Transcript Tuberculosis: a global perspective

New England TB Case Series
January 18, 2006
Ford von Reyn MD
Dartmouth Medical School
Case - 1
33 yo Thai woman working living in northern
New Hampshire, unemployed
February 2004: sore throat, followed by
dysphagia, R neck swelling, 5 pound weight
loss and fever
March 10, 2004 (Boston): cervical node Bx
under CT and US guidance showed AFB and
necrotizing granulomatous inflammation, no
Hx TB exposure, no PPD done
Chest x-ray: next slide
Questions
1. Differential diagnosis?
2. Isolation?
3. Next steps?
Differential Diagnosis
1. Mycobacterial adenitis: TB or non-tuberculous
mycobacteria (NTM)
2. Other bacterial: cat scratch, S. aureus or
Streptococcal spp, tularemia
3. Parasitic: Toxoplasmosis
4. Viral
5. Fungal
6. Sarcoidosis
7. Malignancy: lymphoma, sarcoma, carcinoma
MDR tuberculosis
Defined as resistance to at least INH
and rifampin
Website:
http://www.who.int/tb/publications/wh
o_htm_tb_2004_343/en/index.html
Thailand: approximately 1-2%
Case - 2
March 17, 2004: Started on 4 drug Rx for TB
INH, Rifampin, Pyrazinamide, Ethambutol
April 9, 2004: Positive culture for TB, later
reported as sensitive to all first line drugs
Case - 3
April 19, 2004 (Dartmouth): Referred for evaluation
of poorly responsive tuberculous lymphadenitis
Hx: Neck still painful, no decrease in size
No fever, last night sweats 2 weeks ago
PE: Afebrile
Weight 105 lb
Lungs clear
Tender L supraclavicular area 10 x 10 cm,
woody
induration, no fluctuance
L arm weakness
April 2004 Scrofula
Questions
1. What is the problem?
2. Other studies?
3. Therapy?
Case - 4
April 21: Admitted to DartmouthHitchcock Medical Center for further
increase in size of neck mass
Daily Rx, PZA reduced from 2.0 to 1.2 gm
because of nausea
April 23: Neck aspirate AFB positive
Next steps?
Case - 5
April 28, 2004: Prednisone 80 mg/d
May 4, 2004: Neck still painful and mass
enlarging
I & D at 3 sites by ENT: brown pus, clots, AFB
pos
May 11, 2004: Prednisone D/Ced, fever and
muscle pain developed
Prednisone 20 mg/d resumed, fever cleared
May 14, 2004: Discharged home on 2x weekly
Rx
Case - 6
May 27, 2004: OPD visit. No fevers, still some
leg pain, wounds packed daily, less neck pain,
11 lb weight gain
June 25, 2004: L leg swelling, neg US, clinical
suspicion of DVT, Rx ASA
July 27, 2005: Cont’d decrease in neck swelling,
weight up 20 lbs, continue prednisone 20 mg
Completed 8 mos total Rx in December 2004
Scrofula
• Scrofula = mycobacterial lymphadenitis
• King’s Evil: Medieval term, “cured” by touch
of the king
• Historical: common in Europe in 19th century
(24% of children had evidence of current or
past infection)
Scrofula
• Etiology
M. tuberculosis (MTB)
M. bovis (MB)
Non-tuberculous mycobacteria (NTM)
• Developing countries: MTB> MB>>>NTM
• Developed countries: NTM>>MTB>MB
Lymphadenitis due to MTB
• Age 20-30 most common, F: M ratio is 2:1
• Ethnic: esp Asian (80%), Indian; also African,
Af-Am, Hispanic, Native American
• 3-5% of US TB cases
• Clinical settings
Primary TB (children)
Reactivation TB (adults)
HIV
IRIS (HIV)
Lymphadenitis due to MTB
• Nodes: usu multiple nodes, jugular,
posterior triangle, supraclavicular
• Pathophysiology: systemic dissemination
• Symptoms: weeks to months, fever, wt loss,
fatigue, nt sweats in 20-50%
• Chest x-ray: 30% have findings
• Tuberculin skin test: 70-90% positive
Subclinical TB in HIV: Tanzania
HIV positive ambulatory patients with CD4>200
screened for a TB vaccine trial in Tanzania
Among first 93 patients 14 (15%) met clinical criteria
for active tuberculosis
“Subclinical TB”: 10 patients with no signs,
symptoms or x-ray abnormalities but positive
sputum cultures (DNA typing showed not
contaminants); 3/10 pos AFB smears, 60%
adenopathy
Implications
Need for better diagnostics
Inappropriate INH for latent TB that is really early
active TB
Immune reconstitution syndrome (IRIS) in
HIV/TB
• Fever, lymphadenitis, +/- pulmonary infiltrate, expansion of CNS
lesions, in HIV pos patients on Rx for TB who are then started on
HAART and experience immune reconstitution
• Also called “paradoxical reactions”
• Occurred in 6 (35%) patients started on HAART (for HIV) while on
TB therapy
• All occurred with HAART start <2 mos after TB Rx start (median 22
days), 5/6 had initial CD4<100, more likely if >2 log drop in HIV viral
load
• Smears pos in 4/6, culture pos in 2/6
• Management: distinguish treatment failure, continue TB Rx,
NSIADs for mild Sx, steroids for severe Sx
• Most cases resolve within a few weeks
Lymphadenitis due to MTB - Dx
• Fine needle aspiration (FNA) for
cytology and AFB smear
sensitivity 80%
specificity 90%
• Excisional Bx: second choice for Dx
because of possibility for fistula, sinus
tracts
• Culture: positive in 35%
Lymphadenitis due to MTB - Rx
• Standard 4 drug chemotherapy
• Slow response: common for
enlargement of nodes or new nodes on
Rx, cultures usu negative
• Surgical drainage: for painful lesions
or very slow response on chemoRx
Lymphadenitis due to NTM
• Clinical: indolent lymphadenitis in healthy
children age 1-5 usu due to M. avium complex
• Nodes: upper cervical, salivary area nodes
• Risk factors: unknown (?soil/water exposure
with erupting teeth), BCG protects (Sweden,
Finland)
• Rx: surgical excision; two drug Rx (from
macrolide, ethambutol, rifamycin) may benefit
those who are not surgical candidates
• Incidence: rising in the United States,
No. of cases / 4 year period
Childhood adenitis: Cleveland, US
14
12
10
8
6
MAC
4
M. scofulaceum
2
0
1961 1965 1969 1973 1977 1981 1985 1990
End of 4 year period
-Wolinsky. Clin Infect Dis 1995;20:954-63.
Summary - Scrofula
• Case presentation: slowly resolving drug
sensitive MTB lymphadenitis in a Thai
woman, Rx required 8 mos chemo and
surgical drainage
• Usu demographics: F>M, esp Asian, age
20-30
• Other clinical settings: HIV, IRIS, primary
infection
• Most adult cases in US due to MTB,
childhood cases due to NTM
• Rx for childhood NTM is usually surgery