ORIGINAL ARTICLE Osteoarticular tuberculosis in a general hospital during the last decade

a Rodr guez, M. L. Gu lez erri and A. Gonza G. Ruiz, J. Garc a y Parasitolog a Cl nica, Hospital Universitario `La Paz', Madrid, Spain Servicio de Microbiolog

Objective To study clinical features of skeletal tuberculosis diagnosed in our laboratory

over the last 10 years.

Methods We carried out a retrospective observational study of 26 patients with osteoar-

ticular tuberculosis recording clinical and microbiological data.

Results Pain was the main clinical presentation. The median time from the onset of symptoms to the diagnosis was 8 months. Synovial uid was the most common sample obtained. Bone disease and previous or concurrent pulmonary tuberculosis were the most important predisposing factors. The tuberculin test reaction was positive in 83.3% of the patients. The outcome was favorable in 69% of the patients. Weight-bearing joints were the most commonly involved sites. Conclusions A high degree of suspicion is still needed to avoid a delayed diagnosis that might complicate the outcome. Keywords Bone and joint tuberculosis, osteoarticular Accepted 10 October 2002

Clin Microbiol Infect 2003; 9: 919923 INTRODUCTION Osteoarticular tuberculosis (TB) represents 15% of all cases of tuberculous disease [13] and 10 18% of extra pulmonary involvement [4,5]. Signs and symptoms are frequently nonspecic [1,6] and easily misdiagnosed as brucellosis [7], aspergillar spondylitis [8], tumormetastasis [4] and juvenile rheumatoid arthritis [9]. Moreover, up to 50% of patients do not show concurrent pulmonary disease [3]. Because of this, the disease is difcult to diagnose [10]. The delay in diagnosis may range from months to years [13,6,11,12] and it may damage joints or cause spinal cord compression resulting in paralysis [10]. Therefore, it is very important to maintain a high degree of clinical suspicion, especially in Spain where the TB rate per 100 000 inhabitants is one of the highest among the developed nations (38.5 cases/100 000 inhabitants in 1999) [13]. The aim of this study was to determine the prevalence of skeletal tuberculosis, to evaluate clinical data and the time to diagnosis in cases conrmed by culture in our laboratory over the last 10 years. PATIENTS AND METHODS We carried out an observational retrospective study in a tertiary university hospital, with 1200 beds providing care for 700 000 inhabitants. A case of skeletal tuberculosis (STB) was dened as a patient with one or more osteoarticular samples (bone biopsy, articular uid, synovial biopsy, etc.) positive for Mycobacterium tuberculosis by culture. We reviewed the charts of 26 patients diagnosed with osteoarticular tuberculosis conrmed by culture from 1991 to 2000. We recorded age, gender, clinical presentation, predisposing factors, time to diagnosis, number and type of samples, yield of samples, treatment and evolution. Allsampleswereculturedinliquidmedia(Bactec 460R, Becton-Dickinson or MB-Bact/Alert 3D,

guez, Corresponding author and reprint requests: J. G. Rodr a y Parasitolog a Cl nica, Hospital Servicio de Microbiolog Universitario `La Paz', Paseo de la Castellana no. 261, 28046 Madrid, Spain Tel: 34 9 17277372 Fax: 34 9 17277372 E-mail: jgarcia@hulp.insalud.es

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920 Clinical Microbiology and Infection, Volume 9 Number 9, September 2003

Organon Teknika, Boxtel, the Netherlands) and on solid medium (Coletsos, Biomedic sl. Madrid, Spain). The cultures were incubated at 37 8C for 5 weeks in liquid media and 8 weeks on solid
Table 1 Main clinical features Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 Age (years) 4 78 72 6 70 60 74 59 52 5 5 20 25 61 2 60 61 49 29 66 65 26 75 75 73 31 Predisposing factors Pulmonary TB Close relatives with pulmonary TB Rheumatoid arthritis previous fracture Parents with AFB in sputum None Knee arthroplasty NIDD and Paget disease Knee neoplasia Kidney recipient, arthritis, pulmonary TB Positive PPD relatives Juvenile rheumatoid arthritis and pneumonia Bronhcopasm and scoliosis Husband with pulmonary TB Kidney recipient and HCV hepatitis Paratracheal adenopathy Bone TB 1 year before, AFB in sputum, silicosis and COPD Previous bone and pulmonary TB Lumbar trauma and pulmonary TB None Breast cancer with bone metastasis Pulmonary TB and silicosis None Knee degenerative arthritis and knee prosthesis Previous TB and knee prosthesis Gout, asthma and COPD HIV positive, intravenous drug abuser and disseminated TB Clinical presentation Pain and swelling Pain Pain and FD ND Pain, swelling and FD Pain Swelling and FD Pain, FD and fever Pain Pain and swelling Pain, swelling and FD Pain and fever Pain Pain and fever Swelling and FD Pain Fistula ND Pain Pain Pain Fever, pain and FD Pain, swelling and FD ND Pain Pain, swelling, fever and FD Site of infection Knee Hip Femur and hip Knee Knee Knee Knee Knee Shoulder and clavicle Ankle Knee Sacrum Knee Sacrum Knee Knee Upper arm Lumbar Lumbar Knee Lumbar Spinal discitis Knee Knee Knee Knee and sacrum Time to diagnosis 2 months >10 years >10 years ND 5 months 4 years 4 months 4 months 3 months 1 year 4 years 1 year 5 months 5 months 3 months PD PD 1 year 2 months 1 year 2 years 1 month 2 years PD 8 months PD Outcome Favorable Favorable FD ND Torpid Favorable Favorable Favorable Favorable Favorable Favorable Favorable Favorable Favorable Favorable ND Favorable Favorable Favorable Favorable Exitus Favorable Favorable ND ND Exitus

medium. The mycobacteria were identied by standard procedures using specic nucleic acid probes (Accuprobe, Gene probe Biomerieux) for M. tuberculosis complex or biochemical tests

TB, tuberculosis; FD, functional disability; AFB, acid-fast bacilli; ND, no data available; NIDD, non-insulin dependent diabetes; COPD, chronic obstructive pulmonary disease; PD, previously diagnosed.

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Ruiz et al Osteoarticular tuberculosis in the last decade 921

(the Niacin test, Niacin reagent strip remel, Lenexan, USA). RESULTS M. tuberculosis was cultured in 1233 patients. Twenty-six of them (2.1%) showed osteoarticular involvement. Twenty-ve patients came from Spain and one patient came from China. There were 16 male and 10 female patients with a male/ female ratio of 1 : 6. The mean and median age was 46 and 60 years, respectively, with a range from 2 to 75 years. The main clinical data are shown in Table 1. Radiological abnormalities were found in 21 of the 26 patients. Out of these 13 had evidence of local radiological abnormalities, ve had local and chest abnormalities and three had chest evidence of tuberculous disease without radiological ndings of osteoarticular involvement. Synovial uid was the most frequent sample received (21 samples) followed by abscess (15), bone tissue (seven) and synovial tissue (ve). The yield of these samples was as follows: bone tissue, 86% (six positives out of seven samples cultured); synovial tissue, 69% (three out of ve); abscess, 66% (10 out of 15) and synovial uid, 66% (14 out of 21). The median time to diagnosis (time from the onset of symptoms to positive culture) was 8 months with an interquartile range of 3.5 24 months. The mean time to diagnosis was 12.3 14.2 months (the mean time was calculated excluding the two outlier patients with more than 10 years of delay in diagnosis). The most important predisposing factors were: concurrent or previous pulmonary tuberculosis (ten patients); bone disease (nine patients); nontuberculous pulmonary disease (four patients); immunodeciency (ve patients) and tuberculosis in a close contact (four patients). Puried protein derivative (PPD) skin test results were recorded in 18 patients. Fifteen were positive (83.3%). Isoniazid, rifampin, pyrazinamide and/or ethambutol were the drugs most commonly used in our patients (21 out of 26). Twelve patients underwent surgery, mainly to obtain samples for culture. The outcome was recorded in 22 cases. Eighteen had a favorable outcome (dened as no relapses or functional disability). Three cases had an unfavor-

able outcome (torpid evolution or functional disability). One patient died of unrelated pulmonary causes. DISCUSSION The association between age and STB is controversial. In our study 50 % of the patients were over 60 years old. Houshian et al. found similar results in a Danish population with a mean age of 66 years [10]. However, other authors mention that patients less than 40 years old are said to constitute the group at the greatest risk for peripheral tuberculous arthritis [2]. Predisposing factors are present in other reports in about 3040% of patients [1,3,6], but some series have shown no predisposing factors [10,11]. We found evidence of previous pulmonary tuberculosis or compatible radiological ndings in 34% of the cases. Moreover, the rate of concurrent pulmonary tuberculosis was 23%, lower than other previously reported [3]. Tuberculosis is more commonly seen in immunosuppressed patients; we found ve cases (19%) that showed some concomitant condition associated with immunosuppression including diabetes mellitus (one patient), renal transplant recipient (two patients), breast cancer with bone metastases (one patient) and one AIDS patient who was also an intravenous drug abuser. This last condition has been described to be an important risk factor [11]. Pain is described as the most frequent clinical complaint [14]. In our series, 20 patients (83%) showed pain as the main clinical feature followed by functional disability and swelling. The osteoarticular areas involved are compared with other cases reviewed in the literature in Table 2. Several reports have shown the spine as the most common location [3,6,10]. However, our data suggest the knee as the most frequently involved area. This increased involvement of the knee may be owing to the vulnerability of these joints to trauma and the high prevalence of osteoarthritis. Lower extremities were the most frequent sites recorded in younger (014 years) and elderly (over 60 years) patients. Middle-aged patients, however, showed the spine to be the primary location. Although the PPD skin test remains an important diagnostic tool, several reports notice variable percentages of PPD-negative patients [3,6,9]. From

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922 Clinical Microbiology and Infection, Volume 9 Number 9, September 2003

Table 2 Comparison of involved areas (in percentage) with other reports reviewed Knee Present study (n 26) Al-Saleh et al. [1] (n 27) Garrido et al. [2] (n 52) lez-Gay et al. [3] Gonza (n 32) Houshian et al. [10] (n 95) Evanchik et al. [6] (n 11) 58% 41% 35% 15.6% 7.3% 17.3% Spinal 27% 3.7% 1.7% 50% 50% 39% Hip 8% 15% 14% 0 6.3% 4% Ankle 3.8% 7.4% 8.7% 3.1% 5.2% 8.7% Upper extremities 7.7% 23.4% 37% 6.2% 22% 21.7%

n, number of patients. One patient had tuberculosis in more than one location, spinal and knee. included. Sternoclavicular location included.

Sacroiliac location

18 patients with this test recorded, three were negative: one was an AIDS patient, the second a 2-year-old patient with a knee involvement and the third a 20-year-old male with spinal tuberculosis. Our data support the fact that a negative tuberculin test does not rule out STB. As the literature emphasizes [6,9], tissue samples (bone or synovial) yielded the best results. This fact highlights the importance of biopsy samples, which should always be available in order to reach the diagnosis. The delay in diagnosis of osteoarticular tuberculosis is very common [10]. Some researchers report an important decrease in time to diagnosis of 36 months on average [15], but it often remains misdiagnosed as an entity [6,12]. In our study, the time to the diagnosis ranged from 2 months to more than 10 years and the median time was 8 months. One third of the patients (nine) were not diagnosed until after 1 year. In addition to a low suspicion level, the lack of a rapid microbiological diagnostic method increases the time needed to conrm the clinical suspicion. Currently, the development of molecular techniques of genome amplication shorten the time required, but these techniques are focused on respiratory samples [16] and they are not standardized for extra-respiratory samples. Promising results have been reported in selected nonrespiratory samples [17] but more data are needed to conrm its usefulness as a diagnosis tool. Osteoarticular tuberculosis can be treated with medical therapy alone, surgery or both. Surgical treatment is useful in the management of spinal instability, cord or nerve compression, large abscesses, and drug-resistant mycobacteria or as

a diagnostic procedure to obtain samples [6]. The drugs currently recommended are isoniazid along with rifampin, plus pyrazinamide if the isoniazid resistance rate (IRR) is less than 4%. Ethambutol or streptomycin must be added to the therapeutic regimen if the IRR is unknown or equals 4% [18]. The time required for effective treatment is controversial; the duration of medical treatments ranges from 9 to 12 months and are longer in immunocompromized hosts [1820]. Some series have shown a favorable outcome in 89% of the cases [6]. We found similar data in 18 out of 22 patients (81.8%). Although our study involved a small number of cases, and the results have limited statistical value, it shows how skeletal tuberculosis is actually managed in our environment where the disease remains a public health issue with a low, but signicant, percentage of osteoarticular involvement (15%) [3]. According to the outcome, it is very important to have a high level of clinical suspicion, especially in patients at risk and in countries with a high prevalence of tuberculosis. REFERENCES
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