Arthritic Conditions Affecting the Temporomandibular

L. G. Mercuri and S. Abramowicz

Abstract Keywords Arthritis is the most common inflammatory • Arthritis • Osteoar- joint disease in children and adults. It has mul- thritis • Degenerative joint disease • TMJ tifactorial etiology resulting in joint degenera- reconstruction • TMJ replacement • Rheuma- tion and loss of function. Using a management toid arthritis • Juvenile idiopathic arthritis • classification scheme based on clinical signs, • • Orthognathic symptoms, and imaging, this chapter will pre- • sent an evidence-based discussion for the man- agement of arthritic conditions affecting the Contents temporomandibular joint (TMJ). The common Introduction ...... 1 and significant signs and symptoms of TMJ General Principles ...... 2 arthritic conditions are pain, loss of joint func- tion, joint instability, mandibular dysfunction, Signs and Symptoms of Arthritis ...... 4 and facial deformity due to loss of posterior Diagnosis ...... 5 mandibular vertical dimension as pathologic Low-Inflammatory Arthritis ...... 5 osteolysis decreases the height of the condyle. High-Inflammatory Arthritis ...... 5 Juvenile Idiopathic Arthritis ...... 8 Medical management can ameliorate early- ...... 9 stage disease. Progressive disease may require the employment of invasive procedures, Management of TMJ Arthritic Conditions ...... 12 Noninvasive Modalities ...... 14 whereas in end-stage disease, joint replace- Minimally Invasive Procedures ...... 19 ment is typically required. Surgery ...... 25 Conclusion and Future Directions ...... 30 Cross-References ...... 31 References ...... 31 L.G. Mercuri (*) Department of , Rush University Medical Center, Chicago, IL, USA Clinical Consultant TMJ Concepts, Ventura, CA, USA Introduction e-mail: [email protected] S. Abramowicz Worldwide statistics indicate that the incidence of Oral and Maxillofacial Surgery and Pediatrics, Emory arthritis is 3.2%. Arthritis affects females more University and Children’s Healthcare of Atlanta, Atlanta, than males (2.7:1) and can lead to joint destruc- GA, USA tion, deformity, and disability in 10–15% of e-mail: [email protected]

# Springer International Publishing AG 2017 1 C.S. Farah et al. (eds.), Contemporary Oral Medicine, https://doi.org/10.1007/978-3-319-28100-1_32-1 2 L.G. Mercuri and S. Abramowicz patients. Arthritic conditions are the second most pathology (e.g., arthritis or osteoarthrosis) or frequent cause of outpatient complaints among extra-articular factors (e.g., joint hypermobility patients with chronic diseases (Rodrigo and or sensitization, peripheral or central) (Michelotti Gershwin 2001). By 2030, an estimated 67 million et al. 2016). Americans aged 18 years or older are projected to have diagnosed arthritis (Hootman and Helmick 2006). Approximately 1 in 250 children under the General Principles age of 18 have some form of arthritis or rheumatic condition; this represents approximately 294,000 TMJ arthritic conditions can be classified as children in the United States (Sacks et al. 2007). low-inflammatory or high-inflammatory types Arthritis has many causes; however, the com- (Table 1) (Mercuri 2006). Table 2 describes the mon result is the degeneration of the affected joint basic clinical, laboratory, and imaging character- surfaces resulting in loss of joint function. The istics of each of these conditions. cause of the arthritic condition determines the Low-inflammatory arthritic conditions are pur- clinical characteristics and rate of degeneration ported to begin in the matrix of the articular surface of the joint surfaces. of the joint, with the subcondylar and capsule The prevalence of significant temporomandib- becoming secondarily involved. The two classic ular joint (TMJ) arthritis resulting in joint degen- types of low-inflammatory arthritis are: first, degen- eration, dysfunction, and/or joint pain is erative joint disease, or primary osteoarthritis (OA), unknown. Previous studies have provided esti- produced by intrinsic degeneration of articular car- mates that the incidence of TMJ arthritic condi- tilage typically the result of age-related functional tions ranges from 1% to 84% of the general loading; and second post-traumatic arthritis. population (Westesson and Rohlin 1984). Even though these low-inflammatory arthritic Changes consistent with degenerative TMJ dis- conditions often involve the TMJ, these seldom ease are found in approximately 70% of the require invasive surgical intervention provided patients who undergo arthroscopy for TMJ disor- they are managed appropriately in the early stages ders; however, degenerative changes are clinically (Henderson et al. 2015; Tanaka et al. 2008; Wang diagnosed in less than 10% of patients (Israel et al. et al. 2012). Patients with low-inflammatory type 1991). Examination of the TMJ at autopsy reveals have been shown to have low leukocyte counts in degenerative changes in at least 40% of speci- the synovial fluid and laboratory findings consis- mens. However, estimates of the number of indi- tent with low-level inflammatory activity (e.g., viduals in the United States seeking treatment for erythrocyte sedimentation rate [ESR] and TMJ pain or dysfunction are substantially lower at C-reactive protein [CRP]), and the affected joint 1.9–3.4% (Westesson and Rohlin 1984). shows focal degeneration on imaging (Fig. 1) The diagnostic criteria used to differentiate (Mercuri 2006). between “arthritis” and the biologically different “ ” osteoarthrosis is not effective due to their shared Table 1 Classification of TMJ arthritic conditions multiple clinical signs and symptoms (Michelotti (Mercuri 2006) et al. 2016). There are discrepancies in estimates Low- Osteoarthritis (degenerative joint of the prevalence of each of these conditions inflammatory disease) because the association between pain, dysfunc- disorders Post-traumatic arthritis tion, and joint morphology is complex. Gross High- Infectious arthritis fl morphologic abnormalities can be present in the in ammatory Rheumatoid (ARA and JIA) disorders Metabolic absence of TMJ pain and dysfunction (Pereira (Gouty arthritis, psoriatic et al. 1994). Furthermore, the distinction between arthritis, lupus, ankylosing the diagnoses of “arthralgia” and “arthritis” is spondylitis, Reiter’s syndrome, difficult since the signs and symptoms overlap. arthritis associated with ulcerative colitis) “Arthralgia” may be due to intra-articular Arthritic Conditions Affecting the Temporomandibular Joint 3

Table 2 The basic clinical, laboratory and imaging characteristics of low and high inflammatory TMJ arthritic conditions TMJ findings Low-inflammatory High-inflammatory Pain Localized Diffuse TMJ involvement Unilateral or bilateral Bilateral Clicking Rare Absent Crepitation Present Rare Rheumatoid factor Rare Present ESR Often normal Elevated CPP Normal Elevated CRP May be elevated Elevated Imaging Erosive and exophytic Erosive Asymmetric bone loss Symmetric bone loss ESR erythrocyte sedimentation rate, CPP cyclic citrullinated peptide antibody, CRP C-reactive protein a b

AE EAC

LAT

c

EAC

Fig. 1 Sagittal (a), coronal (b) and axial (a) reconstruc- articular surface flattening and sclerosis (open black arrow) tions of the left TMJ from a multi-detector CT scan dem- with a small anterior osteophyte (white arrows). Where onstrating articular surface remodelling and early, low- EAC= external auditory canal and LAT = lateral. (Images inflammatory, osteoarthritis. There is joint-space narrowing courtesy of Clinical Associate Professor Andy Whyte, which is most marked anterolaterally (dotted black arrows), Perth Radiological Clinic, Perth WA, Australia) 4 L.G. Mercuri and S. Abramowicz

Fig. 2 Patient with JIA demonstrates open bite deformity of high-inflammatory arthritis due to diffuse degeneration of the involved

High-inflammatory arthritic conditions primar- ily involve both the synovial cells and of the Signs and Symptoms of Arthritis joint. The classic type of high-inflammatory arthritis is rheumatoid arthritis (RA). Other types The most common symptom of TMJ arthritic of high-inflammatory arthritic conditions include conditions is pain. The pain arises from the soft metabolic arthritic diseases such as gout (Oliveira tissues around the affected joint that are under et al. 2014), pseudogout (Laviv et al. 2015), pso- tension, as well as the masticatory muscles that fl riatic arthritis (Crincoli et al. 2015), lupus are in re ex protective co-contraction because of ’ erythematosus (Jordan and D’Cruz 2016), anky- Hilton s Law. This orthopedic principle states that losing spondylitis (Arora et al. 2013), infectious the neural supply innervating a joint is the same as arthritis (Gayle et al. 2013), Reiter’s disease that innervating the muscles that move that joint (Mansour et al. 2013), and the arthritis associated and the overlying skin (Hébert-Blouin et al. with ulcerative colitis (Sarlos et al. 2014). 2014). This law provides for the protection of an Although these arthritic disorders may be his- injured or pathologically affected joint by causing fl tologically and pathologically different, clinical the surrounding musculature to re exively con- findings and management are often similar. In all tract in response to intra-articular injury or pathol- instances the TMJ can be involved, and surgical ogy, thus safeguarding it from further damage. intervention may be required to alleviate symp- Pain has also been postulated to arise from the toms and correct associated end-stage functional subchondral bone that is undergoing destruction and esthetic problems. Patients with high- as the result of the arthritic process (Mercuri inflammatory type arthritis have high leukocyte 2006). fi counts in the synovial fluid, laboratory findings Other common and signi cant signs and symp- consistent with high-inflammatory activity (e.g., toms of TMJ arthritic conditions are loss of joint rheumatoid factor [RF] and cyclic citrullinated pep- function, joint instability, and facial deformity due tide antibody [CCP]) and show diffuse degeneration to loss of posterior mandibular vertical dimension of the involved joints on computed tomography as pathologic osteolysis decreases the height of (CT) imaging (Figs. 2, 5,and6)orbonemarrow the condyle(s) (Figs. 2, 3, and 9) (Mercuri 2006). edema and effusion on magnetic resonance imaging (MRI) (Figs. 7 and 8)(Mercuri2006). Arthritic Conditions Affecting the Temporomandibular Joint 5

Fig. 3 Facial deformity due to loss of posterior mandibular vertical dimension (a) as pathologic osteolysis decreases the height of the right condyle (b) resulting in right mandibular deviation

fl Diagnosis low-in ammatory arthritis imaging (Fig. 4) (Mercuri 2006). It is rare that a patient with a low-inflammatory The diagnosis of TMJ involvement in a patient arthritic condition presents with an acute attack with a widespread late-stage arthritic condition is unless there is a recent history of trauma that has usually obvious, since other joints will manifest aggravated preexisting disease. In those situations, the disease process. The diagnostic challenge imaging helps to determine the contribution of any occurs if the first affected joint is the TMJ. A long-standing articular degeneration to the trau- comprehensive history and clinical examination matic episode. However, minimal flattening of the are essential. If there is minimal correlation condyle and/or eminence has been demonstrated in between the history and physical findings, imag- 35% of persons with asymptomatic TMJs. There- ing and laboratory examination may be helpful fore, it has been concluded that minimal flattening (Mercuri 2006). is probably of no clinical significance (Brooks et al. 1992; Campos et al. 2008). Low-Inflammatory Arthritis High-Inflammatory Arthritis Among individuals with TMJ disorders (TMJD), 11% have symptoms of low-inflamma- The characteristic CT imaging features of high- tory arthritis (Mejersjö and Hollender 1984). inflammatory arthritic conditions include diffuse The characteristic radiographic imaging fea- narrowing of the entire joint surface and the tures of low-inflammation arthritis or post- appearance of multiple peri-articular cysts traumatic arthritis are focal joint bony degener- (Fig. 5). These cysts are thought to be the result ation and the appearance of osteophytes of erosion from the inflamed synovium at its (Fig. 1). The image may be characterized by reflection near the insertion of the joint capsule. hypertrophic changes about the affected joint as The margins of these cysts are “fuzzy” during the opposed to atrophic changes seen in high- acute stage and become sclerotic during the inflammatory types of arthritis (Figs. 2, 5,and chronic stage. The uniform narrowing of the 6). Subchondral focal degeneration, the joint space is thought to be due to enzymatic so-called Ely’s cyst may also be seen on digestion of the surface (Mercuri 2006). 6 L.G. Mercuri and S. Abramowicz

a b

EAC

LAT

d c

EAC

LAT

Fig. 4 Low inflammatory osteoarthritis of moderate to are from a different patient and demonstrate similar fea- marked severity in the left TMJ demonstrated on sagittal tures including multiple subcortical cysts (black arrows), and coronal reconstructions from multi-detector CT scans marked loss of joint space in the superolateral aspect of the in two patients. Images a and b show diffuse joint space joint and a calcified intra-articular body (dotted white narrowing and articular surface flattening (open black arrows). Where EAC = external auditory canal and LAT arrows), articular and sub-articular sclerosis and an ante- = lateral. (Images courtesy of Clinical Associate Professor rior osteophyte (white arrow). There is a small subcortical Andy Whyte, Perth Radiological Clinic, Perth WA, (Ely’s) cyst in the condyle (black arrow). Images c and d Australia)

There is characteristic erosion and flattening of the which are classified as homogeneous, shaggy, or anterior and posterior condylar surfaces and a speckled. Homogeneous, the most common ANA generalized osteopenia of the condyle and tempo- pattern, is seen primarily in lupus erythematosus but ral bony components (Figs. 6, 7, and 8) (Tamimi occurs in other diseases as well; shaggy (peripheral and Hatcher 2016). or rim) is more specific to lupus erythematosus and Serum rheumatoid factor is positive in only is often associated with increased disease activity; 70–80% of adult RA patients and is rarely positive speckled is characteristic of mixed connective tissue in juvenile idiopathic arthritis (JIA). The lupus disease. In lupus erythematosus, the titers are higher erythematosus test demonstrates a polymorpho- than those in other rheumatic diseases (Rodrigo and nuclear cell filled with antinuclear antibody Gershwin 2001). (ANA) complexes. More frequently used tests Anti-cyclic citrullinated peptide (anti-CCP) are the fluorescent ANA tests, the results of antibody testing is particularly useful in the Arthritic Conditions Affecting the Temporomandibular Joint 7 a b

EAC

LAT

Fig. 5 Sagittal (a) and coronal (b) reconstructions of the glenoid fossa and articular eminence (dotted, open white right TMJ from a multi-detector CT scan in a patient with arrows). Where EAC = external auditory canal and LAT = high inflammatory arthritis. There is diffuse erosion of both lateral. (Images courtesy of Clinical Associate Professor sides of the joint (open black arrows) giving a grossly Andy Whyte, Perth Radiological Clinic, Perth WA, irregular condylar contour and a more smoothly expanded Australia) a b

EAC LAT

Fig. 6 Multi-detector CT with sagittal (a) and (b) recon- into subcortical bone. In addition to patchy sclerosis which structions of the right TMJ. In addition to extensive erosion is marked in the condylar neck, there is scattered ill-defined and deformity of both articular surfaces (open, black osteopenia (radiolucency) in both the condyle and glenoid arrows), there is “bone on bone” contact (white arrows) fossa (dotted white arrows). (Images courtesy of Clinical suggesting focal bony ankylosis. Ill-defined lucencies Associate Professor Andy Whyte, Perth Radiological (black arrows) represent synovial proliferation extending Clinic, Perth WA, Australia) diagnosis of RA, with high specificity, presence disease. Anti-CCP antibodies have not been early in the disease process, and ability to identify found at a significant frequency in other diseases patients who are likely to have severe disease and to date and are more specific than rheumatoid irreversible damage. However, its sensitivity is factor for detecting rheumatoid arthritis (Niewold low, and a negative result does not exclude et al. 2007). 8 L.G. Mercuri and S. Abramowicz

Fig. 7 Seronegative inflammatory arthritis of the right can occur in inflammatory arthritis secondary to weaken- TMJ. (a) Right TMJ: The disc is anteriorly displaced. ing of the disc attachments by inflammation. (b) Left TMJ: The lower and to a lesser extent, upper joint spaces are Minimal anterior disc displacement is present. There is no markedly distended by high signal fluid/synovial prolifer- evidence of intra-articular inflammation, the cortices are ation. There is erosion of the superior condylar cortex intact, and there is no marrow edema. C condyle, AE (white dashed arrow) and edema of the bilaminar zone articular eminence and EAC external auditory canal (white arrow). High signal marrow edema is present in (Images courtesy of Clinical Associate Professor Andy the condyle (C) and articular eminence. Disc displacement Whyte, Perth Radiological Clinic, Perth WA, Australia)

Table 3 There are seven main types of JIA, but catego- polyarthritis, (5) psoriatic arthritis, (6) enthesitis rizing conditions is not easy as very often there is overlap (inflammation at tendon/ligament insertion into between the different categories bone) related arthritis, and (7) undifferentiated The seven types of JIA arthritis (Petty et al. 2004) (Table 3). Oligoarthritis Affects four or fewer joints Clinical findings vary and depend on the loca- Extended Affects more joints after the tion, subtype of arthritis, and duration of disease oligoarthritis initial 6 months (i.e., limp, morning stiffness, difficulty walking/ Polyarthritis Affects more than four joints running). Children may exhibit extremity over- Enthesitis-related Affects where the tendons attach growth, undergrowth, or asymmetries such as JIA to the bones Psoriatic arthritis Psoriasis with associated joint leg length discrepancies in the axial skeleton. inflammation Depending on the duration of symptoms, patients Systemic JIA Affects the organs as well as the may have muscular atrophy around the affected joints joints and contractures. Detection of synovitis is a Undifferentiated Does not fit into a single category key aspect of JIA diagnosis and management and arthritis may prevent long-term disability (Abramowicz et al. 2016). JIA patients who also have TMJ involvement Juvenile Idiopathic Arthritis can have a dual diagnosis of active arthritis and muscle-related pain. However, subjective Juvenile idiopathic arthritis (JIA) is the most com- finding of jaw pain is not always predictive of monly diagnosed high-inflammatory rheumato- TMJ synovitis (Abramowicz 2013a). Limited logic condition in children. It is diagnosed based mouth opening and deviation of jaw when open- on medical history, clinical presentation, radio- ing have high sensitivity and specificity for syno- graphic findings, and laboratory abnormalities. vitis (Abramowicz 2013b). Open bite develops as There are seven categories of JIA: (1) systemic the result of disease-related condylar bone loss onset, (2) oligoarthritis, (3) rheumatoid factor pos- (Fig. 2). However, gadolinium enhanced MRI itive polyarthritis, (4) rheumatoid factor negative most accurately demonstrates synovitis (Fig. 8). Arthritic Conditions Affecting the Temporomandibular Joint 9

Fig. 8 Thirteen-year-old female with JIA. (a) Proton den- arrow in b). Diffuse erosion of the condylar cortex (open sity, sagittal MRI scan showing a normally positioned white arrows in b) and subarticular marrow edema (dotted meniscus (M); GF indicates the glenoid fossa and AE the white oval in c). (d) Three months later the patient articular eminence. (b) and (c) Fat saturation T2 sagittal of represented with left knee pain and swelling. A fat satura- the same joint demonstrating distension of the inferior joint tion T2 MRI scan showed a hyperintense joint effusion space by moderately hyperintense fluid and synovial pro- with foci of synovitis (red arrows). JIA was confirmed liferation (white dotted arrows). A trace of hyperintense (Images courtesy of Clinical Associate Professor Andy fluid is present in the upper joint space (white dashed Whyte, Perth Radiological Clinic, Perth WA, Australia)

Management of JIA depends on the severity of disease into their 30s (Handleman and Mercuri disease, number of joints involved, and current 2015). physical limitations (Abramowicz et al. 2011). The etiology is speculative and includes it being a variation of one of the arthritic conditions affecting the TMJ, functional overload, ortho- Condylar Resorption gnathic surgery, or hormonal imbalance (Mercuri 2007; Handleman and Mercuri 2015). Idiopathic or progressive condylar resorption A history of autoimmune and collagen dis- (ICR/PCR) is a severe form of joint degeneration eases should be documented. Referral to a phy- that selectively affects the TMJ of adolescent and sician for rheumatoid factor serology should be young adult females. The period from the teen considered, although this is usually negative in years to the early 20s appears to be the most active ICR/PCR. When pain is reported, it may indicate time for ICR/PCR. Occasionally, the disease goes that the disease is active (Sarver and Janyavula into remission and “burns out” by the mid-20s. 2013). However, some patients continue to have active 10 L.G. Mercuri and S. Abramowicz

Fig. 9 Thirty-three-year- old female patient with PCR who reported that her anterior open bite developed over 2 years after a pregnancy. External lateral profile (a) intra-oral lateral (b) and frontal (c) views. Orthopantomogram (d) and lateral cephalogram (e) (Images courtesy of Dr. Sylvain Chamberlain, Quebec City, Canada)

A history of irregular menstrual cycles, amen- increased anterior facial height with an increase orrhea, or use of oral contraceptives has been in the and negative (Fig. 9e). CT reported in female patients indicating that demonstrates degeneration of condylar bone mid-cycle serum levels of 17β-estradiol should (Fig. 10). The employment of radioisotope scan- be measured, as low levels have been reported ning is controversial. MRI is useful in examina- associated with the development of severe condy- tion of the soft tissues of the TMJ, such as the lar resorption (Gunson et al. 2009). chondral integrity of the condylar head surface, The orthopantogram can provide gross articular disc position and condition, joint effu- examination of condylar anatomy in suspected sion, and marrow edema (Fig. 11). MRI or cone cases, and features of this condition include a beam CT can be used to follow progress of con- loss of condylar bone, thereby decreasing the dylar resorption and subsequent remodeling of the height of the ramus and length of the , condyle in ICR (Hatcher 2013). In addition to and an opening rotation of the mandible demonstrating the position and condition of a resulting in a Class II open bite. The condyle displaced disc and recapture or failure of recapture will appear to have lost mass relative to the rest on opening, MRI is the only imaging technique of the mandible and appear thin or shortened that can accurately demonstrate intra-articular with flattening of the superior and/or anterior inflammation and sub-articular marrow edema curvature (Fig. 9). secondary to erosion of the condylar articular The cephalometric imaging will show mandib- surface. ular divergence relative to the cranial base and A biomedical and drug management approach , shortened posterior facial height, and has been proposed in which an occlusal appliance Arthritic Conditions Affecting the Temporomandibular Joint 11

a

EAC c

b

D EAC D

Fig. 10 A 19 year old female with bilateral ICR/ PCR. A anterior disc displacement (D). Where EAC = external sagittal reconstruction from a multi-detector CT of the left auditory canal. A lateral cephalogram of the same patient TMJ (a) is compared with a fat saturation T2 weighted shows marked mandibular retrognathism and a high max- sagittal MRI scan of the same joint. Extensive condylar illary-mandibular plane angle and anterior lower facial erosion and resorption (open white arrows) is associated height. (Images courtesy of Clinical Associate Professor with high signal marrow edema in condylar marrow (black Andy Whyte, Perth Radiological Clinic, Perth WA, arrow) inferior joint space synovitis (dotted white arrows). Australia) The glenoid fossa is not involved and there is marked which is employed for 6 months to reduce the The approach to management of ICR/PCR mechanical loads on the joint, and the patient is cases should be individualized and based on the placed on a comprehensive series of medications, extent of the disease process. However, if either clonazepam to relax the musculature and decrease condylar resorption is active, in cases requiring loading from , antioxidants, tetracycline extreme mandibular advancements, those with and piroxicam, and an Omega-3 fatty acid diet to compromised function with severely limited decrease inflammation. A biologic, such as movement of the joints, or failure of previous etanercept, is prescribed to reduce the patient’s orthognathic surgery, then total alloplastic TMJ inherent bone resorption capacity (Arnett and replacement (TMJR) prosthesis should be consid- Gunson 2013). ered (Fig. 12) (Mercuri 2007; Handleman and Mercuri 2015; Mehra et al. 2016). 12 L.G. Mercuri and S. Abramowicz

Fig. 11 Bilateral idiopathic condylar resorption (ICR) in a diffuse hyperintense, marrow edema when compared to 16-year-old female with mandibular retrognathism, asym- the normal, low-signal marrow, in the articular eminence metry, alteration in occlusion, right TMJ pain, and (AE) and glenoid fossa (GF) in image b. Mature articular suspected internal derangement. Proton density (a) and surface remodeling of the left TMJ with flattened articular fat saturation T2 (b) sagittal images of the symptomatic surfaces and intact cortices (white dotted arrows) as shown right TMJ. A hyperintense effusion distends the anterior on proton density (c) and fat saturation T2 sagittal (d) recess of the upper joint space (red arrows). There is sequences. The disc (D) is anteriorly displaced and marked anterior disc displacement with swelling and deformed and there is only low grade intra-articular inflam- myxoid degeneration of the posterior band (PB). There is mation. This joint had been symptomatic 2 years previ- extensive resorption of the condylar head (open white ously (Images courtesy of Clinical Associate Professor arrow in a) associated with marked synovitis (white dotted Andy Whyte, Perth Radiological Clinic, Perth WA, oval in b). A tapered condylar stump remains (C) with Australia)

Management of TMJ Arthritic and prevention of disability and disease related Conditions morbidity (Mercuri 2006). An escalating scale for management of TMJ arthritic conditions exists. Noninvasive modalities The goals for the management of TMJ arthritic consist of education, physical therapy, oral appli- conditions consist of pain relief, improvement of ance therapy, diet control, and pharmacologic joint function, diminishing further joint damage, agents. Minimally invasive procedures can also include arthrocentesis, arthroscopy, and/or visco- Arthritic Conditions Affecting the Temporomandibular Joint 13

Fig. 12 Lateral cephalogram of a 15-year-old female with Ventura, CA) and genioplasty (Images courtesy of Dr. ICR/PCR pre- (a)- and 6 years post (b)-bilateral patient- Donald Kalant, Naperville, Illinois, USA) fitted alloplastic (TMJ Concepts, 14 L.G. Mercuri and S. Abramowicz

Fig. 13 Arthritic condition management pyramid (Hochberg 2012)

Surgery

Arthrocentesis, Arthroscopy, Visco-supplementation

Pharmacologic agents

Education, Physical Therapy, Oral Appliance, Soft Diet

Table 4 Management classification scheme for TMJ arthritic conditions based on signs, symptoms, and imaging (Mercuri 2006; Steinbrocker et al. 1949; Kent et al. 1986) Stage Symptoms Signs Imaging Manage I Early Joint pain Little or no esthetic or Mild/moderate erosion of condyle/ Noninvasive disease Muscle pain occlusal changes fossa and eminence # Limited function Minimally Crepitus invasive II Arrested Some joint pain Class II Flattening of condyle and eminence Invasive disease Muscle pain Open bite # Some Salvage joint dysfunction Crepitus III Advanced Joint pain High angle Gross erosion Salvagea disease Muscle pain Class II Loss of height Dysfunction Open bite Ankylosis Retrognathia Ankylosis Coronoid hyper aOrthognathic surgery or total joint replacement should be considered in a patient with JIA supplementation. Surgical interventions consist of Noninvasive Modalities invasive procedures (e.g., bone and joint proce- dures such as and ) or sal- Education, Physical Therapy, Oral vage procedures such as autogenous or alloplastic Appliance Therapy, and Diet Control joint replacement (Fig. 13). A classification and One of the most difficult problems for patients management scheme based on clinical signs, with arthritic conditions is acceptance that the symptoms, and imaging was proposed many disease is chronic, with little likelihood of spon- years ago (Steinbrocker et al. 1949), clarified in taneous complete resolution. Patients with the 1980s (Kent et al. 1986), and enhanced and arthritic conditions must live with their disease. modified recently (Table 4) (Mercuri 2006). Therefore, accurate diagnosis and appropriate patient education are critical to the successful management and quality of life (Mercuri 2006). Arthritic Conditions Affecting the Temporomandibular Joint 15

Fig. 14 Therabite jaw exercising device. Atos Medical, Milwaukee, WI

Physical modalities can reduce inflammation thereafter. This appliance should be full coverage, and pain. Superficial moist heat or localized cold opening the bite 2–3 mm posteriorly. It should may relieve pain sufficiently to permit exercise. allow freedom of movement in all excursions of Therapeutic exercises are designed to increase the mandible with cuspid rise or group function in muscle strength, reduce joint contractures, and lateral excursions and incisal guidance in protru- maintain a functional range of motion. Ultra- sion (Fig. 15) (Mercuri 2006). sound, electro-galvanic stimulation, and massage techniques are also helpful in reducing inflamma- Pharmacologic Agents tion and pain (Mercuri 2006). In an informative There are multiple pharmacologic agents study, active and passive jaw movements, manual employed to decrease pain and inflammation in therapy techniques, correction of body posture, the management of arthritic conditions. Acet- and relaxation techniques were used in the man- aminophen, opioid analgesics, nonsteroidal anti- agement of 20 consecutive TMJ arthritis patients. inflammatory drugs (NSAIDs), COX-2 inhibitors, After treatment (mean 46 days) pain at rest was biologics, nonacetylated salicylate, diclofenac reduced by 80% and there was no impairment in sodium, and/or glucosamine have all been used 37% of patients (Nicolakis et al. 2001). In pursu- with varying results. ing physical therapy, patients should avoid heavy loading exercises that compress the joint. For this Low-Inflammatory Arthritic Condition reason, isometric muscle strengthening exercises, Pharmacologic Management done so as not to cause pain, are best. Assisted, Acetaminophen (paracetamol), nonsteroidal anti- passive range of motion exercises such as with inflammatory drugs, and opioids are effective in one of the commercially available jaw exercising relieving pain but are incapable of reversing car- devices, such as the Therabite (Atos Medical, tilage damage and are frequently associated with Milwaukee, WI) is recommended (Fig. 14) adverse events. Current research focuses on the (Oh et al. 2002; Salter et al. 1984). development of new drugs (such as sprifermin/ Soft diet and the use of an oral appliance have recombinant human fibroblast growth factor-18, been demonstrated to aid in decreasing the load tanezumab/monoclonal antibody against β- across the articulating surfaces of the joint growth factor), which aim for more effectiveness (Casares et al. 2014). A flat plane processed and less incidence of adverse side effects (Zhang acrylic maxillary stabilization occlusal appliance et al. 2016). can be worn 24/7 for 1 month, except while eat- Regenerative therapies (such as autologous ing, during the initial acute phase, then at night chondrocyte implantation (ACI), new generation 16 L.G. Mercuri and S. Abramowicz

Fig. 15 Flat plane processed acrylic maxillary, full coverage, stabilization appliance (Image courtesy of Clinical Associate Professor Ramesh Balasubramaniam, Perth Oral Medicine & Dental Sleep Centre, Perth WA, Australia)

of matrix-induced ACI, cell-free scaffolds, American Academy of Orthopedic Surgeons induced pluripotent stem cells (iPS cells or (AAOS) guideline downgraded the acetamino- iPSCs), and endogenous cell homing) are also phen recommendation level to inconclusive and emerging as promising alternatives, as they have reduced the daily dosage from 4000 to 3000 mg potential to enhance cartilage repair, and ulti- (AAOS 2013). For patients with severe symptoms mately restore healthy tissue. However, despite or who do not respond to acetaminophen, more currently available therapies and research potent drugs should be considered, such as non- advances, there remain unmet medical needs in steroidal anti-inflammatory drugs (NSAIDs). the treatment of low-inflammatory arthritic condi- tions (Zhang et al. 2016). NSAIDs NSAIDs provide anti-inflammatory and The following review highlights current analgesic effects, and have long been used as an knowledge, research progress on pharmacologic important remedy for moderate-to-severe and regenerative therapies for low-inflammatory low-inflammatory arthritic conditions. Acetamin- arthritic conditions and includes key advances and ophen is not regarded as an NSAID as it has little potential limitations of these agents. anti-inflammatory effect. In a meta-analysis com- paring the safety and efficacy between acetamin- Acetaminophen (Paracetamol) Due to its relative ophen and NSAIDs, the NSAIDs were better safety and effectiveness, acetaminophen is overall than acetaminophen in terms of pain relief. recommended as the first-line oral analgesic for Although the efficacy of NSAIDs for manage- mild-to-moderate low-inflammatory arthritic con- ment of low-inflammatory arthritic conditions ditions by most guidelines. The American College has been well documented, their potential adverse of Rheumatology (ACR) and the Osteoarthritis biological affects often restrict their extensive Research Society International (OARSI) guide- application (Zhang et al. 2004). lines recommend up to 4000 mg per day is an It is estimated that adverse effects occur in effective initial treatment for mild-to-moderate approximately 30% of those who take NSAIDs knee or hip low-inflammatory arthritic conditions (Pirmohamed et al. 2004). One percent to two (Hochberg 2012). percent of people using NSAIDs develop gastro- Due to the risk of liver damage, the US Food intestinal (GI) complications per year, which is and Drug Administration (FDA) limited the much higher than those not using NSAIDs (Garcia amount of acetaminophen in prescription combi- and Jick 1994). Although selective COX-2 inhib- nation products to no more than 325 mg per dos- itors appeared safer than traditional NSAIDs, sev- age unit (US FDA 2015). Consistent with the eral commercial drugs have been placed under change made by the FDA, the latest 2013 scrutiny or withdrawn by the FDA. The first Arthritic Conditions Affecting the Temporomandibular Joint 17 approved COX-2 inhibitor Celecoxib (Celebrex, efficacy for arthritic condition management should Pfizer, New York, NY) received an FDA alert for be performed (Zhang et al. 2016). the potential risk of serious adverse cardiovascu- lar events (US FDA 2005a). Rofecoxib (Vioxx, Potential Pharmacologic Management Merck, Kenilworth, NJ) and Valdecoxib (Bextra, for Low-Inflammatory Arthritic Condition Pfizer, New York, NY) were withdrawn from the The unsatisfactory effects and unacceptable side market for associated cardiovascular risks and effects associated with traditional drugs warrants other side effects (US Food and Drug Adminis- a continued search for potential new medications. tration 2004, 2005b). Although few of them have received the regula- Therefore, there is a balance between the effi- tory approval for routine clinical use, a variety of cacy and safety of NSAIDs, and the benefit/risk new low-inflammatory arthritic condition man- ratio should be considered when employing these agement drugs have shown promising results in drugs. It is recommended by OARSI that NSAIDs clinical trials. Based on the potential therapeutic be used at the minimum effective dose and pro- targets, they can be classified as chondrogenesis longed use should be avoided as much as possible inducers, osteogenesis inhibitors, matrix degrada- (Zhang et al. 2008). tion inhibitors, apoptosis inhibitors, and anti- inflammatory cytokines (Zhang et al. 2016). Opioid Analgesics Opioids are used for the man- agement of moderate-to-severe low-inflammatory Bone Morphogenetic Protein-7 Recombinant arthritic pain when NSAIDs and acetaminophen human bone morphogenetic protein-7 (BMP-7), are ineffective or contraindicated (Zhang et al. also called osteogenic protein-1 (OP-1), was a 2008).There has been an increased use of opioids FDA-approved biologic for the treatment of in arthritic disease management (31% in 2003 to bone nonunions and spine fusion (Ong et al. 40% in 2009) (Wright et al. 2014). However, the 2010). A Phase 1 safety and tolerability study frequent adverse effects associated with opioids, first reported the use of BMP-7 in symptomatic including nausea, vomiting, dizziness, constipa- low-inflammatory knee arthritic disease. Thirty- tion, sleepiness, tiredness, and headache, may three patients (mean age 60 years) were injected outweigh the benefits in pain relief (Beaulieu intra-articularly with four doses of BMP-7 or pla- et al. 2008). Opioid abuse is another potential cebo. Participants who received 0.1 and 0.3 mg of risk of using these drugs. Routine use should be BMP-7 showed greater symptomatic improve- avoided, and low effective and tolerated doses are ment and higher OARSI response rate. No dose- recommended if these drugs must be used limiting toxicity was found. Phase 2 study with (Bouloux 2011). 0.1 and 0.3 mg dosing cohorts would be further conducted in future (Zhang et al. 2016). Serotonin–Norepinephrine Reuptake Inhibi- tors (SNRIs) SNRIs are primarily used in the Interleukin-1β Two randomized, double-blind, treatment of depression and other mood disorders. placebo controlled studies attempted interleukin In 2010, the FDA approved duloxetine, a selective (IL)-1β inhibitor for low-inflammatory knee SNRI, for the management of chronic musculo- arthritic disease management (Chevalier et al. skeletal pain including low-inflammatory arthritic 2009; Cohen et al. 2011). Although IL-1β receptor pain (US Food and Drug Administration 2010). It antagonist/antibody was well tolerated, no signif- may be a promising and efficacious way to alleviate icant clinical improvements were reported com- low-inflammatory arthritic pain for patients who are pared with placebo in either study. unable to take other more commonly used drugs. However, AAOS and OARSI have not included β-Nerve Growth Factor Tanezumab, a monoclo- duloxetine in their low-inflammatory arthritic pain nal antibody against β-nerve growth factor, has management guidelines as more large-scale longitu- been tested clinically against low-inflammatory dinal studies to further investigate the safety and arthritic conditions. As compared with the 18 L.G. Mercuri and S. Abramowicz placebo treatment, treatment with tanezumab sig- with notable side effects which can pose long- nificantly reduced knee pain while walking and term treatment challenges, as well as difficulties improved the patients’ global assessment (Lane in the perioperative arena (Kahlenberg and Fox et al. 2010). However, 68% of patients receiving 2011). tanezumab were recorded with adverse events. Sixteen subjects developed rapidly progressive NSAIDs Nonsteroidal anti-inflammatory medica- end-stage low-inflammatory arthritic disease tions (NSAIDs) are used often in the management requiring total joint replacements. These findings of high-inflammatory arthritic conditions in con- prompted the FDA to request the suspension of junction with other medications or as mono- the trials of tanezumab. However, from subse- therapy for acute gout or the seronegative quent assessments, the risk of rapidly progressive spondylo-arthropathies. There is no one NSAID arthritic disease with tanezumab was lower than medication or dose recommended over other med- that with tanezumab/NSAID combination ther- ications (Bays and Gardner 2016). apy, and the rate of joint replacement was compa- rable between tanezumab monotherapy and Corticosteroids Steroids are used commonly in placebo treatment. Therefore, the FDA has agreed the management of the high-inflammatory arthritic to continue the clinical trials of tanezumab for conditions. Glucocorticoids act through the cyto- low-inflammatory arthritic pain management in solic steroid hormone receptor, resulting in conjunction with appropriate safety monitoring increased expression of anti-inflammatory proteins (US Food and Drug Administration 2012). and decreased production of proinflammatory pro- teins (Stahn and Buttgereit 2008). Fibroblast Growth Factor A proof-of-concept The underlying principle in prescribing ste- study has been conducted to evaluate the efficacy roids is that patients should be on the lowest and safety of intra-articular sprifermin (recombi- dose possible for the least amount of time. Some nant human fibroblast growth factor-18) to man- consequences of steroid usage include bone loss, age symptomatic low-inflammatory knee arthritic hypertension, weight gain, steroid psychosis, pain with 180 patients. Sprifermin treatment sig- impaired glucose tolerance, avascular necrosis, nificantly reduced the loss of total and lateral and increased rate of infection. In addition, severe femorotibial cartilage thickness and volume, as hypokalemia may occur from pulse dose steroids. well as the joint space width narrowing in the Important adjunctive therapy includes calcium lateral femorotibial compartment in a dose- and vitamin D, and in some situations, prophylac- dependent manner. No significant difference in tic bisphosphonate therapy and prophylaxis serious adverse events was recorded between against pneumocystis. Special considerations groups (Lohmander et al. 2014). More basic and include patients with high infectious risk, patients clinical studies should be performed to fully with diabetes, and patients with surgical wound investigate this novel low-inflammatory arthritic healing. In addition, steroid usage may increase condition management biologic drug (Zhang et al. the risk of GI bleed in a hospitalized patient set- 2016). ting, and prophylactic proton pump inhibitors should be considered (Narum et al. 2014). Pharmacologic Management for High- Disease modifying anti-rheumatic drugs Inflammatory Arthritic Condition (DMARDs) became the mainstay of RA manage- Over the past two decades, the management of ment in the 1970s. Examples of conventional systemic high-inflammatory arthritic conditions DMARDs are methotrexate, leflunomide, hydro- has been revolutionized by advances in the under- xychloroquine, and sulfasalazine. standing of their pathologic mechanisms and the As a group, these drugs have been shown to development of drugs which directly target them. decrease inflammation and slow radiographic pro- These newer medications have shown great prom- gression of the disease’s effect on articulations; but ise at improving disease outcomes, but they come the degree to which this is accomplished is Arthritic Conditions Affecting the Temporomandibular Joint 19 variable. The timing of DMARD initiation has inflammatory arthritic conditions (Statkute and been debated, but current consensus suggests that Ruderman 2010). Other biologic DMARDs the earlier treatment can be initiated, the better the found to be effective in inhibiting the immune overall outcome for clinical improvement and pre- and cytokine systems in high-inflammatory arthritic vention of erosive disease (Verstappen et al. 2003). conditions include rituximab, abatacept, anakinra, A major difficulty in managing patients with and tocilizumab (Kahlenberg and Fox 2011). high-inflammatory arthritic conditions is that it is By their nature, high-inflammatory arthritic currently impossible to predict which patients will conditions confer an elevated risk of infection. respond to which medication regimen. Current DMARD and biologic therapies suppress the research is ongoing to develop patient-specific immune system through various targets, increas- disease signatures via genetic and proteomic ing this risk. Bacterial infections, particularly approaches. However, the practical application pneumonia and soft tissue infections, are of such advances has not been achieved. Thus, increased with the use of methotrexate, and this practice guidelines typically recommend starting is increased 2–4-fold with the addition of an anti- with conventional DMARD treatment before TNF medication. Similar infectious risks have addition or substitution of biologic DMARD med- been found with other biologic DMARDs as ications. Importantly, the use of DMARDs in well (Mushtaq et al. 2011). combination rather than monotherapy has been Because of the nature of their disease, patients reported more effective in achieving improved with high-inflammatory arthritic conditions have clinical outcomes as well as slowing radiographic many features that can impact perioperative man- progression of the disease (Ma et al. 2010). agement. Thus, consultation with a patient’s rheu- matologist prior to surgery may help to identify Biologic DMARDs The availability of medica- unique risks for that patient and prevent perioper- tions targeted toward specific abnormalities of ative morbidity and mortality. High-inflammatory the immune system, the so-called biologic arthritic patients have an increased risk of infec- DMARDs, has revolutionized the management tion after joint replacement surgery (Bongartz of high-inflammatory arthritic conditions. This et al. 2008). The use of corticosteroids, DMARDs, expanding collection of drugs targets molecules and biologic DMARDs all can increase the risk of which have been shown to play important roles in infection and theoretically impair wound healing. the pathology of these diseases. There is ongoing debate regarding which medica- Because of their cost and side effect profile, the tions to interrupt perioperatively. Current recom- use of biologic DMARDs is typically recommended mendations for perioperative use of these after patients have failed the use of single or combi- medications are summarized in Table 5 nation conventional DMARD therapy. However, in (Kahlenberg and Fox 2011). patients who present with aggressive, erosive high- inflammatory arthritic conditions, the biologic DMARDs can be considered as a component of Minimally Invasive Procedures first-line therapy (Kahlenberg and Fox 2011). The initial choice of a biologic DMARD is A Cochrane Database meta-analysis concluded typically a tumor necrosis factor (TNF) blocking that there was a paucity of high level evidence agent, which includes infliximab, adalimumab, for the effectiveness of interventions for the man- etanercept, and the newer golimumab and agement of TMJ arthritic conditions. Large paral- certolizumab. These agents have varied effects lel groups of randomized clinical trials which on a molecular level including binding soluble include participants with a clear diagnosis of TNFα and induction of apoptosis of TNFα TMJ arthritic conditions should be encouraged, expressing cells. Each of these drugs has a distinct especially studies evaluating some of the possible dosing schedule or mode of administration. How- surgical interventions (de Souza et al. 2012). ever, all appear to have similar benefits in high- 20 L.G. Mercuri and S. Abramowicz

Table 5 Recommendations for perioperative manage- HA injections into an experimentally induced ment of medications used to treat high-inflammatory sheep TMJ low-inflammatory arthritic disease arthritis (Kahlenberg and Fox 2011) model over a 14-month period suggested a possi- Medication Perioperative management ble role for HA in preventing the progression of Steroids Continue at lowest dose the disease. The HA-injected TMJs revealed min- possible; stress dose steroids as indicated imized osteoarthritic changes when compared to Methotrexate Hold doses immediately before control joints injected similarly with saline (Neo and after surgery et al. 1997). Leflunomide Hold at least 1 week prior to In humans, it has been reported that after a surgery 24-month follow-up period after arthrocentesis Hydroxychloroquine Continue perioperatively either with or without the addition of HA, that Sulfasalazine Hold only on day of surgery although both groups benefited from these pro- Anti-TNF drugs Hold for one dose cedures, those patients having arthrocentesis with perioperatively the addition of HA had superior results (Alpaslan Rituximab Optimal timing of surgery when CD20 counts have rebounded and Alpaslan 2001). An in vivo rabbit study com- (3–6 months after last dose) pared intra-articular injections of 1.6-mg prednis- Abatacept Hold 1 month prior to surgery olone and 1.3-mg hyaluronate weekly for 1 month Anakinra Hold 1 week before and after for TMJ low-inflammatory arthritic disease. The surgery HA injected joints demonstrated limited cartilage Tocilizumab Hold dose prior to surgery change, less fibrillation, and the presence of clus- ters of chondrocytes in deficit areas. The prednis- Intra-articular Medications olone treated joint exhibited worsening of the Localized drug delivery via intra-articular injec- cartilage destruction (Shi et al. 2002). tions can minimize ectopic effects while directly A systematic review and meta-analysis of all alleviating joint pain and other symptoms. Intra- randomized, controlled trials of intra-articular HA articular injection of corticosteroids and injections for TMJ disorders concluded that the hyaluronic acid are selectively used in the man- existing evidence was insufficient to either sup- agement of arthritic conditions. port or refute the benefit of HA injections (Shi et al. 2003). Nevertheless, the usefulness of serial Hyaluronic Acid Sodium hyaluronic acid (HA) is HA injections performed after arthrocentesis for an injectable, large, linear glycosaminoglycan the treatment of TMJ low-inflammatory arthritic that is a component in both healthy and arthritic disease and for the maintenance of improvements joint fluid. Intra-articular injection of HA is over a 6-month follow-up period was reported recommended by OARSI as a management option (Manfredini et al. 2009). for painful knee or hip arthritic conditions (Zhang The US FDA has only approved intra-articular et al. 2008). However, the efficacy of HA injection hyaluronic acid (HA) formulations for knee varies. The 2013 edition of the AAOS guideline arthritic conditions. However, these formulations downgraded the recommendation on HA from an are currently being used “off label” (Stafford inconclusive level to a nonaffirming level after 2008) to manage pain in several other joints, excluding the lower strength evidence of its effec- including the TMJ (Tanaka and Detamore 2008; tiveness (Felson 2006). Salk et al. 2006). For TMJ arthritic conditions, there was no difference in outcomes of measured variables Corticosteroids Corticosteroid injection is between the HA group and the placebo and saline recommended by OARSI for patients with control groups. It was concluded that HA did not moderate-to-severe pain who do not respond to appear to be an effective means of treating TMJ oral analgesic and anti-inflammatory agents arthritic conditions (Bertalomi et al. 1993). (Zhang et al. 2008). The American College of Rheu- matology and AAOS conditionally recommended Arthritic Conditions Affecting the Temporomandibular Joint 21 corticosteroids for management of early knee and/or release applications (Gerwin et al. 2006; Larsen for hip arthritic conditions (Hochberg et al. 2012). et al. 2008). Novel systems for sustained release The main limitations of repeated intra-articular will increase the resident time of medications steroid injections are the risks of infection and the within the joint, reducing the need for repeated destruction of articular cartilage, tendon, or liga- intra-articular injections and thus minimizing iat- ment attachments. Repeated intra-articular corti- rogenic damage. Tighter control over release costeroid injections have been implicated in the kinetics would reduce the required medication “chemical condylectomy” phenomenon in the dosage and decrease the risk of ectopic effects TMJ of adults (Møystad et al. 2008; Moskowitz (Mountziaris et al. 2009). et al. 1970; Ringold et al. 2008; Slater et al. 1967; There has been reluctance to use intra-articular Toller 1977). Single injections of steroids into the steroid injections for arthritic TMJs in children TMJ may be helpful for patients over 30 years of because of initial studies reporting cartilage dam- age but are not indicated in younger patients (Tol- age and avascular necrosis. However, these ler 1977). adverse outcomes occurred in adults with arthritic A review of an extensive experience of over conditions, not in children with JIA. Intra- 7000 injections of hydrocortisone into synovial articular injections can be indicated as an adjunct cavities concluded that such treatment was a safe to systemic treatment of JIA, if the TMJs exhibit and effective palliative procedure in the local persistent active arthritis despite systemic therapy. management of arthritic condition (Hollander TMJ injections may also be of use in patients not 1953). However, almost concurrently, caution responsive to systemic medication to provide was recommended with this treatment since the relief during a change in drug therapy steroid might interfere with a local protective (Abramowicz et al. 2016). mechanism and encourage further damage with Intra-articular steroid injections for manage- joint function (Chandler and Wright 1958). ment of TMJ symptoms in JIA have had recent Experimental evidence of histological damage success using triamcinolone acetate or triamcino- to the articular surfaces of the mandibular con- lone hexacetonide. Adverse reactions have been dyles of healthy Macaca irus monkeys was reported to be rare, but they included transient reported after six injections of hydrocortisone facial swelling (Arabshahi et al. 2005), and/or (Poswillo 1970). Intra-articular injections of ste- reversible subcutaneous atrophy at the injection roids are not routinely recommended in patients site (Ringold et al. 2008). These studies reported with low-inflammation arthritic conditions. Injec- that most patients demonstrated an increase in tions should be considered only with evidence of mouth opening. However, repeated injections acute high-inflammation of the joint. In all cases only yield minimal further benefits (Ringold after intra-capsular injection of steroids, et al. 2008). If there is recurrence of TMJ JIA decreased activities within pain free limits should despite intra-articular injections, additional sys- be recommended to prevent acceleration of the temic therapy has been advocated (Abramowicz degenerative process from overactivity and joint et al. 2016). overload (Tanaka and Detamore 2008). The accu- In a study of 24 consecutive adult patients with racy of the placement of intra-articular injections TMJ low-inflammatory arthritic conditions depends upon the experience of the practitioner. An treated randomly with either arthrocentesis alone estimated one-third to one-half of all steroid and (control group) or arthrocentesis plus corticoste- HA injections are inaccurately placed, although the roid injection (CS group) where outcome vari- impact of this extra-articular placement on thera- ables were visual analog scale evaluations (i.e., peutic efficacy and clinical outcome remains masticatory efficiency, joint sounds, and pain unclear (Jackson et al. 2002; Jones et al. 1993). complaints), maximal interincisal opening, and Nano- and microparticles developed from a mandibular motions recorded at baseline and at variety of natural and synthetic materials are 12 months postoperatively, concluded that being investigated for intra-articular sustained arthrocentesis plus intra-articular CS injection 22 L.G. Mercuri and S. Abramowicz produced no better outcomes in terms of range of motion and clinical symptoms in patients with TMJ low-inflammatory arthritic conditions, as compared with those undergoing arthrocentesis alone (Kiliç 2016).

Platelet-Rich Plasma Platelet-rich plasma (PRP) contains several kinds of growth factors including transforming growth factor β1 platelet-derived growth factor, vascular endothelial growth factor, insulin-like growth factor-1, and hepatocyte growth factor (Sánchez et al. 2008). Positive trends and safety profile of PRP have been reported in other studies, suggesting a feasible and potential treatment for low-inflammatory arthritic conditions (Kon et al. 2010;Smythetal.2016). Fig. 16 Arthrocentesis lavage of the left TMJ superior In one study, surgical defects were created joint space. The upper joint space is undergoing a lavage bilaterally in the TMJ condylar fibrocartilage, with lactated Ringer’s solution in a patient with an acute hyaline cartilage, and bone to induce osteoar- disc displacement, limited mouth opening and pain thritic changes in rabbits. PRP was applied to the right joints of the rabbits (PRP group), and the left joints received physiologic saline (control group). PRP responded with substantial MMP secretion, After 4 weeks, the rabbits were sacrificed for which may increase cartilage catabolism. There- histologic and scanning electron microscopy fore, future studies must focus on the synergistic (SEM) examinations. The authors found new actions of PRP in the management of TMJ bone regeneration was significantly greater in the low-inflammatory arthritic conditions (Browning PRP group (P < .011). Although the regeneration et al. 2012). of the fibrocartilage and hyaline cartilage was greater in the PRP group, no statistically signifi- cant difference was found between the two Arthrocentesis groups. SEM showed better ultrastructural archi- Arthrocentesis is defined as the instillation or tecture of the collagen fibrils in the PRP group. removal of fluid or injection of medication into a They concluded that PRP might enhance the joint. In the TMJ, arthrocentesis has been used to regeneration of bone in TMJ low-inflammatory “wash out” TMJ inflammatory mediators, release arthritic conditions (Kütük et al. 2014). the “anchored” disc, disrupt joint adhesions, and When injected into patients with TMJ deliver drugs to the joint (e.g., HA, corticoste- low-inflammatory arthritic conditions, PRP was roids, PRP) to manage pain (Fig. 16). Typically, reported to have performed better than HA in manual TMJ manipulation to the extremes of follow-up in terms of pain reduction and increased function is performed during this procedure. The interincisal mouth opening (Hegab et al. 2015). procedure may be performed under local analge- In cell culture, the effects of PRP on non- sia, conscious sedation, or general . chondrocyte cell lineages within synovial joints, TMJ arthrocentesis provided a statistically sig- such as fibroblast-like synoviocytes, which pro- nificant short-term improvement of pain and duce cytokines and matrix metalloproteinases enhanced function in low-inflammatory arthritic (MMPs) that mediate cartilage catabolism were patients for 6 weeks after TMJ arthrocentesis (Tri- studied. Platelet-rich plasma was shown to con- eger et al. 1999). A possible explanation for the tain a mixture of anabolic and catabolic mediators. relief of symptoms being that debris and These authors found that synoviocytes treated Arthritic Conditions Affecting the Temporomandibular Joint 23

Fig. 18 Arthroscopic examination of the superior joint space of a right TMJ demonstrating early osteoarthritic changes at the posterior slope of the articular eminence. Note the loss of cartilage and exposed bone

symptoms in patients with low-inflammatory TMJ arthritic conditions, as compared with those under- going arthrocentesis alone (Kiliç 2016).

Fig. 17 Arthroscope in the superior joint space of a Arthroscopy right TMJ Arthroscopy is a procedure for diagnosing and managing intra-articular joint problems. A sur- inflammatory cytokines were removed during the geon inserts a narrow tube attached to a fiber- procedure (Quinn and Bazan 1990). optic video camera through a small incision. The The long-term outcome of arthrocentesis in view inside the joint in question is transmitted to a 79 patients (83 joints) with symptomatic TMJ high-definition video monitor (Figs. 17 and 18). low-inflammatory arthritic disease was studied. The value of TMJ arthroscopy lies in the early These patients had not responded to nonsurgical diagnosis and management of arthritic conditions. interventions. In this study cohort, arthrocentesis However, the incidence of low-inflammatory offered long-term favorable outcomes for symp- arthritic conditions on magnetic resonance images tomatic TMJ low-inflammatory arthritic patients (38%) was reported to be significantly lower than who had not responded to nonsurgical treatments that in arthroscopic findings (78%). There was no and otherwise would have required surgery. Sever- significant agreement between these two findings ity of preoperative clinical and computerized tomo- ( p = .108). The κ coefficient was 0.154. There- graphic findings did not predict the success of fore, they concluded that the diagnostic accuracy arthrocentesis. This finding and the lack of correla- of magnetic resonance images for TMJ arthritic tion between the clinical and radiologic findings condition was low and that the early arthritic negates the commonly held belief that the clinical condition could not be diagnosed from magnetic signs and symptoms deteriorate together with resonance images. These authors stated that the radiologic changes (Nitzan et al. 2016). diagnostic accuracy of low-inflammatory arthritic In another study, arthrocentesis plus intra- conditions without arthroscopy is not always articular corticosteroid injection produced no better high. outcomes in terms of range of motion and clinical 24 L.G. Mercuri and S. Abramowicz

Fig. 19 CT reconstruction of a bilateral TMJ ankylosis secondary to ankylosing spondylitis, a high-inflammatory arthritic condition (Images courtesy of Dr. Adriano R Germano, Sao Paulo, Brazil)

The arthroscopic picture varies widely Advanced arthroscopic surgical techniques depending on when during the arthritic process have been reportedly used to perform syn- the procedure is performed and whether disease- ovectomy in more advanced-stage RA where modifying therapeutic agents are concurrently used hypertrophic synovium or granulation tissue is (Holmlund 1991). For patients with rheumatoid found. The removal of such tissue may arrest the arthritis, the early features of synovial involvement disease process in that joint. These techniques may be increased vascularity and capillary hyper- demand considerable skill and must always be emia and the more severe the disease, the more performed under direct vision. Bleeding can these features will be observed. The same is true obscure the visibility and these procedures should of the cartilage, in which the findings may vary be limited to patients with well-defined lesions in from early superficial changes such as localized the hands of highly skilled arthroscopists areas with fibrillation, to lesions and exposure of (Holmlund 1991; Bjornland and Larheim 1995). subchondral bone. Late-stage marked fibrosis or Diagnostic and surgical arthroscopy has ankylosis makes arthroscopy impossible and con- decreased the morbidity and cost of invasive TMJ traindicates its usefulness. procedures; nevertheless, it is essential to under- In early-stage RA, arthroscopic lysis and stand that there are limitations to their use. In certain lavage has been reported to alleviate symptoms stages of TMJ arthritic conditions, it is in both the knee (Jayson and Dison 1968) and the contraindicated to attempt to insert an arthroscope. TMJ (Holmlund et al. 1986). The explanation for These include cases with marked clinical impair- the relief of symptoms being that debris and other ment of mobility due to fibrosis or bony ankylosis inflammatory products are removed (Gynther and (Fig. 19). Such cases, as well as those exhibiting Holmlund 1998). In cases with only minor areas imaging consistent with pronounced granulation of synovial inflammation, sometimes found in tissue or suspected villus formation, are all best early-stage RA, subsynovial injection of small managed by open TMJ procedures (Heffez 1991; volumes of corticosteroids during arthroscopy Holmlund 1991; Murakami 1992). and/or HA has been reported as helpful in reduc- ing symptoms and increasing function (Kopp et al. 1987; Vallon et al. 2002). Arthritic Conditions Affecting the Temporomandibular Joint 25

Surgery Arthroplasty High condylar shave; a procedure incorporating End-stage disease represents the worst condition limited removal of the damaged articular surface or disease state of an organ system, at which point of the condyle, while maintaining the height of the in time, the organ is functioning minimally or not ramus, the articular disk, and the surrounding soft at all. Systemic examples include end-stage renal tissue including the lateral pterygoid muscle attach- disease, in which the kidneys have essentially shut ments superiorly and inferiorly, has been advocated down and the patient requires dialysis or renal in severe, unremitting TMJ low-inflammatory transplantation to accomplish the essential roles arthritic conditions (Henny and Baldridge 1957). of the kidney; and end-stage cardiac disease, in Reshaping the articular surfaces to eliminate which the heart is functioning very poorly with osteophytes, erosions, and irregularities found in minimal cardiac output and a compromised ejec- TMJ low-inflammatory arthritic condition refrac- tion fraction, and may need mechanical support tory to other modalities of treatment has also been (e.g., left ventricular assist device) or cardiac employed for these cases (Dingman and Grabb transplantation for the patient to survive, consid- 1966). ering the vital role of the cardiovascular system While both techniques reportedly provided (Mercuri 2012). pain relief, there are concerns about resultant Applying the term “end-stage” to disorders mandibular dysfunctions, dental , affecting the functional joints of the human facial asymmetries, and the potential for develop- body, end-stage joint disease indicates a joint ment of further bony articular degeneration, disk that is so negatively affected architecturally by disorders or loss and ankylosis, and led to the disease or injury that severe functional impair- development of techniques for interposing autog- ment is the result for the patient. As with all enous tissues and alloplastic materials (Figs. 20, other joints in the body, the TMJ is affected by 21, 22, and 24) (Mercuri 2006). all the end-stage joint diseases such as develop- mental disorders, neoplasia, trauma, failed prior Osteotomy joint surgery, fibrous or bony ankylosis, or Preexisting TMJ pathology with or without symp- arthritic conditions (Mercuri 2012). toms that can lead to unfavorable orthognathic When considering surgical management of surgery outcomes include: arthritic conditions, end-stage TMJ arthritic conditions, multiple fac- neoplasia, severe trauma, internal derangements, tors should be evaluated. First, a check for any idiopathic condylar resorption, condylar hyper- effects the patient’s medication might have on plasia, osteochondroma, congenital deformities, coagulation and wound healing. Positioning the and nonsalvageable joints (Wolford 2003). patient for a long anesthetic due to joint deformi- Patients with an active low- or high- ties may lead to pressure necrosis of overlying inflammatory arthritic condition, and concomitant fragile skin. Cervical spine involvement and or resultant maxillofacial skeletal discrepancies, potential for cervical myelopathy in arthritic who undergo orthognathic surgery have had patients requires critical care in the positioning mixed outcomes (DeClercq et al. 1994; of the head for surgical access and can add to the Handleman and Mercuri 2015; Kerstens et al. hazard of cervical cord injury (Mercuri 2006). 1990; Moore et al. 1991; Wolford et al. 2002). In For functionally unacceptable open bites in those conditions, as in active, early stage TMJ early-Stage II cases (Table 4), the management arthritic disease, early erosive condylar and fossa options of arthroplasty or orthognathic surgery to bony changes result in loss of posterior mandibular close the open bite can be considered. In patients height (Figs. 2 and 3). Since the TMJs are the with an end-stage TMJ arthritic condition com- foundation of the mandible, the resultant pathology binedwithanopenbite,totaljointreplacement offers a poor base upon which to build any maxil- (TJR) should be considered (Mercuri 2006). lofacial functional skeletal reconstruction. 26 L.G. Mercuri and S. Abramowicz

Fig. 20 CT of a left autogenous costochondral graft reconstruction (Image courtesy of Dr. Michael Miloro, Chicago, Illinois, USA)

Fig. 21 “Bird ” clinical appearance and lateral cephalometric image of a patient with JIA and TMJ involvement

Further, the degenerative and osteolytic to manage maxillofacial skeletal discrepancies in changes the joint components undergo in these patients with an arrested arthritic condition (Sinn conditions make the compromised bony compo- 1992). A 10-year retrospective study of 16 chil- nents of the TMJ (condyle, eminence, and fossa) dren with JIA, who had mandibular advancement highly susceptible to failure under the new func- surgery (genioplasty and/or sagittal split ramus tional loading that will be developed after ortho- osteotomy), concluded that after evaluation of gnathic surgical repositioning of the maxillofacial esthetics, TMJ pain, and mandibular function skeleton. that all patients had improved and that the pro- Despite this, successful outcomes have been cedures performed were safe without complica- reported using orthognathic surgical procedures tions (Oye et al. 2003). Arthritic Conditions Affecting the Temporomandibular Joint 27

Fig. 22 Clinical appearance and lateral cephalometric image of patient with JIA and TMJ involvement 1 week post bilateral alloplastic TMJ replacements, LeFort I osteotomy and genioplasty

Bioengineered Tissue Autogenous Total Joint Replacement A bioengineered TMJ disc might be indicated to Long-term clinical results of autogenous replace unsalvageable articular discs caused by costochondral TMJ reconstruction in adult trauma, disease, or Wilkes Stage III and IV inter- patients have been reported as satisfactory nal derangements (Wilkes 1990), or as a compo- (Fig. 20). This observation is based on a 10-year nent of a bioengineered total TMJ replacement mean follow-up clinical study of 16 patients. All unit. The utility of bioengineered discs is a point cases were unilateral and four were reported pre- of debate because complete disc removal without operatively as severe TMJ arthritic conditions disc replacement, although controversial, has (Lindqvist et al. 1988). There was no indication yielded satisfactory long-term results (i.e., as to whether these four cases were decreased pain and improved joint mobility). low-inflammatory or high-inflammatory arthritis, Also, surgical placement and attachment of the although based on the pathophysiology of these disc to surrounding structures is of the utmost disease processes, it is suspected that these concern (Detamore et al. 2007). patients had low-inflammatory TMJ arthritic con- Because the disc must move with opening and ditions, which are demographically more com- closing of the jaw, the device might be prone to mon unilaterally than is high inflammatory TMJ failure if it does not possess adequate mechanical arthritis. integrity to oppose all the forces associated with A retrospective clinical follow-up study (mean ginglymo-arthrodial articulation. Bioengineered 5-year; range 2–11 years) concluded that despite a total joint implant constructs also might be 10% infection rate and an unpredictable growth contraindicated for use in reactive or inflamma- rate in younger patients (requiring later corrective tory environments such as in the high- ), autogenous free costochondral inflammatory arthritic conditions, where the grafting was also a successful method for recon- underlying autoimmune process likely will struction of portions of the mandible and its tem- destroy the regenerated tissue as it typically does poral articulation in the reconstruction of to autogenous tissues in such cases (Salash et al. 22 patients (14 unilateral) (Obeid et al. 1988). 2016). 28 L.G. Mercuri and S. Abramowicz

Costochondral grafts may be used to success- relapse of systemic disease. Since most JIA fully construct or reconstruct the ramus-condyle patients do not have persistent disease throughout unit. This observation is based on a retrospective their adult lives, orthognathic surgery can be con- study of 26 patients (7 growing and 19 non- sidered once skeletal growth ceases. This can be growing), with a mean follow-up period of monitored with serial lateral cephalograms or an approximately 4 years. Pre-reconstruction diagno- MRI with contrast. If possible, in patients with ses included “autoimmune arthritis” and “degen- stable disease, open bite and clockwise rotation of erative joint disease” (Perrott et al. 1994). the mandible should be treated with a Le Fort I The rationale for the use of autogenous osteotomy with autorotation of the mandible. This costochondral grafting in the management of the eliminates mandibular surgery and therefore functional and esthetic consequences of any might eliminate possible condylar resorption that end-stage TMJ arthritic condition was suggested can occur after bilateral sagittal split osteotomies by MacIntosh. He concluded that absolute guide- (Abramowicz et al. 2016). lines for determining the appropriate time to oper- Children with JIA may require orthognathic ate on these patients do not exist, but reported that surgery or total TMJ reconstruction including a quiescent period of 2 years, during which the condylectomy, synovectomy, and . number of affected body articulations remains Autogenous replacement with temporalis flap stable, coupled with radiographic evidence of and costochondral graft or alloplastic total joint unaltered TMJs and unchanged jaw position- replacement (TJR) are surgical options in such occlusion, offered reasonable expectations for cases (Abramowicz et al. 2016). postsurgical stability (MacIntosh 1992; MacIn- tosh 1994; MacIntosh 2000). Alloplastic TMJ Replacement A study of 76 costochondral grafts in Successful reconstructive surgery in large joints 57 patients with a mean follow-up period of involves alloplastic replacement. Early problems of 53 months (range 24–161 months) reported that material failure have been resolved and most designs, a preoperative diagnosis of ankylosis was associ- regardless of their implantation sites, involve the use ated with a high complication rate, suggesting of convex metal (chrome-cobalt) against concave caution with the use of autogenous costochondral ultrahigh molecular weight polyethylene. Earlier grafts in end-stage arthritic condition patients materials were stabilized to host bone surfaces with (Saeed and Kent 2003). Current orthopedic sur- rapid curing polymethylmethacrylate cement yield- gery literature does not discuss the use of autoge- ing unacceptable failure rates from latent cement- nous bone in TMJ reconstruction in a nongrowing bone interface loosening and host bone osteolysis, patient affected by end-stage arthritic disease. but newer femoral implants are made to be press- Instead total alloplastic joint replacement is fitted to achieve osseointegration and longer-term recommended and utilized (Wiesel and Delahay wear even in younger individuals (Herberts et al. 2011). 1989). There are few reports discussing jaw recon- To date, there are two categories of TMJ TJR struction in JIA patients with a facial skeletal devices approved by the Food and Drug Adminis- deformity. Because of improvements in early tration for implantation in the United States. First, diagnosis, aggressive early treatment, and new stock (off-the-shelf) devices which the surgeon medications, surgeons in developed countries must “make fit” at implantation (Zimmer Biomet rarely encounter severe micrognathia, open bite TMJ Replacement System, Jacksonville, FL, USA; and clockwise rotation of the mandible (e.g., bird Nexus CMF, Golden, CO, USA). Second, custom ) (Figs. 21 and 22) (Abramowicz et al. 2016). (patient-fitted) devices which are “made to fit” each Theoretically, because JIA is a systemic dis- specific case (TMJ Concepts Patient-Fitted Total ease, it is possible that even if the affected condyle TMJ Replacement System, Ventura, CA, USA; is removed with the synovium, recurrence of the Nexus CMF, Golden, CO, USA) (Figs. 23 and 24). TMJ component of the disease may occur with Arthritic Conditions Affecting the Temporomandibular Joint 29

Fig. 23 Stock TMJ total joint replacement devices. (a) Zimmer Biomet TMJ replacement system, Jacksonville, FL, USA (cast metal-on-all UHMWPE); (b) Nexus CMF, Golden, CO, USA (cast metal-on-cast metal)

Fig. 24 Custom TMJ total joint replacement devices. (a) wrought metal mesh backed); (b) Nexus CMF, Golden, TMJ Concepts patient-fitted total TMJ replacement sys- CO, USA (cast metal-on-cast metal) tem, Ventura, CA, USA (wrought metal-on-UHMWPE-

Alloplastic TMJ replacement is advocated replacement was initially discussed in two com- because it avoids the need for a second operative prehensive reviews of the surgical management of site and its potential morbidity decreases operat- TMJ arthritic condition (Zide et al. 1986; Kent ing room time and allows for simultaneous man- et al. 1986). dibular advancement with predictable long-term In a separate study, it was reported that allo- results and stability (Mehra and Wolford 2000). plastic TMJ reconstruction achieved statistically An early alloplastic total TMJ system (Vitek II – significant improved subjective and objective Kent, Houston, TX) was reported successful in the results than did reconstruction with autogenous management of TMJ end-stage arthritic condi- bone. The conclusion was that alloplastic TMJ tions (Stern et al. 1986). Alloplastic total TMJ replacement was more appropriate for adult 30 L.G. Mercuri and S. Abramowicz patients with low-inflammatory or high- diagnoses consistent with a low-inflammatory inflammatory arthritic conditions compared to TMJ arthritic conditions. Twenty-seven (5%) had those managed with autogenous sternoclavicular diagnoses consistent with high-inflammatory or costochondral graft (Frietas et al. 2002). TMJ arthritic conditions. After a mean follow-up TMJ replacement with an alloplastic prosthesis period of 31.8 months (range 2–48 months), the is advocated in cases with a major vertical dimen- data revealed a significant improvement in subjec- sion problem, loss of disc and the entire condylar tive variable (pain, function, diet) visual analogue head with chronic pain, hypomobility, malocclu- scores and improvement in measured maximum sion, such as seen in advanced end-stage arthritic incisal opening in the high-inflammatory diagno- conditions (Kent and Misiek 1994). sis group. There was a significant improvement in In a report of 86 total alloplastic joints (27 VK subjective variable (pain, function, diet) visual II (Houston, TX) and 59 TMJ, Inc. (Golden, CO) analogue scores and improvement in measured implanted to reconstruct end-stage arthritic condi- maximum incisal opening in the low-inflamma- tion patients, with a median follow-up of tory diagnosis group (Mercuri 2006). 14.5 months (range 1–120 months), an overall The subjective and objective outcomes of success rate of 94% was reported. However, four end-stage arthritic conditions and other patients patients required replacement of the VK II devices implanted with patient-fitted alloplastic TMJR due to foreign body giant cell reactions devices after 19–24 years of service. At a median (Speculand et al. 2000). of 21 years after surgery, there was a statistically A series of seven high-inflammatory patients significant improvement (P < .001) for mouth whose TMJs were replaced with TMJ, Inc. opening, TMJ pain, jaw function, and diet. The (Golden, CO) devices, with a mean follow-up of longest follow-up of patients also reported a sta- 30 months (range 8–50 months), reported tistically significant improved quality of life improved subjective (pain and diet) and objective (Wolford et al. 2015). (inter-incisal opening) scores. The conclusion was Considering the orthopedic experience, the that patients with a TMJ high-inflammatory literature comparing autogenous versus allo- arthritic condition should consider alloplastic plastic TMJR in end-stage arthritic conditions, TMJR to restore function and facial esthetic and the long-term success reported in the oral (Saeed et al. 2001). and maxillofacial surgery literature with these In a study of six high-inflammatory patients devices (Leandro et al. 2013;Wolfordetal. after alloplastic TMJR to examine improvement 2015), it appears that alloplastic TMJR should in respiratory status and correction occlusal dis- be considered appropriate management for late crepancies reported that after surgery, symptoms Stage II and Stage III TMJ arthritic conditions of daytime sleepiness and nighttime snoring (Table 4). improved and each patient’s ability to masticate solid foods improved significantly. Postoperative cephalograms revealed that both posterior airway Conclusion and Future Directions space and ramus height were significantly improved as did the dental occlusion. Mean oxy- The 2016 report from the most recent Interna- gen saturation significantly improved 1-month tional RDC/TMD Consortium Network Work- post reconstruction, whereas apnea-hypopnea shop concluded that one of the unsolved issues indices did not change significantly (Mishima regarding TMJ arthritic conditions was the lack of et al. 2003). a reference standard. The sampling of TMJ syno- A Techmedica/ TMJ Concepts (Ventura, CA) vial fluid to determine inflammatory mediator prospective registry was reviewed to determine levels was considered a step forward. Therefore, the outcomes of TMJR after implantation with this group recommended exploration using these these devices in low- and high-inflammatory results as reference standard biomarkers to arthritic patients. Sixty patients (12%) had Arthritic Conditions Affecting the Temporomandibular Joint 31 improve identification of patients with early-stage American Academy of Orthopaedic Surgeons. Treatment TMJ arthritis (Michelotti et al. 2016). of osteoarthritis of the knee. 2nd ed. Rosemont: Amer- ican Academy of Orthopaedic Surgeons; 2013. This workgroup suggested future directions Arabshahi B, Dewitt EM, Cahill AM, Kaye RD, Baskin should include a systematic review of standards KM, Towbin RB, Cron RQ. Utility of corticosteroid for the diagnosis of arthritis for all joints in col- injection for temporomandibular arthritis in children laboration with rheumatology and orthopedic col- with juvenile idiopathic arthritis. Arthritis Rheum. – fi 2005;52:3563 9. leagues. Further, after gathering scienti c data, Arnett GW, Gunson MJ. Risk factors in the initiation of this group recommended forming a study group condylar resorption. Semin Orthod. 2013;19:81–8. to propose new diagnostic criteria for TMJ arthri- Arora P, Amarnath J, Ravindra SV, Rallan tis (of local or systemic genesis), including a M. Temporomandibular joint involvement in ankylos- fl ing spondylitis. BMJ Case Rep. 2013;2013: simple diagnostic owchart. Finally, it was bcr2013009386. recommended that subgroups of arthritis, with Bays AM, Gardner G. Pharmacologic therapies for rheu- and without pain, with and without tissue destruc- matologic and autoimmune conditions. Med Clin N tion, be included in future discussions and devel- Am. 2016;100:719–31. Beaulieu AD, Peloso PM, Haraoui B, Bensen W, opment of diagnostic criteria (Michelotti et al. Thomson G, Wade J, Quigley P, Eisenhoffer J, 2016). Harsanyi Z, Darke AC. Once-daily, controlled-release tramadol and sustained-release diclofenac relieve chronic pain due to osteoarthritis: a randomized con- trolled trial. Pain Res Manag. 2008;13:103–10. Cross-References Bertalomi CN, Gay T, Clark GT, Rendell J, Shetty V,Liu C, Swann DA. Use of sodium hyaluronate in treating ▶ Classification of Orofacial Pain temporomandibular joint disorders: a randomized, ▶ Clinical Evaluation of Oral Diseases double-blind, placebo-controlled clinical trial. J Oral – ▶ Maxillofac Surg. 1993;51:232 42. Clinical Evaluation of Orofacial Pain Bjornland T, Larheim TA. Synovectomy and discectomy ▶ Diagnostic Imaging Principles and Applica- of the temporomandibular joint in patients with arthritic tions in Head and Neck Pathology disease compared with discectomy in patients with ▶ Internal Derangements of the Temporomandib- internal derangement. A 3-year follow-up study. Eur J Oral Sci. 1995;103:2–7. ular Joint Bongartz T, Halligan CS, Osmon DR, Reinalda MS, ▶ Sleep Bruxism Bamlet WR, Crowson CS, Hanssen AD, Matteson EL. Incidence and risk factors of prosthetic joint infec- tion after total hip or in patients with rheumatoid arthritis. Arthritis Rheum. 2008;59: References 1713–20. Bouloux GF. Use of opioids in long-term management of temporomandibular joint dysfunction. J Oral Abramowicz S, Cheon J, Kim S, Bacic J, Lee EY.Magnetic Maxillofac Surg. 2011;69:1885–91. resonance imaging of temporomandibular joints in Brooks SL, Westesson PL, Eriksson L, Hansson LG, children with arthritis. J Oral Maxillofac Surg. Barsotti JB. Prevalence of osseous changes in the tem- 2011;69:2321–8. poromandibular joint of asymptomatic persons without Abramowicz S, Susarla HK, Kim S, Kaban LB. Physical internal derangement. Oral Surg Oral Med Oral Pathol. findings associated with active temporomandibular 1992;73:118–22. joint inflammation in children with juvenile idiopathic Browning SR, Weiser AM, Woolf N, Golish SR, arthritis. J Oral Maxillofac Surg. 2013a;71:1683–7. SanGiovanni TP, Scuderi GJ, Carballo C, Hanna Abramowicz S, Kim S, Susarla HK, Kaban LS. Platelet-rich plasma increases matrix meta- LB. Differentiating arthritic from myofascial pain in lloproteinases in cultures of human synovial fibro- children with juvenile idiopathic arthritis: preliminary blasts. J Bone Joint Surg Am. 2012;94:e1721–7. report. J Oral Maxillofac Surg. 2013b;71:493–6. Campos MI, Campos PS, Cangussu MC, Guimarães RC, Abramowicz S, Kim S, Prahalad S, Chouinard AF, Kaban Line SR. Analysis of magnetic resonance imaging char- LB. Juvenile arthritis: current concepts in terminology, acteristics and pain in temporomandibular joints with etiopathogenesis, diagnosis, and management. Int J and without degenerative changes of the condyle. Int J Oral Maxillofac Surg. 2016;45:801–12. Oral Maxillofac Surg. 2008;37:329–34. Alpaslan GH, Alpaslan C. Efficacy of temporomandibular Casares G, Thomas A, Carmona J, Acero J, Vila joint arthrocentesis with and without injection of CN. Influence of oral stabilization appliances in intra- sodium hyaluronate in treatment of internal derange- articular pressure of the temporomandibular joint. ments. J Oral Maxillofac Surg. 2001;59:613–8. Cranio. 2014;32:219–23. 32 L.G. Mercuri and S. Abramowicz

Chandler GN, Wright V. Deleterious effect of intra- rheumatoid arthritis. J Oral Maxillofac Surg. articular hydrocortisone. Lancet. 1958;2:661–3. 1998;56:147–51. Chevalier X, Goupille P, Beaulieu AD, Burch FX, Bensen Handleman CS, Mercuri LG. Chapter 7: Idiopathic/pro- WG, Conrozier T, Loeuille D, Kivitz AJ, Silver D, gressive condylar resorption: an orthodontic perspec- Appleton BE. Intraarticular injection of anakinra in tive. In: Kandasamy S, editor. TMD and – osteoarthritis of the knee: a multicenter, randomized, a clinical guide for the orthodontist. New York: double blind, placebo-controlled study. Arthritis Springer; 2015. Rheum. 2009;61:344–52. Hatcher DC. Progressive condylar resorption: pathologic Cohen SB, Proudman S, Kivitz AJ, Burch FX, Donohue JP, processes and imaging considerations. Semin Orthod. Burstein D, Sun YN, Banfield C, Vincent MS, Ni L, 2013;19:97–105. Zack DJ. A randomized, double-blind study of AMG Hébert-Blouin MN, Tubbs RS, Carmichael SW, Spinner 108 (a fully human monoclonal antibody to IL-1R1) in RJ. Hilton’s law revisited. Clin Anat. 2014;27:548–55. patients with osteoarthritis of the knee. Arthritis Res Heffez LB. Arthroscopy. In: Kaplan AS, Assael LA, edi- Ther. 2011;13:R125. tors. Temporomandibular disorders: diagnosis and Crincoli V, Di Comite M, Di Bisceglie MB, Fatone L, treatment. Philadelphia: Saunders; 1991. p. 628–62. Favia G. Temporomandibular disorders in psoriasis Hegab AF, Ali HE, Elmasry M, Khallaf MG. Platelet-rich patients with and without psoriatic arthritis: an obser- plasma injection as an effective treatment for temporo- vational study. Int J Med Sci. 2015;12:341–8. mandibular joint osteoarthritis. J Oral Maxillofac Surg. de Souza RF, Lovato da Silva CH, Nasser M, 2015;73:1706–13. Fedorowicz Z, Al-Muharraqi MA. Interventions for Henderson SE, Lowe JR, Tudares MA, Gold MS, Almarza the management of temporomandibular joint osteoar- AJ. Temporomandibular joint fibrocartilage degenera- thritis. Cochrane Database Syst Rev. 2012;18(4): tion from unilateral dental splints. Arch Oral Biol. CD007261. doi:10.1002/14651858.CD007261.pub2. 2015;60:1–11. DeClercq CA, Neyt LF, Mommaerts MY, Abeloos JV, De Henny FA, Baldridge OL. Condylectomy for the persis- Mot BM. Condylar resorption in orthognathic surgery: tently painful temporomandibular joint. J Oral Surg. a retrospective study. Int J Adult Orthod Orthognath 1957;15:24–31. Surg. 1994;9:233–40. Herberts P, Ahnfelt L, Malchau H, Strömberg C, Detamore MS, Athanasiou KA, Mao J. A call to action for Andersson GB. J. Multicenter clinical trials and their bioengineers and dental professionals: directives for the value in assessing total joint arthroplasty. Clin Orthop. future of TMJ bioengineering. Ann Biomed Eng. 1989;249:48–55. 2007;35:1301–11. Hochberg MC. Osteoarthritis: the rheumatologist’s per- Dingman RO, Grabb WC. Intra-capsular temporomandib- spective. HSSJ. 2012;8:35–6. ular joint arthroplasty. Plast Reconstr Surg. Hochberg MC, Altman RD, April KT, Benkhalti M, 1966;38:179–85. Guyatt G, McGowan J, Towheed T, Welch V, Felson DT. Clinical practice. osteoarthritis of the knee. N Wells G, Tugwell P, American College of Rheumatol- Engl J Med. 2006;354:841–8. ogy. American College of Rheumatology 2012 recom- Frietas RZ, Mehra P, Wolford LM. Autogenous versus allo- mendations for the use of nonpharmacologic and plastic TMJ reconstruction in rheumatoid-induced TMJ pharmacologic therapies in osteoarthritis of the hand, disease. J Oral Maxillofac Surg. 2002;58(Suppl 1):43. hip, and knee. Arthritis Care Res. 2012;64:465–74. Garcia RL, Jick H. Risk of upper gastrointestinal bleeding Hollander J. Intra-articular hydrocortisone in arthritis and and perforation associated with individual allied conditions. J Bone Joint Surg non-steroidal anti-inflammatory drugs. Lancet. Am. 1953;35:983–90. 1994;343:769–72. Holmlund A. Connective tissue pathology: Arthridities. In: Gayle EA, Young SM, McKenna SJ, McNaughton Thomas M, Bronstein S, editors. Arthroscopy of the CD. Septic arthritis of the temporomandibular joint: Temporomandibular Joint. Philadelphia: WB case reports and review of the literature. J Emerg Saunders; 1991. p. 276–81. Med. 2013;45:674–8. Holmlund A, Hellsing G, Wredmark T. Arthroscopy of the Gerwin N, Hops C, Lucke A. Intraarticular drug delivery in temporomandibular joint: a clinical study. Int J Oral osteoarthritis. Adv Drug Deliv Rev. 2006;58:226–42. Maxillofac Surg. 1986;15:715–21. Gunson MJ, Arnett GW, Formby B, Falzone C, Mathur R, Hootman JL, Helmick CG. Projections of US prevalence of Alexander C. Oral contraceptive pill use and abnormal arthritis and associated activity limitations. Arthritis menstrual cycles in women with severe condylar Rheum. 2006;54:226–9. resorption: a case for low serum 17 beta-estradiol as a Israel HA, Saed-Nejad F, Ratcliffe A. Early diagnosis of major factor in progressive condylar resorption. Am J osteoarthrosis of the temporomandibular joint: correla- Orthod Dentofac Orthop. 2009;136:772–9. tion between arthroscopic diagnosis and keratin sulfate Gynther GW, Holmlund AB. Efficacy of arthroscopic lysis levels in the synovial fluid. J Oral Maxillofac Surg. and lavage in patients with temporomandibular joint 1991;49:708–11. symptoms associated with generalized osteoarthritis or Arthritic Conditions Affecting the Temporomandibular Joint 33

Jackson DW, Evans NA, Thomas BM. Accuracy of needle Microfixation TMJ replacement system. Int J Oral placement into the intra-articular space of the knee. J Maxillofac Surg. 2013;42:1007–13. Bone Joint Surg Am. 2002;84-A:1522–7. Lindqvist C, Jokinen J, Paukku P, Tasanen A. Adaptation Jayson MIV, Dison AL. Arthroscopy of the knee in rheu- of autogenous costochondral grafts used for temporo- matoid disease. Ann Rheum Dis. 1968;27:503–11. mandibular joint reconstruction: a long-term clinical Jones A, Regan M, Ledingham J, Pattrick M, Manhire A, and radiologic follow-up. J Oral Maxillofac Surg. Doherty M. Importance of placement of intra-articular 1988;46:465–70. steroid injections. BMJ. 1993;307:1329–30. Lohmander LS, Hellot S, Dreher D, Krantz EF, Kruger DS, Jordan N, D’Cruz D. Current and emerging treatment Guermazi A, Eckstein F. Intraarticular sprifermin (recom- options in the management of lupus. Immunotargets binant human fibroblast growth factor 18) in knee osteo- Ther. 2016;5:9–20. arthritis: a randomized, double-blind, placebo-controlled Kahlenberg JM, Fox DA. Advances in the medical treatment trial. Arthritis Rheum. 2014;66:1820–31. of rheumatoid arthritis. Hand Clin. 2011;27:11–20. Ma MHY, Kingsley GH, Scott DL. A systematic compar- Kent JN, Misiek DJ. Controversies in disc condyle replace- ison of combination DMARD therapy and tumour ment for partial and total temporomandibular joint necrosis inhibitor therapy with methotrexate in patients reconstruction. In: Worthington P, Evans JR, editors. with early rheumatoid arthritis. Rheumatology. Controversies in oral and maxillofacial surgery. Phila- 2010;49:91–8. delphia: WB Saunders; 1994. p. 397–435. MacIntosh RB. Current spectrum of costochondral and Kent JN, Carlton DM, Zide MF. Rheumatoid disease and dermal grafting. In: Bell WH, editor. Modern practice related arthropathies. II – Surgical rehabilitation of the in orthognathic and reconstructive surgery, vol. 2. Phil- temporomandibular joint. Oral Surg. 1986;61:423–39. adelphia: WB Saunders; 1992. p. 904–49. Kerstens HC, Tuinzing DB, Golding RP, van der Kwast MacIntosh RB. The case for autogenous reconstruction of WA. Condylar atrophy and osteoarthrosis after the adult temporomandibular joint. In: Worthington P, bimaxillary surgery. Oral Surg. 1990;69:274–80. Evans JR, editors. Controversies in oral and maxillofa- Kiliç SC. Does injection of corticosteroid after cial surgery. Philadelphia: WB Saunders; 1994. arthrocentesis improve outcomes of temporomandibu- p. 356–80. lar joint osteoarthritis? A randomized clinical trial. J MacIntosh RB. The use of autogenous tissue in temporo- Oral Maxillofac Surg. 2016;74:2151–8. mandibular joint reconstruction. J Oral Maxillofac Kon E, Buda R, Filardo G, Di Martino A, Timoncini A, Surg. 2000;58:63–9. Cenacchi A, Fornasari PM, Giannini S, Marcacci Manfredini D, Bonnini S, Arboretti R, Guarda-Nardini M. Platelet-rich plasma: intra-articular knee injections L. Temporomandibular joint osteoarthritis: an open produced favorable results on degenerative cartilage label trial of 76 patients treated with arthrocentesis lesions. Knee Surg Sports Traumatol Arthrosc. plus hyaluronic acid injections. Int J Oral Maxillofac 2010;18:472–9. Surg. 2009;38:827–34. Kopp S, Carlsson GE, Haraldson T, Wenneberg B. Long- Mansour AM, Jaroudi MO, Medawar WA, Tabbarah term effect of intra-articular injections of sodium ZA. Bilateral multifocal posterior pole lesions in Reiter hyaluronate and corticosteroids on temporomandibular syndrome. BMJ Case Rep. 2013;2013:bcr2013009253. joint arthritis. J Oral Maxillofac Surg. 1987;45:929–35. Mehra P, Wolford LM. Custom-made TMJ reconstruction Kütük N, Baş B, Soylu E, Gönen ZB, Yilmaz C, and simultaneous mandibular advancement in autoim- Balcioğlu E, Özdamar S, Alkan A. Effect of platelet- mune/connective tissue diseases. J Oral Maxillofac rich plasma on fibrocartilage, cartilage, and bone repair Surg. 2000;58(Suppl 1):95. in temporomandibular joint. J Oral Maxillofac Surg. Mehra P, Nadershah M, Chigurupati R. Is alloplastic tem- 2014;72:277–84. poromandibular joint reconstruction a viable option in Lane NE, Schnitzer TJ, Birbara CA, Mokhtarani M, Shel- the surgical management of adult patients with idio- ton DL, Smith MD, Brown MT. Tanezumab for the pathic condylar resorption? J Oral Maxillofac Surg. treatment of pain from osteoarthritis of the knee. N 2016;74:2044–54. Engl J Med. 2010;363:1521–31. Mejersjö C, Hollender L. Radiography of the temporoman- Larsen C, Ostergaard J, Larsen SW, Jensen H, Jacobsen S, dibular joint in female patients with TMJ pain or dys- Lindegaard C, Andersen PH. Intra-articular depot for- function. Acta Radiol Diagn. 1984;25:169–76. mulation principles: role in the management of postop- Mercuri LG. Surgical management of TMJ arthritis. In: erative pain and arthritic disorders. J Pharm Sci. Laskin DM, Green CS, Hylander WL, editors. Tempo- 2008;97:4622–54. romandibular joint disorders: an evidence-based Laviv A, Sadow PM, Keith DA. Pseudogout in the tempo- approach to diagnosis and treatment. Chicago: Quin- romandibular joint with imaging, arthroscopic, opera- tessence; 2006. p. 455–68. tive, and pathologic findings. Report of an unusual Mercuri LG. A rationale for total alloplastic temporoman- case. J Oral Maxillofac Surg. 2015;73:1106–12. dibular joint reconstruction in the management of idio- Leandro LF, Ono HY, Loureiro CC, Marinho K, Guevara pathic/progressive condylar resorption. J Oral HA. A 10-year experience and follow-up of Maxillofac Surg. 2007;65:1600–9. 300 patients fitted with the Biomet/Lorenz 34 L.G. Mercuri and S. Abramowicz

Mercuri LG. End-stage TMD and TMJ reconstruction. In: Obeid G, Guttenberg SA, Canole PW. Costochondral Miloro M, Ghali G, Larsen P, Waite P, editors. grafting on condylar replacement and mandibular Peterson’s principles of oral & maxillofacial surgery, reconstruction. J Oral Maxillofac Surg. vol. 52. 3rd ed. Ipswich: PMPH, USA Ltd.; 2012. 1988;48:177–82. p. 1173–86. Oh DW, Kim KS, Lee GW. The effect of physiotherapy on Michelotti A, Altergren P, Goulet JP, Lobbezoo F, post-temporomandibular joint surgery patients. J Oral Ohrbach R, Peck C, Schiffman E, List T. Next steps Rehabil. 2002;29:441–6. in development of the diagnostic criteria for temporo- Oliveira INF, Gomes RCF, dos Santos RR, Oliveira TP, mandibular joint disorders (DC/TMD): recommenda- Pereira LLC, Mainenti P. Gout of the temporomandib- tions from the International RDC/TMD Consortium ular joint: report of a case. Int Arch Otorhinolaryngol. workshop. J Oral Rehabil. 2016;43:453–67. 2014;18:316–8. Mishima K, Yamada T, Sugahara T. Evaluation of respira- Ong KL, Villarraga ML, Lau E, Carreon LY, Kurtz SM, tory status and mandibular movement after total tem- Glassman SD. Off-label use of bone morphogenetic poromandibular joint replacement in patients with proteins in the United States using administrative rheumatoid arthritis. Int J Oral Maxillofac Surg. data. Spine. 2010;35:1794–800. 2003;32:275–9. Oye F, Bjornland T, Store G. Mandibular osteotomies in Moore KG, Gooris PJ, Stoelinga PJ. The contributing role of patients with juvenile rheumatoid arthritic disease. condylar resorption in orthognathic surgery: a retrospec- Scand J Rheumatol. 2003;32:168–73. tive study. J Oral Maxillofac Surg. 1991;49:448–60. Pereira FJ, Lundh H, Westesson PL, Carlsson LE. Clinical Moskowitz R, Davis W, Sammarco J, Mast W, Chase findings related to morphologic changes in TMJ SW. Experimentally induced corticosteroid arthropa- autopsy specimens. Oral Surg. 1994;78:288–95. thy. Arthritis Rheum. 1970;13:236–43. Perrott DH, Umeda H, Kaban LB. Costochondral graft Mountziaris PM, Kramer PR, Mikos AG. Emerging intra- construction/reconstruction of the ramus/condyle unit: articular drug delivery systems for the temporomandib- long-term follow-up. Int J Oral Maxillofac Surg. ular joint. Methods. 2009;47:134–40. 1994;23:321–8. Møystad A, Mork-Knutsen BB, Bjørnland T. Injection of Petty RE, Southwood TR, Manners P, Baum J, Glass DN, sodium hyaluronate compared to a corticosteroid in the Goldenberg J, He X, Maldonado-Cocco J, Orozco- treatment of patients with temporomandibular joint Alcala J, Prieur AM, Suarez-Almazor ME, Woo P, osteoarthritis: a CT evaluation. Oral Surg Oral Med International League of Associations for Rheumatol- Oral Pathol Oral Radiol Endod. 2008;105:e53–60. ogy. International League of Associations for Rheuma- Murakami K. Arthroscopy of the temporomandibular joint. tology classification of juvenile idiopathic arthritis: In: Bell WH, editor. Modern practice in orthognathic second revision, Edmonton, 2001. J Rheumatol. and reconstructive surgery, vol. 1. Philadelphia: WB 2004;31:390–2. Saunders; 1992. p. 608. Pirmohamed M, James S, Meakin S, Green C, Scott AK, Mushtaq S, Goodman SM, Scanzello CR. Perioperative Walley TJ, Farrar K, Park BK, Breckenridge management of biologic agents used in treatment of AM. Adverse drug reactions as cause of admission to rheumatoid arthritis. Am J Ther. 2011;18:426–34. hospital: prospective analysis of 18 820 patients. BMJ. Narum S, Westergren T, Klemp M. Corticosteroids and risk 2004;329(7456):15–9. of gastrointestinal bleeding: a systematic review and Poswillo D. Experimental investigation of the effects of meta-analysis. BMJ Open. 2014;4:e004587. intra-articular hydrocortisone and high condylectomy Neo H, Jun-ichi I, Kurita K, Goss AN. The effect of on the mandibular condyle. Oral Surg. hyaluronic acid on experimental temporomandibular 1970;30:161–73. joint osteoarthrosis in sheep. J Oral Maxillofac Surg. Quinn JH, Bazan NG. Identification of prostaglandin E2 1997;55:1114–9. and leukotriene B4 in the synovial fluid of painful. Nicolakis P, Burak EC, Kollmitzer J, Kopf A, dysfunctional temporomandibular joints. J Oral Piehslinger E, Wiesinger GF, Fialka-Moser V. An Maxillofac Surg. 1990;48:968–74. investigation of the effectiveness of exercise and man- Ringold S, Torgerson TR, Egbert MA, Wallace ual therapy in treating symptoms of TMJ osteoarthritis. CA. Intraarticular corticosteroid injections of the tem- Cranio. 2001;19:26–32. poromandibular joint in juvenile idiopathic arthritis. J Niewold TB, Harrison MJ, Paget SA. Anti-CCP antibody Rheumatol. 2008;35:1157–64. testing as a diagnostic and prognostic tool in rheuma- Rodrigo JJ, Gershwin ME. Management of the arthritic toid arthritis. QJM. 2007;100:193–201. joint. In: Chapman MW, editor. Chapman’s orthopae- Nitzan DW, Svidovsky J, Zini A, Zadik Y. Effect of dic surgery. 3rd ed. Philadelphia: Lippincott, Williams arthrocentesis on symptomatic osteoarthritis of the tem- & Wilkins; 2001. p. 2551–72. poromandibular joint and analysis of the effect of pre- Sacks JJ, Helmick CG, Luo Y, Ilowite NT, Bowyer operative clinical and radiologic features. J Oral S. Prevalence of and annual ambulatory health care Maxillofac Surg. 2016;75(2):260–7. doi:10.1016/j. visits for pediatric arthritis and other rheumatologic joms.2016.08.017. conditions in the United States in 2001–2004. Arthritis Rheum. 2007;57:1439–45. Arthritic Conditions Affecting the Temporomandibular Joint 35

Saeed NR, Kent JN. A retrospective study of the Stafford RE. Regulating off-label drug use – rethinking the costochondral graft in TMJ reconstruction. Int J Oral role of the FDA. N Engl J Med. 2008;358:1427–9. Maxillofac Surg. 2003;32:606–9. Stahn C, Buttgereit F. Genomic and nongenomic effects of Saeed NR, McLeod NMH, Hensher glucocorticoids. Nat Clin Pract Rheumatol. R. Temporomandibular joint replacement in 2008;4:525–33. rheumatoid-induced disease. Br J Oral Maxillofac Statkute L, Ruderman EM. Novel TNF antagonists for the Surg. 2001;39:71–5. treatment of rheumatoid arthritis. Expert Opin Investig Salash JR, Hossameldin RH, Almarza AJ, Chou JC, Drugs. 2010;19:105–15. McCain JP, Mercuri LG, Wolford LM, Detamore Steinbrocker O, Traeger CH, Batterman RC. Therapeutic MS. Potential indications for tissue engineering in tem- criteria in rheumatoid arthritis. JAMA. poromandibular joint surgery. J Oral Maxillofac Surg. 1949;140:659–62. 2016;74:705–11. Stern NS, Trop RC, Balk P. Total temporomandibular joint Salk RS, Chang TJ, D'Costa WF, Soomekh DJ, Grogan replacement in a patient with rheumatoid arthritis: KA. Sodium hyaluronate in the treatment of osteoar- report of a case. JADA. 1986;112:491–5. thritis of the ankle: a controlled, randomized, double- Tamimi D, Hatcher D, editors. Specialty imaging. tempo- blind pilot study. J Bone Joint Surg romandibular joint. Philadelphia: Elsevier; 2016. Am. 2006;88:295–302. p. 452–3. Salter RB, Hamilton HW, Wedge JH, Tile M, Torode IP, Tanaka E, Detamore M, Mercuri LG. Degenerative disor- O'Driscoll SW, Murnaghan JJ, Saringer JH. Clinical ders of the temporomandibular joint: etiology, diagno- application of basic research on continuous passive sis and treatment. J Dent Res. 2008;87:296–307. motion for disorders of synovial joints. A preliminary Toller P. Use and misuse of intra-articular corticosteroids in report of a feasibility study. J Orthop Res. the treatment of TMJ pain. Proc Soc Med. 1984;1:325–42. 1977;70:461–3. Sánchez M, Anitua E, Azofra J, Aguirre JJ, Andia I. Intra- Trieger N, Hoffman CH, Rodriquez E. The effect of articular injection of an autologous preparation rich in arthrocentesis of the temporomandibular joint in growth factors for the treatment of knee OA: a retro- patients with rheumatoid arthritis. J Oral Maxillofac spective cohort study. Clin Exp Rheumatol. Surg. 1999;57:537–40. 2008;26:910–3. US Food and Drug Administration. FDA public health Sarlos P, Kovesdi E, Magyari L, Banfai Z, Szabo A, advisory: safety of Vioxx. Silver Spring: FDA. 2004. Javorhazy A, Melegh B. Genetic update on inflamma- Available at http://www.fda.gov/drugs/drugsafety/post tory factors in ulcerative colitis: review of the current marketdrugsafetyinformationforpatientsandproviders/ literature. World J Gastrointest Pathophysiol. ucm106274.htm.Accessed25Sep2015. 2014;5:304–21. US Food and Drug Administration. Information for Sarver D, Janyavula S. Condylar degeneration and diseases healthcare professionals: Celecoxib (marketed as – local and systemic etiologies. Semin Orthod. Celebrex). Silver Spring: FDA. 2005a. Available at 2013;19:89–96. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrug Shi ZD, Yang F, He ZX, Shi B, Yang MZ. Comparative SafetyInformationforPatientsandProviders/ucm124655. study on effects of sodium hyaluronate and predniso- htm. Accessed 25 Sep 2015. 59 US lone injections on experimental temporomandibular US Food and Drug Administration Information for joint osteoarthritis of rabbits. Chinese J Repair healthcare professionals: Valdecoxib (marketed as Reconstr Surg. 2002;16:5–10. Bextra). Silver Spring: FDA. 2005b. Available at http:// Shi Z, Guo C, Awad M. Hyaluronate for temporomandib- www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafety ular joint disorders. Cochrane Database Syst Rev. InformationforPatientsandProviders/ucm124649.htm. 2003;1:CD002970. Accessed 25 Sep 2015. Sinn DP. Mandibular deficiency secondary to juvenile US Food and Drug Administration. FDA clears Cymbalta to rheumatoid arthritis. In: Bell WH, editor. Modern prac- treat chronic musculoskeletal pain. Silver Spring: FDA. tice in orthognathic and reconstructive surgery, vol. Vol 2010. Available at http://www.fda.gov/NewsEvents/News 3. Philadelphia: WB Saunders; 1992. p. 2506–11. room/PressAnnouncements/ucm232708.htm. Accessed Slater R, Gross A, Hall J. Hydrocortisone arthropathy – an 25 Sep 2015. experimental investigation. Can Med Assoc US Food and Drug Administration. Tanezumab arthritis advi- J. 1967;97:374–7. sory committee briefing document. Silver Spring: FDA. Smyth NA, Haleem AM, Ross KA, Hannon CP, Murawski 2012. Available at http://www.fda.gov/downloads/ CD, Do HT, Kennedy JG. Platelet-rich plasma may AdvisoryCommittees/CommitteesMeetingMaterials/ improve osteochondral donor site healing in a rabbit Drugs/ArthritisAdvisoryCommittee/UCM295205.pdf. model. Cartilage. 2016;7:104–11. Accessed 25 Sep 2015. Speculand B, Hensher R, Powell D. Total prosthetic Vallon D, Ackerman S, Nilner M, Petersson A. Long-term replacement of the TMJ: experience with two systems follow-up of intra-articular injections into the temporo- 1988–1997. Br J Oral Maxillofac Surg. mandibular joint in patients with rheumatoid arthritis. 2000;38:360–9. Swed Dent J. 2002;26:149–58. 36 L.G. Mercuri and S. Abramowicz

Verstappen SM, Jacobs JW, Bijlsma JW, Heurkens AH, fitted temporomandibular joint prosthesis: the van Booma-Frankfort C, Borg EJ, Hofman DM, van Techmedica/TMJ concepts device. J Oral Maxillofac der Veen MJ. Five-year follow-up of rheumatoid arthri- Surg. 2015;73:952–60. tis patients after early treatment with disease-modifying Wright EA, Katz JN, Abrams S, Solomon DH, Losina antirheumatic drugs versus treatment according to the E. Trends in prescription of opioids from 2003–2009 pyramid approach in the first year. Arthritis Rheum. in persons with knee osteoarthritis. Arthritis Care Res. 2003;48:1797–807. 2014;66:1489–95. Wang XD, Kou XX, Mao JJ, Gan YH, Zhou Zhang W, Jones A, Doherty M. Does paracetamol (acet- YH. Sustained inflammation induces degeneration aminophen) reduce the pain of osteoarthritis? A meta- of the temporomandibular joint. J Dent Res. analysis of randomized controlled trials. Ann Rheum 2012;91:499–505. Dis. 2004;63:901–7. Westesson PL, Rohlin M. Internal derangement related to Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman osteoarthrosis in temporomandibular joint autopsy RD, Arden N, Bierma-Zeinstra S, Brandt KD, Croft P, specimens. Oral Surg Oral Med Oral Pathol. Doherty M, Dougados M, Hochberg M, Hunter DJ, 1984;57:17–22. Kwoh K, Lohmander LS, Tugwell P. OARSI recom- Wiesel SW, Delahay JN, editors. Essentials of orthopedic mendations for the management of hip and knee oste- surgery. 4th ed. New York: Springer; 2011. oarthritis, Part II: OARSI evidence-based, expert Wilkes CH. Internal derangements of the temporomandib- consensus guidelines. Osteoarthr Cartil. ular joint. Pathological variations. Northwest Dent. 2008;16:137–62. 1990;69:25–32. Zhang W, Ouyang H, Dass CR, Xu J. Current research on Wolford LM. Concomitant temporomandibular joint and pharmacologic and regenerative therapies for osteoar- orthognathic surgery. J Oral Maxillofac Surg. thritis. Bone Res. 2016;4:15040. 2003;61:1198–204. Zide MF, Carlton DM, Kent JN. Rheumatoid disease and Wolford LM, Reich-Fischel O, Mehra P. Changes in TMJ related arthropathies. I. Systemic findings, medical dysfunction after orthognathic surgery. J Oral therapy, and peripheral joint surgery. Oral Surg. Maxillofac Surg. 2002;61:655–60. 1986;61:119–25. Wolford LM, Mercuri LG, Schneiderman ED, Movahed R, Allen W. Twenty-year follow-up study on a patient-