An epidemiological survey showed that the rate of NTM strain isolation was up to 22.9% in 2010 in China [7]. The clinical manifestations of NTM diseases include respiratory tract infections, disseminated infections, skin and soft tissue infections, lymphadenitis, ocular infections, and so on [8].
Skin and soft tissue infections (SSTIs) caused by NTM are underrecognized, due to their wide spectrum of clinical presentations and histopathological findings that are often nonspecific [9, 10]. The manifestation of skin disease presents with nodules, subcutaneous abscesses, pustules, ulcers, or combinations thereof [4]. The patient in our case was presented with the manifestation of nodules, ulcers.
Multi-disciplinary collaboration is necessary for diagnosis, including the clinician, the histopathologist, the microbiologist, and infectious disease specialists [4, 10]. In this case, the patient developed a right forehead mass with fever, and the wound did not heal after the mass resection. The broad-spectrum antibiotic treatment was not effective. Histopathological findings showed purulent inflammation with infiltration of lymphocytes and neutrophils. Finally, the right frontal skin biopsy tissue was cultured nontuberculous mycobacteria, so the diagnosis of the nontuberculous mycobacterial disease was established. Culture is still the gold standard, because of limited sensitivity and specificity of symptoms, radiology, and direct microscopy of clinical samples [4].
Disseminated NTM diseases present as two distinct clinical syndromes [4]. The patient’s head CT showed bone destruction in the corresponding site of the lesion. Chest CT scan showed irregular bone destruction in the sternum stem and bilateral clavicle sternum, bone changes in the sternum and cervical vertebrae. Thus NTM bone disease was not excluded. The corresponding bone tissue NTM cultural examination is required. This patient could have disseminated NTM disease, but the diagnosis of disseminated NTM disease requires blood or bone marrow culture positive. Currently, positive evidence for blood or bone marrow culture was absent.
A variety of modalities including tissue culture and polymerase chain reaction (PCR) assays are crucial in order to identify the organism [10]. Reviewing the case, we re-stained the skin tissue which was excised on April 3, 2018 with acid-fast staining, and the results showed positive (see Fig. 5). Then the Mycobacterium avium (M. avium) was identified by PCR. Owing to the uncertainty of manual operation and sampling, we consider that acid-fast staining of the tissue slices was related to the content of tissue samples and the thickness of slices, so there is a certain rate of missed diagnosis.
M. avium is one of the important pathogens in disseminated disease, whereas M. intracellular is one of the common respiratory pathogen [11]. The disseminated NTM disease mainly occurred in immunocompromised patients, especially in HIV-infected patients. The patient in our case was previously healthy and HIV negative and her CD4/CD8 lymphocyte count was normal. However, we tested the patient for IFN-γ autoantibodies and the result was positive.
Neutralizing anti–interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency similar to advanced HIV infection [12]. High titers of IFN-γ autoantibodies are mainly found in patients with the disseminated non-tuberculous mycobacterial disease and are more common in East Asian women who have not been treated with exogenous interferon gamma [13]. IFN-γ autoantibodies are evidence of acquired immunodeficiency that should be examined in cases of unexplained disseminated NTM infections in Asian-born persons [14]. In our case, the patient developed an NTM infection without a history of immunodeficiency and other chronic diseases, but IFN-γ autoantibodies proved to be positive. Hence acquired immunodeficiency should be considered, such as adult-onset immunodeficiency syndrome.
Treatment can be challenging, as it can be dependent on multiple factors, including the causative organism, the patient’s immunological status, and the extent of disease involvement [10]. The optimal regimen against disseminated MAC is clarithromycin, ethambutol, +/−rifabutin, whether a three-drug regimen alone in this setting would be adequate is not known. The optimal duration of treatment is also unknown, but 6 to 12 months of chemotherapy is usually recommended [11, 15]. Specific treatment for IFN-γ autoantibodies associated NTM infection is not codified and required prolonged, multiple-drug regimens. Using immunomodulation strategies is still debated, and long-term suppressive treatment should be taken into account for persisting high levels of neutralizing antibodies [14].
According to the culture results and drug susceptibility test, clarithromycin, ethambutol, protionamide, amoxicillin-clavulanate potassium regimen were given to treat NTM infection for our patient. One month later, the patient’s right forehead wound gradually healed and there was no new rash.
In summary, chronic Mycobacterium avium skin and soft tissue infection complicated with scalp osteomyelitis possibly secondary to anti-interferon-γ autoantibody formation. This case underscores the need for clinicians to be aware of the potential for NTM infection when a patient presenting with unexplained rashes, poor efficacy to medical therapy and surgery. When NTM infection is detected in an immunocompetent patient, IFN-γ autoantibodies–associated immunodeficiency should be considered.