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.

[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.

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.

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.

La anemia hemolítica en lepra: comentarios a propósitos de un caso con reacción leprosa tipo II, eritema nudoso necrótico resistente a la talidomida / Hemolytic anemia in leprosy: discussion of a case whith type II reactional leprosy and thalidomide resistant erythema nodosum necroticans

Se presenta y comenta el caso de un paciente masculino de 44 años con lepra lepromatosa nodular con reacción leprosa tipo II que mostraba eritema nudoso necrótico y una anemia hemolítica importante. El paciente mostró talidomidorresistencia. Con este motivo se discuten los mecanismos que se han involucrado en la patogenia de la anemia en los enfermos de lepra, sobre todo la de tipo hemolítico y se concluye indicando que tal vez intervinieron varios factores en este paciente para causar la anemia hemolítica.

La anemia hemolítica en lepra: comentarios a propósitos de un caso con reacción leprosa tipo II, eritema nudoso necrótico resistente a la talidomida / Hemolytic anemia in leprosy: discussion of a case whith type II reactional leprosy and thalidomide resistant erythema nodosum necroticans

Se presenta y comenta el caso de un paciente masculino de 44 años con lepra lepromatosa nodular con reacción leprosa tipo II que mostraba eritema nudoso necrótico y una anemia hemolítica importante. El paciente mostró talidomidorresistencia. Con este motivo se discuten los mecanismos que se han involucrado en la patogenia de la anemia en los enfermos de lepra, sobre todo la de tipo hemolítico y se concluye indicando que tal vez intervinieron varios factores en este paciente para causar la anemia hemolítica. (AU)

Stimulation of K-C1 cotransport in rat red cells by a hemolytic anemia-producing metabolite of dapsone.

Dapsone, a sulfone compound used in the treatment of leprosy and, more recently, Pneumocystis carinii pneumonia, produces as a major side effect a hemolytic anemia. This anemia is characterized by oxidation of hemoglobin to methemoglobin and increased splenic uptake of red blood cells. Using a rat model, Grossman and Jollow (J. Pharmacol. Exp. Ther. 244: 118-125, 1988) found that dapsone hydroxylamine (DDS-NOH), a dapsone metabolite, is responsible for its hemolytic effect in vivo. DDS-NOH also promotes hemoglobin binding to SH groups on rat red cell membrane proteins (Budinsky et al., FASEB J. 2: A801, 1988). Since the binding of hemoglobin and other reagents (e.g., N-ethylmaleimide) to membrane SH groups has been associated with increased K transport in red blood cells, we examined the effect of DDS-NOH on K efflux from rat red blood cells in vitro. Cells shrink when exposed to DDS-NOH (100 microM) in media with plasma-like ionic composition. This shrinkage is prevented if extracellular K is raised to 110 mM or if intra- and extracellular Cl are replaced by methylsulfate (MeSO4), suggesting involvement of a K-Cl cotransport pathway. Indeed, 100 microM DDS-NOH produces a 4- to 5-fold increase in K efflux in cells containing Cl but less than a 2-fold increase in cells containing MeSO4. This stimulatory effect is specific for K; Na efflux is slightly inhibited by 100 microM DDS-NOH. The concentrations of DDS-NOH required for half-maximal stimulation of Cl-dependent K efflux (53 microM) is similar to its half-maximal hemolytic concentration in rats (approximately 100 microM). Furthermore, the stimulation of Cl-dependent K efflux by DDS-NOH is greater than 80% reversed by subsequent treatment of the cells with dithiothreitol, suggesting involvement of SH groups. Our results indicate that DDS-NOH exposure stimulates an apparent K-Cl cotransport in rat red blood cells, resulting in cell shrinkage under physiological ionic conditions. Since shrinkage of red blood cells renders them less deformable (Mohandas et al., J. Clin. Invest. 66: 563-573, 1980), this suggests a pathophysiological mechanism whereby DDS-NOH exposure in vivo could promote increased splenic uptake of red blood cells and hemolytic anemia.

Dapsone-associated Heinz body hemolytic anemia in a Cambodian woman with hemoglobin E trait.

A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.