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Many of the effects of thallium poisoning are nonspecific and occur over a variable time course.53 When combined, however, a clear toxic syndrome can be defined (Table 102–1). Alopecia and a painful ascending peripheral neuropathy are the most characteristic findings.7,27,67,74 Because of the delayed development of alopecia, the diagnosis of thallotoxicosis is often delayed. In fact, with acute exposures, a dose-dependent latent period of hours to days may precede initial symptoms.53,68 When death occurs, it is usually the result of coma with loss of airway protective reflexes, respiratory paralysis, and cardiac arrest.
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Unlike most other metal salt poisonings, diarrhea is often modest or even absent in thallium toxicity.15 The most common symptom is abdominal pain, which may be accompanied by vomiting and either diarrhea or constipation.21,50,53,65,88,108,109 Constipation may be a result of decreased intestinal motility and peristalsis caused by direct involvement of the vagus nerve.15,68 Rarely, severe symptoms occur, such as hematemesis, bloody diarrhea, or ulceration of the mucosal lining.
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Pleuritic chest pain was described in a small series of poisoned patients.62 Another patient was reported to have developed “chest tightness” shortly after drinking thallium-poisoned tea.67 The etiology for this finding is uncertain, although it may also relate to involvement of the vagus nerve.
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Tachycardia and hypertension frequently occur in patients with thallotoxicosis and usually develop during the first or second week after acute ingestion. A poor prognosis may be associated with a persistent and pronounced tachycardia. No exact mechanism has been determined for these cardiovascular effects of thallium toxicity. Some authors theorize that they result from autonomic neuropathic dysfunction directly related to involvement of the vagus nerve,74 but others have noted early electrocardiographic (ECG) changes, such as prolongation of the QT interval, T wave flattening or inversion, and nonspecific ST segment abnormalities, which might suggest direct myocardial injury.8,12,65,68,85 Another theory suggests that the direct stimulation of ATPase in the chromaffin cells by thallium may lead to increased output of catecholamines, resulting in sinus tachycardia.5,67
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Neurologic symptoms usually appear 2 to 5 days after exposure. Patients may develop severely painful, rapidly progressive, ascending peripheral neuropathies.7,8,23,62 Pain and paresthesias are present in the lower extremities (especially the soles of the feet), and although numbness is present in the fingers and toes, there is also decreased sensation to pinprick, touch, temperature, vibration, and proprioception.7,91 The weight of bedsheets on the lower extremities may be sufficient to cause excruciating pain.62,64 Motor weakness is always distal in distribution, with the lower limbs more affected than the upper limbs.12,68
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Symptoms of confusion, delirium, psychosis, hallucinations, seizures, headache, insomnia, anxiety, tremor, ataxia, and choreoathetosis are common. The onset of these symptoms is variable and most likely dependent on dose. Ataxia may develop within 48 hours after ingestion. Insomnia occurs in most patients and may progress to total reversal of sleep rhythms. Coma may occur, especially with larger exposures.12,53,68,88 All cranial nerves can probably be affected by thallium, although abnormalities of cranial nerves I, V, and VIII have not been reported. Cranial nerve III involvement, as evidenced by ptosis, is common and may be asymmetric.12 Nystagmus, another common finding, demonstrates involvement of cranial nerves IV and VI.12 Cognitive abnormalities may persist for months after exposure.59
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Thallium is toxic to both the retinal fibers and the neural retina.92 In cases of a large, single ingestion of thallium, approximately 25% of patients may develop severe lesions of the optic nerve.68,88 Optic neuropathy may lead to optic atrophy and a permanent decrease in visual acuity. In the early stages, the optic disk shows signs of neuritis, which is red and poorly defined, and later develops pallor from resultant optic nerve atrophy. In patients exposed to multiple small doses, nearly 100% suffer optic nerve injury.65 Visual complaints may be delayed in comparison to other neurologic findings92 and may include decreased acuity and central scotomata. Other described ophthalmic effects are noninflammatory keratitis, cataracts, and the color vision defect of tritanomaly (blue color defect).99,100
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Kidney function may remain normal in mild cases of thallium poisoning, even though the kidney has greater bioaccumulation than any other organ. Changes in kidney function in patients with severe thallotoxicosis include oliguria, diminished creatinine clearance, elevated blood urea nitrogen, and albuminuria.5,62,65,68 These findings correlate with morphologic studies in thallium poisoned rats, demonstrating abnormalities in the renal medulla, mainly in the thick ascending limb of the loop of Henle, that occur by the second day after exposure and resolve by the tenth day.5
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Alopecia is the most common and classic manifestation of thallium toxicity.67,103 Typically occurring as the presenting symptom in patients with chronic exposures after an acute exposure, hair loss begins in approximately 10 days and is maximal within 1 month.27,67,71 Facial and axillary hair, especially the inner third of the eyebrows, may be spared, but in some cases, full beards, as well as all scalp hair, are lost.83 Microscopic inspection of the hair reveals a diagnostic pattern of black pigmentation of the hair roots of the scalp in approximately 95% of poisoned patients,11,67,88,103 which can be found within 3 to 5 days of initial exposure11,65 (Fig. 102–1). In patients with recurrent exposures, several bands may be noted on the hair shaft, demonstrating multiple exposures. Initial hair regrowth is very fine and unpigmented but usually returns to normal after mild exposure.65 In patients with severe exposures, alopecia may be permanent. Other dermatologic effects that are observed include acne, palmar erythema, and dry scaly skin that results from sebaceous gland damage.103 Mees lines appear within 2 to 4 weeks after exposure67,75,88 (Fig. 89–4).
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Other less common findings include hepatotoxicity,44 hypochloremic metabolic acidosis,88 anemia, and thrombocytopenia.54,88
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In animal models, thallium is teratogenic.32,34 In humans, one study evaluated 297 children born in a region in which the population’s urine thallium concentrations were higher than normal because of industrial contamination of their environment.22 Urine thallium concentrations in the exposed children were as high as 76.5 μg/L. Although these children had a slightly higher than expected incidence of congenital abnormalities, no causal relationship could be established with regard to thallium exposure.22
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There are few human reports of acute thallium poisoning during pregnancy. A comprehensive literature review demonstrated 25 cases, which included acute and chronic exposures that occurred during all trimesters.39 Thallium slowly traverses the placenta and is able to cause characteristic fetal toxicity,24,73 which manifests initially as decreased fetal movement, possibly as a consequence of fetal paralysis. The classic clinical signs and symptoms of thallium poisoning are described both in the fetus after abortion and in neonate after viable delivery.24,65,73,81 However, the outcome of the pregnancy may be normal despite significant maternal toxicity.24,46 The only consistent finding is a trend toward prematurity and low birth weight, especially in children exposed during the first trimester.39 One author recommends continuing the pregnancy as long as the mother is clinically improving.24 It is reasonable to conclude that a fetus exposed to thallium during organogenesis has the potential for permanent injury. Those exposed later in pregnancy may recover without deficit if their exposures are limited and the mother recovers. If the exposure occurs closer to term, the child may be born with overt toxicity such as alopecia, dermatitis, nail growth disturbances, and permanent CNS injury.65
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These few case reports and animal studies provide confusing and sometimes contradictory results. It seems that fetal outcome is determined by both the trimester of pregnancy and the extent of maternal toxicity. However, because there are insufficient data to predict the outcome of pregnancy complicated by maternal thallium poisoning, no specific course of action can be recommended other than extensive fetal monitoring and aggressive treatment for the mother. When a viable child is delivered, it is important to note that thallium is eliminated in breast milk, and that ongoing evaluation of maternal toxicity is essential because nursing may result in continued exposure for the child.37