Chronic Candidiasis Research Articles

Vulvovaginal candidiasis: etiology, pathogenesis, diagnosis, treatment

The article represents the main problems of diagnosis and treatment of patients with vulvovaginal candidiasis (VVC). It is noted that C. albicans causes candidiasis in 75-80% of cases. Clinical forms of VVC include acute VVC and chronic (recurrent) vulvovaginal candidiasis (HRVVC). The main diagnostic approaches in the treatment and prevention of disease recurrence are described. The article presents data on the use of Clotrimazole vaginal cream 2% (Esparma) to treat VVC.

Autoimmune polyendocrinopathy syndrome type 1: new conceptions on pathogenesis and extended clinical symptoms

The objective was to present the caseof autoimmune polyendocrinopathy syndrome type 1 (APS1) and new clinical aspects and current knowledge of its pathogenesis.Materials and methods. This article includes clinical data, laboratory parameters, treatment and follow­updata of the patient with APS1. Also, a review of the latest data in world literature was made.Results and discussion. The described patient has two main criteria for APS1: hypoparathyroidism and chronic mucosal candidiasis, as well as some additional ones such as: autoimmune thyroiditis with hypothyroidism, type 1 diabetes, malabsorption syndrome. Periodic seizures and gait abnormality may be due to a chronic inflammatory demyelinating polyneuropathy. The diagnosis of APS1 is to detect the genetic anomaly underlying the syndrome: mutations in the AIRE gene and identification of organspecific antibodies. International studies have shown that 100 % of patients with APS1have autoantibodies that interact with interferon omega, so tests for such autoantibodies can help to get quick diagnosis. The treatment consists of correction of endocrine insufficiency with hormone replacement therapy, and specific treatment of other diseases common to APS1.Conclusions. APS1 is extremely diverse in its symptoms and the progression of the disease causes the expanding of clinical spectrum of its components. Therefore this syndrome must be diagnosed in the early stages, taking into account high morbidity and mortality. The main purpose of treatment is to preserve the patient’s life and maintain its quality good. Awareness of this rare autoimmune polyendocrine disorder can help a doctor to recognize it and treat timely, preventing potential death­related illnesses.

Chronic mucocutaneous candidiasis associated with a novel frameshift mutation in IL-17 receptor alpha

Background: Chronic mucocutaneous candidiasis (CMCC) has traditionally encompassed endocrinopathy, autoimmunity, and infection of the skin, nails, oral and genital mucosa. It is typically caused by Candida albicans, an organism that is found to be commensal in healthy individuals. To date, most patients with CMCC have mutations in AIRE or STAT1. While chronic Candida spp. infection is a feature of multiple profound T cell deficiencies, it has also been identified in rare cases involving selective immune defects, including interleukin-17 receptor A (IL-17RA) deficiency. An association between Staphylococcus aureus infections and candidiasis due to IL-17RA deficiency has recently been proposed. Aim: We sought to identify the genetic defect in a patient presenting with recurrent oral thrush and S. aureus infections, but otherwise unremarkable immune workup. Methods: Whole exome sequencing and Sanger confirmation was performed, and protein expression analysis utilized to assess the impact of the genetic aberration. A comprehensive immune workup was completed to characterize any possible deficits in his immune system. Results: Next generation sequencing techniques identified a homozygous mutation in IL17RA, c.1696insAG, resulting in the frameshift mutation p.Q566fs. Western blot analysis confirmed the loss of IL-17RA expression. Conclusion: We describe here a novel frameshift mutation in IL17RA. Clinically, the patient was a diagnostic challenge as he did not present with a classic CMCC phenotype. This case emphasizes the importance of genetic analysis in patients presenting with recurrent infections. Statement of novelty: We identify a novel frameshift mutation in IL17RA in a patient presenting with recurrent bacterial and fungal mucocutaneous infections.

Strongyloides stercoralis infection in a patient with rheumatoid arthritis and type 2 diabetes mellitus: a case-based review

Strongyloides stercoralis (S. stercoralis), a human intestinal nematode, can lead to hyper/disseminated (HD) infection in patients treated with corticosteroids. Here, we report a case of strongyloidiasis in a 58-year-old female with a history of rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM). The patient presented with abdominal pain and gastrointestinal (GI) bleeding. Stool was negative for parasitic agents in the first direct smear examination, and the patient with the probable diagnosis of Helicobacter pylori (H. pylori) infection or Crohn's disease received antibiotics and corticosteroids. Parasitic agents were not detected in further direct stool examinations, and the patient with the diagnosis of pneumonia, chronic kidney disease (CKD), ulcerative colitis, sepsis, and candidiasis received fungal, antibiotic, and corticosteroids medications. Low sensitivity of direct smear and the lack of using two methods in diagnosing intestinal parasitic infections led to delayed detection. In the fourth direct stool examination, rhabditiform larva of S. stercoralis was reported. The treatment of corticosteroids was discontinued and albendazole was started. A literature review was conducted by searching Medline, Embase, Scopus, and Web of Science with the keywords S. stercoralis, strongyloidiasis, RA, and T2DM. Our case indicates that screening S. stercoralis infection in high-risk groups, especially those who are candidates for corticosteroids medications, must be implemented using at least two diagnostic techniques.

T-cell mitochondrial dysfunction and lymphopenia in DOCK2-deficient patients

This study delineates the mitochondrial defects in DOCK2-deficient T cells contributing to the T cell lymphopenia characteristic of this primary immunodeficiency.

Autoimmune Regulator is required in female mice for optimal embryonic development and implantation†.

Autoimmune Regulator (AIRE) regulates central immune tolerance by inducing expression of tissue-restricted antigens in thymic medullary epithelial cells, thereby ensuring elimination of autoreactive T cells. Aire mutations in humans and targeted Aire deletion in mice result in multiorgan autoimmune disease, known in humans as autoimmune polyglandular syndrome type 1 (APS-1). APS-1 is characterized by the presence of adrenal insufficiency, chronic mucosal candidiasis, and/or hypoparathyroidism. Additionally, females often present with gonadal insufficiency and infertility. Aire-deficiency (KO) in mice results in oophoritis and age-dependent depletion of follicular reserves. Here, we found that while the majority of young 6-week-old Aire-KO females had normal follicular reserves, mating behavior, and ovulation rates, 50% of females experienced embryonic loss between gestation day (GD) 5.5 and 7.5 that could not be attributed to insufficient progesterone production or decidualization. The quality of GD0.5 embryos recovered from Aire KO mice was reduced, and when cultured in vitro, embryos displayed limited developmental capacity in comparison to those recovered from wild-type (WT) mice. Further, embryos flushed from Aire KO dams at GD3.5 were developmentally delayed in comparison to WT controls and had reduced trophoblastic outgrowth in vitro. We conclude that AIRE does not play a direct role in uterine decidualization. Rather, reduced fertility of Aire-deficient females is likely due to multiple factors, including oophoritis, delayed preimplantation development, and compromised implantation. These effects may be explained by autoimmune targeting of the ovary, embryo, or both. Alternatively, altered embryonic development could be due to a direct role for AIRE in early embryogenesis.

Differential Mucosal Gene Expression Patterns in Candida-Associated, Chronic Oral Denture Stomatitis.

Denture stomatitis is a common condition manifested by inflammation of the oral mucous membrane beneath a denture. The objective of this study was to compare the transcriptome of human palatal mucosa with chronic oral stomatitis-associated Candida albicans infection to that of healthy oral mucosa. Oral palatal biopsies were obtained from 17 healthy and 15 C. albicans-infected stomatitis subjects for whole transcriptome analyses. The presence of C. albicans was confirmed by cytology and cultivable methods. The clinical severity of the stomatitis was evaluated by the Newton Classification (Class II or III). For transcriptome analyses a false discovery rate (FDR) of <0.05 was used, and the effects of age, race, and gender were evaluated by principle component analysis (PCA). Specific differentially expressed genes identified by mRNA array data were confirmed by measurements of salivary protein expression using multiplex analyses. Microarray analysis of mRNA expression indicated that in C. albicans stomatitis there were 3034 genes-in-play that were differentially expressed and met the FDR < 0.05 criteria. Two hundred thirty five (235) genes were up-regulated >2-fold, and 71 genes were down-regulated >2-fold. Five of the 6 most significant gene ontology pathways involve inflammation and activation of the immune response with CD28 and CTLA signaling of T cells. There was strong up-regulation of TLR2, CD14, MYD88, IKKA, and NFKB as the dominant toll-like receptor-signaling pathway. The expression of several extracellularly expressed inflammatory protein genes was up-regulated in candidiasis, and 2 were confirmed as up-regulated within the saliva using protein multiplexing analyses. Neutrophil recruitment and activation, epithelial suppression, and T-cell activation appear as major pathways in chronic oral candidiasis. Tissue up-regulation of TLR2 pathways, as well as potential C. albicans binding proteins, was observed, whereas keratin and adhesion molecule synthesis were down-regulated. Several candidate biomarkers to potentially identify the presence of oral candidiasis were differentially expressed in tissues and saliva.

Chronic Mucocutaneous Candidiasis in Autoimmune Polyendocrine Syndrome Type 1.

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is an autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene, characterized by the clinical triad of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency. CMC can be complicated by systemic candidiasis or oral squamous cell carcinoma (SCC), and may lead to death. The role of chronic Candida infection in the etiopathogenesis of oral SCC is unclear. Long-term use of fluconazole has led to the emergence of Candida albicans strains with decreased susceptibility to azoles. CMC is associated with an impaired Th17 cell response; however, it remains unclear whether decreased serum IL-17 and IL-22 levels are related to a defect in cytokine production or to neutralizing autoantibodies resulting from mutations in the AIRE gene.

Signs heralding appearance of thymomas after extended thymectomy for myasthenia gravis.

Thymomas appear very rarely after extended thymectomy for early-onset myasthenia gravis (EOMG). We describe 2 such cases that highlight potential early warning signs. In their 20s, one woman and one man developed EOMG (AChR antibody-positive), requiring extended transsternal removal of hyperplastic thymi at ages 35 and 27, respectively. Their myasthenia gravis was readily controlled for the next 10 and 7 years before deteriorating in both, with appearance of late clinical features and anticytokine autoantibodies suggesting underlying thymomas, namely respiratory infections, genital herpes, chronic candidiasis, and alopecia in the woman and erythroderma and lichen planus in the man, followed by Pseudomonas, Klebsiella, and cytomegalovirus infections plus chronic hepatitis during intensifying immunosuppressive therapy. Type B thymomas were then detected. Despite surgery or radiotherapy, and intensive drug therapy, the patients died 7 and 1 years later. Certain infections/dermatologic manifestations that associate with long-standing thymomas may herald their late appearance, despite previous thymectomy.

Evolution of drug resistance in an antifungal-naive chronic Candida lusitaniae infection

Management of the limited number of antimicrobials currently available requires the identification of infections that contain drug-resistant isolates and the discovery of factors that promote the evolution of drug resistance. Here, we report a single fungal infection in which we have identified numerous subpopulations that differ in their alleles of a single gene that impacts drug resistance. The diversity at this locus was markedly greater than the reported heterogeneity of alleles conferring antibiotic resistance in bacterial infections. Analysis of genomes from hundreds of Clavispora (Candida) lusitaniae isolates, through individual and pooled isolate sequencing, from a single individual with cystic fibrosis revealed at least 25 nonsynonymous mutations in MRR1, which encodes a transcription factor capable of inducing fluconazole (FLZ) resistance in Candida species. Isolates with high-activity Mrr1 variants were resistant to FLZ due to elevated expression of the MDR1-encoded efflux pump. We found that high Mrr1-regulated Mdr1 activity protected against host and bacterial factors, suggesting drug resistance can be selected for indirectly and perhaps explaining the Mrr1 heterogeneity in this individual who had no prior azole exposure. Regional analysis of C. lusitaniae populations from the upper and lower lobes of the right lung suggested intermingling of subpopulations throughout. Our retrospective characterization of sputum and lung populations by pooled sequencing found that alleles that confer FLZ resistance were a minority in each pool, possibly explaining why they were undetected before unsuccessful FLZ therapy. New susceptibility testing regimes may detect problematical drug-resistant subpopulations in heterogeneous single-species infections.

Satureja khuzistanica Jamzad essential oil and its anti-candidal activities against clinical isolates of Candida albicans isolated from women with candidiasis

Satureja khuzistanica Jamzad is known as antiseptic and analgesic agent in folk medicine. The aim of this investigation was to evaluate the anti-candidal activity of S. khuzistanica aerial parts essential oil against clinical isolates of Candida albicans, which were isolated from women with chronic recurrent candidiasis. For this purpose, the chemical composition of hydro-distilled essential oil was determined by GC and GC-MS analysis. Then, the anti-candidal activity of essential oil and its main component (carvacrol) were determined. Carvacrol (94.1%) was the main component of essential oil, followed by β-bisabolene, p-cymene and γ-terpinene. S. khuzistanica essential oil had strong anti-candidal activity against clinical isolates of C. albicans via inhibition of germ tube formation and induction the huge punctures in the cytoplasmic structures. The cell membranes were intact in presence of essential oil or carvacrol. S. khuzistanica essential oil as the main source of carvacrol can be used for treatment of C. albicans related infections.

Candidiasis mucocutánea crónica: una mirada al entendimiento genético

Chronic mucocutaneous candidiasis is an infectious phenotype characterized by recurrent or persistent infections in the skin, nails and mucous membranes produced by Candida sp. This is secondary to any alteration in the antifungal immunity, in which not only the production of IL-17, but any defect in the differentiation of the T lymphocytes towards their TH17 profile, play a fundamental role and will unchain a susceptibility to this infection; that depending on the genetic etiology, can be a syndromic manifestation with other associated infectious and endocrinological clinical characteristics. Here, we review in a practical, clear and concise manner, the genetic defects so far found to be involved in the appearance of chronic mucocutaneous candidiasis.

Chronic Mucocutaneous Candidiasis Due to Gain-of-Function Mutation in STAT1

Background: Chronic mucocutaneous candidiasis (CMC) is a heterogeneous group of primary immunodeficiency diseases characterized by susceptibility to chronic or recurrent superficial Candida infection of skin, nails, and mucous membranes. Gain-of-function mutations in the STAT1 gene (STAT1-GOF) are the most common reported cause of CMC. We describe here the clinical and genetic findings for 3 patients with CMC caused by novel gain-of-function mutations in STAT1-GOF.

Esophageal Ulcers in Primary Biliary Cholangitis: A Rare Cause of Hematemesis in the Setting of Portal Hypertension and Esophageal Varices

A previously unseen manifestation of primary biliary cholangitis with portal hypertension and a new type of esophageal ulcer that should be explored as a possible alternate source of bleeding in PBC patients to expedite early recognition and treatment. We present a case of a 71-year-old Caucasian female with PBC presented with hematemesis. EGD revealed cratered and linear ulcers with irregular shapes and blood intermittently oozing from the center in the esophagus in between >5mm non-bleeding esophageal varices in the middle and lower one third of the esophagus. Bipolar cautery was used successfully to halt bleeding from the ulcers and she was discharged with appropriate outpatient follow up with recommendations of non-selective beta blockers and follow-up EGD. Our patient had unexpected and unusual cause of hematemesis in the form of multiple esophageal ulcers in-between variceal columns. Nonvariceal bleeding in the presence of varices is extremely uncommon in PBC. Cirrhosis causing portal hypertension can cause an abnormally enlarged and thickened submucosal veins known as varices. In events of ischemia, these thickened veins cannot compensate further as they have reached maximal dilatation and have minimal reserve, thus resulting in ulcers. Other differentials such as endoscopic band ligation, sclerotherapy, recent nasogastric tube placement, stress ulcers, caustic ingestion, antibiotics use, chronic non-steroidal anti-inflammatory drugs (NSAID) usage, CMV, HSV, Candida, GERD, or Behcet's were ruled out. Given that upon endoscopic examination, the esophageal ulcers were found to bleeding instead of the varices, they should be considered in the differential in the etiology of hematemesis in primary biliary cirrhosis and thoroughly searched for during an endoscopic procedure for early treatment and subsequent secondary prevention.1813_A Figure 1. Esophageal Ulcers and Varices in Primary Biliary Cholangitis1813_B Figure 2. Ulcers in between Esophageal Varices

Assessment of Candidiasis Infections among Patients Visited in Hospital

Background: Candida is the shortened name used to describe a class of fungi that includes more than 150 species of yeast. The present study was conducted to assess Candidiasis infections among patients. Methods: The present study was conducted in the department of Microbiology on 114 cases. Clinical examination was done for the diagnosis. Microbiological culture assessment was done in all cases. Swab was taken from the lesion of the patients and was incubated in Sabouraud’s dextrose agar medium for assessment of culture growth characteristics. All the samples were incubated in the culture medium at 37°C for 1–2 days. Counting of the yeast colonies was done 48 hours after incubation. Results: Age group 11-20 years had 12 males and 7 females, 21-30 years had 18 males and 16 females, 31-40 years had 24 males and 15 females and 41-50 years had 10 males and 12 females. Most common type was denture induced candidiasis (DIC) seen in 20 males and 14 females, acute atrophic candidiasis (AAC) seen in 18 males and 15 females, acute pseudomembranous candidiasis (APC) seen in 12 males and 10 females, chronic hyperplastic candidiasis (CHC) in 10 males and 8 females and angular cheilitis in 4 males and 3 females. The difference was significant (P< 0.05). Common species was C. albicans (52), C. Krusei (32), C. tropicalis (20) and C. pseudotropicalis (10). Conclusion: Candidiasis is a common opportunistic infection. Most cases were seen in males and most common type identified was Candida Albicans.

A TYPICAL MEDIAN RHOMBOID GLOSSITIS: A CASE REPORT

Median rhomboid glossitis or glossal central papillary atrophy is characterized by an area of redness and loss of filiform papillae, situated on the dorsum of the tongue in front of the circumvallate papillae. Smoking, denture wearing, use of corticosteroid sprays or inhalers, and human immunodeficiency virus are few of the predisposing factors. Previously, this condition was believed to be a developmental defect of the tongue, caused by a failure of the tuberculum impar to be covered by the lateral processes of the tongue; however, now, it is thought to be due to chronic candidiasis. This paper presents an atypical case of rhomboid glossitis in a 4-year-old girl, discussing the clinical presentation, etiological factors, and differential diagnosis.

Клініко-цито-морфологічна діагностика кандидозу слизової оболонки верхніх відділів травного тракту з хронічним гастродуоденітом у підлітків

Objective: to study the features of clinical and cytological characteristics of the gastric mucosa in chronic gastroduodenitis in adolescents with chronic candidiasis of the digestive tract.Materials and methods. In total 164 adolescents with chronic gastroduodenitis were examined, including 22 patients with the Helicobacter pilory association, 32 children with Candida-Helicobacter pylori infection, 78 — with chronic candidiasis of the digestive tract, and 32 noninfected patients. Diagnosis of chronic candidiasis of the digestive tract in case of its clinical signs was carried out by an accessible, simple and cheap method of cytological examination of the oral mucous membrane scraping and the gastric biopsy sample prints taking during the endoscopy.Results. In adolescents with chronic gastroduodenitis and infection tropic to the digestive tract mucosa caused by Helicobacter pilory and Candida, there were destructive diffuse lesions in form of multiple erosions revealed, combined with hyperplastic gastric and duodenal mucosal changes, the frequency of which correlates with the duration increasing of chronic gastroduodenitis and does not depend on Неlicobacter pylori detection.Conclusions. In the chronic gastroduodenitis development and progression in adolescents, not only Helicobacter pilory, but also other microorganisms play a crucial role. This suggests the differentiated pathogenetic treatment need of the disease.

Natamycin in the treatment of chronic recurrent vulvovaginal candidiasis associated with intestinal candidiasis

This article discusses the natamycin therapy outcomes in 50 patients with a combination of chronic recurrent vulvovaginal candidiasis (CRVC) and intestinal candidiasis dysbiosis (ICD) and analyses the features of the clinical manifestations of CRVC against the background of the ICD, the species composition and sensitivity patterns of Candida cultures isolated from women with vaginal and intestinal discharge to various antimycotics.

A single-center 18-year experience with oral candidiasis in Brazil: a retrospective study of 1,534 cases.

Despite the large number of published studies about oral candidiasis and associated risk factors, reports of large single-center retrospective studies on the prevalence of oral candidiasis, risk factors, and the oral candidiasis types diagnosed more frequently in oral diagnostic reference centers are scarce. The objective of the present study was to retrospectively survey the demographic and clinical profiles of 1,534 patients diagnosed with candidiasis and treated at the Center for Diagnosis of Oral Diseases (CDOD), Pelotas Dental School, Federal University of Pelotas between 1997 and 2014. Using a retrospective, cross-sectional, epidemiological design, data on race, gender, age, systemic diseases, oral candidiasis type and location, symptoms, and harmful habits such as smoking and alcohol consumption were collected. The statistical analysis was performed using STATA version 13.1. Risk factors for chronic atrophic candidiasis (CAC) were evaluated using Poisson regression with robust variance (p ≤ 0.05). The majority of patients with oral candidiasis seen at the CDOD over the 18-year period of analysis were Caucasian women, aged 51-60 years, nonsmokers, and nondrinkers, with no systemic disease, and who wore some form of dental prostheses. CAC was the single most common clinical type of candidiasis detected, and the most frequently affected oral site was the palate. These data from a large single-center in Brazil agree with previous evidence about the clinical and demographic profiles of patients with oral candidiasis.

Antimicrobial Photodynamic Therapy to Control Clinically Relevant Biofilm Infections.

Biofilm describes a microbially-derived sessile community in which microbial cells are firmly attached to the substratum and embedded in extracellular polymeric matrix. Microbial biofilms account for up to 80% of all bacterial and fungal infections in humans. Biofilm-associated pathogens are particularly resistant to antibiotic treatment, and thus novel antibiofilm approaches needed to be developed. Antimicrobial Photodynamic therapy (aPDT) had been recently proposed to combat clinically relevant biofilms such as dental biofilms, ventilator associated pneumonia, chronic wound infections, oral candidiasis, and chronic rhinosinusitis. aPDT uses non-toxic dyes called photosensitizers (PS), which can be excited by harmless visible light to produce reactive oxygen species (ROS). aPDT is a multi-stage process including topical PS administration, light irradiation, and interaction of the excited state with ambient oxygen. Numerous in vitro and in vivo aPDT studies have demonstrated biofilm-eradication or substantial reduction. ROS are produced upon photo-activation and attack adjacent targets, including proteins, lipids, and nucleic acids present within the biofilm matrix, on the cell surface and inside the microbial cells. Damage to non-specific targets leads to the destruction of both planktonic cells and biofilms. The review aims to summarize the progress of aPDT in destroying biofilms and the mechanisms mediated by ROS. Finally, a brief section provides suggestions for future research.