The Renin-Angiotensin System: The Challenge behind Autoimmune Dermatological Diseases.

Autoimmune dermatological diseases (AIDD) encompass a diverse group of disorders characterized by aberrant immune responses targeting the skin and its associated structures. In recent years, emerging evidence suggests a potential involvement of the renin-angiotensin system (RAS) in the pathogenesis and progression of these conditions. RAS is a multicomponent cascade, primarily known for its role in regulating blood pressure and fluid balance. All of the RAS components play an important role in controlling inflammation and other immune responses. Angiotensin II, the main effector, acts on two essential receptors: Angiotensin Receptor 1 and 2 (AT1R and AT2R). A disturbance in the axis can lead to many pathological processes, including autoimmune (AI) diseases. AT1R activation triggers diverse signaling cascades involved in inflammation, fibrosis and tissue remodeling. Experimental studies have demonstrated the presence of AT1R in various cutaneous cells and immune cells, further emphasizing its potential contribution to the AI processes in the skin. Furthermore, recent investigations have highlighted the role of other RAS components, beyond angiotensin-converting enzyme (ACE) and Ang II, that may contribute to the pathophysiology of AIDD. Alternative pathways involving ACE2, Ang receptors and Ang-(1-7) have been implicated in regulating immune responses and tissue homeostasis within the skin microenvironment. Understanding the intricate involvement of the RAS in AIDD may provide novel therapeutic opportunities. Targeting specific components of the RAS, such as angiotensin receptor blockers (ARBs), ACE inhibitors (ACEIs) or alternative RAS pathway modulators, could potentially ameliorate inflammatory responses, reduce tissue damage and lessen disease manifestations. Further research is warranted to outline the exact mechanisms underlying RAS-mediated immune dysregulation in AIDD. This abstract aims to provide a concise overview of the intricate interplay between the RAS and AIDD. Therefore, we elaborate a systematic review of the potential challenge of RAS in the AIDD, including psoriasis, systemic sclerosis, vitiligo, lupus erythematosus and many more.

Interferon-Free Regimens and Direct-Acting Antiviral Agents for Delta Hepatitis: Are We There Yet?

Chronic delta hepatitis is a global health problem. Although a smaller percentage of chronic HBV-infected patients are coinfected with the hepatitis delta virus, these patients have a higher risk of an accelerated progression to fulminant "delta hepatitis", cirrhosis, hepatic decompensation, and hepatocellular carcinoma, putting a financial strain on the healthcare system and increasing the need for a liver transplant. Since its discovery, tremendous efforts have been directed toward understanding the intricate pathogenic mechanisms, discovering the complex viral replication process, the essential replicative intermediates, and cell division-mediated viral spread, which enables virion viability. The consideration of the interaction between HBV and HDV is crucial in the process of developing novel pharmaceuticals. Until just recently, interferon-based therapy was the only treatment available worldwide. This review aims to present the recent advancements in understanding the life cycle of HDV, which have consequently facilitated the development of innovative drug classes. Additionally, we will examine the antiviral strategies currently in phases II and III of development, including bulevirtide (an entry inhibitor), lonafarnib (a prenylation inhibitor), and REP 2139 (an HBsAg release inhibitor).

Is There a Time and a Place for the Gluten-Free Diet in Potential Celiac Disease?

Potential celiac disease (PCD) is characterized by the absence of villous atrophy on duodenal biopsies (Marsh 0 or 1) despite positive celiac serology and HLA DQ2 or DQ8 heterodimers. Recent epidemiological studies report that PCD represents one fifth of the total CD diagnoses. Compared to patients with CD, the majority of adult patients with PCD show lower rates of nutrient deficiencies and extraintestinal symptoms at diagnosis. Recommending a gluten-free diet (GFD) to PCD patients depends on whether they have symptoms or not. A significant clinical improvement is reported by symptomatic patients, but for asymptomatic PCD, diet implementation is still a matter of debate. Some questions remain to be answered: does PCD serve as an intermediary phase leading to the progression of true CD? Is it reasonable to hypothesize that PCD and active CD represent different manifestations of the same condition? Is there a potential for both underdiagnosis and overdiagnosis of CD in those who may have the condition? Additional research is required to address these inquiries and ascertain the specific subset of people with potential progression to overt CD, as well as to determine the potential advantages of early implementation of a GFD for these individuals. The investigation of risk factors in CD warrants examination of variables such as the timing of diagnosis, the genetic profile, the extent of gluten exposure, and the composition of the microbiome.

Emergency colectomy for massive rectal bleeding in a patient with well-controlled ulcerative colitis receiving Vedolizumab.

Ulcerative colitis (UC) is a chronic inflammatory condition, with a relapsing-remitting course. The case presented poses some valid questions regarding short-term and long-term management of patients with UC, and if the outcome (colectomy) could have been delayed or even prevented. Rectal bleeding is a cardinal symptom in patients with UC and it occurs among all patients during active disease. Massive rectal bleeding is an uncommon, but serious, complication of UC accounting for 0.1-1.4% of admissions. It is, nonetheless, noteworthy that instances of acute significant lower gastrointestinal bleeding accompanied by hemodynamic instability are infrequent. The rate of colectomy appears to be positively impacted by biological treatment. However, a refractory condition is still the primary reason for surgery, indicating a pressing need for new treatment approaches. Here we present the case of a young male patient who developed massive rectal bleeding and underwent emergent colectomy with ileostomy while having clinical and biological remission (normal calprotectin levels) at week 10 of Vedolizumab treatment.

Predictors of slow responsiveness and partial mucosal recovery in adult patients with celiac disease.

Aim: The present study aims to determine the rate of mucosal recovery and predictors of persistent mucosal damage after gluten free diet (GFD). Background: Celiac disease (CD) is a complex multi-systemic autoimmune disease triggered by exposure to dietary gluten in genetically predisposed individuals. There is still little evidence on the best method for assessing GFD adherence and mucosal recovery during treatment. Methods: The retrospective study included only adult patients (age≥18 years old), with biopsy-proven CD evaluated at a tertiary referral centre between 2016 and 2021. We performed a logistic regression analysis to identify factors associated with partial mucosal recovery (MR) after GFD. We included in the multivariate analysis parameters available at the time of CD diagnosis. Results: A total of 102 patients were enrolled, two thirds were females, median age of 39 years (yrs). The initial biopsy analysis showed different stages of villous atrophy (VA) in 79 (77.4%) cases, while in 23(22.5%) cases showed mild enteropathy (Marsh 1, 2). After at least 12 months of GFD, 26 (25.5%) patients had persistent VA despite good or excellent adherence to GFD. Younger patients (< 35yrs), who showed severe mucosal damage (Marsh 3c lesions) and who had increased anti-gliadin antibody (AGA) levels were at risk for failure to obtain mucosal recovery (MR). Logistic regression analysis demonstrated that complete mucosal atrophy (P=0.007) and high AGA antibody levels (cutoff 129 U/ml, P=0.001) were independent risk factors for lack of mucosal improvement after at least 12 months of GFD. Interestingly, genotype, tTG-IgA antibody levels, or duration of GFD levels did not influence the occurrence of MR. Conclusion: Although AGA seropositivity has lost much of their diagnostic significance in recent years due to the introduction of the more sensitive and specific antibody tests, our study reported that patients aged < 35 yrs, who showed severe mucosal damage (Marsh 3c lesions) and who had increased AGA antibody levels at diagnosis were at risk for failure to obtain MR. The elevated AGA levels at diagnosis could be used as a prognostic tool for assessing MR.

Risk Scores for Prediction of Major Cardiovascular Events in Non-Alcoholic Fatty Liver Disease: A No Man's Land?

Over the past 100 years, cardiovascular disease (CVD) has become a leading cause of mortality and morbidity in developed countries, and similar trends have occurred for chronic liver disease. Subsequent research also indicated that people with non-alcoholic fatty liver disease (NAFLD) had a twofold increased risk of CV events and that this risk was doubled in those with liver fibrosis. However, no validated CVD risk score specific for NAFLD patients has yet been validated, as traditional risk scores tend to underestimate the CV risk in NAFLD patients. From a practical perspective, identifying NAFLD patients and assessing severity of liver fibrosis when concurrent atherosclerotic risk factors are already established may serve as an important criterion in new CV risk scores. The current review aims to assess current risk scores and their utility for the prediction of CV events among patients with NAFLD.

Replacing the Burden of the Gluten Free Diet: Then, Now, and the Future.

Without a doubt, a majority of diseases are food-pattern-related. However, one disease stands out as an increasingly more common autoimmune-mediated enteropathy triggered by the ingestion of gluten. Celiac disease (CD) is an old disease, with changing clinical patterns, affecting any age, including infancy and adolescence, and becoming more frequent among the elderly. The gluten-free diet (GFD) has been the sole provider of clinical, serological, and histological improvement for patients with CD for more than seven decades. Nowadays, complete avoidance of dietary gluten is rarely possible because of the wide availability of wheat and other processed foods that contain even more gluten, to the detriment of gluten-free products. Undeniably, there is a definite need for replacing the burdensome GFD. An add-on therapy that could control the dietary transgressions and inadvertent gluten consumption that can possibly lead to overt CD should be considered while on GFD. Nevertheless, future drugs should be able to provide patients some freedom to self-manage CD and increase food independence, while actively reducing exposure and mucosal damage and alleviating GI symptoms. Numerous clinical trials assessing different molecules have already been performed with favorable outcomes, and hopefully they will soon be available for patient use.

Making a Comeback: Syphilitic Hepatitis in a Patient with Late Latent Syphilis-Case Report and Review of the Literature.

Treponema pallidum infection has emerged in recent years as an important community threat and burden to the health care system. Here, we report the case of a patient with cholestatic liver disease secondary to late latent syphilis. A 41 year-old male patient was referred to the clinic for assessment of an abnormal liver function panel. Ultrasound of the abdomen demonstrated an intense liver echogenicity, normal bile ducts, and no ascites. Virologic study revealed negative results for antibodies against common viral hepatitis and metabolic and autoimmune disease. The patient was tested for syphilis and a positive result was reported. The patient was diagnosed with late latent syphilis and syphilitic hepatitis and initiated benzathine penicillin at G 7.2 million units total, delivered as three doses of 2.4 million units intramuscular each at one-week intervals. He was assessed monthly and by the end of the sixth month, he had nonreactive VDRL (seroconversion), which confirmed recovery. Syphilitic hepatitis is an overlooked type of hepatitis and should be kept in mind as a differential diagnosis in an abnormal liver panel of uncertain etiology. Health care providers should be advised that higher levels of ALP may be the single landmark in cases of syphilitic hepatitis.

An Underrated Diagnosis of Superior Mesenteric Artery Syndrome: A Case Report.

Superior mesenteric artery syndrome (Wilkie's syndrome) is a rare cause of intestinal obstruction caused by a congenital or acquired reduction of the aorto-mesenteric angle leading to duodenal compression. We present the case of a 51-year-old female patient with a previous history of breast cancer. She was admitted to the Emergency Department with acute onset of recurrent vomiting, intense abdominal pain especially in the epigastric region, and abdominal distension. The ultrasound showed an absence of lower abdominal quadrants with an enlarged and distended stomach reaching the pelvis. The computer tomography scans confirmed the diagnosis of superior mesenteric artery syndrome. Conservative management was implemented, and using a nasogastric tube, and upped endoscopy approximately 4000 mL of fluid were aspirated with clinical improvement shortly after. The patient resumed a high-calorie diet and five months later, the patient was completely asymptomatic.

Helicobacter pylori prevalence and risk factors among children with celiac disease.

BACKGROUND/AIMS: The relationship between Helicobacter pylori and celiac disease (CD) remains controversial. The aim of this study was to assess the prevalence and risk factors for H. pylori infection among children diagnosed with CD. MATERIALS AND METHODS: This study included 70 patients diagnosed with CD at a tertiary referral center in Romania. Age, gender, and indicators of environmental conditions were evaluated via interviews with the children's caretakers. A multivariable logistic regression analysis was performed to identify the independent predictors for H. pylori infection. RESULTS: Of the 70 patients, 37 (52.9%) were females, and the mean age was 4.04±3.26 years. H. pylori infection was diagnosed in 23 (32.8%) patients, of whom 12 (52.1%) were females, and the mean age was 6.2±4.5 years. Of the total number of children with CD and H. pylori infection, 18 (78.2%) had milder forms of enteropathy (Marsh I-II), whereas the remaining 5 (21.7%) had villous atrophy compared to the other 47 (67.2%) patients who were negative for H. pylori-infection and showed more severe intestinal damage. The development of H. pylori infection was independently related to children with one parent only [odd ratio (OR), 9.04; 95% confidence interval (CI), 1.29-62.89; p<0.001], living in houses without sanitary facilities (OR, 3.88; 95% CI, 1.27-14.22; p=0.016), belonging to low-income families (OR, 8.52; 95% CI, 2.52-71.39; p=0.002), and of parents with a prior history of gastritis (OR, 2.68; 95% CI, 1.49-14.50; p=0.004). CONCLUSION: Children with CD and H. pylori infection had milder forms of enteropathy compared to children who are negative for H. pylori, suggesting that H. pylori infection may confer some protection against the development of severe degrees of villous atrophy.

Celiac disease: 10-year experience in a Romanian tertiary center.

AIM: To evaluate the experience of a single coeliac center over a 10-year-observational period. MATERIAL AND METHODS: Between January 2003 and December 2013 a total of 195 consecutive patients admitted with celiac disease were tested by multiple duodenal biopsies, anti-tissue transglutaminase and anti-gliadin antibodies, and baseline demographic, clinical, biological and immunological parameters. RESULTS: Patients were divided into two major groups according to the clinical features and number of signs and symptoms present upon admission: gastrointestinal (131, 67.17%) and non-gastrointestinal (64, 32.8%). Anti-tissue transglutaminase and anti-gliadin antibodies showed seropositivity in 109/158. Histological samples were available in 152 cases, according to Marsh-Oberhuber classification 11.18% being type 0, 17.76%, type I-II, and 71.05% type III. Correlations between anti-tissue transglutaminase antibody titers and Marsh-Oberhuber classification were found to be statistically significant. Body mass index was available in 96 cases. We found that severe atrophy was predominant in patients with a BMI<18 kg/m2. CONCLUSIONS: Celiac disease has an increasing prevalence and can be diagnosed at any age. Histology samples were indicative of different stages of villous atrophy. The disease prevalence is significantly higher among women. There was no statistically significant correlation between Marsh classification and BMI values.

Metastatic carcinoid tumor--atypical presentation.

Carcinoid tumor is a slow-growing type of neuroendocrine tumor, originating in the enterochromaffin cells and secreting mainly serotonin. Neuroendocrine tumors (NETs) are found throughout the intestinal tract, the appendix and terminal ileum being the most common locations, and are classified by site of origin and by degree of differentiation, with well-differentiated lesions representing those tumors formerly referred to as carcinoid tumors. The clinical symptoms are characterized by flushing, diarrhea, abdominal pain, and/or bronchial constriction and occur almost exclusively in patients with liver metastases due to the release of bioactive peptides and amines directly into the systemic circulation. We report the clinical, serological and histological diagnosis of a 67-years-old male patient with congestive heart failure secondary to carcinoid heart disease in the context of liver metastases of an ileum carcinoid tumor.

Efficacy of Helicobacter pylori eradication therapy in cirrhotic patients with peptic ulcer disease.

UNLABELLED: Few studies have been focused on the role of Helicobacter pylori eradication in cirrhotic patients with peptic ulcer and the reported results are conflicting. AIM: To evaluate the efficacy of proton pump inhibitor (PPI)-based triple therapy on peptic ulcer course in patients with liver cirrhosis. MATERIAL AND METHODS: This prospective study was carried out in a tertiary-care hospital. Of the 63 consecutive cirrhotic patients with peptic ulcer identified by endoscopy 39 (22 males, 14 females, aged 53 to 62 years) entered the study. The patients with peptic ulcer and H. pylori infection received eradication therapy, while H. pylori negative patients received PPI treatment. H. pylori eradication was confirmed by rapid urease test and histological examination. Follow-up endoscopies were performed at 6 and 12 months. The patients with peptic ulcer recurrence were treated with PPI. RESULTS: Of the 39 selected patients 22 (56.4%) were H. pylori positive, and 17 (43.6%) were H. pylori negative. H. pylori was eradicated in 63.6% (14/22) of the patients. During the follow-up period 2 H. pylori negative patients died from variceal bleeding and hepatic encephalopathy, respectively, and one H. pylori positive patient did not return for further assessment). Ulcers recurring within 1 year were found in 14 of 36 (38.8%) patients. Peptic ulcer recurred in 4 of 21 (19.0%) H. pylori positive patients and in 10 of 15 (47.6%) H. pylori negative patients at study entry. Patients' age (p = 0.018), Child-Pugh stage (p = 0.019), peptic ulcer site (p = 0.008), and H. pylori negative status (p = 0.004) were significantly related to ulcer recurrence. CONCLUSIONS: Eradication of H. pylori infection in patients with liver cirrhosis and peptic ulcer disease could be helpful, but does not protect all cirrhotic patients from peptic ulcer recurrence. Most relapsed ulcers were gastric ulcers in H. pylori negative patients.

Superior mesenteric artery syndrome: an unusual case of intestinal obstruction.

Superior mesenteric artery (SMA) syndrome is an uncommon cause of proximal intestinal obstruction, frequently occurring in patients who have had an important weight loss. The diagnosis can be difficult and usually is made by exclusion. The most characteristic symptoms are postprandial epigastric pain, fullness, voluminous vomiting and eructation. These symptoms are due to the compression of the third portion of the duodenum against the posterior structures by a narrow-angled SMA and surgical management is necessary. We report a case of SMA syndrome in a 23 year old patient, with a long history (since childhood) of voluminous vomiting, epigastric pain and an important weight loss. We performed small bowel enteroclysis, upper gastrointestinal series and endoscopy, biopsy of gastric and duodenal mucosa, abdominal computer tomography and ultrasonography to establish the diagnosis. Finally, the patient successfully underwent duodenojejunal anastomosis with a postoperative favourable outcome.

[Clinical profiles of ulcerative colitis]. / Consideratii diagnostice în rectocolita ulcero-hemoragica.

Ulcerative colitis is a worldwide disorder, although its precise incidence varies; it is an inflammatory disorder that affects the rectum and extends proximally to affect a variable extent of the colon. The aim of this study is to evaluate clinical and laboratory data in a retrospective study made in 421 patients recovered between 1999-2003 in the gastroenterology unit.

[Treatment of cholestatic liver disease]. / Tratamentul sindromului de colestaza.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic cholestatic liver diseases, biochemically characterized by an elevated serum bilirubin, alkaline phosphatase and gamma-glutamyl transferase. Although PBC and PSC have their own distinctive clinical, immunological, radiological and histological features, both diseases show a necro-inflammatory process, predominantly confined to the bile ducts within the portal tracts. In most patients the disease gradually progress and may lead to cirrhosis and liver failure. Transplantation may than be the only therapeutic option left.

[A case of stromal gastric tumor-uncommon clinical and pathological entity]. / Un caz de tumora stromala gastrica--raritate clinica si histopatologica.

Stromal gastric tumors represents an uncommon entity with difficult diagnosis, both preoperative and pathological. We present the case of a patient admitted for abdominal pain, with palpable tumor in epigastrium and right hypochondrium; abdominal echography, barium enema and abdominal CT-scan were not able to precise the involved organ. Operative exploration found at the level of horizontal portion of the stomach a solid tumor, which was resected, with good subsequent evolution. Pathologic diagnosis was stromal gastric tumor. We present latest news concerning diagnosis, prognostic and treatment for this type of tumor.

[Splenic hydatic cyst. Observations upon 38 cases of splenic echinococcosis]. / Chistul hidatic splenic. Observatii asupra a 38 de cazuri de echinococoza splenica.

15 patients with spleen hydatic cysts have been operated between 1986-1998, in percentage of 4.6% from the total number of hydatic cysts--8 females and 7 males with mean age of 44 years (17-70). They have been admitted for abdominal pain (66.6%) and at the clinical examination they presented a cystic tumor at the level of the spleen. In all the patients we performed splenectomy. In conclusion the hydatic cyst of the spleen is rare, but possible, the treatment being only surgical.

[Adult celiac disease(gluten enteropathy]. / Boala celiaca a adultului (enteropatia glutenica).

Celiac sprue is a disease in which there is malabsorption of nutrients by that portion of the small intestine which is damaged, a characteristic though not specific lesion of the small intestinal mucosa and prompt clinical improvement following withdrawal of certain cereal grains from the diet. We present a 41 years old patient with a history of diarrhea, treated as enterocolitis for several years, in which the gluten-free diet brought a clinical improvement.