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Clinical and radiological assessment of rhinomaxillary syndrome in Hansen’s disease
How to cite this article: do Espírito Santo RB, Serafim RA, Loureiro RM, Sumi DV, de Mello RA, Nascimento IF, et al. Clinical and radiological assessment of rhinomaxillary syndrome in Hansen’s disease. Indian J Dermatol Venereol Leprol 2022;88:483-93.
More than four million people today live with Hansen’s disease, and 200,000 new cases are diagnosed every year. Lifetime effects of Hansen’s disease manifest as changes to bones of the face, hands and feet, resulting in physical impairment, secondary complications and facial changes that can be detrimental to quality of life, particularly among the elderly.
This study aimed to perform a detailed characterization of rhinomaxillary syndrome and its clinical manifestations in older persons treated in the past for Hansen’s disease.
This was a cross-sectional study to characterize rhinomaxillary syndrome among older persons (age 60+ years) resident at Pedro Fontes Hospital, Cariacica, Espírito Santo, Brazil. Computed tomography images were examined with three-dimensional reconstructions to assess alterations to maxillofacial bones according to criteria for radiological rhinomaxillary syndrome. Participants were examined to assess facial alterations according to criteria for clinical rhinomaxillary syndrome.
Rhinomaxillary syndrome was investigated in 16 participants (ten females and six males), median age 70 (range 60–89) years, age at diagnosis 20 (6–43) years and time since diagnosis 46 (26–70) years. Four participants fully met radiological rhinomaxillary syndrome criteria, four partially. All participants with full radiological rhinomaxillary syndrome presented with facial changes which met criteria for clinical rhinomaxillary syndrome, including “saddle nose” (loss of nasal dorsal height and shortened length of nose, due to cartilaginous and/or bone collapse), concave middle third of the face with sunken nose, maxillary retrognathia and inverted upper lip.
Clinical histories were incomplete for some participants because records were lost at the hospital over time.
Until Hansen’s disease is eliminated from endemic countries, persons affected will continue to present with rhinomaxillofacial alterations caused by Mycobacterium leprae infection. Clinical protocols for assessment and long-term care need to include otorhinolaryngological evaluation, mainly to prevent secondary complications. When rhinomaxillofacial bone changes are suspected, this evaluation should be supported by computed tomography imaging, if available.
Plain Language Summary
Hansen’s disease, also known as leprosy, is an infectious disease caused by a bacterium, Mycobacterium leprae. More than 200,000 new cases of Hansen’s disease are diagnosed each year worldwide. If the disease is diagnosed too late, it can alter bones in the skull, leading to facial changes and disfigurement. These are associated with stigma and with other medical complications. These bone alterations have been examined in skulls from archaeological sites, and the associated changes have been called “rhinomaxillary syndrome.” In living persons affected by Hansen’s disease, rhinomaxillary syndrome can be assessed by computed tomography imaging of maxillofacial bones, but a simpler method of looking at external changes to the face could also be useful in clinical practice, particularly in the countries where Hansen’s disease is endemic. The authors used both techniques in a group of elderly people from Brazil to evaluate a set of diagnostic criteria based on changes to the face which matched the underlying bone alterations. This simpler method could be incorporated into clinical guidelines to improve the assessment and care of persons affected by Hansen’s disease. When rhinomaxillofacial bone changes are suspected, clinical evaluation should be supported by computed tomography imaging where these facilities are available.
Delayed diagnosis of Hansen’s disease increases the risk of disabilities.1-4 Hansen’s disease-related changes to bones, particularly of the hands, feet and face,5 impact on quality of life and contribute to stigmatization.6,7 Rhinomaxillofacial changes caused by Mycobacterium leprae infection of the nasal passages and the palate includes collapse of the bridge of the nose, resorption of the central part of the maxilla and inflammation of the floor and walls of the nasal cavity and hard palate.8,9 The degree of bone alteration correlates with the type of the disease at diagnosis, ranging from little or no detectable change in the tuberculoid type to severe changes at the “lepromatous” pole.8,9
Rhinomaxillary syndrome was defined in 1992 to identify Hansen’s disease in skulls from archaeological sites based on changes to the pyriform aperture, orbital bones and alveolar process of the maxilla.10-12 Rhinomaxillary syndrome criteria may have clinical utility in providing a standardized method for grading rhinomaxillofacial changes in persons affected by Hansen’s disease.13
The aim of our study was to perform the first in vivo investigation of rhinomaxillary syndrome using computed tomography imaging with three-dimensional reconstructions, to determine whether rhinomaxillary syndrome correlated with a clinical definition based on facial profile alterations.
Older persons (age 60+ years) affected by Hansen’s disease resident at the Hospital Colônia Pedro Fontes, Espírito Santo, Brazil, were invited to participate when they required medical assessment as part of routine care between September 2015 and December 2016. Demographic data and medical history were obtained by interview and from medical records. All participants received general medical, dermatological and otorhinolaryngological examinations.
Computed tomography imaging
Participants attended the Radiology and Computed Tomography Service at Hospital Universitário Cassiano Antônio Moraes, Espírito Santo, Brazil, for computed tomography scans of the head. Images were acquired in a 64-section multidetector computed tomography scanner (Aquilion, Toshiba Medical Systems Corp., Tochigi, Japan) with parameters 120 kVp, 100 mAs, 1.125 mm spiral pitch factor. Field of view was limited to the maxillofacial area. Three-dimensional reconstructions and cephalometrics were generated from volumetric data by DePuy Synthes TRUMATCH CMF Solutions (DePuy Synthes Inc., PA 19380, USA). Cephalometrics comprised maxillary height and width, nasofrontal angle, ANS angle (A=A point, N=nasion and S=Sella turcica mid-point) and maxillary volume measured at Le Fort 1 level.
Rhinomaxillary syndrome is defined by changes to: (I) anterior nasal spine; (II) alveolar processes of maxilla; (III) nasal surface of the palatine process of the maxilla; (IV) oral surface of the palatine process of the maxilla; (V) nasal turbinates and septum; (VI) pyriform aperture and (VII) posterior alveolar margins of the maxilla.11 To identify rhinomaxillary syndrome from computed tomography images, we combined criteria III and IV because both sides of the hard palate can be examined in physical remains but not in computed tomography images. To criteria VI, we added resorption of the nasal bones which are part of the pyriform aperture but usually absent from paleopathological specimens. Abnormalities were graded as “severe” or “mild to moderate” [Figure 1]. Full or partial radiological rhinomaxillary syndrome was based on assessment of the number and severity of alterations. “Fully met” required severe resorption of anterior nasal spine (criterion I) and severe loss of sharpness of pyriform aperture and/or resorption of nasal bones (criterion VI) plus at least one of the other criteria rated severe and one rated mild to moderate. Partial radiological rhinomaxillary syndrome typically required two–three severe plus two–three mild-to-moderate bone alterations. Computed tomography images were examined independently and in parallel by two radiologists.
Clinical rhinomaxillary syndrome
Assessment of clinical manifestation of rhinomaxillary syndrome was based on clinical rhinomaxillary syndrome criteria comprising four facial profile alterations: (1) saddle nose, characterized by loss of nasal dorsal height and shortened length of nose, due to cartilaginous and/or bone collapse; (2) concave middle third of the face with sunken (retracted) nose, caused by erosion of the zygomatic process and enlargement and loss of the pyriform shape of the nasal aperture; (3) reduced maxillary projection (maxillary retrognathia/reduced ANS) and (4) inverted upper lip because of reduced maxillary height.13 Alterations were scored: saddle nose (no = 0, mild = 1, moderate = 2 and severe = 3); concave middle third of face with sunken nose (no = 0, either = 1 and both = 2); maxillary retrognathia (reduced ANS) (no = 0 and yes = 1) and inverted upper lip (no = 0 and yes = 1). The sum of scores was categorized: normal = 0, mild = 1, moderate = 2–4 and substantial (clinical rhinomaxillary syndrome) = 5–7.
This study was approved by the Research Ethics Committee of the Health Sciences Center of the Federal University of Espírito Santo (no. 4.248.419, August 31, 2020). Informed consent including for use of images was obtained from all participants.
Sixteen former Hansen’s disease patients participated (ten females and six males) with median age 70 (range 60–89) years, age at diagnosis 20 (6–43) years and time since diagnosis 46 (26–70) years. Original Hansen’s disease diagnosis by Madrid Classification was the “lepromatous” form in 13 patients, “borderline” in two and “tuberculoid” in one patient [Table 1]. Most patients had received two–three courses of dapsone monotherapy during the 1960s to 1980s; seven had received multidrug therapy (dapsone, rifampicin and clofazimine). Type 1 and 2 reactions before, during or after Hansen’s disease treatment were recorded for ten patients.
|ID||Age||Sex||Madrid classification at diagnosisa||Age at diagnosis||Delay (months)b||Monotherapy start year (drug)c||Months of monotherapy (drug)c||Multidrug therapy start year||Months of multidrug therapy||Hansen’s disease reactionsd||Reaction therapye|
|P1||87||M||L||42||1970 (D)||144 (D)||2000||12||II||P, T|
|P2||77||M||L||27||1977 (D)||156 (D)||None||III||P|
|P3||89||M||L||43||1978 (D)||None||II||P, T|
|P5||62||F||L||25||2||1978 (D) 1990 (R)||None||II||II||P, T|
|P7||77||F||L||31||60||1975 (C) 1979 (R) 1983 (D)||300 (D)||Yes||II||II||T|
|P8||76||M||L||6||12||1969 (D) 1984 (C) 1984 (R)||252 (D)||Yes|
|P9||79||F||L||9||1960 (D) 1984 (C) 1990 (D)||None|
|P10||79||F||L||11||1959 (D) 1975 (C) 1979 (R)||Yes|
|P11||60||F||L||17||3||1976 (D) 1979 (R)||180 (D) 36 (R)||Yes|
|P13||70||M||L||26||1963 (D) 1984 (R) 1988 (C)||300 (D) 60 (R) 36 (C)||Yes|
|P14||76||F||L||23||1968 (D) 1984 (C) 1987 (R)||60 (D) n/r (C)|
|P15||61||F||L||15||48||1972 (D) 1975 (C) 1978 (D)||36 (D) 180 (C) 96 (D)||None||II||T|
|P16||66||M||B||40||36||1970 (D) 1980 (C)||120 (D)||None||II||II||P, T|
Maxillofacial bone changes
All participants had alterations to the alveolar process of maxilla to varying degrees (eight severe and eight mild to moderate) [Table 2]. The second most frequent alteration was resorption of the anterior nasal spine, observed in 12/16 participants (six severe). Resorption of nasal bones was observed in ten/16 participants (five severe), loss of sharpness of the pyriform aperture in ten/16 (five severe) and atrophy of the inferior and middle nasal turbinates in eight/16 (one severe) and seven/16 (two severe). Three participants had severe perforation of the nasal septum and eight had thinning of the hard palate with bony discontinuities [Table 2]. None had perforated palate.
|Anterior nasal spine||Alveolar
process of maxilla (anterior)
|Hard palate (palatine process of maxilla)||Nasal
process of maxilla (posterior)
|I||II||III + IV||V||VI||VII|
|Osteitis||Resorptionb||Resorptionb||Thinning with bony discontinuities||Perforationb||Atrophyb||Atrophyb||Loss of sharpnessb||Resorptionb|
Clinical rhinomaxillary syndrome and radiological rhinomaxillary syndrome
Four participants (P1, P2, P7 and P8) fully met the criteria for radiological rhinomaxillary syndrome [Table 2], all of whom had facial profile changes which met criteria for clinical rhinomaxillary syndrome [Table 3]. Four participants (P9, P11, P13 and P15) had partial radiological rhinomaxillary syndrome, of whom three had moderate and one had mild facial profile changes. Three cases (P1, P7 and P8) with bone alterations meeting criteria for full radiological rhinomaxillary syndrome are illustrated in Figures 2-4, together with one case (P10) with bone alterations which did not meet radiological rhinomaxillary syndrome criteria [Figure 5]. Cephalometrics for P1, P7, P8 and P10 are reported in Table 4.
|ID||1. Saddle nose||2. Concave middle third of the face with sunken nose||3. Maxillary retrognathia (reduced ANS)a||4. Inverted upper lip||Overall grading of facial changes (score)||Clinical rhinomaxillary syndromeb||Radiological rhinomaxillary syndromec|
|ID||Age||Sex||Maxillary height (mm)||Maxillary width (mm)||Maxillary volume (cm3)||Nasofrontal angle (°)||ANSa (°)||Clinical RMSb||Radiological RMSc|
This group of elderly adults previously treated and cured of Hansen’s disease displayed at least one maxillofacial bone alteration consistent with the pathophysiological effects of clinical Mycobacterium leprae infection. All participants had alterations to the alveolar process of the maxilla and most presented with resorption of the anterior nasal spine, but the number of other bones affected and the degree of alterations varied widely. Maxillofacial bone alterations in four participants met the criteria for radiological rhinomaxillary syndrome fully, while four participants had partial radiological rhinomaxillary syndrome. Participants with full radiological rhinomaxillary syndrome presented with substantial facial changes including saddle nose, concave middle third of face with sunken nose, inverted upper lip and maxillary retrognathia. In all four full radiological rhinomaxillary syndrome patients, these alterations met a set of criteria defining “clinical RMS.”
Maxillofacial bone changes assessed in vivo by computed tomography imaging have been described in only one previous study.14 This study of ten former Hansen’s disease patients residing in a National Sanatorium in Japan reported a range of alterations similar to those observed in our participants with four of ten participants having severe maxillary changes and saddle nose, and three of ten having no bone alterations.
Strengths and weaknesses
A limitation of our study is the lack of a control group to differentiate age-related changes to the maxilla. However, Kasai et al. reported that Hansen’s disease-related changes occur predominantly in the median frontal part with characteristic interruption of the U-shaped process, as we also observed in our participants, compared with the typical horizontal and vertical age-related atrophy of the maxillary alveolar processes.14 Furthermore, reported evidence of substantial age-related maxillary bone loss is limited, although some may be secondary to poor nutrition, loss of teeth (all participants had a partially or completely edentulous maxilla) and changes in mechanical function.15 In our cases of full and partial rhinomaxillary syndrome, maxillofacial bone changes were consistent with those considered to be pathognomonic of Hansen’s disease.8
We had incomplete clinical histories for some participants because records were lost over time. Resorption and atrophy of nasal bones can be a consequence of trauma which may not have been recorded in medical histories. Similarly, we did not have complete records to support our assessment of differential diagnoses such as syphilis and mucocutaneous leishmaniasis,11 and less common rhinological diseases such as granulomatosis with polyangiitis and nasal extranodal lymphoma.16 Although two researchers assessed and graded facial changes independently, this remains a subjective process, and our clinical rhinomaxillary syndrome criteria require validation.
Availability of computed tomography scanning even in endemic countries means that assessment of rhinomaxillofacial bone changes, where suspected, could become a component of specialist care, primarily to prevent secondary complications. We propose that clinical protocols for Hansen’s disease are extended to include otorhinolaryngological evaluation, supported by imaging where necessary. In the meantime, practical steps need to be taken at the health system level to ensure timely diagnosis and prompt treatment initiation to prevent Hansen’s disease-related disability.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.