Anti‐isthmus autoimmunity in a novel feline acquired alopecia resembling pseudopelade of humans*

Pseudopelade is a primary scarring (cicatricial) alopecia of humans characterized by lymphocyte‐rich inflammation centred around the hair follicle isthmus. Lymphocyte folliculotropism is associated with isthmus apoptosis and, ultimately, follicular destruction and dermal fibrosis. In a cat, an acquired alopecia was diagnosed as pseudopelade based on the following criteria: (i) an adult‐onset, patchy to diffuse nonpruritic hair loss; (ii) an early folliculo‐destructive phase in which lymphocytes and dendritic cells accumulated in and around the follicular isthmus; and (iii) a late stage in which the lower segments of hair follicles underwent atrophy and were replaced by fibrosing tracts. Additionally, immunological investigations characterized the cytotoxic phenotype of isthmotropic lymphocytes and demonstrated the presence of circulating IgG autoantibodies specific for multiple follicular antigens. Altogether, the results of the present study suggest an immune‐mediated pathogenesis for this case of feline pseudopelade, similarly to that causing alopecia areata in humans and other mammalian species.     

Severe bilaterally symmetrical alopecia in a horse

A 9-year-old Tennessee Walking Horse gelding was presented for diagnosis of the cause of extensive alopecia. Complete hair loss was noted over the head, neck, shoulder, thigh, and proximal limbs, but the trunk, distal limbs, pelvic area, mane, and tail were unaffected. The alopecic areas were visually noninflammatory with no exudate or crust except on the shoulder and along the back, where multifocal patchy areas of alopecia with scales and crust were evident. The horse was slightly pruritic. Microscopically, the hair bulbs, inner and outer root sheaths of inferior segments, and perifollicular regions were infiltrated by small to moderate numbers of small lymphocytes. Similar inflammation was occasionally evident in isthmus follicular walls as well as some apocrine glands. No sebaceous glands were affected. Immunohistochemistry confirmed that the small lymphocytes were CD3(+) T lymphocytes. The epidermis from the skin with scale and crusts along the horse's back exhibited mild to moderate hyperplasia, mild lymphocytic exocytosis, mild eosinophilic dermatitis, and diffuse parakeratosis with numerous budding yeasts, consistent with Malassezia spp. The final disease diagnosis was made as alopecia areata with Malassezia dermatitis. Alopecia areata could be a contributing underlying factor for Malassezia dermatitis.     

Alopecia areata in Eringer cows

Alopecia areata is a hair loss disorder in humans, dogs and horses with a suspected autoimmune aetiology targeting anagen hair follicles. Alopecia areata is only sporadically reported in cows. Recently, we observed several cases of suspected alopecia areata in Eringer cows. The aim of this study was to confirm the presumptive diagnosis of alopecia areata and to define the clinical phenotype and histopathological patterns, including characterization of the infiltrating inflammatory cells. Twenty Eringer cows with alopecia and 11 Eringer cows without skin problems were included in this study. Affected cows had either generalized or multifocal alopecia or hypotrichosis. The tail, forehead and distal extremities were usually spared. Punch biopsies were obtained from the centre and margin of alopecic lesions and normal haired skin. Histological examination revealed several alterations in anagen hair bulbs. These included peri‐ and intrabulbar lymphocytic infiltration, peribulbar fibrosis, degenerate matrix cells with clumped melanosomes and pigmentary incontinence. Mild lymphocytic infiltrative mural folliculitis was seen in the inferior segment and isthmus of the hair follicles. Hair shafts were often unpigmented and dysplastic. The large majority of infiltrating lymphocytes were CD3⁺ T cells, whereas only occasional CD20⁺ lymphocytes were present in the peribulbar infiltrate. Our findings confirm the diagnosis of T‐cell‐mediated alopecia areata in these cows. Alopecia areata appears to occur with increased frequency in the Eringer breed, but distinct predisposing factors could not be identified.     

The cutaneous histology of dermatomyositis in collie dogs

Cutaneous lesions of 36 collie dogs affected with dermatomyositis were reviewed. The most common histologic features were follicular atrophy and perifollicular inflammation in 30 dogs, which correlated with alopecia clinically. Other less common findings included formation of colloid bodies, basal cell vacuolation, and subepidermal vesiculation. Results indicated that the most diagnostic cutaneous histologic features of dermatomyositis may be follicular atrophy and inflammation.     

Degenerative mucinotic mural folliculitis in cats

A novel form of mural folliculitis is described in seven cats. Clinically, all cats exhibited generalized alopecia with scaling or crusting that was more pronounced over the head, neck, and shoulders. The face and muzzle of all cats was unusually thickened. Six of seven cats were progressively lethargic but did not demonstrate any other consistent systemic abnormalities. Histologically, there was severe mixed inflammation of the wall of the follicular isthmus in all cats, accompanied by some follicular destruction in five cats. Sebaceous glands were not affected. All cats had variable, but often striking, follicular mucin deposition, as well as epidermal hyperkeratosis and crusting. The cause of the severe mural folliculitis was not identified, and all cats responded poorly to immunomodulating therapy. Follicular mucinosis may be a nonspecific finding, likely reflective of the follicular lymphocytic milieu, and does not always herald follicular lymphoma.     

Follicular dysplasia in two cows

The histological features of a follicular dysplasia with pigmentary changes is reported in two adult cows, one a black Brangus-cross and the other a black Angus. Adult onset of diffuse alopecia was present in both cows. Skin biopsies exhibited follicular distortion and atrophy, with melanin clumping in follicular epithelium, hair bulb matrix cells, hair shafts, and infundibular keratin. Both animals were clinically normal apart from the alopecia. This report confirms and expands on the infrequently reported syndrome of follicular dysplasia in cattle.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Effects of cyclosporine A on clinical and histologic abnormalities in dogs with sebaceous adenitis

OBJECTIVE: To evaluate the effects of cyclosporine A in the treatment of sebaceous adenitis in dogs. DESIGN: Open-label clinical trial. ANIMALS: 12 dogs with sebaceous adenitis. PROCEDURE: Dogs were treated with cyclosporine A at a dosage of 5 mg/kg/d (2.3 mg/lb/d), PO, for 12 months and reevaluated every 4 months. A clinical score was calculated by grading the extent of alopecia and severity of follicular casts as absent, mild, moderate, or severe in each of 17 body regions. Biopsy specimens were obtained and examined histologically and by means of immunohistochemical staining. RESULTS: Mean clinical score was significantly decreased, compared with baseline score, after 4 months of treatment and remained low after 8 and 12 months. Histologically, the severity of inflammation was significantly decreased, as were numbers of macrophages, CD3+ T cells, and major histocompatibility complex class II-expressing cells. The percentage of hair follicles with sebaceous glands increased, suggesting regeneration of sebaceous glands. Clinical signs recurred when cyclosporine administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of cyclosporine A at a dosage of 5 mg/kg/d may reduce the inflammation associated with sebaceous adenitis in dogs. Long-term treatment appears to be neccessary to control the disease.     

Vaccine-induced ischemic dermatopathy in the dog

Post-rabies vaccination alopecia associated with concurrent multifocal ischemic dermatopathy was identified in three unrelated dogs. All dogs received subcutaneous rabies vaccine dorsally between the scapulae several months prior to observation of the initial area of alopecia at the vaccination site. All three dogs developed multifocal cutaneous disease within 1–5 months after the appearance of the initial skin lesion. Cutaneous lesions were characterized clinically by variable alopecia, crusting, hyperpigmentation, erosions, and ulcers on the pinnal margins, periocular areas, skin overlying boney prominences, tip of the tail, and paw pads. Lingual erosions and ulcers were observed in two dogs. Histopathologic examination of the skin revealed moderate to severe follicular atrophy, hyalinization of collagen, vasculopathy, and cell-poor interface dermatitis and mural folliculitis. Hypovascularity was demonstrated by diminished Factor VIII staining of blood vessels. Nodular accumulations of lymphocytes, plasma cells, and histiocytes in the deep dermis and panniculus also were noted at the rabies vaccination site. An atrophic, ischemic myopathy paralleling the onset of skin disease was identified in two dogs. Histological examination of muscle biopsy specimens demonstrated perifascicular atrophy, perimysial fibrosis, and complement (C) _5b-9 (membrane attack complex) deposition in the microvasculature of both dogs with myopathy. Marked improvement of the skin disease was obtained with oral pentoxifylline and vitamin E.     

Adult-onset hair loss in Chesapeake Bay retrievers: a clinical and histological study

Ten Chesapeake Bay retriever (CBRS) dogs with hair loss were recruited in collaboration with the American Chesapeake Club. All dogs had nonpruritic, noninflammatory, regionalized hair loss affecting the same areas of the body in male and female dogs. Hormonal investigations showed increased adrenal and sex steroid concentration in seven cases. Histopathology revealed follicular hyperkeratosis and plugging, follicular atrophy, and occasional melanin clumping with malformed hair shafts. This study suggests that hair loss in CBRS is a breed syndrome in which young adult dogs have hair loss characterized by unusual histological features and abnormal steroid production. A familial predisposition seems likely and selective breeding might reduce the occurrence of this condition.     

MHC class II expression by follicular keratinocytes in canine demodicosis--an immunohistochemical study

MHC class II proteins present fragments of extra cellular antigen to stimulate CD4(+) T lymphocytes. Aim of this study was the detection of MHC class II antigens on different cutaneous cells in canine demodicosis. Histopathological and immunohistochemical examination of skin biopsies from 44 dogs with demodicosis is reported. The control group consisted of skin biopsies taken from 10 necropsied dogs without obvious skin lesions. The immunohistological assessment of the MHC class II expression revealed MHC class II proteins on different cell types of infiltrating inflammatory cells, i.e. APCs (antigen-presenting cells), macrophages, T lymphocytes and B lymphocytes. The plasma cells, however, only showed expression in 32 (73%) of 44 cases. Generally it was noticeable that most plasma cells but never all of them expressed MHC class II. Neutrophils, mast cells and eosinophils were MHC class II negative. Furthermore, in 39 biopsies (89%) from dogs with demodicosis MHC class II positive follicular keratinocytes were found. The control group did not show MHC class II expression on epithelial cells. Concerning the endothelial cells, a total of 25 biopsies (57%) showed MHC class II expression in which different vascular plexuses were affected by staining. This examination shows that MHC class II expression in the skin of dogs suffering form demodicosis is elevated. Especially the MHC class II expression by follicular keratinocytes seems to be conspicuous. We hypothesize that this is in association with the development and the maintenance of follicular inflammation.     

Alopecia areata with lymphocytic mural folliculitis affecting the isthmus in a thoroughbred mare

A 13-year-old, thoroughbred mare was presented with an 8-year history of multifocal, generalized, noninflammatory alopecia and a 3-month history of alopecia, erythema and scaling of the white star on the forehead and muzzle. Histopathological examination of biopsy samples from multiple sites on the body (mane, neck, shoulder, flank and gluteal region) showed a subtle lymphocytic inflammatory infiltrate affecting and surrounding the anagen hair bulbs, consistent with a diagnosis of alopecia areata. The biopsy sample from the star on the forehead showed atrophic hair follicles with perifollicular and mural mononuclear folliculitis affecting the isthmus. Immunohistochemical staining with a CD3 marker confirmed the T-lymphocytic origin of the inflammatory infiltrate in all the samples. The concurrent presence of lymphocytic infiltration at the bulbar and isthmic level of the hair follicles in the same horse is unusual. This finding may represent a variation of the histological appearance of alopecia areata.     

The Sow Endosalpinx at Different Stages of the Oestrous Cycle and at Anoestrus: Studies on Morphological Changes and Infiltration by Cells of the Immune System

The aim of this study was to investigate the morphological changes of the sow endosalpinx and the distribution of leukocytes throughout the oestrous cycle and at anoestrus. Nineteen crossbred sows (Swedish Landrace x Swedish Yorkshire) at late dioestrus (three), prooestrus (three), oestrus (three), early dioestrus (three), dioestrus (three) and anoestrus (four) were used. Oviductal samples from three different parts (isthmus, ampulla and infundibulum), taken immediately after slaughter, were fixed, embedded in plastic resin and stained with toluidine blue or stored in a freezer at -70 degrees C until analysed by immunohistochemistry (prooestrus and anoestrus) with an avidin-biotin peroxidase method. Quantitative and qualitative examinations of oviductal epithelium and subepithelial connective tissue were performed by light microscopy. During all stages, a lower degree of morphological changes (pseudostratification, mitosis and secretory granules) was found in the isthmus compared with ampulla and infundibulum. In ampulla and infundibulum, pseudostratification, mitotic activity and secretory granules of the epithelium were high at prooestrus/oestrus. Cytoplasmic protrusions of epithelial cells with some extruded nuclei were prominent in ampulla and infundibulum at all stages except for oestrus and early dioestrus. Lymphocytes as well as CD2- and CD3-positive cells were the predominant immune cells in the epithelial layer. The numbers of lymphocytes and CD3-positive cells did not differ among segments and stages. Numbers of CD2-positive cells did not differ between prooestrus and anoestrus while the numbers were significantly higher in the infundibulum than in ampulla and isthmus. Neutrophils were only occasionally found and mainly in the infundibulum. In the subepithelial connective tissue layer, the two most commonly observed immune cell types were lymphocytes and plasma cells. The numbers of lymphocytes as well as CD2- and CD3-positive cells was lower in isthmus than in the other segments (p < or = 0.001). Higher numbers of plasma cells (p < or = 0.001) were found in infundibulum than in ampulla and isthmus. The numbers of lymphocytes and plasma cells were not significantly different between stages of the oestrous cycle. However, the number of neutrophils differed and were highest at prooestrus in ampulla and infundibulum. The numbers of CD2-, CD3- and CD79-positive cells did not differ between prooestrus and anoestrus whereas for CD14- and SWC3-positive cells, the numbers were higher at prooestrus (p < or = 0.05) than at anoestrus. In the oviduct, the morphology differed in ampulla and infundibulum with oestrous cycle stages, which indicates an effect by ovarian steroid hormones. The immune cell infiltration was less influenced by cyclic changes. However, the immune cell infiltration (in the connective tissue) in the upper part, especially infundibulum, differed significantly from the one in the lower part, isthmus, indicating different immune functions within various parts of the oviduct.