Rhinitis medicamentosa

Rhinitis medicamentosa also known as ‘rebound congestion’ or rebound or chemical rhinitis, is inflammation of the nasal mucosa caused by the overuse of topical nasal decongestants (topical vasoconstrictors) ¹. Symptoms are exacerbated by the preservative benzalkonium chloride in the nasal preparations ². Rhinitis medicamentosa classifies as a subset of drug-induced rhinitis. Patients with rhinitis often self-medicate with over-the-counter drugs such as decongestant nasal sprays. However, prolonged use of these sprays may result in rebound congestion of the nasal mucosa. As a result, patients become trapped in a vicious cycle of overuse and dependence that can last for months or years in a condition called rhinitis medicamentosa.

Topical decongestants are typically used in the relief of nasal congestion due to allergic rhinitis, acute or chronic rhinosinusitis, nasal polyps, or upper respiratory tract infection. The earliest nasal decongestants mainly derived from ephedrine, where there were reports of rebound congestion after prolonged use. This situation was found to develop as early as 3 days and up to 4 to 6 weeks of use ³. However, with the emergence of modern vasoconstrictors, such as the imidazoline derivatives, the risk of developing rhinitis medicamentosa is considered to be small or non-existent.

How long does rhinitis medicamentosa last?

It takes approximately one year for complete recovery in cases of long-term overuse ⁴.

What causes rhinitis medicamentosa?

The cause of rhinitis medicamentosa is primarily by the prolonged use (more than 7 to 10 days) of topical nasal decongestant. However, intranasal cocaine use has also been reported to cause a similar condition ¹.

The nasal mucosa vascular system can divide into resistance vessels (arterioles) which are predominantly regulated by alpha-2 adrenoreceptors, and capacitance vessels (venous plexus) regulated by both alpha-1 and alpha-2 adrenoreceptors. Stimulation of these receptors leads to the decongestants effect; where there is vasoconstriction of the large venous sinusoids and collecting veins, leading to decreased blood flow and subsequently decreased nasal edema and rhinorrhoea.

Contributing factors of nasal congestion include parasympathetic nervous system stimulation, the release of local mediators including mast cells, eosinophils, basophils; which subsequently stimulates the release of histamine, tryptase, kinins, prostaglandins, and leukotrienes, inducing an overall change in nasal resistance and capacitance vessels ⁵. There is exudation of plasma through superficial capillaries, and increase mucin production by goblet cells.

Multiple histological changes have been described in rhinitis medicamentosa based on animal studies. These include loss of nasociliary function, goblet cell hyperplasia, epithelial edema, squamous cell metaplasia, increased mucus production, increased number of lymphocytes, plasma cells, fibroblasts, and epidermal growth factor receptor. However, results in human studies have been inconclusive ⁵.

Topical nasal decongestants

Topical nasal decongestants can classify as either beta-phenylethylamine derivatives or imidazoline derivatives. Beta-phenylethylamine derivatives mimic the effects of the sympathetic nervous system stimulation by producing vasoconstriction via the activation of alpha-1 adrenoreceptors. Rebound vasodilation may occur due to weak affinity towards beta–adrenoreceptors. Imidazolines, on the other hand, produces its effect mainly via alpha-2 adrenoreceptors. This difference in adrenoreceptor sensitivity makes the imidazoline agents more effective at decreasing mucosal blood flow due to its vasoconstrictive effect to both capacitance and resistance vessels in the nasal mucosa.

Comparatively, imidazole group demonstrates a more potent and longer-acting effect. For example, 0.1% xylometazoline hydrochloride works within a few minutes and lasts up to 10 hours, while 1% phenylephrine works within 15 to 20 minutes with effects lasting 2 to 4 hours.

Types of intranasal decongestant (adrenoreceptor activity)

• Beta-phenylethylamine derivatives
• Ephedrine HCl (alpha-1, alpha-2, beta-1, beta-2)
• Phenylephrine HCl (alpha-1)
• Imidazoline derivatives (primarily alpha-2 agonists)
• Naphazoline HCl
• Oxymetazoline HCl
• Xylometazoline HCl

Benzalkonium chloride

A common antimicrobial preservative benzalkonium chloride used in the topical nasal preparations has correlations with exacerbation of rhinitis medicamentosa, as it may increase the risk of developing rhinitis medicamentosa by inducing mucosal swelling ⁶. However, this is arguably open to debate as there is no evidence of worsening congestion in those who use intranasal corticosteroids containing benzalkonium chloride ⁷.

Rhinitis medicamentosa pathophysiology

Several hypotheses have been postulated with rhinitis medicamentosa, although the exact pathophysiology is still unknown ⁸:

• Hypothesis 1: Chronic vasoconstriction leads to ischemia of the nasal mucosa, which predisposes to interstitial edema
• Hypothesis 2: Fatigue of the constrictor mechanisms occurs resulting in reactive hyperemia and congestion; this subsequently correlates with reduced sensitivity to endogenous catecholamines, where the adrenoreceptors become refractory to nasal decongestants, necessitating higher dosage of medication (tachyphylaxis)
• Hypothesis 3: Alteration in vasomotor tone results in increased vascular permeability and edema
• Hypothesis 4: The beta-adrenoreceptor activity may outlast the alpha effects leading to rebound vasodilatation

Rhinitis medicamentosa symptoms

The patient typically reports a recurrence of nasal obstruction or congestion, particularly without runny nose on a background of prolonged use of an intranasal decongestant. Severe nasal congestion may lead to oral breathing, dry mouth, and snoring. Clinical examination will reveal nasal mucosa swelling, erythematous and granular appearances. Pale and edematous appearances have also been noted ⁹. As the disease progresses, the nasal membrane becomes atrophic and crusty ¹⁰.

Rhinitis medicamentosa possible complications

Rhinitis medicamentosa complications may include:

• Chronic ethmoiditis ¹¹
• Atrophic rhinitis ¹¹
• Septal perforation
• Chronic rhinosinusitis
• Turbinate hyperplasia

Rhinitis medicamentosa diagnosis

The diagnosis of rhinitis medicamentosa is based on clinical grounds and there are no definitive biochemical tests or imaging studies that can confirm this. Therefore, careful assessment of symptoms, history, and examination is imperative in formulating an accurate diagnosis. It is also vital to acknowledge that other sinonasal conditions may co-exist with rhinitis medicamentosa.

Rhinitis medicamentosa treatment

The treatment of rhinitis medicamentosa involves the discontinuation of the topical decongestant. Patients must receive counsel that the nasal congestion may temporarily worsen upon discontinuation of the topical decongestant so that they do not perceive it as treatment failure. The use of intranasal corticosteroids has been reported to minimize the symptoms of rebound congestion in both animal studies and several small human trials ⁵. Other treatment modalities during withdrawal period involve the use of short-course oral corticosteroids (e.g., prednisone, 0.5 mg per kg for five days), oral antihistamines and inferior turbinate steroid injections, oral adenosine and mast cell stabilizing agents; however, these recommendations are based on limited case reports ⁵.

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