History
A male Pinzgauer-cross calf was born hairless with a thickened crusty skin and was maintained for 3 months. The calf failed to thrive before becoming anorexic and lethargic shortly before euthanasia by IV injection of pentobarbital at 3 months of age. The calf had developed disseminated pustules and nodules over the trunk with cutaneous ulcers on the muzzle and distal portions of the limbs. This calf was the first in the herd of 40 cattle that had these clinical signs. The calf was the offspring of a Pinzgauer heifer and a Hereford bull. A more detailed history for the calf was not available.
Clinical and Gross Findings
At necropsy, the calf had severe generalized alopecia with the exception of the preputial skin (Figure 1). Large areas of the skin, especially the trunk, were covered with thick layers of keratin, resulting in an elephant skin–like appearance. The thickened keratin layer had crisscrossed, deep fissures that extended into the dermis. There were scattered dermal pocks (≤ 7 mm in diameter) over the trunk, thigh regions, and shoulders. Over the carpal and tarsal joints, the skin was smooth. The skin of the muzzle and distal portions of the limbs had multiple small (≤ 5-mm-diameter) areas of ulceration. All subcutaneous and internal lymph nodes were moderately to severely enlarged (eg, the right prescapular lymph node measured 7 × 3 × 2 cm). The oral mucosa had extensive erosions, and the tongue had a focal area of hyperkeratosis over the fossa linguae. The teeth were erupted and apparently normal. There were a few small areas of epithelial hyperplasia and hyperkeratosis in the esophagus and all forestomachs (rumen, reticulum, and omasum). No notable gross lesions were present in other organs and tissues, including bone marrow, eyes, and liver.
Photographs of a 3-month-old sexually intact male Pinzgauer-cross calf with generalized alopecia, hyperkeratosis, and pocks. The calf failed to thrive and was euthanized at 3 months of age. A—The calf is hairless with thick scaly epidermis that has an elephant skin–like appearance. The hairlessness and thickened crusty skin had been present since birth. B—Crusts, scales, fissures, and ulceration of the skin are apparent on the nasal planum and muzzle. The teeth were apparently normal. C—The distal portion of the left forelimb has multifocal areas of ulceration. The other 3 limbs were similarly affected. D—The rumen has multifocal areas of epithelial hyperplasia and hyperkeratosis (arrow).
Citation: Journal of the American Veterinary Medical Association 256, 7; 10.2460/javma.256.7.779
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic Findings
Histologically, severely affected areas of skin contained rare hair follicles and were covered with thick layers of compact keratin (Figure 2). The few hair follicles present in these areas were small and often contained clumps of keratin with no discrete hair shafts, whereas others contained hair shafts that were angled, thin, and fragmented. Thick layers of lamellar to compact keratin covered an epidermis of normal thickness (3 to 5 layers of keratinocytes; Figure 3). Multifocally, the epidermis had severe ballooning degeneration with cytoplasmic eosinophilic inclusions in degenerate keratinocytes. These lesions were associated with suppurative folliculitis and pustular epidermitis with gram-positive cocci. Areas of hyperkeratosis were colonized by large numbers of yeast bodies consistent with Malassezia sp (identified with periodic acid–Schiff staining). In the rumen mucosa, nodular lesions had evidence of ballooning degeneration with cytoplasmic eosinophilic inclusions in keratinocytes.
Photomicrograph of a section of skin from the calf in Figure 1. A—Hair follicles are few and hypoplastic. The epidermis is covered with thick layers of compact keratin. The cellular crust is likely the residue of an epidermal pustule (arrow). Notice dilated apocrine glands (arrowhead). H&E stain; bar = 200 μm. B—Hair follicles are hypoplastic, and some are distended by clumps of keratin with no discrete hair shafts (arrowhead) or angled, thin, and fragmented hair shafts (arrow). H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 256, 7; 10.2460/javma.256.7.779
Photomicrographs and transmission electron micrograph of sections of the skin. A—The skin surface is covered with thick layers of lamellar to compact keratin. H&E stain; bar = 50 μm. Inset—Malassezia organisms (highlighted as purple ovals between turquoise keratin fakes) are present in areas of mild to moderate lamellar hyperkeratosis. Periodic acid–Schiff stain; bar = 10 μm. B—The epidermis has severe ballooning degeneration with cytoplasmic eosinophilic inclusions in degenerate keratinocytes (arrows). H&E stain; bar = 25 μm. Inset—Cytoplasmic viral capsids were oblong (approx 250 × 100 nm) and had a rough surface, suggestive of parapoxvirus. Uranyl acetate and lead citrate stain; bar = 100 nm.
Citation: Journal of the American Veterinary Medical Association 256, 7; 10.2460/javma.256.7.779
Electron microscopy of the skin sections revealed oblong to brick-shaped (approx 250-nm-long and 100-nm-wide) viral particles consistent with poxvirus in areas of ballooning degeneration. However, the quality of the electron microscopic images did not allow definitive identification of the viral particles. On the basis of the viral particles’ size, shape, and structured surface, parapoxvirus was considered most likely. The quality of the skin samples was not sufficient for detailed ultrastructural analysis of the epidermis, especially the keratinized layers. Immunohistochemical analysis of sections of skin did not identify bovine viral diarrhea virus antigen.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: severe, diffuse hypotrichosis; extensive, compact, orthokeratotic hyperkeratosis with severe colonization by yeast bodies consistent with Malassezia sp; suppurative luminal folliculitis with gram-positive cocci; and multifocal epidermal ballooning degeneration with cytoplasmic inclusion bodies in keratinocytes consistent with poxvirus.
Case summary: follicular dysplasia with suspect ichthyosis and concurrent yeast and poxviral-associated dermatitis and bacterial folliculitis in a Pinzgauer-cross calf.
Comments
The Pinzgauer-cross calf of the present report had a combination of follicular dysplasia and suspected ichthyosis, which was complicated by surface Malassezia infection, bacterial folliculitis, and poxviral dermatitis. Bovine viral diarrhea virus antigen was not detected immunohistochemically in skin specimens from of this calf, and an underlying bovine viral diarrhea virus–induced immune deficiency in this case was excluded.
Alopecia may result from failure of hair unit formation, failure of hair growth, or hair loss. In the case described in this report, hairlessness was present at birth, which suggested a primary rather than secondary process. Histologically, the morphology of affected hair follicles was most consistent with follicular dysplasia, which explained the clinically observed alopecia; the alopecia was presumed to be a result of reduced production and quality of the hair shaft (hypotrichosis). From findings of genetic studies,1–3 an autosomal recessive component for follicular dysplasia has been described for cattle, such as Herefords, Polled Herefords, Ayrshires, Guernseys, Jerseys, Holsteins, and Black Angus. A mutation in exon 1 of the krt71 gene has been linked to hypotrichosis in Polled Hereford cattle.4
Although most common in calves, follicular dysplasia or congenital hypotrichosis has been identified in all domestic veterinary species.5 A lethal form of hypotrichosis in Holstein-Friesian and Japanese native cattle is thought to be inherited as an autosomal recessive trait. The lethal form of congenital hypotrichosis often results in death of the calf within hours after birth. A viable form of congenital hypotrichosis has been reported for Guernseys, Jerseys, Holsteins, Ayrshires, and Hereford cattle. In those affected calves, hypotrichosis develops as generalized alopecia associated with excessive scaling, infundibular hyperkeratosis, easily broken and misshapen hair shafts, keratinocyte degeneration, and dilated apocrine glands. There have been reports5,6 of congenital hypotrichosis associated with abnormalities in tooth development (hypotrichosis and anodontia) in cattle; however, tooth development was apparently normal in the calf of the present report. Nongenetic causes of hypotrichosis in calves at birth include iodine deficiency, adenohypophyseal hypoplasia, maternal ingestion of the toxic plant Veratrum album, and intrauterine infection with bovine viral diarrhea virus. There was no evidence to support any of these non-congenital causes of hypotrichosis in this case.
Hyperkeratosis may be a secondary feature of follicular dysplasia or hypotrichosis. Secondary hyperkeratosis is orthokeratotic (involving loss of keratinocyte nuclei) rather than parakeratotic (involving retention of keratinocyte nuclei), and the deposited orthokeratotic keratin may range from a basket weave to compact composition. For the calf of the present report, the history of thick scaly skin since birth, severity of the hyperkeratosis, and compactness of the deposited orthokeratotic keratin were suggestive of ichthyosis.
Ichthyosis is a rare skin condition that affects cattle, dogs, pigs, chickens, mice, and llamas,4 among other animals. Two inherited autosomal recessive forms of ichthyosis in cattle, ichthyosis fetalis and ichthyosis congenita, have been reported. Ichthyosis fetalis is generally fatal, and affected animals usually survive for only a few days after birth. This disease has been described for Norwegian Red polled, Friesian, and Brown Swiss calves, and this entity most closely resembles human harlequin ichthyosis.7 Hairlessness is associated with ichthyosis fetalis, which develops as large, horny, plates separated by deep clefts. Microtia, cataracts, thyroid hypoplasia, and eversion of mucocutaneous junctions are common features of this type of ichthyosis. These abnormalities were not apparent in the case described in the present report.
Ichthyosis congenita, a milder variant of ichthyosis, has been described for several breeds of cattle, including Jersey, Pinzgauer, Chianina and Holstein-Friesian crossbreeds.5 The lesions of ichthyosis congenita are similar to but less severe than those of ichthyosis fetalis and are often localized to the skin over the abdomen, inguinal areas, joint regions, and the muzzle. Ichthyosis congenita most closely resembles human lamellar ichthyosis. Given the older age and clinical signs of the calf of the present report, ichthyosis congenita was suspected.
The accumulation of excessive keratin associated with ichthyosis, or secondary to hypotrichosis, coupled with impairment of the permeability barrier promotes the colonization and subsequent infection of the skin with microorganisms. In the case described in the present report, the surface Malassezia infection, bacterial folliculitis, and poxviral dermatitis likely represented lesions secondary to the congenital or suspected congenital abnormalities. Florid inflammation can often distort normal tissue architecture as a result of hypercellularity, edema, and fibrosis, thereby masking underlying disease processes. Degenerative lesions in the dermal or submucosal tissues may result from ischemia secondary to pox lesions. Parapoxviruses cause bovine papular stomatitis, pseudocowpox, and ecthyma contagiosum, all of which are common in the United States. In contrast, infections with orthopoxviruses, such as cowpox, are rare. For the calf of the present report, development of infection with a parapoxvirus during suckling or after transfer by a fomite seemed probable. In this case, ancillary testing of affected skin specimens by means of electron microscopy and special stains (eg, periodic acid–Schiff stain) were important for identifying pathogens, and immunohistochemical analysis was performed to exclude bovine viral diarrhea virus infection as a contributing factor. On the basis of the history and combined findings of the necropsy, histologic examination of tissue specimens, and ancillary tests, a multilevel diagnosis was provided for the calf: congenital follicular dysplasia and suspected ichthyosis congenita complicated by surface Malassezia infection, bacterial folliculitis, and poxviral dermatitis.
References
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2. Miller WH Jr, Scott DW. Black-hair follicular dysplasia in a Holstein cow. Cornell Vet 1990;80:273–277.
3. Scott DW. Congenital and hereditary skin diseases. In: Color atlas of farm animal dermatology. 2nd ed. Oxford, England: Blackwell Publishing Ltd, 2008;59–67.
4. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy & Palmer's pathology of domestic animals. 6th ed. Philadelphia: WB Saunders, 2016;509–736.
5. USDA Research, Education & Economic Information System. A deletion mutation in KRT71 is associated with congenital hypotrichosis in Hereford cattle. Available at: reeis.usda.gov/web/crisprojectpages/0213533-identification-of-the-causal-mutation-for-hypotrichosis-in-hereford-cattle.html. Accessed Mar 29, 2018.
6. Drögemüller C, Distl O, Leeb T. Partial deletion of the bovine ed1 gene causes anhidrotic ectodermal dysplasia in cattle. Genome Res 2001;11:1699–1705.
7. Chittick EJ, Olivry T, Dalldorf F, et al. Harlequin ichthyosis in two greater kudu (Tragelaphus strepsiceros). Vet Pathol 2002;39:751–756.
