History

A 1-year-old 11.3-kg (24.9-lb) Nigerian Dwarf doe was evaluated because of a 3-month history of progressive skin disease. The disease was characterized by alopecic and pustular skin lesions originating around the mouth. The lesions progressed to include the udder and then spread to the remainder of the face and eventually down the neck to the thorax, flanks, and back. The lesions continued to spread despite an injection of an antimicrobial and a corticosteroid (drugs not known) by the primary care veterinarian. The goat was also receiving topical applications of chlorhexidine and miconazole shampoo, which did not improve the lesions. Despite the severity of the lesions, the goat was not pruritic and did not appear systemically affected by the pustular disease. During the preceding 2 weeks, the goat appeared to have lost weight despite a good appetite. The goat lived on a farm with other goats as well as horses, chickens, dogs, and cats. No other animal on the farm had clinical signs of skin disease. The goat had not received any medications 1 month prior to the onset of the lesions. The goat had no other notable medical history.

Clinical Findings

Generalized, severe scaling and crusting with abundant large debris was present especially around the head, dorsum, and flanks (Figure 1). On closer examination, there were numerous large multifocal to coalescing pustules present. The same areas affected by scaling and pustular disease were also affected by alopecia (absence of hair) and hypotrichosis (diminished hair coverage). There was moderate lichenification of the affected areas. The goat's hooves, including the coronary bands, and mucous membranes were unaffected.

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Photographs of the face (A) and cervical region (B) of a 1-year-old Nigerian Dwarf doe that was evaluated because of a 3-month history of progressive severe generalized alopecia, crusting, and pustular disease. The image of skin in the cervical region illustrates the large multifocal to coalescing pustules with crusts associated with the disease.

Citation: Journal of the American Veterinary Medical Association 253, 8; 10.2460/javma.253.8.997

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Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →

Cytologic and Histopathologic Findings

Hair samples were collected from the goat for examination; the trichogram was unremarkable. Results of the analysis of material collected from superficial and deep skin scrapings were likewise unremarkable. Cytologic examination of impression smears prepared by rupturing an intact pustule revealed nondegenerate neutrophils with acantholytic keratinocytes (Figure 2). The acantholytic keratinocytes appeared angular and elongate, lacking the rounder edges typically observed in canine and feline acantholytic keratinocytes. No bacteria or yeast were observed.

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Photomicrograph of an impression smear of a ruptured pustule from the goat in Figure 1 revealing an angular acantholytic keratinocyte (arrow) with nondegenerate neutrophils. There is an absence of infectious agents. Modified Romanowsky stain; bar = 10 μm.

Citation: Journal of the American Veterinary Medical Association 253, 8; 10.2460/javma.253.8.997

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The goat was lightly sedated, and following the infusion of a local anesthetic, 4 biopsy punch specimens (8 mm in diameter) were collected from the lesions along the cervical region. These specimens were submitted to the University of Georgia Veterinary Diagnostic Laboratory for examination. Histologic examination of sections of affected skin revealed a hyperplastic epidermis, with 2- to 4-mm-diameter, raised, subcorneal pustules. Pustules were filled with myriad neutrophils admixed with individual, round to elongated, hypereosinophilic acantholytic keratinocytes (Figure 3). The underlying superficial keratinocytes had cytoplasmic vacuolation (edema) and neutrophilic exocytosis. The overlying stratum corneum had mild orthokeratotic hyperkeratosis. Moderate numbers of neutrophils, lymphocytes, plasma cells, and macrophages infiltrated the superficial dermis. Dermal collagen fibers were separated by abundant clear space (edema). There were no microorganisms evident in Gram-stained or periodic acid-Schiff-treated sections.

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Photomicrographs of a section of affected haired skin from the goat in Figure 1. A—In this section, there is an intact subcorneal pustule, which contains numerous neutrophils and acantholytic keratinocytes. H&E stain; bar = 200 μm. B—In a higher-magnification view of a subcorneal pustule, notice that the acantholytic keratinocytes have abundant, eosinophilic cytoplasm and sharply demarcated, angular cell borders. H&E stain; bar = 20 μm.

Citation: Journal of the American Veterinary Medical Association 253, 8; 10.2460/javma.253.8.997

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Morphologic Diagnosis and Case Summary

Morphologic diagnosis: severe, chronic, multifocal to coalescing, neutrophilic epidermitis with subcorneal pustules, orthokeratotic hyperkeratosis, and acantholytic keratinocytes.

Case summary: pemphigus foliaceus (PF) in a goat.

Comments

Differential diagnoses considered for a progressive generalized pustular dermatitis in a young goat include immune-mediated skin disease, drug eruption, infectious disease (eg, bacterial pyoderma or dermatophytosis), and neoplasia. In the case described in the present report, the history and dermatologic, cytologic, and histologic examination findings were consistent with a diagnosis of PF. Exfoliative toxin-producing staphylococci and pustular dermatophytosis can mimic PF both histologically and clinically.^1,2 To exclude these dif-ferential diagnoses, histologic examination of Gram-stained and periodic acid-Schiff-treated sections of skin biopsy specimens was performed and did not highlight the presence of any organisms. The goat had no history of prior pharmaceutical administration, thereby excluding drug eruption.

Pemphigus foliaceus is categorized as a rare blistering autoimmune disease that is characterized by the loss of cell adhesion between keratinocytes and the formation of acantholytic keratinocytes. In the epidermis, keratinocytes are adhered to each other via desmosomes and adhered to the basement membrane via hemidesmosome-anchoring fibril complexes.³ Blistering autoimmune diseases are caused by autoantibodies that target and destroy proteins in the adhesion structures.³ Pemphigus foliaceus is considered a superficial variant of the pemphigus disease group and is usually characterized by pustular skin disease with associated crusts and erosion. For human blistering diseases, specific major autoantigens, such as desmoglein-1 (PF), desmoglein-3 (pemphigus vulgaris), and desmoglein-3 and plakins (paraneoplastic pemphigus) have been identified.^3,4 In dogs with PF, the major autoantigen is desmocollin-1⁵; autoantibodies against desmoglein-1 have only a minor role in the pathogenesis of the disease.³ In goats with PF, a specific autoantigen has yet to be identified.

In animals with PF, once the desmosomal attachments have been disrupted and the keratinocytes have been detached, they become free-floating cells that are referred to as acantholytic keratinocytes, which are identifiable in cytologic preparations. The classic cytologic feature of PF is the presence of acantholytic keratinocytes surrounded by nondegenerate neutrophils, as observed in the cytologic preparations from the goat of the present report.

Initial diagnostic testing in cases of suspect PF includes cytologic examination of pustule impression smears in an attempt to identify acantholytic keratinocytes. As mentioned previously, other disease processes can mimic PF; therefore, cytologic detection of acantholytic keratinocytes is not specific to PF.³ Examination of a biopsy specimen of an intact pustule, not crust, is critical to provide evidence to support a diagnosis of PF. Application of special stains to paraffin-embedded sections of affected skin samples can be performed to aid in the exclusion of infectious disease, as was done in the case described in the present report. Other diagnostic testing includes microbial culture of a ruptured pustule sample and dermatophyte culture of multiple hair samples obtained from the border of crusts. Histopathologic findings typical of PF include broad subcorneal or intragranular pustules composed predominately of neutrophils with variable numbers of eosinophils and isolated or clustered acantholytic cells.³ Skin-fixed intercellular epidermal IgG has been detected in horses, cats, goats, and dogs with PF via direct immunofluorescence testing, which helps support a diagnosis of PF.^6,7 Indirect immunofluorescence testing to identify circulating pemphigus autoantibodies has been documented as inconsistent and unreliable in veterinary medicine.³ In 3 case reports where direct immunofluorescence testing was used to confirm PF, the result of indirect immunofluorescence testing was positive in only 1 of the cases.^6,8,9

To date, PF in humans, cats, horses, dogs, and goats has been documented.^3,10 Among humans, associations have been made with certain human leukocyte antigen groups and ethnic backgrounds.¹¹ Among dogs, a similar genetic predisposition has been identified, with Akita and Chow Chow breeds being overrepresented.³ Minimal information on the overall prevalence of PF in veterinary medicine is available; however, in 1 study,⁷ PF prevalence was approximately 0.3% in the studied canine population. Likely because of a low incidence, breed predispositions for canine PF are either not known or have not been reported. Ultraviolet light has also been reported as a trigger for PF in dogs and humans, but no link has been indicated in other species.^3,12 Drug triggers for PF in cats and dogs have been reported, but similarly, no link has been indicated in other species.¹¹ Given the duration of clinical signs in the goat of the present report and the lack of pharmaceutical use prior to lesion onset, drug-induced PF was perceived to be less likely.

To the authors' knowledge, there are only 6 case reports of PF in goats.^{6,8–10,13,14} Because there is such little evidence, no conclusions can be drawn about prevalence or sex or age predilection for PF among goats. The reported ages of affected goats ranged from 3 months to 7 years, with 4 females and 2 males being affected.^{6,8–10,13,14} Treatment of PF relies on administration of immunosuppressive treatments. Although a range of drugs have been effective in the treatment of PF in humans and small animals, often a lack of pharmacological data and unfavorable safety profile or financial constraints limit the use of these drugs in large animal species. In the reported caprine cases, documented treatments of PF included administration of aurothioglucose,⁸ prednisone with aurothioglucose,⁶ dexamethasone-21-isonicotinate,¹⁴ dexamethasone sodium phosphate with gold sodium thiomalate,¹³ and prednisolone followed by methylprednisolone.¹⁰ Treatment or outcome was not reported for 1 goat.⁹ Positive results of treatment for this skin disease were reported for the other goats with the exception of the animal treated with prednisolone and aurothioglucose.⁶ The prednisolone-aurothioglucose treatment was the only drug protocol that resulted in temporary remission with subsequent relapse of PF.⁶ The 2 goats that were treated with the dexamethasone-21-isonicotinate or prednisolone followed by methylprednisolone achieved resolution of the skin disease but were ultimately euthanized because of suspected adverse treatment effects, namely recurrent mastitis and poor growth, respectively.^10,14 In the case described in the present report, the doe died of undetermined causes before appropriate immunosuppressive therapy could be initiated.