Association of Yersinia Infection With Kawasaki Disease: A Prospective Multicenter Cohort Study.

BACKGROUND: Yersinia infection is known to present with Kawasaki disease (KD)-like symptoms although differentiating the 2 has been a challenge. The present study aimed to describe the clinical characteristics and prevalence of Yersinia infection presenting with KD-like symptoms. METHODS: The present, prospective, multicenter study enrolled patients who received a diagnosis of KD between January 2021 and January 2022 at 2 hospitals in Tokyo. Stool samples were collected within 3 days of the start of KD treatment, and cultures were performed for Yersinia . Clinical history and symptoms suggestive of Yersinia infection were also evaluated. RESULTS: During the study period, 141 KD patients were screened and 117 patients with evaluable stool samples were registered. Only 1 patient was positive for Yersinia pseudotuberculosis , which was detected from both stool and blood cultures. The patient was refractory to KD treatment but improved after initiation of appropriate antibiotic therapy. CONCLUSIONS: Routine screening for Yersinia is not appropriate for patients with KD and should be limited to certain patients in high-risk areas and those who are refractory to the standard KD treatment.

Yersinia pseudotuberculosis: an unexpected cause of fever and a hot joint.

Yersinia pseudotuberculosis is a Gram-negative zoonosis which occasionally infects humans via ingestion of contaminated food and water, and typically causes a self-limiting gastrointestinal tract infection. Patients who are immunocompromised, have haemochromatosis or liver cirrhosis are more likely to develop serious complications such as bacteraemia. We present the case of a 76-year-old man with fever and an acutely tender, swollen right knee. Blood cultures were positive for Y. pseudotuberculosis, and 16s ribosomal PCR analysis of his knee aspirate confirmed septic arthritis. He was treated with intravenous ceftriaxone and made an excellent recovery following knee washout. Interestingly, our patient did not have any of the classic risk factors described in the literature, or history of exposure to the pathogen to explain his diagnosis. To our knowledge, this is only the second confirmed case of Y. pseudotuberculosis bacteraemia with septic arthritis, and the first to involve the knee joint.

Yersinia pseudotuberculosis infection in Kawasaki disease and its clinical characteristics.

BACKGROUND: The etiology of Kawasaki disease (KD) is unknown. Reportedly, there is an association between KD and Yersinia pseudotuberculosis (YPT). Steroid therapy for KD patients with high risk of cardiac sequelae (CS) has been reported; however, the number of reports is limited. METHODS: We conducted a prospective study of 108 patients with newly diagnosed KD in one year to determine how many KD patients have positive anti-YPT antibody titers and/or positive anti-YPT-derived mitogen (YPM) antibody titers. In addition, we tried to identify clinical differences between KD patients in whom YPT infection was or not a contributing factor. We also compared clinical characteristics of patients treated with the protocol of the Randomized controlled trial to Assess Immunoglobulin plus Steroid Efficacy for Kawasaki disease (RAISE) study (RAISE group) and with the conventional Intravenous immunoglobulin (IVIG) protocol (conventional group). RESULTS: Eleven patients (10%) were positive for anti-YPT and/or anti-YPM antibodies (positive group) and 97 (90%) were negative (negative group). Cardiac sequelae (CS) occurred significantly more frequently in the positive than the negative group (two patients, 18% vs one patient, 1%, p = 0.027). Forty patients were in the RAISE group. Two of 40 (5%) in the RAISE group and one of 68 (1.47%) in the conventional group had CS (p = 0.55). CONCLUSIONS: KD patients with YPT infection had CS significantly more frequently and treatment with RAISE protocol did not decrease the frequency of CS in our cohort, nor did YPT infection affect risk scores of no response to IVIG. However, our sample size was overly small to draw such conclusions. Further investigation in a larger cohort is necessary to confirm our findings. Additionally, further research is needed to determine whether early diagnosis of YPT can prevent KD from developing and reduce the incidence of CS.

The histopathological mimics of inflammatory bowel disease: a critical appraisal.

The pathological diagnosis of inflammatory bowel disease (IBD) is often difficult because biopsy material may not contain pathognomonic features, making distinction between Crohn's disease, ulcerative colitis and other forms of colitides a truly challenging exercise. The problem is further complicated as several diseases frequently mimic the histological changes seen in IBD. Successful diagnosis is reliant on careful clinicopathological correlation and recognising potential pitfalls. This is best achieved in a multidisciplinary team setting when the full clinical history, endoscopic findings, radiology and relevant serology and microbiology are available. In this review, we present an up-to-date evaluation of the histopathological mimics of IBD.

[First case of lung abscess due to Yersinia pseudotuberculosis in Japan].

A 63-year-old previously healthy man was admitted to our hospital with diarrhea that had lasted for about 4 weeks, high fever and dyspnea. Chest computed tomography showed consolidation with a low-density area in the right middle lobe and small nodules with feeding vessels in the right upper lobe. On Day 8, a cavity was observed in the consolidation, and the lymph nodes in the mediastinum became necrotic. Yersinia pseudotuberculosis (serotype 4b) was cultured from blood, bronchial washing fluid, and lung tissue specimens. We diagnosed the lung lesions as septic pulmonary embolism caused by enterocolitis. We started treatment with tazobactam/piperacillin. It has been reported that high-dose ceftriaxone (CTRX) is effective, but CTRX at normal doses and other beta-lactams are less effective or even ineffective. Therefore, we changed to CTRX (4g/day) on Day 5, CTRX (2g/day) on Day 8, and oral cefditoren pivoxil (600 mg/day; a third-generation cephalosporin) on Day 18. Antibiotic therapy resulted in a favorable response. The patient was discharged from our hospital on day 25 in good health. To the best of our knowledge, this is the first case of a lung abscess caused by Y. pseudotuberculosis reported in Japan.

Difficulties in diagnosing terminal ileitis due to Yersinia pseudotuberculosis.

We report three patients with terminal ileitis and positive fecal cultures with Yersinia pseudotuberculosis. From one patient, a virulence plasmid (pYV)-negative Y. pseudotuberculosis was isolated, which represents the second finding of a pYV-negative isolate associated with human disease. All patients were treated with ciprofloxacin and fully recovered. Since conventional culture methods for yersiniosis are gradually replaced with molecular tests not recognizing Y. pseudotuberculosis, we recommend to include a specific culture medium or to apply a specific polymerase chain reaction (PCR) assay on fecal samples from patients suspected of terminal ileitis.

Haemophilia-associated Yersinia pseudotuberculosis serotype O:1 septicaemia: the role of iron.

Septicaemia and septic arthritis due to Yersinia pseudotuberculosis are rare diseases with high mortality rates. Reactive arthritis caused by Yersinia infection is a well-known complication but septic arthritis is found at a much lower frequency. It has already been established that there is a relationship between yersiniosis and iron but there are currently no data about yersiniosis and haematological disorders such as haemophilia. We report a case of septic arthritis due to Y. pseudotuberculosis as an early manifestation of Yersinia septicaemia in a patient with severe haemophilia A. The patient had no history of immunosuppression and presented with a repeat case of haemarthrosis with a fever of unknown origin. Furthermore, he suffered from acute-on-chronic renal failure and non-ST segment elevation myocardial infarction. Arthrocentesis and blood culture tested positive for Y. pseudotuberculosis. Iron deposits at localized sites in the synovium in patients with haemophilia have been described, and as Yersinia infections are common in patients with secondary iron overload, we felt that a review of the literature was in order. Severe Yersinia infection is often associated with iron overload, a condition that might occur as a side effect in the treatment of haemophilia. Iron overload, which plays an important role in the pathogenesis of haemophilic arthropathy, may have increased the virulence of Y. pseudotuberculosis in the present case.

Acute encephalopathy and tubulointerstitial nephritis associated with Yersinia pseudotuberculosis.

We report the case of a 28-month-old boy with encephalopathy and acute tubulointerstitial nephritis possibly associated with Yersinia pseudotuberculosis (Yp) infection. He was transferred to our center because of impairment of renal function and altered consciousness. He had fever for 5 days after recurrent vomiting and diarrhea. Computed tomography scan was normal, but electroencephalogram (EEG) analyses showed generalized slow wave patterns. Continuous hemodialysis was undergone and then his renal function was improved, but altered consciousness persisted. Single photon emission computed tomography (SPECT) revealed abnormally low signals at entire field, which suggested that he was suffered from encephalopathy. Phenobarbital administration and post-encephalopathy rehabilitation were started, and he recovered in fully premorbid state with normal EEG and SPECT findings on the 33rd hospital day. Various bacterial cultures were negative, but both Yp antibody and Yp-derived mitogen (YPM) antibody, the antibody of a specific Yp exotoxin, had an extremely high titer. This is the first report of encephalopathy potentially caused by Yp, indicated by the presence of a high Yp and YPM antibody titer.

Yersinia pseudotuberculosis colitis presented with severe gastrointestinal bleeding.

We report an adult case of Yersinia pseudotuberculosis colitis who presented with severe gastrointestinal bleeding. A 25-year-old male had admitted with fever, vomiting, body aches, and massive lower gastrointestinal bleeding. Since diagnostic tests were unremarkable and the patient's hemodynamic condition was unstable, emergency explorative laparotomy was performed. During the operation, localized wall thickening and ulcers were seen in the cecum. Right hemicolectomy was performed. Histological examination showed non-caseation granulomas in mesenteric lymph nodes and transmural inflammation in the cecum. Y. pseudotuberculosis serology, based on histological suspicion, was positive. The patient was discharged with cure 12 days after the operation following gentamicin treatment. To our knowledge, there are only two reports about massive lower gastrointestinal bleeding due to Y. pseudotuberculosis. Although this is a rare entity, lower gastrointestinal bleeding due to Y. pseudotuberculosis should be taken into consideration in the differential diagnosis of patients presenting with massive lower gastrointestinal bleeding, as a possible cause.

[To the differential diagnosis of arthritis of pseudotuberculous and chlamydial etiology].

AIM: to define main differential diagnostic criteria for arthritides of chlamydial and pseudotuberculous etiology and to improve patient examination tactics. SUBJECTS AND METHODS: Forty-six patients with pseudotuberculosis and 41 patients with chronic urogenital chlamydial infection with articular involvement were examined. A bacteriological method of polymerase chain reaction (PCR), agglutination test, enzyme immunoassay (EIA) (IgA, IgG, IgM), indirect hemagglutination (IHA) test were used to diagnose pseudotuberculosis. Diagnostic techniques for chlamydiasis involved cultural, direct immunofluorescence (DIF), real-time PCR, and EIA (IgM, IgG, IgA). RESULTS: Patients with pseudotuberculosis developed polyarthritis and oligoarthritis in 56 and 39%, respectively. The development of arthritides was accompanied by fever in 89%, exanthema in 57%, gastrointestinal lesion in 56%, hepatomegalia in 78%. The pseudotuberculous etiology of the disease was confirmed by the agglutination test in 71% of the patients and by IHA in 7%. EIA revealed IgG in 78% of the patients, IgA in 11%, and IgM in 29%. PCR of synovial fluid (SF), synovial shell, and other biological substrates revealed Yersinia pseudotuberculosis DNA in 43%. Chlamydiasis and polyarthritis developed in 71 and 19%, respectively. The diagnosis of chlamydiasis was verified by EIA detection of IgG and IgA in 76 and 27% of cases, respectively. DIF, PCR, and culture studies of urethral scrapes found Chlamydia in 9, 32, and 29% of cases, respectively. Examination of SF and synovial shells revealed Chlamydia trachomatis in 24% of the patients and culture studies detected the pathogen in 21%. CONCLUSION: Asymmetrical polyarthritides mainly involving the knee joints are the most common arthritides of pseudotuberculous etiology. EIA detection of serum IgG and IgA and PCR study of SF are optimal diagnostic tools. Artritides of chlamydial etiology are asymmetrical oligoarthritides predominantly involving the knee and ankle joints. Examination of urethral and cervical canal scrapes, SF by culture and PCR studies and that of serum IgA and IgG by EIA are optimal diagnostic tests.

Analysis of Kawasaki disease showing elevated antibody titres of Yersinia pseudotuberculosis.

AIM: To elucidate a clinical difference between patients with Kawasaki disease documented with Yersinia pseudotuberculosis infection and patients with Kawasaki disease without Yersinia pseudotuberculosis infection. PATIENTS AND METHODS: From January 1985 to July 2004, 452 patients were diagnosed with Kawasaki disease. Forty-two patients had elevated antibody titres of Yersinia pseudotuberculosis and/or positive stool culture (Yersinia-positive group). Three hundred and thirty patients had no elevated antibody titres (Yersinia-negative group). We compared the clinical characteristics retrospectively. RESULTS: The age of onset in the Yersinia-positive group (3.05+/-2.20 y) was significantly higher than that in the Yersinia-negative group (2.31+/-2.05 y) (p=0.03). The age-adjusted statistical analysis demonstrated that the incidence of coronary artery lesions (dilatations plus aneurysms) in the Yersinia-positive group (22/42, 52.4%) was significantly higher than in the Yersinia-negative group (105/330, 31.8%) (p=0.001), and the incidence of additional administration of immunoglobulin in the Yersinia-positive group (13/36, 36.1%) was significantly higher than in the Yersinia-negative group (41/256, 16.0%) (p=0.004). CONCLUSION: Our data suggest that Yersinia pseudotuberculosis infection might play a role in the developing mechanism of poor response to therapy and the tendency to develop coronary artery lesions in Kawasaki disease patients.

[Yersinia lipopolysaccharide and its biological activity].

The data on the structure and biological activity of the lipopolysaccharide (LPS) of Yersinia as an important virulence factor are analyzed. The biological effects of LPS are characterized by dose dependence: small doses stimulate the intensity of phagocytosis, while large doses decrease phagocytic activity and produce cytotoxic effect. Yersinia LPS plays an important role in the development of such consequences of yersiniosis as reactive arthritis, erythema nodosum, Reiter's syndrome. Yersinia LPS is a widespread component for the diagnostics of yersiniosis and pseudotuberculosis.

Mesenteric adenitis caused by Yersinia pseudotubercolosis in a patient subsequently diagnosed with Crohn's disease of the terminal ileum.

Although the association between inflammatory bowel disease and gastrointestinal infections has been suggested, the mechanisms involved in the pathogenesis of Crohn's disease (CD) are still undetermined. We report the case of a man, who presented with mesenteric adenitis initially due to a Yersinia pseudotubercolosis infection, who was later diagnosed with Crohn's disease. This case is in keeping with recent evidence in the literature which suggests that CD is a disease linked to abnormal immune responses to enteric bacteria in genetically susceptible individuals.

[Yersinia pseudotuberculosis type 4a infection meeting the diagnostic criteria for Kawasaki disease complicated by disseminated intravascular coagulation].

We report a case of Yersinia pseudotuberculosis (Y. ptbc) infection complicated by disseminated intravascular coagulation (DIC) that presented as Kawasaki disease (KD). A 9-year-old girl had been well until two days before, when she developed a fever, exanthem, and abdominal pain. An erythematous macular rash was observed in the perineum, and she had a strawberry tongue. The patient was admitted to Kawasaki Medical School Hospital because the macular rash spread over her entire body, and edema of her hands and conjunctivitis subsequently developed. Echo cardiography showed dilation of the left coronary artery. Thrombocytopenia and an elevated total fibrin degeneration product level were noted on the third hospital day, and the prothronmbin and partial-thromboplastin times were prolonged. Her clinical presentation was typical of KD and DIC. A stool culture and a blood culture were negative. Serologic tests were positive for antibodies to Y. ptbc. The antibody titer against Y. ptbc-derived mitogen was not elevated after her recovery. Y. ptbc infection should be considered in an older child whose clinical findings fulfill the criteria for KD complicated by DIC.

Bacteriemia y absceso hepático secundarios a infección por Yersinia pseudotuberculosis / Bacteriemia and hepatic abscess secondary to Yersinia pseudotuberculosis infection

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