Discussion
There is currently no universal treatment for equine sarcoids. The ultimate goal in treatment is to remove all tumour cells. It is imperative to take into account all factors when choosing a suitable regimen for each case, however finances and compliance of the client and horse may become the most influential factors.
A variety of topical chemotherapy agents are used such as acyclovir and 5% fluorouracil. However, one study suggested that the former drug has little benefit (Haspeslagh et al. 2017), but the latter has produced good results as an adjunct to surgery or cryotherapy (Knottenbelt and Kelly 2000).
AW5-LUDES cream is a compounded medication available for veterinary surgeon application only from Equine Medical Solutions as a special product, produced and prescribed to an individual horse as per the United Kingdom licensing Cascade (GOV.UK, 2022). It was previously referred to as AW3 or AW4 in older preparations and has been widely used in this country. A protocol is created for each case, determined by the appearance/type of sarcoid, location and response to previous treatments (Knottenbelt and Walker 1994). The cream contains 5-fluorouracil, thiouracil, heavy metal salts and steroid, and is produced in several different concentrations. Initially a single application of AW3-LUDES cream was reported to be successful in 80% of cases when 50,000 lesions were studied in 100 horses (Knottenbelt and Walker 1994). However, a later study of AW4-LUDES cream reported only 35% success rate when it was used as the primary treatment in periocular sarcoid cases (Knottenbelt and Kelly 2000). It is worth noting, however, that periocular sarcoids are characteristically different and potentially more difficult to treat than sarcoids in other areas of the body.
Localised pain and swelling are expected from 24 hours after application of AW5-LUDES cream, and horses may be dull and reluctant to ambulate for a period of 4-6 days. These signs are usually resolved by oral phenylbutazone treatment. The tumour mass is noted to blacken and develop a well-defined border with the surrounding healthy tissue. Histological findings support preferential penetration of the abnormal tissue, although it is suggested that stronger preparations may have deeper and less specific effects. Scarring has been recorded, usually causing solely cosmetic issues, and delayed wound healing can present in more mobile areas (Knottenbelt and Walker, 1994). Collateral damage to adjacent healthy tissues due to runoff or misapplication, and poor results due to non-compliance of application may also occur. Prior to application, it is important to consider the underlying anatomy and, therefore, potential complications. These may include haemorrhage, neuropathies and associated paralysis, necrosis of healthy tissues and associated infection, or in more severe cases, loss of sight (Knottenbelt and Kelly, 2000). Extensive eyelid necrosis and loss of the underlying globe has been reported in one case, however the horse had undergone previous home treatments unbeknown to the treating veterinarian (Knottenbelt and Kelly, 2000). The use of AW5-LUDES cream is now contraindicated around the eye or overlying the facial nerve (Knottenbelt 2019), and alternative treatment methods are recommended where complications encountered are likely to be severe and life changing. The authors have also encountered a horse that developed septic arthritis of a metacarpophalangeal joint following the application of AW5-LUDES to a sarcoid located on the dorsal fetlock; the treatment had resulted in widespread necrosis of the skin, subcutaneous and dorsal joint capsule (unpublished observation).
Following the presentation of this horse, an internal review was conducted which found 1595 similar lesions treated in the 3 years prior, of which this was the only case of evisceration. Since use of the cream started, the manufacturer has had no other evisceration cases reported (Knottenbelt, personal communication, 2021).
Evisceration of the abdominal contents can be a fatal event in horses and has been recorded following castration (Moll et al. 1995), due to acute abdominal dehiscence of a ventral laparotomy incision (Hann et al. 2022) or subsequent to penetrating abdominal wounds (Netto et al. 2006). Prognosis for survival decreases with increasing time, deteriorating condition of the horse, length of intestine eviscerated, intestinal damage or contamination, and the requirement for intestinal resection anastomosis (Van der Velden 1988; Thomas et al. 1998). Survival rates of young horses undergoing surgical repair for evisceration post castration is reported to vary from 36.4% (Hutchins and Rawlings 1972) to 87.5% (Hunt and Boles 1989), although rapid surgical intervention was instigated in those cases with better outcomes. Following dehiscence of the linea alba post laparotomy, secondary closure is usually performed rather than mesh placement due to infection in the tissues. This technique however requires suture placement 5cm from the edge of the wound (Tulleners et al. 1983; Freeman et al, 2002), which due to the extent of the tissue devitalisation in this case was not possible
It is possible that the lesion being treated in this horse was a different neoplasm. Most suspected sarcoids are not confirmed histologically prior to treatment as tissue biopsy can be contraindicated (Ragland et al. 1970). Similar-looking lesions can include fibrosarcoma, fibroma or neurofibroma (Knottenbelt and Kelly 2000). It is worth noting that the response of these other tumours to AW5-LUDES cream is unknown. Verrucous or fibroblastic sarcoids and similar appearing neoplasms seem to be most commonly contained within the epidermis and dermis (Murray et al. 1978). Around the eye however, deeper invasion into the subcutis and musculature is a frequent finding and is associated with a negative prognosis as the muscles become distorted and weakened (Knottenbelt and Kelly 2000). It is possible that sarcoids in other locations may invade in a similar way, but unfortunately samples of the tissue were not submitted for histopathology in this case. More information is required on the invasive nature of sarcoids in different locations and hallmarks of this kind of tumour behaviour.
This case report describes a serious complication following treatment with AW5-LUDES cream. It is worth noting that there is minimal recently published evidence surrounding the use of AW5-LUDES cream in a variety of locations. The evidence surrounding periocular sarcoids should be interpreted with caution, although it may guide decision making where sarcoids are suspected to have invaded more extensively. Referral of the horse was carried out in a timely manner with minimal damage to the intestines and did not contribute to the decision to euthanase the horse. Severe necrosis of apparently previously healthy surrounding tissues was the precluding factor for difficulty in defect closure and guarded prognosis.