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What's new in allergy and immunology

What's new in allergy and immunology
Authors:
Anna M Feldweg, MD
Elizabeth TePas, MD, MS
Literature review current through: Feb 2022. | This topic last updated: Feb 22, 2022.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ASTHMA AND COPD

Dupilumab for children ≥6 years old with moderate-to-severe asthma (November 2021)

Dupilumab, a monoclonal antibody that blocks interleukin (IL)-4 and IL-13 signaling, is now approved by the US Food and Drug Administration (FDA) for children 6 years of age and older with moderate-to-severe persistent asthma and eosinophilia or dependency on oral glucocorticoids. Approval is based upon trials in adolescents and adults and a single randomized trial in 408 children 6 to 11 years of age with moderate-to-severe asthma that showed a significant reduction in the annual rate of severe exacerbations requiring treatment with systemic glucocorticoids in children treated with dupilumab compared with placebo (rate ratio 0.35, 95% CI 0.22-0.56) [1]. Because dupilumab is also approved for use in selected children with moderate-to-severe atopic dermatitis (AD), it may be particularly useful in children with comorbid refractory asthma and AD. (See "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies", section on 'Add on a biologic agent'.)

DRUG HYPERSENSITIVITY

Identifying patients at high risk for true beta-lactam allergy (November 2021)

Allergy to penicillin is the most common drug allergy, but the majority of patients with this label are not actually allergic. In a retrospective study of 410 adults referred to drug allergy centers specifically for urticarial eruptions occurring in association with a beta-lactam antibiotic, three questions proved useful for identifying patients at high risk for true allergy [2]:

Did the urticaria develop after the first dose (ie, dose 1) (versus after subsequent doses)?

Did the urticaria develop within 1 hour of the inciting dose?

Did the urticaria resolve within 1 day of stopping the beta-lactam in question?

Patients answering yes to all three questions (named the 1-1-1 criterion by the investigators) had a high risk of a positive allergy evaluation (PPV = 90 percent). Such patients should not be re-exposed to beta-lactams and should be referred to an allergy specialist if future beta-lactam use is deemed medically important. (See "Penicillin allergy: Immediate reactions", section on 'Historical features that predict true allergy'.)

FOOD ALLERGY AND INTOLERANCE

Peanut oral immunotherapy in children less than four years of age (January 2022)

Data suggest the efficacy of peanut oral immunotherapy (OIT) increases as the age at treatment onset decreases. This finding was confirmed in a prespecified subset of children <4 years of age who were part of a trial of children with peanut allergy randomly assigned to peanut OIT (minimum daily maintenance dose target 250 mg, maximum 2000 mg) or placebo [3]. In these younger patients, desensitization after two years of maintenance therapy and sustained unresponsiveness (SU) after six months of avoidance was reported in 71 and 21 percent versus 2 and 2 percent in the treatment and placebo groups, respectively. Whether those with SU have developed permanent tolerance or whether additional children would develop SU after a longer course of maintenance therapy remains to be determined. (See "Oral immunotherapy for food allergy", section on 'Efficacy'.)

Inhaled albuterol for acute abdominal pain due to IgE-mediated food allergy (September 2021)

Acute abdominal pain is common with immunoglobulin E (IgE)-mediated food reactions and can be prolonged and difficult to manage. Beta agonists relax visceral smooth muscle and have been used to treat other causes of visceral pain. In a retrospective study of 57 patients with peanut allergy who had a positive oral food challenge, treatment with albuterol (8 to 10 inhalations of 100 mcg MDI) was associated with faster onset of improvement (12.5 versus 65 minutes) and time to complete resolution of abdominal pain (32.5 versus 90 minutes) [4]. While these results suggest that high-dose albuterol may hasten resolution of abdominal pain due to IgE-mediated allergy, the study approach had several significant potential biases. Thus, randomized trial confirmation is needed before routine use in clinical practice. (See "Oral food challenges for diagnosis and management of food allergies", section on 'Medical treatment for a reaction'.)

IMMUNODEFICIENCY

Additional COVID-19 vaccine primary series dose for immunocompromised individuals (August 2021, Modified February 2022)

COVID-19 vaccines are less effective among patients with certain immunocompromising conditions than in the general population; additional vaccine doses have been associated with improved effectiveness in this population. We agree with recommendations from the Advisory Committee on Immunization Practices (ACIP) in the United States that individuals with such conditions (table 1) receive an additional mRNA vaccine dose as part of their primary COVID-19 vaccine series (eg, following two doses of an mRNA vaccine or one dose of Ad26.COV2.S vaccine) [5,6]. This additional primary series dose is distinct from the booster dose, which such patients should additionally receive, although at a shorter interval than recommended for the general population. (See "COVID-19: Vaccines", section on 'Immunocompromised individuals'.)

Responses to COVID-19 vaccination in patients with inborn errors of immunity (November 2021)

Data on immune responses to COVID-19 vaccination in patients with inborn errors of immunity (IEIs, formerly called primary immunodeficiencies) are limited but generally encouraging [7-10]. Although patients in these studies had various types of IEI, the majority were able to generate anti-spike antibodies. Reduced responses were seen in individuals with baseline CD3+T counts <1000 cells/mL, CD19+B cell counts <100 cells/mL, or patients who had received rituximab prior to vaccination. Of note, in a group of four patients completely lacking B cells (X-linked agammaglobulinemia), peripheral blood mononuclear cells showed robust interleukin-2 and interferon gamma production when stimulated with different peptide mixtures from SARS-CoV-2. In some cases, responses were more vigorous than that of the controls. These findings support vaccination for COVID-19 in patients with IEI; any of the available vaccines are appropriate. (See "Immunizations in patients with primary immunodeficiency", section on 'Issues related to SARS-CoV-2 vaccination'.)

Allogeneic processed thymus tissue transplant for congenital athymia (November 2021)

Thymic transplant using tissue harvested during infant cardiac surgery is the preferred therapy for complete DiGeorge syndrome, a form of severe combined immunodeficiency secondary to congenital athymia, but it is not widely available. Without treatment, the disease is uniformly fatal in early childhood. In 10 single-arm, open-label studies, 95 treatment-naïve children with congenital athymia underwent surgical transplantation with an allogeneic processed thymus tissue product at a median age of nine months. Estimated survival was 77 percent (95% CI 0.67-0.84) at one year, with 94 percent of patients who survived the first year alive at a median follow-up of 10.7 years [11]. The most common cause of death was infection, followed by cardiopulmonary complications. Based on these data, the US Food and Drug Administration (FDA) approved this allogeneic processed thymic tissue product for the treatment of congenital athymia, which may increase the availability of thymic transplant over time. (See "DiGeorge (22q11.2 deletion) syndrome: Management and prognosis", section on 'Cultured thymic transplant'.)

URTICARIA AND ANGIOEDEMA

Impact of pregnancy on chronic urticaria (November 2021)

The impact of pregnancy on disease activity in chronic urticaria has been largely unstudied. In an international study of 288 pregnancies, patients with either chronic spontaneous urticaria (the majority) or chronic inducible urticaria completed questionnaires. During pregnancy, 51 percent reported improved symptoms, 29 percent reported worsening symptoms, and 20 percent noticed no change [12]. Patients with more than one pregnancy reported similar changes during each pregnancy. These findings inform counseling of patients with chronic urticaria regarding their likely disease course during pregnancy. (See "Chronic spontaneous urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history", section on 'Impact of pregnancy'.)

VACCINES AND VACCINE HYPERSENSITIVITY

Evaluation and management of immediate allergic reactions to SARS-CoV-2 vaccines (November 2021)

An international panel of experts in allergy, infectious disease, and emergency medicine released recommendations for the evaluation and management of immediate allergic reactions to SARS-CoV-2 vaccines, based on a systematic review and meta-analysis [13]. These recommendations, which include not performing empiric testing in patients with past anaphylaxis to polyethylene glycol (PEG) or polysorbates, and referring patients who experienced anaphylaxis to the first dose of an mRNA vaccine to an allergist or completing vaccination with a different vaccine, are consistent with our approach. Most patients are able to complete the vaccination process. (See "COVID-19: Allergic reactions to SARS-CoV-2 vaccines", section on 'Immediate reactions to an initial dose'.)

OTHER GENERAL ALLERGY AND IMMUNOLOGY

Tralokinumab for atopic dermatitis (February 2022)

Adults with persistent, moderate-to-severe atopic dermatitis (AD) despite optimal topical therapy may require systemic immunomodulatory therapy to achieve adequate disease control. In a recent randomized trial of 380 adults with moderate-to-severe AD, more patients assigned to subcutaneous tralokinumab, a fully human monoclonal anti-interleukin-13 antibody, achieved a 75 percent improvement in the Eczema Area and Severity Index at 16 weeks compared with placebo (56 versus 36 percent, respectively) [14]. All patients were allowed to use a midpotency topical corticosteroid as needed. Treatment was general well tolerated. Conjunctivitis was more common in patients receiving tralokinumab than in those receiving placebo. These findings support the efficacy of tralokinumab for adults with AD; this and other studies were the basis for US Food and Drug Administration approval of tralokinumab for this indication. However, long-term studies are needed before its use becomes routine. (See "Treatment of atopic dermatitis (eczema)", section on 'Tralokinumab'.)

New naming convention for therapeutic monoclonal antibodies (January 2022)

The number of therapeutic monoclonal antibodies (mAbs) continues to increase. In order to reduce sound-alikes and specify structural components of the immunoglobulins, the World Health Organization International Nonproprietary Names (INN) Programme has developed four new suffixes to be used instead of "mab" for antibodies developed from 2022 onward [15]. Unmodified immunoglobulins will end in "tug"; mAbs with an engineered constant region will end in "bart"; bifunctional mAbs will end in "mig"; and variable region fragments will end in "ment." (See "Overview of therapeutic monoclonal antibodies", section on 'Naming convention for therapeutic mAbs'.)

Newly identified allergens (November 2021)

New allergens are being identified at an increasing rate. Information about the taxonomic, biochemical, molecular, and/or genetic characteristics of newly identified allergens are submitted to the Allergen Nomenclature Sub-Committee (ANSC) of the World Health Organization/International Union of Immunological Societies (WHO/IUIS) Nomenclature Committee. The ANSC is an international network of experts that reviews submissions of newly recognized allergens, assigns a unique name to each, and maintains the Allergen Nomenclature Database (ANDB). As of late 2021, the database contained 1036 allergens, 106 of which had been submitted in the preceding three years [16]. (See "Allergen sampling in the environment", section on 'Identifying novel allergens'.)

Pediatric fatalities associated with over-the-counter cough and cold medications (November 2021)

Manufacturer labelling and US Food and Drug Administration recommendations strongly advise against the use of over-the-counter cough and cold medications (CCM) in young children. A new report describes fatalities identified by a United States surveillance system and associated with CCM ingestion in children <12 years of age from 2008 to 2016 [17]. During this period, there were 40 reported deaths; the majority occurred in children <2 years old and involved diphenhydramine. Root cause analysis determined that 13 deaths occurred after deliberate supratherapeutic administration by a caregiver with the goal of sedating or harming the child. Health care providers should continue to educate caregivers on the dangers of CCM in children and maintain a high index of suspicion for child abuse with a low threshold for toxicology testing in infants and young children with unexplained signs or symptoms compatible with drug toxicity. (See "Physical child abuse: Diagnostic evaluation and management", section on 'Toxicology'.)

Topical ruxolitinib for atopic dermatitis (October 2021)

Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is a new short-term therapy for atopic dermatitis (AD). In two randomized trials that enrolled over 1200 adolescents and adults with mild to moderate AD (<20 percent of body surface area affected) not controlled by topical prescription medications, more individuals assigned to ruxolitinib cream (0.75% or 1.5%) achieved clear or almost clear skin and reduced pruritis with no increase in adverse effects compared with vehicle [18]. Based on these findings, topical ruxolitinib has been approved by the US Food and Drug Administration for the short-term treatment of mild to moderate AD in immunocompetent individuals with the characteristics of the study participants. Although topical ruxolitinib appears promising, more data are needed regarding its systemic absorption and long-term safety before its use becomes routine. (See "Treatment of atopic dermatitis (eczema)", section on 'Topical ruxolitinib'.)

Oral upadacitinib versus subcutaneous dupilumab for atopic dermatitis (October 2021)

Evidence continues to mount that upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is effective for moderate to severe atopic dermatitis (AD). In a recent randomized trial of nearly 700 adults with moderate to severe AD, more individuals assigned to oral upadacitinib achieved a 75 percent improvement in the eczema area and severity index at 16 weeks compared with subcutaneous dupilumab (71 versus 61 percent, respectively) [19]. Adverse events including rare but serious infections such as herpes zoster and eczema herpeticum were more common in individuals receiving upadacitinib. These findings are encouraging regarding the efficacy of upadacitinib. However, pending results of long-term studies and more detail on adverse effects of upadacitinib, we suggest use of dupilumab for selected patients with moderate to severe atopic dermatitis. (See "Treatment of atopic dermatitis (eczema)", section on 'JAK inhibitors'.)

Occult mastocytosis in patients with severe Hymenoptera sting anaphylaxis and normal tryptase (October 2021)

Moderate to severe Hymenoptera sting anaphylaxis is a common presenting sign of indolent systemic mastocytosis and warrants measurement of a basal serum tryptase (BST). However, patients with Hymenoptera sting anaphylaxis and a normal BST can still have a mast cell disorder. In a large prospective series of 351 adults with Hymenoptera allergy, no obvious signs of mastocytosis, and normal BST, the KITD816V gene mutation was detected in 8 percent of all peripheral blood samples and in 18 versus 2 percent of samples from patients with the most severe anaphylaxis compared with lower-grade reactions [20]. These findings suggest that testing of peripheral blood for KITD816V can detect occult mastocytosis in patients with severe venom anaphylaxis, even when BST is normal, and should be obtained when available. (See "Diagnosis of Hymenoptera venom allergy", section on 'Screening for occult mastocytosis'.)

REFERENCES

  1. Dupilumab https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761055s031lbl.pdf.
  2. Sabato V, Gaeta F, Valluzzi RL, et al. Urticaria: The 1-1-1 Criterion for Optimized Risk Stratification in β-Lactam Allergy Delabeling. J Allergy Clin Immunol Pract 2021; 9:3697.
  3. Jones SM, Kim EH, Nadeau KC, et al. Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study. Lancet 2022; 399:359.
  4. Frugier C, Graham F, Samaan K, et al. Potential Efficacy of High-Dose Inhaled Salbutamol for the Treatment of Abdominal Pain During Oral Food Challenge. J Allergy Clin Immunol Pract 2021; 9:3130.
  5. CDC - An Additional Dose of mRNA COVID-19 Vaccine Following a Primary Series in Immunocompromised People. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-08-13/02-COVID-Dooling-508.pdf (Accessed on August 14, 2021).
  6. Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html (Accessed on February 24, 2022).
  7. Hagin D, Freund T, Navon M, et al. Immunogenicity of Pfizer-BioNTech COVID-19 vaccine in patients with inborn errors of immunity. J Allergy Clin Immunol 2021; 148:739.
  8. Delmonte OM, Bergerson JRE, Burbelo PD, et al. Antibody responses to the SARS-CoV-2 vaccine in individuals with various inborn errors of immunity. J Allergy Clin Immunol 2021; 148:1192.
  9. Squire J, Joshi A. Seroconversion after coronavirus disease 2019 vaccination in patients with immune deficiency. Ann Allergy Asthma Immunol 2021; 127:383.
  10. Amodio D, Ruggiero A, Sgrulletti M, et al. Humoral and Cellular Response Following Vaccination With the BNT162b2 mRNA COVID-19 Vaccine in Patients Affected by Primary Immunodeficiencies. Front Immunol 2021; 12:727850.
  11. Markert ML, Gupton SE, McCarthy EA. Experience with cultured thymus tissue in 105 children. J Allergy Clin Immunol 2022; 149:747.
  12. Kocatürk E, Al-Ahmad M, Krause K, et al. Effects of pregnancy on chronic urticaria: Results of the PREG-CU UCARE study. Allergy 2021; 76:3133.
  13. Greenhawt M, Abrams EM, Shaker M, et al. The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach. J Allergy Clin Immunol Pract 2021; 9:3546.
  14. Silverberg JI, Toth D, Bieber T, et al. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. Br J Dermatol 2021; 184:450.
  15. Balocco R, De Sousa Guimaraes Koch S, Thorpe R, et al. New INN nomenclature for monoclonal antibodies. Lancet 2022; 399:24.
  16. Sudharson S, Kalic T, Hafner C, Breiteneder H. Newly defined allergens in the WHO/IUIS Allergen Nomenclature Database during 01/2019-03/2021. Allergy 2021; 76:3359.
  17. Halmo LS, Wang GS, Reynolds KM, et al. Pediatric Fatalities Associated With Over-the-Counter Cough and Cold Medications. Pediatrics 2021; 148.
  18. Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol 2021; 85:863.
  19. Blauvelt A, Teixeira HD, Simpson EL, et al. Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol 2021; 157:1047.
  20. Šelb J, Rijavec M, Eržen R, et al. Routine KIT p.D816V screening identifies clonal mast cell disease in patients with Hymenoptera allergy regularly missed using baseline tryptase levels alone. J Allergy Clin Immunol 2021; 148:621.
Topic 8363 Version 10977.0

References

1 : Dupilumab https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761055s031lbl.pdf.

2 : Urticaria: The 1-1-1 Criterion for Optimized Risk Stratification inβ-Lactam Allergy Delabeling.

3 : Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study.

4 : Potential Efficacy of High-Dose Inhaled Salbutamol for the Treatment of Abdominal Pain During Oral Food Challenge.

5 : Potential Efficacy of High-Dose Inhaled Salbutamol for the Treatment of Abdominal Pain During Oral Food Challenge.

6 : Potential Efficacy of High-Dose Inhaled Salbutamol for the Treatment of Abdominal Pain During Oral Food Challenge.

7 : Immunogenicity of Pfizer-BioNTech COVID-19 vaccine in patients with inborn errors of immunity.

8 : Antibody responses to the SARS-CoV-2 vaccine in individuals with various inborn errors of immunity.

9 : Seroconversion after coronavirus disease 2019 vaccination in patients with immune deficiency.

10 : Humoral and Cellular Response Following Vaccination With the BNT162b2 mRNA COVID-19 Vaccine in Patients Affected by Primary Immunodeficiencies.

11 : Experience with cultured thymus tissue in 105 children.

12 : Effects of pregnancy on chronic urticaria: Results of the PREG-CU UCARE study.

13 : The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

14 : Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial.

15 : New INN nomenclature for monoclonal antibodies.

16 : Newly defined allergens in the WHO/IUIS Allergen Nomenclature Database during 01/2019-03/2021.

17 : Pediatric Fatalities Associated With Over-the-Counter Cough and Cold Medications.

18 : Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies.

19 : Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial.

20 : Routine KIT p.D816V screening identifies clonal mast cell disease in patients with Hymenoptera allergy regularly missed using baseline tryptase levels alone.