Pediatric Allergy and Immunology
How do you perform an allergy assessment?
History •Family history in 1st degree relatives increases risk •1 parent with allergic disease - child risk is 25% •2 parents with allergic disease - child risk 50-75% Other atopic diseases in family usually present •Atopic dermatitis, allergic rhinitis, asthma •Upon further questioning there has usually been previous reaction, perhaps milder, to same allergen upon exposure Physical Examination •Many patients have more than 1 body system involved •HEENT - pale boggy nasal turbinates, bluish discoloration •DERM - pruritis, erythematous plaques •PULM - wheezing may be audible
How do you manage urticaria?
Identify & avoid any known triggers (med, supplement, infection) •Cause not found in up to 80% of cases Acute or idiopathic urticarial •H1 antihistamine used orally Chronic urticarial or acute urticarial not responding to H1 antihistamine •H2 antihistamine added to H1 antihistamine regimen Recurring or chronic urticarial •May require steroids to control - rarely recommended •If concern for progression to anaphylaxis -> rx Epipen w/ education for use
What is atopic dermatitis?
Chronic relapsing skin disorder that can begin in infancy •"Hyperirritable skin" Exacerbated by anxiety/stress, climate (extremes of temps/humidity), irritants, allergens, infections Pathogenesis complex & multifactorial •Genetics, immunologic abnormalities, impaired skin barrier function, environmental interactions, infectious triggers Type I immunoglobulin E mediated hypersensitivity reaction Atopic trio/Atopic March - comorbid asthma + allergic rhinitis + atopic dermatitis •Prevalence is approximately 11-15% Risk factors: •Family history - ~70% of patients have a positive fam hx of atopic diseases •Food allergy - 30-80% of patients with atopic dermatitis are sensitized to certain foods •Occurs in the first year of life in 60% of cases; by 5yo in nearly 85% of cases
What should be on the DDX for PIDDs?
Consider other conditions that increase susceptibility to infection •Allergic rhinitis •Asthma •Cystic fibrosis •Primary ciliary dyskinesia •FB aspiration •Conditions interfering with skin barrier function r/o 2ndary/acquired causes of immune deficiency •Malnutrition •Aging •Protein loss via gastroenteropathy •Kidney disease •Lymphatic malformations •Certain drugs (glucocorticoids, immunosuppressive meds, DMARDs, chemo) •Malignancy - blood cell malignancies •Bone marrow failure •Chronic infections - AIDS Single site of infection? •r/o underlying anatomic defects & FBs
What is allergic rhinitis?
IgE-mediated allergic response to aeroallergens •Seasonal AR: primarily airborne pollens w/ seasonal patterns •Spring: trees •Late spring/summer: grasses •Summer/fall: weeds Perennial AR: indoor allergens •Dust mites, animal dander, mold, cockroaches Episodic AR: intermittent exposure to indoor allergens •"I visited Nana's house, and she has 10 cats" Epidemiology Most common d/o of infancy/childhood •10-25% of general population •Children/teens > adults
What are the symptoms of food allergies?
IgE-mediated food allergy Single system involvement of: •Skin •GI tract •Respiratory tract •Multisystem involvement in anaphylaxis Non-IgE-mediated food allergy •Presents in infancy as: •Proctitis/proctocolitis •Enteropathy •Enterocolitis
What are the symptoms of atopic dermatitis?
Symptoms •Patient's c/o pruritis - the "itch that rashes" •Dry skin & pruritus (severe) are the cardinal signs of atopic dermatitis •Severe pruritis -> lichenification & 2ndary infection (Staph aureus) PE findings •Papules & plaques +/- scales •+/- edema, erosion, crusts •Dermatographism characteristic •Location: flexural surfaces, neck, eyelids, forehead, face, wrists, dorsum of hands & feet •Varies by age
What is atophy?
The result of complex interactions between multiple genes and environmental factors •Implies specific immunoglobulin E (IgE)-mediated diseases such as allergic rhinitis, asthma, food allergy
What is anaphylaxis versus anaphylactoid reactions?
Anaphylactoid reaction: d/t non immunologic mechanisms •Direct, nonspecific mast cell & basophil activation but are not immune mediated - exact mechanism unknown •Examples: rxns to opiates and radiocontrast materials Symptoms/PE findings •Similar to adults - range from mild skin findings à fatal reaction Cutaneous symptoms - 90% of patients present w/ •Urticaria, angioedema, flushing, warmth •Absence of dermal symptoms does not r/o anaphylaxis Respiratory tract •Rhinorrhea, oropharyngeal edema, laryngeal edema, hoarseness, stridor, wheezing, dyspnea, asphyxiation Cardiovascular system •Tachycardia, hypotension, shock, syncope, arrhythmias Gastrointestinal system •Nausea, abdominal pain, diarrhea, vomiting Neurologic system •Syncope, seizures, dizziness, sense of impending doom A clinical diagnosis can be made when there is acute onset of symptoms w/ involvement of skin and/or mucosal tissues along with one of the following: •Respiratory compromise •Reduced BP •OR end-organ dysfunction •Basically, a total or 2 affected organ systems
What are asthma syndromes and exacerbating factors?
Asthma syndromes - classified by what causes symptoms •Allergic •Extrinsic* - most common form •Dust mites, pollen, mold, pet dander Exacerbating factors: •URIs •Exposure to allergens/irritants •Smoke, air pollution, strong odors, fumes •Exercise •Emotions •Change in weather/humidity •GERD •ASA use
How do you treat anaphylaxis?
Biphasic reaction - recurrence of anaphylactic symptoms after initial remission •w/in 4-6 hours after initial reaction Protracted anaphylaxis - s/s persisting for hours or days despite treatment •Rare •Rule of thumb for patient education regarding anaphylaxis •If you need your EpiPen, you need to call 911
What are the complications associated with atopic dermatitis?
Defective cell-mediated immunity -> increased susceptibility to bacterial/viral/fungal infections of skin Bacteria - often patients w/ atopic dermatitis (90%) colonized with S. aureus •2ndarily infected atopic dermatitis - impetigo •Topical abx: Muporicin •Local areas of infection •Oral abx: cephalosporins, dicloxacillin, augmentin •For multifocal disease or infection around eyes, mouth that is difficult to treat topically •Cultures if patients not responding, hx of multiple abx, concern for resistant organism Herpes simplex superinfection of affected skin - eczema herpeticum •Vesiculopustular lesions in clusters, become hemorrhagic •Coxsackieviruses produce similar lesions HPV and molluscum common in kids with atopic dermatitis
What are complement system disorders?
Deficiency of early components in classic complement pathway •Associated w/ encapsulated bacteria Deficiency of late components of complement cascade •Associated w/ neisserial infections C1, C2, C4 deficiency at risk for autoimmune diseases (SLE) Deficiency of C1-inhibitor -> hereditary angioedema
What are drug reactions?
Definition: unwanted, negative consequence associated w/us eof a drug or biologic agent Classification of adverse drug reactions: Immunologic •Less common 5-10% Nonimmunologic •More common 75-80% Etiology: •PCN and cephalosporins - most common allergic drug rxns in PEDs Risk factors for drug rxn: •Previous drug exposure •Increasing age - > 20 yo •Parenteral or topical routes •Higher dose •Intermittent repeat exposure •Genetic predisposition to slow drug metabolism •Leading to longer exposure Atopic history does NOT predispose to development of drug rxns •May indicate greater risk of serious rxn if one does occur
What are food allergies?
Food intolerance (i.e., lactose intolerance): a nonimmune reaction •Food allergy or hypersensitivity reaction: an immune reaction to glycoproteins & occur in genetically predisposed persons 2 types •IgE-mediated reactions: rapid onset after allergen ingestion •PEDs: cow's milk, eggs, peanuts, soybean, wheat, tree nuts, fish, shellfish - 90% of rxns •Non-IgE-mediated reactions: occur hours to days after allergen ingestion •Manifest as GI symptoms Epidemiology •Genetically predisposed •6-8% of children affected vs 2-10% of adults
What are the different types and locations of PIDDs?
Gingivitis, poor wound healing, omphalitis, granulomas, abscesses w/o pus •-> neutrophil/phagocyte defect Recurrent sinopulmonary infections •-> humoral or B-cell defect Infections w/ opportunistic infections or severe viral infections •-> T-cell or combined immunodeficiency Neisseria infections or early-onset autoimmunity •-> may represent complement defect
What is the PIDD history you will see in children?
Growth & Development: •Weight, height, head circumference plotted on growth charts •Children w/ chronic disease or immunodeficiency - poor weight gain, weight loss •Functional assessment regarding: motor, language, cognitive, social & emotional •Chronic disease and certain PIDDs, syndromic immunodeficiencies such as DiGeorge syndrome, can lead to delay in developmental milestones Immunization history: •Adverse effects from live-virus vaccines (rotavirus, varicella, polio) •Live-attenuated vaccines given early in infancy a threat to children w/ PIDDs •OPV, bcg vaccine •Develop infections despite immunization consider measuring antibody response Medications: •Use of glucocorticoids •Maternal use of immunosuppressive meds (azathioprine well known to cause lymphopenia in newborn)
How do neutrophil disorders present?
In general neutrophil d/o present w/: •Abscesses, lymphadenitis, gingivitis, poor wound healing, delayed separation of umbilical cord or poor pus formation Neutropenia = absolute neutrophil count < 1,500/mm3 in white children > 1 year of age •Somewhat lower in black children
Where does atopic dermatitis occur?
Infants •Areas involved: face, scalp, cheeks, extensor surfaces of extremities •Diaper area is spared! Differentiates from diaper dermatitis (type of contact dermatitis) Older children •Areas involved: antecubital/popliteal fossa, head, neck Adolescents/adults •Lichenified plaques on flexural areas, head and neck
What are important characteristics of asthma in a child?
Inflammation d/t inflammation from inflammatory cells, chemical mediators, chemotactic factors -> Bronchial hyperresponsiveness •Airways constrict in response to allergens, irritants, viral infections, exercise Airway remodeling •Edema, increased mucus production, influx of inflammatory cells into airway tissue, epithelial cell denudation = chronic inflammation Remember the atopy triad? •Asthma (wheezing) •Atopic dermatitis* •Type I hypersensitivity reaction •Strongest predisposing factor for asthma •Allergies
What is the innate immune system?
Innate (fast & generalized) Protection offered by skin & mucous membranes •Hair, hair-like structures in bronchi (cilia), tear fluid, sweat, urine, bowel muscles Protection offered by defense cells & proteins •Scavenger cells: Phagocytes/leukocytes •Enzymes Natural killer cells •Search for cells that have changes in surface & then destroy cell surface using toxins
What is the diagnostic work up for chronic urticaria?
No specific lab work-up, recommendations against unless history suggests potential etiology (i.e., other s/s of thyroid disease - check TSH, s/s of infection - check CBC, otherwise will find incidentalomas)
What is urticaria and angioedema?
Pathophysiology Urticaria - swelling of the dermis d/t inflammatory mediators released from skin mast cells •Acute urticaria < 6 weeks •Etiology: likely to be food, medication, insect sting, infection, blood transfusion, contact agent In PEDs viral illnesses responsible for majority of acute urticaria •Chronic urticaria > 6 weeks •Etiology: less likely to be found, often idiopathic •Physical urticaria are lesions d/t physical stimuli (dermatographia, cold, heat, and/or exercise and pressure) Angioedema - swelling below the dermis •Hereditary Type I: majority, d/t decreased production of C1-esterase inhibitor Hereditary Type II: normal levels C1-esterase inhibitor but function reduced (not as effective
What is considered the "child with atopic disease" with recurrent infections?
Pitfalls: •Chronic allergic rhinitis can be misdiagnosed as recurrent URIs •Children w/ atopic disease often have coughing or wheezing @ URIs •RAD/asthma but misdiagnosed as pneumonia or bronchitis Are more prone to recurrent/persistent URIs - sinusitis, rhinitis, OM •Thought to be d/t enhanced adherence of pathogens to inflamed respiratory epithelium, increased mucosal permeability or altered immune response Immune deficiencies that coexist w/ atopy •Selective IgA deficiency, Common variable immune deficiency (CVID), chronic granulomatous disease (CGD), DiGeorge syndrome Normal growth & development PE findings characteristic of atopy •Allergic shiners •Allergic salute •Morgan-Dennie lines Lab's characteristic of atopy •Total IgE - if normal excludes IgE-mediated allergy •If elevated is suggestive of allergy but alone is not diagnostic
What are the presentations of a child with an immunodeficiency primary versus secondary?
Primary •Often present during first years of life •Most often affect B cell function (humoral system) •B cell deficiency or combined B and T cell abnormality •Isolated T cell defects and phagocytic cell, complement & other innate immune defects less common Overall incidence 1:10,000 •Diagnosed PID in US 2005 1:2,000 •Rate of infections drops significantly after early childhood •Increased susceptibility to malignancy & autoimmunity Secondary •Present later, occur well after infancy •More often affect T cells (cellular system) More common than primary immunodeficiency •50 d/o leading to 2ndary immunodeficiency have been identified •HIV/AIDS, diabetes mellitus, malignancy, immunosuppressive drugs, prematurity •Increased susceptibility to malignancy & autoimmunity
What is the prognosis of atopic dermatitis?
Prognosis •Chronic, relapsing skin d/o tends to be more severe/prominent in young children •Symptoms b/c less severe in 2/3 of children •Complete remission in 20% of children •Widespread early onset dx w/ asthma & allergic rhinitis, family hx of atopic dermatitis and elevated IgE serum levels -> more persistent course Prevention •Trim fingernails to avoid excoriations/2ndary infxn from scratching •Think about potential underlying food allergy in younger children who do not respond to usual therapies •Not a common trigger in adults but in infants/young children
What is the diagnostic work up for asthma in a child?
Pulmonary function tests •Spirometry - (> 5 yo) •Airflow obstruction (aka asthma) = decreased FEV1/FVC ratio <75% •> 12% increase in FEV1 @ bronchodilator therapy supports asthma diagnosis Biomarker measurement •Exhaled nitric oxide (FeNO) - reflects eosinophilic airway inflammation •Gives info on who may respond to corticosteroid treatment •Aids in monitoring response to therapy & dose optimization •Detects nonadherence to corticosteroid therapy CXR •Performed with 1st episode of asthma or recurrent episodes of undiagnosed cough/wheeze to r/o anatomic abnormalities
What is the DDX of asthma in children?
Remember that not all coughs/wheezes are asthma Upper airway diseases •Allergic rhinitis, sinusitis Obstruction involving large airways •Tracheal or bronchial foreign body •Paradoxical vocal cord motion •Vascular rings or laryngeal webs •Enlarged lymph nodes or tumor Obstruction involving small airways •Viral bronchiolitis or obliterative bronchiolitis •Cystiic fibrosis •Bronchopulmonary dysplasia (chronic lung dx of prematurity) Other •Recurrent cough not caused by asthma (infection, habit cough, postnasal drip) •Aspiration from swallowing mechanism dysfunction or GERD •HF/pulmonary edema
What are the 4 groups of hypersensitivity disorders of the immune system?
Type I - Immediate hypersensitivity reaction & late-phase reaction Type II - Cytotoxic antibody reaction •Anaphylatoxins (C3a, C4a, C5a) released Type III - immune complex reactions Type IV - cellular immune-mediated (delayed hypersensitivity) reactions
What are primary immune deficiency disorders (PIDDs)?
aka Inborn Error of Immunity (IEI) •Inherited defects of the immune system •Rare •Are at risk for chronic, debilitating infections •-> severe, recurrent or unusual (opportunistic) infections -> 400 different forms of PIDDs •Universal newborn screening for SCID Can be diagnosed in infancy, childhood or adulthood •Timing and presentation depend on disease severity 4 Main Groups of PIDDs: •Antibody deficiencies •Combined T- and B-cell immunodeficiencies •Phagocyte d/o •Other deficiencies of innate immunity including complement deficiencies
How do you diagnose anaphylaxis?
clinical diagnosis
What are the symptoms of urticaria?
•Raised erythematous lesions w/ pale centers that are intensely pruritic •Vary in size •Occur anywhere on the body •Arise suddenly and resolve w/in 1-2 hours but resolve w/in 24 hours
What is the treatment of serum sickness?
•Self-limited •Resolves w/in 1-2 weeks Symptomatic relief •Pruritis - antihistamines •Fever/joint pain - NSAIDs, severe cases systemic glucocorticoids an option Prevention •Allergy skin testing DOES NOT predict likelihood of serum sickness development, NOT INDICATED •For future prevention avoid exposure to implicated cause/agent
What is the diagnostic work up of insect allergies?
•Skin test to detect presence of venom specific IgE •Venom specific serum IgE antibodies PEDs patients - if hx of anaphylaxis to stinging insect venoms •Tryptase level to screen for underlying mast cell d/o in addition to assessing specific IgE
What are the symptoms of angioedema?
•Swelling main symptom •Generally, not pruritic - may initially be painful •Persist for longer than 24 hours •Life-threatening if upper airway involved
What is skin testing?
•Allergen put into skin via prick/puncture/intradermal injection •Allergen diffuses through skin to interact with IgE that is bound to mast cells •Cross-linking of IgE -> mast cell degranulation -> histamine release -> central wheal & erythematous flare •Measure those 15-20 min after allergen applied Most sensitive method to detect allergen-specific IgE
What is the diagnostic work up of atopic dermatitis?
•CLINICAL DIAGNOSIS - based on history and PE findings Skin testing versus serum IgE testing •Helpful in assessing contribution of food or environmental allergies to disease if history suggests this as factor Skin biopsy •Little value but sometimes performed to r/o other DERM conditions that mimic atopic dermatitis
How do you approach the child who has recurrent infections?
4 types •The "normal" child •The child w/ atopic disease •The child w/ a chronic condition •The child w/ an immunodeficiency •Primary immunodeficiency •Secondary immunodeficiency •Goal: differentiate the child with a PIDD/IEI from the 'normal child
What is important to know about a child and a positive PCN allergy?
A word about PCN allergy and cross reaction with cephalosporins •Child with positive reaction to PCN skin testing •Cross reaction w/ cephalosporin less than 2% •1st-generation cephalosporin more likely to cross reaction than 2nd or 3rd generation Complications •Anaphylaxis more steroid complication of IgE-mediated drug reactions •à death if untreated
How do you manage angioedema?
ACT EARLY TO PRESERVE AIRWAY. Airway protection always 1st! •Airway involvement = admission Medical therapy •H1 & H2 histamine blockers •Subq or IM epinephrine Chronic angioedema •H2 blockers and corticosteroids Hereditary angioedema •C1 esterase inhibitors (eg, Cinryze), a kallikrein inhibitor or a selective bradykinin B2 receptor antagonist •Discontinue suspect medications •Can have rebound edema (worse than initial symptoms) after initial response to therapy
What is the adaptive immune system?
Adaptive (more specific, has memory) T lymphocytes •T helper cell: uses chemical messengers to activate other immune system cells in order to start adaptive system •Cytotoxic T cell: Detect cells infected by virus/tumors and destroy them •Some T helper cells b/c memory T cells @ infection is beat B lymphocytes •Activated by T helper cells which then multiply & transform into plasma cells •Plasma cells make large amts antibodies and release into blood (very specific process) •Some activated B cells transform into memory cells Antibodies in blood/bodily fluids •Made by B lymphocytes (compound of protein & sugar), creation provoked by antigens on germs •Detect germs and attach to them - must match exactly, like key in lock •Activate other immune system cells •Activate proteins that help in immune response
What are lymphocyte disorders?
Agammaglobulinemia •Genetic: x-linked or autosomal recessive disorder •Presentation: increased risk of infection w/ bacteria as well as enteroviruses & giardia Common variable immunodeficiency (CVID) •Low IgG levels w/ low IgA or IgM levels •Reduced number of memory B-cell subsets, mild T-cell lymphopenia •Presentation: at risk for infection (sinus/pulm/GI - recurrent diarrhea), autoimmunity, immune dysregulation, B-cell lymphomas Hyper-IgM syndrome •Genetic: most commonly X-linked d/t CD40L deficiency •Considered a combined immunodeficiency DiGeorge syndrome •Presentation: hypocalcemia, congenital heart disease, T-cell immunodeficiency, deletions on chromosome 22q11.2
What are other tests you can do for a work up of asthma in a child?
Allergy skin testing •Include in eval of all children w/ persistent asthma (not during exacerbation) •Positive skin test results correlate strongly to bronchial allergen provocation challenges, but skin tests are less risky •Indicates aeroallergens: pollens, mold, dust mite, pet dander Serum IgE testing •Less sensitive than skin testing •More expensive •Requires several days for results
What is the diagnostic work up of allergic rhinitis?
Allergy testing Skin tests (prick testing) •Immediate/accurate results •Positive tests correlate w/ nasal & bronchial allergen provocative challenges Serum IgE tests •Useful for scenarios of diffuse dermatitis, dermatographism, poor tolerance to skin testing •Not recommended to do broad screening test w/o considering symptoms •Cons: cost, not immediate results, reduced sensitivity compared to skin tests •CBC - eosinophils - not helpful •Total serum IgE - not helpful Nasal smear for eosinophils Pros: •Predictive of good clinical response to nasal corticosteroid sprays Cons: •Not sensitive •Not often done in clinical practice
What is an allergen?
An antigen that triggers an IgE response in genetically predisposed persons
What are common causes of anaphylaxis in children?
Anaphylaxis: Type I IgE-mediated reactions resulting from many causes
What is considered the "normal" child with recurrent infections?
Avg child: 4-8 respiratory infections/year •Mean duration of viral respiratory symptoms = 8 days •Can have symptoms for > 2 weeks •Ex: child has 10 viral resp infections/year - will have symptoms for almost 6 mo First 2 years of life: •No more than 1 episode of pneumonia or no more than 2 episodes of uncomplicated OM •Normal growth & development •Respond quickly to treatment •Recover completely •Appear healthy in between infections
What is the treatment for food allergies?
Avoidance •Educate HOW TO AVOID •Food label screening is priority •Educate WHEN TO INTIATE THERAPY if accidental ingestion occurs •If food allergen ingested & symptoms of IgE-mediated reaction occur - epinephrine & 911 •Antihistamines not advised as severity of rxn unpredictable Oral immunotherapy - ingesting increasing amts of food allergen to achieve desensitization •Pharmaceutic-grade peanut protein containing relevant allergens now FDA approved for oral immunotherapy in children 4-17 •Not a cure but mitigates allergic rxn if accidental ingestion Caregiver education •Encourage exclusive breastfeeding for first 4-6 mo in infant who is high-risk for atopic disease (or extensively hydrolyzed formula) •Introduce solids one at a time btw 4-6 mo of age •Maternal avoidance diets during pregnancy/lactation or avoidance of allergenic foods for infants > 6 mo - not proven in the literature •i.e., even for high-risk infant's early introduction of peanut into diet decreases development of peanut allergy Complications •Anaphylaxis -> death •Monitor patients on the growth chart and for nutritional deficiencies •2ndary to food avoidance •Children w/ multiple food allergies or one of food allergies is cow's milk
What is the treatment for allergic rhinitis?
Based on disease severity, impact on patient, what patient can/willing to do Patient education regarding: •Avoidance of triggers •Car windows up, house windows down •Pets that are indoor/outdoor off beds and furniture •Shower AM and PM - allergens 'stick' to us Pharmacologic therapies •Intranasal corticosteroids •Oral/intranasal antihistamines •Oral decongestants •Leukotriene modifiers Immunotherapy •Subq vs sublingual Complications •60% of kids with AR have symptoms of bronchial hyperresponsiveness (asthma)
What will you see at the age of onset with PIDDs?
Birth - 6 mo •Congenital neutropenia/other phagocyte defects - infections in first several months of life •Severe combined immunodeficiency (SCID)/other serious combined immunodeficiencies 6 mo - 2 years •Fall into 4 types of sick children we discussed previously •Immunodeficiencies present at 7-12 mo as maternal IgG disappears 2 years-6 years •Fall into 4 types of sick children we discussed previously •Less serious antibody deficiencies and combined immunodeficiencies present at this age 6-18 years •Unusual for recurrent infections to first present beyond 6 years of age •Defects of adaptive memory may present in young adulthood •CVID presents in adolescence •Think about HIV and other STIs in adolescent population presenting with recurrent infection •2 or > episodes of bacterial meningitis or sepsis à think complement or other innate immune defect
What are common food allergies in childhood that parents often are curious as to whether they will outgrow it?
Cow's milk allergic patients •w/ multiple other food allergies, asthma & allergic rhinitis Egg allergy only (no other atopic disease) •66% develop tolerance to egg by 5 yo If they do have other atopic disease •32% of those will still be sensitive to egg by 16 yo Soy and wheat allergy •Oral tolerance in 25-29% of kids by age 4 •Oral tolerance in 45-56% of kids by age 6 or 8 •Oral tolerance in 65-69% of kids by age 10 or 12 Peanut allergy •20% of kids outgrow their peanut allergy Tree nut allergy •9% of kids develop oral tolerance Seafood allergies •Typically follow you for life
What are neutrophil disorders?
Cyclic neutropenia •21-day cycles of low neutrophil counts that then recover Autoimmune neutropenia •Develops in children btw 5 and 24 months, may persist, responds to G-CSF Chronic granulomatous disease •d/t defective intracellular neutrophil killing of bacteria that produce catalase •-> recurrent infections with catalase-positive bacteria & fungi •Caused by abnormal phagocytosis-associated generation of microbicidal oxygen metabolites by neutrophils, monocytes, and macrophages
What is the treatment for insect allergies?
If positive specific IgE testing: •Benefit to immunotherapy •Administer venom immunotherapy to patients w/ hx of systemic life-threatening rxn fron insect sting + positive IgE serum testing. •Need autoinjector of epinephrine for rescue •Encourage to wear medical information jewelry/bracelet If only experience cutaneous symptoms do not require testing, immunotherapy or epinephrine since risk of life-threatening reaction low
What is the diagnostic work up of a food allergy?
IgE-mediated food allergy Skin testing •Choose what to test for based off history à •Can also monitor wheal size to predict if child has outgrown allergy In vitro serum IgE testing •Confirms clinical allergy found in skin testing •Various 'levels' or values determine how likely symptoms are to occur and help decide if food challenge necessary/safe/valuable Oral food challenge •Standard of diagnosis •Determine if child has developed oral tolerance to the food allergen Skin testing vs serum-specific IgE testing •Positive skin or serum testing alone does not equate clinical reactivity - interpret with history •Not a screening tool •History dictates what food allergens should be evaluated with skin test/serum test •Cannot predict severity of allergy or amount required to elicit reaction •Only risk for reaction can be inferred from positive test
What is the diagnostic work up for PIDDs?
Initial diagnostic work-up guided by type & location of infections + •CBC w/ differential à attention total absolute lymphocyte count •Lymphopenia suggestive of T cell deficiency •CMP •UA •ESR/CRP •IgG, IgM, IgA, IgE levels •Total complement measurement (CH50) if hx of sepsis or neisserial infection •HIV if delayed onset severe infection or unexplained lymphopenia •Antibody titers to vaccine antigens: tetanus, diptheria, pneumococcus Genetic testing •Gives definitive diagnosis, implications for treatment and long-term monitoring - performed by geneticist/specialist
What is the treatment for atopic dermatitis?
Lifestyle modifications Skin hydration* •Avoid irritant clothing (i.e., wool) •Avoid dry environments •Lukewarm baths, mild soaps [Cetaphil], pat dry, apply emollients immediately after Emollients and moisturizers •Ointments - most moisturizing •Aquaphor, Vaseline •Eucerin (cream) Controlling pruritis •Oral H1 antihistamines: 1st generation - diphenhydramine (Benadryl) , hydroxyzine •Oral H1 antihistamine: 2nd generation - fexofenadine (Allegra), cetirizine, (Zyrtec) or loratadine (Claritin) Pharmacological options: Topical corticosteroids* - mainstay of treatment •Low-potency corticosteroid cream or ointment (desonide 0.05%, hydrocortisone 2.5%) •Medium- to high-potency corticosteroids (fluocinolone 0.025%, triamcinolone 0.1%, betamethasone dipropionate 0.05%) Topical calcineurin inhibitors (immunomodulators) •pimecrolimus (Elidel) 1% cream, tacrolimus (Protopic ) 0.03 to 0.1% ointment Phosphodiesterase 4 inhibitor: crisaborole (Eucrisa) Monoclonal antibody inhibiting IL-4 and IL-13: dupilumab (Dupixent), tralokinumab Oral immunosuppressants : cyclosporine Non-pharmacological options: •Ultraviolet B (UVB) phototherapy
What is the treatment of insect allergies?
Local reactions •Clean site, apply cold compress, administer oral antihistamine, analgesics •Remove stinger promptly •Large local reaction - ddx cellulitis, less likely if occurring within 24-48 hours after sting •Oral corticosteroid X 4-5 days rather than abx (as you would for cellulitis) Systemic reactions •Epinephrine - cornerstone of therapy •Anaphylactic reaction - IM epinephrine asap, call 911 •Antihistamines can be given at same time as epi •Corticosteroids to prevent prolonged symptoms •Severe reactions •IV fluids, epinephrine, O2, respiratory support in ICU Prevention •Provide patients with epinephrine autoinjector •Referral to allergist •Instructions on how to prevent insect stings •Exterminating infested areas, avoid eating/drinking outdoors, wear long pants/shoes, avoid bright colored clothes, fragrances or hairspray •Note common insect repellants are NOT effective against Hymenoptera
What is serum IgE testing?
Measures level of antigen-specific IgE in serum •Example: type of immunoassay (ELISA), specifically ImmunoCAP System More useful in patient's with: •Dermatographism •Extensive dermatitis •Those that cannot discontinue medications (antihistamines) that interfere with skin testing Presence of specific IgE antibodies suggests sensitization but not sufficient for diagnosis of allergic disease •Use with entire clinical picture: H&P, presence of specific IgE antibodies and correlation with IgE-mediated symptoms
What are the symptoms of insect allergies?
Normal reactions to insect stings - 90% of children •Localized pain, swelling, erythema at sting site subsiding w/in 24 hours Late-phase, IgE-mediated reactions •Large local reactions - large swelling, contiguous to sting site that develops over 24-48 hours & resolves w/in 2-7 days •Most have similar reactions with subsequent stings
What are the symptoms of serum sickness?
Occur 7-21 days after administration of drugs, foreign proteins or infections •Onset of symptoms more rapid (w/in 1-4 days) in previously sensitized individuals •Fever •Polyarticular arthralgias •Lymphadenopathy •Cutaneous lesions - urticaria, angioedema, erythema multiforme, morbilliform rash, palpable purpura, serpiginous rash at interface of dorsal and palmar or plantar aspects hands/feet Rare complications: •Carditis •Glomerulonephritis •GBS (Guillian-Barre Syndrome) •Encephalomyelitis •Peripheral neuritis
What are important characteristics to know regarding a child with PIDDs as it relates to other illnesses?
Other illnesses: •Severity of childhood illnesses - roseola, febrile illnesses •Past hospitalizations, injuries, accidents, surgeries, prolonged school absences •ROS of other immune problems including allergies, anaphylaxis, arthritis, autoimmunity Family history: •Similar diseases in family, unexplained death, autoimmune disease •Inquire about consanguinity - many immunodeficiencies are autosomal recessive pattern Social history: •Home, parents' work environment, daycare explored for exposures to illness, allergens, tobacco, contaminated water supply, pets, farm animals, toxins, solvents or locale near industrial plant Infection history: •Age of onset, duration, frequency, sites, organisms cultured - if any, treatment, response to therapy• ***Any severe infection in an otherwise immunocompetent host is sufficient enough for an immunodeficiency work-up***
What is serum sickness?
Pathophysiology •Type III reaction hypersensitivity reaction where antibody binds to antigen forming immune complexes that cause vascular injury or end-organ damage Common inciting agents •Blood products •Foreign proteins - antivenoms •Medications - PCNs, sulfanamides, minocycline, cefaclor, hydantoins, thiazides Incidentally, availability of human-derived biologics, bioengineered antibodies & alternative pharmacotherapies significantly reduced incidence of serum sickness
What is the treatment of asthma?
Patient/caregiver education: •Environmental control of potential allergens •Reduction of exposure to nonspecific irritants such as 2nd hand tobacco smoke •Pharmacologic therapy options -> Vaccinations •Annual influenza •Pneumonia vaccine Pharmacologic Options Anti-inflammatory •Inhaled corticosteroids: short vs long •Lowest possible dose to control/minimize risk & impairment from disease •Aerochamber - 'spacer' •Best practice for children < 8 yo Other options - severe asthma •Long-acting beta2 agonists (adding to ICS may be more beneficial than doubling ICS dose), leukotriene modifiers (to try and minimize/off set steroid ICS use), biologic agents, anticholinergic agents, allergen immunotherapy, oral corticosteroids
What is the follow up to asthma in children?
Peak flow monitoring w/ written asthma action plan •Most helpful for self monitoring Rules of Two or > 1 MDI canister/month or daily use = poor control •Needs follow-up for adjustment of treatment plan •Re-evaluate after changes made to treatment plan w/in 4-6 weeks •Once asthma controlled reassess q 1-6 mo Asthma needs to be controlled at least 3 mo before attempting to 'step-down' therapy Exacerbations •Administration of short acting bronchodilators •Course of systemic corticosteroids Complications •Status asthmaticus - requires supplemental oxygen, continuous bronchodilation, IV corticosteroids, blood gas monitoring, magnesium sulfate and/or hospitalization
What is the asthma approach to therapy in children?
Stepwise approach (involving step-up or step-down in therapy based on control of symptoms) •Short-acting bronchodilator (i.e., albuterol/levalbuterol) for everyone Rules of Two: daytime symptoms occurring 2 or more times per week or nocturnal awakenings 2 or more times per month = need for daily anti-inflammatory medication •Step 2: Low-dose long-acting inhaled corticosteroid
What are insect allergies?
Stinging insect hypersensitivity - an allergic reaction to Hymenoptera •Includes bees, yellow jackets, wasps, hornets, fire ants •Biting insects such as kissing bugs, bed bugs, blackflies, and deerflies have also caused anaphylaxis •Typically, insect sting allergy manifests after several uneventful stings In children large local reactions are more common •Reactions in adults generally more severe à can lead to death
What are the symptoms of allergic rhinitis?
Symptoms •Clear rhinorrhea •Nasal congestion/obstruction •Pruritis of the eyes, ears, nose and palate •Sneezing •Lacrimation/conjunctival injection •Postnasal drainage (PND) -> cough Physical Exam Findings HEENT exam •Pale/bluish boggy and edematous turbinate's w/ clear watery secretions •'Allergic salute' •Lymphoid hyperplasia of posterior oropharynx and/or visible mucous •'Allergic shiners' •'Dennie Morgan lines' •Retracted TM from ETD (Serous OM) Skin exam - look of evidence of atopic dermatitis Lung exam - asthma may coexist
What is the clinical presentation of asthma?
Symptoms Cough SOB •Chest tightness •Breathlessness •Dyspnea on exertion (DOE)/exercise intolerance Wheezing Note: 1/3 of children DO NOT wheeze d/t poor aeration from airway obstruction •Asymptomatic periods between exacerbations •Nocturnal symptoms common Physical Exam Findings •Increased RR (tachypnea) •Tachycardia •Prolonged expiratory phase •Decreased O2 sats •Acute exacerbations Severe episodes •Pulsus paradoxus •Retractions •Cyanosis •Agitation •Inability to speak •Tripoding •Diaphoresis
What are the symptoms of drug reactions?
Symptoms/PE findings •Immediate (anaphylactic) reaction - occurs w/in 60 min of administration •Accelerated reaction - 1-72 hours after administration •Dermatologic manifestation - rash •Serum sickness reaction •Late reaction - after 72 hours •Dermatologic manifestation - desquamating dermatitis, SJS, TEN, serum sickness Skin prick testing best way to determine if true IgE-mediated rxn and supports diagnosis of type I hypersensitivity reaction •Available for penicillin, local anesthetics, muscle relaxants, vaccines, insulin •Not for most other medications •If skin testing positive - avoid PCN •Drug challenges & drug desensitization are possible if PCN absolutely needed
How do you manage PIDDs?
Treatment - tailored to specific diagnosis •Infections promptly recognized & aggressively treated Empiric abx therapy pending cx •Prophylactic and/or post-exposure abx administered depending on type of d/o •Only irradiated, leukocyte-filtered, virus-inactivated products used if blood/platelet transfusions needed Additional recommendations: •No live-virus vaccines (MMR, varicella, OPV, rotavirus, intranasal influenza) •Patient w/ SCID, family members should not receive live viral vaccines •Clean water sources - boiling water •Bottled water not acceptable •All blood products given to patients with PIDDs need to be cytomegalovirus (CMV) negative & irradiated •Limit sick contacts
What is considered the "child with immunodeficiency " with recurrent infections?
•Can have a defect in one or more components of the immune system Adaptive immune system components: •B cells (humoral antibody system) •T cells (cellular system) Innate immune system components: •Phagocytic cell system Complement system
What is the diagnostic work up of serum sickness?
•ESR - elevated •CBC - thrombocytopenia •Complement levels (C3, C4) - depressed Skin biopsy •Immune deposits of IgM, IgA, IgE or C3 •UA - proteinuria, hematuria or both Diagnosis made by: •Hx of exposure to inciting agent •Characteristic history/PE findings •Labs showing circulating immune complexes & depressed complement levels
What are the clinical manifestations of PIDDs?
•Family hx of immunodeficiency or unexplained early death (b/f age 30) •Failure to thrive •Need for IV abx and/or hospitalization to clear infection •6 or more ear or respiratory tract infections w/in 1 year •2 or more serous sinus infections or pneumonias w/in 1 year •4 or more new ear infections w/in 1 year •2 or more episodes of sepsis or meningitis in a lifetime •2 more more months of antibiotics w/ little effect •Recurrent or resistant oral or cutaneous candidiasis •Recurrent deep skin or organ abscesses •Infection caused by unusual microbial organism and/or in unusual location •Complications from live vaccine (rotavirus, varicella, bcg vaccine) •Chronic diarrhea •Nonhealing wounds •Extensive skin lesions •Persistent lymphopenia •Unexplained autoimmunity or fevers • Granulomas •Hemophagocytic lymphohistiocytosis •Lymphoma in childhood •Features typical of syndromic PIDs
What is keratosis pilaris?
•Highly associated w/ atopic dermatitis •Asymptomatic •Horny follicular papules on extensor surfaces of arms
What is the birth history of PIDD kids?
•Maternal illness (HIV, CMV), risky behaviors, exposure to toxins, rx meds, illicit drugs, tobacco, alcohol -> increased risk 2ndary immunodeficiency •Length of gestation, birth weight, neonatal problems (jaundice, resp distress, need for NICU), need for transfusions should be recorded •Feeding hx including food intolerance, duration of breastfeeding, possible hx of GERD (could predispose to aspiration pneumonia) reviewed •Delayed detachement of umbilical cord -> persistent attachment > 30 days suggestive of leukocyte-adhesion defect •Newborn screening for PIDDs -> often detects SCID in normal appearing newborns
What is the diagnostic work up of acute urticaria and angioedema?
•No specific lab work-up •Clinical diagnosis Recurrent angioedema without urticaria: •Evaluate for HAE with complement levels (C1, C4)
What is severe combined immunodeficiency (SCID)?
•Occurs b/c of mutations of several genes whose products are crucial for development & function of both T cells, B cells and natural killer cells Occurs in 1st year of life •Early death d/t overwhelming infection if not diagnosed promptly •Newborn screening UNIVERSAL in US for T cell deficiency (via dried blood spots or DBS) •w/o screening diagnosis is not made until 1 or > severe infections Infants appear 'normal' at birth/early infancy •Maternal IgG antibodies are transferred prenatally & provide protection for initial months of life as well as the fact that young infants are initially cocooned often If not diagnosed in infancy, they develop: •Recurrent infections d/t bacteria, viruses, fungi & opportunistic pathogens •Presentation: failure to thrive, severe bacterial or viral infections, chronic diarrhea, eczema-like skin rash, absent lymphoid tissue •CXR: absent thymic shadow •CBC w/ diff: absolute lymphocyte count very low Treatment : •Hematopoietic stem cell transplantation (HSCT) -> cure •Best w/in first 3 mo of life or b/f onset of SCID associated chronic infections •Protective measures •Isolation from sick contacts, IGIV, antimicrobial prophy, no live-virus vaccines
What is considered the "child with chronic disease" with recurrent infections?
•Poor growth/failure to thrive •Sickly appearance PE findings c/w chronic disease •Cystic fibrosis •GERD •Congenital heart disease •Chronic aspiration •Think about underlying anatomic defect •Barrier failure, inadequate clearance of secretions, obstruction, CV problems, FB, resistant organisms, continuous reinfection