Minireviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. May 19, 2020; 10(5): 95-100
Published online May 19, 2020. doi: 10.5498/wjp.v10.i5.95
Abdominal pain related to adulterated opium: An emerging issue in drug addicts
Maryam Vahabzadeh, Bruno Mégarbane
Maryam Vahabzadeh, Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Bruno Mégarbane, Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Paris-Diderot University, INSERM UMRS-1144, Paris 75010, France
ORCID number: Maryam Vahabzadeh (0000-0002-6234-1834); Bruno Mégarbane (0000-0002-2522-2764).
Author contributions: Vahabzadeh M and Mégarbane B have developed the framework of the paper; Vahabzadeh M wrote the first draft; Vahabzadeh M and Mégarbane B worked in subsequent drafts; all authors confirmed the last version before submission. The authors read and approved the final manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Bruno Mégarbane, MD, PhD, Professor, Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Paris-Diderot University, INSERM UMRS-1144, 2 Rue Ambroise Paré, Paris 75010, France. bruno.megarbane@lrb.aphp.fr
Received: December 23, 2019
Peer-review started: December 23, 2019
First decision: February 20, 2020
Revised: April 7, 2020
Accepted: April 23, 2020
Article in press: April 23, 2020
Published online: May 19, 2020

Abstract

Lead may contaminate opium, heroin and illicit opiates and is particularly observed in Iran. Lead, a natural heavy metal is able to interfere with several organ functions after ingestion or inhalation. Lead poisoning manifestations are non-specific and thus lead poisoning remains difficult to diagnose. Among the manifestations, abdominal pain is almost the most frequent symptom causing patients to seek medical care. In patients with a history of opium addiction presenting with moderate-to-severe abdominal pain, lack of diagnosis of lead toxicity may thus result in time-consuming and unnecessary medical work-ups that can end up in invasive surgery. This paper aims to briefly review abdominal pain as an emergency issue and the leading symptom of lead poisoning that brings most of the patients to healthcare facilities. All published adult cases and case series of opium addicts admitted with abdominal pain due to lead-adulterated opium consumption have been reviewed. A trend of increasing numbers of lead poisoning cases has recently emerged among opium addicts in Iran. Due to the non-specific manifestations and hazardous effects, psychiatrists and emergency physicians should consider lead poisoning in patients with a past or present history of opium addiction referred for acute abdominal pain, particularly in case of colicky abdominal pain.

Key Words: Addiction, Opium, Lead, Poisoning, Abdominal pain, Toxicity

Core tip: Lead may contaminate opium, heroin and illicit opiates, as is particularly observed in Iran. Abdominal pain is almost the most frequent symptom bringing the patients to medical care. Psychiatrists and emergency physicians should be aware of this complication and consider lead poisoning in opiate users referred for acute abdominal pain. Specific early management is crucial to improve prognosis.



INTRODUCTION

Toxicity from heavy metals can occur following their overload in the body due to exposure to various sources. Considered as one of the highly toxic heavy metals, lead is naturally available in metallic and organic forms and can interfere with the function of several organs such as the central nervous system, the liver, the kidneys, the hematopoietic and cardiovascular systems[1]. Different sources of exposure are responsible for lead toxicity in humans, mainly drinking water, paint, occupational exposure and leaded gasoline[2]. Metallic lead can enter the body via ingestion (depending on the age and nutritional status) and inhalation (depending on the particle size)[3]. However, the majority of lead poisonings are due to ingestion and its consequent absorption occurs in the smaller intestine resulting in its accumulation in blood, bone, and fatty tissues[4].

Also known as plumbism, lead poisoning is still one of the main areas of concern in the developing world including Iran. Even though cases due to occupational lead poisoning have declined, overall metallic lead poisoning has markedly increased over the past few years[5].

Lead poisoning is difficult to diagnose due to non-specific manifestations. The main symptoms and signs include moderate-to-severe abdominal pain (also known as lead colic), appetite loss, constipation, anemia, liver and renal function impairment, and neurologic complications. Major risk factors for lead toxicity are young age (children), lack of minerals and protein in the diet, as well as poor socioeconomic conditions[4]. However, another notable major and recently recognized risk factor for lead poisoning is addiction to opium.

Lead poisoning due to abuse of contaminated opium was first reported in 1970s[6,7] and subsequently in 1989 following lead-contaminated heroin[8]. Interestingly, lead poisoning has been reported from lead-contaminated opium available in the Iranian market[9] while opium samples were confirmed to be contaminated with lead in Kerman province of Iran[10]. Failure to detect or misdiagnosis of lead poisoning in patients with a history of opium addiction presenting with abdominal pain may result in time-consuming gastrointestinal work-ups or even unnecessary abdominal surgery[11]. The current paper aims to review abdominal pain as the leading emergent symptom of lead poisoning referring opiate addicts to healthcare facilities. To address this goal, we reviewed all published cases and series of adult drug addicts presenting with abdominal pain attributed to lead poisoning from lead-adulterated opium.

LEAD TOXICITY
Chemical properties of lead

Lead is a bluish-gray silvery metal with atomic number of 82 and two isotopes 206Pb and 208Pb, and is available in two forms of metallic (also called inorganic) and organic lead (tetraethyl and tetramethyl lead). Lead has no particular taste or smell, and at atmospheric pressure, melts at 621.3 °F (327.4 °C), and boils at 1740 °C[12].

Exposure to lead

Exposure to lead may result in multisystemic toxicity. The risk of exposure to lead is higher among children and those with certain occupations. However, lead exposure in the workplace alone does not count as significant source of poisoning[13].

Upon exposure, lead is mainly absorbed from the gastrointestinal and respiratory systems. Over days to years, it accumulates in the body, particularly in bones, before manifestations occur. Also known as plumbism, lead poisoning is defined as abnormally elevated concentrations of lead in the blood resulting in non-specific symptoms and signs. Depending on the severity of poisoning, it can cause gastrointestinal manifestations such as abdominal pain and constipation, in addition to anemia, impairment of the nervous system, liver, kidney, heart, and reproductive system as well as developmental impairment in children. The exact mechanism by which lead exerts its toxic effects on the GI is not yet known. However, some theoretical mechanisms are change in luminal ion transport, impairing intestinal motility, and spasmodic contractions in smooth muscles of the intestinal wall. The latter is considered to be one of the major causes of abdominal pain in lead-poisoned patients. The limit of concern for blood lead level (BLL) in children is 5 µg/dL, while it is much higher for adults (above 25 µg/dL)[14].

Over the past decade, one concerning source of exposure to lead was reported to be lead adulterated opium in Iran, although identified last century[6,7]. Iran lies in the major pathway of opium trafficking in the Middle East. According to the United Nations Office on Drug and Crime, 74% of the world opium seizures and 25% of the world heroin and morphine seizures in 2012 occurred in Iran[15]. Therefore, opium addiction is one of the major governmental and health challenges in the country. Although not yet widely reported, lead-contaminated opium has caused increasing numbers of poisonings to be referred to emergency departments and clinical toxicology centers.

REVIEW OF LEAD POISONING REPORTS DUE TO ADULTERATED OPIUM

Masoodi et al[9] first reported three male patients from Iran with acute abdominal pain, abnormal liver function tests, and anemia due to chronic oral opium use. None of the patients had occupational exposure and their chief complaint was abdominal pain and varying degrees of constipation. All patients were withdrawn from opium while two with BLLs above 80 µg/dL received chelating agent (CaNa2EDTA). All were asymptomatic with normal laboratory tests after 3-4 wk of follow-up.

Further reported cases of lead poisoning due to lead-contaminated opium are depicted in Table 1, with the country of patient origin and additional clinical and laboratory data.

Table 1 Reports of lead poisonings due to adulterated-opium abuse and their supplementary data.
Type of studyCountryGender–age/mean age (y/o)Route of abuseMajor clinical findingsLaboratory findingsBLL (µg/dL)TreatmentRef.
Case reportIranM-34IngestionAP, N/VAnemia, basophilic stippling of erythrocytes, elevated liver enzymes95CaNa2EDTA[9]
Case reportIranM-57IngestionAP, nausea, severe constipationAnemia, elevated liver enzymes81CaNa2EDTA[9]
Case reportIranM-45IngestionEpigastric and periumbilical APAnemia, elevated liver enzymes37.5Opium cessation[9]
Case reportIranM-65IngestionAP, Burton's line, generalized ileus, N/VAnemia, elevated liver enzymes150Dimercaprol + CaNa2EDTA[11]
Case reportIranM-25Ingestion and inhalationAP, malaise, N/V, weakness, excess sweating, dark urine, generalized bone painAnemia, elevated liver enzymes350Dimercaprol + CaNa2EDTA[16]
Case reportNetherlandsM-40IngestionAPAnemia, basophilic stippling, elevated liver enzymes86Dimercaprol + CaNa2EDTA[17]
Case reportIranM-40IngestionParesthesia in upper and lower extremities, low muscle strength, abdominal tenderness, late onset quadriplegiaAnemia, elevated liver enzymes> 200Dimercaprol + CaNa2EDTA, followed by Succimer[18]
Case reportIranM-32IngestionAP, constipation, loss of appetiteBasophilic stippling50Dimercaprol[19]
Descriptive, cross-sectionalIranM/F-average age: 41.8 ± 13.5IngestionAP, anorexia, weight loss, constipation, nauseaAnemiaAverage: 145 ± 61NA (referred to toxicologists)[20]
Descriptive, retrospectiveIranM-20 to 39InhalationAbdominal crampsAnemiaAverage: 109 ± 37.6Dimercaprol ± CaNa2EDTA[21]
Case reportIranM-38Ingestion and inhalationSevere AP, Burton’s line, muscle weakness, myalgias, and bad temperBasophilic stippling73Dimercaprol + CaNa2EDTA, DP[22]
Case reportSingaporeF-40Ingestion and inhalationSevere lower APAnemia, punctate basophiliaNACalcium gluconate, calcium disodium versenate[7]
Case reportSingaporeM-63IngestionAPAnemia, punctate basophiliaNACalcium gluconate, calcium disodium versenate[7]
Case reportUnited KingdomM-46InhalationColicky AP, constipation, irritability and malaiseExtravascular haemolytic anaemia with punctate basophilic stippling113.8CaNa2EDTA[23]
Case reportIranM-32IngestionDysarthria and progressive upper limb weakness following a refractory AP, constipation, nausea and headacheAnemia, high liver function tests and bilirubin256DP[24]
Case reportIranF-36IngestionSever colicky AP, NV, Pleuritic chest pain, ejection fraction 30%, massive bilateral pleural effusionAnemia (hypochromic- microcytic)78CaNa2EDTA[25]
Case seriesIranM/F-average age: 50.4 ± 13.4IngestionAcute sever APAnemiaAverage: 76.2NA[26]
Case seriesNetherlandsM-average age: 44IngestionAP, NVAnemia, elevated liver enzymesAverage: 179.4CaNa2EDTA[27]
Case seriesIranM-average age: 49.82 ± 11.52IngestionAP, Loss of Appetite, Sleep Disturbance, Fatigue, ConstipationAnemiaAverage: 93.36 ± 27.84DP[28]

As shown in Table 1, the majority of cases of lead poisoning due to lead-contaminated opium[9,11,16-28] are surprisingly reported from Iran with the dominance of men. The case reports from The Netherlands[17,27] and the United Kingdom[23] also concerned two Iranians, one immigrant abusing opium from Iranian suppliers and one Persian citizen addicted to inhalational opium, respectively.

According to Table 1, the main features of lead poisoning are portrayed as gastrointestinal, hepatic and hematologic disorders. Manifestations in opium abusers were clearly attributable to the elevated BLL in comparison with non-addicts; hence, determination of BLL in suspected cases can definitively confirm the diagnosis[29]. Although abdominal pain is usually seen with BLL above 80 µg/dL, these reports are good evidence for the assumption that occurrence of abdominal pain, is not related to BLL[25]. On the other hand, there was a significant correlation between BLL and duration of drug abuse in opium addict cases (r = 0.398, P = 0.022). The odds ratio of having BLL ≥ 100 µg/dL in oral opium users was 2.1 (95%CI: 0.92-4.61; P = 0.43)[30].

It is not exactly known how much lead is added to opium samples in the Iranian black market. However, chemical analysis of a sample by atomic absorption spectrometry, recognized as the method of choice, showed 35.2 mg of lead per 100 g of opium[19]. In another study from Iran, random samples from various sources were analyzed using atomic absorption spectrometry, and the mean concentration of lead in the samples was 1.88 ± 0.35 ppm[10]. Chia et al[7] reported the level of lead in contaminated opium samples to be 33.8 mg per 100 g of opium.

Chronic abuse of opium with such low levels of lead over months to years results in lead accumulation and consequently severe plumbism. This poisoning can be easily misdiagnosed as it mimics several other medical conditions such as surgical acute abdomen, withdrawal symptom, crisis of sickle cell anemia, cholecystitis, acute porphyria, and nephrolithiasis[20,31]. Therefore, lead poisoning should be considered in the differential diagnosis of patients with moderate to severe abdominal pain.

All symptomatic patients with high BLL should undergo treatment following medical consultation with a clinical toxicologist. The treatment plan essentially consists of oral opium cessation, probably with the help of rehab programs, in addition to the administration of chelating agents such as dimercaprol (BAL: British anti-lewisite), CaNa2EDTA, succimer (DMSA: dimercapto-succinic acid), and more rarely D-penicillamine[2]. Decision on which chelator should be used depends on the BLL, clinical manifestations, and laboratory results[14].

Complications of lead poisoning are reversible, providing early diagnosis and appropriate treatments are made; however, neurotoxicity may be permanent following significantly elevated BLLs and delayed specific treatment[18]. Timely detection and proper therapies for lead poisoning in an opium-addicted individual with the chief complaint of abdominal pain cannot only obviate the need for unnecessary medical evaluations or procedures and decrease its perilous complications such as loss of consciousness and paralysis[32] but also reduce the financial burden on patients and healthcare systems.

CONCLUSION

Despite a decrease in the frequency of occupational lead poisoning, a new trend of lead poisoning has recently emerged among opium addicts, mainly in Iran. Because of non-specific manifestations and hazardous effects of lead poisoning, this critical poisoning should be considered in the medical approach to any patient with a history of opiate addiction presenting to the emergency department with acute abdominal pain and particularly colicky abdominal pain.

ACKNOWLEDGEMENTS

The authors would like to acknowledge Mrs Alison Good, Scotland, United Kingdom, for her helpful review of this manuscript.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Psychiatry

Country/Territory of origin: France

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B, B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P- Reviewer: Movahed A, Seeman MV S- Editor: Gong ZM L- Editor: A E- Editor: Liu MY

References
1.  Flora SJ, Pachauri V. Chelation in metal intoxication. Int J Environ Res Public Health. 2010;7:2745-2788.  [PubMed]  [DOI]
2.  Papanikolaou NC, Hatzidaki EG, Belivanis S, Tzanakakis GN, Tsatsakis AM. Lead toxicity update. A brief review. Med Sci Monit. 2005;11:RA329-RA336.  [PubMed]  [DOI]
3.  Markowitz M. Lead poisoning: a disease for the next millennium. Curr Probl Pediatr. 2000;30:62-70.  [PubMed]  [DOI]
4.  Goyer RA. Lead toxicity: current concerns. Environ Health Perspect. 1993;100:177-187.  [PubMed]  [DOI]
5.  Radfar SR, Nematollahi P, Farhoudian A, Noroozi A. Lead Poisoning among Opium Users in Iran: A Possible New Emerging Epidemic in the Region. Iran J Public Health. 2017;46:1152-1153.  [PubMed]  [DOI]
6.  Beattie AD, Mullin PJ, Baxter RH, Moore MR. Acute lead poisoning: an unusual cause of hepatitis. Scott Med J. 1979;24:318-321.  [PubMed]  [DOI]
7.  Chia BL, Leng CK, Hsii FP, Yap MH, Lee YK. Lead poisoning from contaminated opium. Br Med J. 1973;1:354.  [PubMed]  [DOI]
8.  Antonini G, Palmieri G, Millefiorini E, Spagnoli LG, Millefiorini M. Lead poisoning during heroin addiction. Ital J Neurol Sci. 1989;10:105-108.  [PubMed]  [DOI]
9.  Masoodi M, Zali MR, Ehsani-Ardakani MJ, Mohammad-Alizadeh AH, Aiassofi K, Aghazadeh R, Shavakhi A, Somi MH, Antikchi MH, Yazdani S. Abdominal pain due to lead-contaminated opium: a new source of inorganic lead poisoning in Iran. Arch Iran Med. 2006;9:72-75.  [PubMed]  [DOI]
10.  Aghaee-Afshar M, Khazaeli P, Behnam B, Rezazadehkermani M, Ashraf-Ganjooei N. Presence of lead in opium. Arch Iran Med. 2008;11:553-554.  [PubMed]  [DOI]
11.  Mokhtarifar A, Mozaffari H, Afshari R, Goshayeshi L, Akavan Rezayat K, Ghaffarzadegan K, Sheikhian M, Rajabzadeh F. Cholestasis and seizure due to lead toxicity: a case report. Hepat Mon. 2013;13:e12427.  [PubMed]  [DOI]
12.  NIH National Library of Medicine. Toxnet. [cited 23 December 2019].  Available from: https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~eYQ9Cx:3.  [PubMed]  [DOI]
13.  Royce S. Case studies in environmental medicine: lead toxicity.  ATSDR. Atlanta, USA: US Department of Health and Human Services, 1992.  [PubMed]  [DOI]
14.  Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR. Goldfrank's toxicologic emergencies.  New York, USA: McGraw-Hill Medical, 2015.  [PubMed]  [DOI]
15.  United Nations Office on Drugs and Crime. World Drug Report 2014. [cited 23 December 2019].  Available from: http://www.unodc.org/wdr2014/.  [PubMed]  [DOI]
16.  Fatemi R, Jafarzadeh F, Moosavi S, Amin FA. Acute lead poisoning in an opium user: a case report. Gastroenterol Hepatol Bed Bench. 2008;1:139-142.  [PubMed]  [DOI]
17.  Verheij J, Voortman J, van Nieuwkerk CM, Jarbandhan SV, Mulder CJ, Bloemena E. Hepatic morphopathologic findings of lead poisoning in a drug addict: a case report. J Gastrointestin Liver Dis. 2009;18:225-227.  [PubMed]  [DOI]
18.  Beigmohammadi MT, Aghdashi M, Najafi A, Mojtahedzadeh M, Karvandian K. Quadriplegia due to lead-contaminated opium--case report. Middle East J Anaesthesiol. 2008;19:1411-1416.  [PubMed]  [DOI]
19.  Jalili M, Azizkhani R. Lead toxicity resulting from chronic ingestion of opium. West J Emerg Med. 2009;10:244-246.  [PubMed]  [DOI]
20.  Meybodi FA, Eslick GD, Sasani S, Abdolhoseyni M, Sazegar S, Ebrahimi F. Oral opium: an unusual cause of lead poisoning. Singapore Med J. 2012;53:395-397.  [PubMed]  [DOI]
21.  Soltaninejad K, Flückiger A, Shadnia S. Opium addiction and lead poisoning. J Sub Use. 2011;16:208-212.  [PubMed]  [DOI]
22.  Afshari R, Emadzadeh A. Short communication: case report on adulterated opium-induced severe lead toxicity. Drug Chem Toxicol. 2010;33:48-49.  [PubMed]  [DOI]
23.  Azizi A, Ferguson K, Dluzewski S, Hussain T, Klein M. Chronic lead poisoning in an Iranian opium smoker resident in London. BMJ Case Rep. 2016;2016:bcr2016215965.  [PubMed]  [DOI]
24.  Razmeh S, Abdollahi M, Poranian M. Motor Neuron Disease Due to Exposure to Lead. Clin Med Diagn. 2016;6:126-127.  [PubMed]  [DOI]
25.  Ameri M, Aghabiklooei A. Lead poisoning with presentation of acute abdomen and narcotic bowel syndrome in opium user woman. Gulhane Med J. 2018;60:116-118.  [PubMed]  [DOI]
26.  Sadeghi A, Soleimani H, Nasseri-Moghadam S, Radmard AR. Lead contaminated opium as unusual cause of abdominal pain-case series. Ir J Radiol. 2017;14:e48278 [abstract].  [PubMed]  [DOI]
27.  van't Klooster CC, Uil JJ, van der Leeuw J, Eppens EF, Marczinski SC. Unusual Cause of Abdominal Pain and Anemia. Clin Chem. 2017;63:1806-1809.  [PubMed]  [DOI]
28.  Farzaneh E, Habibzadeh A, Mehrpour O. Lead Toxicity among Oral Opium Addicts with Abdominal Pain: A Case Series of 17 Cases. Ind J Forens Med Toxicol. 2017;11:22-25.  [PubMed]  [DOI]
29.  Salehi H, Sayadi AR, Tashakori M, Yazdandoost R, Soltanpoor N, Sadeghi H, Aghaee-Afshar M. Comparison of serum lead level in oral opium addicts with healthy control group. Arch Iran Med. 2009;12:555-558.  [PubMed]  [DOI]
30.  Ghaemi K, Ghoreishi A, Rabiee N, Alinejad S, Farzaneh E, Amirabadi Zadeh A, Abdollahi M, Mehrpour O. Blood Lead Levels in Asymptomatic Opium Addict Patients; a Case Control Study. Emerg (Tehran). 2017;5:e69.  [PubMed]  [DOI]
31.  Tsai MT, Huang SY, Cheng SY. Lead Poisoning Can Be Easily Misdiagnosed as Acute Porphyria and Nonspecific Abdominal Pain. Case Rep Emerg Med. 2017;2017:9050713.  [PubMed]  [DOI]
32.  Karrari P, Mehrpour O, Abdollahi M. A systematic review on status of lead pollution and toxicity in Iran; Guidance for preventive measures. Daru. 2012;20:2.  [PubMed]  [DOI]