Lockwood, Diana NJ

Omer, Haroun

Saba M, Lambert

LSHTM Research Online

Lambert, Saba M; Haroun, Omer; Lockwood, Diana NJ (2016) Val-idation of the Leprosy Type 1 Reaction Severity Scale in Ethiopia.LEPROSY REVIEW, 87 (1). pp. 113-117. ISSN 0305-7518Downloaded from: http://researchonline.lshtm.ac.uk/4651210/DOI:Usage GuidelinesPlease refer to usage guidelines at http://researchonline.lshtm.ac.uk/policies.html or alterna-tively contact researchonline@lshtm.ac.uk.Available under license: Copyright the publishersLETTER TO THE EDITORValidation of the Leprosy Type 1 Reaction SeverityScale in EthiopiaSABA M. LAMBERT*,**, OMER HAROUN* &DIANA N.J. LOCKWOOD**Department of Clinical Research, Faculty of Infectious and TropicalDiseases, London School of Hygiene and Tropical Medicine(LSHTM), London, United Kingdom WC1E 7HT**All Africa Leprosy Rehabilitation and Training (ALERT) Center,Addis Ababa, EthiopiaAccepted for publication 3 November 2015Leprosy Type 1 Reactions (T1R) are immune-mediated events leading to nerve damage andpreventable disabilities. They manifest clinically with erythema and oedema of skin lesionsand tender peripheral nerves with loss of function. Up to 30% of patients with borderlineleprosy are affected by T1R.1 Although T1R can occur at any time, the frequency is higher inthe first six months of MDT treatment.2 T1R are treated with corticosteroids.3 Clinical trialsare needed to assess not only efficacious and safe second line drugs but also to assess the bestregimens of prednisolone in terms of dosage, length of treatment and rate of decrease.A tool which enables clinicians to assess the severity of T1R is useful in definingoutcomes in clinical trials. The lack of uniformity surrounding interpretation of data hashindered development of internationally accepted treatment protocols and guidelines, whilealso making trialling of new therapeutic agents difficult. Using a validated clinical severityscale for leprosy reactions improves research quality and provides a tool to promoteuniformity and comparability of research.A Severity Scale for T1R, based on the INFIR clinical severity scoring system, wasdeveloped and prospectively validated in Bangladesh and Brazil.4 The scale consists of 21items to assesses three components of T1R.4 The first section looks at skin involvement usingnumber of affected lesions, the degree of inflammation and the presence of peripheral oedema(Score A). The second section is a measurement of sensory function of the nerves by usinggraded Semmes-Weinstein monofilaments (SWM) to assess sensation in the hands and feet,and cotton wool for corneal sensation (Score B). The third section uses a standard measure ofmuscle power (MRC grading) to assess the motor function of the nerves of the face, hands andfeet (Score C). The sum of the total for each section (A, B, and C) gives the overall severityscale score with a range of 0–63 (Appendix 1). The maximum score possible for sections A,Correspondence to: (e-mails: saba.lambert@lshtm.ac.uk; sabalambert@hotmail.com)Lepr Rev (2016) 87, 113–1170305-7518/16/064053+05 $1.00 q Lepra 113B and C are 9, 24 and 30 respectively. A mild T1R is characterised by a score of 4 or less; amoderate T1R by a score between 4·5 and 8·4 and a severe T1R is a score of 9 or more.This Severity Scale for T1R has so far been used in clinical trials on intravenousmethylprednisolone in Nepal,5 on azathioprine in India6 and in the on-going TENLEP studiesin India.7 In order to use such a scale in a trial on ciclosporin efficacy in T1R, we needed tovalidate it in the population in which the study was to be conducted. The validation exercisein Ethiopian patients is described here.MethodsPatients presenting with signs and symptoms of T1R at the Leprosy Clinic at ALERTHospital in Addis Ababa were recruited between February 2010 and August 2010. Ethicalapproval was granted by the London School of Hygiene and Tropical Medicine (5426/Dec2008) and ALERT and AHRI Ethical Review Committee (PO22/08).Inclusion criteria were patients aged 18 or more presenting with T1R. Patients unable orunwilling to give informed consent were excluded. All patients gave informed consent toparticipate in the assessment. Patients could be presenting with new T1R or be on treatmentfor T1R. Patients were examined independently, on the same day, by a health worker whowas trained to use the scale and by an experienced leprologist who categorised the reaction asmild, moderate or severe. Neither assessor was aware of the result of the others examination.The scoring was done on pre-prepared scoring sheet which listed skin finding and results ofvoluntary muscle testing and sensory testing.The results were entered into an Access database and the data was analysed using theStatistical Package for Social Sciences (SPSS version 20).Results135 patients with T1R were examined using the T1R severity scale assessment sheet.The severity of the T1R was categorised by the specialist as mild in 43 (32%), moderate in34 (25%) and severe in 38 (28%) patients. Another 20 patients (15%) with no signs of activeT1R but on prednisolone treatment were assessed. Median scores for each category werenone ¼ 0 ^ 1·69; mild ¼ 3·0 ^ 2·55; moderate ¼ 6·5 ^ 2·55 and severe ¼ 19·0 ^ 9·70.The box-plot in Figure 1 illustrates the score distribution clearly.The differences in the scores between the group with no active reaction and the mildgroup, the mild group and the moderate group and the moderate group and the severe groupwere all statistically significance (P , 0·001, Independent sample t test). The group ofpatients graded as having severe TIR had the widest confidence interval, and there is anoverlap between each category.DiscussionThis is the first report of the use of the T1R Severity Scale in Ethiopia and it shown that it is avalid tool for assessing the severity of T1R in Ethiopian patients and can be used todifferentiate between mild, moderate and severe T1R. Some limitations were noted. TheS.M. Lambert et al.114reliability of the tool could have been tested by doing a further inter-observer validationexercise but due to limitations in clinic staff this was not possible in this context. This hasbeen done previously in Bangladesh and Brazil4 and there is no reason to expect than trainedEthiopian health care workers would score differently. VMT and SWM in the assessment ofnerve function impairment (NFI) have been shown to be reliable.8Old NFI can constantly raise the score in the absence of active T1R. A way of adjustingthe score to take into account the effect of old NFI needs to be investigated. In the Azalepstudy patients were asked whether their nerve damage had been present for more than6 months.6 Old NFI, i.e. greater than 6 months duration, may not respond to treatment but it isalso difficult for patients to accurately time the loss of nerve function, especially when acuteNFI occurs in a nerve that already has some pre-existing permanent impairment. A set ofquestions that define old nerve damage and its importance should be tested. This work needsdeveloping and validatingWe also noticed that because the scoring system is not equally weighted, neurologicalparameters are more heavily represented. This may reflect the importance of nerve functionimpairment but may not adequately reflect treatment requirements. For example, it is verydifficult to associate a value of 7 (which equates to moderate T1R) to a patient who has severereaction in the skin of the face but nerves are unaffected. Such a patient would clinically be40.0030.0020.00Total severity score10.000.00None (n=20) Mild (n=43) Moderate (n=34) Severe (n=38)Specialist assessment of T1R severityFigure 1. Box plot of Clinical Severity Scores by specialist severity classification showing medians, interquartileranges and minimum and maximum scores. Legend: Box-and-whisker plot of Clinical Severity Score. Participantswere classified as follows: n ¼ 20 None (CSS median ¼ 0; range:0–4; SD ¼ 1·29); n ¼ 43 Mild (CSSmedian ¼ 3·0; range:0–8·5; SD ¼ 2,55); n ¼ 34 Moderate (CSS median ¼ 6·5; range 0·5–10·5; SD ¼ 2·55)and n ¼ 38 Severe (CSS ¼ 19; range ¼ 4·5–38·5; SD ¼ 9·70).Validation of Leprosy Type 1 Reaction Scale 115graded as severe and treatment would be given accordingly despite a moderate score on theseverity scale. A study assessing whether adjusting the weighting would be useful could becarried out in conjunction with a study assessing the minimally important difference (MID)from a patient perspective in scores derived from the scale before and after treatment. This isimportant because it provides a meaningful patient centred outcome measure of change. Thisstudy should be performed in a population in which the scale has been validated. Knowingthe magnitude of the change in score required to achieve a MID would facilitate powercalculations for clinical trials.Although we have validated the T1R Severity Scale in Ethiopian patients with T1R,further studies are warranted to determine its utility in future clinical studies as well as aconsensus on how to report scores in studies to allow easy comparison and pooling of results.AcknowledgementsWe would like to thank the participants who gave up their time and enrolled in the study, thestaff at ALERT hospital, especially those in the physiotherapy department, and Dr S. Walkerfor providing the original scale and debating its uses. This work was supported by a grantfrom Hospital and Homes of St Giles as part of the ciclosporin studies.References1 SmithWC, Anderson AM,Withington SG et al. Steroid prophylaxis for prevention of nerve function impairment inleprosy: randomised placebo controlled trial (TRIPOD 1). BMJ 2004/05/26 ed, 2004; 328(7454): 1459.2 Croft RP, Nicholls PG, Steyerberg EW et al. A clinical prediction rule for nerve-function impairment in leprosypatients. Lancet 2000/05/23 ed, 2000; 355(9215): 1603–1606.3 Walker SL, Lockwood DN. Leprosy type 1 (reversal) reactions and their management. Lepr Rev 2009/03/12 ed,2009; 79: 372–386.4 Walker SL, Nicholls PG, Butlin CR et al. Development and validation of a severity scale for leprosy type 1reactions. PLoS Neglected Tropical Diseases. 2008/12/24 ed, 2008; 2(12): e351.5 Walker SL, Nicholls PG, Dhakal S et al. A phase two randomised controlled double blind trial of high doseintravenous methylprednisolone and oral prednisolone versus intravenous normal saline and oral prednisolone inindividuals with leprosy type 1 reactions and/or nerve function impairment. PLoS Neglected Tropical Diseases,2011; 5: e1041.6 Lockwood DNJ, John AD, Darlong J et al. RCT of Azathioprine versus prednisolone in the treatment of Type 1Reaction. International Leprosy Congress - Hidden Challenges. Brussels; 2013. p. 231.7 Wagenaar I, Brandsma W, Post E et al. Two randomized controlled clinical trials to study the effectiveness ofprednisolone treatment in preventing and restoring clinical nerve function loss in leprosy: the TENLEP studyprotocols. BMC Neurology, 2012; 12: 159.8 Anderson AM, Croft RP. Reliability of Semmes Weinstein monofilament and ballpoint sensory testing, andvoluntary muscle testing in Bangladesh. Lepr Rev, 1999; 70: 305–313.S.M. Lambert et al.116Appendix 1. Clinical Severity Scale for T1RsCriteria 0 1 2 3 ScoreA1 Degree of inflammation of skin lesions None Erythema Erythema and raised UlcerationA2 Number of raised and/ or inflamed lesions 0 1–5 6–10 >10A3 Peripheral oedema due to reactions None Minimal Visible but not affecting functionsOdema affecting functionA SOREHANDS Purple 2g Monofilament scores Orange 10g Monofilament score ScoreNerves 0 0.5 1 1.5 2 2.5 3B1 Rt TrigeminalFelt Not feltB2 Lt TrigeminalFelt Not feltB3 RtUlnarAll sites felt1 sites not felt2 sites not felt3 sites not felt1 sites not felt2 sites not felt3 sitesnot feltB4 LtUlnarAll sites felt1 sites not felt2 sites not felt3 sites not felt1 sites not felt2 sites not felt3 sitesnot feltB5 RtMedianAll sites felt1 sites not felt2 sites not felt3 sites not felt1 sites not felt2 sites not felt3 sites not feltB6 LtMedianAll sites felt1 sites not felt2 sites not felt3 sites not felt1 sites not felt2 sites notfelt3 sites not feltFEET Orange 10g Monofilament score Pink 300g Monofilament score ScoreNerves 0 0.5 1 1.5 2 2.5 3B7 Rt. Post.tibial All sites felt1 sites not felt2 sites not felt3 sites not felt1 sites not felt2 sites not felt3 sites not feltB8 Lt. Post.tibialAll sites felt1 sites not felt2 sites not felt3 sites not felt1 sites not felt2 sites not felt3 sites not feltB SCORENerves 0 1 2 3 ScoreC1 Rt. Facial MRC=5 MRC=4 MRC=3 MRC<3C2 Lt.  Facial MRC=5 MRC=4 MRC=3 MRC<3C3 Rt. Ulnar MRC=5 MRC=4 MRC=3 MRC<3C4 Lt. Ulnar MRC=5 MRC=4 MRC=3 MRC<3C5 Rt. Median MRC=5 MRC=4 MRC=3 MRC<3C6 Lt. Median MRC=5 MRC=4 MRC=3 MRC<3C7 Rt. Radial MRC=5 MRC=4 MRC=3 MRC<3C8 Lt. Radial MRC=5 MRC=4 MRC=3 MRC<3C9 Rt. Lateral Popliteal MRC=5 MRC=4 MRC=3 MRC<3C10 Lt. Lateral Popliteal MRC=5 MRC=4 MRC=3 MRC<3C SCORETotal Score Score of A + B + CValidation of Leprosy Type 1 Reaction Scale 117

Validation of the Leprosy Type 1 Reaction Severity Scale in Ethiopia.

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Validation of the Leprosy Type 1 Reaction Severity Scale in Ethiopia.

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