immunology allergic disorders
Overview of Allergic and Atopic Disorders
Treatment of Allergic and Atopic Disorders
Emergency treatment Removal or avoidance of allergic triggers H1 blockers Mast cell stabilizers Anti-inflammatory corticosteroids and leukotriene inhibitors Immunotherapy (desensitization) Severe allergic reactions (eg, Treatment ) require prompt emergency treatment with If the airways are affected (eg, in Treatment ), securing an airway is the highest priority. Treatment may include Patients who have severe allergic reactions should be advised to always carry a prefilled, self-injecting syringe ofepinephrineand oral antihistamines and, if a severe reaction occurs, to use these treatments as quickly as possible and then go to the emergency department. There, patients can be closely monitored and treatment can be repeated or adjusted as needed. Removal or avoidance of allergic triggers is the primary treatment and Prevention for allergy. However, when patients are sensitized to multiple allergens, complete avoidance is essentially impossible. Antihistamines block histamine receptors; they do not affect histamine production or metabolism. There are 4 different histamine receptors: H1, H2, H3, and H4. Antihistamines that block the H1 receptor (H1 blockers) are a mainstay of treatment for allergic disorders. H2 blockers are used primarily for gastric acid suppression and but are useful for certain allergic reactions; they may be indicated as adjunctive therapy for Treatment , Oral H1 Blockers relieve symptoms in various atopic and allergic disorders (eg, seasonal hay fever, Products that contain an oral H1 blocker and a sympathomimetic (eg,pseudoephedrine) are widely available over-the-counter for use in adults and children ≥ 12 years. These products are particularly useful when both an antihistamine and an intranasal decongestant are needed; however, they are sometimes contraindicated (eg, if patients are taking a monoamine oxidase inhibitor [MAOI]). Oral H1 blockers are classified as First-generation: Sedating Second-generation: Nonsedating (better thought of as less sedating) First-generation antihistaminesare widely available without prescription. They easily cross the blood-brain barrier. All have significant sedative and anticholinergic properties; they pose particular problems for older patients and for patients with glaucoma, benign prostatic hyperplasia, constipation, orthostatic hypotension, delirium, or dementia. Second-generation antihistaminesare also widely available without prescription. They do not cross the blood-brain barrier as easily as first-generation antihistamines. Second-generation antihistamines are usually preferred except when sedative effects may be therapeutic (eg, for nighttime relief of allergic symptoms, for short-term treatment of insomnia in adults or nausea in younger patients). Antihistamines may be given by various routes, including Oral (multiple—see table Oral H1 Blockers ) Intranasal (azelastineorolopatadineto treat rhinitis) Ocular (eg,azelastine,emedastine,ketotifen, levocabastine,olopatadine, or pemirolast [not available in the US] to treat conjunctivitis) Cutaneous (eg,diphenhydramine,doxepin) Mast cell stabilizers block the release of mediators from mast cells. Mast cell stabilizers are used when other drugs (eg, antihistamines, topical corticosteroids) are ineffective or not well-tolerated. They are also frequently used in patients with mast cell disease when mast activation and release of mediators overwhelms conventional antihistamines. These drugs may be given Orally (cromolyn,ketotifen) Intranasally (eg,azelastine, cromolyn) Ocularly (eg,azelastine, cromolyn,lodoxamide,ketotifen,nedocromil,olopatadine, pemirolast) Several ocular and intranasal drugs (eg,azelastine,ketotifen,olopatadine, pemirolast) are dual-acting mast cell stabilizers/antihistamines. Corticosteroids can be given intranasally (see tables Inhaled Nasal Corticosteroids and Oral corticosteroidsare indicated for the following: Allergic disorders that are severe but self-limited and not easily treated with topical corticosteroids (eg, Treatment of Acute Asthma Exacerbations , severe widespread Disorders refractory to other measures Ocular corticosteroidsare used only when an ophthalmologist is involved because infection is a risk. Nonsteroidal anti-inflammatory drugs (NSAIDs) are typically not useful, with the exception of topical forms used to relieve conjunctival injection and itching due to allergic conjunctivitis. A combination ofazelastine/fluticasone(137 mcg/50 mcg) is available. Initial dose is 1 spray in each nostril twice a day. Leukotriene modifiers (eg, Mild persistent asthma;Montelukast,zafirlukast, orzileuton Seasonal allergic rhinitis:Montelukast Urticaria:Montelukastorzafirlukast Anti-IgE antibody ( Immunomodulators ) is indicated for the following: Moderately persistent or severe asthma refractory to standard treatment Chronic idiopathic urticaria refractory to antihistamine therapy Nasal polyps Exposure to allergen in gradually increasing doses (hyposensitization or desensitization) via injection or orally or in high doses sublingually can induce tolerance. This therapy is indicated when allergen exposure cannot be avoided and drug treatment is inadequate. Mechanism is unknown but may involve induction of the following: IgG antibodies, which compete with IgE for allergen or block IgE from binding with mast cell IgE receptors Interferon-gamma, IL-12, and cytokines secreted by TH1 cells Regulatory T cells For full effect, injections are initially given once or twice a week. Dose typically starts at 0.1 to 1.0 biologically active units (BAU), depending on how sensitive the patient appears to be, and is increased weekly or every 2 weeks by≤2 times with each injection until the maximum tolerated dose (the dose that begins to elicit moderate adverse effects) is established;patients should be observed for about 30 minutes postinjection during dose escalation because anaphylaxis may occur after injection. Subsequently, injections of the maximum tolerated dose should be given every 2 to 4 weeks year-round; year-round treatment is better than preseasonal or coseasonal treatment, even for seasonal allergies. Allergens used are those that typically cannot be avoided: Pollens House dust mite feces Molds Venom of stinging insects Insect venoms are standardized by weight; a typical starting dose is 0.01 mcg, and usual maintenance dose is 100 to 200 mcg. Animal dander desensitization is ordinarily limited to patients who cannot avoid exposure (eg, veterinarians, laboratory workers), but there is little evidence that it is useful. Desensitization for peanut is available, and desensitization for other food allergens is under study. Desensitization for penicillin and certain other drugs and for foreign (xenogeneic) serum can be done. Adverse effectsare most commonly related to overdose, occasionally via inadvertent IM or IV injection of a dose that is too high, and range from mild cough or sneezing to generalized urticaria, severe asthma, anaphylactic shock, and, rarely, death. Adverse effects can be prevented by the following: Increasing the dose in small increments Repeating or decreasing the dose if local reaction to the previous injection is large (≥2.5 cm in diameter) Reducing the dose when a fresh extract is used Reducing the dose of pollen extract during pollen season is recommended.Epinephrine, oxygen, and resuscitation equipment should be immediately available for prompt treatment of anaphylaxis. Treatment None Oral immunotherapy for Prevention uses defatted peanut flour. Dose escalation is done using 5 incremental doses from 0.5 mg to 6 mg over one day given in a health care setting. This initial regimen is followed by a daily dose starting at 3 mg and increasing by 50 to 100% every 2 weeks over 22 weeks before reaching the maintenance dose of 300 mg once a day. Each increase in dose is given in a health care setting. If the initial dose is tolerated, subsequent doses are taken daily for 2 weeks; they can be taken at home. After patients successfully tolerate the 300-mg dose in a health care setting, they must take the 300-mg daily dose indefinitely to maintain desensitization. Forpregnant womenwith allergies, avoidance of the allergen is the best way to control symptoms. If symptoms are severe, an antihistamine intranasal spray is recommended. An oral antihistamine should be used only if antihistamine intranasal sprays are inadequate. Duringbreastfeeding,nonsedating antihistamines are preferred. Sedating antihistamines can be used, but they may cause drowsiness and irritability in the infant. If a sedating antihistamine is required, the infant should be monitored for these effects. Antihistamine intranasal sprays are preferred to oral antihistamines. If oral antihistamines are essential for controlling symptoms, they should be taken immediately after breastfeeding.Cyproheptadineis contraindicated during breastfeeding because it lowers prolactin levels and thus may reduce lactation. 