Vaccination in paediatric patients with auto-immune rheumatic diseases: a systemic literature review for the European League against Rheumatism evidence-based recommendations.

OBJECTIVES: To analyze available evidence on vaccinations in paediatric patients with rheumatic and autoinflammatory diseases. This evidence formed the basis of the recently constructed European League against Rheumatism (EULAR) recommendations for vaccination of these patients. METHODS: A systematic literature review in the MEDLINE and EMBASE databases was conducted using various terms for vaccinations, paediatric rheumatic and autoinflammatory diseases and immunosuppressive drugs. Only papers on paediatric patients (<18 years of age) were selected. A panel of 13 experts in the field graded methodological quality and extracted data using predefined criteria. RESULTS: 27 papers were available. No studies were found on autoinflammatory diseases. 14 studies considered live-attenuated vaccines. Evidence so far supports the safety and immunogenicity of non-live composite vaccines, although studies were underpowered to accurately assess safety. Live-attenuated vaccines did not cause disease flares or severe adverse events, not even in patients on methotrexate and low dose glucocorticosteroids. Seven patients on anti-TNFalpha therapy were described receiving the live-attenuated measles, mumps, rubella (n=5) or varicella (n=2) booster without severe adverse events. CONCLUSIONS: Data on safety and efficacy of vaccinations in paediatric patients with rheumatic diseases is reassuring, but too limited to draw definite conclusions. More research is needed on the safety and efficacy of especially live-attenuated vaccines in patients with rheumatic and autoinflammatory diseases using high dose immunosuppressive drugs.

EULAR recommendations for vaccination in paediatric patients with rheumatic diseases.

Evidence-based recommendations for vaccination of paediatric patients with rheumatic diseases (PaedRD) were developed by following the EULAR standardised procedures for guideline development. The EULAR task force consisted of (paediatric) rheumatologists/immunologists, one expert in vaccine evaluation, one expert in public health and infectious disease control, and one epidemiologist. A systematic literature review was conducted in MEDLINE, EMBASE, and abstracts of the EULAR and American College of Rheumatology meetings of 2008/9. The level of evidence and strength of recommendation were based on customary scoring systems. Delphi voting was applied to assess the level of agreement between task force members. 107 papers and eight abstracts were used. The majority of papers considered seasonal influenza (41) or pneumococcal (23) vaccination. 26 studies were performed specifically in paediatric patients, and the majority in adult rheumatoid arthritis and systemic lupus erythematosus patients. Fifteen recommendations were developed with an overall agreement of 91.7%. More research is needed on the safety and immunogenicity of (live-attenuated) vaccination in PaedRD, particularly in those using biologicals, and the effect of vaccination on prevention of infections.

[First case of chikungunya diagnosed in the Netherlands]. / Chikungunya voor het eerst gediagnosticeerd in Nederland.

A 52-year-old man was seen in the Diagnostic Centre for Tropical Diseases of the Havenziekenhuis, Rotterdam, presenting with arthralgia, fever and exanthema following a stay in Mauritius. Infection with the Dengue virus infection is a common diagnosis for this combination of complaints, but nowadays chikungunya should also be considered. This is particularly the case when a patient has visited a country in or around the Indian Ocean. Risk areas are La Réunion and Mauritius, where, in February 2005 and April 2005 respectively, epidemics broke out. Chikungunya is a viral infection. The causative virus is an Alpha virus, transmitted by mosquitoes. The symptoms include arthralgia, myalgia, diffuse maculopapular rash, fever and headache. In contrast to dengue, chikungunya is not associated with haemorrhagic diathesis. Treatment takes place in response to the symptoms, since there is no targeted therapy available. The main preventive measure is to prevent mosquito bites. The disease is not deadly and healing is spontaneous. To our knowledge this is the first case of chikungunya diagnosed in the Netherlands during this epidemic. The disease has recently been reported in Italy, where native mosquitoes transmit it.

[Fever and exanthema as manifestations of the second stage of syphilis]. / Koorts en exantheem als manifestatie van het secundaire stadium van syfilis.

A man aged 30 had been suffering from episodes of fever for several weeks. He had diarrhoea and had developed generalized maculopapular exanthema that also affected the palms of his hands and soles of his feet. After viral causes were excluded the symptoms proved to be caused by syphilis. His condition was complicated by uveitis. The patient recovered after a single dose of benzyl penicillin and local mydratics and corticosteroid eye drops. The incidence of syphilis is rising and its clinical spectrum is broad. Therefore in patients with fever and exanthema of unknown origin this disease should be considered. One should be aware of the wide variety of complications that can result from syphilis.

Mouse models of colorectal cancer and liver metastases.

Colorectal cancer (CRC) is one of the most common malignancies in the western world. Its high mortality rates are particularly related to the occurrence of liver metastases. Many mouse models have been developed to evaluate the various features of CRC in human. Since none of the existing mouse models mimics all the characteristics of human CRC, it is of crucial importance that the optimal model is chosen for each experiment to resolve a specific experimental question. Currently used mouse models for CRC include chemically induced CRC models, genetically engineered mouse models and models in which colon tumors are implanted in recipient mice. Recently, conditional mouse models have been created in which a gene of interest can be (in)activated in a time- and tissue-specific manner. All models have their advantages and limitations. This review highlights the most commonly used mouse models for CRC and its liver metastases, their usefulness and shortcomings, as well as recent improvements, particularly regarding intravital (tumor) imaging.