Torque Teno Virus plasma level as novel biomarker of retained immunocompetence in HIV-infected patients.

PURPOSE: To predict the course of immune recovery (IR) in HIV-1-infected patients after initiation of combined antiretroviral therapy (cART) by determination of the plasma concentration of Torque Teno Virus (TTV). TTV has been identified as marker for risk assessment in immunosuppressed patients after transplantation procedures. Here, TTV was analyzed in HIV-1-infected therapy-naïve patients to evaluate its use as predictor of the course of IR for guidance of individualized treatment. METHODS: TTV DNA was quantified in plasma samples of 301 therapy-naïve HIV-1-infected patients and correlated to CD4+ cell count, HIV viral load, presence of the herpes viruses CMV, EBV and HHV-8, age and sex. Patients were classified according to their initial CD4+ cell count and to the extent of CD4+ T-cell increase within the first year of cART. RESULTS: TTV DNA was detectable in 96% of the patients' plasma samples with a median TTV plasma concentration of 5.37 log10 cop/ml. The baseline CD4+ cell count was negatively correlated with TTV plasma concentration (p = 0.003). In patients with a CD4+ cell recovery < 50 cells/µl, the median TTV plasma concentration was significantly higher compared to patients with a CD4+ cell recovery of > 200 CD4+ cells/µl (5.68 log10 cop/ml versus 4.99 log10 cop/ml; p = 0.011). TTV plasma concentration in combination with baseline CD4+ cell count were significantly correlated to CD4+ cell recovery (p = 0.004). For all other parameters considered, no significant correlation for CD4+ cell recovery was found. CONCLUSION: Within the cohort, the significantly elevated TTV plasma concentration in patients with diminished CD4+ cell recovery indicates a more profound immune defect. Baseline TTV plasma concentrations and CD4+ cell count are predictive for the course of immune recovery in HIV-1-infected patients with severe immunodeficiency.

Severe pulmonary haemorrhage syndrome in leptospirosis in a returning traveller.

Clinical presentation of leptospirosis ranges from asymptomatic infection to fulminant, life-threatening disease. Pulmonary involvement in terms of severe pulmonary haemorrhage syndrome (SPHS) has recently become a more frequently reported facet of leptospirosis and correlates with high mortality rates. It has not yet been described in returning German travellers. We present a case of a healthy young man developing massive pulmonary haemorrhage and severe ARDS requiring mechanical ventilation and high-dose catecholamines after travelling to Indonesia. Leptospirosis was verified by blood PCR as well as serology and treated with high-dose, intravenous penicillin. Outcome was favourable, the patient recovered completely. Leptospirosis and SPHS should be taken into account as an emerging infectious disease in patients with fever and lung involvement.

Intrahepatic cholestasis of pregnancy (ICP): case report and review of the literature.

Intrahepatic cholestasis of pregnancy (ICP) represents the most common pregnancy-related liver disease in women. Women frequently present in the third trimester with pruritus and elevated serum bile acid and/or alanine transaminase levels. Clinical symptoms quickly resolve after delivery; however, recurrence in subsequent pregnancies has to be expected. Intrahepatic cholestasis of pregnancy is associated with increased perinatal complications, such as premature delivery, meconium staining of the amniotic fluid, respiratory distress, low Apgar scores, and even stillbirth. The risk for the fetus is significantly increased with maternal serum bile acid levels above 40 µmol/L, which characterize severe ICP. An important factor for ICP development is a rise of gestational hormones leading to cholestasis in genetically predisposed women. Variants in the bile salt export pump (BSEP) and the multidrug resistance protein 3 (MDR3) are most often identified in ICP. Here, we give an overview of the current literature on ICP and present the case of a woman with recurrent severe ICP. A common BSEP polymorphism as well as a rare MDR3 mutation may underlie the development of ICP in our patient. She had a premature delivery with meconium staining of the amniotic fluid. The neonate showed signs of respiratory distress with a low Apgar score. This case emphasizes that women with severe ICP have an increased risk for perinatal complications. Furthermore, severe ICP was associated with a MDR3 mutation, which has already been described in adult patients with liver cirrhosis. Thus, ICP may unmask an underlying MDR3 defect, which may predispose to development of hepatobiliary diseases such as gallstone disease, liver fibrosis/cirrhosis, as well as hepatobiliary malignancies. Therefore, genetic testing should be considered in women with severe as well as early onset ICP. Furthermore, regular follow-up should be discussed for women with genetic variants.

Allergic sensitization to pegylated interferon-α results in drug eruptions.

BACKGROUND: The introduction of pegylated interferon (PEG-IFN)-α in the treatment of chronic hepatitis C has led to an increase in sustained virological response. Despite reduced immunogenicity of the pegylated form in comparison with native interferon (IFN)-α, a high frequency of adverse cutaneous reactions has been reported with pegylated IFN-α. Here, we aimed to investigate the immunological mechanisms underlying pegylated IFN-α-induced drug eruptions. METHODS: Hepatitis C patients suffering from drug eruptions in association with administration of pegylated interferons were enrolled in the study (n = 22). Subjects were tested for sensitivity to pegylated IFN-α2a , pegylated IFN-α2b , or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylated IFN-α-associated exanthemas, as well as from localized inflammatory skin reactions at pegylated IFN-α injection sites, were analyzed for the expression of relevant chemokines by quantitative real-time PCR and immunohistochemistry. RESULTS: A subset of patients suffering from pegylated IFN-α-associated exanthemas displayed positive intradermal tests to PEG-IFNs but not to conventional IFN (11/22). In selected patients, this observation correlated with the presence of pegylated IFN-specific T cells (3/11). Chemokine profiles of inflammatory skin reactions at the injection sites reflected an IFN-α-signature, whereas lesional skin of exanthemas showed induction of TH2-associated chemokines. CONCLUSIONS: Our results indicate that specific sensitizations are one cause of exanthemas under therapy with PEG-IFNs. Clinical proof-of-concept analyses demonstrate that affected patients may benefit from a switch to conventional, nonpegylated drugs, enabling IFN-α therapy continuation without drug-associated skin eruptions.

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature.

Hyperargininemia is caused by deficiency of arginase 1, which catalyzes the hydrolysis of L-arginine to urea as the final enzyme in the urea cycle. In contrast to other urea cycle defects, arginase 1 deficiency usually does not cause catastrophic neonatal hyperammonemia but rather presents with progressive neurological symptoms including seizures and spastic paraplegia in the first years of life and hepatic pathology, such as neonatal cholestasis, acute liver failure, or liver fibrosis. Some patients have developed hepatocellular carcinoma. A usually mild or moderate hyperammonemia may occur at any age. The pathogenesis of arginase I deficiency is yet not fully understood. However, the accumulation of L-arginine and the resulting abnormalities in the metabolism of guanidine compounds and nitric oxide have been proposed to play a major pathophysiological role. This article provides an update on the first patients ever described, gives an overview of the distinct clinical characteristics, biochemical as well as genetical background and discusses treatment options.

Patients with manifest hepatic encephalopathy can reveal impaired thermal perception.

OBJECTIVES: Previous evoked potential studies indicated central impairments of somatosensory function in patients suffering from hepatic encephalopathy (HE). The aim of this study was to quantify the somatosensory perception in patients with minimal and overt HE. MATERIALS AND METHODS: Forty-two patients with liver cirrhosis and HE up to grade 2 and 12 age-matched healthy controls underwent a comprehensive graduation of HE including the West Haven criteria, the critical flicker frequency (CFF), and neuropsychometric testing. Quantitative sensory testing, standardized by the German Research Network on Neuropathic Pain, was performed on both hands. RESULTS: Pain and mechanical detection thresholds were unchanged in HE. Tests of thermal processing revealed that patients with HE of grade 2 perceive cold at lower temperatures (cold detection threshold) and need a higher temperature difference to distinguish between warm and cold (thermal sensory limen). These impairments correlated with the CFF. A correction for attention deficits by performing partial correlations using neuropsychometric test results canceled these correlations. CONCLUSIONS: The present findings demonstrate an impairment of temperature perception in HE. The extent of this impairment correlates with HE severity as quantified by the CFF. The attenuation of the correlations after correction for attention deficits suggests a strong role of attention deficits for the impaired thermal perception. Thus, it provides initial evidence for a central impairment of thermal processing in HE due to alterations in high-level processes rather than due to peripheral neuropathic processes, which are a frequent complication in patients with liver cirrhosis.

Genetic variants in adult liver diseases.

In the last decades, understanding of genetic variants contributing to liver disease development has considerably improved through novel genotyping techniques. Genetic variants of single genes are known to be decisive for the development of monogenetic liver diseases of varying severity. Identification of genetic variants is an important part of the diagnostic process, e. g. the majority of patients with high iron [Fe] (HFE)-associated hemochromatosis carry the homozygous mutation p.C282Y. Detection of mutations in genes encoding hepatobiliary transport proteins like familial intrahepatic cholestasis 1 (FIC1), bile salt export pump (BSEP), or multidrug resistance protein 3 (MDR3) is the basis to differentiate various forms of intrahepatic cholestasis. Moreover, genetic variants in a variety of genes are known to act as disease modifiers and represent risk factors for disease progression and the development of cirrhosis or even hepatocellular carcinoma. Success of drug treatment or appearance of severe side effects can also be influenced by specific genetic variants. All these aspects underscore the increasing importance of genetic variants, which in the future may help to identify patients at risk for disease progression or help to guide treatment decisions. In the present overview, specific frequent genetic variants are summarized that play roles in monogenetic liver diseases, forms of intrahepatic cholestasis, gallstone development, fatty liver disease, drug-induced liver injury, and liver disease progression as well as hepatocellular carcinoma development.

Beyond fibrosis: stellate cells as liver stem cells.

The high regenerative potential of the liver is driven by parenchymal and non-parenchymal cells, which restore the original liver mass after injury by cell proliferation. The contribution of stem- and progenitor cells to liver regeneration is mainly observed when hepatocyte proliferation is impaired. However, the origin of stem/progenitor cells and their effectivity to restore injured liver is currently discussed controversially. Hepatic stellate cells, which are mainly known for their contribution to fibrosis in chronic liver diseases, were recently identified as mesenchymal stem cells (MSC) of the liver. Stellate cells are also involved in liver regeneration and fulfill a dual function by supporting neighboring cells and developing into liver epithelial cells. This demonstrates that stellate cells not only exhibit the same expression profile and differentiation potential but also functional similarities to MSC of other organs, which are at present intensively studied by many groups for their therapeutic use in liver diseases.

TIPS geometry influences patency.

OBJECTIVE: The purpose of this study was to evaluate potential causes of Transjugular intrahepatic portosystemic shunt (TIPS) dysfunction. MATERIAL AND METHODS: We retrospectively evaluated 26 patients who required TIPS revision (group I) and 24 patients who did not require any further intervention (group II) within the first two years following TIPS implantation. The distance of the distal end of the stent to the hepatocaval junction was measured. Furthermore, the angle between the stent and the portal vein (inflow) and the angle between the stent and the hepatic vein (outflow) were measured. Furthermore, the following data were evaluated: pre- and postinterventional portal pressure gradients, maximal postinterventional flow and blood values [C-reactive protein (CRP), bilirubin, glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)]. RESULTS: Compared with control subjects, patients who required TIPS revision showed a significantly longer distance from the distal end of the stent to the hepatocaval junction (I: 17.3 ±â€Š10 mm, II: 6.7 ±â€Š5.7 mm, p < 0.001). There was a statistically significant correlation between the above named distance and the time to revision (Pearson's correlation coefficient, r = 0.5, p = 0.01). In addition, patients with TIPS revision had a significantly larger angle of portalvenous inflow (alpha angle) than the control group (I: 100.5 ±â€Š31.5°, II: 64.5 ±â€Š31.6°, p < 0.001). CONCLUSION: Our results show that the distance from the end of the stent to the hepatocaval junction and the angle of portalvenous inflow are technical factors that may influence the shunt's patency rate. Of these two, the distance to the hepatocaval junction can be influenced easily by the interventionalist.

Cortical activation associated with asterixis in manifest hepatic encephalopathy.

OBJECTIVES: Severe hepatic encephalopathy gives rise to asterixis, a striking motor symptom also called flapping tremor, which is characterized by a sudden ceasing of muscle tone in all muscles of a limb. In this study, we aimed at scrutinizing the cortical activation associated with asterixis and unraveling the underlying pathophysiological mechanisms. MATERIAL AND METHODS: We recorded simultaneously neural activity with magnetoencephalography (MEG) and muscle activity with surface EMG in nine patients with manifest hepatic encephalopathy showing asterixis. Asterixis events were detected semiautomatically and served as triggers for averaging MEG signals. Evoked responses averaged time-locked to asterixis events were subjected to equivalent current dipole (ECD) modeling. Additionally, we localized the strongest cortico-muscular coherence in the frequency of the co-occurring tremulousness. RESULTS: Evoked fields averaged time-locked to asterixis events were best explained by a single dipolar source in the contralateral primary motor cortex (M1, Talairach coordinates of mean localization: -40, -20, and 64; Brodmann area 4). This dipole showed a twofold field reversal, that is biphasic wave, with frontal dipole orientation at 49 ms before flap onset and 99 ms after flap onset. Conversely, two maxima with occipital dipole orientation were observed 2 ms and 160 ms after flap onset. Cortico-muscular coherence for the tremulousness was likewise localized in the contralateral M1 confirming earlier findings in the present patient cohort. CONCLUSIONS: Our results reveal an involvement of M1 in the generation of asterixis. As also tremulousness, also called mini-asterixis, was shown to originate in M1, asterixis and mini-asterixis may share common pathophysiological mechanisms.

[A 55-year-old woman with cough, fever, swelling of joints, and exanthema after a trip to Ecuador]. / 55-jährige Patientin mit Husten, Fieber, Gelenkschwellungen und Exanthem nach einem Urlaub in Ecuador.

A 55-year-old woman presented 18 months after a trip to Ecuador with night sweat, malaise, and an unclear lesion of the lung. Computed tomography of the lung showed a nodular lesion of 14 mm. Antibodies against Histoplasma capsulatum were detected in the complement fixation text (CFT) and IgG western blot. Re-examination of a formalin fixed paraffin embedded (FFPE) lung-biopsy revealed yeasts after silver staining, compatible with H. capsulatum , which was verified by extraction and amplification of DNA from FFPE. After therapy with itraconazole 400 mg/day, the patient showed an uneventful clinical recovery without regression of the lung lesion. The serological follow-up examination after 17 months showed CFT without pathological findings.

Full genome ultra-deep pyrosequencing associates G-to-A hypermutation of the hepatitis B virus genome with the natural progression of hepatitis B.

Human APOBEC3 (A3) cytosine deaminases are antiviral restriction factors capable of editing the genome the hepatitis B virus (HBV). Despite the importance of the human A3 protein family for the innate immune response little is known about the clinical relevance for hepatitis B. The aim of this study was to utilize ultra-deep pyrosequencing (UDPS) data to analyse the phenomenon of G-to-A hypermutation of the complete HBV genome and to relate it to fundamental characteristics of patients with chronic hepatitis B. By analysing the viral population of 80 treatment naïve patients (47 HBeAg-positive and 33 HBeAg-negative), we identified an unequal distribution of G-to-A hypermutations across the genome. Our data indicate that G-to-A hypermutation occurs predominantly in a region between nucleotide positions 600 and 1800 a region which is usually single stranded in matured HBV particles. This implies that A3 likely edits HBV in the virion. Hypermutation rates for HBeAg-negative patients were more than 10-fold higher than those of HBeAg-positive patients. For HBeAg-negative patients higher hypermutation rates were significantly associated with the degree of fibrosis. Additionally, we found that for HBeAg-positive chronic hepatitis G-to-A hypermutation rates were significantly associated with the relative prevalence of the G1764A mutation, which is related to HBeAg seroconversion. In total, our data imply an important association of hypermutation mediated by A3 deaminases with the natural progression of chronic hepatitis B infections both in terms of HBeAg seroconversion and disease progression towards cirrhosis.

Long-term clearance of hepatitis C virus following interferon α-2b or peginterferon α-2b, alone or in combination with ribavirin.

Sustained virologic response (SVR) is the standard measure for evaluating response to therapy in patients with chronic hepatitis C (CHC). The aim of this study was to prospectively assess the durability of SVR in the pivotal studies of peginterferon (PEG-IFN) α-2b or IFN α-2b. We conducted two phase 3b long-term follow-up studies of patients previously treated for CHC in eight prospective randomized studies of IFN α-2b and/or PEG-IFN α-2b. Patients who achieved SVR [undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of treatment] were eligible for inclusion in these follow-up studies. In total, 636 patients with SVR following treatment with IFN α-2b and 366 with SVR following treatment with PEG-IFN α-2b were enrolled. Definite relapse (quantifiable serum HCV RNA with no subsequent undetectable HCV RNA) was reported in six patients treated with IFN α-2b and three patients treated with PEG-IFN α-2b. Based on these relapses, the point estimate for the likelihood of maintaining response after 5 years was 99.2% [95% confidence interval (CI), 98.1-99.7%] for IFN α-2b and 99.4% (95% CI, 97.7-99.9%) for PEG-IFN α-2b. Successful treatment of hepatitis C with PEG-IFN α-2b or IFN α-2b leads to clinical cure of hepatitis C in the vast majority of cases.

An unusual presentation of a common infection.

A 40-year-old Ghanaian woman presented with fever and exanthema. She had anemia, leukopenia, increased erythrocyte sedimentation rate (ESR), creatinin kinase, lactate dehydrogenase (LDH), and liver enzymes. She was diagnosed with schistosomiasis and was cured with praziquantel. During the following years, she developed polymyositis, chronic nephritis, and life-threatening perimyocarditis. High numbers of Epstein-Barr virus (EBV)-encoded RNA copies were demonstrated in CD8+ T-lymphocytes from endomyocardial biopsies. There was no evidence of any underlying immunosuppression or an EBV-related malignancy. Chronic active EBV infection was diagnosed, a clinical picture not described in an adult African previously. Interestingly, among all therapy attempts, only rituximab was effective at stabilizing the disease.

Plasmodium knowlesi infection imported to Germany, January 2013.

Plasmodium knowlesi was known as a plasmodium of macaques until P. knowlesi transmission to humans was recognised in Borneo and later throughout South-East Asia. We describe here a case of a P. knowlesi infection imported to Germany from Thailand. The patient had not taken antimalarial chemoprophylaxis and suffered from daily fever attacks. Microscopy revealed trophozoites and gametocytes resembling P. malariae. P. knowlesi malaria was confirmed by PCR.

[Hepatic cholestasis resulting from a long-standing enterothorax: a case report]. / Langjähriger Enterothorax als ungewöhnliche Ursache einer Cholestase: ein Fallbericht.

BACKGROUND: Due to the lack of symptoms an enterothorax frequently remains undetected in adults. Most symptomatic patients complain about bowel obstruction and a surgical repair of the diaphragmatic defect, particularly with a mesh, is mandatory. METHODS: This report presents the case of a 72-year-old female patient with a history of an upside-down stomach presenting with a painless jaundice and signs of liver cirrhosis. CLINICAL COURSE: The preoperative work-up revealed an enterothorax with compression of the main bile duct. Explorative laparotomy showed a liver cirrhosis with distinct intrahepatic cholestasis, a hydropic gallbladder and confirmed a right-sided diaphragmatic defect with an enterothorax. After reposition of the intestine, a cholecystectomy, bile duct revision and the closure of the diaphragmatic defect using a mesh were performed. CONCLUSION: Diaphragmatic defects are the basis for the formation of an enterothorax which may be associated with a complicated clinical course. Therefore, in cases of coincidental diagnosis, even in asymptomatic patients, surgical repair should be performed in order to prevent serious complications as presented in this case.

Hepatosplenic morbidity due to Schistosoma mansoni in schoolchildren on Ukerewe Island, Tanzania.

The study was conducted to assess infection intensity and morbidity due to Schistosoma mansoni in schoolchildren on Ukerewe Island in Lake Victoria, Tanzania, East Africa. Three hundred and sixty pupils who have never been treated previously were enrolled (180 males/180 females, age 6-17 years [median 10 years]) in three different schools of the island. Double stool samples were collected from each pupil and egg excretion was classified according to WHO recommendations. Ultrasound investigations were performed in accordance with the WHO Niamey-Belo-Horizonte protocol. Male (112/180, 62.2%) and female (104/180; 57.7%) pupils were infected (difference, not significant [n.s.]). In the positive 216 cases, egg excretion varied from 1 to 2,440 eggs per gramme stool (epg) [median 165 epg]. There were 69/216 (31.9%) who had a low grade, 105/216 (53.2%) had a moderate and 42/216 (14.8%) had a heavy infection. There was no significant difference between male and female sex nor with regard to age groups. There were 354/360 children who underwent sonography: 321 (90.7%) had splenomegaly, 316 (89.3%) showed a left lobe and 109 (30.9%) had a right lobe hepatomegaly. Overt signs of portal fibrosis (PF) were present in 19 children (5.4%) out of whom 11 presented with echogenic thickening of peripheral portal and 8 with thickening of central portal branches. Non-specific portal wall changes were seen in 6 children (1.7%). Association of PF to quantitative egg excretion was not seen (median in PF, 172 epg vs. median in non PF, 168 epg; difference, n.s.). Portal vein dilatation was seen in 101/354 (28.5%) cases. In Ukerewe, the prevalence of S. mansoni infection and infection intensity in children is high, yet overt hepatic morbidity is low as compared to other endemic foci. Non-specific ultrasonographic abnormalities including hepatosplenomegaly and portal vein dilatation were seen frequently but the fraction attributable to schistosomiasis is difficult to assess.

Plasma levels of vitamin E and carotenoids are decreased in patients with Nonalcoholic Steatohepatitis (NASH).

OBJECTIVES: Oxidative stress is suggested to play an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). The present study was aimed to compare plasma levels of antioxidants in patients suffering from NASH and healthy controls. METHODS: Plasma levels of the antioxidants α-tocopherol, γ-tocopherol, lutein, zeaxanthin, ß-cryptoxanthin, lycopene, α-carotene ß-carotene were determined in 57 patients with biopsy-proven NASH and 40 healthy controls. RESULTS: Levels of α-tocopherol (22.4 vs. 26.8 nmol/ ml; p<0.01), lutein (0.19 vs. 0.33 nmol/ml; p<0.0001), zeaxanthin (0.04 vs. 0.08 nmol/ml; p<0.0001), lyco?pene (0.15 vs. 0.42 nmol/ml; p<0.0001), α-carotene (0.03 vs. 0.06 nmol/ml; p<0.005) and ß-carotene (0.25 vs. 0.39 nmol/ml; p<0.01) were significantly decreased in NASH patients compared to controls. Age, aminotransferase status (ALT, AST) and BMI were not correlated with the levels of tocopherols or caro?tenoids. CONCLUSIONS: Given the decreased levels supplementation of lipophilic antioxidants might be a rational treatment option for patients with NASH.

TB or not TB? Difficulties in the diagnosis of tuberculosis in HIV-negative immigrants to Germany.

BACKGROUND: Immigrants to Germany and their children are at particular risk for tuberculosis (TB). - METHODS: 35 Patients (10 male / 25 female aged 2 - 59 years (median 33 years) originating mostly from high incidence countries in Asia (19 (54.3%)) in Africa (14 (40.0%) and East Europe (2 (5.7%)), attended at the Tropical Medicine Unit were analysed. - RESULTS: Primary clinical presentation was most frequently lymphadenitis (13 (37.1%)). Other organs involved included bones (7 (20.0%)), central nervous system (5 (14.3%)), urogenital organs (3 (8.6%)), lung (3 (8.6%)), mediastinum, (2 (5.7%)) and abdomen (2 (5.7%)). ESR was abnormal in 21/28 (75.0%), CRP in 20/35 (57.1%), and protein electrophoresis in 22/26 (84.6%) cases. The tuberculin skin test was strongly positive in all 15 cases where the test had been performed. Tuberculosis interferon gamma release assay (TB-IGRA) was positive in all 35 cases (100%). PCR for nucleic acids of Mycobacterium (M.) tuberculosis complex was positive in only 7/20 (35.0%) cases. M. tuberculosis was identified in 32/35 (91.4%), M. bovis in 2 (5.7%) cases. 1 case was diagnosed clinically. All patients were negative for HIV. Typical histopathology was seen in the 29 cases, where biopsies had been taken. Chest-X-ray did not reveal specific pulmonary lesions in the majority of cases (22/35 (62.9%)). Diagnosis of TB was mostly delayed (4 to 299 weeks, (median 8)). The most frequent primary suspicion was a malignancy (17/35 (48.6%)) while TB was initially suspected in 5 cases only. Diagnosis of TB is impeded by its multifaceted presentation especially in immigrants.

Sunitinib induced pyoderma gangrenosum-like ulcerations.

Pyoderma gangrenosum is a non-infectious neutro?philic skin disease commonly associated with underlying systemic diseases. Histopathological and laboratory diagnostics are unspecific in the majority of the cases and the diagnosis is made in accordance with the clinical picture. Here, we report the case of a 69-year old man with progredient pyoderma gangrenosum-like ulcerations under treatment with sunitinib due to hepatocellular carcinoma. A conventional ulcer therapy did not lead to a regression of the lesions. Solely cessation of sunitinib therapy resulted in an improvement of the ulcerations. Sunitinib is a multikinase inhibitor that targets the PDGF-α- and ?ß-, VEGF-1-3-, KIT-, FLT3-, CSF-1- and RET-receptor, thereby impairing tumour proliferation, pathological angiogenesis and metastasation. Here, we demonstrate that pyoderma gangrenosum-like ulcers may represent a serious side effect of sunitinib-based anti-cancer treatment.