Depression, a major comorbidity of psoriatic disease, is caused by metabolic inflammation.

Psoriatic disease is a chronic, systemic immune-mediated inflammatory disorder comprising three major domains, skin, vascular and bone/joint inflammation. It is known for a long time that psoriatic disease is associated with a number of conditions such as hypertension, dyslipidemia, diabetes (metabolic syndrome) and depression. Up to one out of five people with psoriasis show concomitant depression. In the past, this was attributed to psychological stress of suffering from a chronic condition that is often visible and itchy, leading to stigmatization and adding to a significant burden of disease. Recent data provide evidence that depression associated with psoriatic disease is linked to the specific inflammatory pattern with IL-23, IL-17 family cytokines, TNF, IL-6 and IL-8 causing neuroinflammation and subsequently depression or depressive behaviour and/or anxiety. Psoriatic disease shows a distinct pattern of immune cells (e.g. dendritic cells, Th17 cells, neutrophils), mediators (e.g. IL-17A/F, IL-23, TNF) and tissue-related factors in all major domains that is different from other inflammatory dermatoses. There is a striking similarity between the inflammatory pattern in psoriatic disease and neuroinflammation that leads to depression. A number of risk factors have been identified in psoriatic disease, the most important of which are obesity and tobacco smoking. Obesity is known as a major risk factor for depression and anxiety due to its inflammatory signature. Apart from psychotherapy and anti-depressive medication, targeted treatments for psoriasis, including TNF, IL-17 and IL-23 inhibitors, can improve depression/depressive symptoms. The review summarizes the current knowledge about depression as a comorbidity in psoriatic disease.

Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study.

BACKGROUND: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. OBJECTIVE: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. METHODS: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. RESULTS: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. CONCLUSION: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies.

BACKGROUND: The persistence of the SARS-CoV2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Questions remain as to which cohorts require SARS-CoV2 boosters. However, there is a critical lack of data on the dynamics of vaccine responses in patients with chronic inflammatory diseases (CID) undergoing immunosuppressive/disease modifying anti-rheumatic (DMARD) treatment. Here, we present the first data regarding the decline of the vaccine-induced humoral immune responses in patients with CID. METHODS: 23 patients with CID were monitored clinically and for anti-spike IgG and IgA levels, neutralization efficacy and antigen-specific CD4+ T cell responses over the first 6 months after SARS-CoV2 vaccination. 24 healthy individuals were included as controls. RESULTS: While anti-spike IgG-levels declined in CID patients and healthy controls, patients receiving anti-TNF treatment showed significantly greater declines at 6 months post second vaccination in IgG and especially neutralizing antibodies. IgA levels were generally lower in CID patients, particularly during anti-TNF therapy. No differences in SARS-CoV2 spike-specific CD4+ T-cell frequencies were detected. CONCLUSION: Although the long-term efficacy of SARS-CoV2 vaccination in CID patients undergoing disease-modifying therapy is still not known, the pronounced declines in humoral responses towards SARS-CoV2 6 months after mRNA vaccination in the context of TNF blockade should be considered when formulating booster regimens. These patients should be considered for early booster vaccinations.

Small dense LDL cholesterol in human subjects with different chronic inflammatory diseases.

BACKGROUND AND AIMS: Chronic inflammatory diseases (CID) are associated with a profound increase in cardiovascular (CV) risk resulting in reduced life expectancy. However, LDL-cholesterol is reported to be low in CID patients which is referred to as the "LDL paradoxon". The aim of the present study was to investigate whether LDL-particles in CID exhibit an increased content of the highly atherogenic small-dense LDL subfraction (sdLDL). METHODS AND RESULTS: In this prospective, single center, observational study we enrolled 141 patients with CID (RA n = 59, inflammatory bowel disease (IBD) n = 35, ankylosing spondylitis (SpA) n = 25, Psoriasis n = 22) in 2011 through 2013 to evaluate sdLDL levels before as well as 6 and 26 weeks after initiation of different anti-cytokine therapies (anti-TNFα, anti-IL-6R antibodies). sdLDL levels were compared to 141 healthy individuals in a case control design. Compared to healthy controls, all CID patients displayed a significantly higher sdLDL content within the LDL cholesterol fraction: RA 35.0 ± 9.2% (p < 0.001), SpA 42.5 ± 10.5% (p < 0.001), IBD 37.5 ± 7.1% (p < 0.001), Psoriasis 33.6 ± 4.6% (p < 0.01). Furthermore, the sdLDL/LDL ratio was significantly higher in male compared to female RA subjects (p < 0.05). Neither anti-TNFα nor anti-IL6R medication altered sdLDL levels despite a significant improvement of disease activity. CONCLUSION: In several different chronic inflammatory disease entities, LDL-cholesterol is shifted toward a pro-atherogenic phenotype due to an increased sdLDL content which might in part explain the LDL paradoxon. Since premature CV disease is a major burden of affected patients, specifically targeting lipid metabolism should be considered routinely in clinical patient care. CLINICAL TRIALS: Registration at German Clinical Trial Register (DRKS): DRKS00005285.

Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells.

The transcription factor Evi1 has an outstanding role in the formation and transformation of hematopoietic cells. Its activation by chromosomal rearrangement induces a myelodysplastic syndrome with progression to acute myeloid leukemia of poor prognosis. Similarly, retroviral insertion-mediated upregulation confers a competitive advantage to transplanted hematopoietic cells, triggering clonal dominance or even leukemia. To study the molecular and functional response of primary murine hematopoietic progenitor cells to the activation of Evi1, we established an inducible lentiviral expression system. EVI1 had a biphasic effect with initial growth inhibition and retarded myeloid differentiation linked to enhanced survival of myeloblasts in long-term cultures. Gene expression microarray analysis revealed that within 24 h EVI1 upregulated 'stemness' genes characteristic for long-term hematopoietic stem cells (Aldh1a1, Abca1, Cdkn1b, Cdkn1c, Epcam, among others) but downregulated genes involved in DNA replication (Cyclins and their kinases, among others) and DNA repair (including Brca1, Brca2, Rad51). Cell cycle analysis demonstrated EVI1's anti-proliferative effect to be strictly dose-dependent with accumulation of cells in G0/G1, but preservation of a small fraction of long-term proliferating cells. Although confined to cultured cells, our study contributes to new hypotheses addressing the mechanisms and molecular targets involved in preleukemic clonal dominance or leukemic transformation by Evi1.

T-cell receptor diversity prevents T-cell lymphoma development.

Mature T-cell lymphomas (MTCLs) have an extremely poor prognosis and are much less frequent than immature T-cell leukemias. This suggests that malignant outgrowth of mature T lymphocytes is well controlled. Indeed, in a previous study we found that mature T cells are resistant to transformation with known T-cell oncogenes. Here, however, we observed that T-cell receptor (TCR) mono-/oligoclonal mature T cells from TCR transgenic (tg) mice (OT-I, P14) expressing the oncogenes NPM/ALK or ΔTrkA readily developed MTCLs in T-cell-deficient recipients. Analysis of cell surface markers largely ruled out that TCR tg lymphomas were derived from T-cell precursors. Furthermore, cotransplanted non-modified TCR polyclonal T cells suppressed malignant outgrowth of oncogene expressing TCR tg T lymphocytes. A dominant role of an anti-leukemic immune response or Tregs in the control of MTCLs seems unlikely as naïve T cells derived from oncogene expressing stem cells, which should be tolerant to leukemic antigens, as well as purified CD4 and CD8 were resistant to transformation. However, our results are in line with a model in which homeostatic mechanisms that stabilize the diversity of the normal T-cell repertoire, for example, clonal competition, also control the outgrowth of potentially malignant T-cell clones. This study introduces a new innate mechanism of lymphoma control.

[Comorbidities and psoriasis. Impact on clinical practice]. / Komorbiditäten und Psoriasis. Konsequenzen für die Praxis.

Psoriasis is a genetically determined, chronic inflammatory systemic disease. Besides skin symptoms, patients with moderate to severe forms of psoriasis show an association with other diseases, referred to as comorbidities. Metabolic disorders (e.g. diabetes mellitus, insulin resistance, dyslipidemia mainly in obese patients) and cardiovascular diseases (e.g. arterial hypertension, coronary artery disease, myocardial infarction and stroke) are of importance as they can increase patients' mortality. In addition, psychiatric diseases are more frequent in psoriasis patients and influence the therapeutic approach. The dermatologist in most cases is the primarily consulted physician for patients with psoriasis and therefore plays the role as a gatekeeper managing therapy. He is responsible for the early diagnosis of comorbidities and insuring their appropriate management. The anti-psoriatic treatment has to be adapted to existing comorbidities and their systemic treatments. The following article provides information on psoriatic comorbidities and their consequences for daily practice.

Smoking and alcohol intake in severely affected patients with psoriasis in Germany.

BACKGROUND: Smoking and alcohol may contribute as triggering factors for psoriasis and are substantial for managing severely affected psoriasis patients. OBJECTIVES: To evaluate the general state of smoking and alcohol intake in a group of hospitalized, severely affected patients with psoriasis in comparison with the general population of Germany. METHODS: A retrospective, multicentre study analysing data from 1,203 patients with severe psoriasis was performed. RESULTS: 43.3% of all patients were found to be active smokers (males: 46.6%; females: 39.2%) with a higher likelihood as the control group (odds ratio, OR, 2.08, 95% confidence interval, CI, 1.81-2.39; p < 0.0001). 14.9% of all patients were found to be excessive drinkers (female patients: 5.5%; male patients: 22.3%), more likely than the control group (OR 3.10, 95% CI 2.53-3.80; p < 0.0001); males had an OR of 2.86 (95% CI 2.29-3.56; p < 0.0001) and females an OR of 5.12 (95% CI 3.12-8.39; p < 0.0001). CONCLUSION: Smoking and alcohol intake are independently associated with severe forms of psoriasis. Disease severity is correlated with smoking in both genders as well as with alcohol intake in female patients.

Impact of comorbidities on the management of psoriasis.

Psoriasis is associated with numerous comorbidities that have a major impact on severely affected patients. Besides psoriatic arthritis, other diseases such as metabolic syndrome and cardiovascular diseases are becoming of major importance. In particular, patients with severe forms of psoriasis are at a higher risk of developing cardiovascular diseases and myocardial infarction. In a recent study, a reduction in life expectancy was shown for this subgroup of patients. An increased prevalence of concomitant diseases leads to an increased intake of concomitant medication; thus, it is easy for comorbidities and their treatments to interact with routinely used antipsoriatic therapies and complicate the management of severely affected patients. This patient subgroup has a strong need of sufficient treatment not only for their severe skin symptoms, but also for preventing the possible development of comorbidities and their long-term complications. As dermatologists are often one of the first and most often consulted health care specialists for patients with psoriasis, advanced knowledge of the comorbid state of these patients should influence clinical management and lead to new standards of care. This article will summarize the current knowledge on comorbidities in psoriasis and their impact on patient management.

Comedication related to comorbidities: a study in 1203 hospitalized patients with severe psoriasis.

BACKGROUND: Psoriasis is a common dermatological disorder characterized by an immune-mediated chronic inflammation which is associated with a variety of other diseases commonly referred to as comorbidities. The treatments for these diseases may interfere with the course and the treatment of psoriasis. Little is known on the general drug intake of patients with psoriasis. OBJECTIVES: To gain more insight into the general drug intake of patients with severe psoriasis. A correlation of comedication to respective diseases could lead to a better knowledge of comorbidities. METHODS: Data on demographics, comedication and comorbidities from 1203 patients with severe psoriasis in Germany were analysed. As a control group data from 7099 subjects from the German National Health Survey 1998 were used. RESULTS: Patients with severe psoriasis are receiving significantly more different systemic drugs on average than the general population, with the most prominent difference in multidrug treatment. Drugs used in the treatment of arterial hypertension, diabetes mellitus and other diseases of the metabolic syndrome as well as oral anticoagulants and anticonvulsant agents showed the greatest differences. Special characteristics of antihypertensive drug treatments could be determined. CONCLUSIONS: The data obtained in this study provide the basis for an improved management of patients with psoriasis. Knowledge of existing comedication and comorbidities may lead to the ability to treat psoriasis and comorbidities at the same time more safely and to use possible synergistic effects.

Dimethylfumarate inhibits nuclear binding of nuclear factor kappaB but not of nuclear factor of activated T cells and CCAAT/enhancer binding protein beta in activated human T cells.

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder in which T-cell-mediated immune responses are thought to play a prominent role. Fumaric acid esters (FAEs) have proved to be an effective systemic treatment for psoriasis. The FAE dimethylfumarate (DMF) strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells. Additionally, it has been demonstrated that the nuclear translocation of the activated transcription factor nuclear factor kappaB (NF-kappaB) is inhibited in human endothelial cells and fibroblasts activated with tumour necrosis factor-alpha. The NF-kappaB pathway plays a major role in regulating inflammatory cytokine production as well as in cell differentiation and apoptosis. T-cell survival is also dependent on the activation of NF-kappaB and it has been demonstrated in vitro that DMF is an inducer of apoptosis in human T cells. The influence of FAEs on the expression of nuclear transcription factors in T cells has not yet been investigated. OBJECTIVES: The effects of DMF and its main metabolite, methylhydrogenfumarate (MHF), were assessed on the nuclear binding of NF-kappaB, nuclear factor of activated T cells (NF-AT) and CCAAT/enhancer binding protein beta (C/EBPbeta) in purified human T cells. METHODS: To examine the effect of DMF and MHF on the nuclear binding of NF-kappaB, NF-AT and C/EBPbeta in human T cells and fibroblasts, an enzyme-linked immunosorbent assay (ELISA) was used. The binding activity of these transcription factors was measured by its absorbance in an ELISA plate reader at 450 nm. Conspicuous results were confirmed by performing electrophoretic mobility shift assays. RESULTS: DMF inhibited nuclear binding of NF-kappaB1, but not of NF-AT or C/EBPbeta, in purified human T cells. No effect of MHF on any of these transcription factors could be seen. To verify our results, we used the same assay to show the inhibitory effect on the nuclear binding of NF-kappaB1 in human fibroblasts (as previously published). CONCLUSIONS: The results of this study provide evidence for a specific effect of DMF on NF-kappaB. The data support previous results where NF-kappaB-dependent mediators and surface molecules were suppressed by DMF, but not those activated by other nuclear transcription factors.

[Lymphadenitis colli due to non-tuberculous mycobacteria (NTM): a case-series and review of the literature]. / Lymphadenitis colli durch nichttuberkulöse Mykobakterien (NTM) im Kindesalter -- Eine Fallserie und Literaturübersicht.

OBJECTIVE: Lymphadenitis colli due to NTM should always be considered in children with cervical Lymphadenitis. For Germany there is a lack of data concerning the incidence, the epidemiology, the diversity and frequency of the different bacteria, the diagnosis, the clinical manifestation and the medical treatment. METHODS: By means of a questionnaire, which was retrospective for 1985 to 1994 and was sent to 277 children's hospitals in Germany, we collected data on Lymphadenitis colli in Germany. In our study we also incorporated cases from the "National Laboratory for Mycobacteria" in Borstel as well as six cases from our hospital in Mainz. Therefore our data includes both clinical (28) and laboratory (30) cases. Additionally we screened the literature on "Lymphadenitis colli in children due to NTM". RESULTS: A total of 51 cases of Lymphadenitis due to NTM could be identified. The illness occurs typically in young children up to six years of age. The most frequent cause were species of the Mycobacterium avium-intracellulare-scrofulaceum complex. Except for the local diagnosis of a cervical Lymphadenitis other clinical symptoms are missing, just as specific laboratory parameters with a subacute or chronic course. The tuberculin skin test can be false positive. The diagnosis is confirmed by biopsy and histology as well as through microbiological tests. CONCLUSIONS: The best treatment is complete surgical excision, whereas the importance of additional or exclusive treatment with Clarithromycin, Rifabutin and other antibiotics could not be clarified completely. But in patients with AIDS Rifabutin and other drugs could perhaps be useful, even for prophylaxis. Also if complete excision is impossible, treatment with certain drugs (Clarithromycin or Azithromycin in combination with Rifampicin) will be recommended. It still remains in question if NTM infections in children are really increasing.

[Non-tubercular mycobacterial infection of the lungs due to Mycobacterium smegmatis]. / Nichttuberkulöse Mykobakteriose der Lungen durch Mycobacterium smegmatis.

Nontuberculous mycobacteriosis due to M. smegmatis is a rarity. We report on the case of a 51 year old male HIV-seronegative patient without predisposing bronchopulmonary disease, but with a state after gastrectomy and splenectomy who developed unproductive cough, night sweat and weight loss. The chest radiograph and thoracic CT showed wide-spread bilateral patchy infiltrations. Histological examination of transbronchial biopsies revealed chronic carnificating pneumonia. A perhoracic fine-needle biopsy showed caseating epitheloid cell granulomas with acid fast bacilli. These were identified as M. smegmatis by PCR with subsequent sequencing. Acid fast bacilli could not be detected microscopically neither in sputum nor in bronchial secretions, however M. smegmatis has been repeatedly detected by culture in these materials. In neither material tubercle bacilli have been detected by nucleic acid amplification (NAT) or culture. Immunologic investigations revealed a reduced number of CD4+ lymphocytes and a reduction of interferon alpha- and -gamma-synthesis by peripheral blood mononuclear cells. Treatment with Rifabutin, Ethambutol, Clarithromycin and Ofloxacin resulted in complete clinical and roentgenological resolution.

The fate of bacillus Calmette-Guerin after intravesical instillation.

PURPOSE: Long-term activation of immunocompetent cells of the bladder wall as well as case reports of systemic infections some months or years after intravesical bacillus Calmette-Guerin (BCG) therapy imply that mycobacteria may persist in the body. Therefore. we investigated the fate of BCG in patients after uncomplicated intravesical instillation therapy. MATERIAL AND METHODS: A total of 49 patients were included in the study, from whom various numbers of specimens were used for mycobacterial culture and molecular biological detection techniques. In 23 patients who received a total of 128 instillations urine, sputum, venous blood and bladder biopsies were screened for BCG by acid-fast staining and culture at different times before and after instillation. From 16 of the 23 patients and from an additional 26 a total of 180 bladder biopsies obtained at intervals 3 to 30 months after instillation were screened for mycobacterial 16S ribosomal DNA by a nested polymerase chain reaction protocol. RESULTS: No viable BCG was found in venous blood or in 127 of 128 sputum specimens before and 2 hours after instillation. Two of 56 bladder biopsies were culture positive. In urine BCG was detected in 96.4% of the specimens after 2 hours and in 67.9% after 24 hours after instillation. The number of positive specimens decreased and it was 27.1% on day 7 immediately before the next instillation. In 14 of 44 bladder biopsies (31.8%) mycobacterial ribosomal DNA was found within 1 week after the sixth instillation. A positive polymerase chain reaction was evident up to 24 months in between 4.2% and 37.5% of the investigated biopsies. After 30 months no ribosomal DNA was evident in the 6 samples available for testing. CONCLUSIONS: Nontraumatic intravesical instillation of BCG is not accompanied by systemic mycobacterial spread. Local persistence during the instillation course is evident since viable BCG is commonly found in the urine. Long lasting and persistent BCG DNA in the bladder wall may account for long-term immuno-activation. However, the remaining BCG may be a possible source of late systemic infections.

Reduction of side effects of intravesical therapy with bacille Calmette-Guérin by pentoxifylline?--an in vitro approach.

Immunotherapy with intravesical bacille Calmette-Guérin (BCG) is the treatment of choice against superficial bladder cancer recurrences. However, this therapy is associated with side effects that are considered to be the result of inflammatory cytokines. Since pentoxifylline is known to interfere with the production of cytokines, this drug was tested in vitro with regard to a later clinical application in BCG-treated patients. The cytokine release and the cytotoxicity of interleukin-2 or BCG-stimulated mononuclear cells were analyzed, and the growth of BCG under the influence of pentoxifylline was assayed. The results showed an inhibition of cytokine release of stimulated mononuclear cells. The cytotoxicity of BCG-stimulated mononuclear cells but not of lymphokine-stimulated mononuclear cells against bladder carcinoma cells was significantly inhibited. Restimulation with fresh BCG restored cytotoxicity. Direct coincubation of BCG and pentoxifylline resulted in a reduction of mycobacterial metabolism. From these data, we conclude that the use of pentoxifylline to reduce BCG-related side effects should be tested further in a clinical study.

Low in vitro production of interferon-gamma and tumor necrosis factor-alpha in HIV-seronegative patients with pulmonary disease caused by nontuberculous mycobacteria.

We studied 32 HIV-seronegative patients with pulmonary disease caused by nontuberculous mycobacteria (NTM). Immunologic studies included lymphocyte subset analysis by flow cytometry, measurement of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) production following in vitro stimulation of diluted whole blood (DWB) and peripheral blood mononuclear cells (PBMC) by phytohemagglutinin (PHA), anti-CD3 as well as purified protein derivative of tuberculin (PPD), and in four cases with different amounts of the very mycobacterium, which caused disease in these patients. Data were compared to those of 30 HIV-seronegative patients with disease by Mycobacterium tuberculosis (MTb). Following alpha-CD3-stimulation of PBMC, NTM patients showed lower IFN-gamma (P < 0.00005) and lower TNF-alpha (P < 0.02). For a subgroup of tuberculin skin test-positive NTM patients we found significantly lower PPD-induced IFN-gamma releases in cultured DWB (P < 0.0002) and PBMC (P < 0.0004) compared to MTb patients. Data for PPD-induced TNF-alpha release for this subgroup were also significant (P < 0.001 and P < 0.05, respectively). The four NTM patients with poor PPD-induced IFN-gamma response hardly showed increased cytokine production on stimulation with their specific mycobacterium. The lower production capacity of IFN-gamma and TNF-alpha of NTM patients compared to the MTb patients points to an immunologic imbalance forming the basis for their increased susceptibility to pulmonary infections by nontuberculous mycobacteria.

Sensitivity of BCG to modern antibiotics.

The viability of bacillus Calmette-Guérin (BCG) in intravesical instillation therapy has been demonstrated to be crucial for the prevention of bladder tumour recurrence. The aim of the present study was to determine the effects of modern antibacterial chemotherapeutics on BCG viability, particularly cycloserine, which has been recommended in the treatment of BCG-induced sepsis. The minimal inhibitory concentrations (MICs) of 32 antibacterial drugs potentially effective against the Connaught BCG strain were measured in vitro by the radiometric BACTEC 460TB method. The MICs were compared with the drug concentrations achievable in blood and urine. Susceptibility testing of cycloserine was performed with three different strains (Connaught, Tice and RIVM), using the modified proportion method, as defined in the German guidelines for anti-tuberculosis drug testing. The Connaught BCG strain was highly susceptible to fluoroquinolones, but was resistant to beta-lactams, macrolides (except clarithromycin), and some aminoglycosides. It was also sensitive to doxycycline and gentamicin at dosages that typically occur in the urine of patients after a normal dose. Connaught BCG was susceptible to all the tuberculostatic drugs tested, except for pyrazinamide. All the BCG strains analysed were resistant to cycloserine. During intravesical BCG instillation therapy, simultaneous administration of fluoroquinolones, doxycycline or gentamicin should be avoided. In cases of severe systemic complications, or if one of the antituberculosis drugs is not tolerated, fluoroquinolones may be used. Cycloserine is no longer recommended for the early treatment of BCG sepsis.

Extensive mediastinal lymphadenopathy in an adult immunocompetent woman caused by Mycobacterium avium complex.

We report a case of extensive mediastinal lymphadenopathy in a 29-year-old immunocompetent woman, which was thought to be caused by Mycobacterium tuberculosis (MTB). Chest radiographs showed deterioration while the patient was receiving antituberculous medication for 8 months. After isolation of Mycobacterium avium complex (MAC) from a lymph node aspiration biopsy and switch to a MAC-specific therapeutic regimen, the lesion almost completely disappeared within 1 year. To our knowledge, this is the first report of an extensive mediastinal lymphadenopathy caused by MAC in an immunocompetent adult.