Skin manifestations in vasculitis and erythema nodosum.

Cutaneous lesions are frequent in medium-sized and small vessel systemic vasculitides. The classic cutaneous manifestation of vasculitis is palpable purpura; however the clinical manifestations greatly depend on the size of the vessels affected. They usually do not affect prognosis but relapsing or intractable forms have been described. When skin manifestations are only one of the clinical signs of vasculitis, treatment with corticosteroids and, when indicated, an immunosuppressant, is mandatory, which usually leads to the rapid disappearance of cutaneous lesions. Conversely, when skin lesions are isolated, the diagnosis can be more challenging, but initial treatment may be less aggressive, e.g., dapsone or colchicine, reserving corticosteroids only for those patients in whom the former are ineffective. Erythema nodosum (EN) is the most frequent septal panniculitis. In general it is characterized by the sudden eruption of one or more erythematous and tender nodules or plaques located mainly over the extensor sides of lower extremities. EN resolves with complete "restitutio ad integrum" of the skin in 3-6 weeks. Relapses are uncommon but in patients with idiophatic, streptococcal or EN associated with other upper respiratory tract infections they are more frequent. The main treatment of EN is that of the underlying associated conditions, if demonstrated. Aspirin and other NSAIDs in full doses are often sufficient.

[Takayasu arteritis: a chronic vasculitis that is rare in children]. / Takayasu-arteriitis: een chronische vasculitis, zeldzaam bij kinderen.

Takayasu arteritis was diagnosed in two children, a 15-year-old girl and a 10-year-old boy. The girl had suffered from fatigue, malaise, abdominal pain and weight loss for several months, but no clear cause could be found. A few weeks later, when a blood pressure of 222/155 mmHg was measured, the possibility of renal artery stenosis was considered and imaging studies revealed indications for Takayasu's disease. The patient was given methylprednisolone followed by a combination of prednisone and, initially, cyclophosphamide, later methotrexate. This resulted in a clinical remission of the inflammatory process. The boy presented with increasing fatigue and variable episodes of fever. After 3 years, sarcoidosis or Castleman's disease were considered. Imaging studies revealed aortic stenosis. He underwent stenting of the involved vessel segment. Takayasu arteritis is a chronic vasculitis of unknown origin, affecting mainly the aorta and its main branches. As a result of the inflammation, stenosis, occlusion or dilatation of the involved vessels may occur and cause a wide range of symptoms. Especially in the early phase, the symptoms often are non-specific. One should look for hypertension, blood pressure differences between the two arms, decreased peripheral pulsation or bruits over the aorta and its major branches. Radiological examination may consist ofangiography, magnetic resonance imaging or CT-scans. Treatment consists of corticosteroids and other immunosuppressants, such as cyclophosphamide, methotrexate, azathioprine, and antagonists of tumour-necrosis factor alpha. In addition, balloon dilatation or stenting is often necessary.

[Kidney transplant survival rates and surgical complications in kidney transplants in children; experiences in the Emma Children's Hospital AMC]. / Niertransplantaatoverleving en chirurgische complicaties bij kinderniertransplantaties; ervaringen in het Emma Kinderziekenhuis AMC.

OBJECTIVE: To describe surgical complications, and patient and kidney transplant survival rates in children who have had a kidney transplant. DESIGN: Retrospective. METHOD: Data were analysed concerning the children who had been treated with a renal transplantation in the period 1985-2001 because of terminal renal insufficiency in the Emma Children's Hospital of the Academic Medical Centre in Amsterdam, The Netherlands, with arbitrary end date October 7, 2002. RESULTS: In the study period, 55 primary kidney transplantations were performed on 24 girls and 31 boys. 13 living related and 42 post mortem transplantations were performed. The extra-peritoneal approach was performed in all recipients. Up to October 7, 2002, 14 surgical complications (25%) developed: 4 cases of renovascular thrombosis, 4 urinary leakages, 6 urethral strictures, 1 urethral necrosis, 5 haematomas and 3 lymphoceles. 6 patients lost their grafts due to surgical complications (11%); 4 due to thrombosis, 1 due to urethral necrosis and 1 due to haemorrhage or haematoma. Due to hypertension secondary to the underlying kidney disease 2 patients died within one year after transplantation from hypertensive encephalopathy and cerebral bleeding respectively. The one- and five-year graft survival was 83% and 74% for living related transplantations respectively, and for post mortem transplantations 78% and 68% respectively. The main causes of graft loss were chronic rejection (9/21; 43%), acute rejection (4/21; 19%), thrombosis (4/21; 19%) and surgical complications (2/21; 10%). Primary nonfunction was the only factor with a negative prognostic value for graft survival.

Fc-receptor function in minimal change nephrotic syndrome of childhood.

This study was undertaken to establish whether the Fc-receptor function of circulating monocytes (CM) and/or of splenic macrophages (SM) is modified during the course of minimal change nephrotic syndrome (MCNS) of childhood. The Fc-receptor function of SM was ascertained by measuring the spleen to liver uptake ratio 40 min after IV injection of heat-damaged autologous erythrocytes labeled with 99Tc, whereas the Fc-receptor function of CM was determined by a "rosetting" test. The Fc-receptor function was followed in six girls presenting with a MCNS and receiving no therapy at the time of testing. The Fc-receptor function of SM was decreased in five patients during an acute phase of MCNS. In four of these five patients, the Fc-receptor function of CM was also altered. No significant correlations were observed between the Fc-receptor blockade and the C3, C3d, C4, C3PA or immune complex-plasma levels. The Fc-receptor blockade was persistent in three girls during remission. A prior incubation of CM with trypsin did not completely reverse the Fc-receptor blockade. Further studies are now being pursued in order to determine whether this persisting abnormality is inherited and mainly observed in relapsing nephrotic syndrome.

Relation between biological IgA abnormalities and mesangial IgA deposits in isolated hematuria in childhood.

Indications for renal biopsies in isolated hematuria in childhood remain difficult to define. Their limitation to patients presenting with either a macroscopic or a familial hematuria [Trachtman et al. 1984] bears the potential risk of missing the diagnosis of IgA-associated nephropathies (Berger disease and Henoch-Schönlein nephritis) which may manifest themselves by microscopic hematuria only. In order to reevaluate the association between biological IgA abnormalities and mesangial IgA deposits, iterative and concomitant determinations of IgA plasma levels, of IgA immune complexes and of IgA production by lymphocytes in vitro have been performed over a one-year period in two groups of hematuric children presenting with mesangial IgA deposits (14 cases) or not (13 cases). The incidence of positivity of each test was significantly higher in the former group of patients than in the latter. However, the best discrimination between both groups was observed when the three tests were repeated and/or considered together (97% vs 15% of positivity). In Berger disease and Henoch-Schönlein nephritis, IgA immune complexes were the only IgA abnormality more frequently detected in patients presenting with hematuria than in patients presenting with no hematuria at the time of testing. It is proposed to add IgA abnormalities to macroscopic or familial hematuria as indications for renal biopsies in isolated hematuria in childhood.

Peripheral B-lymphocyte markers and function in IgA nephropathy.

Peripheral blood B-lymphocyte markers and functions were observed in 21 patients with IgA nephropathy (IgA NP) and in 16 controls. IgA NP B lymphocytes expressed significantly higher positivity with Leu 1 (CD 5) monoclonal antibody than controls. CD 5 positive B lymphocytes are thought to be a distinct subset of the B cells (autoregulatory B lymphocytes) inducible in IgA NP by lipopolysaccharide (LPS) stimulation parallel to the higher expression of surface IgM heavy chain positivity. The activated state of IgA NP B lymphocytes has been proved by their higher OKIa (HLA-DR) positivities but lower IOB1a (CD 21, C3d-receptor) and decreased IgG-Fc-receptor (ox-rosette) expression. IgA NP B lymphocytes showed a higher IgA but also IgG and IgM polyclonal immunoglobulin production than control B lymphocytes in co-cultures with T lymphocytes. Not only regulatory T lymphocyte subsets but also serum derived from IgA NP patients stimulated the immunoglobulin production of IgA NP B cells.

Characteristics of peripheral and peritoneal white blood cells in children with chronic renal failure, dialyzed or not.

OBJECTIVE: To explore further the mechanisms leading to immune deficiency in chronic renal failure and the role of dialysis treatment in these mechanisms. DESIGN: Cross-sectional and longitudinal analysis. PATIENTS: We studied 39 children treated with peritoneal dialysis (PD), 23 children treated with hemodialysis (HD), 33 children not yet dialyzed [chronic renal failure (CRF)], and 27 healthy children. Peritoneal cells were also obtained from PD children for analysis. METHODS: White blood cells (WBCs) were isolated from blood and peritoneal dialysis effluent by centrifugation. The number of CD2+, CD4+, and CD8+ T cells, B cells, and natural killer cells were measured by flow cytometry. RESULTS: The total peripheral blood lymphocyte count was lower in PD children (2.6 x 10(9)/L), HD children (2.1 x 10(9)/L), and CRF children (2.0 x 10(9)/L) compared with healthy children (3.1 x 10(9)/L, p < 0.05). The B lymphocyte count was also lower in PD children (0.34 x 10(9)/L), HD children (0.22 x 10(9)/L), and CRF children (0.33 x 10(9)/L) compared with healthy children (0.52 x 10(9)/L, p < 0.01). Numbers of CD4+ T cells were not different, but numbers of CD8+ T cells were lower in PD children (0.56 x 10(9)/L), HD children (0.63 x 10(9)/L), and CRF children (0.53 x 10(9)/L) compared with healthy children (0.77 x 10(9)/L, p < 0.05). The count of natural killer cells was lower in PD children (0.21 x 10(9)/L), HD children (0.17 x 10(9)/L), and CRF children (0.18 x 10(9)/L) compared with healthy children (0.50 x 10(9)/L, p < 0.0001). The CD4/CD8 ratio of lymphocytes in peritoneal effluent was 0.8 versus 1.9 in peripheral blood (p < 0.001). The CD2/CD19 ratio was not different. The cell subsets remained stable during the first year of PD treatment. The CD2/CD19 ratio in peritoneal effluent was higher in children with a peritonitis incidence > or = 1 per year. CONCLUSIONS: The reduced numbers of B lymphocytes, CD8+ T cells, and natural killer cells found in CRF children, dialyzed or not, may favor the frequent occurrence of infections.

Dialysate cancer antigen 125 levels in children treated with peritoneal dialysis.

Peritoneal mesothelial cells are important for local host defense and membrane integrity. Dialysate cancer antigen 125 (dCA125) has been shown to be a good marker for the mesothelial cell mass in adult peritoneal dialysis (PD) patients. In children on PD, no information is available yet. We measured dCA125 in 65 dialysate samples from 24 PD children with a median age of 9.2 years (range: 2-18 years) and a median treatment time of 2.6 years (range: 0.1-9.3 years) on PD. The median dCA125 concentration was 8 U/mL (range: 2.3-30.7 U/mL), and the CA125 appearance rate (CA125AR) was 66.5 U/min/1.73 m2 (range: 18-282 U/min/1.73 m2). On cross-sectional analysis, a negative correlation was found between dCA125 and duration of PD treatment (r = -0.3, p = 0.04). No relation was found between age and dCA125 or CA125AR when the first measurement from each child was considered. No correlation was found between dCA125 and the mass transfer area coefficient of creatinine (MTACcreat). Longitudinal analysis showed a negative trend in CA125AR with duration of PD treatment (p = 0.03). No relation was found between peritonitis incidence and dCA125 or CA125AR. In conclusion, no influence of age on dCA125 and CA125AR was found. Levels of dCA125 declined with the duration of PD treatment, reflecting mesothelial cell mass, but they did not correlate with the MTACcreat or the peritonitis incidence in stable PD children.

[Renal osteodystrophy in two children : a comparison of the effects of 1 alpha-hydroxycholecalciferol (author's transl)]. / Comparaison de deux cas d'ostéodystrophie rénale sévère chez l'enfant, traités par la 1 alpha hydroxycholecalciferol (1 alpha OHD).

Two children suffering from renal osteodystrophy were treated by 1 alpha hydroxycholecalciferol (1 alpha OHD3) 1 microgr. each day, for 18 months. In both the level alkaline phosphatase decreased at the same time as endogenous immunoreactive CT increased, iPTH did not change steadily, whereas plasma creatinine rise. As plasma calcium concentration did not increase, it is suggested that the increase in endogenous CT concentration is a part of the favourable response to the treatment by 1 alpha OHD3.

[Pathogenesis of IgA nephropathies]. / Pathogénie des néphropathies à IgA.

The loss of kidney function in IgA nephropathy results from matrix overproduction by mesangial cells stimulated by IgA circulating complexes (IgA-CC) deposited in the mesangial area. High IgA-CC plasma concentrations are at least partly secondary to a genetically induced overproduction of undergalactosylated IgA molecules poorly cleared by the liver.

Nephrotic syndrome in children: from bench to treatment.

Idiopathic nephrotic syndrome (INS) is the most frequent form of NS in children. INS is defined by the association of the clinical features of NS with renal biopsy findings of minimal changes, focal segmental glomerulosclerosis (FSGS), or mesangial proliferation (MP) on light microscopy and effacement of foot processes on electron microscopy. Actually the podocyte has become the favourite candidate for constituting the main part of the glomerular filtration barrier. Most cases are steroid sensitive (SSINS). Fifty percents of the latter recur frequently and necessitate a prevention of relapses by nonsteroid drugs. On the contrary to SSINS, steroid resistant nephrotic syndrome (SRINS) leads often to end-stage renal failure. Thirty to forty percents of the latter are associated with mutations of genes coding for podocyte proteins. The rest is due to one or several different circulating factors. New strategies are in development to antagonize the effect of the latter.