Updated: Jun 06, 2018
Author: Aaron Z Hoover, MD, FAAD; Chief Editor: Dirk M Elston, MD 



Orf, also known as ecthyma contagiosum, contagious pustular dermatitis, infectious labial dermatitis, scabby mouth, or sore mouth, is a viral disease first described in humans in 1934 by Newson and Cross.[1] It is endemic in sheep and goat herds worldwide but can be found in other ruminants. It causes skin lesions on lips, muzzle, ears, eyelids, nostrils, and, less commonly in genitalia, udders, and feet of infected animals.[2] Orf is transmitted to humans through direct contact with an infected animal or, less commonly, contaminated fomites. Although extremely rare, human-to-human transmission has been reported. Lesions occur most commonly on the hands. Orf is frequently seen in ranching communities[3, 4] and in those who process the animals for consumption. It typically has a self-limited course with spontaneous resolution in 4-8 weeks after progressing through distinct stages. A typical clinical presentation of a reddish weeping nodule of orf located on the thumb is shown in the image below.

An early lesion of orf (papular stage). An early lesion of orf (papular stage).


Orf is caused by infection with the orf virus that belongs to the Parapoxvirus genus, which also includes the milker's nodule virus.[5] Parapoxvirus is a member of the family Poxviridae, which are double-stranded DNA viruses known to be the largest of all animal viruses.[6]

The orf virus is a cylindrical virus measuring 260 X 160 nm. Its surface tubules form a long crisscross design that is seen on negatively stained preparations by electron microscopy. This virus resists physical damage and persists through the winter months on hedges, feeding troughs, fences, harnesses, and barns.[7] It can remain viable on the wool of animals and on items that remain at room temperature for years.[8, 9]

The orf virus is able to produce a homolog of anti-inflammatory cytokine, interleukin (IL)‒10, which contributes to localized suppression of immunity.[10, 11] Orf also produces protein that inhibits IL-2 and granulocyte macrophage-colony stimulating factor and a vascular endothelial growth factor homolog.[12] The B2L major envelope protein has lipase activity and immunomodulating properties.[13]

Orf is transmitted by direct contact inoculation usually via a wound in the skin. Humans acquire the infection from contact with infected animals, carcasses, or contaminated, nonliving material. Orf is very common among shepherds, veterinary surgeons, and farmers' wives who bottle-feed young lambs, as well as in butchers, cooks, and meat porters from handling infected carcasses. It has been also linked to exposures at petting zoos and livestock shows.[14]

Autoinoculation to the genital area and face can occur, but human-to-human transmission is rare and there are reports in the literature of six possible cases.[7, 15, 16, 17] Nosocomial human-to-human was reported in patients on a burn unit.[18]



The majority of orf infections go unreported because the disease is self-limited, and those infected are able to recognize orf and do not seek medical attention.


No racial predilection exists for orf.


Orf occurs more commonly in men owing to the fact that men more likely to have an occupational exposure (eg, ranching, veterinary medicine, animal slaughter).[19]


Lesions are more common in adults but have been report in children with exposure to animals on farms and petting zoos.[19]


Orf is an occupational hazard of ranchers, veterinarians, butchers, shearers, and shepherds.


Orf has been reported in people who prepare sheep or goats for religious feasts. The most common is the Muslim practice of Eid ul-Adha, but it also has been reported in Jewish Passover and Christian Easter celebrations.[20, 21, 22, 23]


The prognosis of orf is excellent. The orf lesions usually heal completely with no scarring in about 35 days (4-8 wk). Scarring can occur if secondary infection or trauma to the lesion occurs.

Immunocompromised patients with orf can have progressive, destructive lesions requiring medical interventions such as antiviral therapy, reduction of immunosuppression, and surgical debridement. However, reports exist of immunosuppressed individuals with large, fungating lesions that have been refractory to treatment and required amputation.

Mortality from orf has not been reported.

Patient Education

Most patients infected with orf are farmers or people who handle animals; therefore, they are usually familiar with the disease. Those who are unacquainted with this condition must be reassured that the disease typically runs a benign self-limited course, and they should be instructed on proper wound care. They must also be informed that recurrences due to repeat infection may occur but generally result in lesions that are less pronounced than the primary infection.

Further information is available for on orf infections in both humans and animals at the US Centers for Disease Control and Prevention (CDC) Web site.[24] See Orf Virus (Sore Mouth Infection).




Orf occurs in humans with an occupational or household exposure to the virus via infected animals or fomites. The hands are where 95% of cases occur (see the image below).[25] The lesions may be pruritic and are generally painless. If the lesions are painful, then secondary infection should be suspected.[26] With orf, a low-grade fever may occur but usually subsides within 3-4 days. Systemic symptoms such as lymphadenopathy, erysipelaslike lesions, and erythema multiforme can occur in up to one third of cases.[27] Large, fungating orf lesions or multiple lesions have been reported in patients who are immunosuppressed, burn patients, atopic dermatitis patients, and one patient with scleroderma.[26, 28]

A classic location of orf on the index finger. A classic location of orf on the index finger.

Physical Examination

Orf appears as a solitary lesion or as a few lesions on the fingers, hands, or forearms, and orf has even been reported on the face, scalp, and groin.[29] The orf lesion starts as a small, firm, red-to-blue papule then progresses through a series of 6 stages.  The fully developed orf lesion is typically 2-3 cm in diameter, but it may reach 5 cm.

After incubation of 3-7 days, the orf infection goes through six clinical stages, each lasting about 1 week, as follows:

  • Stage 1 (maculopapular) - A red elevated lesion (see the image below)

    An early lesion of orf (papular stage). An early lesion of orf (papular stage).
  • Stage 2 (targetoid) - A bulla with an irislike configuration (nodule with a red center, a white middle ring, and a red periphery) as shown below

    The target phase associated with edema. The target phase associated with edema.
  • Stage 3 (acute) - A weeping nodule

  • Stage 4 (regenerative) - A firm nodule covered by a thin crust through which black dots are seen (see example below)

    The regenerative stage of orf with a central crust The regenerative stage of orf with a central crust.
  • Stage 5 (papillomatous) - Small papillomas appearing over the surface

  • Stage 6 (regressive) - A thick dry crust covering the resolving lesion


Orf infections can be associated with fever, lymphangitis, lymphadenopathy, erythema multiforme,[30, 31] and secondary bacterial infections. Papulovesicular eruptions and bullous pemphigoid‒like eruptions are very rare complications of orf.[32, 33, 34] Blindness has been reported when the diseases affects the eye.[35] Immunocompromised patients can develop giant orf, multiple lesions, and recurrent lesions; these can take longer or may fail to spontaneous resolve.[36] A swan-neck deformity of the index finger has also been reported.[23] Pregnancy and fetal development have not been reported to be adversely affected by this viral infection.[37]

Orf lesion (arrow) associated with erythema multif Orf lesion (arrow) associated with erythema multiforme.


Depending on the stage of the lesion, dermoscopic examination can demonstrate various findings to include a well-defined nodule with a central crust, white structureless areas, a blue-gray area, orange-yellow streaks, white shiny streaks, dotted vessels, hairpin vessels, an erythematous ring, a yellow-white ring, and a fine peripheral scale.[38, 39]



Diagnostic Considerations

Other considerations include the following:

  • Cowpox

  • Pseudocowpox (milker’s nodule)

  • Furuncle

  • Pyoderma

  • Herpetic whitlow

  • Cat scratch disease

  • Atypical mycobacteria infections

  • Deep fungal infections

  • Pyogenic granuloma

  • Squamous cell carcinoma, keratoacanthoma type

  • Syphilitic chancre

  • Primary inoculation by tuberculosis

  • Tularemia

  • Anthrax[40]

Differential Diagnoses



Laboratory Studies

The diagnosis of orf is usually made based on the history of contact with infected animal and the presence of a typical clinical lesion, but there are laboratory studies that can aid in the diagnosis.

Polymerase chain reaction (PCR) can definitively identify the virus and is available from the US Centers for Disease Control and Prevention (CDC) (telephone 404-639-4129).[41, 42, 43] Clinicians should contact their state health department to coordinate PCR testing.

Conventional histopathology of an orf skin biopsy may be of significant diagnostic value (see below).

No serologic tests are routinely performed for orf, but a detectable antibody response may be present.[44] Serology cannot distinguish orf virus from other parapoxviruses such as paravaccinia (pseudocowpox) virus.

Confirmation of the clinical diagnosis of orf can be made by electron microscopy with negative staining of the crust or a small biopsy specimen. Electron microscopy has also been performed on fluid obtained from the orf lesion.[45] It demonstrates classic ovoid cross-hatched virions but cannot be used to distinguish orf virus from other parapoxviruses.

Tissue culture with passage of the orf virus to sheep cell cultures is an option; however, the growth of the virus is slow and inconstant.

Histologic Findings

The epidermis usually shows marked pseudoepitheliomatous hyperplasia. Necrosis of the epidermis with ulceration occurs in the center of the lesion. The orf viral infection causes intranuclear and intracytoplasmic inclusion bodies with vacuolization and disaggregation of keratinocytes. Pyknosis of individual keratinocytes occurs. A dense inflammatory infiltrate of plasma cells, macrophages, histiocytes, and lymphocytes is also observed in orf.



Medical Care

Although orf is a self-limited disease, symptomatic treatment with moist dressings, local antiseptics, and finger immobilization is helpful. Secondary bacterial infection of orf is not uncommon and must be treated with topical or systemic antibiotics. Several case reports describe orf successfully treated with topical imiquimod resulting in rapid regression of the lesions.[46, 47, 48] Imiquimod has been effective in both immunocompetent and immunocompromised patients. Regimens range from once every other day to twice-daily application topically to the lesion. The use of interferon alfa-2a and 2b has also been reported in refractory giant orf lesions in immunocompromised patients.[49, 50] Reports also describe effective treatment of orf with cidofovir cream and cidofovir intravenously.[51, 52, 53]

Surgical Care

Because of its self-limited nature, surgical procedures are usually reserved for immunocompromised patients who do not respond to conservative measures.[27] Cryotherapy (liquid nitrogen) has been reported to speed the recovery process from orf treatment.[54, 55] Shave excision is a procedure that can be diagnostic and therapeutic for small orf lesions. For large exophytic orf lesions, dissection from the underlying dermis has been performed.[56] If an orf lesion is persistent, curettage and electrodesiccation may be curative. Amputation should only be used as a last resort. Recurrences and delayed healing have been reported after surgical treatment.[19, 50]


The best preventive measure in animals is an orf vaccination every 6-8 months. The orf vaccine is an attenuated vaccine, and, therefore, recently vaccinated animals do pose an infection risk to humans.[57] Once an animal is infected, it should be put in isolation.

To prevent infections in humans taking preventive measures is essential. It is recommend to wear nonpermeable rubber or latex gloves when handling sheep or goats, especially if there is a cut or sore present on the mouth/muzzle area. Practice good hand washing with warm soapy water for 20 seconds or by using a waterless alcohol-based hand sanitizer when soap is not available.[24] Protective immunity after infection is incomplete, so reinfection can occur unless precautions are taken.[21]

Patients who are immunosuppressed or persons with compromised skin barriers (eg, trauma, skin disease) must avoid contact with infected animals because they have an increased susceptibility for contracting the orf infection.



Medication Summary

Several case reports describe orf successfully treated with topical imiquimod, interferon alpha-2a, cidofovir cream, and cidofovir intravenously.[46, 47, 48, 51, 52, 53]

Topical Skin Products

Imiquimod (Aldara, Zyclara)

Imiquimod induces secretion of interferon alpha and other cytokines; the mechanisms of action are unknown. Use in orf is off-label.

Antivirals, CMV

Cidofovir (Vistide)

Cidofovir is a nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses. Use in orf is off-label.

Biological Response Modifiers

Interferon alfa 2b (Interferon alfa-2b, Intron A)

Interferon alfa-2b is a protein product manufactured by recombinant DNA technology. Interferon alfa has antiviral, antiproliferative, and antiangiogenic properties, and it stimulates the immune system. Use in orf is off-label.