Smallpox Clinical Presentation

  • Author: Aneela Naureen Hussain, MD, FAAFM; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Nov 17, 2011
 

History

The incubation period of smallpox ranges from 7-17 days but is usually 10-12 days. During the incubation period, patients are not contagious.

The prodromal phase of smallpox lasts 2-4 days and is characterized by the following:

  • Fever (38.8-40°C [101-104°F])
  • Severe headache
  • Backache
  • Pharyngitis
  • Nausea
  • Vomiting (rare)
  • Prostration
  • Enanthema on the mucous membranes of the tongue and the oropharynx

As many as 10% of fair-skinned individuals with smallpox may also present with a fine, erythematous, macular rash during the prodromal phase.

Virus shedding and subsequent infectivity are maximal at the beginning of the enanthema, and they last until scab separation of the skin lesions. For a few days, the virus can be found in respiratory secretions, skin lesions, and contaminated objects.

Respiratory infectivity occurs with face-to-face contact, although reports of infection due to viral spread through ventilation systems are well documented.

The characteristic rash of smallpox begins after the prodromal phase. Small, red macules first appear on the face and then spread to the extremities and trunk. Over 1-2 days, the macules develop into firm, 2- to 3-mm papules. Within 1-2 more days, the papules evolve into 2- to 5-mm vesicles.

Most patients with smallpox report severe headaches and spinal pain. Few patients develop neuropsychiatric symptoms (hallucinations, delirium, depression and psychosis, manic depression). Autopsies of patients with smallpox have demonstrated perivenular demyelination.

Ten to 20% of patients with smallpox develop ophthalmologic complications (variola residua). Conjunctivitis is most common, appearing 5 days after rash onset. Some patients develop painful pustules and bulbar conjunctivitis. During epidemics, corneal ulceration was common (complicated by bacterial superinfection and perforation).

Two to 5% of children develop osteomyelitis (osteomyelitis variolosa), due to viral invasion of the bone rather than as a result of secondary infection. Radiographic surveys in children have found rates as high as 20%.

Depending on the presenting clinical symptoms, other diseases, such as meningococcemia, leukemia, herpes viruses, and drug eruptions, must be ruled out. A meticulous drug history should be obtained.

Next

Physical Examination

The initial cutaneous lesions of smallpox appear as small, red spots on the face, in the mouth and pharynx, and on the forearms. Initially, smallpox lesions are small papules, but they change into vesicles and pustules within 1-2 days. The initial lesions are shotty and do not disappear with pressure.

These spots develop into sores that break open and spread large amounts of the virus into the mouth and throat. The patient becomes most contagious at this time.

Around the time the sores in the mouth break down, a rash appears on the skin, starting on the face, spreading to the arms and legs, and progressing to the hands and feet. Usually, the rash spreads to all parts of the body within 24 hours. As the rash appears, the fever reduces and the patient may start to feel better.

By the third day of the rash, it turns into raised papules. By the fourth day, the papules fill with a thick, opaque fluid and often have a depression in the center that resembles an umbilicus (bellybutton), which is a major distinguishing characteristic of smallpox. At this time, the fever often rises again and remains high until scabs form over the papules. (See the images below.)

After exposure to the smallpox virus, a symptom-frAfter exposure to the smallpox virus, a symptom-free incubation period follows. It normally lasts 10-12 days but may vary from 7-17 days. Smallpox begins with fever, headache, and severe backache. A rash appears after 2-4 days and progresses through characteristic stages of papules, vesicles, pustules, and, finally, scabs. The scabs desquamate at the end of the third or fourth week. Courtesy of the World Health Organization. Smallpox rash at days 3, 5, and 7 of evolution. LeSmallpox rash at days 3, 5, and 7 of evolution. Lesions are denser on the face and extremities than on the trunk. They also appear on the palms of the hand and have a similar appearance. Courtesy of the World Health Organization. Unvaccinated infant with the ordinary form of the Unvaccinated infant with the ordinary form of the variola major strain of smallpox has centrifugally distributed umbilicated pustules on day 3 in the course of the disease. Reprinted with permission from the World Health Organization (WHO).

By days 4-7 after the appearance of the rash, the lesions develop into 4- to 6-mm pustules. The pustules are sharply raised and are usually round and firm to the touch, as if a small, round object is present under the skin. Many of the pustules become confluent, particularly on the face. In the past, these pustules have been described as deep-seated, particularly on the palms and soles; however, this is likely due to thick stratum corneum at those sites. (See the images below.)

Unvaccinated infant with the ordinary form of the Unvaccinated infant with the ordinary form of the variola major strain of smallpox has centrifugally distributed umbilicated pustules on day 5 in the course of the disease. Reprinted with permission from the World Health Organization (WHO). Unvaccinated infant with the ordinary form of the Unvaccinated infant with the ordinary form of the variola major strain of smallpox has centrifugally distributed umbilicated pustules on day 7 in the course of the disease. Reprinted with permission from the World Health Organization (WHO).

The pustules reach their maximal size by day 10. By the end of the second week after the rash appears, most of the sores have formed scabs. The scabs begin to separate, leaving marks on the skin that eventually become pitted scars. Most scabs separate by the third week after the rash appears. The person is contagious until all of the scabs are gone.

All skin lesions tend to be in the same stage of development at any given time in the course of the infection.

Compared with unvaccinated persons, vaccinated individuals who contract smallpox tend to have less severe toxemia, fewer constitutional symptoms, and smaller and fewer numbers of lesions, which tend to be more superficial and to mimic those of chickenpox.

The smallpox rash has a centrifugal distribution, with more lesions on the arms and legs than on the trunk. Rash on the palms and soles is common. In comparison, a chickenpox rash has a centripetal distribution, with more lesions on the trunk and with fewer or no lesions on the palms and soles.

Most patients with smallpox report severe headaches and spinal pain. Few patients develop neuropsychiatric symptoms (hallucinations, delirium, depression and psychosis, manic depression). Autopsies of patients with smallpox have demonstrated perivenular demyelination.

Ten to 20% of patients with smallpox develop ophthalmologic complications (variola residua). Conjunctivitis is most common, appearing 5 days after rash onset. Some patients develop painful pustules and bulbar conjunctivitis. During epidemics, corneal ulceration was common (complicated by bacterial superinfection and perforation).

Two to 5% of children develop osteomyelitis (osteomyelitis variolosa), due to viral invasion of the bone rather than as a result of secondary infection. Radiographic surveys in children have found rates as high as 20%.

Flat-type smallpox is slower to evolve, but it results in confluent, velvety macular lesions and is associated with severe prostration. (See the image below.)

Flat-type smallpox on day 6 of the rash. Courtesy Flat-type smallpox on day 6 of the rash. Courtesy of the US Centers for Disease Control and Prevention.

Variola minor is characterized by constitutional symptoms, with fewer and smaller skin lesions than variola major. (See the images below.)

The ordinary form of the variola minor strain of sThe ordinary form of the variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after the onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from the World Health Organization (WHO). The ordinary form of the variola minor strain of sThe ordinary form of the variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after the onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from the World Health Organization (WHO). The ordinary form of the variola minor strain of sThe ordinary form of the variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after the onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from the World Health Organization (WHO).

An excellent algorithm for evaluating generalized vesicular or pustular rash illness is provided on the CDC Web site; this was compiled jointly by the CDC and the American Academy of Dermatology Task Force on Bioterrorism.

Summary of criteria

Major criteria for diagnosing smallpox include the following:

  • Febrile prodrome occurring 1-4 days before rash onset - Fever greater than 102°F and at least 1 of the following: prostration, headache, backache, chills, vomiting, severe abdominal pain
  • Classic smallpox lesions - Round and well circumscribed; may be umbilicated or confluent
  • Lesions in same stage of development on any 1 part of the body

Minor criteria for diagnosing smallpox include the following:

  • Centrifugal distribution of rash - Greatest concentration of lesions on the face and distal extremities
  • First lesions on the oral mucosa/palate, face, forearms
  • Patient appears toxic or moribund
  • Slow (several days each stage) evolution of rash from macules to papules to pustules to scabs
  • Lesions on the palms and soles
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Contributor Information and Disclosures
Author

Aneela Naureen Hussain, MD, FAAFM  Assistant Professor, Department of Family Medicine, State University of New York Downstate Medical Center; Consulting Staff, Department of Family Medicine, University Hospital of Brooklyn

Aneela Naureen Hussain, MD, FAAFM is a member of the following medical societies: American Academy of Family Physicians, American Medical Association, American Medical Women's Association, Medical Society of the State of New York, and Society of Teachers of Family Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Fazal Hussain, MD, MBBS  Director, Clinical Research, King Faisal Cancer Centre

Fazal Hussain, MD, MBBS is a member of the following medical societies: American College of Radiology

Disclosure: Nothing to disclose.

Maqsood Alam, MD  Fellow, Department of Infectious Diseases, State University of New York Downstate Medical Center

Maqsood Alam, MD is a member of the following medical societies: American Medical Association and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Dennis J Cleri, MD, FACP, FAAM, FIDSA  Chairman, Graduate Medical Education Committee, Professor of Medicine, Associate Professor of Infection Disease, Seton Hall University; Director, Internal Medicine Residency Program, St Francis Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

John L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Consulting fee Consulting; Celgene Honoraria Safety Monitoring Committee; GSK - Glaxo Smith Kline Consulting fee Consulting; TenXBioPharma Consulting fee Safety Monitoring Committee

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Michael D Gober, MD Resident Physician, Department of Dermatology, Hospital of the University of Pennsylvania

Michael D Gober, MD is a member of the following medical societies: American Academy of Dermatology and American Medical Association

Disclosure: Nothing to disclose.

Duane R Hospenthal, MD, PhD Chief, Infectious Disease Service, San Antonio Military Medical Center, Brooke Army Medical Center; Professor of Medicine, Uniformed Services University of the Health Sciences

Duane R Hospenthal, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Society for Infectious Diseases, International Society of Travel Medicine, and Medical Mycology Society of the Americas

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

Julie R Kenner, MD, PhD Consultant, Clinical Research, Medical Affairs, VaxGen, Inc; Private Practice, Kenner Dermatology Center

Julie R Kenner, MD, PhD is a member of the following medical societies: American Academy of Dermatology and American Society of Tropical Medicine and Hygiene

Disclosure: Nothing to disclose.

Michelle Pelle, MD Clinical Assistant Professor, Division of Dermatology, Department of Medicine, University of California at San Diego

Michelle Pelle, MD is a member of the following medical societies: American Academy of Dermatology, California Medical Association, Medical Dermatology Society, and Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Victoria P Werth, MD Professor of Dermatology and Medicine, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, Philadelphia Veterans Affairs Medical Center

Victoria P Werth, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American College of Rheumatology, Medical Dermatology Society, Phi Beta Kappa, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

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Smallpox virion. Courtesy of US Centers for Disease Control and Prevention.
After exposure to the smallpox virus, a symptom-free incubation period follows. It normally lasts 10-12 days but may vary from 7-17 days. Smallpox begins with fever, headache, and severe backache. A rash appears after 2-4 days and progresses through characteristic stages of papules, vesicles, pustules, and, finally, scabs. The scabs desquamate at the end of the third or fourth week. Courtesy of the World Health Organization.
Smallpox rash at days 3, 5, and 7 of evolution. Lesions are denser on the face and extremities than on the trunk. They also appear on the palms of the hand and have a similar appearance. Courtesy of the World Health Organization.
Flat-type smallpox on day 6 of the rash. Courtesy of the US Centers for Disease Control and Prevention.
This patient with smallpox survived toxemia to succumb to secondary tissue damage days after this photo was taken. Courtesy of the US Centers for Disease Control and Prevention.
Smallpox vaccination with bifurcated needle. Reconstituted vaccine is held between the prongs of the needle and injected subcutaneously by multiple punctures; 15 rapid strokes, at right angles to the skin over the deltoid muscle, are made within a 5-mm area. Courtesy of the World Health Organization.
Smallpox vaccination. Evolving primary vaccination appearance. Courtesy of the US Centers for Disease Control and Prevention.
Typical temperature chart of a patient with smallpox infection (from Henderson, 1999).
Characteristic skin lesion of variola viral infection on the arms and the legs of an adolescent. Photo used with the permission of the World Health Organization (WHO).
Small child with pustular lesions due to variola viral infection. Photo used with the permission of the World Health Organization (WHO).
Infant with advanced lesions due to variola viral infection. Photo used with the permission of the World Health Organization (WHO).
Unvaccinated infant with the ordinary form of the variola major strain of smallpox has centrifugally distributed umbilicated pustules on day 3 in the course of the disease. Reprinted with permission from the World Health Organization (WHO).
Unvaccinated infant with the ordinary form of the variola major strain of smallpox has centrifugally distributed umbilicated pustules on day 5 in the course of the disease. Reprinted with permission from the World Health Organization (WHO).
Unvaccinated infant with the ordinary form of the variola major strain of smallpox has centrifugally distributed umbilicated pustules on day 7 in the course of the disease. Reprinted with permission from the World Health Organization (WHO).
The ordinary form of the variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after the onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from the World Health Organization (WHO).
The ordinary form of the variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after the onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from the World Health Organization (WHO).
The ordinary form of the variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after the onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from the World Health Organization (WHO).
Adult with variola major with hundreds of pustular lesions centrifugally distributed. Photo from Fitzsimmons Army Medical Center slide file.
Hemorrhagic-type variola major lesions. Death usually ensued before typical pustules developed. Reprinted with permission from the World Health Organization (WHO). 1988; 10-14, 35-36.
 
 
 
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