Introduction

Hair cycle arrest, previously called alopecia X, is a common disorder of noninflammatory hair loss in dogs.^1–4 It occurs most commonly in plush-coated or Nordic-breed dogs.^1–5 The exact pathogenesis is not understood and different authors use different disease names including adult-onset growth hormone responsive dermatosis (hyposomatotropism), castration-responsive alopecia, gonadal sex hormone dermatosis, biopsy-responsive alopecia, and congenital adrenal hyperplasia-like syndrome.^1–6 This variety of names reflects varying views on the pathogenesis and can be confusing to clinicians trying to diagnose and treat this condition. Diagnosis is made by ruling out other causes of noninflammatory alopecia, particularly endocrine diseases such as hypothyroidism and hyperadrenocorticism, and combining clinical impression with dermatohistopathologic findings.^1,3,4 Multiple therapies, including melatonin, mitotane, trilostane, androgens, microneedling, laser therapy, and surgical castration, have been used with variable results in different dog breeds and dogs of varying sexual status.^3,6–11 Cost of medication and laboratory monitoring, safety, availability, and lack of efficacy can be obstacles to using these treatments.

Recently, the deslorelin acetate^a canine contraceptive implant was reported to produce hair regrowth in certain plush-coated and Nordic-breed dogs affected with hair cycle arrest.^12,13 These studies were limited to clinical observation of response to treatment, and in one of these studies hair regrowth only occurred in sexually intact male dogs.¹² The purpose of this report is to broaden awareness of this treatment option by describing the clinical and histologic response of hair cycle arrest to deslorelin implant treatment in two sexually intact male keeshonden.

Case Report

Two unrelated sexually intact male keeshonden, 4 yr old and 5 yr old, from the same household were examined for a 2-yr and 3-yr, respectively, history of progressive noninflammatory alopecia and skin hyperpigmentation. Hair loss began in both dogs on the dorsal lumbar and caudal thigh regions and progressed to involve the trunk; the distal limbs and head were unaffected. Pruritus was not reported. Previous diagnostic tests included complete blood count, serum biochemical profile, urine cortisol to creatinine ratio, serum thyroid panel (total thyroxine [T4], free T4, total triiodothyronine [T3], free T3, T3 and T4 autoantibodies, thyroglobulin autoantibody, and thyroid-stimulating hormone), and dermatophyte fungal culture. All results were within normal reference ranges or were negative. The dogs were receiving year-round monthly topical flea and tick preventive and monthly oral heartworm preventive, and vaccinations were current. Previous therapies included a variety of oral antibiotics, a hydrolyzed protein diet, oral fatty acid supplementation, and 3 mg oral melatonin capsules for 2 yr (approximately 0.15 mg/kg q 12 hr for each dog), with no change in hair growth or skin coloration. The dogs were reported to be in good systemic health.

On dermatologic examination, the major findings were bilaterally symmetric severe noninflammatory alopecia and hyperpigmentation. The entire trunk and caudal thighs were affected with variable degrees of hair loss (Figure 1A). In some regions, only primary hairs were absent, and in other areas, there was loss of both primary and secondary hairs. The few existing secondary hairs had a dull, crimped, wool-like appearance. The skin was severely hyperpigmented with generalized mild gray to black scale. The skin and hair coat on the head and distal limbs appeared normal. Skin impression cytology demonstrated no microorganisms or inflammatory cells, deep skin scrapings for Demodex mites were negative, and trichogram demonstrated no hair shaft abnormalities or Demodex mites. Based on the history and signalment, clinical findings, and previous laboratory findings, the diagnosis considered most likely was hair cycle arrest. Skin biopsy was performed. Three 8-mm punch biopsy specimens from alopecic areas were obtained using a local anesthetic^b and submitted for histological examination.

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Histopathology revealed a predominance of kenogen follicles (hairless telogen) with excessive trichilemmal keratinization and moderate-to-severe follicular hyperkeratosis (Figure 2A). In some follicles, trichilemmal keratinization expanded the outer root sheath, creating flame follicles. Moderate multifocal hyperpigmentation was present in all layers of the epidermis. There was mild hair follicle dysplasia. No inflammation was evident in any sections examined. These findings combined with the clinical appearance and history were supportive of a diagnosis of hair cycle arrest.

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Treatment options discussed with the owners included surgical castration, trilostane, and deslorelin implant. Surgical castration was declined. Trilostane was declined because of concerns about potential adverse effects and cost of medication and monitoring. Based on information in a recently published abstract, a 4.7 mg deslorelin acetate implant^a was injected subcutaneously in the interscapular space.¹³ Upon re-examination 3.5 mo later, there was profuse regrowth of hair in all previously affected areas (Figure 1B). The new hairs appeared softer in texture and lighter in color than seen previously. It was not clear if these new hairs were primary or secondary hairs because they were longer and straighter than expected for secondary hairs; however, a predominance of secondary hairs might have accounted for the altered texture and color compared with the previous hair coat. Skin hyperpigmentation appeared unchanged. Skin punch biopsy was repeated, using the same protocol in approximately the same body regions, to evaluate histopathologic response. Anagen follicles predominated, although about one in five of the follicular units remained in kenogen phase or telogen with retained hair shafts surrounded by moderate follicular hyperkeratosis (Figure 2B). Epidermal hyperpigmentation persisted and appeared more diffuse than in the initial samples. Over the following months, the owners reported the dogs’ hair coats continued to improve. At the time of writing of this report, 14 mo after a single deslorelin implant, the owners report the dogs’ hair coats remain full, although lighter in color than before the hair loss began. No adverse effects were reported from the implant.

Discussion

Although hair cycle arrest is not a life-threatening disease, it can be very distressing to dog owners because of the cosmetic defect. The findings in this case report are important for several reasons. First, excellent clinical response in two sexually intact male dogs of this particular breed is documented. Secondly, the histological changes in hair follicles provide further support for the effectiveness of this treatment. Third, the prolonged clinical response in these two dogs indicates that efficacy may persist long after the expected medical duration of the implant. Fourth, there were no evident adverse effects detected in these two dogs.

Hair cycle arrest is well recognized by breeders and owners of Nordic-breed dogs and is a frequent reason for consultation with a veterinarian. The large number of terms used in the past to describe this disorder and the overlap of clinical signs with multiple causes of noninflammatory alopecia leads to confusion in diagnosis and treatment. Hair cycle arrest is a disease in which history and patient signalment must be combined with clinical impression (distribution of hair loss and lack of skin inflammation), laboratory results, and histopathologic criteria to make a diagnosis.^1,3,4 Histopathology of this disease is characteristic of a group of noninflammatory alopecic conditions in dogs including cyclic flank alopecia, pattern alopecia, hyperestrogenism, follicular dysplasia, hypothyroidism, and hyperadrenocorticism.^2,6 There is no single definitive diagnostic test, nor is there definitive treatment.

Deslorelin acetate is a gonadotrophin-releasing hormone agonist that, when administered via implant, provides low-dose long-term suppression of pituitary-adrenal gonadotrophin production and release.¹⁴ It is approved in Europe and Australia for nonsurgical temporary contraception in male dogs and ferrets, and in the United States for treatment of adrenal disease in ferrets; it is used in other species, such as cats and birds, for contraception and treatment of reproductive disorders.^14,15 It is important to note that written client consent was obtained in both cases of this report. The only published study on deslorelin treatment efficacy for canine hair cycle arrest was recently described in a specialty journal.¹² Sixteen sexually intact male dogs with hair cycle arrest were treated with the 4.7-mg deslorelin implant, and twelve had hair regrowth that persisted for at least 12 mo after beginning therapy. None of the spayed female dogs responded to therapy; sexually intact female dogs and castrated male dogs were not included in the study. The implant was repeated 6 mo after the initial implant in all responding dogs, so it is not clear if a single implant would have provided the same treatment effect. In contrast, the two dogs of this report had hair regrowth persist well past 6 mo from a single implant, suggesting the effect on hair follicles might endure longer than the reported duration of the implant. No keeshonden were included in the other study. The histologic response in the dogs of this report was not complete. Changes consistent with hair cycle arrest persisted histologically even though there was clinical improvement. This suggests that not all follicles responded to the implant or that more time might be needed for all follicles to normalize. Serial biopsies over a greater period of time might detect this. Deslorelin implants are generally safe; reported adverse effects are those anticipated with the reproductive effects of the implant, such as decreased testicular size and semen quality.¹⁴ Ease of client compliance is also an appealing aspect.¹⁴

A variety of other therapies have been used for hair cycle arrest. Response to surgical castration has been reported to occur in male dogs, although hair loss recurs in many dogs according to anecdotal report.^3,4 Owners of sexually intact male dogs might object to surgical castration, as was the case for the dogs in this report.

Trilostane is another therapy that has been investigated for hair cycle arrest in dogs. Efficacy has been demonstrated in other dog breeds, including Pomeranians, poodles, and Alaskan malamutes.^5,8 It is not clear if other Nordic-breed dogs would respond similarly or if sexual status has an effect on response. Medication and monitoring costs, in addition to potential adverse effects, can deter some owners from pursuing trilostane therapy. Mitotane has also been used; however, higher costs and increased risk of adverse effects are a concern.⁷

One aspect of diagnosis that was not investigated in the dogs reported here was an extended adrenocorticotropic-releasing hormone stimulation test^c to examine adrenal androgens. Previous reports show elevated 17-hydroxyprogesterone, either baseline or post–adrenocorticotropic-releasing hormone administration, in affected animals that responded to oral trilostane.^5,8

Oral melatonin is a relatively safe nonprescription supplement that is reported to induce hair regrowth in 40% of dogs with hair cycle arrest; however, some dogs have had recurrence of hair loss while receiving melatonin.³ In these two dogs, 3-mg melatonin capsules by mouth twice daily (approximately 0.15 mg/kg q 12 hr for each dog) for nearly 2 yr was unsuccessful. This dose is lower than that reported to produce full or partial hair regrowth in 18/29 sexually altered dogs, including 3 spayed female keeshonden.⁷ It is possible that a higher dose of melatonin might have resulted in hair regrowth for the dogs of this report; however, the owners were not interested in pursuing that therapy any longer.

Recently, microneedling and low-level laser therapy were reportedly used successfully for dogs with noninflammatory alopecia.^10,11 Two spayed female Pomeranian dogs affected with hair cycle arrest had complete hair regrowth with microneedling treatments; both of those dogs had failed to respond to deslorelin acetate implant.¹⁰ Low-level laser therapy produced hair regrowth in a variety of breeds of dogs with a variety of noninflammatory alopecic conditions.¹¹ Although these results are promising, these therapies might not be available to general veterinary practitioners, and the possibility of breed and sex differences in response to therapy needs to be considered.

Conclusion

In summary, we report the clinical and histologic response of the hair coat in two sexually intact adult male keeshonden with hair cycle arrest treated with a single deslorelin implant. Histologic changes were not fully reversed, so the deslorelin implant might not be a definitive treatment; however, the persistence of hair regrowth over at least 14 mo provided excellent cosmetic results. This treatment has been reported as not effective in spayed female dogs, and deslorelin use has not been reported in all dog breeds most commonly affected by hair cycle arrest.^10,12 The long-term efficacy of this therapy is unknown; it might provide an affordable, safe, and simple management option for sexually intact male keeshonden and other Nordic-breed dogs with hair cycle arrest.