Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 18, Issue 2, 2018

Background and Objective: Rheumatoid arthritis (RA) is a predominant inflammatory autoimmune disorder. The incidence and prevalence of RA is increasing with considerable morbidity and mortality worldwide. The pathophysiology of RA has become clearer due to many significant research outputs during the last two decades. Many inflammatory cytokines involved in RA pathophysiology and the presence of autoantibodies are being used as potential biomarkers via the use of effective diagnostic techniques for the early diagnosis of RA. Currently, several disease-modifying anti-rheumatic drugs are being prescribed targeting RA pathophysiology, which have shown significant contributions in improving the disease outcomes. Discussion: Even though innovations in treatment strategies and monitoring are helping the patients to achieve early and sustained clinical and radiographic remission, the high cost of drugs and limited health care budgets are restricting the easy access of RA treatment. Both direct and indirect high cost of treatment are creating economic burden for the patients and affecting their quality of life. Conclusion: The aim of this review is to describe the updated concept of RA pathophysiology and highlight current diagnostic tools used for the early detection as well as prognosis - targeting several biomarkers of RA. Additionally, we explored the updated treatment options with side effects besides discussing the global economic burden.

Background and Objective: Systemic lupus erythematosus (SLE) is a diverse autoimmune disorder, evoked in response to self-immune system that leads to immune complex depositions and organ damage. The exact mechanism of SLE pathogenesis is still unclear but certain genetic and environmental factors have been suggested that could influence its pathogenesis. Discussion: The modulation in B- and T- cell responses and genetic variations could lead to abnormal lymphocyte functions and the production of antibodies against the indigenous proteins and the immune complex depositions. Conclusion: The present review highlights the various causatives of SLE, particularly the genetic alteration in B- and T-cell-related proteins. We have also delineated some of the available therapeutic strategies for the treatment of SLE.

Background and Objective: Migraine and systemic autoimmune diseases are 2-3-fold more common in women and various studies have reported an association between the two pathologies. Methods: This review takes into account epidemiological studies involving migraine and systemic lupus erythematosus, antiphospholipid syndrome, Sjogren's syndrome, and other diffuse connective tissue diseases. This scientific literature analysis consists of the main articles found in Medline with a search up to April 2017. Results: Many epidemiological studies were carried out on patients suffering from systemic lupus erythematosus. Results showed that headache and migraine are more prevalent in systemic lupus erythematosus patients compared to controls, especially migraine with aura. Patients with Lupus and migraine show a higher lupus activity and association with Raynaud and/or antiphospholipids in these populations are contradictory. There are not enough data to establish an association between antiphospholipid syndrome and migraine. However, data are more consistent between antiphospholipid carrier condition and migraine. Systemic sclerosis is a rare disease, for this reason the amount of available data on this disorder are scanty. However, some studies reported an association between headache, migraine and systemic sclerosis, especially where gliotic brain lesions and Raynaud are coexisting. Finally, large propensity cohort population based studies suggested that systemic autoimmune diseases are more frequent in patients suffering from migraine. Conclusion: An attempt at explaining the possible link between these disorders and migraine is discussed at the end of the review. Several autoimmune alterations are shared by most autoimmune diseases and headache types. Endothelial dysfunction is the only alteration that is common among all these disorders.

Background and Objective: Statins, 3-hydroxyl-3-methyl-glutharyl Coenzyme A reductase inhibitors showed their therapeutic potential in the treatment of atherosclerosis-related diseases. Recently, the properties of statins, separate from their lipid lowering activity have attracted much attention. These properties that cover a wide area of physiopathological activities including cell maturation, immune response regulation, tissue fibrosis, endothelial activity and are called pleiotropic activity. Many in vitro studies demonstrated significant, statins-dependent regulation of immune system reactivity, reduction of pro-inflammatory and pro-fibrotic cytokines as well as suppression of endothelial activity and damage. Methods: The present study reviewed the potential utility of statins as a concomitant regimen in the treatment of various connective tissue diseases. To address this we performed a methodical search though Pubmed database searching for term statins and pleiotropic effects and connective tissue disease or rheumatology. Results: One hundred and thirty one prominent research and review papers were identified and analyzed. Majority of research papers focused on laboratory models of statins activity, only a few of them analyzed data from human studies. Conclusion: Statins may have a therapeutic potential as a concomitant treatment for connective tissue diseases, that has been elegantly proven in many animal and laboratory studies. They deep interfere with immunological mechanism of autoantigen presentation, expressions of adhesion molecules. These phenomena may be recognized as the most important mode of action. Less is known about the potential of statins in clinical practice. Many small trials examined therapeutic potentials in various autoimmune diseases with contradictory results, disabling making the final conclusions. The future human studies should answer what patients population may benefit with concomitant statins' treatment.

Background: Familial Mediterranean Fever (FMF) is one of the most common hereditary auto-inflammatory diseases especially among Arabs, Armenians, Jews, and Turks characterized by recurrent attacks of fever, abdominal pain and arthritis.Whether the prevalence of ankylosing spondylitis (AS) is increased in FMF patients is a matter of debate. This review will summarize all the literature data relevant to this topic. Methods: We searched all the articles through PubMed and Embase databases from 1963 until 2017 addressing the relationship between AS and FMF patients. Results: The prevalence of AS among FMF patients is highly variable. However, a significant relationship was found to exist between MEFV gene mutations and AS. Most patients with coexistent MEFV gene mutations and AS were human leucocyte antigen B27 (HLA-B27) negative. The effect of these mutations on AS severity and prognosis was not significant. Conclusion: Large based population studies are needed to further assess the existence of MEFV gene mutations among AS patients and their effect on the clinical course of the disease in addition to assessment of AS prevalence in patients with FMF.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide that causes a spectrum of diseases including neonatal hyperbilirubinemia, acute and chronic hemolysis after exposure to oxidative stress. Aim of the Work: This five years retrospective study was carried out to study the demographic, clinical and laboratory data of 1000 patients with G6PD deficiency anemia registered in Hematology Unit, Pediatric Department, Tanta University Hospital. Patients and methods: Data were collected from patient's files, from November 2011 to November 2016, using the pre-designed questionnaires to obtain the complete history, clinical presentation and laboratory investigations including the complete blood count, red blood cells morphology, liver and renal functions and quantitative assay of G6PD enzyme activity by spectrophotometric method. Results: Males were more commonly affected than females (932 males versus 68 females). The highest prevalence of hemolytic crisis in G6PD deficiency patients was found within the age group of 1-3 years (920 patients; 92%) with mean age of the first presentation of 22.8±15.54 months. Patients presented mainly with pallor (1000 patients; 100%), dark red urine (896 patients; 89.6%) and jaundice (878 patients; 87.8%) after 24-72 hours of exposure to the precipitating factors (mean: 36±17.73 hours). Diets were the most common precipitating factor of hemolysis in patients with G6PD deficiency (834 patients; 83.4% of studied cases) especially fava beans (326 patients; 32.6%) and falafel (194 patients; 19.4%) which were the most common precipitating food products causing hemolysis followed by chick pea (108 patients; 10.8%), broad bean (76 patients; 7.6%), green pea (44 patients; 4.4%), pea nuts (38 patients; 3.8%), lentil (28 patients; 2.8%), and lastly black eyed peas (20 patients; 2 %). Infections were the 2nd most common cause of hemolysis (124 patients; 12.4%) including pneumonia (34 patients; 3.4%), tonsillitis (32 patients; 3.2%), typhoid fever (28 patients; 2.8%), hepatitis A (18 patients; 1.8%) and urinary tract infection (12 patients; 1.2%). Drugs were the least common cause of hemolysis (42 patients; 4.2%) including diclofenac sodium (24 patients; 2.4%), ibuprofen (8 patients; 0.8%), acetylsalicylic acid (4 patients; 0.4%), co-trimoxazole (4 patients; 0.4%) and nitrofurantion (2 patients; 0.2%). There was normocytic normochromic anemia with reticulocytosis and Heinz bodies in pre-transfusion complete blood picture in all studied cases. G6PD assay show marked decrease in enzyme level at time of presentation in all cases with the commonest G6PD enzyme level of 3-4 U/gm Hb (592 patients; 59.2%). Conclusion and Recommendations: G6PD deficiency anemia presented mainly with pallor, dark red urine and jaundice after exposure to certain diets, drugs and diseases and therefore patients with G6PD deficiency should avoid exposure to these precipitating factors of hemolysis. We can also recommend large neonatal screening programs to detect cases of G6PD deficiency before the occurrence of acute hemolysis and molecular studies to detect G6PD enzyme variant in Egypt.

Background: The patients with schizophrenia are at increased risk for problems regarding metabolic parameters due to their lifestyle and antipsychotic treatment. Objective: In this study, we aimed to evaluate the levels of adiponectin, leptin, irisin in patients with schizophrenia who were nondiabetic, nonobese and under antipsychotic treatment. Method: 5 ml sample of venous blood was collected from each participant. Blood cells were separated from the serum. The serum samples were stored in a -80°C freezer. Biochemical analyses were performed on these samples. Adiponectin, leptin and irisin levels were measured by Enzyme Linked Immunosorbent Assay method. Results: The study included 88 subjects. Of them, 44 were patients with schizophrenia and 44 were healthy controls. There were no statistically significant results when the c-reactive protein, adiponectin, leptin and irisin levels were compared between the schizophrenia and the control group (p>0.05). Conclusion: In our study, adiponectin, leptin and irisin levels in patients with schizophrenia did not present a statistically significant difference from healthy controls. Therefore, there is a need for studies including more participants to investigate the level of irisin in patients with schizophrenia.

Background: Allergy to Anisakis simplex (s.) is spreading due to the increased consumption of raw, smoked or marinated fish. In man, Anisakis s. can directly attack the gastrointestinal mucosa, provoking a parasitosis known as anisakiasis, or giving rise to the formation of IgE and, finally, inducing IgE-mediated reactions like urticaria, angioedema and anaphylactic shock. During recent years, a dietary approach to Anisakis s. infestation has also been addressed. Methods: A total of 620 patients with urticaria, angioedema, or both and a history of anaphylaxis following consumption of raw, smoked or marinated fish were recruited, evaluated for specific IgE levels to Anisakis s. and subjected to Skin Prick test. Following 18 month fish-free diet, patients were reevaluated at 6, 12 and 18 months, respectively. Patients undergoing diet were selected among those who had a clinical history with multiple accesses to first aid. Results: After 6-month fish-free diet, we recorded an improvement of symptoms and a remarkable reduction of specific IgE levels. The extension of the diet over 6 months in some cases resulted in a further reduction of specific IgE levels. Conclusion: Data obtained confirm the importance of a fish-free diet in patients with severe symptoms since a new antigenic exposure coincides with a relapse of symptoms and increased IgE levels. This last point should be kept in mind and carefully evaluated in patients at risk for anaphylaxis or angioedema.

Background: Primary immunodeficiencies (PIDs) are inherited disorders in which one or several components of the immune system are defective. Immunoglobulin replacement therapy is the mainstay of treatment for patients with impaired antibody production. However, recurrent infections would continue to occur in some patients due to the other high frequent concomitant defects, such as mannose-binding lectin (MBL) deficiency. Methods: A total of 51 PID patients participated in this cross-sectional study. A detailed questionnaire was completed by interviewing patients in order to record demographic, clinical and laboratory data. The levels of MBL were determined in the serums of patients by a sandwich enzyme-linked immunosorbent assay (ELISA) technique. Results: MBL deficiency was found in 29.4% of cases; 11.8% patients had mild, 3.9% patients had moderate and 13.7% patients had severe MBL deficiency. In patients with MBL deficiency, the rate of meningitis, sepsis, pneumonia, and otitis media was higher than patients with normal MBL levels. Immunoglobulin replacement therapy reduced the rate of infectious complications in PID patients; however, these reductions were more apparent in patients with normal MBL levels than patients with MBL deficiency. Conclusion: Antibody deficient patients with a concomitant immune defect in MBL production have higher rates of recurrent infections despite receiving Immunoglobulin replacement therapy.