|Year : 2018 | Volume
| Issue : 2 | Page : 64-68
Relationship of clinical deterioration in leprosy patients while on multidrug therapy with their glucose-6-phosphate dehydrogenase levels
Abhishek Sharma1, D Ramachandra Reddy1, Prathap Reddy2, Bhumesh Tyagi3, Shivanu Mathon1, Suryash Jain1
1 Department of Dermatology, Venereology and Leprology, TMMC and RC, Moradabad, Uttar Pradesh, India
2 Department of Medicine, Sundaram Foundation, Chennai, Tamil Nadu, India
3 Department of Medicine, TMMC and RC, Moradabad, Uttar Pradesh, India
|Date of Web Publication||26-Mar-2019|
Department of Dermatology, Venereology and Leprology, TMMC and RC, Moradabad, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is known to cause haemolysis in patients with Hansen's disease receiving dapsone containing multidrug-therapy (MDT). However, sparse recent data are available on this topic from India.
Methods: All patients aged over 10 years with Hansen's disease receiving MDT who presented with clinical deterioration to our tertiary care teaching hospital in Moradabad, Uttar Pradesh, India, were included in the study. G6PD levels were estimated in all of them. Once G6PD deficiency was confirmed dapsone was stopped and rescue therapy was initiated.
Results: Between March 2015 and June 2016, 50 patients (mean age 34 ± 13.3 years) were included. G6PD deficiency was found in 14.3% patients. Peripheral blood smear showed Heinz bodies and bite cells in all of them. Mean pretreatment G6PD levels were 19.5 (range 17.5 – 25) units/g haemoglobin, mean serum bilirubin was 3.3 (range 1.6-9.2) mg/dL. Nineteen patients had lepra reactions (type 1 = 5 type 2 = 14). Ten patients required packed red blood cell transfusion.
Conclusions: Our observations suggest that checking for G6PD levels before initiating dapsone containing MDT can be helpful in reducing the occurrence of haemolytic complications.
Keywords: Dapsone, Glucose-6-phosphate dehydrogenase, Haemolysis, Leprosy
|How to cite this article:|
Sharma A, Reddy D R, Reddy P, Tyagi B, Mathon S, Jain S. Relationship of clinical deterioration in leprosy patients while on multidrug therapy with their glucose-6-phosphate dehydrogenase levels. J Clin Sci Res 2018;7:64-8
|How to cite this URL:|
Sharma A, Reddy D R, Reddy P, Tyagi B, Mathon S, Jain S. Relationship of clinical deterioration in leprosy patients while on multidrug therapy with their glucose-6-phosphate dehydrogenase levels. J Clin Sci Res [serial online] 2018 [cited 2019 Sep 17];7:64-8. Available from: http://www.jcsr.co.in/text.asp?2018/7/2/64/254978
| Introduction|| |
Leprosy or Hansen's disease is a chronic granulomatous debilitating disease involving the peripheral nerves, skin and some other tissues. It is caused by Mycobacterium leprae which is an acid-fast bacillus and was discovered by Gerhard Henrik Armauer Hansen in 1873. The disease is prevalent in Brazil, South East Asia (India, Nepal and Bhutan) and some parts of Africa (Tanzania, Madagascar and Mozambique). The WHO 2015 census reports a total of 175,000 leprosy cases worldwide with 210,000 new cases. As much as, 59% of cases of these were from India followed by 14% from Brazil and 8% from Indonesia. In India, as of 1st April 2014, a total of 86,000 cases were recorded, thereby giving a prevalence rate of 0.68/10,000 population. Of these, a staggering 23% has been reported from Uttar Pradesh itself.
With the introduction of multidrug therapy (MDT) regimen, there has been a fall in the incidence as well as the prevalence of the disease. One of the chief drugs in the MDT regimen is dapsone (diaminodiphenyl sulphone). One of the important side-effects of dapsone is haemolysis, which leads to the destruction of red blood cells (RBCs) in the body, thereby leading to anaemia. This haemolysis is more pronounced in people having a genetic deficiency of enzyme glucose-6-phosphate dehydrogenase (G6PD) which protects the RBCs from oxidative stress. G6PD deficiency is an X-linked recessive disorder where there is spontaneous haemolysis in response to certain triggers such as food (fava beans), drugs (dapsone and isoniazid) and intercurrent illness. In India, G6PD deficiency is prevalent in various groups of populations with the maximum cases seen in parsees (15%) and minimum seen in Muslims (2.5%). It is a well-known fact to rule out G6PD deficiency before starting MDT in leprosy patients, but many a times, due to financial constraints or lapse at the part of the leprologist, G6PD deficiency is not tested, and as a result severe haemolysis is seen in leprosy patients which at times even requires blood transfusion. Keeping this in mind, the aim of the current study was to establish a direct relationship in clinical deterioration of leprosy patients while on MDT with their G6PD levels.
| Material and Methods|| |
The present study was conducted in the Department of Dermatology, Venereology and Leprology at the Teerthanker Mahaveer Medical College and Research Centre, Moradabad, Uttar Pradesh, India. All leprosy patients visiting the outpatient department and emergency services were screened for inclusion in the study. Patients of either gender or aged 10 years or more, who were previously diagnosed with leprosy, on MDT and were now showing signs of clinical deterioration, were included in the study. Those patients who declined to sign an informed consent form or those who refused to continue follow-up for a minimum of 6 weeks were excluded from the study.
A detailed history was obtained, and a thorough clinical examination was carried out along with anthropometric variables which were duly recorded in the pro forma. Slit skin smear and a skin punch biopsy for histopathological analysis were also performed. The laboratory investigations included complete blood count (CBC), liver function tests, kidney function tests, peripheral blood smear for Heinz bodies and bite cells, G6PD levels and serology testing for human immunodeficiency virus, hepatitis B and C viruses.
Once G6PD deficiency was confirmed in the patient, dapsone was stopped in the MDT schedule, and rescue therapy for haemolysis was given with iron supplementation along with ascorbic acid and proteins for a minimum of 6 weeks. Those patients who were severely anaemic with a haemoglobin level of <6 g/dL were given packed red cell transfusion.
| Results|| |
The study was conducted between March 2015 and June 2016 during which 83 previously diagnosed and on MDT Hansen's disease patients presented with signs and symptoms of clinical deterioration. After applying the above-mentioned inclusion and exclusion criteria, 33 patients were excluded, out of which 20 patients declined to sign the informed consent form and 13 refused follow-ups leaving only 50 patients who were finally enrolled in the study.
Their mean age was 34 ± 13.3 (range 12–65) years; the male to female ratio was 4.5:1. In all 50 patients, peripheral smear showed Heinz bodies and bite cells. The findings of general physical examination are as shown in [Table 1]. Peripheral blood findings are shown in [Table 2].
|Table 1: General physical examination of 50 leprosy patients with clinical deterioration|
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|Table 2: Peripheral blood findings of 50 leprosy patients with clinical deterioration|
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Of the 50 patients enrolled in the study, 10 patients required packed red cell transfusion as they had severe haemolysis and haemoglobin levels were below 6 g/dL. The haemoglobin distribution in leprosy patients (mean, minimum and maximum) at the time of enrolment in the study and after 3 months of follow-up is shown in [Figure 1].
|Figure 1: Haemoglobin levels in 50 leprosy patients with clinical deterioration at the time of enrolment and at follow-up after 3 months|
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Of the total 50 patients, four patients were in the tuberculoid tuberculoid pole, 19 patients were in borderline tuberculoid pole, three patients in borderline lepromatous pole, five patients in lepromatous leprosy pole, while five patients had Type 1 leprosy reaction and 14 patients had Type 2 Leprosy reaction.
Serum biliruibin, G6PD profile in leprosy patients with clinical deterioration are shown in [Figure 2] and [Figure 3] respectively.
|Figure 2: Serum bilirubin in of 50 leprosy patients with clinical deterioration|
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|Figure 3: Glucose-6-phosphate dehydrogenase profile of 50 leprosy patients with clinical deterioration after 3 months of follow-up. G6PD = Glucose-6-phosphate dehydrogenase|
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Comparison of the observations from the present study with previously published studies, is shown in [Table 3].
| Discussion|| |
The present longitudinal study was carried out at a tertiary care centre in Western Uttar Pradesh with the main aim of establishing a relationship between the clinical deterioration state of Hansen's disease patients taking MDT with their G6PD levels. The last established study of a similar nature was done two decades earlier. In our study, the patients were from Moradabad and nearby villages who were available for periodic follow-up. Leprosy not only affects the patient pathologically but also psychologically. It is still looked down as a stigma in our country and is associated with a lot of evil social practices.
Leprosy is a disease which affects all age groups. In children where the immune status is not fully established, it occurs as indeterminate leprosy. In our patient group, the youngest patient is a 12-year-old while the oldest is 65-year-old which clearly points towards the vast age group affected by the disease. In the present study, more males were affected as compared to females. Similar male dominance has been reported by previous studies also, and this could be attributed to the X-linked recessive pattern of inheritance of the enzyme deficiency.,
In the present study, the minimum weight recorded was 40 kg with an average weight being 58.6 ± 12.3 kg. It is a well-known fact that leprosy is related with malnutrition which in turn has a role to play in cell-mediated immunity. It is for this reason, the disease has also been implicated in developing part of the world.
At the time of admission, the minimum haemoglobin level recorded was 5 g/dL where two packets of packed cell infusion were administered to the patient. The average haemoglobin level at the time of presentation was 8.5 g/dL while a maximum of 10.5 g/dL which implies that every patient at the time of enrolment was anaemic. There was no previous record of G6PD level estimation available with any of the patients, however, monthly CBCs and liver profile records were available with most of the patients. Dapsone normally causes haemolysis while this haemolysis is exaggerated in people with G6PD enzyme deficiency. In the background of haemolysis, there is compensatory homeostatic reticulocytosis to compensate for the loss of erythrocytes. Since these reticulocytes are nucleated they are able to synthesize new proteins and the enzyme G6PD necessary to safeguard itself against the oxidative stressors. As a result of this in the compensatory phase, the G6PD enzyme level is generally higher than normal but as the erythrocytes mature and lose the nucleus the level falls and reaches normal (6.4–18.7 U/g Hb) and below normal values. This theoretical aspect of G6PD deficiency is practically observed by us in this study where the average G6PD level observed at the time of the first presentation was 19.9 u/g Hb with 25 U/g Hb being the maximum recorded value. After stopping dapsone and providing rescue therapy in all patients while packed cell infusion in 10 patients, the average G6PD level observed after 3 months of regular follow-up was 6.3 U/g Hb with the minimum recorded level being 5.7 u/g Hb. At the end of 3 months, the average Hb was 11.9 g/dL while the maximum obtained value was 13.6 g/dL. This clearly points towards dapsone and G6 PD deficiency being the culprit for the clinical deterioration of Hansen's disease patient.
Once the G6PD deficient patient's erythrocytes are exposed to oxidative stress of dapsone in MDT, there is oxidation of reactive sulfhydryl groups on globin chains, which will become denatured and precipitate as dark inclusions inside the cell which are known as Heinz bodies. These Heinz bodies on passing through splenic cords are plucked by the macrophages thereby leading to the formation of an abnormally shaped cell known as bite cell or degmacyte.
In December 2005, the Government of India declared Leprosy as eliminated from the country thereby implying that there were <1/10, 000 cases on treatment. However, the disease as well as its related morbidity and mortality has been on the rise and does not seem to be going down anytime soon. A disease which is plagued by social stigma along with a waxing and waning course of its own has to be dealt with very carefully by the clinicians. It is of the utmost importance to remember before starting the MDT in leprosy patients that their G6PD levels should be checked with peripheral smear being the confirmatory test with the presence of Heinz bodies and bite cells. In case G6PD deficiency is found in the patient dapsone should be avoided in the MDT regimen or administered in pulse dosage. This will not only help to prevent future complications in the patient but will also help control Leprosy as once the patient faces the haemolytic complications of MDT; the natural tendency is to blame the drugs and stop MDT which in turn leads to downgrading.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]