Scleroma (rhinoscleroma) in a Nigerian maxillo-facial practice

Int. I. Oral Surg. 1977: 6:270-279 (Key words: rhinoscleroma; scleroma)

Scleroma (rhinoscleroma) in a Nigerian maxillo-facial practice Review and case reports M. B. EDWARDS, G. D. D. ROBERTS AND T. J. STORRS

Dephrtment o[ Dental Science, Royal College o/ Surgeons o] England, London, England and Maxillo-lacial Unit, ABU Hospital, Kaduna, Nigeria

~13STaaCT-- Scleroma (rhinoscleroma), a chronic granulomatous disease of tho upper respiratory tract, is endemic within a confined distribution of geographic loci. Sporadic cases and those arising in poorly defined loci may be unexpected and difficult to diagnose. Three cases from a maxillo-facial unit in northern Nigeria are described, of which two simulated intranasal neoplasms and the third had atypical clinical features. These cases form the first substantial description of scleroma in Nigeria, a country that is part of an irtdefinite focus of the disease. The epidemiology, clinical features, pathology and diagnosis of scleroma are reviewed.

(Received ]or publication I0 July, accepted i i August 1976)

Scleroma is a destructive granulomatous disease that may affect any part of the upper respiratory tract including the main bronchi, and spread to the contiguous structures of the oral cavity, lachrymal apparatus and middle ear. Because the major site of origin is the nasal submucosa the condition is synonymously known as rhinoscleroma. However, the generic term scleroma is now widely preferred in order to avoid the false impression that the disease is confined to the nose. Sderomatous granulomas contain a non-motile, Gram-negative bacillus from the Klebsiella group of enterobacteria, first associated with the lesion by YON

FmSCH 14 in 1882. Most investigators have favoured the Frisch bacillus, now characterized K. rhinoscleromatis, as the sole causal agent but it has proved difficult to reproduce the typical lesion experimentally. A maerophage-rich pneumonia can be produced by intranasal inoculation of the bacillus in mice4e, but only recently have progressive granulomas been demonstrated ~1 in an experimental animal model. The sclerosis implicit in the name of the condition occurs in the final phase of the disease. The range of early clinical features is such that unexpected cases, outside or at the fringe of endemic regions, may pose

SCLEROMA IN NIGERIA diagnostic problems. The three cases described here were found in northern Nigeria where scleroma has not been described in detail, and they prompted a review of the major features of the disease.

Epidemiology The numerical incidence of scleroma is not documented but it may be regarded as a rare disease. The condition most frequently arises in the age range 15-40 years, and despite early reports to the contrary, there appears to be no sex predilectionU. Its global distribution is remarkable in being confined to foci without common climatic or geographic features, which range in size from a few hundred square kilometres to upward of 200,000 km 2 3s. Both endemic foci and sporadic eases are largely restricted to a zone between latitude 56~ and 30~ Within endemic areas there is often a microfocal or familial distribution in closed triballY, communal and rural communitiesZ4 where there m a y be genetic predisposition. Prolonged contact with infected subjects in overcrowded conditions disseminates the disease, which is of low infectivity. The geographic distribution of scleroma has been comprehensively reviewed by Muz'zKA & GtmrNA33 and only salient features are referred to here. The first formal record of the disease 20 was from eastern Europe, where it has been referred to as "Slavic leprosy ''eS, mad the Ukraine, Byelorussia, Poland, Rumania, Hungary and Czechoslovakia still form a giant focus, separate from pockets of endemic disease in northern Italy and Yugoslavia. A single and atypical case has been described in Finland~o. Sporadic cases in western Europe have usually been amongst immigrants from endemic areas, such as one of the few cases found in Sweden,s. Increasing mobil-

271

ity of populations across Europe could influence the future pattern of sporadic infection. In the near and Middle East scleroma has been found in Turkey and Iraq, and the disease is newly reported in Iranl. In the adjacent Soviet republics of Kazakh, Uzbek and Turkmen there is a large focus and the further Asian distribution includes a large area of central and northern India 43. In the F a r East there is a prominent focus in Indonesia (chiefly Sumatra) and in the highlands of New Guinea 32. A n isolated Australian case has been observed~ in a Sicilian immigrant. Scleroma m a y have been present in central and South America for several centuries and now a m a j o r focus is described there that includes southern Mexico, E1 Salvador and part of Guatemala 3., a large focus in Colombia and a smaller zone in Chile. A possible focus is predicted~a in southern California but cases in North America are otherwise sporadic 88~ 45.

The largest African focus includes most of the United A r a b Republic and there are loci in Morocco and Algeria. Occasional cases are seen in the Sudantz. In central Africa there is a poorly defined endemic area involving part of Uganda, where there may be a specific tribal incidence in Bantu of the former Western provinceZg, s7, and the adjoining highland areas in Rwanda, Burundi and Tanzania 4t. A single case, an immigrant from India, has been reported r from South Africa. F r o m Nigeria reports of the disease are largely anecdotal~7, widely distributed, and poorly documented. It has been observed le both at Ibadan in the south-west and at Zaria in the north central region close t o Kaduna, the source of the cases described here. These observations lend some weight to the prediction 8~ of a separate African focus about the Gulf of Guinea, involving Nigeria, Togo and Ghana.

272

EDWARDS, ROBERTS AND STORRS

Clinical teatures Scleromatous infection is characterized by extreme chronicity. Major reviewsS, 36,3s,42, ~ of the clinical course of scleroma suggest that there is much overlap between the three classic stages of the disease, the atrophic exudative phase, the granulomatous phase and the phase of cicatrization, but this scheme still offers a convenient key to understanding of the condition. Primary infection leads to the atrophic phase which may be prolonged and is accompanied by symptoms akin to that of atrophic rhinitis. The granulomatous stage gradually replaces the atrophic and catarrhal. Granulomas may either be diffuse and infiltrative or localized, often to one nasal passage, to produce an exophytic, sometimes pedunculated turnout that may hang from the nostril~7. This tumourous localization of scleroma is not a well-recognized aspect of the diseasOg, 46 and is in distinct contrast to the progressive and destructive spread of submucosal ~ a n u l o m a s into the nasopharynx, larynx and trachea, which is a classic feature of untreated cases. Such infiltration m a y also spread along the nasolachrymal duct (dachryoscleroma) s and rarely along the Eustachian tube, or laterally via the ostium into the maxillary sinuslO,47. A very few cases have been deseribed~ of middle-ear involvement in scleroma, and some of these appear to be prim a r y infections not continuous with nasopharyngeal lesions. A natural result of proliferating granulomas is bone destruction or displacement s, t h e radiographic features of which have been the subject of a recent reportSg. The inferior turbinate is particularly susceptible and loss of the nasal bones produces a "saddle nose" deformity similar to that found in nasal leprosy. Extension into the ethmoid air cells 10 paves the way for lateral spread to the orbit with subsequent prop-

tosis, or to the sphenoid and cranial cavity, Involvement of the maxilla and oral cavity occurs in a number of different ways. Nasal granulations m a y invade the incisive canal and then expand to destroy the floor of the nose3; this can produce gross palatal fenestration and loss of teeth. Extension from the anterior nose can destroy the bony premaxilla with extrusion of the teethS6 or there may be a diffuse infiltration of soft tissue across the pyriform fossa. This process leads to the formation of either sinuses or polypoid masses of soft tissue in the labial sulcus10,11. Submucosal infiltration m a y enlarge the upper lip and ultimately fuse it to the alveolar process, as well as producing a grotesque, nodular enlargement of the gingivae and palatal mucosa. More commonly the palate, uvula and palatine fauces are infiltrated from the nasopharynx and the disease m a y spread to involve the base of the tongue. These changes are associated with progressive immobilization of the palatopharyngeal arch. By direct extension o r by the formation of separate primary sites of infection the larynx, trachea and main bronchi may be affected. Spread of scleroma to cervical lymph nodes is uncommon 4, and not all reports are authenticated by the demonstration of KlebsieUa within the affected lymphoid tissue, but the infection may be associated with reactive changes in regional lymph nodes~6. Secondary infection of the destructive lesions may also produce lymphadenitis. A small proportion of the pseudolymphomatous enlargements of cervical nodes described as "sinus histiocytosis with massive lymphadenopathy" have recently been associated with classic scleroma or a high level of antibody to K. rhinoscleromatis s~, but it is not yet clear whether there is an underlying connection between the two conditions. Equally rare is carcinomatous change in epithelium overlying scleromatous granulomas ~6. Such change m a y usu-

SCLEROMA IN NIGERIA ally be related to the effect of therapeutic irradiation rather than to the effect of chronic infection. The symptoms of the granulomatous phase of scleroma worsen in step with the degree of expansion and infiltration and may progress from nasal obstruction to dysphagia, coughing, hoarseness, dysphonia, conductive deafness and, rarely, facial nerve paralysis~. The disfigurement associated with untreated disease is complicated by the progressive fibrosis which characterizes the cicatricial stage and causes permanent dysfunction and deformity, including microstomia. In this phase tumourous granulomas harden to a cartilaginous consistency and become radiopaque.

Pathology The essential factor in the pathology of scleroma is the microbial parasitization of macrophages that congregate to form granulomas. In this respect there is an underlying similarity between scleroma and diseases such as tuberculosis, Ieprosy, teishmaniasis and blastomycosis, alI of which are characterized by chronicity and local tissue destruction. In scleromatous granulomas the proportion of macrophages is usually high and the accompanying lymphoid cells are predominantly plasma cells, many of which contain Russell bodies, a characteristic feature. Parasitized macrophages enlarge to form a vacuolated, finely granular, mononuclear giant cell, first described by MIKULICZ30 in 1877. The Mikulicz cell contains intact and fragmented bacteria within enlarged phagosomes that are often ruptured and coalescent2L The extra- and intra-cellular content of bacteria appears to be highest in early and acutely inflamed granulomas and there is progressive reduction in bacillary load as the lesion matures and undergoes fibrosis. Cicatrization is accomplished by progressive enlarge-

273

ment of fibrous septa that form a framework within the granulomas and a concomitant reduction in the numbers of macrophages. An important pathogenic attribute of K. rhinoscleromatis is an extracelluJar mucopolysaccharide or "slime coat" that is produced in abundance within tissuese~. This material appears to be immunogenic and could also confer resistance to digestion by macrophages. Since the disease progresses in the presence of circulating antibody it is likely that cell-mediated immunity is fundamental to the elimination of the infection and that tissue destruction is a by-product of immune elimination.

Diagnosis Biopsy, bacterial culture and to a lesser extent serological investigations are used to confirm the clinical diagnosis. The recognition of early scleroma is probably the most difficult area of diagnosis: the histoIogical appearances are of non-specific inflammation and the retrieval of Klebsielta from nasal swabs is inconstant40. Atrophic and syphilitic rhinitis, and chronic diphtheria may be considered in differential diagnosis. In the early granulomatous phase small polyps and ulcerating plaques may resemble early nasal lepromatous leprosy0, which can be recognized by a nasal smear positive for acid-fast lepra bacilli. The bacteriological and immunological diagnosis of leprosy is a definitive procedure that will resolve any clinical problems arising from the similar pattern of nasal disease in scleroma. While progressive florid granulations in the nasal cavity with nasal deformity and gradual immobilization of the soft palate are considered to be characteristic of scleroma, atypical presentations in this phase may resemble rhinosporidiosis, the rarer rhino-entomophthoromycosis85 or paranasal aspergillosisZL Gumma or mid-line

274

EDWARDS, ROBERTS AND STORRS

granuloma may be suspected if there is rapid palatal ulceration and fenestration. Both granulomas and plaques distinctly resemble malignant lesions, especially laryngeal cancer; exophytic granulomas imitate benign neoplasms 4~. The microscopic structure of the granuloma suggests the diagnosis but without the demonstration of bacilli it is not strictly pathognomonic. In histological preparations the Klebsiella is not distinctly acid-fast and the capsular polysaccharide is weakly PASpositive, and only faintly stained by the Giemsa technique. No staining method appears to be as reliable as the silver impregnatiota method of Warthin-Starry (or Warthin-Faulkner), first developed for the demonstration of spirochaetes. The bacillus can be best retrieved for culture from finely divided samples of granulation tissue rather than from nasal swabs40, 41. After primary culture the specific biochemical attributes of the strain ea can be demonstrated. Serotyping for capsular antigenic structure usually reveals Klebsiella of capsular type 3. A high titre of circulating antibody to capsular antigens may be demonstrable and a complement fixation test has met with some diagnostic SUCCESS27.

Treatment The stages of treatment in scleroma can be conveniently divided into a) emergency procedures, usually the preservation of the airway, b) chemotherapy and c) reparative and reconstructive surgery. In neglected cases obstruction in the upper respiratory tract may be a presenting feature and acute cases may require tracheostomy. If the airway is impaired in the nasal passage, dilatation and indwelling intubation of the nose for as long as can be tolerated has been recommended4~, rather than the more exacting wholesale removal of granulations

which, before chemotherapy, may lead to extensive atrophic changes in the mucosa and possibly to dissemination of the disease. Dilatation may also be employed in the treatment of tracheal and bronchial lesions. The development of effective chemotherapy has greatly improved prognosis in what was once regarded as an inexorable and often fatal disease. K. rhinoscleromatis may be sensitive to streptomycin, ampicillin, sulphonamides, tetracycline, erythromycin and chloramphenicol but after quantifying the effectiveness of these agents, S s a u 41 emphasized that bactericidal agents, particularly ampicillin, sulphamethoxazole-trimethoprim combinations and streptomycin (which previously was the drug of choice), are more effective than bacteriostatic preparations. ProIonged combination therapy for 4-6 weeks at high dosage may be necessary to produce negative retrieval of organisms from serial biopsies. After successful treatment the extent of residual tissue destruction, the availability of special surgical skills, and the requirements of the patient combine to influence the level of reparative surgery. Simple removal of residual granulations will be of great benefit and the reconstruction of the nasal alae may be effeeted by skin grafts. Tumourous masses may be extirpated but the removal of a discrete tumour followed by chemotherapy of incipient lesions is one of the few instances when surgery can precede the use of drugs. Gingivectomy or alveolectomy may be performed as necessary. Palatal fenestrations m a y be closed by mucosal flaps or by obturators, but more complex forms of plastic repair may be contra-indicated if there is marked fibrosis. Epiphora and other complications of nasolachrymal duct involvement may be controlled by dachryo-cysto-rhinostomy. There are two types of treatment that require further investigation and documen-

S C L E R O M A IN N I G E R I A tation. T h e first is the use of corticosteroids in c o m b i n a t i o n with antibiotics, which is said t o be of s o m e benefit in controlling the g r a n u l o m a t o u s phase. T h e second is vaccination, the experimental d e v e l o p m e n t of w h i c h is m e n t i o n e d in the Russian literature but is not reviewed here.

Case Reports CASE 1 A 40-year-old negroid female of the Tiv tribe of north central Nigeria had a painless turnout occluding the left nostril that had been noticed for 2 years (Fig. 'la). The provisional clinical diagnosis was of polyposis or benign neoplasia. There were a few friable granulations in the right nostril but no other change in the upper respiratory tract was detected. Incisional biopsy showed an inflammatory lesion containing plasma cells with Russell bodies and focal neutrophil infiltration, covered by at-

Fig. 1. Localized granulomas in scleroma, a, Case 1, mass in left nostril, b, Case 2, complete nasal obstruction and Mar ulceration.

275

tenuated and partly ulcerated nasal epithelium. These appearances were considered to be nonspecific inflammation. Under endotracheal anaesthesia the whole turnout was easily excised and there was no obvious destruction of the nasal wall. The lesion had a s m o o t h surface and measured 3.5 cm at its greatest diameter. It was firm when cut and the exposed surface was homogeneous and creamy yellow. Sections showed an unencapsulated lesion composed of sheets of plasma ceils and granular mononuclear histiocytes, some of giant proportions, incompletely divided by broad fibrous septa (Fig. 2a, b). The reticulin framework of the lesion, stained by silver impregnation, was strikingly elaborate. The Warthin-Faulkner method readily demonstrated bacilli within the Mikulicz cells (Fig. 2c) and a diagnosis of scleromagranulomatous stage with early fibrosis was made. CASE 2 A 40-year-old negroid woman from the Kagon tribe of northern Nigeria had a painless tumour that blocked and distended the nose (Fig. lb). The lesion had been present for at least 5 years, and protruded from both nostrils which were extensively ulcerated at the alae. In addition there was a polypoid granulomatous mass attached to the left posterior pillar of the fauces. Radiographs showed displaced nasal bones and a moderately radiopaque tumour. Shace there was impairment of the airway the nasal tumour was excised under endotracheal anaesthesia with considerable loss of mucosa; this was repaired at the same time using a split skin graft from the thigh held into the nostrils by tubing. Successful take of this graft was about 25 % by area but a reasonable functional and aesthetic result was obtained. The provisional clinical diagnosis had been polyposis or benign neoplasia, though it was recognized that neither designation explained the presence of the pharyngeal lesion. The histological features of the fragmented nasal tumour comprised an admixture of vacuolated and granular histiocytes with plasma ceils. The demonstration of bacilli within the enlarged histiocytes confirmed the diagnosis of scleroma. CASE 3 A 28-year-old negroid man had a diffuse swelling measuring 2 X 2 cm in the left upper lip that partly obliterated the buccal sulcus and

276

E D W A R D S , ROBERTS A N D STORRS

Fig. 2. Histology of typical scleromatous granulomas (Case 1). a, sheets of enlarged histiocytes and scattered plasma cells incompletely divided by fibrous septa. H & E, X 60. b, detail of histiocytes (Mikulicz cells) and a Russell body (r). H & E, X 250. c, single Mikulicz cell containing numerous bacilli. Warthin-Faulkner, oil immersion, X 1,200.

filled out the nasolabial fold. This had given some discomfort for about 1 month. Adjacent teeth were normal and there was no distinct radiographic change about their apices; a minor thickening of the left antral mucosa was suspected. There were n o other manifestations of systemic disease and the clinical differential diagnosis was between nasolabial cyst and neoplasia. F r o m a buccal flap extending to the pyriform aperture, t h e lesion was exposed and removed by sharp dissection a n d curettage. This procedure revealed minor erosion of the cortical plate of the maxilla to the Mar margin, and a minute defect in communication with the lateral wall of the nose beneath the inferior turbinate. Microscopic examination showed a diffuse infiltration of fibrous tissue and muscle

by a granuloma rich in large histiocytes. Within some vacuolated histiocytes rod-shaped bacilli were demonstrated by the WarthinF a u l k n e r method. These failed to stain acidfast with a method for leprosy bacilli. The changes were regarded as consistent with early granulomatous infiltration in scleroma. F o u r months later the patient was recalled and the operation site, a n t r u m and nose were explored. Scar tissue was retrieved from the buccal sulcus, the antrum was clear but the nasal mucosa over the left inferior turbinate was enlarged and inflamed. Biopsy of the latter revealed only non-specific inflammation in which bacilli could not be detected. There was n o clinical evidence of early leprosy. The patient was then lost to follow-up.

SCLEROMA IN NIGERIA

Discussion Scleromatous infiltration frequently extends from the nose to involve structures which are the province of the oral surgeon. The condition is accorded a place in a major text of oral pathology ~5 but is likely to be of incidental interest only to those who do not practise within endemic areas. The cases recorded here comprise the first substantial reports of scleroma in Nigeria. They illustrate some of the diagnostic problems that m a y arise especially in cases from poorly defined foci. The tumourous presentation of scleroma (cases 1 and 2), which imitates benign neoplasia, is a particular source of diagnostic confusion. Excision biopsy of these exophytic lesions may be attempted and our experience is that they are easy to define and extirpate, though there may be attendant Ioss of an area of nasal mueosa. F r o m an epidemiological view-point, discrimination between early scleroma in the atropic, catarrhal phase, ozaena and nasal lepromatous leprosy may be of significance, since regions of endemic ozaena, such as that in U g a n d a % and the global distribution of leprosy overlap the more confined pattern of scleroma loci. Ozaena may be attributable to Klebsiella infection and there has often been speculation over a possible connection between ozaena and scleroma~7, although the bacterial strains involved appear to be biochemically distinct from each other es. In the case of leprosy, recent studies 0 have emphasized that intranasal lesions and symptoms similar to atrophic rhinitis often predominate in early lepromatous leprosy when the typical infiltration of skin m a y be minimal. On occasions (see case 3) l e p r o m a t o u s leprosy and scleroma may be considered together in differential diagnosis and the histological appearances may be very similar 19. As the disease develops the dermal and neuro-

277

pathological manifestations of leprosy should become apparent but definitive bacteriological investigations should be employed in any instance in which there is doubt. The immunopathology of scleroma is intriguing and merits more exhaustive study than is at present reported, The parasitization of maerophages in the presence of circulating antibody, and the formation of destructive granulomas are characteristic of diseases that are influenced by cell-mediated immunity. In several such diseases welldefined clinical stages may be related to points on a spectrum of immunological reactivity in which, broadly speaking, a reduction in the number of causative organisms is associated with heightened manifestations of cell-mediated immunity 44. It is not clear to what extent the clinicaI phases of scleroma can be related to distinct changes in immunity or how often the disease m a y stabilize at an intermediate stage, but observations in familial microfoci ~4 have suggested that subclinical and possibly stable forms of the atrophic phase m a y occur. The localized, tumourous granuloma could also be an example of stabilized disease. In granulomatous scleroma there appears to be neither the anergy nor massive bacillary load that characterize for example, polar lepromatous leprosy, but infiltration may be progressive, suggesting that immunological defences are incomplete. Certainly a reduction in the number of viable organisms accompanies cicatrization and this may indicate an increasing measure of immunity. In summary, it may be said that scleroma is an uncommon and complex disease but an important source of morbidity in endemic foci. The relative effectiveness of chemotherapy m a y be expected to influence the incidence of scleroma, but increasing mobility of populations could also extend the distribution of sporadic cases. Clinicians in ear, nose and throat, and max-

278

E D W A R D S , ROBERTS A N D STORRS

illo-facial units outside e n d e m i c regions should be alert to the diagnosis of occasional cases, and those that arise in indefinite l o c i should be d o c u m e n t e d in case the focal boundaries need to be redefined. Acknowledgements - The authors (G.D.D.R. and T.J.S.) who were seconded to the maxiUofacial unit, Kaduna, wish to express their thanks to Dr. R. SI-IXMIAfor his guidance and permission to publish cases under his care. The advice of Professor B. COHEN in the preparation of the manuscript and the assistance of E. B. BRAIN and G. ELIA in t h e preparation of illustrations is gratefully acknowledged.

References 1. ALAVl, K., KOHOLrr, E. & DUTZ, W.: Two cases of scleroma in Iran. J. Clin. Pathol. 1971: 24: 360-362.

2. BADRAWY,R.; Dacryoscleroma. Ann. Otol. Rhinol. Laryngol. 1962: 71: 250-254. 3. BAORAWY, R.: Affection of bone in rhinoscleroma. I. Laryngol. Otol. 1966: 80: 160167. 4. BADRAWY, R. & EL-SHENNAWY, M.: Affection of cervical lymph nodes in rhinoscleroma. J. Laryngol. Otol. 1974: 88: 261269. 5. BARBARY, A,, EOUAD, H. & FATr-HI, A.: Scleroma affecting the middle ear cavity with report of three cases. Ann. Otol. Rhinol. Laryngol. 1974: 83: 107-110. 6. BARTON, R. P.: A clinical study of the nose in lepromatous leprosy. Lepr. Rev. 1974: 45: i35-144. 7. BECKER, B. J. P. & DORFMAN, R. F.: Rhinoscleroma (scleroma) - report of a case in South Africa. S. AfT. Med. J. 1956: 30: 581-584. 8. BOTROS, G., HAMILTON, P. K., FLOYD, T. M., MtSFTI, A. & IMAN, A.: Scleroma in Egypt. Ann. Otol. Rhinol. Laryngol. 1954: 63: 1031-1055. 9. BULTEAU, V.: Rbinoscleroma. Med. J. Aust. 1963: 1: 783-784.

10. CHATTERJI, P., VERMA, S. M. & MATHUR, J. S.: Seleroma of the antrum and ethmoid. ]. LaryngoI. Otol. 1969: 83: 917-923. 11. DUDANI, I. C. & KHANNA, J. N.: Rhinoscleroma of the maxilla. J. Indian Dent. Assoc. 1972: 44: 99-104.

,12. EDINGTON, G. M.: Personal communication, 1973. 13. EImALL~, HAMZA, A.: Personal communication, 1974. 14. FRrscrI, A. YON: Zur aetiologie des Rhinosklerom. Wien. Med. Wochenschr. 1882: 32: 969-972. 15. GORLIN, R. J. • GOLDMAN, H. M.: Thoma's oral pathology, Vol. 2, 6th ed. C. V. Mosby Company, St. Louis 1970, p. 724. 16. GRAHNE, B., SImALA, U., MEImMA~, L. & KUNNAS, K.: Rhinoscleroma in Finland. Acta OtolaryngoL 1972: 74: 430-435. 17. GREWAL, R. S.: Rhinoscleroma - an unusual mode of presentation. Int. Surg. 1966: 45: 646--649. 18. HAGQVIST, G., H E - - S O N , H., ST~NSTROM, B. & WALLERSTROM, A.: Scleroma in Sweden. Acta Med. Scand. 1966: 179: 189-195. 19. HANDOUSA, P. & ELWI, A. M.: Some clinicopathological observations on scleroma. J. Laryngol. Otol. 1958: 72: 32-47. 20. HEBRA, F. VON: ~ b e r ein eigentfimliches Neugebilde Naserrhinosklerom. Wien. Med. Wochenschr, 1870: 20: 1-5. 21. HOFFMAN, E. O.: The etiology of rhinoscleroma. Int. Pathol. 1967: 8:~74-77. 22. HOFFMAN, E. O., I_x3OSE, L. D. & HARxiN, J. C.: The Mikulicz cell in rhinoscleroma. Am. J. Pathol. 1973: 73: 47-54. 23. KAUFFMANN, F.: On the serology of the Klebsiella group. Acta Pathol. Microbiol. Scand. 1949: 26: 381-406. 24. KRASlLNIKOV, A. P., IZRAITEL, N. A. & KRYLOa, I. A.: Focal incidence of scleroma. ]. Hyg. EpidemioL Microbiol. Immunol. 1971: 15: 243-257. 25. LAMI'ERT, F. & LENNERT, K.: Sinus histiocytosis with massive lymphadenopathy fifteen new cases. Cancer 1976: 37: 783789. 26. LELE, M. V.: Oi'al manifestations of rhinoscleroma. J. Indian Dent. Assoc. 1969: 41: 277-281. 27. LEVlNE, M. G. & HoY'r, R. E.: Scleroma: Complement fixation test. Proc. Soc. Exp. Biol. Med. 1947: 65: 70-72. 28. MALOWANY, M. S., CHESTER, B. ,~ ALLERHAND, J.: Isolation and microbiologic differentiation o{ Klebsiella rhinoscleromatis and Klebsiella ozaenae in cases of chronic rhinitis. A m . J. Clin. Pathot. 1972: 58: 500-553. 29. MARTIN, J. A. M.: Disease of the ear, nose and throat in tropical Africa. /. Laryngol. Otol. 1967: 81: 1079-1098.

SCLEROMA IN NIGERIA 30. Mmr.rLrcz, L: r das Rhinosklerom (Hebra). Langenbecks Arch. Klin. Chit. 1877: 20: 485-534. 31. Mmo~Ev, B., Mt~-t~otm, E. S., AAL, O. A. & EL HASSAN, A. M.: Primary aspergilloma of paranasal sinuses in the Sudan. Br. J. Surg. 1969: 56: 132-137. 32. M~mRELL, T. G. C.: Rhinoscleroma in the western highlands of New Guinea. Trans. R. Soc. Trop. Med. Hyg. 1966: 60: 681688. 33. Mr_rZYKA, M. M. & GtrBrNA, K. M.: Problems of the epidemiology of scleroma. I Geographical distribution. L Hyg. Epidemiol. Microbiol. Immunol. 1971: 15: 233-

41.

42.

44.

242. 34, MuzYr~, M. M. & GtmrNA, K. M.: Problems of the epidemiotogy of scleroma. II - Aspects of the problem of endemic focus formation. I. Hyg. Epidemiol. MierobioI. Immunol. I972: I6: 8-20. 35. ONUIGBO,H. C., GUGNANI,H. C., OKAFOR, B. C. & M:SCH, K. A.: Nasal entomophthorosis in an Igbo from Nigeria. J. Laryngol. 0;ol. 1975: 89: 657--661. 36. QVEVEDO, J.: Sclerorna in Guatamala. Ann. Otol. Rhinol. Laryngol. 1949: Sg: 613-645. 37. ROLAND, P. E.: Scleroma in Uganda. J. Laryngol. Otol. 1961: 75: 1040-1047. 38. SHAW, H. J. & MARTrN, H.: Rhinoscleroma - a clinical perspective. J. Laryngol. OtoL 1961: 75: 1011-1039. 39. SrmnATA, M. A., EL-SXLL~, R. & MA~qDOt.rR, M. A.: Radiographic study of scleroma. J. Laryngol. Otol. 1975: 89: 12431261. 40. S ~ , A., PANDHI, S. C. & PRAKASH, O.:

Aetiopathogenesis of scleroma. ]. LaryngoL Otol. 1969: 83: 133-139. SSAL:, C. L. K.: T h e management of rhinoscleroma. J. Laryngol. Otol. 1975: 89: 9199. STEFFBN, T. N. & SMITrI, I. M.: Scleroma K. rhinoscleromatis and its effect on mice. Ann. OtoL Rhinol. Laryngol, 1961: 70: 935-952. TALVALKAR, G. V.: Some observations on rhinoscleroma. L Postgrad. Med. 1969: 1 5 : 69-76. TURK, J. L. & EDWARDS, M. B.: Immunological aspects of infection. In: COHEN, B. & KRAbmR, I. R. H. (eds): Scientific [oundations o[ dentistry. Heinemann, London 1976, p. 143. W i t o o ~ % C. D.: Rhinoscleroma - a case report. Arch. Otolaryngol. 1967: 85: 223225. YAssmr, A., BADRAWY, R. & MoKrrridL M.: Localized forms of rhinoscleroma. J. Laryngol. Otol. 1971: 85: 269-274. YASSIN, A. & S~t~WAT, F.: Unusual features of scleroma. I. LaryngoI. Otol. 1966: 8 0 : 524-529. ZWmFACH, E~: Rhinoscleroma. J. Laryngol. Otol. 1955: 69: 321-330. -

43.

45.

46.

47.

48.

279

Address:

M. B. Edwards Department o] Dental Science Royal College o] Surgeons o/England 35-43, Lincoln's Inn Fields London, WC2A 3PN England