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Orf virus infection

Orf virus infection
Author:
Ossama Abbas, MD
Section Editor:
Ted Rosen, MD
Deputy Editor:
Abena O Ofori, MD
Literature review current through: Jan 2024.
This topic last updated: Dec 21, 2022.

INTRODUCTION — Orf is a highly contagious, zoonotic, self-limited viral infection that threatens individuals who handle sheep and goats. The cause of orf is the orf virus. Other terms for orf include "ecthyma contagiosum," "infectious pustular dermatitis," and "contagious pustular dermatitis" [1-4].

In humans, orf usually presents as an evolving, erythematous nodule on the hand (picture 1A). The infection typically resolves spontaneously within six to eight weeks.

The risk factors, clinical features, diagnosis, and management of orf virus infection will be reviewed here. Other zoonotic infections are reviewed separately. (See "Zoonoses: Animals other than dogs and cats" and "Zoonoses: Dogs" and "Zoonoses: Cats".)

VIROLOGY — The epitheliotropic orf virus is the prototype of the Parapoxvirus genus of Poxviridae family [1-4]. The virus has a linear double-stranded DNA genome and replicates within the host cell cytoplasm. The genome consists of a central core containing highly conserved genes that encode transcription and replication machinery; genes encoding factors associated with virulence, immune modulation, and pathogenesis are located outside the core region at both ends of the genome [3].

TRANSMISSION — Orf virus is highly contagious. Loss of epithelial barrier integrity (ie, abrasion or other skin break) is the most important predisposing factor for infection [1-4].

Transmission to humans can occur through direct contact with an infected lesion on a living or deceased goat or sheep. Infected animals usually exhibit scabbed sores on or around the mouth, and the infection is commonly known as sore mouth or scabby mouth disease in sheep or goats [5]. Infections may also occur on the legs or udder teats, particularly in female animals that are nursing infected young.

In addition, infection can occur through contact with fomites previously contaminated by infected animals, such as farm buildings, wool, knives, buckets, equipment, and fences [4,6]. Orf virus is resilient and resistant to drying and freezing and can remain viable for months to years [4,7].

Autoinoculation and human-to-human transmission are rare [6].

RISK FACTORS — Orf is most often an occupational hazard. Populations most at risk include shepherds, wool shearers, butchers, farmers, and veterinarians [1,2,4,7]. Less often, infection occurs in individuals with nonoccupational contact with sheep and goats, such as zoologic garden visitors and people who slaughter sheep or goats for traditional rituals [4,6-11].

PATHOGENESIS — Orf virus causes a vesiculoulcerative infection of keratinized skin and mucosa that replicates in regenerating epidermal keratinocytes [1-4]. Multiple virulence factors contribute to immune evasion and the establishment of infection [3,4]. Host immunity, especially the cell-mediated immune response, plays a major role in limiting the severity of infection.

Virulence factors of the orf virus include proteins with anti-inflammatory functions (eg, viral-vascular endothelial growth factor, orf virus interleukin-10, ovine interferon resistance protein, a granulocyte-macrophage colony-stimulating factor inhibitory factor, and chemokine binding protein) and proteins that promote virus survival and host cell manipulation or exploitation (eg, orf virus-encoded deoxyuridine triphosphate [dUTP]ases, nuclear factor kappa-B modulatory factors, ankyrin repeat proteins, and gene 125-encoded proteins) [3].

CLINICAL MANIFESTATIONS — In immunocompetent patients, orf typically presents as a single asymptomatic lesion (approximately 1 cm in diameter) on the dorsa of hands or fingers that evolves in appearance over time (picture 1A-B) [1,2,4]. Examples of less frequent sites include the head [12], axilla [13], and genitals [14]. Multiple lesions may also occur (picture 2).

Orf lesions commonly appear three to seven days after inoculation and progress through six clinical stages over the course of six to eight weeks, ending in resolution. The duration of each stage is approximately one week [1-4,6-8]:

Maculopapular stage (solitary erythematous papule) (picture 1B)

Target stage (papule or nodule with gray-white, necrotic center and red outer halo) (picture 3)

Acute-nodular weepy stage (draining papule or nodule) (picture 1A)

Regenerative-nodular dry stage (firm, crusted papule or nodule) (picture 4)

Papilloma stage (papule or nodule with a papillomatous surface and dry crust) (picture 2)

Regression stage (lesion progressively shrinks in size and resolves, generally without residual scar) (picture 4)

Rarely, fever, malaise, and lymphadenopathy accompany the skin lesion [4,15].

Immunocompromised patients, especially patients with inherited or acquired T cell dysfunction, may develop atypical, painful, persistent giant orf lesions up to several centimeters in diameter [16-23]. Tumor-like and pyogenic granuloma-like morphologies may occur in these patients. Rarely, giant orf occurs in immunocompetent individuals [24].

COMPLICATIONS — Potential complications include secondary bacterial infections and lymphangitis. In addition, orf is occasionally associated with the induction of secondary immunologic reactions, such as erythema multiforme [25,26], widespread papulovesicular eruptions [15,27], id reactions [28,29], and autoimmune blistering diseases [26,30-34].

Anti-laminin 332 antibodies may play a role in orf-induced autoimmune blistering disease. In a case series of five patients with orf-induced autoimmune blistering disease, anti-laminin 332 antibodies were identified in all patients [34].

HISTOPATHOLOGY — Microscopic findings may vary depending on the clinical stage of the lesion. Characteristic features of orf include (picture 5) [3,4,35]:

Overlying crust

Parakeratosis

Irregular epidermal hyperplasia

Keratinocyte ballooning and degeneration

Intraepidermal vesiculation

Intracytoplasmic and intranuclear inclusions within vacuolated keratinocytes (picture 6)

Increased dermal vascularity

Papillary dermal edema

Mixed inflammatory cell infiltrate

DIAGNOSIS — The patient history and physical examination are usually sufficient for diagnosis. The collection of findings that strongly support the diagnosis include:

Acute development of a papule or nodule exhibiting features consistent with one of the stages of orf

Recent exposure to an infected sheep or goat or objects contaminated by an infected sheep or goat

When the diagnosis is in doubt, a biopsy or molecular testing can aid in confirming the diagnosis [2-4]. A shave or punch biopsy can either reveal features supportive of viral infection (eg, intracytoplasmic and intranuclear inclusions within vacuolated keratinocytes) and other supportive features of orf or identify findings that are more consistent with other diseases. (See 'Histopathology' above.)

Although not available in all settings, both standard and real-time polymerase chain reaction (PCR) testing are rapid and sensitive methods for diagnosing orf, with real-time PCR being highly sensitive [4,36,37]. A skin biopsy provides an adequate specimen. Other less widely used methods for confirming the diagnosis include cell culture and electron microscopy [2,4]. In addition, a sensitive and specific recombinase-aided amplification (RAA) assay for orf virus detection has been developed. In a study of 45 nasal scab skin samples examined by RAA and real-time PCR, the clinical performance of RAA was comparable with that of real-time PCR assay, while being faster, less expensive, and technically simpler [38].

DIFFERENTIAL DIAGNOSIS — The clinical differential diagnosis is extensive. In particular, orf should be distinguished from milker's nodule and cutaneous anthrax, infections that may also result in vesiculoulcerative lesions following contact with animals:

Milker's nodule – Milker's nodule (also known as paravaccinia) is a parapoxvirus infection humans can acquire from dairy cows. Milker's nodule usually appears as one or more red-blue, smooth, verrucous, or vesicular nodules on the hand or arms and may be clinically indistinguishable from orf lesions (picture 7). Like orf, milker's nodule typically spontaneously resolves over the course of several weeks. The history of acquisition from contact with cows rather than sheep or goats is helpful for distinguishing these diseases.

Cutaneous anthrax – Cutaneous anthrax is an infection that may result from contact with infected animals, animal meat, hides, or wool. Bacillus anthracis, a gram-positive bacillus, is the causative organism. Affected patients typically present with a nonpainful papule that subsequently vesiculates and evolves into an ulcer with black eschar (picture 8). Gram stain, culture, and polymerase chain reaction (PCR) tests can confirm the diagnosis. (See "Clinical manifestations and diagnosis of anthrax", section on 'Cutaneous anthrax'.)

Other infections that may present with papules or nodules that may be mistaken for orf virus infection include giant molluscum, atypical mycobacterial infections, paronychia (picture 1B), cutaneous leishmaniasis, herpetic whitlow, tularemia, and sporotrichosis. Neoplastic entities, such as keratoacanthoma and pyogenic granuloma, are also in the differential diagnosis [4,18,39,40]. The patient history and clinical findings are often sufficient for differentiating orf from these disorders.

TREATMENT — In immunocompetent patients, treatment is not necessary since the infection spontaneously resolves within several weeks. Topical antiseptics can be used to minimize risk for secondary bacterial infections [1,4].

Immunocompromised patients may develop giant persistent lesions and may require intervention for resolution. Case reports describe successful treatment with cryotherapy, electrocautery, curettage, imiquimod, intralesional interferon injections, or topical cidofovir [4,18,20-23,41]. Wide local excision has been performed for refractory infections that cannot be managed with less invasive therapies, but recurrence after excision is common [4]. No randomized trials evaluating the efficacy of therapies have been performed.

PREVENTION — Reinfection with orf virus can occur. However, reinfection is commonly characterized by decreased lesion size and faster resolution [1,2,4].

Use of nonpermeable gloves when handling infected animals may reduce risk for human infection. Orf virus vaccines have been used in animals but appear only partially effective and are not available for use in humans [42,43].

SUMMARY AND RECOMMENDATIONS

Virology and transmission – Orf is a cutaneous viral infection caused by infection with the orf virus, a parapoxvirus that infects sheep and goats. Humans may acquire the infection from contact with infected animals or contaminated fomites. Populations most at risk for orf include shepherds, wool shearers, butchers, farmers, and veterinarians. (See 'Virology' above and 'Transmission' above and 'Risk factors' above.)

Clinical manifestations – Orf usually manifests as a solitary papule or nodule that evolves through six clinical stages over the course of six to eight weeks (picture 1A-B). Multiple and giant lesions may also occur, particularly in immunocompromised patients. (See 'Clinical manifestations' above.)

The six clinical stages of orf include the maculopapular stage, target stage, acute-nodular weepy stage, regenerative-nodular dry stage, papilloma stage, and regression stage. Fever, malaise, or lymphadenopathy occasionally accompany the skin lesion. (See 'Clinical manifestations' above.)

Diagnosis – Orf usually can be diagnosed based upon the patient history and physical examination. A biopsy or molecular testing can aid in confirming the diagnosis in difficult cases. (See 'Diagnosis' above.)

Treatment – Orf generally spontaneously resolves within several weeks. Persistent infection may occur in immunocompromised patients. Data on treatment of persistent infection are limited. Treatments that have seemed beneficial in case reports include cryotherapy, electrocautery, curettage, imiquimod, intralesional interferon injections, or cidofovir. Recurrence is common after wide local excision. (See 'Treatment' above.)

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