3-year-old female Holstein, Bos taurusIn a herd of 190 Holstein lactating cows, 9 cows died or were euthanized at 1 to 3 weeks after the onset of the clinical signs of fever, skin lesions, nasal discharge, decrease in milk production, and weight loss. Other characteristics of the skin lesions were multiple alopecia, dry scaling on the head, neck, vulva, and udder.

Gross Description:  

The lymph nodes, spleen, adrenal glands, kidneys, and liver were enlarged. The renal cortex was discolored and had multifocal to coalescing yellowish-gray nodules on both the capsular and cut surfaces.

Histopathologic Description:

The interstitium throughout the renal cortex is replaced by multifocal to coalescing accumulations of inflammatory cells, mainly consisting of lymphocytes, macrophages, and multinucleated giant cells with moderate numbers of plasma cells. The arterioles are radially surrounded by the infiltrate. While some tubules are replaced with the infiltrate, other tubules throughout the cortex consisted of diffuse mild vacuolation and contain eosinophilic stippled proteinaceous material. In addition, some areas show tubular and glomerular degeneration and necrosis, with protein casts and cellular debris in the tubular lumen.

Granulomatous inflammation with multinucleated giant cells was also detected in the adrenal glands, pancreas, thyroid, heart, mammary glands, liver, uterus, skin, and lymph nodes. The condition in the heart, mammary glands, and skin was accompanied with eosinophilic infiltration.

Morphologic Diagnosis:  

Nephritis and diffuse, moderate to severe lymphogranulomatous inflammation.

Lab Results:  

At clinical onsetAt necropsy (9 days after the onset)
Temperature (°C)38.139.3
Heart rate (/min)8490
Respiration rate (/min)5630
White blood cells (/ml)9,100 12,300
Packed cell volume (%)3136
Plasma protein level (g/dl)9.69.6

Flow cytometry analysis of the peripheral blood showed that the numbers of CD14+ monocytes (43.9%) and CD8 lymphocytes (19.1%) were significantly higher in the affected cows than in the normal lactating cows (CD14+ monocytes, 20.3 -¦ 1.6%; CD8 lymphocytes, 10.9 -¦ 1.3%). Further, the percentages of WC1 (3.5%) and IgM+ lymphocytes (6.7%) were significantly lower in the affected cows than in the normal lactating cows (WC1+ cells, 12.7 -¦ 2.5%; IgM+ cells, 15.9 -¦ 2.6%). 

No pathogens were isolated from the carcass.


Hairy vetch toxicosis

Contributor Comment:  

The outbreaks of the disease that were detected in various counties were characterized by systemic granulomatous inflammation; in cattle that is usually found to be induced by the ingestion of hairy vetch.

The granulomatous inflammation with the presence of multinucleated giant cells and the distribution of the lesions on the tissues are characteristics that are similar to those reported in hairy vetch toxicosis,(2,4,6) citrus pulp toxicosis,(3,7) and di-ureido isobutane (DUIB) toxicosis(1,5) in cattle. Various organs including the kidneys, heart, liver, spleen, adrenal glands, thyroid, lymph nodes, skin, and mammary gland are usually affected in these diseases.

Although the cause of the disease is an enigma, histopathological features suggest that a type 4 hypersensitivity reaction (key event) may play a role in the inflammatory reaction (pathogenesis).(6) We suggest that a plant constituent absorbed by the cows acts as an antigen that evokes a type 4 hypersensitivity reaction and granulomatous response. Alternatively, lectins may act as immunostimulants that directly stimulate T lymphocytes to initiate the inflammatory cytokine response that characterizes the disease. However, in this case, the diet that was fed to cows in the farm did not contain vetch, citrus pulp, or DUIB.

JPC Diagnosis:  

Kidney: Nephritis, granulomatous, multifocal, moderate, with tubular degeneration and necrosis.

Conference Comment:  

Hairy vetch toxicosis is a diagnosis of exclusion, and the provided history of multiple lactating cows being affected is a typical presentation. Holstein and Angus cattle are most susceptible; and while the granulomatous inflammation is disseminated throughout a wide range of tissues in most cases, the lesion seems to be most frequently seen in the skin and the most severe lesions are seen in the kidney.(3,4) The heart is another common location in cattle, which distinguishes the disease from that in horses whom do not get myocardial involvement in addition to their lack of eosinophils in the granulomatous inflammation.(3)

The disease resembles a type 4 hypersensitivity reaction, although its pathogenesis is likely multifactorial as not all animals exposed develop lesions and lactating animals appear to be more susceptible.(4) The toxic principle was originally identified as prussic acid which is found in the seeds of Vicia villas Roth (hairy vetch),(3) a forage commonly cultivated as winter cover or in row crop rotations due its nitrogen-fixing ability. Other feed additives have been implicated (DUIB and citrus pulp), and this case serves as a reminder there are potentially other sources of a hapten or antigen capable of disease induction. 


1. Breukink HJ, Gruys E, Holzhauer C, Westenbroek AC: Pyrexia with dermatitis in dairy cows. Vet Rec 103: 221-222, 1978

2. Fighera RA, Barros CS: Systemic granulomatous disease in Brazilian cattle grazing pasture containing vetch (Vicia spp). Vet Hum Toxicol 46: 62-66, 2004

3. Hargis AM, Ginn PE. The integument. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Elsevier Mosby; 2012:1018.

4. Iizuka A, Haritani M, Shiono M, Sato M, Fukuda O, Hagiwara A, Miyazaki S, Tanimura N, Kimura K, Nakazawa K, Kobayashi M, Takahashi T, Saito T, Fukai K: An outbreak of systemic granulomatous disease in cows with high milk yields. J Vet Med Sci 67: 693-699, 2005

5. Johnson B, Moore J, Woods LW, Galey FD: Systemic granulomatous disease in cattle in California associated with grazing hairy vetch (Vicia villosa). J Vet Diagn Invest 4: 360-362, 1992

6. Matsukawa K, Okada M, Kubo M: Pathomorphological findings of DUIB (1,1-Diureide isobutane) intoxication cases in dairy cattle. J Coll Dairying 10: 197-204, 1983 (in Japanese with English summary)

7. Panciera RJ, Mosier DA, Ritchey JW: Hairy vetch (Vicia villosa Roth) poisoning in cattle: update and experimental induction of disease. J Vet Diagn Invest 4: 318-325, 1992

8. Saunders GK, Blodgett DJ, Hutchins TA, Prater RM, Robertson JL, Friday PA, Scarratt WK: Suspected citrus pulp toxicosis in dairy cattle. J Vet Diagn Invest 12: 269-271, 2000

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1-1. Kidney

1-2. Kidney

1-3. Kidney

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