TABLE IV-114 Risk Factors for Active Tuberculosis Among Persons Who Have Been Infected With Tubercle Bacilli 1 page

^rOld infection = 1.

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ГУ-115. The answer is A.(Chap. 165) The chest radiograph shows a right upper lobe infiltrate with a large cavitary lesion. In this man from an endemic area for tuberculosis, this finding should be treated as active pulmonary tuberculosis until proven otherwise. In addition, this patient's symptoms suggest a chronic illness with low-grade fevers, weight loss, and temporal wasting that would be consistent with active pulmonary tuberculosis. If a patient is suspected of having active pulmonary tuberculosis, the initial management should include documentation of disease while protecting health care workers and the population in general. This patient should be hospitalized in a negative-pressure room on airborne isolation until three expectorated sputum samples have been demonstrated to be negative. The samples should preferably be collected in the early morning because the burden of organisms is expected to be higher on a more concentrated sputum The sensitivity of a single sputum for the detection of tuberculosis in confirmed cases is only 40% to 60%. Thus, a single sputum sample is inadequate to determine infectivity and the presence of active pulmonary tuberculosis. Skin testing with a purified protein derivative of the tuberculosis mycobacterium is used to detect latent infection with tuberculosis and has no role in determining whether active disease is present. The cavitary lung lesion shown on the chest imaging could represent malignancy or a bacterial lung abscess, but because the patient is from a

high-risk area for tuberculosis, tuberculosis would be considered the most likely diagnosis until ruled out by sputum testing.

ГУ-116. The answer is A.(Chap. 165) Initial treatment of active tuberculosis associated with HIV disease does not differ from that of a non-HIV-infected person. The standard treatment regimen includes four drugs: isoniazid, rifampin, pyrazinamide, and ethambutol (RIPE). These drugs are given for a total of 2 months in combination with pyridoxine (vitamin B₆) to prevent neurotoxicity from isoniazid. After

the initial 2 months, patients continue on isoniazid and rifampin to complete a total of 6 months of therapy. These recommendations are the same as those of non-HIV-infected individuals. If the sputum culture remains positive for tuberculosis after 2 months, the total course of antimycobacterial therapy is increased from 6 to 9 months. If an individual is already on antiretroviral therapy (ART) at the time of diagnosis of tuberculosis, it may be continued, but often rifabutin is substituted for rifampin because of drug interactions between rifampin and protease inhibitors. In individuals not on ART at the time of diagnosis of tuberculosis, it is not recommended to start ART concurrently because of the risk of immune reconstitution inflammatory syndrome (IRIS) and an increased risk of medication side effects. IRIS occurs as the immune system improves with ART and causes an intense inflammatory reaction directed against the infecting organism(s). There have been fatal cases of IRIS in association with tuberculosis and initiation of ART. In addition, both ART and antituberculosis drugs have many side effects. It can be difficult for a clinician to decide which medication is the cause of the side effects and may lead unnecessarily to alterations in the antituberculosis regimen. ART should be initiated as soon as possible and preferably within 2 months. Three-drug regimens are associated with a higher relapse rate if used as a standard 6-month course of therapy and, if used, require a total of 9 months of therapy. Situations in which three-drug therapy may be used are pregnancy, intolerance to a specific drug, and in the setting of resistance. A five-drug regimen using Rifampin, isoniazide, pyrazinamide, ethambutol (RIPE) plus streptomycin is recommended as the standard retreatment regimen. Streptomycin and pyrazinamide are discontinued after 2 months if susceptibility testing is unavailable. If susceptibility testing is available, the treatment should be based on the susceptibility pattern. In no instance is it appropriate to withhold treatment in the setting of active tuberculosis to await susceptibility testing.

IV-117. The answer is B.(Chap. 165) The aim of treatment of latent tuberculosis is to prevent development of active disease, and the tuberculin skin test (purified protein derivative [PPD]) is the most common means of identifying cases of latent tuberculosis in high-risk groups. To perform a tuberculin skin test, 5 tuberculin units of PPD are placed subcutaneously in the forearm The degree of induration is determined after 48 to 72 hours. Erythema only does not count as a positive reaction to the PPD. The size of the reaction to the tuberculin skin test determines whether individuals should receive treatment for latent tuberculosis. In general, individuals in low-risk groups should not be tested. However, if tested, a reaction larger than 15 mm is required to be considered as positive. School teachers are considered low-risk individuals. Thus, the reaction of 7 mm is not a positive result, and treatment is not required. A size of 10 mm or larger is considered positive in individuals who have been infected within 2 years or those with high-risk medical conditions. The individual working in an area where tuberculosis is endemic has tested newly positive by skin testing and should be treated as a newly infected individual. High-risk medical conditions for which treatment of latent tuberculosis is recommended include diabetes mellitus, injection drug use, end-stage renal disease, rapid weight loss, and hematologic disorders. PPD reactions 5 mm or larger are considered positive for latent tuberculosis in individuals with fibrotic lesions on chest radiographs, those with close contact with an

infected person, and those with HIV or who are otherwise immunosuppressed. There are two situations in which treatment for latent tuberculosis is recommended regardless of the results on skin testing. First, infants and children who have had close contact with an actively infected person should be treated. After 2 months of therapy, a skin test should be performed. Treatment can be discontinued if the skin test result remains negative at that time. Also, individuals who are HIV positive and have had close contact with an infected person should be treated regardless of their skin test results.

IV-118. The answer is C.(Chap. 165) T-lymphocyte release of interferon-gamma in response to highly specific tuberculosis antigen stimulation is the basis for the commercially available interferon-gamma release assays (IGRAs). IGRAs are more specific than tuberculin skin testing caused by less cross-reactivity with non-mTB organisms, including Bacillus Calmette-Guerin and nontuberculous mycobacteria. The absolute sensitivity of IGRAs is not clearly known because of the difficulty in establishing a gold standard, but most studies demonstrate superior performance in detecting latent tuberculosis in low-incidence settings. They also are more user friendly because there is no administration expertise, interpretation is less subjective, and results do not require a second visit. The results are far less clear in settings of high tuberculosis or HIV burden. The tuberculin skin testing booster phenomenon, a spurious conversion caused by serial testing, does not occur with IGRAs; however, a tuberculin skin test may cause a false-positive IGRA result. In the United States, IGRA is preferred for most persons older than 5 years of age being screened for latent tuberculosis.

ГУ-119. The answer is E.(Chap. 165) Bacillus Calmette-Guerin (BCG) is derived from an attenuated strain of Mycobacterium bovis. It has been available since 1921. Many vaccines are available, but they vary in efficacy from 0% to 80% in clinical trials. The vaccine protects infants and young children from serous forms of tuberculosis, including meningitis and miliary disease. Side effects from the vaccine are rare, but BCG dissemination (BCGitis) may occur in patients with severe combined immunodeficiency or advanced HIV-induced immune suppression. BCG cross-reacts with tuberculin skin testing, but the size of the response wanes with time. BCG vaccination is currently recommended in countries with a high ТВ prevalence. It is not recommended in the United States because of the low prevalence of disease and cross-reactivity with tuberculin skin testing. Infants with unknown HIV infection status, infants of mothers with known HIV infection, and HIV-infected individuals should not receive BCG vaccination.

ГУ-120. The answer is B.(Chap. 167) The chest computed tomography shows a "tree-in-bud" pattern in the peripheral right lung and bilateral bronchiectasis. This pattern is consistent with bronchiolar inflammation and is typical of nontuberculous mycobacterial infection. Nontuberculous mycobacteria, such as Mycobacterium avium complex (MAC), may cause chronic pulmonary infections in normal hosts and those with underlying pulmonary disease immunosuppression. In normal hosts, bronchiectasis is the most common underlying condition. In immunocompetent patients without underlying disease, treatment of pulmonary infection with MAC is considered on an individual basis based on symptoms, radiographic findings, and bacteriology. Treatment should be initiated in the presence of progressive pulmonary disease or symptoms. In patients without any prior lung disease, no structural lung disease, and who do not demonstrate progressive clinical decline, M. avium pulmonary infection can be managed conservatively. Patients with underlying lung disease, such as chronic obstructive pulmonary disease, bronchiectasis, or cystic fibrosis, or those with a history of pulmonary tuberculosis should receive antibiotics. This patient has both clinical and historic reasons for antibiotic treatment. The

appropriate regimen in this case is clarithromycin (or azithromycin), ethambutol, and rifampin (or rifabutin) for 12 months after culture sterilization (typically 18 months). The combination of pyrazinamide, isoniazid, rifampin, and ethambutol is effective treatment for M. tuberculosis infection, which is not present here. Other drugs with activity against MAC include intravenous and aerosolized aminoglycosides, fluoroquinolones, and clofazimine.

ГУ-121. The answer is C.(Chap. 168) Pyrazinamide (PZA) is the first-line treatment for Mycobacterium tuberculosis. Addition of PZA for 2 months to isoniazid and rifampin allows the total duration of treatment to be shortened from 9 months to 6 months. PZA has no utility in the treatment of nontuberculous mycobacteria. Ethambutol has no serious drug interactions, but patients must be closely monitored for optic neuritis, which may manifest with decreased visual acuity, central scotoma, or difficulty seeing green (or red). All patients initiating therapy with ethambutol should have a visual and ophthalmologic examination at baseline. In the United States overall, isoniazid resistance remains uncommon. Primary isoniazid resistance is more common in patients with tuberculosis born outside the United States. Rifampin is a potent inducer of cytochrome P450 system and has numerous drug interactions. The Centers for Disease Control and Prevention has guidelines for managing antituberculosis drug interactions including rifampin. Rifabutin is a less potent inducer of hepatic cytochromes. Rifabutin is recommended for HIV-infected patients who are on antiretroviral therapy with protease inhibitors or non-nucleoside reverse transcriptase inhibitors (particularly nevirapine) in place of rifampin.

ГУ-122. The answer is E.(Chap. 169) Neurosyphilis has generally been thought to be a late complication of syphilis infection, but this is now known to be inaccurate. Within weeks after infection, the central nervous system is invaded with treponemal organisms. The vast majority of cases are asymptomatic. Abnormal protein levels within the cerebrospinal fluid (CSF) or positive CSF Venereal Disease Research Laboratory (VDRL) test can be seen in up to 40% of individuals with primary or secondary syphilis and 25% of cases of latent syphilis. In symptomatic cases, neurosyphilis can have a variety of manifestations that are typically considered in three broad categories: meningeal, meningovascular, and parenchymal syphilis. Meningeal syphilis is dominated by headache, neck stiffness, and cranial nerve abnormalities. Meningovascular syphilis has signs of meningitis but also can include a vasculitis complicated by stroke. Parenchymal syphilis does indeed represent a late manifestation of disease. Changes in personality, dementia, Argyll Robertson pupils, and paresis are typical findings.

It can be difficult to determine which patients with syphilis required a lumbar puncture to assess for central nervous system involvement of the disease. However, it is quite important because the treatment of neurosyphilis requires 14 days of treatment with intravenous penicillin. Clearly, any patient with a positive test result for syphilis with concerning neurologic symptoms should undergo a lumbar puncture. Some experts also recommend lumbar puncture in all patients with syphilis who are HIV positive. However, this is controversial with others recommending lumbar puncture only if the CD4 count is less than 350/uL. Other instances in which a lumbar puncture is recommended is in the setting of a very high titer rapid plasma reagin (RPR) or VDRL (>1:32) or failure of the RPR or VDRL to fall by a factor of 4 after appropriate treatment. Thus, all of the patients presented would be recommended to undergo a lumbar puncture.

IV-123. The answer is D.(Chap. 169) The patient's clinical examination is consistent with primary

syphilis and he should receive appropriate therapy. In primary syphilis, 25% of patients will have negative nontreponemal tests for syphilis (rapid plasma reagin or Venereal Disease Research Laboratory). A single dose of long-acting benzathine penicillin is the recommended treatment for primary, secondary, and early latent syphilis. Ceftriaxone is the treatment of choice for gonorrhea, but this lesion is not consistent with that diagnosis. Ceftriaxone given daily for 7 to 10 days is an alternative treatment for primary and secondary syphilis. Acyclovir is the drug of choice for genital herpes. Herpetic lesions are classically multiple and painful. Observation is not an option because the chancre will resolve spontaneously without treatment and the patient will remain infected and infectious. Given the appearance and clinical history, there is no indication for tissue biopsy or surgical resection.

ГУ-124. The answer is E.(Chap. 171) The patient has Weil's syndrome caused by infection with Leptospira interrogans. L. interrogans is a spirochete that is acquired through contact with an infected animal. Species that commonly transmit the organism to human include rats, dogs, cattle, and pigs. The organism is excreted in urine and can survive in water for months. For a human to become infected, susceptible individuals typically have indirect contact with infected animal urine through contaminated water sources and other wet environments. Tropical human environments, rodent infestations, and large populations of infected dogs are also important for transmission. Leptospirosis occurs only sporadically in the United States with most cases occurring in Hawaii.

Clinically, leptospirosis can take many manifestations, including subclinical infection, a self-limited febrile illness, and Weil’s disease. Leptospirosis is classically a biphasic disease. After the acute exposure, fevers last for 3 to 10 days. During this time, the patient will complain of malaise and myalgias. Conjunctival suffusion (dilated conjunctival blood vessels without drainage) is common as are pharyngeal edema, muscle tenderness, and crackles on lung examination. Weil’s disease is the most serious form of leptospirosis and occurs during the immune phase of the disease. Clinically, severe jaundice in the absence of hepatocellular injury is a striking feature of the disease. In addition, acute kidney injury, hypotension, and diffuse hemorrhage are common. The lungs are the most common site of hemorrhage, but the gastrointestinal tract, retroperitoneum, pericardium, and brain can also be affected. The diagnosis is most often made by serologic assays because culture of the organism takes several weeks. Treatment of leptospirosis is typically intravenous penicillin, ceftriaxone, or cefotaxime.

Acute alcoholic hepatitis can produce fevers and malaise, but a more marked increase in liver enzymes would be expected with the aspartate aminotransferase elevated out of proportion to alanine aminotransferase. Disseminated intravascular coagulation in the setting of an infection would demonstrate abnormalities of coagulation, which were not present here. Microscopic polyangiitis is a small to medium vessel vasculitis that could cause pulmonary hemorrhage and acute renal failure. Rarely, the liver can be affected as well. However, the urinalysis does not suggest acute glomerulonephritis because no casts or red blood cells are present. Rat-bite fever causes intermittent fevers, polyarthritis, and a nonspecific rash.

IV-125. The answer is E. (Chap. 172) Tickborne relapsing fever (TBRF) is a spirochetal infection caused by any one of several species of Borrelia. The Borrelia are small spirochetes that are transmitted to humans through the bite of an infected tick. The tick that transmits TBRF is Ornithodoros spp., which feeds on a variety of squirrels and chipmunks that live near freshwater lakes. TBRF is endemic in several areas of the western United States, southern British Columbia, the Mediterranean, Africa, and the plateau regions of Mexico and South and Central America. In the United States, TBRF is rarely reported east of Montana, Colorado, New Mexico, and Texas. The general areas where TBRF is contracted is in the forested and mountainous regions of these states, although it can be contracted in the limestone caves of central Texas. Only 13 counties in the entire United States have had 50% of all cases reported in the United States.

After an incubation period of about 7 days, an individual infected with TBRF will begin to experience fevers that can reach as high as 106.7°F (41.5°C). Symptoms that accompany the fevers include myalgias, chills, nausea, vomiting, abdominal pain, confusion, and arthralgias. The average duration of a first episode is 3 days. If the disease is not recognized and treated, the fever will recur after a period of about 7 days. The duration of fevers is typically shorter with repeated episodes but will continue to relapse about every 7 days until the disease is treated. Diagnosis of TBRF requires detection of the spirochetes in the blood during a febrile episode or serologic conversion. TBRF is typically treated with doxycycline or erythromycin for 7 to 10 days.

The other options should be on the differential diagnosis for an individual with recurrent and relapsing fevers. In addition, this list would also include yellow fever, dengue fever, malaria, rat-bite fever, and infection with echovirus 9 or Bartonella spp. Brucellosis is a bacterial infection most commonly transmitted by ingestion of contaminated milk or cheese, which this patient did not report. Colorado tick fever is a viral infection transmitted by the bite of a Dermacentor andersoni tick that is endemic in the western areas of the United States. The pattern of fever is slightly different from TBRF because the

cycle is 2 to 3 days of fever followed by 2 to 3 days of normal temperature. Leptospirosis often has two phases of fever. The first occurs during the acute infection, lasting 7 to 10 days. In some individuals, the fever recurs 3 to 10 days later during the immune phase. The typical route of infection is prolonged contact with infected rodent droppings in wet environments. Lymphocytic choriomeningitis is a viral infection that is most commonly transmitted via contact with urine or droppings from common house mice. This illness usually has two phases as well. During the first phase that occurs 8 to 13 days after exposure, an individual will experience fevers, malaise, and myalgias. In the second phase of illness, symptoms more typical of meningitis occur.

IV-126. The answer is C. (Chap. 174) About 8% of individuals affected by Lyme disease have cardiac involvement during the second stage of disease. Caused by Borrelia burgdorferi, Lyme disease is transmitted by the bite of an infected Ixodes tick. The first phase of the disease represents localized infection and is characterized by the presence of the erythema migrans rash. The second stage of the disease represents disseminated infection. The most common manifestations of this stage are new annular skin lesions, headache, fever, and migratory arthralgias. When cardiac involvement is present, the most common presentation is related to conduction abnormalities, including all categories of heart block. Diffuse cardiac involvement can occur with acute myopericarditis and left ventricular dysfunction. The cardiac involvement typically resolves within a few weeks even without treatment. Acute myocardial infarction (MI) can cause complete heart block, particularly in the event of an inferior MI. However, this patient has minimal risk factors for cardiac disease, is otherwise healthy, and has no symptoms to suggest this as a cause. Chagas disease is caused Trypanosoma cruzi, an parasite endemic to Mexico and Central and South America. Sarcoidosis is a systemic disease that pathologically demonstrates the diffuse presence of noncaseating granulomas in a variety of tissues. Conduction abnormalities, including complete heart block and ventricular tachycardia, can be the presenting symptoms of the disease. More commonly, sarcoidosis would have pulmonary manifestations. Although sarcoidosis is certainly possible in this patient, it would be a diagnosis of exclusion because his risk factors make Lyme disease more likely. Subacute bacterial endocarditis can also result in complete heart block if the endocarditis progresses to develop a valve ring abscess. The patient with subacute bacterial endocarditis would present with a more acute illness than this patient with fevers, weight loss, and most likely secondary signs of endocarditis such as Osler nodes, splinter hemorrhages, and Janeway lesions.

IV-127. The answer is A. (Chap. 173) Lyme serology tests should be done only in patients with an intermediate pretest probability of having Lyme disease. The presence of erythema migrans in both patient B and patient E is diagnostic of Lyme disease in the correct epidemiologic context. The diagnosis is entirely clinical. Patient C’s clinical course sounds more consistent with systemic lupus erythematosus, and initial laboratory evaluation should focus on this diagnosis. Patients with chronic fatigue, myalgias, and cognitive change are occasionally concerned about Lyme disease as a potential etiology for their symptoms. However, the pretest probability of Lyme is low in these patients, assuming the absence of antecedent erythema migrans, and a positive serology is unlikely to be a true positive test result. Lyme arthritis typically occurs months after the initial infection and occurs in about 60% of untreated patients. The typical attack is large joint, oligoarticular, and intermittent, lasting weeks at a time. Oligoarticular arthritis carries a broad differential diagnosis, including sarcoidosis, spondyloarthropathy, rheumatoid arthritis, psoriatic arthritis, and Lyme disease. Lyme serology is appropriate in this situation. Patients with Lyme arthritis usually have the highest IgG antibody

responses seen in the infection.

IV-128 and IV-129. The answers are D and D, respectively. (Chap. 173) This patient’s rash is a classic erythema migrans lesion and is diagnostic for Lyme disease in her geographic region. In the United States, Lyme disease is caused by infection with Borrelia burgdorferi. Partial central clearing, a bright red border, and a target center are very suggestive of this lesion. The fact that multiple lesions exist implies disseminated infection rather than a primary tick bite inoculation in which only one lesion is present. Potential complications of secondary Lyme disease in the United States include migratory arthritis, meningitis, cranial neuritis, mononeuritis multiplex, myelitis, varying degrees of atrioventricular block, and (less commonly) myopericarditis, splenomegaly, and hepatitis. Third-degree or persistent Lyme disease is associated with oligoarticular arthritis of large joints and subtle encephalopathy but not frank dementia. Borrelia garinii infection is seen only in Europe and can cause a more pronounced encephalomyelitis.

Acute Lyme disease involving the skin or joints (or both) is treated with oral doxycycline unless the patient is pregnant or younger than 9 years old. Amoxicillin and macrolides (azithromycin) are less effective therapies. Ceftriaxone is indicated for acute disease in the presence of nervous system involvement (meningitis, facial palsy, encephalopathy, radiculoneuritis) or third-degree heart block. It may also be used for treatment of patients with arthritis who do not respond to oral therapy. First-generation cephalosporins are not active against B. burgdorferi. Although the rash of erythema migrans may look like cellulitis caused by staphylococci or streptococci, there is no proven efficacy of vancomycin for Lyme disease.

IV-130. The answer is E. (Chap. 174) This clinical vignette describes an individual infected with Ehrlichia chaffeensis, the causative agent of human monocytic ehrlichiosis (HME). This rickettsial infection is transmitted through the bite of an infected deer tick and is most common in the southeast, south-central, and mid-Atlantic states. In 2008, the incidence was highest in Arkansas, Oklahoma, and Missouri. This patient is at risk given his occupation, which requires him to spend a significant amount of time outdoors. The time from incubation to symptoms of infection is about 8 days. The most prominent symptoms of HME are nonspecific and include fevers, malaise, headaches, and myalgias. Nausea, vomiting, diarrhea, cough, confusion, and rash are less common. HME can be quite severe with 62% of all individuals requiring hospitalization and a mortality rate of about 3%. In severe cases, septic shock, adult respiratory distress syndrome, and meningoencephalitis can occur. Laboratory findings are helpful in suggesting possible HME. Common findings are lymphopenia, neutropenia, thrombocytopenia, and elevations in aminotransferases. If a bone marrow biopsy is done, the marrow is hypercellular, and noncaseating granulomas can be observed. Diagnosis of HME relies on polymerase chain reaction detection of E. chaffeensis nucleic acids in peripheral blood. Morulae are seen only rarely (<10%) in the cytoplasm of monocytes on peripheral blood smears. Paired sera demonstrating a rise in antibody titers to above 1:64 over a course of about 3 weeks can also be confirmatory. Treatment of HME is oral or intravenous doxycycline that is continued for 3 to 5 days after fever has resolved.

In rare instances, systemic lupus erythematosus could present with a fulminant illness that could include pancytopenia and liver function abnormalities. However, it would be more likely to have a rash and renal involvement, which this patient did not exhibit. Antibody testing for double-stranded DNA and Smith antigens would not be helpful in this case. Because the patient had a normal lumbar puncture result, further testing of the cerebrospinal fluid is unlikely to yield the diagnosis. This testing is most

common used to diagnose viral encephalitides or meningitis such as West Nile virus and herpes simplex virus. The presence of noncaseating granulomas on bone marrow biopsy is a nondiagnostic finding. In the appropriate clinical setting, this could be suggestive of sarcoidosis. However, sarcoidosis does not present with a fulminant febrile illness over a matter of days. Moreover, although a chest radiograph may demonstrate hilar adenopathy or lung infiltrate, this, too, is a nondiagnostic finding.

Date: 2016-04-22; view: 900