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Smallpox-or a Mimic?


Smallpox, which is caused byinfection with poxvirus variola,may follow variouscourses. An erythematouseruption can precede theappearance of tense, deep-seatedpapules that rapidly transform intovesicles. The lesions may be sparseor so numerous that they becomeconfluent.

Smallpox, which is caused byinfection with poxvirus variola,may follow variouscourses. An erythematouseruption can precede theappearance of tense, deep-seatedpapules that rapidly transform intovesicles. The lesions may be sparseor so numerous that they becomeconfluent.Typically, the incubation periodof variola major is 12 to 14 days, witha range of 7 to 17 days. Approximately30% of infected patients die of thedisease.1Routine immunization againstsmallpox was halted in the UnitedStates in 1972 and is not now recommended.Immunity for persons whohave received the vaccine is thoughtto be 3 to 5 years; the duration ofresidual partial immunity is notknown. Vaccine given to a patientwithin 4 days of exposure can preventsmallpox or significantly lessenthe severity of the disease. Personswho have had smallpox cannot contractthe disease again.1PRESENTATIONProdromal symptoms includethe acute onset of malaise, fever, rigors,vomiting, headache, and backache.Delirium develops in about 15%of patients; 10% of light-skinned patientshave an erythematous rash.Two or 3 days after the prodrome,just as the fever peaks, a discrete,maculopapular rash appears onthe face, hands, forearms, and mucousmembranes of the mouth andpharynx. Commonly, the palms andsoles also are involved.Initially, the lesions are peripheral(A); they move centrally within afew days. During week 2, the rashspreads to the legs and the trunk.The lesions quickly progress frommacules and papules to vesicles, thento umbilicated, pustular vesicles,which become crusty scabs between8 and 14 days after onset. Thesecrusts leave depressions and depigmentedscars that are more prominenton the face (B). The resultant faciallesions have been attributed tothe destruction of sebaceous glandswith subsequent granulation tissueshrinkage and fibrosis.2Flat, or malignant, smallpox.This variant occurs in 2% to 5% ofpatients and is attributable to thelack of an adequate cell-mediatedimmune response. The infection ischaracterized by severe systemictoxicity and the slow evolution of flat,soft, focal skin lesions that coalescebut do not become pustular. Theskin takes on a fine-grained reddishcolor that resembles crepe rubber.Mortality among unvaccinated personsis 95%.Hemorrhagic smallpox. Fewerthan 3% of patients have this variant.Extensive petechiae; mucosal hemorrhage;and intense toxemia, includinghigh fever, headache, backache, andabdominal pain, are present. Hemorrhagicsmallpox occurs more commonlyin pregnant women. Generally,patients die before the typical pox lesionscan develop.DIAGNOSISThe CDC Interim Smallpox ResponsePlan and Guidelines givesspecific instructions for reporting suspectedcases of the disease and for collecting,processing, and shipping specimensto an appropriate laboratoryfor evaluation.3 State and local publichealth authorities need to be contactedas well. The following is a conciseoverview of the detailed guidelines.Obtain vesicular fluid by openinglesions with the blunt edge of a sterilescalpel. Harvest a droplet of fluid andplace on a clean slide for microscopicexamination; allow the sample to airdry in a safe location. Scabs may beremoved with forceps and placed ina sterile tube. Label all materialscarefully.Safely secure all specimens forshipping. The CDC laboratory prefersat least 3 separate slides or a steriletube with 3 or 4 scabs for each patienttested. The CDC's Biosafety Level 4reference laboratory tests specimenswith viral cultures that require isolationof the virus and characterizationof its growth on chorioallantoic membraneor cell culture.Differential diagnosis. The diagnosisof smallpox requires astuteclinical evaluation. Most commonly,the clinical diagnosis can be confusedwith chickenpox; Cases 1 through 4illustrate manifestations of chickenpoxand its sequelae in adults and children.Also consider erythema multiformewith bullae (Case 5) and allergiccontact dermatitis in the differential.Chickenpox, which is caused bythe varicella-zoster virus, presentswith a mild viral prodrome and cropsof papulovesicular lesions. Severalclinical clues can help distinguishsmallpox from chickenpox (Table).Meningococcemia (Case 6) andacute leukemia (Case 7) need to be includedin the differential for hemorrhagicsmallpox.TREATMENTSupportive care--intravenousfluids and fever and pain control medication--is the mainstay of therapy.Antibiotics are used to treat secondarybacterial infections.Currently, no antiviral agentshave proved effective for the treatmentof smallpox. Adefovir dipivoxil,cidofovir, and ribavirin have shownsignificant in vitro antiviral activityagainst poxviruses; however, theirefficacy as therapy for this disease isuncertain. Cidofovir shows the mostpromise in animal models.4




CDC Public Health Emergency Preparedness &Response. Facts about smallpox. Available at:http://www.bt.cdc.gov/DocumentsApp/FactSheet/SmallPox/About.asp. Accessed December 7, 2001.


Fenner F, Jezek Z, Ladnyi ID, et al, eds. Smallpoxand Its Eradication

(History of International PublicHealth,

No. 6). Geneva: World Health Organization;1988.


CDC Interim Smallpox Response Plan andGuidelines; draft 2.0: 11/21/01. Available at:http://www.bt.cdc.gov/DocumentsApp/Smallpox/RPG/index.asp. Accessed December 14, 2001.


De Clercq E. Vaccinia virus inhibitors as a paradigmfor the chemotherapy of poxvirus infections.

Clin Microbiol Rev.



  • Fitzpatrick TB. Dermatology in General Medicine.4th ed. New York: McGraw-Hill; 1993:2596-2602.
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