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Allergy and Immunology > MEDICAL TOPICS
Rhinitis Medicamentosa
Article Last Updated: May 2, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Craig F Garfield, MD, MAPP, Assistant Professor of Pediatrics, Department of Pediatrics, Feinberg School of Medicine, Northwestern University; Evanston Northwest
Editors: Orval Brown, MD, Director of Otolaryngology Clinic, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Texas Southwestern Medical Center at Dallas; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; John E McClay, MD, Assistant Professor, Department of Otolaryngology, Division of Pediatric Otolaryngology, Children's Medical Center, University of Texas Southwestern Medical School; Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine; Maureen Strafford, MD, Arnold P Gold Foundation Associate Professor, Departments of Anesthesiology and Pediatrics, Tufts University and Tufts-New England Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
rhinitis medicamentosa, RM, overuse of intranasal vasoconstrictive medications, topical nasal decongestants, rebound swelling, overuse of nasal spray
Background
Rhinitis medicamentosa (RM) is a condition of rebound nasal congestion brought on by overuse of intranasal vasoconstrictive medications. This disorder typically occurs after 5-7 days of medication use. Many reasons for the initial use of the medication are possible, and eliciting the reason for use of vasoconstrictive medications is important. As the patient continues using medication, tachyphylaxis occurs, resulting in increased frequency and shorter duration of action for the offending medication.
Pathophysiology
Debate exists about how decongestant nasal sprays cause the classic rebound swelling of RM. Because prolonged topical nasal decongestants bring on the disorder, understanding how these medications affect the nasal mucosa is helpful.
Topical nasal decongestants fall into 2 general classes, as follows:
- Sympathomimetic amines, including ephedrine and phenylephrine
- Imidazoles, including oxymetazoline and xylometazoline
All sympathomimetic amines act on both alpha-receptors and some beta-receptors. Imidazoles act on the more selective alpha2 receptors. Sympathomimetic drugs contract the smooth muscle of the venous erectile tissue causing mucosal shrinkage and decreasing airway resistance. The venous erectile tissue is sensitive to both alpha and alpha2 stimulation, but the imidazole action on alpha2 receptors is probably responsible for the decrease in mucosal blood flow because resistance vessels are most sensitive to alpha2 agonists. With prolonged vasoconstriction, the mucosa become less responsive to the drug and a reversal to vasodilatation occurs. Patients may develop tachyphylaxis— a rapidly decreasing response to a drug following administration of the initial doses— resulting from the need for more frequent doses to provide adequate decongestion.
The secondary vasodilatation is not well understood. One theory suggests that the sympathomimetic amines, which have activity at both alpha and beta sites, have a longer beta effect that outlasts the alpha effect and causes rebound swelling. A second theory postulates that prolonged vasoconstriction causes tissue hypoxia with a resulting reactive hyperemia, rebound swelling, and vasodilatation. A third theory postulates that alpha2 agonists stimulate a negative feedback loop that involves the presynaptic nerve endings. With prolonged use of these agonists, a decrease in endogenous noradrenaline would occur, and, once the exogenous drug disappears, a rebound congestion develops. A fourth theory suggests that the medication causes increased parasympathetic activity, vascular permeability, and edema formation by altering vasomotor tone, thus creating the rebound congestion.
Nasal medications containing the quaternary ammonium benzalkonium chloride (BKC), a preservative that prevents the growth of microorganisms, cause more rebound congestion than the same decongestant administered preservative-free. BKC, therefore, may aggravate RM.
Frequency
United States
In a study conducted over 10 years in an otolaryngology (ENT) office, the incidence of RM was 1%. In another study, an ENT practitioner diagnosed RM in 52 out of 100 consecutive noninfectious patients presenting with nasal obstruction.
International
Similar frequency ranges occur in Europe.
Mortality/Morbidity
With continued usage, RM leads to chronic sinusitis, atrophic rhinitis, and permanent turbinate hyperplasia. However, in neonates, who are obligate nose breathers, prolonged use of topical vasoconstrictor causes RM and consequent apnea and cyanosis. After the withdrawal of the offending medication, patients recover. No deaths are reported.
Age
Peak incidence occurs in young and middle-aged adults.
History
- Symptoms are confined to the nose and consist of chronic nasal congestion.
- Physician must ask about nose spray usage to diagnose RM, as patients frequently neglect to mention these over-the-counter medications.
- The frequency and duration of nasal spray use is also important.
- Patients often try to increase both the dose and the frequency of topical decongestants.
Physical
- Physical findings are confined to the nose.
- The nasal mucous membranes may appear hyperemic, granular, and boggy with areas of increased tissue friability and punctate bleeding.
- The mucus is usually clear and minimal unless an accompanying sinus infection is present. However, reports exist of the mucosa appearing pale and anemic with nasal of discharge that is stringy, profuse, and mucoid.
- The use of topical 4% cocaine to induce local vasoconstriction and shrinkage is usually ineffective in RM.
Causes
- Topical nasal vasoconstrictive medication
- Sympathomimetic amines include ephedrine and phenylephrine
- Imidazoline derivatives include oxymetazoline and xylometazoline
- BKC, a preservative used in nasal preparations, is thought to worsen RM, though debate is taking place in the literature
- Medications that cause stuffy nose and may cause an increase in vasoconstrictor use
- Antihypertensives, such as reserpine, hydralazine, guanethidine, methyldopa, and prazosin
- Beta-blockers, such as propranolol and nadolol
- Antidepressants and antipsychotics, including thioridazine, chlordiazepoxide-amitriptyline, and perphenazine
- Cocaine
- Associated factors that cause nasal stuffiness
- Allergy
- Deviated nasal septum
- Upper respiratory infection (URI)
- Sinusitis
- Pregnancy or other conditions with high levels of estrogen, such as puberty in boys and girls, menarche, estrogen replacement therapy, and oral contraceptive use
Allergic Rhinitis
Nasal Polyps
Sinusitis
Other Problems to be Considered
Deviated nasal septum
URI
Vasomotor rhinitis
Cocaine abuse
Pregnancy
Lab Studies
- A nasal smear with a preponderance of eosinophils indicates allergic rhinitis.
Imaging Studies
- RM is diagnosed based on history and physical examination findings; sinus imaging studies may be helpful to rule out sinusitis.
- Rhinosterometry
- This test is a direct noninvasive optical surgical microscope that angles in a 3-dimensional coordinate system to achieve accurate measurements, within 0.2 mm.
- Researchers use rhinosterometry to estimate nasal mucosal reactivity to histamine provocations and to quantify nasal mucosa swelling.
Histologic Findings
Histopathological studies carried out in animals and humans show the effects of topical nasal medications on nasal mucosa. In guinea pigs treated with vasoconstrictive nose drops, nasal goblet cells underwent hyperplasia. The squamous cells also became hyperplastic, perhaps in an attempt to better protect the nasal mucosa. Other findings include increased vascularity, edema of the corium, mononuclear infiltration, and glandular hyperplasia. Histochemically, evidence exists of increased secretory activity, increased phagocytosis, and disturbance of vasomotor tone, leading to vascular dilatation, increased permeability, and edema formation. Epidermal growth factor receptor staining appears to increase in the hyperplastic epithelium of humans with RM. Electron microscopy of treated rabbits shows evidence of abnormal cilia structure and function, epithelial changes suggestive of edematous infiltration, and histological changes leading to increased permeability.
Medical Care
The primary treatment is immediate withdrawal of the offending medicine. For those patients unable or unwilling to immediately stop, several methods may ease the withdrawal process.
The first 7 days are often the most difficult for weaning or withdrawal. Have the patient immediately stop using the medication on their best side, while using the nasal spray as desired in the other nostril. Encourage patients to discontinue or decrease use, as soon as they feel comfortable. Remind patients that their good nostril will open up, at which point they may discontinue spraying the opposite side. Assist patients in resuming normal sleep habits by encouraging the use of a sedative antihistamine, which should help with sleep and congestion if an allergic component is present as long as no significant airway obstruction is present. Encourage patients to naturally lubricate the nose by mixing a saline nasal solution using half a teaspoon of salt in 8 ounces of lukewarm water, then delivering it into the nostrils using a small rubber ear syringe, Water Pik or nasal rinse device (ie, NeilMed).
- Nasal corticosteroids
- Several prescription nasal preparations are helpful in reducing local inflammation.
- Additionally, the patient may psychologically feel better by continuing to use a nasal spray until the congestion is gone.
- Systemic decongestants: These are particularly helpful in those patients who began using vasoconstrictive nasal medications to help with allergic rhinitis. As the symptoms associated with allergic rhinitis are relieved, the intranasal medication can be discontinued.
- Oral corticosteroids: Although necessary only in rare severe cases, short-course oral corticosteroids, as described below, are the most effective way to break the cyclic use of topical vasoconstrictors. Often the oral corticosteroids are used for 5-10 days, with nasal corticosteroids started at the same time and continued until the process is corrected.
Consultations
Consult an otorhinolaryngologist if a patient's case is complicated and refractory to treatment or if the primary care physician is unsure of diagnosis.
Nasal corticosteroids, systemic decongestants, or oral corticosteroids may ease withdrawal of the offending medication in patients unable to stop using nasal vasoconstrictive medications.
Nasal corticosteroids help reduce local inflammation without systemic effect, possibly by reducing nasal congestion sooner. Oral corticosteroids are rarely necessary. The adult literature suggests using oral corticosteroids (eg, prednisone 40 mg/d for an average-weight adult, tapering over 7-10 d).
Several different nasal steroids are available, including budesonide, fluticasone, mometasone, beclomethasone, flunisolide, and triamcinolone. These products differ in their delivery systems; some have chlorofluorocarbon (CFC) propellants (CFCs are currently being phased out because of environmental and physiologic hazards), while newer agents offer an aqueous delivery system. Although these products all are equally effective at equipotent doses, they differ in their potency and half-life, which accounts for the difference in dosing frequency (ie, qd versus tid) and the total amount of sprays per dose (ie, 1-2 sprays versus 3-4 sprays). Two intranasal corticosteroids commonly used for children, budesonide and fluticasone, are described below.
Drug Category: Corticosteroids
Elicit anti-inflammatory and immunosuppressive properties, and they cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.
| Drug Name | Budesonide (Rhinocort, Rhinocort AQ) |
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| Description | Alters level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved.
This product may help patients through the difficult first week by reducing inflammation. Methods are uncertain for treating RM in children. Drug safety is the same as when used for allergic rhinitis. Titrate dose to the least amount needed. |
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| Adult Dose | 2 sprays (32 mcg/spray) per nostril bid or 4 sprays per nostril qd |
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| Pediatric Dose | <6 years: Not established
>6-11 years: 1 spray (32 mcg/spray)/nostril qd; may increase to 2 sprays/nostril qd if necessary
>11 years: Administer as in adults |
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| Contraindications | Documented hypersensitivity; infections of nasal mucosa; wound in nasal tract; tuberculosis of the respiratory tract |
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| Interactions | Concomitant use with PO or PO inhaled corticosteroids can enhance the toxicities of corticosteroids |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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| Precautions | Rare cases of nasal septal perforation; common adverse effects include nasal stinging, throat irritation, nasal dryness, epistaxis, and headache |
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| Drug Name | Fluticasone (Flonase) |
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| Description | Has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak hypothalamic-pituitary-adrenocortical axis inhibitory potency when applied topically.
This product may help the patient through the difficult first week by reducing inflammation. Titrate dose to the least amount needed. Contains 50 mcg per actuation. |
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| Adult Dose | 2 sprays (50 mcg/spray) per nostril qd |
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| Pediatric Dose | <4 years: Not established
>4 years: 1-2 sprays per nostril qd; once controlled, maintain at lowest dose possible (ie, 1 spray per nostril qd) |
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| Contraindications | Documented hypersensitivity; infections of nasal mucosa; wound in nasal tract; tuberculosis of the respiratory tract |
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| Interactions | Concomitant use with PO or PO inhaled steroids can enhance the toxicities of corticosteroids |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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| Precautions | Rare cases of nasal septal perforation; common adverse effects include nasal stinging, throat irritation, nasal dryness, epistaxis, and headache |
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Drug Category: Decongestants
These drugs may be helpful in patients with a component of allergic or seasonal rhinitis as an underlying cause of their RM. They stimulate alpha-adrenergic receptors of vascular smooth muscle. This leads to constriction of dilated arterioles within the nasal mucosa and reduced blood flow to the engorged area.
| Drug Name | Pseudoephedrine (Sudafed) |
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| Description | One of many systemic decongestants that may be used.
Stimulates vasoconstriction by directly activating alpha-adrenergic receptors of the respiratory mucosa. Induces also bronchial relaxation and increases heart rate and contractility by stimulating beta-adrenergic receptors. |
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| Adult Dose | 60 mg q4-6h or 120 mg SR q12h; not to exceed 240 mg/d |
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| Pediatric Dose | <2 years: 4 mg/kg/d PO divided q6h
2-5 years: 15 mg PO q6h; not to exceed 60 mg/d
6-12 years: 30 mg PO q6h; not to exceed 120 mg/d
>12 years: Administer as in adults |
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| Contraindications | Documented hypersensitivity; severe anemia; postural hypertension or hypotension; closed-angle glaucoma; head trauma; cerebral hemorrhage |
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| Interactions | Propranolol, MAOIs, and other sympathomimetic agents may increase toxicity of pseudoephedrine; methyldopa and reserpine may reduce effects of pseudoephedrine |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
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| Precautions | Caution in cardiovascular disease, diabetes mellitus, prostatic hypertrophy, and increased intraocular pressure |
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Further Outpatient Care
- Follow up in 1-2 weeks to support the patient, assess the status of the residual obstruction in patients with mechanical nasal obstruction, and to evaluate the turbinates for possible permanent hyperplasia.
Deterrence/Prevention
- Avoid topical vasoconstrictors in the future. Studies showed that those with a history of RM who successfully stop using the offending medication have a rapid onset of rebound congestion upon repeat use of topical vasoconstrictor medication, even for only a few days.
Complications
- Most patients are able to eventually discontinue topical nasal medication. In those who are unable, reports exist of permanent hyperplasia requiring intervention varying from submucosal electrocautery or cryotherapy to partial turbinate destruction by laser or surgical resection.
Prognosis
- Studies showed that nearly all patients were able to eventually stop using the offending medication.
- Those who used topical preparations again, even 1 year later, had rapid rebound congestion within a few days.
Patient Education
- The key to treatment and prevention of RM lies in educating the patient about the consequences of using nasal vasoconstrictors for longer than 5-7 days.
- Once informed that the cause of the chronic congestion is their medication, most patients immediately begin withdrawing.
Medical/Legal Pitfalls
- Failure to recognize that a treatable condition, such as deviated septum or allergic rhinitis, may have been the cause for starting nasal decongestant medication
- Failure to elicit a history of use of nasal decongestant medication in a patient with chronic stuffy nose
Special Concerns
- Pregnancy
- Rhinitis of pregnancy affects as many as 20% of women. High estrogen levels during pregnancy tend to increase acetylcholine levels.
- The direct cholinergic action leads to swelling and congestion of the nasal mucosa.
- Estrogen levels are highest in the third trimester.
- Therapy for a pregnant patient with RM is the same as outlined above. The patient's obstetrician should be consulted before starting any medications.
- Neonates
- One report exists of a healthy neonate prescribed phenylephrine for noisy breathing, sternal retractions, and perioral cyanosis.
- The parents continued to administer the medication every 3-4 hours for 12 days. By then, the infant had developed RM resulting in hypoxia, right ventricular hypertrophy (RVH), apnea, and cyanotic spells.
- This patient required bilateral nasal stents formed from a #4 endotracheal tube (ETT). Irrigation and suctioning were performed prior to each feeding to maintain patency. As a precaution, an apnea monitor was thought to be helpful until the RM resolved.
- Oral pseudoephedrine was also recommended, with close monitoring of blood pressure for 1 hour after the dose. This patient recovered completely.
- Careful use of nasal Decadron drops or a nasal steroid spray can help wean these patients as well.
- Nasal stuffiness in infants may warrant a workup for gastroesophageal reflux.
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Rhinitis Medicamentosa excerpt Article Last Updated: May 2, 2006
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