British Journal
of Oral Surgery (1976),
13, 271-277
REDDENING OF THE UPPER CENTRAL INCISORS ASSOCIATED WITH PERIAI’ICAL GRANULOMA IN LEPROMATOUS LEFROSY J. R. RENDALL, M.B.B.S., M.R.C.P. and A. C. MCDOUGALL, M.D., M.R.C.P. Cochrane Annexe, The Slade Hospital, Oxford
Summary. Four years after starting treatment for lepromatous leprosy in England a male Pakistani aged 26 was found to have red discoloration of the upper central incisor teeth. A radiograph suggested periapical abscess on the right with haziness in a corresponding area on the left. Right apicectomy was performed with removal of a solid mass attached to the apex, sections revealing a lepromatous infiltrate with acid-fast fragments of Mycobacterium Zeprae in the cytoplasm of foamy macrophages. Clinical and archaeological evidence for the frequent involvement of these teeth in lepromatous leprosy is reviewed. The upper incisor area is relatively cool, a factor which may be of critical importance for the lodgement and multiplication of this bacillus, as it is in other body sites in lepromatous leprosy.
INTRODUCTION THE widespread anergic form of leprosy termed lepromatous may involve almost any tissue of the body, though it shows a preference for skin, eyes, nose, upper respiratory tract, testicle and superficially placed nerves in the face, neck and limbs. The presence of considerable numbers of bacilli in the circulating blood of lepromatous patients has been known for many years; recently Drutz et al. (1972) and Shankara Manja et al. (1972) have studied their total numbers and viability, emphasising the heavy and persistent dissemination of Mycobacteriunz leprae into all parts of the body in this form of leprosy. Published work on transport of bacilli into dental pulp, coronal pulp, capillaries, odontoblasts and dental tubules, together with case reports of red discoloration of the incisors and the occurrence of periapical granulomas, has been reviewed in detail (Danielsen, 1970). In a large volume of material from Danish mediaeval burial grounds, virtually pathognomanic changes for lepromatous leprosy have been described (Moller-Christensen et al., 1952; Moller-Christensen, 1953, 1961, 1965) involving the nose, anterior nasal spine, maxillary alveolar process and hard palate. Following the observations of Binford (1956) Brand (1959) and Shepard (1965, 1967), there is now increasing evidence that the leprosy bacillus, in both man and the experimental animal, favours situations appreciably lower than 37°C. We here report a patient with lepromatous leprosy and red discoloration of the upper incisors in whom a periapical granuloma contained foamy Virchow cells and fragmented leprosy bacilli. The findings are discussed with particular reference to the factor of low temperature in the anatomical area concerned. Received 3.9.75.
Accepted 28.9.75 271
272
Radiograph appearances
BRITISH
JOURNAL
OF ORAL
SURGERY
FIG. I of the upper central incisors. Normal tooth structure in association suggesting periapical abscess or granuloma (arrowed) on the right, haziness of the periapical area on the left.
CASE
with with
REPORT
In 1967, the patient, a male Pakistani then aged Ig years, complained of redness and irritation in the right eye, which was diagnosed successively as trachoma and iridocyclitis, responding only partially to topical steroids and antibiotics. In rg6g he developed fever and malaise, accompanied by a butterfly rash on the face with swelling of the right nostril and a number of ulcerated, I cm lesions down the front of both legs. Examination at that time confirmed a nodule on the nostril together with thickening of the skin of the cheeks and ears, ulcerations on the lower legs ,and considerable loss of sensation around the lower legs, ankles and feet, and along the medial border of the left forearm Ophthalmological examination was negative for trachoma, but showed and hand. punctate opacities in the right cornea, with beaded and opaque corneal nerves. Routine The following investigations examination of other body systems was within normal. were normal: WR, VDRLT, blood biochemistry, Hb, total WBC and differential count, urine analysis, serum proteins, fluorescent Coombs test and anti-nuclear factor. Radiographs of chest and maxillary sinuses; normal. Slit-skin smears from both ears and the main skin lesions were highly positive for acid-fast bacilli, and biopsies of skin and left superficial peroneal nerve were typical for lepromatous leprosy, with large numbers of bacilli in macrophages, Schwarm and perineurial cells. Treatment was with Dapsone (DDS) in routine dosage, but changed to Rifampicin 600 mg daily in mid-1972; this was continued for a period of 20 months until he was reinstated’ on Dapsone. Reactional problems in the form of Erythema Nodosum Leprosum (ENL) on the skin, together with orchitis and neuritis, were controlled with
PERIAPICAL
GRANULOMA
IN LEPROMATOUS
LEPROSY
275
mediaeval times and subsequently confirmed by clinical observation and radiography (Lechat and Chardrome, 1955; Michman and Sagher, 1957; MarkChristensen, 1961). The cause of pink or red discoloration of the maxillary incisors in lepromatous leprosy is far from clear. In the most comprehensive study in the literature in which 400 teeth were examined, the pinkish appearance was (Itakura, qqo), attributed to ‘the escape of free haemoglobin into dental canals’, consequent upon leprous involvement of the pulp and rupture of numerous small blood vessels involved in the pathological process. Asano (1958) thought the red colour was due to a combination of lipoid material with lipofuchsin following hyaline and lipoid degeneration of the pulp, a condition ‘unique to leprosy’. Subsequent publications, including electron microscopy (Sakai & Matsumoto, 1968) have added little to the aetiology of this discoloration, but have supported the predilection for the upper central incisors. Recently, however, attention has been drawn to pathological changes in parts of the tooth which might more reasonably account for pink or red discoloration; thus Danielsen (1970) has fully summarised the literature on leprous involvement of pulp and its capillaries, odontoblasts, and dentinal tubules, and Miranda and Miranda (I 973) have described bacillary invasion and necrosis in small dentinal canals and lymphatic spaces in association with leprotic pulpitis. Whilst leprosy may spread from one area of the body to another either directly, or by lymphatic or neural pathways, there is now increasingly strong evidence for a continuous bacteraemia in the lepromatous form of this disease (Drutz et al., 1972; Shankara Manja et al., 1972). Previous studies (Itakura, 1940; Pellegrino, 1968) have indicated strongly that bacilli are carried to the pulps in the blood stream. Following the development of lepromatous granulation tissue at this level, the process proceeds in an apical direction (Danielsen, 1970), not infrequently resulting in the formation of a periapical granuloma as in the present case (Garrington & Grump, 1968; Pellegrino, 1968,197o). Although periapical granulomas have been reported also in canines and molars, the predilection in lepromatous leprosy is for the upper central incisor region. Danielsen (1970) has listed the evidence which could explain this in terms of (I) proximity to the heavily affected nasal cavity, or (2) repeated subclinical traumatic injuries, bearing in mind the propensity of this bacillus to cause nerve damage. Our patient had suffered from repeated manifestations of the immune-complex syndrome known to leprologists as Erythema Nodosum Leprosum during the 2 years preceding apicectomy, and this raises the possibility of repeated osteomyelitis as a local manifestation of reactional pathology. However, the cytology of the granuloma and the proportions of immunoglobulins in plasma cells, together with the absence of either necrotising vasculitis or fibrinoid degeneration of collagen, suggest a simple combination of lepromatous inflammation and secondary infection in this case. The influence of heavy nasal involvement histopathologically (Job et al., 1966; McDougall et al., 1975) on the palate and oral gingiva, and hence on teeth, is difficult to assess. Archaeological material shows lesions on both sides of the hard palate and furthermore, clinicians (Brand, 1962; Barton, 1974) have emphasised what may be an important point in the development of lesions in the mouth, namely that mouth-breathing consequent upon lepromatous infiltration of the nasal passages may expose the oral epithelium to the cooling influence of air, and thus to a factor which may encourage the growth of Mycobacteriwn leprae. Clearly this possibility complicates interpretation of blood or lymphatic spread
276
BRITISH
JOURNAL
OF ORAL
SURGERY
direct from nasal to oral cavities. In fact there is evidence (Tonzetich et al., 1964; Brown and Goldberg, 1966) that anterior teeth are relatively cool under a fairly wide range of conditions, and in a study of patients undergoing endodontic therapy, Selden (1966) inserted a 3o-gauge bead thermistor probe through the root canal into the periapical region and recorded periapical temperatures which were lower than those of mouth temperatures in every instance. These results have led us to re-investigate intra-oral temperatures under a wide range of conditions in normal subjects (Rendall & McDougall, Ig75), with particular regard to the upper incisors and their supporting tissues. While bearing in mind that factors such as oxygen and carbon dioxide tension, microvessel architecture (Kanan & Ryan, Ig75), trauma, reactional episodes and contiguous nasal pathology may all have a bearing on the remarkable predilection of this disease for the upper central incisor region, it would appear that low temperature (Binford, 1956; Brand, 1959; Shepard, 1965, 1967) is of considerable importance, as it is in other body areas typically affected in lepromatous leprosy. Current publications on leprosy in the nose (Shehata et al., Ig74), in the mouth, larynx and pharnyx (Barton, 1974) and in the soft palate (Reichert, 1974) strongly support the factor of low tissue temperature for the lesions observed. Further research on the dental manifestations of lepromatous leprosy may provide important information on the intracellular and metabolic needs of Mycobacterium Zeprae, which continues to evade all attempts at in vitro culture. ACKNOWLEDGEMENTS We are grateful to Dr K. D. Crow for permission to report the clinical findings and to Mr R. Thexton for performing the apicectomy (Princess Margaret Hospital, Swindon, England). A. C. McDougall is supported by grants from the Medical Research Council and the British Leprosy Relief Association (LEPRA, London, England). REFERENCES ASANO, M. (1958). La Lepro, 27, 398. BARTON, R. P. E. (1974). Leprosy in India, 46, 130. BINFORD, C. H. (1956). Public HeaZth Report, 71, 995. BRAND, l?. W. (1959). International Journal of Leprosy, 27, I. BRAND, I?. W. (1962). Personal communication to Mailer-Christensen (1965) in ‘New knowledge of leprosy through paleopathology’, International Journal of Leprosy, 33,,
603.
BROWN, A. C. & GOLDBERG,M. P. (1966). Archives of Oral Biology, II, 973. DANIELSEN, K. (1970). Tandlaegebladet, 74, 603. DRUTZ, D. J., CHEN, T. S. H. & WEN-HSIANG Lu (1972). New EnglandJournal of Medicine,
287, 1.59.
GARFZINGTON,G. E. & CRUMP, M. C. (1968). Oral Surgery, Oral Medicine and Oral Pathology, 25, 427. InternationaZJournaZof Leprosy,. HJBRTING-HANSEN, E., KLBFT, B. & SCHMIDT, H. (1965).
33983.
ITAKURA, T. (1940). Acta Japonica Medicinae Tropicalis, 2, 105. JOB, C. K., KARAT, A. B. A. & KARAT, S. (1966). Journal of Laryngology and Orology,. 80, 718. British Journal of Dermatology, 92, 475. KANAN, M. W. & RYAN, T. J. (1975). LECHAT, M. & CHARDROME,J. (1955). Annales de la Societk Beige de Medecine Tropicale,
McL?%%%, A. C., REES, R. J. W., WEDDELL, A. G. M. & KANAN, M. W. (1975). Journal of Pathology, IIS, 215.
PERIAPICAL
GRANULOMA
IN LEPROMATOUS
LEPROSY
273
FIG. 2
Apic:ectomy specimen
with attached granuloma. G, granuloma. inclination).
A,
tooth apex (oblique
steroids and thalidomide from mid-1973 onwards. Late in 1974, he was noted to have red discoloration of the upper central incisor teeth, most marked on the right. This was most intense at the gum margin, fading and disappearing at about the mid-crown. A radiograph (Fig. I) suggested periapical abscess on the right side and showed haziness in a corresponding area on the left. Sensation to electrical and thermal stimuli was absent on the right and impaired on the left. Apicectomy I/ was performed with removal of a solid mass attached to the apex (Fig. 2). Post-apicectomy radiograph showed normal filling-in of the bony cavity. /I is being kept under review. Histopathology (Fig. 3). The tissue was fixed in formol-zenker solution, embedded in wax, cut at 4 pm and stained with (I) haematoxylin and eosin, (2) modified Masson’s trichrome, (3) the Fite-Faraco modification of Ziehl-Neelsen for bacilli and (4) immunoperoxidase for immunoglobulins in plasma cells. The main mass or tissue consisted of foamy lepromatous (Virchow) cells, together with polymorphs, lymphocytes, plasma cells and occasional eosinophils. Nerve filaments were not found on a long search. Blood vessels did not show evidence of swelling or necrosis and collagen was normal in appearance. Immuno-peroxidase staining showed that plasma cells contained IgA and IgG in approximately equal proportions. Modified Ziehl-Neelsen staining revealed considerable numbers of granular (i.e. non-solid-staining) acid-fast bacilli in the cytoplasm of macrophages. Adjacent soft tissue at the periphery of the specimen showed areas of foamy lepromatous cells containing occasional acid-fast dots of bacillary material, with admixtures of lymphocytes and plasma cells, the latter often in dense collections.
274
BRITISH
JOURNAL
OF ORAL SURGERY
FIG. 3 Histopathology of periapical granuloma. The pleomorphic infiltrate included numerous partially degenerate macrophages, in the cytoplasm of which were acid-fast fragments of Mycobacterium Zeprae(arrowed). Fite-Faraco modification of Ziehl-Neelsen stain. Original magnification. x 1250.
DISCUSSION Ulceration of the gum in leprosy was described in the Middle Ages and loss of the upper central incisors in the early part of the sixteenth century. Central incisor ‘paradentitis’ was recorded in 1894 by de la Sota, and Pinkerton (1938) described in detail the frequent involvement of the lingual aspect of the upper alveolar process with consequent loosening of the upper central incisors. Although leprologists have long been accustomed to associate loosening or loss of teeth in this area with lepromatous leprosy, its significance in terms of anatomy, bacteriology and pathology was not appreciated until the discoveries of Moller-Christensen (1952, 1953, 1961, 1965) in his examination of Danish mediaeval skeletons from These included a number of changes which are now leprosy burial grounds. accepted as pathognomonic for leprosy, and of particular interest were those designated ‘facies leprosa’-(I) atrophy of th e anterior nasal spine, (2) atrophy and recession of the alveolar process in the premaxillary region, (3) inflammatory changes in the superior surface of the hard palate. From the archaeological evidence it was considered likely that changes in the maxillary alveolar process had accounted for loosening or complete loss of the upper central incisors. In reporting a leprotic granuloma of the maxilla (Hjsrting-Hansen et al., 1965) attention was drawn to this unusual sequence of events, whereby specific bone changes in this area were first found in the skeletons of victims of leprosy in
CERVICO-FACIAL INFECTION WITH MYCOBACTERIUM CHELONEI
A tuberculoid
279
FIG. I follicle composed of epithelioid cells and associated Langhans type giant cells without evidence of true caseation. H. & E. x 300.
Laboratory Investigations Haematology. At the time of the biopsy, the W.B.C. was 6300 per c.mm.,
the distribution of cells was normal, no abnormal cells were present. The haemoglobin was 13.9 g/IO0 InI. Histology. The soft tissue removed surgically consisted of fibrous and granulation tissue diffusely infiltrated with inflammatory cells, including scattered multi-nucleated Langhans type giant cells. Follicular aggregations of epithelioid cells with giant cells and no caseation gave a tuberculoid appearance (Fig. I). Necrotic foci of degenerating polymorphonuclear leucocytes with a surrounding zone of palisading histiocytes were present in other areas (Fig. 2). Special stains did not reveal the presence of acid-fast bacilli or fungi; and no birefringent material was seen. The appearances suggested atypical tuberculosis or cat scratch disease. Microbiology. A swab taken at the time of the biopsy showed only blood; no organisms were cultured aerobically or anaerobically on blood agar. However, the semi-solid material expressed from the external drainage wound 21 days later consisted of pus cells with sparse contaminating coagulase negative staphylococci and haemolytic streptococci. No acid or alcohol fast organisms were seen. Some of this material was sent to the T.B. Laboratory of the Royal Free Hospital for further examination, where a rapidly growing acid fast organism was isolated on Lowenstein Jensen medium. This organism was later identified at the Public Health Laboratory, Dulwich Hospital and at the T.B. Reference Laboratory, Cardiff as Mycobacterium chelonei subsp. abscessus. Further material expressed 17 days later consisted of exudate, sparsely infected with coagulase positive staphylococci. No acid fast bacilli were present in the direct film or subsequently. 13/3--E
of Oral Surgery (1976),
13, 271-277
REDDENING OF THE UPPER CENTRAL INCISORS ASSOCIATED WITH PERIAI’ICAL GRANULOMA IN LEPROMATOUS LEFROSY J. R. RENDALL, M.B.B.S., M.R.C.P. and A. C. MCDOUGALL, M.D., M.R.C.P. Cochrane Annexe, The Slade Hospital, Oxford
Summary. Four years after starting treatment for lepromatous leprosy in England a male Pakistani aged 26 was found to have red discoloration of the upper central incisor teeth. A radiograph suggested periapical abscess on the right with haziness in a corresponding area on the left. Right apicectomy was performed with removal of a solid mass attached to the apex, sections revealing a lepromatous infiltrate with acid-fast fragments of Mycobacterium Zeprae in the cytoplasm of foamy macrophages. Clinical and archaeological evidence for the frequent involvement of these teeth in lepromatous leprosy is reviewed. The upper incisor area is relatively cool, a factor which may be of critical importance for the lodgement and multiplication of this bacillus, as it is in other body sites in lepromatous leprosy.
INTRODUCTION THE widespread anergic form of leprosy termed lepromatous may involve almost any tissue of the body, though it shows a preference for skin, eyes, nose, upper respiratory tract, testicle and superficially placed nerves in the face, neck and limbs. The presence of considerable numbers of bacilli in the circulating blood of lepromatous patients has been known for many years; recently Drutz et al. (1972) and Shankara Manja et al. (1972) have studied their total numbers and viability, emphasising the heavy and persistent dissemination of Mycobacteriunz leprae into all parts of the body in this form of leprosy. Published work on transport of bacilli into dental pulp, coronal pulp, capillaries, odontoblasts and dental tubules, together with case reports of red discoloration of the incisors and the occurrence of periapical granulomas, has been reviewed in detail (Danielsen, 1970). In a large volume of material from Danish mediaeval burial grounds, virtually pathognomanic changes for lepromatous leprosy have been described (Moller-Christensen et al., 1952; Moller-Christensen, 1953, 1961, 1965) involving the nose, anterior nasal spine, maxillary alveolar process and hard palate. Following the observations of Binford (1956) Brand (1959) and Shepard (1965, 1967), there is now increasing evidence that the leprosy bacillus, in both man and the experimental animal, favours situations appreciably lower than 37°C. We here report a patient with lepromatous leprosy and red discoloration of the upper incisors in whom a periapical granuloma contained foamy Virchow cells and fragmented leprosy bacilli. The findings are discussed with particular reference to the factor of low temperature in the anatomical area concerned. Received 3.9.75.
Accepted 28.9.75 271
272
Radiograph appearances
BRITISH
JOURNAL
OF ORAL
SURGERY
FIG. I of the upper central incisors. Normal tooth structure in association suggesting periapical abscess or granuloma (arrowed) on the right, haziness of the periapical area on the left.
CASE
with with
REPORT
In 1967, the patient, a male Pakistani then aged Ig years, complained of redness and irritation in the right eye, which was diagnosed successively as trachoma and iridocyclitis, responding only partially to topical steroids and antibiotics. In rg6g he developed fever and malaise, accompanied by a butterfly rash on the face with swelling of the right nostril and a number of ulcerated, I cm lesions down the front of both legs. Examination at that time confirmed a nodule on the nostril together with thickening of the skin of the cheeks and ears, ulcerations on the lower legs ,and considerable loss of sensation around the lower legs, ankles and feet, and along the medial border of the left forearm Ophthalmological examination was negative for trachoma, but showed and hand. punctate opacities in the right cornea, with beaded and opaque corneal nerves. Routine The following investigations examination of other body systems was within normal. were normal: WR, VDRLT, blood biochemistry, Hb, total WBC and differential count, urine analysis, serum proteins, fluorescent Coombs test and anti-nuclear factor. Radiographs of chest and maxillary sinuses; normal. Slit-skin smears from both ears and the main skin lesions were highly positive for acid-fast bacilli, and biopsies of skin and left superficial peroneal nerve were typical for lepromatous leprosy, with large numbers of bacilli in macrophages, Schwarm and perineurial cells. Treatment was with Dapsone (DDS) in routine dosage, but changed to Rifampicin 600 mg daily in mid-1972; this was continued for a period of 20 months until he was reinstated’ on Dapsone. Reactional problems in the form of Erythema Nodosum Leprosum (ENL) on the skin, together with orchitis and neuritis, were controlled with
PERIAPICAL
GRANULOMA
IN LEPROMATOUS
LEPROSY
275
mediaeval times and subsequently confirmed by clinical observation and radiography (Lechat and Chardrome, 1955; Michman and Sagher, 1957; MarkChristensen, 1961). The cause of pink or red discoloration of the maxillary incisors in lepromatous leprosy is far from clear. In the most comprehensive study in the literature in which 400 teeth were examined, the pinkish appearance was (Itakura, qqo), attributed to ‘the escape of free haemoglobin into dental canals’, consequent upon leprous involvement of the pulp and rupture of numerous small blood vessels involved in the pathological process. Asano (1958) thought the red colour was due to a combination of lipoid material with lipofuchsin following hyaline and lipoid degeneration of the pulp, a condition ‘unique to leprosy’. Subsequent publications, including electron microscopy (Sakai & Matsumoto, 1968) have added little to the aetiology of this discoloration, but have supported the predilection for the upper central incisors. Recently, however, attention has been drawn to pathological changes in parts of the tooth which might more reasonably account for pink or red discoloration; thus Danielsen (1970) has fully summarised the literature on leprous involvement of pulp and its capillaries, odontoblasts, and dentinal tubules, and Miranda and Miranda (I 973) have described bacillary invasion and necrosis in small dentinal canals and lymphatic spaces in association with leprotic pulpitis. Whilst leprosy may spread from one area of the body to another either directly, or by lymphatic or neural pathways, there is now increasingly strong evidence for a continuous bacteraemia in the lepromatous form of this disease (Drutz et al., 1972; Shankara Manja et al., 1972). Previous studies (Itakura, 1940; Pellegrino, 1968) have indicated strongly that bacilli are carried to the pulps in the blood stream. Following the development of lepromatous granulation tissue at this level, the process proceeds in an apical direction (Danielsen, 1970), not infrequently resulting in the formation of a periapical granuloma as in the present case (Garrington & Grump, 1968; Pellegrino, 1968,197o). Although periapical granulomas have been reported also in canines and molars, the predilection in lepromatous leprosy is for the upper central incisor region. Danielsen (1970) has listed the evidence which could explain this in terms of (I) proximity to the heavily affected nasal cavity, or (2) repeated subclinical traumatic injuries, bearing in mind the propensity of this bacillus to cause nerve damage. Our patient had suffered from repeated manifestations of the immune-complex syndrome known to leprologists as Erythema Nodosum Leprosum during the 2 years preceding apicectomy, and this raises the possibility of repeated osteomyelitis as a local manifestation of reactional pathology. However, the cytology of the granuloma and the proportions of immunoglobulins in plasma cells, together with the absence of either necrotising vasculitis or fibrinoid degeneration of collagen, suggest a simple combination of lepromatous inflammation and secondary infection in this case. The influence of heavy nasal involvement histopathologically (Job et al., 1966; McDougall et al., 1975) on the palate and oral gingiva, and hence on teeth, is difficult to assess. Archaeological material shows lesions on both sides of the hard palate and furthermore, clinicians (Brand, 1962; Barton, 1974) have emphasised what may be an important point in the development of lesions in the mouth, namely that mouth-breathing consequent upon lepromatous infiltration of the nasal passages may expose the oral epithelium to the cooling influence of air, and thus to a factor which may encourage the growth of Mycobacteriwn leprae. Clearly this possibility complicates interpretation of blood or lymphatic spread
276
BRITISH
JOURNAL
OF ORAL
SURGERY
direct from nasal to oral cavities. In fact there is evidence (Tonzetich et al., 1964; Brown and Goldberg, 1966) that anterior teeth are relatively cool under a fairly wide range of conditions, and in a study of patients undergoing endodontic therapy, Selden (1966) inserted a 3o-gauge bead thermistor probe through the root canal into the periapical region and recorded periapical temperatures which were lower than those of mouth temperatures in every instance. These results have led us to re-investigate intra-oral temperatures under a wide range of conditions in normal subjects (Rendall & McDougall, Ig75), with particular regard to the upper incisors and their supporting tissues. While bearing in mind that factors such as oxygen and carbon dioxide tension, microvessel architecture (Kanan & Ryan, Ig75), trauma, reactional episodes and contiguous nasal pathology may all have a bearing on the remarkable predilection of this disease for the upper central incisor region, it would appear that low temperature (Binford, 1956; Brand, 1959; Shepard, 1965, 1967) is of considerable importance, as it is in other body areas typically affected in lepromatous leprosy. Current publications on leprosy in the nose (Shehata et al., Ig74), in the mouth, larynx and pharnyx (Barton, 1974) and in the soft palate (Reichert, 1974) strongly support the factor of low tissue temperature for the lesions observed. Further research on the dental manifestations of lepromatous leprosy may provide important information on the intracellular and metabolic needs of Mycobacterium Zeprae, which continues to evade all attempts at in vitro culture. ACKNOWLEDGEMENTS We are grateful to Dr K. D. Crow for permission to report the clinical findings and to Mr R. Thexton for performing the apicectomy (Princess Margaret Hospital, Swindon, England). A. C. McDougall is supported by grants from the Medical Research Council and the British Leprosy Relief Association (LEPRA, London, England). REFERENCES ASANO, M. (1958). La Lepro, 27, 398. BARTON, R. P. E. (1974). Leprosy in India, 46, 130. BINFORD, C. H. (1956). Public HeaZth Report, 71, 995. BRAND, l?. W. (1959). International Journal of Leprosy, 27, I. BRAND, I?. W. (1962). Personal communication to Mailer-Christensen (1965) in ‘New knowledge of leprosy through paleopathology’, International Journal of Leprosy, 33,,
603.
BROWN, A. C. & GOLDBERG,M. P. (1966). Archives of Oral Biology, II, 973. DANIELSEN, K. (1970). Tandlaegebladet, 74, 603. DRUTZ, D. J., CHEN, T. S. H. & WEN-HSIANG Lu (1972). New EnglandJournal of Medicine,
287, 1.59.
GARFZINGTON,G. E. & CRUMP, M. C. (1968). Oral Surgery, Oral Medicine and Oral Pathology, 25, 427. InternationaZJournaZof Leprosy,. HJBRTING-HANSEN, E., KLBFT, B. & SCHMIDT, H. (1965).
33983.
ITAKURA, T. (1940). Acta Japonica Medicinae Tropicalis, 2, 105. JOB, C. K., KARAT, A. B. A. & KARAT, S. (1966). Journal of Laryngology and Orology,. 80, 718. British Journal of Dermatology, 92, 475. KANAN, M. W. & RYAN, T. J. (1975). LECHAT, M. & CHARDROME,J. (1955). Annales de la Societk Beige de Medecine Tropicale,
McL?%%%, A. C., REES, R. J. W., WEDDELL, A. G. M. & KANAN, M. W. (1975). Journal of Pathology, IIS, 215.
PERIAPICAL
GRANULOMA
IN LEPROMATOUS
LEPROSY
273
FIG. 2
Apic:ectomy specimen
with attached granuloma. G, granuloma. inclination).
A,
tooth apex (oblique
steroids and thalidomide from mid-1973 onwards. Late in 1974, he was noted to have red discoloration of the upper central incisor teeth, most marked on the right. This was most intense at the gum margin, fading and disappearing at about the mid-crown. A radiograph (Fig. I) suggested periapical abscess on the right side and showed haziness in a corresponding area on the left. Sensation to electrical and thermal stimuli was absent on the right and impaired on the left. Apicectomy I/ was performed with removal of a solid mass attached to the apex (Fig. 2). Post-apicectomy radiograph showed normal filling-in of the bony cavity. /I is being kept under review. Histopathology (Fig. 3). The tissue was fixed in formol-zenker solution, embedded in wax, cut at 4 pm and stained with (I) haematoxylin and eosin, (2) modified Masson’s trichrome, (3) the Fite-Faraco modification of Ziehl-Neelsen for bacilli and (4) immunoperoxidase for immunoglobulins in plasma cells. The main mass or tissue consisted of foamy lepromatous (Virchow) cells, together with polymorphs, lymphocytes, plasma cells and occasional eosinophils. Nerve filaments were not found on a long search. Blood vessels did not show evidence of swelling or necrosis and collagen was normal in appearance. Immuno-peroxidase staining showed that plasma cells contained IgA and IgG in approximately equal proportions. Modified Ziehl-Neelsen staining revealed considerable numbers of granular (i.e. non-solid-staining) acid-fast bacilli in the cytoplasm of macrophages. Adjacent soft tissue at the periphery of the specimen showed areas of foamy lepromatous cells containing occasional acid-fast dots of bacillary material, with admixtures of lymphocytes and plasma cells, the latter often in dense collections.
274
BRITISH
JOURNAL
OF ORAL SURGERY
FIG. 3 Histopathology of periapical granuloma. The pleomorphic infiltrate included numerous partially degenerate macrophages, in the cytoplasm of which were acid-fast fragments of Mycobacterium Zeprae(arrowed). Fite-Faraco modification of Ziehl-Neelsen stain. Original magnification. x 1250.
DISCUSSION Ulceration of the gum in leprosy was described in the Middle Ages and loss of the upper central incisors in the early part of the sixteenth century. Central incisor ‘paradentitis’ was recorded in 1894 by de la Sota, and Pinkerton (1938) described in detail the frequent involvement of the lingual aspect of the upper alveolar process with consequent loosening of the upper central incisors. Although leprologists have long been accustomed to associate loosening or loss of teeth in this area with lepromatous leprosy, its significance in terms of anatomy, bacteriology and pathology was not appreciated until the discoveries of Moller-Christensen (1952, 1953, 1961, 1965) in his examination of Danish mediaeval skeletons from These included a number of changes which are now leprosy burial grounds. accepted as pathognomonic for leprosy, and of particular interest were those designated ‘facies leprosa’-(I) atrophy of th e anterior nasal spine, (2) atrophy and recession of the alveolar process in the premaxillary region, (3) inflammatory changes in the superior surface of the hard palate. From the archaeological evidence it was considered likely that changes in the maxillary alveolar process had accounted for loosening or complete loss of the upper central incisors. In reporting a leprotic granuloma of the maxilla (Hjsrting-Hansen et al., 1965) attention was drawn to this unusual sequence of events, whereby specific bone changes in this area were first found in the skeletons of victims of leprosy in
CERVICO-FACIAL INFECTION WITH MYCOBACTERIUM CHELONEI
A tuberculoid
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FIG. I follicle composed of epithelioid cells and associated Langhans type giant cells without evidence of true caseation. H. & E. x 300.
Laboratory Investigations Haematology. At the time of the biopsy, the W.B.C. was 6300 per c.mm.,
the distribution of cells was normal, no abnormal cells were present. The haemoglobin was 13.9 g/IO0 InI. Histology. The soft tissue removed surgically consisted of fibrous and granulation tissue diffusely infiltrated with inflammatory cells, including scattered multi-nucleated Langhans type giant cells. Follicular aggregations of epithelioid cells with giant cells and no caseation gave a tuberculoid appearance (Fig. I). Necrotic foci of degenerating polymorphonuclear leucocytes with a surrounding zone of palisading histiocytes were present in other areas (Fig. 2). Special stains did not reveal the presence of acid-fast bacilli or fungi; and no birefringent material was seen. The appearances suggested atypical tuberculosis or cat scratch disease. Microbiology. A swab taken at the time of the biopsy showed only blood; no organisms were cultured aerobically or anaerobically on blood agar. However, the semi-solid material expressed from the external drainage wound 21 days later consisted of pus cells with sparse contaminating coagulase negative staphylococci and haemolytic streptococci. No acid or alcohol fast organisms were seen. Some of this material was sent to the T.B. Laboratory of the Royal Free Hospital for further examination, where a rapidly growing acid fast organism was isolated on Lowenstein Jensen medium. This organism was later identified at the Public Health Laboratory, Dulwich Hospital and at the T.B. Reference Laboratory, Cardiff as Mycobacterium chelonei subsp. abscessus. Further material expressed 17 days later consisted of exudate, sparsely infected with coagulase positive staphylococci. No acid fast bacilli were present in the direct film or subsequently. 13/3--E
