Haemophagocytic lymphohistiocytosis: an inherited primary form and a reactive secondary form.
Explore the source record for details and available documents.
Diagnosis, Differential↗
Biomedical subjects
J I Henter
Publications and source records attributed to J I Henter.
Allogeneic bone marrow transplantation for hemophagocytic lymphohistiocytosis in Sweden.
Six children (aged 9 months to 10 and 5/12 years) with hemophagocytic lymphohistiocytosis (HLH) have undergone allogeneic BMT in Sweden. In two of the children unrelated donors were used. Parents were available as donors in two of the cases and siblings in the other two. Conditioning before BMT consisted of etoposide, busulfan and cyclophosphamide with the addition of ATG in two cases and OKT 3 in one case. For post-transplant immunosuppression, i.v. methotrexate and cyclosporin A (CsA) were used in five cases, and in one child CsA was combined with methylprednisolone. Of the six children, four are alive and well 2 and 3/12 to 3 and 1/12 years after BMT. One child, who had an unrelated donor with one DR-antigen mismatch, died 30 days after BMT of fulminant grade IV GVHD. Another patients, seropositive for CMV, received marrow from an unrelated HLA-A, -B, -DR and -DP identical donor. After an initially uneventful course, CMV was isolated from her leukocytes. Seven months after BMT she developed a progressive obstructive chronic bronchiolitis and succumbed to respiratory insufficiency 14 months after the transplant. This study supports the view that BMT is the treatment of choice in HLH, particularly if an HLA-identical related donor is available.
Bone Marrow Transplantation↗
Bone marrow transplantation in two children with congenital amegakaryocytic thrombocytopenia.
Two thrombocytopenic infants with essentially normal initial bone marrow morphology were believed to have idiopathic thrombocytopenic purpura. However, they failed to respond to steroids and intravenous immunoglobulins and had a normal platelet recovery after transfusions. The diagnosis was revised to congenital amegakaryocytic thrombocytopenia after bone marrow biopsies, which revealed a marked paucity of megakaryocytes. Repeated biopsies disclosed gradually decreasing numbers of megakaryocytes and increasing marrow hypoplasia. At the ages of 42 and 22 months the children underwent allogeneic bone marrow transplants, one of them with an unrelated marrow donor. Both patients are well with good engraftment of donor marrow and normal peripheral blood counts, 31 and 12 months after BMT, respectively.
Bone Marrow Transplantation↗
Incidence of celiac disease in northwest Stockholm.
Explore the source record for details and available documents.
Celiac Disease↗
Kala-azar in a one-year-old Swedish child. Diagnostic difficulties because of active hemophagocytosis.
A one-year-old Swedish boy developed kala-azar six months after a holiday in Spain. Upon visiting the hospital after one week of illness he demonstrated clinical and laboratory findings of fever, splenomegaly and cytopenia. A fine-needle aspiration biopsy of the spleen revealed hemophagocytosis and he had increased serum levels of the cytokines tumor necrosis factor-alpha and interferon-gamma. Initially, a diagnosis of hemophagocytic lymphohistiocytosis was made. Re-evaluation of the spleen smears and of the bone marrow aspiration revealed Leishmania parasites and subsequent therapy with sodium stibogluconate was successful. This patient illustrates the interesting similarities between these two disorders involving the mononuclear phagocyte system as well as the problems involved in differential diagnosis. This case also reminds us of the possibility of contracting visceral leishmaniasis in Mediterranean countries.
Animals↗
Familial hemophagocytic lymphohistiocytosis and viral infections.
A retrospective study was performed in 32 children with hemophagocytic lymphohistiocytosis, 16 of whom had affected siblings. Altogether 22 of these children, of whom the majority (13/22) were familial cases, had clinical or laboratory signs of infection. Laboratory analysis demonstrated Epstein-Barr virus in five children, cytomegalovirus in three and human parvovirus in two. Two siblings with onset of familial hemophagocytic lymphohistiocytosis within one month of each other, both of whom demonstrated serological indications of a recent human parvoviral infection at onset, are described. It is concluded that a viral infection cannot serve as the sole criterion for distinguishing a virus-associated hemophagocytic syndrome as an entity separate from familial hemophagocytic lymphohistiocytosis. Instead, it is suggested that viral infections may elicit a bout of the familial hemophagocytic lymphohistiocytosis disorder in genetically predisposed individuals.
Child, Preschool↗
Lipoprotein alterations in children with bacterial meningitis.
Abnormalities in serum lipids, including hypertriglyceridemia, are common during infectious disorders. However, the lipoprotein pattern during infections, particularly in children, has been investigated to only a limited extent. We have monitored alterations in serum lipoproteins in eight children with a severe bacterial infection (meningitis) by a quantitating method measuring cholesterol and triglycerides in each major class. The levels of triglycerides in serum and in low-density lipoproteins were markedly elevated during the infection, whereas the amount of cholesterol in high-density lipoproteins was decreased. The cholesterol to triglyceride ratio was decreased in low-, as well as in high-density lipoproteins. These lipoprotein abnormalities may, at least in part, be explained by a depressed lipolytic activity of lipoprotein lipase, the key enzyme for removal of triglycerides in man. Serum triglycerides and the levels of cholesterol in high-density lipoproteins, as well as the ratio between these parameters, may be used as indicators of inflammatory activity.
Child, Preschool↗
Cerebromeningeal haemophagocytic lymphohistiocytosis.
We describe 3 children with a progressive encephalopathy that was characterised by irritability, convulsions, cranial nerve palsies, ataxia, nystagmus, walking difficulties, delayed psychomotor development, hemiplegia/tetraplegia, visual disturbance, vomiting, neck stiffness, and non-specific signs of raised intracranial pressure. A final diagnosis was made in all 3 patients from necropsy material. The clinical features were ascribed to multiple inflammatory, predominantly lymphocytic, reactions and raised intracranial pressure. This condition is an atypical form of haemophagocytic lymphohistiocytosis, which normally presents with fever, hepatosplenomegaly, and cytopenias. By contrast, the disease pattern in our 3 children was dominated by cerebromeningeal involvement, which can precede the typical systemic symptoms of haemophagocytic lymphohistiocytosis. An awareness of this condition is important because treatments are available.
Brain Diseases↗
Hypercytokinemia in familial hemophagocytic lymphohistiocytosis.
Familial hemophagocytic lymphohistiocytosis (FHL) is a frequently missed and almost uniformly fatal childhood disorder. It is characterized by fever, hepatosplenomegaly, cytopenia, coagulopathy, and hypertriglyceridemia. The pathogenesis of FHL is not known but the above clinical and laboratory findings are compatible with reported in vitro and in vivo effects of several inflammatory cytokines. We measured circulating interferon-gamma (IFN-gamma), tumor necrosis factor/cachectin (TNF), and interleukin-6 (IL-6) in nine children with FHL. During active disease, elevated IFN-gamma was detected in seven of seven children, TNF in six of six, and IL-6 in two of six children studied. Thus, important inflammatory cytokines are augmented in active FHL and may contribute to the pathogenesis of the disease. Soluble CD8 was also increased in seven of seven children, which suggests a pathophysiologic importance of cytotoxic T lymphocytes. Because FHL appears to be associated with a systemic hypercytokinemia, our results also indicate that studies of FHL may contribute to the understanding of cytokine effects in vivo. Moreover, FHL is a hereditary disorder, suggesting that the hypercytokinemia is caused by a genetic defect in cytokine regulation.
CD8 Antigens↗
Familial hemophagocytic lymphohistiocytosis. Clinical review based on the findings in seven children.
Clinical, laboratory, and histological findings in FHL of diagnostic importance were intermittent fever, hepatosplenomegaly, peripheral blood cytopenia, hypertriglyceridemia, hypofibrinogenemia, and a lymphohistiocytic accumulation with hemophagocytosis in the mononuclear phagocytic system. Fine-needle aspiration biopsy from the spleen appeared to be a useful method for revealing hemophagocytosis. The treatment of induction and relapses, as well as the maintenance therapy, included administration of teniposide, etoposide, and corticosteroids. The regimen had to be individualized for each child since the clinical course was highly variable. Half of the children given successful induction therapy (3/6) are still alive with over a 3-year survival after diagnosis.
Antineoplastic Combined Chemotherapy Protocols↗
Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis.
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.
Adolescent↗
The contribution of ultrafiltration pressure for glomerular hyperfiltration in young nephrectomized rats.
UNLABELLED: Ablation of renal tissue in infancy is followed by increased ultrafiltration pressure, enlarged filtering area and decreased hydraulic conductivity of the glomerular capillaries. This study examines the effect of a calcium channel blocker, felodipine, on ultrafiltration pressure and renal function in rats uni-nephrectomized at 5 days of age. The rats were treated with felodipine from 24 to 60 days of age or left untreated. Sham-operated untreated rats were used as controls. Arterial blood pressure levels were similar in the three groups of rats. Glomerular filtration rate and renal plasma flow in the left kidney were significantly higher in treated and untreated rats than in sham-operated untreated rats; significantly higher values were also found in treated than in untreated rats. Single nephron glomerular filtration rate was significantly higher in treated and in untreated than in sham-operated untreated rats, but was not different in treated and untreated rats. Ultrafiltration pressure was significantly higher in untreated rats than in treated and in sham-operated untreated rats. Ultrafiltration coefficient (Kf) was significantly higher in treated rats than in untreated and sham-operated untreated rats. Hydrolic conductivity of the glomerular capillaries was significantly lower in untreated than in treated and in sham-operated rats, but was not different in treated and sham-operated rats. Glomerular volume was higher in treated and untreated rats than in sham-operated rats. CONCLUSION: high ultrafiltration pressure is not an absolute requirement for the hyperfiltration that follows infant nephrectomy.
Animals↗
Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society.
Explore the source record for details and available documents.
Histiocytosis, Non-Langerhans-Cell↗
Molecular and serologic analysis of IgG1 deficiency caused by new forms of the constant region of the Ig H chain gene deletions.
Selective IgG1 deficiency is a rare disease. We report a familial form of IgG1 deficiency, in which IgG1 was undetectable in a 5-yr-old girl with a history of asthma and respiratory tract infections. Her father had an IgG1 level that was one-third of the mean amount found in normal healthy controls. The defect in the proband was caused by a homozygous deletion of the structural gene for C gamma 1. A Southern blot analysis demonstrated that the maternal haplotype contained a deletion encompassing C gamma 1, C psi epsilon 1, C alpha 1, C psi gamma, and C gamma 2, whereas the deletion on the paternal haplotype was confined to the C gamma 1 gene. Neither of these deletions has previously been reported. IgG1 normally constitutes the dominant isotype for antibodies directed against protein Ag, including viral proteins. We have analyzed the immune response to a number of different protein and polysaccharide Ag in the patient and her parents. In the proband, antiviral antibodies were restricted to the IgG3 and IgG4 subclasses. However, the total amount of IgG directed against several viruses was below the concentration found in normal seropositive individuals. The father and the paternal grandfather, both with low serum IgG1 levels, also had asthma, thus indicating a possible causal relationship.
Adult↗
[Chickenpox during pregnancy--risks for mother and child].
Explore the source record for details and available documents.
Adult↗
Identification of individual tumor necrosis factor/cachectin-producing cells after lipopolysaccharide induction.
A method to detect single tumor necrosis factor alpha (TNF alpha)-producing cells, based on immunofluorescence staining, is presented. We have developed a rapid and simple procedure to permeabilize blood leukocytes for antibodies without causing cell aggregation. Using monoclonal as well as polyclonal TNF alpha-specific antibodies cytoplasmic TNF alpha could be detected in lipopolysaccharide (LPS)-stimulated monocytes in identical ways. In addition, one out of 15 tested fresh blood samples from healthy blood donors contained occasional TNF alpha-producing cells. We found a well-defined staining of the intracellular TNF alpha with a local, polar accumulation in a juxtanuclear position of the cell. This finding most probably indicated the presence of the monokine in the Golgi organelle because the sequential staining for TNF alpha and the Golgi zone by specific antibodies coincided. Thus, we believe the TNF alpha accumulation at this site reflects the production rather than cellular uptake of the cytokine, since the incubation of blood leukocytes with recombinant TNF alpha did not lead to any detectable staining. By performing two-color staining of cell surface antigens and cytoplasmic TNF alpha of LPS-stimulated blood leukocytes we could demonstrate that monocytes exclusively contributed to the TNF alpha synthesis. At the peak of the response, which occurred 2-3 h after LPS exposure, 50-60% of the blood monocytes produced TNF alpha. We noted a rapid decline in the number of TNF alpha-producing cells already 6 h after initiation of these cultures.
Antibodies, Monoclonal↗
Longitudinal analysis of infantile growth in children with celiac disease.
The aim of the present study was to describe linear growth of infants with celiac disease, using the "ICP-growth model". Supine length during the first three years of life was studied longitudinally in 63 infants with diagnosed celiac disease. "Undisturbed" linear growth was seen during the first six postnatal months followed by reduced growth during the second half of the first year. After 1.5 years of age a pattern of catch-up growth was observed, leading to an average attained length at 3 years of age similar to that of the controls. According to the "ICP-growth model", normal linear growth can mathematically be represented during the first 3 years of life by an Infancy component with the addition of a Childhood component, the latter acting from the second half of the first postnatal year. The onset of the Childhood component (assumed to represent the age at which growth hormone begins to influence linear growth significantly) was delayed by about an average of 3 months, which is in agreement with the observed reduction in gain during the second half of the first year of life. Children suffering from celiac disease and with "late" onset of the Childhood component were shorter at 1, 2 and 3 years of age than those with "normal" onset. The results of this investigation show that ICP-based growth charts are helpful in detecting and monitoring growth for children with celiac disease, and indicate a possible mechanism whereby malabsorption (and perhaps secondary malnutrition) leads to reduced growth velocity.
Age Factors↗
Shiga-like toxin production and connective tissue protein binding of Escherichia coli isolated from a patient with ulcerative colitis.
A 15-year-old girl with her first relapse of ulcerative colitis was treated with salicylazosulfapyridine, steroids, metronidazole and parenteral nutrition for 4 weeks without significant improvement. Her faecal specimens were negative for established intestinal pathogens, but strains of Escherichia coli producing Shiga-like toxin and expressing binding of fibronectin and collagen were repeatedly isolated. Neutralizing antibodies to Shiga-like toxin were detected in serum samples. Improvement was achieved during treatment with mecillinam to which the E. coli strains were sensitive.
Adolescent↗