REVIEW

CURRENT
OPINION Management of cervicofacial nontuberculous
lymphadenitis in children
John E. McClay a and Carla Garcia b

Purpose of review
To review the body of literature on the treatment options for nontuberculous cervicofacial lymphadenitis in
children, focusing on the most recent reports describing outcomes utilizing either observation alone,
medical therapy or various forms of surgical intervention.
Recent findings
Large studies have defined the time course of the disease and the safety and efficacy in treating
nontuberculosis cervicofacial lymphadenitis with a wait-and-see approach.
Summary
Nontuberculosis cervicofacial lymphadenitis is a disease with several stages that provides for various
treatment options. All treatment regimens – wait-and-see approach, medical therapy, and surgical
excision – have their risks and benefits. The current body of literature allows the otolaryngologist an
assortment of treatment choices that permits him to tailor the treatment with an individualized approach
for each family’s preferences.
Keywords
cervical lymphadenitis in children, cervicofacial lymphadenitis in children, macrolide therapy,
nontuberculous mycobacterium, wait-and-see-approach

INTRODUCTION
Nontuberculous Mycobacterium species (NTM) are a
common cause of lymphadenitis in young healthy
children, particularly between the ages of 1 and
5 years [1–5]. These mycobacterium species are
ubiquitous in the environment and are found
in animals, soil, milk, and food. Ingestion of
contaminated material leads to infection in the
jugulo-digastric, submandibular, and preauricular
nodal groups in over 90% of cases, as these nodal
groups protect the oral cavity and oropharynx.
Less than 5% of the cases affect intrathoracic nodes
[4,6]. There is no human-to-human transmission of
these species.
The most accepted treatment modality for NTM
lymphadenitis has been and still is complete
excision of the node. However, with the advent of
macrolide antibiotic therapy for these infections,
successful treatment without surgical intervention
has been described. This article will review the
recognized literature describing various medical
and surgical treatment modalities for NTM infec-
tions and will highlight the current literature
defining the natural course of the disease.
EPIDEMIOLOGY
There is certain geographic distribution of NTM
species all over the world. In the United States,
cervicofacial NTM is more often seen in the
midwestern and southwestern parts of the country
[7]. Organisms most commonly found in soil
are Mycobacterium (M.) scrofulaceum, M. flavescens,
M. avium complex (MAC, which contains M. avium
and M. intracellulare), M. gastric, M. terrae, M. fortu-
itum, and M. chelonae. In addition to these, water
also contains M. kansasii, M. marinum, M. gordonae,
and M. xenopi [7].
MAC causes the majority of NTM cases
occurring in the cervicofacial region, accounting
&&
for between 70 and 90% [5,7,8 ,9–12]. Mycobacte-
rium haemophilum, a slow growing bacterium that
a
Frisco ENT for Children, Frisco and bMedical City Dallas, Dallas, Texas,
USA
Correspondence to John E. McClay, MD, Frisco ENT for Children, 11445
Dallas Parkway, Suite 240, Frisco TX 75033, USA. Tel: +1 214 494
4150; e-mail: jtmcclay@aol.com
Curr Opin Otolaryngol Head Neck Surg 2013, 21:581–587
DOI:10.1097/MOO.0000000000000005

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 Pediatric otolaryngology

KEY POINTS

Cervical nontuberculous mycobacterium shows several
stages of disease progression ranging from a palpable
lymph node to a fistulized tract.

The natural course of the disease can result in
resolution of infection without medical or surgical
intervention, with 70% resolved in 6 months, and most
all resolved by 12 months.

In the early stages of the disease, treating NTM
cervical infections with a macrolide with or without a
rifampin for the first 2 months may decrease the time
course of the disease.

Complete surgical excision is still the preferred method
of treatment, but in certain locations, can result in
permanent injury to the facial nerve.
FIGURE 1. Eighteen-month-old girl with three right-sided

There is no role for incision and drainage of the cervicofacial lymph nodes infected with nontuberculous
disease, but incision and curettage can be helpful in
mycobacterium. The preauricular and submental nodes are
selected cases.
in early Stage 1, and the submandibular node has skin
changes and is in late stage 1.

requires lower temperatures and hemin or ferric Symptoms are often present for 4–6 weeks before
ammonium citrate to grow, was not originally the diagnosis of an NTM infection is suspected,
appreciated as a common cause of disease [10]. as routine staphylococcal or streptococcal infections
However, it seems to be responsible for roughly of lymph nodes are more prevalent. When local
15–30% of cervicofacial NTM in recent reports infection spreads, satellite lesions may arise in
&&
[8 ,9]. The remainder is comprised of the other adjacent lymph nodes and skin (Fig. 1) [4].
&&
species, such as M. scrofulaceum [5,7,8 ,9–12]. Other Rarely, a cervical imaging study [computed
species cultured in NTM cervicofacial infections tomography (CT), ultrasonography, or MRI] is
include M. kansasii, M. chelonae, M. fortuitum, needed to delineate the number and size of affected
&&
M. xenopi, and M. simiae [5,7,8 ,9,10]. In northern lymph nodes. CT findings usually consist of ring
and central Europe, however, M. malmoense causes enhancement, minimal inflammatory stranding of
a significant proportion of reported cases of NTM the subcutaneous fat, and no abscess formation in
infections in the cervicofacial region [7]. early stages, with cystic collections and suppuration
in later stages (CT scan of Fig. 4). Calcium deposits
may be seen on plain films [4,11].
CLINICAL PRESENTATION
Lymphadenitis due to NTM infection is character-
ized by an evolving pattern over the time course of
the disease. Left untreated, the infected lymph
nodes progress from a somewhat palpable node to
a fistulized lesion draining purulence and debris.
Penn et al. at Georgetown have divided this
progression into four stages. Stage I often presents
as a well circumscribed painless, firm mass, 1–6 cm
in diameter (average 3.5 cm [4,9]) without pain
or erythema, and with or without adherence to
overlying skin (Fig. 1). Following enlargement, the
lymph node may liquefy becoming fluctuant,
heralding Stage II. Stage III represents the phase
when overlying skin changes occur, with thinning
of the surrounding epidermis and violaceous
discoloration (Fig. 2). In the final stage, Stage IV, FIGURE 2. Five-year-old boy with a left submandibular node
the necrotic collection fistulizes to the skin (Fig. 3). infected at Stage 3.

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 Cervicofacial nontuberculous lymphadenitis McClay and Garcia
FIGURE 3. Same five-year-old boy 4 weeks later with his left
submandibular node progressed to Stage 4 wherein it
fistulized. Note the smaller size node and the scab at the
drainage site.
DIAGNOSIS
Differential diagnosis in these infections mainly
includes lymphadenitis encountered more fre-
quently with staphylococcal or streptococcal infec-
tions, tuberculosis itself, and other granulomatous
diseases. Routine serological tests are usually
normal, with a small portion of patients showing
mild leukocytosis. Specialized blood tests such as the
Interferon gamma release assays (IGRA) may be
useful adjuncts to differentiate between tuberculosis
and NTM adenitis. One IGRA, the Quantiferon-
tuberculousis gold assay, has greater specificity for
tuberculosis as it includes antigens absent in most
NTM infections, with the exception of M. kansasii,
M. marinum, and M. szulgai [7]. A tuberculin skin test
(Tuberculin Skin test or purified protein derivative)
should be obtained and is usually intermediately
reactive (less than 10 mm wheal) or negative
when NTM infection is present compared with
grossly positive reaction (greater than 15 mm wheal
size) in true tuberculosis infections. Different series
report positive indurations in 8–50% of the NTM
infected cases [3,4,11,13–15]. Chest radiographs
are usually normal in NTM infections, but may be
abnormal in children with tuberculosis.
The diagnosis of NTM lymphadenitis is also
based on microbiologic and histopathologic find-
ings. Fine needle aspiration (FNA) of the affected
node can be a valuable diagnostic tool and provides
tissue to help differentiate NTM from other infec-
tions or lesions. Histopathology findings include
microabscesses, ill-defined granulomas, noncaseat-
ing granulomas, and scarce giant cells (Fig. 5).
Cultures can be obtained with FNA and are positive
in about 50–88% of the cases, and positive
stains have been reported from 52 to 92% [12,15].
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Currently, with the advent of molecular testing,
detection has increased, and more species have been
identified, with a sensitivity of at least 84%.
TREATMENT
Several treatment modalities have been used over
the last four to five decades in attempts to control
and cure these infections. The most accepted treat-
ment modality for NTM lymphadenitis both past
and present is complete excision of the node or
nodes. Cure rates are excellent, with successful treat-
ment reported in the range of 92–98% in four large
studies of 50, 55, 57, and 82 children [11,12,16,17].
Incision and drainage (I&D) on the contrary is
fraught with failure up to 90% of the time. In these
same large series that report excellent results with
complete excision, successful treatment with I&D is
in the 10–16% range in roughly 95 children com-
bined [11,12,16,17]. A persistent draining fistula was
reported in these failed cases, despite treatment with
adjuvant medical therapy in most. It is important
to note that some of these reports did not use
macrolides or other antituberculosis medications.
Although total excision is thought to be
curative, it is not always advisable. Several factors
may make surgical excision difficult and risky.
Infected skin and subcutaneous tissue resulting in
dermal necrosis can cause disfiguring of normal
anatomy creating a surgical field wherein visualiza-
tion of branches of the facial nerve becomes unclear.
In addition, caseating lymph nodes can adhere to
surrounding structures, including the facial nerve
branches, making identification of the underlying
motor nerves difficult, even when facial nerve
monitoring and intraoperative nerve stimulation
are utilized. Temporary facial nerve weakness has
been reported in 20% of surgical cases, and perma-
nent facial weakness has been described in 2% [18].
In those cases wherein complete excision is
fraught with potential complications, curettage
has been advocated. Both Kennedy and Olson
[18,19] reported complete success in treating
13 and seven patients, respectively, with incision
and curettage, with follow-up of 16–23 months.
Kennedy suggested that curettage is best carried
out when the affected lymph node begins to show
signs of fluctuation. Even surgeons who described
great success with complete surgical excision tech-
niques have utilized and reported success with
curettage for debulking large necrotic lesions [17].
Adjuvant medical therapy was often employed
in these NTM infections when surgical intervention
was utilized. Traditional antibiotics were unsuccess-
ful in helping resolve the infection. However, in the
late 1990s, Hazra, Lindeboom, and Berger et al.
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 Pediatric otolaryngology

FIGURE 4. Three-year old-girl with NTM infection in several large jugulo-digastric chain lymph nodes (a) with CT scan
showing ring enhanced lymph nodes (b) nodes at time of excision (c) and child several months postoperation (d). NTM,
nontuberculous Mycobacterium species.

[3,20,21] reported the effective use of macrolide
antibiotics in two, five, and eight patients,
respectively. Hazra et al. [3] reported 50% success
(five of 10 patients) utilizing medical therapy
with clarithromycin (20–30 mg/kg per day in two
divided doses) and ethambutol (15 mg/kg per
dose once daily) or rifampin (6–20 mg/kg per
day). Two patients received azithromycin rather
than clarithromycin. Berger et al. [21], in a small
prospective study, showed a favorable response in
eight children using clarithromycin (7.5 mg/kg per
dose twice daily) and rifabutin (5 mg/kg per day)
when complete surgical excision was not feasible.
These achievements encouraged the trials of
medical therapy with macrolides for the next
decade.
One of the largest of these studies was reported
by Luong et al. [1] in which 55 children with NTM
cervical adenitis were evaluated. Of the 55 children,
45 underwent a trial of medical therapy prior
to surgical intervention. This usually consisted of
clarithromycin alone (n ¼ 15) or in combination

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 Cervicofacial nontuberculous lymphadenitis McClay and Garcia
FIGURE 5. Excised lymph node showing caseating
granulomas.
(n ¼ 30) with antituberculous therapy, that is
rifampin or ethambutol; or multidrug antituber-
cular therapy. Thirty of 45 (67%) responded well,
without the need of surgical intervention. Even in
the 15 patients who received antibiotic therapy
that still had surgical excision, six of 15 (40%)
were responding well at 2 months of medical
therapy.
Twenty-three of 30 (77%) of these children
that responded to medical therapy alone in the
study by Luong et al. showed regression by 2 months
of therapy. Selecting out the children receiving
macrolide therapy alone, 13 of 15 (87%) children
responded by 2 months of therapy. These numbers
are biased as the children chosen to receive
clarithromycin alone had small lesions and were
diagnosed in Stage 1. However, Luong et al. [1]
did feel like antibiotic therapy interrupted the
natural progression of the disease, resulting in
minimization of the palpable lymph node and/or
prevention of fistulization of the majority treated
infected nodes.
Most of the reports for NTM lymphadenitis
therapies are retrospective descriptions of manage-
ment at one or more institutions. To our knowledge,
only one randomized controlled (un-blinded)
clinical study has been performed, favoring excision
as the preferred method of treatment [5]. Linde-
boom et al. studied 100 children with microbio-
logically proven NTM cervicofacial lymphadenitis
(diagnosed with FNA) that were randomly assigned
to undergo surgical excision or to receive 12 weeks
of antibiotic therapy with clarithromycin (15 mg/kg
in two divided doses) and rifabutin (5 mg/kg once
daily). There were no differences with respect to
mean duration of swelling, location of the adenitis,
and size or stage of the lymph node swelling before
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treatment allocation. The primary end-point was
cure (defined as 75% regression of the swelling, cure
of fistula, and total skin closure without recurrences
for 6 months). The cure rates for surgical excision
were 96%, compared with 66% of medical treat-
ment. About 11% of isolates in the medical treat-
ment arm were resistant to the antibiotics used,
but none of the patients considered to have
treatment failures had resistant bacteria. Surgical
complications were seen in 28% of the 50 patients
treated surgically, with one patient having per-
manent dysfunction of the marginal branch of
the facial nerve.
On the basis of all these reports, if a trial
of medical therapy is entertained, one possible
approach consists of starting on a macrolide alone
if the lesion is small and the disease is encountered
in an early stage. A combination regimen with
a macrolide antibiotic (either azithromycin or
clarithromycin) and a rifamycin (i.e rifampin or
rifabutin), would be utilized in larger lesions at
later stages. In general, oral combination antibiotic
therapy, compared with monotherapy, helps pre-
vent the development of resistance [14]. The length
of antibiotic therapy is not well established; most
of the reports have studied at least 8–12 weeks
of therapy. Luong et al. [1] did show that at least
77% of the medical responders showed improve-
ment or regression of the disease by 2 months
of treatment. Certainly, longer medical regimens
may be required to achieve clinical resolution of
the disease.
Obtaining a culture for the specific Myco-
bacterium species would be optimum and guide
initial and subsequent medical therapy. Although
susceptibility testing for NTM has not been well
standardized, the Clinical and Laboratory Standards
Institute recently defined criteria for antimicrobial
susceptibility testing and established breakpoints
[22]. Specific antibiotic choices for each NTM infec-
tion are listed in Table 1 [22–25].
All this treatment information, however, needs
to be digested in the context of two recent large
series published over the last 5 years evaluating
no treatment at all – the wait-and see-approach.
In 2008, Zeharia et al. [9] published their report
from Israel on 92 children treated conservatively
with watchful waiting from 1990 to 2004. In most
of their cases, the affected lymph nodes under-
went violaceous changes with discharge of purulent
material for 3–8 weeks. Total resolution of the
infection was achieved within 6 months in
71% of patients and within 9–12 months in the
remainder. At the 2-year follow-up, a skin-colored,
flat scar in the region of the drainage was noted.
There were no complications. Then, in 2011,
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 Pediatric otolaryngology

Table 1. Antibiotic choices for nontuberculous mycobacterium species

NTM Antibiotic choices

M. avium complex Treatment of choice is the combination of a macrolide, rifampin/rifabutin, and ethambutol. MAC
(MAC, which contains species are usually susceptible to amikacin. Other antibiotics that may be considered include
M. avium and M. intracellulare) ciprofloxacin (<25% of the isolates being susceptible) and parenteral linezolid (<50% of the
isolates being susceptible) [22]
M. haemophilum Clarithromycin þ rifabutin, may consider adding ciprofloxacin
M. scrofulaceum Clarithromycin þ clofazimine, with or without ethambutol, isoniazid, rifampin, streptomy-
cin þ cycloserine. Scrofulaceum may show in-vitro resistance to isoniazid, rifampin, ethambutol,
pyrazinamide, amikacin, and ciprofloxacin [25]
M. kansasii A macrolide, rifampin/rifabutin, ethambutol, trimethoprim-sulfametoxazole, isoniazid,
ciprofloxacin, linezolid, and amikacin are antibiotics of choice; isolates of M. kansasii should
only be tested for rifampin (if susceptible, will also be susceptible to rifabutin), and
clarithromycin, if resistant to rifampin other antibiotics should be tested
M. chelonae Isolates are susceptible to macrolides, linezolid, tobramycin, ciprofloxacin (about 20%
susceptible), doxycycline (about 20% susceptible), amikacin (about 50% susceptible), and
imipenem (about 60% susceptible) [22]
M. fortuitum Ciprofloxacin, levofloxacin, trimethoprim-sulfametoxazole, linezolid, imipenem, amikacin,
cefoxitin (about 50% susceptible), doxycycline (about 50% susceptible), clarithromycin/
azithromycin (about 20% susceptible); rarely, in cases of pretreatment with quinolones,
isolates of M. fortuitum can become resistant to that class of antibiotics [22]
M. simiae Choices include a macrolide, trimethoprim-sulfametoxazole, amikacin, and moxifloxacin (about
60% susceptible) [22]; a case report showed successful treatment with combination of
clarithromycin, ethambutol, and ciprofloxacin in a child with disseminated infection [23]
M. xenopi Clarithromycin/azithromycin, rifampin/rifabutin, ethambutol, moxifloxacin, amikacin, and
streptomycin [22]

MAC, M. avium complex.

&&
Lindeboom et al. [8 ] from the Netherlands, who
have reported extensively on the diagnosis and
treatment of this disease over the last 15 years,
published a prospective study on a group of children
with advanced stage NTM cervicofacial infections
they did not want to operate on. All children with
enlarged NTM lymphadenitis without skin dis-
coloration were treated with surgical excision. How-
ever, 50 children with NTM infections characterized
by fluctuation of the lymph node and discoloration
of the skin were randomly assigned to receive
either antibiotic therapy (n ¼ 25) with 12 weeks
of clarithromycin and rifabutin or a wait-and-see
(no antibiotics, only monitoring) approach (n ¼ 25).
There was no statistical difference between the
two groups, with the median time for resolution
of disease for the antibiotic group versus the
wait-and-see group totalling 36 versus 40 weeks,
&&
respectively [8 ]. Adverse effects of antibiotic
therapy included gastrointestinal complaints, fever,
and reversible extrinsic tooth discoloration.
CONCLUSION
Cervicofacial NTM infections can present to
otolaryngologists in varying stages, sizes, and sites
in the neck and face. All these factors create unique
concerns in treatment. Even though complete
surgical excision is the treatment of choice, lesions
surrounding the trunk or branches of the facial
nerve at any stage or progression of disease, but
especially in later stages, may increase the risk for
temporary or permanent injury to the associated
nerves. Additionally, large lesions with significant
skin involvement may require resection of a sub-
stantial amount of normal skin and tissue to obtain
optimum closure.
Luckily, the literature published over the last
several years allows for flexibility in treatment
courses. Not only has medical therapy shown
to be successful, but close observation with a
wait-and-see approach also has good results,
even though the time with disease is prolonged.
Counseling the parents of these children who
have cervicofacial NTM infections about the disease
itself, the risk and benefits of all three approaches –
surgery, medical therapy, and the wait-and-see
approach – promotes an open discussion and
realistic expectations about the disease as well as
allowing for individualized care for these children
and families.
Acknowledgements
None.

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 Cervicofacial nontuberculous lymphadenitis McClay and Garcia
Conflicts of interest
There are no conflicts of interest.
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