Rhinitis Medicamentosa

Article Author:
Nur Wahidah Wahid
Article Editor:
Carl Shermetaro
Updated:
2/4/2019 9:53:31 PM
PubMed Link:
Rhinitis Medicamentosa

Introduction

Rhinitis medicamentosa (RM), also known as ‘rebound congestion’ is inflammation of the nasal mucosa caused by the overuse of topical nasal decongestants.  It classifies as a subset of drug-induced rhinitis. 

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.[1] However, with the emergence of modern vasoconstrictors, such as the imidazoline derivatives, the risk of developing RM is considered to be small or non-existent.

Etiology

The cause of this condition 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. 

Physiology of nasal congestion 

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.[2] There is exudation of plasma through superficial capillaries, and increase mucin production by goblet cells. 

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 (BKC)

A common antimicrobial preservative benzalkonium chloride (BKC) used in the topical nasal preparations has correlations with exacerbation of RM, as it may increase the risk of developing RM by inducing mucosal swelling.[3][4][5]. However, this is arguably open to debate as there is no evidence of worsening congestion in those who use intranasal corticosteroids containing BKC.[6][7][8]

Epidemiology

It occurs most commonly in young and middle-aged adults with a similar rate in men and women. The incidence has been reported to range from 1% to 9% of otolaryngology clinics.[9] This figure may be an underrepresentation due to over-the-counter availability of these medications.

Pathophysiology

Several hypotheses have been postulated with rhinitis medicamentosa, although the exact pathophysiology is still unknown[2][10][11]:

  • 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

Histopathology

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.[2] 

History and Physical

The patient typically reports a recurrence of nasal congestion, particularly without rhinorrhea 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.[12] As the disease progresses, the nasal membrane becomes atrophic and crusty.[13]

Evaluation

The determination of RM 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 RM.

Treatment / Management

The treatment of RM 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.[2]  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.[2]

Differential Diagnosis

  • Allergic rhinitis
  • Non-allergic rhinitis
  • CPAP-related rhinitis
  • Rhinosinusitis

Prognosis

It takes approximately one year for complete recovery in cases of long-term overuse.[14]

Complications

  • Chronic ethmoiditis[15]
  • Atrophic rhinitis[15]
  • Septal perforation
  • Chronic rhinosinusitis
  • Turbinate hyperplasia

Consultations

In complicated cases or where diagnosis is unclear, further expert input from the allergist, immunologist, or otorhinolaryngologist is advised.

Deterrence and Patient Education

Patients should receive education on the side-effects of overusing intranasal decongestant before prescribing the medication. It is understandably challenging as these medications are generally readily available over the counter.

Patients should be warned that repeated short term use, of an intranasal decongestant even after a year of discontinuation can cause recurrence of RM.[16]

Enhancing Healthcare Team Outcomes

Rhinitis medicamentosia is a preventable condition, and therefore awareness about the complication of overuse among both healthcare professionals and patient is essential. All members of the interprofessional team should help manage the condition, from the clinician, who may prescribe the agents that cause it or treat it, to the pharmacist who can detect a trend in medication use that leads to it, to the nurse who can counsel and help the patient use medication correctly. Interpofessional collaboration can alleviate patient suffering in this condition.


References

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[2] Ramey JT,Bailen E,Lockey RF, Rhinitis medicamentosa. Journal of investigational allergology     [PubMed PMID: 16784007]
[3] Graf P,Hallén H, Effect on the nasal mucosa of long-term treatment with oxymetazoline, benzalkonium chloride, and placebo nasal sprays. The Laryngoscope. 1996 May;     [PubMed PMID: 8628089]
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[14] Hallén H,Enerdal J,Graf P, Fluticasone propionate nasal spray is more effective and has a faster onset of action than placebo in treatment of rhinitis medicamentosa. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 1997 May;     [PubMed PMID: 9179430]
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[16] Graf P,Hallén H, One-week use of oxymetazoline nasal spray in patients with rhinitis medicamentosa 1 year after treatment. ORL; journal for oto-rhino-laryngology and its related specialties. 1997 Jan-Feb;     [PubMed PMID: 9104748]