Leprosy as a clinical correlation of anatomy

Clinical Anatomy 7:131-138 (1994)

Leprosy as a Clinical Correlation of Anatomy KRISHNAN SUBRAMANHM AND SANDY C. MARKS, JR.

Department of Anatomy, Faculty of Medicine, Universio of Malaya, Kuala Lumpur, Malaysia ( K S ) , and Department of Cell Biology, University of Massachusetts Medical School, Worcester (S. C.M.)

Leprosy is a chronic mycobacterial infection of superficial tissues which occurs in part because of a select immune incompetence in certain individuals. The major debilitating effects of the disease are the result of neurological deficits secondary to infiltration of Schwann cells by M. leprae and resorption of phalanges and bone near the palate. An understanding of the manifestations of the disease is based upon anatomical principles. We illustrate some of these in several clinical correlations. o 1994 Wiley-Liss, Inc.

Key words: leprosy, Schwann cells, phalanges, palate, anatomy

INTRODUCTION Leprosy (Hansen's disease) is a chronic infectious

disease caused by Mycobacterum leprae which presents a wide spectrum of clinical signs and symptoms. About 60% of the estimated 5.5 million patients with leprosy worldwide are afflicted with disabilities and deformities (Noordeen et al., 1992) and it is these crippling physical effects which set the disease apart from many other diseases (Smith et al., 1980). T h e debilitating manifestations, primarily seen in untreated or relapsed patients, are due to destruction of peripheral nerves and result from loss of motor and sensory function. Furthermore, in advanced untreated disease there is damage to other tissues including bone.

Since 1977, we have been studying several clinical aspects of leprosy in relation to bone and soft tissue involvement in the oro-facial region (Subramaniam and Marks, 1978; Marks and Subramaniam, 1978; Sub- ramaniam et al., 1983b; Nah et al., 1985; Marks and Grossetete, 1988; Marks et al., 1991), the progression of bone destruction (Subramaniam et al., 1983a, 1993), and extremity bone loss (Marks, 1979). In order to understand the abnormal structure and function observed in our patients, we relied on an appreciation of normal anatomy. We have found the clinical manifestations of leprosy to be an excellent example of anatomical correlations in clinical practice, and will illustrate some of these perspectives in this paper. We begin with

a brief background on the classification, immunology, and principal clinical features of leprosy (Ridley and Jopling, 1966; Sansonetti and Lagrange, 1981; Jopling, 1984).

THE DISEASE Leprosy is probably the oldest disease on record,

first described in India around 600 B.C. Children and young adults have a greater susceptibility and develop the disease after an average incubation period of between 2 and 7 years; the route of transmission is still not fully understood. Only a small portion of infected individuals develop signs of the disease while the majority develop a sub-clinical infection. In the case of the susceptible host, the type of leprosy will be deter- mined by the way in which the immune cells respond to the challenge. All patients show evidence of depressed cell-mediated immunity (CMI), the degree of depression varying between the two polar groups, lepromatous and tuberculoid, with maximal depression being manifested in the untreated lepromatous patient. T h e borderline forms are intermediate types within a

Received for publication September 11, 1993; revised November 3, 1993. Address reprint requests to Dr. Sandy C. Marks, Jr., Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655.

0 1994 Wiley-Liss, Inc.

132 Subramaniam and Marks

broad spectrum. There is a wide variation in the way the disease affects different persons, sometimes involving only a single nerve or blemish and in other cases involving multiple tissues and sites. Host response (immune competence) is responsible for the extremes in variation and not the degree of virulence of the my- cobacterium as originally thought. Lepromatous leprosy, the most immunologically incompetent form, is also the most destructive and associated with immune- complex related reactional states (Scheepers and Lem- mer, 1992; d e Messias et al., 1993).

Leprosy bacilli (M. leprae) have a predilection to enter cutaneous nerves or nerve trunks in the cooler body sites and their target is the Schwann cell. Subse- quent destruction of these nerves results in anaesthesia around affected skin and/or muscle weakness (the ulnar and common peroneal nerves are most often affected). Skin lesions are either hypopigmented or granuloma- tous because of bacillary infiltration. M . leprae has a temperature optimum of 33°C (Rendall et al., 1976) and cannot grow at 37°C. Thus, it is the cooler, superficial parts of the body which are affected, not those at core temperatures. In lepromatous leprosy, tissues that bear the brunt of the disease are superficial nerves, skin, eyes, the reticulo-endothelial system including superficial bone-marrow spaces, mucosa of nose, mouth, larynx and pharynx, smooth and skeletal muscle in these regions, and the testes. Skin lesions may present as macules, papules, or nodules. Bone damage is confined to the hands, feet, and skull and is often accelerated by persistent infections of which patients are unaware because of regional sensory deficits. In the hands and feet, the phalanges undergo slow resorption, gradually shortening the digits. In the skull, atrophy of the anterior nasal spine, loss of maxillary alveolar bone, and perforations of the palate known as facies leprosa are well established (Moller-Christensen, 1961). T h e cur- rent treatment protocol includes multi-drug therapy because of the recent emergence of drug-resistant strains (Jopling, 1984) (WHO Study Group, 1982).

IMPORTANCE OF CLINICAL ANATOMY Even with this brief description of the disease its

complexities with respect to differential diagnosis, treatment, and rehabilitation of deformities are obvious and underscore the breadth of anatomical data needed. T h e clinical management of leprosy involves a large number of medical specialties. Pathologists, radiolo- gists, neurologists, immunologists, and dermatologists often participate in the initial diagnosis using a variety of techniques that draw upon surface and radiographic anatomy, neuroanatomy, cellular immunology, and histology. Treatment of the initial disease and its

unpredictable exacerbations and correction of deformities require internists, neurologists, ophthalmolo- gists, otorhinolaryngologists, dental surgeons, ortho- pedic surgeons, and maxillofacial-plastic surgeons, who rely on basic and specialized anatomy of the head and neck, limbs, trunk, and central and peripheral nervous systems. T h e treatment of individual patients is coordinated by the leprologist, who also man- ages the systemic chemotherapy and dermatological manifestations.

I t has been said that to know leprosy is to know medicine (Joshua-Raghavar, 1983). Our experience suggests that leprosy also demonstrates a wide spectrum of clinical anatomy which we shall illustrate below.

THE CLINICAL ANATOMY OF LEPROSY Nerve Involvement

Infection of peripheral nerves is an integral part of leprosy although permanent nerve damage is not an inevitable sequel of infection (Bryceson and Pfaltzgraff, 1979). T h e pattern of nerve involvement is consistent and predictable. Nerves are most severely affected where they lie superficially just under the skin. Nerves that are commonly involved are the ulnar, radial, and median (upper limb), common peroneal and posterior tibia1 (lower limb), and the facial and great auricular (head and neck). Bacillary infiltration in the ulnar and common peroneal nerve commonly occurs at their most superficial sites, posterior to the medial epicondyle of the humerus and the lateral surface of the neck of the fibula, respectively. Ulnar nerve involvement usually presents with the following classical motor and sensory nerve deficits. T h e little and ring fingers are flexed at the proximal interphalangeal joints and hyperextended at the metacarpophalangeal joints (right hand in Figure 1); there is impaired power of adduction and abduction of fingers and adduction of the thumb. Together, these deformities are referred to as claw-hand. Another feature of ulnar nerve involvement is flattening of the hypothenar eminence due to atrophy of the hypothenar muscles (seen on the left palm in Figure 1). T h e patient will be unable to make a fist. Sensory loss is confined to the ulnar side of the hand.

Damage to the common peroneal nerve causes anaesthesia on the lateral side of the calf and the dorsum of the foot. T h e motor deficit produces difficulty in dorsiflexion and eversion against pressure during the initial stages. In advanced stages, there is footdrop with a high stepping gait. T h e dropped foot can be reposi- tioned (by dorsiflexing) using a simple practical device called a toe spring support (Fig. 2); this is also the most common deformity of the foot, requiring reconstructive

Fig. 1. Hands of a 62-year-old Chinese male with advanced tuberculoid leprosy. The distal phalanges of all digits have been resorbed and the typical claw deformity of ulnar nerve paralysis is illustrated. Atrophy of the ulnar-innervated intrinsic muscles of the hand has produced flattening of the hypothenar eminence and prominent metacarpals due to atrophy of the dorsal interossei (large arrows). The presence of a nodule of the radial side of the left hand (small arrow) suggests that the superficial branch of the radial nerve is also involved in this patient, this nodule being a leprous granuloma due to bacillary infiltration. This patient also had foot drop on the left side but no resorption of the anterior nasal spine.

Fig. 2. A young adult Chinese male with early borderline leprosy whose main functional deficit is foot drop due to the infiltration by M. leprae of the common peroneal nerve at its most superficial site. Functional rehabilitation has been accomplished by an elasticized sling which hooks into a strap which maintains the foot in dorsiflexion.

Progressive phalangeal resorption in the left hand of an elderly Chinese male with lepromatous leprosy.

Advanced resorption of phalanges, porotic changes (arrowheads) in the metatarsal heads, and resorption of the first metatarsal head (arrow) of a 63-year-old Chinese male with lepromatous leprosy.

Fig. 3.

Fig. 4.


surgery. T h e foot must be protected with shoes and socks (Fig. 2) because of the possibility of ulcers arising from the anaesthetic dorsum.

Skeletal Changes: Limbs Bone changes, mainly confined to the hands, feet,

and skull, have been attributed to the neurovascular disturbances causing vasodilatation (Sehgal, 1979). However, other studies have shown that osteoclasts at the sites of resorption could account for the bone loss (Job et al., 1966; Marks, 1979). Other local exacerbat- ing factors include inflammation, secondary infection, trophic ulcers, and repeated trauma. Bone changes are usually seen after long-standing untreated lepromatous disease.

In the hands, distal phalanges undergo slow resorption, causing shortening of the fingers (Fig. 3). T h e nails gradually shrink away as the terminal phalanges disappear. T h e middle and proximal phalanges may also undergo atrophy but the metacarpal and carpal bones are usually spared (Jopling, 1984). Neurotrophic manifestations lead to severe loss of hand function.

Atrophic changes also occur in the phalanges of the foot, leading to thinning and ultimate loss of toes (Fig. 4). However, unlike the hand, the metatarsal and tarsal bones can be involved as well, often the result of persistent osteomyelitis. Osteoporosis of the metatarsal heads leads to their resorption (Fig. 4) and their shafts

becoming thin and tapered. Tarsal bone disintegration is a neglected but important aspect of foot deformity (Jopling, 1984; Warren, 1972).

Skeletal Changes: Maxillofacial Destruction of facial cartilages and bones is the

direct result of their infiltration by lepromatous granu- lomatous tissue and secondary infection (Reichart, 1976). T h e main area of destruction is the naso-maxillary complex (Moller-Christensen, 1961) involving the anterior nasal spine (ANS) and the septa1 cartilage sup- ported by it, the maxillary anterior alveolar bone supporting the incisors, and the palatine process of the maxilla.

The ANS is the anterior spinous extension of the maxilla in the midline and is consistently palpable irrespective of ethnicity or age (Subramaniam et al., 1985). In lateral radiographs it appears as a distinct radiodense projection (Fig. 5A). T h e fully palpable ANS with the supporting nasal framework is a characteristic topographical feature seen in a side profile of the face (Fig. 6).

If the ANS is barely palpable (the radiographic image as seen in Figure 5B) or not palpable at all (radiographic image depicted in Figure 5C), this indicates pathological atrophy, which in leprosy is often associated with bony lesions of the nasal septum, nasal frame, and turbinates (Moller-Christensen, 1961). In the most

Fig. 5. Lateral radiographs of the base of the nose illustrating the normal, prominent nasal spine (arrow in A) and its progressive resorption in patients with leprosy (arrows in Band C). N = nasal cartilages; F = finger of patient holding film.

Leprosy as a Clinical Correlation of Anatomy 135

Fig. 6.

Fig. 7.

Facial profile of a 72-year-old Indian male with lepromatous disease. There has been little resorption of the anterior nasal spine and no nasal collapse.

Facial profile (A) and front view (B) of a 36-year-old Chinese male with advanced lepromatous disease which has destroyed the anterior nasal spine and the nasal septum. This patient also has paralysis of the right facial nerve, producing drooping of the right side of the mouth and blindness in the right eye secondary to corneal dehydration and scarring.

advanced cases, resorption of the nasal cartilages and bones leads to total collapse of the external nose (Fig. 7A), and septum (Fig. 7B) as well as perforations of the palatine shelves. Severe naso-maxillary changes are seen in lepromatous leprosy and are characteristic of advanced cases of untreated disease. In these patients, the facial nerve is usually involved, resulting in paralysis of facial muscles (Fig. 7B). Blindness due to lagophthalmos is a disastrous complication.

T h e loss of alveolar bone in the anterior maxilla has been extensively studied both clinically and radio- graphically. It is again a manifestation of advanced lepromatous leprosy and is quantified using established radiological landmarks for accurate determina- tion of alveolar bone loss (Subramaniam and Marks, 1978). In healthy adults without periodontal disease, the interproximal alveolar bone at the central incisors should extend close to the cemento-enamel junction (CEJ). In such cases, the distance between the apical foramen of an incisor and the alveolar bone crest would be the same as the distance between the apical foramen and CEJ. T h e former value over the latter expressed as a percentage gives alveolar bone support, in this case

100%. In Figure 8A the alveolar bone support is 90%. Taking into account factors of dental attrition and minimal periodontal pathology, this would be considered within the normal range by most clinicians. In advanced untreated leprosy, alveolar bone resorption leads to tooth mobility and the ultimate loss of the incisors. Figure 8B shows one such case which has only 64% bone support (or 36% loss). I t is interesting to note that following initiation and continuity of treatment the rate of alveolar bone resorption is arrested despite the presence of local factors like plaque and gingival inflammation, which in normal adults would accelerate alveolar bone loss, a paradox (Subramaniam et al., 1994).

Periodontal Manifestations It is well known that the periodontal diseases are the

most common diseases in man and leprosy is no excep- tion (Subramaniam et al., 1983b). T h e periodontal diseases, unless controlled, gradually lead to loss of attachment between the tooth and its supporting structures (the periodontal ligament and alveolar bone), tooth mobility, and alveolar bone resorption. When the peri-

Fig. 8. Dental radiographs of the maxillary incisors in two patients with lepromatous leprosy. In one (A) there is minimal resorption. In the other (B), a 58-year-old Malay male, more than a third of the alveolar bone around the central incisors has been resorbed. Arrows in A from top to bottom mark the apical foramen, the alveolar crest, and the cemento-enamel junction.

Fig. 9. A, B, C, D Clinical photographs of the dentition of four patients with lepromatous disease illustrating variations in dental plaque that surprisingly do not directly correlate with alveolar bone resorption.

Leprosy as a Clinical Correlation of Anatomy 137

odontal diseases are uncontrolled, the rate of alveolar bone loss is directly proportional to the severity of the disease as measured by several clinical indices which record the level of plaque accumulations, degree of gingival inflammation, extent of tooth mobility, and pocketing of the gingival sulcus (Rateitschak et al., 1989). This spectrum of severity of the periodontal diseases has been observed by us in patients with leprosy and irrespective of the initial accelerated level of bone loss, the progression of bone loss was virtually arrested following treatment of leprosy (Subramaniam et al., 1983a, 1994). T h e healthy periodontium, with minimal plaque and pink, stippled gingiva (Fig. 9A), is likely to have full bone support. Overall plaque levels of around 30% with mild to moderate periodontitis (Fig. 9B) can still preserve much of the periodontium and provide moderate alveolar bone support in which case the teeth will not be mobile. Further progression of the disease compounded by lack of oral hygiene will lead to severe periodontitis with purulent discharge, loss of attachment, alveolar bone support, and mobile teeth (Fig. 9C). Figure 9D is a combination of excessive plaque accumulation due to absence of oral hygiene maintenance (in advanced leprosy this is usually due to hand deformities, which severely limit oral hygiene), advanced periodontitis, recession of the gingiva, and excessive mobility. Gross neglect will also result in destruction of the tooth crown due to untreated caries.

Microscopy of Leprosy T h e characteristic histological feature of leprosy is

the presence of acid-fast mycobacteria in macrophages and Schwann cells of superficial tissues. T h e local concentration of bacteria varies indirectly with the degree of immune competence, being greatest in the lepromatous form of the disease. In these patients suc- cessful treatment leads to fragmentation of the acid-fast bacteria but not necessarily to their disappearance (Jop- ling, 1984; Bryceson and Pfaltzgraff, 1979).

T h e cellular basis for bone loss in leprosy has been studied in bone biopsies taken from maxillary alveolar bone (Marks and Subramaniam, 1978) and extremities of patients undergoing surgical procedures for management of documented bone loss (Marks, 1979). In both situations, accelerated osteoclastic activity was demon- strated by the histochemical reaction for acid phosphatase (Fig. 10). Except for elevated number and enzyme activity in sites of active bone loss, osteoclasts in these patients were not morphologically abnormal, sug- gesting that bone loss in leprosy results from accelera- tion of a normal physiological event and not aseptic bone necrosis.

Fig. 10. Bone biopsies from a metatarsal head (A) and alveolar margin of the anterior maxilla (B) from patients with lepromatous leprosy and radiographic evidence of bone resorption in these areas. These sections were stained histochemically for acid phosphatase, an enzyme found in its highest skeletal concentration in osteoclasts an their mononuclear precursors. Osteoclasts (arrows) are con- spicious on bone (b) surfaces and adjacent mononuclear cells also exhibit a strong reaction for this enzyme. Osteoclasts in sites of bone loss are more numerous than in areas without resorption and stain heavily for this enzyme. Lightly counterstained with toluidine blue. v = blood vessel. A = X 240; B = X 425.

CONCLUSIONS These case studies illustrate the wide variety of

applied anatomy seen in leprosy and can be used by those teaching anatomy as clinical correlations. It is our hope that this presentation of the anatomical bases for understanding a disease will encourage others to de- scribe similar examples with didactic value.

ACKNOWLEDGMENTS T h e authors thank the Director and Staff of the

National Leprosy Control Centre, Sungei Buloh, Ma-


laysia, for their cooperation, Mr. Chiew Hock Koon for

ticipated in these studies. Part of this work was sup- ported by the University of Malaya (grant 135/77, the

Program for Research in Leprosy, and '''gate- Palmolive (Malaysia) Sdn Bhd.

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Leprosy as a clinical correlation of anatomy