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Background: The treatment of chronic refractory moderate-to-severe atopic dermatitis (AD) has traditionally relied on broad-spectrum systemic anti-inflammatory agents. With the introduction of biologics and Janus kinase inhibitors (Jakinib), the step management of moderate-to-severe AD is rapidly changing; however, guidelines have yet to provide formal recommendations for how to best incorporate these agents into the treatment plan. Objective: To summarize the updated evidence-based medical treatment for AD, including a proposed position for biologics and Jakinibs in the treatment algorithm. Methods: A literature search of several medical literature data bases for guidelines, position papers, systematic reviews, and clinical trials from 2012 to 2022 on the treatment of moderate-to-severe AD was conducted to prepare this narrative review. Results: Emollients and topical corticosteroids are the mainstay for treating acute flares and for maintaining chronic control. Second-line topical agents include calcineurin inhibitors, e.g., tacrolimus and pimecrolimus; crisaborole; and ruxolitinib. For acute flares, cyclosporine is preferred over systemic corticosteroids. For chronic treatment, phototherapy should be considered before systemic anti-inflammatory agents. Of the traditional anti-inflammatory agents, cyclosporine is the first-line choice, with methotrexate and azathioprine equal secondary choices. Although abrocitinib may have better efficacy then dupilumab based on indirect comparisons, abrocitinib requires closer monitoring for adverse events. Based on package labeling, Jakinibs, e.g., abrocitinib and upadacitinib, should be used only after failure with other systemic agents, including biologics (e.g., dupilumab and tralokinumab). Biologics and Jakinibs should be considered before the traditional systemic anti-inflammatory agents. Conclusion: Clinicians should consider a modified step management for AD as they await the development of national and international guideline recommendations for how best to position the biologics and Jakinibs into the AD treatment algorithm.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.

Background: The management of chronic rhinosinusitis with nasal polyps (CRSwNP) is evolving, with an emphasis on treating the underlying type 2 inflammation. Objective: The objective was to summarize the updated evidence-based medical and surgical treatment recommendations for CRSwNP, including the position of biologics in the treatment algorithm. Methods: This review compared and contrasted the therapeutic recommendations presented by the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 and the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis 2021. Results: The long-term use of intranasal corticosteroids and the short-term use of oral corticosteroids are strongly recommended, whereas corticosteroid-eluting implants are considered an option. Although the use of saline solution rinses is recommended, there is uncertainty as to whether irrigation is more effective than sprays. Oral aspirin (ASA) desensitization, followed by ASA ≥ 300 mg daily for patients with ASA-exacerbated respiratory disease may be considered. In general, the use of antifungal agents offers no benefit and potential harm. Although the use of oral antibiotics for an acute exacerbation is still debated, oral and topical antibiotics are discouraged for subacute or chronic use. Antileukotrienes are inferior to intranasal corticosteroids and are unlikely to provide added benefit when used concomitantly. It is unlikely that the benefit of oral antihistamines and decongestants outweigh the potential harm. Dupilumab is recommended for severe CRSwNP when consensus-determined criteria are met. Omalizumab may be an option with concomitant poorly controlled asthma. Mepolizumab and reslizumab may be used, particularly in patients with concomitant uncontrolled asthma. In allergic fungal rhinosinusitis, oral and topical antifungals, antileukotrienes, allergen immunotherapy, and omalizumab are therapeutic options. Although surgical intervention is recognized to be of benefit for CRSwNP, there are no evidence-based criteria to indicate when maximum medical treatment has failed. Conclusion: An evidence-based CRSwNP treatment algorithm for when to recommend surgery and/or initiate or discontinue biologics to maximize quality of life and cost-effectiveness is still lacking.

To review GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methods and discuss the clinical application of conditional recommendations in clinical guidelines, specifically in the context of anaphylaxis.Articles that described GRADE, evidence synthesis, evidence to recommendation frameworks, and shared decision making were used to discuss conditional recommendations of the 2020 Anaphylaxis GRADE guideline.A narrative review detailing concepts of GRADE and approaches to translate conditional recommendations to individualized and contextualized patient care.GRADE methods encourage a nuanced relationship between certainty of evidence and strength of recommendations. Strength of recommendation must incorporate key factors, including the balance between benefits and harms, patient values and preferences, and resource allocation (costs), with equity, feasibility, and acceptability also often included as considerations. GRADE guidelines provide recommendations that are characterized by directionality (for or against) and strength (strong or conditional). A conditional recommendation is tailored to context and primarily applied through a lens of patient preferences related to the likelihood of outcomes of importance and a shared decision-making approach. Although the 2020 Anaphylaxis GRADE guideline better informs the practice of anaphylaxis prevention through (1) identification and mitigation of risk factors for biphasic anaphylaxis and (2) evaluation of the use of glucocorticoid and/or antihistamine pretreatment, all GRADE recommendations, although directional, are conditional and as such should not be universally applied to every circumstance.Clinical guidelines provide an important opportunity to critically appraise evidence and translate evidence to practice. Patients, practitioners, and policy makers should appreciate the strength of recommendation and certainty of evidence and understand how this affects guideline applicability and implementation.

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to

The American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) has published a supplement to this issue featuring the new Clinical Practice Guideline: Allergic Rhinitis. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 14 recommendations developed address the evaluation of patients with allergic rhinitis, including performing and interpretation of diagnostic testing and assessment and documentation of chronic conditions and comorbidities. It will then focus on the recommendations to guide the evaluation and treatment of patients with allergic rhinitis, to determine the most appropriate interventions to improve symptoms and quality of life for patients with allergic rhinitis.

The review compares and contrasts seven major United States and international allergic rhinitis guidelines from 2008 to 2017.Despite many treatment options for allergic rhinitis, patients often report lack of therapeutic control and a reduced quality of life. Guidelines intended to improve allergic rhinitis care have been evolving into evidence based, systematic reviews, with less reliance on consensus of expert opinion characteristic of more traditional guidelines. The first Grading of Recommendations Assessment, Development, and Evaluation-based guideline developed in the United States for seasonal allergic rhinitis was first published in 2017.When critically analyzing the allergic rhinitis guidelines that use the rigorous Grading of Recommendations Assessment, Development, and Evaluation methodology, different groups of expert authors, using the same reference articles, will, at times, reach different conclusions regarding the quality of the evidence and the strength of the recommendation. Factors potentially contributing to these divergent determinations include: lack of objective primary outcome measures in allergic rhinitis, poorly defined Minimal Clinically Important Difference, failure to include all interested parties in guideline development, for example, patients, and subjectivity inherent in the expert panel.

Food allergy and anaphylaxis appear to be increasing in the United States, especially in young children, and preparedness is paramount to successful emergency management in the community. Although the treatment of choice for anaphylaxis is epinephrine delivered by autoinjection, some devices are challenged by less user-friendly designs or pose the risk of injury, especially in young patients. Human factors engineering has played a larger role in the development of more recent epinephrine autoinjector technologies and will continue to play a role in the evolution and future design of epinephrine autoinjectors.To discuss contemporary issues related to the identification and management of anaphylaxis, current and future epinephrine autoinjector design, and unmet needs for the treatment of special populations, namely, young children weighing less than 15 kg.The literature was reviewed and select articles retrieved to support expert clinical opinions on the need for improved recognition of anaphylaxis, epinephrine autoinjector design, and unmet needs in special populations.Anaphylaxis may be underrecognized and poorly defined in infant- and toddler-aged children, current devices may not be adequate to safely treat these patients (ie, inappropriate needle length), and health care professionals may not be aware of these issues.As epinephrine autoinjector technology continues to evolve, device characteristics that promote safe, user-friendly experiences and give clinicians and their patients confidence to successfully treat anaphylaxis during an emergency, without injury, will be favored.

I. Leonard Bernstein, MD; James T. Li, MD, PhD; David I. Bernstein, MD; Robert Hamilton, PhD, DABMLI; Sheldon L. Spector, MD; Ricardo Tan, MD; Scott Sicherer, MD; David B. K. Golden, MD; David A. Khan, MD; Richard A. Nicklas, MD; Jay M. Portnoy, MD; Joann Blessing-Moore, MD; Linda Cox, MD; David M. Lang, MD; John Oppenheimer, MD; Christopher C. Randolph, MD; Diane E. Schuller, MD; Stephen A. Tilles, MD; Dana V. Wallace, MD; Estelle Levetin, PhD; and Richard Weber, MD

Allergic rhinitis (AR) is one of the most common diseases affecting adults. It is the most common chronic disease in children in the United States today and the fifth most common chronic disease in the United States overall. AR is estimated to affect nearly 1 in every 6 Americans and generates $2 to $5 billion in direct health expenditures annually. It can impair quality of life and, through loss of work and school attendance, is responsible for as much as $2 to $4 billion in lost productivity annually. Not surprisingly, myriad diagnostic tests and treatments are used in managing this disorder, yet there is considerable variation in their use. This clinical practice guideline was undertaken to optimize the care of patients with AR by addressing quality improvement opportunities through an evaluation of the available evidence and an assessment of the harm-benefit balance of various diagnostic and management options.The primary purpose of this guideline is to address quality improvement opportunities for all clinicians, in any setting, who are likely to manage patients with AR as well as to optimize patient care, promote effective diagnosis and therapy, and reduce harmful or unnecessary variations in care. The guideline is intended to be applicable for both pediatric and adult patients with AR. Children under the age of 2 years were excluded from the clinical practice guideline because rhinitis in this population may be different than in older patients and is not informed by the same evidence base. The guideline is intended to focus on a limited number of quality improvement opportunities deemed most important by the working group and is not intended to be a comprehensive reference for diagnosing and managing AR. The recommendations outlined in the guideline are not intended to represent the standard of care for patient management, nor are the recommendations intended to limit treatment or care provided to individual patients.The development group made a strong recommendation that clinicians recommend intranasal steroids for patients with a clinical diagnosis of AR whose symptoms affect their quality of life. The development group also made a strong recommendation that clinicians recommend oral second-generation/less sedating antihistamines for patients with AR and primary complaints of sneezing and itching. The panel made the following recommendations: (1) Clinicians should make the clinical diagnosis of AR when patients present with a history and physical examination consistent with an allergic cause and 1 or more of the following symptoms: nasal congestion, runny nose, itchy nose, or sneezing. Findings of AR consistent with an allergic cause include, but are not limited to, clear rhinorrhea, nasal congestion, pale discoloration of the nasal mucosa, and red and watery eyes. (2) Clinicians should perform and interpret, or refer to a clinician who can perform and interpret, specific IgE (skin or blood) allergy testing for patients with a clinical diagnosis of AR who do not respond to empiric treatment, or when the diagnosis is uncertain, or when knowledge of the specific causative allergen is needed to target therapy. (3) Clinicians should assess patients with a clinical diagnosis of AR for, and document in the medical record, the presence of associated conditions such as asthma, atopic dermatitis, sleep-disordered breathing, conjunctivitis, rhinosinusitis, and otitis media. (4) Clinicians should offer, or refer to a clinician who can offer, immunotherapy (sublingual or subcutaneous) for patients with AR who have inadequate response to symptoms with pharmacologic therapy with or without environmental controls. The panel recommended against (1) clinicians routinely performing sinonasal imaging in patients presenting with symptoms consistent with a diagnosis of AR and (2) clinicians offering oral leukotriene receptor antagonists as primary therapy for patients with AR. The panel group made the following options: (1) Clinicians may advise avoidance of known allergens or may advise environmental controls (ie, removal of pets; the use of air filtration systems, bed covers, and acaricides [chemical agents formulated to kill dust mites]) in patients with AR who have identified allergens that correlate with clinical symptoms. (2) Clinicians may offer intranasal antihistamines for patients with seasonal, perennial, or episodic AR. (3) Clinicians may offer combination pharmacologic therapy in patients with AR who have inadequate response to pharmacologic monotherapy. (4) Clinicians may offer, or refer to a surgeon who can offer, inferior turbinate reduction in patients with AR with nasal airway obstruction and enlarged inferior turbinates who have failed medical management. (5) Clinicians may offer acupuncture, or refer to a clinician who can offer acupuncture, for patients with AR who are interested in nonpharmacologic therapy. The development group provided no recommendation regarding the use of herbal therapy for patients with AR.

Rodents (Rodentia) are the largest order of mammals in the world, with estimates ranging from 1,500 to 2,000 different documented species. The order includes commonly known mammals, such as rats, mice, guinea pigs, hamsters, and gerbils. The order Rodentia also includes beavers, muskrats, porcupines, woodchucks, chipmunks, squirrels, prairie dogs, marmots, chinchillas, voles, lemmings, and many others, although significant human exposure to these rodents is uncommon. The presence of 2 sets of incisors (top and bottom), used for chewing, is the common characteristic of rodent species. Incidentally, rabbits, hares, and a few other species make up the Lagomorpha order and therefore are not classified as rodents. Figure 1 shows an abbreviated taxonomy of the order Rodentia.2 Figure 1 Taxonomy of the order Rodentia. Adapted from Taxonomy of Common Rodent and Rodent-like pets.2 The common house mouse (Mus musculus) is a small, primarily nocturnal mammal. Although usually considered to be pests, mice also are popular pets. Mice are known to invade and establish residence in homes and other buildings, including schools, to obtain food and can at times be harmful, causing structural damage. Certain rodents, such as the deer mouse, can also spread diseases such as hantavirus through their feces and possibly also through their urine and saliva.3,4 Mice also are commonly used in research laboratories, where laboratory animal handlers come into contact with their allergens. Mice tend to have litter sizes of 4 to 8 pups and can have 6 to 8 litters per year, depending on the availability of food. Their life span in the wild is less than 1 year because of predation, although under laboratory conditions they can live as long as 2 years.5 Mice have the ability to jump 12 inches up and down 8 feet to the floor. They can run up almost any vertical surface, including wood, brick, metal pipes, wire mesh, and cables, and can run along suspended electric wires and ropes. They can squeeze through a 1/4-inchdiameter hole, travel upside down, cling from 1/4-inch hardware mesh, swim well, and survive at 24 °F for many generations.6 Rats are long-tailed mammals also of the order Rodentia. The most important rats from a human perspective are the black or roof rat, Rattus rattus, and the brown or Norway rat, Rattus norvegicus. The Norway rat is found in every state of the United States, whereas the roof rat tends to be found in coastal states. Rats usually can be distinguished from mice by their larger size. Rats also can serve as vectors for certain pathogens, such as Lassa fever. They are popular as pets but also are commonly used in research laboratories, where laboratory animal handlers come into contact with their allergens.6 Rats tend to be nocturnal and search for food and water between dusk and dawn; however, they will come out in daylight if their habitat is overcrowded or food is lacking. They require daily water; prefer traveling along edges, pipes, and rafters; and can even travel along overhead utility lines. They prefer to not cross open spaces to avoid predation, and although they have poor visual acuity, they have acute senses of smell, taste, hearing, and touch using their whiskers. Rats tend to have litter sizes of 5 to 12, and they can have up to 9 litters per year, depending on food supplies. Their life span generally is less than 1 year. Rats can pass through openings as small as 3/4 inch, theycan climb up vertical surfaces and even inside vertical pipes, and they can crawl horizontally on any type of pipe or conduit. They can jump vertically 24 inches and fall more than 50 feet and survive. They are able to swim under water for up to 30 seconds, tread water for up to 3 days, and swim up to ½ mile in open water. This permits them to enter buildings through drains and toilets.7 Although guinea pigs (Cavia porcellus), hamsters (Mesocritecus auratus), and gerbils (Gerbillus jerboa) also are rodents, they usually are kept as pets in a confined area and usually are not considered to be pests. Patients who keep such pets clearly can develop allergic symptoms after sensitization; however, other than in the case of laboratory animal workers, exposure to such rodents can usually be contained, and complete abatement, should it become necessary, is easily accomplished with removal of the offending animal.

These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology. The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing "The diagnosis and Management of Rhinitis: An Updated Practice Parameter." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.