Milker's nodule, first described in the literature in 1799, is a localized, cutaneous, and mostly benign infection caused by a DNA virus of the genus Parapoxvirus.[1] See the image below.
View Image
Milker’s nodules. Courtesy of Professor Raimo Suhonen and DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/viral/s/milkers3.jpg).
The disease is a zoonosis endemic to and common in cattle worldwide. Infections in cattle are also known as bovine papular stomatitis. Human disease is contracted through direct transmission (ie, handling of infected cow teats, calf muzzles, or other sites of active bovine infection) or through indirect transmission (ie, handling of virally contaminated objects).
The course of milker's nodule is usually self-limited, running from 14-72 days, with infrequent systemic symptoms and little or no scarring.
Viral replication produces intracytoplasmic inclusions and cytopathic changes in epidermal keratinocytes along with epidermal and dermal reactive changes.
The etiologic organism is the milker's nodule virus, also called paravaccinia virus. The milker's nodule virus is a 140 X 310-nm, double-stranded DNA poxvirus, a member of the cylindrical subgroup. Paravaccinia is resistant to desiccation, cold, and heat up to 56°C and can persist in the environment. Under electron microscopy, it is cylindrical with convex ends, and it is covered with a uniform diagonal criss-cross pattern of parallel ropelike structures. On electron microscopy, the DNA core is surrounded by a protein coat, which is wrapped by 2 narrow parallel coats. Mature virus particles are located within keratin fibrils in the stratum corneum.
Some studies suggest that bovine papular stomatitis virus, which may clinically cause an identical lesion in humans, is an organism distinct from milker's nodule virus. A recent study shows a very close DNA homology between papular stomatitis of Finnish reindeer and milker's nodule virus type 1.[2, 3]
Milker's nodule virus can be propagated in tissue culture. It can be distinguished from orf virus by DNA hybridization, though not by ultrastructural studies.[4]
Milker's nodules are caused by a double-stranded DNA virus of the genus Parapoxvirus. Milker's nodule is a zoonosis endemic to and common in cattle worldwide.
Human milker's nodules are contracted through direct transmission (ie, handling of infected cow teats, calf muzzles, other sites of active bovine infection) or through indirect transmission (ie, handling of virally contaminated objects).
Evidence suggests that milker's nodule virus (traditionally associated with disease contracted from papulonodular lesions on cow teats) and bovine papular stomatitis virus (traditionally isolated from erosive lesions on calf muzzles) may be different though closely related viruses. It seems that they may both cause milker's nodule in humans. In fact, each may cause both types of lesions in cattle.
Milker's nodule is an occupational disease, mainly affecting milkers and farm workers caring for dairy cattle, as well as stockyard workers, butchers, and veterinarians.[5] Because infection generally results in immunity, lesions are most commonly seen in persons new to these occupations or in those who have sporadic contact, such as new milkers, pet owners, and veterinary students.[6] The disease is commonly known among agricultural workers to be benign; therefore, it is rarely reported to doctors or other medical personnel in that setting. Sporadic cases and occasional epidemics occur.
The prognosis is excellent in milker’s nodules, a self-limited disease that results in little or no scarring.
Lymphangitis, lymphadenitis, and fever, which may last from a few days to a few weeks, may occur in milker's nodules patients.
No reports exist describing milker's nodule infection during pregnancy; however, two reports exist of orf virus, a related Parapoxvirus, being contracted in the third trimester (33rd and 34th wk), resulting in maternal lesions but normal-term infants.[7]
Patients typically have no previous history of milker's nodule. Patients with milker's nodules have had recent contact with infected cows, calves, or viral fomites. (Milker's nodules are contracted from cows; orf nodules are contracted from sheep or goats.)[8] The incubation period for milker's nodules may be as brief as 4 days or as long as several weeks.
Lesions of milker's nodules are often solitary, and they may be pruritic or painful. Some authorities divide the clinical course of milker's nodules into six stages, each lasting roughly 1 week, as follows:
Erythematous maculopapular
Target (a papulovesicular lesion with a red center, white ring, and red periphery)
Acute weeping nodule (characterized by loss of epidermis over the center)
Lesions of milker's nodules are usually found on the fingers, the hands, and the forearms and are nearly identical to those seen in orf.[9] Usually, only a few or even a single lesion is present. Occasionally, many lesions are distributed in a larger area, such as a burn site.[10, 11] See the image below.
View Image
Milker’s nodules. Courtesy of Professor Raimo Suhonen and DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/viral/s/milkers3.jpg).
Classic milker's nodules lesions are 0.5-1.5 cm in diameter, firm, movable, dome-shaped papules or nodules. Milker's nodules may be red or purplish red in color, or they may have a targetlike appearance. Central ulceration or crust may occur. Lesions typically have a grayish coating in the target stage and a verrucous surface in the papillomatous stage.
Milker's nodules often present with a vascular appearance resembling pyogenic granuloma. Milker's nodules are on average smaller than orf lesions, but they may not be distinguishable on a clinical basis. Variant lesions may include vesicles, scaly patches, and erosions. (The patient's history guides the differential diagnosis in these cases.) Local lymphadenopathy may be present.
A focused physical examination should be performed. The following findings have been described in patients with milker's nodules:
Various reports caution against the possibility of bacterial superinfection in milker's nodules, although the authors' literature search did not find any reported cases.
Reports exist of generalized exanthem, erythema multiforme, or bullous erythema multiforme following infection with milker's nodule.[12] One case reported spontaneous resolution of exanthem at 1 week.
The diagnosis of milker’s nodule primarily rests on a history of contact with infected animal and presence of a typical clinic lesion. Although no laboratory tests are diagnostic of milker's nodule, the clinician may wish to perform tests to help rule out other entities on the list of differential diagnoses. Specific tests would be suggested by the clinical presentation of each patient as well as the expected time until results from definitive tests can be returned. Note the following:
Viral culture in milker's nodules: Viral tissue culture of milker's nodule virus on bovine or human cells may be available. This procedure takes several weeks, and tissue culture differences between orf and milker's nodule are subtle.
DNA hybridization: Milker's nodule virus can be distinguished from orf virus by DNA hybridization to the relatively less conserved terminal regions.
Bacterial culture in milker's nodules: Culture and sensitivity can direct therapy if suspicion exists of bacterial superinfection.
Polymerase chain reaction (PCR) in milker's nodules: The “pan-pox” assay is a recently developed PCR assay that can be used for screening and diagnosis of human and animal poxvirus infections. Many laboratories worldwide have access to the technology used in this assay.[13] PCR can differentiate milker’s nodule and orf.[14]
Electron microscopy in milker's nodules[15, 16] can be rapidly performed on either crust or biopsy material without refrigeration or special preservative solutions. Particles may stay infectious for extended periods. Electron microscopy can be useful in demonstrating virus particles; however, it cannot distinguish between milker's nodule, orf, and bovine papular stomatitis.
The histologic appearance of milker’s nodule varies with the stage of the disease and is similar to orf. H&E stain of early lesions shows ballooning of keratinocytes, spongiform appearance of vacuolated cells with wispy eosinophilic cytoplasm, vesicle formation, prominent cell membranes, and pyknotic nuclei. There may be eosinophilic intracytoplasmic viral inclusions and rarely intranuclear inclusions.[17] Later in the course of disease, milker’s nodules demonstrate irregular acanthosis with pronounced deep extensions of thin rete ridges. Epidermal necrosis is variable.[18]
In the dermis, a dense infiltrate of lymphocytes and histiocytes, a marked increase in dermal capillaries, and epidermal and dermal edema are observed. Other authors report a mixed infiltrate also including eosinophils, neutrophils, and plasma cells.
Most milker's nodules resolve by 5-7 weeks without treatment. Some reports of the related orf virus infection advocate prophylactic antibiotics to prevent local superinfection. Antiviral medications are not effective.[6] Direct local care for milker's nodules at avoiding secondary infection.
Milker's nodule is typically small, and the natural history is self-limited with spontaneous healing; however, superficial shave excision or curettage in conjunction with cautery of the base will remove lesions. The rationale for this technique, reported in the literature by some authors, is to decrease the amount of virion, which may promote more rapid healing and perhaps prevent lymphadenitis and progression of the lesion to a larger size.[19]
Isolate clinically infected animals from contact with humans who have not had previous exposure. Animals have typical lesions of circinate or horseshoe-shaped crusted erosions around the moist surfaces of the mouth and the nose or papules and erosions around the teats. They may have alopecia of lesions on hair-bearing surfaces. Lesions can be recurrent or chronic in cows.
No medications are usually administered to improve the course of milker's nodules, which is usually benign and limited. Symptomatic treatment can be given. However, one case report from Croatia describes a woman with milker’s nodules and lymphangiitis of the right arm. Treatment with amoxicillin and clavulanic acid at 2 g for 10 days completely resolved the lymphangiitis.[20]
Justin J Finch, MD, FAAD, Assistant Professor, Director of Clinical Photography, Director of the Center for Cutaneous Laser Surgery, Department of Dermatology, University of Connecticut Health Center
Disclosure: Nothing to disclose.
Coauthor(s)
Steven Brett Sloan, MD, Associate Professor, Department of Dermatology, University of Connecticut School of Medicine; Residency Site Director, Connecticut Veterans Affairs Healthcare System; Assistant Clinical Professor, Yale University School of Medicine
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Academy of Dermatology;UpToDate;Medical Review Institute of America<br/>Received income in an amount equal to or greater than $250 from: American Academy of Dermatology; Medical Review Institute of America.
Specialty Editors
Michael J Wells, MD, FAAD, Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology
Disclosure: Nothing to disclose.
Paul Krusinski, MD, Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine
Disclosure: Nothing to disclose.
Chief Editor
William D James, MD, Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine
Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.
Additional Contributors
Franklin Flowers, MD, Department of Dermatology, Professor Emeritus Affiliate Associate Professor of Pathology, University of Florida College of Medicine
Disclosure: Nothing to disclose.
Acknowledgements
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Gary W. Cole, MD, and Lily L. Tinkle, MD, PhD, to the development and writing of this article.
Hautaniemi M, Ueda N, Tuimala J, Mercer AA, Lahdenperä J, McInnes CJ. The genome of pseudocowpoxvirus: comparison of a reindeer isolate and a reference strain. J Gen Virol. 2010 Jun. 91:1560-76.
Wolff, Klaus, Richard Johnson, and Thomas Fitzpatrick. Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology. 6th Ed. New York, NY: McGraw-Hill Professional; 2009. 768.
){kind=link}