The Foot 24 (2014) 176–179
Contents lists available at ScienceDirect
The Foot journal homepage: www.elsevier.com/locate/foot
Foot and ankle tuberculosis: Case series and literature review夽 Muhammad Korim ∗ , Rizwan Patel, Patricia Allen, Jitendra Mangwani University Hospitals Leicester, Gwendolen Road, Leicester LE5 4PW, United Kingdom
a r t i c l e
i n f o
Article history: Received 15 February 2014 Received in revised form 13 May 2014 Accepted 16 July 2014 Keywords: Tuberculosis Foot Ankle Fusion Treatment Diagnosis
a b s t r a c t Foot and ankle tuberculosis (TB) is a rare presentation of skeletal TB. The uncommon site along with low index of clinical suspicion in the western world leads to delays in the diagnosis and treatment. This can make joint sparing procedures less successful, especially in the midfoot where the joints can often be interconnected. Plain radiographs have low sensitivity and specificity and cross sectional imaging in the form of MRI or CT is more reliable. Treatment involves the use of multiple anti-tuberculous drugs in the first instance, followed by surgery to address any symptomatic deformity and/or secondary degenerative changes. We present our experience on the management of this rare problem and review the literature on the clinical presentation, diagnosis, imaging modalities and treatment. © 2014 Elsevier Ltd. All rights reserved.
1. Introduction
2. Materials and methods
Tuberculosis (TB) is an infection caused by the bacteria Mycobacterium tuberculosis that most often affects the lungs, but occurs in many locations within the body. Bones and joints are involved in 1–3% of cases and only about 10% of osteoarticular TB affects the foot and ankle [1–5]. The rarity of the problem and a low index of suspicion in the western world often lead to delayed diagnosis and potentially worse outcomes [2,3]. Extra-pulmonary TB favours those with sub-optimal immune function and includes the very young, the elderly and those with underlying conditions such as HIV and renal failure [6]. The incidence of TB in the UK remains high compared to most Western European countries, despite the stabilisation of TB rates since 2005. Although there is published literature on the management of osteoarticular TB, there is a relative paucity of large studies on the presentation and management of this condition in the foot and ankle in the western world. This article reports on two cases of foot and ankle TB highlighting the diagnostic pitfalls leading to delay in the initiation of treatment. The literature on the outcomes of treatment of TB in the foot and ankle is also reviewed.
2.1. Case 1
夽 No financial support or grant has been received in the production of this manuscript. ∗ Corresponding author at: 33 West Avenue, Leicester LE2 1TS, United Kingdom. Tel.: +44 07792746502; fax: +44 01162706001. E-mail addresses: [email protected], [email protected] (M. Korim). http://dx.doi.org/10.1016/j.foot.2014.07.006 0958-2592/© 2014 Elsevier Ltd. All rights reserved.
A 66 year old Asian patient with diabetes presented with a 2year history of left foot pain and difficulty walking. The patient was seen in primary care with unexplained pain/swelling and had been treated symptomatically. He had no constitutional symptoms. The patient had visited India a few times in the last two years. Examination findings included swelling on the dorsum of the talonavicular joint area with localised warmth and diffuse tenderness. Radiographs showed talar head destruction. An MRI scan was arranged to clarify whether this was an infective process or Charcot’s arthropathy and the radiological features are illustrated in Fig. 1. The swelling was biopsied under image guidance and the histology confirmed granulomatous caseating necrosis consistent with tuberculosis. The patient was started on multimodal anti-tuberculous therapy and over the next year his symptoms improved. However, the patient was never pain free and needed periods of splintage in an aircast boot. The patient completed his anti-tuberculous treatment and was discharged by the infectious disease unit. After 18 months, the patient was still struggling to mobilise and radiographs confirmed advanced collapse and degeneration in the talonavicular joint. It is planned for him to have a talonavicular joint arthrodesis when he returns to the UK. 2.2. Case 2 A 50 year old Asian woman with psoriasis presented with an 18 month history of right ankle pain to the rheumatologists.
M. Korim et al. / The Foot 24 (2014) 176–179
177
Fig. 1. Radiographs and MRI of talonavicular joint TB with erosions on talar head and.
The patient’s inflammatory markers were normal as well as a quantiferon test. She was treated for presumed psoriatic arthropathy of the ankle joint. The patient had two steroid injections in the ankle joint and was on methotrexate and leflunomide when she was seen in the foot and ankle clinic. The patient was noted to have a swollen and warm right ankle with reduced range of movement. Radiographs showed bony destruction in the tibia and talus and erosion of the fibula as illustrated in Fig. 2. An urgent arthrotomy and biopsy was arranged. Macroscopically, thick grey synovium was found in the joint space and advance joint degeneration was present. The histology showed granulomatous inflammation with epitheloid granuloma
including multinucleate giant cells and a peripheral rim of lymphoid cells. The patient was started on multimodal therapy and is on a second course of treatment due to recurrence of the disease. Her last radiographs showed advanced degeneration and deformity in the ankle joint and the patient is likely to require an ankle arthrodesis in the near future. 3. Discussion The two cases illustrate some of the difficulties faced by orthopaedic surgeons when confronted with potential
Fig. 2. Radiographs showing advanced destruction of the tibiotalar joint and syndesmosis.
178
M. Korim et al. / The Foot 24 (2014) 176–179
Table 1 Summary of main foot and ankle TB series illustrating time to diagnosis and treatment required. Study
N
Location
Time to diagnosis/months
Mittal et al. [3]
44
n/a
0 (0)
Dhillon and Nagi [2]
75
2–23
4 (6)
Choi et al. [11]
15
Samuel et al. [10]
16
Chen et al. [5]
29
Foot 37-Bone, 7-soft tissue Foot/ankle Osseus-21, articular/soft tissue-54 Ankle-10, forefoot-2, midfoot-3 Ankle joint-6 Tendon/bursa-5 Bone-4 Ankle and peritalar joints
osteoarticular TB in the foot and ankle. A high index of suspicion and prompt cross sectional imaging is required to reach an early diagnosis. Delayed diagnosis has potentially worse outcomes with an osseous lesion increasing in size and eventually involving the articular cartilage, leading to joint collapse and secondary degenerative changes. In our case series, the diagnosis was made more than one year after onset of symptoms. Both cases had risk factors for alternative diagnosis (Charcots arthropathy and Psoriatic arthropathy for cases 1 and 2, respectively) which is more common than foot/ankle TB in the western world. Case 1 illustrates the importance of a high index of suspicion for the diagnosis as the patient was treated symptomatically in primary care for about 2 years. Case 2 illustrates the importance of early cross sectional imaging in cases of unexplained arthropathy of the ankle joint, even when the blood tests are not suggestive of infection. The patient was treated for presumed psoriatic arthropathy with steroid injections and disease modifying agents by the rheumatology department. It is likely that this worsened her ultimate outcome, even if it is difficult to know if the ankle joint articular surface would have been salvageable. The ankle and talonavicular joints in the two patients had advanced secondary degenerative changes after completion of medical therapy. Complex reconstructive procedures are likely to be required in the foreseeable future. The main series from the Indian subcontinent reported an overall arthrodesis rate of 18% (33/179) as is illustrated in Table 1. There are many factors which may explain the better outcomes. A higher index of suspicion together with the diagnosis being made on clinicradiological findings alone [3,7] may lead to earlier initiation of medical treatment. There are a few case reports in the literature which suggest that delayed diagnosis leads to inferior outcomes [8,9]. However, a delayed diagnosis was still present in the larger case series and yet the arthrodesis rate was low [2,3,5,10,11]. When the soft tissue TB was excluded from the overall figures, the arthrodesis rate was still relatively low at 29% (33/113).
3.1. Clinical findings The calcaneum and midtarsal joints are more often affected [2,3]. Skeletal TB symptoms include joint swelling, limited range of motion, bony tenderness, limping and muscle spasms. Systemic symptoms such as fever, night sweats, malaise, anorexia and weight loss may be present. Other features that should raise suspicion include ongoing symptoms for several months, HIV positive status, ethnicity and recent immigration from or prolonged travel to a high-prevalence country, exposure to known or possible TB individuals. In the foot, swelling, deformity and localised signs of inflammation should be sought. Groin lymphadenopathy may be present. Discharging sinuses and ankylosis are late features. A high index of
Arthrodeses(debridement)/N
23 (1–120)
5 (10)
12 (1–36)
5 (10)
12 (1–48)
19 (10)
suspicion is required as there is considerable overlap with inflammatory arthritis. The differential diagnosis of tuberculous arthritis includes subacute or chronic pyogenic arthritis, traumatic arthritis, and pauci-articular rheumatoid arthritis, pigmented villonodular synovitis and amyloidosis [5,10,11]. 3.2. Pathogenesis 3.2.1. Osseous and articular TB Articular TB exhibits a slowly progressive course. The initial lesion is either in the bone or the synovium, and one subsequently infects the other. The infected granulation tissue from the synovium forms a pannus at the periphery of the articular surface. When the infectious process reaches the subchondral region, either by direct osseous spread or through the pannus, gaining access to the margins of the cartilage and spreading below it, the articular cartilage detaches from the bone. The cartilage, however, remains intact for a long time, and its destruction occurs much later because the exudate in tuberculous arthritis does not have proteolytic enzymes [10]. In the midfoot, this has disastrous consequences as the joints are interconnected. If there is widespread involvement, this can lead to collapse of the arches which may require extensive reconstructive efforts. Other forms include a central granuloma which is commonly encountered in children and affects the phalanges or metatarsals [1]. 3.2.2. Classification of articular TB Four stages of TB arthritis were proposed by Martini and Ouahes and refined by Chen et al. [5]. In stage 1 there is infection of the synovial lining with little bony erosion or localised osteoporosis. Stage 2 has marked erosions or areas of frank TB osteomyelitis, but the joint space is maintained. Stage 3 is characterised by more synovial and bony involvement with a loss of joint space. In stage 4 there is involvement of more than 1 peritalar joint surface or concomitant pyogenic arthritis with substantial disorganisation of osseous architecture [5]. 3.3. Imaging In most cases, the radiographic features of osteoarticular tuberculosis are nonspecific [2,3,10]. Radiographic features are usually noted 2 to 5 months after disease onset and only a joint effusion may be apparent in the very early stage [11,12]. The typical radiographic presentation of tuberculous arthritis is characterised by juxta-articular osteoporosis, peripheral osseous erosions, and gradual reduction of joint space, known as the Phemisters triad [11,12]. Lytic areas of destruction and marginal erosions are typically seen along the articular margins in weight-bearing articulations, such
M. Korim et al. / The Foot 24 (2014) 176–179
as the hip, knee, and ankle [12]. However, in contrast to pyogenic arthritis, there is relative preservation of the joint space in the early disease stages owing to the lack of proteolytic enzymes in the exudate. Severe osteopenia is characteristically noted, and, especially in adults, there is a lack of sclerosis or periostitis in the early stage when the disease is active. Severe joint destruction and, eventually, sclerosis and fibrous ankylosis are noted in the late stages when active infection has resolved [1,11,12]. Cross sectional imaging is more reliable at picking up early disease. MRI is good at looking at soft tissue architecture and collections. CT scan is useful to delineate the bony anatomy and delineate cortical breaks or collapse of the articular surface. It is useful to plan reconstructive procedures. It is important to note that the radiologic features lag behind the actual healing process and Dhillon and Nagi [2] recommended at least 6–7 months of multimodal therapy before repeating crosssectional imaging to reduce the rate of false positives for disease progression. 3.4. Biochemical and haematological tests Haematological and biochemical tests provide supportive evidence for ongoing sepsis (WCC, CRP and ESR) and bone activity (ALP), but do not provide a definite diagnosis. Interferon gamma release assays such as T-SPOT and QuantiFERON-TB Gold used for testing for the presence of TB, however, are limited as they do not distinguish between active and latent cases of TB as they merely assess the immune response against mycobacterium TB antigens [13]. The National Institute of Clinical Excellence (NICE) recommends that all patients with non-respiratory TB should have a chest X-ray to exclude or confirm co-existing respiratory TB [14]. 3.5. Histological diagnosis Osteoarticular TB is a paucibacilliary lesion and is therefore difficult to demonstrate the AFB on culture from the lesions. Molecular diagnostics such as line probe assays or nucleic acid amplification tests (NAAT) has also been shown to be a reliable alternative diagnostic tool compared to isolation of tubercular bacilli [13]. Biopsies can be carried out by fine needle aspiration or guided by imaging modalities such as computed tomography [15]. 3.6. Medical management Initial empirical therapy is the same as the standard regime for active respiratory TB. The ‘standard recommended regimen’ includes 6 months of isoniazid and rifampicin including supplementation with pyrazinamide and ethambutol in the first 2 months [14]. A few major side effects associated with the ‘standard recommended regimen’ include skin rashes, jaundice, confusion, visual impairment, and shock. The suspected offending agent should be stopped and the patient referred to a clinician urgently. Minor side effects include anorexia, joint pain, abnormalities in hand and foot sensation, flu syndrome, and orange urine [16]. Symptomatic management is often all that is required, but urgent referral to a physician may be required.
179
3.7. Surgical management Adequate and prolonged medical therapy is the mainstay of treatment. Surgery is reserved for biopsy to establish the diagnosis, debridement of abscesses despite medical treatment, joint resection with or without arthrodeses. Debridement of sequestrum is not required as they resolve with medical treatment. Sinus tract excision may accelerate the healing process and curettage of juxtaarticular cavities may prevent joint collapse [2]. Splintage and restricted weight bearing may be important in some cases to reduce the risk of articular surface collapse and this may be achieved in a number of ways. 4. Conclusions Foot and ankle TB is a rare diagnosis requiring a high index of suspicion to allow early initiation of medical treatment. Prompt cross sectional imaging and tissue diagnosis is mandatory before initiation of prolonged multimodal medical therapy. Delayed diagnosis could lead to potentially worse outcomes. Surgical intervention is rarely required and reserved for making a diagnosis, preserving or reconstructing affected joints. Conflict of interest There was no conflict of interest in the preparation of this manuscript. References [1] Dhillon MS, Aggarwal S, Prabhakar S, Bachhal V. Tuberculosis of the foot: an osteolytic variety. Indian J Orthop 2012;46:206–11. [2] Dhillon MS, Nagi ON. Tuberculosis of the foot and ankle. Clin Orthop Relat Res 2002;398:107–13. [3] Mittal R, Gupta V, Rastogi S. Tuberculosis of the foot. J Bone Joint Surg Br 1999;81:997–1000. [4] Spiegel DA, Singh GK, Banskota AK. Tuberculosis of the musculoskeletal system. Tech Orthop 2005;20:167–78. [5] Chen S-H, Lee C-H, Wong T, Feng H-S. Long-term retrospective analysis of surgical treatment for irretrievable tuberculosis of the ankle. Foot Ankle Int 2013;34:372–9. ´ [6] Rowinska-Zakrzewska E. Extrapulmonary tuberculosis, risk factors and incidence. Pneumonol Alergol Pol 2011;79:377–8. [7] Watts HG, Lifeso RM. Tuberculosis of bones and joints. J Bone Joint Surg Am 1996;78:288–98. [8] Dalldorf PG, Banas MP, Marquardt JD. Tuberculosis of the foot: a case report. Foot Ankle Int 1994;15:157–61. [9] Bozkurt M, Do˘gan M, Sesen H, Turanli S, Basbozkurt M. Isolated medial cuneiform tuberculosis: a case report. J Foot Ankle Surg n.d.;44:60–3. [10] Samuel S, Boopalan PRJVC, Alexander M, Ismavel R, Varghese VD, Mathai T. Tuberculosis of and around the ankle. J Foot Ankle Surg;50:466–72. [11] Choi WJ, Han SH, Joo JH, Kim BS, Lee JW. Diagnostic dilemma of tuberculosis in the foot and ankle. Foot Ankle Int 2008;29:711–5. [12] De Backer AI, Mortelé KJ, Vanhoenacker FM, Parizel PM. Imaging of extraspinal musculoskeletal tuberculosis. Eur J Radiol 2006;57:119–30. [13] Norbis L, Miotto P, Alagna R, Cirillo DM. Tuberculosis: lights and shadows in the current diagnostic landscape. New Microbiol 2013;36:111–20. [14] NICE guidelines [CG117]. Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control; 2011. [15] Perkins MD. New diagnostic tools for tuberculosis. Int J Tuberc Lung Dis 2000;4:S182–8. [16] Treatment of tuberculosis guidelines; n.d.
Contents lists available at ScienceDirect
The Foot journal homepage: www.elsevier.com/locate/foot
Foot and ankle tuberculosis: Case series and literature review夽 Muhammad Korim ∗ , Rizwan Patel, Patricia Allen, Jitendra Mangwani University Hospitals Leicester, Gwendolen Road, Leicester LE5 4PW, United Kingdom
a r t i c l e
i n f o
Article history: Received 15 February 2014 Received in revised form 13 May 2014 Accepted 16 July 2014 Keywords: Tuberculosis Foot Ankle Fusion Treatment Diagnosis
a b s t r a c t Foot and ankle tuberculosis (TB) is a rare presentation of skeletal TB. The uncommon site along with low index of clinical suspicion in the western world leads to delays in the diagnosis and treatment. This can make joint sparing procedures less successful, especially in the midfoot where the joints can often be interconnected. Plain radiographs have low sensitivity and specificity and cross sectional imaging in the form of MRI or CT is more reliable. Treatment involves the use of multiple anti-tuberculous drugs in the first instance, followed by surgery to address any symptomatic deformity and/or secondary degenerative changes. We present our experience on the management of this rare problem and review the literature on the clinical presentation, diagnosis, imaging modalities and treatment. © 2014 Elsevier Ltd. All rights reserved.
1. Introduction
2. Materials and methods
Tuberculosis (TB) is an infection caused by the bacteria Mycobacterium tuberculosis that most often affects the lungs, but occurs in many locations within the body. Bones and joints are involved in 1–3% of cases and only about 10% of osteoarticular TB affects the foot and ankle [1–5]. The rarity of the problem and a low index of suspicion in the western world often lead to delayed diagnosis and potentially worse outcomes [2,3]. Extra-pulmonary TB favours those with sub-optimal immune function and includes the very young, the elderly and those with underlying conditions such as HIV and renal failure [6]. The incidence of TB in the UK remains high compared to most Western European countries, despite the stabilisation of TB rates since 2005. Although there is published literature on the management of osteoarticular TB, there is a relative paucity of large studies on the presentation and management of this condition in the foot and ankle in the western world. This article reports on two cases of foot and ankle TB highlighting the diagnostic pitfalls leading to delay in the initiation of treatment. The literature on the outcomes of treatment of TB in the foot and ankle is also reviewed.
2.1. Case 1
夽 No financial support or grant has been received in the production of this manuscript. ∗ Corresponding author at: 33 West Avenue, Leicester LE2 1TS, United Kingdom. Tel.: +44 07792746502; fax: +44 01162706001. E-mail addresses: [email protected], [email protected] (M. Korim). http://dx.doi.org/10.1016/j.foot.2014.07.006 0958-2592/© 2014 Elsevier Ltd. All rights reserved.
A 66 year old Asian patient with diabetes presented with a 2year history of left foot pain and difficulty walking. The patient was seen in primary care with unexplained pain/swelling and had been treated symptomatically. He had no constitutional symptoms. The patient had visited India a few times in the last two years. Examination findings included swelling on the dorsum of the talonavicular joint area with localised warmth and diffuse tenderness. Radiographs showed talar head destruction. An MRI scan was arranged to clarify whether this was an infective process or Charcot’s arthropathy and the radiological features are illustrated in Fig. 1. The swelling was biopsied under image guidance and the histology confirmed granulomatous caseating necrosis consistent with tuberculosis. The patient was started on multimodal anti-tuberculous therapy and over the next year his symptoms improved. However, the patient was never pain free and needed periods of splintage in an aircast boot. The patient completed his anti-tuberculous treatment and was discharged by the infectious disease unit. After 18 months, the patient was still struggling to mobilise and radiographs confirmed advanced collapse and degeneration in the talonavicular joint. It is planned for him to have a talonavicular joint arthrodesis when he returns to the UK. 2.2. Case 2 A 50 year old Asian woman with psoriasis presented with an 18 month history of right ankle pain to the rheumatologists.
M. Korim et al. / The Foot 24 (2014) 176–179
177
Fig. 1. Radiographs and MRI of talonavicular joint TB with erosions on talar head and.
The patient’s inflammatory markers were normal as well as a quantiferon test. She was treated for presumed psoriatic arthropathy of the ankle joint. The patient had two steroid injections in the ankle joint and was on methotrexate and leflunomide when she was seen in the foot and ankle clinic. The patient was noted to have a swollen and warm right ankle with reduced range of movement. Radiographs showed bony destruction in the tibia and talus and erosion of the fibula as illustrated in Fig. 2. An urgent arthrotomy and biopsy was arranged. Macroscopically, thick grey synovium was found in the joint space and advance joint degeneration was present. The histology showed granulomatous inflammation with epitheloid granuloma
including multinucleate giant cells and a peripheral rim of lymphoid cells. The patient was started on multimodal therapy and is on a second course of treatment due to recurrence of the disease. Her last radiographs showed advanced degeneration and deformity in the ankle joint and the patient is likely to require an ankle arthrodesis in the near future. 3. Discussion The two cases illustrate some of the difficulties faced by orthopaedic surgeons when confronted with potential
Fig. 2. Radiographs showing advanced destruction of the tibiotalar joint and syndesmosis.
178
M. Korim et al. / The Foot 24 (2014) 176–179
Table 1 Summary of main foot and ankle TB series illustrating time to diagnosis and treatment required. Study
N
Location
Time to diagnosis/months
Mittal et al. [3]
44
n/a
0 (0)
Dhillon and Nagi [2]
75
2–23
4 (6)
Choi et al. [11]
15
Samuel et al. [10]
16
Chen et al. [5]
29
Foot 37-Bone, 7-soft tissue Foot/ankle Osseus-21, articular/soft tissue-54 Ankle-10, forefoot-2, midfoot-3 Ankle joint-6 Tendon/bursa-5 Bone-4 Ankle and peritalar joints
osteoarticular TB in the foot and ankle. A high index of suspicion and prompt cross sectional imaging is required to reach an early diagnosis. Delayed diagnosis has potentially worse outcomes with an osseous lesion increasing in size and eventually involving the articular cartilage, leading to joint collapse and secondary degenerative changes. In our case series, the diagnosis was made more than one year after onset of symptoms. Both cases had risk factors for alternative diagnosis (Charcots arthropathy and Psoriatic arthropathy for cases 1 and 2, respectively) which is more common than foot/ankle TB in the western world. Case 1 illustrates the importance of a high index of suspicion for the diagnosis as the patient was treated symptomatically in primary care for about 2 years. Case 2 illustrates the importance of early cross sectional imaging in cases of unexplained arthropathy of the ankle joint, even when the blood tests are not suggestive of infection. The patient was treated for presumed psoriatic arthropathy with steroid injections and disease modifying agents by the rheumatology department. It is likely that this worsened her ultimate outcome, even if it is difficult to know if the ankle joint articular surface would have been salvageable. The ankle and talonavicular joints in the two patients had advanced secondary degenerative changes after completion of medical therapy. Complex reconstructive procedures are likely to be required in the foreseeable future. The main series from the Indian subcontinent reported an overall arthrodesis rate of 18% (33/179) as is illustrated in Table 1. There are many factors which may explain the better outcomes. A higher index of suspicion together with the diagnosis being made on clinicradiological findings alone [3,7] may lead to earlier initiation of medical treatment. There are a few case reports in the literature which suggest that delayed diagnosis leads to inferior outcomes [8,9]. However, a delayed diagnosis was still present in the larger case series and yet the arthrodesis rate was low [2,3,5,10,11]. When the soft tissue TB was excluded from the overall figures, the arthrodesis rate was still relatively low at 29% (33/113).
3.1. Clinical findings The calcaneum and midtarsal joints are more often affected [2,3]. Skeletal TB symptoms include joint swelling, limited range of motion, bony tenderness, limping and muscle spasms. Systemic symptoms such as fever, night sweats, malaise, anorexia and weight loss may be present. Other features that should raise suspicion include ongoing symptoms for several months, HIV positive status, ethnicity and recent immigration from or prolonged travel to a high-prevalence country, exposure to known or possible TB individuals. In the foot, swelling, deformity and localised signs of inflammation should be sought. Groin lymphadenopathy may be present. Discharging sinuses and ankylosis are late features. A high index of
Arthrodeses(debridement)/N
23 (1–120)
5 (10)
12 (1–36)
5 (10)
12 (1–48)
19 (10)
suspicion is required as there is considerable overlap with inflammatory arthritis. The differential diagnosis of tuberculous arthritis includes subacute or chronic pyogenic arthritis, traumatic arthritis, and pauci-articular rheumatoid arthritis, pigmented villonodular synovitis and amyloidosis [5,10,11]. 3.2. Pathogenesis 3.2.1. Osseous and articular TB Articular TB exhibits a slowly progressive course. The initial lesion is either in the bone or the synovium, and one subsequently infects the other. The infected granulation tissue from the synovium forms a pannus at the periphery of the articular surface. When the infectious process reaches the subchondral region, either by direct osseous spread or through the pannus, gaining access to the margins of the cartilage and spreading below it, the articular cartilage detaches from the bone. The cartilage, however, remains intact for a long time, and its destruction occurs much later because the exudate in tuberculous arthritis does not have proteolytic enzymes [10]. In the midfoot, this has disastrous consequences as the joints are interconnected. If there is widespread involvement, this can lead to collapse of the arches which may require extensive reconstructive efforts. Other forms include a central granuloma which is commonly encountered in children and affects the phalanges or metatarsals [1]. 3.2.2. Classification of articular TB Four stages of TB arthritis were proposed by Martini and Ouahes and refined by Chen et al. [5]. In stage 1 there is infection of the synovial lining with little bony erosion or localised osteoporosis. Stage 2 has marked erosions or areas of frank TB osteomyelitis, but the joint space is maintained. Stage 3 is characterised by more synovial and bony involvement with a loss of joint space. In stage 4 there is involvement of more than 1 peritalar joint surface or concomitant pyogenic arthritis with substantial disorganisation of osseous architecture [5]. 3.3. Imaging In most cases, the radiographic features of osteoarticular tuberculosis are nonspecific [2,3,10]. Radiographic features are usually noted 2 to 5 months after disease onset and only a joint effusion may be apparent in the very early stage [11,12]. The typical radiographic presentation of tuberculous arthritis is characterised by juxta-articular osteoporosis, peripheral osseous erosions, and gradual reduction of joint space, known as the Phemisters triad [11,12]. Lytic areas of destruction and marginal erosions are typically seen along the articular margins in weight-bearing articulations, such
M. Korim et al. / The Foot 24 (2014) 176–179
as the hip, knee, and ankle [12]. However, in contrast to pyogenic arthritis, there is relative preservation of the joint space in the early disease stages owing to the lack of proteolytic enzymes in the exudate. Severe osteopenia is characteristically noted, and, especially in adults, there is a lack of sclerosis or periostitis in the early stage when the disease is active. Severe joint destruction and, eventually, sclerosis and fibrous ankylosis are noted in the late stages when active infection has resolved [1,11,12]. Cross sectional imaging is more reliable at picking up early disease. MRI is good at looking at soft tissue architecture and collections. CT scan is useful to delineate the bony anatomy and delineate cortical breaks or collapse of the articular surface. It is useful to plan reconstructive procedures. It is important to note that the radiologic features lag behind the actual healing process and Dhillon and Nagi [2] recommended at least 6–7 months of multimodal therapy before repeating crosssectional imaging to reduce the rate of false positives for disease progression. 3.4. Biochemical and haematological tests Haematological and biochemical tests provide supportive evidence for ongoing sepsis (WCC, CRP and ESR) and bone activity (ALP), but do not provide a definite diagnosis. Interferon gamma release assays such as T-SPOT and QuantiFERON-TB Gold used for testing for the presence of TB, however, are limited as they do not distinguish between active and latent cases of TB as they merely assess the immune response against mycobacterium TB antigens [13]. The National Institute of Clinical Excellence (NICE) recommends that all patients with non-respiratory TB should have a chest X-ray to exclude or confirm co-existing respiratory TB [14]. 3.5. Histological diagnosis Osteoarticular TB is a paucibacilliary lesion and is therefore difficult to demonstrate the AFB on culture from the lesions. Molecular diagnostics such as line probe assays or nucleic acid amplification tests (NAAT) has also been shown to be a reliable alternative diagnostic tool compared to isolation of tubercular bacilli [13]. Biopsies can be carried out by fine needle aspiration or guided by imaging modalities such as computed tomography [15]. 3.6. Medical management Initial empirical therapy is the same as the standard regime for active respiratory TB. The ‘standard recommended regimen’ includes 6 months of isoniazid and rifampicin including supplementation with pyrazinamide and ethambutol in the first 2 months [14]. A few major side effects associated with the ‘standard recommended regimen’ include skin rashes, jaundice, confusion, visual impairment, and shock. The suspected offending agent should be stopped and the patient referred to a clinician urgently. Minor side effects include anorexia, joint pain, abnormalities in hand and foot sensation, flu syndrome, and orange urine [16]. Symptomatic management is often all that is required, but urgent referral to a physician may be required.
179
3.7. Surgical management Adequate and prolonged medical therapy is the mainstay of treatment. Surgery is reserved for biopsy to establish the diagnosis, debridement of abscesses despite medical treatment, joint resection with or without arthrodeses. Debridement of sequestrum is not required as they resolve with medical treatment. Sinus tract excision may accelerate the healing process and curettage of juxtaarticular cavities may prevent joint collapse [2]. Splintage and restricted weight bearing may be important in some cases to reduce the risk of articular surface collapse and this may be achieved in a number of ways. 4. Conclusions Foot and ankle TB is a rare diagnosis requiring a high index of suspicion to allow early initiation of medical treatment. Prompt cross sectional imaging and tissue diagnosis is mandatory before initiation of prolonged multimodal medical therapy. Delayed diagnosis could lead to potentially worse outcomes. Surgical intervention is rarely required and reserved for making a diagnosis, preserving or reconstructing affected joints. Conflict of interest There was no conflict of interest in the preparation of this manuscript. References [1] Dhillon MS, Aggarwal S, Prabhakar S, Bachhal V. Tuberculosis of the foot: an osteolytic variety. Indian J Orthop 2012;46:206–11. [2] Dhillon MS, Nagi ON. Tuberculosis of the foot and ankle. Clin Orthop Relat Res 2002;398:107–13. [3] Mittal R, Gupta V, Rastogi S. Tuberculosis of the foot. J Bone Joint Surg Br 1999;81:997–1000. [4] Spiegel DA, Singh GK, Banskota AK. Tuberculosis of the musculoskeletal system. Tech Orthop 2005;20:167–78. [5] Chen S-H, Lee C-H, Wong T, Feng H-S. Long-term retrospective analysis of surgical treatment for irretrievable tuberculosis of the ankle. Foot Ankle Int 2013;34:372–9. ´ [6] Rowinska-Zakrzewska E. Extrapulmonary tuberculosis, risk factors and incidence. Pneumonol Alergol Pol 2011;79:377–8. [7] Watts HG, Lifeso RM. Tuberculosis of bones and joints. J Bone Joint Surg Am 1996;78:288–98. [8] Dalldorf PG, Banas MP, Marquardt JD. Tuberculosis of the foot: a case report. Foot Ankle Int 1994;15:157–61. [9] Bozkurt M, Do˘gan M, Sesen H, Turanli S, Basbozkurt M. Isolated medial cuneiform tuberculosis: a case report. J Foot Ankle Surg n.d.;44:60–3. [10] Samuel S, Boopalan PRJVC, Alexander M, Ismavel R, Varghese VD, Mathai T. Tuberculosis of and around the ankle. J Foot Ankle Surg;50:466–72. [11] Choi WJ, Han SH, Joo JH, Kim BS, Lee JW. Diagnostic dilemma of tuberculosis in the foot and ankle. Foot Ankle Int 2008;29:711–5. [12] De Backer AI, Mortelé KJ, Vanhoenacker FM, Parizel PM. Imaging of extraspinal musculoskeletal tuberculosis. Eur J Radiol 2006;57:119–30. [13] Norbis L, Miotto P, Alagna R, Cirillo DM. Tuberculosis: lights and shadows in the current diagnostic landscape. New Microbiol 2013;36:111–20. [14] NICE guidelines [CG117]. Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control; 2011. [15] Perkins MD. New diagnostic tools for tuberculosis. Int J Tuberc Lung Dis 2000;4:S182–8. [16] Treatment of tuberculosis guidelines; n.d.
