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Year : 2015  |  Volume : 60  |  Issue : 1  |  Page : 108
Dapsone-induced methemoglobinemia in a patient of leprosy

1 Department of Dermatology, 167 MH, C/O 56 APO, India
2 Department of Medicine, 167 MH, C/O 56 APO, India

Date of Web Publication26-Dec-2014

Correspondence Address:
Joyjit Das
Department of Dermatology, 167 MH, C/O 56 APO
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.147895

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How to cite this article:
Das J, Katyal A, Naunwaar D. Dapsone-induced methemoglobinemia in a patient of leprosy. Indian J Dermatol 2015;60:108

How to cite this URL:
Das J, Katyal A, Naunwaar D. Dapsone-induced methemoglobinemia in a patient of leprosy. Indian J Dermatol [serial online] 2015 [cited 2022 Sep 27];60:108. Available from:


Methemoglobinemia is a rare possible diagnosis when patients present with cyanosis and other features of hypoxia that are unrelated to cardiopulmonary causes. Methemoglobinemia is usually symptomatic, when methemoglobin (metHb) levels are more than 15% of the total hemoglobin (Hb) value. [1]

A 22-year-old man presented to our hospital with complaints of exertional dyspnea, headache, and cyanosis of 3 days duration. He was on dapsone-based (100 mg OD) multi-drug therapy for Hansen's disease (borderline tuberculoid) since 6 months. He had no history of orthopnea, chest pain, palpitations, cough, syncope, weight loss, edema, hemoptysis, or exposure to chemicals. His past history was negative for heart disease, pulmonary disease, or similar complaints. The patient had central [Figure 1] and peripheral cyanosis, normal vital signs, and SO 2 value of 85% by pulse oximetry. Radial artery and venous blood [Figure 2] was dark colored. Arterial blood gas (ABG) analysis revealed the following values: PH - 7.44, PCO 2 - 39.8 mmHg, PO 2 - 147.5 mmHg, oxygen saturation (SO 2 ) - 99%, Hb - 15 gm/dL, H + - 36 nmol/L, Na + - 141 mmol/L, Ca 2+ - 7.4 mmol/L, Cl− - 95 mmol/L, and HCO 3 - 26.5 mmol/L. All other relevant hematological, biochemical, and radiological parameters were within normal limits. Patient was administered 100% O 2 inhalation for initial 2 days, but there was no improvement in cyanosis and SO 2 by pulse oximetry remained 85%. Repeat ABG revealed almost same values. He was given oral vitamin C (500 mg/day) and observed thereafter. There was a gradual increase in SO 2 level with value of 90% a week later and 99% after 2 weeks. Patient was asymptomatic, no cyanosis was evident [Figure 3], and there was change in color of venous blood by this time [Figure 4]. Dapsone was discontinued since the date of hospitalization.
Figure 1: Central cyanosis at presentation

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Figure 2: Chocolate-brown colored venous blood at presentation

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Figure 3: Complete resolution of cyanosis after 2 weeks

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Figure 4: Normalization of venous blood color after 2 weeks

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Methemoglobin is formed by oxidation of the heme iron of hemoglobin to the ferric state. Methemoglobin has very high oxygen affinity and virtually no oxygen is delivered to the tissues. Methemoglobinemia may be congenital or acquired. Congenital methemoglobinemia arises from mutations that stabilize iron in the ferric state (e.g., HbM Iwata (α87His→Tyr )) or from mutations that impair the enzymes that reduce methemoglobin to hemoglobin (e.g., methemoglobin reductase, NADP diaphorase), and manifest early in life. [2]

Many pharmacological agents and toxins have propensity to cause methemoglobinemia [Table 1]. The time of onset of symptoms and duration depend on the agent and its concentration. For many agents, the onset is within hours, but is delayed for others such as dapsone and nitroethane. Cyanotic discoloration of skin due to dark-colored methemoglobin is typically observed at levels greater than 15% and is often one of the earliest clinical manifestations. As methemoglobin levels rise, severity of signs and symptoms increases [Table 2]. [3]
Table 1: Agents causing methemoglobinemia

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Table 2: Methemoglobin concentrations and symptoms

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Dapsone is metabolized in the liver by N-acetylation and N-hydroxylation. Dapsone hydroxylamine is a strong oxidant and responsible for inducing methemoglobinemia. Dapsone induced methemoglobinemia is not related to G6PD activity and significant variation in magnitude of clinical manifestation is observed. [4]

In patients presenting with cyanosis and symptoms of hypoxia, blood oxygen level is determined by the pulse oximetry derived SO 2 and the ABG derived PO 2 and SO 2 . Pulse oximetry measures the relative absorbance of two wavelengths of light (660 and 940 nm), that correspond to the absorption of oxyhemoglobin (O 2 Hb) and deoxyhemoglobin (HHb), respectively. Although metHb absorbance at 660 nm is similar to that of HHb, metHb absorbance at 940 nm is markedly greater than that of either HHb or O 2 Hb. This leads to falsely low value of SO 2 . The ABG derived PO 2 reflects dissolved plasma oxygen content. The PO 2 may remain within the normal range in patients of methemoglobinemia. The SO 2 measured by ABG analysis is calculated from the blood pH, the PO 2 , and the standard Hb oxygen dissociation curve. Hence, the SO 2 measured by ABG analysis may be falsely elevated. Clue to the diagnosis of methemoglobinemia is the presence of a saturation gap, the difference between the SO 2 measured by ABG analysis and pulse oximetry. Typically, this saturation gap is greater than 5% in cases of methemoglobinemia. [5],[6]

CO-oximetry is the appropriate method for detecting and measuring metHb level. The CO-oximeter measures light absorbance of different wavelengths that correspond to the absorption characteristics of HHb, O 2 Hb, carboxyhemoglobin, and metHb; providing a more accurate measurement of SO 2 . [7]

Intravenous injection of methylene blue at an initial dose of 1-2 mg/kg (0.1-0.2 mL/kg of a 1% solution) is effective for emergency therapy. Milder cases and follow up of severe cases can be treated orally with methylene blue (60 mg three to four times each day) or ascorbic acid (300-600 mg/day). [8] Ascorbic acid decreases oxidative stress, protecting RBC from hemolysis and also reduces methemoglobin formation. [9]

As dosage of Dapsone in leprosy treatment usually does not produce significant methemoglobinemia, clinician must be aware of this adverse effect for safely using Dapsone in practice.

   References Top

do Nascimento TS, Pereira RO, de Mello HL, Costa J. Methemoglobinemia: From diagnosis to treatment. Rev Bras Anestesiol 2008;58:651-64.  Back to cited text no. 1
Benz EJ. Disorders of hemoglobin. In: Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J, editors. Harrison's Principles of Internal Medicine, 18 th ed. New York: McGraw-Hill; 2012. p. 852-61.  Back to cited text no. 2
Hopkins U. Methemoglobinemia - Toxalert. Maryland Poison Center Newsletter 2000;17:1-4.  Back to cited text no. 3
Hall RP, Mickle CP. Dapsone. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy, 2 nd ed. Philadelphia: Saunders; 2007. p. 239-53.  Back to cited text no. 4
Abu-Laban RB, Zed PJ, Purssell RA, Evans KG. Severe methemoglobinemia from topical anesthetic spray: Case report, discussion and qualitative systematic review. CJEM 2001;3:51-6.  Back to cited text no. 5
Hamirani YS, Franklin W, Grifka RG, Stainback RF. Methemoglobinemia in a young man. Tex Heart Inst J 2008;35:76-7.  Back to cited text no. 6
Barker SJ, Badal JJ. The measurement of dyshemoglobins and total hemoglobin by pulse oximetry. Curr Opin Anaesthesiol 2008;21:805-10.  Back to cited text no. 7
Blanc PD. Methemoglobinemia. In: Olson KR, editor. Poisoning and Drug Overdose, 3 rd ed. Norwalk: Appleton and Lange; 1999. p. 217-9.  Back to cited text no. 8
Atyabi N, Yasini SP, Jalali SM, Shaygan H. Antioxidant effect of different vitamins on methemoglobin production: An in vitro study. Vet Res Forum 2012;3:97-101.  Back to cited text no. 9


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]

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1 Dapsone
Reactions Weekly. 2015; 1537(1): 102
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