Spirochetal

Question 1

Lyme Disease

Answer 1

Multisystem illness caused by spirocheteBorrelia burgdorferi
Vector-borne disease transmitted to humans by infected ticks of the Ixodes genus
Lyme disease - most common vector-borne illness in the US, accounting for 29,959 reported cases in 2009
Emergence of Lyme disease is probably due to the explosion of deer and tick populations with the reforestation of the northeastern United States; subsequent contact between ticks and humans as people move into deer habitats
Also endemic in the rest of North America, Europe, and Asia

Question 2

Stage 1 of Lyme Disease

Answer 2

Stage 1 is also known as primary or early localized infection; occurs within 30 days of the tick bite
Most patients present with a characteristic expanding rash (erythema migrans) at the site of the tick bite 7-14 days after the tick is removed
Other nonspecific symptoms include fatigue, myalgias, arthralgias, headache, fever, chills, and neck stiffness

Question 3

Stage 2 or early disseminated disease of Lyme Disease

Answer 3

occurring generally weeks to months after the bite

Musculoskeletal and neurologic symptoms are the most common; less common symptoms are cardiac and dermatologic

Question 4

Stage 3 or chronic Lyme disease

Answer 4

happens months to years after infection, which sometimes involves a period of latency
Musculoskeletal (mainly joints) and neurologic systems are most commonly affected

Question 5

Systemic Manifestations of Lyme Disease

Answer 5

Fever is generally low grade
Fatigue is common
Myalgias and arthralgias occur early
Frank arthritis (i.e. joint swelling, redness, pain) usually is a later manifestation but can occur in the early disseminated phase
Flulike illness (undifferentiated febrile illness) may occur
Lyme disease with typical flulike symptoms of fevers, chills, myalgias, arthralgias, and malaise (without rash)
Season of onset, epidemiologic likelihood of a tick bite, paucity of respiratory and GI symptoms, and prompt response to antiborrelial therapy are diagnostic clues

Question 6

Cutaneous symptoms of Lyme Disease

Answer 6

Classic rash, erythema migrans (EM), is present in about 75% of patients.
Neither pruritic nor painful (although it can be either), some patients may have the rash but not notice it
EM can occur in the same patient more than once
20% of patients withLyme diseasehave multiple lesions (from hematogenous dissemination)
Borrelial lymphocytoma, a nodule usually found on the ear lobe or areola of the nipple, develops in some patients early in the course of disease (more common in Europe)

Question 7

Neurologic symptoms of Lyme Disease

Answer 7

Headache of Lyme disease typically is described as waxing and waning, and the severity varies from mild to severe, even in patients with frank meningitis
Facial weakness, which is similar to a typical Bell palsy and which can be the presenting symptom of Lyme disease; 25% of patients with borrelial facial palsy have bilateral involvement, which may be sequential and is a point of differential diagnostic significance (Lyme responsible for 34% of facial palsy)
Radicular pain can occur and present as acute disk disease
Late Lyme disease can cause paresthesias or pain due to peripheral neuropathy and personality, cognitive, and sleep disturbances from chronic encephalopathy
Neurologic syndromes caused by Lyme disease involve nearly every part of the CNS and peripheral nervous system

Question 8

Cardiovascular involvement of Lyme Disease

Answer 8

< 10% of patients with untreated Lyme disease; more common in males
Palpitations, lightheadedness, and syncope may be a manifestation of varying degrees of heart block, including complete heart block, which occurs in 50% of patients with cardiac involvement
Lyme disease is an important reversible cause of heart block
Chest pain and dyspnea can occur in the setting of Lyme pericarditis, myocarditis, and myopericarditis

Question 9

Joint Involvement of Lyme Disease

Answer 9

Migratory pain may occur from myositis, tendonitis, and bursitis, classically wax and wane over hours or days
Later, arthritis occurs generally with swelling, redness, and pain in one or a few large joints, typically the knees
Synovitis occasionally occurs in early-disseminated phase

Question 10

Ocular Involvement of Lyme Disease

Answer 10

Red, itchy eyes are the most commonocular symptom; blurred vision and eye pain can occur from keratitis and iritis

Question 11

Lyme Disease Workup

Answer 11

Solitary, typical EM requires no laboratory testing whatsoever
Positive culture forB burgdorferi, or
Two-tier testing interpreted using established criteria, where positive immunoglobulin M (IgM) is sufficient only when 30 days or less from symptom onset or positive immunoglobulin G (IgG) is sufficient at any point during illness
Single-tier IgG immunoblot seropositivity using established criteria
CSF antibody positive forB burgdorferiby enzyme immunoassay (EIA) or immunofluorescence assay (IFA), when the titer is higher than it was in serum

Question 12

Rocky Mountain spotted fever

Answer 12

Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by the organismRickettsia rickettsii
RMSF can be lethal, it is curable
RMSF is the most common rickettsial infection
Organism is endemic in parts of North, Central, and South America, especially in the southeastern and south-central United States
2 principaltick vectorsof RMSF in North America areDermacentor variabilis(dog tick), in the eastern United States, andD andersoni, in the Rocky Mountain region and Canada

Question 13

RMSF - Etiology and Pathophysiology

Answer 13

Ticks become infected by feeding on the blood of infected animals, through fertilization, or by transovarial passage
Rickettsiae are transmitted from tick to human during feeding; needs to be attached to a host for 6-10 hours for rickettsiae to be released from the salivary glands, although transmission may not occur for 24 hours
Infection possible for people who remove ticks from other people or animals via contact with tick tissues and fluids
Notable characteristics ofR rickettsiiinclude its marked tropism for endothelial cells that line blood vessels and its enhanced ability to invade throughout the body compared with other rickettsiae; model examples of vasculitis with localization in endothelial cells
Pathophysiologic effect of endothelial cell injury is increased vascular permeability, which results in edema, hypovolemia, hypotension, and hypoalbuminemia

Question 14

RMSF suspicion

Answer 14

Hallmark of RMSF is a petechial rash beginning on the palms of the hands and soles of the feet
High index of suspicion for RMSF in patients with the following:
Febrile illness
History of potential tick exposure
Travel to endemic area
Presentation in the spring or fall
RMSF should be considered in patients with unexplained febrile illness even if they have no history of a tick bite or travel to an endemic area (history of a tick bite is reported by only 70% of patients)

Question 15

RMSF - Presentation

Answer 15

Fever greater than 102°F - 94%
Fever within 3 days after tick bite - 66%
Headache, frequently severe - 86%
Myalgias - 85%
CNS symptoms - 25% of patients develop signs of encephalitis (ie, confusion, lethargy); may progress to stupor, delirium, seizures, or coma
Cardiovascular (myocarditis; relative bradycardia; arrhythmias - 7-16% of patients; hypotension - 7-17% of patients)
GI symptoms - anorexia, nausea, vomiting, diarrhea, and abdominal pain
Also may have insomnia and photophobia

Question 16

Some Lab Findings for RMSF

Answer 16

White blood cell (WBC) count - Leukopenia is present initially, then mild leukocytosis; patients usually have a normal WBC count
Platelets - Thrombocytopenia (< 150,000 cells/µL) occurs in 32-52% of patients; abnormalities indicative of DIC are present in severely ill patients
Hemoglobin and hematocrit - Anemia is present in 5-24% of patients
Aminotransferase levels - Mildly elevated in 36-62% of patients
Hyponatremia - Present in 19-56% of cases
Bilirubin levels – Increased in 8-9% of patients.
Mild cerebrospinal fluid pleocytosis with monocyte predominance
Azotemia - Develops in 12-14% of cases
Prothrombin time and activated partial thromboplastin time - May be elevated
Anemia, an increased blood urea nitrogen (BUN) level, or abnormal liver function test results are found in 30% of patients. Late findings associated with advanced disease include signs of multiorgan failure, such as elevated BUN, creatinine, and creatinine kinase levels.

Question 17

Serology workup of RMSF

Answer 17

Diagnosis is confirmed based on indirect immunofluorescent antibody (IFA) test results, latex agglutination, or enzyme immunoassay. Serology specific forR rickettsiiinfection develops within 6-8 weeks. Serologic test results are negative prior to convalescence.

Question 18

Blood and Lumbar puncture workup of RMSF

Answer 18

Blood Culture
Isolation ofR rickettsiifrom the blood is possible, but few laboratories perform this isolation

Lumbar puncture
Lumbar puncture usually is performed as part of the workup for suspected meningitis. Pleocytosis is found in 34-38% of cases. Usually 10-100 cells/µL with either lymphocytic or polymorphonuclear cell predominance are found. Increased protein is found in 30-35% of cases; the glucose level usually is normal.

Question 19

RMSF - Treatment

Answer 19

In adults with Rocky Mountain spotted fever (RMSF), the drug of choice is doxycycline
Chloramphenicol is an alternative, although doxycycline is preferable because tetracyclines have been shown to be associated with a higher survival rate than chloramphenicol
In vitro and in ovoR rickettsiiare also susceptible to rifampin
Doxycycline therapy also treats Lyme disease, ehrlichiosis, and relapsing fever—entities often clinically confused with RMSF
1997, AAP revised treatment options for children with RMSF: doxycycline became the preferred drug choice for treating children of any age because of the potential for severe or fatal cases.
Short courses of doxycycline to treat RMSF do not cause significant dental staining
Corticosteroids suppress active disease, which is assumed to be due to inflammatory mechanisms

Question 20

RSMF - Prognosis

Answer 20

Mortality rates in RMSF vary according to the following criteria:
Delay in diagnosis
Delay in effective antibiotic treatment - In a 1995 study, antirickettsial therapy within the first 5 days of illness reduced the risk of mortality 5-fold compared with treatment initiation after the 5-day mark[9]
Age
Race
Gender - Mortality risk is higher in males
Severity of the disease
Presence of chronic alcohol abuse
Presence of glucose-6-phosphate-dehydrogenase deficiency
The mortality rate in untreated cases of RMSF is 20-25%; rates can be as low as 5% with proper antibiotic therapy and as high as 70% in untreated elderly individuals

Question 21

RMSF - Prevention

Answer 21

Protective measures against tick bites include the following:
Avoid dogs with ticks and tick-infected areas
Use protective, light-colored clothing that covers arms and legs; tuck pants in socks to protect legs
Apply tick-repellent chemicals, such as diethyltoluamide (DEET, Autan) or permethrin, to pants and sleeves
Search the entire body every 3-4 hours when in an infested area; common areas of attachment are in scalp, pubic, or axillary hair

Question 22

Syphilis

Answer 22

Syphilis is an infectious venereal disease caused by the spirocheteTreponema pallidum
Syphilis is transmissible by sexual contact with infectious lesions, from mother to fetus in utero, via blood product transfusion, and occasionally through breaks in the skin that come into contact with infectious lesions
Syphilis has a myriad of presentations and can mimic many other infections and immune-mediated processes in advanced stages
Hence, it has earned the nickname “the great impostor” - its complex and variable manifestations of the disease prompted Sir William Osler to remark, “The physician who knows syphilis knows medicine”
Three genera of spirochetes cause human infection:
Treponema,which causes syphilis,yaws, andpinta (syphilis is T pallidum)
Borrelia,which causesLyme diseaseandrelapsing fever
Leptospira,which causesleptospirosis

Question 23

Acquired Syphilis

Answer 23

In acquired syphilis,T pallidumrapidly penetrates intact mucous membranes or microscopic dermal abrasions and, within a few hours, enters the lymphatics and blood to produce systemic infection
Incubation time from exposure to development of primary lesions, which occur at the primary site of inoculation, averages 3 weeks but can range from 10-90 days
(CNS) is invaded early in the infection; during the secondary stage, examinations demonstrate that more than 30% of patients have abnormal findings in the cerebrospinal fluid (CSF)
During the first 5-10 years after the onset of untreated primary infection, the disease principally involves the meninges and blood vessels, resulting in meningovascular neurosyphilis
Later, the parenchyma of the brain and spinal cord are damaged, resulting in parenchymatous neurosyphilis

Question 24

Syphilis - Pathophysiology

Answer 24

Regardless of the stage of disease and location of lesions, histopathologic hallmarks of syphilis include endarteritis (which in some instances may be obliterative in nature) and a plasma cell–rich infiltrate
Endarteritis is caused by the binding of spirochetes to endothelial cells (mediated by host fibronectin molecules bound to the surface of the spirochetes)
Resultant endarteritis can heal with scarring
Syphilitic infiltrate reflects a delayed-type hypersensitivity response toT pallidum; in certain individuals with tertiary syphilis, this response by sensitized T lymphocytes and macrophages results in gummatous ulcerations and necrosis
Antigens ofT palliduminduce host production of treponemal antibodies and nonspecific reagin antibodies
Immunity to syphilis is incomplete

Question 25

Syphilis Stages- Primary Syphilis

Answer 25

Primary syphilis is characterized by the development of a painless chancre at the site of transmission after an incubation period of 3-6 weeks
The lesion has a punched-out base and rolled edges and is highly infectious
Histologically, the chancre is characterized by mononuclear leukocytic infiltration, macrophages, and lymphocytes
Inflammatory reaction causes an obliterative endarteritis
Spirochete can be isolated from the surface of the ulceration or the overlying exudate of the chancre
Whether treated or not, healing occurs within 3-12 weeks, with considerable residual fibrosis

Question 26

Syphilis Stages- Secondary Syphilis

Answer 26

Secondary syphilis develops about 4-10 weeks after the appearance of the primary lesion
During this stage, the spirochetes multiply and spread throughout the body.
Systemic manifestations are variable; include malaise, fever, myalgias, arthralgias, lymphadenopathy, and rash
Widespread mucocutaneous lesions are observed over the entire body and may involve the palms, soles, and oral mucosae. Most often, the lesions are macular, discrete, reddish brown, and 5 mm or smaller in diameter; however, they can be pustular, annular, or scaling; all lesions contain treponemes
Other skin findings of secondary syphilis are condylomata lata and patchy alopecia; condylomata lata are painless, highly infectious gray-white lesions that develop in warm, moist sites

Question 27

Syphilis Stages- Latent Syphilis

Answer 27

Latent syphilis is a stage at which the features of secondary syphilis have resolved, though patients remain seroreactive
Some patients experience recurrence of the infectious skin lesions of secondary syphilis during this period
1/3 of untreated latent syphilis patients go on to develop tertiary syphilis
2/3 remain asymptomatic
Currently, tertiary syphilis disease is rare
. When it does occur, it mainly affects the cardiovascular system (80-85%) and the CNS (5-10%), developing over months to years and involving slow inflammatory damage to tissue
3 general categories of tertiary syphilis are gummatous syphilis (also called late benign), cardiovascular syphilis, and neurosyphilis

Question 28

Syphilis stages- Gummatous syphilis

Answer 28

Gummatous syphilis is characterized by granulomatous lesions, called gummas, which are characterized by a center of necrotic tissue with a rubbery texture
Gummas principally form in the liver, bones, and testes but may affect any organ
Histological examination shows palisaded macrophages and fibroblasts, as well as plasma cells surrounding the margins
Gummas may break down and form ulcers, eventually becoming fibrotic
Treponemes are rarely visualized or recovered from these lesions

Question 29

Syphilis Stages- Cardiovascular syphilis

Answer 29

Cardiovascular syphilis occurs at least 10 years after primary infection
Most common manifestation is aneurysm formation in the ascending aorta, caused by chronic inflammatory destruction of the vasa vasorum, the penetrating vessels that nourish the walls of large arteries
Aortic valve insufficiency may result

Question 30

Syphilis Stages- Neurosyphilis

Answer 30

If the spirochete invades the CNS, syphilitic meningitis results. Syphilitic meningitis is an early manifestation, usually occurring within 6 months of the primary infection. CSF shows high protein, low glucose, high lymphocyte count, and positive syphilis serology
Meningovascular syphilis occurs as a result of damage to the blood vessels of the meninges, brain, and spinal cord, leading to infarctions causing a wide spectrum of neurologic impairments
Parenchymal neurosyphilis includes tabes dorsalis and general paresis. Tabes dorsalis develops as the posterior columns and dorsal roots of the spinal cord are damaged; posterior column impairment results in impaired vibration and proprioceptive sensation, leading to a wide-based gait; disruption of the dorsal roots leads to loss of pain and temperature sensation and areflexia
Cortical damage to the brain leads to general paresis, formerly called “general paresis of the insane,” which mimics other forms of dementia. Impairment of memory and speech, personality changes, irritability, and psychotic symptoms; may advance to progressive dementia.
The Argyll-Robertson pupil, a pupil that does not react to light but does constrict during accommodation, may be seen in tabes dorsalis and general paresis

Question 31

Congenital Syphilis

Answer 31

Congenital syphilis is a veritable potpourri of antiquated medical terminology
Treponemes readily cross the placental barrier and infect the fetus, causing a high rate of spontaneous abortion and stillbirth
Within the first 2 years of life, symptoms are similar to severe adult secondary syphilis with widespread condylomata lata and rash; “snuffles” is the mucopurulent rhinitis caused by involvement of the nasal mucosae
Later manifestations of congenital syphilis include bone and teeth deformities, such as “saddle nose” (due to destruction of the nasal septum), “saber shins” (due to inflammation and bowing of the tibia), “Clutton’s joints” (due to inflammation of the knee joints), “Hutchinson’s teeth” (in which the upper incisors are widely spaced and notched), and “mulberry molars” (in which the molars have too many cusps)
Tabes dorsalis and general paresis may develop as in adults, with 8th cranial nerve deafness and optic nerve atrophy as well as a variety of other ophthalmologic involvement leading to blindness being additional features

Question 32

Syphilis - Etiology and risk factors

Answer 32

Transmission of T pallidum occurs via penetration of the spirochetes through mucosal membranes and abrasions on epithelial surfaces
Primarily spread through sexual contact but can be spread by exposure to blood products and transferred in utero
T pallidum is a labile organism that cannot survive drying or exposure to disinfectants; thus, fomite transmission (e.g. from toilet seats) is virtually impossible risk
Risk factors of syphilis include the following:
Unprotected sex, promiscuous sex, and intravenous drug use are the major risk factors
Health care workers are at occupational risk

Question 33

Syphilis Workup

Answer 33

T pallidumcannot be cultivated in vitro and is too small to be seen under the light microscope
Serologic testing is considered the standard method of detection for all stages of syphilis
In suspected acquired syphilis, first perform nontreponemal serology screening using the Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), or the recently developed ICE Syphilis recombinant antigen test; VDRL positive within a couple weeks
Sensitivity of the VDRL and RPR tests are estimated to be 78-86% for detecting primary syphilis, 100% for detecting secondary syphilis, and 95-98% for detecting tertiary syphilis
Specificity ranges from 85-99% and may be reduced in individuals who have coexisting condition
Because of the possibility of false-positive results, confirmation for any positive or equivocal nontreponemal test result should follow with a treponemal test

Question 34

Syphilis - Treatment

Answer 34

The following regimens are recommended for penicillin treatment:
Primary or secondary syphilis - Benzathine penicillin G 2.4 million units intramuscularly (IM) in a single dose
Early latent syphilis - Benzathine penicillin G 2.4 million units IM in a single dose
Late latent syphilis or latent syphilis of unknown duration - Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals
Pregnancy - Treatment appropriate to the stage of syphilis
In patients with a history of penicillin allergy, skin testing is recommended. Patients who are skin test negative can receive conventional treatment with penicillin; skin test positive patients should be desensitized in the hospital. Make every effort to document penicillin allergy before choosing an alternative treatment, because the efficacy of alternative regimens is questionable in all stages of syphilis. Many treatment failures have been reported.
Tetracycline, erythromycin, and ceftriaxonehave shown antitreponemal activity in clinical trials; however, they currently are recommended only as alternative treatment regimens in patients allergic to penicillin

Procaine toxicity
Some experience severe anxiety, fever, hallucinations, hyperventilation, convulsions; circulatory collapse

Jarisch-Herxheimer reaction
Following the initiation of treatment, the dying treponemes release inflammatory molecules; trigger a cytokine cascade
Symptoms include myalgias, fever, headache, and tachycardia, sometimes with exacerbation of whatever current syphilitic lesions are manifested (eg, rash or chancre)
The reaction is common, develops within several hours after beginning antibiotic treatment, and usually clears within 24 hours after onset
Etiology is unclear, although it may be due to an immunological reaction to the rupture of spirochetes
Management of this reaction often involves symptomatic treatment (e.g. with antipyretics and analgesics) and observation