Pathology in Practice

Virginia A. Charney Animal Disease Diagnostic Laboratory and the Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

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Balazs Toth Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

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Laurent L. Couëtil Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

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Margaret A. Miller Animal Disease Diagnostic Laboratory and the Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

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History

A 4-month-old female Huacaya alpaca was evaluated because of a poor coat and failure to thrive. According to the owner, the cria was born small and weak, with a skin condition. There had been no weight gain during the 3 months preceding the evaluation, despite its good appetite and the provision of good-quality nutrition.

Clinical and Gross Findings

On physical examination, the cria had generalized dry, scaly, lichenified skin, especially on the head, neck, dorsal aspect of the trunk, tail head, and limbs, with a rough coat (Figure 1). There were also crusts and pustules along the upper lips, conjunctivitis, and misshapen toenails.

Figure 1—
Figure 1—

Photographs of a 4-month-old alpaca evaluated because of a poor coat and failure to thrive. The alpaca's coat was dull and unkempt (A), and its toenails were overgrown and misshapen (B); hair loss and hyperkeratotic scales were particularly prominent on top of the head (C).

Citation: Journal of the American Veterinary Medical Association 243, 12; 10.2460/javma.243.12.1701

Hematologic evaluation (CBC), serum biochemical analysis, fecal flotation, microscopic examination of a skin scraping and crust preparation, serum antibody testing for bovine viral diarrhea virus (BVDV), buffy coat PCR assay for BVDV, and measurement of serum zinc concentration were performed to rule out systemic inflammation, BVDV infection, gastrointestinal tract parasitism, ectoparasitism, and zinc-responsive dermatosis. The CBC and serum biochemical analysis results were mostly unremarkable except for mild regenerative anemia, which was attributed to Eimeria macusaniensis infection (diagnosed on the basis of results of fecal flotation). Findings of the microscopic examination of the skin scraping and crust preparation were unremarkable. Serum zinc concentration was 0.25 μg/mL (reference range, 0.33 to 1.57 μg/mL). The alpaca was seronegative for BVDV, and results of the buffy coat PCR test were negative.

The owner elected to euthanize the alpaca because of its poor prognosis for complete resolution of the lesions. At necropsy, the coat was thin and dry with gray keratin flakes scattered through the fleece. The toenails were overgrown. The thymus was small (approx 5 × 10 × 30 mm); peripheral lymph nodes were enlarged (up to 3.5 × 2.5 × 2.0 cm).

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

Histopathologic Findings

Samples of various tissues and organs, particularly skin from affected areas, thymus, and peripheral lymph nodes, were processed for histologic examination. In sections of affected skin, the epidermis had marked orthokeratotic hyperkeratosis (Figure 2) with a few scattered serocellular crusts that contained degenerated neutrophils. Hair follicles were in various growth stages, and most contained hair shafts; however, follicular infundibula were distended by orthokeratotic lamellar keratin, and that portion of the hair shafts was degenerated. No dermatophytes or other microorganisms were detected in additional skin sections stained with periodic acid–Schiff stain. Multifocally, mainly beneath crusts, there was mild perivascular dermal infiltration by a few lymphocytes and plasma cells. Despite the marked thickening of the epidermal and infundibular stratum corneum, there were only 2 to 4 nucleated cell layers in the epidermis or infundibular epithelium (Figure 3).

Figure 2—
Figure 2—

Photomicrograph of a section of skin from the neck of the alpaca in Figure 1. Notice the severe lamellar hyperkeratosis of the epidermis and follicular infundibula. H&E stain; bar = 500 μm.

Citation: Journal of the American Veterinary Medical Association 243, 12; 10.2460/javma.243.12.1701

Figure 3—
Figure 3—

Higher-magnification photomicrograph of the section of skin in Figure 2. Notice the marked thickening of the epidermal and follicular stratum corneum by orthokeratotic hyperkeratosis without epithelial hyperplasia. Multiple hair shafts are present in the follicle at left. The superficial dermis lacks substantial leukocytic infiltration. H&E stain; bar = 25 μm.

Citation: Journal of the American Veterinary Medical Association 243, 12; 10.2460/javma.243.12.1701

Histologic examination of the thymus revealed moderate cortical atrophy; however, thymic corpuscles were well formed. The examined lymph nodes had numerous primary and secondary follicles with germinal centers. Other organs and tissues were histologically unremarkable.

Morphologic Diagnosis and Case Summary

Morphologic diagnosis: epidermal and follicular infundibular orthokeratotic hyperkeratosis.

Case summary: ichthyosiform dermatosis consistent with congenital ichthyosis in an alpaca.

Comments

Ichthyosis is a term for a heterogeneous group of cornification disorders that are characterized by hyperkeratosis and accumulation of scales.1,2 In most cases, lesions are present at birth.1,3 Although rare, affected cattle, dogs, pigs, chickens, mice, and alpacas and a llama have been described.1–3 The pathogenesis is either an accelerated keratinocyte turnover that causes abnormal cell maturation and excessive keratin accumulation or an abnormal retention of keratin secondary to increased cohesiveness between the stratum corneum cells.1

In humans, a diagnosis of ichthyosis is made on the basis of clinical signs, histologic evaluation of skin samples, proliferation indices (autoradiographic determination of tritiated thymidine uptake by epidermal keratinocytes), and genetic characteristics.1,4 In veterinary species, mainly camelids and cattle, a definitive diagnosis is made on the basis of histopathologic findings. Lamellar ichthyosis in humans is considered most like the disease in other animals.1 Lamellar ichthyosis in humans is an autosomal recessive disease, which is usually identified at birth and is thought to be caused by a defect of keratinocyte transglutaminase.1,2,5 This results in decreased cross-linking of loricrin and involucrin, which interferes with formation of the cornified cell envelope.1,2 Histologically, compact orthokeratotic hyperkeratosis and mild acanthosis are evident.1

In cattle, 2 forms are known: ichthyosis fetalis, which is fatal, and ichthyosis congenita. Both conditions are uncommon. Ichthyosis fetalis is identified at birth and involves all cutaneous surfaces. The skin of affected calves is hairless and covered by thick cornified plaques separated by deep fissures. Ichthyosis congenita, or congenital ichthyosis, is a milder form with variable severity of hyperkeratosis; it may be clinically apparent at birth or not noticeable until several weeks later. The skin is thickened and covered by scales with partial alopecia.1 For the few cases of congenital ichthyosis that have been reported in cattle, growth retardation and persistent skin abnormalities were described.6,7 Cattle with ichthyosis fetalis are usually stillborn or euthanized, and cattle with ichthyosis congenita are managed on the basis of their clinical signs.8

The ichthyosiform dermatosis in the alpaca of this report was consistent with congenital ichthyosis. The generalized cutaneous hyperkeratotic plaques and scales were present at birth. Histologic changes included prominent laminated orthokeratotic hyperkeratosis of the epidermis and infundibula of the hair follicles, with minimal epidermal hyperplasia as described in cattle with congenital ichthyosis1 and in humans with lamellar ichthyosis.5

The minimal inflammation and presence of hair follicles in all stages of growth ruled out an infectious or primary follicular disease. Zinc deficiency was the leading differential diagnosis in this case because it can result in generalized hyperkeratosis.9 Zinc-responsive dermatitis is one of the most common skin diseases in alpacas and accounted for 32% of the dermatologic diagnoses in 72 South American camelids made by attending veterinarians in a survey in the United Kingdom10 and 8% of 68 alpacas in a recent retrospective study9 performed at a US referral hospital. It is possible that marginal zinc deficiency contributed to the hyperkeratosis in the alpaca of the present report; however, zinc-responsive dermatosis is generally a more inflammatory and hyperplastic disease and does not result in an accelerated toenail growth.9 Unfortunately, serum zinc concentration is not an accurate predictor of zinc-responsive dermatosis; thus, diagnosis is mainly established by exclusion and response to treatment.11 Treatment in this case was not attempted because the alpaca had failed to thrive since birth, despite good-quality nutrition and adequate appetite.

References

  • 1. Ginn P, Mansell J, Rakich P. Skin and appendages. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's pathology of domestic animals. 5th ed. Edinburgh: Elsevier Saunders, 2007;553–781.

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  • 2. Belknap EB, Dunstan RW. Congenital ichthyosis in a llama. J Am Vet Med Assoc 1990; 197:764767.

  • 3. Saperstein G. Congenital defects and hereditary disorders in ruminants. In: Smith BP, ed. Large animal internal medicine. 3rd ed. St Louis: Mosby, 2002;1465–1555.

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  • 4. Hazel M, Marks R. Clinical, histologic and cell kinetic discriminants between lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma. Arch Dermatol 1985; 121:489493.

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  • 5. Cao X, Lin Z, Yang H, et al. New mutations in the transglutaminase 1 gene in three families with lamellar ichthyosis. Clin Exp Dermatol 2009; 34:904909.

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    • Search Google Scholar
    • Export Citation
  • 6. Molteni L, Dardano S, Parma P, et al. Ichthyosis in Chianina cattle. Vet Rec 2006; 158:412414.

  • 7. Raoofi A, Mardjanmehr SH, Nekoei S. Ichthyosis congenita in a calf in Iran. Vet Rec 2001; 149: 563.

  • 8. Gentile A, Testoni S. Inherited disorders of cattle: a selected review. Slov Vet Res 2006; 43:1516.

  • 9. Scott DW, Vogel JW, Fleis RI, et al. Skin diseases in the alpaca (Vicugna pacos): a literature review and retrospective analysis of 68 cases (Cornell University 1997–2006). Vet Dermatol 2011; 22:216.

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    • Search Google Scholar
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  • 10. D'Alterio GL, Knowles TG, Eknaes EI, et al. Postal survey of the population of South American camelids in the United Kingdom in 2000/01. Vet Rec 2006; 158:8690.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Clauss M, Lendl C, Schramel P, et al. Skin lesions in alpacas and llamas with low zinc and copper status—a preliminary report. Vet J 2004; 167:302305.

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Contributor Notes

Dr. Toth's present address is Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.

Address correspondence to Dr. Charney (vreynol@purdue.edu).
  • Figure 1—

    Photographs of a 4-month-old alpaca evaluated because of a poor coat and failure to thrive. The alpaca's coat was dull and unkempt (A), and its toenails were overgrown and misshapen (B); hair loss and hyperkeratotic scales were particularly prominent on top of the head (C).

  • Figure 2—

    Photomicrograph of a section of skin from the neck of the alpaca in Figure 1. Notice the severe lamellar hyperkeratosis of the epidermis and follicular infundibula. H&E stain; bar = 500 μm.

  • Figure 3—

    Higher-magnification photomicrograph of the section of skin in Figure 2. Notice the marked thickening of the epidermal and follicular stratum corneum by orthokeratotic hyperkeratosis without epithelial hyperplasia. Multiple hair shafts are present in the follicle at left. The superficial dermis lacks substantial leukocytic infiltration. H&E stain; bar = 25 μm.

  • 1. Ginn P, Mansell J, Rakich P. Skin and appendages. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's pathology of domestic animals. 5th ed. Edinburgh: Elsevier Saunders, 2007;553–781.

    • Search Google Scholar
    • Export Citation
  • 2. Belknap EB, Dunstan RW. Congenital ichthyosis in a llama. J Am Vet Med Assoc 1990; 197:764767.

  • 3. Saperstein G. Congenital defects and hereditary disorders in ruminants. In: Smith BP, ed. Large animal internal medicine. 3rd ed. St Louis: Mosby, 2002;1465–1555.

    • Search Google Scholar
    • Export Citation
  • 4. Hazel M, Marks R. Clinical, histologic and cell kinetic discriminants between lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma. Arch Dermatol 1985; 121:489493.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Cao X, Lin Z, Yang H, et al. New mutations in the transglutaminase 1 gene in three families with lamellar ichthyosis. Clin Exp Dermatol 2009; 34:904909.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Molteni L, Dardano S, Parma P, et al. Ichthyosis in Chianina cattle. Vet Rec 2006; 158:412414.

  • 7. Raoofi A, Mardjanmehr SH, Nekoei S. Ichthyosis congenita in a calf in Iran. Vet Rec 2001; 149: 563.

  • 8. Gentile A, Testoni S. Inherited disorders of cattle: a selected review. Slov Vet Res 2006; 43:1516.

  • 9. Scott DW, Vogel JW, Fleis RI, et al. Skin diseases in the alpaca (Vicugna pacos): a literature review and retrospective analysis of 68 cases (Cornell University 1997–2006). Vet Dermatol 2011; 22:216.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. D'Alterio GL, Knowles TG, Eknaes EI, et al. Postal survey of the population of South American camelids in the United Kingdom in 2000/01. Vet Rec 2006; 158:8690.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Clauss M, Lendl C, Schramel P, et al. Skin lesions in alpacas and llamas with low zinc and copper status—a preliminary report. Vet J 2004; 167:302305.

    • Crossref
    • Search Google Scholar
    • Export Citation

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