Vitamin D toxicity complicating the treatment of senile, postmenopausal, and glucocorticoid-induced osteoporosis. Four case reports and a critical commentary on the use of vitamin D in these disorders.

Hypervitaminosis D developed in four patients with osteoporosis or osteomalacia. All patients were given pharmacologic doses of vitamin D, had reduced baseline levels of renal function, and became hypercalcemic with acute renal failure. Measured 25-hydroxyvitamin D (25-OH D) levels were elevated in three patients; levels were not determined in a fourth patient who became normocalcemic when vitamin D therapy was discontinued. Published data on the use of vitamin D for prophylaxis or treatment of any form of osteoporosis fail to document benefits superior to those of calcium alone or calcium with estrogens and fluoride. Data on the use of 25-OH D show no greater benefit than for vitamin D. The use of 1,25-dihydroxyvitamin D (1,25-OH2 D) plus calcium may be superior to the use of calcium alone in some forms of osteoporosis. Vitamin D toxicity is associated with enhanced resorption of bone in some patients. Morbidity included extended hospitalization, dialysis, and chronic renal failure. Pharmacologic doses of vitamin D cannot be recommended for any form of osteoporosis.

Presentation, treatment, and prognosis of idiopathic inflammatory muscle disease in a rural hospital.

Twenty-seven adult patients with dermatomyositis or polymyositis were retrospectively evaluated over a mean of four and a half years. Eighty-five percent (23) met the suggested criteria of Bohan and Peter (New England Journal of Medicine, 1975) for definite or probable disease, while 15 percent had possible disease. Upper and lower limb girdle strength was given a value (0 to 5) and averaged. Initially, 26 percent were severely weak and 59 percent moderately weak. All patients were treated with steroids. Within three months, 64 percent had little to no weakness and no patients were severely impaired. These proportions remained relatively constant throughout the study. Eight less severely ill patients received alternate-day prednisone. Only two still require treatment; the remainder have been in remission for a mean period of 19 months. Of 19 who received daily prednisone, five also required cytotoxic drugs and 11 still require treatment. A comparison of the results of this study with those of major urban referral centers reveals that the patients in this study constituted a generally less ill population with a better prognosis. Forty-one percent (11) of patients were able to discontinue all forms of therapy and remain in remission. Thirty percent (eight) achieved remission with only alternate-day steroid therapy, an approach that has been discouraged in the past. Two patients (7 percent) had overt malignancies within one year before to three years after diagnosis of myositis. However, in no instance did a search for occult malignancy give positive results. Cancer detection was accomplished by following clues from history and physical examinations. It is questioned whether extensive evaluations for occult malignancies in patients with idiopathic myositis are cost-effective.

Systemic steroid therapy for acute gout: a clinical trial and review of the literature.

Nonsteroidal antiinflammatory drugs are frequently used as initial therapy in acute gout. In select cases, however, colchicine has been recommended as an alternative therapy. A review of the literature raises significant concerns regarding the cost to benefit ratio of using colchicine in this setting. A survey of alternative forms of therapies showed few studies investigating the efficacy and side effects of a short course of oral steroids, and little support for this modality in standard textbooks. Our preliminary study suggests that a short course of oral corticosteroid therapy can be used effectively for acute gout when NSAIDs are contraindicated. The use of prednisone 30 to 50 mg or its equivalent initially, and gradually tapered over 10 days, results in clinical resolution without rebound arthropathy or steroid complications in most patients. As a result, we rarely use colchicine in the management of acute gout in our practice.

Myoadenylate deaminase deficiency--muscle biopsy and muscle culture in a patient with gout.

AMP deaminase activity was undetectable by a sensitive spectrophotometric assay in the muscle biopsy of a 37-year-old man with gout and exercise-related cramps and myalgia. Venous ammonia failed to rise after ischemic exercise, but the diagnostic value of this test is uncertain because changes of plasma ammonia after exercise varied greatly in different normal individuals. In the patient, AMP deaminase activity was normal not only in erythrocytes, leukocytes and cultured fibroblasts but also in muscle cultures. Presence of AMP deaminase in muscle cultures was probably due to the expression of a fetal isoenzyme under separate genetic control from adult muscle AMP deaminase.

Spinal arachnoiditis. What is the clinical spectrum? II. Arachnoiditis induced by Pantopaque/autologous blood in dogs, a possible model for human disease.

Experimentally induced chronic arachnoiditis was studied over a one-year period in beagle dogs. All animals demonstrated severe extensive changes at postmortem which were strikingly similar to those reported in man. Arachnoid inflammation, fibrosis, and adhesions were often associated with nerve roots embedded in collagen. These changes were present in all four experimental dogs, and were absent in four controls. In spite of having pathologically severe changes of arachnoiditis, two of four dogs appeared clinically normal. We suggest that the clinical appearance of chronic arachnoiditis in this animal model may reflect the human experience, wherein presentations may vary from merely complaints of back pain to severe sensory-motor impairment.

Septic bursitis: presentation, treatment and prognosis.

Forty-nine episodes of septic bursitis in 45 patients were reviewed. Our experience concurs with previous studies: (1) the most frequently involved sites were the olecranon (63%) and prepatellar (27%) bursae; (2) Staphylococcus aureus was the commonest pathogen (78%); (3) skin breakage, trauma and/or occupational risk factors were significantly associated with infections (74 and 92% of olecranon and prepatellar episodes, respectively); (4) bursal fluid white blood cell (WBC) counts varied widely (350-392,500 WBC/mm3); and (5) a significant number of patients failed to respond to initial oral antibiotics. In addition to these points, we have been impressed with several clinical observations that merit special emphasis: (1) cellulitis adjacent to the affected bursae was frequent (89%) and often extensive; (2) profound edema occurred in 11% of affected limbs; (3) clinical resolution was slow, occurring at a mean of greater than 5 weeks, but at times requiring as long as 20 weeks to return to baseline status.

Thrombophlebitis in systemic lupus erythematosus.

Thrombophlebitis occurred in 14 (12.2%) of 114 patients with active systemic lupus erythematosus (SLE). Abnormal clotting occurred despite the presence of thrombocytopenia or circulating anticoagulants in some of the patients, and the development of pulmonary emboli was verified in seven. Although infrequently reported, the association of thrombophlebitis with active SLE is apparently not uncommon. While there were no features that distinguished this group of patients from other groups of patients with SLE, there are some possible mechanisms. Recognition of this complication of SLE is important because of the frequent occurrence of SLE-induced pleuritis and its similarity to the pain of pulmonary emboli.

Lack of association of HLA B27 with radiographic sacroiliitis in inflammatory bowel disease.

In 89 patients with inflammatory bowel disease, only one out of 11 patients with radiographic sacroiliitis was found to possess the HLA B27 antigen, while three out of four patients with ankylosing spondylitis were B27 positive. This suggests that sacroiliitis in inflammatory bowel disease may not always be a precursor of ankylosing spondylitis.

Familial polyarticular osteochondritis dissecans masquerading as juvenile rheumatoid arthritis.

A boy with polyarticular osteochondritis dissecans presented with clinical features of juvenile rheumatoid arthritis. Examination of the synovial fluid of an involved joint demonstrated inflammatory characteristics. Osteochondritis dissecans was present in the patient's mother and brother. Human leukocyte antigens HLA A-2, BW-15 and CW-4 were identified in the affected individuals.

Hepatic osteodystrophy after liver transplantation in a patient with primary biliary cirrhosis.

A patient is presented who developed hepatic osteodystrophy after orthotopic liver transplantation in association with persistently low serum 25-hydroxyvitamin D levels. After successful liver transplantation there was a delay in the return to normal of the serum 25-hydroxyvitamin D levels until oral supplementation with vitamin D was instituted. This case emphasizes the need for effective treatment of hepatic osteodystrophy with vitamin D especially in patients considered for transplantation.

Methotrexate pharmacokinetics in patients with rheumatoid arthritis.

Few studies have evaluated the pharmacokinetics of low dose oral methotrexate (MTX) therapy. MTX pharmacokinetics were studied in 10 patients with classic rheumatoid arthritis (RA) after a single 7.5 mg oral dose. MTX was rapidly absorbed. Peak concentrations varied considerably, ranging from 0.31-0.72 microM. Measurable drug concentration was found in all patients at 24 h after the dose. CL/F-MTX = 145 +/- 52 ml/min/1.73 m2 and elimination half-life was 4.5 +/- 0.89 h. Oral MTX given as a single weekly dose has predictable pharmacokinetics. Further studies to examine what relationship exists, if any, with efficacy and toxicity of MTX in RA must be undertaken.

Calcium oxalate microcrystalline-associated arthritis in end-stage renal disease.

Chronic renal failure is known to be associated with secondary hyperoxalemia and the deposition of calcium oxalate in visceral organs, bones, and cartilage. We report the identification of calcium oxalate crystals in the synovial fluid of three patients with chronic renal failure. In one patient, calcium oxalate crystals were also identified within synovium and cartilage. Crystals were pleomorphic and bipyramidal. Some crystals were rod-like and had positive birefringence, thus tending to be confused with calcium pyrophosphate dihydrate when observed with only compensated polarized light microscopy. In one patients asymptomatic effusions were associated with joint capsule calcification, but otherwise normal knee radiographs. The other two patients had bilateral knee pain, one having coexistent features of osteoarthritis and the other chondrocalcinosis. Samples of proliferative synovium, joint capsule, and cartilage from the patient with chondrocalcinosis showed abundant calcium oxalate crystals, and not calcium pyrophosphate dihydrate or calcium hydroxyapatite. Thus, radiographically typical chondrocalcinosis may be due to calcium oxalate. Joint disease in chronic renal failure may be associated with calcium oxalate as well as the previously recognized apatite deposition.

Osteomalacia and weakness complicating jejunoileal bypass.

Five years following jejunoileal intestinal bypass surgery for obesity, a patient developed debilitating weakness and muscle pain. Osteomalacia was suspected clinically by radiographic and laboratory abnormalities and confirmed by bone biopsy. Malabsorption was documented as well as secondary hyperparathyroidism. Successful treatment of this syndrome with vitamin D and calcium identified a medically reversible disorder which obviated the need for surgical reanastomosis.