Cutaneous Manifestations of Multisystemic and Metabolic Defects in Animals

Baldy calf syndrome of female Holsteins, as the name implies, is associated with hypotrichosis. This autosomal recessive trait is lethal to male fetuses. Affected calves appear normal at birth but lose condition and patches of hair beginning 1–2 months later. The skin then becomes thickened and wrinkled, and the ear tips may curl. Calves salivate profusely and become emaciated, and affected female calves die by 6–8 months of age. The underlying metabolic defect is not known.

A similar-appearing syndrome, known as congenital anemia, dyskeratosis, and progressive alopecia, is described in polled Hereford calves of either sex. Anemia and small size are noted at birth and become progressively more severe. Alopecia, abnormal curly hair, and hyperkeratosis begin around the muzzle and ear margins and become more extensive as calves mature. Later, the skin becomes markedly wrinkled, and neurological abnormalities develop. Calves have diarrhea and die before they are 6 months old.

Familial vasculopathy has been described in German Shepherd Dogs and Parson Russell Terriers. In these dogs, skin lesions develop shortly after the first set of puppy vaccinations and seem to be exacerbated after subsequent vaccinations. The main cutaneous signs are footpad swelling and depigmentation that may progress to ulceration; all footpads are typically affected. Crusting and ulceration of the ears and tail tips and depigmentation of the nasal planum are also features. As dogs mature, the disease may resolve; however, pad lesions may be so severe that euthanasia is warranted. No known treatment is uniformly effective, although some dogs appear to respond to high dosages of corticosteroids. A severe form of neutrophilic vasculitishas been described in young Chinese Shar-Pei dogs and may be familial (1).

Familial dermatomyositis is an idiopathic inflammatory disease of the skin and muscles of young Collies and Shetland Sheepdogs (see images of dermatomyositis in a Collie and in a Sheepdog). The mode of inheritance is reported to be autosomal dominant in Collies; however, there is some evidence of an unidentified infectious agent in the pathogenesis. Vasculopathy is associated with early inflammatory stages of the disease in the skin and muscle; in both tissues, the eventual sequela is atrophy.

The onset of familial dermatomyositis is typically by age 6 months, although adult onset has been recorded. Progression of lesions is variable, and individual pups in a litter can be affected mildly to severely. Skin lesions consisting of erosion, crusts, and alopecia appear on the face, ear tips, tail tips, and lateral surfaces of the extremities. These lesions occur in areas of increased trauma and are exacerbated by heat and sun exposure. The muscles affected most severely are on the head and extremities.

Familial dermatomyositis, Collie

Image

Courtesy of Dr. Robert Dunstan.

Familial dermatomyositis, Sheepdog

Image

Courtesy of Dr. Karen A. Moriello.

Diagnosis is established by evaluation of littermates and family history, skin biopsy, electromyography, and muscle biopsy, which must be performed early in the disease course. No treatment exists, although there are anecdotal reports of benefit from corticosteroids, vitamin E, omega-3 fatty acids, and pentoxifylline (10 mg/kg, PO, every 12 hours, longterm). However, severely affected dogs rarely respond satisfactorily to these treatments.

Exfoliative cutaneous lupus erythematosus (gene variant unc93b1 autosomal recessive) of German Shorthaired Pointers is first noted when dogs are approximately 6 months old. It begins with scaling and crusting on the head and dorsum and quickly progresses to generalized scaling with erythema (see exfoliative cutaneous lupus erythematosus images). The dermatopathy appears to be either painful or pruritic.

Affected dogs become febrile and develop lymphadenopathy. Some develop a poorly characterized enteropathy; most lose condition. As the name implies, skin biopsy specimens reveal features of lupuslike dermatitis. The disease is progressive and ultimately fatal. No successful treatment has been reported. A genetic test is available.

Exfoliative cutaneous lupus erythematosus, dog

Image

Courtesy of Dr. Karen A. Moriello.

Hereditary zinc deficiency syndromes are best known in cattle and have also been described in dogs. In cattle, these syndromes include hereditary parakeratosis, lethal trait A46, edema disease, and hereditary thymic hypoplasia. Affected breeds include Friesian, Shorthorn, Angus, and Black Pied. These syndromes all become apparent within days to weeks of birth and are characterized by symmetrical, generally acral, hyperkeratosis; crusting and unthriftiness; increased susceptibility to infection; and early death. Affected calves exhibit conjunctivitis, ptyalism, rhinitis, and diarrhea and often succumb to pneumonia.

In most cattle breeds, the trait appears to be autosomal recessive and associated with intestinal malabsorption of dietary zinc, which is more or less responsive to dietary zinc supplementation. In some breeds, the defect in absorption is absolute, and parenteral zinc administration is needed to achieve remission. Because such treatment is rarely feasible in production animals, these are lethal traits.

Diagnosis is established by excluding dermatophilosis, biopsying skin (which shows mostly parakeratosis), measuring serum zinc levels, and finding thymic and lymph node hypoplasia postmortem.

In dogs, there are two familial zinc deficiency syndromes. In white Bull Terriers, lethal acrodermatitis (gene variant mkln1) is characterized by retarded growth; progressive, acral, hyperkeratotic dermatitis; and pustular dermatitis around mucocutaneous junctions. These clinical signs are apparent by 10 weeks and are later accompanied by diarrhea, pneumonia, and death before dogs are 2 years old. In older dogs, footpad hyperkeratosis and paronychia contribute substantially to morbidity. Severity of cutaneous disease can be ameliorated somewhat by control of secondary bacterial and Malassezia infections; with aggressive medical treatment, affected dogs' lives can be prolonged. Dogs do not, however, respond to oral zinc therapy.

A familial zinc-responsive dermatopathy that manifests mostly as cutaneous lesions responsive to supplemental oral zinc occurs in Alaskan Malamutes, Siberian Huskies, and German Shorthaired Pointers. Clinical signs develop at or after weaning and consist of crusting and hyperkeratosis of mucocutaneous junctions and skin on extremities. Often, bitches will develop clinical signs associated with estrus or whelping and lactation. Secondary Malassezia infections are common. Diagnosis is established by skin biopsy and response to oral zinc supplementation.

Tyrosinemia, described in a German Shepherd puppy, was compared to a type of tyrosinemia in humans and thus thought to be hereditary. Clinical manifestations included erosions and ulcerations of the footpads and nose, bullous lesions and depigmentation of skin, loss of claws, and eye lesions. This condition must be differentiated from familial vasculopathy of German Shepherd Dogs (described above). In the puppy, serum tyrosine levels were 20–30 times above normal, and urine specimens contained similarly high tyrosine concentrations.

Porphyria is an inherited defect in the metabolism of hemoglobin and its byproducts. In cattle, accumulation of aberrant porphyrins in skin increases sensitivity to ultraviolet light. Cattle experience two types of inherited porphyries:

• Bovine protoporphyria has been reported in crossbred Limousin cattle and is inherited as an autosomal recessive trait. Clinical signs include photodermatitis and photophobia. Affected calves may die; however, mature animals may be less severely affected.

• Bovine erythropoietic porphyria is more common and more severe. It is reported in several breeds (including Shorthorn, Holstein-Friesian, and Hereford) as an autosomal recessive trait. In addition to severe photosensitivity, clinical signs include red-brown discoloration of teeth, bones, and urine; regenerative anemia; and stunted growth. Teeth and urine from affected animals fluoresce orange under a Wood’s lamp. Skin biopsy is also useful in diagnosis.

Porphyria has been described in cats and swine but does not result in photosensitivity.

Leukocyte adhesion deficiency in Holstein cattle is an inherited disease (autosomal recessive) with many manifestations. It is fatal before adulthood. Skin lesions are frequently observed in affected calves and include dermatitis and vasculitis. Diagnosis is by molecular methods with PCR assay of fresh or fixed tissue providing identification of affected, carrier, and normal cattle.