01Approach to the Critical Patient/attcp63

Immediate priorities

›Airway and breathing threats

›Respiratory compromise signs

›ARDS from severe relapsing fever (rare but life-threatening)

›Acute pulmonary edema especially in louse-borne relapsing fever

›Hemodynamic instability

›SBP < 90 mmHg

›MAP < 65 mmHg

›If shock or ARDS, escalate to resuscitation bay immediately

›IV access, continuous monitoring

›Fluid resuscitation with crystalloid 30 ml/kg

›Jarisch-Herxheimer reaction recognition

›Occurs within 2 hours of first antibiotic dose

›TBRF incidence approximately 19%

›LBRF incidence approximately 56%

›JHR hallmarks

›High fever spike

›Rigors and diaphoresis

›Tachycardia and transient hypotension

›All patients observed for minimum 4 hours after first antibiotic dose

›JHR management is supportive

›Vasopressors if hemodynamically unstable during JHR

›Neurologic emergency recognition

›Meningoencephalitis pattern

›Altered mental status

›Seizures

›Cranial nerve palsy especially CN VII facial palsy

›If neurologic involvement, escalate to IV ceftriaxone and infectious disease consult

02History/hx82

Presentation pattern

›Fever pattern

›Abrupt onset high fever lasting 3 to 6 days

›Followed by spontaneous crisis with drenching sweats

›Afebrile interval approximately 7 days before relapse

›Typically 3 to 5 relapses if untreated

›LBRF tends to fewer relapses than TBRF

›Relapsing pattern highly specific for this diagnosis

›Associated symptoms

›Headache

›Often severe

›Meningoencephalitis overlap

›Rigors and chills

›During fever spike onset

›Distinct from mild chills of other infections

›Myalgias and arthralgias

›Diffuse musculoskeletal pain

›May mimic influenza early

Exposure history

›Tick exposure context

›TBRF risk settings

›Sleeping in rustic cabins or lean-tos in western US

›Caving especially in Texas

›Rodent-infested dwellings

›Tick bite often not recalled

›Ornithodoros soft ticks feed briefly at night

›Bites are painless

›Geographic risk states

03Physical Exam/exam77

Vital signs

›Temperature and fever pattern

›High fever often above 39 C during febrile episodes

›Hyperpyrexia possible in severe cases

›Spontaneous defervescence with crisis

›Tachycardia

›Proportional to fever

›Worsens during JHR

›Blood pressure

›Hypotension during crisis and JHR

›SBP below 90 mmHg requires intervention

›Respiratory rate

›Elevated with fever and systemic illness

›Greater than 30 per minute as severity marker

›Pulmonary edema or ARDS if progressive

Skin and mucous membranes

›Rash patterns

›Petechial macular or papular rash

›Present in 4 to 50% of cases

›Typically appears as primary fever wanes

›Jaundice

›More common in louse-borne relapsing fever

›Hepatic involvement indicator

›Hemorrhagic signs

›Epistaxis

›Often profuse in LBRF

›Thrombocytopenia-related

›Petechiae and ecchymoses

04Differential Diagnosis/ddx60

Life-threatening mimics

›Malaria

›ICD-10 B50 to B54 range

›Most critical to exclude in travelers with relapsing fever

›Thick and thin peripheral smear required

›Differentiating features

›Cyclical fever pattern Plasmodium vivax and ovale

›Smear shows ring forms or schizonts

›Sepsis from other sources

›ICD-10 A41.9

›Endocarditis with relapsing fevers

›New murmur and embolic phenomena

›Blood cultures essential

›Growth of Staphylococcus or Streptococcus

›Meningococcemia

›ICD-10 A39.2

›Purpuric rash versus papular rash

›Rapid progression to septic shock

Tick-borne illness mimics

›Human granulocytic anaplasmosis

›ICD-10 A77.49

›Especially mimics B miyamotoi hard-tick relapsing fever

›Leukopenia, thrombocytopenia, elevated transaminases

›Differentiation

›Morulae in neutrophils on smear

›PCR for Anaplasma phagocytophilum

›Rocky Mountain spotted fever

›ICD-10 A77.0

05Laboratory Tests/lt73

Peripheral blood smear

›Diagnostic smear evaluation

›Wright or Giemsa stained smear during febrile episode

›Sensitivity approximately 70% during active fever

›Spirochetes visible as spiral organisms in blood

›Optimal timing

›During febrile phase before treatment

›Sensitivity decreases during afebrile intervals

›Enhanced techniques

›Acridine orange staining increases detection sensitivity

›Dark-field or phase-contrast microscopy of wet mount preparations

›Buffy coat preparation concentrates organisms

Molecular and serologic testing

›PCR and NAAT testing

›PCR more sensitive than microscopy

›Performed early ideally before treatment

›Can detect and differentiate RF Borrelia species

›Semimultiplex real-time PCR

›Simultaneously classifies soft-tick hard-tick and louse-borne groups

›Reference laboratory submission may be required

›B miyamotoi PCR

›Essential for hard-tick relapsing fever diagnosis

›Standard Borrelia burgdorferi PCR will not detect

›Serology

›IFA and EIA available

›Not standardized for relapsing fever Borrelia species

›Cross-reacts with B burgdorferi causing Lyme serologic false positives

›Paired acute and convalescent samples most useful

06Diagnostic Tests/dt75

Scoring Systems

›Risk stratification for relapsing fever

›No validated relapsing-fever-specific scoring tool exists

›Clinical severity guided by features

›High-risk features driving ICU disposition

›Severity indicators

›Thrombocytopenia below 50 x10^9/L

›Neurologic involvement

›Hemodynamic instability

›Sepsis scoring

›qSOFA for rapid bedside assessment

›RR greater than or equal to 22 per minute

›SBP less than or equal to 100 mmHg

›Altered mental status

›SOFA score for organ dysfunction in ICU patients

›Serial assessment guides ICU management

›ACEP Level C recommendation for sepsis severity tools

MRI

›MRI brain indications

›Neuroborreliosisis or meningoencephalitis evaluation

›White matter T2 signal changes in encephalitis

›Meningeal enhancement with gadolinium

›MRI spine

›Myelitis from spirochetal CNS invasion

›Radiculopathy evaluation

›Limitations in acute setting

›Availability and time constraints

›CT head preferred for urgent exclusion of hemorrhage or mass

07Disposition/dispo45

Admission indications

›Inpatient admission criteria

›All confirmed or strongly suspected relapsing fever cases

›Antibiotic initiation and JHR monitoring required

›Minimum 4-hour observation after first dose

›Thrombocytopenia

›Platelet count below 100 x10^9/L

›Active bleeding risk

›Inability to tolerate oral medications

›Nausea and vomiting during febrile episode

›IV antibiotic pathway

›Neurologic involvement

›IV antibiotics required

›Observation for complications

›ICU indications

›Hemodynamic compromise

›Septic shock with vasopressor requirement

›JHR-related prolonged hypotension

›ARDS or respiratory failure

›Mechanical ventilation requirement

›HFNC escalation

›Severe hemorrhage

›Life-threatening bleeding with thrombocytopenia

›Platelet transfusion and product support

›Severe meningoencephalitis

›Altered mental status and seizures

›Neurologic intensive monitoring

08Treatment/t84

Antibiotic therapy

›First-line antibiotics for adults

›Doxycycline oral for uncomplicated TBRF

›100 mg PO twice daily for 5 to 10 days

›Preferred agent for tick-borne relapsing fever

›Tetracycline oral as alternative

›500 mg PO four times daily for 10 days

›Class I recommendation based on evidence

›Erythromycin oral for tetracycline-allergic adults

›500 mg PO four times daily for 10 days

›Lower relapse rates reported with tetracyclines

›LBRF treatment

›Single-dose tetracycline 500 mg PO may suffice

›Higher JHR risk with tetracyclines versus penicillin

›Lower relapse rates with tetracyclines

›Single-dose erythromycin 500 mg PO alternative

›Better JHR profile than tetracycline

›Guideline-supported for louse-borne disease

›Penicillin G associated with increased relapse rates in TBRF

›Avoid as monotherapy for tick-borne disease

Parenteral therapy

›IV antibiotics for neurologic involvement or inability to take PO

›Ceftriaxone IV first-line for CNS relapsing fever

›2 g IV once daily for 10 to 14 days

›Preferred for meningoencephalitis and pregnancy

›Penicillin G IV alternative for LBRF without CNS

›Risk of higher relapse rate versus tetracyclines

›Use when tetracycline and ceftriaxone contraindicated

›IV doxycycline when PO not tolerated

›100 mg IV twice daily

›Transition to oral when tolerating

›Avoid in pregnancy

Jarisch-Herxheimer reaction management

›JHR anticipation and prevention

›Inform patient before antibiotic initiation

›Occurs within 30 minutes to 2 hours of first dose

›Self-limited in most cases lasting 2 to 8 hours

›Monitor for 4 hours minimum after first dose

›Continuous vital signs monitoring

›IV access maintained

›JHR treatment

›Supportive care primary approach

›IV fluid bolus for hypotension

›Norepinephrine 0.01 to 0.3 mcg/kg/minute if persistent hypotension

›Antipyretics for fever during JHR

›Acetaminophen 650 mg PO or IV q4 to 6 hours PRN

›Avoid NSAIDs if thrombocytopenic

›Meptazinol may diminish JHR severity in LBRF

›Not widely available in North America

›Anti-TNF-alpha Fab shown efficacy in LBRF trials

›Do not stop antibiotics for JHR

›Continue antimicrobial therapy

›Treat JHR symptoms supportively

Supportive care

›Fluid resuscitation

›IV crystalloid for dehydration from rigors and sweats

›Lactated Ringer or normal saline

›Reassess after each bolus for response

›If cardiogenic pulmonary edema suspected

›Cautious fluid strategy

›Diuresis consideration

›Hemorrhage management

›Thrombocytopenia with active bleeding

›Platelet transfusion threshold less than 50 x10^9/L with active bleeding

›Fresh frozen plasma for coagulopathy

›Epistaxis management

›Nasal packing for severe epistaxis

›ENT consultation for refractory bleeding

›Antipyretics for fever

›Acetaminophen 650 to 1000 mg PO or IV every 6 hours

›Preferred over NSAIDs

›Avoid aspirin with thrombocytopenia

›Cooling blankets for hyperpyrexia

›Temperature above 40 C

Contraindications and cautions

›Antibiotic cautions

›Amoxicillin for B miyamotoi hard-tick relapsing fever

›In vitro resistance demonstrated

›Avoid as monotherapy

›Tetracyclines in pregnancy

›Contraindicated after first trimester

›Use ceftriaxone instead

›Doxycycline in children under 8 years

›Dental staining and bone effects

›Erythromycin preferred

›Relapse awareness

›Some relapse despite adequate therapy

›Especially with penicillin in TBRF

›Repeat course of doxycycline for relapse

09Special Populations/sp74

Pregnancy

›Pregnancy risks in relapsing fever

›Spontaneous abortion

›Transplacental spirochete transmission

›Risk highest during spirochetemic febrile phase

›Neonatal relapsing fever

›Premature delivery and neonatal death risk

›Neonatal fever evaluation must include LP

›Higher maternal mortality

›Hepatic failure and hemorrhage risks elevated

›Treatment in pregnancy

›Ceftriaxone IV first-line at all trimesters

›2 g IV daily for 10 to 14 days

›Crosses placenta but no teratogenicity established

›Erythromycin oral as alternative

›500 mg PO four times daily

›Generally safe in pregnancy

›Avoid doxycycline and tetracyclines

›Contraindicated after first trimester

›Dental and bone effects in fetus

›Monitoring in pregnancy

›Fetal monitoring when viable gestation

›JHR may trigger fetal distress

›Obstetrics consultation before antibiotic initiation

›Maternal oxygenation target SpO2 greater than or equal to 95%

›Fetal oxygen delivery dependent on maternal saturation

›Aggressive pulmonary support if respiratory compromise

10Background/b84

Epidemiology

›Incidence and distribution

›TBRF in North America

›Western US states most affected

›Cases often cluster around cabin exposures

›LBRF globally

›Ethiopia and East Africa endemic

›Epidemic in displaced populations and refugee camps

›Hard-tick relapsing fever B miyamotoi

›Northeastern and upper midwestern US

›Exact incidence unknown and likely underreported

›Case fatality rates

›Untreated LBRF 4 to 40% historically

›High in epidemic settings without treatment

›Treated TBRF case fatality rate less than 5%

›Treatment markedly reduces mortality

›Pregnancy increases case fatality rate

›Perinatal mortality significant in endemic areas

›Seasonality and demographics

›Summer and autumn predominance for tick-borne types

›Ornithodoros tick activity peak

›LBRF year-round in endemic settings

›Louse activity not seasonally restricted

›No sex predilection

›Exposure risk determines case distribution

Pathophysiology

›Spirochetemia mechanism

›Borrelia enters bloodstream after tick or louse feeding

›Incubation 2 to 18 days depending on species

›Organisms multiply in blood during febrile phase

›Antigenic variation drives relapsing pattern

›Variable membrane proteins undergo sequential switching

›New antigenic variant escapes immune clearance

›Each relapse caused by new serotype

›Immune pathogenesis

›Cytokine storm during spirochetemia

›TNF-alpha, IL-6, and IL-8 surge

›Mediates fever rigors and hemodynamic changes

›JHR mechanism

›Mass spirochete destruction releases lipoproteins

›Massive cytokine release within hours of antibiotic initiation

›Parallels JHR in syphilis and leptospirosis

›Organ injury mechanisms

›Thrombocytopenia

›Immune-mediated platelet destruction

›Sequestration in enlarged spleen

›Hepatic injury

›Direct spirochetal invasion

›Immune-mediated hepatocyte damage

›Neurologic invasion

›Blood-brain barrier penetration

›Spirochetes detectable in CSF in meningitis cases

›Cardiac involvement

›Myocarditis from direct invasion and immune injury

›Conduction abnormalities possible

Therapeutic Considerations

›Antibiotic selection rationale

›Doxycycline preferred for TBRF

›Superior relapse prevention compared to penicillin

›Single-dose regimens less effective than multi-day courses

›Tetracycline class mechanism

›Inhibits protein synthesis at 30S ribosomal subunit

›Bacteriostatic against Borrelia species

›Ceftriaxone for CNS disease

›Superior CSF penetration

›Beta-lactam bactericidal against Borrelia

›JHR prevention and management considerations

›Cannot be reliably prevented with current agents

›Slower antibiotic administration not proven preventive

›Pre-treatment with TNF-alpha inhibitors investigational

›Patient and staff preparation essential

›IV access before first dose

›Vital sign monitoring protocol established

›Treatment failure and relapse

›Relapse after treatment most common with penicillin

›Repeat a full course of doxycycline

›Confirm diagnosis by repeat smear or PCR

›Persistent B miyamotoi in immunocompromised

›Prolonged therapy may be required

›Infectious disease guidance essential

›Prevention principles

›Tick bite prevention in endemic areas

›Insect repellents with DEET or permethrin

›Rodent control in cabin and dwelling settings

›Louse control for LBRF prevention

›Personal hygiene and delousing programs

›Clothing changes and fumigation in camp settings

11Patient Discharge Instructions/pdi44

copy discharge instructions

›Relapsing fever home care instructions

›Take all antibiotics exactly as prescribed

›Finish the entire course even if feeling better

›Do not skip doses

›Rest and hydration

›Drink plenty of fluids especially water

›Rest until fever has fully resolved

›Photosensitivity precaution with doxycycline

›Avoid prolonged direct sun exposure

›Use sunscreen and protective clothing

›Warning signs to return to emergency room

›High fever returning after seeming to improve

›May indicate a relapse episode

›Relapsing pattern is characteristic of this illness

›Severe shaking or rigors that do not settle within a few hours

›May indicate a reaction to antibiotics

›Nosebleed that does not stop with 15 to 20 minutes of pressure

›Go to the ER immediately

›Vomiting blood or black tarry stools

›Emergency return immediately

›Confusion or unusual behavior

›Neurologic involvement requires urgent care

›Difficulty breathing or chest pain

›Return to emergency immediately

›Yellowing of skin or eyes (jaundice)

›Sign of liver involvement

›Facial drooping or weakness

12References/r22

Guidelines and key sources

›Infectious disease guideline sources

›IDSA guidelines on tick-borne illnesses

›Include recommendations for doxycycline as first-line for tick-borne infections

›CDC relapsing fever clinical guidance

›Diagnostic and treatment recommendations for TBRF and LBRF

›WHO guidelines for louse-borne relapsing fever in refugee settings

›Single-dose regimens for mass treatment contexts

›Key clinical evidence

›Dworkin et al studies on tick-borne relapsing fever epidemiology and treatment outcomes

›Western US TBRF case series

›Doxycycline versus penicillin relapse rates

›Cadavid and Barbour: neuroborreliosis in relapsing fever

›CNS invasion and meningitis management

›Bryceson et al: louse-borne relapsing fever in Ethiopia

›JHR characterization and meptazinol trials

›Schwan and Piesman: B miyamotoi hard-tick relapsing fever

›Epidemiology in Ixodes tick populations

›Coding standards

›ICD-10 A68.0 louse-borne relapsing fever

›ICD-10 A68.1 tick-borne relapsing fever

›ICD-10 A68.9 relapsing fever unspecified

›SNOMED CT relapsing fever disorder concept

Evidence & Review