Intestinal lymphangiectasia in children: A favorable response to dietary modifications

Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification.Intestinal lymphangiectasia (IL) is a rare1-4 benign disease characterized by focal or diffuse dilation of the mucosal, submucosal, and subserosal lymphatics.2,5 In addition to being an important cause of protein losing enteropathy (PLE),6 IL is frequently associated with extraintestinal lymphatic abnormalities.5 Depending on the underlying pathology IL can be classified as primary or secondary disease.1,2,4,5 Primary IL (PIL) probably represents a congenital disorder of mesenteric lymphatics.1,3 The IL can be secondary to diseases like constrictive pericarditis, lymphoma, sarcoidosis, and scleroderma.1 A secondary disorder should always be ruled out before labeling IL as primary, this is by testing for proteinuria, rheumatic, neoplastic, and parasitic infection.1,3 Recently, a functional form of PIL with typical endoscopic and pathological findings but without clinical symptoms has been reported.3 The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction.1,2,4 Palliative treatment with lifelong dietary modification is the most effective and widely prescribed therapy.6 Limiting the dietary fat intake reduces chyle flow and therefore, protein loss.1 Once protein level is within the normal range, recurrence of enteric protein loss can be prevented by total parenteral nutrition (TPN) and medium chain triglycerides (MCT).1 In cases of secondary IL, treating the underlying primary disorder may be curative.2 Although the therapeutic approach for this disorder have gained a lot of attention lately, few studies have considered the therapeutic effects, nutritional condition, and long-term results in PIL patients.4 Here, we report 2 patients with PIL who were diagnosed by endoscopy and biopsy, and showed positive response to dietary modifications. We present these particular cases to highlight the effect of dietary modifications on the clinical status of patients with IL.     

Detection of human papillomavirus infection by molecular tests and its relation to colonic polyps and colorectal cancer

Objectives:

To prospectively examine the association between human papilloma virus (HPV) colonization of the colonic mucosa and the development of colorectal polyps (CRPs), and colorectal cancer (CRC) in Saudi Arabia.

Methods:

A case control study was performed between January 2013 and December 2014. All eligible patients underwent standard diagnostic colonoscopy. Patients with polyps or colorectal cancer were considered cases, while those with any other endoscopic findings were controls. Biopsy samples from polyps and tumors, and/or from normal colonic mucosa were acquired. Human papilloma virus colonization was detected using a hybrid capture technique of samples taken from both normal tissue, and CRPs and CRC. The association between HPV and CRPs/CRC was evaluated.

Results:

A total of 132 patients were recruited. The mean age was 53 (±15.9) years. Sixty patients had endoscopically detectable CRPs/CRC, and 72 had either inflammation or normal endoscopic evaluations. Only 4 (0.8%) of the 132 samples that were collected and analyzed were positive for the HPV gene. Statistical analysis did not identify any significant association between HPV colonization and the presence of CRPs/CRC. The only significant predictor of detecting CRPs/CRC on colonoscopy was symptomatic presentation (odds ratio=11.072, 95% confidence interval 4.7-26.2, p<0.001).

Conclusion:

Human papilloma virus colonic colonization is rare in Saudi Arabia. An association between HPV colonization and CRP/CRC development could not be identified in this cohort of patients.Colorectal cancer (CRC) is one of the most common malignancies worldwide,1 and one of the leading cancers in the Saudi population.2-6 Human papillomavirus (HPV) infection has been associated with benign (warts)7 and malignant (pre-cancer and cancer) genitals,8 perianal,9 and oral lesions10 as well as with rectal cancer through large cohort and case-control studies.11-15 Preventive measures such as mass vaccination campaigns have reduced the incidence of HPV-related genital lesions.16,17 However, the role of HPV in the pathogenesis of colorectal polyps (CRPs) and adenomas is still undetermined despite some evidence that suggest an association between HPV and CRC exists.18,19 Based on the well-recognized etiologic role of HPV in cervical, ano-genital, and oro-pharyngeal carcinogenesis, a possible role of HPV 16/18 in the pathogenesis of colon cancers and polyps has been proposed, and western publications have suggested that HPV colonization in the colonic mucosa may contribute to the development of CRC.20,21 Other studies have contradicted this hypothesis.22 Such an association if proven may largely influence the development of preventive strategies against CRC, such as mass vaccinations and patient education campaigns. The aim of this study is to prospectively examine the association between HPV colonization of the colonic mucosa and the development of CRP and cancer in the Kingdom of Saudi Arabia.     

X-ray repair cross-complementing protein 1 and 3 polymorphisms and susceptibility of breast cancer in a Jordanian population

Objectives:

To elucidate the contribution of x-ray repair cross-complementing (XRCC) protein 1 399Gln, XRCC3 241M, and XRCC3-5’-UTR polymorphisms to the susceptibility of breast cancer (BC) in a Jordanian population.

Methods:

Forty-six formalin fixed paraffin embedded tissue samples from BC diagnosed female patients, and 31 samples from the control group were subjected to DNA sequencing. Samples were collected between September 2013 and December 2014.

Results:

The XRCC1 Arg399Gln genotype did not exhibit any significant correlation with the susceptibility of BC (odds ratio [OR]=1.45, 95% confidence interval [CI]: 0.60-3.51) (p=0.47). Likewise, XRCC3 M241T genotype did not show significant correlation with BC (OR=2.02, 95% CI: 0.50-8.21) (p=0.40). However, distribution of XRCC3-5’UTR (rs1799794 A/G) genotype showed a significant difference between the patient and control group (OR=0.73, 95% CI: 0.06-8.46) (p=0.02).

Conclusion:

The XRCC3-5’UTR (rs1799794) G allele frequency was higher in cancer patients while XRCC1 (rs25487) and XRCC3 (rs861539) did not show any significant correlation with susceptibility of BC in the selected Jordanian population. Contribution of other environmental factors should be studied in future works, as well as the response of cancer therapy.Breast cancer (BC) incidence in Jordan has been estimated at 1,237 cases in 2012, with a prevalence of 4,260 cases over 5 years, and mortality rate up to 426 cases.1 Genetic predisposition contributes to less than 10% of BC cases, which raises a demand for further research into new genetic markers of BC risks.2 Fewer than 5% of BC cases have been found to be mutated at breast cancer 1 (BRCA1) early onset and BRCA2 genes, and approximately 40% of familial BC families have been identified for genetic predisposition.3 Unfortunately, mammalian cells are habitually exposed to genotoxic agents, such as ionizing radiation that can lead to DNA damage. Many double strand break,4 and single strand break (SSB) repairing proteins have been identified including DNA repair protein homolog, or RAD tecombinase, or x-ray repair cross-complementing (XRCC)s family proteins.5 Deficiency in repairing system might contribute to cancer development due to the loss of genetic integrity and genome instability.6 Mutation in DNA repair proteins is very rare.7 Therefore, many studies have been conducted to evaluate the role of allelic polymorphisms in DNA repair genes involved in cancers development.8,9 Genetic polymorphisms in DNA repair genes XRCC1, and XRCC3 have been screened to find an association with the risk of BC.10-12 Studies have demonstrated an association between XRCC1 and XRCC3 polymorphisms, and certain cancers subsuming colorectal cancer,13 lung cancer,14 pancreatic cancer,15 head and neck cancer,16 gastric cancer,17 esophageal cancer,18 melanoma skin cancer,19 oral squamous cell carcinomas,20 lung cancer risk,21 bladder cancer,22 and BC.23 Furthermore, a meta-analysis study supported the contribution of XRCC1 Arg399Gln polymorphism in susceptibility of BC in the American population.24 On the other hand, no relationship has been found between XRCC1 and XRCC3 polymorphisms and the risk of BC,25 lung cancer,26 bladder cancer,27 prostate cancer,28 lung cancer risk,29 cutaneous malignant melanoma,30 furthermore, it may decrease the risk for myeloblastic leukemia31 and non-melanoma skin cancer.32 Alcoholism, abortion, and non-breast feeding have been associated with increased risk of BC with contribution of XRCC1 399Gln and XRCC3 T241M polymorphisms.11 Moreover, family history,12 age group,33 polycyclic aromatic hydrocarbon-DNA adducts, fruit and vegetable and antioxidant intake, and non-smokers have been suggested to be associated with the risk of BC in interaction with XRCC1 or XRCC3 polymorphisms.34 The aim of the current study was to elucidate the contribution of XRCC1 399Gln, XRCC3 241M and XRCC3-5’-UTR polymorphisms in the susceptibility of BC in the Jordanian population. This study is intended to establish a reference point for future single nucleotide polymorphism (SNP) studies in the Jordanian population, which may contribute to the development of a national cancer database.     

Recognition of oxidized albumin and thyroid antigens by psoriasis autoantibodies: A possible role of reactive-oxygen-species induced epitopes in chronic plaque psoriasis

Objectives:

To investigate the role of reactive-oxygen-species (ROS) induced epitopes on human-serum-albumin (HSA) and thyroid antigens in psoriasis autoimmunity.

Methods:

This study was performed in the College of Medicine, Qassim University, Buraidah, Saudi Arabia between May 2014 and February 2015. The study was designed to explore the role of ROS-induced epitopes in psoriasis autoimmunity. Singlet-oxygen (or ROS)-induced epitopes on protein (ROS-epitopes-albumin) was characterized by in-vitro and in-vivo. Thyroid antigens were prepared from rabbit thyroid, and thyroglobulin was isolated from thyroid extract. Immunocross-reactions of protein-A purified anti-ROS-epitopes-HSA-immunoglobulin G (IgGs) with thyroid antigen, thyroglobulin, and their oxidized forms were determined. Binding characteristics of autoantibodies in chronic plaque psoriasis patients (n=26) against ROS-epitopes-HSA and also with native and oxidized thyroid antigens were screened, and the results were compared with age-matched controls (n=22).

Results:

The anti-ROS-epitopes-HSA-IgGs showed cross-reactions with thyroid antigen, thyroglobulin and with their oxidized forms. High degree of specific binding by psoriasis IgGs to ROS-epitopes-HSA, ROS-thyroid antigen and ROS-thyroglobulin was observed. Immunoglobulin G from normal-human-controls showed negligible binding with all tested antigens. Moreover, sera from psoriasis patients had higher levels of carbonyl contents compared with control sera.

Conclusion:

Structural alterations in albumin, thyroid antigens by ROS, generate unique neo-epitopes that might be one of the factors for the induction of autoantibodies in psoriasis.Psoriasis, a chronic skin disorder is known to be the most prevalent autoimmune disorder in humans.1 It is characterized by hyperplasia of the epidermis, infiltration of leukocytes of dermis and epidermis as well as dilatation and proliferation of blood vessels, which are likely to be triggered by multiple factors such as drugs, physical and psychological stress, bacterial infections, or injury.2 Psoriasis appears in different clinical variants and the most frequently is the plaque psoriasis (also known as psoriasis vulgaris), presents with scaly red plaques on common areas, such as on scalp, the back, dorsal skin of the elbows, and ventral skin of knees.3 Although, the role of immunologic and environmental factors in the pathogenesis of plaques psoriasis has been proposed, but the precise etiology of disease remains poorly understood.1,3 It is well documented that oxidative stress is one of the major factors involved in the pathogenesis of psoriasis4-6 and now it has been well established that excess generation of reactive oxygen species (ROS) by the immune system play a vital role in the development of psoriasis.7 Cellular events such as cell proliferation, apoptosis, cell differentiation, and immune response are influenced by ROS, and these events are altered in psoriasis patients.4-7 Although the exact pathogenesis of psoriasis is unknown, but the occurrence of autoimmune reactions has been assumed,8-10 the presence of autoantibodies and various underlying immunologic abnormalities in the affected sites of these patients have also been reported.8,11-15 The autoimmune etiology has been also proposed on the basis of its association with various autoimmune diseases,8,10 but the precise mechanism of generation of autoantibodies in psoriasis remains unclear.Thyroid disorders have a high prevalence in medical practice; they are associated with a wide range of diseases with which they may or may not share etiological factors. One of the organs which best show this wide range of clinical signs of thyroid dysfunctions is the skin.16-18 Thyroid abnormalities are well documented in psoriasis patients, thyroid gland causes an increase of epidermal growth factor levels, which has an important role in keratinocytes proliferation in psoriasis.19-21 In addition, a high prevalence of thyroid associated autoimmunity has also been reported in patients with psoriasis.20 Moreover, elevated ROS levels are often seen to be associated with thyroid dysfunctions, and now it is proposed that the thyroid hormones influence the ROS steady-state environment in the cell.22-24 The most common idea is the hyperthyroidism, which enhances the ROS production that perturbs the ROS steady-state environment to facilitate the cellular damage or damage to the cellular components as also reported in psoriasis patients.22,25 Therefore, it is assumed that in psoriasis, cells or cellular components are continuously exposed to oxidative stress, so that alterations in conformation and function of these cellular components may occur, which may results in modification of their biological properties. In view of these, this study was aimed to investigate the role of ROS-induced epitopes on albumin and thyroid antigens in psoriasis autoimmunity. To test this, ROS-modified epitopes were generated on albumin and antibodies against ROS-modified-albumin (anti-ROS-modified-epitopes antibodies) were experimentally generated. Cross-reactions of affinity purified anti-ROS-modified-epitopes immunoglobulin Gs (IgGs) with native- and ROS- modified thyroid antigen, thyroglobulin or human DNA were determined. Our data showed that anti-ROS-modified-epitopes-IgGs showed immunospecificity with thyroid antigen, thyroglobulin and with their oxidized forms. Importantly, the antigen(s) binding characteristics of naturally occurring chronic plaque psoriasis antibodies to ROS-modified epitopes, thyroid antigen, ROS-modified thyroid antigen, thyroglobulin, ROS-modified thyroglobulin, human DNA, and ROS-modified human DNA were determined.     

Prevalence and risk factors of clopidogrel non-response among Saudi patients undergoing coronary angiography

Objectives:

To estimate the prevalence of clopidogrel non-response and identify its risk factors among Saudi patients.

Methods:

This cross-sectional study was conducted at Prince Sultan Cardiac Center, Riyadh, Kingdom of Saudi Arabia between January and June 2013, to assess the degree of platelet inhibition using the VerifyNow assay (Accumetrics, San Diego, CA, USA) after receiving clopidogrel standard loading dose. Clopidogrel resistance was defined as ≤15% platelet inhibition or >213 P2Y12 reaction units (PRU).

Results:

Three hundred and four patients were included in the study. The mean age was 60.3 ± 11.4 years, and 73% were males. Clopidogrel doses were 300 mg (57%), 600 mg (27%), and 75 mg (16%). All patients used aspirin (81 mg in 94%). Approximately 66% (200/304) showed in vitro clopidogrel non-response, 54% had low platelet inhibitions, and 61% had high post-loading PRU. Using multivariate regression analysis that included all significant characteristics; only diabetes (odds ratio [OR]: 2.36, 95% confidence interval [CI]: 1.30-4.27, p=0.005) and higher preloading PRU (OR: 2.39, 95% CI: 1.40-4.11, p=0.002) remained significantly associated with higher clopidogrel non-response while myocardial infarction (OR: 0.34, 95% CI: 0.15-0.81, p=0.014) remained significantly associated with lower clopidogrel non-response. The associations of morbid obesity and diuretics use with higher clopidogrel non-response were slightly attenuated.

Conclusion:

Our findings indicate a high rate of clopidogrel in-vitro non-response among Saudi patients undergoing coronary angiography.Platelets play a critical role in the pathogenesis of atherothrombotic diseases such as coronary artery disease (CAD). The rupture of atherosclerotic plaques initiates a complex process of platelet adhesion, activation, and aggregation.1 Recently, clopidogrel and aspirin were the cornerstones of oral antiplatelet therapy for preventing ischemic events of atherothrombotic disease such as myocardial infarction and stroke.2,3 Clopidogrel was shown to be even more effective than aspirin in preventing such events of atherothrombotic disease.4 Clopidogrel is a prodrug and the active metabolite is generated by the cytochrome P450 system.5 The active metabolite acts by inhibiting platelet aggregation in response to adenosine diphosphate (ADP) through binding and blocking the platelet P2Y12 receptors.5 Variability in individual responsiveness to the antiplatelet effects of clopidogrel may lead to the occurrence of thromboembolic events despite regular antiplatelet therapy.6,7 This may be clinically translated into poor procedural and long-term morbidity and mortality outcomes.8,9 The prevalence of clopidogrel non-response (resistance) is highly variable in different studies and populations. A review10 estimated the non-response rate to range from 4-30%. This variability is partly caused by the lack of standard definition and the different assessment methods of clopidogrel non-response.11,12 A number of studies examined the patients characteristics associated with clopidogrel non-response but failed to identify any, probably due to small sample sizes and the presence of multiple confounding factors.13-15 Although, approximately 84% of Saudi patients admitted with acute coronary syndrome are treated with clopidogrel,16 there is lack of estimates of clopidogrel non-response and the associated risk factors in this population. The objective of the current study was to estimate the prevalence of clopidogrel non-response and to identify its risk factors among Saudi patients undergoing coronary angiography at a specialized cardiac center in Kingdom of Saudi Arabia (KSA).     

Kimura disease: No age or ethnicity limit

Kimura disease is a chronic inflammatory disease that mainly manifests as a lump in the cervical region. Although the underlying pathophysiology is not clear yet, the diagnosis can be established based on specific histopathological characteristics. The first case of this disease was described in China, as well as the majority of subsequent cases that were also described in the Far East countries made Kimura disease traditionally a disease of adult patients of Asian descent. This report describes the occurrence of Kimura disease in pediatric non-Asian patient with a similar clinicopathologic presentation.Although Kimura disease can be grouped under inflammatory disease of chronic nature, the underlying cause is still to be investigated. The disease usually present with enlarged, but painless cervical lymph node or subcutaneous masses in the cervical region.1,2 Clinical and histological characteristics of Kimura disease (primary allergic reaction or an alteration of immune regulation) help to differentiate it from angiolymphoid hyperplasia with eosinophilia (an arteriovenous malformation with secondary inflammation mostly involving dermal or subcutaneousparts), which were previously thought to be the same disease.1,2 Most cases have been reported in adult patients from the Far East of Asia.1,2 Elevation of inflammatory mediators that are usually elevated in autoimmune disorders made hypersensitivity a possible underlying pathophysiological mechanism of this disease.1,2 Patients usually present with non-tender mass in the cervical region with elevated eosinophils count and high levels of serum immunoglobulin type E (IgE).2 Unfortunately, there are no specific radiological characteristics of that disease.2 The only way to diagnose Kimura disease is through its histopathologic features, which necessitate a surgical biopsy.1,2 Treatment usually start with medical therapy and if that fail or show no spontaneous resolution then surgical excision would be the choice at that point with radiotherapy reserved for selected cases.1,2 The main objective of presenting this case report is to emphasize that Kimura disease can involve pediatric Saudi patients in contrast to what was historically described as a disease of adult Asian only. Secondary, it is to support what had been reported of occurrence of the disease in non-Asian patient with a similar clinicopathologic presentation of the Asian patients.2,3     

Pemphigus and pregnancy: Analysis and summary of case reports over 49 years

Pemphigus is a group of immune-mediated bullous disorders, which often cause fragile blisters and extensive lesions of the skin or mucous membranes, such as in the mouth. This disease could be life-threatening in some cases. During pregnancy, its condition will become more complicated due to the change in the mother’s hormone level and the effect of drug therapy on both the mother and her fetus. Thus, it will be more difficult to identify the clinical manifestations and to establish the treatment plan. In this article, we present a comprehensive review of pemphigus and pregnancy by analyzing 47 cases of pemphigus reported between 1966 and 2014, with diagnosis before or during pregnancy. The aim of this study is to make a comprehensive review of pemphigus and pregnancy, provide organized and reliable information for obstetricians, dermatologists, physicians, and oral medicine specialists.Pemphigus is characterized by widely distributed bullae and erosions on the skin and mucosa membranes. There are mainly 3 types of pemphigus: Pemphigus vulgaris (PV), Pemphigus foliaceus (PF), and other variants of pemphigus.1,2 The pathogenesis of pemphigus is associated with autoantibodies directed against transmembrane glycoproteins of desmosomes, which causes steric hindrance to homophilic adhesion of desmogleins, and results in the formation of Dsg1-depleted desmosomes in PF and Dsg3-depleted desmosomes in PV.3,4 Pemphigus usually affects the elderly, and genetics play an important role in predisposition.5,6 Pemphigus could involve one or more mucosae, while PV often shows extensive lesions of the oral mucosa.7,8 When it occurs in pregnancy, the condition becomes more complex.9 Early diagnosis and individually adjusted therapy are needed to avoid any risk for mother or child.10 The purpose of this article is to make a comprehensive review of the pemphigus and pregnancy, and provide organized and reliable information for clinicians.

Basic demographics

The existing reseasrch is mainly focused on case reports and retrospective studies. References were retrieved by an electronic search strategy “(pemphigus [MeSH Terms]) AND pregnancy [MeSH Terms] Filters: Case Reports” on PubMed, and a total of 62 cases were reviewed. Of the 62 cases, 14 were excluded based on abstract, which indicated discussion about gestational pemphigoid, and 7 were excluded because they were non-English. Finally, we included 41 relevant case reports according to their titles and abstracts. These 41 case reports between 1966 and 2014 involved 47 women identified with pemphigus before (n=21 cases) or during pregnancy (n=26 cases). These cases of pemphigus and pregnancy have been reported in different populations, Asia, Europe, and North America, with more than in Africa, South America, and Oceania (Figure 1). A recent study from the United Kingdom has suggested an incidence of PV of 0.68 cases per 100,000 persons per year. The incidence varies in different areas, being more common in the Near and Middle East than in Western Europe and North America.11-14Open in a separate windowFigure 1Regional distribution of 47 cases of pemphigus and pregnancy between 1966 and 2014.We analyzed the characteristics of 21 patients with pemphigus diagnosed before pregnancy. Among them, 71.4% were diagnosed as PV, 19% as PF, 4.8% as Pemphigus vegetans, while the remaining was indefinite. The age of onset of pemphigus was generally 20-42 years old (mean age 27.35±5.73), with a mean interval of 3.16±2.11 years between disease onset and pregnancy. The pemphigus course was characterized by exacerbation (61.9%), improvement (9.5%), and remaining stable (28.6%) during the pregnancy. The newborn status is meaningful for our conclusion. The incidence of neonatal pemphigus was as high as 57.1% (including 38.1% of PV and 19% of PF). In contrast, the percentage of healthy neonates was only 33.3%, which may be considered to be publication bias (15-31

Table 1

Characteristics of 21 patients with pemphigus diagnosed between 1966 and 2013.Open in a separate windowIt seems to be quite a rare phenomenon that pregnancy as a triggering factor of PV seems to be quite a rare phenomenon.13 4,14,19,32-52

Table 2

Characteristics of 26 patients with pemphigus diagnosed during pregnancy between 1966 and 2013.Open in a separate window

Effects on the mother

If a pregnant woman becomes sick (such as pemphigus), she is more likely to suffer from disorders of the neuroendocrine system and immune system due to the state of high pressure.53 According to the current study, the mother’s condition may exacerbate, enter into remission, or remain stable during the pregnancy.54 The disease is aggravated most likely during the first, second trimester, and postpartum, then is relived during the third trimester.15 This may be due to the increased level of endogenous corticosteroid hormone chorion and subsequent immunosuppression.40,55 Although some literature reports the postpartum flare of pemphigus due to the rapid drop of corticosteroid hormones levels, the postpartum status in our study was optimistic, only 2 cases (9.5%) of pemphigus diagnosed before pregnancy and 8 cases (30.8%) of pemphigus diagnosed during pregnancy exacerbated after delivery.19,56 However, some patients with pemphigus during pregnancy may not show any obvious changes, especially those patients in remission.9,15

Effects on the mode of delivery

Goldberg et al32 and Fainaru et al14 indicated that the trauma of vaginal delivery can result in extension and deterioration of the wound. In a cesarean section, patients who receive long-term steroid therapy will increase the risk, and the disease itself, and corticosteroid therapy may complicate wound healing. Therefore, delivery by cesarean section is the absence of additional benefits. Except for obstetric contraindications, vaginal delivery is recommended. Although it is a potential risk that local blisters may result in passive transfer of antibodies to the fetus through the breast milk, breastfeeding is not contraindicated.

Effects on the pregnancy outcome

Pregnancy outcome includes live birth, stillbirth, spontaneous abortion, and induced abortion.57 Pemphigus vulgaris in pregnancy may result in abortion, fetal growth retardation, intrauterine death, premature delivery, and in approximately 30% neonatal PV of the newborns.58 In this article, we will discuss the 3 most common outcomes of pemphigus in pregnancy: normal fetal outcome, neonatal pemphigus, and stillbirth.

Normal fetal outcome

Most of the patients with pemphigus can give birth to a normal full-term, healthy newborn through vaginal delivery or cesarean section, depending on the collaborative efforts of the dermatologist and obstetrician.56 In our study, although there were only 7 (33.3%) healthy neonates from the cases with pemphigus diagnosis before pregnancy, we considered it likely to be an underestimate due to the less frequent reports of successful deliveries than that of neonatal adverse outcomes.

Neonatal pemphigus

Neonatal pemphigus is a rarely reported transitory autoimmune blistering disease. It is clinically characterized by transient flaccid blisters and erosions on the skin and rarely on the mucous membranes.17 The disease can be self-healing at 2-3 weeks without special treatment, and does not have long-term clinical significance. No new vesicles or bullae appears in the newborn after birth. Neonatal PV has never been reported to persist beyond the neonatal period and progress to adult disease.17,34,35,39 Neonatal pemphigus is mainly due to the transplacental transmission of antibodies, and only a very small amount of immunoglobulin G (IgG) is synthesized by the neonate itself.36,59 Pemphigus IgG is found both in the fetal circulation and fixed to the fetal epidermis in a characteristic intercellular distribution, while IgA, IgM, IgE, and IgD generally do not participate in the passive transport.60 Contrary to PV, PF in pregnant women rarely leads to neonatal skin lesions.61 The absence of skin disease in the newborns may be due to low transfer of IgG4 autoantibodies through the placenta, and the “immunosorbent” effect of the placenta to contain desmosomes and desmogleins.62-65 This is because to the distribution and cross-compensation of the pemphigus antigens desmoglein 3 and 1 in neonatal and adult skin or mucosa are different.60

Stillbirth

In the literature, the rate of stillbirth in pemphigus during pregnancy was reported to range from 1.4-27%.18,33,56,66 In contrast to the high percentage of some previous observations, pregnancy ended in stillbirth in only one case (4.8%) of pemphigus diagnosed before pregnancy and 2 cases (7.7%) of pemphigus diagnosed during pregnancy in our study. The occurrence of stillbirth emphasizes the management problems encountered when a pemphigus patient becomes pregnant.56,66No relevance has been indicated between maternal treatment regimen and fetal outcome.38,67 Instead of particular medications, adverse pregnancy outcomes seem to be correlated more closely to poor maternal disease control, higher maternal serum, and umbilical cord blood antibody titers.38

Treatment options

Almost all types of pemphigus patients experience severe worsening of the disease after delivery if there is a lack of treatment during pregnancy (n=66). Treatment is often required to control both maternal diseases and fetal outcomes.68 The current study suggested that standard therapy gives priority to systemic glucocorticoids, alone or in combination with other immunosuppressive agents such as immunosuppressant, intravenous immunoglobulin (IVIg) or plasmapheresis.15,32,69 If the disease worsens during the first trimester, a medical termination of pregnancy may be considered, and if it happens during the second and third trimester, application of corticosteroids is a safe treatment.20 The treatment of pemphigus patients diagnosed during pregnancy is similar to the treatment before pregnancy.38

Glucocorticoids

The use of systemic steroids is considered safe in pregnancy, and glucocorticoid remains the first-line agent for treatment with low dosages when patients are mildly ill.70 Some corticosteroids such as prednisone (FDA pregnancy category B), featured with a fast action and high pharmacological effect, can be safely used as immunosuppressive drugs during pregnancy as they do not readily cross the placenta. Prednisone is the safest drug compared with other less used glucocorticoids such as dexamethasone and betamethasone.71,72 The dose of prednisone/prednisolone should be reduced to the lowest effective dose, and standardized doses are still experimental.15,19,32,56

Immunosuppressants

Immunosuppression of steroid-sparing agents are needed when pemphigus has to be controlled by larger doses of medications. Azathioprine is the most widely used steroid-sparing agent for pemphigus.73,74 Cyclosporine is believed to be less effective in the treatment of pemphigus, but it is the safest corticosteroid-sparing agent in pregnancy.38,69 Mycophenolatemofetil, cyclophosphamide, and methotrexate are strongly discouraged or even contraindicated in pregnancy.38,72

Intravenous immunoglobulin

There is moderate evidence suggestive of an effective and safe effect of IVIg as an auxiliary therapy in pregnancy patients with pemphigus.75-77 Therefore, when pregnancy is associated with significant medical problems or disease states, clinicians may need to consider using IVIg early.78

Plasmapheresis

Plasmapheresis is a useful alternative immunosuppressive therapy in pregnancy, which can be used as adjuvant therapy, combined with systemic corticosteroids, reducing the dosage of glucocorticoid treatment.21In conclusion, the patients may suffer from pemphigus before or during pregnancy. The condition of pemphigus and pregnancy can interact with each other and make the treatment and prognosis of these diseases more complicated, presenting challenges for the clinician. Pregnancy may precipitate or aggravate pemphigus, and new born babies of such patients may have a normal outcome or neonatal pemphigus, or, rarely, a stillbirth. Current treatment of pemphigus coexisting with pregnancy priorities systemic glucocorticoids, alone or in combination with other immunosuppressive agents such as immunosuppressants, IVIg or plasmapheresis. The number of reported cases of pemphigus in pregnancy is too small to predict the change of conditions for an individual patient. In summary, pemphigus and pregnancy is still an indistinct area that needs collaborative work by obstetricians, dermatologists, neonatologists, endocrinologists, and oral medicine specialists, to establish a mechanism of multi-disciplinary treatment.     

A cross-sectional study of anxiety and marital quality among women with breast cancer at a university clinic in western Saudi Arabia

Objectives:

To examine relationship between the quality of marital relationship and anxiety among women with breast cancer (BC) in the Kingdom of Saudi Arabia (KSA).

Methods:

This cross-sectional study recruited a consecutive series of 49 married women with BC seen in the Al-Amoudi Breast Cancer Center of Excellence at King Abdulaziz University, Jeddah, KSA in early 2013. Participants completed the Hospital Anxiety and Depression Scale, Spouse Perception Scale, and Quality of Marriage Index forms, and answered questions on demographic and cancer characteristics.

Results:

Anxiety symptoms indicating “possible” anxiety disorder were present in 10.4% and “probable” anxiety disorder in 14.6% (25% total). No significant relationship was found between the quality of marital relationship and anxiety symptoms (B=-0.04, standard error=0.05, t=-0.81, p=0.42). Anxiety was primarily driven by low education, poor socioeconomic status, and young age.

Conclusion:

Anxiety symptoms are prevalent among married women with BC seen in a university-based clinic in the KSA. Further research is needed to determine whether a diagnosis of BC adversely affects marital relationship, and whether this is the cause for anxiety in these women.Breast cancer (BC) is the most common cause of cancer death in women worldwide,1 and the Kingdom of Saudi Arabia (KSA) is no exception.2 Breast cancer has become a particular problem in Arab countries due to its late stage at presentation and its increased occurrence among young women.3 Both during and after treatment, even if the cancer goes into remission, concerns regarding recurrence, effect on the marital relationship, and frequent medical visits for monitoring, often result in high levels of anxiety (including post-traumatic stress-like symptoms).4-8 Anxiety and other mood symptoms are not benign in women with BC, as they are associated with increased mortality and cancer recurrence.9,10Studies in Western countries (United States, Canada, England, Australia, and Germany) indicate a prevalence of significant anxiety ranging from 4-45% in BC patients, depending on anxiety measure, cutoff score, geographical region, and time since diagnosis11-14 (compared with 15-37% of cancer patients in general with anxiety during the first year after diagnosis).15 The most commonly used measure of anxiety symptoms in BC patients is the Hospital Anxiety and Depression Scale (HADS), which assesses for “possible” and “probable” anxiety disorder (with a sensitivity and specificity of approximately 80%).12,16,17 Using this measure, the prevalence of “probable” anxiety disorder in BC patients ranges from 2-23% and “possible” anxiety disorder is present in an additional 19-22% (21-45% combined).11,13,18 Although factors that increase risk of anxiety in women with BC are poorly understood, a few studies largely from Western countries report more symptoms in younger persons and Caucasians, immigrants, those with lower education, later disease stage, and lower social support.8,11,13,19 In one of the few studies from an Eastern country,20 anxiety levels among BC patients from Bangkok, Thailand, were significantly higher among those with poor problem solving skills, more pain and fatigue, and poorer family functioning. Although research is limited almost entirely to the US and other Western countries, studies indicate that support from a spouse (especially emotional support) improves the adjustment of women to BC,21-25 and may even impact survival.26 Not all studies, however, report that having a marital partner buffers against the stress of BC.27,28 The demands of caregiving, the effects of BC and its treatments on sexual relationship, and coping with psychological changes in a BC patient can all lead to lower well-being in a spouse, and decrease his ability to provide support.24 Our exhaustive review of the literature uncovered several studies that have examined the prevalence of emotional reactions to BC in the Middle East, finding that 19-73% of women had significant anxiety symptoms.22,29-34 In those studies, anxiety was associated with poorer physical functioning, the presence of metastatic disease, higher education, lower social support, duration of marriage, and spouse’s level of anxiety. With regard to KSA, there has been a significant increase in the incidence of BC, which occurs at a younger age than in Western countries.35 A recent review of research on coping with BC, however, revealed not a single study from KSA.36 Our review identified only 2 studies37,38 that examined the prevalence or correlates of anxiety in Saudi cancer patients (none specifically in BC), and only one study39 that examined attitudes of Saudi males toward BC. The first study examined anxiety in 30 hospitalized patients with cancer (9 with BC) at the King Khalid National Guard Hospital in Jeddah, KSA.37 Researchers found that anxiety symptoms assessed by the Hamilton Anxiety Scale were significantly higher in cancer patients compared with 39 patients with a range of chronic illnesses; 3 patients with cancer (10%) had a clinical diagnosis of generalized anxiety disorder based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. The second study examined non-pain symptoms in 124 cancer patients (27% with BC) at King Faisal Specialist Hospital in Riyadh, KSA.38 The most frequently reported non-pain symptoms were fatigue (80%), loss of appetite (72%), dry mouth (69%), and anxiety (61%). Finally, researchers examined attitudes toward BC among males accompanying female patients to outpatient clinics at King Abdulaziz Hospital in Jeddah, KSA. When men were asked what they would do if their wives were diagnosed with BC, 9.4% said they would leave their wives.39Given the current knowledge gap on this subject in KSA, we decided to: 1) determine the prevalence of anxiety symptoms in married women seen in an urban-based university outpatient clinic in Jeddah; 2) identify the correlates of anxiety symptoms (especially marital quality [MQ]); and 3) determine whether the relationship between MQ and anxiety differed between Saudi nationals and immigrants. We hypothesized that anxiety symptoms would be prevalent, that higher MQ would be strongly and inversely related to anxiety symptoms, and that this relationship would be particularly strong in women who were Saudi nationals (where cultural factors might have the most influence).     

Combined effect of a mixture of tetracycline,acid, and detergent,and Nisin against Enterococcus faecalis and Actinomyces viscosus biofilms

Objectives:

To evaluate the combined effect of a mixture of tetracycline, acid, and detergent (MTAD) and Nisin against Enterococcus faecalis (E. faecalis) and Actinomyces viscosus (A. viscosus) biofilms.

Methods:

This study was conducted between June and December 2013 in collaboration with Dental Caries Research Chair, College of Dentistry, King Saud University, Riyadh, Saudi Arabia. Single-species biofilms (n=9/species/observation period) were generated on membrane filter discs and subjected to 5, 10, or 15 minute incubation with MTADN (MTAD with 3% Nisin), 5.25% sodium hypochlorite (NaOCl), or normal saline. The colony forming units were counted using the Dark field colony counter.

Results:

A 100% bactericidal effect of 5.25% NaOCl was noted during the 3 observation periods; a significant reduction (p=0.000) in mean survival rates of E. faecalis (77.3+13.6) and A. viscosus (39.6+12.6) was noted after 5 minutes exposure to MTADN compared with normal saline (78000000+5291503) declining to almost no growth after 10 and 15 minutes. The survival rates of the E. faecalis and A. viscosus biofilm were no different after treatment with MTADN and 5.25% NaOCl at the 3 observation periods (p=1.000).

Conclusion:

A combination of MTAD and Nisin was as effective as NaOCl against E. faecalis and A. viscosus biofilms.Infected root canals have a complex microbial flora that may exist as a loose collection in mist canal lumen or as dense aggregates (biofilms) adhering to the dentinal walls.1 The biofilms offer a conducive environment for bacterial growth and survival resulting in persistent periapical infections leading to potential therapeutic failure.2,3 To avoid unfavorable outcomes due to the presence of residual microbes, after cleaning and shaping, several chemical irrigants have been applied in the root canals. Because of its potent antimicrobial activity against both planktonic and biofilm bacteria, sodium hypochlorite (NaOCl) has been used conventionally for decades as an irrigating solution.4,5 Despite its proven efficacy as an irrigating agent in recommended concentrations, the toxic effects of NaOCl on vital tissues have been a major concern.6For removal of smear layers during root canal treatment a mixture of tetracycline, acid, and a detergent (MTAD) comprising of an aqueous solution containing 3% doxycycline, 4.25% citric acid, and 0.5% polysorbate (80 detergent) with minimal erosive effects on dentin surfaces have also been used as a final rinse.7,8 The antimicrobial effect of MTAD is primarily believed to be due to doxycycline and resistance to doxycycline is not uncommon among the bacteria isolated from the root canals.9 The lower potency of MTAD compared with NaOCl against biofilm bacteria observed in clinical practice could possibly be due to resistance against the doxycycline component of MTAD.4 Nisin, an antimicrobial peptide produced by Lactococcus Lactis, used extensively as a preservative in dairy products is composed of 34 amino acid residues, including unusual amino acids such as Lanthionine and B-methyl-lanthionine.10,11 It inhibits proliferation of most gram-positive bacteria, is heat-stable, odorless, colorless, tasteless, non-toxic peptide and is considered safe by the U.S. Food and Drugs Administration.12,13 Nisin when used in conjunction with MTAD has been shown to induce a significant inhibitory effect against Enterococcus faecalis (E. faecalis)14,15 and some Gram-positive bacteria associated with persistent intracanal infections.16,17 Data regarding assessment of efficacy of the combined use of MTAD and Nisin against biofilm bacteria is limited, and this study was performed to evaluate in vitro the bactericidal effect of the combined use of MTAD and Nisin against E. faecalis and Actinomyces viscosus (A. viscosus) biofilm bacteria.     

Thrombus aspiration during primary percutaneous coronary intervention associated with reduced platelet activation

Objectives:

To determine the effect of thrombectomy on platelet function in patients undergoing primary percutaneous coronary intervention (PPCI) for ST segment elevation myocardial infarction (STEMI).

Methods:

This retrospective study included 413 consecutive STEMI patients who underwent PPCI between March 2012 and September 2013 at Kartal Kosuyolu High Specialty Education and Research Hospital, Istanbul, Turkey that were assigned to the thrombus aspiration (TA) group or the non-TA group. Platelet count and mean platelet volume (MPV) were obtained at baseline and 24 hours (h), 48 h, and 72 h post PPCI.

Results:

Baseline MPV was similar in both groups, whereas the baseline platelet count was higher in the TA group (p=0.42 and p=0.002). The platelet count was higher in the TA group 24 h post PPCI (p=0.02), but was similar in both groups 48 h and 72 h post PPCI (p=0.18 and p=0.07). The MPV 48 h and 72 h post PPCI was higher in the non-TA group than in the TA group (8.4 ± 1.3 fL versus 8.7 ± 1.6 fL [p=0.04] and 8.5 ± 1.1 fL versus 8.9 ± 1.5 fL [p=0.04]).

Conclusion:

Thrombectomy reduced platelet activity via removal of thrombi from the coronary arteries in patients undergoing PPCI for STEMI.In acute ST-segment elevation myocardial infarction (STEMI), the main initiating factor is atherosclerotic plaque rupture or erosion, then platelets become activated and aggregated leading to acute coronary artery occlusion.1 Primary percutaneous coronary intervention (PPCI) is the standard treatment in patients with STEMI.2 In recent years, implementation of adjunctive mechanical and pharmacological therapies during PPCI, including manual thrombus aspiration (TA), has improved myocardial reperfusion and clinical outcome in STEMI patients.3-5 In daily practice, thrombectomy devices are used to remove thrombi or to prevent embolization of thrombi and plaque during PPCI.6 Platelet volume is a marker of platelet activation and is measured via mean platelet volume (MPV).7 An increase in MPV can occur in cases of acute myocardial ischemia, acute myocardial infarction, coronary atherosclerosis,8,9 and early stent thrombosis (ST).10 The Percutaneous Coronary Intervention in Acute Myocardial Infarction (TAPAS) study5 showed that TA therapy during PPCI decreases mortality and reinfarction rate.5 We speculate that the good results obtained with TA therapy are not only related to improved tissue perfusion but also may be related to reduced platelet activation. Therefore, the present study aimed to determine the effect of thrombectomy on platelet function and ST in patients undergoing PPCI for STEMI.     

Management of rhino-orbital mucormycosis

Mucormycosis is an uncommon acute invasive fungal infection that affects immunocompromised patients. It progresses rapidly and has poor prognosis if diagnosed late. Early detection, control of the underlying condition with aggressive surgical debridement, administration of systemic and local antifungal therapies, hyperbaric oxygen as adjunctive treatment improves prognosis and survivability.Mucormycosis also known as zygomycosis and phycomycosis is an uncommon, opportunistic, aggressive fatal fungal infection caused by fungi of the order Mucorales, frequently among immunocompromised patients. This fungal infection begins from the sinonasal mucosa after inhalation of fungal spores; the aggressive and rapid progression of the disease may lead to orbital and brain involvement.1-4 In the past, the mortality rate of the rhino-cerebral type was 88%, but recently the survival rate of rhino-cerebral mucormycosis averages 21-73% depending on the circumstances.1 Mucormycosis is classified according to anatomical site into rhino-cerebral, which is the most common, central nervous system, pulmonary, cutaneous, disseminated, and miscellaneous.1,2,4-6 The rhino-orbito-cerebral is the most common form of mucormycosis.3 The most common predisposing factor is uncontrolled diabetes mellitus (DM), especially when the patient has a history of ketoacidosis, these species thrive best in a glucose rich and acidic environment.3,4,6,7 Immunosuppressive drugs such as steroids, neutropenia, acquired immune deficiency syndrome, dialysis patients on deferoxamine, malnutrition, hematologic malignancy, and organ transplant patients are also at risk of affection by the fungi.1,4-7 This case report describes a case of rhino-orbital mucormycosis affecting a diabetic female with good prognosis and satisfactory healing. Our objective in presenting this particular case is to emphasize that early diagnosis and proper management leads to good prognosis and high survivability.     

Sublingual varices in relation to smoking,cardiovascular diseases,denture wearing,and consuming vitamin rich foods

Objectives:

To identify potential risk factors such as smoking, cardiovascular diseases (CVD), denture wearing, and consuming vitamin rich foods, and its relation to the development of sublingual varices (SLV).

Methods:

This cross-sectional observational study was conducted on patients who attended the Department of Dentistry at The University of Jordan Hospital, Amman, Jordan between February and May 2013. Clinical examinations and inspections of 391 patients (203 males and 188 females), 13-74 years of age were conducted to determine the presence of SLV. Sublingual varices were classified into 2 categories: grade 0 (few or none visible), and grade one (moderate or severe). Frequency distributions of both SLV and risk factors were obtained. Multiple logistic regression analysis and Chi-square test were used to analyze the influence of individual risk factors on the incidence of SLV.

Results:

There were 88 subjects (22.5%) who had SLV. In the multivariate logistic regression model, SLV were significantly associated with age (odds ratio [OR]: 2.27, p=0.008) with highest occurrences in the eighth decade of life, gender (OR: 2.74, p=0.001), smoking (OR: 2.93, p=0.002), denture wearing (OR: 2.03, p=0.044), and CVD (OR: 4.01, p=0.00).

Conclusion:

The presence of SLV could be indicative of some potential risk factors including old age, female gender, and denture wearing, and may alert the dental clinician to recognize underlying systemic conditions, particularly CVD.Sublingual varices (SLV) are dilated tortuous veins that may be seen along the ventral surface of the tongue or floor of mouth, and tend to become more prominent with age. However, in a young population, such vascular lesions could be part of Fabry, or Osler syndrome.1 Sublingual varices may be noticed by patients, or more commonly by dentists. They are often confused with the main veins running from the tip of the tongue backwards, and should be differentiated from primary malignant melanomas of the tongue base.1 Several explanations have been suggested concerning the pathogenesis of SLV; it is known that the ageing process, including changes in the connective tissues and venous walls is associated with an increase in the incidence of varices.2-4 Kaplan and Moskona5 reported that varicosities increased from 11.1-41.1% between ages 50-99 years. Few studies in the literature1,2-4,6-10 investigated the relation between SLV and some potential risk factors, such as cardiovascular diseases (CVD), smoking, denture wearing, and consuming foods rich in vitamins, such as vegetables. Furthermore, portal hypertension,6 and varicose veins of the leg2 have been claimed to have a possible connection and association with SLV. Differences in the incidence of SLV between males and females has been the subject of a recent survey.1 The relation between SLV and CVD remains controversial; whereas some studies found no relation,4,6 other older studies reported an association.2,3 A recent study1 of 281 consecutive adults aged 40-92 years demonstrated a strong association between CVD and SLV. Similarly, controversy regarding the relation between SLV and smoking still exists, and there is one study published in the English literature investigating the relation between SLV and smoking.1 Smoking was established as a predisposing factor for CVD, particularly hypertension.11 Hedström and Bergh1 found that SLV was significantly associated with smoking. However, Kroeger et al12 reported a preventive effect of smoking on the development of varicose veins of the leg. Ettinger and Manderson,2 in their study of SLV found a relation between sublingual veins and varicose veins of the leg. Sublingual varices were also ascribed to vitamin C deficiency in older age groups. A study of 22 elderly vegetarians aged 57-75 years found a much lower incidence of sublingual petechiae and varicosities than generally reported in an older population.7 However, the literature did not support a link between SLV and diabetes,13 or denture wear.8-10 In Jordan, a recent study showed that more than 48% of adult males were current smokers.14 In addition, more than 60% of patients who attended the United Nations Relief and Works Agency (UNRWA) primary health care clinics in Jordan were diagnosed with hypertension.15 Hence, it is expected that SLV could be a common finding among a Jordanian population. Therefore, the aim of this study was to assess the influence of potential risk factors including CVD, smoking, denture wearing, and consuming vitamin rich foods on the incidence of SLV among the young, middle aged, and elderly population.     

Pattern of drugs use and association with anti-mutated citrullinated vimentin antibody in rheumatoid arthritis

Objectives:

To demonstrate the pattern of disease-modifying antirheumatic drugs (DMARDs) use in Saudi and non-Saudi rheumatoid arthritis (RA) patients, and to evaluate the association of DMARDs use with anti-mutated citrullinated vimentin (anti-MCV) positivity and other factors.

Methods:

Retrospectively, for a period of 7 years (2007-2014), we studied 205 RA patients, at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. All patients used DMARDs. Pattern of use for all 6 DMARDs was almost the same among Saudis and non-Saudis with no significant difference (p>0.05) for each DMARD; MTX was the most commonly used DMARD (71-76%).

Results:

There was no association between anti-MCV positivity and different DMARDs use. Methotrexate was used 76 times as combination, scoring the highest in this respect. There was a significant correlation (p<0.05) between Plaquenil with Methotrexate and with Sulfasalazine; Leflunomide with anti-TNF and with Prednisolone; age with Methotrexate and with Plaquenil; anti-MCV positivity with Prednisolone. Saudi/non-Saudi status showed no correlation with all factors or drugs. There was no significant association between DMARDs and comorbidity.

Conclusion:

Similar to worldwide results, MTX was the most commonly used DMARD; with the addition of anti-TNF to increase the effect, and folic acid to minimize the side effects. In this cohort, the pattern of use for all DMARDs was similar among Saudis and non-Saudis; treatment depended neither on anti-MCV positivity nor on the presence of comorbid conditions. A study of the association of DMARDs with disease activity is recommended.The effective treatment of rheumatoid arthritis (RA) can be achieved by disease-modifying antirheumatic drugs (DMARDs) that decrease joint damage with improvement of symptoms and functional abilities.1 The DMARDs have been classified into synthetic (sDMARDs) and biological.2 The sDMARDs are traditional drugs; such as methotrexate (MTX), sulfasalazine, leflunomide, and hydroxychloroquine (Plaquenil).2 The sDMARDs also include synthetic glucocorticoids (such as Prednisolone).3 If an sDMARDs is not effective after a trial of 3 months,4 they are usually combined with a biological DMARD, such as tumor necrosis factor alpha (TNF-α) blockers.1 To achieve disease remission in approximately 50 of people and improved overall outcomes, the DMARDs should be started very early in the disease.5 The frequently used DMARDs include MTX (the most commonly used one), Plaquenil (hydroxychloroquine), Azulfidine (sulfasalazine), and Arava (leflunomide), either as monotherapy, or in combination.1 Methotrexate is the most commonly used DMARD wordwide,6,7 and is the first line of treatment;8-10 even according to the treatment guidelines from the American College of Rheumatology (2012),11 and the European League Against Rheumatism (2010).12 Methotrexate is usually combined with folic acid (a vitamin),13 in order to reduce its adverse effects including nausea, vomiting or abdominal pain (gastrointestinal), hematologic, pulmonary, and hepatic.10 Methotrexate is teratogenic, thus, pregnancy should be avoided.8,10 Prednisolone (a synthetic glucocorticoids) can be used in the short term, while waiting for slow-onset drugs to take effect,1 and also as an injections into individual joints.1 Although its long-term use reduces joint damage, it also results in osteoporosis and susceptibility to infections, and thus is not recommended.1 A better effect can be achieved by combining MTX with anti-TNF than with MTX monotherapy.14 The response rate is better when switching from MTX monotherapy to MTX plus anti-TNF than combined DMARDs to MTX plus anti-TNF.14 In this study, our aim was to determine the pattern of disease modifying antirheumatic drugs use, and their association with anti-mutated citrullinated vimentin antibody (anti-MCV) in rheumatoid arthritis patients.     

Prevalence and severity of plaque-induced gingivitis in a Saudi adult population

Objectives:

To evaluate the prevalence and severity of plaque-induced gingivitis among a Saudi adult population in Riyadh region.

Methods:

Three hundred and eighty-five eligible participants in this cross-sectional study were recruited from routine dental patients attending the oral diagnosis clinic at Al-Farabi College in Riyadh, Saudi Arabia from June 2013 to December 2013. A clinical examination was performed by 2 dentists to measure the gingival and plaque indices of Löe and Silness for each participant.

Results:

The prevalence of gingivitis was 100% among adult subjects aged between 18-40 years old. Moreover, the mean gingival index was 1.68±0.31, which indicates a moderate gingival inflammation. In fact, males showed more severe signs of gingival inflammation compared with females (p=0.001). In addition, the mean plaque index was 0.875±0.49, which indicates a good plaque status of the participants. Interestingly, the age was not related either to the gingival inflammation (p=0.13), or to the amount of plaque accumulation (p=0.17). However, males were more affected than females (p=0.005).

Conclusion:

The results of this study show that plaque accumulation is strongly associated with high prevalence of moderate to severe gingivitis among Saudi subjects.Plaque-induced gingivitis is the most common form of periodontal disease,1 which is considered to be the second most common oral disease after dental caries, affecting more than 75% of the population worldwide.2,3 In 2000, the United States Surgeon General released a report calling interest to the ‘‘silent epidemic’’ of dental and oral diseases, mainly dental caries and periodontal diseases suffered by millions of people throughout the US.4 The prevalence of periodontal diseases varies in different studies and different countries as a result of variations in study populations, age of participants, and the procedure of defining and diagnosing this type of disease. In general, gingivitis begins in early childhood, and becomes more prevalent and severe with age.5,6 Epidemiological studies revealed that plaque-induced gingivitis is prevalent among all ages of dentate individuals.7-9 Plaque-induced gingivitis is characterized by the presence of inflammation confined to gingiva without extension into other tooth-supporting structures.10-12 Persistence of this type of inflammation is correlated with the presence of microbial dental plaque. As long as this microbial biofilm is present adjacent to the gingival tissues, the inflammation will not resolve.13 However, it has been shown to be reversible after removing these causative factors.14 The clinical features that can be used as characteristic of gingivitis could be one of the following signs: erythematic and sponginess; changes in contour; bleeding upon stimulation; and presence of calculus, or plaque without clinical attachment loss, or radiographic evidence of crestal bone loss.15 Clinically, the severity and signs of gingival inflammation can be expressed by means of gingival index (GI) of Löe and Silness.16 According to this index, gingival inflammation can be classified as mild, moderate, or severe. However, the presence of these signs of inflammation is considered the initial stage for the more severe and irreversible form of periodontal diseases.17-19 A patient''s susceptibility to develop this type of disease also is highly variable and depends on the host response towards periodontal pathogens,17-19 which may be influenced by both acquired and genetic factors that can modify this susceptibility to infection.12,20 Prevention of dental plaque accumulation and early treatment of gingivitis reduces the risks associated with the development of a more severe, and destructive form of periodontal diseases.11,21 It is well known and documented that gingivitis develops after 10-21 days of accumulation of dental plaque,22 necessitating a daily effort to prevent plaque accumulation. Several studies revealed a significant correlation between reducing the incidence of gingivitis and regular plaque control measures.23-25 The aim of this study was to evaluate the prevalence and severity of plaque-induced gingivitis among a Saudi adult population in Riyadh region.     

The desire to utilize postmastectomy breast reconstruction in Saudi Arabian women: Predictors and barriers

Objectives:

To study factors that influence the desire to utilize breast reconstruction after mastectomy, and to investigate the barriers to reconstruction among women in Saudi Arabia.

Methods:

We conducted a cross-sectional study at 2 surgical centers in Jeddah, Saudi Arabia. A self-administered questionnaire was distributed to all breast cancer patients attending the surgery clinics for follow-up after mastectomy between January and March 2013. Ninety-one patients met the study inclusion criteria. The first part of the questionnaire covered the demographic and socioeconomic information regarding factors that might influence the desire to utilize breast reconstruction including possible barriers. Multivariate logistic regression was used to determine the significant predictors of the desire to undergo reconstruction.

Results:

Overall, 16.5% of patients underwent breast reconstruction after mastectomy. Young age and high educational attainment were significantly associated with an increased desire to undergo reconstruction. The main barriers to reconstruction were the lack of adequate information on the procedure (63%), concerns on the complications of the procedure (68%), and concerns on the reconstruction interfering with the detection of recurrence (54%).

Conclusion:

Age and educational level were significant predictors of the desire to utilize breast reconstruction. Furthermore, modifiable barriers included the lack of knowledge and misconceptions on the procedure. Addressing these issues may increase the rate of breast reconstruction in Saudi Arabia.Surgical resection (mastectomy) is considered the primary treatment for breast cancer. In the past decade, changing attitudes toward breast reconstruction among both patients and providers have led to an increasing number of women seeking breast reconstruction after mastectomy.1 In 2009, there were approximately 86,000 breast reconstruction procedures performed in the United States.2 There has been a significant rise in immediate reconstruction rates, attributable to a notable increase in implant use.3 Many types of breast reconstruction are available including silicone and silane implants, tissue expanders, and pedicle and free musculocutaneous flaps.4,5 Although these reconstruction options have been proven to be oncologically safe,5 and many women still refuse breast reconstruction.6 The choice to proceed with breast reconstruction after mastectomy is difficult, and is affected by many factors. Most breast reconstruction procedures are performed in women younger than 60 years of age.7 The decision to proceed with reconstruction can be influenced by patient factors, physician factors, cancer related factors, and insurance status.7-10 Patient factors include patient age, socioeconomic status, race, site of mastectomy, and patient preference.1 Of these factors, age >50 years is the most common negative predictor of breast reconstruction after mastectomy.8,9,11-13 According to the Saudi Cancer Registry,14 breast cancer has been the most common cancer among Saudi females over the past 12 years. In a recent study, Ibrahim et al15 estimated that the burden of breast cancer in Saudi Arabia will increase by approximately 350% by 2025. In a previously published study, almost half of the general surgeons surveyed reported that they had treated patients who refused breast reconstruction despite its availability.4 Previous studies on the factors influencing postmastectomy breast reconstruction in the Middle East were conducted in Egypt13,14 and we are not aware of any similar studies conducted in Saudi Arabia or the Gulf Region. The objectives of this exploratory study were to study the demographic and socioeconomic factors influencing the desire to utilize postmastectomy breast reconstruction and to evaluate the barriers to postmastectomy breast reconstruction among women in Saudi Arabia.     

Periodontal findings in systemic lupus erythematosus patients and healthy controls

Objectives:

To compare periodontal findings in systemic lupus erythematosus (SLE) patients and healthy controls, and to determine, whether there is a correlation between periodontal parameters and SLE biomarkers.

Methods:

This cross-sectional study was conducted in the Faculty of Dentistry, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia between November 2012 and February 2014. Twenty-five participants diagnosed with SLE and 50 healthy controls were selected. Periodontal assessment consisted of clinical attachment level (CAL), probing depth (PD), bleeding on probing, and plaque scores. For the SLE group, several laboratory tests were obtained, such as, white blood cell count, hemoglobin level, platelet count, anti-nuclear antibody, anti-double-stranded DNA antibody, calcium level, and vitamin D.

Results:

Periodontal findings in SLE patients and controls were not significantly different. The SLE patients who had no flare-ups for more than a year showed significant bleeding on probing and deeper PD compared with those who had flare-ups less than a year before starting the study. The SLE patients with arthritis symptoms showed more CAL than those without arthritis. In the SLE patients, no significant correlation was found between their periodontal findings and SLE biomarkers.

Conclusion:

Periodontal health was not different between SLE patients and healthy controls. In SLE patients however, flare-ups and presence of arthritis had a significant relation with periodontal health.Periodontitis is a common chronic infectious disease that affects most adults. In the Kingdom of Saudi Arabia (KSA), recent data suggests a prevalence of 68%.1 Periodontitis is characterized by chronic gingival inflammation that leads to destruction of the periodontal tissues supporting the teeth, and subsequently, may lead to tooth loss. Although it is primarily initiated by bacteria, the host immune response plays a significant role in its development.2-4 Recently, there has been an increasing interest in the relationship between periodontitis and systemic health. Several studies5-8 have suggested an association between periodontitis and systemic autoimmune diseases, such as rheumatoid arthritis. Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disorder of unknown etiology that has a similar pathobiology to periodontitis. It is characterized by B-cell hyperactivity with an increased immunoglobulin (Ig) G production, and immune complex deposition that results in connective tissue damage.9 In KSA, the prevalence of SLE in the population was reported to be 19.3 in 100,000, with a female to male ratio of 9.8:1.10,11 Current monitoring strategy for SLE patients depends on laboratory testing for acute phase markers and autoimmune serology. Acute phase markers consist of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), which may help to distinguish between lupus flare-ups and infection.12 Autoimmune serology may include anti-double-stranded DNA (anti-dsDNA) antibodies, anti-nuclear antibodies (ANA), and complement (C)3 and C4 levels.13 Anti-dsDNA antibodies are disease markers, and potential predictive markers for flare-ups. It has been found to be positive in 80.1% of cases, and was also found to positively correlate with disease activity, and has shown a capacity to predict future flare-ups.11,14-18 The ANA test is a very sensitive test for diagnosing SLE, but it is not specific as it can also be positive in some chronic infections.19 Periodontitis and SLE are both multifactorial conditions that share several pathogenic characteristics, such as elevated serum levels of beta 2-glycoprotein I-dependent anti-cardiolipin, the IgG Fc receptor, and proinflammatory cytokines.20,21 However, limited and inconsistent data are present on the association between SLE and periodontitis.22-24 Furthermore, no study has assessed if there is a correlation between the severity of periodontitis and SLE biomarkers. This study was conducted to compare the periodontal findings in SLE patients and systemically healthy controls, and to determine whether there is a correlation between periodontal parameters and SLE biomarkers.     

Prevalence of human immunodeficiency virus,hepatitis C virus,and hepatitis B virus infection among heroin injectors in the central region of Saudi Arabia

Objectives:

To calculate the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections among inpatient heroin users, and to study the relationships between these infections and patient demographics.

Methods:

In this retrospective study, heroin users’ inpatient records from the Alamal Hospital, Riyadh, Saudi Arabia were reviewed for HIV, HBV, and HCV screening results, age, number of admissions, education, and marital and occupational status. The study took place between January 2006 and November 2012. The prevalences of HIV, HBV, and HCV and their associations to demographics were evaluated.

Results:

A sample of 357 inpatients Saudi male heroin users (all injectors) aged 40 (±8.6) years with lifetime admissions averaged 5.8 (±5) times were studied. Screening results revealed that 20.1% of subjects were infection-free, 56.6% had a single infection, 13.2% were infected by 2 viruses, and 1.1% were infected by 3 viruses. Prevalence of HBV surface antigen was 7.7%, antibodies for HCV 77.8%, and HIV 9.8%. A significant association was found between positive HCV and positive HIV tests. Furthermore, HCV was more common among patients aged 20-29 years, those who were unemployed, and who had primary, secondary, or postsecondary education. Finally, HBV was associated in patients aged 30-39 years and those with secondary educations.

Conclusion:

Contracting serious contagious viral infections is very common among Saudi heroin injectors at rates similar to those seen among injectors in Western countries. Infection control, education, and harm reduction programs are of paramount importance.Substance users are more vulnerable to human immunodeficiency virus (HIV) and viral hepatitis than the general population.1-3 Specifically, those who inject drugs are at a higher risk for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections.1 Considering these viruses are blood borne infections, they are transmitted efficiently through sharing of contaminated needles and other injection paraphernalia.4-7 In the United States, approximately 9-12% of new HIV cases8,9 and 50% of new HCV cases10 are associated with illicit injection of drugs. The prevalence of HCV among injecting drug users in the industrialized world is greater than 60%.1-5 In Saudi Arabia, very few studies addressed HIV, HBV, and HCV infections in Saudi heroin users who inject drugs. Njoh and Zimm11 described more than 2000 drug users admitted to an addiction treatment center in Jeddah between January 1995 and May 1996 and found a 0.1% prevalence of HIV. In 1996,12 they found a prevalence of HCV seropositivity of 74.6%. In 1995, at the same treatment center, the HBV surface antigen was positive in 12.6% of 349 screened patients, 80% of whom injected drugs.13 Another screening of 344 Saudi injecting drug users in the eastern region, reported a 38% HCV RNA detection rate, and a 12% HBV DNA detection rates.14 No studies were performed to estimate the prevalence of these viral infections in the central region, and those performed in Jeddah (western Saudi Arabia) are old and may not correctly reflect the current status. In this study, we aim to estimate the prevalences of HBV, HCV, and HIV infections among heroin injectors in the Saudi central region and to explore any significant relationships related to patient demographics.     

Association of total antioxidants level with glaucoma type and severity

Objectives:

To compare the mean total antioxidant status (TAS) among 3 glaucoma types, namely: pseudoexfoliation glaucoma (PEG), primary open angle glaucoma (POAG), and primary angle closure glaucoma (PACG), and study its potential association with various clinical glaucoma-parameters.

Methods:

In this case-control study, plasma samples were obtained between September 2013 and October 2014 from 340 glaucoma patients (PEG [n=54]; POAG [n=147]; PACG [n=139]), and 351 controls of matching age, gender, ethnicity, and 5 different systemic co-morbidities from King Abdulaziz University Hospital, Riyadh, Saudi Arabia. The TAS in all samples was determined by a colorimetric-based assay.

Results:

The mean±standard deviation of TAS was significantly lower among cases: 0.77±0.32 than controls: 1.1±0.22, p<0.0001. Moreover, the TAS levels were significantly different across the 3 types of glaucoma: 0.86±0.24 in PEG, 0.47±0.32 in POAG, and 0.98±0.41 in PACG (all p<0.0001). In addition, there was a significant correlation between TAS and age at onset (Pearson correlation coefficient [R] 0.17, p<0.0001), cup/disc ratio (R: -0.13, p=0.004), and number of anti-glaucoma medications (R: -0.16, p=0.001).

Conclusion:

Our findings provide evidence that plasma TAS levels are decreased in patients with glaucoma, more so in POAG and PEG than PACG, supporting the hypothesis that decreased antioxidative defense and/or increased oxidative stress may have a critical role in the pathogenesis of glaucoma.Glaucoma is a progressive optic neuropathy associated with optic nerve damage, and is one of the most leading cause of blindness worldwide.1 Elevated intraocular pressure (IOP) as a result of reduction in normal aqueous outflow is a major causal risk factor that is well supported by animal studies.2-4 Although IOP is considered a major risk factor for glaucoma,2,3 other concomitant factors affecting the pathophysiology of glaucomatous retinal ganglion cell (RGC) death include retinal ischemia,5 nutritional status,6 and oxidative stress.7 There is evidence of oxidative damage in ocular diseases, such as cataract and age-related macular degeneration.8 In addition, significant oxidative damage has been demonstrated in human trabecular meshwork (TM) cells of patients with glaucoma,7 causing elevated IOP and visual field damage.9 Furthermore, our previous studies have documented mitochondrial abnormalities10-12 (oxidative stress marker), and glutathione-S-transferase (antioxidant) gene (GST) polymorphisms to be associated with various types of glaucoma.13 It is clearly evident from the literature, and our own studies, that oxidative stress mechanisms play a critical role in the pathogenesis of glaucoma. Previous studies had demonstrated reduced total antioxidant capacity in aqueous humor and blood samples from patients with glaucoma.14-17 To evaluate the role of oxidative stress in different types of glaucoma we had previously investigated total antioxidants status (TAS) in the plasma of pseudoexfoliation glaucoma (PEG) patients,18 primary angle closure glaucoma (PACG) patients,19 and in the plasma of primary open angle glaucoma (POAG) patients.20 As an extension to these studies, here, we compare the mean TAS level among these 3 glaucoma types, and study the potential association between the TAS level and various clinical parameters important to each type of glaucoma.18-20     

Knowledge of Saudi female university students regarding cervical cancer and acceptance of the human papilloma virus vaccine

Objectives:

To assess the level of knowledge regarding cervical cancer and the acceptance of the human papilloma virus (HPV) vaccine among Saudi female students in health colleges.

Methods:

This cross-sectional study of a convenient sample encompassed 1400 students in Health Colleges at Princess Nora Bint Abdul Rahman University, Riyadh, Saudi Arabia was conducted between December 2013 and February 2014. A self-administrated questionnaire was distributed to all participants. Data collected included socio-demographic data, knowledge of cervical cancer risk factors and clinical presentation, Pap smear, and HPV vaccine acceptance. The questionnaire reliability as tested by Cronbach’s alpha was 0.82.

Results:

The response rate was 89.9%, and data analysis revealed that 95.7% of students had poor knowledge level. The Pap smear was poorly recognized as a screening tool, with 46.7% of students having heard of the test. Senior and medical students had a significantly higher knowledge score. Father’s health profession, high monthly income, and presence of cervical cancer among family members or friends increased the level of knowledge. Vaccine acceptance is influenced by its price, approximately 80% of students thought that an affordable vaccine price should not exceed 300 Saudi Riyals. Perceived barriers to the vaccine were fear of injections and vaccine side effects.

Conclusion:

There is a lack of knowledge and misinformation regarding cervical cancer, Pap smear, and HPV as a major risk factor for cancer of the cervix. These data can be used as a benchmark to formulate effective awareness programs.Cancer of the cervix uteri is a frequent cancer affecting women, and is a leading cause of mortality worldwide.1 The highest incidence rates have been reported from sub-Saharan Africa, Central and South America, Southeast Asia, and Brazil. In contrast, the incidence rates were the lowest in the Middle East, particularly among Muslims and Jews, as compared to other religious groups.2,3 In the Kingdom of Saudi Arabia, carcinoma of the cervix uteri accounts for 2.6% of female cancers, and is ranked ninth among all carcinomas affecting Saudi females.4 The pathogenesis of cervical cancer in Muslim countries might be different from that of Western societies because of differences in cultural and religious factors that influence human behavior, and reduce the risk of exposure to cervical cancer.4-7 Among all known risk factors, persistent infection with high-risk human papillomavirus (HPV) plays a considerable role in the pathogenesis of cervical cancer.8-11 The worldwide HPV prevalence in cervical cancer was estimated to be between 85-99%.10,12 The HPVs are grouped according to their association with cervical cancer and their genomic sequence into oncogenic high, probable high, and non-oncogenic low-risk.11-14 The strong association of oncogenic HPV infection and the development of cervical cancer provides an opportunity for primary prevention through prophylactic vaccination. Human papillomavirus vaccines (bivalent and quadrivalent) have been shown to be immunogenic, safe, and highly effective in preventing chronic infection and precancerous lesions in women.15,16 The vaccine is available in the KSA market, but national campaigns to vaccinate females are not launched yet.Cytological screening based on Pap smear plays a major role in reducing both the incidence and mortality of invasive cervical cancer. In the USA and Canada, the reduction in the incidence of cervical cancer and the subsequent reduction of female mortality rate was attributed to the widespread introduction of the Pap smear screening program as a secondary preventive measure for early detection of cases.17-19 However, in Saudi Arabia, most cases present at advanced stages that require extensive chemoradiation therapy. This might be due to lack of proper screening programs,20,21 and inadequate knowledge among the target population. Noteworthy, most female cancer awareness campaigns in KSA are mainly focused on breast cancer. Appropriate level of knowledge, attitude, and beliefs are key elements for adopting a healthy lifestyle, influencing human behaviors, and accepting newly introduced preventive measures. Concerning cervical cancer, the gap of knowledge of clinical presentation, risk factors, primary and secondary prevention has been documented in several studies both in developed and developing countries.22-24 However, few studies have been reported from Saudi Arabia. The present study was designed to assess the level of knowledge and beliefs regarding cervical cancer, and the acceptance of the HPV vaccine among Saudi university students enrolled in health colleges because of their important role as health care providers to raise community awareness and to modify population behavior.