History and Myths Hansen’s Disease undoubtedly continues to represent today an emergency situation in certain countries. The medical fight against L. comprises three stages: identifying the infected patient, reaching a diagnosis and assisting the patient throughout the therapy, which may last for years. But, in order to achieve this, qualified staff is required, as well as the constant strategic support of a great Organisation, such as the WHO, which is indeed available. Of course, diagnosis needs to take place very early, the therapy needs to be prompt, continuous and controlled, and, what is most important, greater support is required from the wealthier countries.
Of all the diseases which have accompanied mankind from its earliest days, including plague, cholera, smallpox and tuberculosis, leprosy has undoubtedly left the deepest wound; unfortunately this continues to be visible today, and is felt to be so terrible even when simply mentioning its name, that over the last twenty years its name has been often replaced by Hansen’s Disease, in the hope of somehow easing the distress of those who may be affected by it today. We shall therefore briefly attempt to outline how and why this has happened. Debates still exist among palaeontologists as to whether the Egyptian word ukede, the Jewish word zaraath, the Indian word kustha and the Chinese world da feng, all referred in fact to L., or else to another disease or to a range of diseases.

In Susruta Samita, an Indian book dating back to the 6th century B.C., reference is also made to a treatment by means of oil extracted from the plant Hydnocarpus Wigtiana, chaulmoogra oil, a substance that has been skilfully used up to the ‘40s! Ancient Greece and Rome where not very familiar with this disease, and possibly used the terms lepra and elefantiasi to describe other skin diseases; a legend says that the Emperor Constantine was cured from it upon his christening; however it is most likely that in this case the word L. relates to a moral fault, rather than to a real affection. Upon Alexander the Great’s return from India in the 3rd century B.C. and upon Pompey the Great’s return from Egypt in ’62, L. started spreading first in Greece and later in Italy, and it was at that very time that the first clinical descriptions appear to have been recorded (Areteus the Cappadocian).

But it was during that peculiar religious, political and military phenomenon which goes by the name of Crusades that minute spreading of the disease took place in Europe, and within a few years turned into a terrible pandemic; indeed, it was at that very time that the horrible myth started, according to which leprosy and the leper involved people who have been struck by a curse and have to be kept away from the community: You are now dead for the world, so place your hopes in God!!

This was the canonical formula with which the sick was officially acknowledged as dead for society, banished from town, obliged to wear lepers’ clothes and a bell that announced his presence and warned people as he passed by. In certain towns, such as Vicenza, a provision dating back to the 14th century, explicitly instructed guardians to drive outside the town walls any person who had been declared infected by the disease by committees made up of physicians, clergymen and even affected people who had (possibly) recovered. In certain cases the measures were much more inhuman, especially as a result of the belief that lepers were enemies of humanity, people in with the devil, the authors and bearers of calamities, as when in France, following the 1312 plague and out of respect for Philip 5th, in the town of Limoges, 45 of them were burnt to death within one month!

The practice of isolation in lazarettos and leprosariums therefore started in that period: there was no city, town or village which did not have at least one and, according to Mézeray, there were 19,000 in Europe, 33 of which in Northern Italy. This terrible epidemic started to regress towards mid 14th century and to disappear during the 18th century in Central and Western Europe. There were several reasons for this decline: among the most likely, we may list:

1. Patients’ isolation;

2. Higher mortality rate among lepers, during plague, cholera and smallpox epidemics;

3. Improved hygiene conditions;

4. Antagonism between tuberculosis and leprosy;

5. Gradually acquired immunologic resistance.

Endemic foci continued to exist in Spain, Italy, Greece, Southern Russia and Scandinavia, whereas it should be acknowledged that towards mid 19th century Norway faced the problem in a very rational and determined manner, at a time when the number of patients affected amounted to 5,000: within 70 years Norway switched from an incidence of 10/50 out of 100,000 inhabitants, to the complete disappearance of the disease, thanks to a practice of immediate internment and isolation.

Still, the disease had spread through almost all continents. In America, from the Spanish first and from the black slaves later, in Oceania, in the days of the geographical discoveries, and in China, one of the oldest foci known, where a precise description is provided by Sung Szumoth, who died in 682 and called it thai feng. From China it spread to Japan, to Vietnam and gradually throughout Southeast Asia. As from the early 19th century, leprosy conquered the Pacific Islands and in this way, in an epidemic form, it spread to the Hawaiian Islands, to New Caledonia and to the Nauru Island (1912), where its epidemiology was carefully studied, since twelve years after its first appearance, 24% of its inhabitants had been infected. Since the misty Medieval times to mid 19th century, in one of the most exciting periods in the history of medicine, L. also found passionate researchers, and so in: 1847 The Norwegian dermatologists Danielsen and Boeck described on Om Spedalsked lepromatous leprosy; 1863 Virchow described the histopathology of lepromatous L.; 1873 The Norwegian Armauer Hansen, identified the mycobacterium as the agent responsible for the affection; 1919 The Japanese Mitsuda described the reaction to lepromin; 1941 Faget, in Carlville (Louisiana-USA), used promin, a derivative of diaminediphenylsulfone, he published his results in 1943 and confirmed them in 1946. It should however be stressed that d.d.s. had already been synthesizes in 1908 by the German Fromm and Wittmann; 1960 Shepard inoculated the bacillus into a mouse’s plantar cushion; 1964 First alarming reports by Pettit and Rees as to the first cases of resistence to dapsone; 1969 First studies on the bactericidal activity of rifampicin were carried out at the Hansenian Centre of Gioia del Colle (Ba-Italy), confirmed by Rees and his team and by Leiker in 1970; 1971 Kircheimer and Storrs published their experiences with inoculation on the nine-band armadillo. This allowed hope to have available great amounts of bacillary material for the preparation of a vaccine; but these expectations were blighted; 1981 A group of WHO researchers recommended resort to polychemotherapy for the fight against leprosy, which had by now become a primary objective of worldwide healthcare. But, despite these 150 years of study, research work, treatment programmes and great amounts invested by the WHO, as of today, L. does not show signs of surrender. Although, especially in Africa, ever since mid 19th century, the then so-called colonial powers had gradually put together in their territories, directly or through the many philanthropic associations, all the healthcare facilities and measures available at the time, through the construction of villages, hospitals and dispensaries, to fight the most widespread diseases (malaria, tuberculosis, yellow fever, smallpox and leprosy), the decolonising surge which took place in the ‘60s and ‘70s resulted within a few years in the loss of what had been created in 100 years and, when we think of the 20 million victims of AIDS we have today, we perceive the humiliating picture of an agonising continent.

Etiopathogenesis Estimating the number of people affected by L. today in the world is an impossible task: the minimum figure is 2 million, some researchers mention 10 million, but we continue to wonder how this can possibly happen today, in the prime of the antibiotic age; so we should better provide a concise explanations of the reasons thereof:

1. The first reason lies in the fact that, as of today, unlike all other microorganisms, the Hansen bacillus is not cultivable;

2. L. is an exclusively human pathology; it has not been possible to transfer the pathogenesis of the my. on animals, not even on those which are most similar to man;

3. The particular structure of the mycobacterium cellular wall, despite its antigenic aspect, performs its fundamental protective function by means of glycolipids excreted by the bacillus, which make it invulnerable to the lytic activity of the phagocytes; therefore the mycobacterium is able to survive and multiply enormously in the macrophage cytoplasm.

Researchers have worked out that in cases of L. L. up to 7 billion mycobacteria can develop per one gram of tissue. This enormous amount of germs explains the possibility of interhuman contagion.

This is another subject which continues to be debated: having long ago overcome the theory that L. may be a congenital disease, the bacillus has therefore two possibilities of entering a healthy organism: one is “from skin to skin”, through open continuous skin lesions; the other one, much more insidious, takes place through the mucous membrane of the respiratory tract, as in the case of tuberculosis.

Whatever the access means, the mycobacterium is incorporated by the macrophages, which in most cases manage to neutralise it and lyse it; however, in the cases in which the bacillary body degradation process does not take place (possibly owing to the inhibition of the production processes involving the active derivatives of oxygen or nitrogen monoxide, etc.), the phagocyte, which is a mobile cell, behaves exactly as the Trojan Horse: it allows time for the mycobacterium to organise itself and multiply inside it, and almost in symbiosis, within the tissues where it finds an optimal environment for its own development, that is in the sheathes of the large peripheral nerves and in the cutis depth.

This explains the long period of clinical latency, which ranges from the time the bacillus enters the host organism to the first clinical signs of the disease: this period can extend up to ten years.

A good example of this is provided by the case of two American marines who, during World War II had their arm tattooed in Australia: only two and a half years later did they develop a leprous lesion in the tattoo area. Classification and clinical forms There is no other chronic disease that, like L., displays so many clinical variants, corresponding to an equal number of histopathologic aspects, which in turn are the result of the patient’s immune response. From the definitions of lepromatous, ulcerative, anaesthetic, mutilating, nervous and macular L., described by the early leprologists, we have gradually moved on to today’s classification, proposed by Ridley and Jopling, who distinguish: · an, often initial, indeterminate form (I.L). · two polar types: the tuberculoid type (T. T.), marked by a strong immunologic response, and the lepromatous type (L. L.), marked by a weak or negative immunologic response. · other inter-polar forms called borderline (B. T., B. B., B. L.), marked by a variable or unstable response. Owing to this extraordinary polymorphism, the Hansen’s Disease diagnosis often proves a difficult task also for expert physicians, since the clinical onset is extremely varied: it ranges from small areas of cutaneous hypoesthesia, to smaller or larger hypopigmented or slightly erythematous patches of skin, to papular or definitely nodular lesions, which are treated in most cases with all kinds of therapies, thus producing confusion as to the essential morphological significance of the lesion: this results in the true diagnosis being often postponed by a few years, when the bacillary invasion has produced damage in the most sensitive and unrecoverable areas, such as the nervous, eye and osteoarticular systems. Leprous Neuropathy Leprosy sets in a very mischievous manner: hardly ever painful, it reveals on the occasion of burns which bring about the awareness of a pathologic analgesia. As a rule, the patient first looses sensibility to temperature and pain, whilst preserving tactile sensibility: this is often associated with other events, such as anhidrosis, alopecia and vasomotor areflexia, generally in the limb distal locations.

Another symptom involving approximately 30% of patients is the thickening to palpation of the nervous trunks, with an almost always cylindrical (and more rarely nodular) course; this may involve the upper cervical plexus, the supraorbital branch of the trigeminus, the radial, the common peroneal, the sural and the posterior tibial nerves. Special attention should be devoted to the medial and ulnar nerves, which are mixed nerves (sensitive and motor) and when affected involve one of the most invalidating conditions of the disease: the Clawed Hand. With the loss of sensibility in the ulnar and radial region, and subsequently as a result of the paresis or paralysis of the lumbrical and interosseous muscles, and of those of thenar and hypothenar eminence, the hand becomes flat, with the loss of that gesture that distinguishes the human species, that is the adduction and opposition ability of the thumb with the other fingers. Similar lesions appear on the feet, owing to the affection of the nerves in charge of the motor, sensitive and vegetative functions, as a result of which the foot becomes anhidrotic, it looses sensitivity to temperature, touch and pain, with a subsequent progressive atrophy of intrinsic and extrinsic muscles, which leads to the skeletisation of the foot and soon later to the formation of a plantar ulcer, which represents one of the afflictions which are most frequently reported by the patient.

The cases of bone resorption with spontaneous osteolyses are frequent. In a very rare clinical variant, the so-called pure neuritic leprosy, with the total absence of cutaneous symptoms, the my. will only be found in the peripheral nervous sheathes, and should indeed be searched for in the perineural structures through cutaneous breach. Leprosy Reactional State Whilst stabilised nervous lesions sooner or later lead to permanent disability, but thanks to their gradual onset they give the patient time to adjust and find alternative attitudes and movements to handle normal everyday gestures, there is a crucial time in the Hansenian’s life which represents a dramatic moment of his existence.

This is the time of the feared leprosy reactional state. From our hospital’s historical records we have worked out that over the 1928/1950 period, that is before the cortisone age, the fatal outcome in this phase reached 10% of patients and it regularly occurred in the Spring or Autumn period. From a clinical point of view the patient experiences a sudden feeling of discomfort, fever, wide-ranging pains and deep asthenia. Purplish erythematous lesions appear on the skin: these tend to be significant, painful and in the most severe cases they tend to ulceration.

There is a major involvement of other organs, such as eyes, kidneys and the epididymis. Haematochemical parameters display marked proteinuria, high ESR values, intense leukocytosis, alpha 2 hypergammaglobulinemia, PCR, hyperfibrinemia, hypocomplementemia and the presence of immunocirculating complexes. The trigger causes have not yet been clarified, but there certainly are several, the most probable of which is the reaction to mycobaterial antigens or sensitization to the antigens of other cross-reacting germs. The reactive phenomenology we have so briefly covered here, which is however very demanding on physicians, may last months or even years, it can include acute phases and apparent remissions, and at the end of the day leave their mark in the organs and systems which are most sensitive to this immunologic turmoil, such as eyes, kidneys and peripheral nerves. The use of prednisone, thalidomide and other immunosuppressants, through a discerning and experienced procedure, generally reduce the consequent damage. Therapy L. treatment depends today on a number of factors: · the impossibility of an antibiogram owing to the impossibility of my. cultures; · the increasingly frequent detection of resistant strains; · the need to extend the treatment to millions of people who live in the poorest counties in the world, without equipment, dispensaries or qualified staff. For this reason, as from 1981, the WHO has recommended resort to polychemotherapy, which consists of the contemporary administration of the drugs which are presently more active. The first one to be mentioned is Rifampicin, a 99% bactericide on sensitive bacilli; we then have Clofazimine, which certainly has a bacteriostatic and anti-inflammatory action, but results in white cutis taking on a darkish colour. Diaminediphenylsulfone (d.d.s.) has a bacteriostatic action and is generally well- tolerated; however occasionally, especially in patients suffering from a glucose-6-phosphate dehydrogenase deficit, it may bring about haemolytic crises. The dosage recommended by the WHO for these drugs, which are to act in synergy, is of 600 mg Rifampicin once a month, 300 mg of Clofazimine once a month plus 50 mg daily and 100 mg of d.d.s. daily. Of course the dosage and the use of individual drugs should be customised to meet individual tolerance and up to negativisation, that is the disappearance of the bacilli from the nasal mucus and from the skin lesions.

The WHO and the many other philanthropic Associations who are active throughout the world in fighting L. have arranged for the packaging of practical blisters containing the three drugs, together with the applicable directions for use. This aid is mainly distributed in the many areas lacking in healthcare assistance. Leprosy in the world today During the Worldwide Congress held at The Hague in 1986, the WHO person in charge for L., Dr. Nordeen, possibly encouraged by the positive trend shown by the worldwide campaign against poliomyelitis, announced that the WHO had set itself a deadline for the eradication of L. in the world: the deadline was the year 2000, but the unstable conditions of so many States or of entire continents, such as Africa, plus the new scourge of AIDS, have made it impossible to meet this commitment. I am reporting here, without adding any comments, the data relating to the new cases of contagion reported for some Countries in the year 2000: India 495,000, Brazil 78,100, Mozambique 28,500, Indonesia 23,200. As to our own Country, we can state that the old epidemic has finally been defeated, the age-old foci of the Calabria, Liguria and Apulia regions have now ended; there are approximately 400 patients under constant observation, with 3-4 new cases a year involving Italian residents; the feared increased due to immigrants has been very limited, thanks to the work conducted over the last 20 years by the 4 Italian Centres (located in Genoa, Messina, Cagliari and Gioia del Colle), not only in diagnostical and therapeutic terms, but also for the reconstruction carried out on old lesions, thanks to new surgical and physiotherapy techniques.

Translated by interpres sas

Giuseppe Barbieri
Professore a contratto presso la scuola di Specializzazione dell’Università di Bari; Membro della Commissione Ministeriale in qualità di esperto per il Morbo di Hansen da 15 anni.