Allergy And Rhinitis Allergic Rhinitis

The Allergic Response Primary Reaction Phase

• Type I immediate hypersensitivity (see Table 1—4)

• occurs within 5 minutes of allergen exposure with maximum effect at 15 minutes

• allergen recognition by IgE antibodies stimulates mast cells and basophils (via the IgE Fc receptor)

TABLE 1-4. Hypersensitivity Types

Type

Mediators

Reaction

I: Anaphylactic IgE

II: Cytotoxic

IgG, IgM

III: Immune Complex IgG, IgM, ]

IV: Cell-mediated T-cells

V: Interference with Ig Receptor immediate, self-limiting IgE mediated, stimulates mast cells and basophils which release histamine and other inflammatory mediators

IgG, IgM multivalent binding to phagocyte or complement eg, Transfusion reactions, Goodpasture's Syndrome, Bullous Pemphigoid antibody and complement complexes cause increased blood viscosity removed by reticulo-endothelial system eg, Renal Deposition, Arthritis,

Glomerulonephritis, Serum Sickness

Delayed-type Hypersensitivity reaction (T-cell mediated) eg, Graft Rejection, Contact Dermatitis antibody "resembles" a ligand and thus blocks or stimulates the receptor pathophysiology of autoimmunity (eg, Hashimoto's Thyroiditis, Myasthenia Gravis, Graves' Disease)

• degranulation occurs after cross linking of the IgE (via a calcium influx trigger) releasing inflammatory mediators resulting in a net increase in local vascular permeability and proteolysis

• Mediators Released: histamine, serotonin, heparin sulfate peptide, arachidonic acid derivatives (leukotrienes, prostaglandins)

• rechallenged allergens stimulate mast cells more quickly and require less antigen load

Secondary (Late) Reaction Phase

• occurs 4—6 hours after acute phase

• migration of inflammatory cells (neutrophils and eosinophils) and continued activated basophils release a second phase of mediators (mast cells do not remain active)

Diagnosis of Allergy

History and Physical Exam

• Nasal SSx: sneezing, congestion, rhinorrhea

• Ocular SSx: redness, itchiness, watery, conjunctivitis, burning

• Otologic SSx: eustachian tube dysfunction, middle ear effusions

• Laryngeal SSx: scratchiness, dry, irritated, cough

• Other SSx: seasonal pattern (eg, in the upper Midwest tree pollen allergies occur between April—May, grass pollen May—July, weed pollen July—frost, molds year-round), food hypersensitivity, fatigue

• PE: clear rhinorrhea, congested turbinates, periorbital puffiness, nasal tip crease ("allergic salute"), open-mouthed breathing ("adenoid facies"), prominent pharyngeal lymphoid tissue, conjunctivitis

• Associated Disorders: chronic sinusitis (obstruction from mucosal edema), nasal polyps, asthma, otitis media with effusion

Adjunctive Testing

• Nasal Endoscopy: evaluate for nasal polyps, osteomeatal unit obstruction, adenoid tissue

• Nasal Smear: obtained from inferior turbinate mucosa, >25% eosinophils on nasal smear suggests allergy (neutrophils suggest infection)

• Total Serum IgE: not accurate or cost-effective

Skin Allergy Testing

• Scratch Test: scratch skin with placement of allergen or scratch with allergen, has largely been replaced for more objective and more reliable techniques

• Prick Test: series of allergens are inserted by needle into skin, positive "wheal-and-flare" reactions are compared to controls; rapid and safe test, risk of anaphylaxis, misses less sensitive allergy, grading is subjective

• Intradermal Test: similar to prick test except allergen is placed intradermally; more sensitive than prick test, however, more time-consuming and painful, risk of anaphylaxis, and subjective grading

• Skin Endpoint Titration: series of increasing concentrations of specific allergen are introduced intradermally to titrate to a positive response, useful for determining immunotherapy concentrations, highly sensitive and determines quantitative measurements, however, time-consuming

In Vitro Allergy Testing

• Radioallergosorbent Test (RAST): serum reacts with a series of known allergens, radiolabeled anti-IgE identifies specific antigen-IgE complexes

• Enzyme-linked Immunosorbent Assay (ELISA): similar to RAST except fluorescing agents are used for markers of antigen-IgE complexes

• Indications: equivocal skin test results, high risk of anaphylaxis (severe asthma, prior history), skin disorders (eczema), uncooperative patient (children and infants), failed immunotherapy (negative skin test is not an indication for in vitro allergy testing)

• Advantages: highly specific, no risk of anaphylaxis, no effect from skin condition (skin color, eczema, dermatographia) or medications (^-blockers, antihistamines, tricyclics)

• Disadvantages: less sensitive, requires up to 1—2 weeks for results, more expensive

Management

Anaphylaxis

1. ABC's: establish airway, oxygenation, and IV access

2. inject up to 0.3 ml of epinephrine intramuscularly (IM)

3. consider dopamine for hypotension

4. if needed repeat injection of up to 0.3 ml of epinephrine IM

5. add diphenhydramine 50 mg, dexamethasone 4 mg, and cimetidine 300 mg through IV

6. if needed repeat injection of up to 0.3 ml of epinephrine IM

Level 1: Avoidance, Symptomatic Relief

Avoidance: based on specific allergy

• Dust: mattress cover, foam pillows, plastic case, low carpet or hardwood floors, frequent dusting and vacuuming, may apply benzyl benzoate to carpet to kill mites, consider synthetic carpets

• Molds: disinfect bathroom, clean furnace, dehumidify basement, clean refrigerator, avoid gardening, address potential sources of molds indoors (plants, old shoes, curtains)

• Pollens: air conditioning, air cleaners, keep windows closed, avoid cutting grass

• Animals: keep out of bedroom, use special shampoos

• high efficiency particulate air filters may be used for all airborne allergies

• home humidity prevents nasal dryness

• masks may be helpful in unavoidable allergy exposure

Symptomatic Medications

• Nasal Saline Irrigations: removes nasal mucus and crusts, aids in mucociliary clearance, thins tenacious mucus

• First Generation Antihistamines (H^receptor agonists): primarily for sneezing, itching, and rhinorrhea; side effects include sedation, dryness, confusion tolerance, and aggravation of prostatism (eg, diphenylhydramine, chlorpheniramine, promethazine, hydroxyzine)

• Second Generation Antihistamines (H1-receptor agonists): lipophobic (does not cross blood-brain barrier) therefore less sedating, inhibit release of inflammatory mediators (eg, loratadine, astemizole, certirizine, fexofenadine, terfenadine)

• Phenylamines (a-adrenergic antagonist): vasoconstrictive effect decreases mucosal congestion; side effects include central nervous system stimulation (anxiety, anorexia), cardiac arrhythmias, hypertension, seizures, insomnia, psychosis

• Imidazolines (topical adrenergic antagonist) decreases mucosal congestion locally; risk of rebound nasal congestion (rhinitis medicamentosa)

• Topical Glucocorticoids: local reduction of inflammatory cells in nasal mucosa, decreased capillary permeability, reduces edema; minimal side effects (epistaxis, candidiasis, nasal dryness), decreases both acute and late phase reactions

• Cromolyn: stabilizes mast cells preventing release of mediators in acute and late phase reactions, effective only for prophylaxis; minimal side effects (sneezing, epistaxis, nasal irritation)

Level 2: Management of Complicating Factors

• must evaluate and treat potential concurrent disorders which may mimic allergy including vasomotor rhinitis, sinusitis, and rhinitis medicamentosa before changing treatment regimens

Level 3: Chronic Symptoms (Corticosteroids)

• most potent medication for symptomatic relief

• Mechanism of Action: decreases inflammatory migration, blocks arachidonic metabolites, decreases vascular permeability

• may be given orally, nasal aerosols, or via intraturbinal injections

• Side Effects of Oral Corticosteroids: increased gastric acid production (consider prophylactic concurrent ^-blocker), hypertension, masks signs of infection, sodium retention, hypokalemia, posterior subcapsular cataracts, central nervous system stimulation (psychosis, seizures, insomnia), menstrual irregularities, aseptic necrosis of femoral head

Level 4: Immunotherapy

• Indications: unresponsive to medical therapy, severe symptoms, allergens that can not be avoided

• Advantages: suppresses allergy

• Disadvantages: patient must be reliable for multiple injections, requires a chronic regimen (3 years), risk of worsening symptoms and anaphylactic shock

• Contraindications: pregnancy (anaphylaxis risks hypoxia in fetus), autoimmune disorders, immunological compromised patients, P-blockers (increases sensitivity to allergens), easily avoidable allergens, noncompliant patients, food allergens

• Mechanism of Action: uncertain, initial small doses of allergen cause a rise in allergen-specific IgG which prevents binding of IgE, IgE may also become "exhausted"

Churg-Strauss Syndrome

• Pathophysiology: unknown etiology, causes angiitis and allergic granulomatosis

• Triad: hypereosinophilia, allergic rhinitis, asthma

• Other SSx: nasal polyposis, nasal obstruction, septal lesions, lung lesions, systemic vasculitis

• Rx: corticosteroids

Nonallergic Rhinitis

Infectious Rhinitis

Viral Rhinitis (Coryza, Common Cold)

• Pathogenesis: spread via infected droplets

• Common Viral Pathogens: rhinovirus (most common, >100 types), parainfluenza, adenovirus, enterovirus, respiratory syncytial virus

1. Dry Prodromal Stage (initial phase): nasal drying and irritation, low-grade fever, chills, general malaise, anorexia

2. Catarrhal Stage (second stage): watery clear rhinorrhea, anosmia, congestion, lacrimation, worsening of constitutional symptoms

3. Mucous Stage: thickened rhinorrhea (greenish and foul smelling if secondarily infected), improved constitutional symptoms

• Dx: clinical history and exam

• Rx: no cure for the common cold; antibiotics should be given for suspected bacterial infections only; symptomatic therapy includes decongestants (topical and systemic), antihistamines, ipratropium bromide sprays, hydration, humidification, nasal saline irrigations, analgesics, mucolytic agents

Bacterial Rhinitis

• typically secondarily infected viral rhinitis

• Common Bacterial Pathogens: Pertussis, Diphtheria, Group A Streptococcus, Chlamydia

• SSx and Stages: similar to above, however, rhinorrhea may be thickened, greenish, and foul smelling

• Dx: clinical history and exam

• Rx: antibiotic regimen, symptomatic therapy similar to viral rhinitis

Rhinoscleroma

• noncontagious

• Pathogen: Klebsiella rhinoscleromatis (Frisch's bacillus)

• Risks: endemic to East Europe, North Africa, South Asia, Central and South America

1. Catarrhal: persistent purulent rhinorrhea, nasal honeycomb-color crusting

2. Granulomatous: small, painless granulomatous nodules in upper respiratory tract (including glottis and subglottis)

3. Sclerotic: lesion heals with extensive scarring (dense fibrotic narrowing of nasal passage)

• Dx: biopsy and culture, serum antibodies

• Histopathology: Mikulicz's cell (foamy histocytes containing the bacteria, "moth eaten" cytoplasm), Russell bodies (bloated plasma cells with bifringent inclusions), pseudoepitheliomatous hyperplasia

• Rx: long-term antibiotics as dictated by culture and sensitivity, debridement, consider laser excision or cryotherapy

Rhinosporidiosis

• Pathogen: Rhinosporidium seebri (sporangium with a thick-walled cyst)

• Risks: endemic to Africa, Pakistan, India, Sri Lanka, spread from contaminated water (public bathing)

• SSx: friable, "strawberry" red (vascular) polypoid nasal lesion (epistaxis, obstruction)

• Histopathology: pseudoepitheliomatous hyperplasia, submucosal cysts, fungal sporangia with chitinous shells

• Rx: surgical excision with cauterization of the base and oral antifungal agents, corticosteroid injections, may consider dapsone

Rhinocerebral Mucormycosis (see Paranasal Sinus) Phaehyphomycosis (see Paranasal Sinus) Nonallergic Chronic Rhinitis

• Causes: recurrent or chronic inflammation of the nose and sinus secondary to a variety of causes including vasomotor disease, irritant and toxin exposure, persistent environmental factors (changes in temperature and humidity), pregnancy, medications, endocrine disease (diabetes, thyroid disease), infections, granulomatous disease

• SSx: congestion, nasal obstruction, watery rhinorrhea, congested nasal mucosa, throat-clearing, fatigue, malaise

• Granulomatous Nasal Diseases: tuberculosis, leprosy, rhinoscleroma, syphilis, fungal, protozoan, sarcoidosis, Wegener's disease

• Dx: anterior rhinoscopy, biopsy for suspected granulomatous diseases

• Rx: address underlying cause, symptomatic medications may be used for temporary relief (decongestants, nasal sprays, etc.)

Nonallergic Rhinitis with Eosinophilia Syndrome (NARES)

• nasal eosinophilia without allergy

• SSx: symptoms of perennial rhinitis

• Dx: allergic symptoms with negative allergic tests

• Rx: symptomatic relief similar to allergic rhinitis (nasal corticosteroids, antihistamines, decongestants)

Rhinitis and Pregnancy

• Pathophysiology: unclear, may be multifactorial (cholinergic effects from increased estrogen may contribute)

• SSx: rhinitis, pale-blue mucosa, turbinate hypertrophy, manifests near the end of the first trimester, resolves after delivery

• Dx: avoid skin testing (risk of anaphylaxis), may use RAST testing and nasal cytology

• Rx: refractory to most regimens, conservative management (nasal saline irrigations, avoidance of allergens, may consider nasal steroids), avoid decongestants (may place fetus at risk), consult obstetrician for treatment

Rhinitis Sicca Anterior

• Pathophysiology: dry, raw nasal mucosa secondary to a variety of causes including changes in temperature and humidity, nose picking, dust, and other irritants

• SSx: dryness, nasal irritation, nasal crusting, epistaxis, septal perforation

• Dx: clinical history and exam

• Rx: saline irrigation, topical antibiotics, oil based nasal ointments

Atrophic Rhinitis (Ozena)

• Pathophysiology: mucosal glands and sensory nerve fibers degenerate, epithelium undergoes squamous metaplasia, destroyed mucociliary transport

• Causes: excess nasal surgery (excessive turbinectomy), suspected genetic component (more common in East Asia, Egypt, Greece), endocrine abnormalities, nutritional deficiencies (vitamin A or D, iron deficiency), chronic bacterial infections, trauma and irritant exposure

• SSx: mucosal and turbinate atrophy, wide nasal cavity, nasal crusting, offensive odor, epistaxis, anosmia, may have paradoxical sensation of nasal obstruction

• Dx: anterior rhinoscopy

• Complications: increased risk for secondary infection

• Rx: saline irrigation, oil based ointment impregnated nasal tampons, vitamin A and D and iron supplements, systemic or topical antibiotics (for secondary infections), consider nasal vestibuloplasty or periodic nostril closure for failed medical therapy

Anhidrotic Ectodermal Dysplasia

• Pathophysiology: X-linked genetic disorder resulting in scant mucus production and atrophic rhinitis

• SSx: atrophy of inferior and middle turbinates, fevers, recurrent otitis media, malodorous rhinorrhea, nasal crusting

1. anhidrosis

2. hypotrichosis

3. anodontia

• Rx: pressure equalization tubes, saline irrigations, nasal hygiene, denture appliances

Rhinitis Medicamentosa

• Pathophysiology: semi-ischemic state secondary to any topical nasal decongestants, results in rebound congestion from decreased vasomotor tone, increased parasympathetic activity, increased vascular permeability (also results in decreased ciliary activity)

• may be irreversible if vagal tone becomes atonic

• SSx: mucosal edema, nasal obstruction, dryness, irritation

• Rx: discontinue topical decongestants, aggressive saline irrigation, oral decongestants, nasal steroid spray, may consider nasal stents, submucosal steroids, or short-term oral corticosteroids; avoid by limiting topical decongestants to 3—5 days

Vasomotor Rhinitis

• Pathophysiology: rhinitis secondary to overactive parasympathetic activity from a wide variety of triggers (see below)

• SSx: similar symptomatology to allergic rhinitis except with negative allergy evaluation, morning rhinorrhea, alternating sides, pale nasal mucosa

• Dx: diagnosis of exclusion, negative allergy work-up

Triggers

• Environmental: humidity and temperature changes, dust, smoke, pollution

• Endocrine and Metabolic: pregnancy, oral contraceptives (estrogen inhibits anticholinesterases), hypothyroidism

• Medications: antihypertensives, antipsychotics, cocaine

• Psychotropic: anxiety, stress, exercise

Management

• attempt elimination of irritants and address causal factors if possible

• Medical Management

1. anticholenergic nasal sprays (ipratropium bromide)

2. corticosteroid nasal sprays

3. hypertonic saline nasal sprays

4. may consider short course of oral and topical decongestants or antihistamines

• Surgical Management: indicated for refractory cases

1. Surface Turbinate Cautery: may also consider cryotherapy or laser

2. Septoplasty: removes mechanical points of irritation

3. Partial Turbinectomy: reduction of lower and possible middle turbinates, total turbinectomy risks atrophic rhinitis

4. Division of Parasympathetic Fibers: most commonly section the vidian nerve

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