Non Allergic Rhinitis

Non Allergic Rhinitis by Dr Marjan

1. NON ALLERGIC RHINITIS DR MARJAN

2. The term ‘Non allergic rhinitis' is commonly applied to a variety of rhinitis related problems that cause intermittent rhiorrhoea, nasal congestion, and nasal obstruction unrelated to allergy. Nasal itching and sneezing lesser. Eye symptoms not prominant. 2 or more symptoms(including hypersecretion, post nasal drip) persists >9 months/year Occur more frequently in adults, increases with increase in age, more in females More likely to be perennial than seasonal.

3. PREVALENCE incidence: among in allergy clinic patients 28%-60% have NAR

4. AETIOLOGY  Neurovascular disorder  No specific antibodies  Nonspecific reflex hypersensitivity  Caused by various influences  Change of temperature or humidity  Alcohol , dust, smoke, mechanical irritation, stress, anxiety neurosis, endocrine disorders, rhinitis of pregnancy.  Certain precipitants such as perfume or strong odors are frequently identified  Drugs: (e.g., antihypertensive agents as reserpine or betablockers , oral contraceptives)  Drug abuse: ( imidazoline & catechol derivatives,

5. pathophysiology Nasal functiona and innervation Temp regulation, Olfaction, filteration, humidification of inspired air Nasal lining--> Ig A, protein, enzy for lubrication & protection Secretions trap the particulate matter and propels it towards natural ostia Frequency of 10-15 beats/min

6. Innervation Regulation of mucosal vasculature & glandular secretion- ANS Sympathetic --> NE & neuropeptide Y--> VC nasal musculature (decongestion) Parasympathetic-->ACh, NE & VIP--> increases nasal gland secretion Nasal sensation: 5th CN Afferent ethmoidal nerve--> sensory innervation to epithelium, vessels and glands C fibres(unspecialised afferent sensory fibres) react to pain & temp changes & osmalarity- most imp in NAR

7. C fibres Stimulated by inflammatory mediators(histamine, bradykinin)--> involved in centrally mediated reflexes. Stimulated by irritants: nicotine, smoke, formaldehyde & capsaicin stimulated--> C fibres depolarise --> --> release neuropeptides(substance P, calcitonin gene- related peptide) --> increases vascular permeability & submucosal gland release --> acute stimulation of glandular/endothelial & epitheial cells --> Sensation of itching, rhinorrhea & burning

8. Hyperresponsive afferant arc--> exaggerated efferent arc (parasympathetic-->excessive nasal secretin and nasal congestion, if sympathetic is decresed -->nasal congestion Problem can be intrinic epithelia or CNS regulation quite complex ,numerous factors intricate innervation by sensory, paraympathetic & sympathetic nerves other factors like inflammatoy cascades & multitudes of cellular and protein reactions

9. NON ALLERGIC PERENNIAL RHINITIS TYPES: 1.Vasomotor rhinitis / idiopathic rhinitis/ NANIPER 2 . Non allergic occupational rhinitis 3. Hormonal rhinitis 4.Drug induced rhinitis 5.NARES 6.Rhinitis due to physical and chemical factors 7.Food induced 8. Emotion induced 9. NAR due to atomic obstruction/Atrophic rhinitis/ systemic disorder/ CSF fluid rhinorrhea

10. CLASSIFICATION OF RHNITIS

11. R A Settipane , et al., Update on nonallergic rhinitis, Ann Allergy Asthma Immunol 2001;86:494–508.

12. Vasomotor Rhinitis(IDIOPATHIC RHINITIS)(VMR) Definition – “Heterogeneous group of patients with chronic nasal symptoms that are not immunologic or infectious in origin and are usually not associated with nasal eosinophilia” Dx by exclusion classified as either ‘runners’ (those with predominantly rhinorrhoea) or ‘blockers’ (those with predominantly nasal congestion and blockage), No specific cause found M/c form of NAR. at least 2/3 of all nonallergic rhinitis suffers Symptoms : rhinorrhoea , sneezing, nasal obstruction

13. PATHOPHYSIOLOGY Autonomic imbalance – Parasympathetic dominance produce excessive rhinorrhea Some show more generalized autonomic dysfunction including both the sympathetic and parasympathetic nervous systems Triggered mainly by irritants & change in atmospheric cnditions.

14. SYMPTOMS Variable Mainly – Nasal obstruction – Increased secretion Sneezing and pruritus and conjunctival symptoms are less common

15. Investigation for VMR Negative responses on skin or blood tests for specific IgE Nasal tissue cytologic analysis will not demonstrate eosinophils or other inflammatory cells

16. TREATMENT conservative treatment  Elimination of irritant factors  Antihistamines  Nasal decongestant drops  Oral decongestant drugs  Steroids sprays (e.g., beclomethasone )

17. Surgical Treatment In recalcitrant cases In 1961 GOLDIN- WOOD - transantral vidian neurectomy( Parasympathetic nasal fibers divisions ) Complications: places internal max A, max N, Sup alveolar N in risk Transpalatal-oronasal & orosinual fistula Transethmoidal - bleeding from ethmoidal artery & vision problems Endoscopic transnasal approach

18. Ocupational rhinitis Occupational rhinitis defined as rhinitis caused by exposure to airborne agents present in the work place. Prevalence 5-15% Along with typical symptoms of NAR, will have impaired sense of smell,nosebleeds, crusting, reduced mucociliary clearance, also have hyperreactivity Baraniuk & kaliner - different chemical exposures as-- immunologic, annoyant, irritational & corrosive Immunologic (HMW agents with biologic source) annoyants- seen in pts with heightened olfactory awareness Irritational- when exposure is beyond threshold level. Corrosive(LMW compounds cause non- immunological inflammation),

19. chart

20. pathophysiology  Nose is the portal of entry & materials impact on the mucous surface as a function of aerodynamic equivalent diameter(AED).  Approx 80% of those that have an AED of more than 9 micrometre , 50% of those with 2-9 micrometre AED & 40 % of material wth less than 2 micrometre stick to the nasal wall.

21. Possible that damage and/or stimulation of the epithelial cells and neurons by the irritants may lead to proinflammatory mediators and neuromediators, which may predispose the nasal mucosa to inflammation and infection, subsequently resulting in the symptoms of rhinitis Mainly by neurogenic mechanism : C fibres--> neuropeptide Y--> VD& edema & inflammation Will have associated bronchial and ophthalmic manifestations

22. episodic work related symptoms of rhinitis which usually manifest on weekdays & abate during weekends & holidays. Risk factors for developing occupational rhinitis are: o Exposure{intensity & duration} o Atopy o Smoking

23.  Occupational rhinitis frequently coexists with asthma & conjuctivitis .  Prevention is the best approach . Antihistamines(2nd generation), sodium cromoglycate, topical steroids, antihistamine nasal spray & saline douches are used. (trial & error) Treatment most effective in allergic occupational rhinitis IMMUNOTHERAPY- purified rhodent proteins, wheat flour extracts & natural rubber latex.

24. Exercise-induced rhinitis Due to autonomic dysfunction Clinical findings – Most common: Clear, watery rhinorrhea – Acute nasal congestion – Itching – Sneezing • Up to 20% of elite runners and swimmers experience symptoms during routine workouts Azelastie nasal apray is effective

25. Hormonal rhinitis Often associated with pregnancy (rhinitis of pregnancy) Also seen in puberty post menopausal

26. Rhinitis of pregnancy • Incidence: 20% to 30% of pregnant women • Definition: – New-onset nasal symptoms (usually congestion and/or rhinorrhea) – Absence of other known cause – Lasts >/= 6 weeks – Better towards term – Resolves within 2 weeks after delivery More in pregnant smokers (69%) Neither asthma nor rhinitis are risk factors for pregnancy rhinitis.

27. Pathophysiology: Oestrogens cause vascular engorgement,in the nose--> leading to nasal obstruction and/or nasal hypersecretion. Beta-oestradiol and progesterone --> increase the expression of histamine H1 receptors on human nasal epithelial cells and mucosal microvascular endothelial cells& induce eosinophil migration and/or degranulation. Preexisting chronic rhinitis can worsen, improve , or remain unchanged during pregnancy

28. complications Uncontrolled rhinitis during pregnancy – Severe snoring – Increased risk of • Gestational hypertension • Preeclampsia • Intrauterine growth retardation

29. treatment Reassurance Saline douches Diphenhydramine in first trimester- cleft lip & palate. Chlopheriramine - cat B, can be used. Decongestants not advised- gastroshisis Topical & systemic streoids can be used but cautiously & with limitations Intranasal cromolyn( cat B)

30. Other hormonal rhinitis • Growth hormone – Acromegaly can contribute to rhinitis symptoms • Hypothyroidism – Evidence linking to rhinitis is limited and may merely represent the concomitant occurrence of two common disorders

31. FOOD-INDUCED RHINITIS Watery rhinorrhea – Mostly bilateral & Begins soon after beginning to eat Virtually all foods Underlying mechanisms are largely unknown. Hot and spicy foods , in particular, which contain capsaicin, lead to a watery rhinorrhoea termed ‘gustatory rhinitis’, probably as a result of the capsaicin stimulating the sensory nerves to release neuropeptides and tachykinins. Alcoholic beverages induce symptoms as a result of vasodilation.

32. Dyes and preservatives, as well as sulphites, appear to play a role in a very few cases, whereas some foods may contain clinically relevant concentrations of histamine or other biogenic amines. Some patient may acquire specific IgE to certain foods Consequently development of acute food-induced rhinitis Patients who experience recurrent nasal symptoms after eating virtually any food are rarely found to have an atopic etiology

33. AGE - RELATED RHINITIS • Important changes in nasal physiology in aging – Decrease in total body water content – Decrease in nasal blood flow – Degeneration of mucous glands – Collagen fibers in cartilage and elastic fibers in the dermis become progressively atrophic cause nasal block/ rhinorrhea

34. RHINITIS DUE TO PHYSICAL AND CHEMICAL FACTORS In individuals with sensitized nasal mucous membranes. Cold air-induced rhinitis Cold , dry air  S kier's nose Watery discharge (most prominent feature) Congestion Burning of the nasal mucosa Develop within minutes of exposure to cold air Stop soon after the end of exposure Common in areas with low outdoor relative humidity

35. Cod, dry air causes sensorineural stimulation--> increases tonicity & osmolarity of nasal secretions--> release inflammatory mediators, afferent arc stimulation, increased parasympthetic activity, increased epithelial shedding--> generation of rhinitis symptoms

36. EMOTIONALLY INDUCED RHINITIS Emotional factors such as stress and sexual arousal have been documented to affect the nose, as a result of autonomic stimulation.

37. Drug-induced rhinitis Aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, methyldopa, OCP, psychotropic agents and nasal topical decongestants induce symptoms of rhinitis when they are administered either topically or systemically. predictable ,(known side effects) or unpredictable, based on individual hypersensitiVity ,in particular aspirin

38. Intolerance to aspirin and/or NSAIDs --> predominantly rhinorrhoea (isolated or part of a complex involving hyperplastic rhinosinusitis, nasal polyps and asthma) Intolerance to ACE I , methyldopa or OCP --> predominantly to nasal block. Persistent overuse of the topical nasal vasoconstrictor s --> leads to nasal decongestion by a mechanism involving a rebound effect following withdrawal of these drugs, excessive use of these agents may also lead to nasal hyper-reactivity and hypertrophy of the nasal mucosa, a condition known as ‘ Rhinitis medicamentosa’ .

39. Other drugs -- Mechanism? – Induce changes in nasal function by causing inflammation , through neurogenic effects – Unknown mechanisms • Evidence is anecdotal and not supported by investigation Apart from rhinitis medicamentosa , drug-induced rhinitis may be further classified into: – Local inflammatory type – Neurogenic type – Idiopathic (unknown) type In these mechanism, nasal mucous membrane is often normal (different from rhinitis medicamentosa )

40. Local inflammatory type Main drugs: Aspirin and NSAIDs – Including ASA exacerbated asthma (AEA) “ Triad” of nasal polyposis, asthma and aspirin or other NSAIDs sensitivity Principle mechanism : Inhibition of cyclooxygenase-1 (COX-1)

41. Neurogenic type Sympathetic Parasympathetic Sensory fibres

42. SYMPATHETIC - Adrenergic sympathetic neuron fibres contain Norepinephrine & Neuropeptide-Y (NPY)

43. PATHOPHYSIOLOGY

44. Idiopathic type

45. NARES- Mullarkey and colleagues : characterized the condition on the basis of a presence of > 20% eosinophils in nasal smears of symptomatic patients with perennial symptoms of episodes profuse watery rhinorrhoea, nasal pruritis, incomplete nasal obstruction,,epiphora,sneezing and occasional loss of smell. There is lack of evidence of allergy, as indicated by negative SPT &/or absence of serum IgE antibodies to specific allergens.

46. Triad of nasal polyposis , intrinsic asthma, intolerance to aspirin - sampter’s triad. NARES may be an early expression of the triad In 1/3rdcases it is isolated. 50% of NARES patients without a history of respiratory symptoms, bronchial responsiveness is associated with an increase in the number of sputum eosinophils NARES is a variant of vasomotor rhinitis, and referred to the condition as ‘perennial intrinsic rhinitis’.

47. • Mostly found in middle-aged patients • Extremely infrequently in childhood • <2% of children with nasal eosinophilia • Prevalence general population: Unknown Prevalence -- 13 and 33% in patients with non-allergic rhinitis( About 1/3 of cases of nonallergic rhinitis ) PREVALENCE

48. Pathophysiology • Not clearly understood • Eosinophilia may contribute to nasal mucosal dysfunction • May be due to release of toxic substances contained in eosinophil granules – Major basic protein – Eosinophil cationic protein Result: May damage nasal ciliated epithelium and prolong mucociliary clearance

49. SYMPTOMS Usually more intense nasal symptoms than vasomotor or allergic rhinitis Perennial nasal symptoms and signs Congestion Clear discharge being most prominent Sneezing Pruritus Anosmia

50. Investigation Nasal smears: – If 10% of cells are Eo = Elevated Eo – In NARES, usually large numbers of Eo ( 5–20%) found – No systemic allergy as assessed by allergy skin or blood testing

51. Nasal smears • Both nostrils should be sampled • Samples collection – Blowing mucus into transparent wrap – Cytology brush – Probe – Ultrasonic nebulization of hypertonic saline --Nasal lavge • Transfer samples to slides, fixed, and then treated with Hansel stain • Nasal biopsy is more accurate

52. diagnosis & treatment Nasal eosinophilia in patients with nonallergic rhinitis Generally regarded as a good prognostic indicator for response to treatment with topical steroid therapy If eosinophilic infiltration is massive (e.g., in aspirin sensitivity syndrome ) - Use of oral glucocorticoid may be required to control symptoms

53. Other rhinitis with high nasal Eo BENARS = blood eosinophilia nonallergic rhinitis syndrome – A subtype of NARES – Associated with elevated blood eosinophils Phaeohyphomycosis of maxillo -ethmoid sinus( mycotic infxn) Churg -Strauss syndrome(EGPA)- marked blood vessel inflammation

54. RHINITIS WITH OTHER CELL INFILTRATION

55. Nasal mastocytosis • = Basophilic/metachromatic nasal disease • A histologic diagnosis • Unknown etiology • Hallmark: Mast cell infiltration (frequently > 2,000/mm3) without nasal eosinophilia • Nasal symptoms: – More likely to be secretion/rhinorrhea and congestion/blockage – Without significant sneezing/pruritus

56. O/E : Pale nasal mucosa • This condition are not predisposed to develop aspirin sensitivity, nasal polyps, asthma , or sinusitis . • Treatment : Inflammatory condition – Topical anti-inflammatories – Intranasal cromolyn – Intranasal/oral corticosteroids

57. DIFFERENTIAL DIAGNOSIS Allergic rhinitis ( excluded by appropriate allergy tests) Polyps & sinusitis Congenital and acquired anatomical abnormalities (e.g. nasal septal deviation, adenoid hypertrophy, hypertrophy of nasal turbinates, choanal atresia): Rhinorrhoea, post-nasal drip and nasal blockage Benign and malignant tumours, , granulomas Ciliary defects and cerebrospinal rhinorrhoea. Tumours can lead to unilateral nasal obstruction, bleeding and pain. Rhinorrhoea and nasal congestion, in the absence of pruritis, are also characteristic features of nasal mastocytosis, an extremely rare condition, in which eosinophils are absent and tests for IgE-mediated disease are negative.

58. local causes

59. systemic causes

60. Diagnosis as a step-wise approach Thorough case history, step-wise exclusion of possible differential diagnoses, as follows. If the case history is suggestive of clinically relevant non-infectious rhinitis: check possible stimuli, severity and duration of disease; check drug use (systemic and topical), exposure at work place, hormonal status (pregnancy, hypothyroidism, acromegaly) and involvement of other organs (asthma, hormonal status);

61. Brandt & Bernstein

62. PHYSICAL EXAMINATION O/E- mucosa is boggy & edematous with clear mucoid secretions. Mucosal injection, lymphoid hyperplasia,- tonsils, adenoids,BOT Chemical exposure- areas of blanched mucosa sorrounding prominant vessels Atrophy of mucosa- seen in aging,prior surgery & drug abuse. Look for anatomic abnormalities & features of infection.

63. exclude other nasal disease (rigid nasal endoscopy); exclude allergy: skin prick test, serum IgE-antibodies or nasal provocation testing in selected cases; exclude chronic rhinosinusitis (nasoendoscopy +/− computed tomography (CT) scan); perform nasal cytology (eosinophilia), and if shown to be positive then perform oral Aspirin challenge. Acoustic rhinomanometry - to r/o Nasal valve collapse Validated sell testing Intranasal cold , dry air- as a reproducible diagnostic tool in VMR ( VAS, PIF)

64. THERAPY FOR NONALLERGIC PERENNIAL RHINITIS First, evaluate the severity , confirm the need for therapy. 1.Avoidance--> patient education (specific stimuli (drug- induced, food-induced or occupational rhinitis, chemicals? irritants induced rhinitis) first-line therapy 2.Limited exposure --> eg: occupational rhinitis::use masks/rotective coverings) 3. Vigorous exercise --> decrease nasal congestion by stimulating adrenergic receptors

65. Topical steroids and antihistamines are the two main classes of drugs ( Fluticasone Propionate, Budesonide, Beclomethasone and Azelastine, respectively, have been approved by the Food and Drug Administration (FDA) Azelastine nasal spray --> control of rhinorrhoea, post-nasal drip, sneezing and nasal congestion. Topical nasal steroids -->y used for treatment of more severe symptoms, (more useful in patients with inflammatory pathogenesis is a prominent, eg NARES. Recent evidence suggests that in patients who do not respond to treatment with nasal steroids, treatment with non-conventional therapies such as silver nitrate, botulin toxin and particularly intra-nasal capsaicin may be beneficial

66. Topical nasal corticosteroids Different preparations are available How to use::point the nozzle upwrds and away from the septum Fluticasone propionate &beclomethasone--> FDA Budesonide--> pregnancy, cat B

67. Acts on nasal mucosa--> decreased neutrophl and eosinophil cemotaxis & basophil mediators release. Also decrease mucosal edema and inflammation DECONGESTANTS - topical or systemic --> to decrease mucosal edema, so used initially for increased penetration of nasal spray. NORMAL SALINE -- incresed mucociliary clearance , rinsing increases efficacy of steroids ADE- infrequent. m/c :septal irritation,nasal dryness & crusts, epistaxis,throat dryness and headache. Only 20 % is absorbed 80% swallowed( eliminated by first pass metabolism)

68. ANTIHISTAMINES Oral- limited use, except in sneezing or itching . Can be used orally/ parenterally/ topically. 1st generation- most potent,most effective central/motor/cognitive impairment(anxiety, dizziness, tremor,insomnia,nausea, euphoria)S/E ( as it is lipophilic/ crosses BBB) & anticholinergic S/E- so effective in rhinorrhea Chlorpheniramine , Diphenhydramine, Clemstine

69. 2nd generation- desloratidine, loraidine,cetrizine, levocetrizine, fexofenadine AZELASTINE( topical antihistamine)H1 receptor antagonist- AR P revent synthesis of leukotrienes, kinins, cytokines & prevent expression of intercelluar dhesion molecules & prevents generation of SO free radicals -NAR NARES & VMR Funtl MRI- decreased bood flow to olfactory and sensory processing areas of brain, thus rduces its response to odorants Very useful in presence of mixed rhinitis OLAPATIDINE n/s(0.6%) - FDA approved for pts >12 years of age

70. ANTICHOLINERGIC ORAL - Decreases rhinorrhea- S/E - blurred vision,drying of eyes & mouth, thickened secretion Intra-nasal anticholinergics (Ipratropium Bromide)- selectively inhiits nasal secretion- useful in patients with nasal secretion as the predominant symptom. S/E- epitaxis and dryness- rare, incidence decrease with prolonged use. 0.03%-AR & NAR 0.06%- a/c viral rhinitis In children as yoing as 6 years & in pregnancy (cat B) Initially 2sprays 2-3 times/day, symptom improvement within 1 week, tapered to one spray/twice daily(lowest dose)

71. Nasal decongestants should be avoided or limited to 10 days Intra-nasal capsaicin --> significant and long-term effect in NANIPER Once daily for 5 weeks with intranasal capsaicin --> significantly improve all symptoms throughout a 6-month follow-up in patients suffering from severe chronic non-allergic rhinitis with nasal vasoconstrictor abuse In cases where nasal obstruction is resistant to medical treatment and if the inferior turbinate is hyperplastic, surgical intervention to reduce the size of the turbinate Endoscopic transnasal vidian neurectomies have also been performed by excision, diathermy and cryotherapy.

72. sURGERY In recalcitran cases Correction of anatomical deformity (nasal poly, spur,DNS, HIT) Tissue conservation & mucosal sparing are used whenever possible to maintain normal physiology & prevent atrophic rhinitis

73. COMPLICATION Chronic rhinitis--> sinusitis nasl polyps ETD laryngel dysfunction COM hearing loss Sleep disorderd breathing disorders of smell, malaise, and fatigue

74. THANK YOU