Childhood systemic lupus erythematosus: a review of 30 cases.

We review 30 cases of pediatric systemic lupus erythematosus followed over an 8-year period at our institution. The female to male ratio was 3.3:1; the age at diagnosis ranged between 3.5 and 16 years. On first admission, renal involvement was detected in the majority of the patients, as assessed by laboratory findings and/or clinical manifestations. Other frequently observed symptoms were fever, skin rashes, arthralgias and/or arthritis and serositis. All of the patients were treated with corticosteroids and most of them also received immunosuppressive drugs in order to control disease activity. Two patients were lost to the follow-up, five died and only one of the 23 evaluable patients is off therapy after a median follow-up of 5 years. This study confirms that pediatric systemic lupus erythematosus is a very aggressive disease.

Cyclosporin A in the treatment of juvenile chronic arthritis and childhood polymyositis-dermatomyositis. Results of a preliminary study.

In this study we have investigated the efficacy and safety of cyclosporin A (CyA) in a group of pediatric patients with juvenile chronic arthritis (JCA, 9 cases) and polymyositis-dermatomyositis (PM-DM, 3 cases). Of the 9 JCA patients, 7 had the systemic and 2 the polyarticular form of the disease. All of the patients received CyA after the failure of corticosteroids and/or cytotoxic drugs. CyA was administered for 9 to 48 months at a mean dose of 5 mg/kg/day. Ten patients received corticosteroids with CyA. The results of CyA treatment were satisfactory overall, both in the PM-DM patients and in the JCA patients, as assessed by clinical and laboratory evaluation. CyA-related side effects included alopecia, hypertension, hypertrichosis, tremors, and hirsutism. One JCA patient developed polyserositis with hypoproteinemia of unknown origin while receiving CyA. CyA blood levels did not correlate with clinical efficacy and/or side effects. This study suggests that CyA represents a promising agent for the treatment of JCA and childhood PM-DM.

Salicylic acid disposition in children with rheumatoid arthritis.

The plasma level profile of SA and SUA after a single oral dose of ASA was studied in 8 children with juvenile rheumatoid arthritis, aged 3.5-15.0 years. Pharmacokinetic parameters were on average similar to those reported in the literature for adult subjects, although a somewhat larger intersubject variability was found.

Changes of immunological parameters during auranofin treatment in children affected with juvenile chronic arthritis.

Auranofin [S-triethylphosphine gold-2,3,4,6 tetra-O-acetyl-l-thio-beta-D-glucopyranoside) SK&F 39162) has been administered at 0.1-0.25 mg/kg/day as the sole remission-inducing drug to 46 children affected with juvenile chronic arthritis (JCA). There were 22 males and 24 females; 12 children were affected with pauciarticular onset JCA, 26 with polyarticular onset JCA and 8 with systemic onset JCA. Three sets of efficacy criteria were evaluated quarterly: eight clinical, (Ritchie Index, number of affected, swollen and limited joints, number of joint with increased temperature, morning stiffness, Steinbrocker functional class, physician's disease evaluation), three hematochemical and one therapeutical. In most patients a panel of immunological parameters was routinely performed inclusive of peripheral blood lymphocyte subsets, serum immunoglobulins and C3c-C4 complement components. Patients who showed a definite improvement of at least two out of the three orders of efficacy criteria were classified as responders to auranofin. Out of the 35 patients evaluable after at least six months of treatment there were 24 (68%) responders. Nonresponders had a basal higher level of serum IgA and a basal lower level of serum C4. Both responders and nonresponders presented a reduction of the T4/T8 ratio during auranofin treatment, while only in responders did the basal high levels of IgG and C3c show a definite decrease.

[Pain in Guillain-Barré syndrome]. / Il dolore nella sindrome di Guillain-Barré.

The clinical features of pain were analysed in 31 children with Guillain-Barré Syndrome. Pain may be considered characteristic of childhood GBS. Pain, various painful sensations and dysaesthesias must be emphasised in the early diagnosis of GBS. An attempt was made to identify the meanings of early pain (preceding or accompanying the onset of weakness), late pain, mild or severe sensory symptoms or signs and the role played by triggering or perpetuating factors. Only the application of a diagnosis-therapeutic protocol for childhood GBS, that pays particular attention to the problem, will suggest satisfactory answers to research.

[Psoriatic arthritis and celiac disease in childhood. A case report]. / Artropatia psoriatica in un soggetto con sindrome celiaca associata. Presentazione di un caso clinico in età pediatrica.

A case of a girl followed up for 18 years is reported. At the age of two, the patient presented psoriasis and coeliac disease confirmed by biopsy and by laboratory data. She followed a coeliac diet and at the age of twelve she manifested a rheumatoid arthritis of the left knee without pain, confirmed by laboratory data (RA test, ANA test). In this period, the patient underwent another gastrointestinal biopsy after suspension of the diet; the structural alterations of the gastrointestinal tract being always present, she continued the diet associated with non steroidal antiphlogistic drug therapy for rheumatoid arthritis. The Authors remark the association of diseases, making a comparison with literature data and confirming the current hypotheses. It is interesting to observe that when the patient presented articular symptoms, there was the reappearance of the gastrointestinal symptomatology. Very interesting is the presence of psoriasis: in fact there is the problem whether this case is a psoriatic arthritis with coeliac disease or a juvenile rheumatoid arthritis with coeliac disease and psoriasis. At last, the Authors report the good results obtained by coeliac diet and non steroidal antiphlogistic drugs; a complete remission of articular symptoms and a good puberal and intellectual growth have been observed.

[Double-blind controlled comparison of placebo and paracetamol in patients with G-6-PD deficiency]. / Confronto in doppio cieco controllato tra placebo e paracetamolo in soggetti carenti di G-6-PD.

In this study are reported 17 patients with G-6-PD deficiency. These subjects have been studied with double-blind trial between placebo and Paracetamol, looking for the possible hemolysis induced from drug in these children with G-6-PD deficiency. Hemolysis had been valued by various hematological parameters (Hb, erythrocyte count, reticulocytosis, bilirubinemia, haptoglobin, hemopexin, and survival of erythrocytes marked with Cr). The results (8 cases with placebo and 9 cases with paracetamol) demonstrate that paracetamol have not induced hemolysis in these G-6-PD deficient subjects.

Leigh disease: value of CT in presymptomatic patients and variability of the lesions with time.

Three cases of Leigh disease (subacute necrotizing encephalomyelopathy) have been investigated recently in our institute by CT. Bilateral, low attenuation areas were observed in the basal ganglia in all cases. These areas corresponded to the typical necrosis areas seen pathologically in this disease. In our study there were further interesting CT appearances: the peripheral enhancement of low-density zones and the discovery of the lesions before the clear onset of clinical symptoms.

Ellis-Van Creveld syndrome: description of four cases. Orthopaedic aspects.

Four cases of Ellis-Van Creveld syndrome are reported in which three were in the same family. The clinical and radiological findings were characteristic of the traditional features of the disease. The authors discuss the role of the orthopaedic surgeon in correcting the skeletal deformities.

Ring chromosome 16: a new case.

A 46,XX,r(16) "de novo" karyotype is reported in a 4 7/12-year-old girl. In spite of the mild cranio-facial dysmorphism without visceral malformations in r(16) patients, the proband's phenotype is similar to the other four previous case reports. This could support the hypothesis of a specific "r(16) syndrome".

[Sjögren's syndrome in childhood. Description of a clinical case]. / La sindrome di Sjögren in età pediatrica. Descrizione di un caso clinico.

A case is reported of Sjögren's syndrome in childhood. According to Fox's classification, this patient presented all four inclusion criteria for the diagnosis of the disease. The Authors report the satisfactory evolution of the disease using therapy with FANS and corticosteroids and immunosuppressors during acute exacerbations.

[Cardiac involvement in juvenile rheumatoid arthritis]. / L'interessamento cardiaco in corso di artrite reumatoide infantile.

Four cases with cardiac involvement in patients suffering from systemic outset of juvenile rheumatoid arthritis are reported. The cases were chosen out of 83 juvenile rheumatoid arthritis patients studied from 1975 to 1988. They developed respectively myopericarditis (case 1), myocarditis (case 2), endopericarditis (case 3), myopericarditis (case 4). The drug employed in the acute disease phase was exclusively prednisone; in all subjects the acute inflammatory stage resolved.

[The Guillain-Barré syndrome. The clinico-electrophysiological correlations]. / La sindrome di Guillain-Barré. Correlazioni cliniche-elettrofisiologiche.

The authors refer about clinico-electrophysiological correlations in children with Guillain-Barré syndrome (GBS). The dates confirm the diagnostic and prognostic value of electrodiagnostic studies in GBS, so that the authors suggest an electrodiagnostic protocol. According to the authors, independently of the extent of electrophysiological abnormalities, young age has a favourable influence on the restoration of conduction abnormalities and on the evolution of damage to peripheral neurones.

Chronic autoimmune neutropenia due to anti-NA1 antibody.

A 12-month-old child neutropenic since the age of 8 months, was referred to our institute for a sepsis from Candida albicans. On exploring the cause of neutropenia, an anti-NA1 antibody could be detected in the patient's serum. This antibody seemed to be responsible for the neutropenia because the child's PMN type was NA1+. The reactivity of the autoantibody with the patient's own granulocytes was confirmed by direct and indirect immunofluorescence studies performed on blood and marrow cells. A reduced number of T lymphocytes with poor PHA responsivity has been interpreted as the possible cause of the autoimmune disease. Steroid therapy did not cure the neutropenia but the child's general condition improved.

[Monosomy 7qter: 2 new cases of chromosomal pathology with aspecific disorders of pre- and post-natal development]. / Monosomia 7qter: due nuovi casi di una patologia cromosomica con disturbi aspecifici dello sviluppo pre- e post-natale.

Many cases of 7q deletion associated with mental retardation and multiple malformations have been described, nevertheless it is quite different to recognize common features among these infants. In this paper the cases of two female infants with uncommon facial features and 7q deletion are described. We also try to recognize the phenotypic features of this chromosomal disorder.

Clonal analysis of joint fluid T lymphocytes in patients with juvenile rheumatoid arthritis.

Synovial fluid (SF) lymphocytes from 4 patients with pauciarticular juvenile rheumatoid arthritis (JRA) and 4 patients with polyarticular JRA were examined for their phenotypic and functional characteristics. In all 8 patients there was a high proportion of activated SF T cells, together with an increased proportion of CD2+CD3- and the presence of CD3+CD4-CD8-WT31- lymphocytes. The functional analysis at the clonal level in 5 patients (427 clones) showed a relevant proportion of cytotoxic T cell clones, which were not confined to typically cytolytic phenotypes, but were also present among CD3+CD4+CD8- cultures. Compared to those with pauciarticular JRA, patients with polyarticular disease had a significantly higher proportion of T cell clones with cytotoxic activity. Although derived from a limited number of patients, our data suggest a direct involvement of T cells in the pathogenetic mechanisms that originate and maintain the articular damage, and the possibility of different or more pronounced T cell reactivities in the clinically more diffuse JRA types.

Comparison of growth retarding effects induced by two different glucocorticoids in prepubertal sick children: an interim long-term analysis.

The low interference with growth expected in child for a cortisol analogue, deflazacort (DFZ), prompted us to verify if DFZ could affect growth less than prednisone (PDN). An interim analysis relative to 27 girls and 38 boys (out of 100 expected) aged 3-12 yrs, after a median period of 14 mo.s is reported. Children with connective tissues (CTD) and glomerular disorders (KD) were randomly allocated to DFZ or PDN. Anthropometric measurements and maturity ratings were performed. Mean daily doses of PDN (or DFZ equivalent), from 0.57 to 0.64 mg/kg (DFZ 0.92 to 0.94 mg/kg) to induce control and from 0.19 to 0.39 mg/kg (DFZ 0.34 to 0.36 mg/kg) to maintain disease under control were given in CTD and KD, respectively. The increase in bone age delay over time was significantly greater than for PDN (-4.0 mo/yr) than DFZ (-1.8 mo/yr) in the overall group. The increases in statural age delay and loss over time were significantly greater than for PDN (-5.9 and -5.9 mo/yr) than DFZ (-2.4 and -2.4 mo/yr), only in children with "taller" midparents. Although doses of DFZ 1.1-1.8 times those of PDN were given, growth retardation in PDN-treated children was nevertheless 2.3-2.5 times that in DFZ-ones.

Treatment of acute idiopathic thrombocytopenic purpura (AITP): cooperative Italian study group results.

A cooperative Italian study group on acute idiopathic thrombocytopenic purpura (AITP) has been designed to evaluate efficacy and safety of no treatment at the onset of the disease and sequential treatment with immunoglobulin and high dose steroid. One hundred thirty-eight patients with AITP entered in the trial. Eleven patients were treated before the end of the waiting period because of bleeding. One hundred twenty-seven (92%) received no treatment for the first 10 days of the disease, 65 patients (51.18%) recovered spontaneously, 62 patients were treated with immunoglobulin, and 52 (83.8%) of them responded positively but only 36 (58.06%) permanently. There was no statistical difference between the results obtained with 400 mg/kg for 5 days versus 200 mg/kg. Twenty-four patients were treated with high doses of steroids, 20 (83.3%) with positive response, and 10 (41.66%) were permanently cured. Four (3.14%) of the patients enrolled in the protocol still had active disease at the end of treatment, and 10 relapsed within 4 months after the end of the treatment.

CD3+4-8-WT31-(T cell receptor gamma+) cells and other unusual phenotypes are frequently detected among spontaneously interleukin 2-responsive T lymphocytes present in the joint fluid in juvenile rheumatoid arthritis. A clonal analysis.

T lymphocytes (E rosetting cells) isolated from the joint fluid of four patients with juvenile rheumatoid arthritis (JRA) were first analyzed for surface antigen expression. Approximately 15% of cells were CD25+ (interleukin, IL, 2 receptor positive), in addition, a remarkable proportion of cells expressed the CD2+3- phenotype. CD3+ cells outnumbered the sum of CD4+ and CD8+ cells as well as the cells reactive with the WT31 monoclonal antibody (which recognizes a framework determinant of the alpha/beta T cell receptor). Purified T cells were cloned under culture conditions (1% phytohemagglutinin, PHA plus IL2) which allow clonal expansion of most peripheral blood T lymphocytes. Under these conditions proliferating cells ranged from 25 to 65%; clones (derived from microcultures containing 0.5 or 0.25 cells/well) were tested for cytolytic activity against P815 cells (in the presence of PHA) or against the natural killer (NK)-sensitive K562 target cells. Fifty-four percent and 73% of clones obtained from the two patients with the polyarticular form of the disease displayed cytolytic activity in the lectin-dependent assay. Cytolytic clones were 22 and 29% in the two patients with single joint involvement. About half of all cytolytic clones displayed NK-like activity. Surface antigen analysis revealed that, in addition to conventional CD3+4+8- and CD3+4-8+, a noticeable fraction of clones (50/202) displayed unusual surface phenotypes. In particular, 33/50 coexpressed CD4 and CD8 antigens; 7/50 were CD2+3-4-8- and displayed NK-like activity; 10/50 expressed CD3 but lacked both CD4 and CD8 antigen and did not react with the WT31 monoclonal antibody. In order to allow selective growth of IL2-responsive cells, T lymphocytes were also cloned directly in IL2. As much as 57% of all clones thus obtained (48/84) displayed cytolytic activity. Moreover, about half expressed unusual surface phenotypes including CD2+3-4-8-, CD3+4+8+ and CD3+4-8-WT31-. Given the accumulation at the site of the joint involvement of unusual T cells, most of which displayed cytolytic activity and were likely to represent cells activated in vivo (IL2 responsive), one may speculate that these cells may be involved in the injury process.