The Buzz by HIVE, Issue #9, November 2021
Issue #9, November 2021

We are excited to bring you Issue #9 of The Buzz, with new publications on adverse events following vaccination, a case series on complement measurements in hereditary angioedema, a retrospective analysis of psoriasiform lesion in children taking dupilumab, and two systematic reviews, one in chronic urticaria and the other in food allergy. View archived issues of The Buzz at


Vaccine pharmacovigilance and management of immune and non-immune adverse vaccine events

A new clinical management review article notes that the World Health Organization has listed vaccine hesitancy as one of the 10 most important threats to global health. Providers can help manage hesitancy by understanding how vaccine safety is established in trials and monitored post-marketing. Spontaneous reporting of adverse events not known to have a causal link can help identify rare events not uncovered during clinical trials. The rates of these events then need to be compared to background rates in the general population before any causal link can be suspected.

Immediate allergic reactions are caused by mast cells releasing histamine and other mediators in reaction to an allergen in the vaccine. Reactions can include urticaria, angioedema, hypotension, and anaphylaxis. The triggers can include components of the vaccine or adjuvants, such as PEG or residual media, or natural latex in the vial caps or devices. In some cases, skin prick testing can identify the allergen and support planning for future doses.

The review goes on to describe later immune-mediated reactions, such as Guillain-Barre syndrome and thrombocytopenic reactions, as well as inflammatory reactions.  Vaccine providers should be familiar with both common and rare vaccine reactions and appropriate management. For this review article, physicians can claim Category 1 CME credits by reading the article and completing the post-test at before September 30, 2022.

Read more: [Sosido link] Des Roches A, Graham F, Begin P, Paradis L, Gold M. Evaluation of Adverse Reactions to Vaccines. J Allergy Clin Immunol Pract. 2021;9(10):3584-3597. doi:10.1016/j.jaip.2021.08.002


C1-inhibitor and C4 as diagnostic markers in hereditary angioedema

Stephaniuk and colleagues present a case series of hereditary angioedema (HAE) patients where C4 and C1-inhibitor levels were measured at baseline and again during a mild upper respiratory infection. They postulated that if C1-inhibitor or C4 act as acute phase reactants in HAE patients, the levels may read as falsely normal during an infection or inflammation, potentially causing missed diagnoses. 

Patients included in the case series had confirmed HAE based on angioedema and prior documented low C1-inhibitor functional testing. Other forms of angioedema and those on prophylactic therapy for HAE were excluded. Four patients were included in the case series. Samples were collected at baseline and during mild-to-moderate upper respiratory illnesses.  No significant changes were detected in C1-inhibitor functional levels during the illnesses, however the C4 level did increase to normal range during three illnesses in two separate patients. Two patients also showed elevated CRP during their illnesses. The data suggest that C1-inhibitor is likely a reliable diagnostic marker for HAE, while C4 should not be used alone for screening.

Read more: [Sosido link] Stepaniuk P, Bosonea AM, Pourshahnazari P, Roos A, Kanani A. The role of C1 inhibitor and complement as acute phase reactants: are we missing the diagnosis of hereditary angioedema?. Allergy Asthma Clin Immunol. 2021;17(1):103. Published 2021 Oct 9. doi:10.1186/s13223-021-00607-5


Psoriasiform eruptions in children taking dupilumab for atopic dermatitis

Parker and colleagues present a retrospective analysis of psoriasiform eruptions in children taking dupilumab for atopic dermatitis (AD). They found six cases in children from ages 4-18 years who developed psoriasiform dermatitis, and one additional case of undiagnosed psoriasis that had been masked by the AD. All of the children had severe AD at baseline and five of six experienced a 3-point improvement in IGA with dupilumab treatment. None had a known family history of psoriasis. The new-onset psoriasiform plaques appeared at a median treatment duration of eight months (range, 6- 12 months), at sites typically observed with psoriasis. Lesions were visually distinct from the AD lesions.

Biopsies were not performed, therefore the mechanism for dupilumab-associated psoriasiform lesions in the children in unknown.  One patient had inadequate AD response to dupilumab, switched to ustekinumab to control the psoriasis with tofacitinib and IVIG for the AD. The other patients continued dupilumab while using topical corticosteroid to control the psoriasiform lesions.

Read more: [Sosido link] Parker JJ, Sugarman JL, Silverberg NB, et al. Psoriasiform dermatitis during dupilumab treatment for moderate-to-severe atopic dermatitis in children [published online ahead of print, 2021 Oct 14]. Pediatr Dermatol. 2021;10.1111/pde.14820. doi:10.1111/pde.14820


Systematic review of methotrexate in chronic urticaria

Methotrexate may be a safe and affordable treatment option for chronic urticaria, particularly in developing countries where access to monoclonal antibodies is limited. The authors conducted a systematic review to assess the evidence for the use of methotrexate in chronic urticaria. Nine studies were included in the analysis, three randomized controlled trials, one uncontrolled prospective trial, three retrospective reviews, and two case reports, comprising a total of 127 patients who had received a variety of antihistamines and immunosuppressive agents. The data were too heterogeneous to conduct a meta-analysis.

Methotrexate was primarily orally administered, except for intolerance. Doses were variable, but up to a maximum of 25 mg/week, and most often given once weekly. Treatment duration varied from a few weeks to more than six months. The randomized control trials did not show any benefit of methotrexate over antihistamines alone. In studies where steroid-dependent cases received methotrexate, a benefit was observed with a steroid-sparing effect. Methotrexate may prove helpful in patients with prolonged disease course, not responding to multiple antihistamines, and steroid-dependent cases, however more study is required.

Read more: [Sosido link] Sandhu J, Kumar A, Gupta SK. The therapeutic role of methotrexate in chronic urticaria: A systematic review [published online ahead of print, 2021 Sep 15]. Indian J Dermatol Venereol Leprol. 2021;1-3. doi:10.25259/IJDVL_1145_20


Protocol for a systemic review of food allergy diagnostic test accuracy 

Genuneit and colleagues have published the protocol that will be used to update the European Academy of Allergy and Clinical Immunology guidelines on the diagnosis and management of food allergies. The existing guidelines are nearly 10 years old. A new systematic review will be conducted searching for new data from 2012 through June 2021. The publication prospectively lays out the search strategy and inclusion/exclusion criteria for studies. Oral food challenge will be the comparator, GRADE will be used to evaluate the certainty of evidence and assess heterogeneity, and meta-analysis will be performed if there are three or more studies on the same index test and food.

The authors aim to evaluate the diagnostic test accuracy of any index test, including skin prick tests, specific IgE to extracts, individual allergens, and allergen peptides, basophil activation tests, and mast cell activation tests.  The protocol has been registered on PROSPERO.

Read more: [Sosido link] Genuneit J, Jayasinghe S, Riggioni C, et al. Protocol for a systematic review of the diagnostic test accuracy of tests for IgE-mediated food allergy [published online ahead of print, 2021 Oct 21]. Pediatr Allergy Immunol. 2021;10.1111/pai.13684. doi:10.1111/pai.13684


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