Study guide
15.3 Drug Allergy, Desensitization & Adult Immunodeficiency
ABIM Internal Medicine Exam
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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy
0.1 Exam Format, Question Types & the 2026 Blueprint 0.2 Eligibility, Registration, Fees & Exam-Day Logistics 0.3 Scoring, the Passing Standard & Score Reports 0.4 Building a Blueprint-Weighted Study Plan
2 Chapter 1: Cardiovascular Disease (14% of Exam)
1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection
3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)
2.1 Diabetes Mellitus: Diagnosis, Glycemic Targets & Pharmacotherapy 2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications 2.3 Thyroid Function Testing & Hypothyroidism 2.4 Thyrotoxicosis, Thyroid Storm & Thyroid Nodules 2.5 Adrenal & Pituitary Disorders 2.6 Hypercalcemia, Hypocalcemia & Disorders of Mineral Metabolism 2.7 Osteoporosis & Paget Disease of Bone 2.8 Ovarian, Testicular & Reproductive Endocrine Disorders 2.9 Hypoglycemia, Endocrine Tumors, Polyglandular Syndromes & Severe Hypertriglyceridemia
4 Chapter 3: Gastroenterology & Hepatology (9% of Exam)
3.1 Esophageal Disease 3.2 Stomach & Duodenal Disease and Gastrointestinal Hemorrhage 3.3 Inflammatory Bowel Disease 3.4 Celiac Disease & Irritable Bowel Syndrome 3.5 Diverticular Disease & Colorectal Cancer Screening 3.6 Viral Hepatitis, Steatotic & Alcohol-Associated Liver Disease 3.7 Cirrhosis & the Complications of Portal Hypertension 3.8 Acute Pancreatitis 3.9 Chronic Pancreatitis & Biliary Tract Disease 3.10 Inherited, Autoimmune & Drug-Induced Liver Disease 3.11 Small Intestinal Disease, Ischemia & Gastrointestinal Complications of HIV
5 Chapter 4: Infectious Disease (9% of Exam)
4.1 Lower Respiratory Tract Infections & Sepsis Syndromes 4.2 Viral Respiratory Pathogens & Tuberculosis 4.3 Central Nervous System Infections 4.4 Skin, Soft Tissue, Bone & Joint Infections 4.5 Infective Endocarditis & Cardiovascular Infection 4.6 Clostridioides difficile & Catheter-Related Bloodstream Infection 4.7 HIV Diagnosis, Antiretroviral Therapy & Prevention 4.8 Opportunistic Infections & Sexually Transmitted Infections 4.9 Fever of Unknown Origin, Neutropenic Fever & Toxic Shock 4.10 Travel-Related Illness, Vector-Borne Disease & Outbreaks 4.11 Infection Prevention, Nosocomial Infection & Postexposure Prophylaxis 4.12 Rheumatic Fever, Poststreptococcal Disease, Enteric & Hepatic Infections
6 Chapter 5: Pulmonary Disease (9% of Exam)
5.1 COPD: Diagnosis, GOLD Classification & Initial Pharmacotherapy 5.2 Interventions That Reduce COPD Mortality & Exacerbation Management 5.3 Asthma: Diagnosis, Stepwise Therapy & Status Asthmaticus 5.4 Interstitial Lung Disease & Idiopathic Pulmonary Fibrosis 5.5 Sarcoidosis, Hypersensitivity Pneumonitis & Occupational Lung Disease 5.6 Pulmonary Embolism: Diagnosis, Risk Stratification & Anticoagulation 5.7 Pulmonary Hypertension & Sleep-Disordered Breathing 5.8 Acute Respiratory Distress Syndrome & Mechanical Ventilation 5.9 Pleural Disease, Empyema & Pneumothorax 5.10 Bronchiectasis, Cystic Fibrosis & Restrictive Lung Disease 5.11 Evaluation of Cough, Dyspnea, Hemoptysis & the Solitary Pulmonary Nodule
7 Chapter 6: Rheumatology & Orthopedics (9% of Exam)
6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease
8 Chapter 7: Hematology (6% of Exam)
7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation
9 Chapter 8: Medical Oncology (6% of Exam)
8.1 Breast, Lung, Colorectal & Prostate Cancer 8.2 Oncologic Emergencies 8.3 Genitourinary & Gynecologic Malignancies 8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary 8.5 Complications of Cancer & Its Treatment 8.6 Cancer Prevention, Survivorship & Psychosocial Care
10 Chapter 9: Nephrology & Urology (6% of Exam)
9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria
11 Chapter 10: Neurology (4% of Exam)
10.1 Acute Ischemic Stroke: Syndromes & Reperfusion 10.2 Transient Ischemic Attack, Secondary Prevention & Hemorrhagic Stroke 10.3 Headache & Facial Pain 10.4 Seizures, Epilepsy & Movement Disorders 10.5 Multiple Sclerosis & Neuromuscular Junction Disorders 10.6 Motor Neuron Disease & Acute Peripheral Neuropathy 10.7 Cranial Neuropathies & Neuro-Ophthalmology 10.8 Peripheral Neuropathies, CNS Tumors & Other Neurologic Disorders
12 Chapter 11: Psychiatry & Behavioral Health (4% of Exam)
11.1 Major Depressive Disorder & Medical Mimics 11.2 Antidepressant Pharmacotherapy & Treatment-Resistant Depression 11.3 Bipolar Disorder, Mood Stabilizers & Lithium Toxicity 11.4 Anxiety, Stress-Related & Obsessive-Compulsive Disorders 11.5 Alcohol Use Disorder & Withdrawal 11.6 Pharmacotherapy for Alcohol & Opioid Use Disorder 11.7 Toxidromes, Psychiatric Emergencies & Suicide Risk Assessment 11.8 Psychotic, Somatic Symptom, Factitious & Personality Disorders 11.9 Eating Disorders, Sleep Disorders & Sexual Health
13 Chapter 12: Dermatology (3% of Exam)
12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses 12.2 Acne, Rosacea & Cutaneous Infections 12.3 Herpes Zoster & Autoimmune Blistering Diseases 12.4 Nodules, Tumors & Cutaneous Oncology 12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions 12.6 Pigment Disorders, Alopecia, Nail Disease & Photosensitivity 12.7 Vascular Dermatoses, Environmental Injury & Cutaneous Signs of Systemic Disease
14 Chapter 13: Obstetrics & Gynecology / Women's Health (3% of Exam)
13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications
15 Chapter 14: Geriatric Syndromes (3% of Exam)
14.1 Comprehensive Geriatric Assessment & Frailty 14.2 Falls, Gait Assessment & Polypharmacy 14.3 Urinary Incontinence & Pressure Injuries in Older Adults 14.4 Mild Cognitive Impairment, Dementia & Its Subtypes 14.5 Delirium & the Pharmacotherapy of Cognitive Disorders 14.6 Palliative Care, Hospice & Advance Care Planning 14.7 Chronic Wounds, Nutrition, Swallowing, Constipation & Hip Fracture 14.8 Sensory Impairment, Dizziness, Elder Mistreatment & Care Settings
16 Chapter 15: Allergy & Immunology (2% of Exam)
15.1 Anaphylaxis: Recognition & Emergency Management 15.2 Urticaria & Angioedema 15.3 Drug Allergy, Desensitization & Adult Immunodeficiency 15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions 15.5 Rhinitis, Conjunctivitis, Eosinophilic & Mast Cell Disorders
17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology
16.1 The USPSTF Framework & Evidence-Based Cancer Screening 16.2 Cardiovascular & Metabolic Screening and Primary Prevention 16.3 Adult Immunization & Vaccines in Special Populations 16.4 Clinical Epidemiology, Biostatistics & Study Design
18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)
17.1 Principles of Bioethics & Decisional Capacity 17.2 Informed Consent, Treatment Refusal & Special Scenarios 17.3 Surrogate Decision-Making, Advance Directives & Confidentiality 17.4 Patient Safety Science, Medical Error & Diagnostic Reasoning 17.5 Quality Improvement Methods, Health Disparities & Health Equity
19 Chapter 18: Perioperative Medicine & Medical Consultation
18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications
20 Chapter 19: Ophthalmology (1% of Exam)
19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease
21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)
20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders
15.3 Drug Allergy, Desensitization & Adult Immunodeficiency
Key Takeaways Explain This Topic AI
Drug allergy other than drug-induced urticaria and angioedema is a separately enumerated blueprint subsection.
Primary humoral immunodeficiency, cellular immunodeficiency other than HIV, and complement deficiency are enumerated under primary immunodeficiency disorders.
The great majority of patients labeled penicillin-allergic tolerate penicillin on formal evaluation, and delabeling reduces use of broader and inferior alternatives.
Common variable immunodeficiency presents in adults with recurrent sinopulmonary infection, bronchiectasis and low immunoglobulin levels with poor vaccine response.
Terminal complement deficiency predisposes to recurrent neisserial infection and requires meningococcal vaccination including serogroup B.
Last updated: August 2026
- 1. Drug Allergy & Desensitization
- Penicillin Allergy & Cephalosporin Cross-Reactivity
De-labeling Penicillin Allergy: Approximately 10% of the US population carries a documented penicillin allergy label; however, > 90% to 95% of these patients are NOT truly allergic when evaluated with formal Penicillin Skin Testing (PST) or direct oral Amoxicillin challenge. Mechanisms for false labeling include waning of drug-specific IgE antibodies over time (~10% per year) and childhood misattribution of viral exanthems as drug allergies.
Cephalosporin Cross-Reactivity Biology: Cross-reactivity between penicillins and cephalosporins is determined primarily by the chemical structure of the R1 side chain , rather than the shared core four-membered beta-lactam ring.
First- and Second-Generation Cephalosporins (e.g., Cefazolin, Cephalexin, Cefaclor): Share similar R1 side chains with aminopenicillins; historical cross-reactivity is low (~1% to 2%). (Note: Cefazolin has a unique side chain and does not share R1 with ampicillin/amoxicillin).
Third-, Fourth-, and Fifth-Generation Cephalosporins (e.g., Ceftriaxone, Cefepime, Ceftazidime, Ceftaroline): Have distinct, disparate R1 side chains and demonstrate < 1% cross-reactivity with penicillins.
Clinical Practice Algorithms:
Mild, Non-IgE Cutaneous Reactions (e.g., delayed maculopapular rash): All cephalosporins and carbapenems can be safely administered without prior skin testing.
Severe IgE-Mediated History (Anaphylaxis, Angioedema, Bronchospasm): Use a 3rd/4th generation cephalosporin with a completely distinct R1 side chain (e.g., Ceftriaxone or Cefepime), or perform Penicillin Skin Testing (PST) followed by an oral amoxicillin challenge.
Carbapenems (Meropenem) & Monobactams (Aztreonam): Cross-reactivity with penicillin is < 1% . Aztreonam does not cross-react with penicillins; however, Aztreonam shares an identical R1 side chain with Ceftazidime (do NOT administer aztreonam to patients with true ceftazidime allergy).
Drug Desensitization Protocols
Definition & Mechanism: Temporary induction of clinical tolerance to a drug responsible for an IgE-mediated (Type I) immediate hypersensitivity reaction or aspirin-induced respiratory disease. Performed by administering minute, subthreshold doses of the drug (starting at 1:1,000 to 1:10,000 of the target therapeutic dose) and doubling the dose every 15 to 30 minutes across 12 to 16 sequential steps under continuous cardiac/ICU monitoring.
Mechanism: Gradual, progressive, subthreshold antigen exposure induces slow intracellular depletion of mast cell/basophil granules and downregulates surface IgE receptors without triggering massive systemic degranulation.
High-Yield Clinical Indications:
Neurosyphilis, Congenital Syphilis, or Syphilis in Pregnancy: Penicillin G is the only proven curative bactericidal therapy (doxycycline cannot cross the placental barrier and does not achieve adequate CSF concentrations; desensitization to Penicillin G is mandatory in penicillin-allergic pregnant patients with syphilis).
Severe Bacterial Infections with No Therapeutic Alternative: Enterococcus faecalis infective endocarditis (requires Ampicillin/Penicillin G).
Aspirin-Exacerbated Respiratory Disease (AERD / Samter's Triad): Asthma, chronic rhinosinusitis with nasal polyps, and aspirin sensitivity. Aspirin desensitization improves asthma control, reduces polyp recurrence, and allows antiplatelet therapy after PCI.
Critical Chemotherapy / Biologic Regimens: Platinum compounds (Carboplatin, Cisplatin), Taxanes, or Monoclonal antibodies (Rituximab) in patients with allergic reactions when alternative regimens are inferior.
ABSOLUTE CONTRAINDICATIONS to Desensitization: Severe, non-IgE, T-cell-mediated Severe Cutaneous Adverse Reactions (SCAR), including:
- Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN)
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
- Acute Generalized Exanthematous Pustulosis (AGEP)
Drug-induced liver injury, hemolytic anemia, or interstitial nephritis.
Durability Rule: Desensitization produces temporary tolerance only . If the drug is interrupted for > 24 to 48 hours (or > 4–5 drug half-lives), mast cells resynthesize mediators and reload surface IgE; the patient reverts to full allergic sensitivity and requires repeat desensitization.
2. Adult Primary & Secondary Immunodeficiencies
Immunodeficiency in adult patients frequently presents subtly with recurrent, severe, or unusual sinopulmonary and gastrointestinal infections, bronchiectasis, autoimmune cytopenias, or granulomatous organ infiltration.
- Primary Immunodeficiencies in Adults
- 1. Common Variable Immunodeficiency (CVID)
Epidemiology & Genetics: The most common clinically significant primary immunodeficiency diagnosed in adulthood (bimodal presentation: childhood and young adulthood, ages 20 to 40 years ). Polygenic and heterogeneous; characterized by defective terminal B-cell differentiation into antibody-secreting plasma cells.
Diagnostic Criteria:
Markedly reduced serum IgG (< 400–500 mg/dL) .
Markedly reduced serum IgA and/or IgM (at least 2 standard deviations below age-adjusted normal values).
Impaired vaccine antibody response (demonstrated failure to generate protective specific IgG titers following polysaccharide vaccines [Pneumovax 23] or protein vaccines [Tetanus/Diphtheria toxoids]).
Exclusion of secondary causes of hypogammaglobulinemia.
(Flow Cytometry: Total peripheral CD19+/CD20+ B-lymphocyte counts are typically normal or mildly decreased , but class-switched memory B-cells [CD27+IgD-IgM-] and plasma cells are severely reduced).
Clinical Presentation & Complications:
Recurrent Encapsulated Sinopulmonary Infections: Recurrent otitis media, bacterial sinusitis, and pneumonias caused by Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis , leading to irreversible cylindrical bronchiectasis .
Gastrointestinal Complications: Chronic watery diarrhea, malabsorption, and weight loss caused by Giardia lamblia , Campylobacter jejuni , Salmonella , or Small Intestinal Bacterial Overgrowth (SIBO). Non-infectious CVID enteropathy mimics celiac sprue (villous blunting and intraepithelial lymphocytosis but absence of plasma cells in the lamina propria on intestinal biopsy).
Autoimmune Manifestations (~25–30% of patients): Immune Thrombocytopenia (ITP) and Autoimmune Hemolytic Anemia (AIHA / Evans Syndrome) are the most common autoimmune complications; rheumatoid-like polyarthritis, vitiligo, and pernicious anemia.
Granulomatous Disease: Granulomatous-Lymphocytic Interstitial Lung Disease (GLILD) with noncaseating granulomas on lung biopsy (mimics pulmonary sarcoidosis).
Malignancy Risk: Markedly elevated risk (30- to 40-fold) of Non-Hodgkin B-Cell Lymphoma and gastric adenocarcinoma.
First-Line Treatment: Lifelong Immunoglobulin Replacement Therapy :
Intravenous Immunoglobulin (IVIG 400 to 600 mg/kg IV every 3 to 4 weeks) OR Subcutaneous Immunoglobulin (SCIG weekly) .
Target trough serum IgG level: > 700 to 800 mg/dL (or higher [> 900–1000 mg/dL] in patients with established bronchiectasis).
2. Selective IgA Deficiency
Epidemiology: The most common primary immunodeficiency disorder overall (prevalence ~1 in 300 to 1 in 600 individuals of European ancestry).
Diagnostic Criteria: Undetectable serum IgA (< 7 mg/dL) with completely normal serum IgG and IgM levels , in a patient > 4 years of age with normal antibody responses to vaccines.
Clinical Presentation:
Most patients (> 80%) are completely asymptomatic and diagnosed incidentally.
Symptomatic Patients: Suffer from recurrent mild viral/bacterial upper respiratory tract infections, allergic rhinitis/asthma, atopic eczema, and gastrointestinal infections (particularly Giardia lamblia due to absent mucosal secretory IgA defense).
Autoimmune Associations: Strongly associated with Celiac Disease (Crucial Board Pearl: Celiac screening in IgA-deficient patients requires checking IgG-tissue transglutaminase (tTG-IgG) or IgG-deamidated gliadin peptides; standard tTG-IgA screening will yield a false-negative result!).
Anaphylactic Transfusion Reactions: Up to 30% to 40% of patients with selective IgA deficiency develop circulating anti-IgA antibodies (specifically IgG- or IgE-class anti-IgA). When transfused with standard blood products containing trace donor IgA (packed red blood cells, platelets, fresh frozen plasma), they can develop sudden, severe, life-threatening IgE-mediated anaphylactic transfusion reactions .
Transfusion Management: When blood products are required, administer washed red blood cells (washed with normal saline to remove plasma IgA) or blood products collected from known IgA-deficient donors .
Secondary Immunodeficiencies
Etiology / Mechanism Primary Immunologic Defect Clinical Presentation & Management
Chronic Lymphocytic Leukemia (CLL) & Multiple Myeloma Secondary hypogammaglobulinemia due to neoplastic clonal crowding and suppression of normal polyclonal plasma cells Recurrent encapsulated bacterial sinopulmonary infections.; Management: Prophylactic IVIG (400 mg/kg q3–4w) is indicated for patients with CLL or Multiple Myeloma who have serum IgG < 400–500 mg/dL and recurrent severe bacterial infections despite prophylactic antibiotics.
Nephrotic Syndrome Massive urinary protein loss (> 3.5 g/24h) leading to severe urinary wasting of low-molecular-weight IgG Markedly low serum IgG, but normal serum IgM (larger molecular weight prevents filtration); normal specific vaccine antibody production; patients do not develop classic encapsulated sinopulmonary infections.
Protein-Losing Enteropathy Intestinal lymphangiectasia, severe IBD, or Fontan-associated enteropathy causing enteric loss of immunoglobulins and T-lymphocytes Low serum IgG, IgA, and IgM accompanied by hypoalbuminemia and peripheral lymphopenia.
Anti-CD20 Therapy (Rituximab) Prolonged, profound depletion of circulating CD20+ B lymphocytes lasting 6–12 months Prolonged secondary hypogammaglobulinemia; increased vulnerability to bacterial and viral infections (Enterovirus meningoencephalitis, Hepatitis B reactivation). Requires monitoring of quantitative immunoglobulins and IVIG replacement if severe infections occur.
Anti-TNF-Alpha Therapy (Infliximab, Adalimumab, Etanercept) Impaired macrophage function and breakdown of granuloma formation Reactivation of intracellular pathogens: Latent Tuberculosis , endemic mycoses ( Histoplasmosis, Coccidioidomycosis, Blastomycosis ), and Listeria monocytogenes .; Mandatory: Screen with IGRA/TST and Hepatitis B panel prior to initiating anti-TNF therapy.