Classification of NSAIDs hypersensitivity for the child aged (0-10 years) pediatric population Cena cker cas ce] Keene Gee ieee pent eee eimae Cross-intolerant Non-allergic NSAID Urticaria, Immediate (from COX-1 inhibition Possible reactions hypersensitivity angioedema, _ minutes to several (Non-allergic) (NERD, NECD, NIUAA) dyspnea, rhinitis, hours after exposure) conjuctivitis, anaphylaxis Non-cross- Selective NSAID- Urticaria, Immediate (<1h) IgE-mediated Unknown intolerant induced angioedema, reactions urticaria/angioedema anaphylaxis (Allergic) Janaphylaxis (SNIUAA) Selective NSAID- Various Delayed onset (more T-cell-mediated Unknown induced delayed symptoms than 24 h after reactions (SNIDR) (SIS/TEN, FDE..) exposure)The search for biomarkers * Serum levels of LTE4 * The ratio LTE4/9a,11b-PGF2 * Plasma eosinophil-derived neurotoxin + L-plastin * Serum sphingosine-1-phosphate and urin sphingosine * Serum periostin + Identification of biomarkers in tissuesDiagnosis of NSAIDs hypresensitivity in children Drug provocation test - DPT * The gold standard for the diagnosis of NSAIDs hypersensitivity + In most cases, an open or single blinded procedure is sufficient to establish the diagnosis * DPT testing with the culprit drug is not recommended in patients with a history of severe reactions (anaphylaxis, SJS/TEN, DRESS, or severe organ specific reactions)Drug provocation test - DPT * A relative contraindication of performing DPT in patients with active disease (uncontrolled asthma, flaring urticaria) limiting the use of adrenaline * Medications such as antihistamines, systemic corticosteroids, antileukotrienes should be discontinued prior to performing DPT according to current recommendationsDrug provocation test - DPT + In some cases, additional doses of the drug can be necessary, after a negative observed challenge, and may be given at home in the following days + A DPT should be stopped and treatment initiated immediately with the diagnosis of an allergic response * In cases with a positive DPT, children should be observed for 2-4 hours after the last challenge dose or until patient is stabilized eZAlgorithm for the management of children with NSAIDs hypresensitivity v — Use confirmed alternatives NSAID even it off label ——_____________ I—> [Use confirmed safe alternative NSAID [even it off label | ee Fever-physical cooling, low dose paracetamol, low dose NSAIDs, antiH+NSAIDs | Alternative drugs or therapies itization in selective cases | in-non-phari central acting pain killers, opiates, anesthetics ect |Summary * The diagnosis and management of NSAIDs hypersensitivity in children and adolescents should be performed in specialized centers by experienced medical personnel * Drug provocation tests are useful both for the confirmation of hypersensitivity and the election of safe alternative medications| Summary * COX2-specific medications, although not approved in children have been prescribed and are useful as alternative medications + The natural history of NSAIDs hypersensitivity in children is unknown, so periodical re-evaluation may be warranted