Continuing Education Activity
Orf disease, also known as ecthyma contagiosum or contagious pustular dermatitis, is an occupational disease acquired from infected sheep and goats. Typically, transmission occurs when a person has an area of skin trauma that comes into contact with an infected goat or sheep. Although this condition is generally self-limiting and does not require specific treatment, diagnosing it early will allow measures to prevent it from spreading to other animals and workers, thereby allowing for the maintenance of productivity and decreased associated morbidity. This activity illustrates the evaluation and management of orf disease and highlights the role of the interprofessional team in improving care for patients with this condition.
- Describe the epidemiology of orf disease.
- Summarize the typical clinical course of orf infection in a human.
- Review the most common complications associated with orf disease.
- Explain the importance of collaboration and communication amongst the interprofessional team to enhance care and prevent unnecessary testing for patients affected by orf disease.
Orf disease, also known as contagious pustular dermatitis or ecthyma contagiosum, is a zoonotic infection caused by the parapoxvirus, Orfviridae.
Orf plagues young sheep and goats, which are their natural host range. The virus causes a vesicular papular lesion, prominent in the lips and mouth. Orfviridae is notorious for jumping hosts to human populations after close contact with a zoonotic source that sports active lesions or even via fomites.
Orf virus is a double-stranded DNA virus. As a poxvirus, Orfviridae shares the family’s rare trait for promiscuous mammalian cell entry. They do not require a specific receptor; instead, they utilize ambiguous and commonplace components such as glycosaminoglycans for attachment and fusion into the host cell. Thus, abrasions and breaks on human skin aid in giving access to the basal keratocyte layer with an increased likelihood of infection.
After successful entry, Orfviridae starts pumping out a medley of virulence factors – all with the aim of immunomodulation. Anti-inflammatory proteins, orf “viral” Interleukins, apoptosis inhibitor, and interferon resistance, are all made before any phase of viral replication.
The replication and extranuclear synthesis of the orf virus utilizes a double envelope structure that is unique to Poxviridae. A single extracellular virus is composed of many, individually infectious virions. This feature of Orfviridae and Poxviridae, in general, makes them particularly resilient and even capable of spread via fomites.
Infection is frequently present in livestock with a prevalence as high as 15% for sheep (8% for goats) globally. As a zoonotic infection, host-switch is common to humans in many regions of the world. Orf disease is an occupational hazard, and the incidence is higher in “at-risk” professions such as farmers, veterinarians, employees of slaughterhouses, sheepherders, and butchers.
After a three to five-day incubation period, well-described cutaneous lesions develop, progressing through six stages, about a week in duration.
- Maculopapular - erythematous
- Target lesion - target shaped with a necrotic center and surrounding red halo
- Acute nodular/weepy - draining papule
- Regenerative/dry - firm crusted papule
- Papilloma - papillomatous surface
- Regressive stage - resolution with little if any scarring
Histograms of punch or shave biopsies show acanthosis and a pale vacuolated cytoplasm in affected cells. These contain eosinophilic inclusions in the keratinocyte of the upper epidermis. A spongiform degeneration in follicular structures and polymorphic infiltrate can present in the lower dermis.
History and Physical
A relevant history, especially targeting occupational hazards and recent travel with an emphasis on animal contact, is paramount. Associated orf virus skin lesions are distinctive, polymorphous, asymptomatic, and diagnosed clinically. Hand and digital involvement comprise the majority of affected sites (90%+). However, involvement of the face, scalp, and even genital regions have been described. In immunocompromised hosts, the lesion may attain a large size, colloquially known as giant orf; and can lead to some level of morbidity.
A positive exposure history and a suggestive physical exam are often enough to diagnose or virus infection in the large majority of affected individuals. However, a punch/shave biopsy is diagnostic and the gold standard.
Although not always readily available, a PCR assay for orf disease is highly sensitive in humans. It can be the non-invasive investigation of choice if the diagnosis is in doubt.
Treatment / Management
Orf disease being a zoonotic host-switch illness does not carry a particularly grim prognosis. The lesions are self-limiting, and in immunocompetent patients - symptoms would spontaneously resolve in a 4- to 6-week window.
Most cases rarely require anything more than reassurance and expectant care. However, in immunocompromised hosts, this isn’t always the case. Giant orf can grow to several centimeters, and the resultant morphology may mimic those of tumors and pyogenic granulomata.
Because Orfviridae utilizes a novel viral form of DNA dependent RNA polymerase, topical cidofovir (a potent blocker of the enzyme mentioned above) has found almost ubiquitous use as first-line antiviral therapy, along with mechanical eradication (i.e., cryotherapy, surgical excision, imiquimod, etc.) if needed.
Complications with superinfection and lymphangitis are common; therefore, clinicians often start topical antibiotics prophylactically.
Because of the highly conserved and complex antigenicity of the orf virus, vaccination is particularly effective. Many domesticated sheep and goat populations are routinely vaccinated, with varying levels of success. In humans, recurrence is rare but with diminished severity per incident (as anticipated adaptive immunity).
The two most important differential diagnoses to rule out include those that share zoonotic-exposure history to farm animals and exhibit cutaneous lesions.
Paravaccinia (Milker’s nodules) is a very similar parapoxvirus infection – just arising from cows rather than goats/sheep as in orf disease. Clinically they are indistinguishable and resolve spontaneously within six weeks or so.
Cutaneous anthrax is a bacterial infection from Bacillus anthracis. An eventual “black eschar” evolution is pathognomonic for this lesion. The more infamous pulmonary symptoms can develop in the systemic spread and can be life-threatening. Spores are transmittable from infected animals, wool, and even meat. Gram stain, culture, and even PCR are all available to aid in diagnosis.
Orf disease, being a zoonotic infection, follows a relatively benign course. It usually resolves spontaneously in 6 to 12 weeks and carries a very low rate of human to human spread. A more aggressive course with increased size (giant orf) may appear in immunocompromised hosts, and especially those with cell-mediated immune deficiency. Recurrence is possible but produces a progressively blunted infection.
Secondary bacterial infection and regional adenitis may require antibiotics.
Sporadic immunologic reactions can occur fortuitously with zoonotic infections and especially so with an immunomodulatory virus such as orf. Cases of erythema multiforme, Stevens-Johnson syndrome, and Pemphigoid bullae have all been described. These should be expected and handled carefully.
Deterrence and Patient Education
There is little doubt that educating farmers, herders, and any other at-risk occupation on proper glove-wearing and hand-washing techniques are essential. Seminars for recognizing/diagnosing infected livestock and proper vaccination protocol / inducting herd immunity is also a great starting point.
However, many skeptical populaces would bring fair resistance to any money and or effort at all allocated to preventing a self-limited infection that holds minimal morbidity for the large majority of affected individuals, and few would be so inclined to disagree.
Genuine deterrence is in funding and development towards research and understanding the zoonotic viral host-switch phenomenon, their virulence, and transmissibility. The sheer danger posed, of which our current comprehension of is so grossly inadequate, is simply terrifying.
The recent COVID-19 pandemic has no doubt served as a rude awakening to this fact. Orfviridae shares extensive genetic similarity to the now extinct smallpox, a virus claimed to have taken more lives than every infectious etiology put together; what little genetic drift or shift it would take fill that haunting niche left by variola is a true uncertainty.
Enhancing Healthcare Team Outcomes
It would be very cost-effective if the healthcare providers in rural areas are well versed in the recognition and treatment of orf disease.
Also, surveillance and infection control measures play a pivotal role in the prevention of infection.