We report the case of a 6-year-old girl who presented in December 2002 with fever and a vesicular rash. Initially she was diagnosed with Stevens-Johnson syndrome. The differential diagnosis was expanded, however, when an exposure to a person who was believed to be vaccinated recently against smallpox was revealed. We describe the sequence of events that ensued and the workup for a possible case of disseminated vaccinia.
Recent events have raised interest in certain emerging infectious diseases and bioterrorism. Physicians are not accustomed to dealing with all aspects of the management of diseases such as smallpox. Since vaccination against smallpox has begun, clinical syndromes associated with the use of this vaccine may also require awareness by health care teams. From time to time it will be necessary to differentiate smallpox and reactions to smallpox vaccine from other conditions associated with similar clinical manifestations. A patient recently cared for at our institution illustrates some of these points and may therefore be instructive.
In late December 2002 a 6-year-old girl developed fever and headache. The following day she had conjunctival injection and an erythematous rash on the cheeks. She was seen by her pediatrician who diagnosed viral illness. Ibuprofen and sulfacetamide ophthalmic drops were prescribed. During the next 24 h, she remained febrile, and the rash spread to the neck, back and chest. The skin lesions were erythematous papules and not vesicular. She was admitted to a hospital where cefuroxime and clindamycin were administered. During the next 12 h, the rash spread to involve the entire body and became vesiculobullous and pruritic. She was transferred to the University of Chicago Children’s Hospital (UCCH) and was placed in contact and airborne isolation on arrival.
Her medical history revealed past evidence of mild eczema. She lived in Gary, IN and had not traveled recently. Her immunizations were up to date. At UCCH she was afebrile. Physical examination revealed erythema of the cheeks with a blistering, confluent, erythematous, maculopapular rash on the back. There were vesicles on the trunk, arms and legs and target lesions on the abdomen. The rash involved the palms but not the soles (Fig. 1). She had bilateral conjunctivitis and cracked lips. The oropharynx was erythematous without exudate. There was no lymphadenopathy. The physical examination was otherwise normal.
Laboratory data from UCCH included: white blood cell count 29 000/μl; hemoglobin 11.2 g/dl; platelets 176 000/μl; alanine aminotransferase 356 units/l; aspartate aminotransferase 379 units/l; and total and direct bilirubin 3.8 and 2.6 mg/dl, respectively.
Initial diagnostic considerations included Stevens-Johnson syndrome, toxic shock syndrome, varicella and Kawasaki disease. Antibacterials were discontinued, and intravenous acyclovir was initiated. Varicella-zoster virus and herpes simplex virus direct fluorescent antibodies, performed on a skin vesicle scraping, were nonreactive, and viral culture was negative. Varicella-zoster virus IgG antibody was present in serum, and antibodies to Mycoplasma, herpes simplex virus and hepatitis A, B and C were absent.
On the second hospital day, the child’s grandmother reported that her husband, an Army reservist, had received a smallpox vaccination as part of an immunization campaign for military personnel, before being called up to active duty 2 weeks earlier. He was in close daily contact with the patient for ∼1 week before the onset of her illness.
With this history a diagnosis of disseminated vaccinia was considered. Infection Control practitioners, the Pediatric Infectious Disease Service and the Hospital Epidemiologist were asked to assess the case. Almost simultaneously the CDC was contacted by the inpatient service, presenting them with the information that was available at that time. Photographs of the skin lesions were sent electronically to the Chicago Department of Public Health for diagnostic consideration. Because few physicians had dealt with problems related to smallpox vaccine complications, a team effort was helpful in dealing with this problem. Entry into the patient’s room was limited. A skin biopsy was obtained. Efforts were made to confirm the grandfather’s vaccination status. However, the vaccination history could not be refuted until the grandfather called the hospital hours later that night and denied history of smallpox vaccination. His military superiors later confirmed this history. The skin biopsy was consistent with erythema multiforme.
In response to increased concern for the use of smallpox as a weapon of bioterror, in December 2002 the federal government initiated a smallpox vaccination program. Simultaneously the CDC developed guidelines for clinicians evaluating potential cases of smallpox. 1, 2 In addition, to help clinicians with differentiation between normal and adverse reaction to smallpox vaccine, the CDC has created a training module available at their website. 3
Nevertheless there is still uncertainty regarding the contagiousness of the vaccinia virus found in the smallpox vaccine. 4 Nosocomial spread was described multiple times between 1907 and 1975. The majority of these cases were in young children with underlying dermatologic conditions (particularly eczema). Spread to household contacts has also been reported, with the most typical scenario being transmission from a recently vaccinated child to unvaccinated siblings.
The current vaccination campaign and increased awareness has already led to at least one false alarm reported in the medical literature 5 regarding a possible case of smallpox in a man with papulovesicular rash who actually had a herpes simplex virus type 2 infection.
In retrospect the clinical diagnosis of disseminated vaccinia or eczema vaccinatum was unlikely in our patient, based on the overall appearance of the lesions, the rapid progression of the rash and the limited duration and timing of contact between the patient and the grandfather. However, the case illustrates several points that were important in the context of the smallpox vaccination campaign. Vaccinia infection should be considered in the differential diagnosis of any person presenting with a vesicular rash. Infectious Diseases and Infection Control personnel should be involved promptly whenever there is a suspicion of vaccinia infection, because they will be the least inexperienced specialists in managing such cases. The local Department of Public Health should also be contacted, and the case should be discussed with public health personnel trained to assist with such scenarios. Digital photographs documenting the nature, distribution and evolution of the rash, when shared with consulting physicians and public health authorities, can facilitate remote consultation and can simplify field investigation in many cases, particularly for hospitals geographically isolated from public health resources. For suspected smallpox and disseminated vaccinia infection, contact and airborne precautions should be instituted promptly. In case of contact vaccinia, contact isolation would be sufficient. Personnel (including family and visitors) entering the room should be minimized. A log should be kept of those individuals who do enter the room to allow for epidemiologic follow-up if necessary.
This case is a reminder of the critical need for thorough and well-documented history taking in the era of bioterror preparedness. Individual practitioners appropriately attuned to the possibility of a bioterror attack serve as an important line of defense.
We thank Dr. Lawrence Gottlieb of the Department of Surgery for help in management of the patient and for providing the digital images.