Brodén views are helpful for detecting arthritis of the subtalar joint. Talonavicular arthritis is often accompanied by a loss of the Meary angle (Fig. 19-5B), and calcaneocuboid arthritis is best seen on a medial oblique foot radiograph. Menz and colleagues³⁷⁵noted that osteoarthritis is readily diagnosed on anteroposterior (AP) and lateral radiographs and that these findings show good interobserver reliability. Periarticular bone loss and osteoporosis rarely occur. Magnetic resonance imaging (MRI) may show cartilage thinning and signal change on T2-weighted imaging in the subchondral bone. When subtler forms of arthritis are suspected, computed tomography (CT) is useful to document the severity and extent of the disease, although CT scans are routinely non–weight-bearing images.

Van Saase et al ⁵⁷³ noted the prevalence of first metatarsophalangeal (MTP) joint arthritis to be 28%, lesser MTP joints to be 8%, and the proximal interphalangeal (IP) joints to be 7%. The radiographic prevalence of midfoot and hindfoot joint arthritis has not been reported.

Treatment

Conservative treatment methods, such as weight reduction and activity modification, may reduce symptoms. Thus manual laborers who develop arthritis of the foot or ankle may see pain reduction with more sedentary occupations. Although rest is often advocated, animal studies have shown that increased activity diminishes the symptoms of arthritis and may slow its progression.²⁰³ Cross training may also be beneficial to reduce stress on affected joints while maintaining joint mobility (i.e., joggers may substitute cycling or swimming).

Over-the-counter footwear or prescription footwear can reduce symptoms over bony prominences.¹¹⁵ Orthoses can support unstable areas and areas with rigid deformities. Semiflexible orthoses appear to be better tolerated than rigid orthoses in treating degenerative joint disease of the hindfoot and midfoot. Orthoses that may be considered include ankle–foot orthoses (AFOs) for ankle, hindfoot, and midtarsal deformities; rocker-bottom shoe modifications for decreased ankle, hindfoot, and forefoot motion; molded-leather ankle braces for hindfoot arthritis; and custom-made and prefabricated orthoses for midfoot and forefoot problems. The University of California Biomechanics Laboratory (UCBL) brace is designed to limit the motion of the subtalar joint.

Nonsteroidal antiinflammatory drugs (NSAIDs) are often used as first-line pharmacologic treatment. However, concerns remain regarding potential gastrointestinal and cardiac side effects. All NSAIDs have been linked to an increased cardiac risk.⁵⁰¹

Intraarticular corticosteroid injections can provide significant and sometimes prolonged clinical relief; however, the American College of Rheumatology recommends waiting at least 3 months between injections.¹⁰ Several studies have noted efficacy for up to 2 years; yet some patients experience much shorter relief. This difference is poorly understood. In larger joints, synovial fluid aspiration before steroid injection may increase effectiveness and duration and may reduce clinical relapse.⁵⁸⁴ Side effects include periinjection lipodystrophy; skin atrophy; postinjection flare-reaction (1%-10% of patients), thought to be caused by the crystalline preparation of the steroid); and facial flushing (15% more common in women).

Prolonged steroid use has many side effects, including hypothalamic-pituitary axis suppression and hepatic gluconeogenesis, which worsens glucose intolerance among diabetics. Intraarticular injections have far less systemic side effects than oral preparations, and the effect is usually transient.⁴²⁵

Contraindications to intraarticular steroid injection include preexisting septic arthritis, surrounding cellulitis, injection into a prosthetic joint, preexisting fracture, or coagulopathy. Although septic arthritis has been reported after intraarticular injection (1 in 3,000 to 1 in 50,000 in the knee ⁸⁰) the risk is small with appropriate skin preparation and technique. Cartilage degeneration after intraarticular steroid injection has been noted in animals, but similar complications in humans have not been reported. Steroids may be effective regardless of the type of arthritis. Preoperative fluoroscopic-guided injections (Fig. 19-6) may help determine which joints would be improved by arthrodesis. However, the anesthetic/steroid mixture may leak to adjacent tarsometatarsal joints in up to 20% of cases.²⁸⁹

Figure 19-6 Fluoroscopy and intraarticular midfoot steroid injection.

To date, there are no pharmacologic agents known to halt cartilage destruction or restore the cartilage matrix. However, Sampson and Hilton ⁴⁹⁰ demonstrated that teriparatide (Forteo), a recombinant parathyroid hormone, increases proteoglycan content and inhibits cartilage degeneration in mice. Although this drug is used to treat osteoporosis, further studies may reveal other applications.

The primary surgical indication for degenerative arthritis of the foot or ankle is intractable pain or deformity that is not relieved with local or systemic pharmacologic treatment or biomechanical aids, such as immobilization or bracing. Surgical techniques vary from arthrodesis to excisional arthroplasty to osteotomy. Joint implants, in general, have been disappointing in the forefoot and hindfoot (see later discussion of first MTP implants).

Degenerative Arthritis of the Hindfoot

The hindfoot comprises the subtalar, talonavicular and calcaneocuboid joints and includes the adjacent bones and soft tissue structures. These joints are coupled to provide stability and shock-absorption. As the subtalar joint inverts, the transverse tarsal joint locks, stabilizing the hindfoot and midfoot to allow for toe-off. As the subtalar joint everts, the transverse tarsal joint is unlocked, to allow for shock absorption when the foot is planted.

Pain while walking on uneven ground is a common complaint of patients with subtalar arthritis. Many of these patients have pain directly over the sinus tarsi with deep palpation. Pain over the talonavicular joint or calcaneocuboid joint is often seen with transverse tarsal arthritis.

A prior talar neck fracture (Figs. 19-7 and 19-8) accounts for 50% to 100% of posttraumatic subtalar joint arthritis.⁶⁹

Figure 19-7 Lateral computed tomography scan of a nondisplaced talar neck fracture.

Figure 19-8 Coronal computed tomography scan demonstrating posttraumatic subtalar arthritis.

Pennal noted that up to 60% of patients with talar fractures required subsequent subtalar arthrodesis.⁴³³ In Sanders’ series, 37% of patients with talus fractures required a second surgery; 76% went on to subtalar arthrodesis, 23% had triple arthrodesis, and 11% had pantalar arthrodesis.⁴⁹¹

Up to 17% of intraarticular calcaneal fractures will require a second surgery because of symptomatic subtalar arthritis.⁴¹ Sanders concluded that this is dependent upon the degree of comminution of the subtalar joint, because 23% of Sanders type II fractures, and 73% of Sanders type IV fractures required subtalar arthrodesis (Fig. 19-9).⁴⁹²

Figure 19-9 Left, Normal hindfoot architecture. Right, Sanders type II calcaneus fracture shown in a coronal computed tomography scan.

Subtalar Arthrodesis

Subtalar arthrodesis in the nontrauma setting has reported success rates of 80% to 90% good-to-excellent results.⁴⁸⁵ Unfortunately, when performed in the setting of posttraumatic arthritis, good-to-excellent results are reported in only 50% to 60% of cases.³⁵⁰ Thermann noted 41% fair-to-poor results with secondary subtalar arthrodesis after calcaneal fracture,⁵⁴⁷ and Pennal noted poor results in his small series of early subtalar arthrodesis for talar neck fractures despite high fusion rates in both series. Flemister et al¹⁶³ noted a fusion rate of 96% in a series of 86 subtalar arthrodeses resulting from complications after calcaneal fracture, yet patients only achieved a mean American Orthopaedic Foot and Ankle Society (AOFAS) Hindfoot score of 75 at 2-year follow-up. Because of poor results with secondary arthrodesis after calcaneal fractures, Huefner et al²⁴² reported results of primary subtalar arthrodesis for comminuted calcaneal fractures. This team noted good-to-excellent results in 5 of 6 patients using the AOFAS scoring system. These differences in outcome between primary and secondary subtalar arthrodesis remain poorly understood.³

Complications after comminuted calcaneal fractures include a loss of calcaneal height, loss of talar declination, and anterior ankle impingement. For these patients, many have advocated a bone block subtalar arthrodesis to restore the calcaneal height, and talar declination. Garras et al ¹⁷⁹ reported on the use of frozen structural allograft for this purpose and noted a 90% successful fusion rate using structural autograft.

Saville et al ⁴⁹⁶ reported using the medial approach for hindfoot arthrodesis when severe valgus deformity is present. In their series, 10 patients underwent subtalar arthrodesis, 6 underwent subtalar and talonavicular arthrodesis, and 2 had triple arthrodesis. All wounds healed, and 17 of 18 patients went on to successful fusion over 5.6 months. The authors suggested that when the hindfoot is in extreme valgus, use of a medial approach may help avoid tension-related lateral wound problems and decrease sural nerve complications.

Glanzmann and Sanhueza-Hernandez ¹⁸⁷ reported their results of arthroscopic subtalar arthrodesis. They noted a 100% fusion rate using a posterolateral portal (just lateral to the Achilles tendon) and an anterolateral portal (centered upon the sinus tarsi). Joint preparation is done primarily through the posterolateral portal with a shaver, curette, and motorized burr. Visualization is achieved via a 3.5-mm arthroscope through the anterolateral portal. Lee et al³²⁸ also reported arthroscopic subtalar arthrodesis but with prone positioning through two posterior portals (medial and lateral to the Achilles tendon). Scranton et al⁵⁰⁵ reported on a comparison of open versus arthroscopic subtalar arthrodesis and noted that there was no large difference in operative time: 58 minutes for the open procedure versus 63 minutes for the arthroscopic procedure. The main advantage of an arthroscopic approach is decreased wound issues. However, fusion rates and other parameters have not been shown to be superior to traditional approaches.

Regardless of approach, hindfoot positioning during subtalar arthrodesis can be challenging. Optimally, the calcaneus should be in slight valgus (approximately 5 degrees) relative to the talus. Frigg et al ¹⁷² suggested that visual inspection is inadequate to determine correct hindfoot position, and that the Saltzman-el-Khoury hindfoot alignment view should be used. This weight-bearing, posterior to anterior radiograph is aimed 20 degrees caudal, with the x-ray beam parallel to the medial border of the foot.⁴⁸⁶ Unfortunately, this is impractical in an operative setting.¹⁷² Thus visual inspection and fluoroscopic imaging are most commonly used to determine hindfoot position during surgery.

Graft use (autograft, allograft, or bone substitute) and hardware configuration are additional options the surgeon must consider for hindfoot arthrodesis. The authors routinely use proximal tibial or iliac crest autograft and cannulated lag screw fixation to achieve compression across the joint (Fig. 19-10).

Figure 19-10 A, AP radiograph and B, lateral radiograph of primary subtalar and ankle arthrodesis for pantlar degenerative arthritis.

Frigg et al ¹⁷¹ reported on the use of porous tantalum interposition for ankle and subtalar arthrodesis and found that fusion was successful in nine of nine patients. Tantalum has been used for spine fusions and in the setting of hip and knee surgery. The advantage appears to be rapid ingrowth into the tantalum without donor-site morbidity.

Calcaneocuboid Arthrodesis

The incidence of calcaneocuboid joint arthritis after calcaneal fracture has been reported to be between 33% and 76%, with a higher percentage in joint depression-type fractures.¹⁴² However, those with fractures involving the actual calcaneocuboid joint are typically asymptomatic.²⁹⁴ Astion and Wulker^15,599 both noted that an isolated calcaneocuboid fusion has little effect on the motion of the adjacent joints and that the motion of the calcaneocuboid is small.

Talonavicular Arthrodesis

Isolated arthritis of the talonavicular joint (either resulting from trauma or degeneration) may require isolated fusion. However, arthrodesis of the talonavicular joint has a high nonunion rate. This is likely due to the spheric shape of the joint and the resultant difficulty in exposure and preparation of the joint surfaces. Published reports demonstrate a union rate between 63% and 97%.165,221 Chen et al⁸² reported a 94% union rate using either staples or screws without bone graft for isolated talonavicular joint fusions. Jarrell et al²⁵⁶ compared three methods of fixation and determined that there was no significant difference in load to failure between the three constructs. These studies support the notion that excellent joint surface preparation is more important than either fixation type or use of graft. Indications for talonavicular arthrodesis include isolated arthritis (Fig. 19-11), rheumatoid arthritis, or pes planovalgus deformity.

Figure 19-11 A, Anteroposterior (AP) radiograph demonstrating end-stage talonavicular arthritis. B, AP radiograph of double arthrodesis (talonavicular and calcaneocuboid joints) with plates and screws.

Astion ¹⁵ reported that isolated talonavicular joint fusion limits the subtalar joint to 8% of its native motion. In addition, fusing the talonavicular joint alone behaves similarly to the double hindfoot arthrodesis.⁵⁴⁶

Double Arthrodesis

The double arthrodesis (fusion of the talonavicular and calcaneocuboid joints) may be undertaken when these joints are diseased, while the subtalar joint is spared. Locking of the transverse tarsal joints results in an essentially immobile subtalar joint, and this double arthrodesis functions much like a triple hindfoot arthrodesis.⁸⁹ Beischer et al²⁸ noted that with a double or triple joint hindfoot fusion, the ankle joint range of motion during stance decreases by 33% while the ipsilateral knee range of motion increases by 13%.

Citing less than desireable results after triple arthrodesis, Sammarco et al ⁴⁸⁹ recommended a modified double arthrodesis of the subtalar and talonavicular joints. They noted that all of their patients were satisfied with the result, and only 1 of 16 patients required revision surgery for nonunion. Advantages of this type of double versus triple arthrodesis include reduced operative time and avoidance of potential calcaneocuboid nonunion (reported as 20% with the triple arthrodesis).²⁴

Triple and Pantalar Arthrodesis

The triple arthrodesis is regarded by many as a salvage procedure. Typical indications include posttraumatic hindfoot arthritis, rheumatoid arthritis, or stage III posterior tibial tendon dysfunction. It is a demanding procedure. The purpose is to restore plantigrade position of the foot, with the hindfoot in slight valgus. Not infrequently, a forefoot osteotomy is required to correct forefoot rotation in the coronal plane. Malunion is not uncommon and frequently leads to dissatisfaction for both the surgeon and patient. Resnick et al ⁴⁶¹ demonstrated that placing the calcaneus in too much valgus (Fig. 19-12) increases the force on the deltoid ligament by 76% during weight bearing. In contrast, a varus hindfoot places pressure on the lateral column and fifth metatarsal and may lead to lateral ankle instability and ankle arthritis.

Figure 19-12 Anteroposterior (A) lateral (B) weight-bearing ankle radiographs after triple arthrodesis.

Arthritis in adjacent joints (ankle and tarsometatarsal joints) has been reported after triple arthrodesis in up to 58% of patients in a 21-year follow-up.⁵⁸⁵ Nonunion and avascular necrosis have been reported. Graves²⁰⁰ and Beischer²⁸ noted that 28% to 33% of their patients walked with a limp after triple arthrodesis despite successful fusion.

For those with disabling hindfoot and ankle arthrosis, Acosta et al ² recommended pantalar arthrodesis involving the tibiotalar, subtalar, talonavicular, and calcaneocuboid joints (Fig. 19-13). Although 23 of 27 patients went on to solid fusion, there was a 37% complication rate, and only 5 patients had an excellent result. The authors suggested that, like the triple arthrodesis, this procedure be considered only as a salvage operation.²

Figure 19-13 Anteroposterior (A) and lateral (B) radiographs demonstrating a pantalar arthrodesis. After a triple arthrodesis, an ankle arthrodesis was performed as a staged pantalar arthrodesis.

Degenerative Arthritis of the Midfoot

Midfoot arthritis frequently develops as a sequela of a fracture or dislocation through the Lisfranc joint but may also develop spontaneously because of osteoarthritis or inflammatory arthritis. Thus it generally has a bimodal presentation: those with a traumatic etiology often seek care in their thirties, while those with a nontraumatic etiology often present in their fifties.²⁷⁰ Zonno and Myerson⁶¹¹ suggested that most midfoot pain is due to atraumatic osteoarthritis, although others maintain that trauma is the primary cause of arthritic change in the midfoot. Davitt et al¹²³ hypothesized that midfoot degeneration is the result of metatarsal length differences. The authors noted that a longer second metatarsal correlated with midfoot arthritis. Wearing high-heeled shoes may also contribute to midfoot arthritis.⁶⁰⁶

It should also be noted that arthritis in any of the tarsometatarsal joints in the absence of a history of trauma may represent an early Charcot (joint) deformity. Charcot arthropathy can develop with diabetes as well as with peripheral neuropathy and other neurologic disorders (Fig. 19-14).

Figure 19-14 Anteroposterior (A) and lateral (B) radiographs demonstating marked midfoot arthritis with painful progressive deformity.

Regardless of the cause, the development of midfoot arthritis can be an extremely disabling condition because of the stress placed on the longitudinal arch with weight bearing. A bony prominence may develop on the dorsal aspect of the midfoot because of osteophyte formation, which makes wearing shoes painful. A progressive flatfoot deformity can also develop from instability of the metatarsocuneiform (MTC) joint, with development of a plantar bony prominence and subsequent callus formation. Jung et al ²⁷⁰ noted four presentations associated with tarsometatarsal joint arthritis: no deformity, pes planovalgus, hallux valgus, and the rocker-bottom deformity. Mann et al³⁵⁷ noted that 78% of patients with midfoot arthritis had abnormal foot posture and difficulty with shoe wear.

With continued arthritic change, an abduction and dorsiflexion deformity of the midfoot occurs (Fig. 19-15). This progression of pain and deformity makes ambulation difficult.

Figure 19-15 Anteroposterior (A) and lateral (B) radiographs demonstrating severe peritalar subluxation with inflammatory arthritis.

In examination of the foot, passive manipulation of the midfoot involves abduction of the forefoot and a pronation stress test to determine the location of maximal pain. The piano-key test (Fig. 19-16) is positive when a plantarly directed force applied to the metatarsal head elicits pain in the same tarsometatarsal joint. This is a sensitive indicator of a symptomatic joint or joints.²⁸²

Figure 19-16 The piano-key test is positive when a patient feels pain in their tarsometatarsal joint with a plantarly directed force applied to the metatarsal head.

A complicating factor with midfoot arthropathy is a simultaneous hindfoot deformity. Malalignment at the transverse tarsal joint and a valgus deformity of the hindfoot often are associated with severe midfoot arthritis. A careful preoperative physical examination is necessary to determine the extent of the midfoot and hindfoot malalignment. In the subtle cavus foot with degenerative arthritis, the Coleman block test helps to determine the need for associated hindfoot procedures, such as the addition of a calcaneal osteotomy or creation of plantar flexion through the first MTC joint, with the arthrodesis or opening wedge through the medial cuneiform (Fig. 19-17).

Figure 19-17 A, Cotton osteotomy and placement of dorsal bone graft into medial cuneiform to plantar flex the first ray. B, A lateral radiograph demonstrating the Cotton and calcaneal osteotomy. (Original photographs by J.E. Johnson, MD, and C.B. Hirose, MD.)

Correctable or supple hindfoot valgus associated with medial column arthritis should reduce with proper restoration of alignment (reduction of any varus or rotational deformity, abduction, and dorsiflexion) during the midfoot arthrodesis but any fixed or residual valgus deformity without arthritis should be addressed with a medial displacement osteotomy or lateral column lengthening. Moreover, gastrocnemius recession or Achilles lengthening may be necessary after correction is achieved and bone alignment is restored to obtain a plantigrade foot.

Anatomically, the tarsometatarsal joint is divided into three columns: the medial column (first MTC joint), the middle column (second and third MTC joints), and the lateral column (fourth and fifth metatarsocuboid joints). Radiographically, the medial column is reduced when the medial border of the first metatarsal is aligned with the medial border of the medial cuneiform. The middle column is aligned when the medial border of the second metatarsal is aligned with the medial border of the intermediate cuneiform. For the lateral column, reduction is achieved when the medial border of the fourth metatarsal is aligned with the medial border of the cuboid. On the lateral radiograph, restoration of the first metatarsal declination angle and arch height are imperative.

Arthritic changes such as joint space narrowing can be seen on the weight-bearing anterior posterior radiograph. On the lateral radiograph, midfoot collapse of the tarsometatarsal joints may or may not be seen. The changes may also coincide with pes planovalgus deformities (forefoot abduction with midfoot collapse). Jung et al ²⁷⁰ noted that with primary osteoarthritis of the tarsometatarsal joints radiographs demonstrate a lower medial cuneiform height than that of posttraumatic arthritis.

Menz et al ³⁷⁶ reported that foot structure differs in elderly patients with midfoot arthritis compared with those without. In those with radiographic evidence of naviculocuneiform and talonavicular joint arthritis, they noted significantly flatter feet as evidenced by a small calcaneal inclination and a larger calcaneal first-metatarsal angle.

Treatment

Conservative management of midfoot degenerative arthritis includes a soft or rigid custom-molded orthosis that provides support to the longitudinal arch. A full-length carbon fiber insert may also be used. Rao et al ⁴⁵⁰ demonstrated that these orthotics significantly lessen the load duration and the intensity borne by the midfoot. Ibuki et al²⁴⁹ also reported that carbon fiber foot plates provided equivalent improvements in pain, activity levels, and walking ability when compared with custom-molded semirigid orthotics.

A polypropylene AFO may be used for more advanced degenerative arthrosis. Cast immobilization and, occasionally, a short-leg brace may be used to diminish pain. Unfortunately, as arthritis of the MTC joint progresses, with subsequent loss of the longitudinal arch and abduction of the forefoot, the use of AFOs becomes more limited. An AFO does not reorient the foot but does add support and stability to the foot. In time and with progression of deformity, surgical intervention is indicated.

Surgery consists of an arthrodesis of the involved midfoot joints. Most often, the second and third tarsometatarsal joints are involved. The first metatarsal medial cuneiform articulation is involved less often and the fourth and fifth metatarsocuboid articulation least often.304,447 Whether to include the intercuneiform articulations depends on inspection of these areas for arthrosis. Sangeorzan et al⁴⁹³ infrequently incorporated the intercuneiform joints (1 of 16), whereas Mann et al³⁵⁷ and Horton and Olney²⁴⁰ incorporated them in the arthrodesis technique more often. If any doubt exists, Mann et al³⁵⁷ suggest incorporating the intercuneiform joint within the arthrodesis.

In the patient with a pes planus deformity and abduction of the forefoot, it is important to reestablish the normal alignment of the midfoot at surgery. This is accomplished by bringing the medial Lisfranc joint into normal alignment with the hindfoot by adducting and plantar flexing the first, second, and third MTC articulations. Although a lateral column arthrodesis is much more difficult to achieve, on occasion, it may be necessary to realign the entire Lisfranc joint in the presence of severe deformity. Komenda et al ³⁰⁴ recommended reduction of the lateral column and temporary pin fixation until ambulation is initiated. They found a lateral column arthrodesis typically is unnecessary even in the presence of arthrosis (see Chapter 20).

Promising results have been obtained with interposition arthroplasty for lateral column arthritis,³⁶ and this procedure may be used as a second-stage procedure if needed for continued symptoms. Berlet et al³⁶ performed tendon interposition for fourth and fifth tarsometatarsal arthritis and noted that 6 of 8 patients were satisfied. Shawen et al⁵⁰⁸ used ceramic sphere interposition. Their patients showed an 87% improvement in American Orthopaedic Foot and Ankle Society (AOFAS) scores and, 11 of 11 would undergo the procedure again. Alternatively, reliable results have been reported with arthrodesis of the fourth and fifth tarsometatarsal joints as isolated procedures or in combination with medial column arthrodesis for rocker-bottom deformities in neuropathic conditions.⁴⁴⁷

Multiple fixation methods have been described, including an in situ bone dowel technique,²⁶³ slot graft technique,²⁹⁸ plate and screw fixation,^304,357 as well as Kirschner (K)-wire fixation with bone grafting.⁴⁹³ A plantarly placed plate and screws may offer a mechanical advantage over screws alone³⁶²; however, a comparison of a dorsomedial locking plate with crossed screws (Fig. 19-18) to secure the first metatarsocuneiform joint showed no significant difference in mechanical strength.²⁰⁶

Figure 19-18 Anteroposterior (A) and lateral (B) radiographs of a first, second, and third tarsometatarsal joint arthrodesis, using dorsal locking compression plates.

The potential concern with lateral midfoot arthrodesis as part of a medial column or central column procedure is that it creates an extremely rigid midfoot. In neuropathic conditions, it may be necessary to achieve the additional stability afforded by inclusion of the lateral column joints, but in posttraumatic or inflammatory cases, the authors prefer to avoid arthrodesis of the lateral column.

Whether to perform reduction of a midfoot deformity has been a controversial topic. Johnson and Johnson ²⁶³ reported on patients with mild and moderate midfoot deformities. They performed in situ fusions using K-wire internal fixation with a supplemental autogenous iliac crest graft technique. Nine of 13 patients (70%) reported good or excellent results and three nonunions. The most often fused joints were the second and third tarsometatarsal (66%) joints.

In a review of 16 patients, Sangeorzan et al ⁴⁹³ advocated reduction of the pes planus and abduction deformity and noted 11 of 16 cases with satisfactory results (69%). Few patients had excellent results or a normal foot, but many “returned to work.”

Horton and Olney ²⁴⁰ performed three in situ fusions and six realignment arthrodeses on eight patients (nine feet) for posttraumatic or degenerative arthrosis of Lisfranc joints. They used a five-hole, one-third semitubular plate that spanned the tarsometatarsal joint. An iliac crest graft was packed into the intervals between the tarsometatarsal joints and between the first and second metatarsals. The authors noted a strong correlation between reduction of the deformity and the outcome and reported seven of nine good and excellent results.

Mann et al ³⁵⁷ reported that 38 of 41 patients with primary, traumatic, or inflammatory arthrosis of the midfoot were satisfied. They advocated reduction of the deformity. Eleven patients had an autogenous bone graft placed at the time of arthrodesis.

Komenda et al ³⁰⁴ and Sangeorzan et al⁴⁹³ recommend that the lateral column not be included in the arthrodesis because this area is usually asymptomatic even with significant radiographic evidence of arthrosis. They emphasized that realignment of the midfoot contributes to a successful result. Komenda et al³⁰⁴ stated that if there is 15 degrees of malalignment in the transverse or sagittal plane or greater than 2 mm of displacement, reduction of the deformity is indicated. They did use temporary internal fixation when the lateral column was realigned but did not routinely perform arthrodesis for the lateral column.

Shereff et al ³³³ reported 81% successful results using iliac crest bone graft and K-wire fixation in 16 patients. They found that fusion of the fourth and fifth TMT joints was associated with significantly poorer functional and subjective scores.

The use of an autogenous iliac crest graft often increases the success rate of arthrodesis. Sangeorzan et al ⁴⁹³ stated that an additional graft was not necessary. Komenda et al³⁰⁴ used an ancillary graft in one third of cases and Mann et al³⁵⁷ in one fourth of cases.

The current authors prefer to avoid using iliac crest unless structural defects require its use. However, the use of bone healing and enhancing substrates, such as platelet concentration systems, have shown promise. Han and colleagues demonstrated that platelet-rich plasma (PRP) enhances osteoinductivity.²¹⁶ Landi et al³¹⁷ noted an increase in fusion rates at 3 months as well as an increase in bone density by using a platelet gel in lumbar fusions. Hauschild²²⁹ reported on a successful fusion in a canine tarsal joint by using PRP. Gandhi et al¹⁷⁶ reported on nine patients with foot and ankle nonunions. Using PRP and autologous bone graft at time of revision, the mean time to fusion was 2 months. Bibbo and colleagues⁴⁴ also used PRP for foot and ankle fusions, concluding that PRP increased the fusion rate with low complications.

Electrical, magnetic, or ultrasonographic bone stimulation can also be helpful. Several studies have reported on the positive influence of each of these modalities. Dhawan ¹³¹ reported a faster time to fusion with the use of pulsed electromagnetic field (PEMF) therapy in hindfoot fusions.

The authors believe that realignment with compression screw fixation across the respective TMT joints and a medial column plate as a neutralization or primary construct is needed to obtain a successful result in most cases. There is no consensus on the preferred approach for all midfoot arthritic problems, and the technique used must be tailored to the individual patient’s problem and the surgeon’s experience.

The authors’ preferred approach is to incorporate the medial column joints and to leave the lateral column mobile, in general, a two-incision technique is used for the arthrodesis, with a medial and dorsal incision spaced as far apart as possible to minimize wound-healing problems.

Patient satisfaction after midfoot fusion ranges from very good to acceptable. Nemec and colleagues ⁴¹⁰ noted 90% patient satisfaction. Mann et al³⁵⁷ reported an overall satisfaction of 86%, and Jung et al²⁷⁰ reported an 87% satisfaction. However, Baumhauer⁴³⁰ suggested that patients may only experience 60% reduction in pain.

The magnitude of surgery requires a lengthy postoperative convalescence. After midfoot arthrodesis, most workers have difficulty returning to an occupation that requires standing for a full 8-hour day. Postoperative complications include skin slough, metatarsalgia, and incisional neuromas.43,304,357

Nonunion rates have been reported to be between 3% and 8%, but anecdotal evidence may point to a higher rate.270,341,410 Moreover, in a review of complications associated with midfoot and hindfoot arthrodesis, Bibbo et al⁴³ reported that wound problems can be expected in 3% to 5% of nondiabetic patients undergoing elective arthrodesis procedures, but that rate increased up to 53% in diabetic patients (Fig. 19-19). Given the increasing numbers of diabetic patients in the United States and other countries, every effort should be made to prevent complications by evaluating and treating the vascular, neurologic, and general nutritional status of the patient before arthrodesis. Hindfoot alignment must be considered before midfoot arthrodesis as well, and concomitant osteotomies of staged hindfoot reconstruction, or both, should be considered.

Figure 19-19 Delayed wound healing incision in a patient with diabetes.

Inflammatory Arthropathies

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis, periarticular bone loss, and osteoporosis. It can affect both small and large joints, is generally symmetric, and affects both the upper and lower limbs.⁴⁷² The disease affects 0.3% to 2.1% of the general population, and Rana⁴⁴⁹ has estimated that five million people in the United States suffer from rheumatoid arthritis. RA is two to four times more common in women than in men, yet no predilection exists for any single ethnic group.²⁵⁹ Onset can occur at any age, but the prevalence increases with age, peaking during the third to fifth decades. The disease course generally follows one of three pathways: (1) a relentless, destructive and aggressive course; (2) a monocyclic course notable for a single episode of synovitis without permanent cartilage damage; and (3) a polycyclic course with multiple episodes of attack followed by remissions. Up to 70% of cases follow the polycyclic course.⁵²¹

The actual cause of the disease is unknown; however, genetic and environmental factors may play a role in etiology. Patients with an identical twin who has RA are four times more likely to develop RA than nontwin counterparts.³³⁶ Associations have also been found with viral infections, including cytomegalovirus, rubella, Epstein-Barr virus, and parvovirus.²⁵⁹ These viral agents may mimic portions of human leukocyte antigen (HLA) DR4, which stimulates the immune system to begin attacking the synovial lining of the joint in genetically susceptible individuals. Further etiologic studies are needed to fully elucidate the cause of RA.

The disease can affect all joints of the body but has a predilection for the small joints of the hand and foot. Much attention has been centered on rheumatoid deformities of the hand in terms of initial involvement of individual joints; with acute onset, however, the feet are involved slightly more often than the hand (15.7% vs. 14.7%) (Short et al cited by Calabro ⁶⁵). Foot and ankle symptoms account for more than 50% of the presenting complaints in those initially diagnosed with RA. In addition, it has been estimated that 85% to 90% of patients with RA will eventually experience foot or ankle problems.^565,569

Moreover, persons affected with mild-to-moderate rheumatoid arthritis with concomitant foot involvement have marked reduction in mobility and functional capacity.⁵⁸⁷ An increased incidence of foot problems occurs with duration of the disease process,³⁸⁰ and in chronic RA, Michelson³⁸⁰ reported that ankle and hindfoot symptoms were much more common (42%) than forefoot symptoms (28%) in a series of 99 patients followed in an outpatient setting. In chronic rheumatoid arthritis, symmetric involvement is common. Early on, however, asymmetric involvement may be observed.

History and Physical Examination

Early complaints of patients with RA involve poorly defined forefoot pain and metatarsalgia. Typically, these complaints result from synovitis and an intraarticular effusion, which lead to painful ambulation. Poorly defined metatarsalgia can indicate an interdigital neuroma; in time, however, synovitis and deformity can make the diagnosis more straightforward. Zielaskowski ⁶¹⁰ has reported an association of rheumatoid synovitis, nodule formation, and interdigital neuroma.

A variable course of presentation occurs in the symptomatic rheumatoid foot. Nonspecific forefoot swelling is characterized by tenderness to palpation and pain on ambulation. The most common forefoot deformities are hallux valgus, subluxation or dislocation of the lesser MTP joints, and fixed hammer toe or claw toe deformities of the lesser toes (Fig. 19-20).

Figure 19-20 A, Clinical photograph of hallux valgus deformity with subluxation of the lesser metatarsophalangeal joints and complex hammer toe deformities. B, Plantar clinic photograph demonstrating lesser toe dislocation and plantar keratoses. C, Hallux varus deformity clinical photograph with lateral soft tissue attenuation and rupture.

Rheumatoid arthritis can be divided into the following four stages based on physical examination and radiographic findings:

Stage I: Discomfort and synovitis; no bone deformity or significant joint space narrowing

Stage II: Early involvement with flexible deformity; minimal erosive changes

Stage III: Fixed soft tissue deformity; significant erosive joint changes

Stage IV: Severe hallux valgus, dislocation of the lesser MTP joints with fixed hammer toe or claw toe deformities, pes planovalgus (flatfoot), and hindfoot arthroses; articular destruction on radiographs

Forefoot

In the early stages of rheumatoid arthritis, specific changes in the foot include inflammation of the synovium, with distention of the MTP joint capsule. Synovial proliferation leads to chronic capsule distention, resulting in loss of integrity of both the MTP joint supporting capsular structures and the collateral ligaments. With continued ambulation in the presence of soft tissue instability and with constant dorsiflexion stress on the MTP joints, subluxation and eventual dislocation occur.380,527 As the MTP joints of the lesser toes dislocate, the base of the proximal phalanx eventually comes to rest on the dorsal metatarsal metaphysis (Fig. 19-21).

Figure 19-21 Radiograph of a patient with rheumatoid arthritis. The lesser metatarsophalangeal joints are dislocated, with proximal phalanges resting on the dorsal metatarsal necks.

Progressive contracture of the long flexor tendons and the plantar intrinsic muscles lock the base of the proximal phalanx on the dorsal metatarsal neck. The proximal phalanx becomes fixed in a dorsiflexed position, creating a plantar-directed force on the metatarsal head.¹¹⁵ Simultaneously, the plantar fat pad is drawn distally, leaving only an extremely thin soft tissue covering on the plantar aspect of the metatarsal heads (Fig. 19-22). The loss of the protective plantar fat pad cushion, coupled with increased stress on the underlying skin, can lead to the development of intractable plantar keratotic (IPK) lesions and, in time, ulceration of the plantar skin (Fig. 19-23).

Figure 19-22 A, Normal alignment and balance of the metatarsophalangeal (MTP) joints and toes. Fat pad is centered beneath metatarsal heads. B, As rheumatoid deformity progresses, an imbalance occurs with progressive dorsal subluxation of the MTP joints and deformities of the lesser toes. The fat pad is drawn distally by the contracting lesser toes. C, End-stage deformity. Dislocation of the MTP joint with proximal phalanx ankylosed to the dorsal aspect of the metatarsal head. This forces the metatarsal head into the plantar aspect of the foot and results in severe callus formation. Lesser toes develop hammer toe deformities that often become severely contracted, and the fat pad is drawn distally and is no longer in a functional position. D, With chronic dorsiflexion deformity of the proximal phalanx at the MTP joint, flexor tendons subluxate dorsally, becoming functional extensors of the MTP joint.

Figure 19-23 Plantar forefoot ulceration after chronic lesser metatarsophalangeal dislocation (From Firestein GS, Budd RC, Harris ED Jr, et al, editors: Kelley’s textbook of rheumatology, ed 8, Philadelphia, 2008, Elsevier.)

The rheumatoid plantar fat pad is also significantly different than those of nonrheumatoid patients. Analysis with liquid gas chromatography demonstrates that the rheumatoid fat pad has a significantly higher ratio of saturated to unsaturated fat, as well as a higher viscosity. This is thought to reduce absorption of energy with foot strike, which may contribute to development of IPK lesions.⁴⁶⁰

Subluxation and dislocation of the lesser toes creates an imbalance between the intrinsic and extrinsic muscles and gives rise to progressive hammering of the lesser toes. Occasionally, a swan-neck deformity of a lesser toe develops, but more often, a hyperextension deformity of the MTP joint occurs in combination with a flexion deformity of the proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints (claw toe deformity). Because of severe contracture of the lesser toes, significant shoe-fitting problems result. Callosities can develop over the dorsal aspect of the PIP joint, causing areas of pressure. Large synovial cysts or rheumatoid nodules can develop in the forefoot and, when located on weight-bearing surfaces, lead to significant difficulty with ambulation. Although, typically, the lesser toes deviate in a lateral direction, medial deviation occasionally occurs. The resultant direction depends, to a great extent, on the direction in which the hallux deviates (varus or valgus).

Michelson et al ³⁸⁰ reported that within the first 1 to 3 years of rheumatoid arthritis, 65% of patients are noted to have MTP synovitis. With chronic rheumatoid arthritis, Vidigal et al⁵⁷⁵ and others^369,527 have reported that approximately two thirds of patients develop subluxation and dislocation of the lesser MTP joints (Fig. 19-24). Michelson et al³⁸⁰ and others^369,565,575 have reported that the incidence of hammer toe or claw toe deformity of the lesser toes varies from 40% to 80%.

Figure 19-24 A, Preoperative radiograph demonstrates lesser metatarsophalangeal (MTP) joint dislocations, marginal erosions with chondrolysis, and relative sparing of the 1st MTP joint. B, Clinical photograph at presurgical follow-up demonstrates hallux valgus deformity with dislocation of lesser MTP joints. C, Thirty-year-old woman demonstrating marginal erosions of the third, fourth, and fifth MTP joints with chondrolysis.D, Eight years later, radiographs demonstrate severe hallux valgus, chondrolysis, and dislocation of lesser MTP joints.

Hallux valgus increases in incidence and severity in the chronic stages of rheumatoid arthritis.⁶⁵ Michelson et al³⁸⁰ and others^527,565,575 have reported a high incidence of hallux valgus in patients with chronic rheumatoid arthritis (59%-90%). With progressive clawing of the lesser toes, little lateral stability is afforded to the great toe, and the hallux migrates laterally to a fixed position either under or over the second and third toes. Progression of the rheumatoid process includes destruction of articular cartilage and resorption of subchondral bone, which tends to destabilize the hallux. As the hallux valgus deformity worsens, the weight-bearing function of the first ray lessens and a greater proportion of weight is borne on the lesser metatarsal heads. Craxford et al¹¹⁷ reported increased pressure beneath the second and third metatarsal heads with chronic rheumatoid arthritis.

With time, the total number of diseased forefoot joints increases, as does the severity of the disease.²⁴⁴ In a longitudinal study, van der Leeden et al⁵⁶⁹ studied newly diagnosed patients with rheumatoid arthritis over an 8-year span, specifically looking at clinical impairment and walking disability. On presentation, 67% of patients had clinically painful and swollen MTP joints, which decreased to 40% to 50% over a 2-year period, while being treated medically. Even though the clinical numbers appeared to stabilize, the severity of radiologic forefoot damage increased. Once forefoot disease is present, deformity tends to progress rapidly over time, especially in the absence of pharmacologic treatment.

Midfoot

Vidigal et al ⁵⁷⁵ reported midtarsal joint involvement in approximately two thirds of patients with chronic rheumatoid arthritis. Chronic synovitis and eventual chondrolysis of the tarsometatarsal joints often occur with chronic disease. Associated with this, flattening of the longitudinal arch occurs in approximately 50% of patients.⁵²⁷ With disease progression, the talar head assumes a plantar medial position (Fig. 19-25) as the soft tissue structures supporting the talar head become attenuated. This midfoot collapse may have a mutlifactorial etiology. Several reports have linked arthritis and ligamentous laxity to pes planus, although others have indicated posterior tibial tendon rupture as the source.^135,281,295 In reality, all of the above likely contribute to the clinical picture.

Figure 19-25 Midfoot arch collapse with migration of the talar head plantarward.

Often with pes planus, a valgus deformity of the hindfoot occurs. The resultant ambulatory pattern is a shuffling, flat-footed steppage gait. Fu and Scranton ¹⁷³ noted that with progressive rheumatoid arthritis the foot changes to a passive weight-bearing platform for ambulation. Usually, because of the limitation of motion at the midfoot joints, a fibrous or bony ankylosis develops, but reduced motion is rarely restrictive.

Occasionally, the first MTC joint becomes extremely hypermobile, with subsequent loss of normal weight-bearing function. Resultant transfer metatarsalgia can occur from this hypermobility. Loss of the longitudinal arch on weight-bearing lateral radiographs is demonstrated by sagging at either the MTC or the naviculocuneiform articulation. Severe deformity can occur over time and make weight bearing almost impossible.

Hindfoot

With hindfoot involvement, a patient might misconstrue subtalar or transverse tarsal joint pain as “ankle” pain. Careful physical examination may be necessary to differentiate these symptomatic areas. Selective injections or imaging studies, such as CT scan or MRI (or both) can provide conclusive information.

Vainio ⁵⁶⁵ reported that 72% of women and 59% of men with chronic rheumatoid arthritis had involvement of either the midtarsal or the subtalar joint but that surgical intervention was relatively infrequent. Clayton⁹¹ reported that the forefoot was involved 10 times more often than the hindfoot. Kavlak²⁷⁸ noted that patients often show an obvious hindfoot valgus position and that a varus hindfoot is seldom seen (Figs. 19-26 and 19-27).

Figure 19-26 Hindfoot valgus in a patient with rheumatoid arthritis. (Courtesy A. Dingman, MD.)

Figure 19-27 Severe hindfoot deformity secondary to rheumatoid arthritis. A, Clinical photograph showing hindfoot valgus position. B, Because of inadequate support to the talus, the talus has assumed an extremely plantar-flexed position with resultant pes planus as shown on the lateral radiograph. C, Peritalar subluxation is notable on the anteroposterior radiograph. D and E, Magnetic resonance images show posterior tibial tendon tendinosis and high-grade signal change within the tendon (arrow denotes diseased posterior tibial tendon).

Changes in the hindfoot occur with much longer duration of rheumatoid arthritis. Spiegel and Spiegel ⁵²⁷ observed that in patients with rheumatoid arthritis of less than 5 years’ duration, only 8% demonstrated hindfoot arthrosis, whereas in those who had had rheumatoid arthritis longer than 5 years, 25% were symptomatic. They concluded that hindfoot arthrosis was an acquired deformity that developed from the mechanical stress of weight bearing.

The underlying pathophysiology with hindfoot involvement relates to progressive destruction of the capsular and ligamentous supporting structures of the subtalar joint. Because subtalar joint function is intimately associated with transverse tarsal joint function, instability of these joints can result in altered function and gait. Often, the end result is a progressive pes planovalgus deformity of the hindfoot (Fig. 19-28).

Figure 19-28 Clinical photograph of a pes planovalgus deformity with talar head subluxation plantarward. (Courtesy A. Dingman, MD.)

Posterior tibial tendon dysfunction with rheumatoid arthritis can lead to a unilateral progressive flatfoot deformity as well.135,360

Keenan et al ²⁸¹ reported that pes planovalgus deformities in patients with rheumatoid arthritis resulted from exaggerated pronation forces on the weakened and inflamed subtalar joint. They demonstrated with electromyographic studies that an increased period of activity of the tibialis posterior muscle occurred, which was interpreted as an “attempt to stabilize” an unstable foot. Flattening of the longitudinal arch also can develop secondary to naviculocuneiform joint deterioration or first metatarsocuneiform joint collapse. In some patients, severe valgus of the hindfoot may be associated with a concomitant valgus deformity of the ankle joint as well (Fig. 19-29).

Figure 19-29 Radiographs depicting bilateral incongruent ankle valgus deformities.

This creates a difficult management situation, with both ankle and hindfoot involvement. Bracing is difficult, and a pantalar fusion may be necessary to realign the foot but presents the patient with a difficult surgical recovery.

With severe, long-standing hindfoot deformity, an Achilles tendon contracture can develop. Although not a primary deformity, it occurs secondarily in relation to a chronic valgus deformity of the hindfoot. At the time of a triple arthrodesis, Achilles tendon lengthening may be necessary.

Gait analysis of patients with chronic rheumatoid arthritis when compared to those of nonarthritic subjects demonstrates delayed and reduced forefoot loading, resulting in a shorter stride length.⁴¹⁹ This effect may be related to pain in the forefoot which, in turn, causes a reduction of the functional lever arm of the foot during push-off.

Platto et al ⁴³⁹ reported an association between impaired ambulation and foot deformity. They observed a greater association between hindfoot disease and gait impairment compared with forefoot disease.⁴³⁹ On the other hand, Shi et al⁵¹² studied 100 feet with rheumatoid arthritis and reported no correlation between a loss of arch height and hallux valgus or forefoot splaying.

Imaging Modalities

The classic radiographic signs of rheumatoid arthritis are that of a synovial inflammatory disease. The hyperemia involved with acute synovitis leads to periarticular osteoporosis,²⁰⁷ and early radiographic examination might reveal only soft tissue swelling and diffuse juxtaarticular osteoporosis. In contrast, normal bone mineralization is usual in psoriasis, reactive arthritis, ankylosing spondylitis, and crystalline arthropathies. Synovial inflammation eventually leads to marginal cortical erosions¹⁸⁸ at the reflection of synovium and capsule attachment (Fig. 19-30). These peripheral erosions eventually progress to central erosions with resultant joint space narrowing, subluxation, and dislocation. Eventual destruction of the articular cartilage occurs as the rheumatoid pannus spreads around the cartilaginous surface. The articular cartilage is thought to be destroyed by proteolytic enzymes, resulting in joint space narrowing.⁶⁴

Figure 19-30 A, Forefoot radiograph demonstrates periarticular erosions of the lesser metatarsal heads. B, Subluxation, dislocation, joint space narrowing, and central erosions of the lesser metatarsophalangeal joints with hallux valgus deformity.

Gold and Bassett ¹⁸⁸ noted that rheumatoid arthritis tends to strike earliest at the first, fourth, and fifth MTP joints. They reported that the medial aspect of the first, second, third, and fourth metatarsals and the lateral aspect of the fifth metatarsal were involved initially. The earliest visible erosions probably occur on the lateral aspect of the fifth metatarsal. The IP joints are typically spared except for the hallux.⁵³⁵ Of interest, in patients with preexisting periarticular erosions, the erosions progress with time, whereas in those patients with preexisting joint space narrowing, it is the joint space narrowing that progresses with time. These two processes seem to be independent of one another.⁵⁶⁷

Midfoot and hindfoot changes include midfoot collapse, pes planus, and subtalar sclerosis. Localized inflammation in the areas of the retrocalcaneal bursa and at the attachment of the Achilles tendon and plantar aponeurosis are common with long-standing disease (Fig. 19-31).

Figure 19-31 Calcification of the Achilles tendon and the Achilles insertion.

Gold and Bassett ¹⁸⁸ reported the talonavicular joint is typically the first tarsal joint to be involved. Although radiographic midfoot arthritic changes are seen in up to 62%, clinically, these are far less symptomatic (27%).⁵⁷⁵ In a series of patients with rheumatoid arthritis who were evaluated with CT scans, Seltzer et al⁵⁰⁶ noted talonavicular joint involvement in 39%, calcaneocuboid involvement in 25%, and subtalar involvement in 29%.

Radiographically, the subtalar joint is involved to a lesser extent than the midfoot, with changes noted in 32% to 42% of patients. Only 21% of rheumatoid arthritis patients actually have clinical symptoms in the hindfoot.380,575 Rarely are all three of the hindfoot joints simultaneously affected.²⁵¹

Hattori and colleagues ²²⁷ noted two distinct patterns of pes planovalgus deformities in the rheumatoid foot. One group demonstrated degenerative changes in both the subtalar and talonavicular joints, with the talar head subluxated plantarward in relation to the navicular. A second group showed only subtalar joint involvement. Neither group demonstrated involvement of the calcaneocuboid joint.

Radiographic progression of rheumatoid arthritis can be evaluated by various methods, but commonly used methods are those described by Larsen,³²¹ Rau,⁴⁵¹ and Steinbrocker.⁵³³ The methods of Rau and Larsen were found to be equivalent, as reported by Tanaka et al⁵⁴² in assessing progression of early rheumatoid arthritis, which indeed affects pharmacologic treatment. Moreover, the magnitude of 5-year disability as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) was associated with joint space–narrowing scores in the first year rather than periarticular erosion.³⁴⁶

Lindqvist et al ³³⁴ noted more rapid radiographic progression in those patients with higher levels of inflammatory markers, such as sedimentation rate and rheumatoid factor. Another report suggested that 59% of 190 patients with early rheumatoid arthritis could be classified as nonprogressive based on radiographic joint changes⁴³² and that radiographic progression may be slowed by treatment with disease-modifying antirheumatic drugs (DMARDs) and other pharmacologic agents, including antibiotics (sulfonamides, doxycycline), salicylates, cytotoxic drugs (methotrexate, leuprolide acetate, cyclophosphamide), NSAIDs, corticosteroids, and cytokine inhibitors (etanercept, infliximab).

In patients with nonspecific pain or diffuse foot pain, or both, with no visible radiographic findings and subtle or minimal clinical findings, a technetium-99 (⁹⁹Tc) bone scan can help to localize disease (Fig. 19-32).⁴²¹