Uveitis in autoimmune hepatitis： A case report

In this case report we describe for the first time an association between autoimmune hepatitis (AIH) and uveitis, without any doubts about other possible etiologies, such as HCV, since all the old reports describe the association of AIH with iridocyclitis before tests for HCV-related hepatitis could be available. A 38-year-old businessman with abnormal liver function tests and hyperemia of the bulbar conjunctiva was admitted to the hospital. Six years before admission, the patient presented with persistent fever, arthralgias, conjunctival hyperemia, leukocytosis and increased ESR, referred to acute rheumatic fever. The presence of systemic diseases, most commonly associated with uveitis, was investigated without results and the patient was then treated with topical corticosteroids. His symptoms resolved. A test for anti-nuclear antibodies was positive, at a titre of 1:320, with a speckled and nucleolar staining pattern. Liver ultrasound showed mild hepatomegaly with an increased echostructure of the liver. Percutaneous liver biopsy was performed under ultrasound assistance. Histological examination showed necroinflammation over the portal, periportal and lobular areas, fibrotic portal tracts, with periportal fibrosis and occasional portal-to-portal bridgings, but intact hepatic architecture. Some hepatocytes showed barely discernible granules of hemosiderin in the lobular area. Bile ductules had not any significant morphological alterations. METAVIR score was A2-F3, according to the modified HAI grading/fibrosis staging. The patient was diagnosed to have AIH with mild activity and fibrosis and was discharged on 25 mg prednisone, entering clinical and biochemical remission, further confirming diagnosis. After discharge the patient continued to have treatment with corticosteroids as an outpatient at a dose of 5 mg. On January 2002 the patient was readmitted to the hospital. A test for anti-nuclear antibodies was positive, at a titre of 1:320, with a speckled and nucleolar staining pattern. Anti-smooth muscle antibody test was also positive (1:160), while anti-LKM antibodies were negative. Ophthalmologic examination revealed inflammatory cells and proteinaceous flare in the anterior chamber of the left eye, and a stromal lesion in the cornea. He was maintained on immunosuppressive therapy (5 mg prednisone plus topical antibiotic therapy for two weeks) and then discharged. A complete remission of the symptoms was registered on follow-up. At present (July 2005), the patient is on prednisone (5 mg) and has no symptoms. Liver function tests are also within the normal range.     

Uveitis and the gut microbiota

Uveitis is a heterogeneous collection of inflammatory diseases of the intraocular uveal tissues and adjacent structures, and they collectively are a significant cause of visual morbidity. In recent years, investigating the contribution of the gut microbiota to autoimmunity, including the development of uveitis, has gained interest. Decreased disease severity has been observed in both the induced experimental autoimmune model of uveitis and the spontaneous RI61H model of uveitis in mice treated with oral broad-spectrum antibiotics and raised in germ-free conditions, implicating a role for the gut microbiota in the development of disease in these models. Also, in support of these findings are the differences in the composition of the microbiota that have been reported in uveitis patients. Proposed mechanisms accounting for the microbiota triggering uveitis include antigenic mimicry and dysbiosis leading to dysregulation of the immune system. An improved understanding of these mechanisms will facilitate potential therapeutic approaches including alteration of the microbiota with probiotic treatment and fecal microbiota transplants.     

Children and Adolescents with Repaired Tetralogy of Fallot Report Quality of Life Similar to Healthy Peers

Objective. The study aims to evaluate and compare self‐reported and parent proxy‐reported quality of life (QOL) in pediatric patients with repaired tetralogy of Fallot (TOF) and determine relationships with residual disease. Design. QOL was prospectively evaluated in children/adolescents with repaired TOF and parents' proxy report using the Pediatric Quality of Life Inventory Generic Core and Cardiac Module scales. The scores were compared with published self and parent proxy‐reported normative data for children considered healthy, chronically ill, and with congenital heart disease. Recent clinical data were reviewed for correlations between QOL and residual disease severity. Results. Twenty child–parent pairs were assessed at median age of 10.9 years (range 8.4–18.7 years). Self‐report was higher than parent proxy report. Compared with peers, self‐reported QOL was higher than for chronically ill children (overall QOL 85 vs. 77, P= 0.007) and similar to healthy children (85 vs. 83, P= 0.44), while proxy report by parent was similar to parents of chronically ill children (overall QOL 77 vs. 74, P= 0.035). Despite moderate pulmonary regurgitation (mean 35%) and right ventricular dilation (mean 114 mL/m²), 76% had a New York Heart Association class of 1, normal B‐natriuretic peptide (24 pg/mL), reasonable exercise tolerance VO₂ max% predicted (mean 77%), and preserved right ventricular ejection fraction (mean 58%, range 44–80%). Overall QOL positively correlated with child's VO₂ max% predicted, when reported by child (r = 0.47, P < 0.05) and parent proxy (r = 0.63, P < 0.05). Conclusions. QOL in children/adolescents with repaired TOF is not proportional to the severity of their residual disease. Self‐reported QOL appears similar to healthy peers while parent proxy reported lower QOL. For both children and parents, QOL positively correlated with the child's exercise capacity. Therefore, comprehensive follow‐up should include cardiac rehabilitation and psychosocial evaluation to ensure an active lifestyle, improve health perception, and prevent later acquired heart disease.     

The Role of Immune System in Idiopathic Anterior Uveitis

Background: Idiopathic anterior uveitis is an anterior segment inflammation in which a detailed medical history, general and ocular physical examination is not associated with any defined clinical syndrome. Alterations in immune system parameters have been reported in patients with idiopathic posterior uveitis; however no data on the role of immune system in idiopathic anterior uveitis has yet been reported. In this study the immune system function in patients with idiopathic anterior uveitis was evaluated. Objective: To evaluate the immune system function in patients with idiopathic non-infectious anterior uveitis. Methods: 51 patients with anterior uveitis, 32 women (62.7%) and 19 men (37.3%), participated in this study. Intensity of intraocular inflammation was scored according to standard uveitis grading system. In all cases, serum levels of immunoglobulins A, G, M and E, C3 and C4 complement components, and autoantibodies against ds-DNA and ACLA, were measured using ELISA method. Results: 49 patients out of 51 (96%) showed altered serum levels of immunological parameters, compared with normal values. Changes in serum immunoglobulin concentration were present in 44 patients, with increased IgA levels being the most common. Serum values of C3 and C4 complement proteins were also increased in 29 subjects. ds-DNA autoantibody was positive in 15 and equivocal in 19 cases. ACLA was positive and equivocal in 3 and 9 patients, respectively. Conclusion: Immune abnormalities found in serum of 49 patients with idiopathic anterior uveitis may play a role in the pathogenesis of this disorder.     

Advancements in the management of uveitis

Uveitis may exist as a clinical manifestation of an underlying systemic disease or may represent an idiopathic entity, sometimes with a very characteristic pattern. Different forms of uveitis have been defined on the basis of three important variables: chronicity, anatomic location, and underlying etiology. The evolving understanding of the immune system has resulted in a more targeted approach to manage patients with different forms of uveitis, although clearly this approach is at a very early stage.Altered patterns of cellular processing and different cytokine expression, including TNF, IL-1, IL-2, IL-6, and IL17, have been defined in uveitis, and this has laid the pathway for targeted therapy. Furthermore, approved biologic therapies for some of the more common autoimmune illnesses have now been tested in uveitis. Adalimumab and infliximab have been the best studied anti-TNF agents and indeed have now been recommended by an expert panel as the first line of treatment for ocular manifestations of Behçet's disease and the second line of treatment for other forms of uveitis. Adalimumab has been recently approved for intermediate uveitis, posterior uveitis, and panuveitis. Other biologic agents have been tested, including daclizumab, a monoclonal antibody directed against IL-2, anti-IL1, and anti-IL-6 receptor agents and therapies that block antigen-presenting cell and T-cell interaction, such as abatacept. In small case series, other biologics such as interferon and rituximab have also been evaluated.Although these biologic therapies have provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is not a disease, but a manifestation of many potential systemic diseases that may have specific individual therapeutic targets. Identification and characterization of these underlying diseases are not always possible and, more importantly, the most effective therapies for each entity have not been defined. In this study, an approach to manage patients with uveitis is presented and current therapy is reviewed.     

Pediatric autoimmune hepatitis in a patient who presented with erythema nodosum: a case report

Background

Autoimmune hepatitis (AIH) is a form of chronic hepatitis with unclear causative factors and is characterized by immunological and auto-immunological manifestations. Several extrahepatic manifestations, such as other autoimmune disorders, are associated with AIH. AIH with dermatological conditions as the initial manifestation is rare. We report the case of AIH in which erythema nodosum (EN) was the first manifestation.

Case Presentation

An 8-year-old girl with several persistent dermatological lesions was referred to our hospital several months ago. Her skin had nodular, painful, dry, and erythematous lesions, predominantly on the extensor areas of both the legs, with some erythematous patches on her face. Physical examination revealed that she had hepatosplenomegaly as well. Skin biopsy indicated EN. The results of the laboratory tests showed increased levels of several liver enzymes. The patient''s International Autoimmune Hepatitis Group (IAIHG) score was a definite indicator of AIH. The results of liver biopsy indicated AIH. Other causes of EN and abnormal liver function were ruled out. The only obvious cause of skin lesions was chronic inflammation due to an autoimmune response. The patient was treated for AIH, and her skin lesions along with other signs and symptoms resolved.

Conclusions

AIH can present with protean clinical manifestations, and is thus associated with the risk of delayed diagnosis. Dermatological manifestations, including EN, could indicate a serious disease, and further investigation might be required. AIH should be considered as the possible diagnosis in such cases.     

Pancreatic Disease in Children and Adolescents

Many childhood pancreatic disorders are rare, although they can represent significant and potentially severe disease. The spectrum of disease is very broad, ranging from the complex and bizarre congenital anomalies to the more typical acquired causes (eg, drug-induced pancreatitis or trauma injury). Genetics appears to play a major role in many childhood pancreas diseases, unlike adults where alcohol is a major factor. Nevertheless, there are similarities, and most of the disorders discussed here can be found in both the pediatric and adult age groups. Some of these disorders may be evolving and may be seen in both young and older patients. Newer imaging modalities and therapeutic endoscopy continue to be studied, although their ultimate role and utility in children has yet to be fully elucidated.     

Acute Asthma in Children and Adolescents

Children and adolescents experiencing acute exacerbations of asthma benefit from the use of β₂-adrenoceptor agonists (β₂-agonists) and systemic corticosteroids. However, there have been conflicting reports regarding the efficacy of inhaled anticholinergic agents.This article summarizes the evidence provided by randomized controlled trials studying the efficacy of adding inhaled anticholinergic agents to β₂-agonists in nonhospitalized children and adolescents with acute exacerbations of asthma. This systematic review of randomized controlled trials suggests that the addition of inhaled anticholinergic agents to β₂-agonists is beneficial in children and adolescents, particularly those with severe exacerbations of asthma. When given in repeated doses, the addition of inhaled anticholinergic agents to β₂-agonists improves lung function and reduces the risk of hospital admission by 25%. Several treatment regimens, namely ipratropium bromide (250 or 500μg per dose) every 20–60 minutes for two to three doses have been tested with similar beneficial effects. The addition of a single dose of an inhaled anticholinergic agent to β₂-agonists improves lung function but does not prevent hospital admission. The review did not identify any beneficial effects of anticholinergic agents in children with nonsevere asthma. Use of anticholinergic agents was not associated with increase in the incidence of nausea, vomiting or tremor.In conclusion, the addition of repeated doses of an inhaled anticholinergic agent to inhaled β₂-agonist is indicated in the emergency room management of children and adolescents with acute asthma, particularly those with severe exacerbations.     

Sex Hormone-Binding Globulin in Children and Adolescents

Sex hormone-binding globulin (SHBG) is a circulating glycoprotein that transports testosterone and other steroids in the blood. Interest in SHBG has escalated in recent years because of its inverse association with obesity and insulin resistance, and because many studies have linked lower circulating levels of SHBG to metabolic syndrome, type 2 diabetes, nonalcoholic fatty liver disease, polycystic ovary syndrome, and early puberty. The purpose of this review is to summarize molecular, clinical, endocrine, and epidemiological findings to illustrate how measurement of plasma SHBG may be useful in clinical medicine in children.