A Practical Guide to Using Oral JAK Inhibitors for Atopic Dermatitis from the International Eczema Council.

BACKGROUND: Janus kinase inhibitors (JAKinibs) have the potential to dramatically alter the landscape of atopic dermatitis (AD) management due to their promising efficacy results from phase 3 trials and rapid onset of action. However, JAKinibs are not without risk, and their use is not appropriate for all AD patients, making this a medication class that dermatologists should understand and consider when treating patients with moderate-to-severe AD. OBJECTIVE: This consensus expert opinion statement from the International Eczema Council (IEC) provides a pragmatic approach to prescribing JAKinibs, including choosing appropriate patients, dosing, clinical and lab monitoring, as well as long-term use. METHODS: An international cohort of authors from the IEC with expertise in JAKinibs selected topics of interest and were formed into authorship groups covering 10 subsections. The groups performed topic-specific literature reviews, consulted up-to-date adverse event (AE) data, referred to product labels and provided analysis and expert opinion. The manuscript guidance and recommendations were reviewed by all authors as well as the IEC Research Committee. RESULTS: We recommend JAKinibs be considered for patients with moderate to severe AD seeking the benefits of rapid reduction in disease burden and itch, oral administration, and the potential for flexible dosing. Baseline risk factors should be assessed prior to prescribing JAKinibs, including increasing age, venous thromboembolisms, malignancy, cardiovascular health, kidney/liver function, pregnancy and lactation, and immunocompetence. Patients being considered for JAKinib therapy should be current on vaccinations and we provide a generalized framework for laboratory monitoring, though clinicians should consult individual product labels for recommendations as there are variations among the JAKinib class. Patients who achieve disease control should be maintained on the lowest possible dose, as many of the observed AEs occurred in a dose-dependent manner. Future studies are needed in AD patients to assess the durability and safety of continuous long-term use of JAKinibs, combination medication regimens, and the effects of flexible, episodic treatment over time. CONCLUSIONS: The decision to initiate a JAKinib should be shared among patient and provider, accounting for AD severity and personal risk/benefit assessment, including consideration of baseline health risk factors, monitoring requirements and treatment costs.

Comorbid Scenarios in Contact Dermatitis: Atopic Dermatitis, Irritant Dermatitis, and Extremes of Age.

Contact dermatitis (allergic and irritant) occurs when the skin encounters haptens that elicit a T cell-mediated hypersensitivity reaction (allergic) or a nonimmunologic, toxic reaction (irritant). Patch testing is the reference standard for diagnosing allergic contact dermatitis (ACD), although positive results are not always relevant. Therefore, the definitive diagnosis of ACD requires an astute clinician able to connect the results of patch testing appropriately with the clinical history and the cutaneous examination findings. Comorbid conditions such as atopic dermatitis can confound the accurate diagnosis of ACD because of the similarities in clinical presentation. Furthermore, both extremes of age can further challenge the diagnostic specificity of ACD owing to the maturing immune system and the space limitations present when the very young are patch tested. The goal of this Continuing Medical Education article is to discuss the challenges of diagnosing ACD in patients with unique comorbidities such as atopic dermatitis, given the morphologic similarities, and when to patch test these patients. Diagnosis of ACD will also be discussed in very young patients with a focus on patch test allergen selection despite the limited geographic space. The most common allergens reported in very young and old patients will also be discussed.

Patch Testing to Mentha piperita (Peppermint) Oil: The North American Contact Dermatitis Group Experience (2009-2020).

Background: Mentha piperita (MP; peppermint) oil has many commercial uses. Objective: To characterize the epidemiology of contact allergy to MP oil 2% petrolatum. Methods: Retrospective analysis of North American Contact Dermatitis Group data (2009-2020). Results: Of 28,128 patients tested to MP, 161 (0.6%) had an allergic reaction. Most allergic patients were female (77.0%) and/or over 40 years of age (71.4%). The most common anatomical sites of dermatitis included face (31.7%; of these, one-third specified lips), hands (17.4%), and scattered/generalized (18.6%). Nearly one-third (30.4%) of reactions were strong (++)/extreme (+++), and 80.1% were considered currently relevant. Common sources included oral hygiene preparations, foods, and lip products. Co-reaction with at least 1 of the other 19 fragrance/plant-related screening test preparations occurred in 82.6% (133/161) of MP-allergic patients, most commonly Cananga odorata oil (42.9%), fragrance mix I (41.0%), hydroperoxides of linalool (35.7%), Compositae mix (35.4%), Jasminum officinale oil (31.9%), Myroxylon pereirae (31.7%), and propolis (28.1%). Co-reaction with at least 1 of the 3 most commonly used fragrance screening allergens (fragrance mix I, fragrance mix II, and/or Myroxylon pereirae) was 59.6%. Conclusions: Twelve-year prevalence of MP allergy was 0.6%. Approximately 40% of cases would have been missed if only fragrance screening allergens were tested.

Photopatch testing: Clinical characteristics, test results, and final diagnoses from the North American Contact Dermatitis Group, 2009-2020.

BACKGROUND: Photoallergic contact dermatitis (PACD) is a delayed hypersensitivity reaction to allergens only in the presence of ultraviolet radiation in sunlight. Photopatch testing (PhotoPT) is necessary to confirm the diagnosis of PACD. There are few published studies of PhotoPT in North America. OBJECTIVE: To summarise the results of patients photopatch tested by members of the North American Contact Dermatitis Group (NACDG), 2009-2020. METHODS: Retrospective analysis of patient characteristics and PhotoPT results to 32 allergens on the NACDG Photopatch Test Series. RESULTS: Most of the 454 tested patients were female (70.3%), 21-60 years old (66.7%) and White (66.7%). There were a total of 119 positive photopatch tests. Sunscreen agents comprised 88.2% of those, with benzophenones responsible for over half of them. Final diagnoses included PACD in 17.2%, allergic contact dermatitis (ACD) in 44.5%, polymorphous light eruption (PMLE) in 18.9% and chronic actinic dermatitis (CAD) in 9.0% of patients. CONCLUSIONS: In 454 patients with suspected photosensitivity referred for photopatch testing in North America, approximately one-fifth had PACD. Sunscreen agents, especially benzophenones, were the most common photoallergens. Other common diagnoses included ACD, PMLE and CAD. Photopatch testing is an important tool for differentiating these conditions.

Occupational Contact Dermatitis in Construction Workers: A Retrospective Analysis of the North American Contact Dermatitis Group Data, 2001-2020.

Background: Construction workers (CWs) are at risk for occupational contact dermatitis (CD) owing to workplace exposures. Objective: Determine the prevalence of occupational allergic CD and characterize common occupational allergens in CWs referred for patch testing in the United States and Canada. Methods: Retrospective cross-sectional analysis of patients patch tested by the North American Contact Dermatitis Group from 2001 to 2020. Results: Of 47,843 patch-tested patients, 681 (1.4%) were CWs. Compared with non-CWs, CWs were more likely to be male (91.0% vs 30.9%) have occupational skin disease (36.9% vs 11.4%) and have hand involvement (37.2% vs 22.5%) (all P < 0.0001). Of 681 CWs, 60.1% (411) had clinically relevant positive patch test reactions, and nearly 1/3 of CWs (128) had occupationally relevant reactions. Most common occupationally relevant allergens were potassium dichromate 0.25% pet. (30.5%, 39/128), bisphenol A epoxy resin 1% pet. (28.1%, 36/128), carba mix 3% pet. (14.8%, 19/128), cobalt (ii) chloride hexahydrate 1% pet. (14.1%, 18/128), and thiuram mix 1% pet. (14.1%, 18/128). Top sources of occupationally relevant allergens were cement/concrete/mortar (20.4%, 46/225), gloves (15.1%, 34/225), and coatings (paint/lacquer/shellac/varnish/stains) (9.8%, 22/225). Conclusions: Occupational CD in North American CWs is common. In this group, frequently identified etiological sources of occupational allergic CD included metals, epoxy resin, and rubber.

Tangled Truths: Unraveling the Link Between Frontal Fibrosing Alopecia and Allergic Contact Dermatitis.

Frontal fibrosing alopecia (FFA) is an increasingly common diagnosis, especially in middle-aged women, and has garnered growing attention in the scientific literature. This variant of lichen planopilaris (LPP) is recognized as a progressive scarring alopecia affecting the frontal and temporal regions of the scalp as well as the eyebrows and occasionally other sites. Although its precise etiology remains elusive, various factors such as genetics, medications, hormonal influences, and environmental exposures-including specific chemicals present in sunscreens-have been implicated in its pathogenesis but without evidence of causality. The potential relationship between contact allergy and FFA has been explored, with some suggesting an increased prevalence of contact allergy among patients diagnosed with FFA. This article aims to explore the potential association between contact allergy and FFA, focusing on the current published literature and implicated allergens.

Allergic or Not: Final Interpretation of Doubtful Patch Test Reactions From the North American Contact Dermatitis Group, 2019-2020.

Background: Doubtful patch test reactions generally do not meet criterion for positivity in patch testing. However, the North American Contact Dermatitis Group (NACDG) allows for doubtful reactions to be coded with a final determination of "allergic/positive" based on the temporal pattern, appearance, known characteristics of the allergen, and/or other supportive patch test reactions. Objectives: To analyze NACDG data from the 2019-2020 patch test cycle to identify patterns in the interpretation and relevance of doubtful reactions. Methods: The frequency and proportions of doubtful reactions were tabulated and analyzed for patterns. Statistical analyses were limited to allergens with ≥30 doubtful reactions to ensure adequate sample size. Results: Of patch-tested patients, 31.9% (1315/4121) had ≥1 doubtful reaction. Of 2538 total doubtful reactions, 46% (n = 1167) had a final interpretation of "allergic/positive." The allergens with the highest proportion of doubtful reactions at the final visit were hydroperoxides of linalool 1% (4.5%), fragrance mix I 8.0% (3.9%), and cetrimonium chloride 0.5% (3.4%). Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) 0.02% (P < 0.001), MI 0.2% (P < 0.001), nickel sulfate hexahydrate 2.5% (P = 0.001), and neomycin sulfate 20.0% (P = 0.003) doubtful reactions were more likely to be interpreted as allergic than nonallergic. Methyldibromoglutaronitrile/phenoxyethanol 0.2% (P < 0.001), oleamidopropyl dimethylamine 0.1% (P < 0.001), formaldehyde 2.0% (P < 0.001), cetrimonium chloride 0.5% (P < 0.001), benzophenone-4 (sulisobenzone) 10% (P < 0.001), iodopropynyl butylcarbamate 0.5% (P < 0.001), cocamidopropyl betaine 1.0% (P = 0.002), and benzisothiazolinone 0.1% (P = 0.012) doubtful reactions were less likely to be interpreted as allergic. Of the 1167 doubtful reactions interpreted as allergic, 84.9% had current relevance. Conclusions: Doubtful reactions were common and approximately one half were coded with a final interpretation of "allergic/positive." Of those, most were clinically relevant. MCI/MI, MI, nickel, and neomycin were more likely to be interpreted as allergic.

More than just methylisothiazolinone: Retrospective analysis of patients with isothiazolinone allergy in North America, 2017-2020.

BACKGROUND: Isothiazolinones are a common cause of allergic contact dermatitis. OBJECTIVE: To examine the prevalence of positive patch test reactions to isothiazolinones from 2017-2020 and characterize isothiazolinone-allergic (Is+) patients compared with isothiazolinone nonallergic (Is-) patients. METHODS: Retrospective cross-sectional analysis of 9028 patients patch tested to methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) 0.02% aqueous, MI 0.2% aqueous, benzisothiazolinone (BIT) 0.1% petrolatum, and/or octylisothiazolinone (OIT) 0.025% petrolatum. Prevalence, reaction strength, concurrent reactions, clinical relevance, and source of allergens were tabulated. RESULTS: In total, 21.9% (1976/9028) of patients had a positive reaction to 1 or more isothiazolinones. Positivity to MI was 14.4% (1296/9012), MCI/MI was 10.0% (903/9017), BIT was 8.6% (777/9018), and OIT was 05% (49/9028). Compared with Is-, Is+ patients were more likely to have occupational skin disease (16.5% vs 10.3%, P <.001), primary hand dermatitis (30.2% vs 19.7%, P <.001), and be >40 years (73.1% vs 61.9%, P <.001). Positive patch test reactions to >1 isothiazolinone occurred in 44.1% (871/1976) of Is+ patients. Testing solely to MCI/MI would miss 47.3% (611/1292) of MI and 60.1% (466/776) of BIT allergic reactions. LIMITATIONS: Retrospective cross-sectional study design and lack of follow-up data. CONCLUSION: Sensitization to isothiazolinones is high and concurrent sensitization to multiple isothiazolinone allergens is common.

Patch Testing With Nickel, Cobalt, and Chromium in Patients With Suspected Allergic Contact Dermatitis.

Background: Allergic contact dermatitis is frequently caused by metals, including multiple metals simultaneously. Objectives: To assess characteristics and associations of positive and clinically relevant patch test (PT) reactions with solitary and concurrent metal sensitization. Methods: A retrospective analysis of PT results for nickel, cobalt, and/or chromium from the North American Contact Dermatitis Group between 2001 and 2018 (n = 43,522). Results: 18.0% had a positive/allergic reaction to nickel sulfate hexahydrate, 7.3% to cobalt chloride hexahydrate, and 3.0% to potassium dichromate. 87.9% patients had a currently relevant reaction to 0, 9.4% to 1, and 2.7% to multiple metals tested. Patients with 1 versus no currently relevant reactions to metal were more likely to have a primary dermatitis site of trunk, feet, and ears; patients with currently relevant reactions to multiple metals had more dermatitis affecting the trunk and ears. Metal sources varied by co-reacting metal, especially for patients with cobalt and chromium allergy. Jewelry was the most commonly identified source of nickel and cobalt for both solitary and concurrent metal allergy. Conclusions: Sensitization to multiple metals occurred in 6% of patients. Allergen sources varied between patients with sensitivity to 1 metal versus those who had concurrent sensitivity to cobalt and/or chromium.

Patch testing while immunosuppressed: potential risks and benefits.

INTRODUCTION: Allergic contact dermatitis (ACD) is a common cutaneous inflammatory skin disorder that is diagnosed via epicutaneous patch testing (PT). ACD may also coexist with other systemic inflammatory conditions such as atopic dermatitis and psoriasis. Many of the treatments used to manage severe ACD, along with other systemic conditions, interact with and suppress the immune system, thereby potentially interfering with the mechanism of PT. There is uncertainty in the literature regarding the effects of immunosuppression on the results of PT. METHODS: A comprehensive literature review was conducted using PubMed and Google Scholar to identify articles relevant to the topic of this review. Only articles available in English were included. AREAS COVERED: This review discusses the impact of immunomodulating therapies on the results of PT. We summarize the available evidence and provide updated recommendations for several immunomodulating drugs commonly used in patients undergoing PT. EXPERT OPINION: In general, the results of PT are most reliable when performed without immunosuppression. If this is not feasible, it is best to have patients on as low a dose of immunosuppression as possible, but it may not be necessary to stop or change an immunomodulating drug prior to PT.