Rhinitis Medicamentosa

Introduction
Background

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.4 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.
Pathophysiology

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.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;7 sympathomimetic amines, which have activity at both alpha and beta sites, have a beta effect that outlasts the alpha effect and causes rebound swelling;8 increased parasympathetic activity, vascular permeability, and edema formation by altering vasomotor tone, thus creating the rebound congestion.9

Nasal decongestants

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
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%.10 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).11,12,13,14,15 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.10

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.

Frequency
United States

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%.16 In another study, an ENT practitioner diagnosed rhinitis medicamentosa in 52 out of 100 consecutive noninfectious patients who presented with nasal obstruction.
International

Similar frequency ranges occur in Europe.
Mortality/Morbidity

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.17 No deaths are reported.
Sex

Rhinitis medicamentosa occurs at a similar rate in men and women.
Age

Peak incidence occurs in young and middle-aged adults.
Clinical
History
Symptoms are confined to the nose and consist of chronic nasal congestion without significant rhinorrhea or sneezing.
Symptoms do not change based on the season or whether the patient is spending time indoors or outdoors.
Information about use of decongestant may not be volunteered by patients, as temporary relief of symptoms is often thought to result from the use of nasal spray. The physician must ask about nose spray usage to diagnose rhinitis medicamentosa.18
The frequency and duration of nasal spray use is also important.
In an effort to control symptoms, patients often try to increase both the dose and the frequency of topical decongestants, which leads to dependency.
The most frequent clinical history is a patient with congestion from a cold or rhinitis who experiences congestion, uses an over-the-counter decongestant for relief, and then continues to use the decongestant for weeks, months, or years. Cessation of the decongestant is followed by rebound congestion within hours that is quite profound, leading to more use of the decongestant. The more the decongestant is used, the shorter the period of relief. This eventually leads to the patient seeking medical care.
Physical
Physical findings are confined to the nasal cavity.
The nasal mucous membranes may appear "beefy-red" with punctate bleeding, granular, or boggy, with areas of increased tissue friability and profuse stringy mucoid discharge. However, reports exist of the mucosa appearing pale and anemic.
The appearance of the nasal mucosa often suggests rhinitis medicamentosa because of the redness and irritation of the mucosa.
Patients with RM often snore, have sleep apnea, and mouth-breath resulting in sore throat and dry mouth complains.
Patients with rhinitis medicamentosa often snore, have sleep apnea, or breathe mostly through their mouths. This can result in sore throat and dry mouth.
Causes

Abuse of topical nasal vasoconstrictive medication use is the only known cause of rhinitis medicamentosa. Sympathomimetic amines include ephedrine and phenylephrine; imidazoline derivatives include oxymetazoline and xylometazoline.

Medications associated with drug-induced rhinitis include the following:
Antihypertensives, such as reserpine, hydralazine, guanethidine, methyldopa, prazosin, doxazosin, reserpine, and chlorothiazide
Beta-blockers, such as propranolol and nadolol
Phosphodiesterase type 5 inhibitors, such as sildenafil, tadalafil, and vardenafil
Hormones, such as exogenous estrogens and oral contraceptives
Antidepressants and antipsychotics, including thioridazine, chlordiazepoxide-amitriptyline, risperidone, and perphenazine
Cocaine
Gabapentin
Nonsteroidal anti-inflammatory drugs (NSAIDs)

Associated factors that cause nasal stuffiness include the following:
Allergic rhinitis, nonallergic rhinopathy
Deviated nasal septum
Basal polyps, ASA triad (ie, nasal polyps, asthma, and aspiring intolerance)
Use of CPAP machine at night for sleep apnea
Upper respiratory infection
Rhinosinusitis
Pregnancy19
Other conditions with high levels of estrogen, such as puberty in boys and girls, menarche

http://emedicine.medscape.com/article/995056-overview