Peripheral mycobacterial lymphadenitis (TB, NTM and BCG)

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1 Peripheral mycobacterial lymphadenitis (TB, NTM and BCG) H Simon Schaaf Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa

2 Questions Peripheral mycobacterial lymphadenitis in low-burden TB countries is mainly caused by M. tuberculosis TRUE or FALSE BCG axillary lymphadenitis >3cm in size needs to be treated with antituberculosis drugs TRUE or FALSE

3 Epidemiology of LN-TB Peripheral TB lymphadenitis is the most common form of extrapulmonary TB, especially in TB endemic areas In children, 8-10% of TB cases present with peripheral lymphadenitis caused by M. tuberculosis (endemic countries) In our experience of culture-confirmed TB cases: - 22% of >1700 cases had peripheral LN-TB - 8% of >1700 cases had only LN-TB (+/- 30% of total) - Of these 90-95% were in the neck-region (cervical, submandibular, pre-post auricular & supraclavicular). - Only 1-2% LN-TB was inguinal, 2% axillary and 1% generalised lymphadenopathy.

4 Epidemiology and Aetiology In non-endemic (low burden TB) countries nontuberculous mycobacteria (NTM), especially M. avium complex (MAC) is the most common cause of peripheral lymphadenitis caused by mycobacteria The increase in NTM-associated lymphadenitis in developed countries where BCG vaccination was discontinued suggests that BCG may have a protective effect in development of NTM-related lymphadenitis. Where M. bovis (bovine TB) is not well controlled, M. bovis may cause substantial LN-TB in children M. bovis BCG as adverse effect of BCG is currently the most common cause of mycobacterial axillary lymphadenitis in infants and children < 2years of age (as AE or combination AE/IRIS in HIV-infected children)

5 Peripheral TB lymph node enlargement

6 Pathogenesis Mostly lymphatic spread from a primary focus in the lung or (to lesser extent?) from tonsils/oropharynx. Often the primary focus has resolved by the time LN-TB presents In some cases lymphatic spread may occur from distal skin site implantation of organism (e.g. foot, or as in BCG vaccine adverse effect) Haematogenous spread may lead to rare cases of generalised peripheral lymphadenitis Inguinal lymphadenopathy need to check for psoas abscess and spinal TB TB lymphadenitis usually develops within 6-12 months of primary infection with M. tuberculosis or other mycobacteria

7 Pathogenesis Starts with granuloma formation and lymphoid hyperplasia. This may progress to caseation and necrosis. Usually >1 lymph node involved, although one node may be more prominent. Nodes become matted due to periadenitis. If left untreated, nodes will undergo liquefaction, leading to cold abscess(es). These are fluctuant nodes often with violaceous discolouration of the overlying skin. Spontaneous drainage with sinus formation may follow (scrofuloderma) If still not treated, nodes may come and go, with fluctuation, drainage and scarring over a long period of even years before final (scarred) healing or calcification

8 Fluctuant supraclavicular node (R) and cervical nodes (L) with violaceous discolouration of the overlying skin typical of TB

9 Clinical findings A history of close contact with TB case (50%) Any age group Painless and non-tender swelling of nodes, usually >2x2 cm diameter and often matted. If secondary bacterial infection occurs, then nodes become red, warm and painful not common Lymph nodes initially firm to hard, but may become fluctuant and present with sinus formation and draining pus Usually not responding to antibiotic treatment and no other local cause for lymphadenopthy

10 Diagnosis Important to know your setting (TB vs NTM) and age of child/location of lymph node (BCG). TB adenitis rarely disseminated and >95% cervical region Constitutional symptoms in about 50-60% of cases only Positive TST and CXR changes indicative of TB especially if known contact with TB source case supports M. tuberculosis LN-TB. CXR changes only in 50% of cases In a non-endemic setting and no BCG received, a positive TST could indicate NTM lymphadenitis Confirmation of diagnosis is by bacteriology and/or histology/cytology. Pus can be sent for culture of mycobacteria. FNA is the method of choice for obtaining material for culture and histology/cytology

11 Differential diagnosis of peripheral lymphadenitis Infections Acute suppurative Bacterial Chronic granulomatous Mycobacteria M.tuberculosis, M.bovis, M.bovis BCG, non-tuberculous mycobacteria (NTM), especially M.avium complex (MAC) Fungi Histoplasmosis, Coccidioidomycosis, Actinomycosis Other Brucellosis, Tuleraemia, Toxoplasmosis, Cat scratch disease, Sarcoidosis Reactive hyperplasia Viral Infectious mononucleosis (EBV), HIV, Mumps, CMV

12 Differential diagnosis of peripheral lymphadenitis Malignancy Non-Hodgkin s lymphoma, particularly Burkitt s lymphoma Kaposi s sarcoma Hodgkin s disease, Neuroblastoma, Rhabdomyosarcoma, Histiocytosis X Congenital malformations Branchial, Thyroglossal and/or Dermoid cysts Deep cavernous haemangioma Unknown Reactive hyperplasia of undetermined etiology From: Marais & Graham. Chapter 35. In: Tuberculosis: a comprehensive clinical reference. Eds Schaaf & Zumla. 2009

13 Complications of peripheral LN-TB Draining abscess formation and scarring Lesions can infiltrate bone and nerves and cause compression of airways 4-month-old baby girl HIV-infected. Mother TB: clinic did not offer IPT despite mother s request. Presented facial swelling 7 th CN LMN palsy and infiltration in skull as well as chronic otorrhoea.

14 Complications of peripheral LN-TB Some patients lymph nodes increase in size or new lymph nodes appear during and even after completion of treatment. Most likely paradoxical reaction (type of IRIS) In these cases: - Exclude drug-resistant TB (history of contact, FNA for culture and DST - Exclude other causes such as lymphoma, NTM, histiocytosis - If mycobacterial culture remains negative, continue treatment and could prolong to 9 months - When treatment completed and confirmed as TB and known DST, with new nodes appearing which remains culture-negative: watch and see

15 Case 5-month-old boy, presented with swelling right suprclavicular area not responding to antibiotics Mom (a nurse), no known TB contact. HIV-negative Good weight gain, healthy and happy baby Clinical examination and CXR normal. BCG scar present FNA = M. tb complex Diagnosis? Management?

16 M. bovis BCG lymphadenitis Occurs in both immunocompetent and immunosuppressed infants (and up to 2 years) Complication of BCG vaccination intradermal route Nodes usually ipsilateral axilla, but may spread to supraclavicular nodes and rarely to ant cervical area Usually palpable firm node <3 cm in diameter, but may increase in size, undergo liquefaction, form sinuses and drain pus. Paradoxical IRIS may occur in HIV-infected infants started on ART. Such cases may have massive fluctuating lymph nodes. Lymph nodes usually resolve over MONTHS and may form sinuses which eventually heal, or may calcify

17 Acute suppurative adenitis 3 weeks after HAART and antituberculosis therapy (BCG IRIS) BCG scar R deltoid area and BCG-IRIS of lymph node in the R axilla

18 Mediastinal adenopathy: Distant (pulmonary) BCG disease

19 Diagnosis BCG lymphadenitis Clinical suspicion infant with R axillary or supraclavicular LN May disseminate; rarely with HIV-infected infants starting cart Infants with SCID (severe combined immunodeficiency disease) are at high risk of disseminated BCG disease FNA is method of choice culture identifies M. tuberculosis complex (includes M. bovis BCG). Phenotypic DST methods identified BCG as INH-resistant, but line probe assay (LPA) does not identify INH resistance in BCG (not inha/katg mutation) Do RD1 PCR or MPT64 test to identify species as M. bovis BCG Know the strain of BCG used in your country different BCG strains have different drug resistance patterns. See article: Ritz N. et al. Susceptibility of Mycobacterium bovis BCG vaccine strains to antituberculous antibiotics. Antimicrob Agents Chemother 2009;53(1):

20 Treatment BCG lymphadenitis If <3 cm only observe it will usually resolve If >3 cm If fluctuant and uncomfortable can aspirate pus to relieve pressure, otherwise observe Do not do incision and drainage fistulas form Treatment does not help resistant to PZA and INH (and in some also ethionamide) If very large can do excision of node if HIV-negative, but not in HIV-infected cases, as infiltration occurs into surrounding tissue. Start cart in all HIV-infected infants to prevent dissemination If disseminated BCG disease: Treatment urgent: Highdose INH, RIF, EMB, fluoroquinolone and 2 nd -line injectable for 9-12 months

21 NTM peripheral lymphadenitis Less common in TB endemic areas, but make up the majority of peripheral lympadenitis (up to 90%) in developed, non-tb endemic countries M. avium complex most common cause (up to 80%), then M. scrofulaceum (USA and Australia) and M. malmoense and M. haemophilum in UK, Scandinavia an Northern Europe. LN disease same neck nodes, usually unilateral, slow onset and rarely any systemic symptoms or other organ involvement

22 Management of NTM LN disease Different resistance patterns for different NTMs, but in vitro DST for these mycobacteria not reliable and difficult to obtain Preferred management in most cases is surgical excision if possible curative in 95% cases Some experts recommend wait and see management If treatment needed, new macrolide-based regimen, together with rifampicin/rifabutin and ethambutol. Treatment should continue for 9-12 months