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Spinal tuberculosis in patients with human immunodeficiency virus infection: Clinical presentation, therapy and outcome
Tubercle and Lung Disease (1996) 77, 329-334 © 1996 PearsonProfessionalLtd
Spinal tuberculosis in patients with human immunodeficiency virus infection: clinical presentation, therapy and outcome E. Leibert*, N. W. Schluger*, S. Bonk *, W. N. Rom* *The Division of Pulmonary and Critical Care Medicine, ~Departments of Medicine and Pathology, New York University Medical Center, and The Bellevue Chest Service, New York, N E USA S U M M A R Y. Setting: Bellevue Hospital, a large public hospital in New York City. Objective: To discern the clinical characteristics of spinal tuberculosis (Pott's disease) in patients with the h u m a n immunodeficiency virus (HIV). Design: Review of all cases of spinal tuberculosis seen at the hospital f r o m 1988 to 1995, with comparison of HIV-positive and HIV-negative cases. C h a r t reviews for all cases were p e r f o r m e d and information regarding signs and symptoms, neurological findings, laboratory and radiographic data, medical and surgical treatment and eventual outcome were recorded. Results: We collected 26 cases of tuberculosis of the spine between July 1988 and June 1995. Seven of our 26 patients (27%) were H I V seropositive. Six of these were PPD+ on presentation. When c o m p a r e d with HIVnegative patients, those with H I V and spinal tuberculosis had similar clinical presentations; most patients had a diagnosis m a d e with percutaneous needle aspiration biopsy of clinically involved areas, and open procedures added little diagnostic information. Most were treated without surgery, and response to antituberculosis therapy was uniformly good. Conclusion: We conclude that clinical presentations of spinal tuberculosis are similar in HIV-positive and -negative patients, and good outcomes can be expected with regard to mycobacterial disease. R E S U M E. Cadre: H6pital Bellevue, un g r a n d h6pital public de New York City. Objectif: D~celer les caract~ristiques cliniques du mal de Pott (tuberculose vert~brale) chez les patients atteints du virus de l'immunod~ficience humaine (VIH). Schema: Etude comparative de t o u s l e s cas de tuberculose vert6brale vus h l'h6pital entre 1988 et 1995 en ~tudiant s~par~ment les sujets V I H positifs et V I H n~gatifs. Etude des dossiers de tousles cas et enregistrement des informations concernant les sympt6mes subjectifs et objectifs, les signes neurologiques, les donn~es radiologiques et de laboratoire, le traitement m~dical et chirurgical et ~ventuellement les r6sultats. R~sultats: Nous avons rassembl6 26 cas de tuberculose vert6brale entre juillet 1988 et juin 1995; 7 de ces 26 patients (27%) 6taient s6ropositifs p o u r le VIH; 6 d ' e n t r e eux ~taient tuberculino-positifs ~ l'admission. L ' a s p e c t clinique de la tuberculose vert~brale est similaire chez les sujets s~ron~gatifs et chez ceux atteints du VIH. Chez la p l u p a r t des patients, le diagnostic a 6t~ acquis grace h une ponction-biopsie-aspiration ~ l'aiguille des zones cliniquement impliqu6es, des interventions ouvertes n ' a j o u t a n t que peu d'informations en mati~re de diagnostic. L a p l u p a r t des cas ont 6t~ trait6s sans intervention chirurgicale et la r~ponse au traitement antituberculeux fut uniform6ment favorable. Conclusion: Nous concluons que l'aspect clinique de la tuberculose vert6brale est similaire chez les sujets V I H positifs et V I H n~gatifs, et que de bons r~sultats peuvent 6tre esp~r6s en ce qui concerne la maladie mycobact~rienne. R E S U M E N. Marco de referencia: Hospital Bellevue, un gran hospital pdblico en la ciudad de Nueva York. Objetivo: D e t e r m i n a r las caracteristicas clinicas de la tuberculosis vertebral (Mal de Pott) en los pacientes infectados con VIH. Metodo: Revisi6n de todos los casos de tuberculosis vertebral vistos en el hospital de 1985 a 1995, c o m p a r a n d o Correspondenceto: WilliamN. Rom, MD, MPH, BellevueHospital 7N24, 462 First Avenue, New York, NY 10016, USA. Paper received31 August 1995. Final version accepted27 February 1996. 329
330 Tubercleand Lung Disease los easos VIH positivos y VIH negativos. Se realiz6 una revisi6n de las fichas cllnicas de todos los casos y se registr6 la informaci6n con respecto a los signos y slntomas, hallazgos neurol6gicos, los datos radiol6gicos y de laboratorio, el tratamiento m~dico y quirdrgico y eventualmente los resultados. Resultados: De julio de 1988 a junio de 1995 reunimos 26 casos de tuberculosis vertebral. De estos 26 pacientes, 7 (27%) eran VIH positivos, de los cuales 6 eran PPD+ en el m o m e n t o de la admisi6n. Las caracterlsticas cllnicas de la tuberculosis vertebral eran similares en los pacientes VIH positivos y VIH negativos. La mayoria de los pacientes tuvieron el diagn6stico por una biopsia obtenida por aspiraci6n percutfinea con aguja de la regi6n cllnicamente comprometida ; los procedimientos quirfirgicos agregaron escasa informaci6n diagn6stica. La mayorla de los casos fueron tratados sin intervenciones quirfirgicas y la respuesta a la terapia antituberculosa fue uniformemente satisfactoria. Conclusi6n: Concluimos que las caracteristicas cllnicas de la tuberculosis vertebral son similares en los pacientes VIH positivos y VIH negativos y que se pueden esperar buenos resultados con respecto a la enfermedad micobacteriana.
INTRODUCTION
METHODS
The recent resurgence of tuberculosis in the US and elsewhere is linked to several underlying causes, but human immunodeficiency virus (HIV) infection has undoubtedly been a key co-factor in the current tuberculosis epidemic in areas such as New York City, where at least 40% of tuberculosis patients also have HIV infection. 1'2 Defects in cell-mediated immunity lead to a greater risk of active disease among patients with tuberculosis infection, 3 and HIV patients with tuberculosis may have altered presentation, natural history, and response to therapy. 4 Satisfactory treatment outcomes for tuberculosis in HIV patients depend on proper diagnosis followed by institution of proper therapy, although previous reports have stressed the difficulties inherent in these aspects of care. 5,6 Delays in diagnosis of tuberculosis have been documented in AIDS patients with tuberculosis, owing to somewhat uncommon clinical presentations in this patient population, and these delays may have adverse effects on eventual outcome] Extrapulmonary presentations of tuberculosis are particularly common in patients with HIV infection, and these presentations may further distract clinicians from the proper diagnosis, s Additionally, optimal length of treatment of tuberculosis in patients with HIV infection is still somewhat controversial, as the recent American Thoracic Society/Centers for Disease Control (ATS/CDC) statement recommends short-course therapy in many circumstances, but data from Zaire indicate a potentially high relapse rate when 6-month regimens are used. 9,1° Although spinal tuberculosis has long been recognized as an extra-pulmonary manifestation of mycobacterial disease, few studies are available concerning presentation, natural history, treatment and outcome of Pott's disease in patients with HIV infection. Shafer and colleagues included four patients with spinal tuberculosis among 199 HIV infected persons with extra-pulmonary tuberculosis, but few specific data were available for these cases. 11 In an effort to elucidate the clinical characteristics of HIV positive patients with spinal tuberculosis, we recently reviewed our experience over several years at Bellevue Hospital, a large public hospital in New York City.
We performed a retrospective review of cases of tuberculosis of the spine seen at Bellevue Hospital from July 1988 to June 1995. Criteria for inclusion were a positive acid-fast smear or culture of biopsy material from vertebral or paravertebral sites, or demonstration of granulomatous inflammation on biopsy specimens. Clinical and demographic data were recorded for each patient, and review of laboratory findings included documentation of chest and spine radiographic studies for all cases; magnetic resonance imaging (MRI) and/or myelographic findings were recorded in the patients in whom they had been performed. RESULTS Clinical features of spinal tuberculosis in patients with HIV infection Our review detected 26 patients with mycobacterial infection of the spine during the study period. Of these, seven were known to be HIV-infected, as documented by positive serological testing by the ELISA method confirmed by Western blot analysis. These seven patients form the cohort for this report.
Demographic characteristics of patients with HIV and spinal tuberculosis The demographic features of the patients with spinal tuberculosis and HIV infection are listed in Table 1. The patients were predominantly men and were likely to be members of racial and ethnic minority groups. Substance abuse and homelessness were common. There were no significant differences in the prevalence of any demographic characteristic between HIV seropositive and HIV seronegative patients, with the exception of a higher percentage of recent immigrants and a lower percentage of injecting drug users among the HIV seronegative groups.
Signs and symptoms of spinal tuberculosis in patients with HIV infection Back pain, fever, and weight loss were common among
Spinal tuberculosis in HIV patients 33 Table 1. Demographic characteristics HIV negative n=19 Age
mean range Gender males females Race African-Americau Hispanic Caucasian Asian Other Risk factors Immigrant for tuberculosis Homeless Injecting drug use Alcoholism
Table 2.
HIV positive n=7
45_+17yr(_+1 SD.) 43_+15 24-81 24-63 13 (68%) 5 (71%) 6 (32%) 2 (29%) 8 (42%) 2 (29%) 3 (16%) 3 (43%) 5 (26%) 0 (0%) 2 (12%) 2 (29%) 1 (5%) 0 (0%) 11 (58%) 1 (14%) 6 (32%) 5 (71%) 1 (5.2%) 6 (86%) 2 (11%) 3 (43%)
Signs and symptoms
Back pain Fever Weight loss Weakness Numbness Flank mass PPD+
HIV-negative
HIV-positive
19 10 11 8 7 4 15
7 5 4 2 0 1 6
(100%) (53%) (58%) (42%) (38%) (21%) (79%)
(100%) (71%) (57%) (29%) (0%) (14%) (86%)
H I V p o s i t i v e a n d H I V n e g a t i v e patients, w h i l e f o c a l f i n d i n g s w e r e less f r e q u e n t l y r e p o r t e d or d e t e c t e d ( T a b l e 2). T h e a v e r a g e d u r a t i o n o f b a c k p a i n p r i o r to
Fig. 1--Cervical lesion. Lateral cervical spine X-ray showing a healed tuberculous abscess with a stable 'swan neck' deformity.
d i a g n o s i s w a s 3 m o n t h s , w i t h a r a n g e o f 3 w e e k s to 2 years. T h e c l i n i c a l p r e s e n t a t i o n s b e t w e e n t h e t w o g r o u p s o f p a t i e n t s w e r e s i m i l a r overall. I n t e r e s t i n g l y , six o f t h e s e v e n o f the H I V s e r o p o s i t i v e p a t i e n t s w e r e c a p a b l e o f m o u n t i n g a d e l a y e d - t y p e h y p e r s e n s i t i v i t y r e s p o n s e as m a n i f e s t e d b y a p o s i t i v e t u b e r c u l i n skin test.
Clinical features of spinal tuberculosis in patients with HIV infection T a b l e 3 lists i m p o r t a n t c l i n i c a l f e a t u r e s o f spinal t u b e r culosis in p a t i e n t s w i t h H I V i n f e c t i o n . N o t a b l y , o n l y t w o p a t i e n t s h a d d e f i n i t e e v i d e n c e o f c u r r e n t or p r i o r p u l m o n a r y t u b e r c u l o s i s , as m a n i f e s t e d b y c h e s t r a d i o g r a p h i c f i n d i n g s . N e u r o l o g i c a l f i n d i n g s w e r e n o r m a l or o n l y mildly impaired in most patients; only one had a moderately s e v e r e deficit. S p i n a l d i s e a s e w a s c o n f i n e d to t h e t h o r a c i c a n d l u m b a r r e g i o n s i n all patients, a n d d i s k space involvement and the presence of a paraspinal mass were common (Figs 1 - 4 ) . E x t r a d u r a l c o m p r e s s i o n ,
Table 3. Characteristicsof HIV+ patients with spinal tuberculosis Chest Patient Age/sex CD4+ PPD Radiograph
Neurological Locationin deficit the spine
1 2 3 4 5 6 7
Mild None None None None None Moderate
34/F 63/M 24/M 59/M 26/M 44/M 48/F
236 ND 22 ND 514 ND 620
LUL = Left upper lobe. RUL = Right upper lobe.
+ + + + + +
Normal Increasedmarkings LUL infiltrate RUL cavity Normal Normal Normal
T9-T12 T8-TI0 T7-T9 L4 T6-T7 T6-T7 L3-L4 Fig. 2~-Lumbar vertebral destruction. Lateral view of destruction of body of L4 vertebra in an HIV+ patient.
332 Tubercle and Lung Disease
Fig. 3--Axial CT scan demonstrating bony destruction of lumbar vertebra (same patient as in Fig. 2). Fig. 5--Extradural compression. CT-myelogram. There is contrast in the subarachnoid space. A mass is compressing the spinal cord, displacing it posteriorly and laterally.
Fig. 4---Paraspinal mass. Thoracic spine CT showing a large paraspinal abscess with bone destruction anteriorly on the vertebral body.
easily demonstrated by computed tomography (CT) m y e l o g r a m or M R I (Figs 5 and 6), was seen in one patient.
Laboratory findings Two of the seven H1V positive patients with spinal tuberculosis had active pulmonary tuberculosis, as demonstrated by positive sputum cultures for Mycobacterium tuberculosis. These two patients had abnormal chest radiographs, as noted above. All seven patients had percutaneous needle biopsy of vertebral bodies or paraspinal masses. Of these, two were acid-fast smear positive, and three demonstrated granulomatous inflammation. All seven specimens were eventually culture positive for M. tuberculosis. Because smear and histopathology o f percutaneous biopsy specimens were negative in two of the seven patients (though as noted above, cultures from these samples were eventually positive), these patients underwent open biopsy in the operating room. Neither sample was acid-fast smear-positive or demonstrated
Fig. 6--Magnetic resonance imaging (MRI). Sagittal MRI showing destruction of the L1 and L2 vertebral bodies with paraspinal mass (abscess) compressing the thecal sac.
granulomatous inflammation. One of the two samples eventually grew M. tuberculosis.
Treatment and outcome of patients with spinal tuberculosis and HIV infection Initial therapy for all patients in the series consisted of
Spinal tuberculosisin HIV patients 333 isoniazid, rifampin, pyrazinamide, and ethambutol. All of the patients had infections with organisms susceptible to all of the 'first-line' anti-tuberculosis medications, and medical treatment consisted of 12 months of therapy. Isoniazid, rifampin, and pyrazinamide were given for the first 2 months of therapy, and isoniazid and rifampin were continued for 10 subsequent months. Surgery was recommended for three of the patients, two of whom had neurologic deficit and one of whom had angulation of the spine. The patient with angulation refused surgery and was treated with bracing. Those with neurologic deficit underwent anterior procedures consisting of transthoracic approaches with abscess drainage, vertebrectomy, and bone grafting. All patients responded to therapy. No patient without neurologic deficit who was treated medically developed angulation of the spine or neurologic impairment. All patients completed a 12-month course of therapy, although one patient died 13 months after diagnosis with cryptococcal meningitis and bacterial sepsis. The two patients who underwent surgery had improvement in neurologic function, although one walks with a cane. The patient who refused surgery to correct spinal deformity still wears a brace and has persistent pain, although with minimal functional limitation.
DISCUSSION Although changes consistent with spinal tuberculosis were described by Hippocrates in 450 BC, the eponym Pott's Disease derives from Sir Percival Pott, who in 1779 described a type of spinal deformity resulting in paraplegia as arising from 'a distemper' with erosions of vertebrae as well as systemic symptoms of cough, malaise, and an ill appearance. Tuberculosis of the spine is now an uncommon disorder in developed countries, and fewer than 1% of cases of tuberculosis reported to public health agencies are cases of Pott's disease: Omari and colleagues 12 reported 19 cases in Los Angeles over 15 years, and Janssens and De Haller reported 26 cases in Geneva over 10 years. 13 In contrast, tuberculosis of the spine has remained prevalent in developing countries. In 1992, the Medical Research Council Working Party on Tuberculosis of the Spine (MRC) 14 reported 265 cases of tuberculous spondylitis at four centers in Korea. Recently, 26 patients with tuberculosis of the spine who presented to our institution over 7 years have been described. 15 The total number of cases of tuberculosis presenting to the hospital during that time period exceeded 1500, so that spinal tuberculosis represented approximately 1.7% of the total number of tuberculosis cases. A leading factor in the recent tuberculosis epidemic has been the co-existing epidemic of HIV infection. Defects in cell-mediated immunity make reactivation or progressive primary tuberculosis extremely common in patients with latent tuberculosis infection, and extra-
pulmonary tuberculosis and unusual presentations of mycobacterial disease are much more likely in patients with underlying HIV infection. Despite this, previously reported series of patients with HIV infection and extrapulmonary tuberculosis have not provided detailed information regarding spinal disease in this population. The largest series of HIV infection and extra-pulmonary tuberculosis included only four patients with Pott's disease, 12 and the seven patients in our current report constitute the largest series in the literature. The seven HIV+ patients in our group had signs and symptoms on presentation typical for Pott's disease, with back pain in all patients. Interestingly, the development of spinal tuberculosis in our patients did not seem to be related to the degree of immunosuppression present. The range of CD4+ cell counts was wide, with several patients having counts in the normal or near normal range. Preservation of cell-mediated immunity (as reflected by delayed-type hypersensitivity reactions to tuberculin) was also noted in six of the seven patients, and only one patient in the series had a history of a prior opportunistic infection. Diagnosis was straightforward in most cases, with acid-fast organisms or characteristic histopathology present in five of the seven patients. All pea'cutaneous specimens were eventually culture positive, indicating that while open biopsy may provide a rapid diagnosis in some cases, less invasive approaches will generally suffice if physicians are willing to begin therapy empirically while awaiting culture results. While the British MRC studies 16 showed that therapy for spinal tuberculosis is effective when given as a 6month course, most physicians prefer a somewhat longer course of therapy for bone and joint tuberculosis, as recommended in the most recent ATS/CDC guidelines. Similarly, although the guidelines allow for short-course therapy in acquired immune deficiency syndrome patients, conflicting evidence exists regarding the efficacy of this approach. Because of concerns about tissue penetration and possible relapse, we chose to treat our patients for 12 months. All patients in our series have had a good outcome using this approach, and in followup there have been no relapses to date. Absolute indications for surgery in patients with spinal tuberculosis do not exist, but we have generally used the presence of neurological defects or spinal instability (as manifested by severe angulation of the spine) as reasons for operative intervention. 17 We could not test the validity of this approach per se in the current study, though it is interesting to note that the one patient who was offered surgery but refused, medical therapy achieved apparent cure, though deformity remained and the patient had persistent pain. In summary, spinal tuberculosis in patients with concomitant HIV infection has a clinical presentation and course similar to what has previously been reported in patients without obvious immunocompromise. When proper anti-tuberculosis therapy is instituted promptly, an excellent outcome can be expected.
334
Tubercle and Lung Disease
References 1. Bloom B R, Murray C J L. Tuberculosis: commentary on a reemergent killer. Science 1992; 257: 1055-1064. 2. Frieden T R, Sterling T, Pablos-Mendez A, Kilburn J O, Cauthen G M, Dooley S W. The emergence of drug-resistant tuberculosis in New York City. N Engl J Med 1993; 328: 521-526. 3. Selwyn P A, Hartel D, Lewis V A e t al. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med 1989; 320: 545-550. 4. Jones B E, Young S M M, Antoniskis D, Davidson P T, Kramer F, Barnes P F. Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiency virus infection. A m Rev Respir Dis 1993; 148: 1292-1297. 5. Theuer C P, Hopewell P C, Elias D, Schecter G F, Rutherford G W, Chaisson R E. Human immunodeficiency virus infection in tuberculosis patients. J Inf Dis 1990; 162: 8-12. 6. Small P M, Schecter G F, Goodman P C, Sande M A, Chaisson R E, Hopewell P C. Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection. N Engl J Med 1991; 324: 289-294. 7. Kramer F, Modilevsky T, Waliany A, Leedom J, Barnes P. Delayed diagnosis of tuberculosis in patients with human immunodeficiency virus infection. Am J Med 1990; 89: 4 5 1 4 5 6 . 8. Hill A R, Premkumar S, Brustein S e t al. Disseminated tuberculosis in the acquired immunodeficiency syndrome era. A m Rev Respir Dis 1991; 144: 1164-1170. 9. American Thoracic Society. Treatment of tuberculosis and
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tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994; 149: 1359-1374. Perriens J H, St Louis M E, Mukadi Y B et al. Pulmonary tuberculosis in HIV-infected patients in Zaire. A controlled trial of treatment for either 6 or 12 months, N Engl J Med 1995; 332: 779-784. Shafer R W, Kim D S, Weiss J P, Quale J M. Extrapulmonary tuberculosis in patients with human immunodeficiency virus infection. Medicine 1991; 70: 384-397. Omari B, Robertson J M, Nelson R J, Chin L C. Pott's disease. A resurgent challenge to the thoracic surgeon. Chest 1989; 95: 145-150. Janssens J P, DeHaller R. Spinal tuberculosis in a developed country. A review of 26 cases with special emphasis on abscesses and neurological complications. Clin Orthoped 1990; 257: 67-78. Medical Research Council Working Party on Tuberculosis of the Spine, Twelfth Report. Controlled trial of short-course chemotherapy in the ambulatory treatment of spinal tuberculosis. J Bone Joint Surg 1993; 75: 240-248. Rezai A R, Lee M, Cooper P R, Errico T J, Koslow M. Modern management of spinal tuberculosis. Neurosurgery 1995; 36: 87-97. Medical Research Council Working Party on Tuberculosis of the Spine, Tenth Report. A controlled trial of six-month and ninemonth regimens of chemotherapy in patients undergoing radical surgery for tuberculosis of the spine in Hong Kong. Tubercle 1986; 67: 243-259. Rezai A R, Lee M, Cooper P R. Pott's disease. In: Tuberculosis. Rom W N, Garay S M, eds, Boston: Little, Brown, 1996: 623-634.
Spinal tuberculosis in patients with human immunodeficiency virus infection: clinical presentation, therapy and outcome E. Leibert*, N. W. Schluger*, S. Bonk *, W. N. Rom* *The Division of Pulmonary and Critical Care Medicine, ~Departments of Medicine and Pathology, New York University Medical Center, and The Bellevue Chest Service, New York, N E USA S U M M A R Y. Setting: Bellevue Hospital, a large public hospital in New York City. Objective: To discern the clinical characteristics of spinal tuberculosis (Pott's disease) in patients with the h u m a n immunodeficiency virus (HIV). Design: Review of all cases of spinal tuberculosis seen at the hospital f r o m 1988 to 1995, with comparison of HIV-positive and HIV-negative cases. C h a r t reviews for all cases were p e r f o r m e d and information regarding signs and symptoms, neurological findings, laboratory and radiographic data, medical and surgical treatment and eventual outcome were recorded. Results: We collected 26 cases of tuberculosis of the spine between July 1988 and June 1995. Seven of our 26 patients (27%) were H I V seropositive. Six of these were PPD+ on presentation. When c o m p a r e d with HIVnegative patients, those with H I V and spinal tuberculosis had similar clinical presentations; most patients had a diagnosis m a d e with percutaneous needle aspiration biopsy of clinically involved areas, and open procedures added little diagnostic information. Most were treated without surgery, and response to antituberculosis therapy was uniformly good. Conclusion: We conclude that clinical presentations of spinal tuberculosis are similar in HIV-positive and -negative patients, and good outcomes can be expected with regard to mycobacterial disease. R E S U M E. Cadre: H6pital Bellevue, un g r a n d h6pital public de New York City. Objectif: D~celer les caract~ristiques cliniques du mal de Pott (tuberculose vert~brale) chez les patients atteints du virus de l'immunod~ficience humaine (VIH). Schema: Etude comparative de t o u s l e s cas de tuberculose vert6brale vus h l'h6pital entre 1988 et 1995 en ~tudiant s~par~ment les sujets V I H positifs et V I H n~gatifs. Etude des dossiers de tousles cas et enregistrement des informations concernant les sympt6mes subjectifs et objectifs, les signes neurologiques, les donn~es radiologiques et de laboratoire, le traitement m~dical et chirurgical et ~ventuellement les r6sultats. R~sultats: Nous avons rassembl6 26 cas de tuberculose vert6brale entre juillet 1988 et juin 1995; 7 de ces 26 patients (27%) 6taient s6ropositifs p o u r le VIH; 6 d ' e n t r e eux ~taient tuberculino-positifs ~ l'admission. L ' a s p e c t clinique de la tuberculose vert~brale est similaire chez les sujets s~ron~gatifs et chez ceux atteints du VIH. Chez la p l u p a r t des patients, le diagnostic a 6t~ acquis grace h une ponction-biopsie-aspiration ~ l'aiguille des zones cliniquement impliqu6es, des interventions ouvertes n ' a j o u t a n t que peu d'informations en mati~re de diagnostic. L a p l u p a r t des cas ont 6t~ trait6s sans intervention chirurgicale et la r~ponse au traitement antituberculeux fut uniform6ment favorable. Conclusion: Nous concluons que l'aspect clinique de la tuberculose vert6brale est similaire chez les sujets V I H positifs et V I H n~gatifs, et que de bons r~sultats peuvent 6tre esp~r6s en ce qui concerne la maladie mycobact~rienne. R E S U M E N. Marco de referencia: Hospital Bellevue, un gran hospital pdblico en la ciudad de Nueva York. Objetivo: D e t e r m i n a r las caracteristicas clinicas de la tuberculosis vertebral (Mal de Pott) en los pacientes infectados con VIH. Metodo: Revisi6n de todos los casos de tuberculosis vertebral vistos en el hospital de 1985 a 1995, c o m p a r a n d o Correspondenceto: WilliamN. Rom, MD, MPH, BellevueHospital 7N24, 462 First Avenue, New York, NY 10016, USA. Paper received31 August 1995. Final version accepted27 February 1996. 329
330 Tubercleand Lung Disease los easos VIH positivos y VIH negativos. Se realiz6 una revisi6n de las fichas cllnicas de todos los casos y se registr6 la informaci6n con respecto a los signos y slntomas, hallazgos neurol6gicos, los datos radiol6gicos y de laboratorio, el tratamiento m~dico y quirdrgico y eventualmente los resultados. Resultados: De julio de 1988 a junio de 1995 reunimos 26 casos de tuberculosis vertebral. De estos 26 pacientes, 7 (27%) eran VIH positivos, de los cuales 6 eran PPD+ en el m o m e n t o de la admisi6n. Las caracterlsticas cllnicas de la tuberculosis vertebral eran similares en los pacientes VIH positivos y VIH negativos. La mayoria de los pacientes tuvieron el diagn6stico por una biopsia obtenida por aspiraci6n percutfinea con aguja de la regi6n cllnicamente comprometida ; los procedimientos quirfirgicos agregaron escasa informaci6n diagn6stica. La mayorla de los casos fueron tratados sin intervenciones quirfirgicas y la respuesta a la terapia antituberculosa fue uniformemente satisfactoria. Conclusi6n: Concluimos que las caracteristicas cllnicas de la tuberculosis vertebral son similares en los pacientes VIH positivos y VIH negativos y que se pueden esperar buenos resultados con respecto a la enfermedad micobacteriana.
INTRODUCTION
METHODS
The recent resurgence of tuberculosis in the US and elsewhere is linked to several underlying causes, but human immunodeficiency virus (HIV) infection has undoubtedly been a key co-factor in the current tuberculosis epidemic in areas such as New York City, where at least 40% of tuberculosis patients also have HIV infection. 1'2 Defects in cell-mediated immunity lead to a greater risk of active disease among patients with tuberculosis infection, 3 and HIV patients with tuberculosis may have altered presentation, natural history, and response to therapy. 4 Satisfactory treatment outcomes for tuberculosis in HIV patients depend on proper diagnosis followed by institution of proper therapy, although previous reports have stressed the difficulties inherent in these aspects of care. 5,6 Delays in diagnosis of tuberculosis have been documented in AIDS patients with tuberculosis, owing to somewhat uncommon clinical presentations in this patient population, and these delays may have adverse effects on eventual outcome] Extrapulmonary presentations of tuberculosis are particularly common in patients with HIV infection, and these presentations may further distract clinicians from the proper diagnosis, s Additionally, optimal length of treatment of tuberculosis in patients with HIV infection is still somewhat controversial, as the recent American Thoracic Society/Centers for Disease Control (ATS/CDC) statement recommends short-course therapy in many circumstances, but data from Zaire indicate a potentially high relapse rate when 6-month regimens are used. 9,1° Although spinal tuberculosis has long been recognized as an extra-pulmonary manifestation of mycobacterial disease, few studies are available concerning presentation, natural history, treatment and outcome of Pott's disease in patients with HIV infection. Shafer and colleagues included four patients with spinal tuberculosis among 199 HIV infected persons with extra-pulmonary tuberculosis, but few specific data were available for these cases. 11 In an effort to elucidate the clinical characteristics of HIV positive patients with spinal tuberculosis, we recently reviewed our experience over several years at Bellevue Hospital, a large public hospital in New York City.
We performed a retrospective review of cases of tuberculosis of the spine seen at Bellevue Hospital from July 1988 to June 1995. Criteria for inclusion were a positive acid-fast smear or culture of biopsy material from vertebral or paravertebral sites, or demonstration of granulomatous inflammation on biopsy specimens. Clinical and demographic data were recorded for each patient, and review of laboratory findings included documentation of chest and spine radiographic studies for all cases; magnetic resonance imaging (MRI) and/or myelographic findings were recorded in the patients in whom they had been performed. RESULTS Clinical features of spinal tuberculosis in patients with HIV infection Our review detected 26 patients with mycobacterial infection of the spine during the study period. Of these, seven were known to be HIV-infected, as documented by positive serological testing by the ELISA method confirmed by Western blot analysis. These seven patients form the cohort for this report.
Demographic characteristics of patients with HIV and spinal tuberculosis The demographic features of the patients with spinal tuberculosis and HIV infection are listed in Table 1. The patients were predominantly men and were likely to be members of racial and ethnic minority groups. Substance abuse and homelessness were common. There were no significant differences in the prevalence of any demographic characteristic between HIV seropositive and HIV seronegative patients, with the exception of a higher percentage of recent immigrants and a lower percentage of injecting drug users among the HIV seronegative groups.
Signs and symptoms of spinal tuberculosis in patients with HIV infection Back pain, fever, and weight loss were common among
Spinal tuberculosis in HIV patients 33 Table 1. Demographic characteristics HIV negative n=19 Age
mean range Gender males females Race African-Americau Hispanic Caucasian Asian Other Risk factors Immigrant for tuberculosis Homeless Injecting drug use Alcoholism
Table 2.
HIV positive n=7
45_+17yr(_+1 SD.) 43_+15 24-81 24-63 13 (68%) 5 (71%) 6 (32%) 2 (29%) 8 (42%) 2 (29%) 3 (16%) 3 (43%) 5 (26%) 0 (0%) 2 (12%) 2 (29%) 1 (5%) 0 (0%) 11 (58%) 1 (14%) 6 (32%) 5 (71%) 1 (5.2%) 6 (86%) 2 (11%) 3 (43%)
Signs and symptoms
Back pain Fever Weight loss Weakness Numbness Flank mass PPD+
HIV-negative
HIV-positive
19 10 11 8 7 4 15
7 5 4 2 0 1 6
(100%) (53%) (58%) (42%) (38%) (21%) (79%)
(100%) (71%) (57%) (29%) (0%) (14%) (86%)
H I V p o s i t i v e a n d H I V n e g a t i v e patients, w h i l e f o c a l f i n d i n g s w e r e less f r e q u e n t l y r e p o r t e d or d e t e c t e d ( T a b l e 2). T h e a v e r a g e d u r a t i o n o f b a c k p a i n p r i o r to
Fig. 1--Cervical lesion. Lateral cervical spine X-ray showing a healed tuberculous abscess with a stable 'swan neck' deformity.
d i a g n o s i s w a s 3 m o n t h s , w i t h a r a n g e o f 3 w e e k s to 2 years. T h e c l i n i c a l p r e s e n t a t i o n s b e t w e e n t h e t w o g r o u p s o f p a t i e n t s w e r e s i m i l a r overall. I n t e r e s t i n g l y , six o f t h e s e v e n o f the H I V s e r o p o s i t i v e p a t i e n t s w e r e c a p a b l e o f m o u n t i n g a d e l a y e d - t y p e h y p e r s e n s i t i v i t y r e s p o n s e as m a n i f e s t e d b y a p o s i t i v e t u b e r c u l i n skin test.
Clinical features of spinal tuberculosis in patients with HIV infection T a b l e 3 lists i m p o r t a n t c l i n i c a l f e a t u r e s o f spinal t u b e r culosis in p a t i e n t s w i t h H I V i n f e c t i o n . N o t a b l y , o n l y t w o p a t i e n t s h a d d e f i n i t e e v i d e n c e o f c u r r e n t or p r i o r p u l m o n a r y t u b e r c u l o s i s , as m a n i f e s t e d b y c h e s t r a d i o g r a p h i c f i n d i n g s . N e u r o l o g i c a l f i n d i n g s w e r e n o r m a l or o n l y mildly impaired in most patients; only one had a moderately s e v e r e deficit. S p i n a l d i s e a s e w a s c o n f i n e d to t h e t h o r a c i c a n d l u m b a r r e g i o n s i n all patients, a n d d i s k space involvement and the presence of a paraspinal mass were common (Figs 1 - 4 ) . E x t r a d u r a l c o m p r e s s i o n ,
Table 3. Characteristicsof HIV+ patients with spinal tuberculosis Chest Patient Age/sex CD4+ PPD Radiograph
Neurological Locationin deficit the spine
1 2 3 4 5 6 7
Mild None None None None None Moderate
34/F 63/M 24/M 59/M 26/M 44/M 48/F
236 ND 22 ND 514 ND 620
LUL = Left upper lobe. RUL = Right upper lobe.
+ + + + + +
Normal Increasedmarkings LUL infiltrate RUL cavity Normal Normal Normal
T9-T12 T8-TI0 T7-T9 L4 T6-T7 T6-T7 L3-L4 Fig. 2~-Lumbar vertebral destruction. Lateral view of destruction of body of L4 vertebra in an HIV+ patient.
332 Tubercle and Lung Disease
Fig. 3--Axial CT scan demonstrating bony destruction of lumbar vertebra (same patient as in Fig. 2). Fig. 5--Extradural compression. CT-myelogram. There is contrast in the subarachnoid space. A mass is compressing the spinal cord, displacing it posteriorly and laterally.
Fig. 4---Paraspinal mass. Thoracic spine CT showing a large paraspinal abscess with bone destruction anteriorly on the vertebral body.
easily demonstrated by computed tomography (CT) m y e l o g r a m or M R I (Figs 5 and 6), was seen in one patient.
Laboratory findings Two of the seven H1V positive patients with spinal tuberculosis had active pulmonary tuberculosis, as demonstrated by positive sputum cultures for Mycobacterium tuberculosis. These two patients had abnormal chest radiographs, as noted above. All seven patients had percutaneous needle biopsy of vertebral bodies or paraspinal masses. Of these, two were acid-fast smear positive, and three demonstrated granulomatous inflammation. All seven specimens were eventually culture positive for M. tuberculosis. Because smear and histopathology o f percutaneous biopsy specimens were negative in two of the seven patients (though as noted above, cultures from these samples were eventually positive), these patients underwent open biopsy in the operating room. Neither sample was acid-fast smear-positive or demonstrated
Fig. 6--Magnetic resonance imaging (MRI). Sagittal MRI showing destruction of the L1 and L2 vertebral bodies with paraspinal mass (abscess) compressing the thecal sac.
granulomatous inflammation. One of the two samples eventually grew M. tuberculosis.
Treatment and outcome of patients with spinal tuberculosis and HIV infection Initial therapy for all patients in the series consisted of
Spinal tuberculosisin HIV patients 333 isoniazid, rifampin, pyrazinamide, and ethambutol. All of the patients had infections with organisms susceptible to all of the 'first-line' anti-tuberculosis medications, and medical treatment consisted of 12 months of therapy. Isoniazid, rifampin, and pyrazinamide were given for the first 2 months of therapy, and isoniazid and rifampin were continued for 10 subsequent months. Surgery was recommended for three of the patients, two of whom had neurologic deficit and one of whom had angulation of the spine. The patient with angulation refused surgery and was treated with bracing. Those with neurologic deficit underwent anterior procedures consisting of transthoracic approaches with abscess drainage, vertebrectomy, and bone grafting. All patients responded to therapy. No patient without neurologic deficit who was treated medically developed angulation of the spine or neurologic impairment. All patients completed a 12-month course of therapy, although one patient died 13 months after diagnosis with cryptococcal meningitis and bacterial sepsis. The two patients who underwent surgery had improvement in neurologic function, although one walks with a cane. The patient who refused surgery to correct spinal deformity still wears a brace and has persistent pain, although with minimal functional limitation.
DISCUSSION Although changes consistent with spinal tuberculosis were described by Hippocrates in 450 BC, the eponym Pott's Disease derives from Sir Percival Pott, who in 1779 described a type of spinal deformity resulting in paraplegia as arising from 'a distemper' with erosions of vertebrae as well as systemic symptoms of cough, malaise, and an ill appearance. Tuberculosis of the spine is now an uncommon disorder in developed countries, and fewer than 1% of cases of tuberculosis reported to public health agencies are cases of Pott's disease: Omari and colleagues 12 reported 19 cases in Los Angeles over 15 years, and Janssens and De Haller reported 26 cases in Geneva over 10 years. 13 In contrast, tuberculosis of the spine has remained prevalent in developing countries. In 1992, the Medical Research Council Working Party on Tuberculosis of the Spine (MRC) 14 reported 265 cases of tuberculous spondylitis at four centers in Korea. Recently, 26 patients with tuberculosis of the spine who presented to our institution over 7 years have been described. 15 The total number of cases of tuberculosis presenting to the hospital during that time period exceeded 1500, so that spinal tuberculosis represented approximately 1.7% of the total number of tuberculosis cases. A leading factor in the recent tuberculosis epidemic has been the co-existing epidemic of HIV infection. Defects in cell-mediated immunity make reactivation or progressive primary tuberculosis extremely common in patients with latent tuberculosis infection, and extra-
pulmonary tuberculosis and unusual presentations of mycobacterial disease are much more likely in patients with underlying HIV infection. Despite this, previously reported series of patients with HIV infection and extrapulmonary tuberculosis have not provided detailed information regarding spinal disease in this population. The largest series of HIV infection and extra-pulmonary tuberculosis included only four patients with Pott's disease, 12 and the seven patients in our current report constitute the largest series in the literature. The seven HIV+ patients in our group had signs and symptoms on presentation typical for Pott's disease, with back pain in all patients. Interestingly, the development of spinal tuberculosis in our patients did not seem to be related to the degree of immunosuppression present. The range of CD4+ cell counts was wide, with several patients having counts in the normal or near normal range. Preservation of cell-mediated immunity (as reflected by delayed-type hypersensitivity reactions to tuberculin) was also noted in six of the seven patients, and only one patient in the series had a history of a prior opportunistic infection. Diagnosis was straightforward in most cases, with acid-fast organisms or characteristic histopathology present in five of the seven patients. All pea'cutaneous specimens were eventually culture positive, indicating that while open biopsy may provide a rapid diagnosis in some cases, less invasive approaches will generally suffice if physicians are willing to begin therapy empirically while awaiting culture results. While the British MRC studies 16 showed that therapy for spinal tuberculosis is effective when given as a 6month course, most physicians prefer a somewhat longer course of therapy for bone and joint tuberculosis, as recommended in the most recent ATS/CDC guidelines. Similarly, although the guidelines allow for short-course therapy in acquired immune deficiency syndrome patients, conflicting evidence exists regarding the efficacy of this approach. Because of concerns about tissue penetration and possible relapse, we chose to treat our patients for 12 months. All patients in our series have had a good outcome using this approach, and in followup there have been no relapses to date. Absolute indications for surgery in patients with spinal tuberculosis do not exist, but we have generally used the presence of neurological defects or spinal instability (as manifested by severe angulation of the spine) as reasons for operative intervention. 17 We could not test the validity of this approach per se in the current study, though it is interesting to note that the one patient who was offered surgery but refused, medical therapy achieved apparent cure, though deformity remained and the patient had persistent pain. In summary, spinal tuberculosis in patients with concomitant HIV infection has a clinical presentation and course similar to what has previously been reported in patients without obvious immunocompromise. When proper anti-tuberculosis therapy is instituted promptly, an excellent outcome can be expected.
334
Tubercle and Lung Disease
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