Presentation on theme: "New England TB Case Series January 18, 2006"— Presentation transcript:
1 New England TB Case Series January 18, 2006 Ford von Reyn MDDartmouth Medical School
2 Case - 133 yo Thai woman working living in northern New Hampshire, unemployedFebruary 2004: sore throat, followed by dysphagia, R neck swelling, 5 pound weight loss and feverMarch 10, 2004 (Boston): cervical node Bx under CT and US guidance showed AFB and necrotizing granulomatous inflammation, no Hx TB exposure, no PPD doneChest x-ray: next slide
3 CXR from Dartmouth but probably the same at Mt A, shows deviation of trachea to left, no infiltrates
5 Questions Differential diagnosis? Isolation? Next steps? NTM lymphadenitis, XXNo isolation needed (except working with wound)Determine drug resistance in Thailand – 2% according to Palwatwichai, Apirak (2001) Tuberculosis in Thailand. Respirology 6 (1), doi: / j x
6 Differential Diagnosis Mycobacterial adenitis: TB or non-tuberculous mycobacteria (NTM)Other bacterial: cat scratch, S. aureus or Streptococcal spp, tularemiaParasitic: ToxoplasmosisViralFungalSarcoidosisMalignancy: lymphoma, sarcoma, carcinoma
7 MDR tuberculosis Defined as resistance to at least INH and rifampin Website: o_htm_tb_2004_343/en/index.htmlThailand: approximately 1-2%CDC suggests Rx for MDR TB if >4% (no data)NTM lymphadenitis, XXNo isolation needed (except working with wound)Determine drug resistance in Thailand – 2% according to Palwatwichai, Apirak (2001) Tuberculosis in Thailand. Respirology 6 (1), doi: / j x
8 Case - 2 March 17, 2004: Started on 4 drug Rx for TB INH, Rifampin, Pyrazinamide, EthambutolApril 9, 2004: Positive culture for TB, later reported as sensitive to all first line drugsRx once daily x 2 weeks, then twice weekly on Tues and Friday
9 Case - 3April 19, 2004 (Dartmouth): Referred for evaluation of poorly responsive tuberculous lymphadenitisHx: Neck still painful, no decrease in sizeNo fever, last night sweats 2 weeks agoPE: AfebrileWeight 105 lbLungs clearTender L supraclavicular area 10 x 10 cm, woody induration, no fluctuanceL arm weakness
12 Questions What is the problem? Other studies? Therapy? DDx is drug resistance, drug dosing, drug absorption, need for drainage. Or, just usual time course of TB adenitis?HIV negative
13 Case - 4April 21: Admitted to Dartmouth- Hitchcock Medical Center for further increase in size of neck massDaily Rx, PZA reduced from 2.0 to 1.2 gm because of nauseaApril 23: Neck aspirate AFB positiveNext steps?
14 Case - 5 April 28, 2004: Prednisone 80 mg/d May 4, 2004: Neck still painful and mass enlargingI & D at 3 sites by ENT: brown pus, clots, AFB posMay 11, 2004: Prednisone D/Ced, fever and muscle pain developedPrednisone 20 mg/d resumed, fever clearedMay 14, 2004: Discharged home on 2x weekly Rx
15 Case - 6May 27, 2004: OPD visit. No fevers, still some leg pain, wounds packed daily, less neck pain, 11 lb weight gainJune 25, 2004: L leg swelling, neg US, clinical suspicion of DVT, Rx ASAJuly 27, 2005: Cont’d decrease in neck swelling, weight up 20 lbs, continue prednisone 20 mgCompleted 8 mos total Rx in December 2004
16 Scrofula Scrofula = mycobacterial lymphadenitis King’s Evil: Medieval term, “cured” by touch of the kingHistorical: common in Europe in 19th century (24% of children had evidence of current or past infection)Latin for swelling of glands (diminuitive of sow).
17 Copperplate engraving by André Du Laurens ( ), an anatomist and Paris court physician, showing King Henry IV of France touching a number of sufferers who are gathered about him in a circle. Legend of the original plate: Des mirabili strumas sanandi vi solis Galliae regibus christianissimis divinitus concessa liber unus. Paris: Apud Marcum Orry, 1609
18 Scrofula Etiology M. tuberculosis (MTB) M. bovis (MB) Non-tuberculous mycobacteria (NTM)Developing countries: MTB> MB>>>NTMDeveloped countries: NTM>>MTB>MBMTB all human. MB from cow’s milk. Bovis was the classic cause before widespread pasteruization of milk
19 Lymphadenitis due to MTB Age most common, F: M ratio is 2:1Ethnic: esp Asian (80%), Indian; also African, Af-Am, Hispanic, Native American3-5% of US TB casesClinical settingsPrimary TB (children)Reactivation TB (adults)HIVIRIS (HIV)Previously predominantly a disease of children (still true in endemic countries). Males dominate in pulmonary TB, females in scrofula. As many as 40% of AIDS pts with TB have lymphadenitis. Immunologic immaturity seems to be a common theme.
20 Lymphadenitis due to MTB Nodes: usu multiple nodes, jugular, posterior triangle, supraclavicularPathophysiology: systemic disseminationSymptoms: weeks to months, fever, wt loss, fatigue, nt sweats in 20-50%Chest x-ray: 30% have findingsTuberculin skin test: 70-90% positiveDoes MB pathophys differ? Wide variation in reports of abnl CXR prob depends on pathophys.
21 Subclinical TB in HIV: Tanzania HIV positive ambulatory patients with CD4>200 screened for a TB vaccine trial in TanzaniaAmong 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% adenopathyImplicationsNeed for better diagnosticsInappropriate INH for latent TB that is really early active TB-Mtei, von Reyn 2003
23 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 reconstitutionAlso 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 loadSmears pos in 4/6, culture pos in 2/6Management: distinguish treatment failure, continue TB Rx, NSIADs for mild Sx, steroids for severe SxMost cases resolve within a few weeks-Navas, 2002Flare of clinical symptoms that had previous improved after initiation of TB Rx. Study done in Madrid. Other feature can be swelling of CNS lesions,
24 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 tractsCulture: positive in 35%Culture pos highest if necrosis.
25 Lymphadenitis due to MTB - Rx Standard 4 drug chemotherapySlow response: common for enlargement of nodes or new nodes on Rx, cultures usu negativeSurgical drainage: for painful lesions or very slow response on chemoRxCulture pos highest if necrosis. Neg cultures suggest that the 15% or so who seem to progress prob have immunologic basis.
26 Lymphadenitis due to NTM Clinical: indolent lymphadenitis in healthy children age 1-5 usu due to M. avium complexNodes: upper cervical, salivary area nodesRisk 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 candidatesIncidence: rising in the United States, increased in Sweden with decreased BCG useMAC cervical adenitis in healthy children occurs during the same age that Ab studies show many children are first encountering the organism. This occurs from age 1-5 when children have started to walk, are cutting teeth and live in close proximity to water and soil.
28 Childhood adenitis: Cleveland, US These are data frmo Dr. Wolinsky on cases of MAC cervical adenitis by 3 year interval among children in Cleveland. There was clearly a sharp increase around 1980 as disease due to scrofulacem was falling. Although the incidence of TB was falling progressively at the same time and might mean there was less cross protective immunity this would not explain the rather sudden increase in 1980.[wolinsky: 2x more common for onset in winter or spring than summer or fall][Pang: western Australia: MAC 74%, scrof 20, TB 4%][Trnka, Czech: 4/100,000 children MAC adenitis, higher in those without BCG][Kuth, Aachen, Germany: increse starting in 1990][John Grange: in crease in south east England starting 1980]-Wolinsky. Clin Infect Dis 1995;20:
29 Summary - ScrofulaCase presentation: slowly resolving drug sensitive MTB lymphadenitis in a Thai woman, Rx required 8 mos chemo and surgical drainageUsu demographics: F>M, esp Asian, age 20-30Other clinical settings: HIV, IRIS, primary infectionMost adult cases in US due to MTB, childhood cases due to NTMRx for childhood NTM is usually surgery