Challenges in Managing a Lepromatous Leprosy Patient Complicated with Melioidosis Infection, Dapsone-Induced Methemoglobinemia, Hemolytic Anemia, and Lepra Reaction.

BACKGROUND Leprosy is an infection caused by Mycobacterium leprae. An extensive literature search did not reveal many reports of melioidosis in association with leprosy. CASE REPORT A 22-year-old woman, who was diagnosed with multibacillary leprosy, developed dapsone-induced methemoglobinemia and hemolytic anemia, complicated by melioidosis. Methemoglobinemia was treated with methylene blue and vitamin C. Two weeks of ceftazidime was initiated to treat melioidosis, and the patient was discharged on amoxicillin/clavulanic acid and doxycycline as melioidosis eradication therapy. However, she developed drug-induced hypersensitivity. Trimethoprim/sulfamethoxazole, as an alternative treatment for melioidosis eradication, was commenced and was successfully completed for 12 weeks. During the fifth month of multidrug therapy, the patient developed type II lepra reaction with erythema nodosum leprosum reaction, which was treated with prednisolone. Leprosy treatment continued with clofazimine and ofloxacin, and complete resolution of skin lesions occurred after 12 months of therapy. CONCLUSIONS Our case highlighted the challenges posed in managing a patient with multibacillary leprosy with multiple complications. Clinicians should be aware that dapsone-induced methemoglobinemia and hemolysis might complicate the treatment of leprosy. Our case also highlighted the safety and efficacy of combining ofloxacin and clofazimine as a leprosy treatment regimen in addition to gradual steroid dose titration in the presence of type II lepra reaction.

Comparison of the Clinical Characteristics and Outcomes between Leprosy-Affected Persons in Sorokdo and the General Population Affected by Chronic Hepatitis C in Korea.

Background/Aims: Patients with Hansen's disease are the most vulnerable to hepatitis C. However, no data on the treatment efficacy of direct-acting antiviral agents (DAAs) are available in this group. Therefore, we elucidated the prevalence and clinical outcomes of hepatitis C in persons affected by leprosy in Sorokdo, Jeollanam-do, Korea. Methods: We retrospectively included 50 leprosy patients with positive hepatitis C virus (HCV) RNA test results (group A) hospitalized at the Sorokdo National Hospital from May 2016 to March 2018 and 73 patients with chronic hepatitis C who were treated with DAAs at the Chonnam National University Hospital (group B) from May 2016 to December 2017. Results: Overall, at the Sorokdo National Hospital, positive HCV antibody and HCV RNA rates were 18.4% and 11.0%, respectively. The mean participant age was 76.5±7 years, and 58% of participants were men. The genotypes were type 1b in 44% (22 out of 50) and type 2 in 56% (28 out of 50). Sustained virologic response was achieved at a rate of 95.5% (21/22) in genotype 1b and 92.9% (26/28) in genotype 2 patients. Ribavirin-induced hemolytic anemia occurred in 57.1% (16/28) of patients with genotype 2. Among these, 28.5% (8/28) received blood transfusions. Conclusions: Treatment efficacy was not different between the leprosy-affected population and the general population. However, severe ribavirin-induced hemolytic anemia requiring transfusion was present in 28.5% of genotype 2 patients. Therefore, we suggest ribavirin-free DAAs for the treatment of genotype 2 hepatitis C in leprosy-affected persons in the future.

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.

Triagem neonatal de deficiência de glicose-6-fosfato desidrogenase e prevalência das mutações G202A (G6PD A-) e C563T (G6PD Mediterrâneo) em Mato Grosso/Brasil / Neonatal Screening for glucose-6-phosphate dehydrogenase deficiency and prevalence of G202A (G6PD A-) and C563T (G6PD mediterranean) mutations in Mato Grosso / Brazil

Objetivos: A deficiência de glicose-6-fosfato desidrogenase (G6PD) está associada a um maior risco de encefalopatia bilirrubínica e de crise hemolítica aguda grave desencadeada por drogas como a primaquina e a dapsona. Conhecer a prevalência dessa deficiência enzimática em área onde a malária e a hanseníase ainda estão presentes e conhecer a prevalência das principais mutações traz subsídios para planejamento de estratégias com vistas à redução de riscos associados a esta deficiência enzimática. Métodos: Estudo descritivo transversal conduzido em uma região do centro-oeste do Brasil. Exame de triagem para deficiência de G6PD foi realizado em 3573 recémnascidos. Exame confirmatório foi necessário em 188 crianças triadas como possíveis portadores de deficiência. Nas crianças em que foi confirmada a deficiência de G6PD foi feita pesquisa das mutações G202A (G6PD A-) e C563T (G6PD Mediterrâneo) por PCR. Resultados: A deficiência de G6PD foi confirmada em 63 crianças, sendo 60 meninos (95,2%) e três meninas (4,8%). O percentual de exames falso-positivos na fase de triagem foi de 66,5%, estando o percentual de falso-positivos associado à temperatura e tempo de transporte das amostras. Entre as crianças que confirmaram deficiência de G6PD, foi mais frequente a história de anemia em familiares e de icterícia neonatal. Houve associação entre hematócrito baixo e deficiência enzimática, mas não com hemoglobina, contagem de reticulócitos ou neutrófilos. A prevalência da deficiência de G6PD (IC95%) foi de 1,76% (1,37; 2,24) entre os recém-nascidos triados e de 3,34% entre os meninos (2,58; 4,25). A mutação C563T não foi identificada em nenhuma criança, mas a mutação G202A estava presente em 58 crianças - 92,06% (IC95%: 83,29 - 97,03): 56/60 meninos e em 2/3 meninas homozigotas. Foi identificado um menino com Kernicterus portador da mutação G202A em hemizigose. Conclusão: O elevado percentual de falso-positivos na etapa de triagem, o tempo necessário entre coleta...

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with an increased risk of bilirubin encephalopathy in neonates and acute hemolytic crisis triggered by drugs such as primaquine and dapsone. In an area where malaria and Hansen's disease are still present, knowing the prevalence of this enzyme defect and determining the prevalence of major mutations is important for planning strategies for reducing the risks associated with this enzyme deficiency. Methods: Sectional study was conducted in a Midwestern region of Brazil. Screening for G6PD deficiency was performed in 3,573 neonates. Confirmatory tests were necessary for 188 positively screened children. After confirmation, PCR investigation was utilized to identify the mutations. Results: G6PD deficiency was confirmed in 63 children: 60 boys (95.2%) and 3 girls (4.8%). The percentage of false-positive cases in the screening phase, 66.5% and was associated with the temperature and transportation time of the samples. Family history of anemia and jaundice was more frequent among the children with confirmed G6PD deficiency. An association between a low hematocrit and enzyme deficiency was observed. However, there was no association with hemoglobin reticulocyte or neutrophils counts. The prevalence of G6PD deficiency (CI95%) was 1.76% (1.37; 2.24) among all screened neonates and 3.34% (2.58; 4.25) among male children. The C563T mutation was not identified in any child. The G202A mutation was present in 58 children - 92.06% (CI95%: 83.29 - 97.03), 56/60 boys and 2/3 homozygous girls. One boy with a hemizygous G202A mutation was identified as having Kernicterus. Conclusion: The high percentage of false-positive results when first screening for G6PD deficiency; the long delay time between the test and result; along with the high cost of the this screening test, are all factors that do not support adding this test to the already established Brazilian neonatal screening programs. The prevalence...

[Leprosy with an unusual course]. / Une lèpre d'évolution atypique.

In developed countries, Hansen disease, or leprosy, is a rare and little-known disease. Over the last few years, its prevalence in New Caledonia has remained stable (0.35 per 10,000 inhabitants). We report the case of an 11-year-old child who presented lepromatous leprosy complicated by a type 2 reaction. Despite appropriate treatment, the course was unusual with fever lasting a few weeks associated with asthenia, weight loss, and biological perturbations such as inflammatory syndrome, anemia, and hyperferritinemia. After a brief review of Hansen disease and its complications, we discuss the different hypotheses that can explain the clinical and biological progression of our patient (hemolytic anemia secondary to dapsone, type 2 reaction, and aspects of hemophagocytic syndrome) and describe therapeutic management, which led to a good outcome.

Recurrent disseminated intravascular coagulation caused by intermittent dosing of rifampin.

Daily rifampin therapy is associated with minimal adverse effects, but administration on an intermittent or interrupted basis has been associated with severe immunoallergic reactions such as hemolytic anemia, acute renal failure, and disseminated intravascular coagulation. We describe a patient with Mycobacterium leprae infection who experienced recurrent episodes of disseminated intravascular coagulation after intermittent exposures to rifampin, and review eight previously reported cases of rifampin-associated disseminated intravascular coagulation. In six (75%) cases, previous exposure to rifampin was reported and seven (87.5%) patients were receiving the medication on an intermittent or interrupted basis. Clinical features of rifampin-associated disseminated intravascular coagulation included fever, hypotension, abdominal pain, and vomiting within hours of ingestion. Average time to reaction was 3-6 doses if rifampin was being administered on a monthly schedule. Three (37.5%) of eight reported cases were fatal. A complete history of previous exposure to rifampin is recommended before intermittent therapy with this medication.

Hemolytic anemia in patients receiving daily dapsone for the treatment of leprosy.

INTRODUCTION: Multidrug therapy for leprosy is currently done with dapsone, clofazimine and rifampicin. Dapsone is known to cause hemolytic anemia (HA) and this adverse event during MDT seems to be more frequent than reported. The aim of this report is to discuss and grade HA due to dapsone during MDT treatment for leprosy. METHODS: This is a retrospective study of 194 leprosy patients from a Leprosy Control Programme Unit in Vit6ria-ES, Brazil. RESULTS: HA was observed in 48 (24.7%) patients and occurred within the first 3 months in 51% of these. Mean hematocrit levels fell from 38.5 to 31.5 and hemoglobin from 12.8 to 10.3. CONCLUSION: Dapsone used in the MDT regime for leprosy decreases the hematocrit and hemoglobin levels due to a low grade hemolysis, which can result in significant anemia.

Dapsone hypersensitivity syndrome in non-leprosy patients: a retrospective study of its incidence in a tertiary referral center in Taiwan.

BACKGROUND: Dapsone hypersensitivity syndrome (DHS) is a potentially life-threatening adverse drug reaction consisting of fever, hepatitis, exfoliative dermatitis, lymphadenopathy and hemolytic anemia. The incidence of DHS is estimated to be 2% in leprosy patients. Because the incidence of this drug eruption may be different in different ethnicities and diseases, we thought to investigate the incidence of DHS in non-leprosy patients. METHODS: This is a retrospective study to examine the incidence, clinical manifestations and prognosis of DHS in non-leprosy patients who were given dapsone at the National Taiwan University Hospital between June 2001 and December 2005. RESULTS: The incidence of DHS among non-leprosy patients was 1.66%. These patients ran a relatively benign course as compared with leprosy patients. CONCLUSION: The incidence of DHS among non-leprosy patients was compatible to that observed among leprosy patients. DHS in non-leprosy patients runs a favorable course with low morbidity in our study.

Agranulocytosis induced by multidrug therapy in leprosy treatment: a case report

Multidrug therapy (WHO/MDT) in multibacillary leprosy consists of treatment with rifampicin, dapsone andclofazimine. However, adverse effects can cause the patient to abandon treatment. We report on a patient whopresented agranulocytosis and hemolytic anemia associated with this treatment regime. We also examined theimportance of laboratory exams for diagnosis and follow-up of the patient, and for early detection of adverse effects, with a view to improving adhesion to treatment and contributing to the eradication of Hansen’s disease as a public health issue.

Agranulocytosis induced by multidrug therapy in leprosy treatment: a case report.

Multidrug therapy (WHO/MDT) in multibacillary leprosy consists of treatment with rifampicin, dapsone and clofazimine. However, adverse effects can cause the patient to abandon treatment. We report on a patient who presented agranulocytosis and hemolytic anemia associated with this treatment regime. We also examined the importance of laboratory exams for diagnosis and follow-up of the patient, and for early detection of adverse effects,with a view to improving adhesion to treatment and contributing to the eradication of Hansen's disease as a public health issue.

Dapsone-induced haemolytic anaemia, hepatitis and agranulocytosis in a leprosy patient with normal glucose-6-phosphate-dehydrogenase activity.

A 21 year old boy with borderline lepromatous leprosy and normal glucose-6-phosphate-dehydrogenase activity developed haemolytic anaemia, hepatitis and agranulocytosis following 19 weeks of multi-bacillary multi-drug therapy. With early administration of antibiotics and G-CSF our patient recovered without residual complications. All patients taking dapsone should be warned to discontinue the drug immediately in the event of fever, chills and sore throat occurring within the treatment period until further investigations are performed.

Efeito hemoprotetor da cimetidina na metemoglobinemia induzida pela dapsona em regime de dose única em ratos / Hemoprotective effect of cimetidine single dosis schedule on dapsone induced methemoglobinemia in rats

A dapsona (4,4-diaminodifenilsulfona), quimioterápico bacteriostático utilizado no tratamento da hanseníase, vem sendo associada a intercorrências clínicas, principalmente devido à sua hemotoxicidade caracterizada por metemoglobinemia e anemia hemolítica. A N-hidroxilação, uma das principais vias de biotransformação da dapsona, vem sendo associada constantemente a quadros de metemoglobinemia decorrentes de sua utilização. Com o objetivo de verificar-se a inibição reversível da via de bioativação toxicológica, sem alterar as vias de destoxificação do composto, a acetilação citosólica, a cimetidina foi administrada concomitantemente à dapsona em ratos machos Wistar, com peso variando entre 200 e 220 g, divididos em 8 grupos (n=6 por grupo), em estudo de dose única...

Efeito de antagonistas de receptores H2 na metemoglobinemia induzida pela dapsona em ratos / ?

Dapsona, farmaco bacteriostatico utilizado no tratamento da hanseniase, vem sendo associado a intercorrencias clinicas, principalmente devido a sua hemotoxicidade. A N-hidroxilacao, uma das principais vias de biotransformacao da dapsona vem sendo associada constantemente a quadros de metemoglobinemia decorrentes do uso da dapsona. Com objetivo de se verificar a inibicao reversivel desta via de bioativacao toxicologica, sem alterar os caminhos de detoxificacao do farmaco, a aceltilacao citosolica, a cimetidina, ranitidina e famotidina foram administradas concomitantemente a dapsona em ratos machos Wistar, com peso variando entre 200 e 250g divididos em 30 grupos (n=6), em estudo de doses unicas e multiplas. Apos as administracoes, os ratos foram submetidos a coleta de sangue

Dapsone-induced hemolytic anemia.

Dapsone, an old drug introduced and used almost exclusively for the treatment of leprosy, is now utilized in an increasing number of therapeutic situations. However, its hemotoxicity is potentially severe and is often dose limiting. Effective countermeasures, based on resolution of the mechanisms underlying dapsone-induced hemotoxicity, could significantly enhance the therapeutic value of the drug. In studies on rat red cells, we have established that the N-hydroxy metabolites of dapsone, DDS-NOH and MADDS-NOH, are direct-acting hemolytic agents, that they are formed in amounts sufficient to account for the hemotoxicity of the parent drug, and that the action of these toxic metabolites in the red cell induces premature sequestration by the spleen. Incubation of rat red cells with hemolytic concentrations of arylhydroxylamines leads to the generation of hydroxyl, glutathiyl, and hemoglobinthiyl radicals, and the formation of protein-glutathione mixed disulfides. Disulfide-linked adducts are also formed between membrane skeletal proteins and hemoglobin monomers, as well as between the monomeric hemoglobin units forming dimers, trimers, tetramers, and pentamers. Profound morphological changes are seen with change from normal discoidocity to an extreme nonspherocytic enchinocyte shape. Parallel studies with human red cells indicate that the response of human cells is qualitatively similar but that there are notable differences in regard to skeletal membrane effects. A working hypothesis for the mechanism underlying dapsone hemolytic activity is proposed.

Intravascular hemolysis and acute renal failure following intermittent rifampin therapy.

Renal failure is a rare complication associated with the use of rifampin. Intravascular hemolysis leading to acute renal failure following rifampin therapy is extremely rare. Two patients with leprosy who developed hemolysis and acute renal failure following rifampin are reported.

Peripheral neuropathy and haemolytic anaemia with cherry red spot on macula in dapsone poisoning.

A young female presented with haemolytic anaemia due to dapsone overdosage. She developed peripheral neuropathy and marked visual impairment with a cherry red spot on the macula, possibly due to toxic retinal vascular damage; both these resolved in due course. Cherry red spot due to dapsone poisoning has not been reported previously.