J. Vet. Med.

A 51, 409412 (2004) 2004 Blackwell Verlag, Berlin ISSN 0931184X

Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

Congenital Bovine Epitheliogenesis Imperfecta: A Report of Three Cases from Iran

B. Dalir-Naghadeh1,3, H. A. Seifi1,4 and A. A. Farshid2
Addresses of authors: Departments of 1Clinical Sciences and 2Pathobiology, Faculty of Veterinary Medicine, Urmia University, PO Box 1177, Urmia, Iran; 3Corresponding author: Tel.: +98 441 277 0508; fax: +98 441 277 1926; E-mail: b.dalir@mail.urmia.ac.ir; 4Present address: Department of Clinical Sciences, School of Veterinary Medicine, Ferdowsi University of Mashhad, PO Box 1793, Mashhad 91775, Iran With 9 gures Received for publication April 28, 2004

Summary
Epitheliogenesis imperfecta is a recessive hereditary condition characterized by the congenital missing of epithelium on the skin and oral mucosa. These lesions vary in size and location but usually consist of irregular patches of discontinuity of hair and squamous epithelium of skin usually on the distal extremities. Aected calves may also have patchy missing epithelium in the oral mucosa and tongue. The defect is usually incompatible with life. In this report, clinical, gross and histopathogical ndings of epitheliogenesis imperfecta were described in two neonatal calves and one stillborn calf. Absence of epithelium over extensive areas of limbs, muzzle,

nostrils, tongue, hard palate, cheeks and esophagus were among the remarkable ndings.

Introduction
Epitheliogenesis imperfecta, also known as aplasia cutis, a congenital discontinuity of the squamous epithelium of the skin and oral mucous membranes (Yager and Scott, 1993) is a variably severe disease that has been reported in domestic animals (Hargis, 1988). This appears to be the rst case series of congenital bovine epitheliogenesis imperfecta in Iran.

Fig. 1. Islands of absence of epidermis and ulcerated areas in limbs and muzzle of rst case.
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Fig. 2. Well-demarcated area of epithelial absence and ulcer on limbs of the aected calf (rst case).

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B. Dalir-Naghadeh et al.

Fig. 3. Absence of epidermis on parts of tongue and teeth maleruption of the aected calf after necropsy (rst case).

Fig. 4. A limb from a calf aected with epitheliogenesis imperfecta (second case) showing absence of epidermis.

Two neonatal calves and one stillborn calf with congenital skin anomalies were presented to Veterinary Clinic of Urmia University over a course of 5 years. Annually about 300 calves are referred to this clinic. The rst case was a 6-day-old female crossbred Holstein calf which was referred because of congenital absence of hair coat, anorexia, depression and bloody staining discharge from mouth. The temperature was 40.2C, heart rate was 128 beats min)1 and respiratory rate was 44 min)1. Examination revealed absence of epidermis especially on limbs distal to the carpus and tarsus (Figs 1 and 2). There was distinct demarcation between normal and abnormal areas. Traumatized parts of the aected areas were covered by tenacious crusts and attempts to lift them caused bleeding. Removal of the crusts revealed a bleeding eshy surface. In addition, there was no epidermis over the muzzle, nostrils and there was discrete absence of epithelium over the dorsal aspect of the tongue and diuse absence on hard palate and incisor teeth maleruption and malocclusion of the incisors (Fig. 3). Haematological changes were leucocytosis, neutrophilia and elevated brinogen levels (900 mg dl)1). In spite of extensive uid and broad-spectrum antibiotics therapy, the calf died on day 2 after admission and was necropsied in the clinic. The second case (Fig. 4) was a 3-day-old crossbred Holstein male calf that featured a clinical picture resembling the rst calf, but extent of cutaneous involvement was more restricted. Vital signs were normal. Haematological changes were not

marked. The calf was treated with broad-spectrum antibiotics and recommended to nurse till slaughter age. The calf was still alive 2 months after admission and thereafter was lost to follow-up. The third case was an 8.5-month aborted female foetus (Figs 5 and 6) from a native cow. There were well-demarcated extensive areas of an absence of epidermis on the lower parts of limbs and also on muzzle, around nostrils, dorsum of tongue, cheeks, hard palate and proximal part of oesophagus. Necropsy was performed in rst and third cases. Gross examination revealed no macroscopical changes in the other organs. For histopathology study, tissue samples were collected with especial reference to skin and oral cavity. The specimens xed in 10% neutral-buered formalin, processed routinely and embedded in paran; 6-lm sections were cut and stained with haematoxylin and eosin. The most signicant histopathological ndings were abrupt absence of squamous epithelium over denuded areas (Figs 7, 8 and 9). In aected areas of skin complete absence of epidermis, hair follicles and glands were noticed. In areas where the epidermal linings terminated (Fig. 8) there were no necrotic changes in the epidermis. Based on the gross and microscopical ndings, a diagnosis of congenital bovine epitheliogenesis imperfecta was made. The major dierential diagnosis for a calf presenting with congenital discontinuity of squamous epithelium include epidermolysis bullosa. Epidermolysis bullosa is characterized by cutaneous blisters in response to trauma (Scott, 1988).

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Fig. 7. Skin section showing area with abrupt absence of squamous epithelium over aected areas (H&E 63).

Fig. 5. Parts of rear limbs of foetus aborted at 8.5 months of pregnancy showing areas of skin without covering epidermis. The yellow colour of hairs on unaected areas is as a result of meconium staining.

Fig. 8. Part of epidermal lining at the junction between the normal skin and aected area showing no evidence of necrotic changes (H&E 400).

Fig. 9. Histopathological section of tongue showing area with no epithelial covering (H&E 63).

Fig. 6. Tongue and oral mucosa of third case aected with epitheliogenesis imperfecta. Note the absence of epidermis especially on the base and apex of the tongue and its diuse absence on hard palate.

Although for dierentiation no attempts was made to create new lesions with friction, but in anamnesis and clinical examination there was no evidence to suggest blister formation.

412 In addition, at dermatohisthopathological evaluation there were no evidence of subepidermal vesicles and key features of epitheliogenesis imperfecta, i.e. complete absence of epidermis, hair follicles and glands were observed. Observations made on areas with epidermal lining showed no necrotic changes, this could be a dierential feature of the cases presented with epidermolysis bullosa. Epitheliogenesis imperfecta is a rare, inherited (autosomal recessive) disease reported in a number of cattle breeds including Holstein, Jersey, Shorthorn, Dutch Black Pied, Swedish Red Pied, German Yellow Pied, Hereford, Ayrshire, Angus, Jersey, Brown Swiss and Sahiwal (Raverty et al., 2000). Although, its pathogenesis is not completely understood, a primary failure of embryonic ectodermal dierentiation is probable. Bovine epitheliogenesis imperfecta may also be associated with brachygnathia, atresia ani, and dental, genitourinary, and ocular abnormalities (Scott, 1988). Foetuses with extensive lesions may be aborted (Yager and Scott, 1993). The defect is usually incompatible with life (Radostits et al., 2000) and aected calves may be aborted or succumb to infection shortly after birth (Jones et al., 1997). Without the protective covering of epidermis, the underlying tissue is easily traumatized and infected. Grossly, lesions consist of circumscribed variably sized areas in which squamous epithelium is absent (Hargis, 1988). The cutaneous defects have predilection for the distal extremities, particularly aecting the claws and the skin over fetlocks and knees, but may involve muzzle, nostril, cheeks, ear margins, tongue and hard palate (Yager and Scott, 1993). The interesting aspect of the aborted foetus of the present report, was involvement of the proximal oesophagus. Laboratory studies of epidermal and dermal tissues from an aected calf revealed not only epidermal abnormalities but also a metabolic defect of dermal broblasts (Angarano, 1993). Tissue-cultured broblasts from aected animals produce

B. Dalir-Naghadeh et al. subnormal amounts of collagen and lipids (Radostits et al., 2000), suggesting that epitheliogenesis imperfecta may be a connective tissue disorder. The prognosis is variable, depending on the size of the lesion. Severely aected animals such as the rst case generally develop septicaemia and die. Mild cases may heal by scar formation or surgical intervention (Angarano, 1993). Although, the second case of this report was alive at least 2 months after admission, but the animal was weak and unthrifty. Currently, there is no genetic test available to determine the carrier status of animals. Preventive measures are limited to selective replacement of breeding stock, including bulls and females (Raverty et al., 2000).

References
Angarano, D. W., 1993: Congenital and hereditary skin diseases. In: Howard, J. L. (ed.), Current Veterinary Therapy 3, Food Animal Practice, pp. 907910. W.B. Saunders, Philadelphia, PA. Hargis, A. M., 1988: Integumentary system. In: Thomson, R. G. (ed.), Special Veterinary Pathology, pp. 169. B.C. Decker, Toronto, ON. Jones, T. C., R. D. Hunt, and N. W. King, 1997: The skin and its appendages. In: Veterinary Pathology, pp. 817871. William and Wilkins, Baltimore, MD. Radostits, O. M., C. C. Gay, D. C. Blood, and K. W. Hinchcli, 2000: Inherited defects of the skin. In: Veterinary Medicine, pp. 1755 1759. W.B. Saunders, Philadelphia, PA. Raverty, S., D. Mcintosh, and J. Coates, 2000: Congenital epitheliogenesis imperfecta in Simmental and Aberdeen Angus, HerefordCross Neonates. Animal Health Center Newslett. Ministry of Agriculture, Food and Fisheries, British Columbia. 10, 3. Scott, D. W., 1988: Congenital and hereditary diseases. In: Large Animal Dermatology, pp. 339. W.B. Saunders, Philadelphia, PA. Yager, J. A., and D. W. Scott, 1993: Congenital and hereditary diseases of skin. In: Jubb, K. V. F., P. C. Kennedy, and N. Palmer (eds), Pathology of Domestic Animals, vol. 1, pp. 554555. Academic Press, San Diego, CA.