Equine sarcoidosis or equine idiopathic granulomatous disease is a rare disorder with various clinical manifestations and unpredictable progression (Reijerkerk et al., 2009; Sargent et al., 2007).
Disease onset can be insidious or rapid. Localised, partially generalised and generalised forms of the disease have been described in horses (Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013), and the disease has also been reported in humans and cattle (Reijerkerk et al., 2009).
Skin lesions characterised by scaling and crusting combined with variable alopecia are the most common clinical signs of the disease. Infrequently, skin nodules or tumour-like masses can occur (referred to as the nodular form of sarcoidosis). Dermatological pathologies are rarely accompanied by pruritus. In the localised form, the lesions are restricted to one area, while the partially generalised form of the disease is characterised by multifocal skin lesions with or without lymphadenopathy. The generalised manifestation of equine sarcoidosis is further distinguished by multisystemic granulomatous inflammation. Clinical signs are unspecific and vary depending on the organ systems affected (Reijerkerk et al., 2009; Schwarz, 2022; Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013; Spiegel et al., 2006).
Pathology
Multiple hypotheses on the aetiopathology of sarcoidosis have been established in veterinary and human medical literature, yet the exact cause of this disease complex remains unknown (Reijerkerk et al., 2009; Ungprasert et al., 2019).
Different risk factors for the development of human sarcoidosis have been identified, suggesting that various infectious or non-infectious aetiological agents might trigger an abnormal host immune response driven by Th1 lymphocytes, which ultimately leads to granuloma formation (Ungprasert et al., 2019). Suspected aetiologic antigens discussed in the veterinary literature include equine herpes virus 2, Borrelia burgdorferi, Mycobacteria spp and hairy vetch (Vicia villosa) toxicosis (Nolte et al., 2020; Oliveira-Filho et al., 2012; Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013; Spiegel et al., 2006).
Multiple hypotheses on the aetiopathology of sarcoidosis have been established in veterinary and human medical literature, yet the exact cause of this disease complex remains unknown
Genetic risk factors seem to play a role in human medicine (Ungprasert et al., 2019), and sex and breed predilections have been suggested in equine sarcoidosis, but solid conclusions have yet to be drawn due to low case numbers or contradictory findings (Schwarz, 2022; Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013). Horses of all ages can be affected, although the disease seems rare in animals under three years of age (Schwarz, 2022; Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013).
Clinical signs
Localised sarcoidosis
In a study reviewing 22 cases of equine sarcoidosis, a localised form was most commonly diagnosed (68.2 percent). One lower leg is typically affected, but in some horses, multiple (two to three legs) can show typical dermatological abnormalities (Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013; Schwarz, 2022). Theoretically, other areas can be affected by localised sarcoidosis; a case with skin lesions in the flank area has been reported (Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013).
Besides the typical crusting and scaling lesions, affected areas may be warm, oedematous and sensitive to touch (Figure 1). In severe cases, lameness may occur (Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013; Spiegel et al., 2006). In many cases, equine sarcoidosis affects the coronary band and subsequently the growth of the hoof horn, resulting in ring formation. This makes the disease a differential diagnosis for coronary band disorders.
Laminitis has been reported in 2 of 17 cases of localised sarcoidosis, most likely as a consequence of coronary band involvement (Schwarz, 2022) (Figure 2).
Affected horses are usually systemically healthy, show no other clinical signs and perform well. However, bloodwork may reveal evidence of chronic inflammation, such as hyperproteinaemia and anaemia, and some cases are accompanied by hypercalcaemia (Schwarz, 2022; Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013).
Partially generalised and generalised sarcoidosis
The partially generalised form of equine sarcoidosis is characterised by multifocal skin lesions with or without peripheral lymphadenopathy (Sargent et al., 2007; Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013).
The generalised form is characterised by granuloma formation in various organ systems. The most commonly affected organs besides the skin include the lungs, lymph nodes and gastrointestinal tract. Granuloma formation has also been reported in the liver, spleen, kidneys, bones and central nervous system (Sargent et al., 2007). While the clinical signs depend on the organ systems affected, weight loss, muscle wasting, anorexia, exercise intolerance and a fluctuating fever are common symptoms of the generalised disease.
Similar to the localised form, bloodwork may indicate chronic inflammation (Sargent et al., 2007). However, there are currently no specific blood markers that point to a diagnosis of sarcoidosis.
Prognosis for survival in both forms of sarcoidosis is poor due to the frequently slow progression of the disease despite treatment, which ultimately results in euthanasia (Reijerkerk et al., 2009; Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013). An increase in affected organs seems to correlate with poorer outcomes (Sargent et al., 2007).
How do I diagnose equine sarcoidosis?
A tentative diagnosis of equine sarcoidosis can be reached based on patient history, clinical appearance and the exclusion of other differential diagnoses. Depending on the form of sarcoidosis, common diseases such as dermatophytosis and dermatophilosis can show a similar clinical picture, thus need to be considered (Reijerkerk et al., 2009; Sargent et al., 2007).
A tentative diagnosis of equine sarcoidosis can be reached based on patient history, clinical appearance and the exclusion of other differential diagnoses
Definitive diagnosis of sarcoidosis is established by histological examination of skin biopsies. Typical histopathological skin lesions include multifocal to diffuse lymphohistiocytic granulomatous infiltration with multinucleated giant cells. Vasculitis may be present in some cases (Reijerkerk et al., 2009; Sargent et al., 2007; Schwarz, 2022).
If the partially generalised or generalised form of equine sarcoidosis is suspected, you should extend the diagnostic work-up to include a complete blood count, serum chemistry profile and medical imaging, the choice of which will depend on the suspected localisation of granulomas. Biopsies of peripheral lymph nodes and, if possible and necessary, ultrasound-guided biopsies of suspected granulomatous lesions of internal organs may be indicated to corroborate the diagnosis (Sargent et al., 2007).
In severe cases of the localised form, radiographs can be taken with regard to laminitis (Schwarz, 2022).
How do I treat equine sarcoidosis?
Treatment of sarcoidosis is based on the suppression of the exaggerated immune response and prevention of further granuloma formation (Reijerkerk et al., 2009; Ungprasert et al., 2019). First-line treatment in human medicine consists of long-term systemic corticosteroids. Doses are adapted depending on the severity of the disease, but a high initial dose tapered over a minimum of a year is generally recommended.
The side-effect profile of long-term corticosteroid medication is complex, and response to therapy may be insufficient. In this case, second-line corticosteroid-sparing agents are indicated, of which methotrexate is most commonly applied. This folate antagonist is also approved for autoimmune diseases, such as rheumatoid arthritis and psoriasis, and the response rate in human sarcoidosis ranges up to 55 percent and more if combined with corticosteroids (Gerke, 2020; Ungprasert et al., 2019). Alternatives include azathioprine, leflunomide and mycophenolate.
Third-line agents are cytokine-specific monoclonal antibodies such as infliximab and adalimumab.
For equine sarcoidosis, the recommended therapy is […] an initially high dose of corticosteroids, with subsequent long-term treatment of tapered doses
For equine sarcoidosis, the recommended therapy is also an initially high dose of corticosteroids, with subsequent long-term treatment of tapered doses. Classically, oral prednisolone is prescribed, but varying doses have been suggested in the literature: 1 to 4mg/kg should be considered for initial treatment lasting at least several weeks. Alternatively, injectable dexamethasone can be used at an initial dose of 0.04 to 0.08mg/kg intramuscularly, but daily administration by a veterinarian may be time-consuming and costly compared to the oral administration of prednisolone (Reed et al., 2017; Reijerkerk et al., 2009; Schwarz, 2022; Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013). Single cases of localised sarcoidosis have been treated with methotrexate with variable response (Schwarz, 2022).
Similar to human medicine, the dose and duration of corticosteroid therapy should be adapted to each patient. The severity of the disease, side effects of the medication that metabolic comorbidities may exacerbate/exaggerate and owner compliance should contribute to the individual treatment plan.
Topical agents are not generally recommended to prevent unnecessary manipulation of the fragile and painful skin (Reijerkerk et al., 2009; Sargent et al., 2007; Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013).
Additional treatment strategies are pentoxifylline and omega-3 fatty acids based on the antifibrotic and anti-inflammatory properties (Schwarz, 2022).
Prognosis
Response to therapy in localised sarcoidosis seems to be highly variable, and spontaneous remission has been reported. Nevertheless, prognosis for the skin lesions tends to be guarded to poor, although prognosis for survival is generally good. The prognosis for generalised and partially generalised cases is, however, considered poor (Reijerkerk et al., 2009; Schwarz, 2022; Sloet van Oldruitenborgh‐Oosterbaan and Grinwis, 2013).
Final thoughts
Generally speaking, larger case studies and research on the pathogenesis of equine sarcoidosis are required to optimise treatment protocols and improve outcomes for affected horses.
