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Naphthalene Mothballs Poisoning Leading to Intravascular Hemolysis: A Case Report
The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–3, 2019 Ó 2019 Elsevier Inc. All rights reserved. 0736-4679/$ - see front matter
https://doi.org/10.1016/j.jemermed.2019.09.047
Selected Topics: Toxicology
NAPHTHALENE MOTHBALLS POISONING LEADING TO INTRAVASCULAR HEMOLYSIS: A CASE REPORT Rizwan Ahmad, MD, Syed Hasan Amir, MD, and Shadab Ahmad Khan, MD Department of Medicine, Jawaharlal Nehru Medical College, Aligarh, India Reprint Address: Rizwan Ahmad, MD, Department of Internal Medicine, Jawaharlal Nehru Medical College, Aligarh 202001, India
, Abstract—Background: Naphthalene is widely used in households as an insect repellent, but its poisoning is rare, especially in adults. Naphthalene is a strong oxidant with a pungent smell. Case Report: We report a case of a 16year-old female who ingested three naphthalene mothballs 3 days prior to admission and presented with history of recurrent vomiting, severe pallor, jaundice, and hemoglobinuria. Investigation found severe hemolytic anemia, indirect hyperbilirubinemia, acute kidney injury, and evidence of intravascular hemolysis. Her urine output was normal throughout the course of illness. She was managed conservatively with i.v. fluid, oral ascorbic acid, and blood transfusion. With treatment our patient improved completely and was discharged in hemodynamically stable condition. She is doing fine after further follow-up. Why Should an Emergency Physician Be Aware of This?: Emergency physician should keep the possibility of poisoning by an oxidizing agent, such as naphthalene, when a patient presents to the emergency department with rapid onset pallor, jaundice, and hemoglobinuria. Ó 2019 Elsevier Inc. All rights reserved.
vascular hemolysis, especially in patients with G6PD deficiency. A 16-year-old girl presented to our emergency department (ED) with rapidly developing severe pallor and jaundice and passage of dark-colored urine. Retrospectively, she reported ingesting three naphthalene mothballs because of poor scholastic performance. She was managed with blood transfusion, i.v. fluid, and oral ascorbic acid. CASE REPORT A 16-year-old girl presented to our ED reporting ingestion of three naphthalene mothballs 3 days earlier, followed by development of retrosternal burning pain, nausea, and vomiting. Three hours after ingestion she started passing dark-colored urine. The next day she developed extreme weakness and yellowish discoloration of her eyes. Her urine color had normalized when she presented to our ED, but her other symptoms persisted. Upon examination, she was found to have tachycardia of 110 beats/min, blood pressure of 110/80 mm Hg, and SpO2 of 99% on room air. Severe pallor and icterus were present on general physical examination. Bilateral fine basal crepitus was present on chest examination. Investigations showed severe anemia (hemoglobin 6.2 g/dL), with MCV 113 fL (reference range 80– 100 fL), MCH 22 pg (reference range 27–33 pg), corrected reticulocyte count <2.5%, neutrophilic leukocytosis (total leukocyte count 22,400/mL, neutrophils 75%), and normal platelet count. Hemoglobin drop
, Keywords—naphthalene poisoning; intravascular hemolysis; hemoglobinuria; AKI
INTRODUCTION Naphthalene mothballs are used as an insect repellent in Indian households. Although their use is very widespread, intentional poisoning with naphthalene mothballs is very rare. Unintentional exposure in children is reported and the manifestation is severe, leading to intra-
RECEIVED: 26 June 2019; FINAL SUBMISSION RECEIVED: 22 September 2019; ACCEPTED: 28 September 2019 1
2
R. Ahmad et al.
continued from day 1 to day 4 up to nadir of 3.2 g/dL. Total bilirubin was raised with indirect hyperbilirubinemia (total bilirubin/indirect bilirubin 7.8/4.2 mg/dL) with aspartate transaminases 130 U/L, alanine transaminases 127 U/L, alkaline phosphatase 458/L, and evidence of intravascular hemolysis (dark-colored urine), sudden hemoglobin drop, indirect hyperbilirubinemia, presence of blood in urine with absent intact red blood cells (RBCs), raised lactate dehydrogenase 1243 U/L (reference range 140–280 U/L), and low serum haptoglobin level <30 mg/dL (reference range 30–200 mg/dL). Renal function test was deranged (creatinine 1.69 mg/dL), G6PD level was normal, and Coombs test was negative. Her urine output was normal throughout the course of her illness. She was treated with blood transfusion, i.v. fluid, and oral ascorbic acid. Oral ascorbic acid 500 mg twice per day was given for 5 days. After 3 days her bilirubin started declining, acute kidney injury (AKI) resolved, and hemoglobin level increased to 7.7 g/dL after transfusion of 3 units packed RBCs. The trend of her biochemical parameters during the hospital stay is shown in Table 1. At her follow-up visit, hemoglobin was 8.8 g/ dL and she is doing fine. DISCUSSION Naphthalene mothballs are commonly used in Indian households. They have a strong pungent odor and work as an insect repellent. Mothballs are not made of naphthalene in Europe since 2008; they are now made with paradichlorobenzene. The United States and Australia are also heading toward banning naphthalene mothballs. New Zealand has banned naphthalene mothballs due to the high toxic risk and China has forbidden the use of naphthalene in mothballs. Paradichlorobenzene is banned in India as a pesticide. Mothballs in India usually contain naphthalene, which is very cheap and easily available. Naphthalene is also used to make resin, dyes, tanning agents, lubricants, and toilet deodorant blocks. Poisoning with naphthalene mothballs is common in children and is usually accidental (1). Naphthalene mothballs poisoning is very rare in adults and is usually intentional, as a means of suicide. In total, 1202 people in the United States were
exposed to naphthalene in 2017, of which 725 were children (<5 years of age) (2). Presentation of naphthalene toxicity can mimic many diseases, making it a challenge for emergency physicians. Naphthalene is an aromatic hydrocarbon. It is derived from crude oil or coal tar. Typical coal tar contains 10% naphthalene by weight. Burning wood or tobacco also produces naphthalene. Its solubility is very poor in water and the content of naphthalene in one mothball can range from 0.5 to 5.0 g (3). The route of naphthalene exposure can be dermal, inhalation, or ingestion. Naphthalene poisoning can involve various organ systems, including the gastrointestinal tract, blood cells, liver, kidney, respiratory system, and nervous system (4). Studies have shown that toxic manifestations of naphthalene are likely due to increased production of free oxygen radicals. These free oxygen radicals result in lipid peroxidation and DNA damage (5). Naphthalene is metabolized in the liver and oxidative stress of these metabolites causes hemolysis and hemoglobinuria. Among metabolites of naphthalene, a-naphthol causes hemolysis and other oxidative effects. Management is mainly supportive. Hemolysis and hemoglobinuria are treated with i.v. hydration and packed RBC transfusion (6). If the patient has methemoglobinemia, addition of methylene blue and Nacetylcysteine may be needed in the treatment plan. In the index case, this patients maintained oxygen saturation of >98%, hence methemoglobinemia was not observed. Ascorbic acid acts as a free radical scavenger and may be useful in such cases (7); however, many such cases have been managed without ascorbic acid, therefore, the role of ascorbic acid is not very strong. AKI occurs in naphthalene poisoning due to intravascular hemolysis and blockage of renal tubules by free hemoglobin molecules (8). AKI is treated with i.v. hydration to maintain urine output, but if AKI is severe, the patient may need renal replacement therapy (9). Our patient received i.v. fluid only and AKI resolved. Cataracts developed in 8 of 21 workers who were occupationally exposed to naphthalene for up to 5 years in a plant manufacturing dye intermediate (10). Most of the naphthalene in the environment comes from wood or fossil fuel burning and the second largest
Table 1. Trend of Biochemical Parameters During Patient’s Admission in Hospital Parameter
Day 1
Day 3
Day 5
Day 6
Day 7
Hemoglobin, g/dL Total leukocyte count/mL Total bilirubin/indirect bilirubin, mg/dL AST/ALT, U/L ALP, U/L Creatinine, mg/dL
6.2 22,400 12.0/7.8 130/127 458 1.8
4.7 27,800 2.7/2.1 36/58 92 1.4
3.2 12,200 2.2/1.2 17/20 90 1.69
4.2 11,200 1.0/0.4 24/33 88 1.1
7.7 17,900 0.8/0.3 20/23 78 0.7
ALP = alkaline phosphatase; ALT = alanine transaminase; AST = aspartate transaminase.
Mothball Poisoning
source is mothballs. In the environment, naphthalene is broken down by micro-organisms and sunlight. The half-life of naphthalene ranges from <1 day in air to >80 days in soil. Naphthalene in the soil can reach underground water and thus enter the food chain. Naphthalene is a potential health and environmental hazard. Globally, naphthalene is being phased out, including in China. India needs urgent action to ban naphthalene mothballs and safely dispose of its remaining stock. Cedar chips, satchels of lavender, bay leaves, cinnamon sticks, cloves, eucalyptus leaves are safe alternatives to naphthalene mothballs. Cloth should be stored after dry cleaning in a well-sealed and airtight container to prevent moths. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? Naphthalene mothball toxicity can present with gastrointestinal symptoms, hemolytic anemia and AKI. Overdose by this poison is uncommon in adults but can prove fatal, especially in patients with G6PD deficiency. Patients with G6PD deficiency are very prone to hemolysis because they tolerate any oxidative stress very poorly, including naphthalene poisoning. Such cases can be a diagnostic challenge for emergency physicians. Therefore, if any patient presents to the ED with rapid-onset pallor and jaundice with concurrent evidence of intravascular hemolysis, the attending physician must consider the possibility of poisoning by an oxidizing agent like naphthalene. Use of decontamination procedures, i.v. hydration, and blood
3
transfusion, along with standard supportive care, can save lives. Acknowledgments—Dr. Mohammad Uwaish Ashraf and Dr. Hamid Ashraf contributed to the writing of the manuscript and choosing the appropriate journal.
REFERENCES 1. Siegel E, Wason S. Mothboll toxicity. Pediatr Clin North Am 1986; 33:369–74. 2. Gummin DD, Mowry JB, Spyker DA, Brooks DE, Osterthaler JM, Banner W. 2017 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 35th annual report. Clin Toxicol 2018;56:1213–415. 3. Kuffner EK. Camphor and moth repellants. In: Goldfrank LR, Flomenbaum NE, Lewin NA, et al., eds. Goldfrank’s Toxicologic Emergencies. 7th ed. New York: McGraw-Hill; 2002:1295–302. 4. Weintraub E, Gandhi D, Robinson C. Medical complications due to mothball abuse. South Med J 2000;93:427–9. 5. Bagchi M, Bagchi D, Balmoori J, Ye X, Stohs SJ. Naphthalene induced oxidative stress and DNA damage in cultured macrophage J744A.1 cells. Free Radic Biol Med 1998;25:137–43. 6. Uthuman AAA, Jayasinghe CS, Fernando AHN. Acute intravascular hemolysis due to naphthalene toxicity: a case report. J Med Case Rep 2019;13:91. 7. Niki E. Action of ascorbic acid as a scavenger of active and stable oxygen radicals. Am J Clin Nutr 1991;54(suppl):1119S–24. 8. Chugh KS, Singhal PC, Sharma BK, et al. Acute renal failure due to intravascular haemolysis in the North Indian patients. Am J Med Sci 1977;274:139–46. 9. Kundra TS, Bhutatani V, Gupta R, Kaur P. Naphthalene poisoning following ingestion of mothballs: a case report. J Clin Diagn Res 2015;9(8):UD01–2. 10. Ghetti G, Mariani L. [Ocular changes caused by naphthalene; clinical and experimental studies]. Med Lav 1956;47:533–8.
https://doi.org/10.1016/j.jemermed.2019.09.047
Selected Topics: Toxicology
NAPHTHALENE MOTHBALLS POISONING LEADING TO INTRAVASCULAR HEMOLYSIS: A CASE REPORT Rizwan Ahmad, MD, Syed Hasan Amir, MD, and Shadab Ahmad Khan, MD Department of Medicine, Jawaharlal Nehru Medical College, Aligarh, India Reprint Address: Rizwan Ahmad, MD, Department of Internal Medicine, Jawaharlal Nehru Medical College, Aligarh 202001, India
, Abstract—Background: Naphthalene is widely used in households as an insect repellent, but its poisoning is rare, especially in adults. Naphthalene is a strong oxidant with a pungent smell. Case Report: We report a case of a 16year-old female who ingested three naphthalene mothballs 3 days prior to admission and presented with history of recurrent vomiting, severe pallor, jaundice, and hemoglobinuria. Investigation found severe hemolytic anemia, indirect hyperbilirubinemia, acute kidney injury, and evidence of intravascular hemolysis. Her urine output was normal throughout the course of illness. She was managed conservatively with i.v. fluid, oral ascorbic acid, and blood transfusion. With treatment our patient improved completely and was discharged in hemodynamically stable condition. She is doing fine after further follow-up. Why Should an Emergency Physician Be Aware of This?: Emergency physician should keep the possibility of poisoning by an oxidizing agent, such as naphthalene, when a patient presents to the emergency department with rapid onset pallor, jaundice, and hemoglobinuria. Ó 2019 Elsevier Inc. All rights reserved.
vascular hemolysis, especially in patients with G6PD deficiency. A 16-year-old girl presented to our emergency department (ED) with rapidly developing severe pallor and jaundice and passage of dark-colored urine. Retrospectively, she reported ingesting three naphthalene mothballs because of poor scholastic performance. She was managed with blood transfusion, i.v. fluid, and oral ascorbic acid. CASE REPORT A 16-year-old girl presented to our ED reporting ingestion of three naphthalene mothballs 3 days earlier, followed by development of retrosternal burning pain, nausea, and vomiting. Three hours after ingestion she started passing dark-colored urine. The next day she developed extreme weakness and yellowish discoloration of her eyes. Her urine color had normalized when she presented to our ED, but her other symptoms persisted. Upon examination, she was found to have tachycardia of 110 beats/min, blood pressure of 110/80 mm Hg, and SpO2 of 99% on room air. Severe pallor and icterus were present on general physical examination. Bilateral fine basal crepitus was present on chest examination. Investigations showed severe anemia (hemoglobin 6.2 g/dL), with MCV 113 fL (reference range 80– 100 fL), MCH 22 pg (reference range 27–33 pg), corrected reticulocyte count <2.5%, neutrophilic leukocytosis (total leukocyte count 22,400/mL, neutrophils 75%), and normal platelet count. Hemoglobin drop
, Keywords—naphthalene poisoning; intravascular hemolysis; hemoglobinuria; AKI
INTRODUCTION Naphthalene mothballs are used as an insect repellent in Indian households. Although their use is very widespread, intentional poisoning with naphthalene mothballs is very rare. Unintentional exposure in children is reported and the manifestation is severe, leading to intra-
RECEIVED: 26 June 2019; FINAL SUBMISSION RECEIVED: 22 September 2019; ACCEPTED: 28 September 2019 1
2
R. Ahmad et al.
continued from day 1 to day 4 up to nadir of 3.2 g/dL. Total bilirubin was raised with indirect hyperbilirubinemia (total bilirubin/indirect bilirubin 7.8/4.2 mg/dL) with aspartate transaminases 130 U/L, alanine transaminases 127 U/L, alkaline phosphatase 458/L, and evidence of intravascular hemolysis (dark-colored urine), sudden hemoglobin drop, indirect hyperbilirubinemia, presence of blood in urine with absent intact red blood cells (RBCs), raised lactate dehydrogenase 1243 U/L (reference range 140–280 U/L), and low serum haptoglobin level <30 mg/dL (reference range 30–200 mg/dL). Renal function test was deranged (creatinine 1.69 mg/dL), G6PD level was normal, and Coombs test was negative. Her urine output was normal throughout the course of her illness. She was treated with blood transfusion, i.v. fluid, and oral ascorbic acid. Oral ascorbic acid 500 mg twice per day was given for 5 days. After 3 days her bilirubin started declining, acute kidney injury (AKI) resolved, and hemoglobin level increased to 7.7 g/dL after transfusion of 3 units packed RBCs. The trend of her biochemical parameters during the hospital stay is shown in Table 1. At her follow-up visit, hemoglobin was 8.8 g/ dL and she is doing fine. DISCUSSION Naphthalene mothballs are commonly used in Indian households. They have a strong pungent odor and work as an insect repellent. Mothballs are not made of naphthalene in Europe since 2008; they are now made with paradichlorobenzene. The United States and Australia are also heading toward banning naphthalene mothballs. New Zealand has banned naphthalene mothballs due to the high toxic risk and China has forbidden the use of naphthalene in mothballs. Paradichlorobenzene is banned in India as a pesticide. Mothballs in India usually contain naphthalene, which is very cheap and easily available. Naphthalene is also used to make resin, dyes, tanning agents, lubricants, and toilet deodorant blocks. Poisoning with naphthalene mothballs is common in children and is usually accidental (1). Naphthalene mothballs poisoning is very rare in adults and is usually intentional, as a means of suicide. In total, 1202 people in the United States were
exposed to naphthalene in 2017, of which 725 were children (<5 years of age) (2). Presentation of naphthalene toxicity can mimic many diseases, making it a challenge for emergency physicians. Naphthalene is an aromatic hydrocarbon. It is derived from crude oil or coal tar. Typical coal tar contains 10% naphthalene by weight. Burning wood or tobacco also produces naphthalene. Its solubility is very poor in water and the content of naphthalene in one mothball can range from 0.5 to 5.0 g (3). The route of naphthalene exposure can be dermal, inhalation, or ingestion. Naphthalene poisoning can involve various organ systems, including the gastrointestinal tract, blood cells, liver, kidney, respiratory system, and nervous system (4). Studies have shown that toxic manifestations of naphthalene are likely due to increased production of free oxygen radicals. These free oxygen radicals result in lipid peroxidation and DNA damage (5). Naphthalene is metabolized in the liver and oxidative stress of these metabolites causes hemolysis and hemoglobinuria. Among metabolites of naphthalene, a-naphthol causes hemolysis and other oxidative effects. Management is mainly supportive. Hemolysis and hemoglobinuria are treated with i.v. hydration and packed RBC transfusion (6). If the patient has methemoglobinemia, addition of methylene blue and Nacetylcysteine may be needed in the treatment plan. In the index case, this patients maintained oxygen saturation of >98%, hence methemoglobinemia was not observed. Ascorbic acid acts as a free radical scavenger and may be useful in such cases (7); however, many such cases have been managed without ascorbic acid, therefore, the role of ascorbic acid is not very strong. AKI occurs in naphthalene poisoning due to intravascular hemolysis and blockage of renal tubules by free hemoglobin molecules (8). AKI is treated with i.v. hydration to maintain urine output, but if AKI is severe, the patient may need renal replacement therapy (9). Our patient received i.v. fluid only and AKI resolved. Cataracts developed in 8 of 21 workers who were occupationally exposed to naphthalene for up to 5 years in a plant manufacturing dye intermediate (10). Most of the naphthalene in the environment comes from wood or fossil fuel burning and the second largest
Table 1. Trend of Biochemical Parameters During Patient’s Admission in Hospital Parameter
Day 1
Day 3
Day 5
Day 6
Day 7
Hemoglobin, g/dL Total leukocyte count/mL Total bilirubin/indirect bilirubin, mg/dL AST/ALT, U/L ALP, U/L Creatinine, mg/dL
6.2 22,400 12.0/7.8 130/127 458 1.8
4.7 27,800 2.7/2.1 36/58 92 1.4
3.2 12,200 2.2/1.2 17/20 90 1.69
4.2 11,200 1.0/0.4 24/33 88 1.1
7.7 17,900 0.8/0.3 20/23 78 0.7
ALP = alkaline phosphatase; ALT = alanine transaminase; AST = aspartate transaminase.
Mothball Poisoning
source is mothballs. In the environment, naphthalene is broken down by micro-organisms and sunlight. The half-life of naphthalene ranges from <1 day in air to >80 days in soil. Naphthalene in the soil can reach underground water and thus enter the food chain. Naphthalene is a potential health and environmental hazard. Globally, naphthalene is being phased out, including in China. India needs urgent action to ban naphthalene mothballs and safely dispose of its remaining stock. Cedar chips, satchels of lavender, bay leaves, cinnamon sticks, cloves, eucalyptus leaves are safe alternatives to naphthalene mothballs. Cloth should be stored after dry cleaning in a well-sealed and airtight container to prevent moths. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? Naphthalene mothball toxicity can present with gastrointestinal symptoms, hemolytic anemia and AKI. Overdose by this poison is uncommon in adults but can prove fatal, especially in patients with G6PD deficiency. Patients with G6PD deficiency are very prone to hemolysis because they tolerate any oxidative stress very poorly, including naphthalene poisoning. Such cases can be a diagnostic challenge for emergency physicians. Therefore, if any patient presents to the ED with rapid-onset pallor and jaundice with concurrent evidence of intravascular hemolysis, the attending physician must consider the possibility of poisoning by an oxidizing agent like naphthalene. Use of decontamination procedures, i.v. hydration, and blood
3
transfusion, along with standard supportive care, can save lives. Acknowledgments—Dr. Mohammad Uwaish Ashraf and Dr. Hamid Ashraf contributed to the writing of the manuscript and choosing the appropriate journal.
REFERENCES 1. Siegel E, Wason S. Mothboll toxicity. Pediatr Clin North Am 1986; 33:369–74. 2. Gummin DD, Mowry JB, Spyker DA, Brooks DE, Osterthaler JM, Banner W. 2017 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 35th annual report. Clin Toxicol 2018;56:1213–415. 3. Kuffner EK. Camphor and moth repellants. In: Goldfrank LR, Flomenbaum NE, Lewin NA, et al., eds. Goldfrank’s Toxicologic Emergencies. 7th ed. New York: McGraw-Hill; 2002:1295–302. 4. Weintraub E, Gandhi D, Robinson C. Medical complications due to mothball abuse. South Med J 2000;93:427–9. 5. Bagchi M, Bagchi D, Balmoori J, Ye X, Stohs SJ. Naphthalene induced oxidative stress and DNA damage in cultured macrophage J744A.1 cells. Free Radic Biol Med 1998;25:137–43. 6. Uthuman AAA, Jayasinghe CS, Fernando AHN. Acute intravascular hemolysis due to naphthalene toxicity: a case report. J Med Case Rep 2019;13:91. 7. Niki E. Action of ascorbic acid as a scavenger of active and stable oxygen radicals. Am J Clin Nutr 1991;54(suppl):1119S–24. 8. Chugh KS, Singhal PC, Sharma BK, et al. Acute renal failure due to intravascular haemolysis in the North Indian patients. Am J Med Sci 1977;274:139–46. 9. Kundra TS, Bhutatani V, Gupta R, Kaur P. Naphthalene poisoning following ingestion of mothballs: a case report. J Clin Diagn Res 2015;9(8):UD01–2. 10. Ghetti G, Mariani L. [Ocular changes caused by naphthalene; clinical and experimental studies]. Med Lav 1956;47:533–8.