eMedicine Specialties > Infectious Diseases > Viral Infections
Parapoxviruses
Updated: May 15, 2009
Introduction
Background
Poxviridae are a family of oval, quite large, double-stranded DNA viruses. The genus Parapoxvirus is included among these viruses, which measure 260 by 160 nm and possess a unique spiral coat that distinguishes them from the other poxviruses. Parapoxvirus species are endemic in hoofed animals (ungulates). Three similar, if not identical, parapoxviruses cause human infections, which relate to direct or indirect contact with infected animals. The zoonotic hosts of Parapoxvirus species are sheep and goats (orf, ie, ecthyma contagiosum virus)[1,2 ]and cattle (bovine papular stomatitis virus in humans and pseudocowpox virus [ie, milker's nodule virus or paravaccinia virus]). Other parapoxviruses have been recognized in New Zealand red deer, Finnish reindeer, red squirrels in the United Kingdom, and harbor seals in the North Sea.
Clinical cutaneous manifestations of infection with the parapoxviruses are quite similar because of the nature of the animal reservoirs; therefore, some authors propose the term farmyard pox for any of the 3 infections.
Pathophysiology
The clinical picture of parapox infection for all 3 infections is essentially identical. In general, infection results in solitary or multiple, relatively painless, cutaneous lesions that heal relatively slowly, usually without complications. Even in immunocompromised hosts, little evidence suggests spread of infection outside external surfaces.
The age distribution of patients is wide. Immunity to paravaccinia virus does not occur; in fact, reinfection occurs.
Frequency
United States
Orf, bovine papular stomatitis, and milker's nodule are viral illnesses endemic to sheep, goats, and cows. No reports contain data specific to the United States.
International
The Parapoxvirus causes worldwide infection of cows, sheep, and goats. Data reported from England and Wales between 1990-1995 indicate an annual mean of 15 cases of Parapoxvirus infections in these animals, significantly less than the reported annual mean of 46 cases between 1978-1968. More cases occur in sheep than in other bovines.
- Human infections occur with higher frequency in the spring and autumn, coinciding with the seasonal slaughtering of lambs and calves; although other reports suggest a higher incidence during the winter, presumably from the use of gorse, a prickly animal feed that may cause trauma and, hence, lead to infection in an animal.
- Because of the relatively benign nature of the infection and its occurrence predominantly among animal caretakers, especially those involved with sheep, infected individuals may not be likely to seek medical attention. Therefore, many authors believe that the infection is more common than actually reported.
Mortality/Morbidity
Bovine pustular stomatitis, orf, and milker's nodule show similar gross lesions; nevertheless, lesions range from inconspicuous pustules to giant tumors, which may be incorrectly diagnosed as malignancy, necessitating amputation of the affected digits. Pain often is negligible.
- Erythema multiforme has been described temporally related to orf and milker's nodule infection.
- Gianotti-Crosti syndrome, also referred to as papular acrodermatitis of childhood, causes self-limited symmetrically distributed papules on the face, buttock and extremities. It has also been reported to be temporally linked to infection with milkers' nodules.
Race
The literature does not mention race as a factor influencing the type and distribution of paravaccinia virus in the population; in fact, the race of the patients in the literature reviewed is not specified.
Sex
Most cases occur in males rather than females. This most likely is caused by the male predominance in the occupations or activities of the infected patients, which include veterinarians, veterinary students, farmers, shepherds, animal caretakers, and farm workers. Nevertheless, women are susceptible to infection. In one series, 6 of 19 subjects were women, reflecting their close contact with animals as farm wives, farm workers, or manual cow milkers.
Age
Most cases occur in young to middle-aged adults, although school-aged children also are infected. Parapoxvirus may not have a predilection for any particular age group because the distribution is associated with patient contact with the affected animals.
Breed
Sheep and cattle parapox infections manifest as pathologic lesions on the animal's oral mucosa (eg, lips, nostrils, eyes) and, occasionally, the most hairless areas of the skin (eg, udders, groin). The virus may be isolated in the mucosal fluids, even without obvious lesions on the skin.
Clinical
History
Parapoxvirus species are resistant to heat, cold, and drying and may persist on fences, feeding troughs, and barn beams. Most patients report direct contact when feeding or treating animals and when visiting or working on farms. Reports rarely show human-to-human transmission.
Physical
- The incubation period lasts 3-7 days. After this time, the lesions usually begin as discrete erythematous macules on the fingers, hands, or forearms; although, several reports show involvement of the face, neck, ear, and periocular area. Lesions may be single or multiple and often progress. The lesions appear targetlike, with a red center, a white middle ring, and a red halo.
- The acute stage occurs by week 2-3. The lesion appears nodular and weeping.
- The regenerative stage occurs by week 3-4. The lesion becomes ulcerated and thin-crusted at its summit.
- By week 4-5, the lesion may become papillomatous over its surface.
- Regression with thick crusting and reduction in elevation occurs by week 6, during which time the lesion eventually disappears.
- An erythematous macule may last for several months but resolves with no residual scarring.
- The diagnosis of Parapoxvirus infection usually is clinical in nature, based on the character of the cutaneous lesion and the exposure history of the infected individual.
Causes
Direct contact with infected animals, either alive or dead, is most typical but is not required for infection; researchers also report transmission from contaminated inanimate objects.
Differential Diagnoses
Staphylococcal Infections
Other Problems to Be Considered
Cutaneous anthrax
Herpetic whitlow
Cutaneous leishmaniasis
Cutaneous fungal infections
Workup
Laboratory Studies
- Electron microscopy of skin tissue[3 ]
- This study allows direct visualization of the Parapoxvirus, and its characteristic appearance is considered the criterion for diagnosis.
- Nevertheless, given the lack of availability of electron microscopy in the areas endemic for infection, light microscopy and traditional histopathologic techniques afford accurate identification of the characteristic cutaneous changes observed in a parapox infection.
Histologic Findings
Histologically, orf and milker's nodule appear identical.[4 ]With orf and milker's nodule, an impressive epidermal proliferation, mild acanthosis, parakeratosis, spongiform keratinocytic degeneration, and viral cytopathic changes occur, including cytoplasmic inclusion bodies and nuclear and cytoplasmic vacuolization. In the dermis, a dense inflammatory infiltrate develops, consisting of mast cells, lymphocytes, polymorphs, eosinophils, and prominent upper-dermal edema. Most notably, capillary dilatation and proliferation give the impression of an angiomatous dermal lesion.
The histological appearance of bovine papular stomatitis shares many features with orf and milker's nodule infections. These include epidermal acanthosis, hyperkeratosis, parakeratosis, intercellular edema, abundant lymphocytic and polymorphonuclear leukocytic infiltrate, and intracellular inclusions (generally not noted).
Treatment
Medical Care
The overall benign nature of this infection is reflected by the success of any of the following treatment methods:
- Waiting for the lesion or lesions to regress
- Performing an excision
- Using direct idoxuridine application with eye involvement
- Administering antimicrobials for bacterial superinfection
Medication
Limited information is available for specific antiviral therapy of human Parapoxvirus infections. However, anecdotal information suggests a possible role of topical idoxuridine in ophthalmic involvement.
Ophthalmic antivirals
Therapy of viral infections begins with mechanical debridement of the involved rim and a rim of normal epithelium. This is followed by the topical instillation of antiviral medications.
Idoxuridine (Herplex)
One of the first halogenated pyrimidine derivatives used for their antiviral effect. Used primarily in herpetic keratitis but was replaced by newer better-tolerated agents and for epithelial infections (especially initial attacks). Infections characterized by the presence of a dendritic shape respond better to this medication than stromal infections. Blocks reproduction of herpes simplex virus by producing incorrect DNA copies, preventing the virus from infecting or destroying tissue.
Dosing
Adult
Initial: 1 gtt into infected eye(s) q1h during the day and q2h at night; continue until definite improvement occurs (usually within 7 d)
Reduce to 1 gtt q2h during the day and q4h at night; to minimize recurrences, continue therapy at reduced dosage for 3-7 d after healing appears complete; not to exceed 21 d
Alternative treatment: Instill 1 gtt q1min for 5 min and repeat q4h (day and night)
Pediatric
Administer as in adults
Interactions
Coadministration with boric acid–containing solutions may result in a precipitate formation, which may cause irritation
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Local effects in the eye may occur, including chemical conjunctivitis, punctate keratitis, and, rarely, allergic blepharodermatitis; because some strains of herpes simplex appear to be resistant, undertake another form of therapy if no lessening of fluorescein staining in 14 d; do not exceed recommended frequency and duration of administration
Follow-up
Deterrence/Prevention
Instruct patients with close direct contact with sheep, cattle, or goats, especially when in contact with herds containing any of these parapoxviruses known to be endemic, to use barrier protection (ie, protective gloves), thereby decreasing the risk of infection.
Complications
- The following complications of a Parapoxvirus infection in humans are rare but do occur.
- Fever
- Transitory lymphangitis
- Lymphadenopathy
- Secondary bacterial infection
- Immunodeficiency reported as lymphoma with concomitant cytotoxic drug therapy and congenital T-cell deficiency - May produce larger lesions
- Lesion dissemination
- No case reports exist of human death caused by these Parapoxvirus infections.
Prognosis
Healing over time is the rule in almost every case.
Miscellaneous
Medicolegal Pitfalls
- The presence of a facial or peripheral extremity eschar in a farm worker or other rural worker can be casually confused with cutaneous anthrax. Anthrax, of course, may have significance regarding biological warfare; therefore, promptly report suspicious cases to proper authorities.
References
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Radtke MA, Günzl HJ, Siemann-Harms U, Augustin M, Coors EA. [Expanding papillomatous nodule on forearm with acute lymphangitis : Case of diagnosis.]. Hautarzt. Apr 24 2009;[Medline].
Mast J, Demeestere L. Electron tomography of negatively stained complex viruses: application in their diagnosis. Diagn Pathol. Feb 10 2009;4:5. [Medline].
Ceovic R, Pasic A, Lipozencic J, Marinovic-Kulisic S, Budimcic D, Sviben M, et al. Milker's nodule--case report. Acta Dermatovenerol Croat. 2007;15(2):88-91. [Medline].
Baxby D, Bennett M. Poxvirus zoonoses. J Med Microbiol. Jan 1997;46(1):17-20, 28-33. [Medline].
Bowman KF, Barbery RT, Swango LJ, Schnurrenberger PR. Cutaneous form of bovine papular stomatitis in man. JAMA. Dec 18 1981;246(24):2813-8. [Medline].
Centers for Disease Control and Prevention. Orf virus infection in humans--New York, Illinois, California, and Tennessee, 2004-2005. MMWR Morb Mortal Wkly Rep. Jan 27 2006;55(3):65-8. [Medline].
Davis CM, Musil G. Milker''s nodule. A clinical and electron microscopic report. Arch Dermatol. Mar 1970;101(3):305-11. [Medline].
de la Torre C. Gianotti-Crosti syndrome following milkers'' nodules. Cutis. Nov 2004;74(5):316-8. [Medline].
Groves RW, Wilson-Jones E, MacDonald DM. Human orf and milkers'' nodule: a clinicopathologic study. J Am Acad Dermatol. Oct 1991;25(4):706-11. [Medline].
Leavell UW Jr, McNamara MJ, Muelling R, et al. Orf. Report of 19 human cases with clinical and pathological observations. JAMA. May 20 1968;203(8):657-64. [Medline].
Muller G, Groters S, Siebert U, et al. Parapoxvirus infection in harbor seals (Phoca vitulina) from the German North Sea. Vet Pathol. Jul 2003;40(4):445-54. [Medline].
Robinson AJ, Petersen GV. Orf virus infection of workers in the meat industry. N Z Med J. Feb 9 1983;96(725):81-5. [Medline].
Schmidt E, Weissbrich B, Brocker EB. Orf followed by erythema multiforme. Eur Acad Dermatol Venereol. 2006;20:612-3.
Schuler G, Honigsmann H, Wolff K. The syndrome of milker's nodules in burn injury: evidence for indirect viral transmission. J Am Acad Dermatol. Mar 1982;6(3):334-9. [Medline].
Shelley WB, Shelley ED. Farmyard pox: parapox virus infection in man. Br J Dermatol. Jun 1983;108(6):725-7. [Medline].
Slattery WR, Juckett M, Agger WA. Milkers' nodules complicated by erythema multiforme and graft-versus-host after allogenic hematopoietic stem cell transplantation for multiple myeloma. Clin Infect Dis. 2005;40:e63-6.
Smith KJ, Skelton HG 3d, James WD, Lupton GP. Parapoxvirus infections acquired after exposure to wildlife. Arch Dermatol. Jan 1991;127(1):79-82. [Medline].
Tompkins DM, Sainsbury AW, Nettleton P. Parapoxvirus causes a deleterious disease in red squirrels associated with UK population declines. Proc Biol Sci. 2002;269:529-33.
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Keywords
viral infection, virus, poxviruses, Parapoxvirus, Poxviridae, Poxvirus, orf, ecthyma contagiosum, bovine papular stomatitis, pseudocowpox, milker's nodule, paravaccinia, farmyard pox
Contributor Information and Disclosures
Author
Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.
Coauthor(s)
Adam M Rotunda, MD, Fellow, Department of Dermatology, David Geffen School of Medicine at University of California at Los Angeles
Disclosure: Nothing to disclose.
Medical Editor
Pranatharthi Haran Chandrasekar, MD, Director of Infectious Disease Fellowship, Professor, Department of Internal Medicine, Harper Hospital, Wayne State University School of Medicine
Pranatharthi Haran Chandrasekar, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.
Pharmacy Editor
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.
Managing Editor
Thomas M Kerkering, MD, Chief of Infectious Diseases, Virginia Tech, Carilion School of Medicine, Roanoke, Virginia
Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society
Disclosure: Nothing to disclose.
CME Editor
Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
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.