Hypervitaminosis A
From Felipedia
Hypervitaminosis A or deforming cervical spondylosis is a crippling degenerative and proliferative bony disorder typically affecting the vertebral column and various long bones in cats fed whole liver (usually beef or sheep, but also pig and chicken) diets. The disorder is caused by excessive intake of vitamin A in the liver. Excessive intake of vitamin A supplements can also produce the disease. In serum, vitamin A is transported in a retinol binding protein and as retinylesters (retinylpalmitate, -stearate) in very-low and low-density lipoproteins.
Chronic hypervitaminosis A in cats is characterized by new bone formation or exostoses, principally involving cervical vertebrae, and in the region of tendon, ligament, and joint capsule attachments. Early changes involve periarticular cartilaginous and osseous hyperplasia of cervical vertebrae, especially the first three diarthrodial joints, without changes in the articular hyaline cartilage or other signs of inflammation. These lesions tend to coalesce, overgrow joints, and cause complete bony ankylosis. Cartilaginous epiphyseal growth plates are seriously disrupted in kittens. In chronic cases, all cervical and cranial thoracic vertebrae may become involved, as well as sternebrae, periarticular regions of long bones and ribs. Nerve roots are often damaged secondary to exostoses encroaching on intervertebral foramina.
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Histopathology
Histopathological changes include subperiosteal proliferation of new woven bone around joints of affected vertebrae and proliferation of cartilage from the margins of the articular hyaline cartilage. There is erosion of adjacent cortical and cancellous bone and fibrous replacement of the myeloid marrow. Periosteal proliferation may involve the tendinous insertions of muscle on the vertebrae and extend into surrounding muscle causing replacement and atrophy of the muscle fibers. In a study using back-scattered scanning electron microscopy, the more recently formed areas of bony proliferation were composed mainly of chondroid tissue surrounded by different degrees of woven bone. As the bony reaction continued, trabecular remodeling occurred leading to progressive substitution of chondroid tissue by woven bone surrounded by apposition of lamellar bone. In this study, there was no evidence of calcified cartilage present. In animals with extensive involvement of the spinal nerve roots, the spinal cord may show atrophy with disappearance of neurons and fibers, especially in the dorsal horns of the gray matter. The underlying pathophysiologic mechanisms are not fully understood, but vitamin A toxicosis does appear to induce bone lesions via a direct effect on skeletal tissue. In young animals, toxicosis results in suppression of both chondrocytic and osteoblastic activity, leading to growth retardation and thinning of cortices. A high intake of vitamin A is necessary for several months or years before cervical exostoses develop, although experimental studies in kittens indicate that radiographic changes in the cervical spine can be detected as early as 15 weeks after beginning a diet rich in vitamin A. After 24 weeks on the diet, the cervical spine from the occiput to C6 became completely rigid. Trauma may be a contributing factor in the pathogenesis due to constant movement of the neck in coat cleaning. It seems that an individual predisposition to disturbances of vitamin A metabolism may be an important factor in the pathogenesis of the disease. There are reports of some cats having no symptoms while others in the household develop typical lesions.
Clinical signs
Clinical signs usually occur in adult cats (e.g., 2 to 10 years of age) of either sex and in any breed. Affected animals may be depressed, walk with pelvic limbs flexed, and may show lameness of one or both thoracic limbs associated with periarticular exostoses around the elbow joints, which, in chronic cases, are typically fixed in a flexed position. There may be ankylosis of the shoulder and carpal joints. Palpable exostoses of the forelimb distal to the elbow or of other regions of the skeleton are relatively uncommon. Cats frequently assume a characteristic rabbit or kangaroo-like sitting posture. The head may be held in a ventroflexed position and there may be scoliosis of the cervical spine, which is frequently palpably rigid. The atlantoaxial joint is often fused, thus preventing any head-neck movement. Manipulation of the neck may be painful. Neurogenic muscle atrophy and signs of cervical hyperesthesia can result from spinal nerves compressed by the bony proliferation. Cutaneous hyperesthesia may be present over the shoulder and neck regions. Affected cats often have an unkempt coat because of inability to groom themselves. Affected cats typically have a fixed stare, presumably associated with reduced movement of the eyeballs caused by the head-neck rigidity. Some animals have a voice change, probably related to proliferative exostoses that compress laryngeal structures (e.g., larynx, laryngeal muscles, and nerves). Some cats may show aggressiveness when handled. Cats with advanced disease tend to become emaciated. In 6 to 8 week-old kittens fed raw sheep liver, severe retardation of skeletal growth was accompanied by delayed eruption, retention, and displacement of the incisor teeth with diffuse hypercementosis of the roots.
Diagnosis
Differential diagnoses for this disease include
Radiographic studies reveal extensive new bone formation and variable autolysis of cervical and rostral thoracic, and sometimes, lumbar vertebrae. In some cats, the skull and the cervical and first few thoracic vertebrae can be rigidly fused. Periosteal exostoses can be seen involving multiple long bone articulations, especially in elbow and shoulder joints, and also ribs (in the region of vertebral articulation), sternebrae (showing irregular bony overgrowth, replacement and deformation of sternebrae with ankylosis of sternebral articulations), pelvic girdle, and hip joints. Curiously, there have been a few instances in which exostoses involving the pelvic girdle and hip joint were the major skeletal changes, without involvement of the cervical spine or forelimbs. Rarely, affected cats showing typical clinical signs have no radiographic abnormalities in the cervical spine.
Vitamin A serum levels are elevated, but other hematologic and blood chemistries are usually normal, including alkaline phosphatase activity, serum calcium, and blood inorganic phosphate levels. Vitamin A concentration is very high in liver and kidney and there is extensive lipoid infiltration of the spleen, and fatty changes in the liver have been observed occasionally.
Treatment
Prognosis of chronically affected cats is guarded to poor. Change in diet may halt further new bone formation and exostoses; however resolution of radiographic changes and clinical signs is unlikely, although some remodeling of bone may occur over a long period. Epiphyseal damage is irreversible. Nevertheless, encouraging improvement in signs has been noted in some cats following removal of liver from the diet (along with use of analgesic drugs, e.g., meloxicam). Rarely, temporary or permanent recovery may occur spontaneously. Note that liver is highly palatable to cats and a change to another diet may be met with resistance. The particular susceptibility of cats to hypervitaminosis A is difficult to explain.
