CLINICAL ANALYSIS OF OSTEOARTICULAR NONTUBERCULOUS MYCOBACTERIAL INFECTION.

OBJECTIVE: The incidence rate of nontuberculous mycobacterial (NTM) infection has been increasing globally in recent years. However, reports of osteoarticular NTM infection are relatively rare. We report the characteristic clinical features of patients with osteoarticular NTM infection. PATIENTS AND METHODS: We examined 14 patients with osteoarticular NTM infection (mean age, 68 years) were treated in our hospital in the 20 years between 1995 and 2015. RESULTS: The rate of osteoarticular NTM infection in whole osteoarticular infection during the same period in our hospital was 2.7%. The NTM species. isolated from the 14 patients included Mycobacterium avium (n = 7), M. intracellulare (n = 5), M. fortuitum (n = 1), and M. kansasii (n = 1). Twelve patients had spinal involvements, and their levels were categorized as thoracic (n = 3), lumbar (n = 4), thoracolumbar (n = 1), and cervicothoracic (n = 4), with an average number of affected vertebra of 4.4. Nine patients had pulmonary lesions, including fibrocavitary (n = 5) and nodular/ bronchiectatic types (n = 4). Nine patients had lesions in sites other than the spinal and pulmonary regions, including the skin (n = 6), rib (n = 2), ilium (n = 2), humerus (n = 2), ulna (n = 1), wrist (n = 1), knee joint (n = 1), femur (n = 2), tibia (n = 1), toe (n = 1), and kidney (n = 1). In the initial examination, 11 patients were misdiagnosed, which delayed the final diagnosis in 7 patients. Six patients received chemotherapy with rifampicin, ethambutol, and clarithromycin, and 8 patients received other macrolide-based therapy. Five patients underwent surgical treatments in former hospitals, and 8 patients underwent surgical treatments (including salvage surgeries) in our hospital. With regard to outcome, 9 patients achieved healing, 2 patients with relapse were healed after retreatment, 1 patient was undergoing treatment, 1 patient had interrupted treatment, and 1 patient died during the treatment period. DISCUSSION: Osteoarticular NTM infection presented widely spread lesions in the spine and other various locations, mostly developed as a part of disseminated infection. Most patients were aged or immunosuppressed, but some patients were healthy individuals with no relevant medical history. Thus, if a patient is diagnosed with disseminated NTM infection, examination for possible lesions in other sites, including the bone and joint, should be performed. Cutaneous lesions, including subcutaneous abscess, were also characteristic. It is worth mentioning that such lesions can develop even under chemotherapy. Given the increasing trend in the overall incidence of NTM infection, awareness that NTM is a causative organism of osteoarticular infection is important.

[HISTOLOGICAL ANALYSIS OF BONE DESTRUCTION IN SPINAL TUBERCULOSIS].

PURPOSE: To investigate the mechanism of bone destruction in spinal tuberculosis (TB) by immunohistochemical analysis of the pathway that includes receptor activator of NF-κB (RANK), receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and osteocalcin (OCN) in affected tissues. MATERIALS AND METHODS: TB bone specimens were obtained from 30 surgically treated spinal TB patients (13 males and 17 females; average age, 67 years). Normal bone specimens were also obtained from 30 osteoarthritis patients (12 males and 18 females; average age, 70 years) who had undergone knee arthroplasty, wherein a piece of the non-weight-bearing part of the femur was obtained as a part of the resected bone for surgery. The two groups of specimens were examined for the expression of RANK, RANKL, OPG, and OCN by immunohistochemistry. RESULTS: Spinal TB specimens were significantly infiltrated by inflammatory cells, and bone resorption by multinucleated osteoclasts was observed. RANKL was predominantly expressed in lymphocytes and osteoblasts, whereas RANK was expressed in mononucleated osteoclast precursors among the inflammatory cells. In contrast, there was no infiltration of the inflammatory cells, and the expression of RANKL/RANK was poor in the control specimens. OCN, a bone formation marker, was expressed in the osteoblasts and in part of the bone matrix in normal tissues; however, it was poorly expressed in the tissues of the spinal TB patients. OPG, a neutralizer of the RANK-RANKL pathway, was expressed in the osteoblasts and stromal cells, and there was no significant difference in the expression between the two groups. DISCUSSION: In the tissues from spinal TB patients, the RANK-RANKL pathway was strongly activated, whereas the expression of its neutralizer OPG was not sufficiently induced. In addition, the bone formation marker OCN was poorly expressed, indicating a paucity of reactive bone formation. These findings are consistent with bone-resorption-predominant destruction, which is commonly observed in osteoarticular TB. Activation of the RANK-RANKL pathway has been considered to be caused by cytokines such as tumor necrosis factor-α and interleukin-6, which also play important roles in the immune response against TB. In severe pulmonary TB, an intense and prolonged immune reaction sometimes leads to tissue destruction and the formation of cavity lesions. Therefore, such an immune reaction against spinal TB may also cause activation of the RANK-RANKL pathway, thereby leading to bone destruction.

[Evaluation using QFT-2G/TBGL/LAM in the patients with osteoarticular tuberculosis of post-treatment period].

PURPOSE: To evaluate results of QFT-2G/TBGL/ LAM in patients who had been completed the antituberculosis treatment for osteoarticular tuberculosis with various periods after the completion of the treatment, MATERIALS AND METHODS: Fifty-five patients who had been completed the antituberculosis treatment for osteoarticular tuberculosis at least one year after the completion of treatment were evaluated using QFT-2G/TBGL/LAM tests. Forty patients with spinal tuberculosis and 15 patients with articular tuberculosis were included. The patients with the period after the completion of the treatment less than 4 years were classifled as short-term group (33 patients) and those with the period not less than 4 years were classified as mid-long-term group (22 patients). The results of the tests were compared between the two groups. RESULTS: The result of QFT-2G test was positive in 60.6% of the patients in short-term group while 45.5% in mid-long-term group (p=0.12). On the other hand, the result of TBGL test was positive in 75.8% of the patients in short-term group whereas 22.7% in mid-long-term group (p=0.0001) and the result of LAM test was positive in 90.9% of the patients in short-term group whereas 63.6% in mid-long-term group (p= 0.01), both of these tests showed significantly low,er positive rate in mid-long-term group. There was no significant difference in the comparisons between patient groups writh/without pulmonary tuberculosis as well as with/without surgical treatment. CONCLUSION: The patients with a history of osteoarticular tuberculosis tend to show positive results of QFT-2-G test for a prolonged period, whereas significantly less positive results of TBGL/LAM tests in mid-long-term.

The Contribution of Deleterious Rare Alleles in ENPP1 and Osteomalacia Causative Genes to Atypical Femoral Fracture.

CONTEXT: Atypical femoral fractures (AFFs) are very rare atraumatic or mild trauma fractures in the subtrochanteric region or femoral shaft. Some unique genetic variants in Asian populations might confer susceptibility to AFF, since the incidence of AFFs is higher in Asian populations. OBJECTIVE: Because rare variants have been found to be causative in some diseases and the roles of osteomalacia causative genes have not been reported, we investigated rare variants in genes causing abnormal mineralization. METHODS: Exome sequencing was performed to detect variants in gene coding and boundary regions, and the frequencies of deleterious rare alleles were compared between Japanese patients with AFF (n = 42) and controls of the 4.7KJPN panel of Tohoku Medical Megabank by whole genome sequencing (n = 4773). RESULTS: The frequency of the deleterious rare allele of ENPP1 was significantly increased in AFF (P = .0012, corrected P [Pc] = .0155, OR 4.73, 95% CI 2.15-10.40). In multigene panel analysis, the frequencies of deleterious rare alleles of candidate genes were increased in AFF (P = .0025, OR 2.72, 95% CI 1.49-4.93). Principal component analysis of bone metabolism markers identified a subgroup of patients with AFF with higher frequencies of deleterious rare alleles in ENPP1 (P = 4.69 × 10-5, Pc = .0006, OR 8.47, 95% CI 3.76-19.09) and the candidate genes (P = 1.08 × 10-5, OR 5.21, 95% CI 2.76-9.86). CONCLUSION: AFF is associated with genes including ENPP1 that cause abnormal mineralization, suggesting that osteomalacia is an underlying condition predisposing to AFF and that higher incident rates of AFFs in Asian populations might be explained by the genetic risk factors including ENPP1.

A case of acute and severe thrombocytopenia due to readministration of rifampicin.

A 49-year-old-woman was diagnosed with tuberculosis of the left humerus. She had received treatment, including rifampicin, for tuberculosis 17 years previously. Treatment was begun with isoniazid, rifampicin, ethambutol, and pyrazinamide, but these were discontinued because of mild neutropenia and thrombocytopenia 2 weeks posttreatment. Rifampicin and ethambutol were readministered after a 4-day interruption; however, generalized purpura appeared several hours later. By the next day, her platelet count was reduced from 160 × 10(3) to 3 × 10(3)/µl. The patient improved rapidly after platelet transfusion and steroid treatment. Readministration of drugs other than rifampicin did not induce thrombocytopenia; therefore, thrombocytopenia was likely due to rifampicin.

[Osteoarticular tuberculosis].

As the incidence of tuberculosis in Japan decreases, osteoarticular tuberculosis becomes relatively rare. Therefore, it is often overlooked or misdiagnosed that leads to cryptic aggravation of the disease. On the other hand, because of population aging in Japan, degenerative conditions such as compression vertebral fracture or osteoarthritis should be considered as differential diagnoses of osteoarticular tuberculosis. In addition, we should beware of extra-pulmonary tuberculosis in the patients who undergo biological agent therapy for rheumatoid arthritis that has been advanced drastically in recent years. Surgical treatment for osteoarticular tuberculosis is still an essential part of its treatment in order to achieve early rehabilitation and rapid healing of the lesion.

Arthroscopic capsular release for painful throwing shoulder with posterior capsular tightness.

Posterior capsular tightness with glenohumeral internal rotation deficit is usually considered to be an acquired condition of the throwing shoulder and is usually treated conservatively. However, because posterior capsular tightness is sometimes irreversible, we have performed arthroscopic capsular release for painful throwing shoulder with posterior capsular tightness. The true loss of internal rotation and posterior stiffness was confirmed by examination with the patient under anesthesia, and contracture of the posterior capsule and the posterior band of the inferior glenohumeral ligamant was observed arthroscopically. Because an extensive adhesion between the capsule and the fascia of the external rotators was noted, a capsular release was performed from 6 o'clock to 11 o'clock (in the right shoulder) to completely expose the muscle belly of the external rotators. Of the first 16 consecutive patients, 4 had no concomitant lesions and underwent posterior capsular release alone. With a minimum of 2 years' follow-up, it was ascertained that the throwing pain completely disappeared in 14 patients and improved in 2. In all, 11 patients returned to their preinjury performance level, and 5 returned to a lower level of function. In the 4 patients who had no concomitant lesions, throwing pain completely disappeared, and all were able to return to their preinjury performance level.

Recurrent anterior shoulder dislocation caused by a midsubstance complete capsular tear.

BACKGROUND: A midsubstance complete capsular tear is one of the well-known causes of anterior glenohumeral instability. However, its prevalence and clinical picture have not been well elucidated. The purpose of this study was to examine the prevalence of isolated complete capsular tears and to assess the clinical features as well as the results of surgical treatment of recurrent anterior glenohumeral instability caused by such tears. METHODS: Three hundred and three shoulders underwent surgery to treat recurrent anterior glenohumeral instability at our institution during a five-year period. Twelve (4.0%) of these shoulders had an isolated complete capsular tear as the main pathological condition. Those twelve patients (nine male and three female) were the subjects of the present study. The average age at the time of the operation was twenty-five years. Patient age; the cause of the initial dislocation; the position of the arm at the initial dislocation; and the findings of the preoperative physical examination, of computed tomographic arthrography, and at surgery were assessed. Eleven patients underwent arthroscopic capsular repair, and one was treated with an open capsular repair. RESULTS: The twelve patients either did not have a Hill-Sachs lesion or had a chondral indentation-type of Hill-Sachs lesion. When assessed with arthrography, the Hill-Sachs lesions were small compared with those in shoulders with an isolated Bankart lesion and, interestingly, they were quite similar in size to those seen with humeral avulsion of the inferior glenohumeral ligament. The average Rowe score for the twelve patients improved from 30.4 points preoperatively to 90.4 points at an average of thirty-one months postoperatively. CONCLUSIONS: The prevalence of isolated complete capsular tears causing recurrent glenohumeral instability was 4.0% (twelve of 303). These tears were associated with either a small or no Hill-Sachs lesion. We believe that a complete capsular tear should be recognized as one of the essential lesions causing recurrent anterior shoulder dislocation. Arthroscopic examination and repair can provide effective treatment.

Postoperative deep surgical-site infection after instrumented spinal surgery: a multicenter study.

A retrospective survey revealed 37 cases (1.1%) of deep surgical-site infection (SSI) among 3,462 instrumented spinal surgeries between 2004 and 2008. Excluding 8 patients who were unclassifiable, we categorized 29 patients into 3 groups of similar backgrounds-thoracolumbar degenerative disease (the DEG group; n = 15), osteoporotic vertebral collapse (the OVC group; n = 10), and cervical disorders (the cervical group; n = 4)-and investigated the key to implant salvage. Final respective implant retention rates for the groups were 40, 0, and 100%, with the OVC group having the worst rate (p < 0.01). In the DEG group with early infection, those whose implants were retained had lower body temperatures, lower white blood cell counts, and a lower rate of discharge at the time of SSI diagnosis (p < 0.05). Implant retention may be affected by initial spinal pathology. In the DEG group, debridement before drainage may be advantageous to implant salvage.

Tuberculous spondylitis in elderly Japanese patients.

BACKGROUND: Although the number of patients with tuberculous spondylitis in Japan is increasing slowly, the proportion of the elderly among these patients is increasing more quickly. The purpose of this study was to describe the clinical features and diagnostic imaging findings in elderly tuberculous spondylitis patients in order to enhance diagnosis of the condition in the elderly population. METHODS: We conducted a retrospective review of 23 patients over 70 years of age previously diagnosed with tuberculous spondylitis. Clinical signs and symptoms, including local pain, fever, and neurological deficits, were analyzed. Routine laboratory tests, including the erythrocyte sedimentation rate, the white blood cell count, and the C-reactive protein level were also reviewed. The results of plain X-rays and magnetic resonance imaging were studied. RESULTS: Patients' signs and symptoms were as follows: local pain in 19 patients (83%); fever in 7 patients (30%) and no fever in 16 patients (70%); and neurological deficits in 13 patients (57%). C-Reactive protein was less than 1.0 mg/dl in 6 patients (26%). Radiography revealed several changes in the affected vertebrae; 3 patients had atypical changes involving only a single vertebra. CONCLUSIONS: It is difficult to diagnose tuberculous spondylitis in the elderly because there are atypical symptoms, a scarcity of inflammatory changes, and degenerative changes normally seen in the elderly may mask the radiographic changes due to tuberculous spondylitis. Tuberculous spondylitis should be considered a possibility in the differential diagnosis of back pain in the elderly, especially in countries with a significant history of tuberculosis in the population.

Spontaneous divergent elbow dislocation after Sauve-Kapandji procedure.

This is a report on an unusual complication of the Sauve-Kapandji procedure in patients with rheumatoid arthritis. Two women with rheumatoid arthritis who previously had an ipsilateral Sauve-Kapandji procedure experienced spontaneous transverse divergent elbow dislocations without evident trauma. Their radiographs showed medial dislocation of the proximal ulna, which was separated from the radial head. The radial head and distal end of the ulnar shaft showed remarkable instability by a pronation and supination motion without the radial and ulnar shafts being separated from each other. Stress radiographic examination showed significant loosening of all ligaments except the medial collateral ligament around the elbow and did not show disruption of the interosseous membrane. A unique chronic twist radioulnar dissociation which consists of gross instability of the radial head and the distal ulna without disruption of the interosseous membrane was considered to cause instability of the humeroulnar joint, which results in medial dislocation of the proximal ulna. This report suggests that there is a direct cause and effect relationship between the residual distal ulnar instability and the development of transverse divergent dislocation of the elbow in patients with rheumatoid arthritis after the Sauve-Kapandji procedure.