathology (e.g. in combination with the use of ophthalmic medication or eyelid eczema) may be associated with the development of dupilumab-associated ocular surface disease (DAOSD). During dupilumab treatment, DAOSD (which can be new-onset OSD or worsening of pre-existing OSD) is observed in approximately one-third of the dupilumab-treated AD patients. Anti-inflammatory ophthalmic treatment improves DAOSD, and dose reduction of dupilumab may also be an effective treatment option. The pathomechanism of DAOSD is still not fully elucidated. In a prospective study low, but stable conjunctival GC numbers were observed in moderate-to-severe AD patients, before and during dupilumab treatment. However, the Mucin 5 AC (MUC5AC) expression of GCs decreased during dupilumab treatment, suggesting an impairment of the GC function by dupilumab treatment. In addition, higher dupilumab tear fluid levels were found in dupilumab-treated AD patients with moderate-to-severe OSD compared to patients with no or mild OSD, whereas the dupilumab serum levels are similar. Clinicians should be aware of the frequent occurrence of OSD in moderate-to-severe AD patients, and a low-threshold referral to an ophthalmologist is recommended.

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.

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.

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.

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.

The aim of our minireview is to provide a brief overview of the diagnosis, clinical aspects, treatment options, management, and current literature available regarding herpes simplex keratitis (HSK). This type of corneal viral infection is caused by the herpes simplex virus (HSV), which can affect several tissues, including the cornea. One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea. After the initial infection, the HSV can establish a latent infection in the trigeminal ganglion, a nerve cluster near the eye. The virus may remain dormant for extended periods. Periodic reactivation of the virus can occur, leading to recurrent episodes of HSK. Factors triggering reactivation include stress, illness, immunosuppression, or trauma. Recurrent episodes can manifest in different clinical patterns, ranging from mild epithelial involvement to more severe stromal or endothelial disease. The severity and frequency of recurrences vary among individuals. Severe cases of HSK, especially those involving the stroma and leading to scarring, can result in vision impairment or even blindness in extreme cases. The cornea's clarity is crucial for good vision, and scarring can compromise this, potentially leading to visual impairment. The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization. Antiviral medications, such as oral Acyclovir or topical Ganciclovir, may be prescribed for prophylaxis. The immune response to the virus can contribute to corneal damage. Inflammation, caused by the body's attempt to control the infection, may inadvertently harm the corneal tissues. Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation. In summary, the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.

Lebrikizumab (Ebglyss®) is a subcutaneous recombinant humanized IgG4 anti-IL-13 monoclonal antibody developed by Almirall S.A. and Eli Lilly and Company for the treatment of atopic dermatitis (AD). In November 2023, lebrikizumab was approved in the EU for the treatment of moderate-to-severe AD in adults and adolescents 12 years and older with a body weight of at least 40 kg who are candidates for systemic therapy. Lebrikizumab was approved for the same indication in the UK in December 2023 and in Japan in January 2024. Lebrikizumab is under regulatory review for the treatment of AD in the USA, Switzerland and Australia. This article summarizes the milestones in the development of lebrikizumab leading to this first approval for AD.

Guidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology.

To produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD.

A multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group supported guideline development by performing systematic evidence reviews, facilitating guideline processes, and holding focus groups with patient and family partners. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed rating the certainty of evidence and strength of recommendations. Evidence-to-decision frameworks, subjected to public comment, translated evidence to recommendations using trustworthy guideline principles.

The panel agreed on 25 recommendations to gain and maintain control of AD for patients with mild, moderate, and severe AD. The eAppendix provides practical information and implementation considerations in 1-2 page patient-friendly handouts.

These evidence-based recommendations address optimal use of (1) topical treatments (barrier moisturization devices, corticosteroids, calcineurin inhibitors, PDE4 inhibitors [crisaborole], topical JAK inhibitors, occlusive [wet wrap] therapy, adjunctive antimicrobials, application frequency, maintenance therapy), (2) dilute bleach baths, (3) dietary avoidance/elimination, (4) allergen immunotherapy, and (5) systemic treatments (biologics/monoclonal antibodies, small molecule immunosuppressants [cyclosporine, methotrexate, azathioprine, mycophenolate, JAK inhibitors], and systemic corticosteroids) and UV phototherapy (light therapy).

Background and Objectives: Atopic dermatitis (AD), also known as eczema, is a common chronic inflammatory skin condition affecting 16.5 million adults in the United States. AD is characterized by an impaired epidermal barrier that can predispose individuals to infection. End-stage renal disease (ESRD) is also commonly complicated by infections due to chronic vascular access and immune-system dysfunction, possibly related to uremia. Multiple studies have reported that renal disease is a common comorbidity in adults with atopic dermatitis. The aim of this study was to determine whether AD is a risk factor for certain infections in patients with ESRD. Materials and Methods: Using the United States Renal Data System, a retrospective cohort analysis was conducted on adult ESRD patients initiating dialysis between 2004 and 2019 to investigate associations between infections and AD in this population. Results: Of 1,526,266 patients, 2290 were identified with AD (0.2%). Infectious outcomes of interest were bacteremia, septicemia, cellulitis, herpes zoster, and conjunctivitis. In all infectious outcomes except for conjunctivitis, patients with the infectious outcomes were more likely to carry a diagnosis of AD. After controlling for demographic and clinical covariates, AD was associated with an increased risk of cellulitis (adjusted relative risk (aRR) = 1.39, 95% confidence interval (CI) = 1.31-1.47) and herpes zoster (aRR = 1.67, CI = 1.44-1.94), but not with bacteremia (aRR = 0.96, CI = 0.89-1.05), septicemia (aRR = 1.02, CI = 0.98-1.08), or conjunctivitis (aRR = 0.97, CI = 0.740-1.34). Conclusions: Overall, after controlling for demographic and clinical covariates and adjusting for person-years-at-risk, AD was associated with an increased risk for some, but not all, infections within the population of patients with ESRD.

Atopic dermatitis (AD) and ocular allergy aka allergic eye disease (AED) are two common conditions that often coexist in patients. However, molecular connections between these two conditions are incompletely understood. While common etiologic components including Th2 immune signaling have been suggested for AD and AED, the mechanism how current Th2-targetd therapies (dupilumab, tralokinumab) for AD can augment conjunctivitis is not well understood.

Differentially regulated genes and pathways relevant for AD disease manifestation are known. In contrast, similar information is not yet available for AED, which could be largely addressed by emerging noninvasive ocular sampling techniques. Emerging evidence indicated a reduction in goblet cell number and mucin production in a subpopulation of AD patients with AD leading to adverse ocular outcomes, while other potential mechanisms could also be involved. Involvement of particular barrier function protein(s) in AED needs further investigation.

Modern cytokine-targeted therapies for AD showed elevated risk for developing conjunctivitis. Recently developed noninvasive sampling techniques should be leveraged to identify AD endotypes associated with AED and with dupilumab-associated ocular outcomes.

Lebrikizumab is a monoclonal antibody that binds with high affinity to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency.

To report integrated safety of lebrikizumab in adults and adolescents with moderate-to-severe atopic dermatitis from phase 2 and 3 studies.

Five double-blind, randomized placebo-controlled studies; one randomized open-label study; one adolescent open-label, single-arm study; and one long-term safety study were summarized in two datasets: (1) placebo-controlled week 0-16 (All-PC Week 0-16) in patients who received lebrikizumab 250 mg every 2 weeks (LEBQ2W) versus placebo and (2) patients who received any dose of lebrikizumab at any time during the studies (All-LEB). Exposure-adjusted incidence rates (IR)/100 patient-years (PY) are provided.

A total of 1720 patients received lebrikizumab (1637.0 PY exposure). In All-PC Week 0-16, the frequency of treatment-emergent adverse events (TEAEs) was similar between treatment groups; most events were nonserious and mild or moderate in severity. The most frequently reported TEAEs were atopic dermatitis (placebo) and conjunctivitis (LEBQ2W). Frequencies of conjunctivitis cluster were 2.5% (placebo) and 8.5% (LEBQ2W), and all events were mild or moderate (All-LEB 10.6%, IR, 12.2). Frequencies of injection site reactions were 1.5% (placebo) and 2.6% (LEBQ2W; All-LEB 3.1%, IR, 3.3). Frequencies of adverse events leading to treatment discontinuation were 1.4% (placebo) and 2.3% (LEBQ2W; All-LEB 4.2%, IR, 4.5).

The safety profile for lebrikizumab consisted of TEAEs that were mostly nonserious, mild or moderate in severity, and did not lead to treatment discontinuation. The safety profile was similar in both adults and adolescents.

GOV: NCT02465606, NCT02340234, NCT03443024, NCT04146363, NCT04178967, NCT04250337, NCT04250350, NCT04392154 Safety of lebrikizumab in adults and adolescents with moderate-to-severe atopic dermatitis: an integrated analysis of eight clinical trials (MP4 34165 KB).

Atopic dermatitis (AD) is a common disease that is associated with atopic and nonatopic comorbidities. There has been a growing interest in this area of AD, because presence or risk of comorbidities can in many ways impact the management of patients with AD. Thus, some treatments for AD may improve its comorbidities as well, whereas others may increase their risk. In this review article, we discuss various comorbidities of AD mostly on the basis of the results of recent multiple systematic reviews and meta-analyses to update readers about this rapidly developing area of dermatology. We emphasize the important information provided by studies presenting both relative risk and absolute risk, and show that AD is associated with, among others, atopic comorbidities such as asthma, rhinitis, and food allergy, nonatopic comorbidities such as ocular, psychiatric, infectious, endocrine, autoimmune, and cardiovascular diseases, and certain cancers. Clinicians need to be aware of these and be cognizant about positive and negative effects of existing and new treatments for AD.

Atopic dermatitis (AD) is associated with different comorbidities.

To develop evidence-based and practical recommendations for comorbidity detection in patients with AD in daily practice.

We employed a modified RAND/UCLA methodology, including a systematic literature review (SLR). A group of six experts on AD was established. We conducted a comprehensive search strategy on Medline, Embase, and Cochrane Library up to June 2020. The selection criteria included studies with AD patients with any comorbidity reporting data on comorbidity prevalence, burden, and management. The included studies quality was assessed. The SLR results were discussed in a nominal group meeting, and several recommendations were generated. The recommendation agreement grade was tested on additional experts through a Delphi process.

The recommendations cover the following issues: 1) Which comorbidities should be investigated at the first and subsequent visits; 2) How and when should comorbidities be investigated (screening); 3) How should patients with specific comorbidities be referred to confirm their diagnosis and initiate management; 4) Specific recommendations to ensure an integral care approach for AD patients with any comorbidity.

These recommendations seek to guide dermatologists, patients, and other stakeholders in regard to early comorbidity identification and AD patient referral to improve decision-making.

Ocular surface diseases (OSDs), including conjunctivitis and blepharitis, are common in atopic dermatitis (AD) patients, but the magnitude and patient characteristics are unclear.

To examine the prevalence of OSDs in adults with AD and identify patient characteristics and risk factors.

We designed a cross-sectional questionnaire-based survey and sent it via a secure public mail to all adult Danes with a hospital diagnosis of AD (ICD-10 code L20.x) registered in the National Patient Register (n = 16 718) between 2000 and 2019 and 7044 (42%) participated. Primary outcomes were OSDs and severity according to Ocular Surface Disease Index (OSDI). Adjusted odds ratios (aOR) were calculated with 95% confidence intervals (CIs) using logistic regression models.

Respondents were mostly females and middle-aged (67.4%, mean [SD] age, 39.0 [15.5] years). Based on Patient-Oriented SCORing Atopic Dermatitis 49% had mild AD, 35% moderate, 10% severe and in 6% AD was inactive; 44.3% reported physician-diagnosed asthma bronchiale and 55.8% rhinitis. The lifetime prevalence of OSDs was 66.6% for conjunctivitis, 63.5% for hordeolum, 11.0% for blepharitis, 9.7% for keratitis, 2.0% for pterygium, 1.5% for symblepharon, 1.1% for keratoconus and 12.7% reported current conjunctivitis. Factors associated with lifetime occurrence of conjunctivitis included mild, moderate, and severe AD (aOR = 1.48 [95% CI, 1.02-2.14], aOR = 1.73 [95% CI, 1.19-2.53], aOR = 2.17 [95% CI, 1.42-3.21]), asthma bronchiale and rhinitis (aOR = 1.76 [95% CI, 1.49-2.07]), childhood-onset of AD (aOR = 1.34 [95% CI, 1.16-1.56]) and systemic AD treatment (aOR = 1.27 [95% CI, 1.08-1.50]). Use of soft and hard contact lenses (aOR = 2.15 [95% CI, 1.65-2.80], aOR = 3.35 [95% CI, 1.62-6.92]) were associated with lifetime occurrence of keratitis. Moderate and severe AD, asthma bronchiale and rhinitis were also associated with a higher OSDI level.

This study identified important patient factors associated with OSDs. Clinicians should be attentive of ocular signs and symptoms in AD patients and ask about these.

Tralokinumab, a fully human immunoglobulin G4 monoclonal antibody that specifically binds to the interleukin-13 cytokine with high affinity, effectively reduces moderate-to-severe atopic dermatitis when given every 2 weeks. The incidence of conjunctivitis is elevated compared to placebo, but severity and etiology have not been examined.

To analyze conjunctivitis data recorded in five randomized, placebo-controlled trials of tralokinumab in adult patients with moderate-to-severe atopic dermatitis.

Overall, 2285 adults with atopic dermatitis were studied up to 16 weeks. Cochran-Mantel-Haenszel weights were applied to calculate adjusted adverse-event incidences.

Incidence of conjunctivitis was higher (7.5%) with tralokinumab compared to placebo (3.2%). Most events were mild or moderate in severity and 78.6% and 73.9% of events resolved during the trial in the tralokinumab and placebo groups, respectively. Two (1.4%) events led to permanent discontinuation of tralokinumab. An increased incidence of conjunctivitis, regardless of treatment group, was associated with more severe baseline atopic dermatitis, and history of allergic conjunctivitis/atopic keratoconjunctivitis, as well as the number of atopic comorbidities. Limitation This analysis reports events up to Week 16 only, with limited confirmation of conjunctivitis and its etiology by an ophthalmologist and insufficient reporting of ophthalmic treatments.

Treatment with tralokinumab was associated with increased incidence of conjunctivitis compared to placebo, but these cases were mostly mild and transient.

Dupilumab is approved to treat moderate-to-severe atopic dermatitis (AD) in several countries in patients as young as 6 years of age. Since its approval, practical issues related to the use of dupilumab for AD have arisen, with particular interest in transitioning from current therapies and managing medication overlap, considerations for special populations of patients with AD, and management of potential adverse events.

This article aims to review the literature addressing several practical management issues related to dupilumab use for AD and to provide a framework for clinical decision-making in these circumstances and sub-populations. Each statement was reviewed, revised and voted on by authors to provide their level of agreement and degree of uncertainty for each statement.

An agreement level > 80% was achieved for all of the statements.

The expert panel provides statements considering the practical management of patients with AD taking dupilumab to inform clinical decision-making in specific but frequently encountered clinical situations.