Contributed by Vandana Baloda, MD & Tung Phan, MD, PhD, D (ABMM)RESULT
POSITIVE for MYCOBACTERIUM AVIUM COMPLEX by DNA Probe
NEGATIVE for MYCOBACTERIUM TUBERCULOSIS COMPLEX by DNA Probe
DIAGNOSIS
Nontuberculous Mycobacterium Lymphadenitis (MAI)
DISCUSSION
Nontuberculous mycobacteria (NTM) are acid-fast bacteria other than Mycobacterium tuberculosis (MTB) [1]. They are widespread and can be isolated from the environmental sources including water, soil, food products, and animals [1,2]. NTM pathogens are classified as rapidly growing or slowly growing . Rapidly growing species grow within seven days and include M. fortuitum, M. abscessus, and M. chelonae. Slowly growing species require several weeks to grow and include M. avium complex, M. marinum, and M. kansasii. NTM can cause a broad range of infections that vary depending on the particular NTM species and the host. In children, NTM cause four main clinical syndromes: lymphadenitis, skin and soft tissue infection, pulmonary disease (predominantly in children with underlying pulmonary conditions), and disseminated disease (predominantly in children with immune compromise) [3].
Non-tuberculous mycobacterial lymphadenitis is due to infection by the atypical mycobacteria, most often M. avium complex (MAC). Atypical mycobacterial infection is the most common cause of chronic lymphadenitis among previously healthy children; in some developing countries, however, tuberculous lymphadenitis is more prevalent than atypical mycobacterial lymphadenitis. The annual incidence is estimated to be 1.2 to 2.1 cases per 100,000 persons, although the incidence appears to have increased in recent years.[4-8]
Patients present with firm, nontender cervical lymphadenopathy that is typically unilateral. In general, constitutional symptoms are absent. Lymph nodes other than those from the cervical area are rarely affected. The mycobacteria are believed to gain access to the patient via the oropharynx, skin, or conjunctiva; involved lymph nodes correspond to those with lymphatic drainage from these sites [6]. Over time, necrosis develops within the infected nodes, and the lymph nodes become fluctuant. Discoloration of the overlying skin and sinus tracts may develop. The PPD test is typically negative or only weakly positive, and the chest radiograph is typically normal. Patients have enlarged, sometimes matted lymph nodes with necrotizing and non-necrotizing granulomas, often with Langhans-type giant cells [6].
Laboratory diagnosis can be established by special stains for microorganisms and culture. All mycobacteria share the characteristic of "acid-fastness," i.e, after staining with carbol-fuchsin or auramine-rhodamine, they do not decolorize with acidified alcohol. Thus, the common term acid-fast bacilli (AFB) are essentially synonymous with mycobacteria [9]. Confirmation of the presence or absence of mycobacteria in clinical specimens has traditionally required culture, because of the relative insensitivity of direct microscopy. In general, clinical specimens that are normally sterile, such as blood, cerebrospinal fluid, or serous fluids, can be inoculated directly onto media. In comparison, nonsterile specimens, such as sputum or pus, must be chemically decontaminated first in order to eliminate common bacteria and fungi that would overwhelm the culture. However, decontamination procedures may inhibit the growth of mycobacteria, especially NTM, as well. Clinical specimens for mycobacterial cultures should be inoculated onto one or more solid media Lowenstein-Jensen media and into a liquid medium such as Mycobacteria growth indicator tube [MGIT] broth. Growth of visible colonies on solid media typically requires two to four weeks generally at 35 to 37°C for slowly growing NTM and 30°C for rapidly growing NTM and M. marinum. Primary cultures in modern liquid media, such as the radiometric BACTEC system, usually produce results within 10 to 14 days. However, this method is not 100 percent sensitive; as a result, it supplements but does not replace traditional solid media. Traditional methods of speciating mycobacterial isolates were based upon growth characteristics on solid media and subsequent biochemical tests, requiring additional weeks for subcultures. These time-consuming methods were replaced with more rapid techniques, including specific nucleic acid probes, which are now available for the most common isolates (M. tuberculosis complex, M. kansasii, M. avium complex, and M. gordonae), and HPLC, which evaluates mycolic acid patterns in AFB smear-positive sputum samples (M. tuberculosis and MAC) and in primary positive cultures and permits identification of some species within hours.
Other newer techniques, which include polymerase chain reaction-restriction length polymorphism analysis (PRA), 16S ribosomal DNA sequencing, multi-gene sequencing, and whole genomic sequencing, also allow NTM to be identified and speciated more reliably and rapidly from clinical specimens [9].
The differential diagnosis of nontuberculous mycobacterial (NTM) lymphadenitis includes other infectious causes of unilateral lymphadenitis (Staphylococcus aureus, Streptococcus pyogenes, Bartonella henselae, M. tuberculosis, viruses, Toxoplasma sp., etc.), benign cysts, and malignancy [4,6]. Historical examination and laboratory findings (blood counts, erythrocyte sedimentation rate, serology, etc.) may be helpful in differentiating NTM lymphadenitis from these conditions. It is important to distinguish it from MTB from NTM as it has different public health and treatment implications. Culture is necessary for a definitive diagnosis. Certain features that are more suggestive of NTM include: younger age (preschool), lack of risk factors for tuberculosis, including being born in a country with low prevalence of M. tuberculosis, normal chest radiograph, negative tuberculin skin testing (TST) results in family members, negative interferon-gamma release assay, ill-defined (non-palisading), irregular, serpiginous, or sarcoid granulomas, polymorphonuclear leukocytes in center of areas of necrosis rather than diffusely scattered, lack of significant caseation and microabscesses [4, 6].
Management of NTM includes surgical and /or antimycobacterial therapy [6, 7]. Surgical excision without antimicrobial therapy is the initial intervention if excision can be performed safely. Antibiotics do not typically influence the course of the disease. Surgical excision of the abnormal lymph nodes is effective therapy and is associated with a very low rate of recurrence. Antimycobacterial therapy for NTM includes macrolide (clarithromycin) and rifabutin for at least 12 weeks [6, 7].
In conclusion, NTM should be suspected in young children (<5 years) with subacute/chronic (i.e, >3 weeks), unilateral, nontender, cervicofacial lymphadenitis that fails to improve or worsens despite antibiotic. Also, it is particularly important to distinguish between NTM and M. tuberculosis lymphadenitis because it has different public health and treatment implications.
REFERENCES
Contributed by Vandana Baloda, MD & Tung Phan, MD, PhD, D (ABMM)
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