LEPROSY: Clinical Synopsis for Palaeopathologists.
Leprosy is a chronic infectious disease mainly, but not solely, of man, and caused by Mycobacterium leprae. The disease has been identified in chimpanzees, Mangaby monkeys, and the armadillo, but these are not considered of significance in the transmission of leprosy in the human population. Within human populations it is, predominantly, a disease associated with poverty, and, because of the mode of transmission, with increased population density. The bacterium is transmitted via exhaled droplets from the nose and mouth, as in coughing and sneezing, from an individual with lepromatous leprosy (vi) to a non-infected individual. In the body, M. leprae has a predilection for cool areas, and this is reflected in the specific organs and tissues involved in the pathological process of the infection. The incubation period of the disease is long, between 3 and 7 years.
The clinical presentation of leprosy is not the same or constant in all persons infected, and there is a spectrum of symptoms and physical signs determined by the immune status of the infected individual both prior to infection and during the course of the disease. Humoral immunity, manifest in antigen-antibody reaction, does not play a significant part in the bodily defense to Mycobacterium leprae. The significant immune reaction in leprosy is cell mediated and depends upon the functional integrity of T lymphocytes circulating in the blood. In a person of low immune status, the clinical presentation is lepromatous leprosy (vi). In a person of high immune status, the clinical presentation is tuberculoid leprosy (vi). There is a continuum of presentations, termed borderline leprosy, between these two polar states. Within these clinical presentations there is no variation in the pathogenicity of the bacterium. The variation is solely due to the immune status of the host, and, during the course of the disease, and dependent upon intercurrent disease and change in general health status, borderline leprosy may upgrade to the tuberculoid end of the spectrum, or downgrade to the lepromatous end. Only lepromatous leprosy is infectious. Established tuberculoid leprosy is not infectious.
Because of the absence of adequate immune response to the invasion of tissues by M. leprae, there is no destruction of M. leprae; this form is multibacillary within bodily tissues. The pathological response is one of continuing destruction of the normal anatomy and function of tissue and organ by the bacteria. The tissues and organs involved in lepromatous leprosy are skin, endothelial cells lining capillaries and small arterioles, lining (mucosa) of the palate and nasal cavity, larynx, eyes, testes, bone, and peripheral nerves in sensory, motor, and autonomic components. The distribution of M. leprae throughout the body is achieved by haematogenous spread. Because, in lepromatous leprosy there are widespread multibacillary lesions, the palaeopathological features are always bilateral.Skin:involvement of the skin, predominantly in cooler areas such as limbs and face (Figure: 1) , consists of multiple flat or raised nodules, of varying size, and colour depending upon skin colour. The nodules, a later development in the disease (Figure: 2), may ulcerate and discharge. All the lesions contain large numbers of M. Leprae. Nodular thickening of the ears develops, and eyebrows and eyelashes become thin. Swelling (oedema) of both lower legs develops (Figure: 3). At first this is only present during the day, but later is present both day and night and is associated with thickening of the skin, (Figure: 4). This clinical sign is manifest skeletally in subperiosteal new bone formation (vi. Bone Changes in leprosy: pathogenesis and palaeopathological diagnostic criteria).
Blood vessels:Endothelial damage in capillaries and small arterioles, directly by M.leprae, results in restriction of arterial blood flow, and consequent ischaemia and death of the tissues supplied by the blood vessels.
Palate and nasal cavity: The soft linings become heavily invaded by large numbers of M.leprae, become inflamed and ulcerated, and produce nasal crusting and a bloody purulent offensive discharge. This, with sneezing and coughing, is the source for the transmission of M.leprae within the population. There is resulting and associated destruction of the bones of the nose (Figure: 5) and the bridge of the nose collapses giving rise to a dished “saucer-like” lateral profile to the face (Figure: 6).
Larynx: Involvement of the larynx by M.leprae is a later feature of the disease and results in hoarseness or loss of the voice.
Eyes: The surface and internal structures of the eyes become invaded by M.leprae and may result in blindness, (Figure: 7). The eyes may also become infected with pathogenic environmental bacteria when the lower eyelids are paralysed (lagophthalmos ) (vi. Ibid.). Infection spreading within the orbit (panophthalmitis) may produce inflammatory changes within the bones of the orbital wall (vi.ibid.).
Testes: The testes may be infected with M.leprae, with consequent tissue destruction, loss of testosterone production, and subsequent predisposition to generalised osteoporosis.
Bone: Bones may be directly infected with M.leprae producing osteomyelitis (Figure: 8). In addition, the long bones of the hands and feet may progressively absorb through concentric diaphyseal remodelling and achro-osteolysis. In vivo, this presents as progressive shortening of the fingers and toes, but with maintenance of nail remnants at their distal ends, (Figure: 9) and (Figure: 10).
Nerves: There is no involvement of the central nervous system (brain and spinal cord). Peripheral nerves involved are subcutaneous and in the limbs and head and neck ie. the areas of coolness. Single or multiple nerve trunks become invaded and destroyed directly by M.leprae . In lepromatous leprosy, unlike tuberculoid leprosy, scarring is insignificant, but the swollen subcutaneous nerve trunks can be seen prominently and can be felt as thickened “cords” beneath the skin, (Figure: 11).
All three modalities of nerve function are involved simultaneously and the resultant symptoms and signs are due to the mixture of sensory, motor, and autonomic dysfunction:
1. Sensory: there is diminution of sensation(hypoaesthesia) and, later in the course of the disease, loss of sensation (anaesthesia) of the skin and deep tissues supplied by the specific nerve involved in the infection. The pattern of anaesthesia in upper and lower limbs has the distribution of “glove and stocking”. The result is predisposition to local injury which is not felt, ulceration (Figure: 12), (Figure: 13) and (Figure: 14). Secondary infection of the injured area by environmental pathogenic bacteria, and spread of these bacteria into deeper tissues including bones and joints (Figure: 15). (vi.ibid.). The loss of the sense of proprioception (awareness of joint movement and position) facilitates painless abnormal joint movement and may result in damage to the surface of joints (vi.ibid.).
2. Motor: motor nerves are those that initiate and control muscle contraction. Loss of motor nerve function results in muscle weakness and later paralysis. All joints have muscle groups acting upon them synergistically in equal and opposite manner in health, and loss of one muscle function in leprosy may not be associated with loss of the opposing muscle action. The result will be a deformity of the limb or limb function such as drop-foot, collapse of the longitudinal arch resulting in flat-foot (ultimately becoming boat-shaped), (Figure: 16). loss of transverse arch of the foot, claw-hand deformity consequent upon hyperextension of the metacarpophalangeal joints, and hyperflexion of interphalangeal joints; (Figure: 17) and (Figure: 18). Initially this is reversible but later in the course of the disease becomes fixed and irreversible. Thus, there may be abnormality of gait, and significant abnormality in hand usage, with an inability to grasp. Facial nerve dysfunction results in lower eyelid paralysis and inability to close the eye (lagophthalmos), (Figure: 19). with subsequent superficial inflammatory eye disease.
3. Autonomic (parasympathetic and sympathetic): These control arterial tone, and dysfunction may result in arteriolar dilatation or contraction, and consequent change ( increased or decreased) blood flow to a specific anatomical area. They also control sweating, and loss of function results in absence of sweating.
Because, in lepromatous leprosy there are widespread multibacillary lesions, the palaeopathological features are always bilateral.
In tuberculoid leprosy the high cell mediated immune response results in destruction of M. leprae. There are no M. leprae present in the lesions. Because the infective process in tuberculoid leprosy is immunologically controlled with death of bacilli, the physical manifestations are anatomically more restricted. Unilateral changes are more likely, and, indeed, even single limb involvement may occur. Nasal, oral, laryngeal, testicular, direct eye, and direct bone changes are absent. There is skin involvement, but the lesions are flat, sometimes few in number, pale in colour, and insensitive.
The symptoms and signs of tuberculoid leprosy due to the secondary effects of peripheral nerve damage are the same as those in lepromatous leprosy. The nerve trunk damage is due, not to the continued presence of M. leprae in the nerve, but to the scarring and locally destructive effects of the immunologically mediated destruction of the bacterium. There is a greater tendency for localised and single peripheral nerve involvement in tuberculoid than in lepromatous leprosy. The localised nerve scarring in subcutaneous nerves can be seen and felt as a nodule on the nerve trunk, (Figure: 20).
The resultant effects of nerve damage and loss of function in tuberculoid leprosy are the same as those in lepromatous leprosy.
PALAEOPATHOLOGICAL DIFFERENTIATION OF LEPROSY
Thus, in the palaeopathological differentiation of lepromatous from tuberculoid leprosy, the following features are significant:
Lepromatous leprosy is associated with multiple and bilateral limb skeletal changes.
Tuberculoid leprosy is associated with, frequently, single limb, or multiple butunilateral limb skeletal changes.
Lepromatous leprosy is associated with rhinomaxillary changes.
Rhinomaxillary changes do not occur in tuberculoid leprosy.
In all forms of leprosy, the pathological developments are continuous throughout life.
Death in leprosy does not occur as a result of Mycobacterium leprae per se, but may be due to the sepsis of other pathogenic bacteria, or to any of the causes of death that affect the general population. Tuberculosis was common in leprosy sufferers in leprosy hospitals, and was a common cause of death.
Keith Manchester MB., BS., BSc., DSc (Hon).