The management of non-tuberculous cervicofacial lymphadenitis in children: A systematic review and meta-analysis

doi:10.1016/j.jinf.2015.02.010

Journal of Infection

Volume 71, Issue 1, July 2015, Pages 9-18

https://doi.org/10.1016/j.jinf.2015.02.010 Get rights and content

Highlights

•
In children, non-tuberculous mycobacterial infections mainly cause lymphadenitis.
•
We did a meta-analysis to determine the optimal management of NTM lymphadenitis.
•
Complete excision has the highest cure rates but can cause facial nerve palsy.
•
Treatment with antibiotics or no intervention is associated with slow resolution.
•
Individualised management based on the location and extent of disease is recommended.

Summary

Objectives

Cervicofacial lymphadenitis is the most common manifestation of infection with non-tuberculous mycobacteria (NTM) in immunocompetent children. Although complete excision is considered standard management, the optimal treatment remains controversial. This study reviews the evidence for different management options for NTM lymphadenitis.

Methods

A systematic literature review and meta-analysis were performed including 1951 children from sixty publications. Generalised linear mixed model regressions were used to compare treatment modalities.

Results

The adjusted mean cure rate was 98% (95% CI 97.0–99.5%) for complete excision, 73.1% (95% CI 49.6–88.3%) for anti-mycobacterial antibiotics, and 70.4% (95% CI 49.6–88.3%) for ‘no intervention’. Compared to ‘no intervention’, only complete excision was significantly associated with cure (OR 33.1; 95% CI 10.8–102.9; p < 0.001). Complete excision was associated with a 10% risk of facial nerve palsy (2% permanent). ‘No intervention’ was associated with delayed resolution.

Conclusions

Complete excision is associated with the highest cure rate in NTM cervicofacial lymphadenitis, but also had the highest risk of facial nerve palsy. In the absence of large, well-designed RCTs, the choice between surgical excision, anti-mycobacterial antibiotics and ‘no intervention’ should be based on the location and extent of the disease, and acceptability of prolonged time to resolution.

Section snippets

Background

Non-tuberculous mycobacteria (NTM) are ubiquitous bacterial organisms found in water, soil and other environmental sites. Although more than 100 different species have been identified, the majority of human NTM disease is caused by fewer than 10 species.¹ In immunocompetent individuals NTM most frequently cause pulmonary infection, lymphadenitis, or skin and soft tissue infections.²

In children, NTM lymphadenitis is the most common manifestation with the cervicofacial region predominantly being

Search strategy

A systematic literature review was performed using Medline, EMBASE and Web of Science (1950–December 2013) using the search terms: (non-tuberculous OR atypical mycobacteria(l)) AND (lymphadenitis OR cervical) AND (treatment OR management). References were hand-searched for additional publications. Criteria for inclusion of publications were: (i) immunocompetent children, (ii) cervicofacial lymphadenitis and (iii) sufficiently detailed description of diagnostic criteria including at least number

Results

The results of the search and selection process are summarised in (Fig. 1). A total of 60 publications were included in the review, comprising three randomised controlled trials (RCTs), four prospective cohort studies, 38 retrospective cohort studies and 15 case reports. The risk of bias in the RCTs is summarised in Table 1.

Discussion

The current evidence for the optimal management of NTM cervicofacial lymphadenitis is limited, as there are only three RCTs, including a total of 200 patients.18, 27, 28 All three RCTs were done in the same centre in the Netherlands, which may limit the generalisability of the results. Ours is the first systematic literature review and meta-analysis of the treatment of NTM cervicofacial lymphadenitis, and includes data from almost 2000 children.

Complete excision was the most frequently reported

Conflict of interest

None declared.

The following references can be found in the supplementary data associated with this paper

40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78.

Acknowledgement

We thank Dr. Leticia Grize from the Biostatistics Unit of the Department of Epidemiology and Public Health at the Swiss Tropical and Public Health Institute in Basel for performing all statistical analysis. NR was supported by grants from the University of Basel (DMS2219) and the Rozalia Foundation. MT was supported by a UK National Institute for Health Research (NIHR) Clinical Lectureship, the NIHR Respiratory Biomedical Research Unit Southampton, and a grant provided by the UK Technology

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Non-tuberculous mycobacteria (NTM) represents an important etiology of cervicofacial lymphadenitis (CFL) and skin/soft tissue infections in children. It can also affect the salivary glands, including the parotid gland, which is unique due to the presence of intra-salivary lymph nodes. There are no established guidelines for treatment of NTM CFL. NTM lymphadenitis was historically surgically treated; recently the literature supports initial medical treatment. Treatment decisions have been dependent on the extent of disease, preference of providers, and risk of surgical complications. The goal is to report our experience in surgical outcomes of NTM CFL with involvement of the parotid gland after pre-operative medical management.
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The management of non-tuberculous cervicofacial lymphadenitis in children: A systematic review and meta-analysis

Highlights

Summary

Objectives

Methods

Results

Conclusions

Section snippets

Background

Search strategy

Results

Discussion

Conflict of interest

The following references can be found in the supplementary data associated with this paper

Acknowledgement

Am J Otolaryngol

J Pediatr

Oral Surg Oral Med Oral Pathol Oral Radiol Endod

Br J Oral Maxillofac Surg

J Pediatr

Int J Pediatr Otorhinolaryngol

J Oral Maxillofac Surg

Int J Pediatr Otorhinolaryngol

An Pediatr (Barc)

Infect Dis Clin North Am

Tuber Lung Dis

Otolaryngol Head Neck Surg

J Pediatr Surg

J Oral Maxillofac Surg

Tuber Lung Dis

Br J Oral Maxillofac Surg

Lancet

Mycobacterium species, non-tuberculosis

Diagnosis of nontuberculous mycobacterial infections

Semin Respir Crit Care Med

Nontuberculous mycobacterial infection in children: a prospective national study

Pediatr Infect Dis J

Nontuberculous mycobacterial infection in children: a 2-year prospective surveillance study in the Netherlands

Clin Infect Dis

Incidence rate of nontuberculous mycobacterial disease in immunocompetent children: a prospective nationwide surveillance study in Germany

Pediatr Infect Dis J

Mycobacterium avium lymphadenopathy among children, Sweden

Emerg Infect Dis

Management of nontuberculous mycobacteria-induced cervical lymphadenitis with observation alone

Pediatr Infect Dis J

Mycobacterial lymphadenitis in children: a prospective study of 105 nontuberculous cases with long-term follow-up

Clin Infect Dis

Nontuberculous mycobacterial lymphadenitis in children

Pediatr Infect Dis J

Antibiotic therapy for nontuberculous mycobacterial cervicofacial lymphadenitis

Laryngoscope

Successful treatment of cervical lymphadenitis caused by mycobacteria other than tuberculosis with rifabutin, clarithromycin and protionamide

Monatsschr Kinderheilkd

Cervical lymphadenitis caused by nontuberculous mycobacteria in immunocompetent children: clinical and therapeutic experience

Head Neck

Conservative wait-and-see therapy versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children

Clin Infect Dis

Non-tuberculous mycobacterial cervical lymphadenopathy

J Paediatr Child Health

Real-time PCR assay using fine-needle aspirates and tissue biopsy specimens for rapid diagnosis of mycobacterial lymphadenitis in children

J Clin Microbiol

Commentary: The natural history of nontuberculous mycobacterial cervical adenitis

Pediatr Infect Dis J

Individual patient- versus group-level data meta-regressions for the investigation of treatment effect modifiers: ecological bias rears its ugly head

Stat Med

Meta-analysis of multitreatment studies

Med Decis Making

Oxford centre for evidence-based medicine – levels of evidence

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

Br Med J

Surgical excision versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children: a multicenter, randomized, controlled trial

Clin Infect Dis

Nontuberculous mycobacterial cervical adenitis: a ten-year retrospective review

Laryngoscope