Whole bowel irrigation in dapsone intoxication with persistent methemoglobinemia.

Dapsone intoxication can be a life-threatening condition due its enterohepatic recirculation pharmacokinetics, and therefore, persistent methemoglobinemia development. We describe a case of a 17-year-old girl who was admitted 4 h after ingesting 5 g of dapsone. She presented methemoglobinemia (39%) and showed clinical signs of toxicity (cyanosis and altered mental status) despite mechanical ventilation. Multiple activated charcoal dosis and methylene blue infusions were performed. Notwithstanding initial improvement, a pattern of peaks and valleys was observed in serial methemoglobinemia measurements, with cyclic states of hypoxemia. On account of enterohepatic recirculation pharmacokinetics, clearance was enhanced by whole bowel irrigation. After 7 days of hospitalization, she was discharged in good general condition.

The usefulness of the SOFA and APACHE II scoring systems for the early prediction of mortality in patients with dapsone poisoning.

The rate of mortality from dapsone poisoning is high because of the long absorption half-life of dapsone. This study aimed to evaluate the usefulness of the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scoring systems for the early prediction of mortality in patients with dapsone poisoning. This is a retrospective and observational study of consecutive patients diagnosed with dapsone poisoning. The SOFA and APACHE II scores were obtained within the first 24 h of admission. Patients were divided into survivor and non-survivor groups. In total, 106 patients were included. The SOFA scores of the survivor and non-survivor groups were 1 (0-8) and 4 (1-10), respectively (p < 0.001). The APACHE II scores of the survivor and non-survivor groups were 9 (1-25) and 14 (3-23), respectively (p < 0.001). Based on these scores and in-hospital mortality cases, the standardized mortality ratios for the APACHE II and SOFA were 1.00 (95% confidence interval (CI): 0.64-1.48) and 1.00 (95% CI: 0.64-1.49), respectively. In the model adjusted for clinically important variables and variables with significant differences between the survivor and non-survivor groups, the area under the curve of the SOFA (0.907; 95% CI: 0.834-0.955) was significantly higher than that of the APACHE II (0.793; 95% CI: 0.703-0.867) (p = 0.008). The SOFA and APACHE II score systems had good discrimination and satisfactory calibration performance in patients with dapsone poisoning. However, the SOFA score was a more useful method in predicting mortality than the APACHE II score.

Metahemoglobinemia inducida por dapsona: presentación de un caso pediátrico / Methemoglobinemia due to Dapsone: a pediatric case report

La metahemoglobinemia es una patología caracterizada por la presencia de altas concentraciones de metahemoglobina en sangre. Esta es una forma oxidada de la hemoglobina, muy afín al oxígeno, que es incapaz de cederlo a los tejidos. Es una entidad poco frecuente, con baja sospecha diagnóstica. Aunque puede ser congénita en recién nacidos con cianosis, es más frecuente la adquirida por fármacos y tóxicos. En la Argentina, no se conoce la incidencia real de esta patología. El objetivo es comunicar un caso de metahemoglobinemia en una paciente pediátrica que ingresó al Hospital Magdalena V. de Martínez con cianosis en la cara y las extremidades, en mal estado general, con el antecedente de ingesta de varios comprimidos de dapsona, y se constató concentración sérica de metahemoglobina del 35%. El tratamiento consistió en la administración endovenosa de azul de metileno. Su evolución fue favorable.

Methemoglobinemia is a condition characterized by a high blood concentration of methemoglobin. Methemoglobinemia is a disorder that occurs when hemoglobin in the blood is oxidized to form methemoglobin, rendering it unable to transport oxygen. Although it can be congenital in cyanotic newborn, it is more often an adverse medication effect. The aim is to report a pediatric methemoglobinemia case, assisted in Magdalena V. de Martínez Hospital, with cyanosis in face and limb, in poor condition, that consumed dapsone accidentally. Her methemoglobin concentration was 35%. Intravenous methylene blue was administered with favorable outcome.

[Methemoglobinemia due to Dapsone: a pediatric case report]. / Metahemoglobinemia inducida por dapsona: presentación de un caso pediátrico.

Methemoglobinemia is a condition characterized by a high blood concentration of methemoglobin. Methemoglobinemia is a disorder that occurs when hemoglobin in the blood is oxidized to form methemoglobin, rendering it unable to transport oxygen. Although it can be congenital in cyanotic newborn, it is more often an adverse medication effect. The aim is to report a pediatric methemoglobinemia case, assisted in Magdalena V. de Martínez Hospital, with cyanosis in face and limb, in poor condition, that consumed dapsone accidentally. Her methemoglobin concentration was 35%. Intravenous methylene blue was administered with favorable outcome.

La metahemoglobinemia es una patología caracterizada por la presencia de altas concentraciones de metahemoglobina en sangre. Esta es una forma oxidada de la hemoglobina, muy afín al oxígeno, que es incapaz de cederlo a los tejidos. Es una entidad poco frecuente, con baja sospecha diagnóstica. Aunque puede ser congénita en recién nacidos con cianosis, es más frecuente la adquirida por fármacos y tóxicos. En la Argentina, no se conoce la incidencia real de esta patología. El objetivo es comunicar un caso de metahemoglobinemia en una paciente pediátrica que ingresó al Hospital Magdalena V. de Martínez con cianosis en la cara y las extremidades, en mal estado general, con el antecedente de ingesta de varios comprimidos de dapsona, y se constató concentración sérica de metahemoglobina del 35%. El tratamiento consistió en la administración endovenosa de azul de metileno. Su evolución fue favorable.

Difference of the clinical course and outcome between dapsone-induced methemoglobinemia and other toxic-agent-induced methemoglobinemia.

CONTEXT: Acquired methemoglobinemia is a potentially fatal condition that leads to tissue hypoxia. Although the clinical features of methemoglobinemia depend on the methemoglobin levels, the clinical course would differ depending on the causative agents. OBJECTIVE: We attempted to clarify this issue by comparing the clinical course of methemoglobinemia caused by dapsone and that caused by other toxic agents. MATERIALS AND METHODS: A retrospective case-control study was performed. All patients with methemoglobinemia and who were admitted to the emergency department (ED) of our hospital from 1 January 2002 to 31 December 2014 were included. RESULTS: Of the 34 patients with methemoglobinemia, 15 ingested dapsone (14 with acute overdose and one with chronic therapeutic use) and 19 had been exposed to other toxic agents, such as sodium nitrites, indoxacarb, primaquine, and lidocaine. The clinical characteristics and the course of dapsone-induced and other toxic-agent-induced methemoglobinemia were compared. There was no significant difference in clinical presentation and methemoglobin level (38.5% vs. 35.0%, p = 0.456) upon their ED arrival between the two groups. However, the methemoglobin level after use of methylene blue and the total dose of methylene blue were higher in patients with dapsone-induced methemoglobinemia than in those with other agent-induced methemoglobinemia (11.9% vs. 1.7%, p = 0.001, 455 mg vs. 144 mg, p = 0.006). The majority of dapsone-induced methemoglobinemia (93.3%) required more than 72 h for normalization of the methemoglobin level, despite the use of methylene blue. Five of the study patients died due to multiorgan failure, and all of whom were inpatients with dapsone-induced methemoglobinemia. CONCLUSION: The clinical course of dapsone-induced methemoglobinemia was worse than that of other toxic-agent-induced methemoglobinemia despite no significant difference in their initial clinical presentation. Continuous treatment with serial monitoring of the serum methemoglobin is necessary for patients with dapsone-induced methemoglobinemia.

Extracorporeal treatments in a dapsone overdose: a case report.

INTRODUCTION: Intentional dapsone intoxication can be life-threatening. There is limited data on the clinical effect of extracorporeal treatments (ECTRs) on dapsone elimination. We describe a case of severe dapsone toxicity treated with different ECTRs. CASE DETAILS: A 23-year-old woman was admitted 2.5 h after ingesting 2.2 g of dapsone. She developed methemoglobinemia (39.9%) and showed signs of toxicity (hemodynamic instability and altered mental status) despite multiple-activated charcoal, methylene blue, vasopressors and endotracheal intubation. Continuous venovenous hemofiltration (CVVH) was then initiated for 5 h, followed by intermittent hemodialysis with hemoperfusion (IHD-HP) for 4 h, and CVVH for another 48 h. The platelet count decreased to 32 × 109/L 3 h after IHD-HP. The elimination half-life of dapsone was 2.0 h during IHD-HP, and 14.2 h during CVVH. Mean dapsone clearance with IHD was 62 mL/min versus 22 mL/min with CVVH. IHD removed 95.3 mg, and CVVH removed 67.8 mg over 3.8 h. No rebound occurred following ECTR cessation. The toxicokinetics of dapsone metabolites were also accelerated during ECTR. The patient was extubated after 3.5 days and discharged without sequelae after 7 days. DISCUSSION: Dapsone clearance was enhanced by ECTR, especially by IHD-HP. However, HP was associated with severe asymptomatic thrombocytopenia.

Incidence and patterns of hemolytic anemia in acute dapsone overdose.

BACKGROUND: Hemolytic anemia is one of the complications related to the chronic consumption of dapsone. However, in acute dapsone overdose, there have been few case reports regarding hemolytic anemia. Herein, we reported the prevalence and patterns of hemolytic anemia in acute dapsone overdose, and compared clinical features including mortality in the non-hemolytic anemia and the hemolytic anemia groups. METHODS: We conducted a retrospective review of 43 consecutive acute dapsone overdose cases that were diagnosed and treated at the emergency department of the Wonju Severance Christian Hospital between January 2006 and January 2014. RESULTS: There were 13 male patients (30.2%) and the ages of all patients ranged from 18 to 93 years with a median of 67 years. The ingested dose varied from a minimum of two 100-mg tablet to a maximum of twenty five 100-mg tablets. All patients had methemoglobinemia irrespective of the presence of hemolytic anemia. Among 43 patients, 30 patients (69.8%) were shown to have hemolytic anemia and hemolytic anemia developed the day after admission and persisted for more than 6 days after admission. Even though mortality rate was not significantly higher in the hemolytic anemia group, the hemolytic anemia group had significantly longer total admission and intensive care unit admission stays than the non-hemolytic group. CONCLUSIONS: A significant proportion of the patients with acute dapsone overdose is associated with occurrence of hemolytic anemia. Hemolytic anemia may be developed the day after admission and persisted for more than 6 days after admission. Therefore, monitoring of serum hemoglobin level is necessary.

Acute visual loss following dapsone-induced methemoglobinemia and hemolysis.

OBJECTIVE: While methemoglobinemia is a possible complication of chronic dapsone therapy or of acute overdose, serious adverse manifestations related to methemoglobin formation remain rare. We present an unusual case with severe ischemic retinal injury. CASE REPORT: A 30-year-old African woman presented with a sudden decrease of visual acuity secondary to retinal ischemia. She was chronically treated with dapsone (50 mg/day) for a dermatologic disease and denied any drug overdose. However, the determination of serum dapsone level on admission revealed a largely supratherapeutic concentration (20,044 µg/ml compared with 1-3.5 ± 0.5 µg/ml for therapeutic levels). The methemoglobin level at admission was 32% (sulfhemoglobin 1.2%), with hemoglobin level, 7.4 g/dl, schistocytes count, 2-5%, lactate dehydrogenase level, 580 IU/l, and haptoglobin level, < 10 mg/dl. The patient had both alpha-thalassemia and sickle cell trait. She was treated with methylene blue, vitamin C, and exchange transfusion. There was no improvement in visual symptoms over time. CONCLUSIONS: In a patient with supratherapeutic serum levels of dapsone, the severity of visual injury was associated with dapsone-induced methemoglobinemia and hemolysis, and perhaps also with some hematologic predisposing factors.

Acute Poisoning with Dapsone and Olanzapine: Severe Methemoglobinemia and Coma with a Favourable Outcome.

Dapsone is a drug commonly used in the treatment of leprosy. In Europe it is rarely prescribed, mostly for the treatment of skin diseases such as dermatitis herpetiformis. Poisoning with dapsone is rare and reports of such cases are of interest for toxicological practice. We describe the only acute dapsone poisoning in a caseload series of 21,000 intoxications treated in the Clinical Toxicology Clinic at St George University Hospital in Plovdiv, Bulgaria between 1999 and 2013. We report on a 36-year-old woman who attempted deliberate self-poisoning with an ingestion of approximately 4.5 g of dapsone and 0.3 g of olanzapine. On admission, the patient was in a state of severe intoxication and comatose. On admission to hospital 9 hours after the ingestion, the methemoglobin level was 51.7%. The patient recovered 8 days later. She received complex treatment including intubation, ventilation, repeated gastric lavage, hemodialysis, blood exchange transfusion and antidote treatment with methylene blue. She was discharged in good clinical condition with minimal organ damage such as mild toxic hepatitis.

[Dapsone-induced methaemoglobinaemia]. / Dapsoninduceret methæmoglobinæmi.

Dapsone is used as an antibiotic for dermatological disorders and may cause methaemoglobinaemia. Specific treatment with intravenous methylene blue is the treatment of choice. We present a case of dapsone-induced methaemoglobinaemia. Arterial blood gas analysis showed that pH was 7.4, PaO2 11.7 kPa, PaCO2 4.5 kPa and bicarbonate concentration 21.9 mmol/l. The methaemoglobin level was found to be 32%. The symptoms were headache and tachycardia. Methylene blue was administered and the methaemoglobin level dropped to 5% within three days.

Acute dapsone overdose: the effects of continuous veno-venous haemofiltration on the elimination of dapsone.

A 15-year-old girl presented after intentional ingestion of dapsone (7.2 g) and small quantities of azathioprine, methotrexate and prednisolone. The resulting methaemoglobinaemia and lactic acidosis persisted despite treatment with methylene blue, multiple-dose activated charcoal and ascorbic acid. Continuous veno-venous haemofiltration for 75 hours was used to treat the dapsone overdose. The patient's serum dapsone concentrations were measured during and after continuous veno-venous haemofiltration. The rate of elimination of dapsone was over three times higher during, compared to after, continuous veno-venous haemofiltration. Continuous renal replacement therapy successfully reduced toxic dapsone concentrations in this patient with a good outcome.

Case files of the medical toxicology fellowship at Banner Good Samaritan Medical Center in Phoenix, AZ: methemoglobinemia following dapsone exposure.

Acquired methemoglobinemia is a common, potentially fatal syndrome that can occur as a result of exposure to numerous xenobiotics. A case report of a 14-month-old female who developed methemoglobinemia following a dapsone ingestion. The child was treated with numerous boluses of methylene blue and ultimately required a continuous infusion of methylene blue. The common causes of methemoglobinemia, as well as the underlying pathophysiology, diagnosis, and treatment strategies are discussed.

Dapsone intoxication: clinical course and characteristics.

BACKGROUND AND OBJECTIVES: Dapsone is used as an antibiotic for leprosy and for dermatological disorders and may cause methemoglobinemia. The aims of this study are to analyze the clinical characteristics of patients presenting to the emergency department (ED) with dapsone ingestion to identify risk factors associated with mortality. METHODS: We conducted a retrospective observational study of adult ED patients with methemoglobinemia because of dapsone intoxication admitted to a tertiary care hospital from September 2003 to December 2008. Data collected included demographic, clinical, and laboratory characteristics, as well as survival to discharge. Characteristics of young (less than or equal to 55 years) and older (greater than age 55) patients were compared. The main outcome was in-hospital mortality. RESULTS: There were 46 patients included in the study. The minimum intoxication dose was two 100 mg tablets and the maximum was 100 tablets. Changes in mental status were more common in the older patients. Methemoglobin levels were slightly higher in the younger patients, but both groups were treated with similar doses of methylene blue. Shock and death were more common in the older patients. CONCLUSIONS: Late presentation to medical care and an altered mental status at the time of presentation were predictive of death after dapsone intoxication. Methemoglobin levels tended to be higher in those who died.

Effectiveness of hemodialysis in acute dapsone overdose-a case report.

The use of dapsone is increasing even though overdose is rarely reported and physicians must be aware of its toxicity and management. Mortality can occur due to methemoglobinemia and hemolytic anemia. Although activated charcoal and methylene blue are recommended, the use of hemodialysis is reported only in few studies. Literature on the kinetic profile indicates that 50% to 80% of dapsone is protein bound and indicates a possibility to dialyze the unbound form. This study describes a case of deliberate severe dapsone overdose with cyanosis, methemoglobinemia, and hemolytic anemia, which improved after repetitive hemodialysis.

A case of dapsone induced methaemoglobinaemia.

BACKGROUND: We present a case of dapsone induced methaemoglobinaemia that occurred in a patient who presented to the Emergency Department of a University Hospital. It is an uncommon condition that requires specific and urgent treatment in severe cases. AIMS: To describe and evaluate the presenting symptoms, signs, diagnosis and management of acquired methaemoglobinaemia. METHODS: We describe a case of acquired methaemoglobinaemia as a result of dapsone ingestion with a literature review. CONCLUSIONS: Acquired methaemoglobinaemia is an uncommon condition that presents with non-specific signs and symptoms. It is caused by a variety of exogenous agents and results in a "saturation gap" between oxygen saturation on pulse oximetery and arterial blood gas analysis. Specific treatment with intravenous methylene blue is the treatment of choice. Full resolution can be expected with treatment but severe cases can be associated with shock and mortality.

Dapsone induced methemoglobinemia : Intermittent vs continuous intravenous methylene blue therapy.

OBJECTIVE: The study compares the decline in blood methemoglobin (MetHb) level in children of dapsone intoxication treated with intermittent and continuous methylene blue therapy. METHODS: Eleven children with history of accidental dapsone ingestion and suggestive clinical features of dapsone intoxication were studied. Patients were randomized into two groups: Gr I (n=5) received intermittent methylene blue therapy, while Gr II (N=6) as continuous infusion. The dose of methylene blue was same in both groups. MetHb level in blood was assessed by spectrophotometer at admission and thereafter 12hrly up to 72 hrs. The decline in MetHb was statistically analyzed with student t-test. RESULTS: Six patients had history of seizure and altered sensorium. Severe anemia was observed in 2 patients. The mean levels of MetHb in Gr II was statistically significant after 12, 24, 36, 48 and 72 hrs of methylene blue therapy as compared to Gr I. CONCLUSION: Continuous I.V methylene blue therapy causes significant decline in MetHb level and is more effective in treatment of methemoglobinemia as compared to intermittent regimen.

Optical coherence tomographic evaluation of macular infarction following dapsone overdose.

A 16-year-old girl had decrease in vision following dapsone overdose. This case demonstrated optical coherence tomography (OCT) evaluation of macular infarction following dapsone poisoning. OCT showed characteristic serial changes as Stage 1: Cystic macular edema, Stage 2: Resolving cystic change and Stage 3: Foveal atrophy. Hence, OCT could show the progression of foveal atrophy from cystic macular edema following dapsone poisoning.

Acute methemoglobinemia following attempted suicide by Dapson.

This report describes the case of an otherwise healthy young adult female, with oral ingestion of 40 unknown tablets. Her clinical course included progressive bluish discoloration of lips and limbs, hemolysis and jaundice. A high PaO2 in the presence of cyanosis and dark blood lead to suspicion of methemoglobinemia. Laboratory results showed methemoglobin level to be 3.8 g/dL (38%). The etiology was traced to dapsone according to patient history; after 3 days it became evident that she had ingested 2 g dapsone in suicidal intent. The therapeutic and diagnostic approach in such patients is discussed. In conclusion, acute methemoglobinemia is an uncommon but potentially treatable disorder.