Orf and Milker's Nodule (Parapoxvirus)

Orf and Milker's Nodule are the most common manifestations of a parapoxvirus infection. Both diseases are acquired through direct contact with infected animals, sheep for orf and cows for Milker's nodule. The most common presentation of Orf is a circumscribed solitary nodule or papule on the fingers or hands. Milker's nodule usually presents with multiple lesions. Both usually resolve within 6 weeks.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Contagious ecthyma

PATHOGENESIS	CHARACTERIZATION
Parapoxvirus	Member of the Poxviridae
Natural hosts	Sheep for orf Cows for Milker's nodule

LABORATORY TESTING
POLYMERASE CHAIN REACTION
Polymerase chain reaction for laboratory diagnosis of orf virus infections. Torfason EG, Gunadóttir S. Department of Medical Virology, Landspítali-University Hospital, PO Box 8733, IS-128 Reykjavik, Iceland.	J Clin Virol. 2002 Feb;24(1-2):79-84. Abstract quote BACKGROUND: The orf virus of sheep and goats is one of several zoonotic parapoxviruses. In the ovine/caprine host it causes contagious ecthyma (contagious pustular dermatitis, scabby mouth), but in humans it normally causes solitary or clustered orf lesions, typically on hands, arms or face. In addition to disease in the animals, the virus can be quite a nuisance as an occupational hazard in farmers and butchers. Clinical diagnosis is often possible, but laboratory diagnosis is sometimes necessary. For virus isolation, primary ovine or bovine cells, not routinely present, are needed. Serological methods exist, but electron microscopy is the most commonly used method. OBJECTIVES: To develop a reliable method for the laboratory diagnosis of orf zoonoses, without virus culture and without access to an electron microscope. STUDY DESIGN: A suitable primer pair was designed for orf polymerase chain reaction (PCR), using the Oligo software and sequence information from GenBank. Orf positive controls and specimens were kindly provided by several public health centers. Molluscum contagiosum specimens were provided by a dermatologist. HSV-1, HSV-2 and VZV positive swab specimens came from our routine diagnostic service. Asymptomatic skin specimens were obtained from sheep heads from the abattoir, and swab specimens from the heads of asymptomatic sheep. Selected amplified orf PCR positive specimens were sequenced to ensure the authenticity of the PCR products. Orf positive specimens were sent to another laboratory for electron microscopy. RESULTS AND CONCLUSIONS: A robust PCR was developed, with very small inter-run variation. All specificity demands were met, and the sensitivity seems to be good or excellent. All negative specificity controls from cell cultures and non-orf viruses were negative. Twenty-two (95.7%) of 23 scab or swab specimens with suspected orf etiology were orf PCR positive. Five of eight skin specimens from sheep heads from the abattoir were positive, and all 11 swab specimens from asymptomatic sheep were negative. Electron microscopy demonstrated orf-like particles in orf-PCR positive specimens. This PCR seems to be suitable as a diagnostic test for orf in humans, but asymptomatic virus shedding in sheep or goats may complicate veterinary applications of the assay.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Ecthyma contagiosum (orf)--report of a human case from the United Arab Emirates and review of the literature. Al-Salam S, Nowotny N, Sohail MR, Kolodziejek J, Berger TG. Department of Pathology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.	J Cutan Pathol. 2008 Jun;35(6):603-7. Abstract quote BACKGROUND: Ecthyma contagiosum (orf) is caused by an epitheliotropic parapox virus. It is a zoonosis usually transmitted to humans from affected sheep or goat through direct contact or contaminated fomites. METHODS: We report a 36-year-old patient with multiple skin lesions on his left hand, first observed 5 days before admission followed by red streaks on the forearm and an erythema on the upper arm 1 day prior to admission. The patient reported that he was working on a sheep farm. RESULTS: Histopathologic examination showed evidence of a viral infection. Subsequent transmission electron microscopy showed typical parapox virus particles, predominantly in the scaled-off layers of degenerated keratinocytes and monocytes. The results were verified and specified by two newly established polymerase chain reaction (PCR) assays and subsequent sequencing of the amplicons: one broadly reacting 'general parapox virus PCR', and one assay which allows--following sequencing--discrimination between individual orf virus strains. CONCLUSION: Despite the multiplicity of the lesions, there was a significant improvement after 2 weeks of treatment. Sequencing showed the uniqueness of this virus compared with previously published strains from other countries.
VARIANTS
Orf involving the head, neck, or perineum	J Am Acad Dermatol 1999;40:815-817

HISTOLOGICAL TYPES

CHARACTERIZATION

General-Skin

Zoned appearance with parakeratosis, papillomatosis, and acanthosis with viral cytopathic changes of cytoplasmic and nuclear vacuolation and cytoplasmic inclusion bodies present within the epidermis

Inclusions (Henderson-Patterson bodies) usually occur in the upper epidermis and are deeply eosinophilic homogenous bodies measuring 3-5 um surrounded by a pale halo-displace nuclei to side

Keratohyalin has a clumped appearance

Cytoplasmic ballooning with vesicles

Necrosis of the epidermis and adnexal epithelium may be present

VARIANTS

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Cowpox and smallpox	Poxviruses
Herpes simplex
Molluscum contagiosum	Henderson-Patterson bodies do not displace the nuclei

TREATMENT
IMIQUIMOD

Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008