Leprosy and Pain: an Old Disease with a New Challenge

Perhaps you have already heard about leprosy in the past. Despite major efforts to eradicate leprosy, this infection still affects 250,000 new individuals per year [1]. The mode of transmission of leprosy is probably person to person through nasal secretions from untreated patients. The disease is well known because of the biblical stories and it was also immortalised via disfigured images from 20th century leper colonies. During this period, any person with skin diseases (i.e. psoriasis, pemphigus or even leprosy) was confined to leper colonies and had to use leper bells as a warning. Terrifying disfigurement, missing limbs and dense scarring were the consequences of contracting leprosy.

Prevalence has fallen substantially in last decades. However, leprosy remains a public health problem in developing countries such as India and Brazil. Leprosy can be defined as a chronic infection caused by Mycobacterium leprae principally affecting the skin and peripheral nerves. The most important development in leprosy control was the introduction of multidrug therapy (MDT) in 1982 following the recommendations of a WHO Study Group on Chemotherapy of Leprosy for Control Programmes. The recommended duration of MDT can range from 6 months to 12 months, and these regimens will eradicate M leprae in most patients [2].

The type of leprosy that patients develop is determined by the host immune response. M. leprae shows a unique tropism for Schwann cells and can cause myelin destruction, leading to neuronal degeneration, and nerve dysfunction that continues after completed of MDT. In clinical practice the most commonly involved nerves are the ulnar, median, radial, peroneal, tibial and facial. Nerve damage in leprosy leads to motor, sensory and autonomic alterations and contributes to deformities (claw hands, drop foot) and secondary disabilities (plantar ulcers, contractures of fingers and toes).

Since leprosy causes severe sensory loss, scant attention has been paid to pain in leprosy, because of the assumption that pain could not occur in these patients. However, chronic pain in leprosy emerges as a challenge during or after MDT. Different pathogenetic mechanisms behind neuropathic pain in leprosy have been suggested, such as inflammatory response on peripheral nerves (neuritis), nerve hypertrophy, entrapment and fibrosis, peripheral and central sensitisation.

The consumption of medications by leprosy patients is often high. In the study of Segasothy et al. [3] regarding analgesic consumption by 235 leprosy patients, the authors found that in 46 (19.5%) patients the total mean intake had been more than 2kg of analgesic preparation and the duration of intake ranged from 2 to more than 20 years. Corticosteroids, especially prednisolone, are commonly used for treating nerve damage in leprosy. They work by controlling the acute inflammation and relieving the pain. Long-term therapy can cause serious adverse effects and a considerable proportion of people treated for nerve damage do not benefit from corticosteroid treatment. Haroun et al. [4] found that prednisone treatment was prescribed in 14 (36%), 23 (59%), and 2 (5%) leprosy patients with no pain, nociceptive pain, and neuropathic pain, respectively.

Leprosy is a stigmatising disease. It is noteworthy that psychological aspects play an important role in the setting and perpetuation of pain. In leprosy patients, depression, anxiety and social exclusion might contribute to the increased or sustained chronic pain condition. In a recent study of our group we found that leprosy patients with chronic neuropathic pain who were also found to have high psychological distress levels had higher pain intensity and a poorer quality of life [5]. Therefore, an appropriate assessment of leprosy-affected individuals suffering from chronic pain must also evaluate the core factors of pain and disability: pain description, affective distress, support, positive coping strategies, negative coping strategies and activity.

The prevention of nerve damage in leprosy is considered an important priority to prevent disabilities. However, the WHO currently disability classification for leprosy patients considers sensory-motor alterations but does not include pain as a disabling condition. It is important that chronic pain, whether neuropathic or not, is considered an “invisible” disability since it causes suffering and disability for many leprosy patients even many years after MDT.

About Felipe Reis

Felipe ReisFelipe Reis is a Brazilian physiotherapy graduated from the Federal University of Rio de Janeiro (1999), specialist in Manual Therapy and Orthopedics Physical Therapy. He has received his Master and Doctoral degree in Medical Science from Federal University of Rio de Janeiro (UFRJ). Actually, he is professor of Physiotherapy at Federal Institute of Rio de Janeiro (IFRJ). His main research fields include: Neuropathic pain in Leprosy, Brain Mapping in Chronic Pain, Neuroscience and Motor Control rehabilitation.

References

[1] Noordeen SK. Leprosy control through multidrug therapy (MDT). Bulletin of the World Health Organization 69(3):263-269 (1991).

[2] Rodrigues LC, Lockwood D: Leprosy now: epidemiology, progress, challenges, and research gaps. Lancet Infect Dis 11(6), 464-470 (2011).

[3] Segasothy M, Muhaya HM, Musa A et al.: Analgesic Use by Leprosy Patients’. International Journal of leprosy 54(3), (1986).

[4] Haroun OM, Hietaharju A, Bizuneh E et al.: Investigation of neuropathic pain in treated leprosy patients in Ethiopia: A cross-sectional study. Pain 153(8), 1620-1624 (2012).

[5] Reis, F. J., et al. Psychological distress and quality of life in leprosy patients with neuropathic painLeprosy review 85(3), 186-193 (2014).

 

Comments

  1. Felipe, thanks again for your answers and important work. Usually the occupational therapists do the sensory testing with Semmes Weinstein monofilaments where i work – I like to screen (there is a nice diabetic screening kit with 5.07 monofilament – Nancy Morgan has a nice one page summary on how to screen). We use a dynamometer for muscle testing (but there is not a lot of standardization for testing). What I would like to achieve is consistent screening ability. It would be helpful if there was a basic screening course for clinicians, especially when we are working with patients at risk (whether fragile diabetics with PVD or in other patients such as ones with leprosy). I suppose it starts with an understanding of peripheral nervous system and vascular anatomy. Obviously, the foot screening is key – where else do you screen and how do you achieve consistency among clinicians?
    Thanks again.

  2. Felipe, ok, I see that mycobacterium leprae prefer a cooler environment (33 C) – lower than most mammals body temp and only a select number of hosts are affected – humans being one -reason why more superficial and distal peripheral nerves affected and not usually the central nervous system. Yes?
    In the past, there were studies looking at ways to try to find other signals to alert patients with leprosy with insensitivity about potentially damaging stimuli (auditory signals with sensors in garments I believe). Trials were done with ‘normals’ and the realization that it was difficult (if not impossible) to find threshold for damaging stimuli as it depended on precondition of tissue – ‘spring gardening analogy’ – if you go out one day and do lots of gardening – manage without blisters but go out again next day – increased risks (obvious on reflection) but still relevant – adaptations to local environment. What are ways they are using now to help minimize risks with insensitivity other than education and ways to improve living conditions? Prevention is key I realize and MDT. Thanks for your research.

    Felipe Reis Reply:

    Hi Stu. Thanks again for your interest in leprosy. M. Leprae affects peripheral nerves (auricular, facial, ulnar, median, radial, perineal and tibial) because these nerves are located in superficial areas (also cooler areas). It is also interesting that the bacillus has a tropism for Schwann cells. To prevent disability the most important procedure is to perform sensory and motor examination. Monofilament of Siemens-Weistein or ballpoint test and manual muscular testing are recommend in the field. We believe that EMG tests and US could identify precisely the nerve damage. However, they are very difficult to implement in the field specially in rural areas of Brazil and India. Patients that completed MDT but still develop nerve damage may be indicated to a surgical procedure called neurolisys. I will be happy if I can answer some new interesting questions.

  3. Felipe, thanks for this important work – I was in the dark about the significance of pain in patients with leprosy – thought the issues were restricted around challenges with insensitivity -more familiar with the work of Dr. Paul Brand prior to the introduction of MDT in 1982 – his work on tendon transfer techniques and serial casting still guides some of the present work in hand therapy (The Gift of Pain and Fearfully and Wonderfully Made were great books).
    It seems like early intervention with MDT is key however patients are still left with residual nerve damage and also pain. I still have trouble with the concepts of nociceptive pain vs neuropathic pain – as well, my thoughts that more peripheral nerves being affected tied in with oxygenated blood flow (oxygen tension), tunnels and the superficiality of the nerves may be misguided if facial nerve is included – any help / insight?

    Felipe Reis Reply:

    Hi Stu. Thanks for your commentary. I am very happy that this post helps you. Tendon transfer in hands and feet in leprosy patients is an important intervention to prevent secondary disabilities such as plantar ulcer (and consequently amputation) and to restore hand function. Paul Brand and Srinivasan were responsible for studies in this area. Tendon transfer procedures are indicates in grade 2 disabilities which means sensory and motor impairment in hands or feet. WHO recommends early diagnosis and MDT to avoid nerve damage. However, some patients develop nerve damage years after MDT discharge. This is possible due to fragments of M. leprae that remains in the body. These fragments can stimulate immunological response and cause and inflammatory process called neuritis. I hope that I helped you.

  4. Artur Gosling says:

    Congrats my dear friend Felipe. Pain in Leprosy is a very underestimated problem, specially after multidrug therapy to eliminate leprosy bacillus. There are reports of leprosy in many countries aroud the world, but with high prevalence of disabilities in countries with low resources. Unfortunatly, a little attention exist for this condition and the consequences such as disabilities, stigma and prejudice are still very strong. Hope to see more studies about pain in leprosy.

    Regards. Artur