Clinical and radiographic study of orofacial alterations in patients with systemic sclerosis

Systemic sclerosis (SS) is an autoimmune disease with great repercussions on the hard and soft tissues of the orofacial region. The aim of this study was to investigate the relationship between mandibular osteolysis and mouth opening measurements, duration of disease and presence/absence of teeth. Twenty-fi ve subjects were selected: 15 diagnosed with systemic sclerosis and 10 healthy controls. The SS patients were grouped according to the presence (group I) or absence (group II) of mandibular osteolysis. The healthy subjects served as the control group (III). All of them underwent panoramic radiography on Ortophos® equipment (Siemens) and were clinically examined, with mouth opening measurement. We observed that group I had a longer duration of the disease than group II (p = 0.003). Groups I and II presented the same mean mouth opening. There was an increasing correlation between mouth opening and duration of the disease in group I (p = 0.095), but this was not observed in group II (p = 0.596). There was no correlation between presence/absence of teeth and osteolysis (p > 0.999), or between presence/absence of teeth and side of osteolysis (p = 0.143). We could conclude that osteolysis seemed to develop in patients with a longer duration of the disease, but did not modify the degree of mouth opening in relation to patients without osteolysis, and the presence/absence of teeth was not signifi cant. On the other hand, in the osteolysis cases, the longer the duration of the disease, the greater the opening of the mouth. Descriptors: Scleroderma, systemic; Clinical trial; Panoramic radiography. Marcelo Marcucci(a) Nitamar Abdala(b) (a) PhD, Department of Stomatology and Oral & Maxillo Facial Surgery, Heliópolis Hospital, São Paulo, SP, Brazil. (b) PhD, Professor of Radiology, Department of Imaging Diagnostics, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. Stomatology Corresponding author: Marcelo Marcucci Rua Pirapora, 248, Paraíso São Paulo SP Brazil CEP: 04008-060 E-mail: marcucci21@gmail.com Received for publication on Sep 05, 2007 Accepted for publication on Dec 13, 2007 Marcucci M, Abdala N Braz Oral Res 2009;23(1):82-8 83 Introduction Systemic sclerosis (SS) is a chronic infl ammatory disease of unknown origin and autoimmune nature characterized by excessive deposition of collagen and glycosaminoglycans in the conjunctive tissue of the dermis and internal organs.1,2 It is a disease of low incidence, with an average of 4 to 19 new cases per million inhabitants and preferentially affects females (4:1).1 The age group most affected is between the third and fi fth decades of life.3,4 Its etiopathogenesis has not been completely clarifi ed. The conjunctive tissue undergoes a fi brosis process that is probably mediated by cytokines produced by lymphocytes and infl ammatory cells, particularly the transforming growth factor beta (TGF-β). The microcirculation undergoes a process of primary vasculitis, which in conjunction with differing vessel thicknesses may cause total obliteration of the vessel due to collagen deposition, thereby leading to clinical manifestations of varying degrees of severity.1,2,3,5 This disease presents a variety of clinical features. Raynaud’s phenomenon is usually its fi rst manifestation, and skin thickening, esophageal dysmotility, restrictive pulmonary disease, pulmonary hypertension, arthralgia, myopathy, myocardiopathy and progressive renal insuffi ciency are also observed.1-3 The thickening of the skin (scleroderma) presents an initial phase of edema that makes the skin swollen and shiny, followed by a hardening phase in which the skin starts to have a dried-out, rough and inelastic appearance, and a third phase in which, in most patients, the skin gradually starts to take on an atrophied and thin appearance.1,3 The orofacial manifestations include stiffness and atrophy of the facial skin that gives the face a mask-like appearance; progressive limitation of mouth opening; skin and mucosa pigmentation (melanoleukoderma) and telangiectasia; hardening and loss of elasticity of the oral mucosa; hardening of the tongue and soft palate; varying degrees of xerostomy; periodontitis; and diffi culty in chewing, speaking and swallowing.6-10 Radiographically, some characteristic alterations caused by systemic sclerosis are observed in the maxillomandibular complex, such as thickening of the periodontal ligament and areas of osteolysis in the mandible. These areas coincide with the insertion zones of the lateral pterygoid, temporal and, particularly, the masseter muscle.11 The aim of the present study was to correlate the clinical variables during the evolution of the disease, mouth opening measurements, presence/absence of teeth and presence/absence of mandibular osteolysis among patients with SS. By doing so, we might be able to fi nd evidence enabling a better comprehension of the alterations to the stomatognathic system and, in the future, institute preventive and/or curative measures that could improve the quality of life of SS patients. Material and Methods For this study, which was developed in the Department of Imaging Diagnostics, Federal University of São Paulo (UNIFESP), 25 patients of both sexes were selected. Fifteen of these individuals (mean age 43.72 ± 7.59 years) had diffuse SS and the other ten (mean age 31.82 ± 12.64 years) were normal. Patients who presented SS in a limited form or in association with other rheumatic diseases were excluded. This study obtained prior approval by the Research Ethics Committee, UNIFESP. All of the 25 subjects underwent oral clinical evaluation and panoramic radiography. The latter was performed on an orthopantomograph (Ortophos Plus PS®, Siemens – Sirona Dental Company, Bensheim, Germany), working at 14 mA and variable kVp of 60.16 for women and 64.14 for men, at a mean magnifi cation of 30%. The images were interpreted by the examiner and the 15 patients were distributed into two groups according to the radiographic fi ndings: with or without the presence of mandibular osteolysis (Figure 1). Thus, a total of three groups were formed: group I, with 7 SS patients presenting mandibular osteolysis; group II, with 8 SS patients without mandibular osteolysis; and group III, with 10 healthy, normal individuals (control group). The patients with SS (groups I and II) were interviewed individually, to gather information such as gender, age, time when the fi rst symptoms appeared and diffi culties in opening their mouths. The length of time that they Clinical and radiographic study of orofacial alterations in patients with systemic sclerosis Braz Oral Res 2009;23(1):82-8 84 had had the disease was obtained from their medical records. Following this, the patients underwent clinical examination to measure their mouth opening. In a comfortably seated position, with the head supported on a hard surface at 90° to the fl oor, the patients were asked to open their mouths as wide as possible, three times. Each movement was measured, and only the largest measurement was used. The same procedure was used to obtain this measurement for the healthy individuals. To make the measurements of maximum mouth opening, we used an adaptation of the linear interincisal distance method.12 The points of a dry-point compass were positioned on the middle third of the incisal aspect of the upper and lower right central incisors at maximum mouth opening, and this measurement was transferred to a ruler graduated in millimeters (Figure 2). The patient was then asked to perform the intercuspidation movement, from which the vertical trespass distance was obtained and subtracted from the compass measurement. If the right central incisors were absent, the left central incisors, right lateral incisors or left lateral incisors would be used, in that order. For the inferential analysis of the clinical variables, Pearson’s linear correlation coeffi cient, Student’s t test and Fisher’s exact test were used. The rejection level adopted for the nullity hypothesis was 0.05 (5%). Results The arithmetic mean and respective standard deviation for the age of the 25 patients was 39.71 ± 7.91 years. The results from the clinical variables studied among the patients with systemic sclerosis can be seen in Tables 1 and 2. Graph 1 shows the distribution of the groups in relation to the variable length of time with the disease. With the aim of investigating whether group I had had the disease for the same length of time as group II, Student’s t test was applied. The result from this showed that group I had had the disease Figure 1 Panoramic radiograph of the mandible presenting bilateral osteolysis of the angle, ascending branch and condyles. Figure 2 Measurement of maximum mouth opening between teeth 11 and 41. Marcucci M, Abdala N Braz Oral Res 2009;23(1):82-8 85 Patient Gender Age (y) Time of disease (y) Mouth opening (mm) Presence of the teeth


Introduction
Systemic sclerosis (SS) is a chronic infl ammatory disease of unknown origin and autoimmune nature characterized by excessive deposition of collagen and glycosaminoglycans in the conjunctive tissue of the dermis and internal organs. 1,2It is a disease of low incidence, with an average of 4 to 19 new cases per million inhabitants and preferentially affects females (4:1). 1 The age group most affected is between the third and fi fth decades of life. 3,4ts etiopathogenesis has not been completely clarifi ed.The conjunctive tissue undergoes a fi brosis process that is probably mediated by cytokines produced by lymphocytes and infl ammatory cells, particularly the transforming growth factor beta (TGF-β).The microcirculation undergoes a process of primary vasculitis, which in conjunction with differing vessel thicknesses may cause total obliteration of the vessel due to collagen deposition, thereby leading to clinical manifestations of varying degrees of severity. 1,2,3,5his disease presents a variety of clinical features.2][3] The thickening of the skin (scleroderma) presents an initial phase of edema that makes the skin swollen and shiny, followed by a hardening phase in which the skin starts to have a dried-out, rough and inelastic appearance, and a third phase in which, in most patients, the skin gradually starts to take on an atrophied and thin appearance. 1,3[8][9][10] Radiographically, some characteristic alterations caused by systemic sclerosis are observed in the maxillomandibular complex, such as thickening of the periodontal ligament and areas of osteolysis in the mandible.These areas coincide with the insertion zones of the lateral pterygoid, temporal and, particularly, the masseter muscle. 11he aim of the present study was to correlate the clinical variables during the evolution of the disease, mouth opening measurements, presence/absence of teeth and presence/absence of mandibular osteolysis among patients with SS.By doing so, we might be able to fi nd evidence enabling a better comprehension of the alterations to the stomatognathic system and, in the future, institute preventive and/or curative measures that could improve the quality of life of SS patients.

Material and Methods
For this study, which was developed in the Department of Imaging Diagnostics, Federal University of São Paulo (UNIFESP), 25 patients of both sexes were selected.Fifteen of these individuals (mean age 43.72 ± 7.59 years) had diffuse SS and the other ten (mean age 31.82 ± 12.64 years) were normal.Patients who presented SS in a limited form or in association with other rheumatic diseases were excluded.This study obtained prior approval by the Research Ethics Committee, UNIFESP.
All of the 25 subjects underwent oral clinical evaluation and panoramic radiography.The latter was performed on an orthopantomograph (Ortophos Plus PS ® , Siemens -Sirona Dental Company, Bensheim, Germany), working at 14 mA and variable kVp of 60.16 for women and 64.14 for men, at a mean magnifi cation of 30%.The images were interpreted by the examiner and the 15 patients were distributed into two groups according to the radiographic fi ndings: with or without the presence of mandibular osteolysis (Figure 1).
Thus, a total of three groups were formed: group I, with 7 SS patients presenting mandibular osteolysis; group II, with 8 SS patients without mandibular osteolysis; and group III, with 10 healthy, normal individuals (control group).The patients with SS (groups I and II) were interviewed individually, to gather information such as gender, age, time when the fi rst symptoms appeared and diffi culties in opening their mouths.The length of time that they had had the disease was obtained from their medical records.
Following this, the patients underwent clinical examination to measure their mouth opening.In a comfortably seated position, with the head supported on a hard surface at 90° to the fl oor, the patients were asked to open their mouths as wide as possible, three times.Each movement was measured, and only the largest measurement was used.The same procedure was used to obtain this measurement for the healthy individuals.
To make the measurements of maximum mouth opening, we used an adaptation of the linear interin-cisal distance method. 12The points of a dry-point compass were positioned on the middle third of the incisal aspect of the upper and lower right central incisors at maximum mouth opening, and this measurement was transferred to a ruler graduated in millimeters (Figure 2).
The patient was then asked to perform the intercuspidation movement, from which the vertical trespass distance was obtained and subtracted from the compass measurement.If the right central incisors were absent, the left central incisors, right lateral incisors or left lateral incisors would be used, in that order.For the inferential analysis of the clinical variables, Pearson's linear correlation coeffi cient, Student's t test and Fisher's exact test were used.The rejection level adopted for the nullity hypothesis was 0.05 (5%).

Results
The arithmetic mean and respective standard deviation for the age of the 25 patients was 39.71 ± 7.91 years.The results from the clinical variables studied among the patients with systemic sclerosis can be seen in Tables 1 and 2.
Graph 1 shows the distribution of the groups in relation to the variable length of time with the disease.With the aim of investigating whether group I had had the disease for the same length of time as group II, Student's t test was applied.The result from this showed that group I had had the disease      for a longer time than group II (p = 0.003).The results relating to the variable of mouth opening measurements among the patients in groups I and II are shown in Graph 2. To compare the means between the two groups, Student's t test was used.The result showed that the two groups had the same mean mouth opening (p = 0.280).
The pattern of the relationship between mouth opening and length of time with the disease according to the groups was investigated by estimating Pearson's linear correlation coeffi cient, as observed in dispersion plots.Pearson's linear correlation coeffi cient was found to be 0.676 (p = 0.095), and therefore it was considered that for the individuals in group I there was a moderate increasing linear correlation between mouth opening and length of time with the disease (Graph 3).For group II, the distribution of information on mouth opening and length of time with the disease did not show any visual relationship (Graph 4).This was also confi rmed by the fi nding that Pearson's linear correlation coeffi cient was 0.223 (p = 0.596).
With regard to the presence of teeth, the patients were classifi ed as possessing a full or a partial set of teeth.Patients were taken to have a partial set of teeth if they did not present a row of back teeth, which could be on one or both sides, in the upper and/or low jaw.Fisher's exact test for this association showed that there was no relationship between presence/absence of teeth and group (p > 0.999).

Discussion
Limitation of mouth opening is a common fi nding in SS cases and is possibly related to the skin thickening that is characteristic of the disease. 6,7,10,13,14The progressive loss of elasticity of the cheeks and lips makes these regions hardened and causes a gradual decrease in the lip perimeter and maximum mouth opening. 7In our study, this limitation was the patients' main complaint in relation to the stomatognathic system, because of their diffi culties in chewing or performing oral hygiene maneuvers, 10 or even in relation to undergoing dental treatment.Some techniques involving active exercises have been indicated with some success in achieving expansion of the mandibular movements. 7,13,14nly a few studies have sought to objectively quantify this reduction in mouth opening in systemic sclerosis cases. 6,10,15In our study, a mean measurement of 47 ± 5.1 mm was obtained among the healthy controls.Among the patients with osteolysis, the mean opening was 31 ± 7.39 mm, while among the patients without osteolysis, the mean was 36 ± 9.47 mm.In both the latter groups, the mean mouth opening was smaller than in the control group (p = 0.003 and p = 0.036 respectively).Comparing only the two groups with SS, the group with osteolysis presented the same mean opening as did the group without osteolysis (p = 0.280).These fi ndings do not agree with those found in the literature, in which the patients with osteolysis presented a slight decrease in opening in relation to those without osteolysis. 10,11n the other hand, when the variable of length of time with the disease was analyzed, it was seen that the patients with osteolysis had a moderate tendency towards increased mouth opening over the course of the years (p = 0.095), while among the pa- tients without osteolysis this trend was not observed (p = 0.596).One possible explanation for this fi nding could be the fact that the most intense skin thickening occurs within the fi rst 18 to 36 months of the disease, which is then followed by a variable period of stability, after which there is a slow and continuous decline, 3 such that the skin takes on an atrophied and thin appearance. 1,16Other factors, such as the number of patients studied, length of time with the disease and method used for measuring the mouth opening may cause variations in these results. 6,17In our sample, the patients reported transitory improvement following the use of an endovenous infusion of 2% lidocaine hydrochloride, which was used to attenuate the skin thickening. 1 Previous studies did not fi nd any direct relationship between the presence of osteolysis and the length of the course of the disease. 6,11,18However, osteolysis is detected between the fi fth and seventh year after diagnosing SS. 19 In our study, we observed that the patients with osteolysis presented a longer mean time with the disease (7.29 ± 1.8 years) than did the patients without osteolysis (5.75 ± 1.49 years) (p = 0.003).Considering that the systemic impairment caused by the disease is greater over the fi rst fi ve years of the disease 1 and the skin involvement is most intense over the fi rst three years, 3 it can be inferred that the emergence of mandibular osteolysis may be related both to the peak of skin involvement and to the visceral involvement, since osteolysis tends to occur in patients with greater visceral involvement. 19he extent of the osteolysis was not quantifi ed in our study but, rather, only its presence or absence.The rarity of the disease and the fact that mandibular osteolysis is present in a mean of 25% of the patients 10,11,17,18 makes it diffi cult to standardize the grades of osteolysis.For this reason, the samples in the literature have included osteolysis to varying extents. 6,17,18Moreover, some patients with the disease for a long time may present only slight degrees of osteolysis, while others who have just had the disease for a short time may present great destruction. 8oncerning the presence/absence of teeth, the results showed that this was unrelated to the presence of osteolysis.That is, osteolysis may develop both in patients with a full set of teeth and in those with only a partial set (p > 0.999).This fi nding confi rms the results from previous studies. 17,18In addition, we investigated the relationship between the side of the osteolysis and the presence/absence of teeth, and found that there was no association (p = 0.143).We did not fi nd any similar study with which we could compare or contrast this information.
We believe that new studies with different samples and methods are needed in order to bring out more evidence regarding the involvement of the stomatognathic system in patients with SS.Thus, longitudinal studies may provide predictive information about orofacial involvement in relation to the course of the disease.

Conclusions
According to our results, the patients with osteolysis presented longer times with the disease than did the group without osteolysis, but the presence of osteolysis did not infl uence the mouth opening measurement.We also observed that there was an increasing correlation between mouth opening and length of time with the disease among the patients with osteolysis, whereas this did not occur in the group without osteolysis.There was no relationship between presence/absence of teeth and osteolysis, or between presence/absence of teeth and side of osteolysis.

Figure 1 -
Figure 1 -Panoramic radiograph of the mandible presenting bilateral osteolysis of the angle, ascending branch and condyles.

Figure 2 -
Figure 2 -Measurement of maximum mouth opening between teeth 11 and 41.

Graph 1 -Graph 2 -
Boxplot of time with the disease (years) according to the groups.Boxplot of mouth opening (mm) according to the groups.

Graph 3 -Graph 4 -
Distribution of mouth opening and time of the disease: Group I. Distribution of mouth opening and time of the disease: Group II.

Table 1 -
Clinical values of group I: patients with osteolysis.

Table 2 -
Clinical values of group II: patients without osteolysis.