Are You Confident of the Diagnosis?
What you should be alert for in the history
Patients who develop cowpox lesions live in (or visit) Western Europe and have direct contact with rodents or with companion animals that hunt rodents (usually cats).
Characteristic findings on physical examination
The cowpox lesion is typical for poxviruses: annular with a leading vesiculobullous edge, an erythematous base, eventually forming a dark eschar in the center. Lesions are usually painful. The upper extremity and face/neck are common areas of infection (patients may nuzzle pet cats or rats). Painful regional lymphadenopathy and fever is common. The eschar may take up to 12 weeks to separate. Cowpox virus infects both the epidermis and the dermis and therefore leaves a scar after healing.
Patients who have been vaccinated for smallpox may have a less severe clinical presentation as vaccinia and cowpox are both orthopoxviruses and provide serologic cross-protection. Cowpox virus infections in humans may be increasing in Western Europe because smallpox vaccination programs were terminated decades ago.
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Expected results of diagnostic studies
Cowpox infection can be confirmed by polymerase chain reaction (PCR) (orthopoxvirus genus, cowpox specific assays) and culture; orthopoxvirus serology may be helpful but can be confounded by a history of exposure to orthopoxviruses in the past (eg, smallpox vaccination). Punch biopsy with specialized immunohistochemistry (IHC) can confirm it as an orthopoxvirus infection.
Diagnosis confirmation
The differential diagnosis includes cutaneous anthrax (cowpox lesions have less edema and are associated with rodent and feline exposure generally), contact vaccinia (laboratory use of vaccinia or contact with a smallpox vaccinee; also, contact with cattle in Brazil can lead to vaccinia infections), parapoxvirus infections (orf, pseudocowpox, sealpox, etc; these can be differentiated by little to no systemic symptoms and contact with different animal hosts).
Who is at Risk for Developing this Disease?
Residents of continental Europe (especially Germany and France) and Great Britain who have contact with rodents or with companion animals that hunt rodents (eg, cats and small dogs). Case reports of transmission from other animals has been reported as well, including elephants and mongooses.
What is the Cause of the Disease?
Etiology
Pathophysiology
The name “cowpox” is a misnomer as this orthopoxvirus is a rodent virus not a bovine virus. Orthopoxviruses may cause local or systemic infections in humans depending on the specific virus and the underlying host immunity. Cowpox virus leads to local infections in humans with normal immune systems. Those with poor immune function and/or underlying T-cell defects of the skin (eg, atopic dermatitis, Darier’s disease) may develop viremia with widespread lesions. Cowpox is endemic to Continental Europe and Great Britain (wherever the bank voles may be found). Nearly any mammal may become infected.
Systemic Implications and Complications
Disseminated infections are rare and are seen in those with significant immunocompromise or abnormal skin T-cell function (eczema, Darier’s disease). Complications may incluude corneal involvement, necrotizing lymphadenitis, bacterial superinfection and cellulitis of the primary lesion, disseminated cutaneous lesions, and death.
Treatment Options
Treatment options for cowpox are summarized in Table I.
Table I.
| Medical | Surgical | Physical |
|---|---|---|
| imiquimod | debridement of lesion not applicable | |
| ST 246® or CMX001®** | ||
** If the patient is immunocompromised.
Optimal Therapeutic Approach for this Disease
Cowpox infection in humans is rare and no clinical trial information is available to guide therapy. Most case reports describe spontaneous resolution of lesions as these patients were normal hosts. Debridement of lesions has been reported in case reports and theoretically may decrease the burden of actively replicating virus. However, if the lesion evolves like other local orthopoxvirus infections, covering the lesion with a dry dressing would be the most logical approach. Imiquimod could be applied safely and may hasten healing.
Patient Management
Cowpox infections are self-limiting and no form of chronic infection exists. Human to human transmission of cowpox virus has not been described.
Unusual Clinical Scenarios to Consider in Patient Management
In a patient with underlying immunocompromise and progressive disease, medical management with either ST 246® a small molecular inhibitor of enveloped virus formation (SIGA Technologies Inc) and/or CMX001® an ether-lipid analogue of cidofovir that inhibits DNA polymerase (Chimerix Inc) (obtained on compassionate use protocols) would be advisable. Both of these agents are in clinical trials and may be obtained via compassionate use/eIND protocols with FDA and local investigational review board (IRB) approval.
What is the Evidence?
Kurth, A, Straube, M, Kuczka, A, Dunsche, AJ, Meyer, H, Nitsche, A. “Cowpox virus outbreak in banded mongooses (Mungos mungo) and Jaguarundis (Herpailurus yagouaroundi) with a time-delayed infection to humans”. PLoS ONE. vol. 4. 2009. pp. e6883(This article summarizes transmission to humans from the mongoose and also summarizes the large range of mammals that may be infected with cowpox virus and therefore potentially pose a risk to humans.)
Moser, A, Rose, C, Haase, O, Kurth, A, Zillikens, D, Schmidt, E. ” Generalised cowpox infection in a patient with Darier's disease”. Br J Dermatol. 2011 Jan 28. (Just as patient's with Darier's disease are at increased risk from the vaccinia virus in the smallpox vaccination, they are at risk of developing disseminated infection with cowpox virus.)
Ninove, L, Domart, Y, Vervel, C, Voinot, C, Salez, N, Raoult, D. “Cowpox virus transmission from pet rats to humans, France”. Emerg Infect Dis . vol. 15. 2009. pp. 781-4. (This case series reports four humans infected by pet rats in France. It provides excellent clinical photographs and descriptions of the cowpox lesions. Patients were primarily treated with surgical debridement.)
Campe, H, Zimmerman, P, Glos, K, Bayer, M, Bergemann, H, Campe, H, Zimmerman, P, Glos, K. “Cowpox virus transmission from pet rats to humans, Germany”. Emerg Infect Dis. vol. 15. 2009. pp. 777-80. (This case series is the sister paper to the France series and demonstrates how a point source (rat breeder) can be traced back to four households with infected rodents and the eventual infection of five humans. Patients who were older and vaccinated for smallpox had less severe clinical disease.)
Baxby, D, Bennett, M, Getty, B. “Human cowpox 1969-93: a review based on 54 cases”. Br J Dermatol. vol. 131. 1994. pp. 598-607. (This case series is the largest to date and summarizes clinical findings as well as the exposure history (usually to domestic cats) which is implicated in transmission of the cowpox virus to humans.)
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