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David A. Warrell



Prevention—live attenuated virus vaccines.

Updated on 31 May 2012. The previous version of this content can be found here.
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Orf (‘ecthyma contagiosum’) is caused by an epitheliotropic parapox DNA virus of sheep and goats that is able to subdue the host’s immune response. It is an occupational zoonosis of people working with these animals. A painful papule/pustule develops, usually on a finger, the site of contact with lesions on the animal’s muzzle. Systemic effects are unusual, but include local lymphadenopathy, fever, erythema multiforme, and other generalized rashes. Spontaneous resolution within 6 weeks is usual. Multiple, giant lesions may develop in the immunosuppressed. Topical cidofovir is effective in severe cases.


Orf virus, a member of the Parapox genus of the Chordopoxvirinae subfamily, causes ‘scabby mouth’ (ecthyma contagiosum, contagious pustular dermatitis), a debilitating disease of sheep and goats. Orf virions are ovoid (approximately 260 × 160 nm), with a characteristic basketweave pattern visible by negatively stained and transmission electron microscopy. Other parapoxviruses infect cattle (pseudocowpox; bovine papular stomatitis virus, BPSV), camels, seals, and reindeer. Full genome sequences of orf and BPSV have been published. The orf virus genome is double-stranded DNA of 135 kbp, encoding a polypeptide homologous to interleukin 10 (IL-10), inhibitors of interferon, interleukin 2 (IL-2), and granulocyte-macrophage colony-stimulating factor (GM-CSF), and a vascular endothelial growth factor. These contribute to the dermal lesions characterized by capillary proliferation and dilatation.


Orf has been recognized for more than 200 years as a disease of mainly young lambs and kids, which contract the infection from one another, or possibly from persistence of the virus in the pastures where the virus can remain viable for long periods in dried scabs from lesions. Human disease is an occupational zoonosis, following contact with infected sheep. Since orf is familiar to veterinarians, shepherds, farmers, abattoir workers, and butchers and is generally self-limiting, it often goes unreported. In the United Kingdom it is known to be prevalent in sheep farming communities in Wales. Outbreaks are associated with the end of the lambing season and with Islamic religious festivals associated with animal sacrifice. Transmission is by direct contact with the animals’ lesions and possibly with fomites. Human to human spread has not been recorded. Infection confers only partial immunity, so that repeated milder attacks are possible.


Orf virus infects skin keratinocytes and excites a brisk immune response locally and in lymphoid tissue, involving CD4+ and CD8+ cells, interferon, and antibody. However, orf virus genome encodes a variety of virulence and immunomodulatory factors that subvert or suppress the host’s immune response, allowing viral replication. These include viral IL-10, interferon resistance protein, chemokine binding protein, GM-CSF, vascular endothelial growth factor, and heparin binding protein. In vaccinology, orf is proving a promising viral vector for delivering pathogen antigens to the immune system, and inactivated virus is immunoenhancing.

Clinical features

In sheep and goats, papules and vesicles appear on the muzzle or nostrils (Fig. and gradually heal without scarring over 4 to 8 weeks, although more persistent infections may occur. In humans, after an incubation period of 2 to 6 days, a painful, small, red, firm papule enlarges to form a flat-topped haemorrhagic pustule or bulla with prominent margin and an eroded, crusted centre, sometimes surrounded by pustular satellite lesions (Fig. The lesion is usually 1 to 3 cm in diameter, but may be as large as 5 cm. They are usually solitary or few in number and commonly occur on the extensor surface of a finger or hand, but also on the palm, forearm, and occasionally the face or scalp. The surrounding skin may be reddened, sometimes diffusely, and erysipelas-like lesions have been described. Lymphangitis or regional lymphadenopathy is not uncommon. Giant, multiple, fungating granulomatous or tumour-like lesions have been reported, usually in immunocompromised patients with haematological malignancies. Patients with atopic eczema may develop widespread eruptions. Slight fever and malaise can occur. Complications include secondary infection, generalized vesicular rashes, usually classified as erythema multiforme, in as many as one-third of cases (Fig., which develop typically 10 to 14 days after the initial lesion, and other generalized rashes. An autoimmune bullous disease, previously designated as bullous pemphigoid, has been reported. A lesion on the precanthal skin resulted in follicular conjunctivitis. Spontaneous recovery without residual scarring is usually complete within 6 weeks.

Fig. Contagious pustular dermatitis (‘orf’) in a lamb.

Contagious pustular dermatitis (‘orf’) in a lamb.

Fig. Typical lesions of orf on a farmer’s hand.

Typical lesions of orf on a farmer’s hand.

Fig. Generalized vesicular eruption ‘erythema multiforme’ complicating orf of the left middle finger in a veterinary student: (a) arms, (b) mouth.

Generalized vesicular eruption ‘erythema multiforme’ complicating orf of the left middle finger in a veterinary student: (a) arms, (b) mouth.


The characteristic lesion in someone exposed to sheep or goats, especially to lambs or kids, allows a clinical diagnosis. This can be confirmed in the laboratory by electron microscopy of a biopsy of the orf lesion, by polymerase chain reaction (PCR), viral culture, and fluorescent antibody staining.

Skin biopsy specimens show distinctive histopathological changes. There is hyperkeratosis with cellular swelling, balloon degeneration and vacuolation in the upper epidermis, and the presence of eosinophilic B type intracytoplasmic inclusion bodies.

Differential diagnosis

In those at occupational risk of orf, differential diagnoses include milkers’ nodules, caused by another parapox virus, and cowpox (Chapter 7.5.4), an orthopoxvirus. Whitlows (felons), including herpetic whitlow (Fig., impetigo, pyogenic granuloma, cutaneous anthrax, and tumours might also cause confusion.

Fig. Herpetic whitlows on adjacent fingers.

Herpetic whitlows on adjacent fingers.

(Courtesy of the late Dr B E Juel-Jensen.)


Secondary infection should be treated if it occurs. Large lesions can be removed surgically, but recurrence can occur in the immunocompromised. Cidofovir (topically or intravenously) and imiquimod (topically) have been used successfully to treat giant or persistent lesions, especially in immunosuppressed patients.


Live attenuated virus vaccines have been used to protect sheep and goats from orf. Farmers should avoid handling animals with obvious lesions.

Further reading

Al-Salam S, et al. (2008). Ecthyma contagiosum (orf)—report of a human case from the United Arab Emirates and review of the literature. J Cutan Pathol, 35, 603–7.Find this resource:

Gill MJ, et al. (1990). Human orf. Arch Dermatol, 126, 356–8.Find this resource:

Groves RW, Wilson-Jones E, MacDonald DM (1991). Human orf and milkers’ nodule: a clinicopathologic study. J Am Acad Dermatol, 25, 706–11.Find this resource:

Haig DM (2006). Orf virus infection and host immunity. Curr Opin Infect Dis, 19, 127–31.Find this resource:

Torfason EG, Gunadóttir S (2002). Polymerase chain reaction for laboratory diagnosis of orf virus infections. J Clin Virol, 24, 79–84.Find this resource: