Rhinitis Medicamentosa


Article Author:
Nur Wahidah Wahid


Article Editor:
Carl Shermetaro


Editors In Chief:
Brian Downs
Ziad Katrib


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
2/4/2019 9:53:31 PM

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 amongst both healthcare professionals and patient is essential.


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Rhinitis Medicamentosa - Questions

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A 32-year-old woman who is pregnant presents with rhinitis medicamentosa. The provider discontinues her nasal sympathomimetics but would like to help ease her symptoms. Which of the following medications would be most appropriate?



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What is commonly associated with chronic use of a nasal decongestant?



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Intranasal decongestants can generally be classified into sympathomimetics and imidazoline derivatives. The sympathomimetic agents primarily act on alpha-1 adrenoreceptors, whereas the imidazoline derivatives act selectively on alpha-2 adrenoreceptors. Which of the following intranasal decongestant are imidazoline derivatives?



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A 35-year-old man with nasal congestion continues to use an over-the-counter intranasal decongestant for four weeks. He complains that he is dependant on the intranasal decongestant spray and that he needs to use it more frequently to obtain relief. Which of the following is the best approach to the management of this patient?



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A 17-year-old female presents complaining of recurrent nasal congestion. She admitted to regular use of intranasal cocaine. She was diagnosed with rhinitis medicamentosa and was advised to avoid the causative drug. At her six month follow-up, she presented with intermittent epistaxis and nasal whistling. Which systemic disease is associated with this complication?



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Rhinitis medicamentosa (RM), also known as ‘rebound congestion’ is characterized by inflammation of the nasal mucosa. Which of the following is the most common causative agent in rhinitis medicamentosa?



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Rhinitis Medicamentosa - References

References

Wallace DV,Dykewicz MS,Bernstein DI,Blessing-Moore J,Cox L,Khan DA,Lang DM,Nicklas RA,Oppenheimer J,Portnoy JM,Randolph CC,Schuller D,Spector SL,Tilles SA, The diagnosis and management of rhinitis: an updated practice parameter. The Journal of allergy and clinical immunology. 2008 Aug;     [PubMed]
Ramey JT,Bailen E,Lockey RF, Rhinitis medicamentosa. Journal of investigational allergology     [PubMed]
Mortuaire G,de Gabory L,François M,Massé G,Bloch F,Brion N,Jankowski R,Serrano E, Rebound congestion and rhinitis medicamentosa: nasal decongestants in clinical practice. Critical review of the literature by a medical panel. European annals of otorhinolaryngology, head and neck diseases. 2013 Jun;     [PubMed]
Graf P, Adverse effects of benzalkonium chloride on the nasal mucosa: allergic rhinitis and rhinitis medicamentosa. Clinical therapeutics. 1999 Oct;     [PubMed]
Blue JA, Rhinitis medicamentosa. Annals of allergy. 1968 Aug;     [PubMed]
Baldwin RL, Rhinitis medicamentosa (an approach to treatment). Journal of the Medical Association of the State of Alabama. 1975 Aug;     [PubMed]
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]
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]
Graf P, Rhinitis medicamentosa: aspects of pathophysiology and treatment. Allergy. 1997;     [PubMed]
Lockey RF, Rhinitis medicamentosa and the stuffy nose. The Journal of allergy and clinical immunology. 2006 Nov;     [PubMed]
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]
Graf P,Hallén H,Juto JE, Benzalkonium chloride in a decongestant nasal spray aggravates rhinitis medicamentosa in healthy volunteers. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 1995 May;     [PubMed]
Graf P, Benzalkonium chloride as a preservative in nasal solutions: re-examining the data. Respiratory medicine. 2001 Sep;     [PubMed]
Scadding GK, Adverse effects of benzalkonium chloride on the nasal mucosa: allergic rhinitis and rhinitis medicamentosa. Clinical therapeutics. 2000 Jul;     [PubMed]
Marple B,Roland P,Benninger M, Safety review of benzalkonium chloride used as a preservative in intranasal solutions: an overview of conflicting data and opinions. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2004 Jan;     [PubMed]
Bernstein IL, Is the use of benzalkonium chloride as a preservative for nasal formulations a safety concern? A cautionary note based on compromised mucociliary transport. The Journal of allergy and clinical immunology. 2000 Jan;     [PubMed]

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