Hemophagocytic lymphohistiocytosis (HLH) comprises familial (primary) hemophagocytic lymphohistiocytosis (FHL)and secondary HLH (SHLH), both clinically characterized by fever, hepatosplenomegaly, and cytopenia. FHL, an autosomal recessive disease invariably fatal when untreated, is associated with defective triggering of apoptosis and reduced cytotoxic activity, resulting in a widespread accumulation of T lymphocytes and activated macrophages. In 1994 the Histiocyte Society initiated a prospective international collaborative therapeutic study (HLH-94), aiming at improved survival. It combined chemotherapy and immunotherapy (etoposide, corticosteroids, cyclosporin A, and, in selected patients, intrathecal methotrexate), followed by bone marrow transplantation (BMT) in persistent, recurring, and/or familial disease. Between July 1, 1994, and June 30, 1998, 113 eligible patients aged no more than 15 years from 21 countries started HLH-94. All had either an affected sibling (n ‫؍‬ 25) and/or fulfilled the Histiocyte Society diagnostic criteria. At a median follow-up of 3.1 years, the estimated 3-year probability of survival overall was 55% (95% confidence interval ؎ 9%), and in the familial cases, 51% (؎ 20%). Twenty enrolled children were alive and off therapy for more than 12 months without BMT. For patients who received transplants (n ‫؍‬ 65), died prior to BMT (n ‫؍‬ 25), or were still on therapy (n ‫؍‬ 3), the 3-year survival was 45% (؎ 10%). The 3-year probability of survival after BMT was 62% (؎ 12%). HLH-94 is very effective, allowing BMT in most patients. Survival of children with HLH has been greatly

We retrospectively studied the incidence of familial hemophagocytic lymphohistiocytosis (FHL) in children during the 16-year period 1971-86. First, all departments of pediatrics, pathology, and infectious diseases were enquired for children with FHL or disorders resembling FHL. Secondly, the causes of death of all children who died during the study period in Sweden (n = 19,542) were also investigated. Files and histological specimens were further studied in selected children. By using a set of inclusion/exclusion criteria, we found 32 children with FHL. The incidence was 1.2/1,000,000 children per year. One child per 50,000 live borns developed FHL during this period. The sex ratio was close to 1:1. Prominent early clinical signs were fever (91%), splenomegaly (84%), hepatomegaly (90%), rash (43%), and lymph node enlargement (42%). Neurological symptoms, which developed in 47%, could totally dominate the clinical picture and develop prior to other symptoms and signs. Common laboratory findings were pancytopenia, hypertriglyceridemia, hypofibrinogenemia, elevated serum transaminases, hyperbilirubinemia, hyponatremia, hypoalbuminemia, and a moderate spinal fluid pleocytosis. Chest X-ray often revealed mostly discrete pulmonary infiltrates. FHL is an underdiagnosed disease and in only 11/32 children was diagnosis made during their lifetime. It is important to be aware of the disorder as potential therapy now exists.

No abstract

No abstract

Pathologists and pediatric hematologist/oncologists of the World Health Organization's Committee on Histiocytic/Reticulum Cell Proliferations and the Reclassification Working Group of the Histiocyte Society present a classification of the histiocytic disorders that primarily affect children. Nosology, based on the lineage of lesional cells and biological behavior, is related to the ontogeny of histiocytes (macrophages and dendritic cells of the immune system). Dendritic cell‐related disorders of varied biological behavior are dominated by Langerhans cell histiocytosis, but separate secondary proliferations of dendritic cells must be differentiated. Juvenile xanthogranuloma represents a disorder of dermal dendrocytes, another dendritic cell of skin. The hemophagocytic syndromes are the most common of the macrophage‐related disorders of varied biological behavior. Guidelines for distinguishing the exceedingly rare malignant diseases of histiocytes from large cell lymphomas through the use of a battery of special studies are provided. Med. Pediatr. Oncol. 29:157–166, 1997. © 1997 Wiley‐Liss, Inc.

No abstract

Shaken baby syndrome has typically been associated with findings of subdural haematoma, retinal haemorrhages and encephalopathy, which are referred to as the triad. During the last decade, however, the certainty with which the triad can indicate that an infant has been violently shaken has been increasingly questioned. The aim of this study was to determine the diagnostic accuracy of the triad in detecting that an infant had been shaken. The literature search was performed using PubMed, Embase and the Cochrane Library up to October 15, 2015. Relevant publications were assessed for the risk of bias using the QUADAS tool and were classified as having a low, moderate or high risk of bias according to predefined criteria. The reference standards were confessions or witnessed cases of shaking or accidents. The search generated 3773 abstracts, 1064 were assessed as possibly relevant and read as full texts, and 30 studies were ultimately included. Of these, 28 were assessed as having a high risk of bias, which was associated with methodological shortcomings as well as circular reasoning when classifying shaken baby cases and controls. The two studies with a moderate risk of bias used confessions and convictions when classifying shaken baby cases, but their different designs made a metaanalysis impossible. None of the studies had a low risk of bias. Conclusion: The systematic review indicates that there is insufficient scientific evidence on which to assess the diagnostic accuracy of the triad in identifying traumatic shaking (very low-quality evidence). It was also demonstrated that there is limited scientific evidence that the triad and therefore its components can be associated with traumatic shaking (low-quality evidence).

This study has been designed to examine the effect of gestational age (GA) on the postnatal development of renal function and has been performed in pre-term (PT) infants (GA=30-34 weeks) and in full-term (FT) infants (GA=39-41 weeks). Postnatal age has ranged from 1-35 days. From 8 hour urine samples collected after spontaneous voiding and a capillary blood sample, determinations have been made of the clearance of creatinine (CCr), the fractional excretion of beta 2-microglobulin (FE beta 2) and the fractional excretion of sodium (FENa). In some infants receiving fluid parenterally, simultaneous determinations were made of the clearance of creatinine and inulin. As judged from this study, CCr is a reliable indicator of the glomerular filtration rate (GFR). GFR was almost the same in newborn PT and FT, but from 0.3--1 week of age GFR increased significantly more rapidly in FT than in PT. From 1--5 weeks of age GFR increased at approximately the same rate in PT and FT infants. The absolute value for GFR in 3--5 weeks old infants was lower in PT than in FT. FE beta 2 was higher in PT than in FT infants during the entire first month of life and FENa was higher in PT than in FT infants during the first week of life, suggesting a glomerular tubular imbalance at least at the level of the proximal tubule in PT infants. It is concluded that different stages of maturation will alter the preconditions for the renal adaptation to extrauterine life during at least the first month of life. Therefore special attention must be paid to the limited renal function in PT during their entire first month of life.