Abstract
Elemental mercury (Hg) is the only metal which evaporates in room temperature and its inhalation may cause toxicity. Hg poisoning may occur by mishandling the metal, particularly in children who play with it. Wide-spectrum of the clinical presentations of chronic Hg poisoning may cause misdiagnosis, particularly when history of exposure is unknown. We report two cases of accidental Hg poisoning, which initially had been diagnosed and treated for brucellosis. The patients were two brothers (7 and 14 years old) who presented with pain in their lower extremities, sweating, salivation, weight loss, anorexia and mood changes on admission. Meticulous history taking revealed that they had played with a ball of Hg since 3 months before admission. The level of urinary Hg was 125.9 and 54.2 9 g/L in the younger and older brother, respectively (normal ≤25 g/L). The patients were successfully treated by dimercaprol and discharged in good condition 24 days after admission. These cases are being reported to emphasize the importance of acrodynia as a differential diagnosis for brucellosis in endemic areas.
Introduction
Mercury or hydrargyrom (Hg) or quicksilver is a highly toxic element and the only metal that evaporates at room temperature. 1 Hg poisoning may occur by mishandling the metal, particularly in children that may play with it. Wide spectrum of the clinical presentations of chronic Hg poisoning may cause misdiagnosis, particularly when the history of exposure is unknown. Brucellosis is the most common zoonosis worldwide, and Iran has been the second country in the world in the prevalence of human brucellosis. 2 Misdiagnosis may occur due to the rare occurrence of Hg poisoning (especially acrodynia) and the high prevalence of brucellosis in Iran. It should be noted that bone and joint pain is one of the possible clinical presentations commonly observed in both diseases. Here we report two cases of accidental Hg poisoning which initially had been diagnosed as and treated for brucellosis before admission to our hospital.
We obtained the approval from the hospital research ethics committee and informed consents from the parents of patients for the treatment and publishing this case study.
Case report
Two brothers (7 and 14 years) were referred to the pediatrics ward of Imam Reza Hospital (Mashhad) with presumptive diagnosis of atypical Kawasaki in January 2008.
The younger brother had a history of pain in his thighs and legs since 2 months prior to admission. His pain had gradually become so severe that he could not sleep, refused walking and missed school for more than a month. He had paroxysmal exacerbation of the pain accompanied with excessive sweating and salivation. The parents complained of his weight loss, anorexia and mood change. The family physician empirically treated him for brucellosis. However, the therapy was ineffective and was stopped after two negative serologic tests (Wright, 2ME and Coombs Wright) for brucellosis.
At the time of admission in our hospital, the boy was irritable and depressed, blood pressure (BP) was 115/90 mm Hg, pulse rate (PR) 146/min, and temperature 37°C. His skin was dry with plantar erythema and papular excoriated rashes in the lower extremities.
The older brother had the same problems, although his story started almost a week later and he had less severe pain. On physical examination, the positive signs were hypertension (125/100 mm Hg), tachycardia (130/min) and excoriated pink papular rashes in lower extremities and buttocks.
On admission, serum sodium, potassium, calcium, creatinin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody (ANA) and anti-DNA, antistreptolysion O (ASO), urinalysis, chest X-ray, MRI of brain and thigh, nerve conduction velocity (NCV) and electromyography (EMG) were normal in both the patients. However, hemoglobin levels were 16.2 and 16.8 g/dl and creatine phosphokinase (CPK) levels were 187 and 69 unit/L (normal 10–90) in the younger brother and the older brother, respectively.
Because of the similar and simultaneous presentation of the two brothers, an environmental toxic exposure was our first diagnosis from the first day of admission but the parents denied it, until the third day when they remembered that for the past 3 months, the boys had been playing with a ball of Hg which they had brought home from a school laboratory. Therefore, their 24-hour urinary Hg concentrations were performed in the research laboratory of Medical Toxicology Research Center by an atomic absorption spectrometer (Perkin Elmer, Model 3030, USA) using the mercuric hydride system (MHS). The results were 125.9 and 45.2 μg/L in the younger brother and older brother, respectively (normal ≤25 μg/L).
Table 1 shows a summary of clinical and abnormal laboratory findings of the two brothers, including their urinary Hg concentrations during hospitalization and after discharge.
Summary of clinical findings and abnormal laboratory results of the two brothers with mercury intoxication (acrodynia)
CPK: creatine phosphokinase, Y: years.
Due to the unavailability of dimercaptosuccinic acid (Succimer) at the time, the patients were treated with dimercaprol (BAL) 3 mg/kg/day for 10 days.
About 10 days after the beginning of chelating therapy, the boys were less irritable but the painful episodes still persisted particularly in the younger brother, and we were forced to use morphine and anti-neuralgic medicines (topiramate, gabapantine and amitriptiline) to relieve the pain. The younger patient was then administered
Discussion
The patients were intoxicated by inhalation of metal Hg vapor and their clinical pictures were compatible with acrodynia. Acrodynia (painful extremities) or pink disease is a characteristic syndrome of Hg intoxication. It is defined by painful, pink discoloration of the hands and feet, irritability, itching, tachycardia, hypertension, polyneuritis, excessive salivation or perspiration, weakness, rashes, and desquamation. 3
In our country, brucellosis is at the top of the list of differential diagnoses for children with any kind of bone and joint problem, especially when they come from rural areas. In humans bone and joint pain due to brucellosis is one of the most common clinical presentations, and simultaneous involvement of two or more people in a family is a common event. 4 Because of the rare occurrence of acrodynia and high prevalence of brucellosis in Iran and close clinical similarities between the two diseases, they were first misdiagnosed and empirically treated for brucellosis.
Table 2 is a summary of several case reports (among children) with final diagnosis of acrodynia, and in none of them Hg poisoning or brucellosis was the primary diagnosis.5–11 According to the referenced data in the table, pheochromocytoma is the most common initial misdiagnosis for acrodynia. Hypertension, excessive sweating, tachycardia and high urine chatecholeamines are common between acrodynia and pheochromocytoma. 5 In our patients, painful extremities, skin rashes and simultaneous involvement of the two brothers are in favor of Hg poisoning. Pheochromocytoma can have familial presentations, but these forms are always part of a syndrome like multiple endocrine neoplasia, Von Hippel-Lindau disease and neurofibromatosis.
Clinical manifestations and primary diagnosis for different diseases in children who were finally diagnosed with mercury poisoning—reported from different countries
CNS: central nervous system, FTT: failure to Thrive, ITP: ideopathic thrombocytopenic purpura, M: months, Y: years.
In our cases, Kawasaki was easily ruled out, as there was no history of fever and all of the inflammatory markers were normal; furthermore their ages and simultaneous involvement of the two brothers were also not consistent with Kawasaki. The conflicting point is that there are reports that have shown increased urinary Hg level in Kawasaki. 12
As indicated inTable 2, hyperthyroidism, Guillain Barré syndrome, sepsis, Lesch-Nyhan syndrome and Fabry disease are other differential diagnoses for Hg intoxication in children.
High hemoglobin which was seen in both of our patients has been reported in another three cases of Hg poisoning. It seems that hemoconcentration in acrodynia is caused by intravascular and extracellular volume depletion.13–15
Dimercaptosuccinic acid (DMSA) is the only US Food and Drug Administration (FDA)-approved chelator for treating Hg poisoning in children.
12
However, due to its unavailability, the patients were treated with BAL and
The educational deficit of the younger patient who revealed more severe toxicity may be due to neurological complications of Hg poisoning.
Conclusion
In the developing world, where brucellosis is common, Hg intoxication should be considered as a differential diagnosis. BAL and
Footnotes
Acknowledgements
We would like to thank Nahid Asgharian; pediatric nurse of Imam Reza hospital, for her technical support. We are very grateful to Dr Kia Balali-Mood for English editing of the final revised manuscript.
The authors declared no conflicts of interest.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.