Allergy & Immunology

01 The Immune System — Essentials

Allergy and immunology sits at the intersection of two problems that look opposite but share the same machinery: an immune system that reacts to things it should tolerate (allergy, hypersensitivity, autoimmunity), and an immune system that fails to respond to things it should fight (immunodeficiency). Understanding how the immune system is supposed to work is the foundation for every note you will write in this clinic.

Innate vs Adaptive Immunity

The innate immune system is the first responder: neutrophils, macrophages, natural killer (NK) cells, dendritic cells, complement proteins, and the physical barriers of skin and mucosa. It reacts within minutes to hours using pattern recognition receptors (toll-like receptors, NOD-like receptors) that identify conserved microbial signatures. The adaptive immune system is slower (days to weeks) but specific and memory-forming: B cells produce antibodies, T cells recognize peptide antigens presented by MHC molecules. Most immunologic disease in the clinic involves dysregulation of one or both arms.

T Cells, B Cells, and Antibodies

T cells mature in the thymus and are classified by surface markers and function: CD4+ helper T cells (Th1 drives intracellular infection response and IFN-γ, Th2 drives allergy and IL-4/IL-5/IL-13, Th17 drives extracellular bacteria/fungi and IL-17, Treg suppresses), and CD8+ cytotoxic T cells that kill virally infected or malignant cells. B cells mature in the bone marrow, recognize antigen through surface immunoglobulin, and after activation differentiate into plasma cells that secrete antibodies. The five immunoglobulin isotypes — IgG (dominant serum antibody, crosses placenta), IgA (mucosal), IgM (first antibody produced), IgE (allergy, parasites), and IgD (B cell receptor) — each have distinct roles you will document repeatedly.

The Gell & Coombs Hypersensitivity Framework

Almost every allergic disease you will document maps to one of four classical hypersensitivity mechanisms, and the physician will frequently reference them by number:

The Atopic March

A scribe will frequently hear the phrase atopic march: the tendency of atopic disease to progress through childhood in a predictable sequence — atopic dermatitis in infancy, food allergy in early childhood, allergic rhinitis in mid-childhood, and asthma later. A positive family history of atopy and early-onset severe eczema are the strongest predictors. Document atopy carefully because it shapes risk assessment and therapy decisions.

02 Scribe Documentation Framework

Allergy/immunology encounters come in a few distinct flavors, and each has its own documentation rhythm. You need to recognize the visit type within the first minute and start pre-populating the correct template.

Encounter Types

• New consult — the most common. A patient is referred for suspected allergy, unexplained anaphylaxis, recurrent infections, chronic urticaria, or drug reaction. Expect a long, detailed HPI and a full review of prior testing and trigger exposures.
• Follow-up — monitoring symptom control, biologic response, immunotherapy progress, or lab trends in a known immunodeficiency.
• Skin test visit — focused around a procedure (prick, intradermal, patch). Document the panel, reaction sizes, controls, and interpretation.
• Drug challenge / desensitization — procedure-based visit documented with incremental doses, vitals, and any reactions.
• Immunotherapy build-up / maintenance — weekly or monthly shot visits.
• Biologic infusion / injection — omalizumab, mepolizumab, dupilumab, etc. Documented with dose, site, pre/post vitals, tolerance.

The Allergy HPI

A high-quality allergy HPI differs from a generic HPI because the diagnosis often hinges on timing, exposure, and pattern. Document these elements for every reaction:

PID HPI — The Infection History

For primary immunodeficiency consults, the HPI is effectively an infection catalog. Capture frequency, severity, organism (when cultured), sites (sinopulmonary, GI, skin, deep/visceral), hospitalizations, IV antibiotic courses, and unusual organisms (Pneumocystis, atypical mycobacteria, invasive candida, opportunists). Document whether infections respond normally to antibiotics or recur promptly after stopping.

03 Allergic Rhinitis & Conjunctivitis Upper Airway

Allergic rhinitis (AR) is the highest-volume diagnosis in most allergy clinics, affecting 10–30% of adults and up to 40% of children. It is IgE-mediated inflammation of the nasal mucosa triggered by aeroallergens (pollens, dust mites, pet dander, molds, cockroach). Though often dismissed as trivial, uncontrolled AR drives sinusitis, otitis media with effusion, worsens asthma, and causes enormous productivity loss.

Pathophysiology

Sensitization occurs when inhaled allergen is processed by dendritic cells, presented to Th2 cells, and drives IgE production. On re-exposure, allergen cross-links mast cell surface IgE, releasing histamine, tryptase, leukotrienes, and prostaglandins — causing the early phase (minutes: sneezing, itching, rhinorrhea). Cytokine-driven recruitment of eosinophils and basophils produces a late phase (4–8 hours later: congestion, persistent symptoms).

Clinical Presentation

The classic tetrad: sneezing, rhinorrhea, nasal itching, and congestion, often with ocular itching, tearing, redness (allergic conjunctivitis), and postnasal drip. Physical findings include pale or violaceous boggy turbinates, clear rhinorrhea, allergic shiners (infraorbital darkening), the allergic salute (transverse nasal crease from rubbing), and cobblestoning of the posterior pharynx. Seasonal AR is driven by pollens (tree in spring, grass in early summer, ragweed/weed in fall). Perennial AR is driven by indoor allergens (dust mite, pet, cockroach, mold).

Classification (ARIA)

Diagnostic Workup

Diagnosis is clinical but confirmed with specific IgE testing — either skin prick testing or serum specific IgE (ImmunoCAP) to the suspected aeroallergens. A panel usually includes regional trees, grasses, weeds, dust mite (Dermatophagoides pteronyssinus and D. farinae), cat, dog, cockroach, and relevant molds (Alternaria, Cladosporium, Aspergillus, Penicillium).

Management

Stepwise therapy per the Joint Task Force 2017 Rhinitis Practice Parameter: allergen avoidance, intranasal corticosteroids (the most effective monotherapy), oral or intranasal second-generation antihistamines, intranasal antihistamines, leukotriene receptor antagonists (with a boxed warning on montelukast for neuropsychiatric effects), and allergen immunotherapy (SCIT or SLIT) for moderate/severe disease unresponsive to pharmacotherapy or as disease-modifying therapy. Intranasal ipratropium helps rhinorrhea; saline irrigation is cheap and effective adjunctive therapy.

04 Asthma (Allergy Perspective) Lower Airway

Asthma is co-managed by allergy and pulmonology. Allergy clinics see asthma primarily when it is allergic-phenotype, uncontrolled on step-up therapy, or a candidate for biologics. GINA 2024 guidelines are the current standard.

Pathophysiology & Phenotypes

Chronic airway inflammation drives bronchial hyperresponsiveness, reversible bronchoconstriction, mucus hypersecretion, and airway remodeling. The two broad phenotypes are Type 2-high (eosinophilic, IgE-driven, allergic, often atopic, biologic-responsive) and Type 2-low (neutrophilic or paucigranulocytic, often obesity-associated, less biologic-responsive).

Severity & Control

Workup & Management

Diagnosis is confirmed by spirometry showing reversible obstruction (FEV1 increase ≥12% and ≥200 mL post-bronchodilator). Allergy clinic specifics: FeNO (fractional exhaled nitric oxide, >25 ppb suggests Type 2 inflammation, >50 ppb strongly so), peripheral eosinophil count, total and specific IgE, and aeroallergen skin testing. Management follows GINA steps 1–5; severe asthma uncontrolled on medium-high dose ICS-LABA triggers biologic consideration (see Section 17).

05 Atopic Dermatitis Cutaneous

Atopic dermatitis (AD, eczema) is a chronic relapsing inflammatory skin disease — the first step on the atopic march. Allergy is often consulted for moderate-severe AD to evaluate allergic triggers, consider systemic therapy, and differentiate allergic from non-allergic skin disease.

Pathophysiology

Dual defect: a compromised skin barrier (often filaggrin loss-of-function mutations, reduced ceramides) and Th2-skewed inflammation (IL-4, IL-13, IL-31 — the itch cytokine). The barrier defect allows allergen and microbe penetration, triggering immune activation; the inflammation worsens the barrier, creating a vicious cycle.

Clinical Presentation

Infants: facial and extensor surface erythematous, weeping plaques. Children and adults: flexural (antecubital, popliteal, neck, wrists, ankles) lichenified plaques with excoriation. Intense pruritus is the defining symptom. Complications include impetiginization (S. aureus), eczema herpeticum (disseminated HSV, a dermatologic emergency), and molluscum.

Management

Trigger avoidance, daily emollients, topical corticosteroids (appropriate potency for body site), topical calcineurin inhibitors (tacrolimus, pimecrolimus), topical PDE4 inhibitor (crisaborole), topical JAK inhibitor (ruxolitinib). For moderate-to-severe disease unresponsive to topicals, systemic options include dupilumab (anti-IL-4Rα, approved down to age 6 months), tralokinumab (anti-IL-13), lebrikizumab, and oral JAK inhibitors (abrocitinib, upadacitinib) per the 2023 AAAAI/ACAAI JTF Atopic Dermatitis Guidelines.

06 Urticaria & Angioedema Cutaneous/Mucosal

Urticaria (hives) and angioedema frequently coexist but have distinct differential diagnoses and management. Getting the subtype right is critical because it drives whether the physician orders C1 esterase inhibitor levels, pursues autoimmune workup, or starts omalizumab.

Urticaria Subtypes

Individual wheals last <24 hours; lesions lasting >24 hours or leaving bruising suggest urticarial vasculitis and require biopsy.

Angioedema Subtypes

Histaminergic (mast cell mediated, usually with urticaria): responds to antihistamines and epinephrine. Bradykinin-mediated (isolated, no urticaria, often laryngeal or GI, poorly responsive to epinephrine): includes hereditary angioedema (HAE) and ACE inhibitor-induced angioedema. HAE is caused by C1 inhibitor deficiency (Type I: low quantity) or dysfunction (Type II: normal quantity, low function), or is HAE with normal C1-INH (Type III, often F12 mutations).

Workup

CSU: CBC with differential, ESR/CRP, TSH and thyroid antibodies, basic chemistries; escalate only if history suggests secondary cause. Isolated angioedema: C4 (low in all HAE types during and between attacks), C1 esterase inhibitor antigenic level, C1 esterase inhibitor functional level, C1q (low in acquired C1-INH deficiency).

Management

CSU follows the EAACI/GA²LEN Urticaria Guideline stepwise approach: second-generation H1 antihistamine at standard dose, up-dose to 4× standard, add omalizumab, then consider cyclosporine. Avoid chronic systemic steroids. HAE on-demand therapy includes C1 esterase inhibitor concentrates (Berinert, Cinryze, Ruconest), icatibant (bradykinin B2 receptor antagonist), and ecallantide. Long-term prophylaxis: lanadelumab (anti-kallikrein mAb), berotralstat (oral kallikrein inhibitor), or C1-INH replacement.

07 Anaphylaxis Emergency

Anaphylaxis is the highest-acuity allergy diagnosis and the one the attending will care most about documenting precisely. Miss an anaphylaxis diagnosis and the patient does not get epinephrine auto-injectors, an action plan, or proper follow-up — decisions with life-or-death consequences.

Definition — WAO 2020 Criteria

Anaphylaxis is highly likely when any one of the following criteria is fulfilled per the World Allergy Organization 2020 Anaphylaxis Guidance:

Ring & Messmer Severity Grading

The Brighton Collaboration case definition provides a 3-level diagnostic certainty framework (Levels 1–3) used in vaccine safety surveillance and research.

Management

Intramuscular epinephrine 0.01 mg/kg (max 0.5 mg adult, 0.3 mg pediatric) into the anterolateral thigh is the first and only life-saving drug — antihistamines and steroids are adjuncts. Supine positioning with legs elevated (unless respiratory compromise dictates otherwise), IV fluids, oxygen, H1 and H2 antihistamines, bronchodilators for wheezing, and glucagon for patients on beta-blockers. Observation period: 2020 AAAAI/ACAAI JTF Anaphylaxis Practice Parameter Update recommends individualized observation (minimum 1 hour for mild, longer for severe, biphasic-risk, or multiple epinephrine doses). Biphasic reactions occur in up to 5% within 1–72 hours.

Scribe Documentation Tips

When documenting the ED or clinic anaphylaxis note, explicitly list which WAO criterion was met. Do not write "possible anaphylaxis" — the physician wants either "meets criteria for anaphylaxis per WAO criterion X" or "does not meet criteria." Also document the exact number of epinephrine doses, the time each was administered, the route (IM thigh vs IV), and the clinical response after each dose. Order a serum tryptase ideally between 15 minutes and 3 hours after symptom onset; baseline tryptase is drawn >24 hours later.

08 Food Allergy & Food Intolerance Immunologic

Food allergy affects ~8% of children and ~10% of adults. The NIAID Expert Panel Food Allergy Guidelines (Sampson criteria) and the AAAAI/ACAAI JTF Food Allergy Practice Parameter are the standard references.

Categories of Adverse Food Reactions

• IgE-mediated food allergy — immediate hypersensitivity (minutes to 2 hours). Top 9 allergens: milk, egg, wheat, soy, peanut, tree nut, fish, shellfish, sesame.
• Non-IgE cell-mediated — food protein-induced enterocolitis syndrome (FPIES, delayed profuse vomiting 1–4 hours after trigger, often with pallor and lethargy), food protein-induced proctocolitis, celiac disease.
• Mixed — eosinophilic esophagitis (EoE), atopic dermatitis with food triggers.
• Oral allergy syndrome (pollen-food allergy syndrome) — cross-reactive IgE between pollen proteins and labile fruit/vegetable proteins (e.g., birch-apple, ragweed-melon). Symptoms are limited to oral pruritus and mild lip swelling and rarely progress to anaphylaxis.
• Alpha-gal syndrome — delayed (3–6 hours) anaphylaxis to mammalian meat after tick bite sensitization to galactose-α-1,3-galactose.
• Non-immunologic intolerance — lactose intolerance, food additive reactions, scombroid poisoning.

Workup

History is primary. Skin prick testing and specific IgE provide sensitization data but not clinical reactivity; test only for foods suggested by history. Component-resolved diagnostics (e.g., Ara h 2 for peanut, Cor a 14 for hazelnut, Ana o 3 for cashew) improve specificity. Oral food challenge remains the gold standard. Basal tryptase if systemic reaction. For FPIES: no IgE testing; diagnosis is clinical per the International FPIES Consensus Guidelines.

Management

Strict avoidance, epinephrine auto-injectors for IgE-mediated, emergency action plan, nutrition referral. Peanut oral immunotherapy (Palforzia) is FDA-approved for ages 4–17 to reduce the severity of reactions from accidental exposure. Early peanut introduction per LEAP trial has changed pediatric prevention.

09 Drug Hypersensitivity Immunologic

Drug reactions span all four Gell & Coombs types. The most common clinic scenarios are penicillin allergy evaluation (often delabeling), NSAID reactions, sulfa allergy evaluation, perioperative anaphylaxis workup, and delayed cutaneous reactions. The 2022 AAAAI/ACAAI JTF Drug Allergy Practice Parameter is the current standard.

Penicillin Allergy

Approximately 10% of Americans carry a penicillin allergy label, but >90% of them are not truly allergic on formal testing. Delabeling improves antibiotic selection, reduces C. difficile, MRSA, and hospital costs. Evaluation uses history stratification (high-risk features include anaphylaxis, SJS/TEN, DRESS, interstitial nephritis, hemolytic anemia), skin prick and intradermal testing with major (PPL — benzylpenicilloyl polylysine, Pre-Pen) and minor (penicillin G) determinants, followed by oral amoxicillin challenge if skin testing is negative. Low-risk patients with distant reactions can often proceed directly to direct oral amoxicillin challenge.

NSAID Hypersensitivity

Multiple mechanisms: COX-1 inhibition causing leukotriene shunting (NERD — NSAID-exacerbated respiratory disease, the Samter's triad of asthma, nasal polyps, and NSAID-induced respiratory reactions); cross-reactive urticaria/angioedema (NIUA); single NSAID IgE-mediated reactions; delayed T-cell reactions. Documentation must specify the drug, dose, timing, and reaction phenotype.

Severe Cutaneous Adverse Reactions (SCARs)

DRESS (drug reaction with eosinophilia and systemic symptoms — latency 2–8 weeks, fever, rash, eosinophilia, hepatitis, lymphadenopathy), SJS/TEN (Stevens-Johnson syndrome/toxic epidermal necrolysis — mucocutaneous blistering with skin detachment), AGEP (acute generalized exanthematous pustulosis). These are Type IV reactions; skin testing and challenge are contraindicated. Drug provocation testing is absolutely contraindicated in SCAR history.

Perioperative Anaphylaxis

Most commonly caused by neuromuscular blocking agents (rocuronium, succinylcholine), antibiotics, chlorhexidine, latex, blue dyes (isosulfan blue), and less commonly induction agents or opioids. Workup includes tryptase at the event, repeat at 1–2 hours and >24 hours, then comprehensive skin testing 4–6 weeks later. Desensitization is performed for essential drugs when no alternative exists — documentation must include incremental doses, vital signs at each step, and any breakthrough symptoms.

10 Insect Sting (Venom) Allergy Immunologic

Stinging Hymenoptera include honeybee, yellow jacket, wasp, hornet, and fire ant. Reactions range from normal local swelling to large local reactions to systemic anaphylaxis. Systemic reactions carry a ~30–60% risk of recurrence without treatment, dropping to <5% with venom immunotherapy.

Mueller Grading of Systemic Sting Reactions

Workup & Management

Skin testing to venom extracts (honeybee, yellow jacket, yellow hornet, white-faced hornet, wasp — fire ant uses whole-body extract) 4–6 weeks after the reaction; if negative, specific IgE and a repeat in 4–6 weeks. Baseline tryptase is mandatory because elevated tryptase suggests underlying mast cell disease and indicates lifelong VIT. Venom immunotherapy (VIT) is indicated for patients with systemic reactions and positive testing; protocols include conventional (15–20 weekly build-up visits), cluster, and rush protocols. Maintenance is typically 5 years, longer if high risk.

11 Latex & Contact Allergies Cutaneous

Latex allergy is IgE-mediated hypersensitivity to natural rubber latex proteins; high-risk groups include healthcare workers, children with spina bifida (repeated surgical exposure), and workers with occupational latex exposure. Symptoms range from contact urticaria to anaphylaxis. Management is strict latex avoidance (latex-free gloves, operating environments) and cross-reactive food avoidance (banana, avocado, kiwi, chestnut — the latex-fruit syndrome).

Allergic contact dermatitis is a Type IV reaction. Common culprits: nickel, fragrance mix, balsam of Peru, neomycin, bacitracin, formaldehyde, rubber accelerators (thiurams, carbamates), para-phenylenediamine (PPD, hair dye), methylisothiazolinone (MI, cosmetics). Diagnosis is by patch testing with standardized allergen panels (T.R.U.E. Test, NACDG panel); readings at 48 and 96 hours (and sometimes day 7). Management is identification and strict avoidance, topical steroids for flares, and a Contact Allergen Management Program (CAMP) list of safe products.

12 Eosinophilic Disorders Inflammatory

Eosinophilic Esophagitis (EoE)

Chronic, immune-mediated esophageal disease with eosinophil-predominant inflammation causing dysphagia, food impaction, chest pain, GERD-like symptoms, and in children feeding difficulties. Diagnosis: endoscopy with biopsy showing ≥15 eosinophils/HPF after excluding other causes. Allergy involvement includes food allergy evaluation; although skin testing and specific IgE have poor predictive value, empiric elimination diets (6-food, 4-food, or 2-food) are a core management strategy alongside PPIs, swallowed topical steroids (budesonide oral suspension, fluticasone), and dupilumab (FDA-approved for EoE).

Hypereosinophilic Syndrome (HES)

Persistent eosinophilia >1,500/µL with end-organ involvement. Variants include myeloproliferative (FIP1L1-PDGFRA fusion, imatinib-responsive), lymphocytic, familial, idiopathic, and overlap with EGPA. Workup includes peripheral smear, flow cytometry, tryptase, B12, vitamin B12, cardiac eval (echo, troponin), skin/tissue biopsy, and molecular studies.

EGPA (Churg-Strauss)

Eosinophilic granulomatosis with polyangiitis: asthma + eosinophilia >10% + systemic vasculitis affecting sinuses, lung, heart, skin (palpable purpura), GI, peripheral nerves (mononeuritis multiplex). ANCA-positive in ~40% (p-ANCA/MPO). Treated with systemic steroids, mepolizumab (anti-IL-5, FDA-approved for EGPA), and in severe disease cyclophosphamide or rituximab.

13 Mast Cell Disorders Inflammatory

Mastocytosis

Clonal mast cell proliferation. Cutaneous mastocytosis: skin-limited, most common in children, includes urticaria pigmentosa (maculopapular cutaneous mastocytosis) and mastocytoma. Systemic mastocytosis: bone marrow and other organ involvement, almost always harbors a KIT D816V mutation; subtypes include indolent SM, smoldering SM, SM with associated hematologic neoplasm (SM-AHN), aggressive SM, and mast cell leukemia. WHO criteria require 1 major (multifocal dense mast cell infiltrates) plus 1 minor, or 3 minor criteria (atypical morphology, KIT D816V, aberrant CD25/CD2/CD30, persistent tryptase >20 ng/mL excluding AHN).

Mast Cell Activation Syndrome (MCAS)

Consensus criteria (Valent): (1) typical episodic multisystem symptoms consistent with mast cell mediator release, (2) objective evidence of mast cell activation (rise in tryptase ≥20% above baseline plus 2 ng/mL within 4 hours of symptoms), and (3) response to mast cell-targeted therapy. Management: trigger avoidance, H1 and H2 antihistamines, leukotriene modifiers, cromolyn, and in select cases omalizumab or avapritinib (KIT inhibitor).

14 Primary Immunodeficiency Diseases Immunodeficiency

More than 450 inborn errors of immunity are now recognized. The clinic sees a handful frequently: CVID, selective IgA deficiency, specific antibody deficiency, X-linked agammaglobulinemia (XLA), chronic granulomatous disease (CGD), complement deficiencies, and in pediatric practice SCID and DiGeorge.

Common Variable Immunodeficiency (CVID)

Most common symptomatic primary antibody deficiency in adults. Recurrent sinopulmonary infections, bronchiectasis, GI disease (nodular lymphoid hyperplasia, chronic diarrhea, giardia), autoimmunity (ITP, AIHA), granulomatous disease, and increased malignancy risk (lymphoma, gastric cancer).

Selective IgA Deficiency

Serum IgA <7 mg/dL with normal IgG and IgM; the most common PID (~1:600). Most are asymptomatic; a subset has recurrent sinopulmonary infection, autoimmunity, atopy, or anti-IgA antibodies that predispose to anaphylaxis with blood products. No specific treatment for the deficiency itself.

X-Linked Agammaglobulinemia (Bruton)

BTK mutation, absent B cells, very low all immunoglobulin classes. Boys present after 6 months as maternal IgG wanes, with severe encapsulated bacterial infections and enteroviral disease. Treat with lifelong Ig replacement.

SCID

Severe combined immunodeficiency — profound T-cell (± B, ± NK) deficiency. Presents in infancy with failure to thrive, persistent diarrhea, thrush, opportunistic infection. SCID is on the universal newborn screen via TREC (T-cell receptor excision circles). Treatment is hematopoietic stem cell transplant (the earlier, the better), gene therapy for selected subtypes, and PEG-ADA for ADA-SCID. Avoid live vaccines and irradiate/CMV-negative blood products.

Chronic Granulomatous Disease (CGD)

Defect in NADPH oxidase (most commonly X-linked gp91phox). Neutrophils phagocytose but cannot kill catalase-positive organisms (Staph aureus, Serratia, Burkholderia cepacia, Nocardia, Aspergillus). Patients develop recurrent abscesses, lymphadenitis, pneumonia, osteomyelitis, and granulomatous inflammation. Dihydrorhodamine (DHR) flow cytometry is the diagnostic test. Treat with antibacterial prophylaxis (TMP-SMX), antifungal prophylaxis (itraconazole), IFN-γ, and HSCT.

Complement Deficiencies

Early complement deficiencies (C1, C2, C4) associate with lupus-like autoimmunity. Late complement deficiencies (C5–C9, properdin, factor D) associate with recurrent Neisseria infections. Screen with CH50 (classical pathway) and AH50 (alternative pathway).

DiGeorge (22q11.2 Deletion)

CATCH-22: Cardiac anomalies, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia. T-cell deficiency severity varies from partial (mild) to complete DiGeorge (SCID-like, requiring thymic or HSCT transplantation).

15 Secondary Immunodeficiency & ALPS Immunodeficiency

Secondary immunodeficiency is far more common than PID. Causes include medications (rituximab, steroids, chemotherapy, anti-seizure drugs), protein loss (nephrotic syndrome, protein-losing enteropathy), malignancy (CLL, multiple myeloma, lymphoma), infection (HIV), malnutrition, and post-transplant immunosuppression. Workup mirrors PID (quantitative immunoglobulins, lymphocyte subsets, vaccine response) but management focuses on reversing the underlying cause and providing Ig replacement or prophylactic antibiotics as indicated.

Autoimmune lymphoproliferative syndrome (ALPS) is a FAS pathway disorder characterized by chronic nonmalignant lymphadenopathy, splenomegaly, autoimmune cytopenias, elevated double-negative T cells (CD3+CD4-CD8-TCRαβ+), and increased lymphoma risk. Treated with immunosuppression (sirolimus, mycophenolate) and splenectomy avoided when possible due to sepsis risk.

16 Allergy/Immunology Procedures Procedures

Skin Prick Testing (SPT)

A drop of standardized allergen extract is placed on the skin (volar forearm or back) and a lancet introduces the allergen into the epidermis. Positive control = histamine; negative control = saline/glycerin. Read at 15–20 minutes. A wheal ≥3 mm larger than saline is considered positive. Antihistamines must be held 5–7 days prior. Document the panel, wheal/flare sizes for each allergen, positive and negative control results, any systemic reactions, and the interpretation.

Intradermal Testing

A small volume (0.02–0.05 mL) of diluted allergen (typically 100–1,000× more dilute than SPT concentrate) is injected intradermally. More sensitive but less specific than SPT; used primarily for venom and drug allergy evaluation, not aeroallergens (high false-positive rate).

Patch Testing

Standardized allergen panels (T.R.U.E. Test 36 allergens, NACDG 80 allergens, or custom series) are applied to the upper back under occlusive chambers. Patches remain in place for 48 hours, then are removed and read at 48 and 96 hours (some allergens require day 7 reading). Reactions are graded: +/- (doubtful), + (weak, erythema, non-vesicular), ++ (strong, edema, vesicles), +++ (extreme, bullous), IR (irritant).

Drug Challenges & Desensitization

Graded drug challenge is the gold standard to rule out drug allergy in low-risk patients: typically 1/10 then full dose with 30-minute observation. Desensitization (temporary tolerance induction) is used when the drug is essential and allergy confirmed; protocols involve 12–16 incremental doubling doses over hours with close monitoring. Document every dose, time, and vital signs.

Oral Food Challenge

The gold standard for diagnosing or excluding food allergy. Performed in a monitored setting with graded doses (typically eighths of a full serving every 15–20 minutes), observation for 2 hours after the final dose. Document dose, time, cumulative amount, symptoms, vitals, treatment, and interpretation.

Venom & Aeroallergen Immunotherapy

See Section 17. Procedural documentation includes extract, vial number/color, dose volume, concentration, injection site, pre/post vital signs, local and systemic reaction.

Skin Biopsy

Performed for urticarial vasculitis (lesions lasting >24 hours, bruising, pain), suspected mastocytosis (stain for tryptase, CD25, CD117), and unclear cutaneous eruptions. Punch biopsy (3–4 mm) is the typical technique.

17 Immunotherapy & Biologics Treatment

Subcutaneous Immunotherapy (SCIT) & Sublingual Immunotherapy (SLIT)

Allergen-specific immunotherapy is the only disease-modifying treatment for allergic rhinitis, allergic asthma, and stinging insect allergy. SCIT involves a build-up phase (weekly for 3–6 months, escalating concentration and volume) and a maintenance phase (every 2–4 weeks for 3–5 years). SLIT uses FDA-approved tablets (grass: Grastek, Oralair; ragweed: Ragwitek; dust mite: Odactra) taken daily. The 2011 AAAAI/ACAAI Immunotherapy Practice Parameter is the current standard.

Biologics in Allergy & Immunology

Hereditary Angioedema Agents

• C1 esterase inhibitor concentrates — Berinert (IV, on-demand), Cinryze (IV, prophylaxis), Ruconest (recombinant, IV, on-demand), Haegarda (SC, prophylaxis).
• Icatibant (Firazyr) — bradykinin B2 receptor antagonist, SC on-demand.
• Ecallantide (Kalbitor) — kallikrein inhibitor, SC on-demand.
• Lanadelumab (Takhzyro) — anti-kallikrein mAb, SC prophylaxis every 2 weeks.
• Berotralstat (Orladeyo) — oral kallikrein inhibitor, daily prophylaxis.
• Antifibrinolytics (tranexamic acid, epsilon-aminocaproic acid) — older prophylaxis option.

Immunoglobulin Replacement (IVIG / SCIG)

For antibody deficiencies (CVID, XLA, specific antibody deficiency, secondary hypogammaglobulinemia with infections). IVIG is given every 3–4 weeks at 400–600 mg/kg; SCIG is given weekly at ~100–150 mg/kg. Document product, dose, infusion rate, pre-medication, vital signs, and any adverse reactions (headache, flushing, rigors, aseptic meningitis with IVIG).

18 Laboratory Testing & Imaging Diagnostics

Immunologic Labs You Will See

• Total IgE — elevated in atopy, parasites, ABPA, HES, IgE myeloma, hyper-IgE syndrome.
• Specific IgE (ImmunoCAP) — quantitative allergen-specific antibody, reported in kUA/L; class 0 (<0.35) to class 6 (>100).
• Tryptase — total tryptase >11.4 ng/mL is elevated; baseline >20 supports mast cell disease; peak during anaphylaxis is most useful 15 min–3 h after symptom onset.
• Quantitative immunoglobulins — IgG, IgA, IgM, and IgG subclasses (IgG1–4) for PID workup.
• Vaccine titers — tetanus (protein antigen) and pneumococcal serotype titers (polysaccharide antigen) pre- and post-Pneumovax.
• Lymphocyte subsets — CD3, CD4, CD8, CD19, CD16/56 by flow cytometry.
• Complement — C3, C4, CH50, AH50, C1-INH antigenic and functional levels.
• DHR — dihydrorhodamine flow assay for CGD.
• T-cell function — mitogen (PHA, ConA) and antigen (candida, tetanus) proliferation assays.
• Newborn screen — TREC for SCID, KREC for B-cell deficiencies (select states).

Imaging in the Allergy Clinic

Less imaging-heavy than other specialties, but you will see: sinus CT (chronic rhinosinusitis, nasal polyps, AFRS), chest CT (bronchiectasis in PID or ABPA, ground-glass in HP, nodules in EGPA), high-resolution CT for hypersensitivity pneumonitis, and occasional MRI for complications.

19 Medications You Must Know Pharmacology

20 Classification Systems Reference

Several systems beyond those already enumerated in disease sections appear in allergy notes. Document the named system whenever the attending references it.

21 Physical Exam — The Allergy Exam

Allergy exams are focused but systematic. Document these elements by system.

Mental status, gait, and cranial nerve exam are added for complex immunodeficiency or vasculitis consults. For atopic dermatitis visits, document body surface area (BSA) affected, EASI score components, lichenification, excoriation, and any signs of secondary infection.

22 Abbreviations Master List Reference

Diagnoses & Conditions

Procedures, Testing & Therapies

Labs & Diagnostics

23 Sample HPI Templates

These templates show the kind of documentation expected in an allergy/immunology clinic note. Use them as frameworks to internalize the rhythm and content of a good allergy HPI.

24 References & Sources

Clinical Practice Guidelines

Landmark Trials & Key Studies

Diagram & Figure Sources