New England TB Case Series January 18, 2006

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New England TB Case Series January 18, 2006

• Ford von Reyn MD
• Dartmouth Medical School

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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

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Questions

• Differential diagnosis?
• Isolation?
• Next steps?

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Differential Diagnosis

• Mycobacterial adenitis TB or non-tuberculous
  mycobacteria (NTM)
• Other bacterial cat scratch, S. aureus or
  Streptococcal spp, tularemia
• Parasitic Toxoplasmosis
• Viral
• Fungal
• Sarcoidosis
• Malignancy lymphoma, sarcoma, carcinoma

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MDR tuberculosis

• Defined as resistance to at least INH and
  rifampin
• Website http//www.who.int/tb/publications/who_ht
  m_tb_2004_343/en/index.html
• Thailand approximately 1-2

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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

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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

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April 2004 Scrofula
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Questions

• What is the problem?
• Other studies?
• Therapy?

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Case - 4

• April 21 Admitted to Dartmouth-Hitchcock 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?

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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

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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 Contd decrease in neck swelling,
  weight up 20 lbs, continue prednisone 20 mg
• Completed 8 mos total Rx in December 2004

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Scrofula

• Scrofula mycobacterial lymphadenitis
• Kings 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)

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Scrofula

• Etiology
• M. tuberculosis (MTB)
• M. bovis (MB)
• Non-tuberculous mycobacteria (NTM)
• Developing countries MTBgt MBgtgtgtNTM
• Developed countries NTMgtgtMTBgtMB

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Lymphadenitis due to MTB

• Age 20-30 most common, F M ratio is 21
• 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)

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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

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Subclinical TB in HIV Tanzania

• HIV positive ambulatory patients with CD4gt200
  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
• -Mtei, von Reyn 2003

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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 lt2 mos after TB
  Rx start (median 22 days), 5/6 had initial
  CD4lt100, more likely if gt2 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
• -Navas, 2002

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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

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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

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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, increased
  in Sweden with decreased BCG use

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Childhood adenitis Cleveland, US
-Wolinsky. Clin Infect Dis 199520954-63.
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Summary - Scrofula

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