Mimicry of lyme arthritis by synovial hemangioma.

To report on the differential diagnosis of lyme arthritis and synovial hemangioma due to similar clinical and radiological signs and symptoms. A 15-year-old boy presented at the age of 9 with recurrent rather painless swelling of the right knee. Altogether four episodes lasting for 1-2 weeks each occurred over a period of 18 months before medical advice was sought. Physical examination revealed only a slightly limited range of motion. Living in an endemic area of borreliosis, he reported a tick bite 6 months prior to onset of his symptoms with erythema migrans and was treated for 10 days with amoxicillin. Serology revealed two positive unspecific bands in IgG immunoblot (p41 and 66) with slight positivity for ELISA. Ultrasound revealed synovial thickening and increased fluid. Despite the weak positive serology a diagnosis of lyme arthritis could not be excluded and intravenous antibiotic treatment with ceftriaxone was started. After two further relapses antiinflammatory therapy including intraarticular steroids were introduced with no long lasting effect. A chronical disease developed with alternate periods of swelling and almost complete remission. Ultrasound as well as MRI demonstrated ongoing signs of synovitis, therefore after further progression, a diagnostic arthroscopy was performed showing an inconspicuous knee joint. A second MRI showed focal suprapatellar enhancement and was followed by open arthrotomy revealing a histopathological proven synovial cavernous juxtaarticular hemangioma. To our knowledge, the differential diagnosis of lyme arthritis and synovial hemangioma has not yet been reported despite obvious clinical similarities. In conclusion, in children and adolescents synovial hemangioma has to be considered in differential diagnosis of recurrent knee swelling. Early diagnosis is important to prevent prolonged suffering from chronic joint swelling with probable joint damages, unnecessary treatment procedures and as well school and sports absenteeism.

Acute febrile neutrophilic dermatosis (Sweet's syndrome) in childhood and adolescence: two new patients and review of the literature on associated diseases.

OBJECTIVES: The objectives of this study were to analyse the literature on Sweet's syndrome in childhood focussing on associated diseases and to suggest possible screening procedures for this group of patients. Furthermore, two new patients with Sweet's syndrome are reported. METHODS: A literature search was performed on Pub med using search terms "sweet* syndrome*" and neutrophil* dermatos*. Patients were subdivided into the following groups: classic/idiopathic, paraneoplastic, and parainflammatory Sweet's syndrome. RESULTS: The literature search revealed 64 patients (including our two patients) who were diagnosed with Sweet's syndrome in childhood and adolescence; 27 (42%) patients were categorized as "classic/idiopathic Sweet's syndrome". In 37 patients (58%) chronic associated diseases were reported. Out of these, 21 (33%) patients were categorized as "parainflammatory Sweet's syndrome" including chronic recurrent multifocal osteomyelitis, vasculitis with aortitis, recurrent infections due to immunodeficiencies, arthritis, and systemic lupus erythematosus. Sixteen (25%) patients were categorized as "paraneoplastic Sweet's syndrome" comprising both malignant and premalignant diseases like leukemia, aplastic anaemia, and Fanconi anaemia. As all five (8%) patients treated with drugs (granulocyte-colony stimulating factor, retinoid acid) suffered from malignant, premalignant, or parainflammatory diseases, these patients were categorized according to the underlying disease. Two new children with Sweet's syndrome and associated diseases are presented here, one of them suffering from recurrent infections and trisomy 21, while the other was diagnosed with CNS vasculitis 5(1/2) years after the primary diagnosis. CONCLUSIONS: Sweet's syndrome should be considered in differential diagnosis of prolonged fever with cutaneous involvement. As most cases of pediatric Sweet's syndrome are associated with other diseases we suggest careful screening and monitoring of these patients especially concerning malignant/premalignant diseases, immunodeficiencies, cardiovascular involvement, autoimmune diseases, and drug associations.

[Purpura Schoenlein-Henoch: results of the Wörlitz 2005 Consensus Conference focusing on diagnosis and therapy]. / Purpura Schoenlein-Henoch - Ergebnisse der Wörlitzer Konsensusgespräche 2005 zum diagnostischen und therapeutischen Vorgehen.

Henoch-Schoenlein Purpura (PSH) is the most frequent vasculitis in childhood. Skin, bowel and joints are characteristically involved. Although renal manifestations are common PSH-nephritis is infrequent but characterized by a poor prognosis. In autumn 2005 diagnosis and treatment were discussed at the 8th consensus meeting in Wörlitz. These results are summarized.

A new model for the determination of limb segment mass in children.

BACKGROUND: The knowledge of limb segment masses is critical for the calculation of joint torques. Several methods for segment mass estimation have been described in the literature. They are either inaccurate or not applicable to the limb segments of children. Therefore, we developed a new cylinder brick model (CBM) to estimate segment mass in children. METHODS: The aim of this study was to compare CBM and a model based on a polynomial regression equation (PRE) to volume measurement obtained by the water displacement method (WDM). We examined forearms, hands, lower legs, and feet of 121 children using CBM, PRE, and WDM. The differences between CBM and WDM or PRE and WDM were calculated and compared using a Bland-Altman plot of differences. FINDINGS: Absolute limb segment mass measured by WDM ranged from 0.16+/-0.04 kg for hands in girls 5-6 years old, up to 2.72+/-1.03 kg for legs in girls 11-12 years old. The differences of normalised segment masses ranged from 0.0002+/-0.0021 to 0.0011+/-0.0036 for CBM-WDM and from 0.0023+/-0.0041 to 0.0127+/-0.036 for PRE-WDM (values are mean+/-2 S.D.). The CBM showed better agreement with WDM than PRE for all limb segments in girls and boys. INTERPRETATION: CBM is accurate and superior to PRE for the estimation of individual limb segment mass of children. Therefore, CBM is a practical and useful tool for the analysis of kinetic parameters and the calculation of resulting forces to assess joint functionality in children.

Phalangeal bone ultrasound is of limited value in patients with juvenile idiopathic arthritis.

OBJECTIVE: In children with juvenile idiopathic arthritis (JIA), alterations of the skeletal system have been described. The aim of this cross-sectional study was to evaluate a phalangeal bone ultrasound device in the assessment of the skeletal status in children with active JIA. METHODS: In 49 children with oligoarticular, polyarticular or systemic JIA, the speed of an ultrasound signal (Ad-SOS) through the phalanges of the dominant hand was measured using the Igea 1200. RESULTS: Children in all subgroups were significantly smaller than those in the reference population, but there were no significant deficits in Ad-SOS. The finger width was reduced only in patients with polyarticular JIA. The Ad-SOS correlated highly with height, but no correlation between the finger width and Ad-SOS, and no correlation between the standard deviation scores of body height and Ad-SOS were seen. CONCLUSIONS: Phalangeal ultrasound is strongly dependent on body and therefore bone size, but other parameters of bone and soft tissues influence the measurements as well. It is not possible to differentiate as to which extent the various components of bone and soft tissue influence the measurement results. Ultrasound might therefore be of limited value in the assessment or screening of the skeletal system in children with JIA.

Development of granulomatous common variable immunodeficiency subsequent to infection with Toxoplasma gondii.

Common variable immunodeficiency (CVID) is a heterogeneous immunodeficiency that is accompanied by granulomatous lesions in 5-10% of cases. Why some patients develop granulomatous disease remains unclear. Here we describe a 12-year-old previously healthy girl who presented with pancytopenia and granulomatous lymphoproliferation subsequent to infection with Toxoplasma gondii. Loosely arranged non-fibrosing granulomas were observed in the liver, lymph nodes and lung, but no Toxoplasma tachyzoites could be demonstrated and polymerase chain reaction (PCR) and culture were negative for Toxoplasma and a wide range of other pathogens. While the patient had a normal peripheral B cell status at presentation, the development of CVID could be observed during the following months, leading to a loss of memory B cells. This was accompanied by an increasingly activated CD4(+) T cell compartment and high serum levels of angiotensin-converting enzyme (ACE), tumour necrosis factor (TNF) and sCD25. Steroid therapy reduced pancytopenia, granulomatous lymphoproliferation and cytokine elevations, but did not improve the B cell status. This is the first report of an association of Toxoplasma infection with granulomatous CVID and provides one of the rare examples where the onset of CVID could be documented subsequent to an infectious disease.

Differential peptide binding motif for three juvenile arthritis associated HLA-DQ molecules.

OBJECTIVE: In the oligoarticular subgroup of juvenile idiopathic arthritis, a strong association has been found with the expression of human leukocyte antigen class II molecules HLA-DQA1 *0401-DQB1*0402 and DQA1*0501-DQB1*0301, whereas DQA1*0501-DQB1*0201 is neutral and DQA1 *0201-DQB1*0201 protective. A presentation of different peptides by these DQ alleles would support their role in the disease process. METHODS: Using a synthetic nonapeptide library, a peptide binding motif was determined for the associated DQA1*0501-DQB1*0301 molecule and compared to the neutral and the protective DQ molecules. RESULTS: A differential motif for the three molecules could be deduced, suggesting that peptides preferentially binding to the associated vs. the neutral/protective DQ-molecules are mutually exclusive. CONCLUSION: These results imply a role for differential peptide presentation in the pathogenesis of oligoarthritic JIA. The search for peptides initiating the disease process might be facilitated which could then lead to therapeutical interventions.

Dexamethasone inhibits CD4 T cell deletion mediated by macrophages from human immunodeficiency virus-infected persons.

Prednisolone slows the loss of CD4 T cells in individuals with human immunodeficiency virus (HIV) disease and inhibits antigen-induced apoptosis of recently HIV-infected CD4 cells in vitro. This study investigated whether dexamethasone inhibits the ability of macrophages to delete CD4 T cells via anti-CD4 antibody or immune-complexed HIV envelope protein gp120. Peripheral blood mononuclear cells from HIV-negative persons were incubated with CD4-reactive ch412 monoclonal antibody or with gp120/IgG immune complexes and resident macrophages, with and without dexamethasone. Dexamethasone inhibited CD4 cell deletion in a dose-dependent manner. The deletion of normal CD4 cells by macrophages from HIV-infected patients also was inhibited by dexamethasone. Furthermore, up-regulation of CD95 expression on T cells exposed to anti-CD4 and gp120/IgG, which predisposes T cells to CD95-mediated apoptosis, is inhibited by dexamethasone in a dose-dependent fashion. Dexamethasone inhibits the macrophage-mediated deletion of CD4 lymphocytes in HIV-infected persons.

Acetyl-11-keto-beta-boswellic acid induces apoptosis in HL-60 and CCRF-CEM cells and inhibits topoisomerase I.

Antiproliferative action of different pentacyclic triterpenes has repeatedly been reported, and some lipoxygenase inhibitors have been shown to induce cell death in various cell systems. Acetyl-11-keto-beta-boswellic acid (AKBA) is a pentacyclic triterpene that inhibits 5-lipoxygenase in a selective, enzymedirected, nonredox, and noncompetitive manner. To investigate a possible effect of AKBA on leukemic cell growth, proliferation of HL-60 and CCRF-CEM cells was assayed in the presence of AKBA and a structural analog without effect on 5-lipoxygenase, amyrin. Cell counts and [3H]thymidine incorporation were significantly reduced in a dose-dependent manner in the presence of AKBA (IC50 = 30 microM) but not amyrin. An additive effect of AKBA with the crosslinking of the CD95 receptor was also observed. Flow cytometric analysis of propidium iodide-stained cells indicated that the cells underwent apoptosis. This was confirmed by flow cytometric detection of sub-G1 peaks in AKBA-treated cells and by DNA laddering. However, because HL-60 and CCRF-CEM do not express 5-lipoxygenase mRNA constitutively, a mechanism distinct from inhibition of 5-lipoxygenase must account for the effect of AKBA. In a DNA relaxation assay with phiX174RF DNA, AKBA inhibited topoisomerase I from calf thymus at concentrations of >/=10 microM. A semiquantitative cDNA polymerase chain reaction approach was used to estimate the relative level of expression of topoisomerases in both cell lines. The data suggest that induction of apoptosis in HL-60 and CCRF-CEM by AKBA may be due to inhibition of topoisomerase I in these cells.

Activation or destruction of T cells via macrophages.

Macrophages (MPhi) affect the T cell response in two mutually exclusive ways: activation or deletion. A MPhi type with T cell activating functions (M1) is able to express and upregulate receptors of the B7 family. IFN-gamma favours this MPhi differentiation pathway via upregulation of CD80 (B7-1) and CD86 (B7-2). The treatment of MPhi with IFN-gamma enhances the alphaCD3-mediated T cell blast transformation and reduces the fraction of deleted T cells. This MPhi type may prevent antibody-mediated T cell destruction by the expression of costimulatory receptors. An IL-10-induced MPhi type (M2) fails to express costimulatory molecules of the B7 family but is an effective cell for T cell destruction. Forming cellular conjugates with T cells through antibodies or immune complexes, M2-MPhi preferentially delete targeted cells in vitro and in vivo.

Elevated major histocompatibility complex class I expression protects T cells from antibody- and macrophage-mediated deletion.

Macrophages are capable of destroying T cells with which they form cellular conjugates. The deletion can be prevented by the simultaneous transmission of costimulatory signals. We show here that T cells with elevated major histocompatibility complex (MHC) class I expression are resistant against macrophage-mediated cytotoxicity. T cells that express the CD45RO isotype, considered memory T cells, exhibit MHC class I antigen at higher density than naive CD45RA T cells and upregulate MHC class I expression promptly when they form cellular conjugates with macrophages. We confirm previous observations that CD45RA T cells are more susceptible to antibody- and macrophage-mediated deletion than memory CD45RO T cells. When MHC class I molecules are masked by specific monoclonal antibody or antibody Fab fragments, CD45RA T cells and CD45RO T cells exhibit equal susceptibility to macrophage cytotoxicity, demonstrating that the difference between CD45RA and CD45RO T cells in their sensitivity to macrophage cytotoxicity is determined by their MHC I expression. Separation of CD4 T cells from CD8 T cells deprives memory CD4 T cells of their resistance against macrophage cytotoxicity, suggesting that memory T cells' resistance against destruction by macrophages is controlled by regulatory T cells.

Staphylococcal enterotoxin B-induced T-cell anergy is mediated by regulatory T cells.

Naive T cells mount a vigorous proliferative response to superantigen (SAg) stimulation in vivo. The proliferative response is followed by a partial deletion of responder T cells. Part of the deletion process has recently been attributed to the action of regulatory cytotoxic T cells that recognize major histocompatibility complex (MHC) class I-associated antigen receptor determinants on the target cell surface. Responder T cells that survived the SAg response were found to be incapable of generating a secondary proliferative response to a SAg challenge. We show here that this 'anergy' is enforced by CD8-positive regulatory suppressive T cells. These regulatory cells inhibit cell division of preactivated T cells but not the Sag response of naive T cells. Regulatory T cells are not generated in the presence of cyclosporin A and, once activated, become inactivated or deleted when restimulated in the presence of this immunosuppressive drug.

Activation-dependent expression of the insulin-like growth factor binding protein-2 in human lymphocytes.

The expression of the insulin-like growth factor binding protein-2 (IGFBP-2) was assayed in mononuclear cells originating from different organs of the immune system. All mononuclear cells studied did express IGFBP-2, but the expression level was found to be dependent on the cell type and origin of the cell. T cells showed a higher expression of IGFBP-2 mRNA than did B cells, and CD34+ stem cells expressed IGFBP-2 mRNA at a high level. Expression was highest in bone marrow and thymus. Stimulation of peripheral mononuclear cells resulted in a marked increase of IGFBP-2 mRNA and also intracellular IGFBP-2, as analysed by fluorescence staining. This increase parallels the increase of other known T-cell activation markers. Furthermore, the increase of intracellular IGFBP-2 seems to precede T-cell blast formation and all T cells in active phases of the cell cycle have high levels of IGFBP-2. Our results provide a basis for further investigations on the contribution of the IGF-system to the regulation of T-cell proliferation and differentiation. IGFBP-2, in particular, may have an important influence in the regulation of T-cell activation and proliferation.

Elevated insulin-like growth factor (IGF) binding protein (IGFBP)-2 and IGFBP-4 expression of leukemic T-cells is affected by autocrine/paracrine IGF-II action but not by IGF type I receptor expression.

We recently found evidence indicating that the source of elevated serum insulin-like growth factor binding protein (IGFBP)-2 in leukemia was the leukemic T-cells. Here we report that locally produced IGF-II affects IGFBP-2 expression and growth of leukemic cells through the IGF type I receptor. We measured IGFBP-2, -4 and IGF type I receptor (IGF-I-R) mRNA by RT-PCR, cell growth and IGFBP-2 secretion (per 10(6) cells). IGF-I-R binding sites were assessed by 125I-IGF replacement studies. Inhibition using an IGF-II antibody showed that tumor cell-derived IGF-II accounts for a significant 25% (P < 0.001) increase in IGFBP-2 secretion and enhanced growth (P < 0.01) of leukemic T-cells after 7 days in culture. IGFBP-2 secretion, but not IGFBP-2 mRNA was specifically increased by IGFs, while no specific effect of insulin was detectable. The addition of 100 ng/ml IGF-II enhanced the IGFBP-2 secretion 2.8-fold, while the use of IGF-I only enhanced IGFBP-2 secretion 1.7-fold, although IGF-I enhanced IGF-II action. Through inhibition using JB1, a peptide inhibiting the IGF signal transduction by blocking the IGF-I-R, we demonstrated the involvement of the IGF-I-R in IGFBP-2 and -4 expression and leukemic cell growth. However, only slight differences in the IGF-I-R mRNA expression were seen for T- and B-cells compared with the differences found for the IGFBP-2 and -4 mRNA or IGFBP-2 secretion. Thus, although IGF-I-R mediates the autocrine/paracrine effects of the IGFs, IGF-I-R mRNA expression is most probably not involved in the differential IGFBP-2/IGFBP-4 expression in leukemic cells.

Superantigen-induced lysis of melanoma cells.

Superantigens like the Staphylococcus enterotoxin A (SEA) can direct cytotoxic T lymphocytes expressing certain T cell receptor V beta regions to lyse MHC class II-positive target cells. This superantigen-dependent cellular cytotoxicity (SDCC) has been extended to MHC class II-negative tumour cells by targeting T cells via conjugates of a tumour-specific monoclonal antibody (moAb) and a superantigen. In the present study the MHC class II-negative human melanoma cell lines G361 and MaRI were tested for susceptibility to SDCC in vitro. Antibodies recognizing the disialoganglioside GD3 and the CD10 antigen were linked to SEA either by a recombinant protein A-SEA fusion protein or an anti-kappa moAb-SEA chemical conjugate. Specific lysis of melanoma cells was dose- and effector to target (E:T) cell ratio-dependent. Introduction of a point mutation into the SEA gene (producing SEAm9) in order to reduce MHC II affinity of the superantigen, which has already been shown to severely diminish superantigen-dependent binding and lysis of MHC class II-positive cells, did not influence antibody-targeted SDCC. Cytotoxicity was equal with both antibodies (anti-GD3 and anti-CD10) and independent of whether protein A-SEA, protein A-SEAm9 or anti-kappa-SEA were used.