FLEX February 2024

C.F. Roy et al.

International Journal of Pediatric Otorhinolaryngology 166 (2023) 111469

nodal matting and adjacent soft tissue edema [12]. Cross-sectional imaging with computed tomography (CT) or mag netic resonance imaging (MRI) may be beneficial in select cases. Find ings on CT include a central hypodense node with dominant peripheral enhancement. In contrast to acute bacterial suppurative lymphadenitis, there is typically little surrounding fat stranding [12,13]. A minority (17.9%) of IPOG members routinely order a CT neck in cases of sus pected NTM lymphadenitis, and this is done predominantly to rule-out other foci, further characterize the extent of disease and assess the relationship of the affected node to critical surrounding structures if operative management is sought. MRI will similarly show a low-density, rim-enhancing lymphade nopathy which may extend to the skin, with minimal surrounding fat stranding [12,13]. MRI may have better soft tissue definition and avoids ionizing radiation, however it is not readily available in some in stitutions and may require sedation or general anesthesia in young children [14]. Close to one in three (29.4%) surveyed IPOG members routinely order a chest radiograph in cases of suspected NTM lymphadenitis, while another half order it selectively. In the pediatric population, pulmonary NTM infection is more typically associated with cystic fibrosis or an underlying immunodeficiency, but has been reported in rare cases in otherwise healthy infants [15]. A chest radiograph may be helpful in identifying intrathoracic involvement and exploring alterna tive diagnoses such as pulmonary tuberculosis or malignancy [8,16]. 6.1.5. Fine needle aspiration and histopathology A minority of authors (14.3%) routinely obtain a FNA for culture or cytology, while approximately half (46.4%) of surveyed IPOG members reserve it for select cases. If performed, aspirated fluid or purulence may be sent for mycobacterial culture, PCR, acid-fast bacilli (AFB) stains and cytology. A recent study of 41 patients with suspected NTM having undergone FNA for mycobacterial culture reported a sensitivity of 45% [17]. On histopathology, NTM will appear as caseating or necrotizing granulomas, granulomatous inflammation, multinucleated giant cells and microabscesses [17,18]. Cytopathology may similarly reveal distinct granulomas or granulomatous inflammation [17]. Although these features are non-specific and other granulomatous conditions such as tuberculosis remain on the differential, they may help strengthen the diagnosis in the appropriate clinical context. A positive stain for acid-fast bacilli (AFB) may also support the diagnosis of NTM lymphadenitis, although it does not distinguish be tween NTM and M. tuberculosis [19]. Additionally, AFB staining is variable in NTM species, and thus absence of staining does not rule out NTM [19]. Some authors advocate for cautious use of FNA, due to a possible risk of encouraging formation of a cutaneous tract/fistula. The few studies reporting on this potential complication report rates of 5 – 30% [3,17]. A causal link between FNA and the development of a fistulous tract may be difficult to establish as fistulisation can also occur as part of the disease ’ s natural history [3,17]. 6.2. Section 2: Initial management and goals of therapy All IPOG members (100%) agreed the practitioner should discuss the natural history of the disease including its various presentations (lymphadenopathy, violaceous skin discoloration, suppuration and possible sinus tract/fistula formation) and expected time to resolution within 6 – 12 months. The three main therapeutic avenues are observation, surgery, or prolonged antibiotics. Most IPOG members deemed clinical resolution was best achieved with complete surgical excision of the affected node when possible. This is consistent with the literature, specifically a 2015 meta-analysis of almost 2000 children, which reported highest adjusted mean cure rates with complete excision (98%, 95%CI 97 – 99.5%),

Table 1 Diagnostic considerations. Diagnostic considerations in suspected NTM

Select cases

Always

Laboratory investigations • Complete blood count (CBC) with differential 18/28 (64.3%)

9/28 (32.1%)

• C-reactive protein (CRP)

12/28 (42.9%)

10/28 (35.7%) 12/28 (42.9%) 17/28 (60.7%)

• Erythrocyte sedimentation rate (ESR)

9/28 (32.1%) 3/28 (10.7%) 2/28 (7.1%)

• Lactate dehydrogenase (LDH)

• Uric acid

14/28 (50%) 1/24 (4.2%)

Microbiology and virology • Mycobacterial culture and/or PCR of discharge

23/24 (95.8%)

• Mycobacterial culture and/or PCR of aspirate 7/24 (29.2%)

11/24 (45.8%) 19/28 (67.9%) 21/28 (75.0%) 19/28 (67.9%) 18/28 (64.3%) 19/28 (67.9%) 10/28 (35.7%) 21/28 (75.0%) 21/28 (75.0%) 12/24 (50.0%) 13/28 (46.4%)

• Tuberculin skin test

6/28 (21.4%) 2/28 (7.1%) 8/28 (28.6%) 5/28 (17.9%) 3/28 (10.7%)

• Interferon gamma release assay

• Bartonella serology

• Toxoplasmosis serology • Cytomegalovirus serology

Imaging • Neck ultrasound

18/28 (64.3%)

• Neck computed tomography

5/28 (17.9%) 1/28 (3.6%) 7/24 (29.2%)

• Neck magnetic resonance imaging

• Chest X-Ray

Fine needle aspiration • Cytology and culture

4/28 (14.3%)

PCR, Polymerase chain reaction.

susceptibility testing is usually of low clinical relevance, as in vitro sus ceptibility tests for most NTM species do not correlate with in vivo response [3]. PCR testing is now available at most institutions and provides a rapid result with a reported sensitivity of 92% [6]. Most IPOG members recommend ordering tuberculin skin tests (TST) and interferon gamma release assays (IGRA) in select cases. The inter pretation and clinical relevance of these tests largely depends on local epidemiology, Bacille Calmette-Gu ´ erin (BCG) vaccination status and tuberculosis risk factors. Antigens used in the TST cross-react between M. tuberculosis and NTM species, whereas IGRAs are more specific for tuberculosis and use antigenic targets which are not expressed by the majority of NTM species causative of lymphadenitis nor BCG vaccina tion [6]. Therefore, a positive TST in a BCG-unvaccinated, immuno competent child with a negative IGRA is suggestive of NTM [6,9]. An induration of greater than 10 mm or 15 mm (in people with or without tuberculosis risk factors, respectively) to the TST is typically considered a “ positive ” result for tuberculosis as per the Centers for Disease Control and Prevention [10]. However more recent data suggests a 5-mm cut-off may be more appropriate for NTM, with a reported increased sensitivity from 54 to 70% in a study of 180 children with chronic cervicofacial lymphadenitis (with no TB exposure or BCG vaccination) [11]. Bartonella, toxoplasmosis and cytomegalovirus serologies, though not routinely ordered, may be considered if suspected in the appropriate clinical setting. 6.1.4. Radiologic investigations A neck ultrasound is commonly ordered as the primary imaging modality. Sonographic features suggestive of NTM lymphadenitis include hypoechogenicity with intranodal liquefactive/cystic necrosis,

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