Methaemoglobinaemia and paralysis of the hemi-diaphragm in a leprosy patient

Leprosy Mailing List – October 22nd, 2008

Ref.: Methaemoglobinaemia and paralysis of the hemi-diaphragm in a leprosy patient.
From: Narasimha Rao P., Hyderabad, India.


Dear Salvatore,

This mail is in response to the LML of Dr Satheeka Kamaladasa, from Sri Lanka, dated 18th Oct. 08, regarding ‘Methaemoglobinaemia and paralysis of the hemi-diaphragm in a leprosy patient’.

Methaemoglobinaemia occurring secondary to dapsone ingestion in leprosy patients is known and also been reported in literature. It usually is not a part of dapsone hypersensitivity syndrome. Methaemoglobinaemia occurs when haemoglobin is oxidized at a rate exceeding the normal enzymatic capacity for haemoglobin reduction. Some individuals are more prone to this condition than others.

Methaemoglobinaemia is characterized by cyanosis in the absence of cardiac or pulmonary disease, and refractory to oxygen administration. The p02 of arterial blood is normal while the measured oxygen saturation is decreased.

The frequently recommended dosage regimen of methylene blue as intermittent bolus dose (is useful in the treatment of methaemoglobinaemia when it occurs due to other causes) is often inadequate when methaemoglobinaemia is secondary to dapsone. This is due to the long half-life of dapsone which provides a continuing oxidative stress that can cause a recurrence of clinically significant methaemoglobinaemia. In dapsone induced methaemoglogbinemia methylene blue infusion is effective, and should be supported by repeated doses of activated charcoal to enhance dapsone elimination. (Dawson AH Whyte IM. Med Toxicol Adverse Drug Exp. 1989 Sep-Oct;4(5):387-92). The efficacy of orally administered activated charcoal is fully comparable to that of haemodialysis in increasing the rate of elimination of dapsone and its metabolite monoacetyldapsone. Activated charcoal is cheap, it can be administered anywhere and its administration rarely involves complications. (Neuvonen PJ, Elonen E, Haapanen EJ. Acta Med Scand. 1983;214(3):215-20). Activated charcoal given orally in multiple doses (20 g X 4/day) which shortens the half-life of dapsone to 12.7 +/- 0.7 hours, from 26 hours which is normal.

When methaemoglobinaemia is fully controlled/ reversed, MDT may be restarted in the patient while withholding Dapsone in the regimen.

Leprosy as cause of phrenic nerve paralysis has not been reported to my knowledge nor have I came across one. However some work has been done and published on the involvement of phrenic nerve in leprosy from the Postgraduate Institute of Medical Education and Research, Chandigarh, India. (Int J Lepr Other Mycobact Dis. 1988 Sep;56(3):389-93). The report states that when phrenic nerve conduction was performed bilaterally in 22 MB leprosy and 18 PB leprosy patients, prolonged phrenic nerve conduction time and/or reduced amplitude of diaphragm muscle action potential beyond 2.5 standard deviations of control mean values was observed in 9 BL-LL patients (4 bilateral) and 6 BT-TT patients (all unilateral). However, the report also states that on fluoroscopy, diaphragm movements were normal in all patients. This study only documented sub-clinical phrenic nerve involvement in leprosy.

Although your patient is in a phase of reaction where neuritis is an associated component, it cannot be attributed as a cause of phrenic nerve paralysis in a patient of leprosy based on the present evidence. While there is a theoretical possibility of phrenic nerve involvement in patients of MB leprosy, other causes for its involvement have to be considered and excluded first, which may be the case in your patient.

Hope this information would be useful to you. Thank you very much for sharing this case with us.

Best regards,

P. Narasimha Rao. M.D. PhD.,
Clinical consultant.
Lepra society -Blue peter research centre
Hyderabad, India.