Vet Clin Equine 18 (2002) 355-369
Jeremy D. Hubert, BVSc, MRCVS, MSa,*,
Ralph E. Beadle, DVM, PhDa, Gary Norwood, DVMb
School of Veterinary Medicine. Department of Veterinary Clinical Sciences. Equine Health Studies Program, Louisiana State University. Baton Rouge. LA 70803.
USA b Backstretch Equine Surgery and Medicine. 539 Bonnabel BOlllevard. Metairie. LA 70005. USA
Equine anhidrosis, dry coat, and nonsweating are all terms used to describe the disease in horses characterized by the inability to sweat effectively in response to appropriate stimuli. Although the epidemiology and clinical signs of the disease have largely been elucidated, anhidrosis is still widely prevalent, and methods of prevention and treatment are being sought. Initial reports date back to the 1920s, when Thoroughbreds from Australia developed this condition after being transported to Malaysia . Later it was reported that such horses improved once they were removed from the tropical environment and maintained 10 to 30 days in a cooler and drier climate. . This article reviews the epidemiology, proposed pathophysiologic mechanisms, clinical features, diagnosis, and treatment.
Epidemiology of anhidrosis
The disease commonly occurs in countries with hot, humid climates including the American Gulf Coast states. The precise prevalence of the disease is unknown; however, it has been estimated that up to 20°/c) of horses in the Miami area of Florida may be affected [3,4]. Anhidrosis was originally assumed to be associated with an acclimatization stress , but a survey conducted in Florida in 1982 showed that more native horses were affected than imported horses . Horses involved in strenuous activities were originally reported to be the most prone to develop anhidrosis , but this does not correlate with a study where only 7 out of 24 affected horses were performance horses . Another study found that the frequency is higher in horses in training and lower in adolescent horses . There is no coat color, age, sex, or breed predilection. A link between anhidrosis and high protein diets has been reported , but this finding was not corroborated in another study . Nonpregnant mares were reported in one study to have a statistically significant higher incidence of anhidrosis .
Clinical signs of anhidrosis
Horses with normal thermoregulatory abilities will be able to reduce their body temperature to within normal limits in approximately 30 minutes after exercise, and the inability to cool out to normal temperatures within this time is indicative that a horse may be suffering from anhidrosis. The predominant' sign of impending anhidrosis is usually tachypnea . Affected horses will have increased respiratory rates at rest, while body temperature and pulse rate are variably increased when compared with those of control horses under identical conditions [2-5]. Horses showing evidence of respiratory distress will have respiratory rates between 60 and 120 breaths per minute . Partially anhidrotic horses will breath rapidly for extended periods of time after being thermally challenged . Horses with acute onset anhidrosis may demonstrate a partial or complete absence of sweating when exposed to appropriate stimuli. A decrease in the rate of sweating also indicates the possibility of anhidrosis. The sweating rate will, however, depend on the intensity of exercise, duration of exercise, and ambient temperature . Horses with long-standing anhidrosis may reveal dry, flaky skin, alopecia, lethargy, anorexia, and a decreased water intake. Areas on the body that may retain the ability to sweat include those under the mane, in the saddle . and halter areas, and in the axillary, inguinal, and perineal regions [2-5].
Thermoregulation in horses
Thermoregulation is attained by two main mechanisms in terrestrial mammals; namely panting and sweating . Heat dispersed via the respiratory tract in exercising horses may account for 15% to 25% of total heat loss, whereas evaporation of sweat accounts for up to 65% of their heat loss . In this regard, it has been calculated that evaporation of 1 liter of sweat can dissipate the amount of heat generated in I to 2 minutes of high-intensity exercise by horses .
During exercise there is an initial rise in temperature, which may be advantageous for performance because it increases the rate of aerobic energy production, thereby minimizing the necessity for anaerobic energy production . As work effort increases, heat production in skeletal muscle can increase more than 50 times [I 0]. This heat is derived from the conver. SiOll of chemical energy into mechanical work. Only 25°/r, of the metabolic energy is converted to mechanical work, with the remainder generating body heat, which must be dissipated during or after exercise . A number of factors can influence the rate at which horses lose heat by the evaporation of sweat. First, the rate at which heat can be dissipated by evaporation depends upon the rate of air movement across the skin and the water vapor pressure difference between the skin and the environment . Thus, when the ambient humidity is high, there is a reduction in the rate at which sweat is evaporated. Second, horses have a large body volume-to skin surface ratio, which results in a relatively small surface area from which evaporation can occur . Finally, it has been shown in humans that there is competition for cardiac output between the skin and muscle during exercise whereby maintenance of cardiovascular function takes precedence over thermoregulatory function . This results in less blood flow to the skin, and ultimately a slower rate of heat loss than would occur if skin blood flow were maintained during exercise . It has recently been shown that nonspecific inhibition of nitric oxide synthase reduces the sweating response and increases the body temperature of exercising horses . These findings suggest that nitric oxide may modulate the sweating response to exercise in horses. It was not determined whether this modulation was acting centrally or peripherally.
Histology of equine sweat glands
Histological evaluation of the horse sweat gland has been performed .They are classified as apocrine, and in normal horses are tubular, with thesecretory portion being coiled and _mbedded within the dermis. A straightand unbranched duct opens into a hair follicle adjacent to the skin surface(Fig. 1).Evans et al  described the secretory tubules of equine sweat glands ashaving two layers: an inner layer of cuboidal secretory epithelial cells, andan enveloping layer of myoepithelium. These myoepithelial cells are restingon a basal lamina  and surrounded by a layer of connective tissue and an outer sheath of fibrocytes . Within this fibrocytic sheath are small blood vessels and nerve fibers . Histochemical staining reveals the presence ofmonoamine oxidase in the nerve fibers suggesting adrenergic fiber innervation . The secretory cells have cytoplasmic protusions that extend intothe lumen of the duct  suggesting an apocrine mode of secretion. Theapocrine mechanism of secretion is further supported by the observationthat the secretory cells do not contain glycogen .
cyclase and subsequent phosphorylation of cellular proteins.
Sweat gland perfusion
An adequate vascular supply is important for umoral stimulation ofsweating. Electron microscopic examinations of blood vessels from anhidrotic horses demonstrated these structures to be normal . Therefore,a structural vascular impairment does not appear to be a contributing factor. However, a dynamic impaired dermal perfusion can occur during intense exercise when fluid loss and maintenance of cardiovascular function results in less blood flow to the skin .
The ultrastructure of sweat glands from anhidrotic horses housed in hothumid conditions has been reported to be abnormal . Reported abnormalities included thickened basal lamina, evidence of poor myoepithelialcontraction, fibrocytes with dilated endoplasmic reticulum and vacuolation,and thickened connective tissues. The secretory cells had a marked reductionof vesicles with increased numbers of mitochondria and less rough endoplasmic reticulum. The luminal microvilli were often absent, and the cells hadbecome flattened; in some cases, secretory granules were replaced by myoepithelium. Cellular debris was often present within the lumen of the duct,and in some cases the lumen was fully obstructed [I 4J. Duct obstruction hasbeen speculated to be a response to prolonged stress and failure of secretion,, and may provide a mechanism of defense. against microbes invading the process than the uncoupling mechanism of desensitization , and may be part of the normal mechanism of receptor turnover within cells.
Downregulation is an actual decrease in the total number of receptors in the cellular pool of receptors or a lower receptor density . This is a slow process, and is a long-term mechanism that may involve altered receptor protein synthesis or altered receptor protein degradation. Downregulation has been shown to be accompanied by a decrease in _-adrenergic receptor messenger RNA concentrations .
Thyroid hormones are known to have modulating effects on adrenergic receptors . Tissues are more responsive to _-adrenergic catecholamines when thyroid hormone concentrations are elevated, and conversely, when hypothyroidism occurs, they are less responsive . In himans, symptoms of hyperthyroidism suggest increased sympathetic drive or increased plasma concentrations of catecholamines . It has also been shown that there is a decreased density of _-adrenergic receptors in hypothyroid animals, decreased receptor coupling to the adenylate cyclase system, and ultimately receptor function is minimized . The role played by thyroid hormones in the pathophysiology of anhidrosis is equivocal. In horses, some of the secondary clinical signs of decreased thyroid function are similar to those of anhidrosis ; however, it has been reported that thyroidectomized horses appear to sweat normally . It has also been reported that there is no statistical difference in T 3 and T 4 plasma concentrations between normal and anhidrotic horses . However, therapy with iodinated casein, a thyroid hormone precursor, has some reports of success . This latter finding allows postulation that there may be a role played by thyroid hormones.
The effect of electrolyte losses incurred during exercise and long-term exposure to a hot humid climate is often thought to be involved in anhidrosis: one common therapeutic approach is oral electrolyte supplementation . Even though significant quantities of electrolytes, including potassium and calcium, are lost in sweat , statistically significant electrolyte abnormalities have not been reported for horse with anhidrosis.
Experimental depletion of extracellular and presumably intracellular Ca ++ in vitro decreased the sweat response, indicating that sweat secretion may be dependent upon concentrations of intracellular calcium . However, hypocalcemia has not been reported as a cause of anhidrosis. Low potassium intake in ponies resulted in a more rapid onset of fatigue during treadmill exercise and decreased sweat production . Although these ponies were hypokalemic, studies have shown that anhidrotic horses have , normal serum potassium concentrations . However, as potassium is maiply intracellular, total body potassium may be depleted, but undetected, and this would help to explain anecdotal reports that some anhidrotic horses respond to oral potassium supplementation.
Diagnosis of anhidrosis
Diagnosis of anhidrosis can be tentatively made based on clinical signs and performance. It should be emphasized that, based on the development of increased respiratory effort and hyperthermia, anhidrotic horses are commonly presented to veterinary practitioners for diagnosis and treatment of respiratory disease. However, a semiquantitative test to evaluate sweating by induction of the sweat response, using dilute concentrations of epinephrine injected intradermally, has been developed, and will provide a more definitive diagnosis . However, epinephrine is not completely suitable for such a diagnostic test because it has both _- and a.-adrenergic receptor agonist properties, and therefore, may cause leukotrichia at the injection sites. Salbutamol sulfate, a specific _ragonist, has been described for use in a semiquantitative test for anhidrosis in Thoroughbred horses . A control of sterile water and six dilutions of salbutamol, from 10-3 w\v to IO'-R w\v, were injected intradermally. The results were read 20 minutes later. Horses with long-standing anhidrosis did not sweat at any of the dilutions. Normal horses sweated in response to the 10-8 w\v dilution, and partially anhidrotic horses responded with dilutions between 10-4 w\v and 10-6 w\v. An unreported, semiquantitative test using terbutaline sulfate, another specific _2-adrenergic receptor agonist, is also diagnostic (R.E. Beadle, personal communication, Louisiana State University, Baton Rouge, LA). The protocol and results are similar to that of the test using salbutamol, except a physiologic saline solution control is used (Figs. 3,4 and 5).
Because there are no known proven treatments for anhidrosis, all of the therapies described for this condition are anecdotal. Treatment of anhidrosis can be categorized into management changes or medical therapy. A combination of both categories is usually necessary for any success in the management of this condition.
The most reliable treatment for anhidrosis is environmental control. This involves management changes directed at removing anhidrotic horses from hot, humid climates and moving them to a cooler, drier environment. Ten to 30 days in such an environment for affected horses has been reported to relieve the signs . In lieu of moving the affected animal, other management changes that are directed to providing a cooler environment may be of some benefit. These changes may include placing the animal in an air-conditioned stall. The use of misting fans and cooling the roof of the barn by running
Fig. 3. Response of normal horse toa semiquantitative test used to diagnose anhidrosis.
Fig. 4. A partial sweater. There is only a minimal response to the intradermal injections of a specific _radrenergic agonist.
Fig. 5. An anhidrotic horse: there is a complete lack of response to the specific _2-adrenergic agoni_t. water on it will help maintain a cooler environment. Exercising the horse during the coolest part of the day is another adjustment that will help manage the disease.
Electrolyte supplementation Horses with anhidrosis have reported serum electrolyte values within normal limits . However, hypokalemia is often suspected in the etiology of anhidrosis . Some practitioners report some success in supplementing with 60 g of KCI or lite salt in the feed. Intubation over several days with two packs of commercial electrolyte replacement product (Enterolyte H.E., Pfizer) has also been used with some success.
A nutritional feed supplement that contains L-tyrosine, ascorbic acid, niacin, and cobalt is commercially available (One AC, MP Co., Phoenix, AZ). Tyrosine is potentially involved in the resensitization of sequestered _rreceptors , and is a precusor for the formation of dopamine and thus catecholamines. However, plasma tyrosine levels are not decreased in anhidrotic horses .
Anecdotal reports among practitioners indicate a success rate of 30-80% using One AC, with the best results seen in moderately affected horses and by placing previously affected animals on the product prior to the beginning of the anhidrotic season. Best results are reported if strenuous training or work is reduced for approximately 3 weeks when started on the supplement. It should be noted that a lessening of the intensity of training or work alone has been reported to relieve the clinical signs of anhidrosis.
Using drugs to decrease sympathetic drive would seem to be logical in treating horses with anhidrosis. Methyl dopa has been used by some practitioners with reported success. An initial dosage of 3000 mg once daily was used increasing to 4000 mg once daily if no positive response in 3-4 days.
In humans, methyl dopa decreases sympathetic outflow from the CNS and is associated with decreased tissue concentrations of norepinephrine and epinephrine . When an anhidrotic horse is treated with this drug, the concentration of epinephrine at the _2-adrenergic receptor site would be expected to decrease, which may allow receptor resensitization. Despite anecdotal reports of success there are no controlled studies of the efficiency of this agent in anhidrotic horses.
Administering iodinated casein orally at 10-15 g per day for 4 to 8 days has been reported to be beneficial in the literature . Practitioners havereported success supplementing with levo-thyroxine (THYRO-L, Vetamix, ShenandQah, IA) at a dose of 0.5-3.0 mg per 100 Ib once a day. Hypothyroidism may exhibit similar clinical signs as anhidrosis, but there has been no documentation of changes in T 3 or T 4 levels in horses living in tropical or semitropical environments or with anhidrosis. Care should be taken when treating a horse with levo-thyroxine supplementation, as the resultant increased metabolic rate could be harmful with the completely anhidrotic horse overheating when exercised in extremely hot and humid weather.
The authors do not recommend the use of clenbuterol, as a prior report  indicates that stimulation of the sweat glands of anhidrotic horses with an exogenous _ragonist results in enhanced prolonged desensitization.
There have been anecdotal reports of return to sweating following acupuncture. This response has been reported to last from a few days to several weeks. There have also been reports of success using homeopathic substances, that is, sulphur and lycopodium in combination.
In humans, it has been shown that glucocorticoids increase the _rreceptor gene in several cell types, and that glucocorticoids may prevent desensitization and restore downregulated receptors [48,49]. Other drugs such as nedocromil sodium and ketotifen have been reported to reduce the down. regulation of _2-receptors as well [50,51].
One practitioner has reported response of anhidrotic horses to rubeolla virus immunomodulation while treating muscle problems (R.V.I., Eudaemonic Corporation, Omaha, NE). Lay persons have reported success by feeding dark beer daily.
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