The Laryngoscope C 2014 The American Laryngological, V
Rhinological and Otological Society, Inc.
Prevalence of Sinonasal Disease in Children With Juvenile Idiopathic Arthritis Carlotta Pipolo, MD; Federica Turati, ScD; Paolo Cressoni, MD; Giampietro Farronato, MD; Francesca Angiero, MD; Umberto Garagiola, MD; Daniele Di Pasquale, MD; Alberto M. Saibene, MD; Riccardo Lenzi, MD; Giovanni Felisati, MD Objectives/Hypothesis: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and is caused by a multitude of well-studied disorders. However, the association between JIA and/or its treatment and sinonasal inflammatory disease (SNID) has never been studied. We therefore investigated this relationship to gain more insight into burdening pathologies connected to JIA. Study Design: Retrospective evaluation. Methods: A retrospective evaluation according to the Lund-Mackay score of cone-beam computed tomography scans (CBCT) performed in 70 children affected by JIA and compared to CBCT scans of 124 healthy controls was conducted. The prevalence of sinonasal opacification and adenoid hypertrophy in patients affected with JIA was compared with findings obtained in unaffected children. Results: JIA was significantly associated with SNID (P 5.030). Of patients with JIA, 18.6% had SNID, whereas in children without JIA, only 8.1% had SNID. The odds ratio values were 5.38 (95% confidence interval [CI]: 1.90-15.26) for treated and 0.92 (95% CI: 0.18-4.83) for untreated JIA. No clear difference was found depending on the duration of JIA. No association was found between adenoid hypertrophy and SNID (P 5.816). Conclusions: Our data suggest that JIA patients, especially when undergoing immunosuppressive therapy, should be subjected to an ear, nose, and throat evaluation. A prospective study including clinical evaluation would be of the utmost importance to provide evidence on which to base comprehensive healthcare for these patients. Key Words: Juvenile idiopathic arthritis, sinusitis, sinonasal disease, cone beam computed tomography, adenoid hypertrophy, Lund-Mackay score. Level of Evidence: 3b. Laryngoscope, 125:291–295, 2015
INTRODUCTION Chronic rhinosinusitis (CRS) is a common disease in children as well as adults. The true prevalence of pediatric CRS is unknown, but symptoms compatible with its diagnosis are reported in up to 20% of patients.1 Diagnosis of CRS is mainly clinical,2 but it is frequently confirmed through additional investigations, such as nasal endoscopy or computed tomography (CT) scans of the paranasal sinuses. CRS is one of the most frequent indications for a CT scan of the paranasal sinuses. However, whereas CT scanning is extremely useful in the symptomatic patient, especially in regard to surgical From the Otorhinolaryngology Unit, Head and Neck Department (C.P., D.D, A.M.S., R.L., G.FELISATI), San Paolo Hospital, University of Milan, Milan, Italy; Department of Epidemiology (F.T.), Institutes for Research, Hospitalization and Health Care–Mario Negri Institute for Pharmacological Research, Milan, Italy; and the Department of Orthodontics and Paediatric Dentistry (P.C., G.FARRONATO, F.A., U.G.), Institutes for Research, Hospitalization and Health Care–IRCCS Foundation Ca’ Granda, University of Milan, Milan, Italy. Editor’s Note: This Manuscript was accepted for publication July 21, 2014. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Carlotta Pipolo, MD, U.O. ORL, Via di Rudinı 8, 20142 Milan, Italy. E-mail: [email protected] DOI: 10.1002/lary.24881
Laryngoscope 125: February 2015
planning, the interpretation of positive CT findings in asymptomatic patients is controversial, because some degree of mucosal thickening and partial opacity can be present without pathological significance. Moreover, even in symptomatic patients, CT findings do not always correlate directly with the severity of symptoms.3 In an effort to objectify evaluation of the severity of CRS and to improve scientific communication between medical figures, numerous CT staging systems have been proposed. Although many believe that a high percentage of normal, healthy patients without sinusitis symptoms have abnormal findings on sinus CT, and that staging systems based solely on CT findings can thus be flawed, a recent report has in fact found good agreement between CT score and symptoms.4 Factors that may promote CRS in children include various allergies, infections, and anatomic abnormalities that can compromise mucus drainage. Immunological incompetence may also be an important etiologic factor for CRS, and is often found in refractory cases.5 Sinusitis in the immunocompromised host is therapeutically challenging: in this clinical subset, aggressive surveillance, across-the-board clinical suspicion, as well as early diagnosis and treatment are all critical aspects of sinusitis management.6 Pipolo et al.: Sinus Involvement in Juvenile Arthritis
291
Fig. 1. Cone-beam computed tomography scan of a juvenile idiopathic arthritis patient assessed with the multiplanar reformation module. The cross indicates the exact position on the other planes. The scan shows opacification of the left and right maxillary sinus and of the anterior ethmoid on the left and anterior and posterior ethmoid on the right. [Color figure can be viewed in the online issue, which is available at www.laryngoscope.com.]
The role of adalimumab (anti-tumor necrosis factor [TNF] monoclonal antibody) has been hypothesized as a risk factor in developing recurrent sinusitis.7 However, data concerning the influence of immunosuppressive drugs on the development of sinonasal inflammatory disease (SNID) are scant, and the role of autoimmune diseases and anti-inflammatory medications (often with consequent immune suppression) is unclear. Among types of autoimmune connectivitis, juvenile idiopathic arthritis (JIA) is the most common form in children, with a prevalence of 16 to 150:100,000.8 Its role as a promoting factor for SNID is still unclear. The objective of this study was to determine whether JIA (in itself and/or its treatment) is associated to a higher prevalence of sinus CT scans opacifications in a pediatric population. Threedimensional cone-beam CT scan (CBCT) findings in patients affected by JIA, treated or not treated with a wide range of anti-inflammatory agents (the majority having immune suppressive effects) were thus compared with findings obtained in unaffected children.
children, control group). All images were reviewed using the Mimics 8.1 software package (Materialise, Leuven, Belgium) in a multiplanar reformation module (axial, sagittal, and coronal slices) (Fig. 1). All images were assessed under standardized conditions at the same workstation. Three independent observers (two rhinologists and a general dentist) viewed all scans; cases of mismatch (seven patients) were discussed and classified by consensus agreement. Age, sex, time of year when CBCT was performed, adenoid hypertrophy (0 5 no hypertrophy, 1 5 partially obstructive, and 2 5 totally obstructive hypertrophy), and sinus opacification (according to the Lund-Mackay score9) were recorded. The Lund-Mackay staging system is currently one of the most validated scores for sinus CT evaluation10,11 and scores each sinus (anterior ethmoid, posterior ethmoid, maxillary, frontal, and sphenoid sinuses) according to the following scale: 0 5 no opacification, 1 5 partial opacification, 2 5 complete opacification. The ostiomeatal complex is scored as 0 5 not occluded or 2 5 occluded.9 Left and right sides are staged separately, and the scores are summed so that a patient’s total Lund score may range from 0 to 24. We considered as pathological (i.e., consistent with SNID) CT scores 5.12 The medical charts of patients affected by JIA were reviewed, and disease duration and therapy (if any) were recorded.
MATERIALS AND METHODS Subjects
Aims
All CBCT scans performed between 2007 and 2013 in patients aged 4 to 19 years, under treatment at the outpatient clinic of the Department of Orthodontics and Paediatric Dentistry, University of Milan, were evaluated retrospectively.
The primary aim of this study was to determine whether JIA itself, and/or its treatment, influences the prevalence of SNID (defined as Lund-Mackay score 5) in children. The secondary aim was to evaluate the influence of adenoid hypertrophy on the prevalence of SNID in children.
Measurements CT scans were performed for temporomandibular joint disorders in 70 patients affected by JIA (study group), and as pretreatment assessment in dysgnathia in all other patients (124
Laryngoscope 125: February 2015
292
Data Analysis The association between JIA, adenoid hypertrophy, and SNID was assessed through the v2 test for independence and by
Pipolo et al.: Sinus Involvement in Juvenile Arthritis
TABLE I. Study Subjects Characteristics According to JIA Status. Children With JIA
Age, quartiles* I
Children Without JIA
No.
%
No.
%
(95% CI: 1.90-15.26) for treated and 0.92 (95% CI: 0.184.83) for untreated JIA. No clear difference was found according to the duration of JIA. No association was found between adenoid hypertrophy and SNID (P 5.816).
23
32.9
22
17.7
DISCUSSION
II
12
17.1
28
22.6
III IV
17 18
24.3 25.7
39 35
31.5 28.2
13 57
18.6 81.4
57 67
46.0 54.0
57 13
81.4 18.6
114 10
91.9 8.1
Inflammatory sinus disease is considered to be one of the most frequent disorders in children, and many studies have examined its clinical prevalence in the pediatric population.13 For obvious reasons (exposure to radiation) no large studies on the prevalence of sinus opacification in CT scans of children have been published in the recent past. However, the use of threedimensional CBCT scanning for various maxillofacial diagnostic purposes is becoming more frequent even in children because this type of beam, which uses an image intensifier, can produce an image with significantly less radiation than traditional CT.14 Many risk factors for SNID have been hypothesized, including adenoidal hypertrophy and septal deviations. Because SNID itself, and especially its complications, might have an important negative influence on the lives of children, the addition or exclusion of further risk factors has to be considered of pivotal importance. For this purpose, we hypothesized that a common autoimmune disease in children, such as JIA, and/or its treatment, might be a risk factor for the development of SNID. Although they may not be fully applicable to SNID, some considerations have been reported concerning opportunistic systemic infections, which might shed some light on the mechanism of development of SNID in JIA. In 2012, Beukelman et al. reported a significant increase in infection rates in JIA patients undergoing therapy with high-dosage corticosteroids, versus those taking no such therapy.15 In 2013, in a large observational study, the same group reported that the incidence of opportunistic infections in JIA patients, which was higher than in the control group, was not influenced by MTX or TNF inhibitor therapy.16 However, the rarity of opportunistic infections limits the validity of these findings. In our study, the JIA group comprised 81% females, which is easily explained by the higher prevalence at all ages of JIA in females than in males, and makes the group more plausible in terms of its representativeness.17 Our data show that 18.6% of patients with JIA have SNID, whereas in children without JIA, only 8.1% have SNID. No significant association between duration of JIA (1–2 years vs. more than 2 years) and incidence of SNID was observed. If JIA treated with immunosuppressive drugs is considered separately from untreated JIA, the OR of SNID is 5.38 for treated JIA versus 0.92 for untreated JIA. This suggests that immunosuppressive medications are risk factors for developing SNID, rather than JIA itself. Because treated JIA is presumably in an active phase, it is difficult to draw definitive conclusions about the effects of immunosuppressive drugs on SNID. Based on these results, there is no association between adenoidal hypertrophy and SNID.
Sex Male Female SNID† No Yes Children with JIA Treatment No
29
41.4
Yes
41
58.6
MTX therapy Etanercept
29 16
NSAIDs
19
Cortisone Total
1 70
124
*Quartiles among children without JIA (i.e., 2 years
9
27
3.80 (1.41–10.26)
4.46 (1.52–13.09)
13 (56.5)
101 (59.1)
1§
1§
10 (43.5)
70 (40.9)
1.11 (0.46–2.67)
1.00 (0.40–2.51)
Adenoid hypertrophy No Yes P 5.816k
*Presence of SNID was defined as Lund-Mackay score 5. † Crude OR. ‡ OR adjusted for age, sex, and season. § Reference category. k P for v2 test. ¶ Any treatment (i.e., methotrexate therapy, etanercept, cortisone) excluding nonsteroidal anti-inflammatory drugs. # The sum does not add up to the total because of some missing values. CI 5 confidence interval; CT 5computed tomography; OR 5 odds ratio; SNID 5 sinonasal inflammatory disease.
A major limitation of our study was that SNID was classified based on sinus opacification on CBCT scan alone, because no clinical data regarding sinonasal symptomatology were available. Nevertheless, although previous studies reported that CT findings do not always correlate directly with the severity of symptoms,3 good agreement between CT scores and symptoms has recently been reported.4 Moreover, the chosen cutoff point (Lund-Mackay score 5) possesses a high positive predictive value as described by Bhattacharyya.12 Additionally, it should be emphasized that the reporting of signs and symptoms, particularly in children, requires some caution. Reliability can be an issue, and often airway symptoms are dismissed and accepted as a normal part of living in a metropolitan area, known for environmental pollution and smog.14 Furthermore, the presence of sinus opacification in a potentially immunocompromised patient undoubtedly should be regarded as being more prone to intervention than normal subjects. Current literature states that almost 80% of JIA patients suffer from some degree of temporomandibular joint disorders18 and will therefore undergo some kind of CT imaging of the maxillofacial area. A thorough evaluation of the neighboring structures, including the sinuses, though initially only on the scan, is therefore to be kept in mind when assessing JIA patients with temporomanLaryngoscope 125: February 2015
294
dibular joint disorders. For clinical diagnosis, CT data must of course be complemented with nasal endoscopy and evaluation by an ear, nose, and throat specialist, then interpreted together with a full history of clinical signs and symptoms, so as to avoid either overemphasizing or overlooking the disease.
CONCLUSION Our data suggest that JIA patients, especially those undergoing immunosuppressive therapy, should be subjected to ear, nose, and throat evaluation. A prospective study, including clinical evaluation, would be of the utmost importance to determine more precisely the incidence of SNID in JIA, and to provide evidence on which to base comprehensive healthcare for these patients.
BIBLIOGRAPHY 1. Clement PA, Gordts F. Epidemiology and prevalence of aspecific chronic sinusitis. Int J Pediatr Otolaryngol 1999;49(suppl 1):S101–S103. 2. Fokkens WJ, Lund VJ, Mullol J, et al. The European position paper on rhinosinusitis and nasal polyps 2012. Rhinology 2012;(suppl 23):1–298. 3. Stewart MG, Johnson RF. Chronic rhinosinusitis: symptoms versus CT scan findings [review]. Curr Opin Otolaryngol Head Neck Surg 2004;12: 27–29. 4. Wittkopf ML, Beddow PA, Russel PT, Duncavage JA, Becker SS. Revisiting the interpretation of positive sinus CT findings: a radiological and symptom-based review. Otolaryngol Head Neck Surg 2009;140:306– 311.
Pipolo et al.: Sinus Involvement in Juvenile Arthritis
5. Shapiro GG, Virant FS, Furukawa CT, Pierson WE, Bierman CW. Immunologic defects in patients with refractory sinusitis. Pediatrics 1991;87:311–316. 6. Decker CF. Sinusitis in the immunocompromised host. Curr Infect Dis Rep 1999;1:27–32. 7. Haroon M, Bond U, Phelan M. Sinusitis: a possible link with adalimumab. Clin Rheumatol 2008;27:1189–1190. 8. Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet 2007;369:767– 778. 9. Lund VJ, Mackay IS. Staging in rhinosinusitis. Rhinology 1993;31:183– 184. 10. Bhattacharyya N. Comparison of symptom scores and radiographic staging systems in chronic rhinosinusitis. Am J Rhinol 2005;19:175–179. 11. Hopkins C, Browne JP, Slack R, Lund V, Brown P. The Lund-Mackay staging system for chronic rhinosinusitis: how is it used and what does it predict? Otolaryngol Head Neck Surg 2007;137:555–561. 12. Bhattacharyya N, Jones DT, Hill M, Shapiro NL. The diagnostic accuracy of computed tomography in pediatric chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg 2004;130:1029–1032.
Laryngoscope 125: February 2015
13. Aitken M, Taylor JA. Prevalence of clinical sinusitis in young children followed up by primary care pediatricians. Arch Pediatr Adolesc Med 1998; 152:244–248. 14. Cha JY, Mah J, Sinclair P. Incidental findings in the maxillofacial area with 3-dimensional cone-beam imaging. Am J Orthod Dentofacial Orthop 2007;132:7–14. 15. Beukelman T, Xie F, Chen L, et al.; SABER Collaboration. Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum 2012;64:2773–2780. 16. Beukelman T, Xie F, Baddley JW, et al.; SABER Collaboration. Brief report: incidence of selected opportunistic infections among children with juvenile idiopathic arthritis. Arthritis Rheum 2013;65:1384–1389. 17. Danner S, Sordet C, Terzic J, et al. Epidemiology of juvenile idiopathic arthritis in Alsace, France. J Rheumatol 2006;33:1377–1381. 18. Billiau AD, Hu Y, Verdonck A, Carels C, Wouters C. Temporomandibular joint arthritis in juvenile idiopathic arthritis: prevalence, clinical and radiological signs, and relation to dentofacial morphology. J Rheumatol 2007;34:1925–1933.
Pipolo et al.: Sinus Involvement in Juvenile Arthritis
295
Rhinological and Otological Society, Inc.
Prevalence of Sinonasal Disease in Children With Juvenile Idiopathic Arthritis Carlotta Pipolo, MD; Federica Turati, ScD; Paolo Cressoni, MD; Giampietro Farronato, MD; Francesca Angiero, MD; Umberto Garagiola, MD; Daniele Di Pasquale, MD; Alberto M. Saibene, MD; Riccardo Lenzi, MD; Giovanni Felisati, MD Objectives/Hypothesis: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and is caused by a multitude of well-studied disorders. However, the association between JIA and/or its treatment and sinonasal inflammatory disease (SNID) has never been studied. We therefore investigated this relationship to gain more insight into burdening pathologies connected to JIA. Study Design: Retrospective evaluation. Methods: A retrospective evaluation according to the Lund-Mackay score of cone-beam computed tomography scans (CBCT) performed in 70 children affected by JIA and compared to CBCT scans of 124 healthy controls was conducted. The prevalence of sinonasal opacification and adenoid hypertrophy in patients affected with JIA was compared with findings obtained in unaffected children. Results: JIA was significantly associated with SNID (P 5.030). Of patients with JIA, 18.6% had SNID, whereas in children without JIA, only 8.1% had SNID. The odds ratio values were 5.38 (95% confidence interval [CI]: 1.90-15.26) for treated and 0.92 (95% CI: 0.18-4.83) for untreated JIA. No clear difference was found depending on the duration of JIA. No association was found between adenoid hypertrophy and SNID (P 5.816). Conclusions: Our data suggest that JIA patients, especially when undergoing immunosuppressive therapy, should be subjected to an ear, nose, and throat evaluation. A prospective study including clinical evaluation would be of the utmost importance to provide evidence on which to base comprehensive healthcare for these patients. Key Words: Juvenile idiopathic arthritis, sinusitis, sinonasal disease, cone beam computed tomography, adenoid hypertrophy, Lund-Mackay score. Level of Evidence: 3b. Laryngoscope, 125:291–295, 2015
INTRODUCTION Chronic rhinosinusitis (CRS) is a common disease in children as well as adults. The true prevalence of pediatric CRS is unknown, but symptoms compatible with its diagnosis are reported in up to 20% of patients.1 Diagnosis of CRS is mainly clinical,2 but it is frequently confirmed through additional investigations, such as nasal endoscopy or computed tomography (CT) scans of the paranasal sinuses. CRS is one of the most frequent indications for a CT scan of the paranasal sinuses. However, whereas CT scanning is extremely useful in the symptomatic patient, especially in regard to surgical From the Otorhinolaryngology Unit, Head and Neck Department (C.P., D.D, A.M.S., R.L., G.FELISATI), San Paolo Hospital, University of Milan, Milan, Italy; Department of Epidemiology (F.T.), Institutes for Research, Hospitalization and Health Care–Mario Negri Institute for Pharmacological Research, Milan, Italy; and the Department of Orthodontics and Paediatric Dentistry (P.C., G.FARRONATO, F.A., U.G.), Institutes for Research, Hospitalization and Health Care–IRCCS Foundation Ca’ Granda, University of Milan, Milan, Italy. Editor’s Note: This Manuscript was accepted for publication July 21, 2014. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Carlotta Pipolo, MD, U.O. ORL, Via di Rudinı 8, 20142 Milan, Italy. E-mail: [email protected] DOI: 10.1002/lary.24881
Laryngoscope 125: February 2015
planning, the interpretation of positive CT findings in asymptomatic patients is controversial, because some degree of mucosal thickening and partial opacity can be present without pathological significance. Moreover, even in symptomatic patients, CT findings do not always correlate directly with the severity of symptoms.3 In an effort to objectify evaluation of the severity of CRS and to improve scientific communication between medical figures, numerous CT staging systems have been proposed. Although many believe that a high percentage of normal, healthy patients without sinusitis symptoms have abnormal findings on sinus CT, and that staging systems based solely on CT findings can thus be flawed, a recent report has in fact found good agreement between CT score and symptoms.4 Factors that may promote CRS in children include various allergies, infections, and anatomic abnormalities that can compromise mucus drainage. Immunological incompetence may also be an important etiologic factor for CRS, and is often found in refractory cases.5 Sinusitis in the immunocompromised host is therapeutically challenging: in this clinical subset, aggressive surveillance, across-the-board clinical suspicion, as well as early diagnosis and treatment are all critical aspects of sinusitis management.6 Pipolo et al.: Sinus Involvement in Juvenile Arthritis
291
Fig. 1. Cone-beam computed tomography scan of a juvenile idiopathic arthritis patient assessed with the multiplanar reformation module. The cross indicates the exact position on the other planes. The scan shows opacification of the left and right maxillary sinus and of the anterior ethmoid on the left and anterior and posterior ethmoid on the right. [Color figure can be viewed in the online issue, which is available at www.laryngoscope.com.]
The role of adalimumab (anti-tumor necrosis factor [TNF] monoclonal antibody) has been hypothesized as a risk factor in developing recurrent sinusitis.7 However, data concerning the influence of immunosuppressive drugs on the development of sinonasal inflammatory disease (SNID) are scant, and the role of autoimmune diseases and anti-inflammatory medications (often with consequent immune suppression) is unclear. Among types of autoimmune connectivitis, juvenile idiopathic arthritis (JIA) is the most common form in children, with a prevalence of 16 to 150:100,000.8 Its role as a promoting factor for SNID is still unclear. The objective of this study was to determine whether JIA (in itself and/or its treatment) is associated to a higher prevalence of sinus CT scans opacifications in a pediatric population. Threedimensional cone-beam CT scan (CBCT) findings in patients affected by JIA, treated or not treated with a wide range of anti-inflammatory agents (the majority having immune suppressive effects) were thus compared with findings obtained in unaffected children.
children, control group). All images were reviewed using the Mimics 8.1 software package (Materialise, Leuven, Belgium) in a multiplanar reformation module (axial, sagittal, and coronal slices) (Fig. 1). All images were assessed under standardized conditions at the same workstation. Three independent observers (two rhinologists and a general dentist) viewed all scans; cases of mismatch (seven patients) were discussed and classified by consensus agreement. Age, sex, time of year when CBCT was performed, adenoid hypertrophy (0 5 no hypertrophy, 1 5 partially obstructive, and 2 5 totally obstructive hypertrophy), and sinus opacification (according to the Lund-Mackay score9) were recorded. The Lund-Mackay staging system is currently one of the most validated scores for sinus CT evaluation10,11 and scores each sinus (anterior ethmoid, posterior ethmoid, maxillary, frontal, and sphenoid sinuses) according to the following scale: 0 5 no opacification, 1 5 partial opacification, 2 5 complete opacification. The ostiomeatal complex is scored as 0 5 not occluded or 2 5 occluded.9 Left and right sides are staged separately, and the scores are summed so that a patient’s total Lund score may range from 0 to 24. We considered as pathological (i.e., consistent with SNID) CT scores 5.12 The medical charts of patients affected by JIA were reviewed, and disease duration and therapy (if any) were recorded.
MATERIALS AND METHODS Subjects
Aims
All CBCT scans performed between 2007 and 2013 in patients aged 4 to 19 years, under treatment at the outpatient clinic of the Department of Orthodontics and Paediatric Dentistry, University of Milan, were evaluated retrospectively.
The primary aim of this study was to determine whether JIA itself, and/or its treatment, influences the prevalence of SNID (defined as Lund-Mackay score 5) in children. The secondary aim was to evaluate the influence of adenoid hypertrophy on the prevalence of SNID in children.
Measurements CT scans were performed for temporomandibular joint disorders in 70 patients affected by JIA (study group), and as pretreatment assessment in dysgnathia in all other patients (124
Laryngoscope 125: February 2015
292
Data Analysis The association between JIA, adenoid hypertrophy, and SNID was assessed through the v2 test for independence and by
Pipolo et al.: Sinus Involvement in Juvenile Arthritis
TABLE I. Study Subjects Characteristics According to JIA Status. Children With JIA
Age, quartiles* I
Children Without JIA
No.
%
No.
%
(95% CI: 1.90-15.26) for treated and 0.92 (95% CI: 0.184.83) for untreated JIA. No clear difference was found according to the duration of JIA. No association was found between adenoid hypertrophy and SNID (P 5.816).
23
32.9
22
17.7
DISCUSSION
II
12
17.1
28
22.6
III IV
17 18
24.3 25.7
39 35
31.5 28.2
13 57
18.6 81.4
57 67
46.0 54.0
57 13
81.4 18.6
114 10
91.9 8.1
Inflammatory sinus disease is considered to be one of the most frequent disorders in children, and many studies have examined its clinical prevalence in the pediatric population.13 For obvious reasons (exposure to radiation) no large studies on the prevalence of sinus opacification in CT scans of children have been published in the recent past. However, the use of threedimensional CBCT scanning for various maxillofacial diagnostic purposes is becoming more frequent even in children because this type of beam, which uses an image intensifier, can produce an image with significantly less radiation than traditional CT.14 Many risk factors for SNID have been hypothesized, including adenoidal hypertrophy and septal deviations. Because SNID itself, and especially its complications, might have an important negative influence on the lives of children, the addition or exclusion of further risk factors has to be considered of pivotal importance. For this purpose, we hypothesized that a common autoimmune disease in children, such as JIA, and/or its treatment, might be a risk factor for the development of SNID. Although they may not be fully applicable to SNID, some considerations have been reported concerning opportunistic systemic infections, which might shed some light on the mechanism of development of SNID in JIA. In 2012, Beukelman et al. reported a significant increase in infection rates in JIA patients undergoing therapy with high-dosage corticosteroids, versus those taking no such therapy.15 In 2013, in a large observational study, the same group reported that the incidence of opportunistic infections in JIA patients, which was higher than in the control group, was not influenced by MTX or TNF inhibitor therapy.16 However, the rarity of opportunistic infections limits the validity of these findings. In our study, the JIA group comprised 81% females, which is easily explained by the higher prevalence at all ages of JIA in females than in males, and makes the group more plausible in terms of its representativeness.17 Our data show that 18.6% of patients with JIA have SNID, whereas in children without JIA, only 8.1% have SNID. No significant association between duration of JIA (1–2 years vs. more than 2 years) and incidence of SNID was observed. If JIA treated with immunosuppressive drugs is considered separately from untreated JIA, the OR of SNID is 5.38 for treated JIA versus 0.92 for untreated JIA. This suggests that immunosuppressive medications are risk factors for developing SNID, rather than JIA itself. Because treated JIA is presumably in an active phase, it is difficult to draw definitive conclusions about the effects of immunosuppressive drugs on SNID. Based on these results, there is no association between adenoidal hypertrophy and SNID.
Sex Male Female SNID† No Yes Children with JIA Treatment No
29
41.4
Yes
41
58.6
MTX therapy Etanercept
29 16
NSAIDs
19
Cortisone Total
1 70
124
*Quartiles among children without JIA (i.e., 2 years
9
27
3.80 (1.41–10.26)
4.46 (1.52–13.09)
13 (56.5)
101 (59.1)
1§
1§
10 (43.5)
70 (40.9)
1.11 (0.46–2.67)
1.00 (0.40–2.51)
Adenoid hypertrophy No Yes P 5.816k
*Presence of SNID was defined as Lund-Mackay score 5. † Crude OR. ‡ OR adjusted for age, sex, and season. § Reference category. k P for v2 test. ¶ Any treatment (i.e., methotrexate therapy, etanercept, cortisone) excluding nonsteroidal anti-inflammatory drugs. # The sum does not add up to the total because of some missing values. CI 5 confidence interval; CT 5computed tomography; OR 5 odds ratio; SNID 5 sinonasal inflammatory disease.
A major limitation of our study was that SNID was classified based on sinus opacification on CBCT scan alone, because no clinical data regarding sinonasal symptomatology were available. Nevertheless, although previous studies reported that CT findings do not always correlate directly with the severity of symptoms,3 good agreement between CT scores and symptoms has recently been reported.4 Moreover, the chosen cutoff point (Lund-Mackay score 5) possesses a high positive predictive value as described by Bhattacharyya.12 Additionally, it should be emphasized that the reporting of signs and symptoms, particularly in children, requires some caution. Reliability can be an issue, and often airway symptoms are dismissed and accepted as a normal part of living in a metropolitan area, known for environmental pollution and smog.14 Furthermore, the presence of sinus opacification in a potentially immunocompromised patient undoubtedly should be regarded as being more prone to intervention than normal subjects. Current literature states that almost 80% of JIA patients suffer from some degree of temporomandibular joint disorders18 and will therefore undergo some kind of CT imaging of the maxillofacial area. A thorough evaluation of the neighboring structures, including the sinuses, though initially only on the scan, is therefore to be kept in mind when assessing JIA patients with temporomanLaryngoscope 125: February 2015
294
dibular joint disorders. For clinical diagnosis, CT data must of course be complemented with nasal endoscopy and evaluation by an ear, nose, and throat specialist, then interpreted together with a full history of clinical signs and symptoms, so as to avoid either overemphasizing or overlooking the disease.
CONCLUSION Our data suggest that JIA patients, especially those undergoing immunosuppressive therapy, should be subjected to ear, nose, and throat evaluation. A prospective study, including clinical evaluation, would be of the utmost importance to determine more precisely the incidence of SNID in JIA, and to provide evidence on which to base comprehensive healthcare for these patients.
BIBLIOGRAPHY 1. Clement PA, Gordts F. Epidemiology and prevalence of aspecific chronic sinusitis. Int J Pediatr Otolaryngol 1999;49(suppl 1):S101–S103. 2. Fokkens WJ, Lund VJ, Mullol J, et al. The European position paper on rhinosinusitis and nasal polyps 2012. Rhinology 2012;(suppl 23):1–298. 3. Stewart MG, Johnson RF. Chronic rhinosinusitis: symptoms versus CT scan findings [review]. Curr Opin Otolaryngol Head Neck Surg 2004;12: 27–29. 4. Wittkopf ML, Beddow PA, Russel PT, Duncavage JA, Becker SS. Revisiting the interpretation of positive sinus CT findings: a radiological and symptom-based review. Otolaryngol Head Neck Surg 2009;140:306– 311.
Pipolo et al.: Sinus Involvement in Juvenile Arthritis
5. Shapiro GG, Virant FS, Furukawa CT, Pierson WE, Bierman CW. Immunologic defects in patients with refractory sinusitis. Pediatrics 1991;87:311–316. 6. Decker CF. Sinusitis in the immunocompromised host. Curr Infect Dis Rep 1999;1:27–32. 7. Haroon M, Bond U, Phelan M. Sinusitis: a possible link with adalimumab. Clin Rheumatol 2008;27:1189–1190. 8. Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet 2007;369:767– 778. 9. Lund VJ, Mackay IS. Staging in rhinosinusitis. Rhinology 1993;31:183– 184. 10. Bhattacharyya N. Comparison of symptom scores and radiographic staging systems in chronic rhinosinusitis. Am J Rhinol 2005;19:175–179. 11. Hopkins C, Browne JP, Slack R, Lund V, Brown P. The Lund-Mackay staging system for chronic rhinosinusitis: how is it used and what does it predict? Otolaryngol Head Neck Surg 2007;137:555–561. 12. Bhattacharyya N, Jones DT, Hill M, Shapiro NL. The diagnostic accuracy of computed tomography in pediatric chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg 2004;130:1029–1032.
Laryngoscope 125: February 2015
13. Aitken M, Taylor JA. Prevalence of clinical sinusitis in young children followed up by primary care pediatricians. Arch Pediatr Adolesc Med 1998; 152:244–248. 14. Cha JY, Mah J, Sinclair P. Incidental findings in the maxillofacial area with 3-dimensional cone-beam imaging. Am J Orthod Dentofacial Orthop 2007;132:7–14. 15. Beukelman T, Xie F, Chen L, et al.; SABER Collaboration. Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum 2012;64:2773–2780. 16. Beukelman T, Xie F, Baddley JW, et al.; SABER Collaboration. Brief report: incidence of selected opportunistic infections among children with juvenile idiopathic arthritis. Arthritis Rheum 2013;65:1384–1389. 17. Danner S, Sordet C, Terzic J, et al. Epidemiology of juvenile idiopathic arthritis in Alsace, France. J Rheumatol 2006;33:1377–1381. 18. Billiau AD, Hu Y, Verdonck A, Carels C, Wouters C. Temporomandibular joint arthritis in juvenile idiopathic arthritis: prevalence, clinical and radiological signs, and relation to dentofacial morphology. J Rheumatol 2007;34:1925–1933.
Pipolo et al.: Sinus Involvement in Juvenile Arthritis
295
