In late 2021, veterinarians in western Santa Catarina, Brazil, began encountering an unusual and severe disease in cattle across multiple farms. Affected animals developed extensive skin lesions, fever and widespread inflammation involving organs including the kidneys, heart and liver. Many died within days.
The cases quickly caught the attention of veterinary pathologists. Systemic granulomatous disease was not new to the region, but the sudden concentration of cases was unusual. Investigators began looking for familiar causes, including hairy vetch and other known dietary triggers. None explained what they were seeing.
A 2026 study published in Comparative Clinical Pathology describes the investigation of 19 cases of systemic granulomatous disease in dairy and beef cattle in Brazil between November 2021 and June 2022.
Systemic Granulomatous Disease Outbreak: 19 Cattle Affected
The first wave of cases occurred between November 2021 and January 2022, when 14 cattle were diagnosed with the disease. Five additional cases appeared between April and June 2022.
The scale of the initial outbreak was particularly striking. During the first period, 14 of 38 cattle submitted for autopsy met the study’s case definition, representing 36.8% of the laboratory’s bovine autopsy diagnoses. During the second period, five of 47 submissions were diagnosed with the condition.
All 19 affected animals were adult cows between 2 and 6 years old. Seventeen were dairy cattle from 10 farms, while two were beef cattle from a single ranch.
Clinical signs included moderate to severe alopecia, often accompanied by pruritus, fever, lethargy and weight loss. Milk production dropped dramatically in affected dairy cows, with reductions reaching as much as 90%. Clinical signs lasted an average of 11.6 days, and many animals died within days of becoming ill.
Postmortem examinations revealed widespread granulomatous inflammation. All cattle had lesions affecting the skin and lymph nodes. The kidneys were affected in 84% of cases, while 79% had heart involvement and 52% had liver lesions. Five cattle also had evidence of hemorrhagic diathesis, with bleeding affecting tissues including the epicardium, gastrointestinal serosa and mucous membranes.
Histologically, affected tissues contained large numbers of macrophages, epithelioid macrophages and multinucleated giant cells, alongside lymphocytes and plasma cells. These findings were consistent with a systemic granulomatous inflammatory process.
The researchers noted that among 1,769 bovine autopsies performed by the laboratory between 2013 and 2022, no cases meeting the study’s definition of systemic granulomatous disease had been identified outside the outbreak period.
The timing suggested something had changed. Investigators needed to determine what the affected cattle had in common.
What Causes Systemic Granulomatous Disease in Cattle?
Systemic granulomatous disease in cattle is most commonly associated with hypersensitivity to hairy vetch (Vicia villosa). Other recognized associations include:
- Other Vicia species, including common vetch and woolly-pod vetch
- Citrus pulp
- Citrinin
- Dicyandiamide
- Di-ureido-isobutane
- Formalin-based silage additives
These became the first places investigators looked.
Researchers examined pastures and stored feed, including silage, haylage and hay, for evidence of Vicia contamination. They also reviewed feed histories with farmers and veterinarians.
Neither Vicia nor citrus pulp was identified. Neither was found in the rumen contents of autopsied cattle, and farmers reported that citrus pulp had not been used on the affected farms.
Investigators also explored infectious causes. Special staining did not identify acid-fast bacteria or fungal organisms, while ancillary virological testing was negative.
With recognized dietary causes and several infectious possibilities ruled out, investigators turned their attention to other potential exposures.
One clue emerged across the affected operations: commercial nutritional supplements.
Commercial Mineral Premixes Emerge as a Common Exposure
The affected dairy farms did not all operate the same way. Some used confinement systems with total mixed rations, while others followed semi-intensive management with pasture access and supplemental silage.
Their diets differed, but all used commercially prepared mineral premixes.
The two beef cattle provided another important piece of the puzzle. They were raised exclusively on pasture and received a high-protein mineral range tub. They had not been exposed to the specialized dietary buffer initially suspected in the dairy cases.
The researchers therefore broadened their investigation to include the commercial premixes used across both production systems.
Products were supplied by two separate companies and marketed for different purposes. Their intended functions included providing essential vitamins and microminerals and supporting feed intake, digestibility and production.
However, investigators could not identify a common raw ingredient across all the products by examining their labels. The companies also did not provide sufficient information about ingredient sourcing, manufacturing processes or recent formulation changes.
The mineral premixes remained a possible common exposure, but the investigation needed more evidence.
A November 2021 Feed Batch Provides Another Clue
The five cases diagnosed between April and June 2022 provided another important piece of information.
All affected farms during this second period were using a particular mineral premix batch manufactured in November 2021. The product was reportedly being used close to its expiration date.
The timing was notable. The initial outbreak had largely subsided by January, coinciding with the gradual depletion of the product batches available on farms and at local feed retailers. The subsequent cases appeared in operations still using the November 2021 batch.
The researchers suggested that exposure to a common product source could explain the geographic clustering of these later cases.
The initial 14 cases had been distributed across multiple counties, spanning distances of up to 90 km. In contrast, the five later cases were more geographically concentrated, with all affected farms using the product from a single retail outlet.
The investigation also connected the findings to a separate outbreak in neighboring Rio Grande do Sul. Between December 2021 and June 2022, seven additional cases of an identical condition were reported across multiple farms. Those cases were also associated with similar products distributed by the same two companies.
Together, the findings suggested that the outbreak extended beyond individual farms or a localized exposure.
What Caused the Cattle Disease Outbreak?
Despite the accumulating evidence, investigators could not identify the substance responsible for the disease.
The researchers considered whether disruptions in feed ingredient supply chains might have altered ingredient sourcing or manufacturing practices, introducing an unidentified factor into the products. However, they could not verify this possibility.
The suspected premixes and their raw ingredients were not available for analytical testing. Investigators also could not establish whether products marketed for dairy and beef operations shared raw materials or manufacturing processes.
The findings establish an epidemiologic association, not a confirmed cause. Without analytical testing or experimental reproduction of the disease, the role of the mineral premixes remains circumstantial.
Even so, the temporal and geographic patterns, the recurrence among cattle exposed to the November 2021 batch and the disappearance of recognized cases after the outbreak period support the possibility of a feed-associated exposure.
Investigating Unexplained Granulomatous Disease in Cattle
Although investigators never identified the cause, the outbreak highlights the importance of looking beyond familiar dietary exposures when investigating systemic granulomatous disease.
When cases appear across multiple farms, you may need to look for connections that aren’t immediately obvious. Commercial supplements and mineral premixes deserve consideration, particularly when affected cattle have different diets or management systems.
A thorough exposure history should include more than feed ingredients. Product suppliers, manufacturing dates, expiration dates and batch numbers may help identify connections between otherwise unrelated herds. Retaining samples of suspected products could also support subsequent laboratory investigation.
The investigators of this outbreak emphasize the need for improved feed traceability, ingredient analyses and regulatory surveillance to help identify potential causes of similar outbreaks.
The investigation connected 19 cases across multiple farms to a potential common exposure. The recurrence of disease among cattle receiving a November 2021 premix batch, combined with similar cases in neighboring Rio Grande do Sul, strengthened the suspicion of a feed-associated outbreak.
Yet the most important question remains unanswered: What was in those products that triggered the disease?
Without access to the premixes for analytical testing, researchers couldn’t determine whether the cause was a contaminant, an ingredient change or another unidentified factor. The investigation stopped short of identifying a culprit.
Still, it offered an important lesson for future outbreak investigations. When cattle develop an unusual disease across multiple operations, the most useful clues may come from looking beyond the animals themselves and tracing the products and exposures they have in common.
