n SCIENTIFIC SECTION I "-I I

REVIEW ARTICLES

Rhinitis medicamentosa

MARTIN J. BLACK, MD, FRCS[C]; KENNETH A. REMSEN,* B SC

Rhinitis medicamentosa, the syndrome of rebound secondary sal mucosa of rabbits. His work to prolonged topical intranasal use of vasoconstrictors, is reviewed. In this was followed that of Lierle and condition the nasal airway is very obstructed; atrophic rhinitis is the most by serious complication. Management consists of withdrawing the offending Moore,9 Walsh and Cannon,10 and alleviating the nasal obstruction by means of any of several Kully,' Lake,2 Ryan'1 and Fabri- treatment modalities. cant."' Despite the early evidence of ill On passe en revue la rhinite medicamenteuse, le syndrome de rebond de la effects of the intranasal use of congestion nasale secondaire a l'usage topique prolongee des vasoconstricteurs vasoconstrictors, advertising con- nasaux. En cette affection l'obstruction des voies aeriennes est prononcee; tinued to illustrate the benefits of la rhinite atrophique s'avere la complication la plus grave. On a effectue this practice without sufficient men- la cure de sevrage en supprimant le vasoconstricteur en cause et en soulageant tion of the deleterious effects asso- l'obstruction nasale par n'importe laquelle de plusieurs modalites du traitement. ciated with prolonged use. Kully' reported in 1945 that no class of Both the otolaryngologist and the soconstrictors. The condition of re- drugs was more widely distributed family practitioner are frequently bound nasal congestion secondary and used than the vasoconstrictors. confronted by the patient troubled to prolonged topical intranasal use At that time there were 240 prod- by a "stuffy" nose. The most com- of vasoconstrictors is appropriately ucts of this kind available. mon causes of this problem are termed rhinitis medicamentosa.' Addiction to nosedrops was well acute viral rhinitis (the common documented in 1946 by Lake,' who cold), , anatomic History of the condition described how one patient "had defects and purulent .1 Af- become so addicted to the use of ter careful consideration of these Vasoconstrictors have been avail- nosedrops that it was necessary to disorders during history-taking and able for intranasal use since the hospitalize her and then get her out physical examination a different 19th century. The alkaloid ephe- of the room while one of the first condition may reveal itself. The drine was first isolated in 1887 assistants went through her belong- patient tells of the frequent use of from the Chinese herb Ma-huang.' ings and removed numerous bottles nosedrops to gain relief of the nasal Shortly afterwards Oliver and of nosedrops". Following these obstruction, and the physician dis- Schafer4 discovered epinephrine in publications little appeared in the covers a hyperemic, edematous na- the adrenal medulla, and 10 years literature until 20 years later, when sal mucosa that shrinks little after later Stolz' and Dakin' produced Stride" reported that up to 5% the intranasal administration of va- it synthetically. The commonly of outpatient consultations in many used was discovered ear, nose and throat units were for From the department of otolaryngology, 5 years later by Barger and Dale.7 rhinitis medicamentosa "a direct Jewish General Hospital, Montreal The discovery of fol- consequence of misguided topical *Fourth-year medical student, McGill lowed in 1930 and that of napha- nasal therapy". Subsequent reports University zoline in 1941.' Early in the 1930s were presented by Blue,'4 May work began in an effort to de- and and Reprint requests to: Dr. Martin J. West1 Baldwin.'" Despite Black, Department of otolaryngology, termine the adverse effects of these the past and recent work describing Jewish General Hospital, 3755 Cote agents in humans. In 1931 Fox8 rhinitis medicamentosa, the intra- St. Catherine Rd., Montreal, PQ described the chronic effect of epi- nasal use of vasoconstrictors is in- H3T 1E2 nephrine and ephedrine on the na- creasing steadily.'" CMA JOURNAL/APRIL 19, 1980/VOL. 122 881 Intranasal use of vasoconstrictors The obvious disparity between are of two main classes: the sym- the therapeutic indications and the pathomimetic amines and the imi- As Kully3 wrote: "The nasal actual use of this class of drug dazole derivatives (incomplete sym- mucosa responds to infection as do evinces the need for better physi- pathomimetics). The latter include other body tissues, with swelling, cian and patient awareness of the , and augmented blood supply, increased limitations of nasal vasoconstrictors. .13" 2 Drugs of either exudation and diapedesis. Shrink- group, when applied intranasally, ing the tissues with medication re- Physiology of the will cause local . verses this physiologic response. In upper respiratory tract2'19 The imidazoles, however, lack the no other tissue of the body is in- systemic effects on the myocardium fection treated by diminishing the The nose serves as a physiologic and bronchioles associated with the blood supply and shrinking the col- air-conditioner, performing three sympathomimetics.20 For this rea- lateral . Such treatment les- main functions: filtering the in- son the use of the imidazoles is sens neither the severity nor the spired air and regulating its tem- preferred. duration of the infection. On the perature and humidity. Anatomic- Sympathomimetics are divided contrary, the typical cause of an ally the nose is well suited to this into two groups on the basis of acute rhinitis may be altered and purpose as the nasal mucous mem- their action on the hypothetical a- prolonged." Boies," in his textbook branes, folded over the turbinates, and a3-receptors in the affected tis- of otolaryngology, stated that de- create a large surface area for im- sues. The a-receptors mediate vaso- congestion is required to promote parting warmth and moisture to the constriction and the ,8-receptors are drainage of the purulent fluid with- inspired air. The nasal mucosa con- responsible for vasodilatation." The in the nasal or sinus cavities asso- sists of -secreting pseudo- decongestion afforded by these ciated with an infectious process in stratified ciliated columnar epi- agents is a direct consequence of the nose or . He thelium and a highly specialized their vasoconstrictive action. The claimed that topically administered form of ciliated in the subepithelial capillaries and arte- vasoconstrictors are useful for this olfactory sensory area. The ciliated rioles, together with the venous purpose but advised that the dura- columnar epithelium is rich in gob- sinuses of the erectile tissue, under- tion of their use be limited to 1 let cells, which secrete approxi- go vasoconstriction. If the vaso- week. Fabricant"8 suggested that, mately 1 litre of mucus per day. constriction is severe or prolonged when judiciously employed, nasal The mucus is transported by the a reversal reaction, secondary vaso- vasoconstrictors aid in promoting cilia as a continuous blanket back- dilatation, occurs and the mucosa adequate drainage from paranasal ward toward the choanae, from becomes increasingly less sensitive sinuses by opening obstructed ostia, where it passes into the naso- to subsequent applications of vaso- and that "a number of sympatho- . Here it is carried to the constrictors; the result is the drug mimetic amines have come to as- lateral pharyngeal wall and is swal- habituation characteristic of rhinitis sume a legitimate place in the oto- lowed, lubricating the pharyngeal medicamentosa. laryngologist's treatment schedule. and laryngeal mucosal surfaces. The cause of the secondary vaso- They afford symptomatic relief for The cilia beat approximately 200 dilatation is not fully understood, the patient with acute coryza, but times per minute, and the mucus but a number of theories have been probably have no therapeutic value. blanket moves at a rate of about advanced. In 1945 Kully' suggested Intranasal vasoconstrictors should 0.5 cm/min. that it was due to either fatigue be used only temporarily - five The two nasal chambers vary in of the constrictor mechanism or days' use, as stated on prescrip- their activity, with alternating con- the presence of an active vasodila- tions, with no refills." gestion of the inferior turbinate on tor in the drug. He and others"4,",' Nasal vasoconstrictors are used one side and decongestion on the believe that "overconstriction might therapeutically in preparation for opposite side. The change occurs produce local submucosal hypoxia nasal operations, as an adjunct in every 20 to 120 minutes in this and reactive hyperemia manifested treating serous otitis media, and for so-called nasal cycle. The cavern- as vasodilatation. Soon after Kully's acute and chronic sinusitis, and are ous tissue on the medial surfaces report was published Ryan,11 work- used prophylactically to prevent the of the turbinates becomes more or ing with rabbits, demonstrated com- barotrauma associated with air less congested with variations in plete absence of epithelial cell cilia travel and scuba diving. They are the temperature and humidity of following the intranasal administra- also used in nursing infants suf- the inspired air. These changes vary tion of either desoxyephedrine fering from a cold. However, of the effective surface area of the (methamphetamine) or naphazoline 22 patients with rhinitis medica- nasal mucosa and, in so doing, hydrochloride. These dramatic mentosa recently studied by Bald- adapt the nasal chambers to changes developed just 5 to 8 days win"6 only 3 initiated drug therapy changes in the environment. after the start of daily use of the on the basis of the indications cited. drug. Ryan also observed subepi- Of the remaining 19 patients 16 Pathophysiologic effects thelial thickening and fibrosis after had allergic rhinitis, 4 had a de- of nasal vasoconstrictors 3 weeks and epithelial cell meta- viated and 3 had an plasia into stratified squamous cells upper infection. Currently nasal vasoconstrictors by the end of 60 days. Boies"7 882 CMA JOURNAL/APRIL 19, 1980/VOL. 122 postulated that the mucus cells of twelve years, the mucous mem- of 2 to 4 weeks. Baldwin" cited the nasal epithelium "may be un- brane was pale and anemic look- three advantages to this method: duly stimulated and may increase ing." This is in contrast to Stride's steroids aid in controlling under- nasal blockage by excess secretion". finding of profuse, stringy, mucoid lying allergy, they aid in reducing Finally, a current concept of Bald- nasal discharge, narrowed airways rebound congestion, and they pro- win's is that "the beta effects [of and edematous mucosa.'3 Blue"4 de- vide a psychologic boost to the pa- topical sympathomimetics], al- scribed congestion of the turbinates tient during withdrawal. though not so pronounced, outlast during the early stages, with the In our clinic we have been trying the alpha effect and thereby lead mucosa becoming pale and boggy the topical use of nonabsorbed to secondary vasodilatation and with long-term use of the agents. steroids - for example, flunisolide tissue congestion". May and West' told of atrophic (Rhinalar) and beclomethasone di- The complications of rhinitis and crusted mucous membranes propionate (Beconase). These pro- medicamentosa, described long ago and an abnormally patent airway vide the local effect without the by Kully3 and Fox,8 include the associated with prolonged nasal de- possible systemic effects. Our initial development of atrophic rhinitis, congestion. Walker25 included poor results have been promising, and sinusitis and otitis media. The per- shrinkage of the nasal mucosa on controlled studies are under way. sistent nasal vasodilatation and examination as a key finding, and When these methods have failed, congestion may impede sinus drain- Lewis and colleagues' reported a systemic therapy with analgesics, an- age and predispose to sinusitis. Si- "rubbery" nasal mucosa on palp- tihistamines, decongestants and cor- milarly, congestion about the eu- ation. ticosteroids has been used.2',`-' 2547 stachian orifices may lead to retrac- The goals in the treatment of Such therapy is not appropriate at tion of the tympanic membranes rhinitis medicamentosa are two- present. and its consequences.3 It is sus- fold: curtailment of the drug ther- Essential to success in the use pected that the epithelial "denuda- apy to allow the nasal epithelium to of any of the protocols mentioned tion" associated with the prolonged return to normal, and treatment of is the patient's total understanding use of certain vasoconstrictors man- the underlying disorder that led to of his or her condition. The cause ifests itself in atrophic rhinitis."16 the original use of nasal vasocon- and effects of the condition must Another possible complication is strictors. be explained, and the patient the exacerbation of hypertension in Probably the simplest and least should be told that after an initial susceptible individuals.' Patients comfortable method for the patient 4 to 7 days of extreme discomfort receiving /3-blockers may be more is complete withdrawal of nasal the nasal obstruction will progres- prone to this complication.'4 medication. As complete bilateral sively subside. cessation of the use of vasocon- Recently Baldwin"6 compared Diagnosis and management strictive agents promptly results in treatment regimens in three groups: of rhinitis medicamentosa rebound congestion and total nasal one using corticosteroids topically, obstruction, Baldwin" suggested another using decongestant-antihis- Rhinitis medicamentosa should discontinuance in only one nostril tamine combinations systemically, be considered in the differential initially. The patient is permitted and the third ceasing the use of a diagnosis of nasal obstruction. The to spray as often as desired in nasal spray as previously described. diagnosis becomes more apparent the other nostril, but once the re- He claimed success in all three when anatomic, allergic and infec- bound phenomenon subsides (in groups: all the patients were able tious causes have been excluded. approximately 1 to 2 weeks) total to discontinue the use of vaso- History-taking is of the utmost im- withdrawal is advocated. A varia- constrictive agents within 2 weeks portance; the patient must be tion of this technique is placement and did not use the drugs during thoroughly questioned concerning of a nasal pack in the resting nos- 6 months of follow-up. the type and concentration of nasal tril to ensure that no nasal spray medication used, and the frequency will be introduced into that cham- Conclusion and duration of use. ber. We have described a common The physical signs of rhinitis Another method described by clinical problem that confronts the medicamentosa tend to vary with May and West' is the patient's use general physician and the otolaryn- the duration of vasoconstrictor use of a saline nasal spray in lieu of gologist. The diagnosis of rhinitis and the underlying condition that the vasoconstrictor. They main- medicamentosa should be consid- led to the initiation of therapy. tained that this has the dual func- ered in all patients presenting with Baldwin16 reported that the nasal tion of moisturizing the nasal mu- a stuffy nose. mucosa is typically hyperemic, con- cosa and providing a psychologic gested and granular, with areas of boost to those in need of a sub- References increased tissue friability and punc- stitute medication. tate bleeding; the mucus is clear A recent technique, described by 1. MAY M, WEST JW: The "stuffy" and often scanty unless there is Baldwin16 and by Saunders and nose. Otolaryngol Clin North Am an 6: 655, i973 associated sinus infection. "In one Gardier,'6 is the intranasal applica- 2. LAKE CF: Rhinitis medicamentosa. patient", Baldwin wrote, "who had tion of dexamethasone with de- Proc Staff Meet Mayo C/in 21: 367, used nasal sprays daily for over creasing frequency over a period 1946 CMA JOURNAL/APRIL 19, 1980/VOL. 122 $83 3. KULLY BM: The use and abuse of 11. RYAN RE: Vasomotor rhinitis med- 20. MEYERS SH, JAWETZ E, GOLDFIEN nasal vasoconstrictor medications. icamentosa viewed histologically. A: Review of Medical Pharmacol- JAMA 127: 307, 1945 Proc Staff Meet Mayo Clin 22: 113, ogy, 5th ed, Lange, Los Altos, Calif, 4. OLIVER G, SCHAFER EA: The phy- 1947 1976, pp 78-91 siological action of extracts of the 12. FABRICANT ND: The overmedicated 21. INNES IA, NICKERSON M: Sympa- suprarenal capsules. J Physiol (Lond) nasal cavity. Am J Med Sci 217: thomimetic drugs, in The Pharmaco- 462, 1949 logical Basis of Therapeutics, 3rd ed, 18: 230, 1895 GOODMAN LS, GILMAN A (eds), 5. STOLZ F: Ueber Adrenalin und 13. STRIDE RO: Nasal decongestant Macmillan, New York, 1965, p 477 Alkylaminoacetobenzcatechin. Ber therapy. Br J Clin Pract 21: 541, 22. LEWIs RS, MAWSON SR, EDWARDS Dtsch Chem Ges 37: 4149, 1904 1967 WG, et al: Essentials of Otolaryn- 6. DAKIN HO: On the physiological 14. BLUE JA: Rhinitis medicamentosa. gology, Heinemann, London, 1967, activity of substances indirectly re- Ann Allergy 26: 425, 1968 p 213 lated to adrenalin. Proc R Soc Lond 15. Idem: Overmedication of the nasal 23. WILENSKY JT, WOODWARD HJ: [Biol] 76: 493, 1905 mucosa. Mod Med 37: 90, 1969 Acute systemic hypertension after 7. BARGER G, DALE HH: Chemical 16. BALDWIN RL: Rhinitis medicamen- conjunctival instillation of phenyl- structure and sympathomimetic ac- tosa (an approach to treatment). J ephrine hydrochloride. Am J Oph- 41: Med Assoc State Ala 47: 33, 1977 thalmol 76: 156, 1973 tion of amines. J Physiol (Lond) 24. CASS E, KADAR D, STEIN HA: Ha- 19, 1910 17. Bo[Es LR: Fundamentals of Oto- zards of phenylephrine topical med- 8. Fox N: The chronic effect of epi- laryngology - A Textbook of Ear, ication in persons taking propra- nephrine and ephedrine on the nasal Nose and Throat Diseases, 5th ed, nolol. Can Med Assoc J 120: 1261, mucosa. A rch Otolaryngol 13: 73, Saunders, Philadelphia, 1978, pp 1979 1931 354-56 25. WALKER JS: Rhinitis medicamen- 9. LIERLE DM, MOORE PA: Effects of 18. FABRICANT ND: Modern Medication tosa. J Allergy 23: 183, 1952 drugs on ciliary activity of mucosa of the Ear, Nose and Throat, Grune, 26. SAUNDERS WH, GARDIER RW: Phar- of the upper respiratory tract. Arch New York, 1951, pp 112-15 macotherapy in Otolaryngology, Otolaryngol 19: 55, 1934 19. PROCTOR DF: Physiology of the Mosby, St Louis, 1976, pp 51-52 10. WALSH TE, CANNON PR: The prob- upper airway, in Handbook of Phy- 27. ENGLISH GM: Otolaryngology, a lem of intranasal medication. Ann siology, 43rd ed, McDowALL RJS Textbook, Har-Row, Scranton, Pa, Otol Rhinol Laryngol 47: 579, 1938 (ed), Lippincott, Philadelphia, 1964 1976, p 287 L'hyperglycemie et les complications du diabRte de type adulte

MARIE-DOMINIQUE BEAULIEU, MD, CCFP

Dans cot article on analyse les principaux travaux ayant 6tudie les effets En 1970 le University Group Dia- de l'hyperglyc6mie et de son traitement sur les complications associ6es au betes Program publiait les resultats diabete de type adulte. Doux constatations s'imposent. D'abord, il ny a pas d'une experience clinique portant encore de consensus sur les valours diagnostiques de la glyc6mie; quelques uniquement sur le diabete de type diab6tologues recommandent un retour A Ia glycimie a jeun. Ensulte, mettaient en un rapport de causalite pr6cis entre l'hyperglyc6mie (et son contrBle) et adulte.1'2 Ces r6sultats les principales complications du diabete n'a pas et6 6tabli. doute l'importance de l'hyperglyce- Tant que l'histoire naturelle du diabete de type adult. et l'efficacit6 mie dans la pathog6nese des com- du traltement sur le pronostic A long terme no seront pas mieux compris, ii plications associees au diabite et no saurait y avoir de place pour le d6pistage systematique du diabete chez 1'efficacite du traitement. Cette etu- les adultes asymptomatiques. Aussi, les individus pr6sentant de l6gires de a souleve une polemique qui anomalies de la glycemie devraient Otre suivis annuellement afin de surveiller dure encore, et le medecin de fa- l'apparition d'un diabete clinique ou de tout autre facteur de risque de mille reste souvent indecis quant a maladie cardlovasculaire. Ils ne devraient etre ni 6tiquetes comme diab6tiques la conduite a prendre devant un ni soumis a un traitement strict. individu presentant un diabete de type adulte modere. La question In this paper the principal investigations into the effects of glycemia and fondamentale reste la meme: dans Its treatment on the complications associated with maturity-onset diabetes mesure l'hyperglycemie est- are analysed. Two points are stressed. First, a consensus is lacking on quelle the diagnostic levels of blood glucose; some diabetologists recommend a elle responsable des complications return to the use of fasting blood glucose values. Second, a definite causal Du Centre Kellogg pour etudes relation between hyperglycemia (and its control) and the main complications superieures en soins de premiere ligne, of diabetes has not been established. hopital Montreal General, Montreal effectiveness of Until the natural history of the condition and the Les demandes de tires a part doivent hypoglycemic treatment on the long-term prognosis are better understood, etre adressees au Dr Marie-Dominique systematic screening for maturity-onset diabetes in asymptomatic adults is Beaulieu, Centre Kellogg pour etudes not justified. In addition, patients with mildly abnormal blood glucose superieures en soins de premiere levels should be followed yearly to monitor the development of overt diabetes ligne, Hopital Montreal General, or other cardiovascular risk factors. They should be neither labelled as 1650, ave Cedar, Montreal, PQ diabetics nor compelled to comply with a strict therapeutic regimen. H3G 1A4 884 CMA JOURNAL/APRIL 19, 1980/VOL. 122