Segregation, immunohistochemical, molecular and functional analyses classify a novel missense variant in fumarate hydratase (FH) as pathogenic.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant cancer predisposition syndrome characterized by cutaneous leiomyomas, uterine leiomyomas, and aggressive renal cancer. Germline variants in the fumarate hydratase (FH) gene predispose to HLRCC. Identifying germline pathogenic FH variants enables lifetime renal cancer screening and genetic testing for family members. In this report, we present a FH missense variant (c.1039T>C (p.S347P)), initially classified as a variant of uncertain significance. Clinical assessment, histopathological findings, molecular genetic studies, and enzymatic activity studies support the re-classification of the FH c.1039T>C variant to "pathogenic" based on ACMG/AMP criteria. Further insights into pathological recognition of FH-deficient renal cancer are discussed and should be recognized. This study has shown how (a) detailed multi-disciplinary analyses of a single variant can reclassify rare missense variants in FH and (b) careful pathological review of renal cancers is obligatory when HLRCC is suspected.

Prevalence of omalizumab-resistant chronic urticaria and real-world effectiveness of dupilumab in patients with omalizumab-refractory chronic urticaria: a single-centre experience.

Chronic urticaria (CU) is characterized by weals (hives) angio-oedema (or both) that last for ≥ 6 weeks, with chronic spontaneous urticaria (CSU) being the most common subtype. Patients with omalizumab-refractory CSU represent an unmet clinical need. In this study, we aimed to assess the prevalence and predictors of omalizumab failure in a large cohort of patients with CU and assess the effectiveness of dupilumab for omalizumab-refractory CU. Of 338 patients with CU, 33 received omalizumab; 69.7% (n = 23) were responders and 30.3% (n = 10) were nonresponders. Bivariate regression demonstrated that female sex [adjusted odds ratio (aOR) 1.53, 95% confidence interval (CI) 1.14-2.06], higher baseline weekly urticaria activity score (aOR 1.05, 95% CI 1.01-1.09) and older age (controlling for sex) (aOR 1.00, 95% CI 1.00-1.01) were associated with omalizumab failure. Of 10 patients with omalizumab-refractory CU, 3 were well controlled with ciclosporin (all children), whereas the 7 adults failed a mean [standard deviation (SD)] of 5.6 (2.6) treatments, including ciclosporin. All seven achieved a complete response with dupilumab, with time to response varying between 1 and 6 months. While our results suggest a favourable efficacy of dupilumab in patients with omalizumab-refractory CU, future confirmatory studies are required.

Cold-induced anaphylaxis triggered by drinking cold water.

Cold urticaria is an inducible urticaria in which hives and angioedema appear after exposure to cold. The symptoms of cold urticaria often are limited to hives/angioedema. However, in up to 20% of cases, cold exposure may trigger anaphylaxis. We report the case of an 11-year-old boy previously diagnosed with chronic spontaneous urticaria who developed facial swelling, itchy hives, difficulty in breathing, vomiting and abdominal pain within 5 minutes of drinking cold water. He received a standard dose of non-sedating second-generation antihistamines at home. He was observed in the emergency room for 2 hours and discharged with an epinephrin autoinjector. During the subsequent outpatient clinic visit, an ice cube test was performed which confirmed the new diagnosis of comorbid cold-induced chronic urticaria. On further questioning, the parents reported occurrence of hives following swimming in the swimming pool. Cold-induced urticaria should be suspected in cases of anaphylaxis associated with cold exposure. Patients with chronic forms of urticaria who present with new anaphylaxis should be assessed for a potential concomitant cold-induced form.

Skin disorders and interstitial lung disease: Part I-Screening, diagnosis, and therapeutic principles.

Numerous inflammatory, neoplastic, and genetic skin disorders are associated with interstitial lung disease (ILD), the fibrosing inflammation of lung parenchyma that has significant morbidity and mortality. Therefore, the dermatologist plays a major role in the early detection and appropriate referral of patients at risk for ILD. Part 1 of this 2-part CME outlines the pathophysiology of ILD and focuses on clinical screening and therapeutic principles applicable to dermatological patients who are at risk for ILD. Patients with clinical symptoms of ILD should be screened with pulmonary function tests and high-resolution chest computed tomography. Screening for pulmonary hypertension should be considered in high-risk patients. Early identification and elimination of pulmonary risk factors, including smoking and gastroesophageal reflux disease, are essential in improving respiratory outcomes. First-line treatment interventions for ILD in a dermatological setting include mycophenolate mofetil, but the choice of therapeutic agents depends on the nature of the primary disease, the severity of ILD, and comorbidities and should be the result of a multidisciplinary assessment. Better awareness of ILD among medical dermatologists and close interdisciplinary collaborations are likely to prevent treatment delays improving long-term outcomes.

Skin disorders and interstitial lung disease: Part II-The spectrum of cutaneous diseases with lung disease association.

Part 2 of this 2-part CME introduces dermatologists to noninfectious inflammatory skin diseases associated with pulmonary involvement. In many cases, dermatologists may be the first physicians recognizing respiratory complications associated with these diagnoses. Because pulmonary involvement is often the leading cause of morbidity and mortality, dermatologists should be comfortable screening and monitoring for lung disease in high-risk patients, recognizing cutaneous stigmata of lung disease in these patients and referring to pulmonary specialists, when appropriate, for prompt treatment initiation. Some treatments used for skin disease may not be appropriate in the context of lung disease and hence, choosing a holistic approach is important. Interstitial lung disease and pulmonary hypertension are the most common pulmonary complications and a significant cause of mortality in autoimmune connective tissue diseases, especially systemic sclerosis, dermatomyositis, and mixed connective tissue disease. Pulmonary complications, notably interstitial lung disease, are also common and life-threatening in sarcoidosis and vasculitis, while they are variable in neutrophilic and autoimmune blistering diseases.

The burden of alopecia areata: A scoping review focusing on quality of life, mental health and work productivity.

Alopecia areata (AA) is a common inflammatory autoimmune disease of the hair which can have a significant negative impact on quality of life (QoL), mental health and productivity. The aim of this scoping review is to elucidate the burden of AA focusing on these three realms. Inclusion criteria included all original manuscripts with no restriction on study type or statistical method written in English (or having an English abstract). For QoL 40 articles were included, 85 for psychiatric comorbidities, and 9 for work/school absenteeism/presenteeism mostly consisting of cross-sectional and observational cohort studies. QoL impairment was detected in over 75% of patients and up to one-third reported extremely severe QoL impairments. Specific QoL dimensions with the greatest impact were embarrassment, social functioning, as well as shopping and/or housework. Cross-sectional studies assessing the psychological burden of adult patients with AA found that the presence of signs of anxiety and/or depression ranged from 30% to 68% and affected all age groups. Rates of work absenteeism and unemployment were significantly higher in AA patients compared to healthy controls. Up to 62% reported making major life decisions including relationships, education and career based on their AA. Additionally, the extensive camouflage techniques and time lost from work led to a strong financial burden for patients and the numerous physician visits added to the healthcare costs. The overall impact of AA stretches much further than simply being an aesthetic concern and can negatively impact every part of an individual's life. An individualized approach and effective treatments will help reduce the psychosocial consequences and distress and return patients to their normal state of health.

The Role of Sex and Gender in Dermatology - From Pathogenesis to Clinical Implications.

BACKGROUND: Sex and gender have increasingly been recognized as significant risk factors for many diseases, including dermatological conditions. Historically, sex and gender have often been grouped together as a single risk factor in the scientific literature. However, both may have a distinct impact on disease incidence, prevalence, clinical presentation, severity, therapeutic response, and associated psychological distress. OBJECTIVES AND PROJECT DESCRIPTION: The mechanisms that underlie differences in skin diseases between males, females, men, and women remain largely unknown. The specific objectives of this review paper are:To highlight the biological differences between males and females (sex), as well as the sociocultural differences between men and women (gender) and how they impact the integumentary system.To perform a literature review to identify important sex- and gender-related epidemiological and clinical differences for various skin conditions belonging to a range of disease categories and to discuss possible biological and sociocultural factors that could explain the observed differences.To discuss dermatological skin conditions and gender-affirming treatments within the transgender community, a population of individuals who have a gender identity which is different than the gender identity they were assigned at birth. FUTURE IMPACT: With the rising number of individuals that identify as non-binary or transgender within our increasingly diverse communities, it is imperative to recognize gender identity, gender, and sex as distinct entities. By doing so, clinicians will be able to better risk-stratify their patients and select treatments that are most aligned with their values. To our knowledge, very few studies have separated sex and gender as two distinct risk factors within the dermatology literature. Our article also has the potential to help guide future prevention strategies that are patient-tailored rather than using a universal approach.

Pharmacological Agents Used in the Prevention and Treatment of Actinic Keratosis: A Review.

Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75-5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy.

Cold urticaria in a pediatric cohort: Clinical characteristics, management, and natural history.

BACKGROUND: Cold urticaria (coldU) is associated with substantial morbidity and risk of fatality. Data on coldU in children are sparse. We aimed to evaluate the clinical characteristics, management, risk of associated anaphylaxis, and resolution rate of coldU in a pediatric cohort. Additionally, we sought to compare these metrics to children with chronic spontaneous urticaria (CSU). METHODS: We prospectively enrolled children with coldU from 2013-2021 in a cohort study at the Montreal Children's Hospital and an affiliated allergy clinic. Data for comparison with participants with solely CSU were extracted from a previous study. Data on demographics, comorbidities, severity of presentation, management, and laboratory values were collected at study entry. Patients were contacted yearly to assess for resolution. RESULTS: Fifty-two children with cold urticaria were recruited, 51.9% were female and the median age of symptom onset was 9.5 years. Most patients were managed with second-generation H1-antihistamines (sgAHs). Well-controlled disease on sgAHs was negatively associated with concomitant CSU (adjusted odds ratio (aOR) = 0.69 [95%CI: 0.53, 0.92]). Elevated eosinophils were associated with cold-induced anaphylaxis (coldA; aOR = 1.38 [95%CI: 1.04, 1.83]), which occurred in 17.3% of patients. The resolution rate of coldU was 4.8 per 100 patient-years, which was lower than that of CSU (adjusted hazard ratio = 0.43 [95%CI: 0.21, 0.89], p < 10-2 ). CONCLUSION: Pediatric coldU bears a substantial risk of anaphylaxis and a low-resolution rate. Absolute eosinophil count and co-existing CSU may be useful predictive factors.

Analysis of Geographic and Environmental Factors and Their Association with Cutaneous Melanoma Incidence in Canada.

BACKGROUND: Over 90% of skin cancers including cutaneous melanoma (CM) are related directly to sun exposure. Despite extensive knowledge on ultraviolet radiation's (UVR) detrimental impact, many still fail to implement sun protection/sun avoidance. Human behavior, attitudes, and cultural norms of individuals and communities heavily depend on the surrounding climate/environment. In many instances, the climate shapes the culture/norms of the society. Canada has vast geographic/environmental differences. METHODS: In the current ecological study, we sought to examine the relationship between various geographic and environmental factors and the distribution of CM incidence by Forward Sortation Area (FSA) postal code across Canada. CM incidence data were extracted from the Canadian Cancer Registry, while environmental data were extracted from the Canadian Urban Environmental Health Research Consortium (greenspace, as measured by the normalized difference vegetation index; annual highest temperature; absolute number and average length of yearly heat events; annual total precipitation [rain and snow]; absolute number and average length of events with precipitation [rain and snow]; and summer UVR index). The above geographic/environmental data by FSA were correlated with the respective CM incidence employing negative binomial regression model. RESULTS: Our analysis highlights that increases in annual average temperature, summer UVR, and greenspace were associated with higher expected incidence of CM cases, while higher number of annual heat events together with highest annual temperature and higher average number of annual rain events were associated with a decrease in CM incidence rate. This study also highlights regional variation in environmental CM risk factors in Canada. CONCLUSIONS: This national population-based study presents clinically relevant conclusions on weather/geographic variations associated with CM incidence in Canada and will help refine targeted CM prevention campaigns by understanding unique weather/geographic variations in high-risk regions.

Utilization of the Psoriasis Epidemiology Screening Tool (PEST): A Risk Stratification Strategy for Early Referral of Psoriatic Arthritis Patients to Minimize Irreversible Erosive Joint Damage.

Psoriatic arthritis (PsA) can affect a diverse range of anatomical sites and its heterogeneous presentation contributes to misdiagnosis and delayed treatment with conventional and biologic disease-modifying antirheumatic drugs (DMARDs). Up to 15% of psoriasis (PsO) patients affected by PsA remain undiagnosed. Early detection and referral to a rheumatologist are crucial to optimize care and minimize irreversible erosive joint damage. To improve the rheumatology referral process, the authors propose a risk stratification tool to identify and triage patients with possible psoriatic arthritis. With the aim of ultimately assisting in early treatment initiation, this risk stratification algorithm can be used in both dermatology and primary care clinics. It is based on the Psoriasis Epidemiology Screening Tool (PEST) combined with the ClASsification criteria for Psoriatic Arthritis (CASPAR). This article intends to provide a rationale for further prospective studies whose objective would be to validate this screening algorithm.

Omalizumab for the Treatment of Bullous Pemphigoid: A Systematic Review of Efficacy and Safety.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease. Current treatment strategies are limited by their efficacy and/or side effect profile and the need for safer and effective alternatives is undeniable. We aimed to conduct a systematic review focusing on the efficacy and safety of omalizumab in BP patients. Embase, PubMed, Cochrane, and clinicaltrials.gov were searched for English and French articles published from inception to July 1, 2021, using search terms "omalizumab" OR "Xolair" OR "IGE025" OR "olizumab" AND "bullous pemphigoid." Screening and data extraction was performed by two raters independently. The primary outcome was complete response (CR), and secondary outcomes were partial response (PR), flare-ups, adverse events/vital status. In total, 22 articles were included, with a total of 56 patients. All patients had a refractory BP with mean disease duration of 13.5 ± 20.2 months (Standard Deviation (SD)) and failed 3.1 ± 1.6 therapies and many remained corticosteroids dependent. Overall, 87.5% of patients responded to treatment (55.4% CR and 32.1% PR), 7.1% discontinued the protocol and only 5.4% were non responders. A third of patients were able to discontinue all other therapies and most others were able to discontinue or taper systemic corticosteroids to <10 mg daily. Flare-ups occurred in 57.7% of patients upon discontinuation of omalizumab and/or steroid tapering, most patients recaptured response thereafter. Omalizumab was well tolerated by most patients. Omalizumab appears to be a promising treatment for BP with a good response rate and safety profile. However, several limitations were identified in current literature, and highlight the need for randomized controlled trials of omalizumab in BP.

Prominent Role of Type 2 Immunity in Skin Diseases: Beyond Atopic Dermatitis.

Type 2 immunity, illustrated by T helper 2 lymphocytes (Th2) and downstream cytokines (IL-4, IL-13, IL-31) as well as group 2 innate lymphoid cells (ILC2), is important in host defense and wound healing.1 The hallmark of type 2 inflammation is eosinophilia and/or high IgE counts and is best recognized in atopic diathesis. Persistent eosinophilia, such as seen in hypereosinophilic syndromes, leads to fibrosis and hence therapeutic Type 2 inhibition in fibrotic diseases is of high interest. Furthermore, as demonstrated in cutaneous T cell lymphoma, advanced disease is characterized by Th1 to Th2 switch allowing cancer progression and immunosuppression. Development of targeted monoclonal antibodies against IL-4Rα (eg, dupilumab) led to a paradigm shift for the treatment of atopic dermatitis (AD) and stimulated research to better understand the role of Type 2 inflammation in other skin conditions. In this review, we summarize up to date knowledge on the role of Type 2 inflammation in skin diseases other than AD and highlight whether the use of Type 2 targeted therapies has been documented or is being investigated in clinical trials. This manuscript reviews the role of Type 2 inflammation in dermatitis, neurodermatitis, IgE-mediated dermatoses (eg, bullous pemphigoid, chronic spontaneous urticaria), sclerodermoid conditions and skin neoplasms.

Extracorporeal Photopheresis and Its Use in Clinical Dermatology in Canada

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US FDA in 1988 for the treatment of Sézary syndrome, a leukemic form of cutaneous T-cell lymphoma (CTCL). Although CTCL remains the only FDA-approved indication, ECP has since been used off-label for numerous other conditions, including graft-versus-host disease (GvHD), systemic sclerosis, autoimmune bullous dermatoses, Crohn's disease, and prevention of solid organ transplant rejection. In Canada, ECP is mainly used to treat CTCL, acute and chronic GvHD, and in some instances systemic sclerosis. Herein, we review the current concepts regarding ECP mechanism of action, treatment considerations and protocols, and efficacy.

Clinical Characteristics, Management, and Natural History of Chronic Inducible Urticaria in a Pediatric Cohort.

BACKGROUND: Some forms of chronic urticaria (CU) can be specifically attributed to a response to a definite trigger, referred to as chronic inducible urticaria (CIndU). We aimed to assess the demographics, clinical characteristics, comorbidities, natural history, and management of pediatric patients with CIndU. METHODS: Over a 6-year period, children presenting to the allergy clinic at the Montreal Children's Hospital (MCH) with CIndU were prospectively recruited. CU was defined as the presence of wheals and/or angioedema, occurring for at least 6 weeks. A standardized diagnostic test was used to establish the presence of a specific form of urticaria. Resolution was defined as the absence of hives for 1 year without treatment. RESULTS: Sixty-four patients presented with CIndU, of which 51.6% were male, with a median age of 12.5 (interquartile range 7.3, 15.9) years. Cold CU and cholinergic CU were the most common subtypes (60.3 and 41.3%, respectively). Basophil counts were undetectable in 48.4% of the cases, and C-reactive protein levels were elevated in 7.8% of patients. Of all cases, 71.4% were controlled with second-generation antihistamines. The resolution rate was of 45.3% (95% confidence interval 33.1-57.5%), based on per-protocol population within the 6-year course of the study. Resolution was more likely in patients who presented with well-controlled urticaria control test scores and elevated CD63 counts and in those suffering from thyroid comorbidity. CONCLUSION: The natural history of CIndU resolution in pediatric patients was relatively low and was associated with elevated CD63 levels, as well as thyroid comorbidity.

Non-Melanoma Skin Cancer Distribution in the Russian Federation.

BACKGROUND: Non-melanoma skin cancer (NMSC) incidence has been increasing steadily around the world. The aim of the study is to describe geographic trends in incidence and mortality of NMSC in Russia between 2007 and 2017 and compare findings to other European countries. METHODS: We used geospatial analysis to map the incident cases and descriptive statistical analysis to analyze trends. Additionally, we assessed the relationship between ethnicity, geographic latitude/longitude, and NMSC incidence/mortality rates. We retrospectively analyzed the data from the Moscow Oncology Research Institute, Ministry of Health of the Russian Federation, for 2007-2017. Routine methods of descriptive epidemiology were used to study incidence and mortality rates by age groups, years, and jurisdictions (i.e., Federal Districts and Federal Subjects). RESULTS: In total, 733,723 patients were diagnosed with NMSC in Russia over the period 2007-2017, of whom 63% were women. The overall age-standardized incidence and mortality rates were 29.64/100,000 and 0.70/100,000, respectively. There was a consistent increase in age-standardized incidence rates over the study period, with a decreasing mortality rate. Geographic mapping revealed north-to-south and east-to-west gradients for NMSC. CONCLUSIONS: This study demonstrated longitudinal trends for NMSC incidence in Russia documenting that skin phototype, latitude/longitude, climate zones, and cultural practices remain dominant risk factors defining the epidemiology of NMSC. Moreover, this work identified several regions in the country (i.e., Republic of Adygea, Samara, Krasnodar Krai, etc.), where patient education/sun awareness campaigns will be useful to help reduce the risk of this malignancy.

Cutaneous Immune-Related Adverse Events (irAEs) to Immune Checkpoint Inhibitors: A Dermatology Perspective on Management [Formula: see text].

Immune checkpoint inhibitors have proven to be efficacious for a broad spectrum of solid organ malignancies. These monoclonal antibodies lead to cytotoxic T-cell activation and subsequent elimination of cancer cells. However, they can also lead to immune intolerance and immune-related adverse event (irAEs) that are new and specific to these therapies. Cutaneous irAEs are the most common, arising in up to 34% of patients on PD-1 inhibitors and 43% to 45% on CTLA-4 inhibitors. The most common skin manifestations include maculopapular eruption, pruritus, and vitiligo-like lesions. A grading system has been proposed, which guides management of cutaneous manifestations based on the percent body surface area (BSA) involved. Cutaneous irAEs may prompt clinicians to reduce drug doses, add systemic steroids to the regiment, and/or discontinue lifesaving immunotherapy. Thus, the goal is for early identification and concurrent management to minimize treatment interruptions. We emphasize here that the severity of the reaction should not be graded based on BSA involvement alone, but rather on the nature of the primary cutaneous pathology. For instance, maculopapular eruptions rarely affect <30% BSA and can often be managed conservatively with skin-directed therapies, while Stevens-Johnson syndrome (SJS) affecting even 5% BSA should be managed aggressively and the immunotherapy should be discontinued at once. There is limited literature available on the management of the cutaneous irAEs and most studies present anecdotal evidence. We review the management strategies and provide recommendations for psoriatic, immunobullous, maculopapular, lichenoid, acantholytic eruptions, vitiligo, alopecias, vasculitides, SJS/toxic epidermal necrolysis, and other related skin toxicities.

Toward Understanding of Environmental Risk Factors in Systemic Sclerosis [Formula: see text].

IMPORTANCE: Systemic sclerosis (SSc) is a severe, chronic, and incurable autoimmune fibrotic skin disease with significant extracutaneous involvement. Low concordance rate in twin studies and unequal geographic distribution of SSc argues for importance of environment in disease initiation and progression. OBJECTIVE: In this manuscript we provide a summary of all investigated potential external risk factors for SSc. DATA SOURCES: A literature search in PubMed and EMBASE database was performed for studies published until January 1, 2020 by 2 reviewers (EN and LO) independently. FINDINGS: Occupational and/or environmental exposures to silica and organic solvents are associated with increased incidence and severity of SSc. Exposure to epoxy resins, asbestos, and particulate air pollution favors increased risk of SSc, but data are based on limited number of observational studies. There is insufficient evidence to conclude an association between SSc development and other occupational (eg, welding fumes) or personal exposures (eg, smoking, vitamin D deficiency). Association of SSc with silicone breast implants has been disproven. Infectious pathogens (eg, Helicobacter pylori and angiotropic viruses) and dysbiosis seem to play a role in SSc development and severity, but their role remains to be clarified. CONCLUSIONS AND RELEVANCE: It may be prudent to counsel our patients with SSc (or those at risk of SSc) to avoid occupations with exposure to silica, organic solvents, asbestos and epoxy resins; restraint from smoking, using cocaine or drugs with pro-fibrotic potential. While the association between low vitamin D and SSc remains to be confirmed, we believe that SSc patients should be encouraged to maintain healthy vitamin D levels as benefits outweigh the risks.

Inhibition of IL-13: A New Pathway for Atopic Dermatitis [Formula: see text].

Dupilumab, a monoclonal antibody against the common receptor of interleukin (IL)-4 and IL-13, was the first biologic therapy approved in Canada for treatment of moderate-to-severe atopic dermatitis (AD). While it is considered safe and effective, dupilumab is not universally effective and 8%-38% of patients develop conjunctivitis, while some patients develop head and neck dermatitis. Thus, new therapeutic options are warranted. While both IL-4 and IL-13 play important roles in the pathogenesis of AD, it has been recently demonstrated that IL-13 is the primary upregulated cytokine in AD skin biopsy samples. A placebo-controlled phase 2b clinical trial evaluating the efficacy and safety of lebrikizumab, an IL-13 inhibitor, in AD demonstrated that, at 16 weeks, Eczema Area and Severity Index (EASI) 75 and Investigator's Global Assessment (IGA) 0/1 were achieved by 60.6% and 44.6% of patients taking lebrikizumab at its highest dose (vs 24.3% and 15.3% of patients taking placebo, respectively). Moreover, treatment with lebrikizumab was associated with rapid improvement of pruritus and low rates of conjunctivitis (1.4%-3.8%). Another IL-13 monoclonal antibody, tralokinumab, was evaluated for safety and efficacy in moderate-to-severe AD. By week 12, among adults receiving 300 mg tralokinumab, 42.5% achieved EASI-75 and 26.7% achieved IGA 0/1 score (vs 15.5% and 11.8% in the placebo group, respectively). Both lebrikizumab and tralokinumab demonstrated acceptable safety profiles in AD (and non-AD) trials with adverse events often being comparable between treatment and control groups. Thus, IL-13 inhibitors may provide a safe and effective treatment alternative for patients with moderate-to-severe AD.