Toxic Enigma: Jaundice, Neuropathy, and Hair Loss

Patient Profile: A Lawyer with Progressive Multi-System Symptoms

A 51-year-old female lawyer, residing in a strictly residential area of Buenos Aires, presented to the emergency department in June 2018. She had a medical history of irritable bowel syndrome and hypothyroidism, the latter managed with levothyroxine 50 µg daily. Her condition had been closely monitored by an endocrinologist.

Exposure Details

The patient had been experiencing myalgia and vertigo for one month, which progressively worsened to include abdominal pain, daily episodes of vomiting (up to three times per day), and increasing asthenia over the prior week. She denied exposure to potential toxins, including alcohol, tobacco, herbal remedies, insecticides, medications other than levothyroxine, or any industrial pollutants in her environment. There were no similar symptoms reported among family members, neighbors, or close contacts.

Unexplained Symptoms: A Month of Neurological and Gastrointestinal Decline

At the time of her initial physical examination, her vital signs were stable, but she exhibited temporal-spatial disorientation, incoherent speech, jaundice, and asterixis (flapping tremor). Subsequent examinations revealed alopecia affecting the scalp, armpits, and eyebrows, brown facial macules, anhidrotic dry skin, plantar hyperkeratosis, and ulcerations on the lower limbs. Additionally, she had generalized hypotonia, weakness, hyporeflexia, and decreased sensitivity in all four extremities.

Physical Examination and diagnostic journey: Clues Pointing to a Hidden Toxic Exposure

Upon admission, the patient was diagnosed with acute liver failure based on laboratory findings:

• Total bilirubin: 10.3 mg/dL

• Direct bilirubin: 5 mg/dL

• Aspartate transaminase (AST): 78 U/L

• Alanine transaminase (ALT): 194 U/L

• Prothrombin time: 40%

• International normalized ratio (INR): 1.7

• Albumin: 2.3 g/dL

• Platelet count: 60,000/mm³

• Lactate dehydrogenase (LDH): 1,130 U/L

• C-reactive protein (CRP): 69 mg/dL

Brain computed tomography (CT) scan and abdominal ultrasound showed no abnormalities. Comprehensive testing ruled out infectious (hepatitis A, B, C, Epstein-Barr virus, cytomegalovirus, HIV) and autoimmune etiologies (negative antimitochondrial antibody, anti-liver-kidney microsomal antibody, smooth muscle antibody, and factor associated with neutral sphingomyelinase activation). Thyroid function was normal, eliminating endocrinological causes.

The presence of alopecia, hyperkeratosis, ulcers, and neurological symptoms raised suspicion of heavy metal poisoning, leading to targeted toxicological testing.

Hospital Presentation & Initial Treatment Approaches

With the diagnosis of acute liver failure of unknown etiology, the patient was hospitalized for further evaluation and supportive treatment, including intravenous hydration, nutritional support, and hepatoprotective measures.

Laboratory Findings & Confirmation of Thallium Poisoning

Heavy metal testing yielded the following key findings:

• Plasma thallium: 12 µg/dL (reference: ≤80 µg/dL)

• Thallium urinary excretion (TLU): 540 µg/g creatinine (reference: 0.4–10 µg/g creatinine, highly elevated)

While her plasma thallium level was not markedly elevated, her urinary thallium excretion was significantly increased, confirming chronic thallium poisoning.

Treatment Strategy: Chelation Therapy for Thallium Poisoning

Upon confirming thallium poisoning, the patient was started on chelation therapy with oral D-penicillamine (250 mg every 6 hours). This agent binds to thallium and promotes its renal excretion. Supportive therapy included electrolyte management, symptomatic treatment for nausea and myalgia, and ongoing monitoring of liver function and neurological status.

Thallium Poisoning: Laboratory Trends and Treatment Response

The patient showed progressive improvement after two weeks of chelation therapy and was discharged with continued outpatient treatment.

• Monthly follow-ups showed a gradual 10% decrease in TLU levels at each visit.

• By six months, all symptoms—including alopecia, neurological deficits, and skin changes—had resolved.

• At the one-year mark, her TLU level normalized to 2.3 µg/g creatinine.

Thallium Poisoning Prognosis: Recovery and Long-Term Outcome

The patient made a full recovery with no residual symptoms. Despite extensive investigation, the source of her thallium exposure remained unidentified. Given the insidious nature of her symptoms and lack of apparent exposure, intentional or environmental exposure was suspected but could not be confirmed.

Conclusion: Key Insights from a Rare Case of Thallium Poisoning

The clinical presentation in this case aligns with previously documented reports of thallium poisoning, which is characterized by a classic triad: abdominal pain, peripheral neuropathy, and alopecia. The timeline of symptom progression is a key diagnostic clue, typically following a predictable sequence: gastrointestinal symptoms (nausea, vomiting, diarrhea) appear within hours of exposure, neurological symptoms (peripheral sensorimotor neuropathy, disorientation, psychosis, seizures) emerge after several days, and alopecia becomes apparent weeks later. Based on the patient’s two- to four-week history of progressively worsening symptoms, the findings strongly suggested chronic thallium toxicity.

Although thallium affects multiple organ systems, acute liver failure as an isolated presentation is rare. Instead, hepatic involvement usually occurs as part of multi-organ toxicity. Neurologically, painful peripheral neuropathy (“burning feet syndrome”) is commonly described, whereas this patient presented with hypoesthesia (reduced sensation) rather than pain, demonstrating the variability in clinical manifestations.

Regarding treatment, the preferred antidote for thallium poisoning is Prussian blue (3 g daily for adults), which enhances fecal elimination of the metal. However, Prussian blue was not administered in this case for three main reasons: (1) lack of immediate availability, (2) the patient’s chronic constipation, which contraindicated its use, and (3) its primary role in acute, rather than chronic, thallium poisoning. Instead, D-penicillamine, a chelating agent, was chosen due to its availability and ability to promote thallium excretion.

Key Takeaways: Recognizing and Managing Thallium Poisoning

• Chronic thallium poisoning is rare and often presents nonspecifically with gastrointestinal, neurological, dermatological, and hepatic symptoms, which can delay diagnosis.

• Alopecia, plantar hyperkeratosis, and peripheral neuropathy are hallmark features of chronic exposure and should prompt heavy metal testing.

• Normal plasma thallium levels do not exclude poisoning; urinary excretion testing is more sensitive in chronic cases.

• Early chelation therapy with D-penicillamine led to full recovery in this case.

• Despite thorough investigation, the source of poisoning was never identified, underscoring the challenges in environmental and toxicological epidemiology.

This case highlights the importance of early recognition of thallium poisoning, as even small doses can be fatal within a short period. The variability of symptoms often leads to misdiagnosis, delaying appropriate management. A high index of suspicion is crucial, especially when unexplained alopecia occurs alongside gastrointestinal and neurological symptoms. Given its rarity and the challenges in pinpointing an exposure source, thallium poisoning remains a toxicological enigma that requires heightened clinical awareness for timely diagnosis and intervention.