Cutaneous Signs of Bioterror Agents

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Cutaneous Signs of Bioterror Agents

• Adam Goldstein, MD, MPH
• Associate Professor
• UNC Department of Family Medicine
• Chapel Hill, NC
• aog_at_med.unc.edu

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Objectives

• Improve ability to
• diagnose and manage cutaneous illness associated
  with suspected cases of bioterror
• Anthrax, plague, tularemia, smallpox, mustard gas

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Why worry?

• Subnational attacks using genetically engineered
  organisms are inevitable
• Biologic agents now join nuclear agents
• Deaths
• 1 KT H-BOMB .6M 2M
• 100 Kg ATX 1M 3M
• (Stansfield Turner, CIA, 2001)

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Anthrax

• Anthrakos coal b/c of black eschar
• B. anthracis is gram-positive sporulating
  bacillus
• Spores are resistant to heat, cold, drying,
  chemical disinfection
• Anthrax is endemic in western Asia (Iran Turkey
  Afghanistan,) western Africa
• (McGovern, Elect Text Dermatol, 1999)

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Anthrax

• Spores viable for years top 6 cm of soil in
  animal products
• Disease transmitted from infected animals or
  products via skin abrasions gt 90 of cases
• Goats gt sheep gt cattle gt horses gt pigs gt dogs

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Anthrax

• Burn dead animals, not buried, to prevent
  long-term environmental contamination

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History of Anthrax

• 1500 B.C. -- Fifth/sixth Egyptian plagues, ?
  Anthrax
• 1600s -- "Black Bane," ? anthrax, kills 60,000
  cattle
• 1876 -- Koch confirms bacterial origin of anthrax
  
• 1880 -- Immunization of livestock against anthrax
  
• 1915 -- German agents in U.S. inject
  horses/cattle with anthrax on way
  to Europe during WW I
• 1937 -- Japan starts biological warfare program
• 1942 -- Britain experiments with anthrax
  
• 1943 -- U.S. begins developing anthrax weapons
• 1945 -- Anthrax outbreak in Iran kills 1 million
  sheep

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Historical

• 1950s and '60s -- U.S. biological program
  continues
• 1969 -- Nixon ends U.S. offensive biological
  program.
• 1970 -- Anthrax vaccine approved by U.S. FDA
• 1972 -- International convention outlaws
  development or stockpiling of biological weapons
• 1978-80 -- Human anthrax epidemic strikes
  Zimbabwe, infecting gt 6,000 and killing 100
• 1979 -- Aerosolized anthrax spores released at
  Soviet military facility, killing 68
• 1991 -- U.S. troops vaccinated for Gulf War I
• 1990-93 -- Terrorists release anthrax in Tokyo
  no injuries

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Historical

• 1995 -- Iraq produced concentrated anthrax in
  biological weapons program
• 1998 -- U.S. approves anthrax vaccinations for
  all military
• 2001 -- Letter with anthrax spores mailed to NBC
  one week after 9/11 terrorist attacks on Pentagon
  WTC. Several die after inhaling.

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Anthrax pilot plant used to produce billions of
anthrax spores at Fort Detrick, Md. U.S.
ended offensive biological weapons research in
1969
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Al Hakam, Iraq's major facility for production of
biological agents. Plant destroyed by Iraqi
workers in 1996.
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Forms of Anthrax

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Pulmonary Anthrax

• Wool-sorters disease
• 18 cases reported in U.S. 1900-1980
• Symptoms vague prodrome with fever, malaise,
  myalgias and cough
• Within days- rapidly developing precordial
  discomfort, cyanosis, stridor, diaphoresis, moist
  rales, pleural effusion and death

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Pulmonary Anthrax

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X-ray findings hemorrhagic mediastinitis, but
not true pneumonia widened mediastinum

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X-ray findings

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Cutaneous Anthrax

• Incubation period 7 days (1-12 range)
• Initial painless papule (head, neck, extremity)
• May resemble spider bite and may itch
• Surrounding erythema edema
• Vesicle or bulla rapidly evolves
• Painless hemorrhage necrosis
• Fluid becomes black
• Lesion ulcerates develops black eschar with
  surrounding edema
• Pearl-like satellite vesicles may occur

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Cutaneous Anthrax

• Lesions progress from
  
• papule - erythema - vesicle - necrosis - ulcer -
  eschar
• with or without antibiotic therapy
• progression d/t toxin
• Lesions may be solitary or multiple (same part of
  body)
• Occasionally associated
• Tender lymphadenopathy
• Fatigue
• Fever and/or chills
• (Caruscci, JAAD 2001)

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Cutaneous Anthrax - Painless Lesions

• Surrounding edema or regional lymphadenopathy may
  be painful.
• Debridement of skin lesions not indicated b/c
  risk of spreading infection

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Cutaneous Anthrax
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Cutaneous Anthrax- painless papule
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Cutaneous Anthrax- vesicle with edema
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Cutaneous Anthrax- early necrosis
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Cutaneous Anthrax- eschar
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Cutaneous Anthrax
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Cutaneous Anthrax
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Cutaneous Anthrax
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Cutaneous Anthrax
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Cutaneous Anthrax
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Cutaneous Anthrax

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Cutaneous Anthrax
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Cutaneous Anthrax
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Cutaneous Anthrax Diagnosis

• Notify local Health Department
• Before doing diagnostic tests
• Mask not required personnel not at risk
• Disease acquired through contact with spores,
  not active bacteria

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Diagnosis

• Swab exudates for Gram stain culture (fresh
  vesicles)
• 4-mm punch biopsy full-thickness (through entire
  dermis)
• permanent sections
• immunohistochemistry studies
• polymerase chain reaction (PCR)
• A second punch biopsy for Gram stain, bacterial,
  fungal atypical mycobacterial cultures
• Send clinical history ( lesion picture if
  possible)
• Negative bx does not r/o cut. anthrax b/c skin
  lesions caused by toxins

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Diagnosis

• Draw 5 mL of blood in red-topped tube
• Transfer to laboratory for isolation of serum
  subsequent storage at 70C- label tube Anthrax
  serology.
• Store serum at 70C for special pick-up.
• Draw 5 mL of blood into a purple-topped tube
• Refrigerate
• Hold for pick-up- PCR diagnostic tests by CDC

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Gram Stain

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Culture (24-36 hours)

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Differential Diagnosis (eschar/ulceration)

• Pruritic and papular arthropod bites
• Brown recluse and other spider bites
• Pustular diseases
• Antiphospholipid antibody syndrome ulcers
• Aspergillosis
• Coumadin or heparin necrosis
• Ecthyma gangrenosum

• Cutaneous leishmaniasis
• Mucormycosis
• Plague
• Rickettsial pox
• Staphylococcal streptococcal ecthyma
• Tropical ulcer
• Tularemia
• Typhus, scrub and tick

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Differential Diagnosis (ulceroglandular)

• Chancroid
• Glanders
• Herpes simplex
• Cutaneous leishmaniasis
• Lymphogranuloma venereum
• Melioidosis

• Cutaneous nocardiosis
• Plague
• Sporotrichosis other deep fungal diseases
• Staphylococcal streptococcal adenitis
• Tuberculosis
• Tularemia

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Treatments

http//www.bt.cdc.gov/agent/anthrax/index.asp
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Treatments

• If suspected anthrax, begin appropriate tx
• Tx regimen differs by symptomatology (systemic or
  localized), location (extremity vs head/neck),
  edema (extensive or not)
• If systemic signs, head or neck location, or
  extensive edema, IV therapy indicated

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• Treatment for cutaneous anthrax patients without
  systemic symptoms, not located on the head or
  neck, not with extensive edema, not in children
  younger than 2 years
• Category Initial oral therapy
  Duration (days)
• Adults Ciprofloxacin, 500 mg bid
  60
• or doxycycline, 100
  mg bid
• Children Ciprofloxacin, 15 mg/kg
  q12h 60
• (not to exceed 1
  g/d)
• or doxycycline gt8
  y o, gt45 kg,
• 100 mg q12h all other children,
  
• 2.2 mg/kg q12h
• 
  
• Pregnant Ciprofloxacin, 500 mg bid
  (preferred) 60
• or doxycycline, 100 mg bid
• Immunocomp Same
  60

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• Treatment of cutaneous anthrax with systemic
  symptoms, extensive edema, involving the head or
  neck, or children lt than 2 yo (same as for
  inhalational anthrax)
• Category IV therapy Duration (days)
• Adults Ciprofloxacin, 400 mg q12h,
  IV initially, oral
• or doxycycline,100 mg q12h, when stable, 60
  days
• and 1-2 additional agents
• Children Ciprofloxacin, 10 mg/kg
  q12h IV initially, oral
• (not to exceed 1 g/d) or when stable, 60
  days
• doxycycline gt8 y old and gt45 kg,
• 100 mg q12h all other,
  2.2 mg/kg
• q12h and 1-2 additional
  agents
• Pregnant Same as for nonpregnant
  Same
• Immunocom and immunocompetent adults
• children
• 
  

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Spider bites Usually painful

• Usually painful
• Bites from spiders of the genus Loxoceles begin
  as pale ecchymotic lesions that rapidly turn
  purple.
• Lesions may ulcerate and develop necrotic
  centers
• Borders are irregular, ill-defined and without
  the significant surrounding edema.

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Spider bites
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Plague

• Boubon is Greek for groin
• Y. Pestis, 200 million deaths in history

http//www.emedicine.com/derm/topic905.htmtarget1
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Plague

• Gram neg nonspore-forming coccobacillus

http//www.emedicine.com/derm/topic905.htmtarget1
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Plague

• Tender, erythematous lymphadenopathy
• Most cases involve bubonic plague
• Tx with streptomycin, gentamicin, tetracycline
  doxycycline

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Plague

• In bloodstream causes septicemia

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Tularemia

• 6 clinical forms
• ulceroglandular, glandular, oropharyngeal or
  gastrointestinal, typhoidal, septicemic, and
  pulmonary
• Sudden onset of
• Fever, chills, headache, generalized myalgias
  and arthralgias
• Incubation 2-10 days
• Ulcer generally seen at bite or inoculation site

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Tularemia

• Painful, pruritic, ulcer w/ RAISED borders

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Tularemia

• Ulcero-glandular 80

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Tularemia

• In 50s and 60s, the U.S. made biologic weapons
  containing tularemia
• Streptomycin and tetracyclines are drugs of choice

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Meliodiosis

• Whitmores disease
• Infectious disease caused by Burkholderia
  pseudomallei
• Endemic in SE Asia and northern Australia
• Common causative agent of community-acquired
  septicemia

(Tran, Clinical Experimental Dermatology, 2002)
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Meliodiosis
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Glanders

• An infectious disease caused by
  bacterium Burkholderia mallei, also called
  farcy
• Primarily affects horses
• Cutaneous via cut or scratch in the skin, with
  ulceration and pus 1-5 days at site
• No cases in U.S. gt 60 years

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Mustard Gas

• Odor/taste (mustard, garlic, onion), color (tan
  to brown to yellow)
• Oily liquid is DNA alkylating
• Absorbed within minutes
• Symptoms begin 2-24 hours later
• Skin erythema followed by vesicles

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Mustard Gas
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Mustard Gas

• Eyes develop conjunctivitis
• Pulmonary symptoms- hoarseness
• Death rate during World War I 3
• Decontaminate w/ 0.5 hypochlorite (1/10 bleach
  to water)

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Smallpox

• Classic generalized exanthem
• Latin word for spotted referring to raised
  bumps on the face and body

http//www.bt.cdc.gov/agent/smallpox/overview/dise
ase-facts.asp
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Smallpox

• Rash, high fever mortality rate 30
• Last natural case Somalia in 1977

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Smallpox (Days 3, 5, 7)
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Smallpox

• Exanthem from vaccination
• 1/100,000
• Vaccinia rash or outbreak of sores
• Generalized vaccinia
• Erythema multiforme

http//www.bt.cdc.gov/agent/smallpox/
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Smallpox

• Exanthem from vaccination
• 1/100,000
• Vaccinia rash or outbreak of sores
• Generalized vaccinia
• Erythema multiforme

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Smallpox

• Exanthem from vaccination
• 1/100,000
• Vaccinia rash or outbreak of sores
• Generalized vaccinia
• Erythema multiforme

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Smallpox

• From Vaccination
• 1/50,000
• Eczema vaccinatum
• Progressive vaccinia
• Postvaccinal encephalitis

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Smallpox

• From Vaccination
• 1/50,000
• Eczema vaccinatum
• Progressive vaccinia
• Postvaccine encephalitis

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Monkeypox Virus
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Monkeypox Virus
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References

• Carucci JA, McGovern TW, Norton AS. Cutaneous
  anthrax management algorithm. J Am Acad Dermatol
  2001 online at http//www.eblue.org/scripts/om.d
  ll/serve?actionsearchDBsearchDBforartartTypef
  ullfreeida121613
• Update Investigation of bioterrorism-related
  anthrax and interim guidelines for exposure
  management and antimicrobial therapy, October
  2001. MMWR Morb Mortal Wkly Rep 200150909-19.
  http//www.cdc.gov/mmwr/preview/mmwrhtml/mm5042a1.
  htm
• Dixon TC, Meselson M, Guillemin J, Hanna PC.
  Anthrax. N Engl J Med 1999341815-26.
  http//content.nejm.org/cgi/content/fall/341/11/81
  5
• Inglesby TV, Henderson DA, Bartlett JT, Ascher
  MS, Eitzen E, Friedlander AM, et al. Anthrax as a
  biological weapon medical and public health
  management. Working Group on Civilian Biodefense.
  JAMA 19992811735-45. http//jama.amaassn.org/iss
  ues/v281n18/ffull/jst80027.html

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Thank you.