A rare case of scrub typhus vasculitis presenting as acute coronary syndrome diagnosed by skin manifestations.

A 48-year-old diabetic man presented with complaints of acute onset chest heaviness with palpitations, anxiety and headache. He had raised troponin-T level and electrocardiogram showed ST elevation myocardial infarction. There was a prior history of fever of 4 days duration with associated abdominal pain. He later developed skin rash and neurological symptoms following admission to the hospital. Dermatological examination revealed purpura and a livedo-like rash. Investigations revealed deranged liver and renal function tests and positive serological tests for scrub typhus. Coronary angiography revealed no evidence of atherosclerosis or any other pathology. He was therefore diagnosed as a case of scrub typhus-induced vasculitis with coronary manifestations and was managed with oral doxycycline. Scrub typhus presenting like an acute coronary syndrome has been reported very rarely previously. In addition, patient had gastrointestinal, central nervous system and hematological involvement which added to the rarity of the case.

An update on the microbiome in vasculitis.

PURPOSE OF REVIEW: To summarize recent evidence regarding the presence and potential role of the microbiome in systemic vasculitides. RECENT FINDINGS: Microbiomic descriptions are now available in patients with small, medium and large vessel vasculitis. The majority of studies have evaluated gastrointestinal inhabitants, with a smaller number of studies describing the nasal, pulmonary or vascular microbiomes. Most published studies are observational and cross-sectional. Dysbiosis is seen frequently in vasculitis patients with reduced microbial diversity observed in nasal, fecal and vascular samples compared with disease and/or healthy controls. Predominant bacteria vary, but overall, patients with vasculitis tend to have more pathogenic and less commensal bacteria in active disease. In the few longitudinal studies available, improvement or resolution of dysbiosis has been observed following vasculitis treatment and improved disease activity. SUMMARY: Dysbiosis and reduced microbial diversity has been identified in patients with small, medium and large vessel vasculitis. Although limited data suggests microbiomes may 'normalize' following immunosuppression, cause or effect cannot be determined. It is hypothesized that microbial disruption in a genetically susceptible individual may trigger excessive host immune activation and vasculitis; however, larger studies with longitudinal and translational design are needed to further our current understanding.

Pulmonary vasculitis due to infection with Mycobacterium goodii: A case report.

A 57-year-old Caucasian woman suffered from dyspnea on exertion. One year following a supposed pulmonary embolism event, a chronic thromboembolic vasculopathy was diagnosed and a pulmonary thromboendarterectomy was performed. However, a granulomatous pulmonary arterial vasculitis was identified upon examination. DNA of Mycobacterium goodii was detected as the most likely causative agent. Anti-inflammatory and anti-mycobacterial therapy was initiated for more than 12 months. Regular PET-CT scans revealed improvement under therapy. The last PET-CT did not show any tracer uptake following 10 months of therapy.

Coronary Vasculitis Induced in Mice by Cell Wall Mannoprotein Fractions of Clinically Isolated Candida Species.

Kawasaki disease (KD) is an inflammatory disease that was identified by Professor Tomisaku Kawasaki in 1961. Candida albicans-derived substances (CADS) such as the hot water extract of C. albicans and Candida water-soluble fractions (CAWS) induce coronary vasculitis similar to KD in mice. An increasing proportion of deep-seated candidiasis cases are caused by non-albicans Candida and are often resistant to antifungal drugs. We herein investigated whether the mannoprotein fractions (MN fractions) of clinically isolated Candida species induce vasculitis in mice. We prepared MN fractions from 26 strains of Candida species by conventional hot water extraction and compared vasculitis in DBA/2 mice. The results obtained revealed that the induction of vasculitis and resulting heart failure were significantly dependent on the species; namely, death rates on day 200 were as follows: Candida krusei (100%), Candida albicans (84%), Candida dubliniensis (47%), Candida parapsilosis (44%), Candida glabrata (32%), Candida guilliermondii (20%), and Candida tropicalis (20%). Even for C. albicans, some strains did not induce vasculitis. The present results suggest that MN-induced vasculitis is strongly dependent on the species and strains of Candida, and also that the MN fractions of some non-albicans Candida induce similar toxicity to those of C. albicans.

99mTC-white blood cell scintigraphy with SPECT/CT in the diagnosis of vascular graft infection. / Gammagrafía con leucocitos marcados y SPECT/TC en el diagnóstico de infección de prótesis vasculares.

AIM: Vascular graft infection is a rare complication with a high morbidity and mortality. Early diagnosis is essential to establish an adequate treatment. We assess the accuracy of 99mTc-WBC scintigraphy with SPECT/CT in the diagnosis of vascular graft infection. MATERIALS AND METHODS: We retrospectively analyzed thirty 99mTc-WBC scintigraphies with SPECT/CT performed in thirty patients with suspicion of vascular prosthesis infection. Studies were considered positive for graft infection if the intensity of activity involving the graft was greater than the liver or bone marrow activity (spine and pelvis). RESULTS: Final diagnosis of infection was established in 10 patients, based on Fitzgerald criteria. Scintigraphy was positive in 11 patients. No false negatives were obtained. The values of sensitivity and specificity were 100% and 95%, respectively, with a PPV of 91% and a NPV of 100%. Twenty five patients had a CT performed prior to scintigraphy, in 9 cases the result was positive and in the remaining 16 was negative. CT sensitivity and specificity obtained in our study were 62.5% and 76% respectively, with a PPV of 55.6% and a NPV of 81.3%. Diagnosis of infection led to prosthesis exeresis in 8 cases (all of them had a positive microbiological study of the extracted material), while the remaining 2 patients were treated with antibiotic therapy alone due to high surgical risk. CONCLUSION: Our results suggest a high accuracy for 99mTc-WBC scintigraphy with SPECT/CT in the assessment of clinically suspected arterial graft infection.

Equine pastern vasculitis in a horse associated with a multidrug-resistant Pseudomonas aeruginosa isolate.

BACKGROUND: Equine pastern vasculitis is an uncommon disorder in horses. Underlying causes are difficult to assess, especially bacterial infections. CLINICAL SUMMARY: A 13-year-old French saddle gelding horse presented for evaluation of a six weeks history of pastern dermatitis. Histopathological examination of skin biopsy samples revealed small vessel vasculitis. A pure growth of a multidrug-resistant Pseudomonas aeruginosa (MRPA) was obtained from a deep skin biopsy. Clinical remission was observed after a six week course of enrofloxacin and lesions did not recur. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first report of a pastern vasculitis associated with MRPA and successfully treated with a six week course of enrofloxacin.

[Cavernous sinus syndrome secondary to thrombophlebitis due to Streptococcus intermedius complicated with vasculitis of the internal carotid artery and brain abscesses]. / Síndrome de seno cavernoso secundario a una tromboflebitis por Streptococcus intermedius complicada con vasculitis de la arteria carótida interna y abscesos cerebrales.

INTRODUCTION: Thrombophlebitis of the cavernous sinus is a severe infectious disease with high mortality and morbidity. It is usually diagnosed at a late stage and requires a number of visits to the emergency department in most cases, and the prognosis is highly dependent on prompt treatment. Despite its severity, evidence regarding treatment with corticosteroids and anticoagulation therapy is scarce and controversial. One of its complications is arteritis, which can be mistaken for medium to large vessel vasculitis, as in this case. CASE REPORT: A 26-year-old female, who visited due to headache and left palpebral oedema. Imaging tests revealed thrombosis in the left cavernous sinus and significant narrowing of the internal carotid artery. The clinical picture was interpreted as secondary to an inflammatory vascular process and treatment with corticosteroids was initiated, with a good response. However, soon afterwards, fever and contralateral palpebral oedema developed. In the blood cultures a growth of Streptococcus intermedius was obtained and thrombophlebitis of the cavernous sinus was diagnosed. Despite initiating antibiotic and anticoagulation therapy, the patient suffered a right hemiplegia secondary to the formation of frontotemporal abscesses. Surgical drainage was performed and the patient progressed well. In the absence of other infectious foci, and due to the oral origin of the germ, a prophylactic multiple exodontia was performed. CONCLUSION: Thrombophlebitis should be considered as a diagnostic option both in headaches with ocular symptoms and in medium to large vessel arteritis so that they can be treated in a timely manner.

TITLE: Síndrome de seno cavernoso secundario a una tromboflebitis por Streptococcus intermedius complicada con vasculitis de la arteria carótida interna y abscesos cerebrales.Introducción. La tromboflebitis del seno cavernoso es una enfermedad infecciosa grave con alta mortalidad y morbilidad. Su diagnóstico suele ser tardío y requiere múltiples visitas a urgencias en la mayoría de casos, y el pronóstico es altamente dependiente de su rápido tratamiento. A pesar de su gravedad, la evidencia con respecto al tratamiento con corticoides y anticoagulación es escasa y controvertida. Entre sus complicaciones se encuentra la arteritis, la cual puede confundirse con una vasculitis de mediano-gran vaso, como en este caso. Caso clínico. Mujer de 26 años, que acude por una cefalea y un edema palpebral izquierdo. En las pruebas de imagen se evidencia trombosis del seno cavernoso izquierdo y una estrechez importante de la arteria carótida interna. Se interpreta el cuadro como secundario a un proceso vascular inflamatorio y se inician corticoides, con buena respuesta. Sin embargo, al poco tiempo se presenta fiebre y edema palpebral contralateral. En los hemocultivos se obtiene un crecimiento de Streptococcus intermedius y se diagnostica una tromboflebitis del seno cavernoso. A pesar del inicio de antibióticos y anticoagulación, sufre una hemiplejía derecha secundaria a la formación de abscesos frontotemporales. Se procede al drenaje quirúrgico y la paciente cursa con buena evolución. Ante la ausencia de otros focos infecciosos, y debido a la procedencia oral del germen, se realiza una exodoncia múltiple profiláctica. Conclusión. Se recomienda considerar la tromboflebitis como una opción diagnóstica tanto en las cefaleas con síntomas oculares como en la arteritis de mediano-gran vaso para su tratamiento oportuno.

Crucial role of NLRP3 inflammasome in a murine model of Kawasaki disease.

Kawasaki disease (KD) is a systemic febrile syndrome during childhood that is characterized by coronary arteritis. The etiopathogenesis of KD remains to be elucidated. NLRP3 inflammasome is a large multiprotein complex that plays a key role in IL-1ß-driven sterile inflammatory diseases. In the present study, we investigated the role of NLRP3 inflammasome in a murine model of KD induced by Candida albicans water-soluble fraction (CAWS) and found that NLRP3 inflammasome is required for the development of CAWS-induced vasculitis. CAWS administration induced IL-1ß production, caspase-1 activation, leukocyte infiltration, and fibrotic changes in the aortic root and coronary arteries, which were significantly inhibited by a deficiency of IL-1ß, NLRP3, and ASC. In vitro experiments showed that among cardiac resident cells, macrophages, but not endothelial cells or fibroblasts, expressed Dectin-2, but did not produce IL-1ß in response to CAWS. In contrast, CAWS induced caspase-1 activation and IL-1ß production in bone marrow-derived dendritic cells (BMDCs), which were inhibited by a specific caspase-1 inhibitor and a deficiency of NLRP3, ASC, and caspase-1. CAWS induced NLRP3 and pro-IL-1ß expression through a Dectin-2/Syk/JNK/NF-κB pathway, and caspase-1 activation and cleavage of pro-IL-1ß through Dectin-2/Syk/JNK-mediated mitochondrial ROS generation, indicating that CAWS induces the priming and activation of NLRP3 inflammasome in BMDCs. These findings provide new insights into the pathogenesis of KD vasculitis, and suggest that NLRP3 inflammasome may be a potential therapeutic target for KD.

Comparative in vitro activity of bacteriophage endolysin HY-133 against Staphylococcus aureus attached to vascular graft surface.

Novel strategies are needed for combating Staphylococcus aureus biofilm in vascular graft infections. We investigated the in vitro activity of bacteriophage endolysin HY-133, daptomycin and rifampin against S. aureus attached to vascular graft surface. Daptomycin showed rapid bactericidal effect on surface-associated S. aureus, while the activity of HY-133 on graft surface-adherent cells was moderate and rifampin did not achieve bactericidal effect. Even in the highest concentrations, all antimicrobials used failed in a complete eradication of the surface-adherent bacteria.

Crescentic poststreptococcal acute glomerulonephritis accompanied by small vessel vasculitis: case report of an elderly male.

BACKGROUND: Poststreptococcal acute glomerulonephritis (PSAGN) in the elderly tends to have a severe clinical course and often presents with crescentic necrotizing glomerulonephritis in the renal biopsy. However, vasculitis lesions are unusual. CASE PRESENTATION: We present a 71-year-old man who was admitted to our hospital for a recurrent gout attack with a rapid decline of renal function. Low C3 levels and a high anti-streptolysin O titer were observed, while myeloperoxidase- and proteinase 3- antineutrophil cytoplasmic antibody (ANCA) were negative. In addition to cellular crescent and necrosis lesions, diffuse peritubular capillaritis and venulitis as well as small arteriole vasculitis in the glomerular hilus were also apparent. Although granular C3c deposits in the capillary wall and hump lesions were not found, immunofluorescent staining for nephritis-associated plasmin receptor (NAPlr) and in situ zymography for plasmin activity were both positive. We thus diagnosed PSAGN accompanied by small vessel vasculitis. Steroid therapy gradually improved the patient's renal function, and hemodialysis was discontinued after 1 month. CONCLUSIONS: In our case, streptococcus infection might have concurrently provoked vasculitis, and NAPlr staining was useful for confirming diagnosis.

Fulminant arterial vasculitis as an unusual complication of disseminated staphylococcal disease due to the emerging CC1 methicillin-susceptible Staphylococcus aureus clone: a case report.

BACKGROUND: Staphylococcus aureus has emerged as a leading cause of invasive severe diseases with a high rate of morbidity and mortality worldwide. The wide spectrum of clinical manifestations and outcome observed in staphylococcal illness may be a consequence of both microbial factors and variability of the host immune response. CASE PRESENTATION: A 14-years old child developed limb ischemia with gangrene following S. aureus bloodstream infection. Histopathology revealed medium-sized arterial vasculitis. The causing strain belonged to the emerging clone CC1-MSSA and numerous pathogenesis-related genes were identified. Patient's genotyping revealed functional variants associated with severe infections. A combination of virulence and host factors might explain this unique severe form of staphylococcal disease. CONCLUSION: A combination of virulence and genetic host factors might explain this unique severe form of staphylococcal disease.

Antinuclear antibodies in scrub typhus: Transient occurrence during acute illness.

BACKGROUND & OBJECTIVES: The pathological hallmark of scrub typhus infection is focal or disseminated vasculitis. As with other infections, antinuclear antibodies (ANA) have been previously described in scrub typhus. However, the underlying mechanisms and implications of this immunological phenomenon is not well understood. In the present work it was assessed whether ANA is associated with illness severity and outcomes. METHODS: In this prospective study spanning one year, patients fulfilling the diagnostic criteria for scrub typhus were recruited. Patients with other acute infective febrile illnesses were taken as controls. ANA positivity was compared between the cases and controls. ANA in scrub typhus was assessed for correlation with disease severity, organ dysfunction and outcomes. RESULTS: The cohort comprised of 149 patients (scrub 89; controls 60) with mean age 46.5 (SD=16.9) yr; 48.3% were female. ANA was detected in 48 (53.9%) patients with scrub typhus and 9(15%) controls (p < 0.001). The ANA pattern was predominantly speckled (93.8%) in both scrub typhus patients and controls. In patients with scrub typhus, ANA positivity was associated with increasing APACHE-III score [Odds ratio (OR) 1.01; 95% CI 0.99-1.03; p = 0.09]. On bivariate analysis, ANA tended to be correlated with acute respiratory distress syndrome (OR 2.32; 95% CI 0.98-5.46; p = 0.06), hepatic dysfunction (OR 2.25; 95% CI 0.94-5.39, p = 0.06) and aseptic meningitis (OR 6.83; 95% CI 0.80-58.05, p = 0.08). The presence of these antibodies did not correlate with duration of hospitalization or mortality. Convalescent sera on 31 ANA positive scrub typhus patients demonstrated persistence of ANA in only 5 (16.1%) patients. INTERPRETATION & CONCLUSION: The disappearance of ANA during the convalescent phase suggests that ANA is expressed during the acute phase of scrub typhus infection. Its association with organ dysfunction warrants further study of the mechanisms and impact of autoantibody formation in scrub typhus.

Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.

BACKGROUND: Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. METHODS AND RESULTS: We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d6-choline and d3-carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. CONCLUSIONS: Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR 4338.

Utility of a blood culture time to positivity-incorporated scoring model in predicting vascular infections in adults with nontyphoid Salmonella bacteremia.

BACKGROUND: Vascular infections (VI) are potentially catastrophic complications of nontyphoid Salmonella (NTS). We aimed to develop a scoring model incorporating information from blood culture time to positivity (TTP-NTSVI) and compared the prediction capability for VI among adults with NTS bacteremia between TTP-NTSVI and a previously published score (Chen-NTSVI). METHODS: This retrospective cohort study enrolled 217 adults with NTS bacteremia ≧ 50 years old. We developed a TTP-NTSVI score by multiple logistic regression modeling to identify independent predictors for imaging-confirmed VI and assigned a point value weighting by the corresponding natural logarithm of the odds ratio for each model predictor. Chen-NTSVI score includes hypertension, male sex, serogroup C1, coronary arterial disease (CAD) as positive predictors, and malignancy and immunosuppressive therapy as negative predictors. The prediction capability of the two scores was compared by area under the receiver operating characteristic curve (AUC). RESULTS: The mean age was 68.3 ± 11.2 years-old. Serogroup D was the predominant isolate (155/217, 71.4%). Seventeen (7.8%) patients had VI. Four independent predictors for VI were identified: male sex (24.9 [2.59-239.60]; 6) (odds ratio [95% confidence interval]; assigned score point), peripheral arterial occlusive disease (9.41 [2.21-40.02]; 4), CAD (4.0 [1.16-13.86]; 3), and TTP <10 h (4.67 [1.42-15.39]; 3). Youden's index showed best cutoff value of ≧7 with 70.6% sensitivity and 82.5% specificity. TTP-NTSVI score had higher AUC than Chen-NTSVI (0.851 vs 0.741, P = 0.039). CONCLUSION: While the previously reported scoring model performed well, a TTP-incorporated scoring model was associated with improved capability in predicting NTSVI.

Late preterm prelabor rupture of fetal membranes: fetal inflammatory response and neonatal outcome.

BackgroundTo characterize the influence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI) on the intensity of the fetal inflammatory response and the association between the presence of the fetal inflammatory response syndrome (FIRS) and short-term neonatal morbidity in the preterm prelabor rupture of membranes (PPROM) between the gestational ages of 34 and 37 weeks.MethodsOne hundred and fifty-nine women were included in the study. The umbilical cord blood interleukin (IL)-6 concentrations were determined using enzyme-linked immunosorbent assay kits. FIRS was defined based on the umbilical cord blood IL-6 concentration and the presence of funisitis and/or chorionic plate vasculitis.ResultsWomen with both MIAC and IAI had the highest median umbilical cord blood IL-6 concentrations and highest rates of FIRS. Women with FIRS had the higher rates of early-onset sepsis and intraventricular hemorrhage grades I and II when FIRS was characterized based on the umbilical cord blood IL-6 concentrations and the histopathological findings.ConclusionThe presence of both MIAC and IAI was associated with a higher fetal inflammatory response and a higher rate of FIRS. Different aspects of short-term neonatal morbidity were related to FIRS when defined by umbilical cord blood IL-6 concentrations and the histopathology of the placenta.

Neurological disease may precede lymphadenopathies in Actinomyces europaeus infection.

Actinomyces species are part of the commensal flora of the mucous membranes of the oropharynx, gastrointestinal tract and female genital tract. Actinomyces europaeus is a short, nonmotile, facultative anaerobic rod first described in 1997, susceptible in vitro to a wide range of b-lactam antibiotics which are regarded as first choice. In this report we described the case of A. europaeus infection in a young female patient admitted to Intensive Care Unit and the possible damage of vascular endothelium due to a chronic progressive actinomycosis that at first involved neck soft tissue, then cervical lymphnodes, and finally extended to the vascular structure.