Interventions for skin changes caused by nerve damage in leprosy
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To find out if any interventions can prevent secondary damage to the skin in people with leprosy, for example:
-
self‐care
-
dressings
-
appropriate footwear
Which of the interventions are the most effective?
Do these interventions reduce social stigma and lead to better quality of life?
Are any interventions harmful?
Background
Prevalence
Four million individuals currently have, or are disabled by, leprosy (Hansen's disease) worldwide. Despite intensive efforts to control the disease, the incidence remains stable, at about 800,000 new cases per year, in affected countries (Lockwood 2002b). The proportion of new cases of leprosy in children under 15 years of age was 18% in 2000 (WHO 2002). Hence person to person transmission remains a problem; there are large numbers of childhood cases and many people suffer from the consequences of leprosy (McDougall 2002). At the beginning of 2003 the number of people currently on drug treatment for leprosy was around 524,000 (WHO 2003). About 612,000 new cases were detected during 2002 (WHO 2003).
South East Asia has the highest prevalence of leprosy followed by the Americas, Africa, the western Pacific, eastern Mediterranean and Europe (WHO 2002). The six most affected countries are India, Brazil, Myanmar, Nepal, Madagascar and Mozambique. Of all people with the disease, 70% to 80% live in India.
Causes
Leprosy is a chronic infectious disease caused by the bacterium Mycobacterium leprae.
Clinical manifestations and complications
The principal manifestations are skin lesions (thickened, cracked skin or skin ulcers) and peripheral neuropathy (inflammation of nerves in the limbs, which become thickened and damaged). Complications result from nerve damage, through immune reactions and also through direct invasion by the M. leprae bacteria. When the small sensory and autonomic nerve fibres in the skin are damaged this initially causes local loss of sensation and loss of the skin's ability to sweat. Damage to peripheral nerves eventually leads to more widespread loss of sensation, skin dryness and reduced function of the muscles supplied by the affected nerve. The dry skin can crack and become infected and ulcerated, and misuse of the affected limb can ultimately result in severe joint deformity and injuries.
The major areas affected by nerve damage in leprosy are the hands (especially the palms), feet (especially the soles) and eyes. The main disability complication of sensory nerve damage is neuropathic ulceration secondary to sensory loss, particularly of the feet. The drug therapy offered to people infected with M. leprae is very efficacious and has low relapse rates. However, even with treatment, many people with leprosy will go on to develop secondary damage to skin and limbs as the nerve damage sustained can not be reversed.
Diagnosis
Leprosy is diagnosed clinically by three principal signs:
-
anaesthetic skin lesions i.e. parts of the skin that are numb and not able to detect painful stimuli such as a pin prick;
-
thickened peripheral nerves that can easily be felt through the skin;
-
positive smear i.e. evidence of the causative bacterium, M. leprae, using microscopic examination of a sample of tissue (skin smear).
Classification
There are two main forms of classification. They are the Ridley‐Jopling scheme and the World Health Organization (WHO) PB/MB (paucibacillary/multibacillary) classification.
Ridley‐Jopling scheme
This classifies leprosy on a scale from 'tuberculoid' to 'lepromatous' based on the clinical appearance and bacterial index of lesions (Lockwood 2002a). 'Tuberculoid' indicates that the body's immunity is good and there are few skin lesions. 'Lepromatous' means that the body does not show a good immune response to the invading bacteria and there is uncontrolled bacterial multiplication, many skin lesions and also lesions in the mucosa of the nose and mouth. Peripheral nerve damage can occur at any point on the scale. Between the extremes of ' tuberculoid' and 'lepromatous' are the 'unstable borderline tuberculoid' and 'borderline lepromatous' forms.
WHO classification
This classification is based on the number of skin lesions (McDougall 2002):
1. single skin lesion (SSL);
2. paucibacillary (PB) ‐ less than 5 lesions (and negative smear at any site);
3. multibacillary (MB) ‐ greater than 5 lesions (and/or positive smear at any site).
This is a simple classification scheme that makes treatment simpler for field workers, but it is less specific than the Ridley‐Jopling scheme. The WHO classification system is the most widely used.
Treatment
Chemotherapy with a combination of drugs (multidrug treatment (MDT)), is used to treat leprosy. The drugs used are rifampicin, dapsone and clofazimine ‐ they are effective in killing bacilli, but do not prevent further nerve damage. Virtually all people affected by leprosy, and registered with their local health authority, are treated with MDT. Other interventions in leprosy care are aimed at prevention and treatment of secondary damage to skin and limbs. The rationale behind the use of, for example, appropriate footwear is to protect feet from damage that can lead to superficial sores on the sole of the feet, and later ulcers and secondary infections (McDougall 2002). Many interventions may help the healing of such ulcers (Srinivasan 1989). Self‐care includes daily management to reducethe effects of nerve function impairment. Education, information and empowerment of people affected by leprosy (and their carers) is part of some leprosy programmes (McDougall 2002).
Impact
Nerve damage can happen before, during and after chemotherapy treatment. It affects approximately 30% of people diagnosed with leprosy (2.6% of PB cases, 37% of MB patients, 2 years after detection and MDT treatment)(Lockwood 2001). Approximately 6% to 9% of new cases with leprosy present with grade 2 disabilities (visible deformity or damage present) and as many as 20% to 56% of patients have established nerve damage at diagnosis (Lockwood 2002b). These figures vary from country to country and between disease types.
Reasons for undertaking this review
The management of leprosy programmes worldwide has moved from clinics dedicated to the treatment of leprosy to primary healthcare services in general. People with leprosy are, after a few days on chemotherapy, no longer infectious and can lead a normal social life. However, long‐term nerve and muscle damage can lead to great psychosocial and financial difficulties, social stigmatisation and decreased quality of life. Care and awareness of limbs is as important as chemotherapy, therefore patient education is considered a central element in treatment (Lockwood 2002c). The key to effective management of leprosy is early diagnosis and treatment, and early recognition and management of nerve damage, combined with effective health education to prevent limb damage. There is variation in practice and a systematic review is needed to identify the most effective prevention and treatment for people affected by leprosy. In this review we want to explore interventions that can prevent and treat secondary damage to skin and limbs.
Objectives
To find out if any interventions can prevent secondary damage to the skin in people with leprosy, for example:
-
self‐care
-
dressings
-
appropriate footwear
Which of the interventions are the most effective?
Do these interventions reduce social stigma and lead to better quality of life?
Are any interventions harmful?
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs).
Types of participants
Anyone with leprosy and damage to peripheral nerves who are on multi‐drug treatment or are post treatment.
Types of interventions
Education, information, self‐care programmes, dressings (i.e. zinc tape, saline, iodine, gauze soaked in different ointments, dry dressings), skin care, footwear or other measures designed to prevent damage.
Types of outcome measures
Participants with no skin/limb damage at trial entry
Primary outcomes
(a) Prevention of skin ulcers, measured at six months and at one year
(b) Prevention of limb deformity, measured at six months and at one year
Secondary outcomes
(a) Prevention of cracked, thick skin
(b) Quality of life measures or other psychological or functional measures, acceptability of intervention
(c) Cost of intervention (i.e. footwear, dressings, self‐care programme)
(d) Adverse events, either those sufficiently serious to stop intervention, or minor ones reported by the participant
All of these secondary outcomes to be measured at six months and one year.
Participants with existing skin ulceration at trial entry
Primary outcome
Healing of existing ulcer (measured as percentage healed at six weeks, six months and at one year)
Secondary outcomes
(a) Prevention of recurrence of the same ulcer
(b) Prevention of other, new ulcers
(c) Prevention of limb deformity
All of these secondary outcomes to be measured at six months and one year.
Tertiary outcomes
(a) Quality of life measures or other psychosocial or functional measures, acceptability of intervention
(b) Days off work, school, or other tasks
(c) Cost of interventions
(d) Adverse events, either those sufficiently serious to stop intervention, or minor ones reported by the participant
Search methods for identification of studies
(1) Electronic databases
Relevant trials will be identified from the Skin Group Specialised Register. We shall also search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 2000), EMBASE (from 1980), CINAHL and LILACS, AMED and OVID‐MEDLINE(R) In‐Process & Other Non‐Indexed Citations.
(a) Search strategy for OVID‐MEDLINE
(i) Search strategy to locate RCTs
Search terms 1‐29, as given in the Cochrane Reviewers' Handbook (Alderson 2004), appendix 5b.2.
(ii) search strategy to locate leprosy studies
30 exp leprosy
31 leprosy.mp.
32 hansen's disease. Mp.
33 or/ 30‐32
34 exp behavior control
35 exp musculoskeletal manipulations
36 Orthopedic Procedures
37 Orthoptics
38 exp patient care
39 Prescriptions, Non‐Drug
40 exp rehabilitation
41 self care
42 self administration
43 self care.mp.
44soak$.mp.
45 orthotic devices
46 orthotic devices.mp.
47 footwear.mp.
48 shoes
49 shoes.mp.
50 podiatry
51 podiatr$.mp.
52 oiling.mp.
53 lotion.mp.
54 exp orthopedic fixation devices
55 splints.mp.
56 plaster cast.mp.
57 patient education
58 education.mp.
59 counseling
60 directive counselling
61 counseling.mp.
62 training.mp.
63 information.mp.
64 self observation.mp.
65 plants, medicinal
66 medical plants.mp.
67 medicinal plants.mp.
68 program$.mp.
69 rehabilitation.mp.
70 daily living.mp.
71 exp health services
72 or/ 34‐72
73 29 and 33 and 72
This is a draft search strategy and it will be modified to include other search terms where necessary.
(b) A similar strategy will be used for EMBASE and the other databases listed above.
(c)We also intend to search for ongoing trials in:
The NHS Trusts Clinical Trials Register in the metaRegister of Controlled Trials (http://www.controlled‐trials.com/)
(2) References from published studies
These will be checked for further trials.
(3) Unpublished literature
Unpublished and on‐going trials will be identified by correspondence with authors and field experts. Grey literature will be sought by contacting experts and searching SIGLE (System for Information on Grey Literature in Europe) on OVID's Silver Platter Internet Service. Digital dissertations will be sought for.
We will search a CD produced of all the papers published in the main leprosy journals back to the 1920s (Leprosy Research Foundation) "Compact disc of leprosy literature, 1913‐1991". Loma Linda, California, USA, 1993.
Some possible experts identified are:
International Leprosy Association Technical Forum
WHO
Leprosy Mission International
Experts on tropical medicine and/ or leprosy will be contacted.
(4) Conference proceedings
The abstracts from conferences will be scanned for further RCTs.
(5) Handsearching
We will hand search key journals for additional studies:
-
Indian Journal of Leprosy
-
International Journal of Leprosy
(All years)
The list of journals and years will be modified if necessary.
(6) Language
There will be no language restrictions when searching for publications.
(7) Adverse events
A search will be made for adverse events. Adverse events bodies will be contacted for relevant information.
Data collection and analysis
(1) Study selection
Firstly, inclusion or exclusion will be based on title and abstract. Studies that are clearlynot randomised trials will be excluded, others will be assessed for eligibility by two reviewers (LMR, LF). Consensus with persisting disagreement will be adjudicated (by AB). A log of excluded studies will be kept, with reasons for exclusions.
(2) Assessment of methodological quality
The quality assessment will include an evaluation of the following components for each included study. Each component will be categorised as adequate, unclear, or inadequate. The quality components criteria will be as suggested by Juni 2001 since there is some evidence that these are associated with biased estimates of treatment effect.
(a) the method of generation of the randomisation sequence;
(b) the method of allocation concealment ‐ it will be considered 'adequate' if the assignment cannot be foreseen;
(c) who was blinded/not blinded (participants, clinicians, outcome assessors);
(d) how many participants were lost to follow up in each arm (split into post‐randomisation exclusion and later losses if possible), and whether participants were analysed in the groups to which they were originally randomised (intention to treat).
In addition the quality assessment will also include:
(e) degree of certainty that the participants have leprosy or complication of leprosy;
(f) baseline assessment of the participants for age, sex, duration and severity of complications;
(g) aims, interventions (with details of how it was done) and outcome measures clearly defined;
(h) use and appropriateness of statistical analyses.
The information will be recorded in a table of quality criteria by two reviewers (LMR, LF). Disagreements will be resolved with a third reviewer (AB). A description of the quality of each study will be given based on a summary of these components. We will also perform an overall quality assessment of included studies. Note that the nature of interventions can make it impossible to meet all criteria adequately for the researcher, i.e. blinding.
(3) Data extraction
This will be performed by two reviewers (LMR, LF), who will independently enter data onto a data extraction form. Discrepancies will be resolved by consensus. Missing data will be obtained from authors where possible. Data will be checked and entered into Review Manager (RevMan) data extraction forms, by one reviewer (LMR). The reviewers will not be blinded to the names of authors, journal or institutions. If possible we will ask authors to confirm our methodological quality rating and the data abstraction.
(4) Analysis
The analysis will be performed by two reviewers (LMR, AB). Typical outcome measures will be: days/weeks/months for ulcers to heal, size of ulcers, number of persons improved, number of days before recovery, number of days off work/school (when applicable), acceptability of intervention (i.e. footwear). Weighted means difference or standardised mean differences will be calculated for continuous outcomes (with 95% confidence interval). The results will be expressed as odds ratio (OR) and 95% confidence intervals (CI) for dichotomous outcomes.
If appropriate the results will be pooled, using a fixed effects model. Sources of heterogeneity will be sought (i.e. country of origin, age group, leprosy classification, grade of impairments, intervention, compliance, outcome assessment) and tests for heterogeneity between studies will be performed using I2. In the presence of moderate levels of heterogeneity (I2>50%) a random effects model will be considered.
Sensitivity analysis will be performed to examine the effects of including or excluding subgroups based on patient factors (i.e. diagnosis or age), treatment factors (i.e. self care characteristics or compliance greater or less than 80%) or study factors (i.e. country of origin, methodological quality). We plan to stratify analyses according to study quality and whether effects differ between subgroups.
If the nature of the included studies does not allow the pooling of results (clinically or statistically) a narrative (qualitative) summary from the studies will performed. Non‐randomised trials will be listed, but not discussed further. Studies relating to adverse effects will be described qualitatively.
