Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction-an experimental study in growing animals

Background: Many chronic liver diseases lead to progressive hepatic fibrosis, a condition that can ultimately result in loss of organ function and severe portal hypertension necessitating hepatic transplantation. Within the last few decades, studies have been conducted to demonstrate the possibility of drug modulation of hepatic fibrogenesis. Regarding biliary obstruction, it has been suggested that administration of corticosteroids could promote better late outcomes for children with biliary atresia submitted to Kasai`s portoenterostomy. Models used to test potential antifibrogenic drugs such as pentoxifylline (PTX) have not included growing animals. Methods: In this experimental study, 119 young rats (21st or 22nd days) were submitted to laparotomy and common bile duct ligation (CBDL) or to sham surgery (SHAM). Animals were allocated into 5 groups, according to surgical procedure, and administered the following solutions: (1) CBDL + distilled water, (2) SHAM + distilled water, (3) CBDL + PTX, (4) CBDL + prednisolone (PRED), and (5) CBDL + PTX + PRED (PTX + PRED). Each group was further divided into 2 subgroups according to the length of the experiment (15 or 30 days). At the end of the defined period, animals were weighed, and a hepatic fragment was collected from each one for analyses. Results: The PTX animals exhibited increased weight gain compared to animals in the PRED or PTX + PRED groups. Animals from the 3 therapeutic groups (PTX, PRED, and PTX + PRED) showed diminished collagen-filled area in portal spaces. Total portal space area was increased in the PTX group. Conclusions: Hepatic fibrosis induced by bile duct ligation in young rats could be modulated by pharmacologic interventions. Administration of PTX or PRED, or the combination of both, resulted in diminished collagen-filled areas in portal spaces. (C) 2009 Elsevier Inc. All rights reserved.

Larva migrans: a case report and review

A case of massive Ancylostoma sp. larval infestation is presented in a patient who had received systemic corticosteroid therapy. What attracts attention in this case is the exuberance and rarity of clinical manifestation. Based on the pertinent literature, we discuss the mechanisms of parasital infection, the natural history of the disease and its treatment.

Refractory pemphigus vulgaris associated with herpes infection: case report and review

BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune disease characterized by blistering of the skin and mucosa, which develops due to the interaction between predisposing genetic and environmental factors. Infections caused by members of the Herpesviridae family have been suggested as a possible triggering factor for PV. OBJECTIVE AND METHODS: In this report, we investigate the presence of herpesviruses in refractory lesions on the right upper eyelid. The lesion has persisted despite the treatment with corticosteroids. Polymerase chain reaction (PCR) and DNA sequence analysis have been used to detect the DNA of HSV 1/2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8. RESULTS: The sample collected from the right upper eyelid has tested positive for HSV 1/2. Sequence analysis has confirmed the PCR results and allowed the identification of the HSV strain as belonging to type 1. After treatment with acyclovir, the lesion of the right upper eyelid has cleared and not relapsed. CONCLUSION: When patients present PV lesions which are refractory to corticosteroid therapy, herpetic infection should be considered.

Acute Upper Limb Ischemia, a Rare Presentation of Giant Cell Arteritis

Giant cell arteritis (GCA) is a systemic large vessel vasculitis, with extracranial arterial involvement described in 10-15% of cases, usually affecting the aorta and its branches. Patients with GCA are more likely to develop aortic aneurysms, but these are rarely present at the time of the diagnosis. We report the case of an 80-year-old Caucasian woman, who reported proximal muscle pain in the arms with morning stiffness of the shoulders for eight months. In the previous two months, she had developed worsening bilateral arm claudication, severe pain, cold extremities and digital necrosis. She had no palpable radial pulses and no measurable blood pressure. The patient had normochromic anemia, erythrocyte sedimentation rate of 120 mm/h, and a negative infectious and autoimmune workup. Computed tomography angiography revealed concentric wall thickening of the aorta extending to the aortic arch branches, particularly the subclavian and axillary arteries, which were severely stenotic, with areas of bilateral occlusion and an aneurysm of the ascending aorta (47 mm). Despite corticosteroid therapy there was progression to acute critical ischemia. She accordingly underwent surgical revascularization using a bilateral carotid-humeral bypass. After surgery, corticosteroid therapy was maintained and at six-month follow-up she was clinically stable with reduced inflammatory markers. GCA, usually a chronic benign vasculitis, presented exceptionally in this case as acute critical upper limb ischemia, resulting from a massive inflammatory process of the subclavian and axillary arteries, treated with salvage surgical revascularization.

Lewis Score - Prognostic value in patients with isolated small bowel Crohn's disease

Background and aims: Small bowel capsule endoscopy (SBCE) allows mapping of small bowel inflammation in Crohn’s disease (CD). We aimed to assess the prognostic value of the severity of inflammatory lesions, quantified by the Lewis score (LS), in patients with isolated small bowel CD. Methods: A retrospective study was performed in which 53 patients with isolated small bowel CD were submitted to SBCE at the time of diagnosis. The Lewis score was calculated and patients had at least 12 months of follow-up after diagnosis. As adverse events we defined disease flare requiring systemic corticosteroid therapy, hospitalization and/or surgery during follow-up. We compared the incidence of adverse events in 2 patient subgroups, i.e. those with moderate or severe inflammatory activity (LS =790) and those with mild inflammatory activity (135 = LS < 790). Results: The LS was =790 in 22 patients (41.5%), while 58.5% presented with LS between 135 and 790. Patients with a higher LS were more frequently smokers (p = 0.01), males (p = 0017) and under immunosuppressive therapy (p = 0.004). In multivariate analysis, moderate to severe disease at SBCE was independently associated with corticosteroid therapy during follow-up, with a relative risk (RR) of 5 (p = 0.011; 95% confidence interval [CI] 1.5–17.8), and for hospitalization, with an RR of 13.7 (p = 0 .028; 95% CI 1.3–141.9). Conclusion: In patients with moderate to severe inflammatory activity there were higher prevalences of corticosteroid therapy demand and hospitalization during follow-up. Thus, stratifying the degree of small bowel inflammatory activity with SBCE and LS calculation at the time of diagnosis provided relevant prognostic value in patients with isolated small bowel CD.

Prophytaxie de l'ostéoporose cortisonique: qui, quand et quoi [Prevention of cortisone-induced osteoporosis: who, when and what?]

Glucocorticoid-induced osteoporosis is a known phenomenon with already an increased fracture risk at 2.5 mg of prednisone daily over 3 months. This risk appears to be independent of bone densitometry results, in contradiction with published guidelines. With the creation of our Department of Musculoskeletal Medicine, we wanted to edict clear recommendations for the prevention of steroid-induced osteoporosis. In addition to the standard general measures to prevent osteoporosis and calcium and vitamin D supplementation, we advocate the use of a specific treatment for osteoporosis in all cases when the duration of corticosteroid therapy is not strictly limited and shorter than 3 months. Bisphosphonates are the treatment of choice, while the analogue of parathyroid hormone remains an alternative in cases with a very high fracture risk.

Infections by protozoa in immunocompromised hosts

Protozoa are among the most important pathogens that can cause infection in immunocompromised patients. They infect particularly individuals with impaired cell immunity, such as those with hematologic neoplasias, those submitted to transplant of solid organs, those under high-dose corticosteroid therapy, and carriers of the human immunodeficiency virus. Among the protozoa that most commonly cause disease in immunocompromised individuals are Toxoplasma gondii, Trypanosoma cruzi, Cryptosporidium parvum, Isospora belli, Cyclospora cayetanensis and microsporidia; the former two cause severe encephalitis and myocarditis, and the others cause gastrointestinal infections. Early diagnosis and prompt institution of specific therapy for each of these organisms are basic measures to decrease morbidity and mortality associated with these infections.

Swallowed topical corticosteroids reduce the risk for long-lasting bolus impactions in eosinophilic esophagitis.

BACKGROUND: Long-lasting food impactions requiring endoscopic bolus removal occur frequently in patients with eosinophilic esophagitis (EoE) and harbor a risk for severe esophageal injuries. We evaluated whether treatment with swallowed topical corticosteroids is able to reduce the risk of occurrence of this complication. METHODS: We analyzed data from the Swiss EoE Cohort Study. Patients with yearly clinic visits, during which standardized assessment of symptoms, endoscopic, histologic, and laboratory findings was carried out, were included. RESULTS: A total of 206 patients (157 males) were analyzed. The median follow-up time was 5 years with a total of 703 visits (mean 3.41 visits/patient). During the follow-up period, 33 patients (16 % of the cohort) experienced 42 impactions requiring endoscopic bolus removal. We evaluated the following factors regarding the outcome 'bolus impaction' by univariate logistic regression modeling: swallowed topical corticosteroid therapy (OR 0.503, 95%-CI 0.255-0.993, P = 0.048), presence of EoE symptoms (OR 1.150, 95%-CI 0.4668-2.835, P = 0.761), esophageal stricture (OR 2.832, 95%-CI 1.508-5.321, P = 0.001), peak eosinophil count >10 eosinophils/HPF (OR 0.724, 95%-CI 0.324-1.621, P = 0.433), blood eosinophilia (OR 1.532, 95%-CI 0.569-4.118, P = 0.398), and esophageal dilation (OR 1.852, 95%-CI 1.034-3.755, P = 0.017). In the multivariate model, the following factors were significantly associated with bolus impaction: swallowed topical corticosteroid therapy (OR 0.411, 95%-CI 0.203-0.835, P = 0.014) and esophageal stricture (OR 2.666, 95%-CI 1.259-5.645, P = 0.01). Increasing frequency of use of swallowed topical steroids was associated with a lower risk for bolus impactions. CONCLUSIONS: Treatment of EoE with swallowed topical corticosteroids significantly reduces the risk for long-lasting bolus impactions.

Alvéolite aux isocyanates chez une couturière [Isocyanate-induced alveolitis in a furniture manufacture worker]

A 41-year-old woman who worked in a furniture plant was admitted to hospital for acute dyspnea that had developed a few hours she marked pieces of "Alcantara" material with a heated metallic blade. The chest x-ray showed a restrictive syndrome. The lymphocyte count was high in the bronchioalveolar lavage fluid with a CD4/CD8 ratio of 0.11, leading to the diagnosis of alveolitis. Investigations at the work place allowed identification and evaluation of the causal agent. Alcantara is a synthetic fabric composed of 70% polyurethane fibers, which when burned produces isocyanate monomers. After eliminating exposure and institution of corticosteroid therapy, the outcome was good with complete recovery. The risk was eliminated by changing the work procedure. This risk has not been reported earlier for furniture manufacture.

Retrospective analysis of complications of immunosuppressive therapies (steroidsand immunosuppressive therapies) in pediatric uveitis

Purpose¦The purpose of this study is to analyze the incidence rate of side effects occurring during systemic therapy (corticosteroids, methotrexate, azathioprine, cyclosporine A or biologic agents) of auto-immune uveitis.¦Material and methods¦Retrospective study including 23 / 71 patients aged between 0-16 years old presenting with a chronic non-infectious uveitis. All children were treated in the Jules-Gonin Eye Hospital and paediatric rheumatology unit of the CHUV (Centre Hospitalier Universitaire Vaudois) between January 2000 and December 31st 2010. Side effects were reported as minor (without subsequent change in systemic medication), moderate (associated with a change in systemic dosage or class of immunosuppressive therapy or in the presence of Cushingoid face or weight gain) or severe (hospitalization or life threatening).¦Results¦52% of boys and 48% of girls are present in the cohort with a mean age at the first visit of 8.1 years (1.7-15.6). Intermediate uveitis consisted of the commonest aetiology with 8 patients (35%), juvenile idiopathic arthritis (JIA) in 7 (30%), Behçet's disease in 3 (13%) and others in 5 (22%). The overall length of therapy was longer for prednisone (26.6 ± 5.4 patient / year), but was similar between methotrexate (22.1 ± 5.4 patient / year) and azathioprine (15.2 patient / year). Moderate side effects were respectively 64% for corticosteroids therapy, 54% with methotrexate and 14% with azathioprine. One severe and one moderate side effect were observed with anti-TNFα respectively stage III anaphylactic shock and pain during injection associated with a redness of the site of injection and limping after the injection.¦Discussion¦Immunomodulating agents allow a rapid decrease in corticosteroid therapy, but one severe side effect was observed with anti-TNFa agents. These agents are considered in most countries as third line therapeutic agents.

A pilot study of the efficacy of IL1 blockade by anakinra in acute calcific periarthritis of the rotator cuff

Background/Purpose: Calcific periarthritis of rotator cuff can induce acute and severe shoulder pain and is accompnied by signs of acute inflammation. The calcific deposits are composed of calcium phosphate crystals such as hydroxyapatite or basic calcium phosphate. These crystals stimulate the production and release of IL1b from macrophages, in an analogous manner to MSU and CPPD crystals. As IL1 blockade is effective in reducing signs and symptoms of inflammation in acute gout, we performed a pilot study to study if it is also effective in calcific periarthritis Methods: 5 consecutive patients were included (mean age: 62, 3 females, 2 males) between March 2011 and March 2012. Symptoms of acute shoulder pain at rest had to be present for _7 days before inclusion, associated with limitation of shoulder mobility and the presence on calcification in the rotator cuff by conventional radiography. None of the patients had responded to at least 48 hours of high doses of NSAIDs. Exclusion criteria included no corticosteroid therapy in the last 2 weeks and the exclusion of other rheumatologic or infectious diseases- .Clinical evaluation consisted of patient assessment of pain (total, rest and activity) by VAS (100mm scale) at days 0, 1, 3, 15, 42 and clinical examination of shoulder mobility at days 0, 3, 15. ESR and CRP were measured at days 0, 3. Plain radiographs were performed at days 0 and 15 and an ultrasound examination (including Doppler) was performed at days 0, 3, 15. Anakinra 100mg daily was administered for 3 consecutive days after the first evaluation (day 0). Rescue analgesics were allowed and recorded. Results: At inclusion, all patients had severe shoulder pain: mean (SD) VAS day pain of 72mm (_25mm), mean VAS night pain of 96 (_ 5) and impaired shoulder mobility. CRP was elevated in all of them (mean of 3X). Treatment with anakinra lead to rapid relief of pain in all patients, starting already on the first night following the first injection. The reduction of VAS pain was particularly striking for rest pain: mean (SD) VAS of 4mm (_ 5) at day 1 and this response was maintained for the 5 patients at the end of the three injections without any need of rescue medication. Mean rest VAS was 6 (_8) at day 3. The effect on day pain was less spectacular: mean (SD) VAS at D1 of 30 (_ 18), at D3 of 27 (_ 11). Shoulder mobility also improved and the CRP normalized in 4 of 5 patients at day 3. At day 42, 4 of 5 the patients were still totally asymptomatic. On X rays and US, the calcifications were reduced in size: mean maximal diameter of 21 mm at day 0 to 12 mm at day 15, but did not disappear in any patient. The main change on US was a significant and rapid (at day 3) reduction of Doppler activity around the calcification. Conclusion: This pilot open study suggests that IL-1_ inhibition may be an interesting therapeutic approach in acute calcific periarthritis, especially in patients who have not responded adequately to NSAIDs. The effect on pain seems to be more rapid (within a few hours) than steroid injection although a randomized controlled study needs to be performed to confirm this observation.

Systemic adalimumab induces peripheral corneal infiltrates: a case report.

BACKGROUND: Tumor necrosis factor-alpha inhibitors are widely used agents in the treatment of immune disorders such as rheumatoid arthritis and inflammatory bowel disease. Despite their anti-inflammatory action, paradoxical drug-induced inflammatory events have been occasionally associated with the use of infliximab, etanercept, and in a lesser extent adalimumab. However, eye involvement is uncommon and anterior uveitis is the only reported ocular adverse manifestation. It can be induced by etanercept, but has also been described during adalimumab therapy. We present here the first report of recurrent peripheral corneal infiltrates following subcutaneous injections of adalimumab. CASE PRESENTATION: A 34 year-old Caucasian woman with Crohn's disease presented to the emergency department with bilateral red eyes and discomfort 36 hours after she received her bimonthly dose of subcutaneous adalimumab. Examination revealed bilateral peripheral corneal infiltrates with characteristic features of immune infiltrates. Symptoms and infiltrates regressed after topical corticosteroid therapy, but recurred after each adalimumab injection over the following weeks. CONCLUSION: Paradoxical immune reactions associated with tumor necrosis factor-alpha inhibitors may result either from hypersensitivity mechanisms, or from immune-complex deposition via anti-adalimumab antibodies. Both mechanisms could explain this newly described manifestation. Care should be taken to search for corneal infiltrates in the event of red eye symptoms during adalimumab therapy since they respond to topical corticosteroids and do not necessarily prompt the discontinuation of the immunosuppressive therapy.

Detection of human parvovirus B19 in a patient with hepatitis

Parvovirus B19 has been associated by some investigators with cases of severe hepatitis. The aim of the present study was to determine the presence of active parvovirus B19 infection among 129 Brazilian patients with non-A-E hepatitis. The patients were assayed for antibodies against parvovirus B19, IgM class, by ELISA. In IgM-positive cases, parvovirus B19 DNA was assayed by PCR in serum and liver tissue and parvovirus VP1 antigen in liver tissue was assayed by immunohistochemistry. Antibodies against parvovirus B19, IgM class, were detected in 3 (2.3%) of 129 patients with non-A-E hepatitis. Previous surgery and blood transfusions were reported by these 3 patients. One patient was a 56-year-old female with severe hepatitis, with antimitochondrial antibody seropositivity and submassive necrosis at liver biopsy, who responded to corticosteroid therapy. Strong evidence for active parvovirus B19 infection was found in this patient, with parvovirus B19 DNA being detected by PCR in liver tissue. Furthermore, parvovirus VP1 antigen was also detected in liver tissue by immunohistochemistry. The other two IgM-positive patients were chronic hepatitis cases, but active infection was not proven, since neither viral DNA nor antigen were detected in their liver tissues. This and other reports suggest a possible relation between parvovirus B19 infection and some cases of hepatitis.

Corticosteroids in acute respiratory distress syndrome

Improving the course and outcome of patients with acute respiratory distress syndrome presents a challenge. By understanding the immune status of a patient, physicians can consider manipulating proinflammatory systems more rationally. In this context, corticosteroids could be a therapeutic tool in the armamentarium against acute respiratory distress syndrome. Corticosteroid therapy has been studied in three situations: prevention in high-risk patients, early treatment with high-dose, short-course therapy, and prolonged therapy in unresolving cases. There are differences between the corticosteroid trials of the past and recent trials: today, treatment starts 2-10 days after disease onset in patients that failed to improve; in the past, the corticosteroid doses employed were 5-140 times higher than those used now. Additionally, in the past treatment consisted of administering one to four doses every 6 h (methylprednisolone, 30 mg/kg) versus prolonging treatment as long as necessary in the new trials (2 mg kg-1 day-1 every 6 h). The variable response to corticosteroid treatment could be attributed to the heterogeneous biochemical and molecular mechanisms activated in response to different initial insults. Numerous factors need to be taken into account when corticosteroids are used to treat acute respiratory distress syndrome: the specificity of inhibition, the duration and degree of inhibition, and the timing of inhibition. The major continuing problem is when to administer corticosteroids and how to monitor their use. The inflammatory mechanisms are continuous and cyclic, sometimes causing deterioration or improvement of lung function. This article reviews the mechanisms of action of corticosteroids and the results of experimental and clinical studies regarding the use of corticosteroids in acute respiratory distress syndrome.