Background
Rhinitis medicamentosa (RM), also known as rebound rhinitis, is a condition characterized by nasal congestion that is triggered by the overuse of topical vasoconstrictive medications, most notably intranasal decongestants; recreational use of intranasal cocaine may also cause a similar condition. [1, 2, 3] Underlying reasons for intranasal decongestant use can usually be identified, such as allergic or nonallergic rhinitis, acute or chronic rhinosinusitis, nasal polyps, night-time use of continuous positive airway pressure (CPAP), or upper respiratory tract infection. With regular daily use, some patients may develop rhinitis medicamentosa in 3 days, whereas others may not have evidence of rebound congestion after 4 to 6 weeks of use. [2] Management of rhinitis medicamentosa is focused on withdrawal of intranasal decongestants and treatment of congestion and underlying conditions with appropriate interventions.
Rhinitis medicamentosa is now generally considered a subset of drug-induced rhinitis that may include the development of congestion and other nasal symptoms from medications that are not administered by the intranasal route. [2] Examples of orally administered agents that may cause drug-induced rhinitis include ACE inhibitors, beta blockers, alpha adrenergic receptor antagonists used in the treatment of benign prostatic hypertrophy, and phosphodiesterase-5 selective inhibitors used to treat erectile dysfunction. [2, 4] Aspirin and other NSAIDs may also produce nasal symptoms in sensitive individuals, sometimes as part of a broader presentation of aspirin-exacerbated respiratory disease (AERD), formerly known as Samter’s Triad, that may include chronic rhinosinusitis with nasal polyps, asthma and aspirin/NSAID sensitivity.
Pathophysiology
The pathophysiology of rhinitis medicamentosa is not well understood. [1] Based on knowledge of the physiology of the nasal mucosa, various hypotheses exist; they mainly focus on dysregulation of sympathetic/parasympathetic tone by exogenous vasoconstricting molecules. Proposed mechanisms describe secondary decrease in production of endogenous norepinephrine through a negative feedback mechanism; [5] a beta effect of sympathomimetic amines that outlasts the alpha effect and causes rebound swelling; [6] increased parasympathetic activity, vascular permeability, and edema formation by altering vasomotor tone, thus creating the rebound congestion. [7] There is also evidence that intranasal cationic adrenergic decongestant drugs may be trapped into cellular endomembrane compartments caused by V-ATPase-dependent sequestration that results in a tissue reservoir of these drugs, influencing the toxicity and pharmacology of these agents. [8]
Nasal decongestants
Nasal decongestants (either administered intranasally or orally) can be classified as either sympathomimetic amines or imidazolines. Sympathomimetic amines (eg, pseudoephedrine, amphetamine, benzedrine, mescaline, phenylephrine, ephedrine) activate sympathetic nerves through presynaptic release of endogenous norepinephrine, which subsequently binds to alpha-receptors and causes vasoconstriction. Rebound vasodilation may be induced through weak affinity toward beta-adrenoreceptors. Imidazolines (eg, oxymetazoline [9] , xylometazoline, naphazoline, clonidine) cause vasoconstriction primarily through alpha2-adrenergic receptors, but may also decrease endogenous norepinephrine though a negative feedback mechanism.
Benzalkonium chloride
Benzalkonium chloride (BKC) is an antimicrobial preservative commonly used in aqueous nasal, ophthalmic, and ocular products, and has long been used at concentrations ≤0.1%. [10] While there are conflicting reports of damage to human nasal epithelia or aggravation of rhinitis medicamentosa associated with intranasal products that contain BKC [11, 12, 13, 14, 15] , intranasal products with BKC are generally safe and well tolerated for short-term and long-term use. [10]
Epidemiology
Frequency
The incidence of rhinitis medicamentosa is uncertain and may be underreported because of over-the-counter availability of intranasal decongestants. In a survey of 119 allergists, 6.7% had rhinitis medicamentosa. In a study conducted over 10 years in an otolaryngology (ENT) office, the incidence of rhinitis medicamentosa was 1%. [16] In another study, an ENT practitioner diagnosed rhinitis medicamentosa in 52 out of 100 consecutive noninfectious patients who presented with nasal obstruction.
Mortality/Morbidity
Rhinitis medicamentosa can lead to chronic rhinosinusitis, atrophic rhinitis, turbinate hyperplasia, psychological dependence, and an abstinence syndrome upon intranasal decongestant withdrawal that may include headaches, sleep disturbances, restlessness, irritability, and anxiety. A case of neonatal respiratory distress syndrome from topical phenylephrine has been reported. [17]
Sex
Rhinitis medicamentosa occurs at a similar rate in men and women.
Age
Peak incidence occurs in young and middle-aged adults.
Prognosis
Prognosis of rhinitis medicamentosa is favorable if underlying factors that led to overuse of intranasal decongestants are addressed and treated or have resolved, and patients adhere to recommendations to limit intranasal decongestants to short-term use.
Studies showed that nearly all patients were able to eventually stop using the offending medication. [18]
Those who used topical preparations again, even 1 year later, had rapid rebound congestion within a few days. [19]
Patient Education
Because rhinitis medicamentosa may occasionally develop after 3 days of intranasal decongestant administration, patients whould be instructed to generally limit intranasal decongestants to short-term use.
The key to treatment and prevention of rhinitis medicamentosa lies in educating the patient about the consequences of using intranasal decongestants for longer than 5–7 days, and often applicable, the need to treat the underlying cause for chronic nasal congestion that led to over use of intranasal decongestants.
