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| TOXICOLOGY SYMPOSIA – REVIEW ARTICLE |
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| Year : 2015 | Volume
: 20
| Issue : 1 | Page : 33-37 |
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Acute hair dye poisoning: Lurking dangers
Subramanian Senthilkumaran1, Ponniah Thirumalaikolundusubramanian2
1 Department of Emergency and Critical Care Medicine, Sri Gokulam Hospital, Salem, Tamil Nadu, India
2 Department of Internal Medicine , Chennai Medical College and Research Centre, Trichy, Tamil Nadu, India
| Date of Web Publication | 19-Feb-2015 |
Correspondence Address:
Dr. Subramanian Senthilkumaran
Department of Emergency and Critical Care Medicine, Sri Gokulam Hospital, Salem, Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0971-9903.151731
Hair dye poisoning has emerged as one of the major causes of deliberate self-harm in the rural areas of developing world. This systematic toxicological literature reviews the pathophysiology and clinical features of hair dye poisoning. Keywords: Hair dye, paranitroanaline, poisoning, super vasmol
How to cite this article:
Senthilkumaran S, Thirumalaikolundusubramanian P. Acute hair dye poisoning: Lurking dangers. J Mahatma Gandhi Inst Med Sci 2015;20:33-7 |
| Introduction | |  |
Hair dye is used for suicidal attempt in the developing world [1] and it is on raise. In ancient India, hair care and hair dressing were a common practice among men and women. It was practiced with elegance and dedication. There were hairdressers as early as 4000 years before the Christian age, and the art of dyeing hair with the henna, indigo (which was extracted from the plant Indigofera tinctoria) and vegetable dyes was known already at that time. [2] Along the centuries, their favorite colors were black or orange-reds. [2] In the 1661 book, the secrets of art and nature as well as, various methods of coloring hair like black, gold, green, red, yellow, and white were explained. [3] The development of synthetic dyes for hair in the laboratory is traced to 1856, and permanent hair colorants have been in commercial use for over 100 years. [4] The toxicity of paraphenyl-diamine (PPD) was first described in a hairdresser in 1924 following exposure due to occupational handling.
Hair dyes and their meachanisms of action
Hair dyes are divided into five categories, based on composition and mechanism of action Gradual hair coloring (using metallic dyes such as salts of lead, bismuth or silver), vegetable hair dyes (such as henna), temporary dyes (water-soluble dyes that withstand only 1-time shampooing), semi-permanent dyes (which can withstand 4-5 times of shampooing) and permanent hair colors. Permanent hair colors are the most popular hair dye products. [5] They may be further divided into oxidation hair dyes and progressive hair dyes.
Oxidation hair dye products consist of two solutions. First is a solution of dye intermediates, e.g., PPD, which has a hydrogen donor and is metabolized by electron oxidation to an active radical by cytochrome P450 peroxidase to form a reactive benzoquinone diamine. These a imines react rapidly with the couplers and preformed dyes, e.g., 2-nitro-p-phenylenediamine, which are added to achieve the intended shades, in an aqueous, ammoniacal vehicle containing soap, detergents and conditioning agents, and/or an oxidized PPD to produce indo dyes. The most frequent couplers are 2,4-diaminoanisole (blue forming coupler), resorcinol (green brown), metaminophenol (magenta/brown) and 1-naphthol (purple blue color), and second is a solution of hydrogen peroxide, usually 6%, in water or a cream lotion. Free ammonia is present to promote the oxidation reaction. The ammoniacal dye solution and the hydrogen peroxide solution, often called as developer, are mixed shortly before application to the hair. The pH of the mixture on the dyed area is about 9.5. Complex reaction takes place, and numerous intermediates are produced on oxidation of PPD. However, the major product formed is Bandrowski's base which is a well-known allergen, mutagen and also highly toxic. [6]
The applied mixture causes the hair to swell and the dye intermediates (and preformed dyes) penetrate the hair shaft to some extent before they have fully reacted with each other along with hydrogen peroxide and formed the hair dye. Progressive hair dyes change the color of hair gradually from light straw color to almost black by reacting with the sulfur of hair keratin as well as oxidizing on the hair surface. [7] Deamination has been suggested as a mode of action of PPD, which results in the production of aniline, most likely to contribute in part to the toxic effects of the compound.
Paraphenyl-diamine [C 6 H 4 (NH 2 ) 2 ] is a key ingredient for most of the hair dyes, and it's used for color enhancement. It is an aromatic amine, and derived from paranitroanaline. In addition, it is not found in nature and many industrial companies produce it commercially from coal tar. It is available in the form of white crystals when it's pure and rapidly turns to brown when it's exposed to the air. It has a molecular weight of 108 Dalton with boiling point of 267°C and melting point of 140°C. It is easily soluble in ethanol, ether, benzene, chloroform, and acetone and partially soluble with agitation in water. Hair dye is available in several forms, and the most common cheap form is stone hair dye, which is available in 20 g pack. Other branded hair dyes like "Godrej", Super Vasmol, 33 Kesh Kala, L'Oreal, Garnier, Color mate, etc., are available in powder or liquid forms. The concentration of PPD in hair dye formulation varies from 70% to 90% in stone hair dye and 2-10% in branded dyes, which are used for giving black color to hair. [8] Exact concentrations of PPD in different formulations are not known because most hair dye formulations are proprietary. PPD is rapidly absorbed into the blood through mucous membranes of the digestive tract after its oral intake. It is acetylated into N-acetyl-PPD and N, N-diacetyl-PPD as major metabolites for detoxification and be excreted in the urine. It is also added to henna (Lawsonia alba) and used in the popular tattooing for its darkening effect.
Hair dye consumption is not an uncommon means of suicidal attempt in the under developed countries probably due to easy availability and affordability. Poison Control Center of Morocco had retrospectively analyzed 374 cases of hair dye poisoning. [9] A study of 150 cases over 10 years was reported from Khartoum, Sudan. [10] Numerous case reports have been published from India, most of which are from Andhra Pradesh. [11],[12]
A three-phase evolution has been observed in PPD intoxication with inflammatory stress characterized by a relative immunodepression in the first 3 days, proinflammatory state (due to rhabdomyolysis) from 3 rd to 6 th day and immunomodulative action (due to oxidative metabolism) from the 6 th day. It causes systemic inflammatory reaction specific to a cytotoxic cell support. [13] The pathophysiologic mechanisms could be due to increased free radical formation, skeletal and cardiac muscle necrosis (scattered coagulation necrosis), formation of highly nephrotoxic quinonediamine (an oxidation product of PPD metabolites), renal tubular occlusion due to myoglobin casts, and acute tubular necrosis. Hoarseness of voice, pneumothorax, cardiac toxicity, hepatitis, hypotension, convulsions, coma, and sudden cardiac death are on the toxic end of the spectrum.
Clinical features
The characteristic triad of features encountered is early angioneurotic edema of face and neck with stridor, rhabdomyolysis with chocolate colored urine and acute renal failure (ARF) could be a confirmative evidence of PPD poisoning even in the absence of laboratory facilities and when history is lacking in case of emergency. [14] These patients have marked oro-facial swelling with swollen hard protruding tongue and edematous bull neck. They have difficulty in breathing secondary to upper respiratory tract edema.
Paraphenyl-diamine provokes one of the most prominent edema, and it appears to be grossly specific and selectively localized in the head and neck. It was suggested that the toxic effect of the PPD might be produced by the conversion of the PPD on mucus surfaces to its oxidation product quinondimine, which is responsible for intense local irritation. Some authors believed that PPD toxicity is due to some effect either on the blood colloids or on vascular permeability. Furthermore, it was believed that the PPD toxicity is due to altered vascular permeability and involvement of the parasympathetic nervous system. [15] Deamination and formation of analine are claimed to be responsible in part for the toxic symptoms. These different views as to the cause of PPD edema appear to be due to the fact that the exact number and nature of the oxidation products are not known. These results were consistent with the view that oxidative stress may be an essential part of the preimmunological phase in the induction of the allergic contact dermatitis by PPD. [16]
Hair dye is a potent nephrotoxic cocktail containing PPD, propylene glycol and resorcinol. The extent of renal involvement in poisoning varies between transient proteinuria and oliguric acute kidney injury (AKI). AKI commonly develops a few days after PPD exposure. The development of AKI in PPD intoxication does not occur in all patients and varies from 47.3% to 100%. [17] Animal studies demonstrated no histological changes in the kidneys of mice when they were exposed to PPD. However, there was strong evidence of severe nephrotoxicity in humans, and histopathological changes of acute tubular necrosis have been described. [18] The mechanisms of kidney injury following hair dye poisoning are many. The PPD itself has a direct toxic effect on kidney due to its aromatic structure, which makes its easy reabsorption and concentration in tubule and can cause ARF. Rhabdomyolysis is the main cause of ARF. Hypovolemia and metabolites of PPD also contribute to AKI. In the series by Ram et al., the incidence of AKI was 70%. [19]
Rhabdomyolysis is a well-known complication of PPD poisoning. PPD causes rhabdomyolysis by promoting calcium release and leakage of calcium ions from the smooth endoplasmic reticulum, followed by continuous contraction and irreversible change in the muscle's structure, which results in deposition of myoglobin cast within the renal tubules and hemolysis causing acute tubular necrosis and AKI. [20] Skeletal muscle biopsy of patients showed scattered coagulation necrosis with associated muscular inflammatory cellular infiltration. The diagnosis is established by the demonstration of myoglobin in the urine and elevated levels of creatine phosphokinase (CPK) and aldolase in the serum. [21] Since myoglobin is a small molecule with a molecular weight of 17 kDa and binds only lightly to the plasma proteins, it escapes easily in the urine. Therefore, the urine may not contain myoglobin if the patient presents late in the course of the disease and the true incidence of myoglobinuric ARF will be underestimated.
Propylene glycol is a viscous, colorless liquid commonly used as a solvent in hair dyes which a potential nephrotoxin. It is associated with hyperosmolality, raised anion gap metabolic acidosis, central nervous system depression, arrhythmias and renal dysfunction. [22] Proximal renal tubular cell swelling and vacuole formation have also been seen in propylene glycol ingestion. [23] However, the characteristic features of rhabdomyolysis and laryngeal edema which typify PPD poisoning are absent. Resorcinol found in hair dyes is a phenol derivative, which may also contribute to renal toxicity. In addition, a few hair dyes also contain lead acetate and bismuth sulfate, which can cause chronic kidney disease or acute interstitial nephritis respectively.
Kallel et al., had observed PPD intoxication in 19 patients over a 6-year period in Tunisia. [24] Clinical symptoms were dominated by cervicofacial edema (79%), chocolate-brown colored urine (74%), upper airway tract edema (68.4%), oliguria (36.8%), muscular edema (26.3%) and shock (26.3%). Rhabdomyolysis and metabolic acidosis were seen in all the patients. ARF was seen in 47.4% and hyperkalemia in 26.3%.
The respiratory syndrome following the oral ingestion of hair dye produces severe airway compromise as a result of direct trauma to the tissues by chemicals and causes dyspnoea and asphyxia secondary to inflammatory edema involving cricopharynx and larynx which frequently warrants an emergency airway intervention. Suliman et al., [25] noted Angioneurotic edema in 68% and emergency tracheostomy had to be done in 15.8%. Senthilkumaran et al., [26] had reported alveolar rupture possibly secondary to trapping of large volume of air which maybe due to intense inspiratory effort as a result of laryngeal edema, which might have contributed to over-distension of the alveoli, and interstitial pulmonary air leak in 2 cases, rather than rupture of bullae. In an autopsy series of eight cases of hair dye poisoning, pneumothorax was noticed in two without any other demonstrable pathology. [27] In view of clinical observations and autopsy evidences of pneumothorax in hair dye poisoning, physicians treating such cases have to consider the possibility of pneumothorax if patient has respiratory distress, as timely intervention saves lives.
Myocarditis is a fatal and a commonly neglected complication of PPD poisoning, due to lack of awareness of this complication among medical community and paucity of data in the medical literature. The incidence of myocarditis was 15% with a high mortality rate of 29%. [28] However, the incidence is bound to vary with patients differing in their susceptibility to PPD, apart from the amount of dye ingested. However, oral ingestion of PPD in doses >10 g especially unbranded stone hair dyes results in extensive myocardial damage. Singh et al., reported a case with right bundle branch block, supraventricular and ventricular ectopics with elevated parameters of myocardial damage, and the patient could not be revived. [29] In another case published by Singh et al., patient developed ST segment elevation and T wave inversion in the anterior chest leads with elevated biochemical parameters and the patient expired. [30] Right bundle branch block is a relatively rare electrocardiographic finding in myocarditis. [31] Cardiac biomarkers suggestive of myocardial necrosis like troponin T/I (>0.1 ng/ml) and CPK-MB were elevated in most of the cases. [32] Transthoracic echocardiography revealed wall motion abnormality and decreased left ventricular systolic function (left ventricular ejection fraction ≤35%) which subsequently improved on follow-up.
In animal studies, it was proved that PPD has a toxic effect on the parasympathetic nerves. In humans, neurotoxicity noticed ranging from drowsiness to coma, paraplegia and paraparesis have been published. In the animal study, it was reported that 89% of the mice fed PPD developed lenticular changes indicating that PPD has cataractogenous effects, which are related to the duration, amount, and individual sensitivity. [33] It was concluded that PPD is potentially toxic to human lens. Exophthalmia and permanent blindness due to optic nerve atrophy following PPD poisoning were reported.
Management of acute hair dye poisoning
Patients should be monitored for respiratory distress and endotracheal intubation has to be performed early if there is stridor due to laryngeal edema, or surgical airway has to be created to prevent hypoxia. As there is no specific antidote for PPD, the treatment is mainly supportive and it depends on the clinical scenario. Antihistamines and steroids are commonly used in the management of airway edema because of the possibility of a hypersensitivity reaction to PPD but there is no evidence to support this mode of treatment. [34] Alkaline diuresis using isotonic saline, sodium bicarbonate, and osmotic diuretics are attempted in the management of myoglobinuria. [35] trials of PPD removal was attempted using hemoperfusion and hemodialysis, with variable results. [36] The PPD is not dialyzable [37] and dialysis is part of supportive therapy. The most consistent predictors of mortality are amount of hair dye ingested, hyperkalemia, hypocalcemia and hyperphosphatemias and mortality rates varied between 0.03% and 60%. [38] Information on the systemic effects and outcome of hair dye poisoning in pregnant mothers and children are limited. [39]
Awareness of this condition, early diagnosis of rhabdomyolysis and AKI and timely institution of appropriate supportive measures will have a better outcome in hair dye poisoning. The time of development of renal failure following PPD intoxication is unpredictable, and hence all patients should be monitored in hospital for development of renal complications.
| Pearls and Pitfalls | | |
- If hair dye poisoning is not recognized early, it has high mortality.
- Early intubation or tracheostomy will be lifesaving.
- Urine may not contain myoglobin if the patient presents late.
- Henna leaf can be the primary offender of AKI due to hemolysis in mixed toxicities. [40]
- Possibility of pneumothorax has be considered if hypoxia persist or cardiorespiratory arrest.
- Serum creatinine kinase level is not a reliable indicator of myocardial injury.
- Sodabicarbonate and mannitol should be used early.
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