xRead - Nonallergic Rhinitis (September 2025)

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BAROODY ET AL

J ALLERGY CLIN IMMUNOL PRACT JUNE 2024

TABLE II. Differential diagnosis of NAR AR (PAR, SAR) MR NARES LAR Gustatory rhinitis Hormonal rhinitis (pregnancy, exogenous estrogen) Drug-induced rhinitis (see Table III) Occupational rhinitis Atrophic rhinitis Senile rhinitis (rhinitis of the elderly) Infectious rhinitis Structural problems (see Table IV)

for NAR revealed 87% concordance before speci fi c IgE testing was performed to assess for atopy. 15 These are useful questions to ask any patient presenting with symptom suggestive of CR to ascertain the likelihood of whether they have NAR or a component of NAR characteristic of MR. On physical examination, the nasal mucosa usually may appear normal or red and beefy. 1,10 Serum IgE is usually normal and often very low, and aeroallergen skin testing or serological tests for speci fi c IgE are negative. 1 Peripheral eosino philia is absent, and nasal eosinophilia is usually absent except with NARES or entopic rhinitis. Patients with NAR typically report a poor or incomplete response to medications approved for the treatment of AR, 1 in contrast to entopic rhinitis (localized allergic rhinitis [LAR]) pa tients who respond well to second-generation H1-antihistamines and INCS and NARES patients who also respond well to INCS. 14 DIFFERENTIAL DIAGNOSIS The differential diagnosis of NAR is summarized in Table II. It is important to carefully differentiate nonallergic rhinitis condi tions including NAR from perennial allergic rhinitis (PAR), sea sonal allergic rhinitis (SAR), or MR because treatment will be less effective if not tailored to the patient ’ s clinical condition. 1,8,30 The majority of NAR patients suffer from NHR with symptoms triggered by changes in temperature, humidity, or barometric pressure and/or exposure to strong odors or perfumes. 30 Alcohol hyperresponsiveness is frequently a trigger for NAR patients; however, 1 study reported it was more common in patients with chronic rhinosinusitis (CRS) with nasal polyps. 37 Gustatory rhinitis is characteristically seen in older patients that experience clear rhinorrhea after eating. It is most often triggered by hot or spicy foods but may be triggered by nonspicy foods as well. 10 Hormonal rhinitis is most commonly diagnosed in pregnant women in the later trimesters of pregnancy and resolves within 2 weeks of delivery but can also be seen in women using estrogen containing oral contraceptives or exogenous estrogen therapy that causes vascular engorgement of the nasal mucosa with subse quent nasal obstruction and/or excessive mucus production. 38 In addition to estrogen, various drugs that can induce rhinitis manifesting as nasal congestion are listed in Table III. TABLE III. Pharmacological agents that induce rhinitis symptoms Centrally acting sympatholytics (eg, clonidine, guanfacine, methyldopa, reserpine) Ganglion-blocking sympatholytics (mecamylamine, trimethaphan) Peripherally acting sympatholytics (eg, prazosin, guanethidine, indoramin, phentolamine) Phosphodiesterase inhibitors for erectile dysfunction (sildena fi l, tadala fi l, vardena fi l) b -Blockers (oral or intraocular) Angiotensin-converting enzyme inhibitors Calcium channel blockers Diuretics (amiloride, chlorothiazide, hydrochlorothiazide) Other antihypertensives (hydralazine) Hormones (oral contraceptives, exogenous estrogens) Psychotropics (chlorpromazine, risperidone, thioridazine) Intranasal decongestants (prolonged use: rhinitis medicamentosa)

Miscellaneous (sarcoid, midline granuloma, chronic granulomatous polyangiitis, relapsing polychondritis, hypothyroidism, Horner syndrome, Sjögren)

symptoms. 32,33 Thus, the major ligand for the TRPV1 receptor is capsaicin and it has been synonymously referred to as the capsaicin receptor by David Julius who was awarded the 2012 Nobel Prize in Physiology for its cloning. 31 Moreover, activation of G coupled proteins by speci fi c ligands such as capsaicin or histamine lowers the activation threshold of this ion channel, which causes release of neuropeptides such as neurokinin A, calcitonin gene e related peptide (CGRP) and substance P, responsible for symptoms of NAR and AR. This potentially helps explain the overlapping pathways observed in MR, which as discussed, accounts for up to 50% of CR patients (Figure 2). 34 Many of the known irritants that cause NAR symptoms acti vate another ion channel called the transient receptor potential ankyrin 1 (TRPA1). 35 Both TRPV1 and TRPA1 are heavily coexpressed on trigeminal sensory nerves and highly coexpress the neuropeptides substance P and CGRP. These ion channels cofunction by forming tetradimers. 36 DIAGNOSIS The diagnosis of NAR requires exclusion of other known causes of rhinitis. Thus, a comprehensive history, physical ex amination, and appropriate diagnostic testing are important to exclude sensitization to aeroallergens and to assess for diseases mimicking rhinitis that can lead to substantial morbidity and even mortality. As mentioned, most patients with NAR endorse 1 or more irritant triggers, such as tobacco smoke, perfumes/ fragrances, and temperature or barometric pressure changes, causing their symptoms. 1 Unlike AR, there is no speci fi c test or biomarker that can establish a diagnosis of NAR. 7 Similar to AR, NAR can be persistent or intermittent, especially if patients are ef fi cient at avoiding nonallergic triggers. Using data derived from logistic regression analysis, the likely probability of diagnosing NAR was calculated to be 96% in a patient who presents with new-onset symptoms at the age of 35 years, no parental history of allergy, absence of outdoor symptoms during the spring, absence of symptoms around cats, and increased symptoms around perfumes and fragrances. 15 For a similar 45 year-old patient, the probability of having NAR was 98%. 15 Analysis of the association between predicted probabilities (ques tionnaire responses) and observed responses (physician diagnoses)