Orf virus infection of human keratinocytes and dermal fibroblasts: Limited virus detection and interference with intercellular adhesion molecule-1 up-regulation.

Orf virus (Parapoxvirus ovis, ORFV) is a dermatotropic virus causing pustular dermatitis in small ruminants and humans. We analysed isolated human primary keratinocytes (KC) and dermal fibroblasts (FB) for cell death and virus replication by infection with a patient-derived ORFV isolate. ORFV infection was associated with rapid induction of cell death in KC allowing for considerable virus removal. Upon infection with ORFV, KC and FB harboured intracytoplasmic ORFV and showed viral protein presence; however, missing virus spread indicated an abortive infection. Upon ORFV exposure, KC but not FB secreted the pro-inflammatory cytokine interleukin (IL)-6. ORFV infection enhanced the frequency of KC expressing intercellular adhesion molecule (ICAM)-1 which was independent of IL-6. Interestingly, ORFV inhibited ICAM-1 up-regulation on infected but not on non-infected KC. Even interferon-γ, a potent inducer of ICAM-1, up-regulated ICAM-1 only on non-infected KC. Transfer of ORFV-free supernatant from infected to non-infected KC induced ICAM-1 on non-infected KC pointing to the involvement of soluble mediator(s). Similarly as in KC, in FB interference with ICAM-1 up-regulation by ORFV infection was also observed. In conclusion, we shed light on epidermal and dermal defense mechanisms to ORFV infection and point to a novel ICAM-1-related immune evasion mechanism of ORFV in human skin.

Human orf complicated by epidermolysis bullosa acquisita.

Orf is a DNA parapoxvirus transmitted to humans by contact with infected goats and sheep. Many complications have been reported after orf infection, including erythema multiforme. A few cases of autoimmune bullous dermatosis complicating orf disease have been reported to date. They are usually characterized by tense blister eruptions with or without mucosal involvement; linear deposition of C3, IgG and/or IgA along the basement membrane; and negativity of indirect immunofluorescence analysis and enzyme-linked immunosorbent assay (ELISA) (performed in four of 11 reported cases). These analyses have targeted antigens of bullous pemphigoid, mucous membrane pemphigoid or epidermolysis bullosa acquisita, except one case of mucosal pemphigoid with antilaminin-332 antibodies. We describe the case of a patient who presented with an ulceration on his finger 10 days after direct contact with a lamb during Eid al-Adha. Four weeks later he developed a severe tense blistering eruption associated with mucous membrane erosions. Indirect immunofluorescence analysis using the patient's serum revealed circulating antibasement membrane IgG that bound the dermal side of salt-split skin. ELISA was positive for recombinant immunodominant NC1 domain of type VII collagen. We finally diagnosed epidermolysis bullosa acquisita complicating probable human orf infection.

Erythema multiforme after orf virus infection.

The case of a 6-year-old boy with multiple, target-shaped lesions and a crusted nodule on his right index finger is presented. Based on clinical findings and the patient's recent contact with sheep and goats, a diagnosis of orf disease associated with erythema multiforme was suspected. Microscopy studies confirmed the presence of parapoxvirus in the primary lesion. Orf-induced erythema multiforme is a rare complication of orf in children, possibly related to the presence of orf virus DNA in erythema multiforme lesions.

Multiple finger nodules and an erythematous rash - a case study.

CASE STUDY: A previously well male, 18 years of age, from a rural community, presented with three painful, itchy nodules on the fingers of his left hand, which had been present for 1 week. He had been prescribed amoxicillin clavulanate but presented again when there was no improvement after 4 days of taking antibiotics. Examination revealed three erythematous and umbilicated nodules without any halo, but with a central depression with exudate (Figure 1a). No specific treatment was instituted at this visit. One week later the patient re-presented with new erythematous lesions on the palms and dorsum of his hands. The original three lesions had improved and were drier than previously (Figure 1b, c). The new lesions disappeared after 2 weeks and the original lesions after 4 weeks, without any other treatment.

'Orf on the ear', in a patient with Guillain-Barré Syndrome.

We report a case of orf on an ear in a patient admitted to hospital following the onset of Guillain-Barré syndrome. While the underlying causes of Guillain-Barré syndrome are not completely understood, immune stimulation appears to play a key role in pathogenesis. Any association between orf infection and Guillain-Barré syndrome has not been documented. A 22-year-old male sheep farmer, who was previously fit and well, presented to his local hospital with a 2-day history of distal upper and lower limb paraesthesia and weakness. He was transferred to a tertiary hospital where the diagnosis of Guillain-Barré syndrome was confirmed. History revealed that he had experienced a mild respiratory illness 3 weeks prior to presentation and an inflamed nodular lesion over his left ear, which had appeared 2 weeks prior to admission. Differential diagnoses of orf, atypical mycobacterial infection, subcutaneous mycosis and a squamous cell carcinoma were considered. Histopathology from a biopsy of the lesion was consistent with orf, which was confirmed by polymerase chain reaction testing. This case is of interest for two reasons: orf has not been described in association with Guillain-Barré syndrome, and orf on the ear is uncommon.

Lamb pays lip service: two cases of ecthyma contagiosum (orf).

Ecthyma contagiosum (orf) is caused by a parapox virus, which results in ulcerative stomatitis of mainly sheep and goats. The disease may be transmitted to humans through direct contact. Complications are rare in healthy individuals, who rarely report the disease. Two married, recreational sheep farmers, were bitten on their index fingers by an affected lamb. While the husband made an uneventful recovery after oral flucloxacillin, his wife was admitted to hospital with necrosis of her finger, cellulitis and lymphangitis requiring intravenous clindamycin. She subsequently developed a generalized maculo-papular rash, which was initially thought to be an adverse drug reaction, but, on hindsight, may have been erythema multiforme associated with orf. Orf is a common zoonosis, rarely reported in general practice. The disease is usually self-limiting and resolves in 6-8 weeks, but complications may occur. The diagnosis should be considered in at-risk occupational and religious groups.

Corynebacterium freneyi Bacterial Septicemia Secondary to Contagious Ecthyma in a Wild Muskox (Ovibos moschatus).

A wild muskox (Ovibos moschatus) with dermatitis typical of contagious ecthyma had secondary bacterial septicemia with Corynebacterium freneyi that included laminitis, hepatitis, and suppurative encephalitis. This case supports the association between orf virus infection and fatal secondary infections, which may have contributed to population declines on Victoria Island, Canada.

[Expanding papillomatous nodule on forearm with acute lymphangitis. Case of diagnosis]. / Papillomatös wachsender Knoten am Unterarm mit akuter Lymphangitis. Diagnosequiz.

Ecthyma contagiosum (orf) is a dermatosis commonly seen in those in contact with sheep. It is caused by Parapoxvirus ovis (orf virus), an oval epitheliotropic DNA parapox virus. The skin disease develops in stages starting as a macule or papule, becoming nodular, and then regressing. Diagnosis is based on history and histology, as well as identifying the virus through cell culture or specified polymerase chain reaction (PCR). The treatment of this self-limited disease is usually symptomatic.

Orf-induced immunobullous disease: A distinct autoimmune blistering disorder.

BACKGROUND: Many complications have been reported after orf infection, including lymphadenopathy, secondary bacterial infection, and erythema multiforme. Rare associations with papulovesicular eruptions, including a bullous pemphigoid-like eruption, have also been described. OBJECTIVES: Our purpose was to clinically, histologically, and immunologically characterize two cases of orf-induced blistering disease, and to determine whether this condition represented a novel disease entity distinct from known immunobullous diseases. METHODS: Two patients were clinically described and skin biopsy specimens were collected for routine histology, direct immunofluorescence studies, and polymerase chain reaction analysis to detect orf viral DNA. Patients' sera were assessed for autoantibodies by indirect immunofluorescence studies using normal-appearing human salt-split skin, by Western blot analysis using keratinocyte extracts, dermal extracts, and recombinant type VII collagen, and immunoprecipitation studies of extracts from biosynthetically radiolabeled human keratinocytes. RESULTS: Two distinctive cases of severe, diffuse blistering eruptions after orf infection are described. In one patient, orf virus DNA was detected in the inciting orf lesion, but not in blistered skin, ruling out disseminated orf infection as a cause of the blisters. In both cases, histology revealed subepidermal blisters with mixed inflammatory cell infiltrates containing neutrophils and eosinophils, direct immunofluorescence microscopy studies demonstrated IgG and C3 deposited at the dermoepidermal junctions of perilesional skin, and indirect immunofluorescence studies demonstrated circulating antibasement membrane IgG that bound the dermal side of salt-split skin. Extensive immunoblot and immunoprecipitation studies failed to reveal a consistent, identifiable autoantigen. LIMITATIONS: We describe only two cases. The autoantigen recognized by circulating autoantibodies was not identified. CONCLUSIONS: Orf-induced immunobullous disease is a unique disease entity that is clinically and immunologically distinct from bullous pemphigoid, epidermolysis bullosa acquisita, and other known immunobullous conditions.

Progressive ORF virus infection in a patient with lymphoma: successful treatment using imiquimod.

Orf virus is a parapoxvirus that infects small ruminants worldwide. We present the case report of a 73-year-old woman with non-Hodgkins lymphoma who developed progressive orf virus lesions that were unresponsive to surgical debridement and to cidofovir therapy. The patient's orf virus infection was successfully treated with topical imiquimod despite progression of her malignancy.

[A case of Orf disease complicated by erythema multiforme]. / Echtyma contagiosum compliqué d'érythème polymorphe : à propos d'un cas.

Ecthyma contagiosum, or Orf, is a specific infection of small ruminants accidentally reaching humans. Few cases have been reported in the literature to date. We report here a case of ecthyma contagiosum occurred in a 9-year-old girl after contact with a flock of ecthyma sheep. This Orf was then complicated by superinfection and then by erythema multiforme. Orf is often underdiagnosed, probably because of small ruminant breeders' knowledge of this disease and its benignity in humans. It is caused by a very resistant Parapoxvirus in the environment. The diagnosis is clinical and anamnestic. Orf is therefore a benign pathology, the course of which is spontaneously favorable outside any specific treatment. However, it is important to prevent certain complications such as superinfections with appropriate local care. Other complications cannot be prevented and require appropriate care.

Acral manifestations of viral infections.

Viruses are considered intracellular obligates with a nucleic acid RNA or DNA. They have the ability to encode proteins involved in viral replication and production of the protective coat within the host cells but require host cell ribosomes and mitochondria for translation. The members of the families Herpesviridae, Poxviridae, Papovaviridae, and Picornaviridae are the most commonly known agents for cutaneous viral diseases, but other virus families, such as Adenoviridae, Togaviridae, Parvoviridae, Paramyxoviridae, Flaviviridae, and Hepadnaviridae, can also infect the skin. Herpetic whitlow should be considered under the title of special viral infections of the acral region, where surgical incision is not recommended; along with verruca plantaris with its resistance to treatment and the search for a new group of treatments, including human papillomavirus vaccines; HIV with maculopapular eruptions and palmoplantar desquamation; orf and milker's nodule with its nodular lesions; papular-purpuric gloves and socks syndrome with its typical clinical presentation; necrolytic acral erythema with its relationship with zinc; and hand, foot, and mouth disease with its characteristics of causing infection with its strains, with high risk for complication.

Two giant orf lesions in a heart/lung transplant patient.

Orf is an infectious ulcerative stomatitis of sheep and goats. The responsible pathogen, parapoxvirus, may be transmitted to humans. Orf lesions are often atypical in immunocompromised individuals. The present report describes two very large exophytic lesions in a 31-year-old transplant patient receiving oral tacrolimus, mycophenolate mofetil and prednisone. Early surgical excision was successful, with no relapse after 14 months.

Suppression of influenza virus infection by the orf virus isolated in Taiwan.

Orf virus (ORFV), a member of parapoxvirus, is an enveloped virus with genome of double-stranded DNA. ORFV causes contagious pustular dermatitis or contagious ecthyma in sheep and goats worldwide. In general, detection of viral DNA and observing ORFV virion in tissues of afflicted animals are two methods commonly used for diagnosis of orf infection; however, isolation of the ORFV in cell culture using virus-containing tissue as inoculum is known to be difficult. In this work, the ORFV (Hoping strain) isolated in central Taiwan was successfully grown in cell culture. We further examined the biochemical characteristic of our isolate, including viral genotyping, viral mRNA and protein expression. By electron microscopy, one unique form of viral particle from ORFV infected cellular lysate was demonstrated in the negative-stained field. Moreover, immunomodulating and anti-influenza virus properties of this ORFV were investigated. ORFV stimulated human monocytes (THP-1) secreting proinflammatory cytokines IL-8 and TNF-α. And, pre-treatment of ORFV-infected cell medium prevents A549 cells from subsequent type A influenza virus (IAV) infection. Similarly, mice infected with ORFV via both intramuscular and subcutaneous routes at two days prior to IAV infection significantly decreased the replication of IAV. In summary, the results of a current study indicated our Hoping strain harbors the immune modulator property; with such a bio-adjuvanticity, we further proved that pre-exposure of ORFV protects animals from subsequent IAV infection.

Erysipeloid infection in a sheep farmer with coexisting orf.

Erysipeloid is a rarely reported zoonotic infection caused by Erysipelothrix rhusiopathiae. We report a case of coexisting erysipeloid and orf infections in a sheep farmer, an association not previously recorded to our knowledge.

Udder orf infection and its role in ovine clinical mastitis caused by Pasteurella haemolytica.

During an experimental study of ovine subclinical mastitis caused by coagulase-negative staphylococci, an outbreak of contagious ecthyma occurred among ewes unvaccinated against parapox virus. The same group of ewes developed a high rate (43.7%) of clinical mastitis caused by Pasteurella haemolytica. The rate of clinical mastitis among ewes vaccinated against parapox virus was very low (3.7%) suggesting that the presence of orf in the unvaccinated ewes was contributing to the high rate of clinical mastitis. An examination of the iron, sodium, potassium and albumin concentration of milk collected from 16 unvaccinated and nine randomly selected vaccinated ewes before experimental infection with coagulase-negative staphylococci or their uninfected control mammary glands indicated significant differences in the iron (p < 0.0001) and sodium (p = 0.01) concentration. Increased iron concentration in the milk may have assisted in the development of udder infection caused by P. haemolytica as iron is easily utilised by this bacterium.

Ehrlichia (Cytoecetes) phagocytophila predisposes to severe contagious ecthyma (Orf ) in lambs.

Eight lambs experimentally infected with Ehrlichia (Cytoecetes) phagocytophila 7 days before exposure to orf virus were compared with control lambs infected with orf virus alone. The dually infected animals differed from the controls in showing skin lesions of greater severity, prolonged viral shedding, and lower antibody titres. Infection with E. phagocytophila had no significant effect on virus-specific lymphocyte proliferation. Such proliferation was detected in the peripheral blood of all lambs as early as 7 days after exposure to orf virus.