Authors: Liang Zhang, Jianping Qin, Shanhong Tang
Institution: Department of Gastroenterology, General Hospital of Western Theater Command
Editor's Note: To help clinicians broaden their horizons and enrich their practical skills in hepatology, Hepatology Digest has invited Dr. Shanhong Tang and his team from the Department of Gastroenterology, General Hospital of Western Theater Command, to create the "Liver Difficult Cases" column. This column compiles "classic cases" encountered by Dr. Tang's team during years of clinical practice and will periodically collect complex or rare clinical cases published in prestigious journals. The focus is on elucidating the diagnostic and treatment approaches for various liver diseases, providing valuable clinical insights for fellow healthcare professionals.Thematic Review
Lead is a toxic heavy metal primarily absorbed through the respiratory or digestive tract. Lead poisoning is often caused by occupational exposure, and its symptoms are nonspecific, including fatigue, abdominal pain, nausea, diarrhea, anemia, muscle paralysis, or limb weakness. In recent years, the incidence of lead poisoning has declined. Therefore, lead poisoning is often overlooked in clinical practice. This article reports a case of lead poisoning caused by long-term use of Tibetan medicine for epilepsy, presenting with retrosternal and abdominal pain along with mild nonspecific signs. After ruling out organic lesions and considering the patient’s history of long-term use of Tibetan medicine and the high-density shadow in the gastrointestinal tract, particularly in the appendix, indicating the presence of heavy metals, the possibility of heavy metal poisoning was considered. Finally, lead poisoning was confirmed through heavy metal testing.
Case Summary
A 15-year-old female patient was admitted to our department on November 2, 2022, due to “retrosternal pain with abdominal pain and vomiting for 20 days.” The patient had experienced retrosternal pain and upper abdominal pain during a trip 20 days prior, with no obvious cause. The pain was paroxysmal, accompanied by nausea and vomiting, but without radiating pain, palpitations, chest tightness, chills, fever, or other discomforts. Defecation and flatulence did not alleviate the pain. The patient was initially treated at a local hospital, where an abdominal ultrasound suggested gastrointestinal distension. The symptoms were relieved after taking Xiangsha Yangwei Wan and the Tibetan medicine Zuo Zhu Da.
Six days later, the symptoms recurred, and the patient was treated at a hospital in Beijing. Liver function tests showed ALT 463 U/L, total bilirubin 50.2 μmol/L, and direct bilirubin 19.96 μmol/L. A complete blood count revealed hemoglobin of 94 g/L. The symptoms improved after acid suppression, stomach protection, and liver protection treatment.
However, on the fifth day, the upper abdominal pain recurred, and the patient vomited several times after eating. She was then treated at a hospital in Qingdao, where liver function tests showed ALT 195 U/L, AST 46 U/L, and total bilirubin 58.5 μmol/L. The hemoglobin level had dropped to 84 g/L. Abdominal CT scan suggested a high-density shadow in the appendix. The symptoms were slightly relieved after acid suppression and antispasmodic treatment, but the pain continued to recur.
For further diagnosis and treatment, the patient was admitted to our department.
Medical History: The patient had a history of epilepsy during childhood, which was controlled with Tibetan medicine, with no seizures since then. She had no history of hypertension, coronary heart disease, diabetes, or hepatitis.
Laboratory Tests: Liver function tests showed total bilirubin 66.8 μmol/L, direct bilirubin 23.7 μmol/L, indirect bilirubin 43.1 μmol/L, ALT 110.2 IU/L, AST 31.2 IU/L, γ-GGT 172.9 IU/L, ALP 99.0 IU/L. Hemoglobin concentration was 91 g/L, with a neutrophil percentage of 76.3% and lymphocyte percentage of 17.3%. Reticulocyte percentage was 0.42%, and high-sensitivity C-reactive protein was 16.87 mg/L. Lipid profile, renal function, electrolytes, tumor markers, and cardiac markers were unremarkable.
Imaging Studies: Abdominal enhanced CT showed no significant swelling of the appendix wall, with a high-density shadow in the lumen. CT scans of the liver, gallbladder, pancreas, and spleen showed no abnormalities. Gastroscopy revealed grade B reflux esophagitis and chronic non-atrophic gastritis with bile reflux. Colonoscopy showed no significant abnormalities. Video electroencephalogram (EEG) did not show any epileptic waveforms.
Diagnosis and Treatment Process
During hospitalization, the patient experienced recurrent retrosternal and upper abdominal pain, characterized by colic, accompanied by nausea, vomiting, and numbness in the scalp and limbs. Treatment included acid suppression, stomach protection, antiepileptic therapy, liver protection, enema, and analgesia, but the symptoms persisted.
During this period, the hemoglobin concentration decreased from 91 g/L at admission to 68 g/L. The patient had no history of gastrointestinal bleeding, such as hematemesis or melena, and her menstrual cycle was regular. Therefore, a bone marrow biopsy was performed to rule out hematological disorders. The biopsy showed active bone marrow hyperplasia with significant erythroid and megakaryocytic proliferation. The bone marrow smear indicated marked erythroid hyperplasia with predominant intermediate and late erythroblasts, and basophilic stippling was easily observed in the cytoplasm. This initially suggested a diagnosis of proliferative anemia with increased megakaryocytes.
Given the patient’s history of using Tibetan medicine for epilepsy control and the presence of high-density shadows in the gastrointestinal tract on CT, along with recurrent abdominal pain that could not be explained by common gastrointestinal diseases, we considered the possibility of heavy metal poisoning. Blood and urine tests for heavy metals were recommended, and the toxicology report revealed elevated blood and urine lead levels (122.3 ng/mL and 273.3 ng/mL, respectively), indicating lead poisoning. Further tests confirmed the diagnosis with blood lead levels at 626 μg/L and urine lead levels at 75.9 μg/L. The patient immediately discontinued Tibetan medicine, and treatment with calcium disodium edetate (CaNa2-EDTA) chelation was initiated (CaNa2-EDTA 1 g + 500 mL 5% glucose intravenously for 3 days, followed by a 4-day break). After treatment, the patient’s abdominal pain, vomiting, and neurological symptoms improved significantly, and her hemoglobin level increased to 98 g/L. After two treatment cycles, blood lead levels returned to normal, and liver function normalized.
Expert Commentary
Lead is a toxic heavy metal primarily absorbed through the respiratory or digestive tract, with lead poisoning often caused by occupational exposure. Due to the underdeveloped blood-brain barrier and immune system in children, lead poisoning poses significant health risks. The nonspecific symptoms of lead poisoning include fatigue, abdominal pain, nausea, diarrhea, anemia, muscle paralysis, or limb weakness. As the incidence of lead poisoning has declined with societal progress, it is often overlooked in clinical practice.
In children, lead poisoning is typically caused by the ingestion of lead-contaminated food. In this case, the patient had a history of intermittent use of Tibetan medicine to control epilepsy symptoms, suggesting that lead entered the bloodstream through the medicine. It is noteworthy that before considering lead poisoning, the patient had been treated at multiple hospitals and had taken Tibetan medicine to relieve abdominal pain. Although Tibetan medicine like Zuo Zhu Da is widely used for treating digestive system diseases, it often contains high levels of heavy metals such as lead and mercury, posing potential health risks with long-term use. Therefore, the patient’s prolonged use of antiepileptic Tibetan medicine and Zuo Zhu Da may have contributed to lead poisoning.
Lead is present in trace amounts in the body, primarily stored in bones, with no biological function. Excessive lead intake is harmful to multiple organs and can cause anemia, cardiovascular diseases, neurotoxicity, and nephrotoxicity. In the vascular system, lead inhibits a series of enzymes involved in hemoglobin synthesis, increasing red blood cell fragility. There is a dose-dependent relationship between lead exposure and the severity of anemia. In this case, the patient also presented with mild to moderate anemia. Notably, before the diagnosis of lead poisoning, bone marrow biopsy results indicated proliferative anemia with increased megakaryocytes. Basophilic stippling was observed in the bone marrow smear, a potential early sign of heavy metal poisoning with important clinical significance.
Lead can cross the blood-brain barrier, causing irreversible damage to the nervous system, affecting children’s normal development. Neurological symptoms, such as depression, anxiety, and peripheral neuropathy, become apparent when blood lead levels exceed 300 μg/L. In children, blood lead levels above 450 μg/L can cause symptoms such as headache, vomiting, numbness, and abdominal pain. Studies have shown that even low levels of lead poisoning can lead to decreased IQ, cognitive and executive function, and attention span. According to the U.S. Centers for Disease Control and Prevention (CDC), blood lead levels exceeding 200 μg/L are considered lead poisoning. In this case, the patient’s retrosternal pain and limb numbness were likely specific symptoms of lead poisoning, considering her history of epilepsy and the absence of epileptic patterns on EEG.
Abdominal pain caused by lead poisoning typically presents as colic. Physiologically, lead inhibits Ca-ATPase activity, leading to smooth muscle spasms. The patient presented with retrosternal and abdominal pain accompanied by mild, nonspecific signs. Reflux esophagitis could explain the retrosternal pain but not the abdominal pain. After ruling out organic lesions through a series of examinations, the history of long-term Tibetan medicine use, gastrointestinal high-density shadows, particularly in the appendix, suggested the presence of heavy metals, leading to the consideration of heavy metal poisoning, ultimately diagnosed as lead poisoning. Treatment primarily involved the use of chelating agents such as CaNa2-EDTA, dimercaptosuccinic acid, dimercaprol, and D-penicillamine. The patient’s symptoms improved significantly with CaNa2-EDTA treatment.
In summary, lead poisoning is often misdiagnosed due to its low incidence and nonspecific symptoms. As gastroenterologists, we must consider abdominal and systemic diseases in patients with abdominal pain, and detailed medical history is crucial for early diagnosis. This case provides a clinical approach and reference for the diagnosis and treatment of similar patients.
