**5. The management of skin NSAID hypersensitivity**

The management of skin reactions to NSAIDs will aim to educate the patient on which drugs to avoid and to provide written therapeutic advice on which

alternatives to NSAIDs are potentially safe, after having tested adequate tolerance to them through SBPCOC.

Depending on the diagnosis and outcome of the SBPCOC, the patient can be advised to avoid only the culprit or all NSAID. Then, there might be a need to investigate the safety of other alternative analgesics. Selective COX-2 inhibitors are often a safe alternative, especially in cross-reactive patients who can tolerate acetaminophen. So, below 5% of patients with skin NH reacted to a selective COX-2 inhibitor [17, 18]. Even in those cases with a COXiB reaction, it is possible that the patient may tolerate other COXib without reaction and therefore an second challenge with an alternative COXIb must be performed [16].

Early presentations of periorbital angioedema as key features of cross-reactive reactions to NSAIDs in an atopic children also precluded the use of potent COX-1 inhibitor NSAID. Paracetamol is often well tolerated in these patients. The use of a cyclooxygenase-2-specific medication may not be feasible in this population, and limits options for other medical antiinflammatory treatment. However, Loh et al. have recently demonstrated that etoricoxib can be used as a safe alternative in older children (mean age 13,5 years) with hypersensitivity to multiple antipyretics [19].

Patient with selective urticaria or systemic anaphylaxis presents a selective pattern of sensitivity to NSAID, and even those with high COX-1 inhibition potency, but non chemically related, can be tolerated [3, 5].

Desensitization with aspirin is recommended by clinical guidelines only in patients with aspirin exacerbated respiratory disease and in cases of NECD or NIUA, in which it is strictly necessary to administer any NSAID as an antiaggregate, anti-inflammatory or analgesic treatment [20]. The desensitization procedure consists of administering progressively increasing doses of aspirin until a reaction is provoked which is as controllable as possible, with the aim of inducing a post-reaction refractory period and which we will use to reach the therapeutic dose, culminating the desensitization process after the administration of a dose of aspirin (or other NSAID) without a reaction.

Rossini et al. have published a multicenter, prospective study that demonstrates that a rapid standardized desensitization protocol in patients with aspirin hypersensitivity undergoing coronary angiography is safe and effective, irrespective of the type of NH which have the patients. A low-dose aspirin could be safely continued without reaction in all patients throughout the next year [20].
