Anaphylaxis
Immediate allergic response: The reaction begins when IgE already bound to mast cells via its high-affinity receptor (FceRI) is cross-linked by an antigen. This stimulates the immediate release of mast cell granules containing performed medators such as tryptase, chymase, and histamine.Late-phase allergic response: The late-phase response(LPR) is mediated in part by newly formed lipid mediators(Includig PGD2, PAF, and leukotrienes LTC4/D4/E4) produced by mast cells and basophils.
HYPERSENSITIVITY REACTIONS
Hypersensitivity reactions are well described in the medical literature and are an essential part of basic pathology. They are mechanisms by which the immune system causes injury to tissues. Normally, an antigen encountered by various cells of the immune system stimulates an inflammatory response that protects the body from the environment. Inflamation, therefore, is both protective and damaging. Hypersensitivity reactions describe the many ways that tissue damage can occur. Table 2-2 describes these reactions according to the classification by Gell and Coombs.
KEY POINTS
Croos-linking of IgE molecules anchored on mast cells by antigen triggers mast cell degranulation, mediator release, and de novo synthesis of lipid-derived mediators.
The immediate allergic response is mediated by mast cells, whereas the latephase allergic response is mediated by other inflammatory cells, including CD4 T lymphocytes, basophils and eosinophils.
Introduction
Definition and Classification
Food allergy refers to a small group of adverse food reactions (AFRs) for which an immunologic mechanism has been identified. The vast majority of these are IgE-mediated (Gell and Coombs classification type I) with immediate postingestion manifestations (minutes to hours), though in few cases other immune mechanisms have been postulated with signs and symptoms manifesting over hours to days. The more inclusive term adverse food reactions includes food intolerance.
Etiology
AFRs can be etiologically classified as food toxicity, poisoning, idiosyncrasy, and pharmacologic reactions. In a minority of cases, food additives (preservatives and food colors) have been implicated in AFRs. In many cases, suspected AFR should be confirmed using double-blind, placebo-controlled food challenge (DBPCFC), which is the gold standard for establishing the diagnosis of AFR.
Epidemiology
Prevalence of Adverse Food Reactions
Nearly 20-25% of parents believe their children suffer from food allergies justifying modification of their diets. Studies of oral food challenge, however, suggest that only 8% of children <3 yrs can be labeled as having a food allergy. The percentage of children affected decreases with age, and by adulthood, the prevalence of food allergies is 1,6%. Cow’s milk allergy affects 2.6% of children in the first 2 yrs of life, whereas egg and peanut allergy have prevalences of 1.5% and 0.5%, respectively. Food allergy is more prevalent in patients with atopy. 30% of children with severe atopic dermatitis (AD) and 10% of those with asthma are found to have food allergies.
Incidence of Food Anaphylaxis
Food is postulated to be a major cause of systemic anaphylaxis and anaphylactoid reactions, with an annual incidence of four cases per million population and an estimated 500 deaths annually.
Foods Commonly Incriminated
Although any food can cause food allergy, only a few foods are believed to cause >90% of clinically significant cases. In children, cow’s milk, wheat, soybeans, eggs, and peanuts are the most common offenders. Peanuts, tree nuts, and crustaceans are the foods likely to be involved in food allergies in adults and are the foods most likely to cause food-induced anaphylaxis.
CAUSES
Pathophysiology
Food Allergens
Major food allergens tend to be glycoproteins with a molecular weight of 10-70 kd that tend to he heat stable and withstand cooking, food processing, and enzymatic proteolysis after ingestion.
Cross-Reactivity In Food Allergy
Skin testing and in vitro radioallergosorbant (RAST) tests demonstrate cross-reactivity within different food families (e.g., peanuts and peas are both in the legume family). This cross-reactivity is usually of no clinical significance, and patients tend to react clinically to a single food (e.g., peanuts and not peas) despite multiple positive skin teats and BAST results. These results should thus be interpreted in the context of clinical presentation.
Clinical cross-reactivity, however, is present in an interesting IgE-mediated reaction known as the oral allergy syndrome (OAS). In OAS, patients with aeroallergen hypersensitivity (to pollens, grass, etc.) may develop oral symptoms (labial pruritus, perioral urticarial rash, etc.) on consumption of certain fresh fruits and vegetables. Cross-reacting allergens involved in OAS are minor antigens that are heat labile and are destroyed by cooking and food processing.
Gl Defense Mechanisms
The GI mucosa is the first-line barrier between the body and foreign food proteins. More than 98% of ingested proteins are broken down to simple nonimmunogenic units (amino acids and oligopeptides) by proteolysis. However, traces of food proteins are absorbed as intact antigens, with consequent development of tolerance to these antigens. The mechanism of tolerance is not completely understood, but it involves both B and T lymphocytes with clonal deletion, anergy, and/or active suppression. GI defense mechanisms mature with age and are possibly enhanced by factors such as consumption of breast milk early in life. This may explain the higher incidence of food allergy in infants compared with adults and the protective role of exclusive breast-feeding in the first year of life.
Natural History
Food allergies are more frequently encountered in children, possibly because of immaturity of GI defense mechanisms and/or immaturity of the immune system. As children with food allergy, confirmed by DBPCFC, get older, they outgrow certain food allergies (e.g., to milk, eggs, and wheat, but not to crustaceans or peanuts). Frequently, their skin tests and RAST assays remain positive despite a negative food challenge. Strict elimination of allergens from the diet Increases the probability that food allergies Will resolve (nearly one-third of children and adults lose clinical reactivity after 1-2 yrs of allergen avoidance). Prevalence of positive food challenges drops from 8% in children (< 3 yrs) to approximately 1.5% in adults.
It is unfortunate, however, that loss of reactivity is food-specific, and that foods associated with most fatal anaphylaxis (peanuts, tree nuts, crustaceans, and fish) are associated with life-long clinical reactivity despite strict elimination.
Infants with non-IgE-mediated food intolerance also respond favorably to allergen avoidance with long-term loss of clinical reactivity. Celiac disease, unfortunately, is an exception, and life-long avoidance of gluten is mandatory for disease control.
PRESENTATION
Types of Food Reactions and Clinical Presentation
IgE-Mediated Immune Reactions to Food
IgE-mediated immune reactions comprise almost all food allergies. Previous exposure to allergenic food, usually intermittently, is required for the development of this type of immune reaction. Antigen-specific IgE attaches to high-affinity IgE receptors on mast cells and basophils where, on binding to their specific allergens, they trigger the process of mast cell (and basophil) activation and degranulation with the release of cytokines and other mediators. Early-phase reactions develop within minutes and frequently are followed by a late-phase reaction a few hours later.
Clinical syndromes associated with type I hypersensitivity reactions range from urticarial rashes (±angioedema) and OAS (see Cross-Reactivity in Food Allergy) to full-blown systemic anaphylaxis with vascular collapse. Systemic anaphylaxis usually starts within a few minutes to an hour after food ingestion. Occasionally, mild oral or skin symptoms may he a prelude to fatal anaphylaxis. Late-onset anaphylaxis almost never starts more than 4 hrs after allergen ingestion.
With more prolonged exposure to an allergenic food, allergic rhinoconjunctivitis and bronchial asthma may manifest, especially in patients with AD.
In a few cases, IgE-mediated food allergy can present as infantile colic, eosinophilic gastroenteritis, and infantile gastroesophageal reflux disease. Diagnosis of the latter group requires a high index of suspicion and endoscopic biopsy.
Food-associated exercise-induced anaphylaxis is a recently established class of food allergy. In this interesting disease, anaphylaxis occurs only if vigorous exercise occurs 1-2 hrs after ingestion of certain foods (or less commonly any food).
Non-lgE-Medlated Immune Reactions to Food
Types II and III of non-IgE-mediated immune reactions as well as cell-mediated food reactions have been implicated in rare cases of AFRs.
Food-induced thrombocytopenia (type II reaction to cow’s milk) has been reported (but is exceedingly rare).
A rare syndrome known as Heiner’s syndrome, first described in 1966, is believed to result from hypersensitivity to cow’s milk. Early aspiration and sequestration of milk in the lungs initiates an immune reaction manifesting as a pneumonia-like disease with pulmonary infiltrates associated with iron-deficiency anemia and pulmonary hemosiderosia. In addition to IgE, patient’s serum contains high levels of a precipitating IgG antibody to cow’s milk. Disease pathology is likely mediated via immune complex and cell-mediated hypersensitivity-type reactions. This rare disease has also been described in breast-fed infanta.
Celiac disease, or gluten enteropathy, is possibly mediated in part by a type IV hypersensitivity to gluten in addition to direct gluten toxicity.
Nonimmunologic Reactions to Food
A variety of mechanisms are involved in several AFRs.
Scombroid fish poisoning is an anaphylactoid type reaction resulting from the action of bacterial decarboxylase on histidine-rich fish meat (tuna, mackerel, bonito, mahi mahi). Histamine is generated enzymatically, and when the fish is ingested, the patient complains of burning mouth sensation, pruritus, flushing, nausea, vomiting, headache, and even vascular collapse.
Similar symptoms can occur as a result of ingestion of histamine-rich foods such as Roquefort and Parmesan cheeses, eggplant, spinach, and red wine. Ingestion of foods rich in serotonin (tomato, pineapple, avocado, and banana) or tyramine (cheese and wine) can be associated with “pharmacologlc” symptoms such as flushing, headaches, and palpitation. These symptoms are much more pronounced in individuals on MAOIs.
Idiosyncratic Intolerance is exemplified by lactose intolerance, which is frequently indistinguishable from GI presentations of IgE-mediated milk allergy. Careful history taking usually resolves the confusion. Asian, Arab, or black ethnic background; later age of onset (over 7 yrs); and occasional association with recent gastroenteritis are associated with lactose intolerance.
Several food-induced GI syndromes are identified that are similar to IgE-mediated syndromes with no evidence of food-specific IgE. These include: gastroenteritis, proctocolitis, enteropathy {e.g., gluten enteropathy), and gastroesophageal reflux diaease. Gluten enteropathy is frequently associated with an intensely pru-ritic vesicular condition known as dermatitis herpetiformis, which affects extensor surfaces and buttocks.
Food-induced migraine is a poorly understood entity that has been reported in some patients with positive DBPCFC. The mechanism is unknown.
MANAGEMENT
Workup
History
Careful history taking is the most powerful diagnostic tool for food allergies. In many cases, physical exam is completely normal and the patient (or family) frequently seeks medical advice for confirmation of a suspected food-induced reaction. A detailed history of previous or current episodes of AFR should include the following:
Food(s) suspected of provoking the reaction.
Description of the reaction: age of onset of first reaction, latency between ingestion and onset of symptoms, rate of progression of the reaction, duration of the reaction, course (i.e., intermittent or chronic), reproducibility and similar episodes in response to other foods or same food in a different form (raw, cooked, or canned), associated events (e.g., exercise, alcohol consumption), how long since last episode.
Systemic manifestations of the reaction:
Cutaneous: hives, pruritus, swelling, flushing
Oral: pruritus; lip, tongue, or throat swelling; difficulty swallowing; change of voice Respiratory: difficulty breathing, stridor, wheezing, cough
GI: nausea, vomiting, abdominal pain/colic, bloating, diarrhea, bloody stool Cardiovascular: dizziness, palpitations, collapse
General: headaches, history of malabsorption, chronic weight loss, delayed developmental milestones, chronic anemia
Severity of the reaction and the need for medical attention (e.g., no treatment needed, phoned or visited primary care physician, ER visit or hospital admission, and nature of treatment received).
Past medical history: allergic rhinitis/conjunctivitis, bronchial asthma; exacerbation of symptoms with food ingestion.
Family history of atopic diseases.
Physical Exam
Physical exam is frequently negative.
In emergency situations, ascertain the cardiovascular and respiratory condition of the patient to rule out anaphylaxis.
If in doubt about the etiology in a patient with cardiovascular collapse and suspicious history or suggestive signs (e.g., hives, wheezes in patient without history of bronchial asthma, protracted or nonresponsive shock state), consider and possibly treat as anaphylaxis. Obtain blood for serum tryptase level (within 4 hrs) for later confirmation.
In nonemergency situations (e.g., elective office visit), look for the following signs:
Cutaneous: urticaria, angioedema, AD/eczema, dermatitis herpetiformis
Respiratory: distress, wheezing
Evidence of upper respiratory allergies (e.g., pale enlarged nasal turbinates, postna-
sal drip, pharyngeal cobblestoning, and pretonsillar throat erythema)
General: dehydration, anemia, malnutrition, failure to thrive (in children)
Food Diaries
Ask the patient to prospectively keep a detailed listing of all ingested foods (and medications) and any APR and AFR-associated events (e.g., exercise) for a few weeks. This is most useful if manifestations are intermittent. It is also more objective than relying on the patient’s recollection of previous events. Analysis of food diaries often reveals unexpected associations and helps to interpret skin tests and EAST assays in the proper context.
Diet Elimination
This technique is useful’in chronic nonintermittent manifestations of suspected food allergies. It involves switching the patient to a diet consisting of foods believed to be the least allergenic in most people (e.g., rice and lamb). Resolution of symptoms suggests a food-related etiology. Reintroduction of selected foods over time Cone new food item every 8-4 days) may help identify culprit foods. This approach ia contraindicated in suspected food-induced anapbylaxis. Care should be taken to avoid malnutrition, vitamin
Carry a syringe filled with epinephrine (adrenaline) auto-injector for emergency treatment
Health care workers with a history of latex sensitivity who must wear gloves should stop wearing latex gloves, and their co-workers should not use powdered gloves.
Blowing up a latex balloon
People with latex allergy should avoid direct contact with all products and devices that contain latex. Latex allergy problems during dental, medical or surgical procedures can be prevented by warning health care providers about latex allergy before any test or treatment. When latex allergic individuals need medical or dental care, the procedures can be conducted in a latex-free area.
ALLERGIC RHINITIS
Definition Allergic rhinitis is defined as allergen-driven mucosal inflammation. More specifically, it is the clinical manifestation of IgE-specific interactions with mast cells. It can be seasonal, perennial, or occupational. The key to diagnosis is that symptoms occur in a temporal relationship with allergen exposures.
Symptoms. Symptoms of watery rhinorrhea, itching, and sneezing during times when pollen counts are high, as in the spring or fall, are consistent with allergic rhinitis. Waxing and waning of symptoms with the seasons are typical of this condition; however, because of late-phase effects, symptoms can persist beyond the pollen seasons.
Perennial allergic rhinitis is defined as symptoms for > 2 hrs/day for > 9 mos of the year. This condition results from chronic exposure to molds, pet danders, or dust mites. Perennial allergic rhinitis is often associated with seasonal exacerbations.
NONALLERGIC RHINITIS. Nonallergic rhinitis is defined as inflammation of nasal mucosa that is not mediated by IgE. Many conditions are associated with this finding:
Infectious rhinitis is acute or chronic, and its etiologies include bacteria, fungi, and viruses. Viruses are the most common cause, History should suggest a recent upper respiratory infection. Symptoms include fever, facial pain or pressure, purulent discharge, decreased sense of smell, and cough.
Vasomotor rhinitis is chronic nasal congestion secondary to excessive vasomotor degranulation. Odors, alcohol, spicy foods, emotions, temperature change, and bright light are known triggers of this problem.
Drugs are frequently incriminated in causing rhinitis, and the most common offenders are anthypertensives, including ACE inhibitors and beta-blockers, as well as aspirin, NSAIDs, oral contraceptives, and cocaine. Samter;s triad is the occurrence of aspirin sensitivity, nasal polyps, and asthma.
Nonallergic rhinitis with eosinophilia syndrome (NARES) is very similar to allergic rhinitis, but skin tests to specific allergens are negative.
Nasal polyps are pale, smooth, round, gelatinous-appearing outgrowths from the nasal passages usually beginning on the lateral nasal wall that are often confused with enlarged nasal turbinates.
Hormonal rhinitis is associated with nasal obstruction and hypersecretion in conjunction with hypothyroidism, pregnancy, or oral contraceptive use. In pregnancy, sysmptoms often develop in the second trimester and remit upon delivery.
Anatomic causes include choanal atresia, adenoild hypertrophy, tumors, foreign bodies, and septal deviation
Presentation
History and Physical exam
A history of seasonal watery rhinorrhea, sneexing, itching, and nasal congestion is typical of allergic rhinitis. Given the long list of conditions that mimic it, a thorough history is important. One should note specific triggers; medication lists; environmental conditions, including whether pets or carpets are present in the home; and family history of atopy. Physical exam often reveals a transverse crease across the bridge of the nose secondary to persistent upward rubbing (the “allergic salute”), Dennie’s lines (folds inferior to the lower lid), conjunctivitis, and allergic shiners (periorbital darkening). Careful evaluation of nasal passages is important for ruling out nasal polyps or anatomic abnormalities, such as septal deviation, tumors, and foreign bodies.
SINUSITIS
Introduction
Background
Sinusitis is closely associated with rhinosinusitis and often occurs secondary to local processes after viral infections. Most often, it is caused by infection. Clinical characteristics are facial pain and pressure, nasal congestion, purulent discharge, cough, postnasal drainage, headache, and pain in the upper teeth. Cough may be especially bothersome. It is a common chronic condition that has significant impact on health care.
Definition
Sinusitis is inflammation of one or more of the paranasal sinuses and is classified as acute, chronic, and recurrent. Although there are no consensus standards defining chronic v acute sinusitis, it is generally accepted that symptoms occurring for S1 mo are consistent with acute sinusitis.
Causes
Pathophysiology Acute sinusitis often develops when the sinus ostia become first obstructed, then infected. Local processes perpetuating this process include ostial narrowing secondary to mucosal inflammation after a viral infection or secondary to chronic changes from allergic disease. Immune deficiency and problems with the mucocilliary transport, as well as predisposing anatomic factors, also lead to ostial narrowing.
Differential Diagnosis
Differential diagnosis is similar to allergic rhinitis
INFECTIOUS ETIOLOGIES, Infectious etiologies are viral, bacterial, or fungal:
Viruses are the most common cause of acute sinusistis and often invade before ensuring bacterial infection.
The most common bacterial etiologies in acute sinusitis are S. Pneumoniae, H.Influenzae, and moraxella caterrhalis(in children). Staphylococcus aureus, coagulase-negative Staphylocuccus, and anaerobic bacteria are more commonly associated with chornic sinusitis. Pseudomonas aeruginosa frequently occurs in patients with cystic fibrosis.
Allergic fungal sinusitis is rare. The hallmark feature is the presence of sinus opacification due to accumulation of “allergic mucin” – namely, thick, inspirssated secretion heavily laden with eosinophils, Charcot-Leyden crystals, and fungal hyphae.
In the immunocompromised patient, infectious fungal sinusitis: Aspergillus fumigatus is the most common cause of fungal sinusitis and should always be considered in an immunocompromised patient.
ALLERGIC RHINITIS. Allergic rhinitis is an IgE-mediated inflammation of the nasal mucosa associated with watery rhinorrhea, allergic conjunctivitis, postnasal drainage, and sneexing that occurs in temporal relationship to allergen exposure.
NONALLERGIC RHINITIS EOSINOPHILLIA NARES is similar to allergic rhinitis, but there is not evidence of allergic disease by skin testing.
MEDICATIONS, Medications, such as aspirin, NSAIDS, beta-blockers, and ACE inhibitors, may cause rhinitis.
RHINITIS MEDICAMENTOSA. Repeated use of topical nasal decongestants may lead to rebound nasal congestion and hypertrophy of the nasal mucosa known as rhinitis medicamentosa.
VASOMOTOR RHINITIS. Vasomotor rhinitis is chronic nasal congestion secondary to excessive vasomotor activity. It has an unknown cause and is exacerbated by odors, temperature changes, and sunlight.
ANATOMIC OBSTRUCTION. Anatomic obstruction by foreign bodies (especially in children), nasal polyps, septal deviation, and tumors should always be considered.
Presentation
Predisposing factors Conditions that disrupt mucocilliary clearance of secretions and promote ostial obstruction predispose patients to sinusitis. These include allergic rhinitis, nasal polyps, occupational rhinitis, and anatomic abnoramalities, such as a foreign body. Sinusitis is less commonly a manifestation of systemic illnesses, such as immunodeficiency(including HIV, IgA, IgG subclass deficiency), cystic fibrosis, immotile cilia syndrome, and Wegener’s granulomatosis.
History and Physical Exam
Patients often complain of purulent rhinorrhea, headache, nasal congestion, facial or dental pain or pressure, postnasal drip, and decrease or absence of olfaction(Hyposmia or anosmia). Acute sinusitis symptoms within the first 7-10 days of illness almost always signify a viral rhinosisnusitis and are recommended to be treated symptomatically rather than with antibiotics.
Signs of sinusitis include a thick purulent discharge, mucosal erythema, thenderness to plapation over the sinuses, fetid breath, and mild periorbital edema. Marked periorbital edama, orbital pain or swelling, diplopia, ophthalmoplegia, and alterations of consciousness are ominous signs and necessitate emergency evaluation to exclude orbital cellulites, cavernous vein thrombosis, meningitis, or brain abscess.
aeroallergans
pollen,mold,cockroach,pet dander,irritants such as cigarette smoke,fossil fuel combustion smoke.
pollen allergy: pollen grains from flowering plants,trees,weeds,grass get dispersed by wind and insects during the pollination season .this causes allergy mainly nasal .prevention :- closing doors and windows during pollination season ,having a bath after playing games ,stay indoors during the afternoons when pollination is highest.
mold: mold is found in wet bathrooms and on damp walls during the winter and rainy season .prevention :keep walls dry, fix pipes with leaks,stay in airy rooms with sunlight.use fungicide if necessary .
cockroach: cockroach excreta and body parts produce intense nasal allergy and wheeze.prevention proper waste disposal,keep kitchen clean,do not litter food,store food in sealed containers,use pesticide sprays regulary ,seal all cracks in the walls.
pet dander : dander of cats ,dogs are known to cause nasal allergy .prevention : avoid cats and keep cats away from living rooms,beds .wasdh hands well after handling pets.wash and bathe pets regularly.
irritants: tobbacco smoke ,exhaust smoke of fossil fuels : stay away from them ,avoid passive smoking as the risk is same as person who smokes tobacco.
chemicals -pesticides ,paints ,wood polish , keep them away from the living area
odours -avoid stong odurs of perfumes and cooking exhaust..
cold air -avoid by covering mouth and nose with dry cloth.
cold and viral infections : avoid close contact with infected patients,use handkerchief while sneezing ,practice handwashing.
house dust: most common cause of nasal allergy .caused by dustmite. increases in cold and damp atmosphere .prevention -wash bedsheets ,curtains in hot boiling water to kill the dust mites weekly once,wet mop rooms daily with water ,use encased pillows and beds .
