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

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

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

>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

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)

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)

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

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

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

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

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

Impaired epidermal barrier due to:

Antigenic and irritant agents penetrate and activate immune cells

Immune dysfunction w/ exaggerated T_h2 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.

Age of onset:

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

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

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

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

Adult stage (puberty +): More localized

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

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

Lab testing/specific allergy testing not routinely recommended

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

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

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

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

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

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.

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

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

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

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.

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

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

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

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

Monobactams (aztreonam): Not considered cross reactive

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)