MEDICINE

Review Article

The Diagnosis and Treatment of Tuberculosis

1 1
Isabelle Suárez* , Sarah Maria Fünger* , Stefan Kröger, Jessica Rademacher,
2 2
Gerd Fätkenheuer* , Jan Rybniker*

T
uberculosis (TB) is one of the ten leading causes
Summary of death worldwide (1). In Germany and other
highly developed countries, however, TB occurs
Background: Around 10 million people worldwide contract tuberculosis every year. relatively seldom and can almost always be treated
According to the World Health Organization (WHO), approximately one-quarter of successfully. The rarity of TB means that not all
the world’s population is latently infected with Mycobacterium tuberculosis. In Ger-
physicians regularly encounter the disease, and the
many, the incidence of tuberculosis was in decline over several decades but rose in
pronounced variability of the symptoms often leads to
2015 to 7.3 new cases per 100 000 persons. In 2018, a total of 5429 new cases
delayed diagnosis. TB is a “medical chameleon,” in
were documented, corresponding to 6.5 new cases per 100 000 persons.
that its manifestations differ widely and almost any
Methods: This article is based on literature retrieved by a selective search in organ may be affected. The trend towards increasing
PubMed and on the authors’ clinical experience. global migration is raising the profile of TB in our
country, to the point where every physician should
Results: Tuberculosis involves the lungs in almost 75% of patients but can generally have basic familiarity with the prevailing recommen-
involve any organ. In Germany, the majority of patients come from high-incidence dations for the diagnosis and treatment of this illness.
countries. If a patient’s differential diagnosis includes tuberculosis, the main tests for This review article describes the clinical presentations
the detection of the pathogen in sputum and tissue samples are culture (the gold and current management of TB, based on a selective
standard), microscopy, and nucleic acid amplification tests. Imaging studies are also survey of publications in PubMed backed up by the
used for diagnosis and follow-up. The standard treatment consists of a combination
authors’ own research and clinical experience.
of isoniazid, rifampicin, ethambutol, and pyrazinamide, followed by a combination of
isoniazid and rifampicin only. Liver damage is one of the more common adverse
Epidemiology
effects of this treatment, arising in 2.4% of patients. Multidrug-resistant tuberculosis,
The World Health Organization (WHO) estimates that
which is rare in Germany (around 100 cases per year), should be treated in special-
1.8 billion people—around one fourth of the global
ized centers.
population—are infected with Mycobacterium tubercu-
Conclusion: Rapid diagnosis and targeted treatment are essential to prevent an losis (2). In 2017, roughly 10 million people contracted
unfavorable course of the disease as well as its transmission to other individuals. TB and 1.6 million died of the disease (1).
In patients presenting with unclear symptoms, tuberculosis should always be In Germany, the incidence of TB decreased from
considered as a differential diagnosis. The diagnosis of latent tuberculosis and the introduction of electronic documentation in 2001
decision-making regarding its treatment are difficult because of the lack of specific up to 2014, when it occurred in 5.6 cases per 100 000
biomarkers and of relevant data from clinical trials. inhabitants. The number of newly diagnosed cases
rose sharply to 7.3 per 100 000 in 2015 (3). A slight
Cite this as:
decrease was noted in 2017 (6.6 cases per 100 000),
Suárez I, Fünger SM, Kröger S, Rademacher J, Fätkenheuer G, Rybniker J:
and the figures for 2018 are practically unaltered
The diagnosis and treatment of tuberculosis. Dtsch Arztebl Int 2019; 116: 729–35.
(5429 cases of TB registered, i.e., 6.5 per 100 000
DOI: 10.3238/arztebl.2019.0729
inhabitants) (4). The trend in numbers of cases docu-
mented was determined largely by changes in mi-
gration and active case finding through screening as
stipulated in §36 of the Protection Against Infection
Act (Infektionsschutzgesetz; IfSG). A large proportion
of the tuberculosis patients in Germany were born in
other countries: 42% in 2001 (5), rising steadily to
1
73% in the latest statistics (6). Particularly in the
* Joint first authors years 2015 (21.5%) and 2016 (16.5%), most of the
2
* Joint last authors TB cases were detected by screening according to
Division of Infectious Diseases, Department of Internal Medicine I, University Hospital Cologne: §36 IfSG. The corresponding figure in 2017 was
Dr. med. Isabelle Suárez, Dr. med. Sarah Maria Fünger, Prof. Dr. med. Gerd Fätkenheuer,
PD Dr. med. Dr. nat. med. Jan Rybniker lower, at 9% (3, 6, 7).
German Center for Infection Research, Cologne–Bonn, Partner Site Cologne:
In 2017, almost three quarters of the cases of TB
Dr. med. Isabelle Suárez, Prof. Dr. med. Gerd Fätkenheuer, PD Dr. med. Dr. nat. med. Jan Rybniker registered in Germany affected the lungs, and four
Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin: fifths of these patients had infectious pulmonary TB
Dr. rer. nat. Stefan Kröger (6). Lymph node Tb accounts for about half of all
Department of Pneumonology, Hanover Medical School: Dr. med. Jessica Rademacher extrapulmonary cases; the rest is accounted for by

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MEDICINE

BOX
of patients, decreasing cellular immunity leads to
reactivation of the LTBI, resulting in postprimary TB
“Red flags” for tuberculosis (TB) (10). Reactivation most commonly occurs within
2 years of primary infection. HIV patients are at very
● TB symptoms high risk of reactivation (10), particularly if their
– Persistent (productive) cough CD4+ T-cell count is low (e1). The risk of TB reacti-
– Hemoptysis vation is therefore around 20 times higher in the case
– Night sweats of untreated HIV infection than for HIV-negative
– Weight loss persons (11). However, the risk of reactivation is also
– Fever increased by other immunosuppressive conditions,
– Abnormal fatigue e.g., diabetes mellitus (e2), terminal kidney failure
– Lymph node swelling (e3), or treatment with inhibitors of tumor necrosis
– Thoracic or abdominal pain factor-alpha (TNF-α) (12).

Clinical presentation of tuberculosis

Latent tuberculosis infection (LTBI)
LTBI is infection with vital, non-replicating TB path-
various other organ manifestations (6). Multidrug- ogens. The infected person has a positive result on
resistant tuberculosis (MDR-TB) continues to immunological testing (e.g., interferon gamma release
account for only a small proportion (3%) of cases in assays; see “Diagnosis” below), but shows no symp-
Germany (6). The subgroup of patients born in the toms of disease. Furthermore, diagnostic tests (at least
countries of the former Soviet Union showed the chest radiography) reveal no sign of active TB. These
highest proportion of MDR-TB cases in 2017 patients are not infectious. In the presence of weakened
(19.3%). For comparison, in the same year the cor- T-cell immunity, however, LTBI can turn into active
responding figure for the subgroup of patients born disease at any time (13). The risk of developing clini-
in Germany was around 1% (6). cally manifest TB is about 5% during the first 18
The prognosis for persons with TB in Germany is months after infection with M. tuberculosis and circa
good overall, with a mortality rate of 1.9% (6). 5% over the remaining life span (14).

Microbiology and pathogenesis Forms of disease

Mycobacterium tuberculosis, the most common TB- Pulmonary tuberculosis
causing pathogen, is a nonmotile, aerobic, rod-shaped The typical symptoms of pulmonary TB include fever,
bacterium. night sweats, abnormal fatigue, productive cough, and
Transmission occurs almost exclusively through hemoptysis. In non-immunocomprised adults the dis-
droplet infection. Whether infection ensues depends ease advances only slowly, in contrast to children and
essentially on: immunocompromised persons, who may experience
● The frequency of contact with a person who has fulminant TB with abrupt onset. Persistence of cough
infectious pulmonary TB for more than 3 weeks should always prompt consider-
● The duration of contact ation of TB (Box).
● The closeness of contact
● The amount and virulence of pathogen transferred Extrapulmonary and disseminated tuberculosis
● The susceptibility of the person exposed (8). In 2017, 1375 (26%) of all TB cases in Germany were
After inhalation, extracellular and intracellular exclusively extrapulmonary (6). Recent data from
bacterial growth takes place preferentially in the well- some industrialized countries show increasing inci-
ventilated upper levels of the lungs, especially in the dence of extrapulmonary manifestations: in some
alveolar macrophages. At 3 to 4 weeks post infection, regions of Spain, 37% of cases of TB detected in 2013
healthy or non-immunocomprised individuals devel- fell into this category (15).
op T-cell immunity, leading to decreased intracellular The clinical symptoms can take many forms and
growth of the bacteria. The bacteria can nevertheless are determined by the specific organ(s) involved.
survive intracellularly—initially without causing Disseminated TB (affecting two or more organ sys-
clinical symptoms. In the course of immune defense tems), previously observed almost exclusively in
mechanisms tuberculous granulomas arise, typically children or in persons with immune suppression, is
with central caseation (9). Especially in children or now increasingly being found in adults with no appar-
immunosuppressed individuals, clinically manifest ent immune defect (16, e4). Most of these patients are
TB may develop shortly after infection. Such cases immigrants from countries with moderate to high TB
are referred to as progressive primary TB. incidence. Various factors such as the language bar-
Most patients, however, develop a latent TB infec- rier and frequent relocation hamper access of asylum
tion (LTBI) accompanied by scarring or calcification seekers and others to the healthcare system, which
of the tuberculous granuloma, which is not always may delay diagnosis and thus facilitate progress of the
visible on diagnostic imaging. In around 5% to 10% disease (16, 18) (e4).

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Diagnosis
The detection of LTBI has to be distinguished from the
diagnosis of active TB. Indirect procedures such as the
interferon-gamma release assays (IGRA) are the modern
standard for diagnosis of LTBI in adults. These assays
detect the secretion of interferon-gamma (IFN-γ) by T

Diagnostic and Interventional Radiology Institute, University Hospital Cologne

lymphocytes, which are stimulated by means of relatively
TB-specific antigens. Prior bacille Calmette–Guérin
(BCG) vaccination usually does not lead to false-positive
results. IGRA are used principally to investigate the
persons who have been in contact with an index patient
who has contagious pulmonary TB. Another indication is
testing for LTBI in advance of administration of drugs to
achieve immunosuppression (see “Preventive treatment”
below). IGRA are not suitable for diagnosis of clinically
manifest TB, because they do not distinguish between
latent TB and active disease.
The principal techniques for diagnosis of active TB
are direct microscopic demonstration of the pathogen, Figure 1: Pulmonary tuberculosis with a large cavity (arrow) in the
upper field of the right lung (chest radiograph, p.a. view)
culture, and nucleic acid amplification tests (NAAT;
generally polymerase chain reaction [PCR]–based
procedures). The sample for testing should be obtained
before the commencement of treatment, and
investigation for M. tuberculosis should be specified
on the request form, as it does not always form part
of the routine program. Open pulmonary tuberculosis
can be excluded if microscopy fails to detect acid-fast

Diagnostic and Interventional Radiology Institute, University Hospital Cologne

rods in samples of sputum collected on three separate
days. Demonstration of M. tuberculosis in culture
also demonstrates infectivity but TB diagnosis by culture
takes several weeks to become positive. Microscopy
of samples of sputum, bronchial secretion, or broncho-
alveolar lavage (BAL) fluid is economical, quick, and
represents a marker for the patient’s infectiousness.
However, its sensitivity is very variable (20% to 80%)
and differs among investigators (19). The specificity of
microscopy is also limited, because it cannot distinguish
M. tuberculosis from nontuberculous mycobacteria
(NTM). At least several days’ culture are required for a
Figure 2: Extrapulmonary manifestation of TB with abscess formation
positive result when fluorescence-based detection sys- around the abdominal aorta (arrow) (abdominal computed tomog-
tems are used, while the growth of visible colonies on raphy, axial section)
solid culture media can take up to 8 weeks. Culture
nevertheless remains the gold standard of TB diagnosis
(20, 21) and is of central importance for resistance test-
ing. NAAT-based methods are characterized by their
swiftness, relatively good sensitivity, and very high spe-
cificity (22). Moreover, many PCR-based methods per- Imaging
mit conclusions regarding resistance to the commonly Biplanar chest radiography remains the standard
used substances to be drawn directly from sputum or method for diagnosis of TB and for monitoring the ef-
other PCR-positive materials, thus enabling early detec- fect of treatment (Figure 1). Computed tomography
tion of monoresistant or multiresistant TB. However, (CT) achieves good results in the assessment of both
comprehensive testing of resistance to all available sub- lymphadenopathy (23) and endobronchial extension
stances, e.g., via whole-genome sequencing of the strain (24) and is superior to chest radiography for evaluation
concerned, requires culture. If extrapulmonary TB is of disease activity (25, 26). Low-dose CT is recom-
suspected, aspirates, biopsy samples, or body fluids mended.
(urine, sperm, stool, cerebrospinal fluid) must also be In primary TB, which is found principally in
investigated using the methods described above. It is children and adolescents, one finds mostly inflamma-
essential to include TB among the differential diagnoses tory infiltrates—similar to lobar pneumonia—accom-
and send material not just for histopathology but also for panied by lymphadenopathy. Around one fourth of
microbiological examination. patients with primary TB have pleural effusion,

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TABLE 1 Resistance to standard drugs

Resistance to at least one substance (INH, EMB, RMP,
Drug treatment of tuberculosis PZA, streptomycin) was recorded for 12% to 14% of
Drug Duration of Dosage Minimum/ patients with TB in Germany between 2013 and 2017;
treatment (mg/kg BW/d) maximum in 3% of cases, multiple resistance (MDR-TB) was
(months) dose (mg) * documented (6). By definition, MDR-TB is present
Isoniazid (INH) 6 5 200/300 whenever resistance at least to INH and RMP is found
Rifampicin (RMP) 6 10 450/600
(20). In patients with monoresistance to RMP or INH, a
fluoroquinolone (moxifloxacin, levofloxacin) can be
Pyrazinamide (PZA) 2 25 1500/2500
used instead. The duration of treatment is then
Ethambutol (EMB) 2 15 800/1600 increased to a total of 6 to 9 months (INH resistance) or
18 to 20 months (RMP resistance), depending on the
* The WHO guidelines only recommend maximum doses for INH and RMP. individual course (20). Patients with MDR-TB should
The minimum doses for INH and RMP and the mimimum and maximum doses for PZA and EMB come not
from the WHO, but from the pertinent consensus-based German guidelines (20). be treated at centers possessing the necessary expertise.
BW, body weight; d, day
Adverse effects of treatment
Severe adverse effects leading to a change in treatment
occur in 4% to 9% of patients who receive the classic
quadruple combination of INH, EMB, RMP, and PZA
(30–32). Most adverse effects, however, are milder, such
as gastrointestinal effects (nausea, vomiting) or exanthe-
whereas cavity formation tends to be rare. Immuno- ma (32), and should initially be treated symptomatically
suppressed persons, the elderly, and the very young (20). Severe hepatic toxicity (elevation of transaminases
are at elevated risk of miliary TB. In this case, to more than 3 to 5 times normal) occurs in 2.4% of cases
multiple pulmonary nodules are seen particularly and may necessitate temporary discontinuation of treat-
clearly on CT (eFigure 1). In postprimary TB there is ment (20, 21, 30, 32). Once the transaminase levels have
often cavity formation with necrosis and tissue de- returned to normal, the four antibiotics can be reintro-
struction, preferentially in the upper lobes. duced one by one, enabling identification of the drug re-
Various imaging modalities are available for diag- sponsible for the toxicity in the given patient. This sub-
nosis and monitoring of extrapulmonary manifes- stance can then be replaced as advised in the guidelines
tations, such as CT, magnetic resonance imaging (20, 33). Ophthalmological examination at 4-week inter-
(MRI), and sonography (Figure 2, eFigure 2, eFigure vals is recommended for early detection of the rare cases
3). An algorithm for the diagnostic imaging of TB is of optic neuroma (<1%) that occur in patients taking EMB
shown in eBox 1. (20, 32). Neurological complications such as peripheral
neuropathy and psychosis are equally rare (<1%) (32, 34).
Drug treatment Neuropathy occurs particularly in high-risk patients (e.g.,
Standard treatment existing pyridoxine deficiency, manifest polyneuropathy,
The standard treatment for pulmonary TB comprises pregnancy) receiving INH and can be avoided by admin-
2 months of quadruple therapy with isoniazid (INH), istering 50 mg/d pyridoxine together with the INH (29).
rifampicin (RMP), ethambutol (EMB), and pyrazin- PZA regularly causes a usually clinically irrelevant elev-
amide (PZA) followed directly by a further 4 months’ ation in serum uric acid. In the context of standard treat-
dual administration of RMP and INH (20, 21, 27, 28) ment, dose adjustment in the presence of kidney failure is
(Table 1). Extrapulmonary and disseminated forms of required only for EMB and PZA.
TBsometimes require more extended treatment: lymph-
node TB, 6 months (20, 29); articular or osseous TB, Preventive treatment
9 months; TB of the central nervous system, 12 months The goal of preventive treatment is elimination of
(20, 21, 28). Particularly in disseminated TB, the “resting” tuberculosis bacteria in persons with LTBI,
duration of treatment should be individually adjusted reducing the likelihood of later reactivation. One indi-
according to the disease course. Doses higher than cation for exclusion of LTBI is newly diagnosed HIV
those listed in Table 1 are generally not necessary. TB infection (eBox 3) (20). A comprehensive list of the
during pregnancy represents an indication for treatment indications for testing (by means of IGRA) and
(eBox 2). In 2018, the Robert Koch Institute reported information on the subsequent preventive measures can
that information on the outcome of treatment was avail- be found in the pertinent guidelines (11, 20). Following
able for 84.5% of TB patients (5025 of 5949 cases) (6). a positive IGRA result, clinically manifest TB must be
The success rate was 81%. The data related to the year excluded before initiation of chemoprophylaxis. This is
2016; owing to the extended nature of treatment for TB, achieved by specific history taking, physical exami-
results for 2017 were not yet available. At 83%, the nation, and review of at least a chest radiograph (20).
success rate for treatment of drug-susceptible TB was The guidelines supply precise directions for preventive
below the WHO target of 90%, but much higher than treatment and describe the advantages and disadvan-
the success rate for drug-resistant TB (72%). tages of the different regimens (20).

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TABLE 2

The estimated risk for the reactivation of tuberculosis during treatment with different biologics and recommendations for screening to detect
latent tuberculosis (modified from [36–38])

Drug Mechanism of action Risk of reactivation Recommendation

Anakinra IL-1 inhibition via receptor antagonism Unknown (theoretical risk of development of IGRA to screen for LTBI before
Canakinumab (anakinra), Ab to IL-1-β (canakinumab, active TB) commencement of treatment*
Gevokizumab gevokizumab)
Mepolizumab Ab to IL-5 (reduction of eosinophil granulocytes) No apparent increase in infection risk No screening (IGRA)
Reslizumab
Tocilizumab Ab to IL-6 receptor (tocilizumab), Ab to IL-6 General infection risk comparable with IGRA to screen for LTBI before
Siltuximab (siltuximab) observations of anti-TNF-α treatment commencement of treatment*
(probably somewhat lower for TB)
Ustekinumab Ab to IL-12 and IL-23 (inhibits T-cell Unknown (theoretical risk of development IGRA to screen for LTBI before
differentiation) of active TB) commencement of treatment*
Secukinumab Ab to IL-17A (secukinumab, ixekizumab), Rather low (theoretical risk of development IGRA to screen for LTBI before
Ixekizumab Ab to IL-17 receptor (brodalumab) of active TB) commencement of treatment*
Brodalumab
Omalizumab Ab to IgE No No screening (IGRA)
Eculizumab Ab to complement factor C5 (inhibits formation No No screening (IGRA)
of membrane attack complex of complement
system)
Blinatumomab Ab to CD3 (T cell) and CD19 (B cell) No No screening (IGRA)
Rituximab Ab to CD20 (B cell) No No screening (IGRA)
Ocrelizumab
Ofatumumab
Obinutuzumab
Alemtuzumab Ab to CD52 (destroys CD52-positive B cells and General infection risk comparable with IGRA to screen for LTBI before
T cells) observations of anti-TNF-α treatment commencement of treatment*
(probably somewhat lower for TB)
Abatacept Fusion protein with binding to CD80/86 Unknown (theoretical risk of development IGRA to screen for LTBI before
(inhibits T-cell response) of active TB) commencement of treatment*

* If the IGRA test result is positive, preventive anti-TB treatment should be carried out before the immunosuppressive treatment.
Ab, Antibody; CD, cluster of differentiation of surface antigens; Ig, immunoglobulin; IGRA, interferon-gamma release assay;
IL, interleukin; LTBI, latent tuberculosis infection; TB, tuberculosis

Chemoprophylaxis in patients receiving Conclusion

immuno suppressive drugs Tuberculosis is a rare disease in Germany nowadays,
Numerous immunosuppressive drugs (biologics) for but for that very reason it should not be forgotten.
the treatment of autoimmune diseases and cancer have A timely specific diagnostic work-up followed by
ben developed in recent years. For many of these sub- prompt treatment can effectively prevent further
stances the degree of risk for reactivation of latent TB is spread of the disease and avoid a severe course of ill-
not yet known. It has been confirmed that treatment ness in the individual patient (39). In industrialized
with TNF-α antagonists is associated with elevated countries, TB occurs most frequently in immigrants
risk. Thus, LTBI has to be excluded before these agents and in persons with impaired immune defenses. The
are given. Testing for LTBI and administration of growing use of immunosuppressive drugs to treat vari-
chemoprophylaxis should also be considered prior to ous illnesses broadens the spectrum of persons at risk.
planned immunosuppression in organ or bone marrow IFN-γ release assays (IGRA) are increasingly being
transplantation. Estimates of the risk for reactivation of applied to detect latent TB infection (LTBI) in these
TB involved in treatment with other immunomodu- groups of patients so that they can receive preventive
latory drugs can be found in Table 2 (35–38). These treatment.
recommendations are based on expert opinion formed
Conflict of interest statement
by experimental findings from animal studies and by Dr. Rademacher has received lecture fees from Omniamed.
clinical observation. The remaining authors declare that no conflict of interest exists.

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34. Kass JS, Shandera WX: Nervous system effects of antituberculosis Corresponding author
therapy. CNS drugs 2010; 24: 655–67. PD Dr. med. Dr. nat. med. Jan Rybniker
35. Cantini F, Nannini C, Niccoli L, et al.: Guidance for the management of Medizinische Klinik I, Universitätsklinik Köln
patients with latent tuberculosis infection requiring biologic therapy in Kerpener Str. 62
rheumatology and dermatology clinical practice. Autoimmun Rev 50937 Köln, Germany
2015; 14: 503–9. [email protected]
36. Mikulska M, Lanini S, Gudiol C, et al.: ESCMID Study Group for Infec-
tions in Compromised Hosts (ESGICH). Consensus document on the Cite this as:
safety of targeted and biological therapies: an infectious diseases per- Suárez I, Fünger SM, Kröger S, Rademacher J, Fätkenheuer G,
spective (Agents targeting lymphoid cells surface antigens [I]: CD19, Rybniker J: The diagnosis and treatment of tuberculosis.
CD20 and CD52). Clin Microbiol Infect 2018; 24 (Suppl 2): 71–82. Dtsch Arztebl Int 2019; 116: 729–35. DOI: 10.3238/arztebl.2019.0729
37. Winthrop KL, Mariette X, Silva JT, et al.: ESCMID Study Group for In- Supplementary material
fections in Compromised Hosts (ESGICH). Consensus document on For e-References please refer to:
the safety of targeted and biological therapies: an infectious diseases www.aerzteblatt-international.de/ref4319
perspective (Soluble immune effector molecules [II]: agents targeting
interleukins, immunoglobulins and complement factors). Clin Microbiol eBoxes, eFigures:
Infect 2018; 24 (Suppl 2): 21–40. www.aerzteblatt-international.de/19m0729

CLINICAL SNAPSHOT
Acute Abdomen in Chronic Anorexia Nervosa
with Episodes of Bulimia
A 48-year-old woman reported acute abdominal pain for the previous 3 hours. Clinical
examination of the underweight patient (BMI 17.4) found a tight abdomen with diffuse
guarding and no bowel sounds. Abdominal computed tomography showed a massively
dilated, tightly filled stomach extending into the pelvis. The duodenal bulb and the
descending part of the duodenum were dilated, but all other small intestinal loops were
narrow. An endoscope was inserted and large quantities of brown fluid and partly
digested food were aspirated. Inspection as far as the descending duodenum revealed
no obstruction. After endoscopy the patient’s abdomen was no longer dilated and she
was free of pain. She reported that before the pain started she had eaten food amount-
ing to around 6000 kcal and drunk 3 liters of cola, all in the space of 1 hour. In contrast
to her bulimic episodes over the foregoing 24 years, she had been unable to induce
vomiting. High small intestinal ileus caused by obstruction of the horizontal segment of
the duodenum due to acute gastric dilatation is a rare, potentially fatal (gastric necrosis,
gastric rupture) complication of extreme overeating.
Dr. med. Anja Hartleb, Luis Geser, Prof. Dr. med. Winfried Häuser, Klinik Innere Medizin I,
Klinikum Saarbrücken, [email protected]; [email protected]
Conflict of interest statement:
The authors declare that no conflict of interest exists.
Translated from the original German by David Roseveare.
Cite this as:
Hartleb A, Geser L, Häuser W: Acute abdomen in chronic anorexia nervosa
with episodes of bulimia. Dtsch Arztebl Int 2019; 116: 735. DOI: 10.3238/arztebl.2019.0735 Dilated stomach extending into the pelvis

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Supplementary material to:

The Diagnosis and Treatment of Tuberculosis

by Isabelle Suárez, Sarah Maria Fünger, Stefan Kröger, Jessica Rademacher,
Gerd Fätkenheuer, and Jan Rybniker

Dtsch Arztebl Int 2019; 116: 729–35. DOI: 10.3238/arztebl.2019.0729

eReferences
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HIV-positive adults not on ART: a systematic review and meta-
analysis. Peer J 2017; 5: e4165.
e2. Yorke E, Atiase Y, Akpalu J, Sarfo-Kantanka O, Boima V, Dey ID:
The bidirectional relationship between tuberculosis and diabetes.
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people with ESRD: a systematic review. Am J Kidney Dis 2013; 61:
33–43.
e4. Odone A, Tillmann T, Sandgren A, et al.: Tuberculosis among
migrant populations in the European Union and the European
Economic Area. Eur J Public Health 2015; 25: 506–12.
e5. Getahun H, Gunneberg C, Granich R, Nunn P: HIV infection-
associated tuberculosis: the epidemiology and the response.
Clin Infect Dis 2010; 50 (Suppl 3): 201–7.
e6. UNAIDS: Joint United Nations Programme on HIV/AIDS.
www.unaids.org/en (last accessed on 29 August 2019).
e7. Karo B, Haas W, Kollan C, et al.: Tuberculosis among people living
with HIV/AIDS in the German ClinSurv HIV Cohort: long-term inci-
dence and risk factors. BMC Infect Dis 2014; 14: 148.
e8. Aabye MG, Ravn P, PrayGod G, et al.: The impact of HIV infection
and CD4 cell count on the performance of an interferon gamma
release assay in patients with pulmonary tuberculosis. PLoS One
2009; 4: e4220.
e9. Telisinghe L, Amofa-Sekyi M, Maluzi K, et al.: The sensitivity of the
QuantiFERON((R))-TB Gold Plus assay in Zambian adults with
active tuberculosis. Int J Tuberc Lung Dis 2017; 21: 690–6.
e10. University of Licerpool: Druginteractions. www.hiv-druginteractions.
org. (last accessed on 29 August 2019).
e11. Seelbach-Göbel: 240. Stellungnahme des DZK in Zusammenarbeit
mit FZB, DGI, DGPI, GPP, DGGG, DRG und DGMP zum Tuberkulo-
sescreening bei Schwangeren im Kontext von § 36 (4) Infektions-
schutzgesetz (IfSG). 2017.
e12. Feiterna-Sperling C, Brinkmann F, Adamczick C, et al.: [Consensus-
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2017; 71: 629–80.

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eBOX 1 eBOX 3

Algorithm for diagnostic imaging in Tuberculosis and HIV infection

tuberculosis
The risk of tuberculosis (TB) is 20 times higher in HIV-positive persons than in
● Radiography those who are negative for HIV (1, e5–e6). The incidence of tuberculosis in the
– Primary imaging procedure for: HIV-infected population in Germany is not precisely known, but is low overall.
– Suspected tuberculosis Nevertheless, because the risk of reactivation is high the German guidelines
– Screening recommend that every new diagnosis of HIV should be followed by IGRA to
– Diagnosis exclude LTBI. In the event of a positive IGRA result, clinically manifest TB must
– Treatment monitoring be definitively ruled out, since failure to recognize active TB might have serious
consequences for the patient. In the nationwide German KlinSurv cohorts, a
● Computed tomography total of 233 cases of active TB were registered in 11 693 HIV patients between
– Secondary procedure for more detail regarding: 2001 and 2011 (e7). When interpreting the IGRA test results, it must be
– Lymphadenopathy remembered that the sensitivity of immunological diagnostic techniques is
– Exclusion of differential diagnoses reduced at low levels of CD4+ T cells (e8–e9). In addition, an HIV test should
– Complications always be carried out—with the patient’s written consent—after a new diag-
– Assessment of tuberculosis disease activity nosis of TB (20).
The course of TB is often atypical in patients with HIV coinfection: in some
● Magnetic resonance imaging cases oligosymptomatic, in others, severe (14). The treatment of HIV/TB co-
– Specific investigation of extrapulmonary infection should take place at a specialized center. The possibility of drug inter-
tuberculosis actions with the antiretroviral treatment (ART) for HIV must always be borne in
mind (e10).
Especially in the presence of reduced levels of CD4+ T cells, the initiation of
ART may be followed by immune reconstitution inflammatory syndrome (IRIS),
characterized by worsening or first occurrence of clinical symptoms (e.g., fever,
lymph-node swelling). In severe or moderately severe cases, prednisolone is
used (1.5 mg/kg body weight for 2 weeks, then 0.75 mg/kg body weight for a
further 2 weeks) (20).

eBOX 2

Tuberculosis and pregnancy

In the event of well-founded suspicion of tuberculosis (TB), chest radiography
is justified even in pregnant women (e11). TB during pregnancy is a clear indi-
cation for treatment. The conventional first-line drugs (RMP, INH, EMB, PZA)
are all considered safe in pregnancy (10). Breastfeeding is possible during
treatment, provided the mother does not have infectious pulmonary TB and
resistance-oriented prophylaxis can be initiated in the child (e12). Tuberculous
mastitis is extremely rare but should be ruled out by clinical examination (e12).

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Diagnostic and Interventional Radiology Institute, University Hospital Cologne

eFigure 1: Typical appearance of miliary tuberculosis in a patient with HIV
(thoracic computed tomography, axial section)
Diagnostic and Interventional Radiology Institute, University Hospital Cologne

eFigure 2: Osseous tuberculosis with a lesion in the tibial head

(arrow) (magnetic resonance imaging, coronal section)

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Diagnostic and Interventional Radiology Institute, University Hospital Cologne

eFigure 3: Multiple ring-like contrast-enhanced foci in cerebral tuberculosis (arrows)

(magnetic resonance imaging, axial section)

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