Owners’ perception of the efficacy of Newmarket bloodroot ointment in treating equine sarcoids

Abstract

A retrospective questionnaire-based survey was used to determine the perceived efficacy of Newmarket bloodroot ointment in treating equine sarcoids. In 49 horses with 74 sarcoids, 64 sarcoids responded either completely (n = 49) or partially (n = 15) while 10 did not respond or worsened. Sarcoids < 2 cm responded better to treatment (P < 0.001) than did larger sarcoids.

Introduction

Sarcoids are cutaneous, fibroblastic tumors that denote the most common skin tumor in horses worldwide affecting all members of the Equidae family (1). Based on appearance, sarcoids have been classified into 6 main groups consisting of occult, verrucose, nodular, fibroblastic, mixed, and malignant types (2). Sarcoids are locally invasive and, although they do not metastasize, their location and size can pose considerable problems for the horse and its use. Their variability in location, size, type, and activity represents a therapeutic challenge for veterinarians and owners and no treatment option has been universally effective (1). Secondary ulceration, infection, and pain associated with some treatments can cause further discomfort for the horse (1,3).

The choice of treatment for sarcoids depends on not only the type, size, and location but also on economic considerations, whether previous treatments have been attempted, and owner compliance (1,4). Options include surgical excision, banding, laser therapy, cryotherapy, radiotherapy, hyperthermia, chemotherapy, immunotherapy, vaccination, and various herbal treatments (1,5). Topical therapies include chemotherapy agents such as 5-fluorouracil (5-FU) and AW3/4-LUDES, acyclovir (an antiviral drug), imiquimod, (an immune-modulator), and bloodroot (1).

Due to the inconsistent outcomes, new treatment options are continuously proposed but scientific evidence supporting their use is often lacking. Bloodroot (Sanguinaria canadensis) is an herbaceous extract from North America that displays cytotoxic and immune-modulating effects due to alkaloids, primarily sanguinarine, contained in its sap. Its use to treat skin growths has been reported since the mid-19th century (6) and its anti-proliferative and apoptotic effects have been increasingly reported in a range of studies investigating cancer cell treatment in human medicine (7–11).

In veterinary medicine, current formulations include XXTERRA (Larson Labs, Fort Collins, Colorado, USA), Newmarket bloodroot ointment (Newmarket Premixes, Catley Cross, Halstead, UK) and Animex (NIES, Las Vegas, Nevada, USA). Anecdotal evidence and case reports are supportive of a possible beneficial role of bloodroot in the treatment of sarcoids. A fibroblastic sarcoid on the limb was reported to slough and heal without complications following application of Animex, and its use was considered suitable for small sarcoids that can be bandaged easily (12). Only 1 small controlled study has been carried out investigating bloodroot’s efficacy for the treatment of 15 sarcoids with XXTERRA reporting a 93% success rate with minimal side effects (13).

To the authors’ knowledge, there is no further objective information on its efficacy and the circumstances in which it may be most appropriate to prescribe such a preparation. Therefore, a survey directed at horse owners who had used Newmarket bloodroot ointment to treat sarcoids was conducted to investigate the hypothesis that the perceived efficacy of Newmarket bloodroot ointment in treating equine sarcoids was at least equal to reported efficacy of other topical ointments. It was also hypothesized that the perceived efficacy of Bloodroot ointment would be independent of sarcoid location, size, and previous treatments.

Materials and methods

The study was designed as a retrospective questionnaire-based survey. Newmarket bloodroot ointment can only be obtained by an owner after consultation with a veterinarian who has examined the horse in question. Owners’ addresses were obtained through Newmarket Premixes, the seller of Newmarket bloodroot ointment and the questionnaire was sent by mail with a stamped-addressed envelope. The information requested included signalment of the horse, sarcoid location, size and number, number of treatments and treatment duration, side-effects encountered as well as previous treatments and their effects.

Sarcoids were considered individually and on a per horse basis. Sarcoids were grouped based on owners’ descriptions according to size as ≤ 2.0 cm, 2.1 to 4.0 cm and > 4 cm. Location was recorded as head, neck, trunk, inguinal/sheath, and legs. Date of first treatment, duration of treatment, and any previous treatments with different modalities were also noted. Information regarding details of treatment such as daily frequency and intervals between treatment sessions were requested. Treatment duration was recorded by calculating total number of days treated and grouped as follows: ≤ 21 d; 22 to 42 d; > 42 d. Response to treatment was recorded as complete (complete resolution of the lesion), partial (decrease in size but lesion still visible), no response (no change in size), and worsened (increase in size) after treatment. Recurrence after completion of the treatment and use of other products were also recorded. Type of sarcoids was not included as it was felt that this information might not have been reliable if based on owners’ description.

Statistical analysis

Data were analyzed with SPSS version 20 (Stata Corp, College Station, Texas, USA) using Fischer’s exact test to compare characteristics of horse and sarcoids between outcome groups.

Results

One hundred and forty horse owners throughout the UK who had previously been prescribed Newmarket bloodroot ointment by their veterinarian for treatment of sarcoids were contacted between May and September 2012 and 57 owners with 58 horses responded to the survey. Nine horses were excluded due to bloodroot having been prescribed and not used or used for a different condition leaving 49 horses with 125 sarcoids to be included in the study. Because the sarcoids in the same area always had identical descriptions, they were counted as one to avoid misleading data, leaving 74 sarcoids for analysis. Treatments were carried out between July 1999 to May 2012 and the study population comprised 7 ponies, 2 donkeys, and 40 horses consisting of a range of breeds including Thoroughbreds (n = 13), Arabians (n = 2), Sports horses (n = 18), and Cobs (n = 7). The group consisted of 26 geldings, 22 mares, and 1 stallion with a variety of uses including dressage (n = 4), eventing (n = 3), general riding (n = 13), hacking (n = 7), a combination of uses (n = 21), and not stated (n = 1). Exact age was difficult to ascertain from the questionnaires as it was not always clear whether the age stated was the current age or age at the time of treatment. Location distribution of sarcoids in the sample was as follows: head (n = 13), neck (n = 5), trunk (n = 38), inguinal/sheath (n = 4), and legs (n = 14).

Small sarcoids were most commonly represented (n = 50), followed by medium (n = 15) and large sarcoids (n = 4), while 5 were of unknown size. Most treatments lasted for ≤ 21 d (n = 46) or 21 to 42 d (n = 15), while treatments > 42 d were uncommon (n = 4); duration was not recorded for 9 sarcoids. Most sarcoids responded (n = 64; 86.5%) either completely (n = 49; 66.2%) or partially (n = 15; 20.3%), while 10 did not respond or worsened (n = 10; 13.5%).

There was no significant difference between response to treatment and age, breed, gender, or location but there was a significant difference between size of sarcoid and response to treatment: 98% (n = 49) of small sarcoids resolved completely, which was significantly more showing complete resolution compared to all other sizes (P < 0.001). Of the 64 sarcoids with recorded duration of treatment, 41 (64.1%) responded completely to treatment, with 26 (63.4%) having been treated for 1 to 21 d, 11 (26.8%) for 22 to 42 d and 4 (9.8%) for > 42 d. Of the sarcoids that partially responded to treatment, 16 (94.1%) were treated for 1 to 21 d; a higher proportion (P = 0.068) compared to the complete response group. Most of the sarcoids responding completely to therapy were < 2.0 cm (84.4%), whereas the larger sarcoids did not respond as well with 3/5 of the non-responding sarcoids being sized > 4.0 cm.

The average follow-up time was 3.5 y and out of 66 sarcoids that showed a response, only 6 (9%) recurred or regrew in that time. A large proportion (75.5%) of the sarcoids that showed a complete response to treatment had not been treated previously but there was no significant association between previous treatments and response to treatment.

Statistical analysis was also performed on a per horse basis rather than per sarcoid yielding similar results. No significant difference was noted between response to treatment and age, gender and location. A significant difference (P = 0.012) was noted between size of sarcoid and response to treatment.

Adverse effects were reported in 16 horses and consisted mainly of hair loss and soreness. Hair loss was most commonly associated with the head and neck area, whereas soreness was often noted on the trunk and legs.

Discussion

The present study evaluated owners’ perception of the efficacy of Newmarket bloodroot ointment in treating equine sarcoids. There are few options for topical treatment of sarcoids that offer easy application for the owner along with minimal side effects, a good response and low recurrence rate. The results of this survey have shown a promising owners’ perception of bloodroot efficacy with 89.2% sarcoids responding and 66.2% resolving completely. This is comparable to Pettersson’s study in 2008 which yielded a response rate of 93% with XXTERRA treatment, a different formulation of the bloodroot (13).

The perceived response rate to Newmarket bloodroot ointment in this study is similar to that reported with other topical therapies. Imiquimod showed a complete regression rate of 60% in 15 sarcoids (14) and acyclovir treatment achieved complete regression in 68% of 47 treated sarcoids (15). AW-LUDES has a reported > 70% response rate overall (16) but response might be location-dependent as only 35% of 159 periorbital sarcoids regressed completely (16). The product contains cytotoxic 5-fluorouracil and thiouracil requiring veterinary application and adverse effects such as severe sloughing of skin and pain are commonly reported.

Smaller sarcoids seemed to respond better to treatment than medium or larger lesions. Although exact details of sarcoid volume and depth were not available, these results could suggest that penetration of the bloodroot ointment into the tumor could be a limiting factor for treatment success. Animex, another formulation of bloodroot, was also most efficacious in treating small sarcoids that are easily bandaged suggesting that size influenced response to treatment (12). A similar conclusion was drawn in a study on acyclovir in which sarcoid size was found to be inversely proportional to the success of the treatment (15).

The impact of previous treatments on the response to subsequent bloodroot application also seemed to play a role in this study. Although exact details of previous treatments in regards to date, type, and response were not always provided by the owners, results suggested that a high percentage of sarcoids that responded completely to therapy had not been previously treated. This illustrates that sarcoids previously treated without success possibly provide a greater challenge to treatment with bloodroot. Most of the sarcoids (2/3) that worsened after treatment had received previous unsuccessful treatment. This may be due to latent tumor cells and bovine papilloma virus in and around the sarcoid being activated by unsuccessful therapy, resulting in the tumor proliferating with increased aggression subsequently (17–19). A similar finding has been reported with AW-LUDES in which response to treatment dramatically decreased if sarcoids had been previously treated without success (20).

In the study herein, duration of treatment was extremely variable among patients, and exact details of treatment protocols were not always provided. Treatment duration, therefore, was categorized as total number of days that bloodroot was applied, but this does not reflect the exact volume of ointment applied or the frequency of bloodroot used per day, which is a limitation of the study. Therefore drawing conclusions from the effect of the duration of treatment on response is difficult. Nevertheless, the results suggest that the group of sarcoids that did not respond to the bloodroot were treated for longer periods than the other groups. The 3 sarcoids that worsened with treatment were treated for shorter periods of 1 to 21 d but this likely occurred because treatment was discontinued soon after worsening was apparent.

A higher proportion of sarcoids was treated for a shorter duration of 1 to 21 d in the partial response group compared to the sarcoids that responded completely to treatment. The reasons for this are not apparent and it could be possible that partially resolved sarcoids would have resolved completely had owners persevered with treatment for longer periods.

Side effects after bloodroot ointment application were infrequently reported and consisted mainly of soreness. Localized pain and inflammation have been reported previously with bloodroot treatment (13) and similar side effects have been reported with AW-LUDES treatment (2). As the side effects in this study were reported by owners, it is unknown if they were limited to the sarcoid area or extended to the normal skin around the tumor. The impact of these side effects on the response to treatment must be considered, as 2 owners of horses that responded partially to treatment reported that the pain/soreness limited their application of the treatment.

A recurrence rate of 9% of the completely resolved sarcoids over 3.5 y is encouraging. Low recurrence rates have been reported for topical imiquimod (of the tumors that resolved completely none recurred after 20 wk) and acyclovir treatment (recurrence of completely resolved sarcoids unreported after 3 y) (14,15). However, it is difficult to make a comparison between treatments as imiquimod does not have a substantial follow-up time and follow-ups for acyclovir were unreported but not actively requested.

Newmarket bloodroot ointment is a mixture of alkaloid extracts from the rhizome of bloodroot and zinc salts. It is made up of 40% w/w 1:3 extract (25% methyl alcohol/75% water) of the dried root of Sanguinaria canadensis, 48% w/w emulsifying ointment, 10% zinc chloride, plus preservatives. It cannot be excluded that any of the other ingredients, particularly zinc chloride, may have partially or predominately contributed to the healing process. A comparative study investigating each individual component would be necessary. It is important to note that the diagnosis was made based on appearance by the veterinarian dispensing the product and some of the treated skin lesions may not have been sarcoids. Finally, judgment of the efficacy of the product was based on owners’ perception rather than objective measurements or inspection by a veterinarian.

In summary, the results of the study suggest that Newmarket bloodroot ointment could be an efficacious first instance topical treatment for small sarcoids with few side-effects. A prospective clinical trial with consistent treatment protocol and accurate measurements of response on a large number of confirmed sarcoids of known types is needed to fully evaluate the potential of this treatment option. CVJ