Associations between tobacco smoking status and patch test results-A cross-sectional pilot study from the Information Network of Departments of Dermatology (IVDK).

BACKGROUND: Earlier studies suggested a potential association between tobacco smoking and nickel sensitization, but little is known about other contact allergens. OBJECTIVES: To investigate the association of smoking status and contact sensitizations as well as subtypes of dermatitis, and to analyse the sensitization profiles of tobacco smokers. PATIENTS AND METHODS: Within the Information Network of Departments of Dermatology (IVDK), we performed a cross-sectional multicentre pilot study comprising 1091 patch-tested patients from 9 departments, comparing 541 patients with a history of cigarette smoking (281 current and 260 former smokers) with 550 never-smokers. RESULTS: We could not confirm the previously reported association between nickel sensitization and tobacco smoking. Moreover, sensitizations to other allergens, including colophony, fragrance mix I, Myroxylon pereirae and formaldehyde, were not increased in cigarette smokers compared with never smokers. Hand dermatitis (50.6% vs. 33.6%) and occupational cause (36.2% vs. 22.5%) were significantly more frequent among cigarette smokers compared with never-smokers as shown by non-overlapping 95% confidence intervals. CONCLUSIONS: Although our study does not allow a firm conclusion on whether smoking status contributes to certain contact sensitizations, it confirms an association of smoking with hand dermatitis and occupational cause.

Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for Pediatric Allergology (GPA), the German Contact Dermatitis Research Group (DKG), the German Society for Pneumology (DGP), the German Society of Otorhinolaryngology, Head and Neck Surgery, the Austrian Society of Allergology and Immunology (ÖGAI), the Austrian Society of Dermatology and Venereology (ÖGDV), the German Academy of Allergology and Environmental Medicine (DAAU), and the German Documentation Center for Severe Skin Reactions (dZh).

Not available.

[Rickettsiosis - Early skin biopsy is essential because of latency in serological findings]. / Rickettsiose.

BACKGROUND: Global travel increasis practitioner's confrontation with very special infectious diseases, like hemorrhagic viral diseases that are traditionally rare in European countries. Prompt diagnosis and subsequent induction of therapy are essential to prevent high rates of severe and lethal complications. ANAMNESIS: A 59-year-old man complained deterioration of general health after a 3-week vacation to South Africa. He presented fever and hemorrhagic erythema with pustula surrounded by necrotic margin on the right calf. COURSE AND THERAPY: On the second day of inpatient treatment, a papulovesiculous, partly hemorrhagic exanthema appeared. With a tentative diagnosis of Rickettsiosis, we performed specific diagnostics by serology and biopsy. Therapy was initiated with doxycycline (200 mg/d) for 7 days. Under this regimen clinical symptoms healed without consequences. Rickettsioses are ubiquitious zoonoses that are caused by various Rickettsia subtypes. The stay in endemic regions together with signs of fever, reduced general health, eschar and exanthema are suspicious for this disease. Therapy should be initiated immediately in cases of clinical suspicion with a characteristic case history. The seroconversion, which appears later in course, should not give reason for avoiding early skin biopsy due to the potentially fatal course of the disease. Biopsy enables early histological proof of a dermal vasculitic inflammation pattern and PCR analysis before subsequent serological controls and proofs.

Early oral presentation of Crohn's disease.

Inflammatory changes of the oral mucosa in children can have a variety of infectious and non-infectious etiologies. We report on a 10-year-old boy with progressive cobblestone-like changes and erosions of oral mucosa over six months, which turned out to be early oral manifestations of Crohn disease.

Lupus erythematosus gyratus repens.

"Lupus erythematosus gyratus repens" is viewed clinically and histologically as an annular variant of a subacute cutaneous lupus erythematosus and was described for the first time in French by the authors Laugier, Lénys and Bulte in 1959 as chronic-recurrent figurate erythema. The current name of the disease goes back to Hewitt et al. (1975) and Laugier (1977). There are only a few cases known thus far in the literature. We report a 74-year-old patient, in whom the clinical and histological patterns corresponded to the presence of lupus erythematosus gyratus repens. Systemic and topical therapy with glucocorticosteroids and administration of antimalarials resulted within several months in nearly complete disappearance of the disease. We give an overview of the literature and discuss the characteristic features of lupus erythematosus gyratus repens and its possible association with drug intake or internal malignancies. A differential-diagnostic distinguishing from other annular configured, peripheral-emphasized dermatoses is required. As a paraneoplastic dermatosis, erythema gyratum repens should not be overlooked in the diagnosis.

Myocardial infarction as an uncommon clinical manifestation of intravascular large cell lymphoma.

Intravascular large cell lymphoma (IVL) is a very rare variant of non-Hodgkin's lymphoma presenting with puzzling clinical manifestations. There is a predilection for the central nervous system, but the tumour often affects also skin, lung, and kidneys while lymphadenopathy and hepatosplenomegaly are usually absent. Myocardial infarction due to IVL has not been reported so far. We here report on a 56-year-old patient who was admitted to our hospital with fever and clinical signs of erysipelas. He had a 6-month history of "collagen vasculitic disease" treated with prednisolone and azathioprine. He received antibiotic treatment, but after transient improvement fever recurred with generalized seizures and myocardial infarction, which required transfer to the intensive care unit where the patient died with signs of an acute cardiogenic shock. Autopsy revealed a generalized high-grade B cell lymphoma of IVL type affecting and obstructing small vessels of a variety of tissues including heart, brain and lungs. The tumorous obliteration of small intramyocardial vessels had led to an acute ischaemia with infarction and subsequent signs of myocardial insufficiency. To the best of the authors' knowledge myocardial infarction as a leading symptom of IVL has not been described.

VEGF production by primary human renal proximal tubular cells: requirement of HIF-1, PI3-kinase and MAPKK-1 signaling.

Renal proximal tubular epithelial cells (PTEC) respond to hypoxia exposure or interleukin-1beta (IL-1beta) treatment with increased vascular endothelial growth factor (VEGF) production. With respect to O2 deprivation, the hypoxia-inducible factor 1alpha/ beta (HIF-1) is the most important transcription factor driving VEGF mRNA expression. HIF-1 is also activated by IL-1beta and may thus be involved in the stimulation of VEGF production by this cytokine. However, the molecular mechanisms of HIF-1 dependent VEGF synthesis are poorly understood. Herein, human PTEC in primary culture were challenged by hypoxic incubation and/or IL-1beta treatment in absence or presence of specific phosphatidylinositol 3-kinase (PI3K) or mitogen activated protein kinase kinase-1 (MAPKK-1) inhibitors for assay of VEGF protein, VEGF mRNA and detection of HIF-1alpha by Western Blotting, EMSA and fluorescence microscopy. In addition, the activities of PI3K and MAPKK-1 were studied following hypoxia and IL-1beta treatment of the cultures. The study shows that PI3K but not MAPKK-1 inhibition resulted in the loss of hypoxic and IL-1beta induced HIF-1alpha accumulation, whereas VEGF synthesis was reduced by either intervention. Thus, PI3K signaling is required for HIF-1alpha accumulation and VEGF synthesis, whereas MAPKK-1 signaling is required for VEGF synthesis only. Furthermore, hypoxia alone was sufficient to activate PI3K in PTEC in contrast to MAPKK-1, whose activity was lowered in hypoxia.

The kidney as a second site of human C-reactive protein formation in vivo.

C-reactive protein (CRP) is the main acute phase reactant in humans. Its production is presumably restricted to the liver but extrahepatic expression by inflamed tissue has not been studied in detail. By real-time PCR and immunohistochemistry we here show that renal cortical tubular epithelial cells (TEC) express CRP mRNA and protein within 6 h after stimulation with conditioned medium (CM) or IL-6, but not IL-1alpha or TNF-alpha. Western blot analysis with monoclonal anti-CRP antibody that recognizes native CRP revealed protein secretion into supernatants of CM-stimulated TEC cultures. While hepatoma-derived Hep3B cells could be induced similarly, peripheral blood mononuclear cells could not. CRP mRNA transcripts were observed in nephrectomized renal allografts with severe acute rejection but not with chronic allograft nephropathy (CAN). Of 19 needle biopsies of acutely rejecting kidney transplants, 15 demonstrated CRP mRNA production with the relative expression levels increasing with the severity of rejection. On the other hand, none of 7 graft biopsies with acute tubular necrosis (ATN) or CAN showed CRP mRNA expression. By using monoclonal anti-CRP antibody, cortical tubules as well as glomerular cells were shown to locally express CRP in rejecting, but not in ATN kidneys. We conclude that inflamed kidneys represent a so far unknown site of CRP formation in vivo. These data shed new light on the acute phase reaction not merely representing a systemic inflammatory pathway but probably being part of the local immune response.

Bactericidal activity of renal tubular cells: the putative role of human beta-defensins.

Renal tubular epithelial cells (RTC) form a barrier between the host and ascending microbes in upper urinary tract infection. Previous studies have shown the ability of the kidney to produce defensins--antimicrobial peptides that play a pivotal role in unspecific host defense. To further clarify the role of renal epithelium for direct antibacterial activity we investigated the expression, regulation and production of antimicrobial peptides by cultured human RTC. Cell culture supernatants of RTC exert strong bactericidal activity against Escherichia coli and Klebsiella pneumoniae, two of the most important pathogens in urinary tract infections. The antimicrobial effect depends on salt concentration, a typical feature of human defensins. RT-PCR of RNA from cultured proximal and distal RTC showed constitutive expression of human beta-defensin 1 (hbd-1) and human beta-defensin 2 (hbd-2) whereas only hbd-1 expression could be detected in RNA preparation from renal biopsy material. Hbd-2 expression of RTC was induced by inflammatory processes as shown by semiquantitative competitive RT-PCR. Coincubation of the cultured cells with IL-1alpha or E. coli promote the strongest hbd-2 induction whereas TNF-alpha and LPS lead to a weaker or no (IL-6) hbd-2 induction. This is the first evidence that human RTC are able to produce antibacterial substances in a biologically relevant amount and that beta-defensins are candidate proteins responsible for this effect.

Evaluation of a new ultrasmall superparamagnetic iron oxide contrast agent Clariscan, (NC100150) for MRI of renal perfusion: experimental study in an animal model.

PURPOSE: To determine the diagnostic value of a new ultrasmall superparamagnetic iron oxide Clariscan, (NC100150) for the evaluation of renal perfusion in an animal model using a 3D-FFE-EPI sequence. MATERIALS AND METHODS: Four groups of four rabbits each were imaged after bolus injection of NC100150, using a 1.5 T MR system (Gyroscan ACS-NT). T2*w MR images in the coronal plane were acquired over 60 seconds with an echo-shifted 3D-FFE-EPI sequence (TR/TE/alpha = 18/25 msec/8 degrees ). Data were transferred to a workstation and converted into concentration curves. Based on the fitted concentration time curves, parameter maps were calculated pixelwise: bolus arrival time (T0), time-to-peak (TTP), mean transit time (MTT), and relative bolus volume (rBV). Maximum signal decrease was determined with respect to the baseline value. RESULTS: Mean MTT increased from 4.2 seconds at a dose of 0.25 mg to 5.9 seconds at 1.0 mg (P < .0001). The maximum signal decrease was observed at 0.75 mg, corresponding to 85% of the baseline value. Transit times of the contrast bolus were accurately calculated for the cortex and the outer medulla, but at the level of the inner medulla no arterial flow profile was identified. No significant difference between the cortex and the outer medulla was found for either T0 or rBV, but medullar TTP and MTT were prolonged with regard to cortical TTP and MTT (6.3 seconds vs. 5.7 seconds, P < .001; 5.7 seconds vs. 4.2 seconds, P < .0001). CONCLUSION: The employed intravascular contrast agent is well suited to assess renal perfusion. By the use of a T2*w3D perfusion sequence, cortical and medullar transit times can be quantified and physiologic information on regional perfusion differences can be obtained.

Inhibition of macrophage inflammatory protein-1 alpha production by Epstein-Barr virus.

Infection with Epstein-Barr virus (EBV) exerts substantially immunomodulating activities in vitro and in vivo. In this context, EBV-induced chemokine production and the influence of EBV on this highly redundant system of inflammatory proteins have hardly been investigated. This study analyzed the production of interleukin-8, RANTES, monocyte chemotactic protein-1, and macrophage inflammatory protein-1 alpha (MIP-1 alpha) on EBV infection of peripheral blood mononuclear cells from immune EBV-seropositive (EBV(+)) and noninfected EBV-seronegative (EBV(-)) individuals. EBV failed to induce the production of MIP-1 alpha in EBV(+) as well as EBV(-) individuals, whereas the other chemokines studied were readily expressed. Moreover, EBV completely down-regulated lipopolysaccharide (LPS)- and phytohemagglutinin-induced MIP-1 alpha production up to 4 hours after induction. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of EBV- and LPS-stimulated cultures revealed that EBV inhibited MIP-1 alpha production on the transcriptional level. This effect was abolished by addition of antiglycoprotein (gp)350/220, a monoclonal antibody against EBV's major envelope glycoprotein, which mediates binding of the virus to the EBV receptor, CD21. However, recombinant gp350/220 protein alone did not inhibit the LPS-induced MIP-1 alpha production, indicating that infection of the target cell is indispensable for this effect. In summary, we demonstrate a new immunomodulating activity of EBV on the chemokine system that probably helps the virus to evade the host's immune system favoring lifelong infection.

Hepatocellular carcinoma: detection with gadolinium- and ferumoxides-enhanced MR imaging of the liver.

PURPOSE: To test the hypothesis that the accuracy of gadolinium- and ferumoxides-enhanced magnetic resonance (MR) imaging is different in small (< or =1.5-cm) and large (>1.5-cm) hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Forty-three consecutive patients with chronic liver disease were enrolled in this study. The imaging protocol included unenhanced breath-hold T1-weighted fast field-echo sequences, unenhanced respiratory-triggered T2-weighted turbo spin-echo (SE) sequences, dynamic gadolinium-enhanced T1-weighted three-dimensional turbo field-echo sequences, and ferumoxides-enhanced T2-weighted turbo SE sequences. Images of each sequence and two sets of sequences (ferumoxides set and gadolinium set) were reviewed by four observers. The ferumoxides set included unenhanced T1- and T2-weighted images and ferumoxides-enhanced T2-weighted turbo SE MR images. The gadolinium set included unenhanced T1- and T2-weighted images and dynamic gadolinium-enhanced three-dimensional turbo field-echo MR images. In receiver operating characteristic (ROC) curve analysis, the sensitivity and accuracy of the sequences were compared in regard to the detection of all, small, and large HCCs. RESULTS: Imaging performance was different with gadolinium- and ferumoxides-enhanced images in the detection of small and large HCCs. For detection of small HCCs, the sensitivity and accuracy with unenhanced and gadolinium-enhanced imaging (gadolinium set) were significantly (P =.017) superior to those with unenhanced and ferumoxides-enhanced imaging (ferumoxides set). The area under the composite ROC curves, or A(z), for the gadolinium set and the ferumoxides set was 0.97 and 0.81, respectively. For large HCC, the ferumoxides set was superior compared with the gadolinium set, but this difference was not statistically significant. Analysis of all HCCs demonstrated no significant differences for gadolinium- and ferumoxides-enhanced imaging. CONCLUSION: For the detection of early HCC, gadolinium-enhanced MR imaging is preferred to ferumoxides-enhanced MR imaging because the former demonstrated significantly greater accuracy in the detection of small HCCs.