Non-allergic rhinitis
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Non allergic rhinitis

Non allergic rhinitis

Presented by Wat Mitthamsiri, MD.

December27, 2013

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  • This topic will not cover occupational rhinitis, nasal polyps, infectious rhinitis, sinusitis, anatomical abnormality and systemic diseases <br />
  • classification of chronic rhinitis is complex, and no mutually agreed-upon scheme has been established <br />
  • classification of chronic rhinitis is complex, and no mutually agreed-upon scheme has been established <br />
  • classification of chronic rhinitis is complex, and no mutually agreed-upon scheme has been established <br />
  • classification of chronic rhinitis is complex, and no mutually agreed-upon scheme has been established <br />
  • classification of chronic rhinitis is complex, and no mutually agreed-upon scheme has been established <br />
  • - Subject recruitment in these studies is likely to have been biased toward allergy <br /> - Of the five epidemiological studies of nonallergic rhinitis, the two most significant, because of their size, are the NRCTF (National Rhinitis Classification Task Force) and the ECRHS (European Community Respiratory Health Survey) <br /> - From biggest 2 studies, ratio of allergic rhinitis prevalence (both pure and mixed) to nonallergic rhinitis prevalence is 3:1 <br />
  • Mucosal appearance may not distinguish between allergic and nonallergic rhinitis, <br />
  • Specific physiologic states, eg sexual arousal and emotional upset <br />
  • Specific physiologic states, eg sexual arousal and emotional upset <br />
  • -Sensory stimulation via the histamine H1 receptor and the bradykinin B2 receptor leading to the release of the tachykinins: substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin A (NKA) <br /> -Regulation of sympathetic ganglionic neurotransmission by the tachykinins and the central stimulation of efferent pathways <br /> -Histamine, via the H3 receptor, may also modify ganglionic sympathetic neurotransmission <br /> -Sympathetic nervous supply within the nose promotes venous sinusoidal constriction by limiting blood flow, via the release of noradrenaline and neuropeptide Y (NPY) <br /> -Inhibition of ganglionic neurotransmission would lead to nasal vascular engorgement and nasal obstruction <br /> -Efferent pathways involving the parasympathetic nervous supply influence primarily glandular secretion, through the release of acetylcholine (Ach) and to a much lesser extent vasoactive intestinal polypeptide (VIP). The release of these mediators and the neural generation of nitric oxide (NO) will also influence vascular tone, leading to vasodilatation <br /> -Local generation of histamine, kinins, prostaglandin (PG) D2 and leukotrienes (LT) C4 and D4, acting through their specific receptors will also lead to nasal vascular engorgement and nasal obstruction <br />
  • -Nasal blockage was the predominant symptom in VMR, whereas AR were more likely to suffer from eye irritation, some sneezing, and rhinorrhea <br /> -Rhinorrhea or congestion, could not differentiate this disorder from perennial AR <br />
  • Nasal smears for eosinophils are usually considered elevated when 10% of cells are eosinophils <br />
  • -Findings from 1 nostril are not reliably representative of the total cell distribution in both nostrils <br /> -Blowing mucus into transparent wrap contain less cellular material, but are adequate for detecting eosinophils and neutrophils <br /> -Hansel stain highlights eosinophil granular contents <br />
  • Phaeohyphomycosis is a heterogeneous group of mycotic infections[1] caused by dematiaceous fungi <br />
  • Divided into Primary and Secondary atrophic rhinitis <br />
  • -Areas with prolonged warm seasons e.g., India, Saudi Arabia <br />
  • -Chronic bacterial infection mentioned: Klebsiella ozaenae, Coccobacillus foetidus ozaena, Pseudomonas aeruginosa, and Proteus spp <br />
  • -Granulomatous diseases (e.g., leprosy, sarcoidosis, Wegener granulomatosis, syphilis, TB) <br />
  • -Inhibition of COX-1 shifts the metabolism of arachidonic acid to the lipooxygenase pathway, resulting in a decrease in available PGE2 <br /> -The decrease in PGE2 results in an increase in cysteinyl leukotriene production by the lipooxygenase pathway involving the enzyme 5-lipooxygenase (5-LO). <br /> -Leukotrienes C4, D4 and E4 (LTC4, D4, E4) are all products of this pathway and are collectively known as cysteinyl leukotrienes, however <br /> -LTC4 that is thought to be the chief cysteinyl leukotriene responsible in the pathogenesisof AEA <br />
  • -Inhibition of COX-1 shifts the metabolism of arachidonic acid to the lipooxygenase pathway, resulting in a decrease in available PGE2 <br /> -The decrease in PGE2 results in an increase in cysteinyl leukotriene production by the lipooxygenase pathway involving the enzyme 5-lipooxygenase (5-LO). <br /> -Leukotrienes C4, D4 and E4 (LTC4, D4, E4) are all products of this pathway and are collectively known as cysteinyl leukotrienes, however <br /> -LTC4 that is thought to be the chief cysteinyl leukotriene responsible in the pathogenesisof AEA <br />
  • -LTC4 synthase is the enzyme responsible for the production of LTC4 <br /> -Allele of the LTC4 synthase gene (allele C) has been identified in individuals with aspirin sensitivity with much higher expression than normal person <br />
  • Sympathetic, parasympathetic and sensory fibres innervate the airways <br /> Those nerves concentrated in Nasal blood vessels, Mucosa, Lesser extent: secretory glands <br />
  • NPY: independently modulate postganglionic cholinergic responses by acting directly on NPY-2 receptors in the nasal mucosa <br />
  • Blunting of the effects of norepinephrine and NPY primarily causing nasal congestion and rhinorrhea <br />
  • -Sensory stimulation via the histamine H1 receptor and the bradykinin B2 receptor leading to the release of the tachykinins: substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin A (NKA) <br /> -Regulation of sympathetic ganglionic neurotransmission by the tachykinins and the central stimulation of efferent pathways <br /> -Histamine, via the H3 receptor, may also modify ganglionic sympathetic neurotransmission <br /> -Sympathetic nervous supply within the nose promotes venous sinusoidal constriction by limiting blood flow, via the release of noradrenaline and neuropeptide Y (NPY) <br /> -Inhibition of ganglionic neurotransmission would lead to nasal vascular engorgement and nasal obstruction <br /> -Efferent pathways involving the parasympathetic nervous supply influence primarily glandular secretion, through the release of acetylcholine (Ach) and to a much lesser extent vasoactive intestinal polypeptide (VIP). The release of these mediators and the neural generation of nitric oxide (NO) will also influence vascular tone, leading to vasodilatation <br /> -Local generation of histamine, kinins, prostaglandin (PG) D2 and leukotrienes (LT) C4 and D4, acting through their specific receptors will also lead to nasal vascular engorgement and nasal obstruction <br />
  • Pattern is similar to those in asthma, and one study found concordance between the course of asthma and that of rhinitis during pregnancy <br />
  • Pattern is similar to those in asthma, and one study found concordance between the course of asthma and that of rhinitis during pregnancy <br />
  • Concomitant use of ipratropium bromide and intranasal corticosteroid or antihistamines has an additive effect in controlling rhinorrhea <br />
  • Azelastine and olopatadine = intranasal antihistamines <br />
  • -Stimulants, such as medications used for management in attention-deficit/hyperactivity disorder <br />
  • -Stimulants, such as medications used for management in attention-deficit/hyperactivity disorder <br />
  • -Laser turbinectomy has been reported to result in preservation of normal nasal cytology and saccharin time <br /> -Saccharin test: place a 1-2 mm in size of particle of saccharin approximately 1 cm behind the anterior end of the inferior turbinate. In the presence of normal mucociliary action, the saccharin will be swept backwards to the nasopharynx and a sweet taste perceived within 1 hr. This test has high false positive and negative result <br />

Non-allergic rhinitis Non-allergic rhinitis Presentation Transcript

  • Nonallergic Rhinitis Wat Mitthamsiri, MD. Allergy and Clinical Immunology Unit, Department of Medicine King Chulalongkorn Memorial Hospital
  • Outline • Definition and classification • Epidemiology • Specific types of nonallergic rhinitis – – – – – – – – Vasomotor rhinitis NARES Rhinitis with other cell infiltration Atrophic rhinitis Medication-related rhinitis Hormonal rhinitis Aging-related rhinitis Rhinitis from other systemic diseases • Treatment
  • Definition • Nonallergic rhinitis • = Periodic or perennial symptoms of rhinitis that are not a result of IgEdependent events D .V. Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Classification DV Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Classification DV Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Classification J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Classification R A Settipane, et al., Update on nonallergic rhinitis, Ann Allergy Asthma Immunol 2001;86:494–508.
  • Classification R. J. Salib, et al., Mechanisms and mediators of nasal symptoms in non-allergic rhinitis, Clinical and Experimental Allergy, 2008; 38, 393–404
  • Classification R A Settipane, et al., Update on nonallergic rhinitis, Ann Allergy Asthma Immunol 2001;86:494–508.
  • Classification R A Settipane, et al., Update on nonallergic rhinitis, Ann Allergy Asthma Immunol 2001;86:494–508.
  • Epidemiology • Prevalence about 7% of U.S. population (About 22 million people) • Combination of both nonallergic and allergic rhinitis, “mixed rhinitis”: – 44–87% of patients with allergic rhinitis – More common than either pure allergic rhinitis or nonallergic rhinitis • Risk factors for nonallergic rhinitis: female sex and age of 40 years D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Epidemiology •Mixed rhinitis = the definite presence of allergic rhinitis in an individual who also experiences chronic rhinitis symptoms, which are not entirely explained by skin test reactivity R A Sittipane, Demographics and Epidemiology of Allergic and Nonallergic Rhinitis. Allergy and Asthma Proc 22:185–189, 2001
  • Epidemiology R A Sittipane, Demographics and Epidemiology of Allergic and Nonallergic Rhinitis. Allergy and Asthma Proc 22:185–189, 2001
  • Epidemiology • A report has observed that – 70% of patients diagnosed with nonallergic nasal disease developed their condition in adult life (age, >20 years) – 70% of patients diagnosed with allergic rhinitis developed their condition in childhood (age, <20 years) R A Sittipane, Demographics and Epidemiology of Allergic and Nonallergic Rhinitis. Allergy and Asthma Proc 22:185–189, 2001 D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Epidemiology R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • Epidemiology • Nonallergic rhinitis: more likely to experience perennial rather than seasonal symptoms • Frequencies of negative skin testing: – 50% in patients with perennial rhinitis – 32% in patients with combined perennial/seasonal rhinitis – 22% in patients with purely seasonal allergic rhinitis R A Sittipane, Demographics and Epidemiology of Allergic and Nonallergic Rhinitis. Allergy and Asthma Proc 22:185–189, 2001
  • Epidemiology: Subclassification • 61% • 33% • 16% • 12% • 4% • 2% Vasomotor rhinitis Nonallergic rhinitis with eosinophils syndrome (NARES) Sinusitis Elevated IgE Blood eosinophilia nonallergic rhinitis syndrome (BENARS) Hypothyroidism R A Sittipane, Demographics and Epidemiology of Allergic and Nonallergic Rhinitis. Allergy and Asthma Proc 22:185–189, 2001
  • Epidemiology: Thailand, adult • A questionnaire survey • Performed on 3,124 subjects living in Bangkok and its vicinity in 2000 • Cumulative prevalence of chronic rhinitis was 13.15% (95% CI =13.13-13.17) – N = 383 • Allergic rhinitis = 152 • Nonallergic rhinitis = 231 C Bunnag, et al., Epidemiology of rhinitis in Thais, Asia Pac J Allergy Immunol. 2000;18:1-7.
  • Epidemiology: Thailand, adult C Bunnag, et al., Epidemiology of rhinitis in Thais, Asia Pac J Allergy Immunol. 2000;18:1-7.
  • Epidemiology: Thailand, adult C Bunnag, et al., Epidemiology of rhinitis in Thais, Asia Pac J Allergy Immunol. 2000;18:1-7.
  • Epidemiology: Thailand, adult C Bunnag, et al., Epidemiology of rhinitis in Thais, Asia Pac J Allergy Immunol. 2000;18:1-7.
  • Epidemiology: Thailand, children • A retrospective, descriptive study • 302 children (ages </=14 years) with chronic rhinitis • Evaluated at the Siriraj Hospital in 2006 • Use of SPT to classified into 2 groups; AR and NAR • Medical records were reviewed P Vichyanond, et al., Clinical characteristics of children with non-allergic rhinitis vs with allergic rhinitis, Asian Pac J Allergy Immunol 2010;28:270-4
  • Epidemiology: Thailand P Vichyanond, et al., Clinical characteristics of children with non-allergic rhinitis vs with allergic rhinitis, Asian Pac J Allergy Immunol 2010;28:270-4
  • Epidemiology: Thailand P Vichyanond, et al., Clinical characteristics of children with non-allergic rhinitis vs with allergic rhinitis, Asian Pac J Allergy Immunol 2010;28:270-4
  • Epidemiology: Thailand P Vichyanond, et al., Clinical characteristics of children with non-allergic rhinitis vs with allergic rhinitis, Asian Pac J Allergy Immunol 2010;28:270-4
  • Epidemiology: Thailand P Vichyanond, et al., Clinical characteristics of children with non-allergic rhinitis vs with allergic rhinitis, Asian Pac J Allergy Immunol 2010;28:270-4
  • Epidemiology: Thailand P Vichyanond, et al., Clinical characteristics of children with non-allergic rhinitis vs with allergic rhinitis, Asian Pac J Allergy Immunol 2010;28:270-4
  • VASOMOTOR RHINITIS (IDIOPATHIC RHINITIS)
  • Definition and prevalence • 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” D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84. • Dx by exclusion R A Settipane, et al., Update on nonallergic rhinitis, Ann Allergy Asthma Immunol 2001;86:494–508. • Prevalence: At least 2/3 of all nonallergic rhinitis sufferers R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Etiology • Likely to result from many different etiologies – Cold air – Exercise – Pungent odors – Tobacco smoke – Alcohol – Specific physiologic states R A Sittipane, Demographics and Epidemiology of Allergic and Nonallergic Rhinitis. Allergy and Asthma Proc 22:185–189, 2001 J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Etiology • Likely to result from many different etiologies – Change in temperature, humidity, and barometric pressure – Certain precipitants such as perfume or strong odors are frequently identified – May occur in the absence of defined triggers R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Etiology R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Pathophysiology • Nasal mucosa often does not show any evidence of inflammation – No significant difference in number of mast cells to allergic patients • No hyperresponsiveness to histamine • But rather increased reactivity to cold dry air • Some reported hypersensitivity to metacholine, capsaicin R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001 J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Pathophysiology • Symptoms and hyperresponsiveness to cold dry air decrease after capsaicin Rx – Sensory neural dysregulation that capsaicinsensitive nerves may be important? J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. • May involve incipient, local atopy (entopy) • Dysfunction of nociceptive nerve sensor and ion channel proteins • Autonomic dysfunction R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Pathophysiology • Autonomic imbalance? – Parasympathetic dominance? • Theoretically can produce excessive rhinorrhea – A few studies found abnormal responses to autonomic tests • Some patients show increased parasympathetic activity • Some show more generalized autonomic dysfunction including both the sympathetic and parasympathetic nervous systems J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Pathophysiology R. J. Salib, et al., Mechanisms and mediators of nasal symptoms in non-allergic rhinitis, Clinical and Experimental Allergy, 2008; 38, 393–404
  • Symptoms • Variable • Mainly – Nasal obstruction (Most common) – Increased secretion (watery rhinorrhea) • Sneezing and pruritus and conjunctival symptoms are less common • Worsen acutely in response to nonspecific provocateurs (as already mentioned) R A Sittipane, Demographics and Epidemiology of Allergic and Nonallergic Rhinitis. Allergy and Asthma Proc 22:185–189, 2001 R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001 J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Symptoms • Patterns of symptom occurrence may be: – Perennial – Persistent – Intermittent – Seasonal R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Exercise-induced rhinitis • 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 J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Cold air-induced rhinitis • • • • Watery discharge 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 J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Gustatory rhinitis • Watery rhinorrhea – Mostly bilateral – Begins soon after beginning to eat • Virtually all foods have been reported to cause symptoms – Hot and spicy foods: most commonly – Beer and wine may produce nasal congestion by direct nasal vasodilation and may exacerbate most forms of rhinitis J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Gustatory rhinitis • Some patient may acquire specific IgE to select 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 J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Pathophysiology • Proposed mechanism: – Vagally mediated mechanisms – Nasal vasodilation – Food allergy – Other undefined mechanisms – Food allergy is a rare cause of rhinitis without associated GI, dermatologic, or systemic manifestations D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Investigation for VMR • Negative responses on skin or blood tests for specific IgE • May exhibit a small number of positive reactions that do not correlate with the clinical symptoms • Nasal tissue cytologic analysis will not demonstrate eosinophils or other inflammatory cells J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • NONALLERGIC RHINITIS WITH EOSINOPHILS SYNDROME (NARES)
  • Prevalence • • • • • About 1/3 of cases of nonallergic rhinitis Mostly found in middle-aged patients Extremely infrequently in childhood <2% of children with nasal eosinophilia Prevalence general population: Unknown D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Symptoms • Usually more intense nasal symptoms than vasomotor or allergic rhinitis • Symptoms – Perennial nasal symptoms and signs – Congestion – Clear discharge being most prominent – Sneezing – Pruritus – Anosmia D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84. J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • 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 R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • Pathophysiology Delayed mucociliary clearance Increased propensity toward infection Recurrent infections Predisposing nasal polyps development Nasal polyps Associated with nasal Eo Nasal Eo may be a precursor for nasal polyps or aspirin intolerance Nasal polyps + Aspirin reaction Aspirin reaction is not the etiology of the eosinophilic rhinosinusitis But mainly a marker of a severe form of NARES that is often associated with asthma, sinusitis, and nasal polyps. D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84. R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • Pathophysiology • 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 R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • Investigation • Nasal smears: – If 10% of cells are Eo = Elevated Eo – But in NARES, usually large numbers of Eo (5–20%) found – No systemic allergy as assessed by allergy skin or blood testing D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84. J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Nasal smears • Both nostrils should be sampled • Samples collection – Blowing mucus into transparent wrap – Cytology brush – Probe – Ultrasonic nebulization of hypertonic saline • Transfer samples to slides, fixed, and then treated with Hansel stain • Nasal biopsy is more accurate D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Investigation • Local allergic rhinitis? – IgE is present in the nasal mucosa but absent from other body tissues – Nasal allergen challenge results in clinical symptoms D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84. J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Investigation • In patients with Hx very suggestive of allergy – 4.7% • • • • Have negative prick tests But a positive nasal challenge And a positive nasal smear for Eo And may have nasal specific IgE – 6% • Have negative prick skin test and nasal challenge • But will have nasal eosinophilia D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • 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 • Churg-Strauss syndrome R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • RHINITIS WITH OTHER CELL INFILTRATION
  • 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 R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • Nasal mastocytosis • PE: 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 R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • ATROPHIC RHINITIS
  • Primary atrophic rhinitis • Epidemiology – Most prevalent: • Developing countries • In subtropical and temperate climate zones • With prolonged warm seasons – Typically afflicts middle-aged adults • More common in women – Not seen in children J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Primary atrophic rhinitis • Atrophy of glandular cells • No known specific cause – But many patients are found to have chronic bacterial infection of the nose and sinuses – Bacterial infection is thought to be primarily or secondarily involved • • • • Klebsiella ozaenae Staphylococcus aureus, Proteus mirabilis Escherichia coli D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84. J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Secondary atrophic rhinitis • • • • More prevalent in developed countries Less severe and less progressive Most commonly occurs in older patients Causes: – Multiple nasal sinus surgeries – Trauma – Irradiation – Granulomatous diseases J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Syptoms • • • • Crusting Purulent discharge Nasal obstruction Halitosis (foul odor or fetor emanating from the patient’s nose) • Recurrent epistaxis J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Empty nose syndrome • Usually follows aggressive resection of inferior +/- middle turbinates • Manifestation: – Symptoms of severe nasal obstruction – Inability to sense airflow through the nose – Profound sense of dyspnea – But • No objective findings of pulmonary disease • Complete patency of the nasal airways J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Signs of atrophic rhinitis • Nasal mucosa: – Ulceration – Covered by thick yellow/brown/green crusts – Possible evidence of bleeding • Nasal cavities: – May be enlarged – Bowing of the lateral nasal wall • Advanced cases: – Saddle nose deformity – Nasal septal perforation J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Signs of atrophic rhinitis Image from http://www.drtbalu.com/images/ar.jpg
  • MEDICATION-RELATED RHINITIS
  • Topical α-adrenergic decongestant • Nasal sprays – Oxymetazoline – Phenylephrine • Repetitive use – More than a few days • Rebound nasal congestion • Most likely due to downregulation of α-agonist receptors (tachyphylaxis) – Long-term use (several months) • Rhinitis medicamentosa J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Rhinitis medicamentosa • Causes – Topical decongestant drugs – Cocaine – Benzalkonium chloride in vasoconstrictor spray products • When used >30 days • May augment local pathologic effects. D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84. J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Rhinitis medicamentosa M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • Rhinitis medicamentosa • Manifestations: – Severe nasal congestion without other significant symptoms – Rarely, septal perforation – Cocaine causes significantly more crusting, bleeding, and septal perforation J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Rhinitis medicamentosa • Physical examination – Erythematous (beefy red), swollen, granular mucosa – Minimal discharge – Areas of punctate bleeding because of tissue friability J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Other drugs J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Other drugs • Mechanism? – Induce changes in nasal function by causing inflammation, through neurogenic effects – Unknown mechanisms • Evidence is anecdotal and not supported by rigorous investigation J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Other drugs • 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) M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • Local inflammatory type • Main drugs: ASA 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) M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • Local inflammatory type Image from http://journals.prous.com/journals/dot/19983411/html/dt340957/images/Bha2.gif M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • Local inflammatory type Image from http://journals.prous.com/journals/dot/19983411/html/dt340957/images/Bha2.gif M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • Local inflammatory type Image from http://journals.prous.com/journals/dot/19983411/html/dt340957/images/Bha2.gif M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • Neurogenic type Sympathetic Parasympathetic Sensory fibres M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • Neurogenic type Sympathetic Adrenergic sympathetic neuron fibres contain - Norepinephrine - Neuropeptide-Y (NPY) M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • Neurogenic type ▼Sympathetic ↓ -Down regulation of the sympathetic nervous system ↓ -Blunting effects of norepinephrine and NPY M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • Pathophysiology R. J. Salib, et al., Mechanisms and mediators of nasal symptoms in non-allergic rhinitis, Clinical and Experimental Allergy, 2008; 38, 393–404
  • Neurogenic type M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • Neurogenic type M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • Idiopathic type M. Varghese ,et al., Drug-induced rhinitis, Clinical & Experimental Allergy, 2010;40, 381–384
  • HORMONAL RHINITIS
  • Hormonal rhinitis • Most frequently encountered hormonal state associated with rhinitis: Pregnancy • Most common causes of nasal symptoms requiring treatment during pregnancy: – Rhinitis of pregnancy – Allergic rhinitis – Rhinitis medicamentosa – Sinusitis D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84. J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • 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 – Peaking in the last 6 weeks of pregnancy – Resolves within 2 weeks after delivery D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84. J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Rhinitis of pregnancy • Pathophysiology: unknown – Condition has been attributed to changes in estrogen or progesterone, or both – Little evidence has emerged to support this assertion • Preexisting chronic rhinitis can worsen, improve, or remain unchanged during pregnancy J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Possible pathophysiology • Massive expansion of blood volume – Increase in nasal vascular pooling • Progesterone-induced, vascular smooth muscle relaxation • Pregnancy-associated hormones may have a direct effect on the nasal mucosa – Increased nasal mucous gland hyperactivity – Increased nasal secretion/rhinorrhea • More bacterial rhinosinusitis R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • Rhinitis of pregnancy • Uncontrolled rhinitis during pregnancy – Severe snoring – Increased risk of • Gestational hypertension • Preeclampsia • Intrauterine growth retardation J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Other hormonal rhinitis • Little knownledge about relationship between the menstrual cycle or use of exogenous ovarian hormones (i.e., oral contraceptives, hormone replacement therapy) and rhinitis • One clinical trial showed that hormone replacement therapy had no effect on quality of life, nasal airway resistance, or nasal mucociliary clearance J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Other hormonal rhinitis • Growth hormone? – Acromegaly can contribute to rhinitis symptoms R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001 • Hypothyroidism? – Evidence linking to rhinitis is limited and may merely represent the concomitant occurrence of two common disorders J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • AGING-RELATED RHINITIS
  • Aging-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 • Retraction of the nasal columella • Downward rotation of the nasal tip J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Previously non-rhinitis person • Result… • Nasal mucosal dryness • Increased nasal airway resistance J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Established allergic rhinitis person • Aging causes: – Gradual diminution in clinical symptoms – Skin tests and in vitro tests for allergy decrease in magnitude • But quality of life related to allergic rhinitis remains significantly impaired in patients older than 65 years J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • RHINITIS FROM OTHER SYSTEMIC DISEASES
  • Diseases related to rhinitis • Granulomatous diseases – Granulomatosis with polyangiitis – Sarcoidosis – Midline granuloma – Wegener granulomatosis • Cystic fibrosis • Ciliary dyskinesia syndromes • Immunodeficiencies R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001 J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Diseases related to rhinitis • Autoimmune/vasculitis – Churg-Strauss syndrome – Systemic lupus erythematosus – Relapsing polychondritis – Sjogren syndrome • Rhinitis sicca R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • Diseases related to rhinitis R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • TREATMENT
  • Treatment of vasomotor rhinitis • Avoidance of factors that may be contributing – Cigarette smoke – Other environmental triggers R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013 • Pharmacologic Rx – Intranasal antihistamines: 1st line treatment – Intranasal corticosteroids: useful in treatment of some forms of nonallergic rhinitis D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Persistent rhinorrhea • Nasal irrigation with saline – May be very helpful any of the forms of nonallergic rhinitis – Extremely important in the management of nasal crusting, as seen in atrophic rhinitis – May have no effect on nasal congestion J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Intermittent watery rhinorrhea • May caused by – Irritant – Cold air exposure – Exercise – Food • Ipratroprium bromide used before symptoms occur can be very effective – Used with caution in patients with preexisting glaucoma or prostatic hypertrophy J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685. R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • Nasal congestion • Intranasal steroid or intranasal azelastine – 1st line pharmacologic Rx – Used on an intermittent or as-needed basis • Nasal cytology: helpful in guiding therapy – Eo predominance (i.e., NARES) → Prefer INS – Absence of Eo → Prefer azelastine • If either agent alone is not completely effective → Try adding the other drug J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Nasal congestion • Intranasal corticosteroids (INS) – In recommended doses: Generally not associated with clinically significant systemic side effects: (In both children and adults) • • • • Hypothalamic-pituitary-adrenal (HPA) axis Ocular pressure or cataract formation Bone density Growth suppression has been reported only with long-term use of beclomethasone dipropionate that exceeded recommended doses or administration to toddlers D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Nasal congestion • Intranasal corticosteroids (INS) – Local side effects: Rare and can be avoided with proper administration technique • Nasal irritation • Bleeding • Nasal septal perforation D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Intranasal cortocosteroids D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Nasal congestion • Intranasal decongestants – Phenylephrine – Imidazoline derivatives (oxymetazoline and xylometazoline) – No effect on Ag-provoked nasal response – No effect on itching, sneezing, or nasal secretion – Not recommended for continuous use • Due to induction of rhinitis medicamentosa D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Nasal congestion • Intranasal decongestants – Side effects • Local stinging or burning • Sneezing • Dryness of the nose and throat – Efficacy and safety of intermittent use of this drug have not been formally studied D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Nasal congestion • Oral decongestants – Pseudoephedrine (restricted prescription) – Phenylephrine (less effective) – Effective at relieving nasal congestion – Side effects: • • • • • Insomnia Loss of appetite Irritability Palpitations Elevated BP D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Nasal congestion • Oral decongestants side effect – Elevated BP • • • • Very rare in normotensive patients Occasionally in controlled HT patients But changes in BP still should be followed Concomitant use of caffeine and stimulants may be associated with an increase in adverse events D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Nasal congestion • Oral decongestants – Used with caution in: • • • • • Cerebrovascular Cardiovascular disease Hyperthyroidism Closed-angle glaucoma Bladder neck obstruction D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Nasal congestion • Oral decongestants…in children – Usually very well tolerated in children >6 years of age – Use in infants and young children has been associated with… • • • • Agitated psychosis Ataxia Hallucinations Even death – ADR can occur even in recommended dose D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Pharmacological Rx summary D V Wallace, et al., The diagnosis and management of rhinitis: An updated practice parameter, J Allergy Clin Immunol 2008;122:S1-84.
  • Other pharmacological Rx • Topical use of capsaicin intranasally – Desensitize sensory neural fibers in the nose – Reducing nasal hyperreactivity – Beneficial effects are delayed – 63% reduction of nasal congestion – 69% reduction of nasal discharge – After 1 month of therapy • Topical application of 15% to 20% silver nitrate might also be effective R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • Rhinitis medicamentosa Rx • Withdrawal from topical decongestant • Treatment of underlying rhinitis disorder • Use of topical/systemic glucocorticoid: – INS bilaterally + discontinueation of decongestant in one nostril and, 1 week later, in the remaining nostril – 1-week tapering course of oral glucocorticoid, with discontinuation of the decongestant on days 2 or 3 R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • Medication-related rhinitis • Change in therapy should be considered • If a particular medication is necessary and irreplaceable? – Topical therapy • In order to avoid drug interactions and/or additional systemic adverse effects J. Corren, et al., Allergic and Nonallergic Rhinitis, Middleton’s Allergy 8th edition, 2013, 664-685.
  • Surgical Rx • Endoscopic vidian nerve section and/or electrocoagulation of the anterior ethmoidal nerve – Parasympathetic supply to the nasal mucosa is divided, resulting in reduced nasal secretion – Recurrence of symptoms due to re-innervation can occur – But enough long-term benefits R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • Surgical Rx • Sphenopalatine ganglion block – Reported to relieve symptoms – Number of blocks required for complete relief range from 2 to 4 • Turbinectomy – In cases of predominant congestion – A variety of surgical procedures available – Can nasal mucosa return to a normal functioning state after radical turbinectomy? R A Sittipane, et al., Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 86:494–508, 2001
  • Surgical Rx of atrophic rhinitis • To reduce the nasal cavity size • Providing tissue augmentation • Means to help restore nasal anatomy toward the premorbid state R A Sittipane, et al., Nonallergic Rhinitis, Am J Rhinol Allergy 27, S48–S51, 2013
  • TAKE HOME MESSAGE
  • Algorithm of rhinitis diagnosis GK. Scadding, Non-allergic rhinitis: diagnosis and management, Curr Opin Allergy Clin Immunol, 2001;1:15-20
  • Algorithm of nonallergic rhinitis Rx AN. Greiner, Overview of the Treatment of Allergic Rhinitis and Nonallergic Rhinopathy, Proc Am Thorac Soc , 2011;8.,121–131.
  • THANK YOU