Allergy and Immunology



Allergy and Immunology


Lori Zimmerman

Shira H. Brown

Laura De Girolami

Milo Vassallo

Elizabeth C. TePas



Food Allergy


Definition

(Pediatr Rev. 2008;29:e23)



  • Immune-mediated adverse rxn to foods affecting skin, GI, or respiratory system


  • Reactions involving 2+ organ systems are defined as anaphylaxis


  • Subdivided into IgE-mediated and non-IgE-mediated processes.


  • Oral allergy syndrome(OAS) is IgE-mediated rxn 2/2 cross-reactivity btw proteins in pollen and those expressed by fresh fruits and vegetables


Pathophysiology

(Gastroenterology 2005;128:1089)



  • IgE-mediated: Infants most susceptible 2/2 immature GI tract barrier mechanisms (secretory IgA, mucous, gut-assoc lymph tissue, acidic environ, and proteases)



    • Most food allergies resolve as IgE levels ↓; levels may inversely correlate w/ tolerance


  • Non-IgE-mediated: Involve antigen-Ab complexes and cell-mediated hypersensitivity


Epidemiology

(J Allergy and Clin Immunol 2006;117:489)



  • >1/3 of parents report adverse food rxn’s in their children, but true food allergy affects ∼6% of pts <5 yo w/ peak at 12 mo; 3%–4% adults w/ true food allergy


  • 35% of children w/ moderate-severe atopic dermatitis have a food allergy


  • Most common allergens in children are cow’s milk (2.5%), eggs (1.5%), peanuts (0.8%), wheat (0.4%), soy (0.4%), tree nuts (0.2%), and shellfish (0.1%)


  • Cow’s milk allergy is most common food allergy in infants and young children during 1st 2 yr of life (∼50% IgE-mediated)


  • Hen’s egg allergy affects 1%–2% of young children (majority are IgE-mediated)


  • OAS affects 50% of adolescents and adults w/ allergic rhinitis to inhalant pollens


Clinical Manifestations



  • IgE-mediated: sx’s begin minutes to 2 hr after exposure: Cutaneous rxn’s (flushing, urticaria, angioedema, rash, pruritus), Res sx’s (sneezing, rhinorrhea, cough, wheezing, hoarseness), GI sx’s (N/V, diarrhea, abdominal pain)



    • Biphasic rxn’s in 25%: Initial improvement in sx’s, then recurrence 1–2 hr later


  • Non-IgE-mediated: Course subacute or chronic w/ sx’s over developing hours to days after ingestion; examples are contact dermatitis, FTT


  • OAS: Usually mild tingling and itching confined to lips, palate, and tongue on contact w/ raw form of offending agent only; <10% progress to systemic symptoms


  • Irritant, nonimmunologic rxn’s common in young children and can be mistaken for allergy (e.g., mild perioral rash after eating berries)


Evaluation



  • History key: Identify culprit foods, time course of rxn, quantity ingested, ancillary factors, Hx of similar sx’s, and FHx and personal history of atopy


  • Presence of food-specific IgE (sensitization) distinct from clinical reactivity; pts should be formally tested only to suspect foods and when there is high pretest probability


  • Skin prick tests (for IgE-mediated disorders): A wheal ≥3 mm > neg control is + test



    • Positive predictive value (PPV) <50%; negative predictive value >95%


    • In <2 yo: Wheal ≥8 mm to milk, egg, peanuts 95% predictive of clinical reactivity


  • CAP-FEIA (formerly RAST): Food-specific IgE w/ greater dx value → 95% PPV for allergic rxn w/ ingestion; IgE <0.35 KIU/L → reaction unlikely


  • Double-blind, placebo-controlled food challenge is gold std for dx; always done in controlled setting; oral challenge usually offered once IgE <2 KIU/L


Management and Prevention:

Avoidance



  • Anaphylaxis: ABCs, w/ intubation for airway protection if needed



    • Epinephrine 0.01 mL/kg of 1:1000 solution IM


    • Histamine blockade: Diphenhydramine + ranitidine (H2 blocker)


    • beta-2 agonist nebulizer treatments for bronchospasm


    • Oral or IV steroids (may blunt later-phase reactions)


    • Observation for 6–8 hr to monitor for late-phase reaction


  • Self-injectable epinephrine for all pts w/ systemic rxn’s or anaphylaxis, pts w/ possible allergy to peanuts, tree nuts, fish or shellfish, and pts w/ risk for severe rxn (i.e., asthma).


  • Antihistamines for OAS and IgE-mediated skin reactions


  • No evidence that delayed intro of solid food >4–6 mo prevents atopic dz (Pediatrics 2008;121:e44)


  • No evidence to support Δ mother’s diet in pregnancy or breast-feeding to prevent allergy



Atopic Dermatitis


Definition –

(J Allergy Clin Immunolog 2006;118:152)



  • Chronic, immune-mediated, inflammatory, pruritic skin dz occurring in pts w/ atopic diathesis, w/ variable clinical pattern depending on age.


Pathophysiology



  • Impaired epidermal barrier due to:



    • Structural abnormalities (inherited defects, trauma, infection, excoriation)


    • Functional abnormalities (decreased water binding, altered pH)


  • Antigenic and irritant agents penetrate and activate immune cells


  • Immune dysfunction w/ exaggerated Th2 response: IgE prod, eosinophilia, and proinflammatory cytokines → hyperactive immune response to environ antigens and allergens w/ cellular signaling and extravasation of inflammatory cells


  • Pruritus mech poorly understood, not just 2/2 histamine (antihistamines not effective for itch)


  • Triggers include stress-induced immunomodulation, food allergens causing urticaria (itch-scratch cycle), inhalant allergens, chemical irritants, skin infection.


Epidemiology:

5%–20% of children worldwide (Lancet 1998;351:1225)



  • Age of onset:



    • 45% in 1st 6 mo of life; evidence breast-feeding ↓ incidence, effect may be transient.


    • 60% during the 1st yr of life; 85% before age 5


  • 30%–40% of children have symptoms that persist into adulthood


  • 80% concordance rate for monozygotic twins; 20% for dizygotic.


Clinical Manifestations



  • Infantile stage (infancy–2 yo): Diaper area spared



    • Erythematous, scaly, crusted lesions on extensor surfaces, cheeks, and scalp


    • May have vesicles or serous exudate in severe cases


  • Childhood stage (2 yo–puberty): Less exudation; more lichenified papules and plaques



    • Involves flexural surfaces, wrists, ankles, and neck


  • Adult stage (puberty +): More localized



    • Lichenified, thickened skin in areas of chronicity


  • W/ severe cases, any area involved, but axillary, groin, and gluteal areas usually spared


Diagnostic Studies

(N Engl J Med 2005;352:2314)



  • Clinical criteria: Evidence of itchy skin + 3 of the following:



    • Involvement of skin creases; generally dry skin


    • H/o asthma or hay fever, or FHx atopy in 1st-degree relative (for patients <4 yo)


    • Onset of sx’s <2 yo


    • Dermatitis of flex surfaces, or cheeks/forehead/outer aspects of ext for pts <4 yo


  • Lab testing/specific allergy testing not routinely recommended


  • Ddx: Psoriasis, contact dermatitis, seborrheic dermatitis, scabies, vit def, drug rxn’s


Management

(Clin Pediatr (Phila) 2007;46:7)



  • Eliminate exacerbating factors: Limit bathing, irritating detergents, wool, scented lotions/perfumes, hot water; ↓ dust in environ; consider food allergy testing


  • Maintain skin hydration w/ emollients: Avoid lotions (worsen xerosis via water evap; use thick creams/ointments instead; Eucerin, petroleum jelly, hydrolated petrolatum) and apply immediately after bathing; use even when asymptomatic


  • Topical steroids: Use should be limited to BID to avoid adverse effects



    • 1%–2.5% hydrocortisone for mild atopic dermatitis


    • 0.1% triamcinolone (medium-potency) for more severe cases


  • Topical calcineurin inhibitors (1% pimecrolimus and 0.03% tacrolimus):



    • Approved as 2nd-line Rx in children >2 yo who respond poorly or intolerant to topical steroids; approx equal strength to low-potency steroids


    • Mechanism; inhibits inflammatory cytokines and mast cell activation


    • May cause transient burning sens, not assoc w/ skin atrophy, safe for use on face


    • Concerns: Possible risk ↑ viral superinfections; FDA “black box warning” regarding possible link to cancers and lack of long-term safety data


  • UV light, systemic steroids, systemic immunosuppressants reserved for severe cases.


  • Rx of pruritus: Antihistamines as sedative, wet dressings, and topical steroids help


Complications



  • Superinfection of eczematous sites; bacterial or viral superinfection (eczema herpeticum)


  • Complications also may arise from the specific Rx listed above, including skin atrophy, breakdown, and hypopigmentation associated w/ topical steroid use.



Drug Allergy

(Ann Allergy Asthma Immunol. 1999;83:665)


Definition



  • Immunologically mediated responses to pharmacologic agents


  • Differs from pseudoallergic/anaphylactoid rxn (i.e., contrast); direct release mediators from mast cells and basophils→classic end organ effects but nonimmune rxn



    • Vanco has both; “red man’s” = pseudoallergic, anaphylaxis = allergic IgE mediated


  • Hypersensitivity: (Gell PGH, Coombs RRA. Clin Aspects Immunol 1975;761)



    • Type I: IgE-mediated (commonly PCN or beta lactam); urticaria, laryngoedema, bronchospasm, cardiovascular collapse immediately after drug admin


    • Type II: Cytotoxic (i.e., acquired hemolytic anemia from large doses of PCN)


    • Type III: Immune complex (i.e., fevers, arthralgias, lymphadenopathy, and urticarial rash 1–3 wk after last drug exposure w/ PCN, sulfonamides, phenytoin)


    • Type IV: Cellular immune mediated (i.e., contact dermatitis w/ topical med use)


  • Can categorize drug rxn by tissue/organ involved (i.e., systemic, cutaneous, visceral)


Penicillins

(JAMA 2001;285:2498)



  • Most common BUT 80%–90% pts reporting PCN allergy not truly allergic by skin test


  • Hx (age, rxn characteristics, timing, route, other meds, response to d/c, Hx taking similar Abx)


  • Immediate rxn (<1 hr): Type I/IgE mediated. Anaphylaxis w/ PCN: 0.004%–0.015%. Usually pts 20–49 yr. Risk not ↑ w/ atopy but if occurs, may be more severe rxn.



    • Skin testing most reliable for IgE-mediated allergy (NOT SJS/TEN or type II–IV). RAST not as reliable; If neg, 97%–99% tolerate drug w/o immediate rxn.


  • Late rxn (>72 hr): Types II–IV. None involve IgE, so skin testing useless.


  • Idiopathic: Most commonly maculopapular/morbilliform rash. Unclear mech. 1%–4%.



    • ↑ w/ EBV, CMV, or leukemia. Also infectious causes of MP rash.


    • If rash strictly MP (nonpruritic, nonurticarial), no signs type I; safe to readmin.


Cephalosporins

(Pediatrics 2005;115:1048)



  • Causes allergic rxn in 1%–3% w/ or w/o hx PCN allergy, but anaphylaxis rare.


  • Rates cephalosporin allergy in pt w/ PCN allergy Hx or skin testing differs w/ gen:



    • Risk ↑ ‘d by 0.5% with 1st generation, likely not most 2nd, 3rd, or 4th.


  • Risk 2/2 to side chains; PCN similar to cefoxitin, cephalothin, cephaloridine; amoxicillin/ampicillin similar to cephalexin, cephradine, cefatrizine, cefaclor, cefprozil


Other Beta-Lactams



  • Carbapenems (imipenem): Are cross-reactive; use w/ caution in PCN allergic


  • Monobactams (aztreonam): Not considered cross reactive


Urticaria and Angioedema


Urticaria

(Allergy 2003;58:1224)



  • Definition: Rapid appearance of wheals, pruritic, central swellings of variable size, almost always surrounded by reflex erythema that blanches w/ pressure.


  • Clinical sx’s: Pruritic, at times burning; transient (1–24 hr) +/- angioedema.


  • Epidemiology (Immunol Allergy Clin N Am 2005.25.353)



    • Incidence 15%–25%. Affects 6%–7% preschool kids, 17% kids w/ atopic dermatitis. 50% w/ urticaria and angioedema, 40% w/ just urticaria, 10% w/ angioedema alone.


Angioedema

(Am J Med 2008;121:282; Immunol Allergy Clin North Am 2005;25:353)

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Jun 19, 2016 | Posted by in PEDIATRICS | Comments Off on Allergy and Immunology

Full access? Get Clinical Tree

Get Clinical Tree app for offline access