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The Temporomandibular Joint in Juvenile Idiopathic Arthritis: Psychosocial, clinical, imaging and parotid saliva biomarkers
Malmö universitet, Odontologiska fakulteten (OD).ORCID-id: 0000-0002-2260-8442
2024 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The disease can affect the temporomandibular joint (TMJ) and cause orofacial growth disturbances, pain, and jaw dysfunction. TMJ arthritis is often asymptomatic and therefore a challenging joint to diagnose. Clinical assessment of the TMJ is hampered by the low sensitivity and specificity of joint pain and the absence of physical findings early in the disease process. More specific methods are therefore needed for diagnosing TMJ arthritis. Saliva and blood are promising as diagnostic fluids for various diseases. Also, adolescents with chronic pain report high rates of psychosocial stress. Psychosocial stress may also be involved in JIA as a trigger and maintaining factor of the disease. Aim: The main aim of this thesis research was to investigate the relation between clinical variables, psychosocial factors, MRI findings, and inflammatory biomarkers in saliva and blood in relation to TMJ involvement in JIA. The secondary aim was to investigate the relation between stress and change in stress over time in comparison with orofacial pain, psychosocial factors, and jaw function in JIA patients. Methods: This was a cross-sectional case-control study and a longitudinal cohort study. Forty-five patients (6-16 years old) with JIA and 16 healthy age- and sex-matched healthy individuals were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The study subjects completed questionnaires regarding psychosocial factors and underwent bilateral MRI of their TMJs. Unstimulated parotid saliva and venous blood samples were collected. Biochemical analyses were performed using a multiplex platform electrochemiluminescence assay from Meso Scale Discovery (MSD) for measuring cytokine concentrations in saliva and blood. A two-year prospective follow-up study was performed in 40 JIA patients from our original baseline study. The JIA patients underwent the same clinical examination and completed the same questionnaires regarding psychosocial factors as in the baseline studies. Results: The JIA patients with orofacial pain had higher degrees of stress, depression, catastrophizing, and jaw dysfunction than did those JIA patients without such pain. These factors were also associated with orofacial pain intensity. Additionally, patients with orofacial pain had higher systemic inflammatory activity. In the two-year follow-up study, we observed that change in stress was associated with changes in catastrophizing, psychological distress, as well as limitations in both general and jaw functions. Regarding TMJ MRI findings, there were no significant differences between JIA patients and healthy individuals in either the inflammatory or damage domain. Moderate/severe TMJ changes in the inflammatory and damage domains were, however, only found in the JIA patients. Among JIA patients, orofacial pain intensity was correlated to TMJ bone marrow edema, and pain in jaw muscles during jaw function was related to both TMJ bone marrow edema and erosion. JIA patients had lower concentrations of interleukin receptor 6 (IL-6R) and glycoprotein 130 (gp130) in parotid saliva than in plasma. Higher concentrations of IL-6 were found in parotid saliva than in plasma. The members of the interleukin-6 family (i.e., IL-6, IL-6R, and gp130) in parotid saliva were found to be explanatory factors for the presence of bone marrow edema and effusion in the JIA patients. Conclusions: Orofacial pain in patients with JIA is associated with stress, psychological distress, jaw dysfunction, and loss of daily living activities. Pain intensity seems to be the major aspect related to these factors. Increased disease activity with more joint involvement seems to be an important factor contributing to orofacial pain in JIA. Myalgia, in addition to arthritis, seems to be an important source of orofacial pain in these patients. Maintaining a low stress level in JIA patients seems to be crucial, as an increase in stress level over a two-year period appears to negatively impact both jaw function as well as psychosocial distress and catastrophizing. There was an overlap of TMJ MRI findings regarding signs of inflammatory and bone tissue changes between JIA patients and healthy individuals. Among, JIA patients, the presence of inflammatory MRI signs, and bone marrow edema seems to worsen orofacial pain intensity. The IL-6 family in parotid saliva is associated with TMJ bone marrow edema and effusion in patients with JIA, suggesting that IL-6 has promising properties as a parotid saliva biomarker of TMJ inflammatory activity. In addition there seems to be local production of the IL-6 family in the parotid gland in JIA patients and healthy individuals. However, parotid saliva does not seem to reflect the plasma content in terms of the investigated biomarkers in JIA.

Abstract [sv]

Juvenil idiopatisk artrit (JIA) är ett samlingsbegrepp för kroniska ledinflammatoriska sjukdomar hos barn. I Sverige insjuknar årligen ungefär 200 barn. För att få diagnosen JIA skall debuten ske före 16 års ålder. Vid JIA kan de flesta leder drabbas med olika problem som följd. Den här avhandlingen fokuserar på käkleden där inflammation (käkledsartrit) på grund av JIA kan orsaka smärta, brosk- och bennedbrytning och nedsatt käkfunktion. Inflammationen kan även påverka tillväxt så att patienterna kan få en liten haka och öppet bett. Samtidigt är det så att många barn med JIA i käkleden inte upplever några symtom, trots en pågående käkledsinflammation. Detta gör det mycket svårt att upptäcka sjukdomen i käkleden tidigt. Idag saknas etablerade och validerade kliniska diagnostiska kriterier för att identifiera patienter med käkledsartrit. Det betyder att metodik för att undersöka patienter och definition av käkledsartrit vid JIA varierar avsevärt, både i det kliniska arbetet och i vetenskapliga studier samt mellan olika kliniker och länder. Syftet med denna avhandling var att undersöka hur smärta och funktion i käksystemet relaterar till generell inflammatorisk aktivitet, biomarkörer i parotissaliv och blod, inflammatoriska förändringar i käkled och psykosociala faktorer, både vid första undersökningen och över en två-årsperiod. Avhandlingen visar bland annat att smärta i käksystemet har tydliga samband med stress och nedsatt käkfunktion där smärtintensiteten verkar vara den viktigaste faktorn. Ökad stress över en två-årsperiod är associerad med försämrad käkfunktion och mående. Det finns ett överlapp av fynd på magnetkamera vad gäller käkledsförändringar mellan patienter med JIA och friska kontroller. Hos patienterna med JIA förefaller benmärgsöden i käkledshuvudet vara relaterat till smärta i käksystemet. När det gäller de inflammationssubstanser vi undersökte i saliv visar denna avhandling att Interleukin-6-familjen möjligen kan ha egenskaper som biomarkör relaterat till benmärgsödem i käkledshuvudet. Sjukdomen JIA är en klinisk utmaning att identifiera, diagnostisera, följa och behandla vad gäller käkleden. Här behövs mycket mer forskning där ett viktigt steg är att etablera valida diagnostiska kriterier. De drabbade barnen kan idag få stora skador i käkleden, ibland med associerad smärta och nedsatt käkfunktion. Sammanfattningsvis visar avhandlingen att stress samt smärta och käkfunktion i hela käksystemet är viktiga faktorer att undersöka och ta med i den kliniska bedömningen och behandlingen. Det överlapp av fynd från käkleden vid undersökning med magnetkamera mellan barn med JIA och friska kontrollen innebär att man behöver tolka fynd från magnetkamera med försiktighet.

Ort, förlag, år, upplaga, sidor
Malmö: Malmö University Press, 2024. , s. 90
Serie
Malmö University Odontological Dissertations, ISSN 1650-6065
Nyckelord [en]
Biomarkers, Juvenile Idiopathic Arthritis, Magnetic resonance imaging, Orofacial pain, Parotid gland, Plasma, Psychological distress, Psychosocial, Saliva, Stress, Temporomandibular joint
Nyckelord [sv]
Biomarkörer, Juvenil idiopatisk artrit, Käkled, Magnetisk resonanstomografi, Orofacial smärta, Saliv, Spottkörtel, Stress
Nationell ämneskategori
Odontologi
Identifikatorer
URN: urn:nbn:se:mau:diva-66397DOI: 10.24834/isbn.9789178773763ISBN: 978-91-7877-375-6 (tryckt)ISBN: 978-91-7877-376-3 (digital)OAI: oai:DiVA.org:mau-66397DiVA, id: diva2:1846159
Disputation
2024-04-19, Faculty of Odontology, Aulan (KL:2370), Smedjegatan 16, Malmö, 09:15 (Svenska)
Opponent
Handledare
Forskningsfinansiär
Region Östergötland, FOU 2-15-14Forskningsrådet i Sydöstra Sverige, FORSS, FORSS-748481Sveriges Tandläkarförbund
Anmärkning

Paper III is not included in the fulltext online

Paper III in dissertation as manuscript

Tillgänglig från: 2024-03-22 Skapad: 2024-03-21 Senast uppdaterad: 2024-03-22Bibliografiskt granskad
Delarbeten
1. Orofacial pain in juvenile idiopathic arthritis is associated with stress as well as psychosocial and functional limitations
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2019 (Engelska)Ingår i: Pediatric Rheumatology, E-ISSN 1546-0096, Vol. 17, nr 1, artikel-id 83Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background The aim of this study was to investigate relations between psychosocial factors, signs and symptoms of orofacial pain and jaw dysfunction in patients with juvenile idiopathic arthritis (JIA). Methods Forty-five patients with JIA (median age 12 years) and 16 healthy matched controls (median age 13 years) were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered the DC/TMD questionnaires regarding psychosocial factors (pain intensity, pain-related disability, depression, stress, catastrophizing, pain locations and jaw function). Results JIA patients with orofacial pain had higher degree of stress, depression, catastrophizing and jaw dysfunction compared to subjects without. In turn, these factors were associated with orofacial pain intensity. Also, patients with orofacial pain had higher systemic inflammatory activity. Conclusions Orofacial pain in patients with JIA is associated with stress, psychological distress, jaw dysfunction and loss of daily living activities. Pain intensity seems to be the major pain aspect related to these factors. In addition, systemic inflammatory activity appears to be an important factor contributing to orofacial pain in JIA.

Ort, förlag, år, upplaga, sidor
BioMed Central (BMC), 2019
Nyckelord
Adolescents, Children, Juvenile idiopathic arthritis, Orofacial pain, Psychosocial, Stress Temporomandibular joint disorders
Nationell ämneskategori
Reumatologi och inflammation
Identifikatorer
urn:nbn:se:mau:diva-17239 (URN)10.1186/s12969-019-0385-7 (DOI)000512605400001 ()31856854 (PubMedID)2-s2.0-85077044869 (Scopus ID)
Tillgänglig från: 2020-05-13 Skapad: 2020-05-13 Senast uppdaterad: 2024-03-21Bibliografiskt granskad
2. Juvenile idiopathic arthritis and the temporomandibular joint: a case-control study of magnetic resonance imaging findings in relation to clinical and psychosocial factors.
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2023 (Engelska)Ingår i: European Journal of Paediatric Dentistry, ISSN 1591-996X, E-ISSN 2035-648X, Vol. 24, nr 1, s. 69-76Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

AIM: In juvenile idiopathic arthritis (JIA), the temporomandibular joint (TMJ) is a particularly challenging joint to assess both clinically and with imaging. The aim of this article is to investigate TMJ magnetic resonance imaging (MRI) findings in relation to clinical and psychosocial factors in patients with JIA and healthy individuals related to TMJ arthritis in JIA.

MATERIALS: In total, 45 patients (6-16 years) with JIA and 16 healthy age- and sex-matched controls were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered questionnaires about psychosocial factors (pain intensity, pain-related disability, depression, stress, catastrophising, pain locations, and jaw function) and underwent bilateral MRI of the TMJ.

RESULTS: There were no significant differences between JIA patients and healthy individuals in any of the TMJ MRI findings. Moderate/severe changes among JIA patients were found only for effusion, synovial thickening, condylar flattening, and erosion, with no moderate/severe changes in healthy individuals. In JIA patients, orofacial pain intensity was related to TMJ bone marrow oedema, and pain in jaw muscles during jaw function was related to TMJ bone marrow oedema and erosion. There were no significant correlations between psychosocial aspects and MRI findings.

CONCLUSION: This study indicates a substantial overlap of TMJ MRI findings in both the inflammatory domain and the damage domain between JIA patients and healthy individuals. In JIA patients, the inflammatory MRI sign of bone marrow oedema seems to influence orofacial pain intensity.

Ort, förlag, år, upplaga, sidor
Società Italiana di Odontoiatria Infantile, 2023
Nationell ämneskategori
Odontologi
Identifikatorer
urn:nbn:se:mau:diva-58549 (URN)10.23804/ejpd.2023.24.01.12 (DOI)000945146900012 ()36853210 (PubMedID)2-s2.0-85149154015 (Scopus ID)
Tillgänglig från: 2023-03-03 Skapad: 2023-03-03 Senast uppdaterad: 2024-03-21Bibliografiskt granskad
3. Parotid saliva and blood biomarkers in juvenile idiopathic arthritis inrelation to temporomandibular joint magnetic resonance imaging findings
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Reumatologi och inflammation Odontologi
Identifikatorer
urn:nbn:se:mau:diva-66389 (URN)
Forskningsfinansiär
Forskningsrådet i Sydöstra Sverige, FORSSRegion ÖstergötlandSveriges Tandläkarförbund
Tillgänglig från: 2024-03-20 Skapad: 2024-03-20 Senast uppdaterad: 2024-03-21Bibliografiskt granskad
4. Increase in stress contributes to impaired jaw function in juvenile idiopathic arthritis: a two-year prospective study
Öppna denna publikation i ny flik eller fönster >>Increase in stress contributes to impaired jaw function in juvenile idiopathic arthritis: a two-year prospective study
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2024 (Engelska)Ingår i: Pediatric Rheumatology, E-ISSN 1546-0096, Vol. 22, nr 1, artikel-id 30Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BackgroundStress in patients with Juvenile Idiopathic Arthritis (JIA) has been found to be associated with orofacial pain, psychological distress, jaw dysfunction and loss of daily activities in a cross-sectional study. The aim of this study was to investigate the relations between stress and change of stress over time versus changes in orofacial pain, psychosocial factors and jaw function over a two-year period in patients with JIA.MethodsThis is a two-year prospective follow-up study involving 40 JIA patients. At baseline (2015) the median age was 12 years and at two-year follow up (2018) 14 years. The JIA patients were examined clinically and with questionnaires at baseline and follow-up with the diagnostic criteria for temporomandibular disorders (DC/TMD) and completed the same set of DC/TMD questionnaires regarding orofacial pain symptoms and psychosocial factors.ResultsChange in stress was associated with change in catastrophizing, psychological distress as well as limitation in general function and jaw function.ConclusionsThis study emphasizes the importance of maintaining a low stress level in patients with JIA since an increase in stress level over a two-year period seems to impair jaw function as well as psychological distress and catastrophizing.

Ort, förlag, år, upplaga, sidor
BioMed Central (BMC), 2024
Nyckelord
Juvenile Idiopathic Arthritis, Orofacial pain, Psychological distress, Psychosocial, Stress, Temporomandibular joint disorders
Nationell ämneskategori
Reumatologi och inflammation Odontologi
Identifikatorer
urn:nbn:se:mau:diva-66380 (URN)10.1186/s12969-024-00966-4 (DOI)001173488700001 ()38409027 (PubMedID)2-s2.0-85186196644 (Scopus ID)
Forskningsfinansiär
Forskningsrådet i Sydöstra Sverige, FORSS, FORSS-748481Sveriges TandläkarförbundMalmö universitetRegion Östergötland, FOU 2-15-14
Tillgänglig från: 2024-03-19 Skapad: 2024-03-19 Senast uppdaterad: 2024-03-21Bibliografiskt granskad

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