AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

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. The disease is a zoonosis endemic to and common in cattle worldwide. Human disease is 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).

The course is usually self-limited, running from 14-72 days, with infrequent systemic symptoms and little or no scarring.

Pathophysiology

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 (MNV), also called paravaccinia virus. It 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 rather than rectangular 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 MNV. A recent study shows a very close DNA homology between papular stomatitis of Finnish reindeer and MNV 1.

MNV can be propagated in tissue culture. It can be distinguished from orf virus by DNA hybridization, though not by ultrastructural studies.

Frequency

United States

Milker's nodule is an occupational disease, mainly affecting milkers and farm workers caring for dairy cattle, as well as stockyard workers, slaughterhouse workers, and veterinary surgeons. Because immunity seems to be conferred by infection, lesions arise in persons new to these occupations or in those who have sporadic contact, such as pet owners. 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.

International

The occurrence internationally is similar to that in the United States.

Mortality/Morbidity

• Lymphangitis, lymphadenitis, and fever, which may last from a few days to a few weeks, may occur.
• No reports exist describing milker's nodule infection during pregnancy; however, 2 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.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients typically have no previous history of milker's nodule.
• Patients 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.)
• The incubation period may be as brief as 4 days or as long as several weeks.
• Lesions are often solitary, and they may be pruritic or painful.
• Some authorities divide the clinical course into 6 stages, each lasting roughly 1 week.
• • 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)
  • Dry, crusted nodular
  • Papillomatous
  • Regressive

Physical

• Lesions are usually found on the fingers, the hands, and the forearms.
• • Usually, only a few or even a single lesion is present. Many lesions are occasionally distributed in a larger area, such as a burn site.
  • Classic lesions are 0.5-1.5 cm in diameter, firm, movable, dome-shaped papules or nodules.
  • They 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.
  • They often present with a vascular appearance resembling pyogenic granuloma.
  • Milker's nodule is on average smaller than orf lesions, but it 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.)
• A focused physical examination should be performed. The following findings have been described:
• • Lymphangitis
  • Regional lymphadenopathy
  • Fever
  • Diarrhea
  • Abdominal cramping

Causes

• Milker's nodules are caused by a DNA virus of the genus Parapoxvirus.
• The disease is a zoonosis endemic to and common in cattle worldwide.
• Human disease is 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 MNV (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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Tuberculosis
Tularemia
Anthrax

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• 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.
• Viral tissue culture of MNV 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.
  • MNV can be distinguished from orf virus by DNA hybridization to the relatively less conserved terminal regions.
• Bacterial culture: Culture and sensitivity can direct therapy if suspicion exists of bacterial superinfection.

Other Tests

• Electron microscopy
• • This study 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.

Procedures

• Skin biopsy
• • A shave biopsy may be performed for hematoxylin and eosin (H&E) tissue histology.
  • A biopsy plus electrocautery of the base handily removes the lesion.

Histologic Findings

H&E stain on paraffin-fixed sections shows a papulonodular morphology with the following findings:

In the epidermis, irregular, mild-to-moderate acanthosis with some pronounced deep extensions of thin rete ridges is observed. Other reported findings include ballooning; spongiform appearance of vacuolated cells with wispy eosinophilic cytoplasm, prominent cell membranes, and pyknotic nuclei; variable epidermal necrosis; vesicle formation; eosinophilic intracytoplasmic inclusions; and possibly intranuclear inclusions. The intense dermal infiltrate may cause an interface appearance and spill over into the epidermis, causing a pustule.

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.

The histopathologic findings in milker's nodule are similar to that in orf lesions.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Most lesions resolve by 5-7 weeks without treatment.
• Some reports of the related orf virus infection advocate prophylactic antibiotics to prevent local superinfection.
• Direct local care at avoiding secondary infection.

Surgical Care

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.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

No medications are known to improve the course of the disease, which is usually benign and limited. Symptomatic treatment can be given.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention:

• 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.

Complications:

• Various reports caution against the possibility of bacterial superinfection, though 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. One case reported spontaneous resolution of exanthem at 1 week.

Prognosis:

• The prognosis is excellent in this self-limited disease that results in little or no scarring.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• No specific medicolegal pitfalls aside from the general considerations about misdiagnosis relate to milker's nodule. Because milker's nodule is relatively benign, precautions against overtreatment may be more applicable.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Br J Med. Cowpox and paravaccinia. Br Med J. Nov 11 1967;4(575):308-9. [Medline].
• Czerny CP, Waldmann R, Scheubeck T. Identification of three distinct antigenic sites in parapoxviruses. Arch Virol. 1997;142(4):807-21. [Medline].
• Davis CM, Musil G, Trochet JA. Electron microscopy for the rapid diagnosis of pseudocowpox and Milker''snodule. Am J Vet Res. Aug 1970;31(8):1497-503. [Medline].
• Davis CM, Musil G. Milker''s nodule. A clinical and electron microscopic report. Arch Dermatol. Mar 1970;101(3):305-11. [Medline].
• Gassmann U, Wyler R, Wittek R. Analysis of parapoxvirus genomes. Arch Virol. 1985;83(1-2):17-31. [Medline].
• Groves RW, Wilson-Jones E, MacDonald DM. Human orf and milkers'' nodule: a clinicopathologic study. J Am Acad Dermatol. Oct 1991;25(4):706-11. [Medline].
• Kouskoukis CE. Milker''s nodules: differential diagnosis. J Dermatol Surg Oncol. Jun 1982;8(6):441, 510. [Medline].
• Kuokkanen K, Launis J, Morttinen A. Erythema nodosum and erythema multiforme associated with milker''s nodules. Acta Derm Venereol. 1976;56(1):69-72. [Medline].
• Lauder IM, Martin B, Martin WB, Nagington J. Milkers'' nodule virus infection and its resemblance to orf. Vet Rec. Jun 25 1966;78(26):926. [Medline].
• Leavell UW Jr, Phillips IA. Milker''s nodules. Pathogenesis, tissue culture, electron microscopy, and calf inoculation. Arch Dermatol. Oct 1975;111(10):1307-11. [Medline].
• Neale EJ, Calvert HT. Milkers'' nodules. Some observations on true and false cowpox apropos anoutbreak in a closed community. Br J Dermatol. Jun 1967;79(6):318-24. [Medline].
• Rossi CR, Kiesel GK, Jong MH. A paravaccinia virus isolated from cattle. Cornell Vet. Jan 1977;67(1):72-80. [Medline].
• Schuler G, Hackl JM. [Multiple atypical milker''s nodes in scalded areas]. Hautarzt. Jul 1982;33(7):388-90. [Medline].
• Schuler G, Honigsmann H, Wolff K. The syndrome of milker''s nodules in burn injury: evidence for indirectviral transmission. J Am Acad Dermatol. Mar 1982;6(3):334-9. [Medline].
• Shelley WB, Shelley ED. Surgical treatment of farmyard pox. Orf, milker''s nodules, bovine papularstomatitis pox. Cutis. Feb 1983;31(2):191-2. [Medline].
• Taieb A, Guillot M, Carlotti D, Maleville J. Orf and pregnancy. Int J Dermatol. Jan-Feb 1988;27(1):31-3. [Medline].
• Tikkanen MK, McInnes CJ, Mercer AA, et al. Recent isolates of parapoxvirus of Finnish reindeer (Rangifer tarandus tarandus) are closely related to bovine pseudocowpox virus. J Gen Virol. Jun 2004;85(Pt 6):1413-8. [Medline]. [Full Text].
• Watson WJ, Meyer MW, Madison DL. Orf virus infection in pregnancy. S D J Med. Dec 1993;46(12):423-4. [Medline].

Article Last Updated: Feb 28, 2007