Smallpox Differential Diagnoses

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

Diagnostic Considerations

The rash of chickenpox was frequently mistaken for that of smallpox during the days of natural infection. Both conditions can result in pustular scarring lesions that involve the face. Varicella typically does not have a prodromal phase, and the evolution of the rash from its appearance to scab separation takes approximately 7 days in varicella. Often, individuals who were previously vaccinated had only a mild prodrome without any rash.

The fever and vesicular rash of herpes zoster and erythema multiforme also were often confused with those of variola major.

Hemorrhagic smallpox, seen in the image below, develops fulminantly and was most often confused with meningococcemia or severe acute leukemia.

Hemorrhagic-type variola major lesions. Death usuaHemorrhagic-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.

Contact dermatitis, although often vesicular, is distinguishable from smallpox lesions because contact dermatitis is pruritic and is not accompanied by fever or constitutional symptoms.

Conditions to consider in the differential diagnosis of smallpox include the following:

  • Rocky Mountain spotted fever
  • Syphilis
  • Varicella-zoster virus
  • Drug eruptions
  • Insect bites
  • Kawasaki disease
  • Measles, rubeola
  • Monkeypox
  • Rubella
  • Generalized vaccinia and eczema vaccinatum
  • Insect bites
  • Viral hemorrhagic fevers (may be confused with hemorrhagic smallpox)
  • Varicella virus
  • Acne
  • Atypical measles
  • Coxsackievirus
  • Acute leukemia
  • Secondary syphilis
  • Rat-bite fever
  • Infectious mononucleosis
  • Toxic erythemas
  • Parvovirus B19
  • Cytomegalovirus
  • Erythema multiforme (Stevens-Johnson syndrome)
  • Molluscum contagiosum
  • Scarlet fever

Differential Diagnoses

Proceed to Workup
 
 
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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