Abstract
Context:
Hair dyes are widely used and very popular xenobiotics. Most of these products contain paraphenylenediamine (PPD) that can cause methemoglobinemia. We here report a case of severe methemoglobinemia that we treated using large amounts of methylene blue.
Case details:
A 30-year-old man visited a regional hospital with cyanosis. He was congenitally blind and had autism. For several weeks, he had mistaken hair dye for toothpaste. When he arrived at a regional hospital, he was drowsy with cyanosis and his initial serum methemoglobin (MetHb) level was 59.5%. After being treated with 2 mg/kg methylene blue (1 mg/kg × 2 administrations), he was transferred to a tertiary university hospital. Upon presentation at the Emergency Department in the tertiary hospital, his MetHb level was found to be 49.4% and his oxygen saturation was 80%. He was then admitted to the intensive care unit. After treatment with 4 mg/kg methylene blue (1 mg/kg × 4 administrations), he successfully recovered.
Discussion:
Because PPD can result in serious methemoglobinemia, clinicians should test it in cyanotic patients who have been exposed to hair dye for an extended period.
Introduction
Paraphenylenediamine (PPD) is a para-nitroaniline derivative that is widely used in hair dyes. 1 In 1924, the first documented case of systemic PPD poisoning was described 2 and since then there have been many reported cases of PPD toxicity. Most of these occurrences were presented as angioedema due to hypersensitivity, acute kidney injury via rhabdomyolysis or intravascular hemolysis. Additionally, PPD has an amine component produced via oxidation that can convert oxyhemoglobin to methemoglobin (MetHb). Methemoglobinemia is a life-threatening condition in which MetHb composes greater than 1–2% of red blood cells. 3 Numerous studies have documented renal failure, angioedema, and rhabdomyolysis. However, there are few reports describing methemoglobinemia induced by PPD. Most of the reported cases were poisoning by PPD ingestion. We here describe a rare case of methemoglobinemia caused by hair dye poisoning due to its misuse as toothpaste.
Case report
A 30-year-old congenitally blind and autistic male with cyanosis was transferred from a regional hospital. He did not have any other medical problem, such as viral hepatitis or hematologic disease, except the above neuropsychiatric problem. He lives with his sister who works in a hair shop, and as a result hair dyes are always present at his home. After several weeks of misusing hair dye as toothpaste, the patient had developed cyanosis and subsequently presented to the outlying regional hospital with acute altered mental status. Brain computed tomography, chest radiography, and routine blood tests, including a complete blood cell count and metabolic panel, were normal. As the patient appeared cyanotic and his oxygen saturation (SpO2) in pulse oximeter was low, a CO-oximeter was used, which recorded MetHb level of 59.5%. He was then treated twice using 1 mg/kg methylene blue and transferred to the Emergency Department in a tertiary university hospital for intensive care.
When he arrived at the emergency department, his blood pressure was 105/47 mmHg, pulse rate was 101 beats/min, respiratory rate was 20 breaths/min, and SpO2 in pulse oximeter was 80%, and his mental status was drowsy and lethargic. However, he did not have any other symptoms such as oropharyngeal edema, throat pain, hoarseness, oliguria, dark colored urine, and generalized edema except mild dyspnea.
In the laboratory tests, an elevation of MetHb fraction of 49.4%, aspartate transaminase (AST) of 50 international unit (IU)/L, alanine transaminase (ALT) of 84 IU/L, and total bilirubin of 1.3 mg/dL were observed. However, leukocyte counts, level of lactic acid, arterial pH, creatinine, creatinine kinase, and electrolytes, including serum sodium, potassium, calcium, and phosphates, were in the normal range (Table 1).
Initial laboratory profiles when transferred to tertiary university hospital.
IU: international unit.
He was treated again with 1 mg/kg methylene blue immediately upon admission to the Emergency Department. He was then shifted to the intensive care unit and received additional three injections of methylene blue. After a total of 6 mg/kg methylene blue injection, his MetHb level decreased to 3%. Three days after admission, he was discharged without any symptoms or signs. The other initial elevated parameters (AST of 36 mg/dL, ALT of 83 IU/L) were found to be decreased in the subsequent laboratory tests. Although follow-up laboratory tests were not performed, an examination after 1 month showed no abnormal signs or symptoms.
Discussion
PPD is a compound that is commonly used in oxidizing hair dyes 4 ; and a number of cases were reported documenting poisoning by this chemical. Abdelraheem et al. reported a case of PPD poisoning that developed into acute kidney injury. 5 Midha et al. described a case that resulted in hypotonic areflexic motor paralysis with acute renal failure. 6 Chrispal et al. reported a series of 13 cases of PPD poisoning, 7 in which the patients demonstrated elevated hepatic transaminases (100%), leukocytosis (92.3%), elevated creatinine phosphokinase (92.3%), metabolic acidosis (84.6%), hypocalcemia (61.5%), hyperphosphatemia (46.2%), and renal failure (38.5%). These cases also presented with cervicofacial edema and pain, cola-colored urine, and oliguria. However, none of the above-mentioned cases developed methemoglobinemia.
In our present study, the patient also had mild elevation of hepatic transaminases apart from methemoglobinemia. But unlike other PPD poisoning reports, there were no evidence of renal failure, rhabdomyolysis, and angioedema, but methemoglobinemia. To our knowledge, there were no reported cases with PPD-induced methemoglobinemia in the English literature, especially not ingested poisoning. Our report describes the first case of methemoglobinemia that resulted from oral mucosal exposure to PPD. Our patient did not have any laboratory abnormalities apart from methemoglobinemia and mild elevation of hepatic transaminases. Because he did not ingest a large amount of the substance, it seems that systemic organ dysfunction did not occur except hepatitis. According to Crispal’s report, it is believed that liver is very susceptible to PPD poisoning. 7 Even if the ALT enzyme is still elevated, we expected it to improve like AST.
Once methemoglobinemia has occurred methylene blue should be given intravenously at a dose of 1–2 mg/kg for 5 min. 8 If the response is inadequate, an additional dose of methylene blue may be given after 1 h. 9 Aniline dye-induced methemoglobinemia is less responsive to methylene blue because the toxic intermediate metabolite phenylhydroxylamine blocks its uptake. 10 In the presented case, the patient needed lots of methylene blue for normalization of MetHb (Figure 1). Although there is no report about correlation of PPD and methylene blue, we believe that there may be interference between them.
MetHb and SpO2 change by methylene blue. Because of the persistence of dyspnea, the patient needed infusion of 1 mg/kg of methylene blue for six times. After 15 h of treatment, all the signs and symptoms disappeared. SpO2: oxygen saturation via pulse oximetry; MetHb: methemoglobin.
Although in theory, PPD may result in methemoglobinemia, most reports do not describe this condition. It is unclear why only few patients develop methemoglobinemia after PPD poisoning. One possibility may be that there are subclinical manifestations of methemoglobinemia that spontaneously resolve via cytochrome-b5 reductase. However, the chronic exposure to PPD in our current case may have resulted in severe methemoglobinemia due to exhaustion of this enzyme.
In conclusion, clinicians should be aware of the possibility that chronic exposure to PPD may be associated with methemoglobinemia. Most importantly, in patients who ordinarily use hair dye and present with cyanosis and low oxygen saturation, physicians should test for methemoglobinemia using a CO-oximeter. If this test is positive, treatment with methylene blue should be considered.