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Regardless of etiology, patients with acute aluminum toxicity develop encephalopathy, myoclonus, and seizures. The encephalopathy manifests as disorientation, confusion, and coma. All symptoms appear to develop within days to a few weeks of receiving massive systemic aluminum exposure (usually to an aluminum salt). Serum concentrations range from barely elevated to extremely elevated. Most patients who manifest toxicity have systemically absorbed aluminum, usually in the presence of CKD. In several case reports of acute aluminum toxicity, the initial exposure to aluminum was associated with alum bladder irrigations for hemorrhagic cystitis.34,59,67 In two patients, these symptoms developed after only weeks of exposure to aluminum containing phosphate binders in the presence of citrate.37 Two neonates with uremia developed neurotoxicity after exposure over a 1 to 2 month period to infant formula with high aluminum content.20 Recovery occurs in patients treated with deferoxamine and or HD.34,58,59 Patients in whom aluminum toxicity is not recognized and or treated late usually die (despite supportive care in the intensive care unit, never recovering a normal mental status).37,77,80
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Two distinct types of chronic aluminum toxicity are reported: occupationally related lung problems, such as asthma and pulmonary fibrosis, and a multisystem syndrome most often noted in HD patients, which was initially described as dialysis encephalopathy syndrome or “dialysis dementia.” As these names only describe one organ system involvement, they should not be used.
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Potroom asthma consists of dyspnea, cough, wheezing, bronchitis, and chest tightness.53 These symptoms may present after only a few months of exposure to the metal fumes of aluminum and aluminum dust. The asthma may improve upon cessation of work in the potroom, although some workers never fully improve.63 These symptoms may be a cause for high turnover in potroom workers and appear to have made long-term follow-up difficult.32,85
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Pulmonary fibrosis from aluminum, termed aluminosis, is very similar to the other pneumoconiosis, like silicosis, and appears to progress in a similar manner. This manifestation develops in workers exposed to aluminum dust. Patients experience cough, shortness of breath, and dyspnea on exertion, and they eventually develop restrictive lung disease.41,54 Abnormal chest radiograph findings include increased pulmonary markings, distortion of pleura and diaphragms, and irregular opacities.23,30,78 Recovery of lung function does not occur, and several patients have died from complications of pulmonary disease such as pneumonia.
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Multisystem Toxicity.
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The other form of chronic aluminum toxicity has multisystem manifestations. It primarily affects three organ systems: hematopoietic, nervous, and musculoskeletal. In patients with CKD, the toxicity appears to occur after months to years of exposure to aluminum salt–contaminated dialysate and or aluminum salt–containing phosphate binders such as aluminum hydroxide and sucralfate. A similar presentation has been reported in a patient using aluminum-coated cookware to boil methadone for IV abuse. The patient experienced 3 months of chronic aluminum toxicity (prior to presentation) after 4 years of processing his methadone this way.21,96 Three industrial workers exposed to aluminum metal powder were reported to have encephalopathy. One of these workers had a brain aluminum concentration 20 times normal.45 One infant with kidney insufficiency developed focal seizures, which eventually progressed to generalized seizures, hypotonia, poor head control, ataxia, and developmental delay in the presence of elevated serum aluminum concentration after 10 months of exposure to aluminum salt–containing phosphate binders.70
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The microcytic hypochromic anemia of aluminum poisoning is unresponsive to iron replacement therapy.31 This clinical finding usually precedes encephalopathy and osteomalacia.79 The encephalopathy is characterized by speech disturbances, EEG abnormalities, myoclonic jerks, and dementia.84 The typical speech disturbances include dyspraxia, dysphasia, stuttering, and possibly mutism.46,74,84 EEG abnormalities include slowing of the normal rhythm and high voltage biphasic or triphasic spikes.47,84 The myoclonic activity can include uncontrolled twitching movements, myoclonus, or seizures.84 The osteopathy and osteomalacia can lead to bone pain and fractures.14,92 Death is common in these patients when aluminum toxicity is not recognized and treated.