Severe cutaneous manifestations in a child with refractory Kawasaki disease.
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Publications and source records attributed to G Simonini.
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OBJECTIVE: Kawasaki disease (KD) is an acute febrile systemic vasculitis, mainly affecting infants and young children. Immunological abnormalities during the acute phase of KD have been described extensively. However, the occurrence of a second immunological disorder in a patient with a history of KD is rarely reported. We evaluated the presence of autoimmune thyroiditis and coeliac disease (CD) in patients with KD diagnosis. METHODS: Ninety consecutive children (57 males and 33 females, median age 5.2 yr, age range 1.6-14.1 yr) with KD were evaluated. All patients were evaluated for thyroid function (thyroid-stimulating hormone, thyroxine and triiodothyronine), anti-thyroglobulin (TgA) and anti-peroxidase (TPOA) antibodies, and antigliadin, anti-endomysium and antitransglutaminase antibodies. CD was confirmed by jejunal biopsy if the specific antibody profile was positive. One hundred and fifty Italian children, matched for age and sex and from the same geographic area, acted as controls. RESULTS: A total of five patients (three boys, two girls; 5.5%; P<0.05) were found positive for coeliac antibodies. In all of these patients the diagnosis of CD was confirmed histologically. Regarding thyroid function and autoantibodies, no patient showed subclinical hypothyroidism or autoimmune thyroiditis. No differences in the familial occurrence of autoimmune diseases between KD patients and controls were found (9.1 and 7.9%, respectively). CONCLUSIONS: Our data showed a higher prevalence of CD in children with KD, and this suggests that children with KD should be monitored carefully for CD. However, there was no increase in the prevalence of autoimmune thyroid diseases in patients with KD or the familial occurrence of autoimmune diseases.
BACKGROUND: The World Health Organization (WHO) has recommended that a severe acute respiratory syndrome (SARS) alert should be raised when two or more healthcare workers (HCW) in the same health care unit fulfil the SARS clinical criteria, with onset of illness in the same 10-day period. However, in a number of European countries (including Italy) data on reasons for sickness absence are not routinely collected within current HCW worker sickness reporting systems, because of concerns about privacy. To help plan for the implementation of the proposed alert system in Italy, we aimed to determine the minimum number of alert cases defining a cluster. PATIENTS AND METHODS: Sickness absences longer than 7 days in HCW employed in three hospitals in 2003, were identified by checking the hospitals' administrative databases. HCW with onset of illness in the same 10-day period were contacted and asked whether they have been diagnosed with pneumonia. RESULTS: Overall, 273 absences > 7 days were recorded and 36 clusters of at least two absences > 7 days were identified; a total of 94 HCW were involved in these clusters. Only two HCW involved in different clusters, reported pneumonia. CONCLUSION: The occurrence of clusters of two or more cases of pneumonia in HCW in the same hospital unit appears to be an uncommon event, and thus the alert system proposed is not likely to result in large numbers of false positive alerts. However, it may be difficult to implement this alert system in countries where clinical data on sickness absences are not routinely collected, and alternative mechanisms should be considered.
OBJECTIVE: To evaluate bone mineral status over 1 yr of etanercept treatment in juvenile idiopathic arthritis (JIA). METHODS: Twenty children (13 female, 7 male) aged 5.2-11.4 yr, with active polyarticular JIA were prospectively enrolled to receive etanercept (0.4 mg/kg, twice weekly). Responders were defined according to the American College of Rheumatology Pediatric 50 definition of improvement. Broadband ultrasound attenuation (BUA) by bone was determined at the left calcaneus to assess bone status at baseline and at 1-yr follow-up. RESULTS: After 12 months of treatment, 15 (75%) patients were considered as responders. At baseline, responders and non-responders did not differ with regard to age, disease duration, core-set variables or BUA and Z-score values (patient's value--age specific normal value/normal group's s.d.). At 6-month and 1-yr follow-up in the whole group, BUA and Z-score values were not significantly different compared with baseline. At 1-yr follow-up, but not at 6 months, all 15 responders, differently from non-responders, showed a significant increase in both BUA and Z-score values: BUA at 1 yr 55.2 +/- 3.3 vs baseline 43.5 +/- 3.2 dB/MHz, P<0.001; Z score at 1 yr -0.3 +/- 0.2 vs baseline 1.5 +/- 0.4, P<0.002. CONCLUSION: For the first time in childhood rheumatic disease this pilot prospective study, although in a small group, shows evidence that 1 yr of etanercept therapy by controlling the underlying disease activity induces a sustained benefit on JIA bone loss. Prospective studies in larger patient samples are needed to confirm these data.
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OBJECTIVES: Autoimmune diseases have been associated with some organ non-specific rheumatological disorders such as rheumatoid arthritis and systemic lupus erythematosus; however, few studies have been performed in an extensive cohort of children with juvenile idiopathic arthritis (JIA). Our objective was to evaluate the thyroid function and the prevalence of antithyroid antibodies, autoimmune thyroiditis and coeliac disease in children with JIA. METHODS: One hundred and fifty-one children (120 female, 31 male, median age 8.3 yr, range 2.4-16.9 yr) with JIA were evaluated. All patients underwent thyroid function tests (u-TSH, free T(4) and free T(3)), antithyroglobulin (TgA) and antiperoxidase (TPOA) antibodies, antigliadin, anti-endomysium and antitransglutaminase antibodies. All patients with raised thyroid stimulating hormone levels, low thyroid hormone levels or positive TPOA and/or TgA values had a thyroid high-resolution sonography examination. Coeliac disease was confirmed by jejunal biopsy if the specific antibodies profile was positive. One hundred and fifty-eight age- and sex-matched Caucasian children from the same geographical area acted as controls. RESULTS: Fourteen (9.3%) patients showed subclinical hypothyroidism, 17 (11.9%) patients showed autoimmune thyroiditis with nine patients also showing a non-homogeneous thyroid parenchyma at ultrasound evaluation. Coeliac disease was demonstrated in 10 (6.6%) patients. Compared with controls, JIA patients had higher prevalence of subclinical hypothyroidism (P < 0.01), autoimmune thyroiditis (P < 0.0001) and coeliac disease (P < 0.005). CONCLUSIONS: JIA children have an increased prevalence of autoimmune thyroiditis, subclinical hypothyroidism and coeliac disease. These data seem to suggest careful monitoring of thyroid function, thyroid autoantibodies and coeliac disease in JIA children.
BACKGROUND: Weight loss is common in juvenile idiopathic arthritis (JIA) and has been positively correlated with an increase in the production of proinflammatory cytokines. OBJECTIVE: To assess if plasma leptin is a mediator of cytokine dependent decreased food intake during inflammatory diseases and if it is increased in JIA. METHODS: Leptin levels were determined in 31 patients with polyarticular disease and in 37 with oligoarticular disease; 32 healthy children served as controls. RESULTS: Patients had significantly reduced body mass index (BMI) compared with controls (17.3 (3) v 19.1 (3) kg/m(2); p<0.005). Leptin was significantly lower in patients than controls (8.1 (4.8) v 10.7 (7.3) ng/ml; p = 0.036), but leptin/BMI values were similar. Absolute (8.2 (4.8) v 8 (4.9); p>0.05) and normalised (0.45 (0.24) v 0.47 (0.24); p>0.05) leptin levels were not significantly different between patients with active and inactive disease and between patients with oligoarticular and polyarticular arthritis (7.8 (4.4) v 8.6 (5.3); p>0.05 and 0.45 (0.23) v 0.48 (0.26); p>0.05, respectively). CONCLUSIONS: Leptin production per unit of fat mass is similar in patients and controls. The hypothesis that high levels of proinflammatory cytokines that characterise JIA might induce an increase of adipocytes leptin production is not supported by the results. Leptin may be a marker of nutritional status of JIA.
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BACKGROUND: Antibodies against cyclic citrullinated peptide (anti-CCP) are considered to be specific for rheumatoid arthritis (RA). OBJECTIVE: To assess the clinical significance of anti-CCP in a cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: Anti-CCP were tested by an enzyme linked immunosorbent assay (ELISA) in serum samples from 109 patients with JIA (30 boys, 79 girls), with a mean age of 8.7 years (range 0.6-20.3) and mean disease duration of 3.6 years (range 3 months to 15.6 years). As control groups, anti-CCP were also tested in sera of 30 healthy children, 25 patients with juvenile onset systemic lupus erythematosus (SLE), and 50 adult patients (30 with RA, 20 with SLE). RESULTS: Positive anti-CCP values were found in sera of two patients with JIA (2%), one with polyarthritis, and one with oligoarthritis. Statistical analysis showed that anti-CCP were not associated with the presence of antinuclear antibodies, raised erythrocyte sedimentation rate, or erosions. In the control groups, none of the patients with juvenile onset SLE and only one of 20 adults with SLE were positive for anti-CCP, but 19/30 (63%) adults with RA showed anti-CCP positivity. CONCLUSIONS: Anti-CCP can be detected in children with JIA, but are less frequently present than in adults with RA.
OBJECTIVE: Oxidative stress contributes to joint inflammation and damage in rheumatoid arthritis. In a mobile inflamed joint, exercise induced multiple cycles of hypoxia-reperfusion injury may lead to the creation of a redox environment in which oxido-reductase systems, by NADPH mechanisms, produce highly reactive chemical species (i.e., oxygen free radicals). We investigated 2 endproducts of lipid peroxidation, malonildialdehyde (MDA) and diene conjugates (DC), and the formation of antibodies against oxidized low density lipoproteins (Ab oxLDL) in juvenile chronic arthritis (JCA), and assessed the role of oxidative phenomena in different phases and subsets of this disease. METHODS: To assess the role of oxidative stress in JCA, we measured the endproducts of lipid peroxidation, MDA and DC, by the increase of absorbance at 586 nm and 234 nm, respectively, and the levels of Ab oxLDL by ELISA in the sera of 58 patients with JCA and 21 healthy controls. Due to crossreactivity between Ab oxLDL and anticardiolipin antibodies (aCL), the sera were also tested by a standard ELISA for IgG-aCL. The patients were divided into 3 subsets: 29 with pauciarticular (pauci), 15 with polyarticular (poly), and 14 with systemic (sys) onset disease, and then were subdivided, according to different variables appropriate to each subset, reflecting active and inactive disease, into 30 active (14 pauci, 8 poly, 8 sys) and 28 inactive (15 pauci, 7 poly, 6 sys). RESULTS: Levels of Ab oxLDL were significantly increased in the whole group of patients (566.6 +/- 263.0 vs 206.6 +/- 136.3 mU/ml; p < 0.001) and in each of the type of onset (pauci 660.8 +/- 272.1, p < 0.001; poly 341.3 +/- 134.7, p < 0.01; sys 497.8 +/- 114.8, p < 0.001) compared to controls. Ab oxLDL were higher in the inactive than in the active group (743.5 +/- 231.9 and 404.4 +/- 169.9; p < 0.001). MDA and DC levels were not increased significantly in patients' sera. No patient was positive for IgG-aCL. CONCLUSION: These findings suggest that MDA and DC cannot be considered major markers of oxidative stress in JCA and that the Ab oxLDL may represent a delayed sign of oxidative stress previously induced by the inflammatory process in patients with JCA.
Oxidative stress, favoring disease progression by a rapid degeneration of endothelial cell function is deeply involved in Systemic Sclerosis (SSc) pathogenesis. Raynaud's phenomenon (RP), present in 90% of patients with SSc, provoking frequent daily episodes of hypoxia-reperfusion injury, produces several episodes of free radicals-mediated endothelial derangement. These events results in a positive feedback effect of luminal narrowing and ischemia and therefore to the birth of a vicious cycle of oxygen free radicals (OFR) generation, leading to endothelial damage, intimal thickening and fibrosis. Thus ischemia and reperfusion are two criticals events that may induce oxidative stress and inactivation of antioxidant enzymes. In RP and SSc, a reduced concentration of ascorbic acid, alpha-tocopherol and beta-carotene as well as low values of Selenium have been reported. This antioxidative potential deficiency increases the propensity to oxidative stress. favoring the development of injury mediated by OFR. We reviewed several antioxidant compounds, aiming at their capacity of reverting endothelial dysfunction and damage, scavenging lipid peroxidation and reducing multiple episodes of hypoxia-reperfusion injury. In order to interrupt SSc vicious cycle, we propose a main strategy for SSc treatment by a supplementation of antioxidants and different kind of drugs with antioxidant property, such as Lazaroids, Resveratrol, Melatonin and Probucol.
OBJECTIVES: To assess the frequency and types of cancer found in children presenting to our Unit with musculoskeletal symptoms over a 10-year period. METHODS: The medical records of patients with musculoskeletal symptoms and a final diagnosis of cancer were reviewed. In each case age, gender, presenting symptoms, laboratory data, diagnostic procedures, provisional and final diagnoses, and time between clinical onset and correct diagnosis were reviewed. RESULTS: An underlying neoplasia was found in 10 of 1,254 patients (<1%) complaining of musculoskeletal symptoms. The types of malignancies found included acute lymphocytic leukemia (ALL) (6 cases), lymphoma (2 cases), neuroblastoma (1 case), and Ewing's sarcoma (1 case). The mean time between disease onset and final diagnosis was 3.2 months. The most common presenting feature was monoarthritis, involving the larger joints such as the elbows, knees or ankles. Juvenile idiopathic arthritis (JIA) was the most frequent provisional diagnosis. In the preliminary hematologic evaluation, eight patients had an increased erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) value. White blood cell (WBC) count was normal in almost all children, with a normal differential count. Lactic dehydrogenase (LDH) was raised in all children. Bone marrow aspirates and lymph node or bone biopsies were necessary to reach the final diagnosis. CONCLUSIONS: A malignancy should always be excluded in children with musculoskeletal symptoms, especially when the clinical pattern is not characteristic of a specific rheumatic disease. Routine laboratory tests may be misleading. The simultaneous presence of high LDH or alpha-hydroxybutyric dehydrogenase (alpha-HBDH) levels and raised ESR or CRP, even with normal blood cell counts, should lead to additional investigations. RELEVANCE: All patients presenting with arthritis or other musculoskeletal symptoms should have a thorough clinical examination. Disproportionate pain levels and an atypical pattern of "arthritis," especially in the presence of systemic manifestations, suggest a possible underlying malignancy.
In 63 patients affected by Systemic Sclerosis (SSc) (limited subset: 40; diffuse subset: 23; early: 30; advanced: 33) the peroxidation product diene-conjugates (DC) and antibodies against oxidised low density lipoproteins (Ab oxLDL) were tested in serum by a spectrophotometer (absorbance 234 mn) and by a standard ELISA respectively. The data were compared with those obtained by 21 healthy subjects. DC was significantly higher in patients (73.3 +/- 37.2 microM/l; p < 0.0001) than in controls (48.4 +/- 16.7) as well as in the limited (80 +/- 48.8; p < 0.05) than in the diffuse subset (64.5 +/- 36.4); and in early (84.1 +/- 31.4; p < 0.05) than in advanced stage of the disease (67.9 +/- 42.5). The levels of Ab oxLDL were significantly higher in SSc patients (309.5 +/- 367.2 mU/ml; p < 0.0001) in all its subsets (limited: 351.9 +/- 351.1, p < 0.0001; diffuse: 207.7 +/- 316.1, p < 0.05; early: 428.9 +/- 417.1, p < 0.001; advanced: 302.7 +/- 89.9, p < 0.0001) than in controls (89.3 +/- 29.1). These antibodies levels were higher in limited subset than in diffuse (p < 0.05) and in early SSc than in advanced SSc (p < 0.05). The highest values of parameters of oxidative stress are found in the early stages, when the episodes of reperfusion after ischemic episodes (Raynaud's phenomenon) are very frequent. Moreover, the damage is higher in the early stages of SSc, with intact microvessels, than in late stages, when microvessels are very reduced in number, destroyed by the worsening of the disease. These data show that the respiratory burst deduced by the lipoperoxidation is higher in SSc than in controls, and may be an important pathogenetic factors involved in tissue changes in SSc.
The Authors report their experience about 40 patients who presented urinary retention by cervico-prostatic obstruction with anesthetic counterindications or limited life expectancy, cured with the urethral prosthesis of Nissenkorn (IUC). Our data permit to say that in selected patients IUC may represent an effective treatment with minimal invasiveness, low cost and few side effects.
This study tested two hypotheses: (1) that simple anthropometric parameters can be used to identify patients at risk of decreased bone mineral content and (2) that an inverse relationship exists between waist:hip ratio (WHR) and bone mineral density (BMD). Bone mineral content (BMC) and BMD were evaluated by dual-energy X-ray absorptiometry in 1873 free-living women. Of these, 1819 (97%) were post-menopausal. One thousand and thirteen women (54%) had normal BMD, 705 (38%) osteopenia and 155 (8%) osteoporosis. Body weight (Wt), body mass index and arm muscle and fat areas were significantly lower in osteoporotics than osteopenics (p < 0.0001) and in these latter than controls (p < 0.0001). However, values of WHR were similar in all groups (p = ns). Body weight was the anthropometric parameter better correlated with BMC (rho = 0.650, p < 0.0001) and only Wt and age were identified as significant predictors of bone mineral status (normal-BMD/osteopenic/osteoporotic) at polytomous logistic regression (p = 0.0001 for each). However, Wt could not be employed as an indicator of bone mineral status at the individual level because of high variations in BMC for the same level of Wt. Under- (< 5th percentile) and normal-Wt (5th-95th percentile) women had the same frequency of osteopenia (39%) while it was lower in over-Wt (> 95th) women (13%). The frequency of osteoporosis was higher in under- than normal-Wt women (37 vs 7%) and none of the over-Wt women had osteoporosis. This study shows that: (1) simple anthropometric measurements cannot be used to select subjects at risk of decreased BMC and, (2) BMD does not vary with WHR.