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Hemolytic anemia in patients receiving daily dapsone for the treatment of leprosy |
Dapsone autoimmune hemolytic anemia. Hemolytic Anemia from Combined Use of Dapsone and Hydrochlorothiazide
Fatigue and generalized weakness are commonly encountered complaints in the emergency department. This case report describes the case of a year-old woman with a medical history significant for Type 2 diabetes, hyperlipidemia, hypertension, and linear IgA bullous dermatosis, who presented with a 6-day history of fatigue and generalized weakness.
Upon investigation, this fatigue was attributed to drug-induced hemolysis, with an underlying drug interaction between dapsone and hydrochlorothiazide potentiating the adverse effect. This case study highlights the need to investigate patients who present with non-specific complaints with a potentially life-threatening cause in mind.
Case Presentation A year-old female presented to the ED complaining of worsening fatigue and weakness for 6 days. She denied any flank pain, fevers, runny nose, chills, headaches, abdominal pain, changes in bowel movements, melena, or urinary complaints such as hematuria or dysuria.
There was no history of recent travel, exposure to sick contacts, or trauma. Her past medical history was significant for Type 2 diabetes, hyperlipidemia, hypertension, and linear IgA bullous dermatosis. The patient was previously on lisinopril for hypertension, however 3 months prior the patient started to notice a diffuse rash with vesicles on her body for which she consulted a dermatologist.
She was deemed to have an allergy to lisinopril, which was discontinued. She was started on prednisone of an unrecalled dose, which was subsequently stopped when the rash subsided. However, the rash came back a few weeks later, and a biopsy confirmed the diagnosis of linear IgA bullous dermatosis. She has been following up with her dermatologist for weekly blood counts.
One week prior to the ED visit, the patient's dapsone dose was increased to mg QD, her hemoglobin was documented at Physical examination showed a pale-appearing female. She had significant conjunctival pallor and icterus without any edema. The rest of the physical examination findings were within normal limits.
She was started on 1 L of normal saline over 1 hour and was given 8 units of insulin. Blood was obtained and showed a complete blood count remarkable for anemia at 7. Total bilirubin levels were elevated at 4. Urine analysis showed a moderate hematuria and the presence of urobilinogen. The fecal occult blood test was negative. Two units of packed cells were transfused while in the ED. The patient was diagnosed with hemolytic anemia, which was thought to be precipitated by dapsone and hydrochlorothiazide.
The offending medications were stopped, and the patient was admitted to the medical service. Hemoglobin level gradually improved, and the patient reported clinical improvement on discharge.
Discussion This is a case of a middle-aged female who presented with complaints of generalized weakness and fatigue. There are no established guidelines on how to approach a patient presenting with non-specific complaints such as fatigue.
Infectious, metabolic, and oncologic processes — many with poor outcomes — are often associated with this presentation. Obtaining a detailed history, specifically looking for inciting events that precipitated the condition, can provide useful diagnostic clues. Elderly patients who visit the ED are taking an average of 4. Neurological causes of weakness have to be evaluated quickly since the management of these conditions is often time sensitive.
In this patient, the review of medications revealed that the patient was prescribed dapsone and hydrochlorothiazide, and physical examination showed the presence of anemia.
The primary step in the approach to any patient presenting with anemia is to determine whether it is acute or chronic. The stool was negative for the presence of occult blood.
She had elevated reticulocyte count, serum lactate dehydrogenase levels, and an unconjugated hyperbilirubinemia with preserved RBC morphology, which was suggestive of acute hemolytic anemia.
Review of medications revealed her use of dapsone and hydrochlorothiazide which pointed us towards the diagnosis of drug-induced hemolytic anemia as a probable cause of her symptoms. However, confirmation of this is beyond the scope of the ED. The management of anemia in the ED primarily focuses on determining the immediately correctable causes and determining the need for blood transfusion. The threshold to initiate blood transfusion in individuals with asymptomatic anemia is less clear.
Since the mechanism of hemolysis is different in both dapsone and hydrochlorothiazide, the combined use of these medications may result in a much higher drop in hemoglobin levels than if they were used alone. This case emphasizes the need to approach the patients with non-specific complaints presenting to the emergency department with broad and potentially life-threatening outcomes in mind.
This is also the first reported case of a combined effect of hemolytic anemia in a patient without G6PD enzyme deficiency taking dapsone and hydrochlorothiazide.
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Giles, MD Gary F. This is a unique case of Lemierre's syndrome in a person who injects drugs PWID without a history of recent oropharyngeal infection or the presence of a central venous catheter.
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❿Dapsone autoimmune hemolytic anemia
- Dapsone autoimmune hemolytic anemia
Users Online: Year : Volume : 5 Issue : 3 Page : Dapsone-induced hypersensitivity syndrome, hemolytic anemia, and severe agranulocytosis. Case report.
Figure 1: Peripheral smear showing severe leukocytopenia and normocytic normochromic RBCs with spherocytes Click here to view.
Figure 2: X-ray of the chest showing bilateral interstitial pneumonia Click here to view. Figure 4: CT of the thorax showing multiple irregular nodules in the lung parenchyma with cavitation and enlarged cervical and mediastinal lymph nodes Click here to view. Related articles Agranulocytosis cavitating pseudomonal pneumonia dapsone dapsone hypersensitivity syndrome DHS hemolytic anemia pseudomonas. Access Statistics. Chest radiograph revealed left lobe consolidation.
Blood culture grew Klebsiella pneumoniae. Bone marrow examination showed marked suppression of myeloid series and maturation arrest consistent with agranulocytosis.
She was treated with granulocyte colony stimulating factor for 6 d and appropriate antibiotics. She also required mechanical ventilation and inotropic support. After 10 d, her clinical recovery coincided with neutrophil count recovery. Various hematological adverse effects of dapsone have been reported, like hemolysis, methemoglobenemia and pulmonary eosinophilia. Although dapsone has been reported to cause agranulocytosis during the treatment of dermatitis herpetiformis and leprosy, there are no case reports of DIA during the management of ITP [ 3 ].
DIA is a rare but catastrophic complication, observed 4—12 wk after the initiation of dapsone [ 2 ]. Hydroxylamine, a metabolite of dapsone is implicated in maturation arrest of neutrophils which leads to agranulocytosis [ 3 ].
Although dapsone is known to induce mild hemolysis, in our case, patient developed significant hemolytic anemia. This case emphasizes that patients receiving dapsone should be regularly monitored for neutropenia and hemolytic anemia. Dapsone for immune thrombocytopenic purpura in children and adults.
Coleman MD. Abstract Dapsone, an old drug introduced and used almost exclusively for the treatment of leprosy, is now utilized in an increasing number of therapeutic situations. Publication types Review. Substances Dapsone 4-amino-4'-hydroxylaminodiphenylsulfone. She denied any flank pain, fevers, runny nose, chills, headaches, abdominal pain, changes in bowel movements, melena, or urinary complaints such as hematuria or dysuria.
There was no history of recent travel, exposure to sick contacts, or trauma. Her past medical history was significant for Type 2 diabetes, hyperlipidemia, hypertension, and linear IgA bullous dermatosis.
The patient was previously on lisinopril for hypertension, however 3 months prior the patient started to notice a diffuse rash with vesicles on her body for which she consulted a dermatologist.
She was deemed to have an allergy to lisinopril, which was discontinued. She was started on prednisone of an unrecalled dose, which was subsequently stopped when the rash subsided. However, the rash came back a few weeks later, and a biopsy confirmed the diagnosis of linear IgA bullous dermatosis. She has been following up with her dermatologist for weekly blood counts. One week prior to the ED visit, the patient's dapsone dose was increased to mg QD, her hemoglobin was documented at Physical examination showed a pale-appearing female.
She had significant conjunctival pallor and icterus without any edema. The rest of the physical examination findings were within normal limits. She was started on 1 L of normal saline over 1 hour and was given 8 units of insulin. Blood was obtained and showed a complete blood count remarkable for anemia at 7. Total bilirubin levels were elevated at 4.
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. Abstract Dapsone, an old drug introduced and used almost exclusively for the treatment of leprosy, is now utilized in an increasing number of therapeutic situations. Publication types Review. Substances Dapsone 4-amino-4'-hydroxylaminodiphenylsulfone.
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. Dapsone has long been known to cause hemolytic anemia, especially in people with G6PD deficiency; it causes a drop in hemoglobin levels up to 3. 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. Mild haemolytic anaemia is common following dapsone treatment and rarely warrants change of therapy, but severe haemolysis occurs in patients with glucose Dapsone can cause a variety of adverse effects including hemolytic anemia, methemoglobinemia, hepatic involvement, cutaneous involvement (exanthematous eruption. Cite this article Bartakke, S. Advocacy Health Policy Journal Club. The fecal occult blood test was negative. Provided by the Springer Nature SharedIt content-sharing initiative. Clin Exp Dermatol ; However, the rash came back a few weeks later, and a biopsy confirmed the diagnosis of linear IgA bullous dermatosis. Blood culture grew Klebsiella pneumoniae.To the Editor: Dapsone is a commonly used second-line drug for immune thrombocytopenia ITP in developing countries as it is economical and efficacious [ 1 ]. Rarely, dapsone can cause idiosyncratic reaction leading to agranulocytosis [ 2 ]. We recently encountered a case who suffered from dapsone induced agranulocytosis DIA and severe hemolysis. A y-old girl was diagnosed as a case of ITP at other center 18 mo ago. However, the other parameters of complete blood counts CBC were not monitored.
After 1 mo, she presented with high grade fever, cough, dyspnea and pallor to our hospital. She was hemodynamically unstable and was admitted in the PICU. Her CBC showed Hb — 6. Peripheral smear showed polychromasia.
Liver function test showed unconjugated hyperbilirubinemia. Chest radiograph revealed left lobe consolidation. Blood culture grew Klebsiella pneumoniae. Bone marrow examination showed marked suppression of myeloid series and maturation arrest consistent with agranulocytosis. She was treated with granulocyte colony stimulating factor for 6 d and appropriate antibiotics.
She also required mechanical ventilation and inotropic support. After 10 d, her clinical recovery coincided with neutrophil count recovery. Various hematological adverse effects of dapsone have been reported, like hemolysis, methemoglobenemia and pulmonary eosinophilia. Although dapsone has been reported to cause agranulocytosis during the treatment of dermatitis herpetiformis and leprosy, there are no case reports of DIA during the management of ITP [ 3 ].
DIA is a rare but catastrophic complication, observed 4—12 wk after the initiation of dapsone [ 2 ]. Hydroxylamine, a metabolite of dapsone is implicated in maturation arrest of neutrophils which leads to agranulocytosis [ 3 ]. Although dapsone is known to induce mild hemolysis, in our case, patient developed significant hemolytic anemia.
This case emphasizes that patients receiving dapsone should be regularly monitored for neutropenia and hemolytic anemia. Dapsone for immune thrombocytopenic purpura in children and adults. Coleman MD.
Dapsone-mediated agranulocytosis: risks, possible mechanisms and prevention. Bhat RM, Radhakrishnan K. A case report of fatal dapsone-induced agranulocytosis in a Indian mid-borderline leprosy patient.
Lepr Rev. PubMed Google Scholar. Paniker U, Levine N. Dapsone and sulfapyridine. Dermatol Clin. Download references. Abhilasha A. You can also search for this author in PubMed Google Scholar. Correspondence to Abhilasha A. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions. Bartakke, S. Indian J Pediatr 87 , Download citation.
Received : 29 June Accepted : 29 January Published : 05 March Issue Date : October Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search SpringerLink Search. Download PDF. Agranulocytosis and hemolytic anemia were attributed to dapsone which was withheld.
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