Variola sine eruptione

CDC Case Definition An illness with acute onset of fever >101°F followed by a rash characterized by firm, deep seated vesicles or pustules in the same stage of development without other apparent cause. Clinically consistent cases are those presentations of smallpox that do not meet this classical clinical case definition (1) hemorrhagic type, (2) flat type, and (3) variola sine eruptione. Laboratory criteria for diagnosis is (1) polymerase chain reaction (PCR) identification of variola DNA in a clinical specimen, or (2) isolation of smallpox (variola) virus from a clinical specimen (Level D laboratory only confirmed by variola PCR). 

The Variola major rash presents in four distinct ways, ordinary, modified, flat, and hemorrhagic. The type of rash presentation is probably associated with the strength of the immune response. Ordinary smallpox is most frequent, whereas the mild modified form, seen primarily in previously vaccinated patients, is uncommon. The most severe presentations, flat and hemorrhagic, are usually fatal but are fortunately rare. Smallpox infection can also occur without a rash. A mild but uncommon variation of variola infection, variola sine eruptione (meaning smallpox without a rash) occurs generally in previously vaccinated people and involves a febrile illness alone. Asymptomatic infections are also possible, yet rare. 

People previously vaccinated for smallpox can develop a febrile illness after exposure to a smallpox case. Typically, fever begins suddenly, reaches 39°C and is associated with headache and occasionally backache. Symptoms resolve within 48h. Serologic studies in these patients have suggested the diagnosis of variola sine eruptione by demonstrating a significant rise in variola antibody titers following the illness (25). 

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