Elizabeth Phillips

Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) have been classified as immediate (or acute) and delayed. Immediate reactions can be further classified into 4 clinical types: NSAID-exacerbated respiratory disease (N-ERD), NSAID-exacerbated cutaneous disease (NECD), NSAID-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria/angioedema/anaphylaxis (SNIUAA). Specifically, the NIUA type references reactions to ≥2 NSAIDs belonging to different chemical groups, involving urticaria and/or angioedema in patients with no underlying chronic spontaneous urticaria. However, there are patients meeting cross-reactive criteria for NIUA phenotype who report reactions that involve 2 organ systems (eg, cutaneous and respiratory; cutaneous and gastrointestinal) and have been termed “blended”. In pediatrics, this type of reaction is recognized and has been termed NSAID-induced urticaria/angioedema/anaphylaxis (NIUAA), an acronym we suggest be extended now to adults. There are small subgroups of N-ERD patients who also report skin symptoms and, alternatively, NECD patients who report respiratory symptoms. These 2 subgroups could be diagnosed as having mixed N-ERD and mixed NECD, respectively. In fact, they are patients suffering from N-ERD or NECD who have had reactions consistent with anaphylaxis.

In the current classifications of NSAID hypersensitivity, the reactions in which NSAIDs act as aggravating factors or cofactors in subjects with sensitization to foods are not included. Recently, this type of reactions has been defined as NSAID-exacerbated food allergy (NEFA) and NSAID-induced food allergy (NIFA), respectively.

This Statement of the World Allergy Organization (WAO) aims to update both the classification of hypersensitivity reactions to NSAIDs and their diagnosis, addressing the novel issues.

Skin diseases are hallmarks of progressive HIV-related immunosuppression, with severe noninfectious inflammatory and hypersensitivity conditions as common as opportunistic infections. Conditions such as papular pruritic eruption are AIDS defining, whereas delayed immune-mediated adverse reactions, mostly cutaneous, occur up to 100-fold more during HIV infection. The skin, constantly in contact with the external environment, has a complex immunity. A dense, tightly junctioned barrier with basal keratinocytes and epidermal Langerhans cells with antimicrobial, innate-activating, and antigen-presenting functions form the frontline. Resident dermal dendritic, mast, macrophage, and innate lymphoid cells play pivotal roles in directing and polarizing appropriate adaptive immune responses and directing effector immune cell trafficking. Sustained viral replication leads to progressive declines in CD4 T cells, whereas Langerhans and dermal dendritic cells serve as viral reservoirs and points of first viral contact in the mucosa. Cutaneous cytokine responses and diminished lymphoid populations create a crucible for exaggerated inflammation and hypersensitivity. However, beyond histopathological description, these manifestations are poorly characterized. This review details normal skin immunology, changes associated with progressive HIV-related immunosuppression, and the characteristic conditions of immune dysregulation increased with HIV. We highlight the main research gaps and several novel tissue-directed strategies to define mechanisms that will provide targeted approaches to prevention or treatment.

It has been 3 years since the coronavirus disease 2019 (COVID-19) pandemic was initially declared, and 2 years have passed since the first COVID-19 vaccines were introduced. Since then, 13.2 billion COVID-19 vaccine doses have been administered worldwide, largely with multiple doses of messenger RNA vaccines. Although mild local and systemic adverse effects after COVID-19 vaccination are common, serious adverse effects following immunization are rare, particularly when compared with the large number of vaccine doses administered. Immediate and delayed reactions are relatively common and present similarly to allergic and hypersensitivity reactions. Despite this, reactions generally do not commonly recur, cause sequelae, or contraindicate revaccination. In this Clinical Management Review, we provide an updated perspective of COVID-19 vaccine reactions, their spectrum and epidemiology, and recommended approaches to evaluation and management.