An overview of the cutaneous porphyrias

This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrin–haem biosynthetic pathway. All the cutaneous porphyrias can have (either as a consequence of the porphyria or as part of the cause of the porphyria) involvement of other organs as well as the skin. The single commonest cutaneous porphyria in most parts of the world is acquired porphyria cutanea tarda, which is usually due to chronic liver disease and liver iron overload. The next most common cutaneous porphyria, erythropoietic protoporphyria, is an inherited disorder in which the accumulation of bile-excreted protoporphyrin can cause gallstones and, rarely, liver disease. Some of the porphyrias that cause blistering (usually bullae) and fragility (clinically and histologically identical to porphyria cutanea tarda) can also be associated with acute neurovisceral porphyria attacks, particularly variegate porphyria and hereditary coproporphyria. Management of porphyria cutanea tarda mainly consists of visible-light photoprotection measures while awaiting the effects of treating the underlying liver disease (if possible) and treatments to reduce serum iron and porphyrin levels. In erythropoietic protoporphyria, the underlying cause can be resolved only with a bone marrow transplant (which is rarely justifiable in this condition), so management consists particularly of visible-light photoprotection and, in some countries, narrowband ultraviolet B phototherapy. Afamelanotide is a promising and newly available treatment for erythropoietic protoporphyria and has been approved in Europe since 2014

Sequelae due to bacterial meningitis among African children: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>African children have some of the highest rates of bacterial meningitis in the world. Bacterial meningitis in Africa is associated with high case fatality and frequent neuropsychological sequelae. The objective of this study is to present a comprehensive review of data on bacterial meningitis sequelae in children from the African continent.</p> <p>Methods</p> <p>We conducted a systematic literature search to identify studies from Africa focusing on children aged between 1 month to 15 years with laboratory-confirmed bacterial meningitis. We extracted data on neuropsychological sequelae (hearing loss, vision loss, cognitive delay, speech/language disorder, behavioural problems, motor delay/impairment, and seizures) and mortality, by pathogen.</p> <p>Results</p> <p>A total of 37 articles were included in the final analysis representing 21 African countries and 6,029 children with confirmed meningitis. In these studies, nearly one fifth of bacterial meningitis survivors experienced in-hospital sequelae (median = 18%, interquartile range (IQR) = 13% to 27%). About a quarter of children surviving pneumococcal meningitis and <it>Haemophilus influenzae </it>type b (Hib) meningitis had neuropsychological sequelae by the time of hospital discharge, a risk higher than in meningococcal meningitis cases (median = 7%). The highest in-hospital case fatality ratios observed were for pneumococcal meningitis (median = 35%) and Hib meningitis (median = 25%) compared to meningococcal meningitis (median = 4%). The 10 post-discharge studies of children surviving bacterial meningitis were of varying quality. In these studies, 10% of children followed-up post discharge died (range = 0% to 18%) and a quarter of survivors had neuropsychological sequelae (range = 3% to 47%) during an average follow-up period of 3 to 60 months.</p> <p>Conclusion</p> <p>Bacterial meningitis in Africa is associated with high mortality and risk of neuropsychological sequelae. Pneumococcal and Hib meningitis kill approximately one third of affected children and cause clinically evident sequelae in a quarter of survivors prior to hospital discharge. The three leading causes of bacterial meningitis are vaccine preventable, and routine use of conjugate vaccines could provide substantial health and economic benefits through the prevention of childhood meningitis cases, deaths and disability.</p

Chronic Q fever diagnosis—consensus guideline versus expert opinion

Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fe­ver Consensus Group and a set of diagnostic criteria pro­posed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006–2012. Of the patients who had proven cas­es of chronic Q fever by the Dutch guideline, 46 (30.5%) would not have received a diagnosis by the alternative cri­teria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch lit­erature-based consensus guideline is more sensitive and easier to use in clinical practice

Phenotypic and genotypic changes in a new clone complex of Neisseria meningitidis causing disease in The Netherlands, 1958-1990

To characterize the phenotypic and genotypic changes that occurred in a new clone lineage of Neisseria meningitidis (lineage III) in the Netherlands, the electrophoretic type (ET) was determined for 79 serogroup B isolates of serotype 4 or subtype P1.4 (or both) obtained between 1958 and 1990 from patients with systemic meningococcal disease. Thirty-five previously described isolates were also included. After its appearance in 1980, lineage III started homogeneously with regard to both genotype (ET-24) and phenotype (B:4:P1.4). After 1984, other clones appeared in the lineage, and the various clones acquired other serotypes (serotypes 14 and 15) and subtypes (P1.2, P1.7, and P1.12), indicating frequent exchange of genetic material between clones. These results indicate that basing a serogroup B vaccine on outer membrane components from a single strain is not a valid strategy for the prevention of meningococcal diseas

Meningococcal disease in The Netherlands, 1958-1990: a steady increase in the incidence since 1982 partially caused by new serotypes and subtypes of Neisseria meningitidis

In order to explain a threefold increase in the incidence of meningococcal disease in the Netherlands during the 1980s, we serotyped and subtyped Neisseria meningitidis isolates recovered between 1958 and 1990 from > 3,000 patients with systemic disease. No single strain could be held responsible for the increase. Apart from the newly introduced strain B:4:P1.4, which became the most prevalent phenotype in 1990 (21% of all isolates), the majority of the cases in 1990 were caused by many different strains that were already present in the Netherlands before 1980. For the period 1980-1990, a shift in the age distribution of patients with meningococcal disease from younger to older age categories was found, particularly with regard to cases due to meningococci of serogroup B; this shift is explained by the changing distribution of serotypes and subtypes within serogroup B. A polyvalent group B, class 1 outer-membrane-protein vaccine of a stable composition could theoretically have prevented approximately 80% of all group B meningococcal infections in the Netherlands during the past 30 year