Rhinitis Medicamentosa – Causes, Symptoms, Treatment

Rhinitis medicamentosa (RM) is a drug-induced, nonallergic form of rhinitis that is associated with prolonged use of topical vasoconstrictors, i.e. local decongestants. Symptoms are exacerbated by the preservative benzalkonium chloride (BKC) in the nasal preparations. Nasal stuffiness is caused by rebound swelling? of the mucosa when the decongestive effect of the drug has disappeared. To alleviate this symptom, patients gradually start using larger doses of the vasoconstrictor more frequently.

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.[rx] 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.

Types of Rhinitis Medicamentosa

Causes of Rhinitis Medicamentosa

The cause of this condition is primarily by the prolonged use (more than 7 to 10 days) of topical nasal decongestants. 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 effect of the decongestant;  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 stimulate the release of histamine, tryptase, kinins, prostaglandins, and leukotrienes, inducing an overall change in nasal resistance and capacitance vessels.[2] There is the 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, the 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?.[rx][rx][rx].
• However, this is arguably open to debate as there is no evidence of worsening congestion in those who use intranasal corticosteroids containing BKC.[rx][rx][rx]

Symptoms of Rhinitis Medicamentosa

• Nasal block without significant rhinorrhoea and sneezing
• These symptoms don’t exhibit seasonal variations
• The patient feels compelled to use nasal topical decongestants
• Usage of these decongestants become more frequent

Diagnosis? of Rhinitis Medicamentosa

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.[rx]

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.[rx] As the disease progresses, the nasal membrane becomes atrophic and crusty.[rx]

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 of Rhinitis Medicamentosa

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.[rx]  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.[rx]

• The use of over-the-counter (OTC) –  saline nasal sprays may help open the nose without causing RM if the spray does not contain a decongestant.^[rx] Symptoms of congestion and runny nose can often be treated with corticosteroid nasal sprays under the supervision of a physician. For very severe cases, oral steroids or nasal surgery may be necessary. For RM caused by topical decongestants, there are anecdotal reports of persons having success by withdrawing treatment from one nostril at a time.
• Benzalkonium chloride – A study has shown that the anti-infective agent benzalkonium chloride, which is frequently added to topical nasal sprays as a preservative, aggravates the condition by further increasing the rebound swelling?.
• Oral prednisolone – Patient with rhinitis medicamentosa is treated with oral prednisolone in doses of 15 mg thrice a day for 5 days, while the nasal decongestant is simultaneously withdrawn in a phased manner. The patient is weaned from steroids by tapering the dose.
• Use of intranasal steroids – This is becoming popular because it causes fewer side effects than systemic? steroids. It can be safely administered for long durations. These patients may derive significant benefit by using intranasal steroids as it helps in simultaneous control of nasal allergy? and also reduces the nasal mucosal infection?, or irritation, often causing pain?, swelling?, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation? and edema?.
• Nasal saline douching – Douching the nose with isotonic saline will help in clearing the nasal cavity of thick mucoid secretions thus enabling the steroid? spray to permeate the nose fully.

Complications

• Septal hematoma
• Septal abscess?
• Avascular necrosis of nasal septal cartilage? leading to saddle deformity
• Nasal obstruction
• Blowout fractures: Extraocular muscle entrapment and diplopia
• Nasolacrimal duct injury: Due to the close relationship of the duct to the nasal bones
• Fracture? of cribriform plate and cerebrospinal fluid (CSF) rhinorrhoea
• Inability to reduce: Fractures that cannot be reduced by closed techniques are candidates for open reduction.[rx]
• Airway compromise and hemorrhage.[rx]
• Nasofrontal duct and or lacrimal duct disruption as a result of direct damage or due to displaced fracture? segments.[rx]
• Facial deformity, as full correction of telecanthus or nasal depression can be difficult to achieve, and some patients will retain a degree of asymmetry. Depending on the surgical approach, patients may experience temporary or permanent paralysis and or anesthesia of the forehead. Scars that cannot be hidden in the hairy scalp or skin folds may be prominent.[rx]
• Infection? of the incision site, soft tissues, and meninges are recognized complications from these injuries.[rx]
• Mucocele formation is a complication of sinus or lacrimal drainage disruption and can become infected.[rx]
• Mental health, as patients with facial injuries are at greater risk of developing post-traumatic stress disorder or anxiety-related disorders. Particularly those who were victims of assault.[rx]

References