Localized Abdominal Idiopathic Lipodystrophy

Localized loss of subcutaneous tissue can occur after panniculitis, injections of corticosteroids and other drugs, or associated with infectious, autoimmune or neurologic diseases. The "idiopathic lipoatrophies" are a group of poorly characterized diseases, with focal disappearance of subcutaneous fat, and usually the thighs, abdomen or the ankles are affected. Three subtypes have been described based on clinical presentation: lipoatrophia semicircularis, annular lipoatrophy of the ankles and centrifugal lipodystrophy. We describe a 52-year-old female patient who developed a localized atrophy of the abdominal areas over a period of 3 months without any inflammatory signs over the evolution of the disease. The patient denied any previous local trauma or medication of any type. The atrophy stabilized, showing no progression over the last 6 years. The histopathological examination was normal except for the absence of subcutaneous fat, although the biopsy was taken down to the fascia. There was no clinical or serologic evidence of autoimmune diseases and laboratory testing for Borrelia burgdorferi infection was negative. Other causes of localized lipoatrophies were excluded and the final diagnosis was localized idiopathic lipodystrophy. Our patient is the second report on an abdominal lipodystrophy, with no previous inflammatory signs, absence of subcutaneous fat and no associated pathogenic factor. There is no established treatment for idiopathic lipodystrophy, and the lesions do not tend to resolve spontaneously.

Cytomegalovirus in colorectal cancer and idiopathic ulcerative colitis

Cytomegalovirus (CMV) is a genus in the family Herpesviridae that has been associated with gastrointestinal syndromes. In this work we looked for a possible association of CMV infection with colorectal cancer and ulcerative colitis (UC). Blood and enteric tissue samples of 14 patients with colorectal cancer and of 21 with UC were subjected to a nested-PCR that amplifies part of the gB gene of CMV and also to immunohistochemistry using a specific monoclonal antibody to IE 76kDa protein of CMV. CMV was detected by nested-PCR in the blood and/or the enteric tissue of nine (64.3%) colorectal cancer and 16 (76.2%) ulcerative colitis patients. In the immunohistochemistry it was observed that 12 (12/21, 57.1%) positive enteric tissue samples of patients with UC and none from patients with colorectal cancer (0/14) were positive to CMV. The positivity of CMV infections in the UC patient group (12/21, 57.1%) showed by both techniques, was significantly higher (p = 0.015) than that observed for colorectal cancer patients (2/14, 14.3%). These results suggest an association of ulcerative colitis with CMV infection of the enteric tissue.

Prognostic Factors in Adult Patients with Idiopathic IgA Nephropathy

Introduction. IgA nephropathy is the dominant primary glomerular disease found throughout the majority of the world’s developed countries. Accurately identifying patients who are at risk of progressive disease is challenging. We aimed to characterise clinical and histological features that predict poor prognosis in adults. Patients and Methods. We performed a single-centre retrospective observational study of biopsy-proven IgA nephropathy. The primary outcome was renal survival and death from any cause, and the secondary outcome was proteinuria remission. Results. Data from 49 cases were available for analysis with a median follow-up of 4 years. There were no deaths. Univariable analyses identified acute renal failure, low estimated glomerular filtration rate for ≥3 months (low eGFR), arterial hypertension, baseline proteinuria, glomerular sclerosis >50% and interstitial fibrosis >50% as poor prognostic markers. Low eGFR persisted significant by multivariable model that used only clinical parameters. Multivariable models with histopathologic parameters observed that tubular atrophy/interstitial fibrosis >50% was independently associated with the primary outcome. Proteinuria remission throughout follow-up had no prognostic value in our revision. Conclusions. Two independent predictors of poor renal survival at time of biopsy were found: low eGFR and tubular atrophy/interstitial fibrosis >50%.

Anti-Phospholipase A2 Receptor Antibodies in the Diagnosis of Idiopathic Membranous Nephropathy

Circulating anti-phospholipase A2 receptor antibodies (anti-PLA2R) have been described in 70% to 80% of the patients with idiopathic membranous nephropathy (iMN), but not in patients with secondary membranous nephropathy or other glomerular diseases. The goal of this study was to evaluate the sensitivity and specificity of the assay for anti-PLA2R in the diagnosis of iMN. Anti-PLA2R IgG, Elisa and immunofluorescence tests were used to detect circulating anti-PLA2R. These tests were applied in 53 patients who had a kidney biopsy. Of these, 38 had histological diagnosis of membranous nephropathy (MN) and the remaining had other glomerular diseases. The MN was classified as idiopathic in 33 patients after clinical exclusion of secondary causes. Anti-PLA2R were positive in 57.6% of the patients with iMN. All patients with secondary membranous nephropathy or other glomerular diseases did not show circulating anti-PLA2R. The sensitivity was 57.6% (CI 39.2-74.5) and specificity 100% (CI 47.8-100), AUC 0.788; p < 0.0001 for the detection of iMN. 71.4% of the iMN patients that tested negative for anti-PLA2R were in partial or complete remission. The detection of anti-PLA2R in the studied population had a specificity of 100% for the iMN diagnosis. Prior treatments seem to make the test negative and contribute to a lower sensitivity.

Idiopathic Hypocomplementaemic Tubulointerstitial Nephritis

Background: Tubulointerstitial nephritis (TIN) is a common cause of kidney injury typically seen in association with drug exposure, infection or autoimmune diseases. However, TIN with interstitial immune complex deposition, without glomerular injury, is rarely observed. Case: We report a case of a 64-yearold Indian woman admitted for dialysis-requiring renal failure, without involvement of other organs. Urinalysis showed blood 3+ and 24h proteinuria of 1.5 g. Renal ultrasound revealed normal sized kidneys with loss of parenchymal-sinus differentiation. Laboratory tests disclosed low C3, positive ANA but negative anti-dsDNA, SSA and SSB. Serum protein electrophoresis was normal. The renal biopsy showed tubulointerstitial nephritis with positive immunoglobulin staining involving the interstitium and tubular basement membrane with glomerular sparing. The patient started prednisolone (1mg/kg/day) without recovery of the renal function. Conclusion: Idiopathic hypocomplementaemic tubulointerstitial nephritis is a rare disease with few cases described in the literature. To our knowledge this is the first case reported in Portugal.

Novel FGFR1 Mutations in Kallmann Syndrome and Normosmic Idiopathic Hypogonadotropic Hypogonadism: Evidence for the Involvement of an Alternatively Spliced Isoform

OBJECTIVE: To determine the prevalence of fibroblast growth factor receptor 1 (FGFR1) mutations and their predicted functional consequences in patients with idiopathic hypogonadotropic hypogonadism (IHH). DESIGN: Cross-sectional study. SETTING: Multicentric. PATIENT(S): Fifty unrelated patients with IHH (21 with Kallmann syndrome and 29 with normosmic IHH). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Patients were screened for mutations in FGFR1. The functional consequences of mutations were predicted by in silico structural and conservation analysis. RESULT(S): Heterozygous FGFR1 mutations were identified in six (12%) kindreds. These consisted of frameshift mutations (p.Pro33-Alafs*17 and p.Tyr654*) and missense mutations in the signal peptide (p.Trp4Cys), in the D1 extracellular domain (p.Ser96Cys) and in the cytoplasmic tyrosine kinase domain (p.Met719Val). A missense mutation was identified in the alternatively spliced exon 8A (p.Ala353Thr) that exclusively affects the D3 extracellular domain of FGFR1 isoform IIIb. Structure-based and sequence-based prediction methods and the absence of these variants in 200 normal controls were all consistent with a critical role for the mutations in the activity of the receptor. Oligogenic inheritance (FGFR1/CHD7/PROKR2) was found in one patient. CONCLUSION(S): Two FGFR1 isoforms, IIIb and IIIc, result from alternative splicing of exons 8A and 8B, respectively. Loss-of-function of isoform IIIc is a cause of IHH, whereas isoform IIIb is thought to be redundant. Ours is the first report of normosmic IHH associated with a mutation in the alternatively spliced exon 8A and suggests that this disorder can be caused by defects in either of the two alternatively spliced FGFR1 isoforms.

Bone marrow fibrosis (pseudo-myelofibrosis) in human kala-azar

Thirty cases of human kala-azar were diagnosed by iliac crest biopsy and myeloculture. Histological analysis of 12 patients showed diffuse thickening of reticulin fibers. To the best of our knowledge, this is the third report describing secondary bone marrow fibrosis (myelofibrosis-like) associated with kala-azar. Patients with positive bone marrow fibrosis (pbmf = 12) were compared to patients without detectable bone marrow fibrosis (wbmf = 18). There were no significant differences in clinical and blood parameters following treatment. All patients showed regression of hepatosplenomegaly.Our findings suggest that associated bone marrow fibrosis is transient and did not interfere in the evolution of treated patients.

Dental and facial characteristics of patients with juvenile idiopathic arthritis

OBJECTIVE: It has been shown that the temporomandibular joint is frequently affected by juvenile idiopathic arthritis, and this degenerative disease, which may occur during facial growth, results in severe mandibular dysfunction. However, there are no studies that correlate oral health (tooth decay and gingival diseases) and temporomandibular joint dysfunction in patients with juvenile idiopathic arthritis. The aim of this study is to evaluate the oral and facial characteristics of the patients with juvenile idiopathic arthritis treated in a large teaching hospital. METHOD: Thirty-six patients with juvenile idiopathic arthritis (26 female and 10 male) underwent a systematic clinical evaluation of their dental, oral, and facial structures (DMFT index, plaque and gingival bleeding index, dental relationship, facial profile, and Helkimo's index). The control group was composed of 13 healthy children. RESULTS: The mean age of the patients with juvenile idiopathic arthritis was 10.8 years; convex facial profile was present in 12 juvenile idiopathic arthritis patients, and class II molar relation was present in 12 (P = .032). The indexes of plaque and gingival bleeding were significant in juvenile idiopathic arthritis patients with a higher number of superior limbs joints involved (P = .055). Anterior open bite (5) and temporomandibular joint noise (8) were present in the juvenile idiopathic arthritis group. Of the group in this sample, 94% (P = .017) had temporomandibular joint dysfunction, 80% had decreased mandibular opening (P = 0.0002), and mandibular mobility was severely impaired in 33% (P = .015). CONCLUSION: This study confirms that patients with juvenile idiopathic arthritis a) have a high incidence of mandibular dysfunction that can be attributed to the direct effect of the disease in the temporomandibular joint and b) have a higher incidence of gingival disease that can be considered a secondary effect of juvenile idiopathic arthritis on oral health.

Susceptibility and prognostic factors in portuguese patients with juvenile idiopathic arthritis

ABSTRACT: Objectives: This study aimed to confirm whether 15 single nucleotide polymorphisms (SNPs) of selected genes are also associated with susceptibility for Juvenile idiopathic Arthritis (JIA) in thePortuguese population. Methods: Our study was conducted on Reuma.pt, the Rheumatic Diseases Portuguese Register, which includes patients with JIA receiving biological therapies and synthetic Disease Modifying Anti Rheumatic Drugs (DMARDs) since June 2001. Fifteen SNPs were investigated using Taqman® SNP genotyping assays in 291 Portuguese patients with JIA and 300 ethnically matched healthy controls. Results: Prior to Bonferroni correction for multiple testing, significant genotype association between one SNP and overall group of JIA was observed (PTPN22 rs2476601). In subgroup analysis, associations between six SNPs and the subgroup of patients with rheumatoid factor (RF)-positive Polyarticular (PTPN2 rs7234029), Extended oligoarticular (PTPN22 rs2476601), Systemic (PTPRC rs10919563, ANGPT1 rs7151781 and TNF rs361525) and Psoriatic JIA (IL2RA/CD25 rs2104286) were found. After Bonferroni correction for multiple testing, 3 genotype associations remained significant in the subgroup of patients with RF-positive polyarticular JIA (PTPN2 rs7234029 [corrected P 0.026]), extended oligoarticular (PTPN22 rs2476601 [corrected P 0.026]) and systemic JIA (ANGPT1 rs7151781 [corrected P 0.039]). Conclusion: Our results provide additional evidence for an association between polymorphisms in genes PTPN2, PTPN22 and ANGPT1 and the risk of RF-positive polyarticular, extended oligoarticular and systemic JIA, respectively, in a Portuguese population.

Influence of nephrotic state on the infectious profile in childhood idiopathic nephrotic syndrome

Patients with idiopathic nephrotic syndrome present alterations in their cellular and humoral immune reactions that predispose them to the development of infectious processes. PURPOSE: To characterize the infectious processes in patients with idiopathic nephrotic syndrome. PATIENTS AND METHODS: Ninety-two children and adolescents with idiopathic nephrotic syndrome were assessed retrospectively. The types of infection were grouped as follows: upper respiratory tract infections; pneumonia; skin infections; peritonitis; diarrhea; urinary tract infection ; herpes virus; and others. The patients were divided into 2 groups: Group I (steroid-responsive) n = 75, with 4 subgroups-IA (single episode) n = 10, IB (infrequent relapsers) n = 5, IC (frequent relapsers) n = 14, and ID (steroid-dependent) n = 46; and Group II (steroid-resistant) n = 17. The incidence-density of infection among the patients was assessed throughout the follow-up period. Comparisons for each group and subgroup were done during the periods of negative and nephrotic proteinuria. RESULTS: The analysis revealed a greater incidence-density of infections during the period of nephrotic proteinuria in all the groups and subgroups, with the exception of subgroup IA. During the period of nephrotic proteinuria, subgroups IC, ID, and Group II presented a greater incidence-density of infections as compared to subgroup IA. For the period of negative proteinuria, there was no difference in the incidence-density of infections between the groups and subgroups. Upper respiratory tract infections were the most frequent infectious processes. CONCLUSION: The nephrotic condition, whether as part of a course of frequent relapses, steroid dependence, or steroid resistance, conferred greater susceptibility to infection among the patients with idiopathic nephrotic syndrome. The results of this study suggest that the best preventive action against infection in this disease is to control the nephrotic state.

Thiamin, selenium, and copper levels in patients with idiopathic dilated cardiomyopathy taking diuretics

OBJECTIVE: To analyze the association of thiamin, selenium, and copper serum levels with cardiac function in patients with idiopathic dilated cardiomyopathy using diuretics, and also to compare them with levels in control patients with no evidence of disease. METHODS: The study comprised 30 patients with heart disease and 30 healthy control individuals. Thiamin was analyzed by measuring the activity of erythrocytic transketolase and the effect of thiamin pyrophosphate. Selenium and copper serum levels were measured by hydride generation and flame atomic absorption spectrophotometry, respectively. RESULTS: Thiamin deficiency was observed in 10% of the control individuals and in 33% of the patients with heart disease (p=0.02). The mean selenium and copper serum levels in control individuals and patients with heart disease were, respectively, 73.2±9.9 µg/L (56.5 to 94.5 µg/L) and 72.3±14.3 µg/L (35.5 to 94 µg/L) (p=0.77); 1.1±0.4mg/L (0.6 to 1.8mg/L) and 1.2± 0.4mg/L (0.6 to 2.2mg/L) (p=0.27). No association between the levels of these nutrients and cardiac function was observed. CONCLUSION: Thiamin deficiency was significantly more frequent in patients with heart disease. No significant difference was observed between the mean selenium and copper serum levels in control individuals and in patients with heart disease. The results suggest possible benefits with thiamin replacement in patients taking diuretics.

Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy

Background:Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients.Objective:Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III.Methods:We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year.Results:During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years.Conclusion:Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation.