PubMed · 8407479
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J G Vestweber, H W Leipold, D J Steffen. 1993-07-15. Difficult dermatologic diagnosis.. https://pubmed.ncbi.nlm.nih.gov/8407479/
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Vitamin D, the major steroid hormone that controls mineral ion homeostasis, exerts its actions through the vitamin D receptor (VDR). The VDR is expressed in many tissues, including several tissues not thought to play a role in mineral metabolism. Studies in kindreds with VDR mutations (vitamin D-dependent rickets type II, VDDR II) have demonstrated hypocalcemia, hyperparathyroidism, rickets, and osteomalacia. Alopecia, which is not a feature of vitamin D deficiency, is seen in some kindreds. We have generated a mouse model of VDDR II by targeted ablation of the second zinc finger of the VDR DNA-binding domain. Despite known expression of the VDR in fetal life, homozygous mice are phenotypically normal at birth and demonstrate normal survival at least until 6 months. They become hypocalcemic at 21 days of age, at which time their parathyroid hormone (PTH) levels begin to rise. Hyperparathyroidism is accompanied by an increase in the size of the parathyroid gland as well as an increase in PTH mRNA levels. Rickets and osteomalacia are seen by day 35; however, as early as day 15, there is an expansion in the zone of hypertrophic chondrocytes in the growth plate. In contrast to animals made vitamin D deficient by dietary means, and like some patients with VDDR II, these mice develop progressive alopecia from the age of 4 weeks.
OBJECTIVE: To determine the response rate of zinc-responsive dermatosis to zinc supplementation, the optimal dosage of zinc required for resolution of lesions, the rate of recurrence of lesions, and to develop recommendations for maintenance dosages of zinc to be administered to dogs with this type of zinc-responsive dermatosis. DESIGN: Retrospective case series. ANIMALS: 17 northern-breed dogs with a diagnosis of zinc-responsive dermatosis. PROCEDURE: Histologic evaluation of skin biopsy specimens and review of medical records. Additional information was obtained from veterinarians and owners via a telephone questionnaire. RESULTS: In 12 of 17 dogs, lesions were unilateral initially, then became symmetrical as the disease progressed. Pyoderma was evident in 5 of 17 dogs, whereas 10 were pruritic. Most lesions initially developed between September and April, and 12 of 17 dogs developed lesions in February, October, and November. Initial dosages of zinc supplement ranged from 0.8 to 4.6 mg/kg of body weight/d (0.36 to 2.09 mg/lb/d). Effective/ maintenance dosages ranged from 0.5 mg/kg (0.23 mg/lb), twice weekly, to 8.0 mg/kg/d (3.6 mg/lb/d). Fifteen of 17 dogs had complete resolution of lesions after zinc supplementation. Lesions recurred in 9 of 16 dogs. Approximately half of the recurrent lesions were a result of a missed dose or a decrease in dosage or frequency of zinc supplementation. CLINICAL IMPLICATIONS: An initial dosage of zinc supplement of 1.0 mg of elemental zinc/kg (0.45 mg of elemental zinc/lb), PO, every 24 hours is recommended. Treatment should be continued for 1 month to determine response to treatment, and the daily dosage should be increased by 50% if the initial dosage is not effective. Dogs are prone to recurrence of lesions if a dose of zinc is missed or the dosage or frequency is decreased.
Lethally X-irradiated LEW rats reconstituted with syngeneic bone marrow and given low-dose Cyclosporine A (CyA) for 5 weeks develop, after withdrawal of CyA, symptoms of disease resembling graft-vs.-host disease (GVHD) as seen after allogeneic bone-marrow transplantation. Symptoms of disease may include acute dermatitis and chronic disease resembling scleroderma. Since anti-class II MHC cytotoxic lymphocytes are generated in this model, it has been proposed as an anti-tumor regimen in humans. We now report that LEW rats treated according to this protocol may, after cessation of CyA administration, paradoxically develop malignant neoplasms. Of 48 experimental animals, 31 developed rapidly progressive subcutaneous and/or intracutaneous tumors commencing at 6 weeks, 13 weeks and 6 months after cessation of CyA. Tumors were of mesenchymal origin, usually high-grade sarcoma, adenocarcinoma or both mesenchymal and epithelial tumors. Such tumor incidence exceeded the incidence of tumor growth in X-irradiated controls, and in rats subjected to thymectomy prior to X-irradiation and CyA administration. CyA by itself induced no tumors. Our results show that total body X-irradiation is required for tumor development but that the presence of CyA-induced autoimmune disease increases the incidence significantly.