Abstract
A 57-year-old man, who was receiving immunosuppressive therapy after liver transplantation, began receiving broad-spectrum antibiotics and antifungals (including amphotericin B liposomal) for a suspected fungal infection of the brain. Four days later, brain biopsy and subsequent culture led to identification of Scedosporium boydii/apiosperumum as the causative pathogen, and voriconazole [dosage and route of administration not stated] was added to his therapy; amphotericin B and other antibacterials were stopped, and voriconazole was continued as monotherapy. After approximately 2 months of antifungal therapy, he developed diffuse bone pain and weakness. His fluoride levels were elevated, but voriconazole concentrations were therapeutic (3.9 µg/mL). Treatment was changed to posaconazole and his symptoms resolved.
Author comment:“[V]oriconazole toxicity manifested as periostitis due to fluoride toxicity, despite voriconazole levels in the therapeutic range.”
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Painful periostitis in the setting of chronic voriconazole therapy
A 72-year-old woman on chronic voriconazole therapy for recurrent histoplasmosis developed a painful forearm mass. Laboratory and imaging findings were consistent with a diffuse periostitis. Her symptoms resolved after discontinuation of voriconazole. To our knowledge, this is the first case of voriconazole-induced periostitis to be reported in a patient with
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Environmental Fluoride 1977 by Rose & Marier
The Associate Committee on Scientific Criteria for Environmental Quality was established by the National Research Council of Canada in response to a mandate provided by the Federal Government to develop scientific guidelines for defining the quality of the environment. The concern of the NRC Associate Committee is strictly with scientific
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Voriconazole-induced periostitis after allogeneic stem cell transplantation
A 64 year old man with a history of resected renal cell carcinoma and acute myelogenous leukemia in first remission, presented 3 months after a non-myeloablative, HLA-matched sibling allogeneic stem cell transplantation with diffuse, migratory arthralgias and myalgias. Joint effusions were noted on exam, and diagnostic arthrocenteses of both knees
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Correlation of pain and fluoride concentration in allogeneic hematopoietic stem cell transplant recipients on voriconazole
Supportive care guidelines recommend anti-mold prophylaxis in hematopoietic stem cell transplant (HSCT) recipients deemed high-risk for invasive fungal infection, leading to long-term use of voriconazole following allogeneic HSCT in patients that remain immunocompromised. Voriconazole has been associated with periostitis, exostoses, and fluoride excess in patients following solid organ transplant, HSCT
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Fluorosis and periostitis deformans as complications of prolonged voriconazole treatment
We describe a case of development of painful periostitis deformans in a 39-year-old woman who was receiving long-term voriconazole treatment for Aspergillus infection as a complication of orthotopic liver transplant. Measurement of fluoride levels strongly supports fluorosis to be the mechanism of the voriconazole-induced periostitis deformans and supports the concept
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"Pre-Skeletal" Fluorosis
As demonstrated by the studies below, skeletal fluorosis may produce adverse symptoms, including arthritic pains, clinical osteoarthritis, gastrointestinal disturbances, and bone fragility, before the classic bone change of fluorosis (i.e., osteosclerosis in the spine and pelvis) is detectable by x-ray. Relying on x-rays, therefore, to diagnosis skeletal fluorosis will invariably fail to protect those individuals who are suffering from the pre-skeletal phase of the disease. Moreover, some individuals with clinical skeletal fluorosis will not develop an increase in bone density, let alone osteosclerosis, of the spine. Thus, relying on unusual increases in spinal bone density will under-detect the rate of skeletal fluoride poisoning in a population.
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Fluoride & Osteoarthritis
While the osteoarthritic effects that occurred from fluoride exposure were once considered to be limited to those with skeletal fluorosis, recent research shows that fluoride can cause osteoarthritis in the absence of traditionally defined fluorosis. Conventional methods used for detecting skeletal fluorosis, therefore, will fail to detect the full range of people suffering from fluoride-induced osteoarthritis.
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Skeletal Fluorosis: The Misdiagnosis Problem
It is a virtual certainty that there are individuals in the general population unknowingly suffering from some form of skeletal fluorosis as a result of a doctor's failure to consider fluoride as a cause of their symptoms. Proof that this is the case can be found in the following case reports of skeletal fluorosis written by doctors in the U.S. and other western countries. As can be seen, a consistent feature of these reports is that fluorosis patients--even those with crippling skeletal fluorosis--are misdiagnosed for years by multiple teams of doctors who routinely fail to consider fluoride as a possible cause of their disease.
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Exposure Pathways Linked to Skeletal Fluorosis
Excessive fluoride exposure from any source -- and from all sources combined -- can cause skeletal fluorosis. Some exposure pathways , however, have been specifically identified as placing individuals at risk of skeletal fluorosis. These exposure pathways include: Fluoridated Water for Kidney Patients Excessive Tea Consumption High-Fluoride Well Water Industrial Fluoride Exposure Fluorinated Pharmaceuticals (Voriconazole
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