Virulence and resistance factors of Nakaseomyces glabratus (formerly known as Candida glabrata) in Europe: A systematic review.

BACKGROUND: Nakaseomyces glabratus (N. glabratus) formerly known as Candida glabrata (C. glabrata), is an endogenous opportunistic pathogen, which is generally located in the gastrointestinal tract but can spread in immunocompromised patients. N. glabratus is the second most common pathogen that causes candidemia in several countries. N. glabratus virulence factors may increase antifungal resistance and reduce the number of available treatment options. High resistance to azoles and increasing resistance to echinocandins have been previously reported in N. glabratus. OBJECTIVE: To establish the distribution of N. glabratus isolates in Europe and its drug susceptibility/resistance in each country over the last 7 years. METHODS: The search was performed across three databases: PubMed, Scopus and Scielo, using the MeSH terms: "Candida glabrata", "Nakaseomyces glabratus", "Europe", "resistance" and "Epidemiology" exclusively in English. All available information from January 2002 to December 2022 was included, excluding reviews, meta-analyses and book chapters. RESULTS: Fifty-seven articles with information on antifungal susceptibility in Europe were retrieved and analysed with a total of 15,400 reported C. glabrata isolates. Remarkably, nations that presented the maximum number of cases during the study period included the United Kingdom (n = 7241, 47.02%), France (n = 3190, 20.71%), Spain (n = 900, 5.84%), Hungary (n = 745, 4.84%) and Italy (n = 486, 3.16%). C. glabrata isolates presented resistance to azoles [voriconazole (n = 2225, 14.45%), fluconazole (n = 1612, 10.47%), itraconazole (n = 337, 2.19%) and clotrimazole (n = 89, 0.58%)], increased resistance to echinocandins, especially to anidulafungin (n = 138, 0.89%), and high sensitivity to amphotericin B. CONCLUSION: The number of candidemia cases associated with triazole-resistant N. glabratus isolates have been increasing in Europe. Therefore, echinocandins and amphotericin B can be considered optional empirical treatments; however, antifungal susceptibility testing is required to determine the best therapeutic options.

Human papillomavirus-related diseases of the female lower genital tract: oncogenic aspects and molecular interaction.

The causal role of human papillomavirus (HPV) in all cancers of the uterine cervix has been firmly established biologically and epidemiologically. Most cancers of both the vulva and the vagina are also induced by HPV. Papillomaviruses are perfectly adapted to their natural host tissue, the differentiating epithelial cell of skin or mucosae, and exploit the cellular machinery for their own purposes. The infectious cycle is initiated once the infectious particles reach the basal layer of the epithelium, where they bind to and enter the cells. The critical molecules in the process of virus replication are the viral proteins E6 and E7, which interact with a number of cellular proteins. In experimental system these interactions have been shown to induce proliferation and eventually immortalization and malignant transformation of cells. Binding of E7 to pRb activates the E2F transcription factor, which then triggers the expression of proteins necessary for DNA replication. Unscheduled S-phase would normally lead to apoptosis by the action of p53. However, in HPV-infected cells, this process is counteracted by the viral E6 protein, which targets p53 for proteolytic degradation. Besides blocking p53 function in regulation of apoptosis, high-risk HPV proteins interact with both extrinsic and intrinsic apoptotic pathways. As an aberration of virus infection, constant activity of the viral proteins E6 and E7 leads to increasing genomic instability, accumulation of oncogene mutations, further loss of cell-growth control and ultimately cancer. The immune system uses innate and adaptive immunity to recognize and combat foreign agents that invade the body, but these methods are sometimes ineffective against human papillomavirus. HPV has several mechanisms for avoiding the immune system. Furthermore, HPV infections disrupt cytokine expression with the E6 and E7 oncoproteins, particularly targeting the expression of interferon genes. Approximately 10% of individuals develop a persistent infection, and it is this cohort who is at risk of cancer progression, with the development of high-grade precursor lesions and eventually invasive carcinoma.

[Skin care and wound management in patients with inherited bullous epidermolysis]. / Njega koze i zbrinjavanje rana u bolesnika s nasljednom buloznom epidermolizom.

Inherited epidermolysis bullosa is a group of diseases characterized by skin/mucous membrane fragility and development of blisters and erosions after insignificant mechanical trauma. It is a multisystemic disease with complications occurring on numerous organs other than the skin. As there is no cure for these diseases, treatment consists of early recognition and therapy of complications, quality wound care and skin protection. Optimal wound treatment depends primarily on the type of the disease, localization and type of wounds. Apart from good skin care, treatment of these patients requires intensive supportive therapy in which various specialists must be involved.

[Manifestations of sexually transmitted diseases on oral mucous membranes]. / Manifestacije spolno prenosivih bolesti na oralnoj sluznici.

Many believe that oral sex is safe sex and does not pose a risk of getting sexually transmitted diseases. Despite the prevalence of oral sex, the number of diagnosed oral and pharyngeal sexually transmitted infection is lower than that of anal and vaginal sex. Oral contact with the genitals can cause tiny micro traumas through which pathological microorganisms that are present in body fluids can come into contact and be transmitted. This article reviews the literature on the role of oral sex in the transmission of sexually transmitted diseases and the corresponding clinical presentation or oral diseases.

Meatal Intraurethral Warts Successfully Treated with 5-fluorouracil Cream.

Condyloma acuminatum relatively rarely involves the urethra, and when it does it is usually only in the most distal portion of the urethra. A number of treatments have been described for urethral condylomas. These treatments are extensive and variable, comprising laser treatment, electrosurgery, cryotherapy, and topical application of cytotoxic agents such as 80% trichloroacetic acid, 5-fluorouracil cream (5-FU), podophyllin, podophyllotoxin, and imiquimod. Laser is still considered to be therapy of choice for treatment of intrauretral condylomata. We present the case of a 25-year-old male patient with meatal intraurethral warts who was successfully treated with 5-FU, after many unsuccessful treatment attempts with laser treatment, electrosurgery, cryotherapy, imiquimod, and 80% trichloroacetic acid.

Molecular variants of human papilloma viruses type 16 and 6 in women with different cytological results detected by RFLP analysis.

HPV infections are common and the presence of the same high-risk type in cervical specimens can be due to reinfection or persistence. Persistent infection is the most important predictor for development of cervical carcinoma. The aim of this study was to validate PCR-RFLP with two sets of primers: MY09/MY11 that amplify a fragment of L1 and P1/P2 that amplify a fragment of E1 ORF. PCR product of MY09/MY11 was digested with a set of 6 restriction enzymes (RE) and PCR product of P1/P2 with a set of 12 RE. Cervical samples from 110 women patients of the University Gynecologic Clinic CHC Zagreb were analyzed. There were 98 (89.1%) PCR positive samples detected with P1/P2 primers, and 94 (85.5%) PCR positive samples detected with MY09/MY11 primers. Seven HPV types were detected with P1/P2-RFLP technique and 17 with MY09/MY11-RFLP PCR positive samples amplified with both primer pairs agreed with each other in 82 samples; 16 samples were only positive with P1/P2 and 12 samples were only positive by MY09/MY11. HPV 16 was detected in 39 samples with MY09/11-RFLP, out of these two variants (two different patterns) were found with P1/P2 using Dde I, Hae III and Eco I. HPV 6 was detected in 9 samples with MY09/11-RFLP, out of these two variants were found with P1/P2 using HinfI. Combining these two PCR-RFLP methods subtypes of HPV 16 and HPV 6 were detected.

[Diagnostic-therapeutic guidelines for men whose partners have HPV genital infection]. / Dijagnosticko-terapijski postupnik za muskarce kojih partnerice imaju HPV-genitalnu infekciju.

Human papilloma virus infection is the most frequent sexually transmitted disease. HPV infections are connected with different diseases such as benign warts, condylomata acuminata, malignant cervical, vulvar, vaginal, penile and anal carcinoma. Peniscopy with HPV detection is a specific diagnostic method for diagnosis of subclinical HPV genital infection in asymptomatic men. Taking the samples for HPV detection from asymptomatic men with curette is more qualitative way of getting enough samples then taking swab with wooden stick or (tongue) depressor. Early diagnosis and treatment of HPV infections in men is of potential benefit because their eradication can reduce the viral reservoir and as the result of that the incidence of CIN, carcinoma in situ and invasive cervical carcinoma can be reduced. For the correct diagnosis and for choosing the adequate therapeutical technique, we suggest diagnostic-therapeutic guidelines for HPV genital infection in men.

Coexistence of Anogenital Psoriasis and Genital Warts - Is There an Optimal Treatment?

The prevalence of psoriasis is 2% of the world's population (1). Inverse psoriasis is characterized by the development of erythematous shiny plaques at intertriginous areas of the body. The prevalence of only anogenital involvement appears to be low, but involvement of the anogenital area together with other areas is found in up to 45% of patients with psoriasis (2). A 21-year-old female student with a 3-month history of mild psoriasis (erythematosquamous plaque on the elbows and nail pitting on the nails of the hand) was referred to our Department. One month earlier, suddenly appearance of erythematous, smooth, clearly demarcated plaques was observed on the labia majora, the mons pubis, the perineal and perianal region together with a brownish hyperkeratotic papule on the pubic region (Figure 1, a-b). The patient underwent excisional biopsy at the Department of Surgery, and the pathohistological finding was unavailable to us. The elbows were treated with corticosteroid-keratolytic preparation, whereas the anogenital lesions were treated with moderately potent topical corticosteroids. In addition to anogenital erythema, on clinical examination we noticed an erythematosquamous plaque on the site of excision with a hyperkeratotic verrucous papule on the edge of the lesion (the Koebner phenomenon on the site of skin injury). In the pubic region, we noticed two hyperkeratotic papules and a few verrucous papules on labia majora. Localized dermatophyte or candida infection were excluded with a KOH test and scrapings culture. Serology for syphilis, HIV, and hepatitis were negative. Cervical Pap smear was normal. Biopsy of erythematosus lesion from the mons pubis was conclusive for psoriasis, and of the keratotic papule with the genital wart with positive HPV 6 and 11. The patient's older sister had chronic plaque psoriasis. We employed physically ablative methods like liquid nitrogen cryosurgery, electrocauterization, and curettage, applied topical agents like 0.5% podophyllotoxin solution, 20% podophyllin, and 80% trichloroacetic acid, and treated the psoriatic lesions with a short course of moderate-potency corticosteroids and tacrolimus ointment. All therapeutic attempts were ineffective for curing both diseases. Our patient either had psoriasis with sparse genital warts or exacerbation of multiple anogenital warts (Figure 2, a-b). Anogenital psoriasis is a skin disease that causes great discomfort. The disease-related quality of life is significantly reduced, especially regarding sexual behavior. Therapy for either anogenital psoriasis or genital warts is not entirely satisfactory. Many topical agents suitable for use on the psoriatic lesions on the body, such as coal tar, anthralin, vitamin D derivatives or retinoids, may be too irritating in the anogenital region. The most useful therapy for treatment of anogenital psoriasis are moderately potent topical corticosteroids and topical tacrolimus or pimecrolimus (1). However, corticosteroid-induced atrophy is possible in intertriginous sites. The Koebner phenomenon isomorphic response is the appearance of new skin lesions on areas of cutaneous injury in otherwise healthy skin (3). About 25% of patients with psoriasis have elicitation of psoriatic lesions by injury to the skin (4). Other than in patients with psoriasis, the Koebner phenomenon can be found in other skin diseases like vitiligo, lichen planus, lichen nitidus, pityriasis rubra pilaris, flat warts, and keratosis follicularis (Darier disease) (5). According to Eyre at al., about 67% patients with psoriasis (4) present with clearing of psoriatic lesions following skin injury (positive "reverse" Koebner reaction) (4). There is no single treatment for genital warts that is 100% effective, and different types of treatment are very often combined. Accepted methods of treatment involve chemical and physical destruction or removal (6). Since psoriasis koebnerizes, any destructive technique may exacerbate the psoriasis. Coexistence of anogenital psoriasis and HPV presents a huge therapeutic problem because a therapy for psoriasis such as corticosteroids can provoke appearance and/or reappearance of HPV infection, while some therapies for anogenital warts, like cryotherapy, curettage, laser ablation, electrosurgery, or surgery can provoke the appearance and/or reappearance of psoriatic infection due to the Koebner phenomenon.

Correlation between Family History and the Age of Onset of Childhood Acne in Relation to Sex and Type of Acne.

Acne vulgaris is a common chronic skin disorder of the pilosebaceous unit with a wide range of clinical presentations, which depend on the age of onset of acne, sex, family history of acne, and genetic factors, especially the genes affecting keratinization and desquamation. This retrospective study investigated pediatric acne using the patients' past medical history, with patients aged from newborns to 15 years of age. Acne were further stratified by 5 parameters: sex, age, family history, acne type, and localization. Our main aim was to investigate the possible association between selected parameters and the presence or absence of family history of acne. We did not find statistically significant correlation between sex, age of onset, and positive family history of acne. Furthermore, we did not find any association between age of onset and family history according to family members (mother/father/brother or sister). However, we found statistically significant correlation between sex and type of acne. This retrospective analysis of pediatric acne in Croatia did not reveal statistically significant correlation between positive family history and sex, age of onset, and clinical type of acne. In analyzing the correlation between family history and localization of acne, however, we found that the number of patients with acne localized on both the face and trunk and positive family history was statistically significant higher than expected.

Acute hemorrhagic edema of infancy: case report.

Acute hemorrhagic edema of infancy (AHEI) is a benign form of leukocytoclastic vasculitis that typically affects children between 4 and 24 months of age. The etiology remains unknown. The potential triggers of AHEI include preceding bacterial or viral infections, immunizations and drugs. The onset of AHEI is often dramatic with petechiae, ecchymoses, and annular, nummular or targetoid purpuric lesions usually appearing on the extremities, face, or ears. We report on a case of AHEI that occurred after upper respiratory tract infection.

Genital Herpes Zoster as Possible Indicator of HIV Infection.

Herpes zoster (HZ) is an acute, cutaneous viral infection caused by the reactivation of varicella-zoster virus (VZV) (1). It is a frequent medical condition with an incidence rate of 2-3 cases per 1000 person/years in the general population and 7-10 cases per 1000 person/years after the age of 50 (1,2). Risk factors and triggers for reactivation of HZV have not yet been determined precisely, but are likely to include malignancies, immune deficiencies, solid organ and bone marrow transplant recipients, autoimmune diseases, psychological conditions, emotional stress, human immunodeficiency virus (HIV) infection, and other patients receiving immunosuppressive therapies (1,3). A 24-year-old IV drug user presented with grouped clusters of vesicles and erosions on an erythematous, edematous base distributed on the left side of the penile shaft and the left infraumbilical region (Figure 1, a and b), with regional lymphadenopathy. He had prodromal symptoms of pain, dysesthesia and burning a few days prior to the appearance of the skin lesion. The patient reported unprotected sexual contacts a few months before the eruptions. The unilateral distribution was highly suggestive of herpes zoster. A Tzanck smear was performed by obtaining scrapings from the base of a fresh vesicular lesion after it had been unroofed; it showed the characteristic presence of multinucleated giant cells that suggested herpes infection. Polymerase chain reaction (PCR) analysis of vesicular fluid yielded positive results for VZV. A 7-day course of acyclovir (800 mg 5 times a day) was initiated. The patient reported marked improvement on the second day of antiviral therapy. The course was uncomplicated, and the lesions healed without postherpetic neuralgia. Serologic tests for syphilis (VDRL/RPR and TPHA) and hepatitis C and B serologic tests were negative, but HIV test (enzyme immunoassays (EIA) for HIV-1 and HIV-2 antibodies were positive, which was later confirmed with Western blot (WB) tests. Because of the positive HIV test, the patient was referred to the Clinic for Infectious Diseases for further treatment. Herpes zoster is painful vesicular skin eruption with unilateral dermatomal involvement, usually with a severe impact on the quality of life in affected patients (1). The risk for developing HZ during a lifetime in patients exposed to VZV infection is 10-30% (4). However, the risk is higher in immunocompromised patients, particularly in cancer patients and HIV-positive patients (1,5,6). HZ is seen approximately 7 times more frequent in patients with HIV infection (5). Reactivated VZV infection may occur at any stage of HIV infection and may be the first clinical evidence of HIV infection. The development of HZ in immunocompromised individuals can be explain by decline in cell-mediated immunity and CD4 count (6). HZ predominantly affects the thoracic region, followed by the head, cervical, and lumbar regions (1). Sacral dermatomes are involved in only up to 2% of cases (1). HZ involving the penis is rarely reported, with only few case reports in the literature (3,7-9). Birch et al. compared VZV and herpes simplex virus (HSV) in specimens obtained from the genital lesions of adults presenting with presumed genital herpes infection (10). They found VZV in nearly 3% of virus-positive genital specimens, which demonstrates that this virus needs to be considered in the differential diagnosis of genital herpetic lesions (10) and that it is possible that genital HZ infection is underdiagnosed. Tzanck smear is a rapid and inexpensive method, but it cannot differentiate VZV from HSV. Genital HZ could be mistaken for zosteriform HSV infection, so a PCR test should be performed to confirm the underlying diagnosis (1). Genital forms of HZ are rare and sometimes clinically difficult to diagnose, especially when the typical zosteriform distribution is lacking; PCR testing is therefore suggested. HZ is considered a possible HIV indicator; an HIV test should therefore be performed. According to our knowledge and literature search, this is the first case report of penile HZ in an HIV-positive patient.

Coexistence of genital lichen sclerosus and genital warts.

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of the genital and extragenital skin. Anogenital warts are benign proliferative lesions caused by human papillomavirus (HPV), which is found in > 95% of lesions. We present two cases of the coexistence of LS and genital warts: one patient with and one without a previous history of genital warts. According to our knowledge and a literature search, only a few cases of the coexistence of LS and genital warts have been reported.

Chronic Recurrent Multifocal Osteomyelitis (CRMO) and Synovitis Acne Pustulosis Hyperostosis Osteitis (SAPHO) Syndrome - Two Presentations of the Same Disease?

The two most common entities among generally rare but under-diagnosed autoinflammatory bone disorders are chronic recurrent multifocal osteomyelitis (CRMO) and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Due to their similarities, many authors consider CRMO to be a subtype of SAPHO syndrome. The aim of this study was to compare clinical, laboratory, and imaging features and outcomes of patients with CRMO and SAPHO. The analysis of the data from 6 children with CRMO (four girls and two boys, age 3.5-14 years) and of 6 children (6 boys, age 13.5-17.5 years) with SAPHO syndrome was performed. The initiating symptoms in all patients with CRMO were bone pain with multifocal bone lesions. There were no skin manifestations. Five out of six patients achieved control with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, while one patient required disease-modifying antirheumatic drugs (DMARDs). The initiating symptom in five patients with SAPHO syndrome were severe acne, while in one patient acne occurred two years after the disease onset. Two patients typically developed inflamed sternoclavicular joints and sternum, while the others showed changes affecting other skeletal regions. Three patients achieved control with NSAIDs and corticosteroids, the others required DMARDs and TNFα inhibitors. In comparison with patients with CRMO, patients with SAPHO suffered more frequent and longer lasting exacerbations. In conclusion, CRMO and SAPHO syndrome have an array of common characteristics, but also a number of differences. Nevertheless, further investigation into the etiopathogenesis is required to establish a definite relationship between CRMO and SAPHO.

Kerion Celsi due to Microsporum canis with a Dermatophytid Reaction.

Microsporum (M.) canis is the most common fungus to cause tinea capitis in Europe, especially in the Mediterranean region and South and Central Europe. Fungal scalp infections caused by M. canis tend to be non-inflammatory. Recently, a growing number of cases of tinea capitis characterized by inflammatory infection caused by M. canis and M. gypseum have been registered. We present a case of highly inflammatory tinea capitis, also known as kerion celsi, caused by M. canis in a 6-year-old-patient. Scalp infections due to M. canis are a growing problem in dermatological practice. Changes in epidemiology, etiology, and clinical patterns of fungal infections due to M. canis are significant. Greater awareness of this problem is needed in order to establish proper diagnosis and successful treatment strategy for these patients.

Sinecatechins and imiquimod as proactive sequential therapy of external genital and perianal warts in adults.

This review about the proactive sequential therapy (PST) of external genital and perianal warts (EGW) is based on the most current available clinical literature and on the broad clinical experience of a group of international experts, physicians who are well versed in the treatment of human papillomavirus-associated diseases. It provides a practical guide for the treatment of EGW, including epidemiology, etiology, clinical appearance, and diagnostic procedures for these viral infections. Furthermore, the treatment goals and current treatment options, elucidating provider- and patient-applied therapies, and the parameters driving treatment decisions are summarized. Specifically, the mode of action of the topical treatments sinecatechins and imiquimod, as well as the PST for EGW to achieve rapid and sustained clearance is discussed. The group of experts has developed a treatment algorithm giving healthcare providers a practical tool for the treatment of EGW which is very valuable in the presence of many different treatment options.

The 2016 European guideline on the management of epididymo-orchitis.

Epididymo-orchitis is a commonly encountered condition with a reported incidence of 2.45 cases per 1000 men in the United Kingdom. This 2016 International Union against Sexually Transmitted Infections guideline provides up-to-date advice on the management of this condition. It describes the aetiology, clinical features and potential complications, as well as presenting diagnostic considerations and clear recommendations for management and follow-up. Early diagnosis and management are essential, as serious complications can include abscess formation, testicular infarction and infertility. Recent epidemiological evidence suggests that selection of fluoroquinolone antibiotics with anti-Chlamydial activity is more appropriate in the management of sexually active men in the over 35 years age group.

Treatment of childhood psoriasis.

Psoriasis is a common disease in children and adolescents. Because of the chronic course of the disease, appropriate choice of therapy in particular stage of the disease, so-called rotation therapy, is of paramount importance. This article provides a review of therapeutic options for childhood psoriasis. Local therapy for psoriasis in children consists of corticosteroid preparations, calcipotriol, tars and dithranol, local retinoids, and local immunomodulators. Phototherapy (narrow band UVB, photochemotherapy PUVA baths) is now a part of psoriasis therapy in children. Systemic therapy retinoids (acitretin) methotrexate, cyclosporine is only used in severe forms of the disease such as erythrodermic, pustular and arthritic psoriasis. All these therapeutic options can be used as monotherapy or in various combinations.

What do we really know about "tinea incognita"?

The term "tinea incognita" refers to diverse clinical presentation of mycotic infections modified by inappropriate use of topical or systemic corticosteroids. A 67-year-old male patient with a five-year history of generalized erythematous plaques on the trunk and extremities, previously treated with topical corticosteroids, is described. The lesions mainly showed a psoriasiform, some eczematous appearance, few of them showing a clinical picture of folliculitis. The native mycologic specimen was negative. The diagnosis was made on the basis of mycologic culture finding of Trichophyton interdigitale growth. Systemic and topical antimycotic therapy administered for two months resulted in complete regression of skin lesions.

Tinea Incognita in a Patient with Crest Syndrome: Case Report.

Tinea incognita is a dermatophytic infection that is difficult to diagnose, usually modified by inappropriate topical or systemic corticosteroid therapy. We report an extensive case of tinea incognita caused by the zoophilic dermatophyte Trichophyton mentagrophytes (var. granulosa) in a 49-year-old female patient with CREST (Calcinosis; Raynaud phenomenon; Esophageal involvement; Sclerodactyly; Teleangiectasia) syndrome. Immunocompromised patients, as well as patients with keratinization disorders, seem to be especially susceptible to dermatophytic infections with atypical clinical presentation that is sometimes bizarre and difficult to recognize. Therefore, close monitoring and mycological skin examination is recommended in order to avoid misdiagnosis and to give the patient the best chance of recovery.

Inflammatory epidermolysis bullosa acquisita in a 4-year-old girl.

This study presents a case of linear immunoglobulin A dermatosis-like epidermolysis bullosa acquisita in a 4-year-old girl showing rapid, widespread and inflammatory skin lesions. The diagnosis was confirmed by histopathology, direct and indirect immunofluorescence, various immunoblotting analyses and enzyme-linked immunosorbent assays. Despite the severe clinical manifestations, the disease was successfully controlled by combination therapy of oral prednisolone and dapsone.