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Difficulties in Diagnosing Extrapulmonary Tuberculosis in Older Patients

Issue Number: Volume 18 - Issue 11 - November 2010 Benjamin H. Han, MD, MPH Matthew L. Russell, MD, MSc
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a highly infectious airborne disease that is classified based on disease symptoms and site of infection. When TB affects the lungs, which is the most common presentation, it is called pulmonary TB. When other parts of the body are infected, this is referred to as extrapulmonary TB. Some common sites of extrapulmonary infection include the lymph nodes, genitourinary tract, peritoneum, skin, pericardium, and meninges. We report a case of TB meningitis in an 89-year-old woman that proved difficult to diagnose, as is typical in elderly individuals. We also discuss the incidence and diagnosis of extrapulmonary TB infections in older patients and highlight the importance of early diagnosis in this population, as these patients tend to experience delays in diagnosis and, subsequently, increased morbidity and mortality, as indicated by autopsy studies. Case Presentation An 89-year-old woman, originally from Haiti, was admitted to the geriatrics service of an inner-city teaching hospital for a 1-week history of diffuse abdominal pain, nausea, vomiting, and fever. She had presented to the emergency department 2 days earlier with the same symptoms, but her workup was unrevealing and she was discharged to home with a recommendation to take acetaminophen to reduce her pain and fever. Upon being admitted to the geriatrics service for persistent symptoms, a review of systems was positive for mild chronic headache and neck aches, but no cough, shortness of breath, neck stiffness, chest pain, or changes in cognition were evident. The patient s medical history included chronic headaches and neck pain for 5 years, cholelithiasis, gastroesophageal reflux disease, diverticulosis, degenerative joint disease, and uterovaginal prolapse. Her regular medications included oxybutynin, omeprazole, and acetaminophen. The patient had moved to the United States from Haiti in 2005 to be with her family, and her last visit to Haiti was over 1 year before her current presentation. The patient s vital signs on admission revealed a temperature of 37.2°C, pulse of 95 beats per minute, blood pressure of 146/79 mm Hg, and respiratory rate of 18 breaths per minute. The physical examination was notable for a diffusely tender abdomen. Cardiac, pulmonary, and neurological examinations were normal, and the patient s family reported no changes in mental status or cognition. Abnormal laboratory findings were restricted to a serum sodium concentration of 130 mEq/L (normal, 136-142 mEq/L) and a serum alkaline phosphatase of 170 U/L (normal, 30-120 U/L). A chest radiograph revealed small bilateral pleural effusions, but was otherwise clear. During hospitalization, the patient had persistent abdominal pain, nausea, vomiting, temperature spikes to 39.4°C, headache, and neck pain. Based on the patient s history and abdominal symptoms, the initial workup focused on an acute abdominal process. Once this was ruled out by multiple imaging studies, other causes of her fever were investigated. Blood and urine cultures and tests for various pathogens were negative, including influenza, human immunodeficiency virus, syphilis, Legionella, and malaria. A transthoracic echocardiogram was negative for valvular vegetations and a computed tomography scan of the brain showed only chronic small-vessel changes. Eventually, a tuberculin skin test and a lumbar puncture were performed. The patient s cerebrospinal fluid (CSF) revealed a protein count of 291 mg/dL (normal, 15-45 mg/dL), glucose of 11 mg/dL (normal, 40-70 mg/dL), and a white blood cell count of 216/µL (normal, <250/µL), with 17% neutrophils and 81% lymphocytes. The patient s tuberculin skin test revealed a 16-mm induration. By report, the patient had no known history of TB, and it was unclear whether she had ever received the Bacille Calmette-Guérin (BCG) vaccine. Magnetic resonance imaging (MRI) of the brain demonstrated nodular leptomeningeal enhancement along the cerebellum at the midline of the vermis (Figure). Based on the CSF and MRI findings, a presumptive diagnosis of TB meningitis was made, and the patient was immediately started on the following daily medications: isoniazid, 300 mg; levofloxacin, 750 mg; pyrazinamide, 1500 mg; rifampin, 600 mg; and dexamethasone, 12 mg. Levofloxacin was chosen instead of ethambutol because of its better CSF penetration, better side-effect profile, and a lower likelihood of the patient s TB being resistant to levofloxacin based on the pulmonary consult recommendations, although the pharmacologic literature on the best drug regimen to overcome drug resistance in TB meningitis is conflicting. The patient s fever resolved and she experienced significant clinical improvement with treatment. The diagnosis of TB meningitis was later confirmed with TB polymerase chain reaction (PCR) testing of the CSF. The patient was discharged from the hospital 11 days after admission. She continued treatment as an outpatient, receiving 4 months of dexamethasone, including taper; 2 months of levofloxacin and pyrazinamide; and 9 months of isoniazid and rifampin. Her symptoms continued to improve with therapy, and her hyponatremia was corrected within 3 months after hospital discharge. Discussion Extrapulmonary TB is a significant public health problem that can present a diagnostic dilemma in older patients, as our

malaise. . individuals 65 years and older accounted for 2500 (10%) of all TB cases in 2008. which may be followed by focal neurological findings. Infarction appears to be most common among patients with longer duration of disease. our differential diagnosis was broad. vomiting. Symptoms and Diagnosis of TB in the Elderly Many TB cases may go unrecognized in the elderly because the disease can present atypically and subtly in this population. there are no clear clinical characterizations in the literature of how various types of TB.1 With a case rate of 6. Typically. identifying lymphocytic pleocytosis. including TB meningitis. may manifest in this population. low-grade fever.000. causing this population to experience additional morbidity and mortality. fever. TB meningitis should have been included in our patient s differential diagnosis.8 These differences. extrapulmonary TB made up 20% of total TB cases in 2008. it is clear that the geriatrics population makes up a large proportion of TB cases. We reached the diagnosis only after she presented to the hospital a second time and an extensive workup for fever of unknown origin was undertaken. and. extrapulmonary cases as a proportion of total TB cases have actually increased. An example of an atypical presentation includes subtle cognitive decline that may be confused with dementia or rapid progression to clinical deterioration. 5. 20% develop a focal neurological deficit and 22% to 56% have autopsy evidence of cerebral infarction.patient s case demonstrates. According to the CDC. Instead. elevated protein. the incidence of active TB has been noted to be two to three times higher in LTC residents. patients with TB meningitis initially present with headache.3% of TB cases among those age 65 years or older between 1985 and 1988 in the United States were diagnosed at autopsy. Classic TB symptoms often are not present. decreased appetite. Of patients with TB meningitis. of which 47. This trend has been observed in the United States and other developed countries. seizures. TB Prevalence In the Elderly According to Centers for Disease Control and Prevention (CDC). meningismus. According to data from the CDC s National Tuberculosis Surveillance System. many symptoms in older patients with active TB may be confused with a variety of clinical manifestations from other chronic diseases and comorbid conditions.4 per 100. According to previous CDC surveys. At the time.4% of extrapulmonary TB cases were meningeal. and increased intracranial pressure. and consistent neuroimaging. and glucose of less than 45 mg/dL in the CSF. Cerebral edema is another potential complication that may lead to altered consciousness. Extrapulmonary TB has also been noted to increase in frequency with advancing age and presents an even greater diagnostic difficulty because of the nature of the organ sites involved and less familiarity with this disease among healthcare providers. as was the case with our patient. and cognitive changes. while most cases of TB in the elderly arise in community-dwelling patients.9 Older patients may also present with unexplained dementia or delirium without fever or nuchal rigidity.299 total TB cases from 1993 to 2006. Using PCR for detecting M. It has also been noted that there may be substantial differences in how elderly patients with pulmonary TB present compared with their younger counterparts. A study by Rieder and colleagues found that 60. Subsequent arachnoiditis can lead to cranial nerve palsies and hydrocephalus. which commonly show basal meningeal enhancement. it appears that antitubercular agents and steroids are relatively ineffective in preventing the progression of cerebrovascular complications once they have begun. stupor or coma. Although TB often manifests differently in the elderly. Elderly residents in long-term care (LTC) facilities are at particularly high risk for both acquisition of new TB infection and reactivation of latent TB. the true scope of TB in the geriatrics population may not be known. Early identification of TB meningitis is imperative because cerebral infarction is a common complication of this disease. Based on the literature review of incidence rates and the subtlety of presentation in elderly patients. may result in a delayed diagnosis in the elderly. hydrocephalus. patients may report vague or unspecified problems such as fatigue.293 (19%) were extrapulmonary. which can be attributed to physiologic changes of aging. or infarctions in the supratentorial brain parenchyma and brain stem. The National Tuberculosis Surveillance System at the CDC has shown that there were 253. causing inflammation of the meninges. While the pathophysiology of how TB meningitis causes cerebral vessel changes is not clear. and even in hindsight it is difficult to identify which factors most strongly suggested the patient s eventual diagnosis of TB meningitis. as many cases are only found at autopsy. Our patient presented with what appeared to be an abdominal process superimposed on her chronic problem of headaches and neck pains. tuberculosis DNA in CSF has a specificity of 98%. making it difficult to diagnose. While the incidence of extrapulmonary and pulmonary TB has 5 decreased. confusion. emphasizing the importance of early identification and treatment. Moreover. or personality changes. with the majority (61%) occurring in individuals who were born in the United States. confirming the diagnosis is much more difficult because more invasive procedures are needed. Diagnosing TB meningitis typically requires a lumbar puncture. TB meningitis results from the rupture of a subependymal tubercle into the subarachnoid space. however. which was the highest case rate observed for any age group. weakness. if untreated. thus.

the geriatric provider needs to pay particular attention to the subtle and atypical ways this disease can present in the aging population. clinicians should include extrapulmonary TB in the differential diagnosis of patients presenting with nonspecific symptoms. Geriatric clients are difficult to interview by how they perceive or be able to describe their condition that s why I think diagnostic tests should be maximized to be able to arrive to a correct diagnosis as soon as possible. especially older individuals. many complications arise. with geriatric clients.REACTION With the proportion of extrapulmonary TB cases growing. This results to increased morbidity and mortality rate of older clients with extrapulmonary TB. thus. it should still be considered even as to how little the manifestations are. such as TB meningitis. Extrapulmonary TB is rare which tends doctors to disregard it in their differential diagnosis. As rare as a disease could occur. In many cases. especially among the elderly. there are no clear characterizations in the literature of how older patients with the disease may present differently from their younger counterparts as stated and described in the journal. . Moreover. So that certain diagnostic tests could be ordered earlier.

Clinical Instructor . Jeremy Astilla.N.Remedios Trinidad Romualdez Medical Foundation Tacloban City College of Nursing Journal On Gerontology Submitted by: Jennylyn D. Isanan BSN III B Group 9 Submitted to: Mr. R.