Prevalence and characteristics of neuropathic pain in the people affected by leprosy in China

Transcription

1 Lepr Rev (2012) 83, Prevalence and characteristics of neuropathic pain in the people affected by leprosy in China SHUMIN CHEN, JINLONG QU & TONGSHENG CHU Shandong Provincial Institute of Dermatology, Shandong, P.R. China Accepted for publication 15 May 2012 Summary Objectives: To determine the prevalence and the characteristics of neuropathic pain among the people affected by leprosy in China. Methods: People affected by leprosy in four leprosy villages were interviewed about neuropathic pain with an interviewer-administrated questionnaire. Results: In a total of 275 patients with leprosy interviewed, 126 (45 8%) reported having symptoms suggestive of neuropathic pain. The pain was severe in 70 (55 5%) patients, moderate in 49 (38 9%) and mild in 7 (5 6%). Of the 126 patients with leprosy, 109 (86 5%) stated that the pain had some impact on their daily life: mild in 13 (10 3%), moderate in 45 (35 7%) and severe in 51 (40 5%). Sleep disturbance caused by pain was reported in 119 (94 4%) patients with leprosy: mild in 13 (10 3%), moderate in 51 (40 5%) and severe in 55 (43 6%). Ninety-six patients with leprosy (76 2%) reported that they had tried analgesics alone or in combination with steroids for the relief of their pain, of which 78 (81 2%) people reported that the treatment was effective. Conclusions: Neuropathic pain is not uncommon in both MB and PB patients who have completed effective antimicrobial treatment. The effectiveness of analgesics alone or in combination with steroids, in the treatment of neuropathic pain in patients with leprosy, needs to be studied. Introduction Hypothesia due to peripheral nerve damage in leprosy is one of the most common characteristics of the disease. Pain in leprosy can occur when there is an acute inflammation in one or more nerves associated with reactions. After appropriate treatment with steroid and anti-inflammatory medications the pain can subside. This type of pain is termed as neurogenic. 1 However, some patients may suffer from chronic pain, termed as neuropathic pain, after successful treatment with antimicrobial drugs. 2 4 Sometimes the pain is so severe that the quality of life is disturbed in a proportion of patients. 2,3 Neuropathic pain is a pain Correspondence to: Shumin Chen, Shandong Provincial Institute of Dermatology, 57, Jiyan Lu, Jinan, Shandong, P.R. China ( Chenshm@public.jn.sd.cn) /12/ $1.00 q Lepra 195

2 196 S. Chen et al. condition initiated or caused by a primary lesion or dysfunction in the nervous system, which differs from nociceptive pain, a pain condition initiated or caused by a noxious stimuli, 1 such as infected ulcer or neuritis in leprosy. Recently a group of experts from the neurologic and pain community redefined the neuropathic pain as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. 5 The underlying pathophysiological mechanism of neuropathic pain has not been fully established. Sprouting of A-beta fibres to the superficial layer of the dorsal horn, ectopic discharge in the dorsal root ganglion and/or in neuroma at the nerve stump, and spinal sensitization have been proposed. 6 Similarly, the mechanism of neuropathic pain in leprosy is also not fully understood. Small-fibre sensory neuropathy possibly due to the involvement of the peripheral nerve by M. Leprae, never fibrosis and entrapment of never fibres due to previous reactions, and ongoing intraneural inflammation may be involved. 1,7 The epidemiological profile of neuropathic pain in patients with leprosy is scant. The first documentation on the neuropathic pain in leprosy was reported by Hietaharju et al. in Bangladesh, in Out of 38 patients with leprosy recruited by local leprosy workers, 16 suffered from moderate or severe chronic neuropathic pain after completion of antimicrobial treatment. In 2004 Stump et al. reported 56% of 358 patients with leprosy interviewed had chronic neuropathic pain in a cross-sectional study among the patients with leprosy presented to a national centre for patients with leprosy in Brazil. 3 In another cross-sectional study conducted recently in Ethiopia, Saunderson et al. reported that 29% of 96 patients with lepromatous leprosy who were treated with multi-drug therapy (MDT) for more than 10 years had neuropathic pain at some point in time. 4 It seems that chronic neuropathic pain is not uncommon among patients with leprosy who have completed effective anti-leprosy treatment. In order to determine the epidemiological feature and the main characteristics of this problem, we conducted a survey among people affected by leprosy who have completed dapsone monotherapy or MDT in China. Patients and Methods This is an institution-based cross-sectional survey, which was conducted in four leprosy colonies from October 2009 to February 2010: three in Shandong province and one in Jiangsu province. The reason for the selection of these four leprosy villages was because there were more people affected by leprosy compared to other leprosy villages in the two provinces. The vast majority of these people affected by leprosy were diagnosed before the 1980s when the Madrid classification of leprosy was used. Indeterminate (I) and tuberculoid (T) categories were classified as paucibacillary (PB) leprosy and borderline (B) and lepromatous (L) categories were classified as multibacillary (MB) leprosy. Few people were diagnosed after the 1980s when spectrum classification was used. Indeterminate (I), tuberculoid (TT) and borderline tuberculoid (BT) categories were classified as PB leprosy, and borderline (BB), borderline lepromatous (BL) and lepromatous (LL) categories were classified as MB leprosy. All the patients with leprosy were cured with dapsone monotherapy or MDT. The study was part of a training course for post-graduate students and was approved by the Shandong Provincial Academy of Medical Sciences. The patients were interviewed by two trained post-graduate students face-to-face with a modified questionnaire based on previous studies. 4,8 The interview was conducted in a meeting room or an examination room (for general diseases). Firstly the investigators were introduced by local leprosy control staff.

3 Neuropathic pain in leprosy-affected people in China 197 The former explained the purpose of the study, and then, asked oral consent from the interviewees before the interview took place. The main questionnaire is the Neuropathic Pain Symptom Inventory which was developed by Bouhassira et al. in Saunderson et al. 4 conducted a study on neuropathic pain among leprosy patients for follow-ups of relapse in 2008, using the main components of the questionnaire. The main components in two questionnaires 4,8 were translated into Chinese and adopted. Briefly, demographic characteristics, and information on leprosy, (time on diagnosis, the type of the disease, treatment regimen and reactions) and neuropathic pain (intensity, the nature of pain and response to treatments, etc.) were included in the questionnaire. A body chart was added into the questionnaire for the drawing of location of the pain, but the questionnaire was not translated back for accuracy. A pilot test for the understanding of the questions was conducted in a small leprosy village with 11 people affected by leprosy. People having a mental problem or having severe health problems were excluded from the study. Pain can be categorised in a variety of different ways, and one division that has been particularly useful is nociceptive pain versus neuropathic pain. Nociceptive pain results from activity in neural pathways caused by actual tissue damage or potentially tissue-damaging stimuli, while neuropathic pain may be present without any readily demonstrable physical findings. 9 Pain in leprosy can be associated with neuritis caused by reactions within peripheral nervous system. In most leprosy cases nerve function impairment and reactions occur within 2 years after diagnosis. 10,11 In order to distinguish nociceptive pain caused by neuritis/reactions from neuropathic pain we defined neuropathic pain as a pain condition which occurred after at least 2 years of anti-leprosy treatment and lasted for at least 3 months (continuous or interrupted) without evidence suggestive of reactions and other causes such as infected ulcers. The intensity of pain was measured with an 11-point Likert scale using a straight line labeled at the left end as no pain and at the right end as worst imaginable pain, 12 and a verbal rating scale (mild-moderate and severe). The location of pain was recorded by using pain drawings. 8 The nature of pain was also asked and recorded. Patients with diabetes were excluded by their history, but blood glucose was not tested. Alcohol consumption was also requested and heavy drinkers (50 ml per day on average for more than 1 year) were also excluded. Disability was assessed with WHO disability grading system and only visual impairments or WHO Grade-2 disability was recorded. Information on the previous history of reactions was extracted from patient s files. Statistical analyses were performed with SPSS software 10.0 for windows. The measurement of the outcomes was analysed using a chi-squared test. For continuous data a t test was applied. Results In total, 275 patients with leprosy were interviewed, including 219 (79 6%) males and 56 (20 4) females. The age at present and at diagnosis, type of leprosy, history of reactions, previous treatment and deformity are presented in Table 1. Out of 275 patients interviewed 126 (45 8%) reported that they experienced symptoms suggestive of neuropathic pain. At the time of interview nine (3 3%) patients still complained of pain. There was no significant difference in the frequency of neuropathic pain between MB

4 198 S. Chen et al. Table 1. Characteristics of 275 ex-leprosy patients by sex Variable Male (n ¼ 219) (%) Female (n ¼ 56) (%) Total (n ¼ 275) (%) p Type of leprosy MB 112 (51 1) 36 (64 3) 148 (53 8) PB 107 (48 9) 20 (35 7) 127 (46 2) Age at diagnosis (yrs on average) Age at present (yrs on average) Main treatment DDS 214 (97 7) 54 (96 4) 268 (97 5) MDT 5 (2 3) 2 (3 6) 7 (2 5) Type 1 reaction Yes 11 (5 0) 2 (3 6) 13 (4 7) No 208 (95 0) 54 (96 4) 262 (95 3) Type 2 reaction Yes 26 (11 9) 7 (12 5) 33 (12 0) No 193 (88 1) 49 (87 5) 262 (88 0) WHO grade-2 disability Yes 208 (95 0) 7 (12 5) 259 (94 2) No 11 (5 0) 5 (8 9) 16 (5 8) MB: multibacillary leprosy; PB: paucibacillary leprosy; MDT: multi-drug therapy; DDS: dapsone. and PB patients. Again, the difference was not significant between male and female (Table 2). All the patients with neuropathic pain had visual deformity and no any patients of the 11 who did not have visual deformity had pain. The average duration of neuropathic pain among the 126 patients was months, ranging from 3 months to 360 months. Majority of the patients described the pain as tingling sensation (54 8%, 69/126), burning in 24 6% (31/126), electronic in 9 5% (12/126), pressure in 8 7 (11/126) and cutting in 2 4% (3/126). The pain was continuous in 61 (48 4%) patients and was recurrent in 65 (51 6%). Six (4 8%) of 126 patients stated that they experienced pain suggestive of allodynia (touch-evoked pain). The average score of the pain was 7 7, ranging from 3 to 10 in the Likert scale. The average score of pain was higher in male than in female (7 91 vs 6 88, P ¼ 0 024). With verbal rating scale, the pain was stated as severe in 70 (55 5%), moderate in 49 (38 9%) and mild in 7 (5 6%). Of the 126 patients, 109 (86 5%) stated that the pain had some impact on their daily life: mild in 13 (10 3%), moderate in 45 (35 7%) and severe in 51 (40 5%). Table 2. Frequency of neuropathic pain among 275 leprosy patients by sex and type of disease Neuropathic pain Variable N ¼ 275 Yes (%) No (%) p Sex M (46 1) 118 (53 9) F (44 6) 31 (55 4) Type of leprosy MB (46 6) 79 (53 4) PB (44 9) 70 (55 1) MB: multibacillary leprosy; PB: paucibacillary leprosy.

5 Neuropathic pain in leprosy-affected people in China 199 One hundred and nineteen (94 4%) patients stated that the pain disrupted their sleeping: mild in 13 (10 3%), moderate in 51 (40 5%) and severe in 55 (43 6%). The most commonly affected nerve was ulnar nerve in 100 (79 4%) patients, followed by tibial nerve in 53 (42 1%), peroneal nerve in 41 (32 5%) and median nerve in 25 (19 8%). Some patients had more than one nerve affected, so that the percentage of total number of nerves affected is more than 100%. No patients reported pain in glove and stocking-like distribution. Of the 126 patients, 96 (76 2%) patients took some medication for pain relief. The most commonly used drugs were analgesics, such as aspirin and paracetamol (acetaminophen) or analgesic compounds. Some patients (28) mentioned they also took steroids alone or in a combination with analgesics. Out of the 96 patients 78 (81 2%) reported that the treatment was effective. A number of factors were analysed with multivariable model for the development of neuropathic pain. No risk factors were found except for a previous history of Type-2 reaction which had significant association (data are not presented). Discussion Studies have demonstrated that neuropathic pain is not uncommon among patients with leprosy who have been effectively treated with antibacterial drugs. Up to 56% of patients experienced it in Brazil 3 and 29% in Ethiopia. 4 The figure in the current survey stands in between (45 8%). The frequency and the nature of neuropathic pain in different type of leprosy are not clear. In two previous studies 2,4 all the patients are MB, and in the Brazilian population % of the patients are MB, but the comparison of neuropathic pain between MB and PB categories of the disease was not reported. PB patients account for 46 2% in the current study. However, the difference in the frequency of neuropathic pain between MB and PB patients is not significant (Table 2). The nature and the severity of neuropathic pain differ in different studies including the current one due to different population studied and methodology used. For example, Gloveand stocking-like pain is reported in 10 (62 5%) of the 16 patients 2 and in 12 (70 6%) out of 17 patients selected for histopathological study. 7 Neuropathic pain in glove stocking-like distribution is also very common in Brazilian patients, 3 but is not reported in a recent study conducted in Ethiopia. 4 In the current group of patients no any patients complain of pain in glove and stocking distribution. As Haanpää et al. pointed out, more studies are needed to clarify the magnitude of the problem among different leprosy populations. 1 The presence of impairments on examination is found to be the only one risk factor for the development of neuropathic pain in the study conducted by Saunderson, et al. 4 In the current study, several factors are also analysed with multivariable model. However, only previous history of Type-2 reactions, not impairment, is found to be associated with the neuropathic pain. The reason is unknown. More studies are needed to clarify the problem. It is interesting to note that vast majority of the patients (81 2%) stated that analgesics alone or in a combination with steroids were effective in the relief of their neuropathic pain. The recommended medication in the treatment of neuropathic pain is antidepressants and anticonvulsants, which is based on the experiences from other causes of neuropathic pain. So far, there is no any report on the effectiveness of analgesics in the treatment of neuropathic

6 200 S. Chen et al. pain in leprosy. The role of analgesics alone or in combination with steroids, in the treatment of neuropathic pain in patients with leprosy needs to be studied in future. The natural history of neuropathic pain in patients with is also not clear and needs to be studied. In the group reported by Stump et al. 3 only 53 (15%) patients had pain at the time of investigation, while 201 (59%) patients complained of it at some time. In the current study only nine (3 3%) patients had pain at the time of interview. It seems that pain in the vast majority of patients can disappear without any intervention. Another possibility for the disappearance of pain is that some patients may take some medication for the relief of their pain, as reported in the current group of patients. Taking analgesics as pain killers is very common practice in leprosy colonies in China, as suggested by the investigation on analgesic use by leprosy patients in Malaysia. 13 Nevertheless, neuropathic pain after effective antileprosy treatment is disturbing and may have some impact on the quality of life in a proportion of patients, which needs to be investigated in the follow-up after cure of the disease. The limitation of the study is recall bias, although the interviewees were likely to tell their stories when the interview took place. The symptoms suggestive of neuropathic pain are retrospectively reported by the interviewees. Especially, in the current study many cured patients are too old to precisely remember the events which happened a long time ago. Apart from this recall bias, identifying neuropathic pain in clinical practice is not an easy task, and the painful sensation cannot be measured objectively. As in previous studies, the diagnosis of neuropathic pain is based primarily on the description of a patient and the findings of physical examination when interview takes place. Therefore, bias in distinguishing neuropathic pain and other types of pain such as nociceptive pain, which happened a long time ago, may be unavoidable (sometimes the two types of pain can coexist, termed as predominant neuropathic or predominant nociceptive types of pain, depending on the predominant clinical picture 14 ), which can result in over- or under-estimation of the prevalence of neuropathic pain in patients with leprosy studied. In conclusion, the results of our survey have confirmed that neuropathic pain is not uncommon in both MB and PB patients with leprosy who have completed effective antimicrobial treatment. The nature and severity of neuropathic pain differ from study to study and the risk factors contributing to the pain is also unclear. The effectiveness of analgesics alone or in combination with steroids, in the treatment of neuropathic pain in leprosy patients, needs to be studied in future. Acknowledgements We would like to express our sincere thanks to the local staff for their cooperation and many thanks will go to the people affected by leprosy who participated in the study. References 1 Haanpää M, Lockwood DN, Hietaharju A. Neuropathic pain in leprosy. Lepr Rev, 2004; 75: Hietaharju A, Croft R, Alam R et al. Chronic neuropathic pain in treated leprosy. Lancet, 2000; 356: Stump PR, Baccarelli R, Marciano LH et al. Neuropathic pain in leprosy patients. Int J Lepr Other Mycobact Dis, 2004; 72:

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