Acute hemolytic crisis complicated with ischemic cardiac injury and methemoglobinaemia following ingestion of naphthalene: a case report

Abstract

Background

Naphthalene is an aromatic hydrocarbon that potentially produces methemoglobinaemia but rarely causes hemolysis, especially in children with underlying glucose-6-phosphate dehydrogenase deficiency. Although ingestion of a single moth ball by an older child may not be life threatening, it can be fatal if ingested by a toddler.

Case presentation

A 2-year-old Singhalese boy developed acute severe hemolysis and methemoglobinaemia following ingestion of a mothball. On admission, the patient was ill and pale. The child was tachycardic and tachypnoiec with oxygen saturation of 76% on air. Blood investigations showed significant anemia, elevated reticulocytes, and evidence of hemolysis in a blood picture, along with elevated lactate dehydrogenase and indirect bilirubin. Child also had ST depressions on electrocardiogram examination with negative troponin-I. He was given four packed red blood cell (PRBC) transfusions and was successfully discharged in 3 days time following optimal supportive treatment. A glucose-6-phosphate dehydrogenase assay confirmed the diagnosis of glucose-6-phosphate dehydrogenase deficiency in this child: 0.9 U/gHb (4.0–13.0 U/gHb).

Conclusion

This case report highlights a rare life-threatening presentation of naphthalene ingestion in a child with previously undiagnosed glucose-6-phosphate dehydrogenase deficiency. Ingestion of even a single moth ball can be fatal in vulnerable children given the altered toxicokinetics of naphthalene in children.

Background

Naphthalene, commonly employed in both industrial and domestic settings, represents a rare cause of poisoning globally and can pose a diagnostic dilemma when exposure to it is not recognized. Naphthalene ingestion can precipitate acute intravascular hemolysis, manifesting with anemia, hematuria, leukocytosis characterized by neutrophil predominance, jaundice, and hepatic and renal impairment. Consumption of just two mothballs containing naphthalene can induce profound hemolytic anemia and hypotension in adults [1]. Ingestion of naphthalene can also trigger methemoglobinaemia [2]. However, in toddlers, the presentation is often vague, and clear history of ingestion is absent in most cases. The risk of complications is much higher in children compared with adults following ingestion of the same dose due to altered toxicokinetics.

Naphthalene, the primary component of mothballs, is present in numerous insecticides and can lead to poisoning in children, typically as a result of accidental ingestion. It is used as a deodorizer and moth deterrent across South Asia, including Sri Lanka. Further, the moth balls are readily available in many local supermarkets [3]. Despite their widespread use, toxicity is only rarely reported, and most of the packets containing moth balls in the market lack safety instructions. Toddlers are more prone to accidental ingestion due to their shiny, whitish attractive appearance (Fig. 1).

Fig. 1

Dark urine at the time of presentation to hospital

While naphthalene toxicity is a recognized risk for hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals, cardiac ischemia secondary to profound anemia is a rare complication not widely documented in literature. This case highlights the life-threatening potential of even small doses of naphthalene in vulnerable pediatric patients. Diagnosis can be delayed in young children due to the absence of a clear ingestion history, emphasizing the importance of recognizing clinical toxidromes and their link to underlying metabolic disorders.

Case presentation

A 2-year-old Singhalese boy was brought with a history of fever for two days. The parents were worried regarding dengue fever, as he was living in an area with high incidence of dengue. Rest of the systemic inquiry was unremarkable. However, on direct questioning, the mother also reported that his urine color was dark (Fig. 2). Physical examination revealed marked pallor and a tinge of icterus. There was no hepatosplenomegaly. He had a pulse rate of 184 beats per minute with good volume, respiratory rate of 42 per minute, and gallop rhythm. Oxygen saturation on air was 76%. His blood pressure was 90/58 mmHg and capillary refill time was 3 seconds.

Fig. 2

Shiny, whitish attractive appearance of moth balls

Initial investigations showed significant anemia with hemoglobin of 3.5 g/dl (9.6 to 15.6 g/dl). The reticulocyte count was 15.2% (0.5% to 1.5%). Lactate dehydrogenase (LDH) was 1263 (range from 155 to 345 units/l). Total serum bilirubin was 7.0 mg/dl (1.5 to 5 mg/dl) with an indirect fraction of 6.8 mg/dl. There was elevated AST of 134 mmol/l, but ALT was normal. Serum creatinine, electrolytes, and blood urea were normal.

Peripheral smear showed microspherocytes and polychromatic cells. Many bite cells and normoblasts were also seen. Apart from mild neutrophil leukocytosis, rest of the smear was normal. An electrocardiogram (ECG) was performed on admission due to low oxygen saturation and tachycardia. ECG showed ST segment depression in anterolateral chest leads—I, aVL, and V3–V6. Troponin-I was borderline elevated at 0.09 ng/ml (< 0.04 ng/ml). His initial oxygen saturation remained at 85% despite high flow oxygen therapy. An arterial blood gas with cooximetry revealed pH 7.29 (7.35–7.45), pCO₂ 34 mm Hg (35–48), pO₂ 167.0 mm Hg (83–108), HCO₃⁻ 19.6 mEq/l (21–28), SaO₂ 88% (95–98), total calculated hemoglobin 3.3 g/dl, oxyhemoglobin 72.1% (95.0–98.0), carboxyhemoglobin 0.0% (0.5–1–5), and methemoglobin 9.7% (< 3.0) with an oxygen content of 15.7 ml/dl (15.0–33.0).

The child was initially resuscitated with a 0.9% saline bolus of 20 ml/kg and oxygen therapy. Vital signs and cardiac rhythm were continuously monitored. Given the acute onset clinical presentation, dramatic clinical progression, and lack of a clear systemic involvement, a potential toxic ingestion was suspected. At this stage, the mother presented the story of her child playing with moth balls 36 hours earlier and that she noted two moth balls went missing. Since the child remained well at home, the parents did not seek medical advice, and the child was brought only after development of fever for its evaluation.

He subsequently, received 40 ml/kg blood transfusions with IV frusemide 1 mg/kg for each 10 ml/kg blood transfusion. By day 2 of hospital admission, ECG changes reversed with normalization of ALT. His hemoglobin had risen to 11.6 g/dl, and oxygen saturation gradually normalized with high flow oxygen therapy. The child was discharged on day 4 of hospital admission. Possible G6PD was suspected on the basis the initial peripheral smear appearance, and a G6PD assay was arranged 3 months after the initial hemolytic crisis. A G6PD assay confirmed the diagnosis of glucose-6-phosphate dehydrogenase deficiency in this child of 0.9 U/gHb (4.0–13.0 U/gHb). Hemoglobin had further risen to 12.8 g/dl. Follow-up was arranged in the pediatric clinic.

Discussion

Naphthalene toxicity, commonly seen following ingestion or inhalation of mothballs, poses significant risks, particularly in pediatric patients. It is a lipophilic compound that can cause oxidative stress, leading to the production of free radicals and depletion of glutathione [1]. Additionally, naphthalene exposure can lead to methemoglobinaemia. While acute toxicity may present with gastrointestinal symptoms, severe cases can cause life-threatening complications such as hemolysis, jaundice, and, as observed in this case, ischemic cardiac injury.

Children with G6PD deficiency have increased susceptibility for acute intravascular hemolytic crisis when exposed to oxidative stress [4]. α-Naphthol, which is the active metabolite of naphthalene can cause increased oxidative stress [5]. It also causes methemoglobinemia, which is rarely life-threatening [6]. But in those with G6PD deficiency, naphthalene can lead to severe hemolysis even with a small dose. Mothballs, a common domestic item contains naphthalene as its main compound, and a single mothball can contain up to 5 g of naphthalene [5]. The lethal dose of naphthalene in a child following acute toxicity is 2–3 g³.

Naphthalene produces excess of free oxygen radicals which results in lipid peroxidation and DNA damage [7]. When this activity occurs in red blood cells, it will result in cell lysis. Protection against oxidative stress is provided by nicotinamide adenine dinucleotide phosphate (NADPH) produced in the pentose phosphate pathway (PPP) [8]. However, when this mechanism is defective in G6PD enzyme deficiency, toxicity results in severe acute hemolysis.

The reported child is unique that the naphthalene toxicity resulted in both methemoglobinaemia and acute severe hemolysis. Further, severe anemia in this child resulted in hypoxic cardiac injury as indicated by the ECG. Although the circumstances of poisoning were in many adult reports of naphthalene toxicity, the relevant history in this child was lacking at the time of presentation leading to a diagnostic dilemma. However, the pattern of clinical toxidrome helped the authors to suspect naphthalene toxicity and, subsequently, to establish the underlying diagnosis of G6PD deficiency. This case further highlights the potential danger posed by mothballs, a common household item, when they are kept within reach of susceptible children. It underscores the importance of taking utmost care and precaution to safely store guard these potentially hazardous household substances to prevent accidental ingestion by children.

Conclusion

This case report highlights a rare life-threatening co-occurrence of severe hemolytic crisis complicated with hypoxic cardiac injury and methemoglobinaemia following naphthalene ingestion in a child with previously undiagnosed G6PD deficiency. Ingestion of even a single moth ball can be fatal in vulnerable children given the altered toxicokinetics of naphthalene in children.