Leprosy or Hansen's disease is a chronic debilitating disease caused by the bacterium Mycobacterium leprae. It is primarily a granulomatous disease of the skin and peripheral nerves, with skin lesions being the usual presentation. The disease has been known since biblical times and left untreated; it can be progressive leading to permanent damage to the skin, nerves, limbs and eyes. Although it is an infectious disease, it is not highly contagious, and the presentation will depend upon the level of immunity in the affected patient. It was originally believed that the horrific trophic lesions of the hands and feet that are so well described in the Old Testament resulted from the infection. It was not until midway through the 20th century that Dr Paul W. Brand, working in South India, recognized that it was not the infection itself but the loss of pain sensation as a consequence of the disease that led those with leprosy to be susceptible to injury.
Paul W. Brand, MD, FRCS, CBE, was born to missionary parents and grew up in the foot hills of Tamil Nadu, just west of what was then Madras in South East India (Figure 1). After higher education in England, he went to Medical School at the University College Hospital, London in 1936. During the blitz of the Second World War, he worked as a junior doctor in London when he first experienced the management of patients with traumatic wounds to the hands and feet. It was in 1946 that he was invited back to India by renowned leprologist Dr Robert Cochrane, who was working at the Christian Medical Centre in Vellore, Tamil Nadu. Brand was horrified to see patients with extensive ulceration of the hands and feet receiving no specific treatment: he was told by the leprologist there that it would be a waste of time to treat them because leprosy patients had ‘non-healing flesh’; another said to him, ‘there is nothing that can be done for these patients, it's just leprosy’ .
Thereafter, Brand made major contributions to the understanding of the pathogenesis, medical and surgical management of the neurological complications of leprosy. In 1952, he was appointed as a Hunterian professor of the Royal College of Surgeons of London, UK; and in 1961, he received the honour in the UK of ‘Commander of the Order of the British Empire’. In 1966, he was invited by the US Public Health Service to head the Leprosy Centre at Carville, LA, where he worked for 20 years before retiring to Seattle in 1986. From 1992 to 1999, he was the international president of the Leprosy Commission and remained active as a popular teacher as an emeritus professor of orthopaedics at the University of Washington, Seattle. He was a few days short of his 89th birthday when he died following an accident in July 2003.
In this review, I will briefly outline his contributions to leprosy before discussing in greater detail his contributions to our understanding and management of diabetic foot problems.
PW Brand: contributions to leprosy
A brief description of the most important of his many contributions to leprosy will be presented here.
Causation of foot and hand ulcerations
Soon after his return to South India as a junior doctor in 1946, the world's foremost leprologist of that time, Dr Robert Cochrane, challenged Brand to explore why people with leprosy developed such horrific lesions as well as deformities in the hands and feet. As a consequence of his research, he discovered that the ulceration and the paralysis found in leprosy were a result of cutaneous anaesthesia and nerve damage not, as originally thought, as a consequence of the infection itself [2-4].
Role of off-loading in healing neuropathic foot wounds
His clinical observation of numerous patients with neuropathic ulcers on weight-bearing areas led to his realization that ‘pain is God's greatest gift to mankind’ . He described pain as the gift that none of us want but none of us can do without. During his time in South India, he pioneered the use of total contact casting in the management of plantar neuropathic ulcers [2, 3, 6, 7]. By removing the ability of the patient to put weight and pressure directly on to the ulcer by means of the cast, he observed rapid healing of ulcers that had been present for months if not years in many cases.
Surgical reconstruction of hands and feet in leprosy
In South India and later at the US National Hansen's Disease Centre in Louisiana, Brand pioneered a number of surgical procedures in the upper and lower limbs for the treatment and subsequent prevention of foot and hand lesions in leprosy [8-10]. Indeed, some of the tendon transfer procedures in the upper limb were later named ‘The Brand Operation’. Later, he popularized the technique of serial casting for the flexion contractures that occurs in the fingers as a result of leprosy, a technique that is still widely used by therapies to treat contractures of diverse aetiology.
Experimental research in leprosy
While at the National Hansen's Disease Centre in the United States, Brand established a well equipped and staffed research unit; his work performed there confirmed the relationship between repetitive pressure and ulceration in the insensitive limb . Moreover, armadillos and mammals found in the southern states of the United States were used for research into leprosy as they are among the few known non-human species that can contract the disease and in whom the leprosy bacillus can be cultured in the foot pad. Interestingly, very recently, DNA samples from wild armadillos in states including Louisiana were found to be genetically very similar to those from patients in the same states who had developed leprosy. Although this is not proof of direct transmission from animal to human, it is highly suggestive .
PW Brand: contributions to the diabetic foot
Loss of sensation in the lower limb can give rise to the same late complications such as foot ulceration and Charcot neuro-osteoarthropathy, whatever the aetiology of the sensory loss [4, 6]. Thus, many of Brand's observations in leprosy are equally relevant and important in the management of the insensitive lower foot in diabetes. His contributions will be considered under three headings, and after their descriptions, relevant subsequent work in the diabetic lower limb will also be described.
There is no doubt that Brand was an excellent clinician with wonderful powers of observation. His observations in leprosy patients who walk barefoot were that the pressures and stresses applied to the foot resulted in ulceration in patients who had lost ‘the gift of pain’ [3, 6]. Later, in an animal model, he was able to confirm the relationship between repetitive moderate stress and ulceration in the hind paw of rats . It was while working in Carville that Brand realized that much of what he had already described in leprosy was transferable to patients with diabetes, as he was seeing increasing numbers of diabetic patients in the insensitive foot clinic.
I realised that here in America in the 1960's, the management of foot ulceration in diabetes was hindered by some of the same misconceptions that I had faced about leprosy in the 1940's. Ulcers in diabetics were still called “diabetic ulcers” rather than neuropathic ulcers. They were looked upon by surgeons as being a reason for amputation, because they were thought to be unlikely to heal and go on to gangrene of the foot [1, 3, 13].
Most, if not all, of his observations in the lower limb in leprosy are transferable to diabetes. Another useful clinical tip from Brand is that ‘any patient with a plantar ulcer who walks into the clinic without a limp must have neuropathy’ [1, 3]. He also realized that basic clinical skills are probably most important in the reduction of foot problems and amputations in patients with diabetes. Once when lecturing to a large audience of physicians in the United States, he was asked, ‘What is the most important thing that we as physicians can do to reduce amputations in diabetes?’ The questioner was probably expecting an answer outlining the most modern scanning techniques or X-rays, but Brand's answer was much more practical:
Every time you see a patient with diabetes always remove the patient's shoes and socks and inspect the feet. If all of us followed this simple rule, this would have a big impact on reducing amputations in diabetes .
His seminal observations of the relationship between insensitivity and foot ulceration were later confirmed in work by my group. In a prospective study, we were able to show that patients with moderate-to-severe sensory loss had a sevenfold annual increased risk of ulceration compared with those with normal sensation . Subsequently, in the North West Diabetes Foot Care Study, we were able to confirm in a large community-based study that simple clinical tests such as a modified neuropathy disability score can be used to predict those at risk of ulceration, confirming Brand's original statement that no expensive equipment is necessary to identify the foot at risk of ulceration in diabetic patients . Indeed, the last American Diabetic Association statement on what should comprise the comprehensive diabetic foot examination adopted these principles of simple clinical tests in the annual review .
Importance of pressure under the insensate foot in the pathogenesis of ulceration
It was just under 50 years ago when Bauman and Brand  published pioneering work on the assessment of pressure between the foot and the shoe. Brand realized that in patients with sensory loss, the ability to perceive high pressures was lost, and he later developed pressure sensitive devices to alert patients as to when the pressure under their feet during walking was too high . These observations represent the principles behind the management of neuropathic plantar diabetic foot ulcers in the 21st century.
Working in Sheffield in the early 1980s, my colleagues and I were able to confirm the importance of high foot pressures in the genesis of plantar ulcers in neuropathic diabetic patients . Later, we were able to show in a longitudinal study that high foot pressures do indeed predict the development of plantar ulcers in this patient population .
In the management of ulcers, it has been shown that while removable cast walkers (RCWs) and the total contact casts (TCCs) relieve pressures under the foot equally well in the laboratory situation, in clinical practice and in randomized trials, the TCC is always superior . Armstrong et al. subsequently showed that the reason for these observations is based on the fact that RCWs are indeed frequently removed . Thus, the concept of a RCW rendered irremovable was developed, and this is often referred to as the ‘instant total contact cast’ . In a randomized trial of this ‘instant total contact cast’ versus the TCC, neither of which is removable, it was confirmed that the RCW is as equally efficacious in healing ulcers as the TCC, provided that it is actually worn . Finally, Piaggesi and colleagues working in Pisa have confirmed the benefits of off-loading in morphological changes in diabetic foot wounds . A wound biopsied after a patient had been wearing an irremovable cast walker for several weeks showed morphological features of an acute healing wound with angiogenesis and granulation. In contrast, patients whose wounds were biopsied without appropriate off-loading showed morphological features of chronic inflammation .
In summary, the principles of healing neuropathic foot wounds in diabetes are virtually identical to those in leprosy originally developed and described by Brand.
Foot skin temperature monitoring
It was Brand who originally observed that prior to breakdown of the skin at the start of an ulcer, an inflammatory state developed that led to a rise in local skin temperature in the affected area. Together with Bergtholdt, he observed that thermography could be used to detect an area of the skin at risk of breakdown, and he concluded that ‘infrared thermography could contribute to the care of the insensate limb’. They thus concluded that ‘if this area prior to breakdown is effectively managed, it may prevent permanent injury’ . It was over 30 years later that Lavery et al. reported the potential therapeutic benefit of self-skin temperature monitoring: in a randomized controlled trial, they showed that in a very high-risk group of patients with previous neuropathic ulceration, those randomized to self-skin temperature monitoring had a significantly reduced ulcer recurrence rate of approximately 8% compared with 30% in the control groups . Patients who received the skin temperature thermometers compared the temperature between both feet on a daily basis, and if there was a sustained rise in one foot compared with the other, a period of rest and consultation with a foot-cared specialist was implemented. Thus, these original observations of Brand have led to a potential therapeutic breakthrough in the recurrence of neuropathic foot ulceration.
It is clear from the aforementioned discussions what a major effect Brand had upon diabetic foot care as it is practiced today in the 21st century. His contributions and the similarities between diabetic foot ulceration and pressure ulcers in leprosy have been a subject of reviews [27, 28]. In comparative studies of patients with leprosy and those with diabetes with foot problems, Pendsey and colleagues highlighted the differences and the similarities between the two. Generally, the clinical appearances of diabetic foot problems were similar to those seen in leprosy, although in India, Charcot neuro-osteoarthropathy was more common in leprosy patients than in those with diabetes. As expected, the prevalence of hand lesions was also higher in leprosy patients .
In summary, the seminal observations by Brand have influenced all of us, whether we realize it or not, in our daily practice in the diabetic foot clinic. Brand was described by his co-author, Philip Yancey, in many books as ‘truly great – but with natural humility’ (personal communication). Brand was a truly dedicated physician who saw his patients not indeed as patients but as friends and family. I will end with a typical quote from him :
Because of where I practiced medicine, I never made much money: but as I look back over a lifetime of surgery, the host of friends who were once my patients bring me more joy than wealth could ever bring.