Early Changes of Peripheral Blood Lymphocyte Subpopulations in Patients with Occupational 2,4-dinitrophenol Poisoning.

2,4-dinitrophenol (DNP), an organic compound which frequently used in industry, is considered to have high toxicity. This study aimed to investigate the early changes of lymphocyte subpopulations in patients with occupational 2,4-DNP poisoning. Totally 9 patients with acute occupational 2,4-DNP poisoning and 30 healthy volunteers as control were enrolled. The patients received immediately comprehensive supportive treatments, including large-dose glucocorticoid and repeated hemoperfusion (HP). The ratio of CD4+/CD8+ T cells were significantly higher in patients upon admission compared to healthy controls (P < 0.01); however, counts of total lymphocytes, CD3+, CD3+CD4+, CD3+CD8+, B (CD19+), and natural killer (NK) cells (CD16+CD56+) were significantly reduced (all P < 0.001). The NK cell count was negatively correlated with initial plasma 2,4-DNP concentration (r = -0.750, P = 0.026). Thus, acute occupational 2,4-DNP poisoning was accompanied by immediate complex immune cell reactions, especially NK cells might play important role in severe 2,4-DNP poisoning.

[Tattooing agents and adverse reactions]. / Tätowiermittel und ihre Unverträglichkeitsreaktionen.

BACKGROUND: Tattoos are regarded as body jewelry and have become widespread in all parts of society. Despite introduction of the tattooing agents' regulation (Tätowiermittelverordnung) in Germany in 2009, consumer protection is incomplete. OBJECTIVES: Prevalence of tattoos and their legal basis, ingredients of tattooing agents, clinical findings of adverse reactions, pathogenesis and therapy. METHODS: The work is based on a selective literature search in PubMed and on the clinical experience of the authors. RESULTS: Adverse reactions by tattooing are a particular problem, because the causing substances are not biodegradable within the tissue. In addition to an agonizing pruritus, the clinical picture is characterized by erythematous plaques. Histopathology reveals different patterns of inflammation, including pseudolymphomatous reactions. Treatment is problematic. In many cases, extensive surgical excision is necessary, which is associated with cosmetic consequences. CONCLUSION: A regulation to assess the safety of tattooing does not exist.

Histopathology and immune histochemistry of red tattoo reactions. Interface dermatitis is the lead pathology, with increase in T-lymphocytes and Langerhans cells suggesting an allergic pathomechanism.

BACKGROUND: The majority of tattoo reactions are affiliated to red pigmented areas and often suspected to be allergic in nature. A sizeable series of biopsies of such reactions has not previously been performed. The aim of this study was to type and grade epidermal and dermal changes in tattoo reactions to red/red nuances by microscopy and immunochemistry relevant for the assessment of a possible allergic pathomechanism. METHODS: Skin biopsies were taken from red tattoo reactions, graded by conventional microscopy and stained for T and B-lymphocytes, Langerhans cells, macrophages and tumour necrosis factor (TNF)-α. RESULTS: The study included 19 biopsies from 19 patients. The culprit colours were red/pink (n = 15) and purple/bordeaux (n = 4). Interface dermatitis was clearly the lead pathology found in 78% of samples, overlapped with granulomatous (in 32%) and pseudolymphomatous reaction patterns (in 32%). Epidermal hyperkeratosis (in 89%) was common as was leakage of red pigment across the dermo-epidermal junction, with transepidermal elimination (in 28%). The dermal cellular infiltration was dominated by T-lymphocytes (in 100%), Langerhans cells (in 95%) and macrophages (in 100%). TNF-α was common. CONCLUSION: The predominant histological pattern of chronic tattoo reactions in red/red nuances is interface dermatitis. T-lymphocytes and Langerhans cells are increased suggesting an allergic pathomechanism. TNF-α may contribute to reactions. In many cases, overlapping reactive patterns were identified.

Patients with tattoo reactions have reduced quality of life and suffer from itch: Dermatology Life Quality Index and Itch Severity Score measurements.

BACKGROUND: Tattoos are a trend with increasing side-effects. The burden of local reaction with swelling, itching and discomfort may impel sufferers to consult medical assistance. OBJECTIVES: To assess tattoo reactions and their influence on quality of life and itching by utilizing the Dermatology Life Quality Index (DLQI) scoring system and Itch Severity Scale (ISS). METHODS: Patients attending the 'Tattoo Clinic' at Bispebjerg University Hospital, Denmark with tattoo problems spanning more than 3 months were invited. Forty patients participated during September-November 2012. Patients attending their routine consultations completed the ISS and DLQI questionnaires. RESULTS: Patients with tattoo reactions experienced reduced quality of life, DLQI score 7.4 and were burdened by itch, ISS score 7.2. Both DLQI and ISS results attained the level of discomfort of known skin diseases such as psoriasis, pruritus and eczema albeit the typical tattooed affected areas are smaller. CONCLUSION/DISCUSSION: Sufferers of tattoo reactions have reduced quality of life and are often burdened by itching attaining the level of other cumbersome afflictions recognized as dermatological diseases associated with itch. Tattoo reactions warrant diagnosis and treatment with same professional intent shared with other skin diseases.

From diamonds to black stone; myth to reality: Acute kidney injury with paraphenylene diamine poisoning.

AIM: We report here, a case series of patients with acute kidney injury (AKI) after ingestion of paraphenylene diamine (PPD) a derivative of analine. It is used as a colouring agent to dye hair, fur and plastic and in photographic films. METHODS: Subjects for the study reported here comprised a cohort of 100 patients coming to this institution with AKI following PPD poisoning. AKI was defined according to RIFLE criteria and PPD poisoning on the basis of history and presenting features. All patients had normal sized kidneys on ultrasonography and no previous co- morbidity. RESULTS: One hundred patients with AKI after PPD exposure were brought to this institute between May 2010 and February 2015. Among these, 56 were females, with mean age of 23.11 ± 7.94 years. Cause of AKI was toxic rhabdomyolysis as indicated by marked rise in muscle enzymes with mean lactate dehydrogenase and creatinine phosphokinase levels of 6665.22 ± 6272.04 and 194 486.66 ± 301 905.80, respectively. Hepatotoxicity with raised aspartate aminotransferase and alanine aminotransferase was a main feature of the studied population. Renal replacement was required in 97% of patients. Complete renal recovery was observed in 77 patients, while 16 died during the acute phase of illness. Respiratory failure and recurrent hyperkalaemia were the main causes of mortality. CONCLUSION: Easy availability and low cost of PPD has lead to a remarkable increase in the use of this substance, especially for suicidal purposes. Awareness of its effects among health professionals, as well as at a societal and government level, is needed at this time.

Paraphenylenediamine Containing Hair Dye: An Emerging Household Poisoning.

Paraphenylenediamine poisoning is among one of the emerging causes of poisoning in Asian countries, because it is a constituent of hair dye formulations and is easily available in market at low cost. Hair dyes are rampantly used in Asian households compared with the western world. Locally, hair dye constituents may have allergic adverse effects, and acute systemic poisoning presents with characteristic angioedema, upper airway obstruction, rhabdomyolysis, methemoglobinemia, myoglobinuria, and acute renal failure. This study reports about the death of a 24-year-old Indian housewife who committed suicide by taking hair dye emulsion. She had an argument with her husband, and because of fit of rage, took a bowlful (80 mL) of hair dye emulsion kept prepared for the use by husband. She developed angioedema, cervical swelling, and rhabdomyolysis and died of acute renal failure within 24 hours. Toxicological analysis of viscera and blood revealed varying levels of paraphenylenediamine. Histopathological samples of kidney showed features of acute tubular necrosis and myoglobin casts in renal tubules. The aim of the study is to create awareness about the adverse effects of the hair dye, its poisoning outcome, and possible preventive measures.

High-frequency ultrasound imaging of tattoo reactions with histopathology as a comparative method. Introduction of preoperative ultrasound diagnostics as a guide to therapeutic intervention.

BACKGROUND AND AIM: Tattoo adverse reactions requiring diagnostic evaluation and treatment are becoming more common. The aim of this study was to assess tattoo reactions by 20-MHz ultrasonography referenced to histopathology as a comparative method. MATERIALS AND METHODS: A total of 73 individuals with clinical adverse reactions in their tattoos were studied. Punch biopsies for reference histology were available from 58 patients. The Dermascan C(®) of Cortex Technology, Denmark, was employed. Total skin thickness and echo density of the echolucent band in the outer dermis were measured. Biopsy served for diagnosis and for determination of the level of cellular infiltration in the dermis. RESULTS: In every tattoo reaction studied, the skin affected was found thicker compared with regional control of the same individual (mean difference 0.73 mm). A prominent echolucent band of mean thickness 0.89 mm was demonstrated, primarily located in the very outer dermis but propagating to deeper dermal layers parallel to increasing severity of reactions. The thickness of the echolucent band correlated with the thickness of cellular infiltration determined by microscopic examination, R = 0.6412 (P < 0.001). Special diagnoses such as granulomatous and pseudolymphomatous tattoo reactions showed no distinct characteristics by ultrasound, but mainly displayed themselves by their advanced inflammatory component. DISCUSSION AND CONCLUSION: It is demonstrated for the first time that ultrasound, with histopathology as the comparative method, can quantify the severity of tattoo reactions and non-invasively diagnose the depth of the inflammatory process in the dermis elicited by the microparticulate tattoo pigment, which itself is too minute to be imaged by ultrasound. Preoperative 20-MHz ultrasound scanning is introduced as a potentially useful method to guide therapeutic interventions by surgery and lasers.

Hair dye poisoning in Bundelkhand region (prospective analysis of hair dye poisoning cases presented in Department of Medicine, MLB Medical College, Jhansi).

AIMS OF STUDY: Hair dye (Paraphenylene di-amine, PPD) poisoning has high morbidity and mortality and its incidence has increased dramatically in the past 4 years. A prospective study was planned to assess the clinical profile and outcome with different treatment approaches. MATERIAL AND METHODS: The material comprised of 1020 cases admitted in Medicine Department of MLB Medical College, Jhansi, U.P. from July 2004 to March 2009. Out of 1020 cases 697 cases were of stone hair dye poisoning and 323 cases were of other branded hair dyes (powdered form containing less amount of Paraphenylene diamine). Diagnosis was made solely on the basis of the history given by cases/attendant and symptoms of neck swelling, black coloured urine and muscular pain. The cases were thoroughly studied for different complications (renal, hepatic and cardiac etc) and were treated accordingly. RESULTS: Out of 1020 cases studied, majority were females in the age group of 15-45 yrs (n=734) while the rest were males. A total of 244 (23.92%) cases expired during treatment. Neck swelling, respiratory distress and whole body muscular pain were most common symptoms at presentation, oliguria, chest pain, palpitation, presyncope/syncope, pain in abdomen, nausea with vomiting and dysphagia were other common symptoms. CONCLUSION: Paraphenylene diamine is highly toxic. Cases who consumed up to 10 gm of PPD usually survived if they presented to hospital within 4 hour of dye ingestion. Severe edema of face, neck and floor of mouth, renal failure and myocarditis were poor prognostic factors. No deaths occurred in cases of Branded Hair dye ingestion.

Clinical profile of acute paraphenylenediamine intoxication in Egypt.

Orientation to paraphenylenediamine (PPD) acute systemic intoxication in Egypt has been increased over the last decade. The aim of this study was to provide more insight into the clinical profile of acute PPD intoxication with reviewing the possible underlying mechanisms. Our study was retrospective. It was conducted over 7 years (2001-2008) on 25 cases with acute PPD intoxication admitted to the Poison Control Center Ain Shams University Hospitals, Cairo, Egypt. The mean age of the cases was 35.34 +/- 10.5 years; the male to female ratio was 18:7. Cervicofacial and laryngeal edema was the dominating presenting manifestation in 72% of the cases, 100% of the cases developed rhabdomyolysis, 80% had impaired renal functions, elevated liver transaminases were detected in 76% of cases, 75% showed hyperkalemia and 16% died due to ventricular arrhythmia. In conclusion, PPD causes serious multisystem toxicity and its selling to the public should be officially restricted.

Methaemoglobinaemia during Holi festival.

We report eight children who developed methaemoglobinaemia after exposure to contaminated colours used during Holi, a traditional festival celebrated in India. Methaemoglobinaemia can be life-threatening, but outcome is good if treated in time with intravenous methylene blue. Physicians might encounter such cases after exposure to Holi colours and hence should be aware of this life-threatening but easily treatable complication.

Acute renal failure owing to paraphenylene diamine hair dye poisoning in Sudanese children.

INTRODUCTION: Paraphenylene diamine (PPD) has traditionally been used as a dark-coloured hair dye. In Sudan, it is used by women to colour their hair and as a body dye when added to henna (Lawasonia alba). Accidental or deliberate ingestion causes severe systemic toxicity. Although a wide variety of complications has been described, there are few reports in children. AIM: To describe the clinical features, management and outcome of PPD intoxication in Sudanese children. METHODS: Data for a 3-year period (2006-2008) were extracted from the medical records of the Paediatric Nephrology Unit, Soba University Hospital. Information included the circumstances of poisoning, gender, age distribution, clinical presentation, biochemical findings and outcome. RESULTS: Over the 3-year period, 17 children (16 female) were admitted to the Paediatric Nephrology Unit with PPD intoxication. Mean age was 13.8 yrs (range 2-18). Thirteen (76.4%) had attempted suicide, three (17.6%) were poisoned as a result of attempted murder and one poisoning (5.8%) was accidental. Eight children (47%) required tracheostomy for severe angioneurotic oedema. Of 12 (71%) who developed acute renal failure (ARF), nine required dialysis and three were managed conservatively. Two children (12%) died and the other 15 recovered with normal renal function. CONCLUSION: PPD intoxication is a life-threatening condition with significant morbidity and mortality in children. Clinical manifestations and outcome are similar to those in adults. Mortality can be reduced by early recognition, prompt referral and aggressive supportive treatment.

Hair dye ingestion--an uncommon cause of acute kidney injury.

INTRODUCTION: Dye containing paraphenylene diamine is not an uncommon cause of renal failure in South India. However, there are very few published reports on renal lesions associated with hair dye ingestion. MATERIAL AND METHODS: We studied 30 consecutive cases (24 males and 6 females) of hair dye induced renal failure seen at our department. All the patients were aged between 18 to 40 years (26.9 +/- 4.95 years). RESULTS: The quantity of dye consumed ranged between 50-100 ml (79.5 +/- 22.45). All patients presented with oliguria and fluid overload. Dyspnea was seen in 24 (80%) while 10 (33.33%) had hypertension. Encephalopathy and seizures were seen in 10 (33.3%). None of the patients had evidence of hemolysis, hematological abnormalities or skin rash. Three patients had elevated SGPT (340 IU/l) which returned to base line after 2 weeks while creatinine phosphokinase (CPK) was elevated in 6(20%) patients. The oliguric phase lasted from 1 to 3 weeks and serum creatinine normalized in 21 (70%) patients. Renal biopsy done in 15 patients (done antemortem in 10 and postmortem in 5) showed evidence of acute tubular necrosis (ATN) in 8, acute interstitial nephritis (AIN) in 7 patients. All patients received dialytic support. Eight (26.6%) patients succumbed. CONCLUSION: Hair dye is an unusual but important cause of acute kidney injury. The commonest renal lesions are acute tubulointerstitial damage. Respiratory and hemodynamic supportive therapy is essential for recovery.

LC-MS-MS analysis of 2,4-dinitrophenol and its phase I and II metabolites in a case of fatal poisoning.

A liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis of biological fluids (blood, urine, gastric content, and bile) collected at autopsy in a case of suspected 2,4-dinitrophenol (DNP) fatal poisoning allowed the determination of DNP and its known metabolites (2-amino-4-nitrophenol and nitro-4-aminophenol). The tentative identification of three conjugated metabolites (DNP glucuronide, DNP sulfate, and 2-amino-4-nitrophenol glucuronide) could be made on the basis of their pseudomolecular ion, isotopic and fragmentation patterns, and retention characteristics. Another DNP metabolite reported in the literature, 2,4-diaminophenol, was not detected in the samples. Postmortem blood concentrations were 48.4 mg/L for DNP and 1.2 mg/L for 2-amino-4-nitrophenol. Gas chromatography-MS screening and quantification in postmortem blood revealed the presence of toxic concentrations of citalopram and its desmethylated metabolite (0.58 and 0.40 mg/L, respectively) and therapeutic or lower than therapeutic levels of olanzapine (0.04 mg/L), desalkylflurazepam (0.02 mg/L), and nordazepam (0.01 mg/L). Based on LC-MS-MS results and on available literature data on DNP poisonings, it was concluded that DNP poisoning played a contributing role, together with citalopram, in the cause of death.

Development of Rapid and Economical Colorimetric Screening Method for p-Phenylenediamine in Variety of Biological Matrices and its Application to Eleven Fatal Cases of p-Phenylenediamine Poisoning.

A rapid colorimetric method for detection of p-phenylenediamine (PPD) in various biological samples is developed. The o-cresol test for acetaminophen detection has been modified to detect PPD in blood, urine, gastric contents, and liver. After precipitating protein with trichloroacetic acid solution (2 mL, 10% w/v), biological specimens were required to convert PPD metabolites to PPD by acid hydrolysis. Finally, o-cresol solution (1 mL, 1% w/v), hydrogen peroxide (200 µL, 3%v/v), and concentrated ammonium hydroxide (0.5 mL) were added in the biological samples. The presence of PPD was indicated by formation of violet color which was turned to bluish green color within 10-15 min. The limit of detection was found to be 2 mg/L in blood, urine, and gastric contents and 2 mg/Kg in liver. This method is also free from any potential interference by p-aminophenol, acetaminophen, and other amine drugs under test conditions. This method was successfully employed to thirteen fatal cases of PPD poisoning.

Clinical manifestations of systemic paraphenylene diamine intoxication.

BACKGROUND: To report clinical symptoms and outcome of systemic paraphenylene diamine (PPD) intoxication. METHODS: Our study was retrospective. It was conducted over 6 yrs (1994-2000) in the medical intensive care unit (ICU) of a university hospital and it concerned 19 patients hospitalized for systemic PPD intoxication. RESULTS: The mean age (+/- SD) was 27.9 +/- 16.8 yrs, the sex ratio was about 0.58 and the Simplified Acute Physiology Score (SAPS II) was 30 +/- 27. At admission, 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%). The biological results were dominated by rhabdomyolysis (100%), metabolic acidosis (100%), acute renal failure (ARF) (47.4%) and hyperkalemia (26.3%) (biological disturbances were more pronounced in patients with ARF). The therapies used were gastric lavage (100%), fluid infusion (100%), mechanical ventilation (84.2%), alcalinization (80%), corticosteroids (84.2%), vasopressors (26.3%) and renal replacement therapy (26.3%). The intoxication evolution was marked by the death of six patients (31.6%); five of them had developed ARF. The mechanical ventilation duration and the ICU stay were both more prolonged in patients who developed ARF. CONCLUSIONS: Clinical manifestations of systemic PPD intoxication were associated with respiratory, muscular, renal and hemodynamic syndromes. ARF occurrence testifies to the severity of the intoxication.

Injection of Xenopus oocytes with mRNA from cultured neurons induces new currents and susceptibility to the damaging action of ruthenium red.

The hexacationic dye ruthenium red produce neuronal death in primary cultures. We injected messenger RNA (mRNA) from cultured neurons into Xenopus laevis oocytes to test whether this treatment can make oocytes sensitive to the damaging action of ruthenium red. Two-microelectrode voltage clamp and resting membrane potential were used to evaluate mRNA expression and to assess the effect of the dye on oocyte survival, when added to the medium or when injected into the cells, at 20, 50, or 100 microM concentrations. Injection of mRNA from cultured cortical or cerebellar granule neurons produced both new outward currents and membrane hyperpolarization. Exposure of mRNA-injected oocytes to extracellular ruthenium red for 24 h induced a remarkable depolarization, but no significant damage was observed. Injection of the dye into buffer-injected oocytes did not cause any change in membrane potential or cell survival, whereas in mRNA-injected oocytes an important depolarization was observed at 24 h after ruthenium red introduction, and 29% of the cells showed serious damage. The results suggest that oocytes become sensitive to intracellular ruthenium red toxicity because they express neuronal-specific proteins involved in cell death.

Chemical monitoring of urine from workers potentially exposed to benzidine-derived azo dyes.

Benzidine (Bzd) and monoacetylbenzidine (MoAcBzd) were found in the urine of workers exposed to benzidine-based azo dyes. A colorimetric screening method, based on the reaction of extracted free aromatic amines with 2,4,6-trinitrobenzene-sulfonic acid (TNBS), was used with a specific electron-capture gas chromatographic (EC-GC) method. Alkaline hydrolyzable conjugates of Bzd and 2,4-diaminoazobenzene (DiAmAzBz) were found together with free DiAmAzBz and traces of 3,3'-dimethylbenzidine (DiMeBzd) and 3,3'-dimethoxybenzidine (DiMxBzd). The presence of a known human bladder carcinogen (Bzd) and its metabolites in the urine of workers exposed to benzidine-based azo dyes is a cause for concern.

Occupational history and genetic N-acetyltransferase polymorphism in urothelial cancer patients of Leverkusen, Germany.

OBJECTIVES: The study was designed to realize possible shifts in the ratio of slow to fast acetylators within a group of 196 urothelial cancer patients in an area with earlier benzidine production. METHODS: The subjects were interviewed for occupational and nonoccupational risk factors. The patients were phenotyped for N-acetyltransferase 2 (NAT2) by Grant's caffeine test. A subgroup of 54 patients was additionally genotyped for NAT2. RESULTS: The antimode in the NAT2 phenotyping with the caffeine test (AFMU: IX ratio) was 1.0, as evidenced by additional genotyping of the subgroup of 54 patients. The prevalence of slow acetylators in the entire group of bladder cancer patients was 55%, in accordance with published figures for European populations. In a subgroup of 40 patients with occupational histories as workers in chemical or rubber industries 65% were slow acetylators. In a further subgroup of 28 cases having specifically worked at chemical production sites of the local chemical industry, 68% were slow acetylators. CONCLUSIONS: In contrast to earlier studies, this study shows no increased prevalence of slow acetylators among urothelial cancer patients in comparison with the normal population. However, in subgroups of cases with a likelihood of past occupational contacts with aromatic amines, there was a trend towards a higher representation of slow acetylators. This finding is in accordance with observations of others that the percentage of slow acetylators in urothelial cancer patients is generally decreasing, possibly because the production of benzidine and benzidine-based dyes ceased in the early 1970s.

Optimization of an analytical method for detecting paraphenylenediamine (PPD) by GC/MS-iontrap in biological liquids.

A method for qualitative and quantitative determination of paraphenylenediamine in biological fluids (blood, urine and gastric content) was developed. This analytical procedure involves deproteneisation or hydrolysis, liquid-liquid extraction, derivatization with TFA followed by GC-MS iontrap analysis. Benzidine was the internal standard used for quantification and the extraction recovery test was about 85%. The detection limit of paraphenylenediamine was determined at 0.1 pg (S/N=10).