49.4 Vector-Borne, Tick-Borne & Rickettsial Illnesses

ABFM Family Medicine Certification Study Guide Exam

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1 Chapter 1: Exam Structure, Blueprint & Clinical Decision-Making

1.1 Exam Blueprint, FMCLA vs. One-Day Exam & Board Scoring 1.2 Clinical Reasoning, Test-Taking Strategy & Ambiguity Management 1.3 Evidence-Based Medicine & Clinical Practice Guidelines in Primary Care

2 Chapter 2: Healthcare Systems, Practice Management & Quality

2.1 Practice Management, Billing, Coding & Documentation 2.2 Quality Improvement, Patient Safety & Diagnostic Stewardship 2.3 Interprofessional Team-Based Care & Care Coordination

3 Chapter 3: Ethics, Law, Biostatistics & Health Equity

3.1 Medical Ethics, Informed Consent & Surrogate Decision-Making 3.2 Biostatistics, Clinical Epidemiology & Diagnostic Test Interpretation 3.3 Social Determinants of Health, Health Equity & Cultural Humility 3.4 Physician Wellness, Burnout Prevention & Professionalism

4 Chapter 4: Lifestyle Counseling & Behavior Change

4.1 Alcohol Use Screening & Brief Intervention 4.2 Illicit Drug & Cannabis Counseling 4.3 Tobacco & Vaping Cessation Counseling

5 Chapter 5: Nutrition, Physical Activity & Chronic Disease Prevention

5.1 Dietary Counseling for Obesity & Chronic Disease Prevention 5.2 Exercise Prescription & Physical Activity Counseling 5.3 Genetic Risk Assessment & Family History Counseling

6 Chapter 6: Routine Adult Immunizations

6.1 ACIP Adult Respiratory Vaccines: Influenza, COVID-19, RSV & Pneumococcal 6.2 ACIP Adult Non-Respiratory Vaccines: Tdap, Shingrix, HPV & Hep B 6.3 Immunizations in Special Populations: Pregnancy, Asplenia & Immunocompromise

7 Chapter 7: Pediatric Health Maintenance & Surveillance

7.1 Newborn Examination & Early Postnatal Care 7.2 Well-Child Care, Developmental Surveillance & Milestones 7.3 Pediatric & Adolescent Screening: Vision, Hearing, Anemia & Lead 7.4 Pediatric Oral Health, Dental Screening & Fluoride

8 Chapter 8: Behavioral Health & Safety Screening

8.1 Primary Care Depression, Anxiety & Behavioral Health Screening 8.2 Domestic Violence, Intimate Partner Violence & Firearm Safety 8.3 Occupational Health & Recreational Safety Counseling

9 Chapter 9: Adult Preventive Screening: Cardiovascular & Metabolic

9.1 Cardiovascular Disease & Hypertension Screening 9.2 Type 2 Diabetes Screening & Prediabetes Risk Stratification 9.3 Abdominal Aortic Aneurysm & Osteoporosis Screening

10 Chapter 10: Adult Cancer Screening: Breast & Gynecologic

10.1 Breast Cancer Screening & Risk-Assessment 10.2 Cervical Cancer Screening & ASCCP Algorithms 10.3 Skin Cancer Clinical Assessment & Counseling

11 Chapter 11: Adult Cancer Screening: Colorectal, Lung & Prostate

11.1 Colorectal Cancer Screening Modalities & Intervals 11.2 Lung Cancer Screening with Low-Dose CT 11.3 Prostate Cancer Screening & Shared Decision-Making

12 Chapter 12: Sexual Health, Infectious Disease Screening & Contraception

12.1 Sexual Health Counseling & Risk-Reduction Strategies 12.2 STI Screening: Chlamydia, Gonorrhea, Syphilis & Trichomoniasis 12.3 Bloodborne Infectious Disease Screening: HIV & Hepatitis C

13 Chapter 13: Reproductive Life Planning, Lactation & Preoperative Care

13.1 Preconception Planning & Comprehensive Contraception Management 13.2 Lactation Support & Breastfeeding Counseling 13.3 Preoperative Medical Evaluation & Pre-Participation Sports Exam

14 Chapter 14: Emergent Cardiovascular Conditions

14.1 Acute Coronary Syndromes & Myocardial Infarction 14.2 Acute Chest Pain Risk Stratification & Triage 14.3 Acute or Critical Valvular Heart Emergencies

15 Chapter 15: Cardiac Arrhythmias, Heart Failure & Hypertensive Crises

15.1 Acute Atrial & Ventricular Arrhythmias 15.2 Acute Decompensated Heart Failure & Cardiogenic Shock 15.3 Hypertensive Emergency & Urgency Management

16 Chapter 16: Vascular & Thromboembolic Emergencies

16.1 Pulmonary Embolism & Deep Vein Thrombosis 16.2 Acute Aortic Syndromes & Peripheral Vascular Emergencies 16.3 Critical Limb Ischemia & Acute Arterial Occlusion

17 Chapter 17: Neurologic Emergencies: Stroke & Altered Consciousness

17.1 Acute Ischemic Stroke & Intracranial Hemorrhage 17.2 Syncope Evaluation & Status Epilepticus 17.3 Acute Delirium, Encephalopathy & Severe Confusion

18 Chapter 18: Neurologic Trauma & Acute Cranial Emergencies

18.1 Concussion, Moderate-to-Severe TBI & Intracranial Injury 18.2 Thunderclap & Acute Severe Secondary Headaches 18.3 Acute Ophthalmologic Emergencies

19 Chapter 19: Acute Abdominal, Pelvic & Gastrointestinal Emergencies

19.1 Acute Abdominal & Pelvic Pain Triage 19.2 Upper & Lower Gastrointestinal Bleeding 19.3 Acute Hepatic Failure, Cholangitis & Severe Jaundice

20 Chapter 20: Acute Pulmonary & Airway Emergencies

20.1 Acute Hypoxic Respiratory Failure & ARDS 20.2 Severe Community-Acquired Pneumonia & Empyema 20.3 Acute Severe Epistaxis & Airway Obstruction

21 Chapter 21: Acute Traumatic Injuries & Wound Care

21.1 Major Trauma Resuscitation & Initial Assessment 21.2 Burn Assessment, Inhalation Injury & Resuscitation 21.3 Laceration Management, Complex Wounds & Animal Bites

22 Chapter 22: Acute Orthopedic & Musculoskeletal Emergencies

22.1 Acute Ambulatory Fractures & Initial Splinting 22.2 Compartment Syndrome & Major Orthopedic Trauma 22.3 Septic Arthritis & Acute Microcrystalline Crises

23 Chapter 23: Severe Infections, Sepsis & Systemic Emergencies

23.1 Sepsis, Septic Shock & Initial Fluid Resuscitation 23.2 Necrotizing Soft Tissue Infections & Severe CNS Infections 23.3 Anaphylaxis Diagnosis, Epinephrine Dosing & Airway Protection

24 Chapter 24: Metabolic, Endocrine & Electrolyte Emergencies

24.1 Diabetic Ketoacidosis & Hyperosmolar Hyperglycemic State 24.2 Critical Electrolyte Emergencies: Dyskalemias & Dysnatremias 24.3 Severe Calcium Abnormalities & Acute Adrenal Crisis

25 Chapter 25: Hematologic, Urologic & Dental Emergencies

25.1 Severe Symptomatic Anemias & Coagulopathic Emergencies 25.2 Testicular Torsion, Priapism & Acute Urinary Retention 25.3 Urgent Odontogenic Infections & Dental Trauma

26 Chapter 26: Psychiatric, Behavioral & Obstetric/Gynecologic Emergencies

26.1 Suicidal Ideation, Acute Agitation & Behavioral Emergencies 26.2 Acute Physical & Sexual Assault Care 26.3 Life-Threatening Vaginal Bleeding & Ectopic Pregnancy 26.4 Environmental Heat Stroke & Severe Hypothermia

27 Chapter 27: Acute Head, Neck & Neurologic Symptoms

27.1 Primary Acute Headaches: Migraine, Tension & Cluster 27.2 Concussion & Minor Closed Head Injury Evaluation 27.3 Transient Ischemic Attack Evaluation & ABCD2 Risk Scoring

28 Chapter 28: Acute Cranial Nerves, Hearing & Sensory Symptoms

28.1 Peripheral Neuropathies: Bell's Palsy, Carpal Tunnel & Radiculopathy 28.2 Acute Tinnitus, Sudden Sensorineural Hearing Loss & Cerumen Impaction 28.3 Acute Dizziness, Benign Paroxysmal Positional Vertigo & Vestibular Neuritis

29 Chapter 29: Acute Upper Respiratory Tract Infections

29.1 Acute Viral Rhinosinusitis vs. Bacterial Rhinosinusitis 29.2 Acute Pharyngitis: Group A Streptococcus & Centor Criteria 29.3 Acute Otitis Media, Otitis Externa & Serous Effusion

30 Chapter 30: Acute Lower Respiratory Infections & Cough

30.1 Influenza, COVID-19 & Viral Respiratory Syndromes 30.2 Acute Bronchitis & Lower Respiratory Tract Infections 30.3 Ambulatory Community-Acquired Pneumonia

31 Chapter 31: Allergic, Nasal & Non-Infectious Pulmonary Conditions

31.1 Allergic Rhinitis & Acute Non-Anaphylactic Allergic Reactions 31.2 Acute Dyspnea in Ambulatory Care 31.3 Interstitial Lung Diseases & Sarcoidosis Presentation

32 Chapter 32: Acute Chest, Cardiac & Vascular Symptoms

32.1 Palpitations Evaluation & Arrhythmia Triage in Primary Care 32.2 Deep Vein Thrombosis & Superficial Thrombophlebitis 32.3 Ambulatory Hypotension & Orthostasis Evaluation

33 Chapter 33: Acute Upper Gastrointestinal Conditions

33.1 Peptic Ulcer Disease & Gastritis 33.2 Dysphagia, Esophagitis & Acute Esophageal Disorders 33.3 Acute Nausea, Vomiting & Foodborne Illness

34 Chapter 34: Acute Lower Gastrointestinal Conditions

34.1 Acute Infectious Diarrhea & Gastroenteritis 34.2 Acute Constipation & Functional Bowel Changes 34.3 Ano-Rectal Disorders: Hemorrhoids, Fissures, Abscesses & Pruritus Ani

35 Chapter 35: Inflammatory, Functional & Malabsorptive GI Disorders

35.1 Acute Flares of Inflammatory Bowel Disease 35.2 Irritable Bowel Syndrome: Diagnosis, Subtyping & Management 35.3 Celiac Disease & Malabsorption Syndromes

36 Chapter 36: Acute Abdominal, Hepatic & Biliary Disorders

36.1 Ambulatory Abdominal & Pelvic Pain Triage 36.2 Acute Cholecystitis, Biliary Colic & Pancreatitis 36.3 Acute Liver Injury & Viral Hepatitis

37 Chapter 37: Acute Abdominal Wall, Hernias & Dental Conditions

37.1 Abdominal Wall, Inguinal & Ventral Hernias 37.2 Acute Dental Pain, Odontogenic Abscess & Aphthous Ulcers 37.3 Acute Edema: Unilateral vs. Bilateral Diagnostic Evaluation

38 Chapter 38: Acute Infectious Dermatoses

38.1 Bacterial Skin Infections: Impetigo, Cellulitis & Cutaneous Abscesses 38.2 Fungal Skin Infections: Tinea Corporis, Cruris, Pedis & Onychomycosis 38.3 Viral Cutaneous Infections: Herpes Simplex, Zoster & Molluscum Contagiosum

39 Chapter 39: Inflammatory, Allergic & Autoimmune Dermatoses

39.1 Atopic Dermatitis, Contact Dermatitis & Eczematous Flares 39.2 Non-Infectious Rashes: Urticaria, Drug Eruptions & Erythema Multiforme 39.3 Cutaneous Malignancies & Premalignant Lesions: AK, BCC, SCC & Melanoma

40 Chapter 40: Acute Shoulder, Elbow & Upper Extremity Injuries

40.1 Rotator Cuff Pathology, Tendinopathy & Shoulder Impingement 40.2 Lateral & Medial Epicondylitis, Olecranon Bursitis & Elbow Sprains 40.3 Wrist & Hand Soft-Tissue Injuries: De Quervain, TFCC & Finger Sprains

41 Chapter 41: Acute Knee, Ankle & Lower Extremity Injuries

41.1 Meniscal Tears, Ligamentous Knee Injuries & Patellofemoral Pain 41.2 Ankle Sprains, Ottawa Ankle Rules & Achilles Tendinopathy 41.3 Plantar Fasciitis, Shin Splints & Overuse Syndromes

42 Chapter 42: Acute Ambulatory Fractures & Dislocations

42.1 Distal Radius, Scaphoid & Common Upper Extremity Fractures 42.2 Metatarsal, Clavicle & Common Lower Extremity Fractures 42.3 Joint Dislocation Management: Nursemaid's Elbow & Shoulder Subluxation

43 Chapter 43: Acute Axial Musculoskeletal Pain & Falls

43.1 Acute Low Back Pain: Red Flags, Strain & Disc Herniation 43.2 Acute Cervical Strain, Whiplash & Axial Neck Pain 43.3 Evaluation of Falls in Ambulatory & Older Patients

44 Chapter 44: Acute Inflammatory Arthropathies & Generalized Pain

44.1 Acute Inflammatory Arthritis & Spondyloarthropathies 44.2 Myalgias, Rhabdomyolysis & Post-Viral Pain Syndromes 44.3 Acute Non-Headache Pain Management Strategies

45 Chapter 45: Acute Renal, Urinary & Genitourinary Conditions

45.1 Uncomplicated UTI, Pyelonephritis & Acute Urethritis 45.2 Hematuria Workup & Glomerulonephritis 45.3 Nephrolithiasis & Acute Urinary Tract Obstruction

46 Chapter 46: Acute Male Genitourinary & Prostatic Conditions

46.1 Acute Prostatitis, Epididymitis & Orchitis 46.2 Acute Scrotal Pain: Torsion vs Appendage, BPH & Male Genital Emergencies 46.3 Acute Urinary Retention & Incontinence Evaluation

47 Chapter 47: Acute Women's Health & Early Pregnancy Care

47.1 Early Pregnancy Diagnosis, Dating & Initial Complications 47.2 Abnormal Uterine Bleeding & Acute Menstrual Disorders 47.3 Premenstrual Syndrome & Premenstrual Dysphoric Disorder

48 Chapter 48: Breast Disorders, STIs & Pediatric Elimination

48.1 Palpable Breast Mass, Mastitis & Nipple Discharge 48.2 Sexually Transmitted Infections: Diagnosis, Staging & CDC Guidelines 48.3 Pediatric Enuresis & Encopresis

49 Chapter 49: Systemic Signs, Metabolic Dysregulation & Miscellaneous Infections

49.1 Acute Fever, Sepsis Screening & FUO in Primary Care 49.2 Acute Hyperglycemia & Symptomatic Hypoglycemia 49.3 Electrolyte Abnormalities: Mild-to-Moderate Disturbances 49.4 Vector-Borne, Tick-Borne & Rickettsial Illnesses

50 Chapter 50: Chronic Cardiovascular Diseases: Hypertension & Ischemia

50.1 Essential Hypertension Management: 2025 AHA/ACC Guideline & JNC Strategies 50.2 Chronic Coronary Artery Disease & Post-MI Secondary Prevention 50.3 Chronic Heart Failure: HFrEF, HFpEF & Quadruple GDMT

51 Chapter 51: Chronic Vascular, Valvular & Dyslipidemic Diseases

51.1 Peripheral Arterial Disease & Claudication 51.2 Chronic Valvular Heart Disease & Murmur Evaluation 51.3 Lipid Disorders & ASCVD Risk-Based Statin Therapy

52 Chapter 52: Chronic Respiratory Diseases: Asthma & COPD

52.1 Chronic Asthma Management: GINA Stepwise SMART Therapy 52.2 Chronic Obstructive Pulmonary Disease: GOLD Recommendations 52.3 Solitary Pulmonary Nodule Evaluation & Fleischner Society Criteria

53 Chapter 53: Chronic Metabolic Diseases: Diabetes Mellitus

53.1 Type 2 Diabetes Management: ADA Pharmacotherapy Algorithms 53.2 Type 1 Diabetes: Basal-Bolus Insulin, CGMs & Diabetic Complications 53.3 Diabetic Microvascular & Macrovascular Disease Surveillance

54 Chapter 54: Obesity, Nutrition & Metabolic Bone Diseases

54.1 Medical & Behavioral Management of Obesity & Incretin Mimetics 54.2 Osteoporosis & Metabolic Bone Disease: DEXA, FRAX & Antiresorptives 54.3 Nutritional Deficiencies: Vitamin D, B12, Iron & Malnutrition

55 Chapter 55: Chronic Endocrine Disorders

55.1 Primary & Subclinical Hypothyroidism, Hyperthyroidism & Nodules 55.2 Adrenal Disorders: Addison's Disease & Cushing's Syndrome 55.3 Hypercalcemia, Hyperparathyroidism & Pituitary Disorders

56 Chapter 56: Chronic Kidney Disease & Venous Disorders

56.1 Chronic Kidney Disease: KDIGO Staging & Renoprotective Therapy 56.2 Chronic Venous Insufficiency, Stasis Dermatitis & Lymphedema 56.3 Chronic Electrolyte & Acid-Base Management in CKD

57 Chapter 57: Chronic Gastrointestinal & Hepatic Diseases

57.1 Gastroesophageal Reflux Disease, Barrett's Esophagus & Dyspepsia 57.2 Chronic Liver Disease: MASLD/NAFLD, Cirrhosis & Portal Hypertension 57.3 Viral Hepatitis B & C: Long-Term Monitoring & DAA Therapy

58 Chapter 58: Colorectal Surveillance & Chronic Pancreaticobiliary Care

58.1 Post-Polypectomy Colorectal Polyp Surveillance Guidelines 58.2 Chronic Pancreatitis & Exocrine Pancreatic Insufficiency 58.3 Chronic Nausea, Gastroparesis & Functional GI Disorders

59 Chapter 59: Chronic Musculoskeletal & Rheumatologic Disorders

59.1 Osteoarthritis: Hip, Knee & Hand Management 59.2 Spinal Conditions: Spinal Stenosis, Spondylolisthesis & Compression Fractures 59.3 Chronic Myopathies & Fibromyalgia Syndrome

60 Chapter 60: Chronic Neurologic & Neurodegenerative Disorders

60.1 Dementia: Alzheimer's, Vascular & Lewy Body Disease 60.2 Parkinson's Disease & Essential Tremor 60.3 Epilepsy: Chronic Antiseizure Medications & Post-Stroke Care

61 Chapter 61: Chronic Peripheral Nerves, Pain & Sensory Disorders

61.1 Diabetic & Chronic Peripheral Neuropathies 61.2 Chronic Pain Syndromes & Chronic Daily Headaches 61.3 Chronic Tinnitus, Presbycusis & Persistent Dizziness

62 Chapter 62: Chronic Psychiatric Disorders

62.1 Major Depressive Disorder & Generalized Anxiety Disorder 62.2 Bipolar Disorder: Maintenance Pharmacotherapy & Lithium Monitoring 62.3 Adult & Pediatric Attention-Deficit/Hyperactivity Disorder

63 Chapter 63: Chronic Behavioral Health & Neurodevelopmental Conditions

63.1 Chronic Behavioral Conditions: PTSD, OCD & Somatization 63.2 Autism Spectrum Disorder & Intellectual Disabilities 63.3 Eating Disorders: Anorexia Nervosa, Bulimia & Binge Eating

64 Chapter 64: Chronic Substance Use Disorders & Tobacco Cessation

64.1 Alcohol Use Disorder: Pharmacotherapy & Relapse Prevention 64.2 Opioid & Stimulant Use Disorders: MOUD & Harm Reduction 64.3 Longitudinal Tobacco Cessation Pharmacotherapy

65 Chapter 65: Chronic Dermatologic Conditions

65.1 Acne Vulgaris, Rosacea & Seborrheic Dermatitis 65.2 Chronic Plaque Psoriasis & Biologic Therapies 65.3 Chronic Eczema, Hidradenitis Suppurativa & Cutaneous Lupus

66 Chapter 66: Chronic Reproductive, Infectious & Geriatric Special Care

66.1 Chronic Menstrual Disorders, Infertility & Sexual Dysfunction 66.2 Menopause Management & Hormone Replacement Therapy 66.3 Chronic HIV Infection Management & Primary Care Integration 66.4 Gender-Affirming Primary Care & Hormone Therapy 66.5 Advance Care Planning, Palliative Care & End-of-Life Symptom Control

67 Chapter 67: Continuity Care: Sleep, Fatigue, Cancer, Pregnancy & the Adult Preventive Visit

67.1 Chronic Insomnia & Obstructive Sleep Apnea 67.2 Chronic Malaise, Fatigue & ME/CFS 67.3 Primary Care During Cancer Treatment & Survivorship 67.4 Routine Prenatal Care & Longitudinal Pregnancy Management 67.5 The Periodic Adult Health Examination & Medicare Annual Wellness Visit

49.4 Vector-Borne, Tick-Borne & Rickettsial Illnesses

Key Takeaways Explain This Topic AI

Lyme disease (Borrelia burgdorferi) is transmitted by Ixodes scapularis deer ticks requiring >=36 to 48 hours of attachment; Early Localized disease presents with Erythema Migrans (EM; expanding annular lesion >=5 cm appearing 7-14 days post-bite), which is a purely clinical diagnosis where serology is CONTRAINDICATED due to a >50% false-negative rate; first-line therapy is oral Doxycycline 100 mg BID for 10-14 days (amoxicillin or cefuroxime in pregnancy).

Laboratory diagnosis of Lyme disease follows the CDC two-tiered algorithm: Tier 1 EIA/IFA followed, if positive or equivocal, by Tier 2 Western blot (or second EIA); both IgM and IgG Western blots are interpreted if symptoms lasted <=30 days, whereas ONLY IgG Western blot is interpreted if symptoms lasted >30 days (due to high false-positive IgM).

Single-dose oral Doxycycline 200 mg prophylaxis within 72 hours of tick removal is indicated ONLY when four strict criteria are met: 1) tick identified as adult/nymphal Ixodes scapularis, 2) attached for >=36 hours (engorged), 3) prophylaxis initiated within 72 hours of removal, and 4) local tick Borrelia infection rate is >=20% (endemic regions: New England, Mid-Atlantic, Upper Midwest).

Rocky Mountain Spotted Fever (RMSF; Rickettsia rickettsii, transmitted by Dermacentor variabilis dog ticks) presents with high fever, severe headache, and a centripetal maculopapular-to-petechial rash starting on wrists and ankles on days 2-4; DOXYCYCLINE IS THE DRUG OF CHOICE FOR ALL AGES (including children <8 years and pregnancy with severe illness) and must be initiated IMMEDIATELY upon clinical suspicion without waiting for serologic confirmation (delaying beyond day 5 increases mortality >20%).

Anaplasmosis (Ixodes tick) infects neutrophils (morulae) while Ehrlichiosis (Amblyomma tick) infects monocytes, both presenting with fever, leukopenia, thrombocytopenia, and transaminitis treated with Doxycycline; Babesiosis (Babesia microti, Ixodes tick) is an intraerythrocytic protozoan causing hemolytic anemia with pathognomonic 'Maltese cross' tetrads on blood smear, treated with oral Atovaquone plus Azithromycin.

Last updated: September 2026

Lyme Disease (Borrelia burgdorferi): Staging & Management

Lyme disease, caused by the spirochete Borrelia burgdorferi (and less commonly Borrelia mayonii in the Upper Midwest), is the most frequently reported vector-borne infection in North America. It is transmitted through the bite of infected blacklegged deer ticks: Ixodes scapularis in the Northeastern, Mid-Atlantic, and North-Central United States, and Ixodes pacificus on the Pacific Coast.

Transmission Biology & Kinetics

Transmission of B. burgdorferi is not instantaneous upon tick attachment. In unengorged ticks, the spirochete resides dormant within the midgut. Upon ingestion of a blood meal, temperature and pH changes trigger spirochetal multiplication, surface protein remodeling (downregulation of OspA, upregulation of OspC), and migration across the hemolymph to the tick's salivary glands. This biological cascade requires a minimum of 36 to 48 hours of tick attachment and feeding . Ticks attached for <24 to 36 hours carry an exceedingly low risk of transmission.

Clinical Staging of Lyme Disease

Lyme disease progresses through three distinct clinical stages if untreated: THE THREE CLINICAL STAGES OF LYME DISEASE

Stage Timing Post-Bite Cardinal Clinical Manifestations
═════════════════════════════════════════════════════════════════════════════════════════
1. Early Localized 7 to 14 days Erythema Migrans (EM) lesion at bite site (>=5 cm);

(Range: 3-30 days) Mild flu-like illness (fever, fatigue, myalgias).

2. Early Disseminated Weeks to months Multiple secondary EM annular lesions;
Neurologic: Cranial nerve VII palsy (Bell's palsy;
unilateral or bilateral), lymphocytic meningitis;

Cardiac: Lyme carditis (AV block: 1st, 2nd, 3rd deg).

3. Late Disseminated Months to years Lyme Arthritis: Recurrent, asymmetric mono/oligo-
arthritis of large joints (classically the knee);

Late Neuro: Subacute encephalopathy, polyneuropathy.

═════════════════════════════════════════════════════════════════════════════════════════
Stage 1: Early Localized Disease & Erythema Migrans (EM)

Morphology of Erythema Migrans :

Occurs in 70% to 80% of infected individuals, appearing at the site of the tick bite after an incubation period of 7 to 14 days (range: 3 to 30 days).

Begins as a red macule or papule that expands outward over days, reaching a diameter of >= 5 cm (often >10 to 15 cm).

The lesion is characteristically erythematous, flat or slightly indurated, warm to the touch, but typically non-pruritic and painless .

While the classic "bull's-eye" or targetoid appearance (central clearing with a red outer ring) is historically emphasized, uniform erythematous plaques without central clearing account for over 60% of EM lesions in North America .

Accompanied by systemic symptoms: low-grade fever, fatigue, malaise, arthralgias, myalgias, and headache.

Caution

THE CARDINAL DIAGNOSTIC PEARL: NEVER ORDER SEROLOGY FOR ERYTHEMA MIGRANS Erythema Migrans (>=5 cm) in an endemic area is DIAGNOSTIC OF LYME DISEASE .

Clinicians must NEVER order serologic testing in early localized disease . Specific IgM and IgG antibodies take 2 to 4 weeks to develop; testing during the acute EM phase has a false-negative rate >50% . A negative serology never excludes early Lyme disease. Empiric antimicrobial therapy must be initiated immediately based on clinical grounds alone.

Antimicrobial Regimens for Early Localized Lyme :

First-Line : Oral Doxycycline 100 mg twice daily for 10 to 14 days (effective, well-tolerated, and concurrently covers co-transmitted Anaplasma phagocytophilum ).

Alternatives in Pregnancy & Lactation :

Oral Amoxicillin 500 mg three times daily for 14 days ;

Oral Cefuroxime axetil 500 mg twice daily for 14 days . (Note: Per AAP and CDC guidelines, short courses of doxycycline [<21 days] are now considered safe in young children <8 years; amoxicillin remains an acceptable alternative in young children).

Stage 2: Early Disseminated Lyme Disease

Arises weeks to months after the initial bite as spirochetes disseminate hematogenously:

Cutaneous : Multiple secondary annular erythematous lesions (smaller than the primary EM lesion, appearing across the trunk and extremities).

Neurologic (Lyme Neuroborreliosis) :

Cranial Neuropathy : Cranial nerve VII (facial) palsy is the most common neurologic manifestation. It may be unilateral or bilateral . In Lyme-endemic areas, bilateral facial palsy is virtually pathognomonic for Lyme disease .

Lymphocytic meningitis: Headache, photophobia, mild nuchal rigidity, and CSF lymphocytic pleocytosis.

Motor/sensory radiculoneuritis (Bannwarth syndrome): Agonizing radicular pain.

Cardiac (Lyme Carditis) :

Occurs in 1% to 4% of untreated patients. Spirochetal infiltration of the cardiac conduction system causes fluctuating atrioventricular (AV) nodal conduction blocks (first-, second-, or third-degree complete heart block).

Management of Early Disseminated Disease :

Isolated Facial Nerve Palsy (normal CSF) : Oral Doxycycline 100 mg twice daily for 14 to 21 days . (Corticosteroids provide no benefit and are not recommended for Lyme facial palsy).

Severe Lyme Carditis (PR interval >=300 ms, 2nd or 3rd degree AV block, or syncope) : Immediate hospital admission, continuous telemetry monitoring, and intravenous Ceftriaxone 2 g IV daily until high-grade block resolves, followed by oral step-down to complete 21 to 28 days total.

Stage 3: Late Disseminated Lyme Disease

Lyme Arthritis : Manifests months to years later in up to 60% of untreated patients. Characterized by recurrent, asymmetric, pauciarticular (mono- or oligo-) arthritis affecting large weight-bearing joints , overwhelmingly the knee (>90% of cases). The affected knee is markedly swollen with a massive, tense effusion, warm to touch, but characteristically only mildly to moderately painful (out of proportion to the dramatic swelling). Synovial fluid analysis reveals an inflammatory effusion (WBC 20,000 to 50,000/mcL with neutrophil predominance).

Management : Oral Doxycycline 100 mg twice daily for 28 days (or amoxicillin 500 mg TID x 28 days). If arthritis persists or recurs after a full oral course, IV Ceftriaxone 2 g daily for 14 to 28 days is indicated.

CDC Two-Tiered Serologic Testing Algorithm

Serologic testing is indicated exclusively for patients with objective signs of disseminated or late Lyme disease (cranial neuropathy, carditis, meningitis, arthritis) or prolonged constitutional symptoms:

First-Tier Test : Highly sensitive Enzyme Immunoassay (EIA) or Immunofluorescence Assay (IFA) .

If the first tier is negative , no further testing is indicated.

If the first tier is positive or equivocal , the laboratory automatically reflexes to the second tier.

Second-Tier Test: Western Blot (or second FDA-cleared EIA) :

Illness Duration <= 30 Days : Both IgM and IgG Western blots are performed and interpreted. An IgM Western blot is positive if >= 2 of 3 specific bands are present (23, 39, 41 kDa). An IgG Western blot is positive if >= 5 of 10 specific bands are present (18, 23, 28, 30, 39, 41, 45, 58, 66, 93 kDa).

Illness Duration > 30 Days : ONLY THE IgG WESTERN BLOT IS INTERPRETED . An isolated positive IgM Western blot in a patient with symptoms lasting >30 days represents a false positive and must be disregarded! CDC TWO-TIERED TESTING FOR LYME DISEASE

First-Tier: Sensitive EIA or IFA
│
┌─────────────┴─────────────┐
▼ ▼
Negative Positive or Equivocal
│ │
Stop Testing ▼
(No Lyme) Second-Tier: Western Blot
│
┌───────────────────────────┴───────────────────────────┐
▼ ▼
Symptoms <= 30 Days Symptoms > 30 Days
│ │
Perform IgM AND IgG Western Blot Interpret IgG Western Blot ONLY
IgM: >= 2 of 3 bands (23, 39, 41 kDa) • IgG: >= 5 of 10 bands
IgG: >= 5 of 10 bands • DISREGARD IgM (High False-Positive!)
Post-Exposure Lyme Prophylaxis Criteria

Prophylactic antibiotics following a tick bite are NOT indicated for every tick encounter. Routine antimicrobial prophylaxis after tick bites is inappropriate.

Important

THE FOUR MANDATORY CRITERIA FOR LYME POST-EXPOSURE PROPHYLAXIS A single dose of oral doxycycline is indicated ONLY when ALL FOUR of the following criteria are satisfied :

The attached tick can be reliably identified as an adult or nymphal blacklegged deer tick ( Ixodes scapularis );

The tick is estimated to have been attached for >= 36 hours (based on engorgement index or known timing);
Prophylaxis can be initiated within 72 hours of tick removal;

The local infection rate of Ixodes ticks with B. burgdorferi is >= 20% (endemic areas: New England, Mid-Atlantic states, Minnesota, Wisconsin).

PROPHYLACTIC REGIMEN : A single oral dose of Doxycycline 200 mg (for children: 4.4 mg/kg up to 200 mg max). If any criterion is missing or if doxycycline is contraindicated, the recommended approach is watchful clinical observation for 30 days.

Rocky Mountain Spotted Fever (RMSF): The Life-Threatening Emergency

Rocky Mountain Spotted Fever (RMSF), caused by the obligate intracellular bacterium Rickettsia rickettsii , is the most lethal tick-borne infection in the United States. Despite its geographic name, RMSF is disproportionately concentrated in the Southeastern and South-Central states (North Carolina, Tennessee, Missouri, Arkansas, Oklahoma).

Vector & Transmission

Transmitted primarily by the American dog tick ( Dermacentor variabilis ) in the Eastern and Central US, the Rocky Mountain wood tick ( Dermacentor andersoni ) in the West, and the brown dog tick ( Rhipicephalus sanguineus ) in the Southwest and Mexican border region. Unlike Lyme disease, R. rickettsii can be transmitted within 6 to 10 hours of tick attachment .

Pathogenesis: Endothelial Tropism

R. rickettsii possesses an exclusive tropism for vascular endothelial cells lining small blood vessels, capillaries, and arterioles. Spirochetal invasion induces widespread endothelial cell necrosis, loss of vascular integrity, microvascular thrombosis, and diffuse microvascular leakage. This systemic vasculitis triggers non-cardiogenic pulmonary edema (ARDS), cerebral edema, acute kidney injury, cutaneous gangrene, and multiorgan failure.

Clinical Presentation & The Centripetal Rash

Initial Symptoms : Following an incubation period of 3 to 12 days, patients develop abrupt, severe constitutional illness: high fevers (>38.9°C / 102°F) , excruciating frontal headache, severe photophobia, prostrating myalgias, nausea, and vomiting.

Evolution of the Classic Rash :

The rash is characteristically ABSENT on days 1 and 2 of illness (present in <15% of patients initially).

Develops on days 2 to 4 as small (1 to 5 mm), blanching, erythematous macules beginning symmetrically on the wrists, forearms, and ankles .

Over subsequent days, the rash spreads centripetally inward to the palms, soles, legs, arms, and trunk .

By days 5 to 6, the lesions evolve into non-blanching petechiae and purpura , coalescing into areas of skin necrosis and gangrene.

Up to 10% to 15% of patients never develop a rash ("spotless RMSF"), which carries the highest mortality rate due to delayed diagnosis.

Laboratory Clues : Marked thrombocytopenia (platelets <100,000/mcL), hyponatremia (serum Na <135 mEq/L resulting from vascular leak and increased ADH release), elevated transaminases (AST/ALT), and leukocytosis with left shift.

Caution

CRITICAL CLINICAL MANDATE: DOXYCYCLINE FOR ALL AGES IN SUSPECTED RMSF Doxycycline is the FIRST-LINE DRUG OF CHOICE FOR PATIENTS OF ANY AGE , including children younger than 8 years and pregnant patients with severe illness.

TREATMENT MUST BE INITIATED IMMEDIATELY UPON CLINICAL SUSPICION without waiting for laboratory confirmation. Initial indirect immunofluorescence antibody (IFA) serologies are universally negative in the first 7 to 10 days of illness.

Delaying doxycycline administration beyond day 5 of illness causes mortality to surge from <2% to over 20% to 30% . The AAP and CDC confirm that short courses of doxycycline do not cause dental staining in young children.

Dosing : Doxycycline 100 mg PO or IV twice daily (children: 2.2 mg/kg/dose twice daily up to 100 mg/dose) continued for at least 3 days after fever resolves and clinical improvement is evident (minimum course: 7 to 10 days).

Anaplasmosis, Ehrlichiosis & Babesiosis COMPARATIVE SUMMARY OF TICK-BORNE INFECTIONS

Illness / Organism Primary Vector & Region Target Cell / Smear Clue Key Laboratory Clues First-Line Drug

═════════════════════════════════════════════════════════════════════════════════════════════════════════════════

Lyme Disease Ixodes scapularis Extracellular spirochete High false (-) serology Doxycycline
(Borrelia burg) Northeast / Midwest (No smear visualization) in early disease 100 mg PO BID

RMSF Dermacentor variabilis Vascular Endothelial Thrombocytopenia, Doxycycline
(Rickettsia rick) Southeast / Central US Cells (Vasculitis) Hyponatremia, high AST 100 mg PO/IV BID

Anaplasmosis (HGA) Ixodes scapularis Neutrophils / Granulocytes Leukopenia, severe Doxycycline
(Anaplasma phag) Northeast / Midwest Intracytoplasmic morulae thrombocytopenia 100 mg PO BID

Ehrlichiosis (HME) Amblyomma americanum Monocytes / Macrophages Leukopenia, Doxycycline
(Ehrlichia chaff) (Lone Star) Southeast Intracytoplasmic morulae thrombocytopenia 100 mg PO BID

Babesiosis Ixodes scapularis Erythrocytes (Intra-RBC) Hemolytic anemia, Atovaquone +
(Babesia microti) Northeast (Islands) "Maltese cross" tetrads high LDH, low haptogl Azithromycin

Human Granulocytic Anaplasmosis (HGA) vs. Human Monocytic Ehrlichiosis (HME)

Anaplasmosis ( Anaplasma phagocytophilum ) :

Vector: Ixodes scapularis (blacklegged tick); co-infection with Borrelia burgdorferi and Babesia microti occurs in up to 10% to 20% of patients.

Target Cell: Invades and replicates within polymorphonuclear neutrophils .

Diagnosis: Peripheral blood smear with Wright-Giemsa stain reveals intracytoplasmic morulae (clusters of microcolonies) within neutrophils in 20% to 70% of acute cases. Confirmed via PCR.

Ehrlichiosis ( Ehrlichia chaffeensis ) :

Vector: Amblyomma americanum (lone star tick) ; concentrated in Southeastern and South-Central states.

Target Cell: Invades and replicates within monocytes and macrophages .

Diagnosis: Peripheral blood smear demonstrates morulae in monocytes (rare, visible in <10%). Confirmed via PCR.

Clinical Presentation : Both present with acute high fevers, shaking chills, severe headache, and myalgias. Rashes are rare in anaplasmosis (<10%) and occur in ~30% of adults with ehrlichiosis. Laboratory hallmarks: profound leukopenia (WBC <3,000/mcL) , thrombocytopenia (platelets <100,000/mcL) , and elevated liver transaminases (AST/ALT).

Treatment : Oral Doxycycline 100 mg twice daily for 10 to 14 days is first-line for both.

Babesiosis ( Babesia microti )

Microbiology : An intraerythrocytic protozoan parasite transmitted by Ixodes scapularis in coastal New England (Nantucket, Martha's Vineyard, Cape Cod, Rhode Island, Connecticut), New York (Long Island), and Minnesota/Wisconsin.

Pathogenesis : Sporozoites invade host erythrocytes, multiplying and lysing red blood cells. Severe, life-threatening babesiosis occurs predominantly in asplenic individuals , immunocompromised hosts, and the elderly.

Clinical Presentation : Malaise, fatigue, high fevers, drenching sweats, followed by overt hemolytic anemia (jaundice, scleral icterus, dark hemoglobinuria, elevated indirect bilirubin, high lactate dehydrogenase [LDH], undetectable haptoglobin, and reticulocytosis) with thrombocytopenia.

Diagnostic Hallmark :

Thin and thick Giemsa-stained peripheral blood smears reveal intraerythrocytic parasites: pleomorphic ring forms (resembling Plasmodium falciparum ) and the pathognomonic "Maltese cross" (tetrad of four merozoites budding together) .

Antimicrobial Therapy :

Mild-to-Moderate Disease : Oral Atovaquone 750 mg twice daily PLUS oral Azithromycin 500 mg on day 1 then 250 mg daily for 7 to 10 days .

Severe / Hospitalized Disease (parasitemia >=10%, severe hemolysis, shock) : Intravenous Clindamycin 600 mg IV every 6 hours PLUS oral Quinine 650 mg every 8 hours , accompanied by urgent red blood cell exchange transfusion .