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348

TOXIC SHOCK SYNDROME

CHAPTER 50

Joshua B. Gaither, MD

1. What is toxic shock syndrome (TSS)?

TSS is characterized by a rapidly progressing constellation of symptoms, caused by one of

several different bacterial exotoxins that act as a superantigen to stimulate an excessive

immune response. The syndrome was ﬁrst described in seven children presenting with high

fever, headache, confusion, conjunctival hyperemia, and gastrointestinal symptoms, which

were accompanied by a scarlatiniform rash and severe shock. All seven cases were linked

to Staphylococcus aureus, which was cultured from infected or mucosal sites, prompting

fears that the bacterium was expressing a newly discovered toxin. Over the past 30 years

the same toxin-mediated syndrome has been described in association with other bacterial

infections, including community acquired methicillin-resistant Staphylococcus aureus

(MRSA), which produces the same toxin, as well as streptococcus infections and clostridial

infections, each of which cause TSS-like symptoms through the production of different

endotoxins.

2. Why did a bacterium begin to express a new and deadly exotoxin in the late

1970s?

Todd’s report led to additional associations between TSS and S. aureus. In retrospect, the

syndrome may have been described as early as 1927. Some researchers believe that the

syndrome may have been responsible for the plague that ended the Golden Age of Athens.

KEY POINTS: RISK FACTORS FOR TSS

1. Air-containing foreign bodies (e.g., tampon, nasal packing)

2. Recent surgery

3. Postpartum

4. Burns

5. Focal infections

3. Who gets TSS?

Menses was associated with 91% of cases reported by 1980, which quickly pointed to the use

of new high-absorbency tampons as a risk factor. Such tampons, made with cross-linked

carboxymethylcellulose and polyester foam, were thought to provide an ideal environment for

the expression of TSS toxin and subsequently were removed from the market. With decreased

use of these tampons and increased awareness of TSS, more recent epidemiological surveys

have found that less than half of all staphylococcal TSS cases are associated with menses.

4. Is tampon use required for the patient to develop TSS?

No. Three of the patients identiﬁed in the 1978 report were male. Although the media focused on

the association with high-absorbency tampons, clinical interest in the syndrome identiﬁed a wide

Chapter 50 TOXIC SHOCK SYNDROME 349

variety of causes in the early 1980s. TSS has been reported in all age groups, in burn and

postsurgical patients, after childbirth, in association with the nasal packing commonly used to

control epistaxis, and in many types of local infections. Recent data have suggested that sinusitis

may be responsible for up to 21% of TSS in the pediatric population.

5. Describe the pathophysiology of TSS.

Three stages have been identiﬁed in the progression of the syndrome:

Local proliferation of the toxin-producing strain of bacteria

Toxin production

Immune response to the toxin, which sets off the inﬂammatory cascade and leads to

multisystem organ involvement

Although many different bacteria from a wide variety of sources have been reported to cause

TSS, the common link between infection and TSS is the production of a superantigen, which

stimulates massive cytokine release and a systemic inﬂammatory response leading to shock.

6. There was heavy media coverage of TSS in the early 1980s because of the

high case fatality rate. Has mortality been reduced?

The initial fatality rate was 13% for the ﬁrst 55 cases, with white females in the 15- to

19-year-old range thought to be at greatest risk. Further analysis of early cases suggests that

signiﬁcant reporting bias was a factor in the high fatality rate, which is now thought to be

stable at 5%. However, there have been few recent epidemiologic studies in the United States.

A more recent French study suggested that less than half of reported staphylococcal TSS

cases were menstrual and that that subset of patients had a 0% mortality rate, while

nonmenstural TSS accounted for 62% of cases and was associated with a 22% mortality rate.

KEY POINTS: COMMON CHARACTERISTICS OF TSS

1. Fever

2. Rash

3. Hypotension—shock

5. History of air-containing foreign body, abscess, local infection, or recent surgery or childbirth

6. Multisystem organ involvement

7. List the criteria for deﬁning a case of S. aureus TSS.

Fever > 38.9°C

Diffuse macular erythematous rash

Desquamation, usually of the palms or soles, after 1 to 2 weeks

Orthostasis or hypotension (with systolic blood pressure ,90 mm Hg in adults or less than

the sixth percentile in children)

Involvement of three or more of the following organ systems:

Gastrointestinal: vomiting or diarrhea

Muscular: myalgias or elevated creatine phosphokinase (twice normal)

Mucous membrane: vaginal, oropharyngeal, or conjunctival hyperemia

Renal: elevated blood urea nitrogen or creatinine (twice normal) or pyuria in the absence of

urinary tract infection

Hepatic: total bilirubin, alanine aminotransferase, aspartate aminotransferase levels at least

twice the upper limit of normal

Hematologic: platelets ,100,000/mm

Central nervous system: disorientation or alteration in consciousness without focal

neurologic signs (when fever and hypotension are absent)

Chapter 50 TOXIC SHOCK SYNDROME350

Negative results for the following, if obtained:

Blood, throat, or cerebrospinal ﬂuid cultures (blood cultures may be positive for S. aureus)

Rise in titer to Rocky Mountain spotted fever, leptospirosis, or rubeola

8. What is Streptococcal TSS?

Several different groups of streptococcus (most commonly Streptococcus pyogenes) can

cause a severe systemic reaction similar to TSS. Their toxin is similar to that of TSS.

Diagnosis requires the isolation of streptococci from a sterile or nonsterile site, hypotension,

and multisystem organ involvement (at least two or more of the following: renal impairment,

coagulopathy causing disseminated intravascular coagulopathy or thrombocytopenia,

hepatitis, adult respiratory distress syndrome, necrotizing soft-tissue infections, or skin

changes similar to those seen in TSS).

9. Describe the rash associated with TSS.

The rash is a macular erythroderma that blanches and is not pruritic. It may be diffuse or

localized and often is described as sunburn-like. It appears early in the illness and fades in

about 3 days. It may be subtle and can be missed in dark-skinned patients.

10. When is desquamation likely to occur?

Loss of skin, usually of the distal extremities, invariably occurs in survivors 5 to 12 days after

the illness starts. Delayed alopecia and ﬁngernail loss may occur later and seem to depend on

the level of hypotension during the acute illness.

11. Given the previously mentioned criteria for TSS, list the differential diagnosis.

Kawasaki disease

Staphylococcal scalded skin syndrome

Streptococcal scarlet fever

Rocky Mountain spotted fever

Leptospirosis

Stevens-Johnson syndrome

Erythema multiforme

Toxic epidermal necrolysis

Sepsis

Drug reactions

Measles

Colorado tick fever

12. Summarize the treatment for TSS.

Supportive care including intravenous ﬂuids for hypotension, with supplemental

vasopressor support as needed

Identiﬁcation and removal of the source of infection (e.g., tampon, abscess, nasal packing)

Antibiotics

13. Do antibiotics help?

No prospective studies show that antibiotics alter the severity or the course of TSS. However,

antibiotics reduce the recurrence rate (which can be 28%) and a delay in antibiotic

administration has been associated with increased mortality in other types of severe sepsis

and septic shock. Therefore early administration of antibiotics is considered the standard care.

14. What antibiotics should I use?

Vancomycin and clindamycin are considered the empiric antibiotics of choice. Clindamycin

has the added advantage of a direct antitoxin effect. When a source organism can be identiﬁed,

additional targeted antibiotic coverage is appropriate. For non-MRSA Staphylococcal TSS, a

penicillinase-resistant penicillin such as Nafcillin should be used, whereas for Streptococcal

TSS high-dose penicillin should be given.

15. Are there other therapies that can help control the immune response to the

toxin?

Intravenous immunoglobulin (IVIG) may decrease mortality rates by up to 3.6 times that of

patients receiving standard therapy; however, data on IVIG have been limited due to the low

incidence of TSS and a clear beneﬁt has not been established. Most authorities currently

Chapter 50 TOXIC SHOCK SYNDROME 351

recommend the use of IVIG for severe cases in which prompt antibiotic and source control fail

to result in clinical improvement. Theoretically, steroids should help attenuate the systemic

response to the toxin, but there are no prospective data to show they are effective. Steroid use

in sepsis is still debated, and steroids are not routinely used in the management of TSS.

16. Do all patients with TSS need admission?

Patients in whom TSS is suspected should be admitted because this toxin-mediated disease

can progress rapidly. In most patients, the systemic signs of illness (e.g., hypotension, fever,

and multisystem organ involvement) are present in the ED, clearly indicating the need for

inpatient supportive care.

BIBLIOGRAPHY

1. Chan KH, Kraai TL, Richter GT, et al: Toxic shock syndrome and rhinosinusitis in children. Arch Otolaryngo

Head Neck Surg 135:538–542, 2009.

2. Cohne AL, Bhatnager J, Reagen S, et al: Toxic shock associated with Clostridium sordellii and Clostridium

perfringens after medical and spontaneous abortion. Obstet Gynecol 110:970–971, 2007.

3. Darenberg J, Ihendyane N, Sjölin J, et al: Intravenous immunoglobulin G therapy in streptococcal toxic shock

syndrome: a European randomized, double blind, placebo-controlled trial. Clin Infect Dis 37:333–340, 2003.

4. Davis JP, Chesney PJ, Wand PJ, et al: Toxic-shock syndrome. N Engl J Med 303:1429–1435, 1980.

5. Descloux E, Perpoint T, Ferry T, et al: One in ﬁve mortality in non-menstrual toxic shock syndrome versus no

mortality in menstrual cases in a balanced French series of 55 cases. Eur J Clin Microbiol Infect Dis 27:37–43, 2008.

6. Hoge CW, Schwartz B, Talkington DF, et al: The changing epidemiology of invasive group A streptococcal

infections and the emergence of streptococcal toxic shock-like syndrome. JAMA 269:384–389, 1993.

7. Lappin E, Ferguson AJ: Gram-positive toxic shock syndromes. Lancet 9:281–290, 2009.

8. Lemaire X, Legout L, Franois C, et al: First case of intrafamily transmission of a new MRSA clone with toxic

shock syndrome toxin-1. Scand J Infect Dis 40:675–676, 2008.

9. Teltscher MS, Dascal A: Toxic Shock Syndrome. In Rakel RE, Bope ET, editors: Conn’s current therapy, ed 60,

Philadelphia, 2008, Saunders Elsevier.

10. Todd J, Fishaut M, Kapral F, et al: Toxic-shock syndrome associated with phage-group-I Staphylococci. Lancet

25;2(8100):1116–1118, 1978.

WEBSITES

CDC website: www.cdc.gov/ncidod/dbmd/diseaseinfo/toxicshock_t.htm

http://emedicine.medscape.com/article/169177-overview

KEY POINTS: TREATMENT FOR TSS

1. IV ﬂuids with pressor support when needed

2. Removal of infectious source

3. Antibiotics

4. Consider IVIG in severe cases refractory to traditional therapy

ACKNOWLEDGMENT

The editors gratefully acknowledge the contributions of Bruce Evans, MD, and Gayle Braunholtz,

MD, authors of this chapter in the previous edition.

352

TETANUS, BOTULISM, AND FOOD

POISONING

CHAPTER 51

John E. Houghland, MD

TETANUS

1. What is the causative agent of tetanus and its mechanism of action?

Clostridium tetani is an obligate anaerobic bacteria whose spores produce two distinct

toxins—tetanolysin, which causes local tissue destruction, and tetanospasmin, which causes

clinical tetanus. Tetanospasmin travels in a retrograde fashion through peripheral nerves to

the central nervous system (CNS) where it crosses to presynaptic neurons and disables

inhibitory neurotransmitter release (g-aminobutyric acid [GABA] and glycine) in both the

autonomic and somatic nervous systems. Spores are extremely resilient, able to survive

household disinfectants, extremes in temperatures and humidity, and for several minutes in

boiling water.

2. What are the forms of tetanus?

Generalized tetanus (.80% of cases) involves rigidity and spasm of all muscles in the

body, usually starting cranially and proceeding caudally.

Localized tetanus is seen with lower toxin loads and peripheral injuries; spasm, rigidity, and

pain are limited to the injured body area.

Cephalic tetanus occurs after a head wound and presents as cranial nerve paralysis (most

commonly lower motor neuron weakness of cranial nerve VII), and frequently proceeds to

generalized tetanus.

Tetanus neonatorum is the most common cause of tetanus worldwide and is caused

by poor umbilical hygiene. It is rare in developed countries and is preventable by

vaccination.

3. How is tetanus contracted?

Tetanus generally originates from a deep wound that facilitates anaerobic bacterial growth

and is usually grossly contaminated with soil, manure, or metal. Other sources include

burns, ulcers, snakebites, middle ear infections, tattooing, piercings, septic abortions,

childbirth, surgery, and intramuscular injections. The low pH of quinine, a common diluting

agent in heroin, may cause more aggressive cases of tetanus by facilitating cellular entry of

the toxin. A prior episode of tetanus is not protective and does not confer lifelong immunity.

4. What are the presentation and prognosis of neonatal tetanus?

Neonatal tetanus presents commonly during the ﬁrst week of life in infants of nonimmunized

mothers. The bacteria enter through the umbilical cord stump, especially after the application

of mud or feces, a practice in some developing countries. General irritability and poor feeding

progress to generalized spasms, pneumonia, and pulmonary or CNS hemorrhage. Toxin load

is high; mortality is variable (10%–100%).

5. What is the presentation of generalized tetanus?

Initial symptoms include masseter and parapharyngeal spasm, causing trismus. Facial and

neck muscle spasms lead to dysphagia, neck pain, and risus sardonicus (the ironic smile of

tetanus). Muscle spasms proceed caudally to the paraspinous and abdominal wall muscles.

Chapter 51 TETANUS, BOTULISM, AND FOOD POISONING 353

Opisthotonos may compromise respiratory function and cause vertebral fractures. Minor

stimuli (e.g., light touch, drafts, or noises), pain, and anxiety may trigger severe spasms.

Death can result from glottis spasm, respiratory failure, and autonomic instability (e.g., labile

hypertension, dysrhythmias, hyperpyrexia, tachycardia, or myocardial infarction); the latter of

which may present late and carries a 40% mortality rate.

6. How do I treat generalized tetanus in the ED?

Initial management involves injection of tetanus immunoglobulin 500 to 6000 IU

intramuscularly at the site of the wound, given prior to surgical debridement of devitalized

tissue to prevent the release of preformed toxin. Metronidazole 500 mg by mouth (PO) or

intravenously (IV) every 6 hours is the antibiotic of choice. Penicillin G, formerly the treatment

of choice, has less penetration into devitalized tissue and abscesses and carries the theoretical

harmful effect of lowering seizure threshold due to GABA antagonism. Other alternatives

include doxycycline, erythromycin, and tetracycline.

7. Where should I admit patients with tetanus?

Patients with tetanus should be admitted to an intensive care unit (ICU) setting, with a dark

and quiet environment to minimize external stimuli.

8. How do I vaccinate someone against tetanus?

Previously unimmunized patients require a primary series: three doses, with the second

dose given 4 to 8 weeks after the ﬁrst, and the third dose given 6 to 12 months later.

Following the primary vaccine series, individuals should receive a booster every 10 years, or

after incurring a tetanus-prone wound if their last vaccination occurred more than 5 years

ago. Tetanus-prone wounds include those with devitalized tissue or gross contamination and

wounds from crush injuries. The Td formulation, which contains a lower dose of the

diphtheria component, should be used in all individuals older than age 7 years. Consider

giving tetanus immunoglobulin in addition to tetanus vaccine to those with grossly

contaminated wounds who lack a primary vaccination series.

9. What is the time course of tetanus?

The incubation period after exposure averages 7 to 10 days (range 1–60 days). The ﬁrst week

of illness is characterized by muscle rigidity and spasm, followed by autonomic disturbances

that last for 1 to 2 weeks. Muscle spasms generally subside after 2 to 3 weeks, but patients

may experience persistent stiffness.

10. What are the side effects of tetanus vaccine?

Side effects are generally limited to local reactions including erythema, induration, tenderness,

nodule, or sterile abscess at the site of infection. Mild systemic reactions can occur and

include fever, drowsiness, “fretfulness,” and anorexia, but all are self-limited.

11. Is tetanus vaccine safe for pregnant and immunocompromised patients?

Tetanus vaccine is a toxoid (inactivated toxin) that is safe and effective in pregnancy and can

help prevent neonatal tetanus. Likewise, it is safe for administration in immunocompromised

patients.

KEY POINTS: TETANUS

1. Tetanus vaccine is safe for pregnant and immunocompromised patients.

2. Metronidazole is the antibiotic of choice.

3. High mortality rate is due to autonomic instability.

Chapter 51 TETANUS, BOTULISM, AND FOOD POISONING354

BOTULISM

12. What is the causative agent of botulism? How does it cause disease?

Botulism is caused by the toxin produced by Clostridium botulinum. This toxin binds to

peripheral presynaptic nerves cholinergic membranes, preventing the release of acetylcholine

and producing a life-threatening, paralytic illness. Adrenergic synapses are unaffected. By

weight, botulism toxin is the most potent toxin known.

13. State the ﬁve ways a patient can contract botulism.

Adult botulism (10%–20% of U.S. cases) results from the foodborne ingestion of

preformed toxin. Undercooked home-canned food is a common source; cases occur in

isolation or in small clusters.

Infant botulism (approximately 60% of U.S. cases) is caused by the ingestion of

C. botulinum spores, which proliferate in the gastrointestinal (GI) tract. It is usually seen

between the ages of 2 weeks and 1 year, with a median age of 10 weeks. Contaminated raw

honey ingestion accounts for only up to 20% of cases. It is believed that changes in gut

ﬂora can also lead to C. botulinum colonization.

Wound botulism (approximately 15%–25% of U.S. cases) is caused by the contamination

of traumatic wounds with C. botulinum spores found in soil. Rare in surgical wounds,

wound botulism is increasing dramatically in the United States. It is seen almost exclusively

in injection drug users, particularly among users of black tar heroin and those who partake

in skin popping (injection into subcutaneous tissue).

Hidden botulism is an idiopathic form, in which the patient’s stool contains C. botulinum,

and the patient has signs and symptoms of clinical botulism, yet no contaminated food or

wound can be identiﬁed.

Iatrogenic botulism is a complication of cosmetic or therapeutic injections. Although

cosmetic doses are too low to cause systemic disease, cases have been reported in

patients receiving higher doses for cosmetic purposes or neuromuscular disorders. Such

patients may present with moderate to severe clinical weakness. Focal neurologic deﬁcits

can be seen by craniofacial migration of injected toxin.

14. What are the differential diagnoses of botulism?

Myasthenia gravis, Lambert-Eaton myasthenic syndrome, Guillain-Barré syndrome, tick

paralysis, diphtheritic neuropathy, stroke syndromes, tetrodotoxin and shellﬁsh poisoning, and

Miller-Fischer variant of Guillain-Barré syndrome.

15. What is the presentation of infant botulism?

Constipation is often the ﬁrst presenting symptom. This can be followed by a weak cry,

prolonged or poor feeding, hypotonia, and decreased gag or suck reﬂex. As in adults, infants

can develop descending motor weakness, ﬂaccid paralysis, and autonomic dysfunction. Unlike

tetanus toxin, botulinum toxin acts peripherally and does not cross the blood-brain barrier;

fever is uncommon and cerebrospinal ﬂuid (CSF) analysis is normal.

16. How does a patient with adult botulism present?

Early symptoms are nonspeciﬁc and usually begin 12 to 36 hours after ingestion (range

6 hours to 8 days) and include nausea, vomiting, weakness, malaise, and dizziness. Prominent

anticholinergic symptoms ensue, including extreme dry mouth, decreased lacrimation,

constipation, and urinary retention. Symmetric cranial nerve palsies occur, sometimes delayed

3 days after the appearance of anticholinergic symptoms. Ocular and bulbar symptoms include

ptosis, diplopia, blurred vision, photophobia, dysphonia, and dysphagia. A ﬂaccid, symmetric,

descending paralysis of the voluntary muscles may follow and can lead to respiratory failure.

17. What is the treatment of classic (food) botulism?

Treatment is mostly supportive, including early elective intubation of patients at risk of

respiratory failure. Type-speciﬁc equine-derived antitoxin is also recommended within

Chapter 51 TETANUS, BOTULISM, AND FOOD POISONING 355

24 hours to arrest the progression of and decrease the duration of paralysis. Anaphylaxis,

more common when higher doses of antitoxin were used, is now a rare adverse event (,1%)

when the recommended one vial is used.

18. What is treatment for infant botulism?

Treatment of infant botulism includes supportive care, including intubation and mechanical

ventilation for respiratory failure. Human botulism immunoglobulin (Baby-BIG) is

recommended, which reduces duration of hospitalization, mechanical ventilation, and tube

feedings. Equine-source antitoxin is not indicated for infant botulism.

19. Are systemic antibiotics indicated for infant botulism?

No. Aminoglycosides are absolutely contraindicated because they may potentiate

neuromuscular blockade and increase duration of symptoms. Antibiotic administration may

cause bacterial lysis in the gut and theoretically increase the free toxin load.

KEY POINTS: BOTULISM

1. Adult botulism presents as nonspeciﬁc anticholinergic symptoms followed by symmetric

cranial nerve palsies and descending paralysis.

2. Infant botulism usually presents as constipation followed by weak cry, prolonged or poor

feeding, hypotonia, and decreased gag or suck reﬂex.

3. Human botulism immunoglobulin (Baby BIG) is available for infant botulism.

20. Are antibiotics indicated in wound botulism?

In addition to surgical debridement, topical antibiotics may be of use in wound botulism, but

their use is unproved.

FOOD POISONING

21. Name the causes of food poisoning.

Food poisoning is caused by viruses (e.g., Norwalk, Calicivirus, or Rotavirus), direct bacterial

invasion or endotoxins (e.g., Escherichia coli, Vibrio vulniﬁcus, Vibrio parahaemolyticus,

Campylobacter, Salmonella, or Yersinia enterocolitica), secreted exotoxins (e.g.,

Staphylococcus aureus, Shigella, Bacillus cereus, Clostridium perfringens, or shellﬁsh-

associated algal toxins), toxins innate in food (e.g., Puffer ﬁsh tetrodotoxin or Amanita

phalloides mushrooms), and parasites (e.g., Giardia lamblia, Cryptosporidium, or Entamoeba

histolytica).

22. What is scombroid and how is it treated?

Scombroid ﬁsh poisoning is caused by ingestion of ﬁsh with high levels of histamine. Multiple

ﬁshes in addition to the scombroid family (e.g., tuna, mackerel, or saury) have been

implicated (e.g., mahi-mahi, sardines, pilchards, anchovies, herring, marlin, and blueﬁsh).

Improperly refrigerated ﬁsh becomes spoiled with bacteria that proliferate and convert

naturally occurring histidine to histamine, which persists despite cooking. Poisoning is

associated with high levels of histamine (.50 mg/100 g contaminated ﬁsh). Affected ﬁsh

typically retain normal appearance and odor. Not a true ﬁsh allergy, poisoning causes

histaminergic symptoms approximately 20 to 30 minutes after ingestion, typically an urticarial

rash of the face, neck, and upper chest. Other symptoms include ﬂushing, nausea, vomiting,

diarrhea, headache, palpitations, abdominal cramping, dizziness, dry mouth, metallic taste in

the mouth, urticaria, and conjunctival injection. Severe hypotension resembling anaphylactic

Chapter 51 TETANUS, BOTULISM, AND FOOD POISONING356

shock and requiring pressor support, as well as acute pulmonary edema, can occur. Treatment

with H1 and H2 antagonists is generally effective.

23. Describe the toxic syndromes associated with ingestion of shellﬁsh.

Algal toxins are produced by numerous species of marine algae that contaminate shellﬁsh,

crustaceans, and some ﬁsh. Diagnosis is based on history of recent ingestion and clinical

picture; treatment is essentially supportive. Syndromes include:

Amnestic shellﬁsh poisoning (ASP) can present with nausea, vomiting, dizziness,

headache, confusion, respiratory difﬁculty, and coma with loss of short-term memory that

may be permanent. The causative agent is domoic acid, a preformed agent with

neuroexcitatory glutaminergic activity, found primarily in infected scallops, mussels, and

crab. Onset is within 24 hours of ingestion.

Diarrhetic shellﬁsh poisoning (DSP) is caused by okadaic acid found in affected

mussels, cockles, scallops, oysters, cockles, whelks, and green crabs. Symptoms are self-

limited, characterized by acute onset within 30 minutes of severe diarrhea, nausea,

vomiting, and abdominal cramps. Recovery generally occurs within 3 to 4 days.

Paralytic shellﬁsh poisoning (PSP) is caused by saxitotoxin in affected mussels,

clams, oysters, scallops, abalone, crabs, and lobster, which blocks sodium channels of

nerve and muscle cell membranes. Initial perioral paresthesias spread to the face, head,

and neck within 30 minutes of ingestion; large ingestion may lead to respiratory arrest and

death within 2 hours.

Ciguatera poisoning occurs after the ingestion of coral reef ﬁsh that contain

ciguatoxin, which stimulates sodium channels at the neuromuscular junction.

Neurologic symptoms occur in .90% of patients, including reversal of temperature

perception (cold objects cause burning or electric shock-like sensation), facial and

perioral paresthesias, coma, and death (overall mortality approximately 0.1%). Non-

neurologic symptoms (e.g., hair loss, arthralgias, myalgias, itching, vomiting, diarrhea,

or insomnia) resolve within a few days; however, severe neurologic symptoms may

persist for weeks or years.

Neurotoxic shellﬁsh poisoning (NSP) is caused by the brevetoxin family of toxins,

commonly found in cockles, mussels, and whelks off the coast of Florida and the Gulf of

Mexico. Symptoms begin 3 to 6 hours after ingestion, last up to 48 hours, and can

include perioral paresthesias, abdominal pain, dizziness, diplopia, gait deﬁcits, chills,

reversed temperature perception, headache, musculoskeletal pain, and respiratory

difﬁculty.

24. Describe the clinical course and treatment for Puffer ﬁsh poisoning.

Puffer ﬁsh poisoning results from the consumption of tetrodotoxin in improperly prepared

Puffer ﬁsh, commonly found in Japan, Singapore, Hong Kong, and Australia. Tetrodotoxin is

resistant to cooking and is produced in the viscera and skin of the ﬁsh; safe consumption is

predicated on expert chefs removing these areas. Tetrodotoxin blocks sodium channels in the

central and peripheral (including autonomic) nervous systems and interferes with axonal

nerve transmission in muscle. Symptoms begin with perioral paresthesias, which can spread

to the entire body, as well as vomiting and dizziness; most patients develop a rapid ascending

paralysis. Tetrodotoxin has direct effects on the respiratory and vasomotor centers in the

medulla oblongata. Gastric lavage and activated charcoal have been recommended for large

ingestions because they can result in respiratory failure, cardiovascular collapse, coma, and

death within 6 hours.

25. Which population of patients is at risk from eating raw oysters?

Patients with pre-existing liver diseases, including cirrhosis and hemochromatosis, have an

80 times higher risk of invasive Vibrio disease and 200 times higher risk of mortality than

those without liver disease. Consumption of raw oysters, especially from warmer waters

between March and November, has a high incidence of V. vulniﬁcus and V. parahaemolyticus.

Chapter 51 TETANUS, BOTULISM, AND FOOD POISONING 357

26. Describe the four stages of Amanita phalloides mushroom toxidrome.

Stage 1: Latent stage: patient remains asymptomatic for 8 to 14 hours post-ingestion.

Stage 2: Violent onset of nausea, vomiting, and diarrhea (often bloody), and severe

abdominal pain lasting 1 to 2 days. This stage may include acid-base disturbances,

electrolyte abnormalities, hypoglycemia, dehydration, and even hypotension. Physical

examination may be signiﬁcant for epigastric tenderness and hepatomegaly with normal

liver function tests.

Stage 3: The patient clinically appears to improve over the next 12 to 24 hours, although

liver function tests begin to rise and renal function begins to deteriorate.

Stage 4: Beginning 2 to 4 days post-ingestion, the patient develops hepatic and renal

failure, with marked rise in liver function tests, cardiomyopathy, hepatic encephalopathy,

convulsions, coma, and death.

KEY POINTS: FOOD POISONING

1. Amanita phalloides toxic patients may appear to be improving before rapid deterioration.

2. Antibiotics are not recommended in children with bloody diarrhea.

3. Patients with liver disease are at highest risk for Vibrio disease from eating raw oysters.

27. What is the time course and geographic incidence of traveler’s diarrhea?

Traveler’s diarrhea is one of the most common illnesses of international travelers, affecting

20% to 60% of travelers. High risk destinations include Latin America, Africa, the Middle East,

and Asia (20%–50% prevalence). Southern Europe, China, Russia, and the Caribbean are

lower risk (up to 15% prevalence). Median time to onset is 6 to 7 days after arrival, although

it may occur at any time, and up to 10 days after travel return. It is usually self-limited, lasting

3 to 4 days; however, 10% of patients may have more than 1 week of symptoms, and 3% may

have more than 1 month of symptoms. Approximately 20% of individuals will have symptoms

of dysentery (e.g., bloody stool, fever).

28. What are some of the more serious complications of traveler’s diarrhea? What

are the causative agents?

Postinfectious inﬂammatory syndromes (e.g., Reiter’s syndrome [arthritis], urethritis, or

conjunctivitis): Campylobacter jejuni, Salmonella, Shigella, Y. enterocolitica

Guillain-Barré syndrome: C. jejuni, especially with Human Leukocyte Antigen (HLA)-B27

Hemolytic uremic syndrome (HUS): Shigella dysenteriae and enterohemorrhagic E. coli

Amebic hepatitis and amebic abscesses: E. histolytica

Bacteremia leading to endocarditis, aortitis, septic arthritis, osteomyelitis: Salmonella

29. Is there any role for prophylaxis against traveler’s diarrhea?

Patients at high risk for complications, including those with inﬂammatory bowel disease,

insulin-dependent diabetes, heart disease, or immunosuppression, may beneﬁt from

prophylaxis. Fluoroquinolones have been shown to have a more than 90% efﬁcacy in

preventing traveler’s diarrhea. Ciproﬂoxacin 500 mg PO once daily can be started 2 days prior

to arrival and taken 1 week after return, up to 3 weeks total. Patients who are otherwise

healthy may wish to consider bismuth subsalicylate (Pepto-Bismol, taken as 524 mg four

times a day) as a nonantibacterial option that has fewer side effects but lower efﬁcacy

(approximately 65%). Campylobacter strains are often resistant to ﬂuoroquinolones;

azithromycin should be considered for prophylaxis in higher risk areas such as South Asia and

Southeast Asia (especially Thailand) (Fig. 51-1).