Although the clinical disease presentation and the visceral pox lesions in cattle caused by lumpy skin disease virus (LSDV) are strongly indicative of lumpy skin disease (LSD), a definitive diagnosis requires laboratory confirmation. Milder forms of LSD can be confused with many different agents or diseases. Allergic reactions and physical trauma to the skin caused by insect and/or tick bites as well as urticaria and photosensitisation also need to be ruled out. These include differentials of several agents that cause skin lesions including viral agents such as parapoxviruses, bovine papular stomatitis virus and pseudocowpox, orthopoxviruses such as vaccinia and cowpox and bovine herpesvirus 2 causing pseudo lumpy skin disease. Since rinderpest has been eradicated (Roeder 2011), it is no longer a differential. Adverse reactions to LSDV vaccines can also occur (so-called Neethling disease) and is characterized by the appearance of skin nodules which are smaller than those caused by virulent LSDV field strain. Other skin diseases in cattle caused by bacterial agents such as hypoderma bovis infection, cutaneous tuberculosis, dermatophilosis and Corynebacterium pseudotuberculosis are also differentials. Additional differentials comprise demodicosis or mange caused by Demodex bovis as well as other skin lesions caused by parasites such as onchocercosis caused by Onchocerca ochengi or besnoitiosis caused by the protozoa Besnoitia besnoiti.
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