Thallium poisoning causes symptoms within hours after ingestion. Initial complaints are related to the gastrointestinal system and include abdominal pain, nausea, vomiting, hematemesis and diarrhea which often contains blood [12]. At this stage, symptoms are nonspecific and can hardly point to a specific cause. However, the appearance of neurological symptoms, usually several hours to a few days after the onset of GI symptoms, can suggest thallium poisoning. Tremors, paresthesia, painful polyneuropathy, facial palsy, seizures, ataxia, psychosis and severe weakness are reported [7] [9], with convulsions and coma being some of the most severe manifestations [13]. If patients are able to survive the initial period in which these symptoms appear, the onset of alopecia approximately 3 weeks after ingestion is one of the definite signs of thallium poisoning. In severe cases, respiratory failure and shock may develop.

• Pain

  Physicians who see the sudden onset of painful peripheral neuropathy and hair loss in patients should consider the possibility of thallium poisoning. [ncbi.nlm.nih.gov]

• Fatigue

  Fatigue and skin pigmentation were observed in all patients. Abnormal liver function tests were found in 6 (42.9%) and delirium and coma were identified in 4 (28.6%). [ncbi.nlm.nih.gov]

  He had health-fanatic patients who had been experiencing symptoms like fatigue, brain fog, digestive troubles, nausea, and skin and hair issues—all symptoms of low-level thallium poisoning. [firstwefeast.com]

  Rapid hair loss Loss of appetite Fatigue Severe pain in the calves of the legs Albuminuria – the presence of albumin in the urine, typically as a symptom of kidney disease. Optic neuritis – inflammation of an optic nerve, causing blurred vision. [naturalhealthgroup.com.au]

  The subjects with higher-than-normal thallium levels also exhibited varying degrees of symptoms consistent with thallium toxicity including cardiac arrhythmias, fatigue, and hair loss. [wellnessdentalcare.com]

• Fever

  The initial symptoms of thallium poisoning may include fever, gastrointestinal problems, delirium, convulsions and coma. [ncbi.nlm.nih.gov]

  Overexposure may cause fatigue, headaches, nausea, vomiting, abdominal cramps, diarrhea, and fever. [rarediseases.org]

  After the seventh dialysis on the 28th day of illness he developed high fever with leucocytosis (17.0 × 10 9 /l) hence the haemodialysis was stopped. [pmj.bmj.com]

  A-Acute Effects : -paresthesias, -ataxia, -alopecia, -fever, -coryza, -abdominal pain, -nausea, -vomiting, -lethargy, -speech disorders, -tremors, -cyanosis, -convulsions, -pulmonary oedema, -bronchopneumonia, -kidney, liver and brain damage, -death. [smart2000.pagesperso-orange.fr]

• Gastric Lavage

  Hemodialysis or hemoperfusion, gastric lavage and the use of laxatives are indicated in early stages of poisoning, but the two most common modalities are the administration of Prussian blue and activated charcoal. [symptoma.com]

  By this time the initial therapeutic measures such as gastric lavage by activated charcoal, forced diuresis, and Prussian blue are not helpful in eliminating thallium. [pmj.bmj.com]

  In an A&E department gastric lavage can be performed if within an hour of ingestion. [patient.info]

• Vomiting

  Characteristic of the condition are abdominal pain, vomiting, bloody diarrhea, tremor, delirium, and alopecia. [medical-dictionary.thefreedictionary.com]

  Acute thallium poisoning produces gastrointestinal symptoms and signs, such as vomiting and acute abdominal pain, in the first few hours after ingestion, and initially is indistinguishable from other causes of acute gastrointestinal toxicity. [ncbi.nlm.nih.gov]

  Abdominal pain, nausea, vomiting and diarrhea that may contain blood are almost always observed. [symptoma.com]

  THALLIUM POISONING Symptoms associated with thallium poisoning include extreme drowsiness (somnolence), nausea, vomiting, abdominal pain, and bloody vomiting (hematemesis). [rarediseases.org]

  Thallium is a heavy metal which causes gastrointestinal illness including abdominal pain, vomiting, and either constipation or diarrhea. [michigan.gov]

• Abdominal Pain

  A case of acute thallium poisoning presenting with sudden abdominal pain, paraesthesiae and irritability is described. [ncbi.nlm.nih.gov]

• Nausea

  He had health-fanatic patients who had been experiencing symptoms like fatigue, brain fog, digestive troubles, nausea, and skin and hair issues—all symptoms of low-level thallium poisoning. [firstwefeast.com]

  Therefore deficiency symptoms of potassium can be signs of thallium toxicity such as: Potassium deficiency – Rapid irregular heart beat, muscle weakness, pins and needles, irritability, nausea, vomiting, diarrhoea, swollen abdomen, cellulite, low blood [naturalhealthgroup.com.au]

  These pains were associated with nausea, several attacks of vomiting, loss of appetite and substernal pain, but were unrelated to the taking of food. [mdedge.com]

  Abdominal pain, nausea, vomiting and diarrhea that may contain blood are almost always observed. [symptoma.com]

• Diarrhea

  Characteristic of the condition are abdominal pain, vomiting, bloody diarrhea, tremor, delirium, and alopecia. [medical-dictionary.thefreedictionary.com]

  Abstract A male worker who handled thallium-containing raw material for glass manufacturing over a period of four years complained of alopecia, abdominal pain, diarrhea and tingling in the four extremities. [ncbi.nlm.nih.gov]

  Abdominal pain, nausea, vomiting and diarrhea that may contain blood are almost always observed. [symptoma.com]

  Thallium is a heavy metal which causes gastrointestinal illness including abdominal pain, vomiting, and either constipation or diarrhea. [michigan.gov]

  People who ingested large amounts of thallium over a short time have reported vomiting, diarrhea, temporary hair loss, and effects on the nervous system, lungs, heart, liver, and kidneys. It has caused death. [nbcnewyork.com]

• Abdominal Cramps

  Overexposure may cause fatigue, headaches, nausea, vomiting, abdominal cramps, diarrhea, and fever. [rarediseases.org]

  Case presentation A 26-year-old man developed nausea, abdominal cramping, and mildly bloody diarrhea, 9 hours after a suicidal ingestion of illegally imported rat poison. [calpoison.org]

  He had noticed severe paresthesia all over his body and abdominal cramps for three days. He also had pain in his abdomen and a few loose stools. [pmj.bmj.com]

  On arrival, he was complaining of severe abdominal cramps and was vomiting. His medical history was significant for depression and alcoholism, but he was not taking any medication. [ncbi.nlm.nih.gov]

• Jaundice

  […] breakdown of the hemoglobin of red blood cells (hemolysis); irregular heart rhythms (ventricular arrhythmias); coma; seizures; bleeding within the intestines (intestinal hemorrhage); and yellowing of the skin, mucous membranes, and whites of the eyes (jaundice [rarediseases.org]

  Hepatic failure or jaundice occurs in extreme cases. Alopecia, a hallmark of thallium poisoning, occurs 7-12 days after other symptoms begin. Hair loss commonly involves the scalp, often involves body hair, and is generally not permanent. [calpoison.org]

  Copper Toxicity can cause vomiting, hematemesis, hypotension, melena, glaucoma, cataracts, jaundice, eye disorders, and gastrointestinal distress. [house.wikia.com]

• Metallic Taste

  The ingestion of lower lethal doses causes gastrointestinal hemorrhage, gastroenteritis, metallic taste, salivation, nausea, and vomiting. [ijoem.com]

• Tachycardia

  Alopecia and painful neuropathy are its cardinal features, others being gastrointestinal disturbances, encephalopathy, tachycardia, ataxia, hepatorenal and cardiac damage etc. [ncbi.nlm.nih.gov]

• Hypertension

  Immediate cardiovascular complications included hypertension, sinus tachycardia, ECG abnormalities and an episode of ventricular fibrillation. [ncbi.nlm.nih.gov]

  ] Other dermatologic findings include crusted eczematous lesions, hypohidrosis, anhidrosis, palmar erythema, stomatitis, and painful glossitis with redness of the tip of the tongue. [23] Other symptoms Cardiovascular symptoms include tachycardia and hypertension [emedicine.medscape.com]

  The patient continued to be tachycardic and hypertensive and subsequently developed renal failure. On hospital day three, the patient developed hypotension that did not respond to fluids. [doi.org]

• Hypotension

  On hospital day three, the patient developed hypotension that did not respond to fluids. The patient required vasopressors and was transferred to a tertiary care center to undergo continuous renal replacement therapy (CRRT). [ncbi.nlm.nih.gov]

  Other symptoms include breakdown of the hemoglobin of red blood cells (hemolysis), a low level of iron in the red blood cells (anemia), and low blood pressure (hypotension). [rarediseases.org]

  In blood, about 70% of it is bound to red cells; it is mainly excreted by the kidneys. 2 Poisoning by thallium causes a variety of symptoms ranging from tachycardia, hypotension, and gastroenteritis to polyneuropathy, alopecia, and dystrophy of nails. [oem.bmj.com]

  Aug 2017 [Refereed] Hyperkalemia due to excessive intake of sweet potato and banana Makoto Onodera, Satoshi Kikuchi, Yasuhisa Fujino, Masayuki Sato and Yoshihiro Inoue Journal of Case Reports in Medical Science 2(1) 1-5 Jan 2017 [Refereed] Prolonged hypotension [researchmap.jp]

• Visual Impairment

  To determine the cause of visual impairment and to document the late eye disturbances in a case of thallium poisoning. [ncbi.nlm.nih.gov]

  Our patient had severe visual impairment and prolonged P100 latency of visual evoked potential due to retrobulbar neuritis. [pmj.bmj.com]

  Abstract Purpose: To determine the cause of visual impairment and to document the late eye disturbances in a case of thallium poisoning. [link.springer.com]

• Alopecia

  Alopecia and painful neuropathy are its cardinal features, others being gastrointestinal disturbances, encephalopathy, tachycardia, ataxia, hepatorenal and cardiac damage etc. [ncbi.nlm.nih.gov]

  In patients with alopecia in whom gastrointestinal and neurologic complaints are observed, thallium poisoning must be included in the differential diagnosis. [symptoma.com]

• Anhidrosis

  One month after the poisoning, Mees lines (transverse white lines on the nails) appear in the nail plate. [22] Other dermatologic findings include crusted eczematous lesions, hypohidrosis, anhidrosis, palmar erythema, stomatitis, and painful glossitis [emedicine.medscape.com]

  Other findings may include crusted eczematous lesions, hypohidrosis (reduced sweating), anhidrosis (absence of sweating), palmar erythema, painful glossitis (sore tongue) with redness of the tip of the tongue, and stomatitis. [dermnetnz.org]

  Other findings may include crusted eczematous lesions, hypohidrosis, anhidrosis, palmar erythema, painful glossitis with redness of the tip of the tongue, stomatitis and hair discoloration. [patient.info]

• Hyperkeratosis

  Approximately 1 month after thallium exposure, Mees lines (transverse white lines on the nails) appear in the nail plate. [22] Other dermatologic findings include well-demarcated hyperkeratosis of the palms and soles, crusted eczematous lesions, hypohidrosis [emedicine.medscape.com]

  Skin and nail symptoms include hardened patches of skin (hyperkeratosis) with unusually deep creases on the palms of the hands and the soles of the feet, unusual darkening of certain areas of the skin (hyperpigmentation), transverse white bands on the [rarediseases.org]

• Peripheral Neuropathy

  We report a case of thallium poisoning who presented initially with gastrointestinal symptoms and later developed neurological features (peripheral neuropathy and delirium). [ncbi.nlm.nih.gov]

• Confusion

  A 45-year-old man developed a painful and rapidly progressive sensory-motor polyneuropathy associated with confusion and convulsions. This resulted in hypoventilation and led to respiratory failure and coma. [ncbi.nlm.nih.gov]

  Subsequent neurologic symptoms typically appear 2-5 days after exposure with a rapidly progressive and severe nerve pain which can be confused with an atypical Guillain-Barré syndrome. [michigan.gov]

• Headache

  Overexposure may cause headaches, drowsiness, confusion, seizures, and life-threatening complications. [rarediseases.org]

  These symptoms can include pain, loss of reflexes, convulsions, muscle wasting, headaches, numbness, dementia, psychosis, and even coma. [medicinenet.com]

  Within three days of being poisoned, victims can suffer headaches, muscle problems, convulsions, coma, delirium, dementia and even psychosis. A dose as small as one gram can lead to death. [news.bbc.co.uk]

  […] most important electrolytes, essentially the loss of potassium as a result of thallium toxicity will cause an electrolytes imbalance leading to the following symptoms which can be signs of thallium toxicity: • Eating disorder • Fatigue • Muscle pain • Headache [naturalhealthgroup.com.au]

• Tremor

  In the second week he developed ophthalmoplegia, nystagmus, and neck tremor and later developed alopecia, and thallium poisoning was suspected. His serum thallium level on the 18th day of illness was 40 980 micro g/ml. [ncbi.nlm.nih.gov]

  After the third dialysis, ptosis and nystagmus improved and after the seventh dialysis he was fully conscious and neck and trunk tremor subsided. [pmj.bmj.com]

  Characteristic of the condition are abdominal pain, vomiting, bloody diarrhea, tremor, delirium, and alopecia. [medical-dictionary.thefreedictionary.com]

  Tremors, paresthesia, painful polyneuropathy, facial palsy, seizures, ataxia, psychosis and severe weakness are reported, with convulsions and coma being some of the most severe manifestations. [symptoma.com]

  Overexposure to tin may damage the nervous system and cause psychomotor disturbances including tremor, convulsions, hallucinations, and psychotic behavior. [rarediseases.org]

• Ataxia

  Alopecia and painful neuropathy are its cardinal features, others being gastrointestinal disturbances, encephalopathy, tachycardia, ataxia, hepatorenal and cardiac damage etc. [ncbi.nlm.nih.gov]

  Tremors, paresthesia, painful polyneuropathy, facial palsy, seizures, ataxia, psychosis and severe weakness are reported, with convulsions and coma being some of the most severe manifestations. [symptoma.com]

  A progressive cerebellar syndrome with impaired ability to coordinate voluntary movements (ataxia) of the arms may also be present. [rarediseases.org]

  Weakness, gait disturbances, and ataxia may also develop. In cases of chronic exposure, signs of basal ganglia damage may be present with Parkinsonian-like symptoms, such as resting tremor. [cdc.gov]

Although poisoning by this heavy metal is quite rare, the combination and onset of GI and neurological symptoms, followed by hair loss, puts thallium at the top of the list as the potential cause [14]. To make the diagnosis, blood or urine levels of thallium are evaluated. Levels of this element may vary depending on the timing of poisoning and sample taking, but in the case of acute poisoning, levels will be very high. Reference values are 0-5 µg/L and certain reports have confirmed values of more than 7,000 µg/L in urine and more than 30,000 µg/L in blood [9] [10]. Additionally, hair sampling and subsequent toxicology evaluation may be performed.

In addition to thallium levels, a full workup including complete blood count (CBC), serum electrolytes, blood pressure monitoring, pulse oximetry and a general assessment of the patient, since the majority of individuals are in poor overall condition. If a strong clinical suspicion of thallium poisoning is made, treatment should be started immediately, before toxicological confirmation.

Treatment principles aim to remove thallium from the circulation, which can be done through several ways. Hemodialysis or hemoperfusion, gastric lavage and the use of laxatives are indicated in early stages of poisoning [10], but the two most common modalities are the administration of Prussian blue and activated charcoal [7]. Both agents can successfully bind to thallium and eliminate it from the circulation and the gastrointestinal tract, respectively [15]. Prussian blue is given in doses of 60 mg/kg q6h through a nasogastric tube, to facilitate removal of thallium from the gut [7]. Supportive treatment consists of fluid administration, antiepileptics such as diazepam and other measures that are necessary to keep the patient from going into shock. It is not recommended to use penicillamine and diethyldithiocarbamate, two frequently used chelating agents because they may redistribute thallium into the central nervous system and worsen the prognosis [7].

The prognosis significantly depends on the dose and onset of treatment. Fatal outcomes are not uncommon and can reach up to 20% according to certain reports, but a fatality ratio of 40% in cluster cases has been observed [9]. Despite adequate treatment, various neurological sequelae may develop permanently, especially in the setting of chronic exposure to thallium. For these reasons, a high dose of clinical suspicion and early treatment may provide significantly better outcomes.

Thallium is a gray to bluish-white water-insoluble heavy metal that mainly exists in the form of thallium salts, which are odorless, tasteless and colorless [2]. Because of its toxicity, thallium was used as a rodenticide and insecticide throughout the world but was eventually banned during the 1970s. Unfortunately, it is still being used in many countries over the world, mainly in Africa. This metal is used for optic lens manufacturing, but also in various other fields of industry. Additionally, it is one of the several radioisotopes used in the medical field (thallium-201), as a contrast agent. Although even minimal concentrations of thallium may cause toxicity, the lethal dose is established to be 10-15 mg/kg [8].

Thallium poisoning is a rare occurrence and medical literature includes data that are primarily gathered from sporadic cases. Toxicity of this substance may occur by various means, but ingestion is by far the most common pathway. Accidental ingestion is most commonly seen, but cases of intentional poisoning by contaminating food have been reported in various parts of the world [3] [9]. Rarely, thallium can be inhaled, which can occur in the setting of occupational exposure or can be absorbed through the skin.

Various models have shown toxic properties of thallium in the human body. Because of its structural similarity with potassium, once thallium enters the body, it becomes involved in various processes in which potassium is either a cofactor or a necessary molecule. Thallium has much higher affinity for the sodium-potassium ATPase pump than potassium [10], which is one of the most important cellular structures in maintaining electrolyte equilibrium and resting membrane potential. When this pump does not perform its function, normal electrolyte transfer and membrane potential is severely impaired. Various processes in the tricyclic acid (TCA) cycle are interrupted as well, including the activity of pyruvate kinase and succinate dehydrogenase [1]. Ribosomal synthesis of amino acids and proteins [5], inhibition of riboflavin formation (one of the key elements in the mitochondrial electron transport chain) and disruption of keratin formation are also known effects of thallium as it gains entry into human cells. Consequently, depletion of ATP and diffuse cell death occurs, which leads to the appearance of symptoms. Keratin formation is disrupted since thallium is able to interfere with cysteine residues and disulfide bonds, thus leading to alopecia that is typically seen in these patients. Additional studies have established that thallium is able to induce significant production of reactive oxygen species (ROS) and cause major oxidative stress, particularly in the central nervous system [11].

Because of its toxicity, the use of Thallium as an insecticide has been banned, which has surely led to a reduced risk for exposure and such strategies can prevent further accidental ingestion of this heavy metal. Ensuring regular follow-ups because of neurological sequelae that can persist is vital in the long-term management of patients.

Thallium is a highly toxic heavy metal that can cause severe and life-threatening complications. Since its initial discovery in the 19th century [1], much has been learned in terms of its mechanism of toxicity, occurrence in nature and treatment. It is known that even minimal concentrations of this metal can cause significant harm, as it does not perform any function in the human body [2]. Thallium poisoning can occur accidentally, through occupational exposure, while intentional poisoning has also been reported, primarily because of its highly potent characteristics [3]. Moreover, the thallium salt, which is the main form in which thallium exists in nature, is colorless, tasteless and odorless [4]. Certain studies have established a striking similarity of thallium and potassium in vivo experiments, which is thought to be vital in the pathogenesis [5]. Because it shares similar characteristics, thallium is able to bind to potassium sites in ribosomes and block protein synthesis, interrupt metabolic pathways of the Krebs cycle in which K+ serves as a cofactor, disrupt the sodium-potassium ATPase pump, but also inhibit synthesis of riboflavin [5] [6]. Additional theories suggest that this metal induces very high rates of oxidative stress and consequent damage to various cell lineages. Combined effects of thallium in the body lead to the appearance of numerous symptoms and most prominent effects are seen in the gastrointestinal tract and nervous system. Initial symptoms appear within several hours after intoxication and include abdominal pain, vomiting, and diarrhea, followed by polyneuropathy, ataxia, tremors, paresthesia and other neurologic symptoms [7], usually after few days. Various other findings may be seen in patients, including ocular and facial palsy, seizures, as well as respiratory failure and shock, but one of the most prominent features is the onset of alopecia approximately three weeks after exposure if patients survive to this period. In patients with alopecia in whom gastrointestinal and neurologic complaints are observed, thallium poisoning must be included in the differential diagnosis. Toxicology analysis may reveal thallium in urine or blood samples and therapy should be started as soon as a strong suspicion of poisoning by this heavy metal is made. Prussian blue and activated charcoal are used due to their capacity to bind to thallium and remove it from the circulation and gut, whereas supportive treatment consisting of blood pressure and ventilation monitoring is vital, as the majority of patients are in poor general condition. Thallium poisoning can be fatal, which is why immediate treatment measures can provide significantly better patient outcomes, but because this form of intoxication is rare, making the diagnosis may present as a significant challenge.

Thallium is a heavy metal that mainly exists in the form of thallium salts, which are odorless, tasteless and colorless. This element is used in various industries, including medical, pharmaceutical and heavy manufacturing. Thallium is a highly toxic substance, however, and because of its characteristics, cases of accidental poisoning and occupational exposure have been documented. Moreover, thallium has shown to be used as a homicidal weapon, as it is extremely potent and can cause severe and life-threatening symptoms. The most common mode of intoxication is ingestion, while much rarer forms include inhalation and absorption through the skin. Current evidence suggests that thallium is able to cause damage to the human organism by substituting potassium in various metabolic processes, as it shares a similar structure with this essential electrolyte once it enters the body. Generation of energy, synthesis of amino acids, proteins and vitamins, and formation of keratin are functions that are known to be impaired when thallium is present in the circulation. The onset of symptoms occurs within hours after exposure and are initially related to the gastrointestinal tract. Abdominal pain, nausea, vomiting and diarrhea that may contain blood are almost always observed. Soon after, thallium causes damage to nervous tissue, which manifests as diffuse pain, weakness, numbness of fingers and limbs, walking and balance disturbances, but also delirium and seizures may be seen. In almost all patients, hair loss will occur about 3 weeks after exposure to thallium and this symptom is considered to be one of the main distinguishing features. The diagnosis is made by obtaining blood and urine levels of thallium. Treatment should be initiated as soon as there is high suspicion for thallium poisoning based on symptoms and aims to eradicate this metal from the body. Various treatment methods have been indicated, but the use of Prussian blue and activated charcoal are the two most effective regimens. These substances are able to bind to thallium and excrete it from the body and are usually given through a nasogastric tube. Despite treatment, thallium poisoning can be fatal and the prognosis depends on the amount of ingested thallium and the onset of treatment.

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