New England TB Case Series January 18, 2006 Ford von Reyn MD Dartmouth Medical School.

New England TB Case New England TB Case SeriesSeries

January 18, 2006 January 18, 2006

Ford von Reyn MDFord von Reyn MD

Dartmouth Medical SchoolDartmouth Medical School

Case - 1Case - 1

33 yo Thai woman working living in 33 yo Thai woman working living in northern New Hampshire, unemployednorthern New Hampshire, unemployed

February 2004: sore throat, followed by February 2004: sore throat, followed by dysphagia, R neck swelling, 5 pound dysphagia, R neck swelling, 5 pound weight loss and feverweight loss and fever

March 10, 2004 (Boston): cervical node Bx March 10, 2004 (Boston): cervical node Bx under CT and US guidance showed AFB under CT and US guidance showed AFB and necrotizing granulomatous and necrotizing granulomatous inflammation, no Hx TB exposure, no PPD inflammation, no Hx TB exposure, no PPD donedone

Chest x-ray: next slideChest x-ray: next slide

QuestionsQuestions

1.1. Differential diagnosis?Differential diagnosis?

2.2. Isolation?Isolation?

3.3. Next steps?Next steps?

Differential DiagnosisDifferential Diagnosis

1.1. Mycobacterial adenitis: TB or non-Mycobacterial adenitis: TB or non-tuberculous mycobacteria (NTM)tuberculous mycobacteria (NTM)

2.2. Other bacterial: cat scratch, Other bacterial: cat scratch, S. aureusS. aureus or or Streptococcal spp, tularemiaStreptococcal spp, tularemia

3.3. Parasitic: ToxoplasmosisParasitic: Toxoplasmosis

4.4. ViralViral

5.5. FungalFungal

6.6. SarcoidosisSarcoidosis

7.7. Malignancy: lymphoma, sarcoma, Malignancy: lymphoma, sarcoma, carcinomacarcinoma

MDR tuberculosisMDR tuberculosis

Defined as resistance to at Defined as resistance to at least INH and rifampinleast INH and rifampin

Website: Website: http://www.who.int/tb/publicatihttp://www.who.int/tb/publications/who_htm_tb_2004_343/en/inons/who_htm_tb_2004_343/en/index.htmldex.html

Thailand: approximately 1-2%Thailand: approximately 1-2%

Case - 2Case - 2

March 17, 2004: Started on 4 drug Rx for March 17, 2004: Started on 4 drug Rx for TBTB

INH, Rifampin, Pyrazinamide, INH, Rifampin, Pyrazinamide, EthambutolEthambutol

April 9, 2004: Positive culture for TB, later April 9, 2004: Positive culture for TB, later reported as sensitive to all first line drugsreported as sensitive to all first line drugs

Case - 3Case - 3April 19, 2004 (Dartmouth): Referred for April 19, 2004 (Dartmouth): Referred for

evaluation of poorly responsive tuberculous evaluation of poorly responsive tuberculous lymphadenitislymphadenitis

Hx: Hx: Neck still painful, no decrease in sizeNeck still painful, no decrease in size

No fever, last night sweats 2 weeks agoNo fever, last night sweats 2 weeks ago

PE: PE: AfebrileAfebrile

Weight 105 lbWeight 105 lb

Lungs clearLungs clear

Tender L supraclavicular area 10 x 10 cm, Tender L supraclavicular area 10 x 10 cm, woody woody induration, no fluctuanceinduration, no fluctuance

L arm weaknessL arm weakness

April 2004 ScrofulaApril 2004 Scrofula

QuestionsQuestions

1.1. What is the problem?What is the problem?

2.2. Other studies?Other studies?

3.3. Therapy?Therapy?

Case - 4Case - 4

April 21: Admitted to Dartmouth-April 21: Admitted to Dartmouth-Hitchcock Medical Center for Hitchcock Medical Center for further increase in size of neck further increase in size of neck massmass

Daily Rx, PZA reduced from 2.0 to Daily Rx, PZA reduced from 2.0 to 1.2 gm because of nausea1.2 gm because of nausea

April 23: Neck aspirate AFB positiveApril 23: Neck aspirate AFB positive

Next steps?Next steps?

Case - 5Case - 5

April 28, 2004: Prednisone 80 mg/dApril 28, 2004: Prednisone 80 mg/d

May 4, 2004: Neck still painful and mass May 4, 2004: Neck still painful and mass enlargingenlarging

I & D at 3 sites by ENT: brown pus, clots, AFB I & D at 3 sites by ENT: brown pus, clots, AFB pospos

May 11, 2004: Prednisone D/Ced, fever and May 11, 2004: Prednisone D/Ced, fever and muscle pain developedmuscle pain developed

Prednisone 20 mg/d resumed, fever clearedPrednisone 20 mg/d resumed, fever cleared

May 14, 2004: Discharged home on 2x weekly May 14, 2004: Discharged home on 2x weekly RxRx

Case - 6Case - 6

May 27, 2004: OPD visit. No fevers, still May 27, 2004: OPD visit. No fevers, still some leg pain, wounds packed daily, less some leg pain, wounds packed daily, less neck pain, 11 lb weight gainneck pain, 11 lb weight gain

June 25, 2004: L leg swelling, neg US, June 25, 2004: L leg swelling, neg US, clinical suspicion of DVT, Rx ASAclinical suspicion of DVT, Rx ASA

July 27, 2005: Cont’d decrease in neck July 27, 2005: Cont’d decrease in neck swelling, weight up 20 lbs, continue swelling, weight up 20 lbs, continue prednisone 20 mgprednisone 20 mg

Completed 8 mos total Rx in December 2004Completed 8 mos total Rx in December 2004

Scrofula Scrofula

• Scrofula = mycobacterial Scrofula = mycobacterial lymphadenitis lymphadenitis

• King’s Evil: Medieval term, “cured” by King’s Evil: Medieval term, “cured” by touch of the kingtouch of the king

• Historical: common in Europe in 19Historical: common in Europe in 19thth century (24% of children had evidence century (24% of children had evidence of current or past infection)of current or past infection)

Scrofula Scrofula

• EtiologyEtiology

M. tuberculosisM. tuberculosis (MTB) (MTB)

M. bovisM. bovis (MB) (MB)

Non-tuberculous mycobacteria (NTM)Non-tuberculous mycobacteria (NTM)

• Developing countries: MTB> MB>>>NTMDeveloping countries: MTB> MB>>>NTM

• Developed countries: NTM>>MTB>MBDeveloped countries: NTM>>MTB>MB

Lymphadenitis due to Lymphadenitis due to MTBMTB

• Age 20-30 most common, F: M ratio is 2:1Age 20-30 most common, F: M ratio is 2:1• Ethnic: esp Asian (80%), Indian; also Ethnic: esp Asian (80%), Indian; also

African, Af-Am, Hispanic, Native AmericanAfrican, Af-Am, Hispanic, Native American• 3-5% of US TB cases3-5% of US TB cases• Clinical settingsClinical settings

Primary TB (children)Primary TB (children)

Reactivation TB (adults)Reactivation TB (adults)

HIVHIV

IRIS (HIV)IRIS (HIV)

Lymphadenitis due to Lymphadenitis due to MTBMTB

• Nodes: usu multiple nodes, jugular, Nodes: usu multiple nodes, jugular, posterior triangle, supraclavicularposterior triangle, supraclavicular

• Pathophysiology: systemic Pathophysiology: systemic disseminationdissemination

• Symptoms: weeks to months, fever, Symptoms: weeks to months, fever, wt loss, fatigue, nt sweats in 20-50%wt loss, fatigue, nt sweats in 20-50%

• Chest x-ray: 30% have findingsChest x-ray: 30% have findings• Tuberculin skin test: 70-90% positiveTuberculin skin test: 70-90% positive

Subclinical TB in HIV: Subclinical TB in HIV: TanzaniaTanzania

HIV positive ambulatory patients with CD4>200 HIV positive ambulatory patients with CD4>200 screened for a TB vaccine trial in Tanzaniascreened for a TB vaccine trial in Tanzania

Among first 93 patients 14 (15%) met clinical Among first 93 patients 14 (15%) met clinical criteria for active tuberculosiscriteria for active tuberculosis

““Subclinical TB”: 10 patients with no signs, Subclinical TB”: 10 patients with no signs, symptoms or x-ray abnormalities but positive symptoms or x-ray abnormalities but positive sputum cultures (DNA typing showed not sputum cultures (DNA typing showed not contaminants); 3/10 pos AFB smears, 60% contaminants); 3/10 pos AFB smears, 60% adenopathyadenopathy

ImplicationsImplications

Need for better diagnosticsNeed for better diagnostics

Inappropriate INH for latent TB that is really Inappropriate INH for latent TB that is really early active TBearly active TB

-Mtei, von Reyn 2003-Mtei, von Reyn 2003

Immune reconstitution syndrome Immune reconstitution syndrome (IRIS) in HIV/TB(IRIS) in HIV/TB• • Fever, lymphadenitis, +/- pulmonary infiltrate, expansion Fever, lymphadenitis, +/- pulmonary infiltrate, expansion

of CNS lesions, in HIV pos patients on Rx for TB who are of CNS lesions, in HIV pos patients on Rx for TB who are then started on HAART and experience immune then started on HAART and experience immune reconstitutionreconstitution

• Also called “paradoxical reactions”Also called “paradoxical reactions”

• Occurred in 6 (35%) patients started on HAART (for HIV) Occurred in 6 (35%) patients started on HAART (for HIV) while on TB therapywhile on TB therapy

• • All occurred with HAART start <2 mos after TB Rx start All occurred with HAART start <2 mos after TB Rx start (median 22 days), 5/6 had initial CD4<100, more likely if (median 22 days), 5/6 had initial CD4<100, more likely if >2 log drop in HIV viral load>2 log drop in HIV viral load

• Smears pos in 4/6, culture pos in 2/6Smears pos in 4/6, culture pos in 2/6

• Management: distinguish treatment failure, continue TB Management: distinguish treatment failure, continue TB Rx, NSIADs for mild Sx, steroids for severe SxRx, NSIADs for mild Sx, steroids for severe Sx

• Most cases resolve within a few weeksMost cases resolve within a few weeks

-Navas, 2002-Navas, 2002

Lymphadenitis due to Lymphadenitis due to MTB - DxMTB - Dx

• Fine needle aspiration (FNA) for Fine needle aspiration (FNA) for cytology and AFB smearcytology and AFB smear

sensitivity 80%sensitivity 80%specificity 90%specificity 90%

• Excisional Bx: second choice for Excisional Bx: second choice for Dx because of possibility for Dx because of possibility for fistula, sinus tractsfistula, sinus tracts

• Culture: positive in 35% Culture: positive in 35%

Lymphadenitis due to Lymphadenitis due to MTB - RxMTB - Rx

• Standard 4 drug chemotherapyStandard 4 drug chemotherapy• Slow response: common for Slow response: common for

enlargement of nodes or new enlargement of nodes or new nodes on Rx, cultures usu nodes on Rx, cultures usu negativenegative

• Surgical drainage: for painful Surgical drainage: for painful lesions or very slow response on lesions or very slow response on chemoRxchemoRx

Lymphadenitis due to Lymphadenitis due to NTMNTM

• Clinical: indolent lymphadenitis in healthy Clinical: indolent lymphadenitis in healthy children age 1-5 usu due to M. avium complex children age 1-5 usu due to M. avium complex

• Nodes: upper cervical, salivary area nodesNodes: upper cervical, salivary area nodes• Risk factors: unknown (?soil/water exposure Risk factors: unknown (?soil/water exposure

with erupting teeth), BCG protects (Sweden, with erupting teeth), BCG protects (Sweden, Finland)Finland)

• Rx: surgical excision; two drug Rx (from Rx: surgical excision; two drug Rx (from macrolide, ethambutol, rifamycin) may macrolide, ethambutol, rifamycin) may benefit those who are not surgical candidates benefit those who are not surgical candidates

• Incidence: rising in the United States, Incidence: rising in the United States, increased in Sweden with decreased BCG useincreased in Sweden with decreased BCG use

Childhood adenitis: Childhood adenitis: Cleveland, USCleveland, US

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Summary - ScrofulaSummary - Scrofula

• Case presentation: slowly resolving Case presentation: slowly resolving drug sensitive MTB lymphadenitis drug sensitive MTB lymphadenitis in a Thai woman, Rx required 8 in a Thai woman, Rx required 8 mos chemo and surgical drainagemos chemo and surgical drainage

• Usu demographics: F>M, esp Usu demographics: F>M, esp Asian, age 20-30 Asian, age 20-30

• Other clinical settings: HIV, IRIS, Other clinical settings: HIV, IRIS, primary infectionprimary infection

• Most adult cases in US due to MTB, Most adult cases in US due to MTB, childhood cases due to NTMchildhood cases due to NTM

• Rx for childhood NTM is usually Rx for childhood NTM is usually surgerysurgery