FC-12 Diagnostic value of skin biopsy in feline symmetric alopecia

Hair loss in Chesapeake Bay retrievers has been increasingly recognized by breeders in recent years. Anecdotal reports suggest an endocrine disorder or follicular dysplasia as the underlying cause, but no scientific study has been done to investigate the underlying problem. A prospective study was carried out in collaboration with the American Chesapeake Club. Affected dogs were recruited into the study. Routine dermatological and hormonal (blood and urine) tests, and skin biopsies were performed. Ten dogs (age 1.5–10 years), seven females (two spayed) and three males (two neutered), were included in the study. All dogs had mild or severe hair loss affecting the lateral ventral chest, flanks, rump and thighs. Affected dogs were clinically healthy. Hormonal tests revealed normal thyroid hormone panels, insulin-like growth factor-1 levels, and urinary cortisol:creatinine ratios in samples collected for ten consecutive days. In six of 10 dogs, an adrenal hormone panel showed slight or moderate increased values pre- and/or post-ACTH stimulation of cortisol (three of six), 17-hydroxyprogesterone (five of six), androstenedione (three of six), estradiol (two of six) and progesterone (six of six). The major histopathologic changes resembled canine flank alopecia and follicular dysplasia with pronounced infundibular hyperkeratosis, mild follicular atrophy, and occasional melanin clumping with dystrophic hair shafts. Chesapeake Bay retrievers suffer from a type of hair loss that is likely related to an abnormal production of adrenal sex hormone. Further studies are currently underway to determine if there is a heritable basis for this disease and to evaluate therapeutic options.
Funding: University of Pennsylvania.     

FC‐10 Adult‐onset hair loss in Chesapeake Bay retrievers: a clinical and histological study

Hair loss in Chesapeake Bay retrievers has been increasingly recognized by breeders in recent years. Anecdotal reports suggest an endocrine disorder or follicular dysplasia as the underlying cause, but no scientific study has been done to investigate the underlying problem. A prospective study was carried out in collaboration with the American Chesapeake Club. Affected dogs were recruited into the study. Routine dermatological and hormonal (blood and urine) tests, and skin biopsies were performed. Ten dogs (age 1.5–10 years), seven females (two spayed) and three males (two neutered), were included in the study. All dogs had mild or severe hair loss affecting the lateral ventral chest, flanks, rump and thighs. Affected dogs were clinically healthy. Hormonal tests revealed normal thyroid hormone panels, insulin‐like growth factor‐1 levels, and urinary cortisol:creatinine ratios in samples collected for ten consecutive days. In six of 10 dogs, an adrenal hormone panel showed slight or moderate increased values pre‐ and/or post‐ACTH stimulation of cortisol (three of six), 17‐hydroxyprogesterone (five of six), androstenedione (three of six), estradiol (two of six) and progesterone (six of six). The major histopathologic changes resembled canine flank alopecia and follicular dysplasia with pronounced infundibular hyperkeratosis, mild follicular atrophy, and occasional melanin clumping with dystrophic hair shafts. Chesapeake Bay retrievers suffer from a type of hair loss that is likely related to an abnormal production of adrenal sex hormone. Further studies are currently underway to determine if there is a heritable basis for this disease and to evaluate therapeutic options. Funding: University of Pennsylvania.     

Oestrogen receptor evaluation in Pomeranian dogs with hair cycle arrest (alopecia X) on melatonin supplementation

The role of oestrogen receptors in dogs with hair cycle arrest (alopecia X) was investigated by immunohistochemistry. The purpose of this study was to determine if hair regrowth in dogs with hair cycle arrest treated with melatonin was associated with a decrease in follicular oestrogen receptors. Fifteen Pomeranians (excluding intact females) with hair cycle arrest were enrolled. Two biopsies were obtained from alopecic areas of the trunk before and after 3 months on melatonin. Haematoxylin and eosin-stained tissues were examined and oestrogen receptor-alpha was demonstrated immunohistochemically. Common histopathological findings included hyperkeratosis, follicular keratosis, excessive tricholemmal keratinization (flame follicles), thin epidermis, few small anagen bulbs, epidermal pigmentation and melanin aggregates within follicular keratin. Melanin aggregates within basal cells and hair were an occasional finding. After 3 months, 40% (six) dogs had mild to moderate hair regrowth. Biopsies from six dogs showed histological evidence of an increase in anagen hairs and eight dogs had a decrease in epidermal pigmentation. Moderate to marked staining intensity of oestrogen receptor-alpha was noted in all sebaceous gland basal cells, all small hair bulbs and follicular epithelium of telogen hairs. There was no oestrogen receptor-alpha staining of nuclei within the epidermis, apocrine glands or dermal fibroblasts. Large anagen hair bulbs had minimal to no oestrogen receptor staining. Hair regrowth was not associated with a change in oestrogen receptor-alpha staining.     

Histologic features of hair follicle neoplasms and cysts in dogs and cats: a diagnostic guide

Hair follicle neoplasms occur in many different species, including humans. In domestic animals, they are most common in dogs. Most hair follicle tumors are benign, but malignant neoplasms can also occur. To diagnose hair follicle neoplasms, a thorough knowledge of follicular anatomy is important, given that follicular tumors are classified according to the differentiation pattern seen in the corresponding part of the normal hair follicle. This review focuses on the key diagnostic features of hair follicle tumors and follicular cysts in dogs and cats.     

Morphologic and immunologic characterization of a canine isthmus mural folliculitis resembling pseudopelade of humans

The clinical, histopathologic and immunopathologic features of a novel form of isthmus mural folliculitis in dogs, which resembles pseudopelade in humans, were characterized. Clinically, dogs exhibited variably distributed foci of alopecia that persisted without treatment or did not respond to immunosuppressive therapy. Histopathologically, mixed mononuclear cell infiltrates, largely lymphocytes, infiltrated the follicular isthmus. Occasionally, inflammation extended above and below the follicular isthmus but did not involve the hair bulb or the epidermis. Severe follicular atrophy and variable atrophy of sebaceous glands occurred in all dogs. Folliculotropic lymphocytes exhibited most commonly CD3 and CD8 (cytotoxic T cells). Autoantibodies specific for the lower hair follicle were detected in the serum of affected patients. Western immunoblotting demonstrated binding of these antibodies to multiple follicular keratinocyte proteins, including hair keratins and trichohyalin. Lack of hair regrowth (in contrast to canine alopecia areata), as well as location of inflammation and extreme atrophy of adnexal units are similar to findings seen in human pseudopelade.     

Antinuclear antibodies (ANA) in Gordon setters with symmetrical lupoid onychodystrophy and black hair follicular dysplasia

Antinuclear antibodies (ANA) were demonstrated in 3 out of 10 Gordon setters with symmetrical lupoid onychodystrophy and in 5 out of 13 Gordon setters with black hair follicular dysplasia. Two dogs showed both symmetrical lupoid onychodystrophy and black hair follicular dysplasia, and one of these was ANA positive. The results suggest that symmetrical lupoid onychodystrophy and black hair follicular dysplasia in the Gordon setter might be autoimmune diseases that are pathogenetically related, which might indicate a common genetic predisposition.     

Alopecia in a black Labrador retriever associated with focal sub‐follicular panniculitis and sebaceous adenitis

A 6‐year‐old entire male black Labrador retriever was presented with nonpruritic multicentric, well‐demarcated alopecia of 12‐weeks duration. Skin biopsies from the margins of alopecic regions showed sebaceous adenitis and sub‐follicular panniculitis. Biopsies from alopecic areas showed severe follicular atrophy with residual fibrous tracts, loss of sebaceous glands and lymphohistiocytic panniculitis beneath individual atrophic hair follicle groups. These features differed from previous reports of pilosebaceous diseases of dogs and appeared to extend the spectrum of inflammatory patterns in presumed immune‐mediated adnexal diseases of this species. During the 12‐month follow‐up, there was partial hair regrowth without treatment but alopecia was permanent in the centre of larger lesions.     

Bald thigh syndrome of Greyhound dogs: gross and microscopic findings

Bald thigh syndrome (BTS) is a disease limited to Greyhound dogs. It is characterized clinically and grossly by bilateral hair loss on the lateral and caudal thighs. The cause of BTS is unknown but may be associated with hypothyroidism or hyperadrenocorticism. Samples of skin, thyroid glands, and adrenal glands from 43 Greyhound dogs with BTS were examined microscopically. Microscopic changes were characterized by dilatation of follicular infundibula, presence of catagen follicles and epidermal hyperplasia. Changes in the skin from these Greyhound dogs suggest an endocrinopathy as the cause; however, we were unable to confirm which one.     

Hyperadrenocorticism associated with sex steroid excess

Diagnosis of sex steroid excess or hyperadrenocorticism in dogs may be challenging. Unlike Cushing's disease, sex steroid excess may have a multitude of manifestations that differ from standard hyperadrenocorticism. In particular, the clinical scenario of a dog with sex steroid imbalance involves one of three systems: dermatologic, reproductive, or hepatic. The history of a dog with hyperadrenocorticism manifesting as sex steroid imbalance often lacks the classical clinical signs of polydipsia and polyuria. Dogs with sex steroid imbalance will often be of specific breeds such as miniature poodles and exhibit trunkal hair loss as the only sign. There is often involvement of the reproductive system, manifested as the growth of perianal adenomas in neutered male or female dogs. The most common laboratory findings consist of elevations in serum alkaline phosphatase and serum alanine transferase. The following article reviews the etiology, common signalment, clinical signs, and laboratory findings associated with atypical hyperadrenocorticism caused by sex steroid imbalance and then explores the medical, surgical, and radiation treatment options.     

An analysis of factors underlying hypotrichosis and alopecia in Irish Water Spaniels in the United Kingdom

A survey on the occurrence of dermatoses in the Irish Water spaniel (IWS) was carried out in the United Kingdom. A group of 20 dogs was selected and examined clinically. All dogs had a nonpruritic, noninflammatory, regionalized hair loss affecting the same areas of the body in males and females, although an initial cyclical pattern associated with the oestrus cycle was identified. Hormonal investigations showed features suggestive of an abnormality of steroidogenesis. Histopathology revealed features similar to canine recurrent flank alopecia (CRFA) and follicular dysplasia associated with abnormal melanization, as in colour dilution alopecia, although the clinical features did not correlate with those conditions. Dietary changes improved coat and skin quality in most of the cases in this series but the role of the diet was not investigated further. This study suggests that hair loss in IWS is influenced by dietary factors and sexual hormones. Abnormalities of the steroidogenic pathways may contribute to the severity of the condition.     

Adrenal steroid hormone concentrations in dogs with hair cycle arrest (Alopecia X) before and during treatment with melatonin and mitotane

The purpose of the study was to evaluate intermediate adrenal steroid hormones (ISH) in neutered dogs with hair cycle arrest (Alopecia X) during treatment with melatonin, and to see if hair re-growth is associated with sex hormone concentrations within the normal ranges. Twenty-nine neutered, euthyroid, and normo-cortisolemic dogs were enrolled in the study (23 Pomeranians, three keeshonds, two miniature poodles, and one Siberian husky). Coat assessment and an ACTH stimulation test were performed pre-treatment and approximately every 4 months for a year post treatment. Melatonin was administered initially at 3-6 mg, every 12 h. Based on clinical progression, each dog was continued on the current dose of melatonin, given an increased dose of melatonin or changed to mitotane. Partial to complete hair re-growth occurred in 14/23 Pomeranians, and partial re-growth in 3/3 keeshond and 1/2 poodle dogs. A Siberian husky dog failed to re-grow hair. Fifteen dogs had partial hair re-growth at the first re-evaluation. Melatonin dosage was increased in eight dogs but only one had improved hair re-growth. On mitotane treatment, partial to complete hair re-growth was seen in 4/6 dogs and no re-growth in 2/6 dogs. No significant decrease in sex hormone concentrations were seen during melatonin or mitotane treatment. Concentrations of ISH in dogs with hair re-growth did not differ significantly from pre-treatment values. At the completion of the study, androstenedione, progesterone and 17-hydroxyprogesterone were still above reference ranges in 21, 64 and 36%, respectively, of dogs with partial to complete hair re-growth. In conclusion, 62% of dogs had partial to complete hair re-growth. However, not all dogs with hair re-growth had concentrations of ISH within the normal range.     

Colonisation status of Malassezia pachydermatis on the hair and in the hair follicle of healthy beagle dogs

Hair and hair follicle carriage of Malassezia pachydermatis was studied in 12 healthy beagle dogs. The yeast was isolated from hair clipped from the lip region at 13 sites in nine dogs but was less frequently recovered from the interdigital spaces on the forefeet and from two sites on the trunk. Population sizes at the lip were significantly greater (P < 0.01) than those at other sites. Skin biopsy specimens were obtained from the same sites and epidermal and follicular tissues dissected following immersion in 1 M CaBr(2). Epidermal carriage of M. pachydermatis was identified in nine biopsy specimens taken from five dogs. Hair follicle carriage was identified in five skin specimens (four foot, one lip) from three dogs. This study indicates that M. pachydermatis is readily recovered from the distal hair in healthy dogs and that hair follicle carriage is infrequent or that populations are low at that site.     

Seasonal flank alopecia in ovariohysterectomized dogs

Recurrent seasonal flank alopecia was recognized in 5 ovariohysterectomized female dogs. The dogs first developed hair loss between 1 1/2 and 4 1/2 years of age. The hair loss began in March or April (spring) and spontaneously resolved in July or August. The dogs were otherwise healthy, and no cause for the condition could be determined.     

Pathogenesis of canine interdigital palmar and plantar comedones and follicular cysts, and their response to laser surgery

This study documents the presence of comedones and follicular cysts of palmar and plantar interdigital skin as an underlying cause of recurrent dermatitis, and describes the use of a carbon dioxide laser to surgically remove lesions. The 28 dogs included in the study had: (i) recurrent lameness, pain, and nodules, or draining sinuses in the dorsal interdigital skin, (ii) failed to respond to antibiotic therapy, and (iii) were negative for Demodex mites and dermatophytes. All 28 had laser surgery; nine dogs had two surgical procedures and two dogs had three surgical procedures for lesion recurrence. Fifteen dogs had skin samples collected for histopathology. Clinical features in ventral interdigital skin included alopecia, callus-like thickening, and comedones. Histological features included hyperkeratosis, acanthosis, comedones and follicular cysts, furunculosis, draining sinuses, and scarring. Surface trauma to the ventral interdigital skin appeared to contribute to lesion development. Laser surgery allowed removal of multiple layers of cysts and adjacent hair follicles and the tracking and removal of sinuses. One dog was euthanized for orthopaedic lameness 1 month after laser surgery, but post-surgical follow-up (1.0-8.0 years - mean 3 years) from the remaining 27 dogs revealed that laser therapy of affected skin and adjacent hair follicles resulted in resolution of interdigital lesions in 25. Two dogs continued to develop interdigital cysts.     

Black-hair follicular dysplasia in a New Zealand Huntaway dog

CASE HISTORY: A 6-year-old intact male New Zealand Huntaway dog had slowly progressive alopecia that was first observed at 12 weeks of age.

CLINICAL FINDINGS: Patchy alopecia was confined to the black-haired areas of the body, and was most evident on the head and dorsum of the body; tan-haired areas of skin appeared normal. Histological examination of black-haired skin revealed distended melanocytes and large aggregates of melanin within, and surrounding, the hair follicles and the epidermis. Macrophages distended with melanin were also visible within the perifollicular and superficial dermis, and follicular lumina were often plugged by keratin that contained aggregates of melanin. The follicles were dysplastic and few hair shafts were visible emerging from follicular infundibula within the sections.

DIAGNOSIS: The clinical and histological findings were consistent with black-hair follicular dysplasia (BHFD).

CLINICAL RELEVANCE: This is the first report of BHFD in a dog in New Zealand, and is the first report in a Huntaway. The most significant effect of BHFD is a predisposition to follicular plugging and secondary bacterial skin infections. Due to the hereditary nature of the follicular dysplasias, breeding from affected dogs should be discouraged. Histological examination of the skin is required to differentiate between the different follicular dysplasias as well as differentiating between follicular dysplasia and follicular atrophy due to endocrinopathy.     

CD34 glycoprotein identifies putative stem cells located in the isthmic region of canine hair follicles

It is widely documented that a pool of multipotent stem cells located in humans and mice hair follicle outer root sheath (bulge region) is involved in the restoration of the whole follicular unit during each anagen phase. To the authors' knowledge, data regarding the location and characterization of hair follicle stem compartment in dogs have not been reported in the recent relevant literature. In this study, we investigated the haematopoietic stem and progenitor cell antigen CD34 as a marker of putative stem cells located in a bulge-like region of canine hair follicles. The presence of CD34 mRNA and glycoprotein was assessed on formalin-fixed, paraffin-embedded canine skin samples by in situ hybridization technique and by standard immunohistochemistry, respectively. A strong expression of CD34 mRNA and glycoprotein was observed in a well-defined area of the hair follicle isthmic region and appeared uniformly concentrated at the level of the basal layer of the outer root sheath. These findings provide compelling support to the hypothesis that in dogs, a subpopulation of basal keratinocytes located in the hair follicle isthmic region and characterized by the selective expression of CD34 is potentially associated with the stem cell compartment of this skin appendage.     

Black hair follicular dysplasia in Large Münsterländer dogs: clinical, histological and ultrastructural features

Four Large Münsterländer cross‐bred dogs affected with black hair follicular dysplasia (BHFD) and one unaffected control littermate were observed, and skin was sampled weekly over the first 19 weeks of life. Affected dogs were born with silvery grey hair, a consequence of melanin clumping in the hair shafts. Hair bulb melanocytes were densely pigmented, and contained abundant stage IV melanosomes but adjacent matrix keratinocytes lacked melanosomes. Melanin clumping was not prominent in epidermal melanocytes in the haired skin but occurred in the foot pads. Follicular changes progressed from bulbar clumping, clumping in the isthmus/infundibulum and finally to dysplastic hair shafts. Alopecia developed progressively in pigmented areas. Silver‐grey hair, melanin clumping, accumulation of stage IV melanosomes within melanocytes and insufficient melanin transfer to adjacent keratinocytes are also classic features of human Griscelli syndrome. The underlying cause in Griscelli syndrome is a defect of melanocytic intracellular transport proteins leading to inadequate and disorganized melanosome transfer to keratinocytes with resultant melanin clumping. In view of the correlation in the phenotype, histology and ultrastructure between both disorders, a defect in intracellular melanosome transport is postulated as the pathogenic mechanism in BHFD.     

Medullary trichomalacia in 6 German shepherd dogs

Medullary trichomalacia is the name proposed for a hair shaft abnormality that was recognized in 6 German shepherd dogs. Affected dogs had multifocal areas of broken hairs, especially on the dorsolateral trunk. Microscopic examination of hair shafts revealed focal areas of loss of architecture, swelling, and apparent softening of the medulla, followed by longitudinal (length-wise) splitting and breakage of the hair shaft. No cause could be found. Affected dogs were otherwise healthy, and apparent spontaneous recovery was the usual outcome. Relapses may occur.     

Alopecia areata in C3H/HeJ mice involves leukocyte-mediated root sheath disruption in advance of overt hair loss

Alopecia areata (AA) can be induced in C3H/HeJ mice by grafting full-thickness AA-affected skin. An 8- to 12-week delay between surgery and overt hair loss onset provides an opportunity to examine disease pathogenesis. Normal haired C3H/HeJ mice were sham-grafted or grafted with AA-affected skin. Mice were euthanatized 2, 4, 6, 8, 10, and 12 weeks after surgery along with chronic AA-affected mice as a positive control. Until 6 weeks after grafting, inflammation was only evident around anagen-stage hair follicles in host skin adjacent to but not distant from the AA-affected graft. From 8 weeks on, AA-grafted but not sham-grafted mice exhibited a diffuse dermal inflammation at distant sites that progressively focused on anagen-stage hair follicles at 10 and 12 weeks. Perifollicular inflammation was primarily composed of CD4+ and CD8+ cells associated with follicular epithelium intercellular adhesion molecule -1 expression. Only CD8+ cells penetrated intrafollicularly by 12 weeks after surgery, although both CD4+ and CD8+ intrafollicular cells were observed in chronic AA-affected mice. Under electron microscopy, intrafollicular lymphocyte and macrophage infiltration associated with hair follicle dystrophy was prominent 10 weeks after surgery, primarily within the differentiating outer and inner root sheaths. This study shows that focal follicular inflammation develops some time in advance of overt hair loss and focuses on the differentiating root sheaths in C3H/HeJ mice. The severity of inflammation and the degree of hair follicle dystrophy induced by the infiltrate appear to reach a threshold level before overt hair loss occurs.     

Alopecia and dermatopathy of the lower back following pelvic fractures in three cats

Abstract   An alopecia and dermatopathy following pelvic fractures associated with vehicular trauma is reported in three cats. The animals presented 3–4 weeks post injury with acute hair loss, glistening appearance of the skin and erosions involving the lower back. Histological examination revealed atrophy of the hair follicles and adnexal structures and follicular telogenization, dermal fibroplasia and mild lymphocytic infiltrate, fibroplasia and inflammation in the panniculus. Vascular damage secondary to the external trauma to blood vessels supplying the skin over the lumbar region and subsequent ischaemia may represent the pathomechanism of this type of alopecia. Focal permanent hair loss can be expected.