Extrapulmonary Tuberculosis: An Overview

MARJORIE P. GOLDEN, M.D., Yale University School of Medicine and Hospital of Saint Raphael, New Haven, Connecticut
HOLENARASIPUR R. VIKRAM, M.D., Mayo Clinic, Scottsdale, Arizona

In the 1980s, after a steady decline during preceding decades, there was a resurgence in the rate
of tuberculosis in the United States that coincided with the acquired immunodeficiency syn-
drome epidemic. Disease patterns since have changed, with a higher incidence of disseminated
and extrapulmonary disease now found. Extrapulmonary sites of infection commonly include
lymph nodes, pleura, and osteoarticular areas, although any organ can be involved. The diag-
nosis of extrapulmonary tuberculosis can be elusive, necessitating a high index of suspicion.
Physicians should obtain a thorough history focusing on risk behaviors for human immunodefi-
ciency virus (HIV) infection and tuberculosis. Antituberculous therapy can minimize morbidity
and mortality but may need to be initiated empirically. A negative smear for acid-fast bacillus,
a lack of granulomas on histopathology, and failure to culture Mycobacterium tuberculosis do
not exclude the diagnosis. Novel diagnostic modalities such as adenosine deaminase levels and
polymerase chain reaction can be useful in certain forms of extrapulmonary tuberculosis. In
general, the same regimens are used to treat pulmonary and extrapulmonary tuberculosis, and
responses to antituberculous therapy are similar in patients with HIV infection and in those
without. Treatment duration may need to be extended for central nervous system and skeletal
tuberculosis, depending on drug resistance, and in patients who have a delayed or incomplete
response. Adjunctive corticosteroids may be beneficial in patients with tuberculous meningitis,
tuberculous pericarditis, or miliary tuberculosis with refractory hypoxemia. (Am Fam Physician
2005;72:1761-8. Copyright © 2005 American Academy of Family Physicians.)

F
rom 1985 until 1992 there was a pulmonary disease, disseminated disease,
resurgence of tuberculosis in the rapid progression, visceral lymphadenopa-
United States that coincided with the thy, tissue abscesses, and negative tubercu-
epidemic of acquired immunodefi- lin skin test. Response to antituberculous
ciency syndrome (AIDS).1 Although the U.S. therapy is favorable and similar to that of
incidence of tuberculosis has since been in patients without HIV infection, although
decline, this disease remains a major problem adverse drug reactions occur more com-
for much of the world, with a global preva- monly in those with HIV infection. It is
lence of infection estimated at 32 percent.2 unclear whether patients with HIV infection
Thus, the percentage of U.S. cases that occur have a higher risk of relapse. Infectious dis-
among foreign-born persons is increasing ease consultation is advisable given complex
(53 percent in 2003).1 Extrapulmonary tuber- drug-drug interactions and the risk of para-
culosis has become more common since the doxical response or immune reconstitution.
advent of human immunodeficiency virus
(HIV) infection.3 Principles of Management
Clinical clues that should prompt suspicion
Extrapulmonary Tuberculosis of extrapulmonary tuberculosis are listed in
and HIV Infection Table 1. Patients with suspected tuberculosis
Extrapulmonary involvement can be seen should have appropriate specimens sent for
in more than 50 percent of patients with acid-fast bacillus (AFB) staining, mycobacte-
concurrent AIDS and tuberculosis.3-5 The rial culture, and histology. Hospitalization
risk of extrapulmonary tuberculosis and is not necessary for tuberculosis to be diag-
mycobacteremia increases with advancing nosed unless clinically indicated. Hospitalized
immunosuppression.6 Unique features of patients in whom infectious (i.e., pulmonary
AIDS-associated tuberculosis include extra- or laryngeal) tuberculosis is suspected should

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Extrapulmonary Tuberculosis
SORT: KEY RECOMMENDATIONS FOR PRACTICE

Evidence
Clinical recommendation rating References

All patients with tuberculosis should have counseling and testing for HIV infection. C 7, 8
All confirmed cases of active tuberculosis should be reported to the local health department. C 7
Adjunctive corticosteroid therapy is recommended, based on limited evidence, in patients with B 7, 9, 10
tuberculous meningitis or pericarditis, and in miliary tuberculosis with refractory hypoxemia.
Patients should be monitored using directly observed therapy whenever feasible to ensure C 12
compliance and prevent emergence of drug resistance.
Patients should be screened for latent tuberculosis infection or active disease before initiation C 42, 43
of therapy with a TNF-G inhibitor.
Patients with pulmonary or laryngeal tuberculosis should be placed in respiratory isolation B 7
until they are no longer infectious.

HIV = human immunodeficiency virus; TNF = tumor necrosis factor.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-
oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 1639 or
http://www.aafp.org/afpsort.xml.

be placed in an airborne-infection isolation room and ethambutol [Myambutol], followed by four to seven
should wear a surgical mask during transport and in months of isoniazid and rifampin) is recommended as
waiting areas.7 Health care workers and visitors entering initial therapy for all forms of extrapulmonary tuber-
the isolation room should wear at least N95 disposable culosis unless the organisms are known or strongly
respirators, as should health care workers performing suspected to be resistant to the first-line drugs.8 For
procedures such as sputum induction, bronchoscopy, jet patients with central nervous system tuberculosis,
irrigation of abscesses, and autopsies. All patients with including meningitis, at least nine to 12 months of
tuberculosis should have counseling and testing for HIV therapy is recommended. Extended therapy also may be
infection. The local health department should be notified required for patients with bone and joint tuberculosis,
of all confirmed cases of tuberculosis.7 delayed treatment response, or drug resistance. Adjunc-
A six- to nine-month regimen (two months of iso- tive corticosteroids may be useful in patients who have
niazid [INH], rifampin [Rifadin], pyrazinamide, and tuberculous meningitis, tuberculous pericarditis, or
miliary tuberculosis with refractory hypoxemia.7-11
Physicians should consider noncompliance, malabsorp-
TABLE 1 tion, and drug resistance as possible reasons for delayed
Clinical Clues to Prompt Suspicion or suboptimal response to appropriate therapy. Directly
of Extrapulmonary Tuberculosis observed therapy is strongly recommended to encour-
age medication compliance.12 A detailed discussion of
Ascites with lymphocyte predominance and negative baseline evaluation, antituberculous therapy, and fol-
bacterial cultures low-up is beyond the scope of this article but can be
Chronic lymphadenopathy (especially cervical) found elsewhere.8
CSF lymphocytic pleocytosis with elevated protein
and low glucose Tuberculous Lymphadenitis
Differential diagnosis of Crohn’s disease and amebiasis Lymphadenitis is the most commonly occurring form
Exudative pleural effusion with lymphocyte predominance, of extrapulmonary tuberculosis. Cervical adenopathy is
negative bacterial cultures, and pleural thickening
most common, but inguinal, axillary, mesenteric, medi-
HIV infection
astinal, and intramammary involvement all have been
Joint inflammation (monoarticular) with negative bacterial
cultures
described.13-17 Although previously considered a disease
Persistent sterile pyuria
of childhood, lymphadenitis has a peak age of onset of 20
Tuberculosis-endemic country of origin
to 40 years, and in the United States it is most common
Unexplained pericardial effusion, constrictive pericarditis,
in women and immigrants. Patients without HIV infec-
or pericardial calcification tion typically present with chronic, nontender lymphade-
Vertebral osteomyelitis involving the thoracic spine nopathy.15,17 Patients with HIV infection usually present
with fever, night sweats, and weight loss.5,18 The nodes are
CSF = cerebrospinal fluid; HIV = human immunodeficiency virus. discrete, firm, and nontender; with time, a firm mass of
matted nodes becomes visible (Figure 1). If untreated, the

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 Extrapulmonary Tuberculosis

Mycobacterium tuberculosis on the fine-needle aspiration

specimen enhances test sensitivity.
During antituberculous therapy (see Principles of
Management), affected nodes may enlarge or new nodes
may appear, representing an immune response to killed
mycobacteria. A similar phenomenon in patients with
HIV infection who begin concurrent antiretroviral ther-
apy is a result of immune reconstitution. Lymph node
excision usually is not indicated. When lymph nodes are
fluctuant and ready to drain, aspiration or incision and
drainage appear to be beneficial.

Pleural Tuberculosis
In the United States, pleural tuberculosis accounts for
about 5 percent of all tuberculosis cases.19 Tuberculous
effusions can follow early postprimary, chronic pulmo-
nary, or miliary tuberculosis. Pleural tuberculosis often
Figure 1. Tuberculous lymphadenitis. Computed tomo-
graphic scan of the neck reveals a heterogeneous mass
is an acute illness with cough, pleuritic chest pain, fever,
in the right posterior cervical space (arrow) with central or dyspnea.
necrosis. Chest radiography typically reveals a small to mod-
erate, unilateral pleural effusion; about 20 percent of
patients have associated pulmonary lesions.20 Computed
tomography (CT) of the chest may show lymphadenopa-
thy, pulmonary infiltrates, or cavitation not obvious on
chest radiography (Figure 2). Pleural thickening of more
than 1 cm is seen in most instances.21
Pleural fluid is exudative with a lymphocyte predom-
inance (i.e., more than 50 percent of white blood cells in
more than 90 percent of effusions)16,20 ; in patients with
less than two weeks of symptoms, an initial predomi-
nance of neutrophils may be seen. Pleural fluid glucose
and pH can be low or normal. AFB smears of pleural
fluid are seldom positive (5 percent of cases) unless the
patient has tuberculous empyema. Pleural fluid cultures
for M. tuberculosis are positive in less than 40 percent
Figure 2. Tuberculous empyema. Computed tomographic
scan showing loculated pleural fluid and pleural thicken-
of cases.20 The combined sensitivity of the analyses of
ing (arrow) in the right chest with associated right lower pleural biopsy specimens (i.e., observation for caseat-
lobe atelectasis. ing granulomas, AFB smear, and culture) is more than
90 percent.20 Tuberculin skin test results are positive
nodes become fluctuant and drain spontaneously with in two thirds of patients. Biochemical markers such as
sinus tract formation. adenosine deaminase, interferon gamma, and lysozyme
Most patients have a positive tuberculin skin test in the pleural fluid can be useful. In one study, 20 a high
result and a normal result on chest radiography.13,15 level of adenosine deaminase (greater than 47 U per
Excisional biopsy of the lymph nodes with histology, L [783 nkat per L]) was seen in 99 percent of tuber-
AFB stain, and mycobacterial culture is the diagnostic culous effusions. In countries with a low prevalence
procedure of choice.16,17 The utility of fine-needle aspi- of tuberculosis, such as the United States, a normal
ration in patients without HIV infection is highly vari- or low level of pleural fluid adenosine deaminase has
able.17 Fine-needle aspiration is more reliable in patients a high negative predictive value and can be used to
with HIV infection because of the higher mycobacterial exclude tuberculous pleurisy.22,23 Pleural fluid PCR for
burden, and in these patients should be the initial diag- M. tuberculosis has a sensitivity of 80 percent and a
nostic procedure.17 Polymerase chain reaction (PCR) for specificity of 100 percent.24

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Extrapulmonary Tuberculosis

A B

Figure 3. Spinal tuberculosis. Magnetic resonance imaging of the spine revealing osteomyelitis involving T10 and T11
vertebral bodies and disc space (A; arrow) and an adjacent multiloculated paravertebral abscess (B; arrow).

Tuberculous pleurisy responds well to medical therapy, Extraspinal tuberculous osteomyelitis often presents
with resorption of pleural fluid in six to 12 weeks. The with local pain and can involve any bone. Involvement
effusion may resolve without therapy, but tuberculosis of adjacent structures may result in complications such as
later recurs. Rare complications include bronchopleural carpal tunnel syndrome, tenosynovitis, and facial palsy.
fistula, empyema, and fibrothorax. Chest radiography shows pulmonary disease in one
half of patients with osteoarticular tuberculosis, but
Skeletal Tuberculosis active pulmonary disease is uncommon.25 Magnetic
Bone and joint tuberculosis may account for up to resonance imaging may be helpful to assess the degree
35 percent of cases of extrapulmonary tuberculosis. Skel- of bony destruction and to identify soft tissue extension
etal tuberculosis most often involves the spine, followed and encroachment on adjacent structures such as the
by tuberculous arthritis in weight-bearing joints and spinal cord.
extraspinal tuberculous osteomyelitis.25-27 To establish the diagnosis of skeletal or articular tuber-
Spinal tuberculosis (Pott’s disease) most commonly culosis, a high index of suspicion is critical. Physicians
involves the thoracic spine. Infection begins in the should consider skeletal tuberculosis in patients with
anteroinferior aspect of the vertebral body with destruc-
tion of the intervertebral disc and adjacent vertebrae
(Figure 3). The resulting anterior wedging and angula-
tion of adjacent vertebral bodies with disc space obliter-
ation are responsible for the palpable spinal prominence
(gibbus) and a classic radiographic appearance. Paraspi-
nal and psoas abscesses can develop, with extensions to
the surface or adjacent tissues (Figure 4). Patients present
with local pain, constitutional symptoms, or paraplegia
secondary to cord compression.
Articular tuberculosis is a slowly progressive mono-
arthritis of the hip or knee. Presentation is indolent
with pain, joint swelling, and decreased range of motion.
Draining sinuses and abscesses are seen in chronic cases.
Systemic symptoms usually are absent. Radiographic
Figure 4. Psoas abscess. Computed tomographic scan of
changes are nonspecific and include soft tissue swelling, the abdomen showing a left iliopsoas abscess (arrow) that
juxta-articular osteopenia, joint space narrowing, and likely originated from tuberculous osteomyelitis involving
subchondral erosions (Figure 5).26 the T12, L1, and L2 vertebrae.

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 Extrapulmonary Tuberculosis

dementia, and a predominant syndrome of encephalitis.

Convulsions can occur at all stages of the illness.
A high index of suspicion is necessary for timely
diagnosis and prompt initiation of therapy. CSF typi-
cally reveals moderate lymphocytic pleocytosis (100 to
500 cells per RL [0.10 to 0.50  109 per L])16 ; initially,
a neutrophilic predominance can be seen. CSF protein
levels range from 100 to 500 mg per dL (1,000 to 5,000
mg per L) and can be extremely high (2 to 6 g per dL
Figure 5. Osteoarticular tuberculosis. Radiograph of the [20 to 60 g per L]), with xanthochromia in the pres-
right knee showing a large effusion, osteopenia, joint ence of subarachnoid block. CSF glucose concentration
space narrowing, and lucencies in the distal femur.
usually is less than 45 mg per dL (2.50 mmol per L).
AFB smears on CSF are positive in 10 to 90 percent of
an indolent clinical course manifesting as osteomyelitis patients; sensitivity can be improved if large volumes of
involving the thoracic spine or monoarticular septic CSF from multiple lumbar punctures are examined, CSF
arthritis with negative bacterial cultures. Arthrocentesis is centrifuged and AFB smears are performed on the pel-
with mycobacterial cultures of synovial fluid yields posi- licle, or an experienced reviewer examines several high-
tive results in up to 80 percent of patients with tubercu- powered fields.16,30,31 CSF culture for M. tuberculosis is
lous arthritis. Synovial biopsy also may be diagnostic positive in 45 to 90 percent of cases but takes four to six
(caseating granulomas on histology or positive mycobac- weeks. CSF PCR for M. tuberculosis has a sensitivity of
terial culture).26,27 Bone biopsy for culture and histology 56 percent and a specificity of 98 percent, and therefore
is required for diagnosis of tuberculous osteomyelitis. should not be used to exclude tuberculous meningitis.32
Surgery may be necessary to drain abscesses, debride An elevated CSF adenosine deaminase level supports the
infected tissue, or stabilize the spine and relieve spi- diagnosis in the appropriate clinical setting.33 A CT scan
nal cord compression.28 In the absence of neurologic of the head with contrast may reveal basilar arachnoidi-
impairment, unstable spine, or spinal cord compression, tis, infarction, hydrocephalus, or tuberculomas.
medical therapy alone (see Principles of Management) 8,28 Empiric antituberculous therapy (see Principles of Man-
should result in an excellent response. agement) should be initiated as soon as clinical, labora-
tory, or imaging findings suggest tuberculous meningitis.
Central Nervous System Tuberculosis Delay in initiation of therapy has been directly associated
Central nervous system tuberculosis includes tuberculous with adverse outcomes. Antituberculous therapy is rec-
meningitis (the most common presentation), intracra- ommended for at least nine to 12 months.8 Adjunctive
nial tuberculomas, and spinal tuberculous arachnoiditis. corticosteroid therapy with dexamethasone (Decadron)
Meningitis results from intense inflammation following for the initial six to eight weeks in patients with tuber-
rupture of a subependymal tubercle into the subarach- culous meningitis has been associated with reduced
noid space.29 The ensuing arachnoiditis encases both mortality and fewer neurologic sequelae.8,11,34 Mortality
cranial nerves and penetrating vessels, leading to cranial is highest in patients younger than five years, those older
nerve palsies and communicating hydrocephalus. Cranial than 50 years, and those in whom illness has been present
vasculitis may lead to focal neurologic deficits. Hyper- for longer than two months.
sensitivity to tuberculoproteins may cause meningismus
and typical cerebrospinal fluid (CSF) findings. Cerebral Abdominal Tuberculosis
edema causes impairment of consciousness, seizures, and Abdominal tuberculosis may involve the gastrointestinal
raised intracranial pressure, whereas tuberculomas can tract, peritoneum, mesenteric lymph nodes, or genito-
manifest as space-occupying lesions.30 urinary tract. Other organs (e.g., liver, spleen, adrenal
An initial phase of malaise, headache, fever, or per- glands) usually are affected as a consequence of miliary
sonality change is followed in two to three weeks by tuberculosis.
protracted headache, meningismus, vomiting, confu-
GASTROINTESTINAL TUBERCULOSIS
sion, and focal neurologic findings. If untreated, men-
tal status deteriorates into stupor or coma.31 Atypical Tuberculous enteritis can result from swallowing of
presentations include a rapid progression simulating infected sputum, ingestion of contaminated food, hema-
pyogenic meningitis, subtle cognitive decline mimicking togenous spread, and direct extension from adjacent

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Extrapulmonary Tuberculosis

organs.35 The intestinal lesions can be ulcerative (most

common), hypertrophic, or ulcero-hypertrophic. Symp-
toms include abdominal pain, diarrhea, weight loss, and
fever. Melena, rectal bleeding, and abdominal tenderness
also can be present. A mass in the right lower quadrant is
palpable in 25 to 50 percent of patients.
The ileocecal area and jejunoileum are the most common
sites of involvement. Complications include obstruction,
perforation, and fistula formation. Rectal lesions usually Figure 6. Testicular tuberculosis. Computed tomographic
present as anal fissures, fistulas, or perirectal abscesses.16 scan of the pelvis showing a large, irregular, mixed solid
Barium contrast studies and colonoscopy may show ulcers, and cystic left testicular mass (arrow).
strictures, a deformed cecum, incompetent ileocecal valve,
or fistulas. An abdominal CT scan can define extralumi- continuous ambulatory peritoneal dialysis.35 Tuberculous
nal pathology, especially lymphadenopathy. peritonitis results from reactivation of latent foci in the
It is essential to distinguish tuberculous enteritis from peritoneum. Patients present with the insidious onset of
Crohn’s disease because initiation of immunosuppres- ascites, abdominal pain, and fever. Peritoneal fluid is exu-
sive therapy in a patient with tuberculous enteritis can dative, with a serum-ascites albumin gradient of less than
lead to dissemination. Definitive diagnosis is based on 1.1 g per dL (11 g per L). Peritoneal fluid leukocyte count
histopathology and culture of biopsy specimens obtained varies from 150 to 4,000 per mm3 (0.15 to 4.00 × 109 per
by colonoscopy or laparotomy. Differential diagnosis of L) with a lymphocytic predominance16; a neutrophilic
tuberculous enteritis includes Crohn’s disease, amebiasis, pleocytosis may be seen with tuberculous peritonitis
neoplasm, Yersinia infection, and actinomycosis.35 A six- complicating continuous ambulatory peritoneal dialysis.36
month course of antituberculous therapy is recommended. Centrifugation of 1 L of peritoneal fluid enhances the yield
Surgery is reserved for patients with complications. of AFB smear and mycobacterial culture. Peritoneal fluid
adenosine deaminase level has a high sensitivity and speci-
TUBERCULOUS PERITONITIS ficity if a cutoff value greater than 33 U per L (550 nkat
The risk of tuberculous peritonitis is greater in patients per L) is used. Peritoneal biopsy guided by laparoscopy or
with HIV infection or cirrhosis and in those undergoing mini-laparotomy can be diagnostic in more than 95 per-
cent of patients and should be strongly considered.35

The Authors GENITOURINARY TUBERCULOSIS

MARJORIE P. GOLDEN, M.D., is an assistant clinical professor at Renal disease may be the result of direct infection of the
Yale University School of Medicine, New Haven, Conn., and a kidney and lower urinary tract or may present as second-
staff member with the Infectious Disease Section at the Hospital ary amyloidosis. Patients present with dysuria, hematuria,
of Saint Raphael, New Haven. Dr. Golden received her medical
degree from Albany (N.Y.) Medical College, and completed an
or flank pain.37,38 More than 90 percent of asymptomatic
internal medicine residency and an infectious disease fellowship patients have sterile pyuria with or without microscopic
at the New England Deaconess Hospital (now the Beth Israel hematuria.37,38 Intravenous pyelography may show a
Deaconess Medical Center), Boston. “moth-eaten calyx” or papillary necrosis. Abdominal
CT scan may reveal renal calcifications, calculi, scarring,
HOLENARASIPUR R. VIKRAM, M.D., was formerly an assistant
clinical professor at Yale University School of Medicine and a hydronephrosis, or evidence of extrarenal disease (e.g.,
staff member with the Infectious Disease Section at the Hospital ureteral strictures; contracted bladder; calcifications in the
of Saint Raphael. Since October 2005, Dr. Vikram has been with vas deferens, seminal vesicles, or prostate). Mycobacterial
the Division of Infectious Diseases, Mayo Clinic, Scottsdale, Ariz. culture of three morning urine specimens establishes the
Dr. Vikram received his medical degree from Bangalore Medical
diagnosis in 90 percent of patients.37 Nephrectomy rarely
College, Bangalore, India. He completed an internal medicine
residency and a chief medical residency at the University of is indicated for persistent flank pain or hypertension.8
Connecticut Health Center, Farmington, and an infectious disease Renal function usually is preserved, except in the setting
fellowship at Yale University School of Medicine. of tuberculous interstitial nephritis.
Male genital tuberculosis usually is associated with
Address correspondence to Holenarasipur R. Vikram, M.D., Division
of Infectious Diseases, Mayo Clinic, 13400 E. Shea Blvd., Scottsdale,
renal tuberculosis. It involves the prostate, seminal
AZ 85259 (e-mail: [email protected]). Reprints are vesicles, epididymis, and testes, in order of incidence.
not available from the authors. Patients usually present with a scrotal mass (Figure 6),

1766 American Family Physician www.aafp.org/afp Volume 72, Number 9 U November 1, 2005
 Extrapulmonary Tuberculosis

A B

Figure 7. Miliary tuberculosis. Chest radiograph (A) and chest computed tomographic scan (B) showing bilateral miliary
nodular pattern.

and diagnosis is made by surgery. Oligospermia is com- TUBERCULOUS PERICARDITIS

mon and may be persistent. Female genital tuberculosis Tuberculous pericarditis develops secondary to contigu-
begins in the endosalpinx and can spread to the peri- ous spread from mediastinal nodes, lungs, spine, or ster-
toneum, endometrium, ovaries, cervix, and vagina.38 num, or during miliary dissemination. The onset may be
Patients present with pelvic pain, infertility, and vaginal abrupt or insidious with symptoms such as chest pain,
bleeding. Response to chemotherapy is excellent for all dyspnea, and ankle edema. Cardiomegaly, tachycardia,
forms of genital tuberculosis; surgery in women is nec- fever, pericardial rub, pulsus paradoxus, or distended neck
essary for large tubo-ovarian abscesses.8 veins may be found on examination.41 Pericardial biopsy
yields a definitive diagnosis more often than pericardial
Other Forms fluid alone.41 In addition to antituberculous therapy,
Three additional forms of extrapulmonary tuberculosis corticosteroids are recommended to hasten resolution of
warrant discussion: miliary tuberculosis, tuberculous symptoms and to reduce reaccumulation of fluid.8,41 The
pericarditis, and tuberculosis associated with tumor risk of progression to constrictive pericarditis or mortal-
necrosis factor-G (TNF-G) inhibitors. ity is not altered by corticosteroids.11 Open pericardial
drainage is favored over repeated pericardiocentesis.41
MILIARY TUBERCULOSIS
TNF-G INHIBITOR–ASSOCIATED TUBERCULOSIS
The term miliary tuberculosis refers to any progressive,
disseminated form of tuberculosis; the disease can occur Two recent reports describe several cases of active tuber-
during primary dissemination or after years of untreated culosis occurring after treatment with the TNF-G inhibi-
tuberculosis. Miliary disease is seen in 10 percent of tors infliximab (Remicade)42 and etanercept (Enbrel),43
patients who have AIDS and pulmonary tuberculosis, mainly in patients with rheumatoid arthritis or Crohn’s
and in 38 percent of those who have AIDS and extra- disease. Tuberculosis was diagnosed sooner after ini-
pulmonary tuberculosis.5 Presenting symptoms include tiation of infliximab than after initiation of etanercept
fever, chills, night sweats, weight loss, and anorexia. (median of 12 weeks versus 12 months).42,43 Extrapul-
Clinical manifestations depend on the organs involved. monary tuberculosis accounted for 52 to 57 percent of
Fulminant disease including septic shock, acute respira- cases. As a result, it is now recommended that patients be
tory distress syndrome, and multiorgan failure has been screened for latent tuberculosis infection or active disease
described. A chest radiograph or CT scan reveals numer- before initiation of therapy with a TNF-G inhibitor.
ous 2- to 3-mm nodules scattered throughout the lung in
more than 85 percent of patients (Figure 7).16,39 Common Author disclosure: Nothing to disclose.
laboratory abnormalities include normochromic anemia,
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1768 American Family Physician www.aafp.org/afp Volume 72, Number 9 U November 1, 2005