Acute Arthritis of the Temporomandibular Joint due to Lyme Disease: A Case Report and Literature Review

Lyme disease is the most frequent tick-borne infectious disease in Europe. It often presents with a wide variety of symptoms. For this reason, affection of the temporomandibular joint (TMJ) caused by Lyme disease (LD) can be misdiagnosed as a common temporomandibular disorder (TMD). The purpose of this case report of a 25-year old woman presenting to the Departments of Orthodontics and Maxillofacial Surgery with extensive symptoms of Temporomandibular Disorder is to illustrate the delayed diagnosis of Lyme disease, which was only made after extensive therapy of the temporomandibular joint. The specialist literature only reports a few cases of patients suffering from Lyme disease with TMJ manifestations. This case report and the relevant literature review aim to emphasize the importance of accurate request of medical history and differential diagnosis of acute TMJ arthritis and arthralgia. Early interdisciplinary diagnosis of Lyme disease and early antibiotic therapy are essential to avoid misdiagnosis and unnecessary, sometimes invasive, therapies.


Introduction
Lyme disease or tick-borne spirochaetosis was rst observed in Lyme in Connecticut, USA in 1975. Within a short period of time cases of illness with joint in ammation after tick bites occurred with striking frequency. Skin manifestations of Lyme disease had already been described in Europe by Alfred One of the main symptoms of an early manifestation is the erythema migrans (EM) occuring in 89% of the cases. The EM is a bluish-red or red expanding patch, which can be more than ve centimeters in diameter, with or without a central punctum. Another clinical manifestation of LD in clinical routine is acute Lyme neuroborreliosis (LN) affecting the nervous system. LN might occur as lymphocytic meningitis, root pain, cranial nerve paralysis (nerve VII) and sometimes as peripheral nerve paralysis (Stanek et (Scerpella T.A. 1992). These authors describe a distinction between early and late manifestation. The early manifestation might appear either localized or disseminated. The early localized stage occurs in 80-90% of the patients and is associated with erythema migrans (EM) (Wilking und Stark 2014; Biesiada et al. 2012). A few days after the infection with borrelia, arthralgia, nausea, fatigue, myalgia, increased body temperature, stiff neck, neurological manifestation and night sweats might be observed. There might be short periods of intense pain in the affected joints, followed by periods of complete recurrence and remission. The early disseminated stage appears after weeks or even months (Harris 1988). The heart, nervous system and brain can also be affected. If the orofacial region is involved, the main symptoms are headaches, neurological symptoms like Bell's paralysis, and/or pain in the masticatory muscles and the temporomandibular joint (TMJ). Laboratory serology is essential for the diagnosis of Lyme disease. Serological diagnostics should only be requested if there is su cient clinical suspicion. For serological examinations serum antibody detection methods such as enzyme-linked immunoassay (ELISA) and immuno uorescent assay (IFA titer) are used. Serological detection is di cult because the diagnostic methods are not standardized and have a low sensitivity. Thus, it is often a tentative diagnosis. Furthermore, there is an inability to detect antibodies in the early stages of LD meaning that an infection might be present despite a negative test result (Lader 1990). Furthermore, serological evidence can no longer be provided after antibiotic therapy.
In the case of an infection with BB, no speci c degenerative and in ammatory evidence is found in the affected joint, neither radiographically nor histopathologically (Scerpella T.A. 1992). Antibiotic treatment should be administered over a period of 14 days (Rauer S., Kastenbauer S. et al.). According to the guidelines, doxycycline is as effective as beta-lactam antibiotics in early neuroborreliosis regarding regression of neurological symptoms with the same tolerability. There are no valid evaluable studies on the effectiveness of combination treatments of antibiotics. (Rauer S., Kastenbauer S. et al.) The most common non-dental pain arises from temporomandibular disorders (TMDs), having become widespread disorders. TMD has similar symptoms to LD, such as undifferentiated neuralgic facial pain, limited mouth opening, disorder of mandibular mobility, ear pain, joint sound and sometimes hypermobility of the joint (Table 1) (Dworkin und Massoth 1994). Persistent pain can lead to a reduction in health-related quality of life and to psychosomatic disorders. Therefore, patients -suffering from LD can be misdiagnosed with TMD and consequently undergo inappropriate treatment. If the LD persists for a long time, it can lead to irreversible chronic manifestations (Lader 1990). In 1996, Heir and Fein showed that in rare cases LD has a manifestation at the temporomandibular joint (TMJ). They emphasized that patients with LD should undergo special treatment and some form of speci c recording of medical history such as a questionnaire (Heir G.M. 1996). In LD the TMJ is the fourth most frequently affected joint (Steere A.C., Dwyer E., Winchester R.J. 1990). So far, there is a paucity of information in the literature and the relationship between TMD and LD is still unclear. A new case with these symptoms in serologically con rmed LD is reported below. This is intended to increase the awareness of dentists to patients who present with TMD symptoms in combination with evidence of LD, so that they can be referred to an appropriate specialist.

Case Presentation
This case report describes a 25-year-old female patient presenting to the Department of Orthodontics at the Centre of Dentistry, Oral and Maxillofacial Surgery at the University Hospital Tuebingen due to acute pain in the right TMJ and mouth opening disorders in 2019. There were no general diseases or allergies in her medical history. The patient stated that she did not consume alcohol or nicotine; she was taking contraceptives. Over a period of 5 years the patient's distal bite was treated with removable and xed orthodontic appliances. The initial examination showed xed retainers in both the upper and lower jaws ( Fig. 1a + b). Despite orthodontic treatment, there was still a slight asymmetric distal occlusion on both sides (Fig. 1c + d). This was slightly more pronounced on the left due to slight mandibular tilt to the left (Fig. 1e). The mouth opening disorder severely restricted the patient in her everyday life. Previously, craniomandibular dysfunction was assumed due to multiple grinding facets on the teeth and bruxism. Therefore, a bruxism splint was already worn at night. Figure 2 showing a panoramic radiograph of the patient showing symmetric but attened condyles with a slightly widened TMJ gap on both sides.
Three months later, the patient reported that she woke up with severe pain in her right TMJ after sleeping and was not able to close her mouth. When repositioning the lower jaw by herself a very loud cracking sound at the right TMJ occured. After that, she had a mouth opening disorder and constant pain. The patient gave this constant pain a score of 7 on the verbal numeric rating scale (VNRS) (0-10). She was prescribed muscle relaxant therapy with Methocarbamol twice a day. Although the pharmaceutical treatment with Methocarbanol resulted in some slight pain relief, it also had some general medical side effects such as circulatory weakness and dizziness. The patient was also referred to the Department of Orthodontics. Due to severe pain a functional analysis of the TMJ was not possible. The mouth opening was limited to 20 mm active and 30 mm passive causing extreme pain. Thus, a muscle spasm was suspected. A dental splint combined with intensive physiotherapy and mouth-opening exercises continued to be recommended as therapy. Mouth-opening exercises and physiotherapy led to a clear deterioration of the condition.
Three months after the rst symptoms, the patient showed an acute deterioration of her health status.
The main symptom was ever-increasing pain in the right TMJ, which worsened throughout the day. She rated the pain 8 on the VNRS. She also showed an increasing active mouth opening restriction to 20 mm and a habitual deviation of the lower jaw to the left (Fig. 3).
The functional and occlusal analysis of the stomatognathic system showed strong dorsal load vectors of the TMJ on the right side. The ventral and caudal traction of the joint was consistently associated with severe pain on the right. Lateral movements of the lower jaw were restricted and painful. Protrusion movement was not possible. There was neither crepitus nor cracking of either TMJ. The patient had a persistent pain-relieving abduction and outward rotation of the left lower mandible (Bonnet position) (Fig. 3b). The suspected diagnosis at this time was a total ventral deviation of the discus on the right side without reduction and with active mouth opening that was painfully blocked. There was a static contact of the rst premolars with the second molars on both sides. The dynamic occlusion had canine guidance on the right side and guidance over the rst premolar on the left. The bite position showed an Angle Class II left 3/4 premolar width (PW) right and ¼ PW left with an overjet of 4 mm and an overbite of 2 mm. Further radiological diagnosis was performed using a MRI scan (Fig. 4-6).
The radiology ndings showed a discrete erosion of the right mandibular condyle and a bone marrow oedema of the right mandible with increased contrast uptake as well as minor joint effusion in the right temporomandibular joint. Furthermore, an anterior dislocation of the right articular disc with suspicion of a tear in the ligament with closed and open mouth was identi ed. In the dynamic sequences, there was slightly restricted translational forward movement with mouth opening on the right side. The position of the left TMJ with open and closed mouth was unremarkable. Thus, the ndings of the MRT con rmed osteoarthritic changes of the mandibular condyle and joint effusion on the right side corresponding with constant pain. The treatment goals were to prevent the progression of structural damage to the right temporomandibular joint, to improve the mouth opening and to reduce the lateral deviation. Therefore, the patient was prescribed NSAID (Ibuprofen 400 mg) 3x/d to reduce the pain, a bite splint in the lower jaw for 24 hours per day, soft diet and regular adjustment of the splint approximately every 2 weeks.
Despite these therapies the patient complained of increasing pain in the right TMJ and a worsening of her general condition. The patient would then stop the splint therapy at her own discretion. She was also referred to the Department of Oral and Maxillofacial Surgery of the University Hospital Tübingen. The pharmaceutical treatment with NSAID 3x/d was changed to Diclofenac 50 mg 2x/day. The new medication did not achieve pain relief and, unfortunately, the patient suffered an allergic reaction to Diclofenac and resulting in an exanthema, swelling of the oral mucosa and nausea.
For further diagnostic investigation, a cone beam computed tomography (CBCT) was performed and showed bone erosion of the right condyle of the TMJ. The image revealed an arthropathic condylar destruction on the right seen as a pointed structure; the cortex is only partly visible. The left mandibular condyle did not show pathologic ndings.
Based on the radiological ndings a mandibulo-maxillary xation (MMF) with elastic loops was applied to stabilize the occlusion. The patient was instructed to follow a liquid diet and intensive physiotherapy was prescribed. However, her condition failed to improve. The MMF was then removed and the jaws were xed using wire ligatures. This xation and immobilization of the mandible led to a remarkable improvement for the rst time in the period of treatment. For further clinical diagnostics the patient was referred to the Department of Rheumatology of the University Hospital Tuebingen. The rheumatoid serology did not yield any ndings indicating a rheumatological disorder. The laboratory examination showed a slightly increased CRP-value of 0.60 mg/L The HLA-B27 examination was negative. The patient's serologic analysis showed a low estrogen level and thus, the contraceptives were discontinued. Further therapy was discussed by an interdisciplinary board (Rheumatology, CMF-Surgeons and Orthodontics) that proceeded to recommend lavage or cortisone injection into the affected TMJ. A cortisone injection in the right TMJ was performed shortly after the interdisciplinary discussion (Fig. 10). After cortisone injection, the patient showed a signi cant improvement generally and the active mouth opening increased to up to 23 mm. However, pain at maximal mouth opening was still felt in the right TMJ.
Management recommendations continued to include a soft diet in order to relieve the TMJ, no forced mouth opening exercises, physiotherapy and an attempt without MMF. Three months later, a blood test revealed a positive incidental serology nding for Bb IgG and IgM antibodies. Based on the serological nding, the diagnosis of Lyme arthritis affecting the right TMJ was con rmed. Cephalosporins (Cefuroxime 1,5 g 3x/d) i.v. for at least 3 weeks was the immediate treatment of choice. Interestingly, the patient could not recall any tick bite. After one week of antibiotic therapy, the patient stated a clear improvement of her condition. A further functional examination of the temporomandibular joints after antibiotic therapy revealed a not reproducible, persistent cracking sound on the right side during active mouth opening.
A CBCT scan obtained three months after the antibiotic therapy con rmed a pronounced improvement of the situation (Fig. 11). The image of the right temporomandibular joint showed an almost continuous cortex with only a few residual lesions. Thus, the condyle had signi cantly improved compared to the previous CBCT scan seven months earlier. The functional and occlusal analysis showed that the lateral restraint no longer existed. However, the static contact and the dynamic occlusion on both sides was unchanged compared to the situation seven months ago. Furthermore, the bite position displayed an Angle Class II left 1/4 PW right and ¾ PW left with an overjet of 4 mm and an overbite of 2 mm. The patient still reported a cracking sound during mouth opening on the right side only but this was not reproducible during the clinical examination.

Discussion
Until today, the manifestation of LD in the TMJ has not been extensively described in the literature. In 1988, Harris was the rst author to described symptoms in the TMJ arising in combination with LD in a younger patient (Harris 1988  and arthralgia in the TMJ region. The therapy was intravenous ceftriaxone after detection of the acute Bb infection by positive serum markers. The authors suggested that in Slovenia joint involvement is present in 15 % of the cases. This statement is consistent with reports of joint involvement in LD across Europe (Cimmino 1998). However, it can be stated that the occurrence of these disorders is much more frequent in the United States, whereby joint involvement appears to be a more frequent clinical sign of LD in the USA than in Europe (Lesnicar und Zerdoner 2007). Almost all cases showed a restriction in mouth opening and an improvement of the symptoms after antibiotic therapy alone.
Often tick bites are not noticed by the affected patients or they cannot remember a bite in the past.
Consequently, LD with affection of the TMJ very often is misinterpreted as a TMD. In the case presented here, the tick bite was unnoticed and the symptoms were interpreted as those of a TMD. The warning symptom EM was absent. However, the possibility of missing symptoms should be considered in every patient and should not be a criterion for excluding a LD diagnosis. Therefore, the presented case aims to raise the awareness of this issue. E. Lader described a case in which Lyme disease was wrongly diagnosed as a temporomandibular joint disorder (Lader 1990). Osiewicz et al. discovered that there is a high prevalence of TMD symptoms in patients with LD (Osiewicz et al. 2019b). The risk of this disease is that it sometimes only becomes apparent in its late phase (Steere 1993; Nadelman und Wormser 1998).
Symptomatically, the patient presented with acute temporomandibular joint arthritis in the classical sense without an affection of any other joint. As the patient did not improve with conventional therapy, a variety of differential diagnoses and causes had to be discussed with an interdisciplinary board. The patient was not aware of any tick bite, nor had a Lyme disease been diagnosed before the onset of the acute temporomandibular joint arthritis. It can be assumed that there must have been an infection with borrelia in the right temporomandibular joint for a longer period of time before the symptoms occurred. This circumstance has been described before (Heir G.M. 1996; Wolańska-Klimkiewicz E., Szymańska J., Bachanek T. 2010; Lesnicar und Zerdoner 2007). It can be assumed that the overloading of the TMJ due to bruxism exacerbated and intensi ed the manifestation at the TMJ. Osiewicz  Cortisone injection in the right TMJ led to a signi cant pain relief and an improvement in the general condition of the patient, whereas splint therapy did not cause any amelioration of symptoms. It can be suggested that cortisone therapy alleviated the in ammation in the TMJ but did not eliminate the cause of the complaints. The initiation of antibiotic therapy ultimately led to a long-term improvement, which could be objecti ed by the CBCT, which showed the recovery of the right mandibular condyle. Xie et al. This case has con rmed that an early antibiotic treatment is important and prevents recurrent arthralgia. This symptom might be caused by Bb in the synovia of the infected joint. A Ceftriaxone-based parenteral antibiotic therapy per day for three weeks is recommended (Cameron et al. 2004). In order to investigate whether the patient has a chronic LD activity or whether this is a consequence of the infection, clinical and laboratory examinations would have to be carried out again after a certain period of time following diagnosis. Furthermore, it is important to clarify whether there are long-term arthritic changes in the TMJ. In 1996, Heir and Fein described three cases and the possibility of a Jarisch-Herxheimer reaction associated with antibiotic therapy in dental procedures. The Jarisch-Herxheimer reaction is a reaction of endotoxine like products released by the death of bacteria or spirochetes during antibiotic treatment.
Symptoms are fever, chills, rigor, hypotension headache tachycardia, hyperventilation, vasodilation with ushing, myalgia and exacerbation of skin lesions. These clinical symptoms are often misinterpreted as an allergic reaction to the antibiotic therapy. They also highlight the fact that Bb can remain inactive and unknown in the tissue for a long period, ultimately emerging as a Jarisch-Herxheimer reaction. Furthermore, the Bb has an a nity to connective tissue such as the periodontium. There is a risk of surgical intervention involving the periodontium. A surgical procedure or a root canal treatment might cause delayed healing because scarring can increase symptoms. (Heir G.M. 1996;Heir G.M. 1997;Heir G.M. 1998) The literature highlights antibiotic therapy as the best therapy available for the treatment of LD (Heir G.M. 1996). So far, no exact therapy for TMJ involvement in LD has been reported in the literature. The prerequisite for a con rmed diagnosis is a well-founded diagnosis, a structured medical history and ndings with accompanying diagnostic therapy. Lyme disease-associated orofacial pain poses special challenges for an interdisciplinary team as well as for the patient due to the variety of possibilities of differential diagnoses. Furthermore, the treatment of TMJ problems always focuses on interdisciplinary treatment and an individual therapy concept for each patient. It is important to think "outside the box" and think ahead, especially when making a diagnosis. In the case of unclear TMJ problems and when the TMD treatment is not successful, the possibility of a LD infection should de nitely be considered as a

Availability of data and materials
All data and materials are accessible on a local server of the Departments of Orthodontics and the Department of Oral and Maxillofacial Surgery at the University Hospital Tuebingen, Germany.

Competing interests
The authors declare that they have no competing interests.

Funding
This research did not receive any speci c grant from funding agencies in the public, commercial or non-pro t sectors.
Authors' contributions CW drafted the manuscript and developed the design. KF, MC, and BK participated in the manuscript and gave clinical input and knowledge. HW and MS participated in manuscript and coordination. All authors read and approved the nal manuscript. OPG before initial presentation of the patient       CBCT right TMJ (07/20)