mycobacterium avium intracellulare complex :: Article CreatorNon-tuberculous Mycobacteria
The author reported a case of mycobacterial infection, which was diagnosed after a lengthy process.
However, the case is actually not one of tuberculosis in the stricter sense: the confirmed species—Mycobacterium avium intracellulare complex—belongs to the group of non-tuberculous mycobacteria. These are often found in the environment and, in cultures, are possibly only contaminants. However, in this case the diagnosis was firmly established following the criteria of the American Thoracic Society (ATS) – the specimens came from otherwise sterile body fluids (1).
Microscopy using different staining methods, as mentioned in the article, is less relevant than cultures and PCR for confirming a diagnosis, since microscopy has lower sensitivity and, in contrast to the other methods, cannot differentiate between species (2). It therefore needs to be emphasized that the diagnostic mistake in the case report consisted mainly in not doing culture and PCR.
Non-tuberculous mycobacteria—such as the described species—display sensitivities to anti-mycobacterial chemotherapy different from Mycobacterium tuberculosis complex. After resistance testing, recommended initial treatment should therefore consist of a combination of clarithromycin, ethambutol, and, if required, rifabutin. By contrast to the treatment described in the article, however, isoniazid is not the treatment of choice (3).DOI: 10.3238/arztebl.2010.0147b
Dr. Med. Norbert HeinrichPD Dr. Med. Michael HoelscherAbteilung für Infektions- und TropenmedizinKlinikum der LMULeopoldstr. 580802 München, Germanyheinrich@lrz.Uni-muenchen.De
PD Dr. Rer. Nat. Elvira RichterForschungszentrum BorstelNationales Referenzzentrum fürMykobakterienParkallee 1823845 Borstel, Germany
In Reply
The number of letters underlines the importance of the topic for readers of Deutsches Ärzteblatt.
Several correspondents pointed out—entirely correctly—that infection with Mycobacterium avium intracellulare, the causative agent of avian tuberculosis, is not a typical from of TB in humans. By contrast to infection with M tuberculosis, no person to person spread exists, nor is the disease notifiable.
For the clinical course, however—and that is the crux of the matter here—no difference exists. Infection of humans with avian TB (M avium) is found almost exclusively in patients with HIV at a late stage of illness and affects mainly the lungs. The clinical presentation in the case report patient was therefore untypical for infection with M avium intracellulare. The patient was not HIV positive, and he did not have neoplastic disease, as Dr Kropp or Professor Dr Schulz assumed.
Because of the lacking clinical differentiation between tuberculosis and infection with M avium, the diagnosis of "tuberculosis of the bone" was chosen—among other reasons, to enable better understanding among non-specialist doctors. The diagnosis suggested by Dr Kropp—"disseminated non-tuberculous mycobacteriosis caused by Mycobacterium avium intracellulare complex"—in an atypical case would have created more confusion than understanding. Since the differentiation and treatment decision is always made only after the causative strain has been identified, I do not see the clinical diagnosis of "tuberculosis of the bone" as erroneous or even incorrect in this case, rather in contrast to Dr Schneider. The diagnosis could certainly have been made earlier if the examination had been thorough enough. The specimen taken in the first diagnostic puncture was sent to a pathology laboratory for suspected malignancy, not to a microbiological lab. The process took the wrong direction right from the outset because the wrong clinical -diagnosis had been made.
As Dr Heinrich and Dr Birkenmaier correctly state, the diagnosis could have been made earlier by using PCR and cultures—had these but been considered. Dr Hauer's mention of the interferon-gamma-release assay (IGRA), which is now available, is an important addition.
Although antibiograms are now done routinely in tuberculosis, their reliability for other mycobacteria is not undisputed. Back then, eight years ago, when much of the current knowledge into M avium did not exist, therapy and its duration were decided on the basis of the causative strain.
All the literature citations mentioned in the readers' correspondence were published much later, at a time when more was known about this infection as an opportunistic infection in HIV patients. But even such new insights can protect patients only if the initial diagnosis is correct.
Dr Fischer rightly points out that, on the basis of the histology results alone, without further disease markers or molecular genetic confirmation, a diagnosis of ALL should have not been made under any circumstances, not should the patient have been subjected to chemotherapy, an invasive form of treatment.
My thanks go to Professor Schilling for pointing out the risk of confusion with CRMO (chronic recurrent multifocal osteomyelitis), which is possible because of lymphocellular infiltration and paravertebral soft tissue inflammation. Because of the clinical course, this initial differential diagnosis became increasingly unlikely, since CRMO does not affect the skull and is not accompanied by psoas abscesses. However, the illness of the patient in this case report bore a merely temporary resemblance to CRMO, which is also characterized by a lengthy process until the correct diagnosis is made.DOI: 10.3238/arztebl.2010.0149b
Dr. Med. Alexander HerzogKlinik für Integrative OnkologieKurstr. 16–1863667 Nidda/Bad Salzhausen, Germanyinfo@fachklinikdrherzog.De
Conflict of interest statementThe authors of all contributions declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors.
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