Nontuberculous mycobacterial cervicofacial lymphadenitis in children; diagnostic performance of the Capilia MAC antibody Elisa test and possible portals of entry

NTM are acid fast bacteria that naturally occur in the environment. They are
found in soil, water, food etc. They form a serious threat of generalized
infections in immunocompromised people. Remarkably, NTM are also a common cause
for (sub)chronic cervicofacial lymphadenitis in otherwise healthy children aged
between 1-5 years. The reported incidence is 0,6-4,5 per 100.000 children below
4 years of age. Children with NTM cervicofacial lymphadenitis generally present
without any symptoms of fever, malaise or fatigue. The clinical course of the
disease is characteristic; at first, a painless mass presents with visible
increase of vascularity. Then, the mass becomes fluctuant. After that,
significant skin changes may cause a violaceous aspect of the lesion and the
skin becomes *parchment-like*. In the last phase, the lesion breaks through the
skin and fistualizes causing a draining wound. Ultrasonographically, all
infected lymph nodes are hypoechoic, often with central necrosis, nodal matting
and adjacent soft tissue oedema. The submandibular lymph node is the most
affected lymph node station.
Lindeboom et al. have shown, in a randomized controlled trial, that surgical
excision is considered to be the most effective treatment compared to wait and
see therapy and antibiotic therapy. Excision of the infected lymph nodes is
considered to be the standard treatment for children with NTM cervicofacial
lymphadenitis with a mean cure rate of 98%. Damage to the mandibular branch of
the facial nerve and excessive scarring are possible complications of this
treatment. The risk of facial paralysis depends on the proximity of the lesion
to the facial nerve and the skills of the surgical team. Permanent facial nerve
damage occurs in approximately 2% of the cases. Other treatment options are
antibiotic therapy or wait and see therapy. However, these therapies have lower
cure rates than surgical treatment.

Diagnosing NTM cervicofacial lymphadenitis is difficult. Definitive diagnosis
requires a positive culture or polymerase chain reaction (PCR) result. However,
these diagnostic procedures must be performed on infected lymph node material.
The only way to obtain this material is by excision of the infected lymph nodes
or by aspirating fine needle specimens. Both procedures are generally performed
under general anesthesia in children. A non-invasive pre-operative diagnostic
test is desired for NTM cervicofacial lymphadenitis to overcome this burden.
The Capilia mac antibody Elisa* test is an in-vitro diagnostic test, which is
developed to determine the levels of serum IgA to the glycopeptidolipid core of
MAC
in serum samples.

It is still largely unknown in which way NTM enter the body. In the literature
it is suggested that direct exposure to the mucosa during eruption be of
importance, concluding that the oral cavity, nose and oropharynx might play a
role as the portal of entry. There is no evidence of another possible portal of
entry and no study has yet assessed the overall oral microbial composition
(microbiome) in this group of patients. In this study, it is hypothesized that
NTM could be found in the oral cavity, nose or oropharynx of patients with
nontuberculous cervicofacial lymphadenitis. An aberrant microbiome could
indicate an increased sensitivity to opportunistic infections.

This study intends to investigate the diagnostic potential of the Capilia mac
antibody Elisa test in children with a clinical suspicion of NTM cervicofacial
lymphadenitis.
Moreover, this study aims at investigating whether NTM possibly access the body
through the oral cavity, nose or oropharynx and if the patients carry an
aberrant oral microbiome. Thus, the study will provide more insight regarding
the pathophysiology of NTM cervicofacial lymphadenitis.

Prospective clinical observational study. Swabs of the tongue, tonsils, gingiva
and nose are taken from patients with suspected NTM cervicofacial
lymphadenitis. Moreover, 6mL blood samples are taken. All procedures are
performed during surgery, which is the current best treatment for patients with
a high clinical suspicion of NTM cervicofacial lymphadenitis. Real-time PCR and
culture are performed on the material obtained by the swabs to confirm the
possible presence of the NTM. To calculate diagnostic test accuracy values, the
results of the Capilia mac antibody Elisa will be compared with the results of
the reference standard being PCR and culture.

The additional risk of the study is small, as it is an abservational study.

Due to the fact that NTM cervicofacial lymphadenitis only occurs in minors, it
is not possible to carry out the study protocol with another patient
population.