Rhinitis medicamentosa (RM), also known as rebound rhinitis or chemical rhinitis, is a condition characterized by nasal congestion without rhinorrhea or sneezing that is triggered by the use of topical vasoconstrictive medications for more than 4-6 days. [1, 2, 3] Underlying reasons for decongestant use can usually be identified, such as allergy, nonallergic rhinoplasty, chronic rhinosinusitis, nasal polyps, night-time use of continuous positive airway pressure (CPAP), or upper respiratory tract infection. In such cases, other clinical signs such as rhinorrhea, postnasal drainage, and headaches may also be seen.
The term rhinitis medicamentosa is also used in some literature to describe adverse nasal congestion due to medications other than topical decongestion, such as oral contraceptives, psychotropic medications, and antihypertensive medications, although different mechanisms are involved.  In order to differentiate between these similar conditions, the latter is called drug-induced rhinitis. Management of rhinitis medicamentosa is focused on withdrawal of nasal decongestants and treatment of congestion and underlying condition with appropriate medications.
The nasal mucosa are rich in resistance blood vessels (small arterioles, arteries, and arteriovenous anastomoses) that drain into capacitance venous sinusoids. The sinusoids are innervated with sympathetic fibers; release of endogenous norepinephrine stimulates alpha-1 and alpha-2 adrenoreceptors, which leads to reduced blood flow, increased venous return into capacitance vessels, and, as a result, decreased nasal congestion. Parasympathetic nervous fibers release acetylcholine, which increases nasal secretions, and vasoactive intestinal peptide (VIP), which causes vasodilation. Upon stimulation, abundant sensory C-fibers release neurokinin A, calcitonin gene-related peptide, and substance P, through which various receptors downregulate sympathetic vasoconstriction, leading to congestion.
Upon stimulation of mast cells, eosinophils, and basophils, a complex milieu of local inflammatory mediators is released. These cells contribute to nasal congestion through the release of histamine, kinins, prostaglandins, and arachidonic acid metabolites. Goblet cells can also be activated by such mediators to increase production of mucin, which, in turn, promotes congestion.
Histologic changes consistent with rhinitis medicamentosa include nasociliary loss, squamous cell metaplasia, epithelial edema, epithelial cell denudation, goblet cell hyperplasia, increased expression of the epidermal growth factor receptor, and inflammatory cell infiltration. [5, 6]
The pathophysiology of rhinitis medicamentosa is not well understood.  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;  sympathomimetic amines, which have activity at both alpha and beta sites, have a beta effect that outlasts the alpha effect and causes rebound swelling;  increased parasympathetic activity, vascular permeability, and edema formation by altering vasomotor tone, thus creating the rebound congestion. 
A new mechanism of trapping of adrenergic decongestant drugs into cellular endomembrane compartments has been demonstrated. Phenylephrine and xylometazoline caused the V-ATPase-dependent sequestration that contributed to a component of the tissue reservoir of both cationic drugs, thus influencing the toxicity and pharmacology of individual agents. Such cytopathology was observed at a fraction of the usual topical concentrations. 
Two classes of nasal decongestants are described: sympathomimetics and 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, xylometazoline, oxymetazoline,  naphazoline, clonidine) cause vasoconstriction primarily through alpha2-adrenoreceptors, but may also decrease endogenous norepinephrine though a negative feedback mechanism.
Benzalkonium chloride (BKC) is a preservative commonly used in aqueous nasal, ophthalmic, and optic products that are available both by prescription and over the counter. It has been in use since 1935, and the American College of Toxicology concludes that it can be safely used as an antimicrobial agent at concentrations ≤0.1%.  Over the past several years, conflicting reports have described damage to human nasal epithelia or exacerbation of rhinitis medicamentosa associated with intranasal products that contain benzalkonium chloride (BKC). [13, 14, 15, 16, 17] More recent review of the literature demonstrates that intranasal products with BKC seem to be safe and well tolerated for short-term and long-term use. 
Natural decongestants (alternative medicine)
Many patients use alternative preparations with decongestant properties. Most of them are oral; intranasal preparations include various menthol-based nasal sprays and onion vapor. The efficacy and safety for such decongestants are not known, and no data are available on rhinitis medicamentosa as a result of long-term use of natural decongestants.
The incidence of rhinitis medicamentosa may be underreported because of over-the-counter availability of 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%.  In another study, an ENT practitioner diagnosed rhinitis medicamentosa in 52 out of 100 consecutive noninfectious patients who presented with nasal obstruction.
Similar frequency ranges occur in Europe.
With continued usage, rhinitis medicamentosa can lead to chronic sinusitis, atrophic rhinitis, and permanent turbinate hyperplasia. Patients develop psychological dependence and an abstinence syndrome upon withdrawal of medication, which consists of headaches, sleep disturbances, restlessness, irritability and anxiety. Rhinitis medicamentosa may predispose patients to chronic sinusitis, otitis media, or atrophic rhinitis. Neonatal respiratory distress syndrome due to the use of topical phenylephrine has been described.  No deaths are reported.
Rhinitis medicamentosa occurs at a similar rate in men and women.
Peak incidence occurs in young and middle-aged adults.
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