Hypersensitivity reaction during enzyme replacement therapy in lysosomal storage disorders. A systematic review of desensitization strategies.

Lysosomal storage diseases (LSDs) are rare genetic metabolic disorders that cause the accumulation of glycosaminoglycans in lysosomes due to enzyme deficiency or reduced function. Enzyme replacement therapy (ERT) represents the gold standard treatment, but hypersensitivity reaction can occur resulting in treatment discontinuation. Thus, desensitization procedures for different culprit recombinant enzymes can be performed to restore ERT. We searched desensitization procedures performed in LSDs and focused on skin test results, protocols and premedication performed, and breakthrough reactions occurred during infusions. Fifty-two patients have been subjected to desensitization procedures successfully. Skin tests, with the culprit recombinant enzyme, deemed positive in 29 cases, doubtful in two cases, and not performed in four patients. Moreover, 29 of the 52 desensitization protocols used at the first infusion were breakthrough reaction free. Different desensitization strategies have proved safe and effective in restoring ERT in patients with previous hypersensitivity reactions. Most of these events seem to be Type I hypersensitivity reactions (IgE-mediated). Standardized in vivo and in vitro testing is necessary to better estimate the risk of the procedure and find the safest individualized desensitization protocol.

Latex allergy - from discovery to component-resolved diagnosis.

Latex allergy is a hypersensitivity response to natural rubber latex (NRL) proteins or rubber chemicals used in the manufacture of latex products. An accurate diagnosis is the first step in the effective management of individuals with latex allergy, especially in high-risk groups, such as healthcare workers and those affected by spina bifida. Diagnosis is based on the clinical history and an accurate allergological evaluation. In the case of type I IgE-mediated hypersensitivity re-actions, which can manifest urticaria, angioedema, rhinoconjunctivitis, asthma and anaphylaxis after latex exposure, skin prick tests or latex-specific IgE (sIgE) antibody detection using sero-logical assays can be performed to confirm sensitization. Instead, in the case of contact dermati-tis, a patch test can be applied to confirm the presence of a type IV T cell-mediated hypersensi-tivity reaction to rubber accelerators or additives. Basophils activation tests or challenge tests may be performed if there's an incongruity between the clinical history and the results of in vivo and in vitro tests. The aim of this review is to analyze the current state of the art of diagnostic techniques for latex allergy and algorithms employed in clinical practice and possible future de-velopments in this field.

miRNAs' Cross-Involvement in Skin Allergies: A New Horizon for the Pathogenesis, Diagnosis and Therapy of Atopic Dermatitis, Allergic Contact Dermatitis and Chronic Spontaneous Urticaria.

Skin inflammation is a common underlying feature of atopic dermatitis, allergic contact dermatitis and chronic spontaneous urticaria. The pathogenetic mechanisms have not been fully elucidated. The purpose of this study was to examine whether miRNA, by regulating inflammatory mechanisms through the modulation of innate and adaptive immune responses, could play a major role in the pathogenesis of these skin conditions. We conducted a narrative review using the Pubmed and Embase scientific databases and search engines to find the most relevant miRNAs related to the pathophysiology, severity and prognosis of skin conditions. The studies show that miRNAs are involved in the pathogenesis and regulation of atopic dermatitis and can reveal an atopic predisposition or indicate disease severity. In chronic spontaneous urticaria, different miRNAs which are over-expressed during urticaria exacerbations not only play a role in the possible response to therapy or remission, but also serve as a marker of chronic autoimmune urticaria and indicate associations with other autoimmune diseases. In allergic contact dermatitis, miRNAs are upregulated in inflammatory lesions and expressed during the sensitization phase of allergic response. Several miRNAs have been identified as potential biomarkers of these chronic skin conditions, but they are also possible therapeutic targets.

An update on nonsteroidal anti-inflammatory drug-induced urticaria.

BACKGROUND: Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter NSAIDs for the treatment of a variety of inflammatory conditions. Urticaria is the most commonly reported immediate cutaneous clinical sign of HR-NSAIDs, but it can be a manifestation of pathophysiologically different clinical entities that require different therapeutic strategies. The aim of this study is to ease the identification of the correct phenotype of HR-NSAIDs in patients reporting urticaria associated with the intake of NSAIDs and provide updated information about their diagnosis and management. METHODS: The study is a narrative review conducted by collecting the most relevant and up-to-date data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity reactions. PubMed and Embase scientific databases were used as search engines to select relevant articles. RESULTS: Patients developing HR-NSAIDs can be divided into two categories: selective responders (SR), who develop reactions after the administration of a single specific NSAID due to an underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical pathways related with prostaglandin metabolism, independently from an underlying immunological mechanism. Five major different categories of HR-NSAIDs have been identified: NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDs-exacerbated respiratory disease (NERD), which are developed by CI patients, and single NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDs-induced delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and therefore are not routinely used in clinical practice. The management in SR patients consists of strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed. CONCLUSION: HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly based on a thorough clinical history and confirmed by a drug challenge test. Clinical management is based on strict avoidance and use of alternative tolerated medications. Overall, all therapeutic decisions depend on the correct identification of the type of reaction the patient experienced.