Genomic, Epigenomic, Transcriptomic, Proteomic and Metabolomic Approaches in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in the developed countries. It is associated with atopic and non-atopic diseases, and its close correlation with atopic comorbidities has been genetically demonstrated. One of the main roles of genetic studies is to comprehend the defects of the cutaneous barrier due to filaggrin deficit and epidermal spongiosis. Recently, epigenetic studies started to analyze the influence of the environmental factors on gene expression. The epigenome is considered to be a superior second code that controls the genome, which includes alterations of the chromatin. The epigenetic changes do not alter the genetic code, however, changes in the chromatin structure could activate or inhibit the transcription process of certain genes and consequently, the translation process of the new mRNA into a polypeptide chain. In-depth analysis of the transcriptomic, metabolomic and proteomic studies allow to unravel detailed mechanisms that cause AD. The extracellular space and lipid metabolism are associated with AD that is independent of the filaggrin expression. On the other hand, around 45 proteins are considered as the principal components in the atopic skin. Moreover, genetic studies based on the disrupted cutaneous barrier can lead to the development of new treatments targeting the cutaneous barrier or cutaneous inflammation. Unfortunately, at present, there are no target therapies that focus on the epigenetic process of AD. However, in the future, miR-143 could be an important objective for new therapies, as it targets the miR-335:SOX axis, thereby restoring the miR-335 expression, and repairing the cutaneous barrier defects.

Stress-induced mast cell activation in glabrous and hairy skin.

Mast cells play a key role in modulation of stress-induced cutaneous inflammation. In this study we investigate the impact of repeated exposure to stress on mast cell degranulation, in both hairy and glabrous skin. Adult male Wistar rats were randomly divided into four groups: Stress 1 day (n = 8), Stress 10 days (n = 7), Stress 21 days (n = 6), and Control (n = 8). Rats in the stress groups were subjected to 2 h/day restraint stress. Subsequently, glabrous and hairy skin samples from animals of all groups were collected to assess mast cell degranulation by histochemistry and transmission electron microscopy. The impact of stress on mast cell degranulation was different depending on the type of skin and duration of stress exposure. Short-term stress exposure induced an amplification of mast cell degranulation in hairy skin that was maintained after prolonged exposure to stress. In glabrous skin, even though acute stress exposure had a profound stimulating effect on mast cell degranulation, it diminished progressively with long-term exposure to stress. The results of our study reinforce the view that mast cells are active players in modulating skin responses to stress and contribute to further understanding of pathophysiological mechanisms involved in stress-induced initiation or exacerbation of cutaneous inflammatory processes.

An overview regarding the relationship between Mollicutes, infertility and antibiotic resistance (Review).

Throughout the past decades, physicians have increasingly conferred regarding the role of Mollicutes in infertility in both male and female patients. Although Ureaplasma and Mycoplasma do not represent a leading cause of infertility, whether dermatovenerologists, gynecologists and urologists should not disregard them when screening patients with infertility problems is discussed in the present review. While these infections are completely asymptomatic in ~80% of cases, they do lead to both chronic inflammation of the genital tract and reproductive disorders. Different Mollicute strains and/or serovars, genomic traits and proteomic markers have been examined in order to understand not only the exact mechanism by which they cause infertility, but also their relationship with the worldwide spreading resistance to antibiotics. The current review provided an overview of the latest studies regarding the new findings on the relationship between Mollicutes, infertility and antibiotic resistance. Awareness should be raised among clinicians to screen sexually active adults wishing to conceive who have failed to achieve a pregnancy; in addition, an antibiogram should be performed and treatment should be carried out according to the guidelines.

Prevalence of Ureaplasma urealyticum, Mycoplasma hominis and Chlamydia trachomatis in symptomatic and asymptomatic patients.

The purpose of the present study was to assess the prevalence of Ureaplasma urealyticum (U. urealyticum), Mycoplasma hominis (M. hominis) and Chlamydia trachomatis (C. trachomatis) in a Romanian population considering the presence or absence of genital symptoms. Urethral and vaginal samples were collected from patients presenting at 'Ponderas' Academic Hospital (Bucharest, Romania) from January 2021 to December 2021. A total of 266 samples were obtained from two groups of patients: Symptomatic subjects with urethritis, prostatitis, vaginitis or both urethritis and prostatitis (n=59; 22%), and asymptomatic subjects (n=207; 78%). Mycoplasma and Chlamydia kits were used to assess the presence of U. urealyticum and M. hominis, and C. trachomatis, respectively. The symptomatic subjects comprised 27 patients with urethritis symptoms, of whom 4 (15%) were infected with U. urealyticum and 1 (4%) was infected with C. trachomatis. In addition, 23 (9%) of the patients had prostatitis-like symptoms, which in 3 (13%) of the patients was associated with U. urealyticum and in 1 patient (4%) was associated with C. trachomatis. None of the symptomatic patients were infected with M. hominis. By contrast, 29 (14%) of the asymptomatic patients were discovered to be infected with U. urealyticum, 13 (6%) were coinfected with both Mollicutes and 4 (2%) were infected with C. trachomatis; only 1 patient was positive for M. hominis alone. Two patients (14%) who presented with U. urealyticum and M. hominis coinfection were also infected with C. trachomatis. No patient with U. urealyticum or M. hominis alone was also positive for C. trachomatis. Therefore, the most frequently identified pathogen populating the genital tract in both males and females was U. urealyticum, followed by coinfection with U. urealyticum and M. hominis, and C. trachomatis. As these infections are asymptomatic in numerous cases, this suggests that a thorough screening should be mandatory.

Reflectance Confocal Microscopy in Monitoring Atopic Dermatitis Treated with Topical Calcineurin Inhibitors.

Atopic dermatitis is a chronic inflammatory skin disease associated with multiple allergies in the atopic march. It has a complex pathogenesis, related to genetic, immune, and environmental factors. Its incidence and prevalence are increasing in the last decades, especially in developed countries. It affects the quality of life due to the recurrent lesions and the associated pruritus. Thus, it is very important to use non-invasive techniques to manage and follow-up the patients with such a heterogenous disease that can have a high impact on some of them. The reflectance confocal microscope is a modern device for in vivo visualization of the epidermis and the upper dermis which could replace in some cases the cutaneous biopsy. We report a case of a patient with atopic dermatitis investigated with the confocal reflectance microscope at the beginning of the topical treatment with calcineurin inhibitors and three weeks after, with favorable evolution. Reflectance confocal microscopy allows the assessment of the dynamic changes in the skin during treatment. Moreover, it can be useful for highlighting discrete changes even in the subclinical stages of the inflammatory process. Future developments, which will lead to the definition and validation of reflectance confocal microscopy criteria for the diagnosis and staging of atopic dermatitis, could help to improve the treatment and prevention strategies of the disease.

Monkeypox 2022: Dermatologists in the frontline on the edge of a new pandemic: A case report.

The world is on the edge of a new pandemic due to the monkeypox virus, an endemic virus from Africa with occurrences in the western hemisphere due to international travel. Contact with respiratory droplets, skin lesions, or bodily fluids from infected animals, direct or indirect contact with contaminated fomites can lead to transmission. A prolonged close contact is required in order for the infection to be spread. The lesions start as papules or macules, develop into pustules, umbilicated vesicles, ulcers, and, finally, into crusty scabs, similar to smallpox. No specific clinically proven treatments for monkeypox infection are currently available, although there are some preventive measures that can be taken. The present study presented the case of a homosexual man with genital monkeypox infection. Currently, there are five confirmed cases of monkeypox in Romania and its incidence is continuously rising. Therefore, dermatovenerologists all over the world should be prepared to recognize the disease, as well as take preventive measures in order to avoid another global pandemic.

Buschke-Löwenstein tumors: A series of 7 case reports.

Giant condyloma acuminatum (GCA), or Buschke-Löwenstein tumor (BLT), represents an infrequent sexually transmitted disease (STD), caused by human papillomavirus (HPV), especially genotype 6 or 11. There are numerous risk factors for HPV, such as multiple sexual partners, homosexuality, prostitution, chronic genital infections, as well as the lack of proper hygiene. HPV infection is a field infection, where large areas of cells at a tissue surface are affected by the HPV virus; therefore, once the GCA is excised, treatment of the whole affected genital area needs to be undertaken. The treatment is classified into topical therapy (podophyllin, 5-FU, radiotherapy, topical photodynamic therapy), excisional therapy (CO2 laser, cryotherapy, electrotherapy, surgery) and immunotherapy (imiquimod). However, the 'gold standard' therapy is represented by wide surgical excision without grafting, since it is considered that healing per secundam is an improved approach, because there is no risk of recurrences on fibrotic tissue. A total of 7 cases of the BLT with comorbidities and particularities are presented and it is recommended that it be taken into consideration that the incidence of the disease is increasing, emphasizing the importance of an early diagnosis, as well as an adequate treatment.

Dermoscopy in the diagnosis of cutaneous lymphoma (Review).

Cutaneous lymphomas are a group of rare and distinct diseases that present varying clinical manifestations, histopathology and prognosis. Optimal and early management relies on accurate diagnosis. Unfortunately, clinical diagnosis in early stages is difficult due to the clinical overlap with other dermatologic conditions. In numerous cases, several consultations and multiple biopsies are required. Dermoscopy is frequently used for the evaluation of melanocytic skin tumors, but its value has been recognized for non-melanocytic neoplasms and inflammatory skin diseases, and in the last few years it has assisted with the diagnosis of cutaneous lymphoproliferative disorders (LPD). Studies have shown that dermoscopy may be useful in the evaluation of cutaneous lymphomas, offering a link between clinical and histopathological examination, but the features are not diagnostic and histopathological confirmation is mandatory. However, dermoscopy can raise suspicion of cancer, leading to a skin biopsy. Furthermore, larger and prospective studies are required to define the exact dermoscopic features of every subtype of cutaneous lymphoma.

Balanitis xerotica obliterans: An observational, descriptive and retrospective clinical study.

Lichen sclerosus is a chronic disease of unknown etiology that can occur in the genital area of both sexes. Balanitis xerotica obliterans (BXO) occurs only in the genital area of men and typically affects the foreskin, penile glans, and/or the meatus. In the present report, an observational, descriptive, and retrospective epidemiological clinical study of available data between January 2006 and December 2020 in patients diagnosed with BXO from the casuistic of CMI DERMAMED (Târgu Mureș, Romania) was performed. During this 15-year period, 164 patients were diagnosed with BXO, of whom 70 (42.8%) were in the 51-60-year-old age group. They presented at the medical consultation at 3-9 months after onset of symptoms, where 124 (75.6%) the patients were found to be with stage III of the disease. The most important comorbidities were found to be diabetes mellitus and obsesity, who were treated with potent steroids (betamethasone and clobetasol) with favorable results, with only nine (5.48%) cases necessitating surgical treatment. In general, BXO is a rare, acquired, non-infectious and chronically inflammatory (autoimmune) skin disease that has an unknown etiology. Although the risk of developing this condition is particularly high in patients in the 40-60-year-old age group, it can occur at any age. In the present report, the majority of the patients presented after a long period of disease development, such that they were already in advanced stages of the condition with clinically subjective symptoms and severe sexual problems. This delay in diagnosis has several causes, including misdiagnosis, psychological issues, and sexual behavior. Diabetes mellitus and overweight/obesity tended to be important comorbidities of BXO since the majority of the patients were also affected by these conditions. These comorbidities can exert an important pathophysiological influence on BXO. The first-line treatment option for this condition is the local application of potent steroids, with favorable effects. Due to the risk of malignant transformation as a result of BXO, it is recommended that these patients should be followed up for a longer period.

Adult female acne: Clinical and therapeutic particularities (Review).

Acne is a chronic inflammatory condition affecting the pilosebaceous unit that was traditionally viewed as a disease of the adolescence. However, over the past several years, an increasing number of adult women have been reported to suffer from this condition. The prevalence of adult female acne ranges between 12 and 54%. Two clinical types can be distinguished in this population, a 'retentional' and an 'inflammatory' type, which usually tend to overlap. In terms of evolution, three main subtypes can be identified: Persistent acne, which is the most frequent subtype, late-onset acne and recurrent acne. This type of acne is mainly mild-to-moderate in severity and may be refractory to conventional treatment. The etiopathogenesis is complex and has yet to be fully elucidated. It appears to involve an interaction among genetic predisposition, hormonal factors, and chronic activation of the innate immune system overlapping with external factors, such as daily stress, Western-type diet, use of tobacco and cosmetics. The treatment may be challenging and a holistic approach is required, with special attention to the individual needs and particularities of adult women. Both topical and systemic treatments are available, with hormonal therapies being of special value in this population. The aim of the present article was to provide up-to-date, evidence-based information on the clinical presentation, etiopathogenesis and treatment of adult female acne.

Cutaneous sarcoidosis of the scalp unmasking systemic involvement: A case report.

Sarcoidosis is a multisystemic granulomatous disease of unknown cause that affects any organ, especially the lungs, eyes, lymph nodes and skin. Skin sarcoidosis occurs in about one-fourth of patients with systemic disease and may also arise in isolation. Skin lesions are divided into two groups, as follows: specific skin lesions where histologic examination shows the typical sarcoid granulomas and non-specific skin lesions. Specific lesions are lupus pernio, infiltrated plaques, maculopapular eruptions, subcutaneous nodules and scars. The most significant non-specific skin lesion seen in sarcoidosis is erythema nodosum. Cutaneous sarcoidosis is known as the 'great imitator' in dermatology, because it can mimic a vast variety of cutaneous lesions. The diagnosis of sarcoidosis is made by exclusion and is supported by the recognition of specific clinical features, the detection of classic histopathologic findings and the exclusion of other granulomatous diseases. We present a case report concerning a single, solitary and asymptomatic lesion on the scalp.

Probiotics and prebiotics in atopic dermatitis: Pros and cons (Review).

Atopic dermatitis (AD) represents a chronic inflammatory skin condition in which the skin barrier is impaired; thus, the permeability is increased. Hence, there is a greater risk of allergic sensitization, as well as a higher pH and lower protection against resident microbes. Since this condition is currently increasing among children, it requires further study, as little is known regarding the pathogenesis that makes the skin prone to chronic relapsing inflammation. Trying to standardize the data regarding the use of prebiotics and probiotics in AD, we encountered tremendous variability in the literature data. Literature abounds in conflicting data: studies regarding prophylactic and therapeutic applications, different types of strains and dosages, applications in young children up to 5 years of age and above, usage of probiotics alone, prebiotics alone or synbiotics combined. There are also conflicting data regarding the outcome of these studies; some confirming a positive effect of prebiotics, probiotics or synbiotics and some showing no efficacy at all. The articles were divided into those assessing probiotics or prebiotics alone and a combination of the two, with studies showing a positive effect and studies proving no efficacy at all. We tried to critically analyze those articles showing weak and strong points. In summary, the most studied probiotics were the strains of Lactobacilli and Bifidobacteria. The Severity Scoring of Atopic Dermatitis (SCORAD) index was used to measure the efficacy of the treatment. Most studies compared their results with a placebo group and the efficacy when seen in moderate to severe forms of AD in patients with other allergic diseases present. However, the results are difficult to interpret, as in many studies the authors suggest that the disease may have a tendency to improve in time in some groups of patients.

Skin endometriosis: A case report and review of the literature.

Skin endometriosis is a rare disease with variable clinical and histopathological characteristics that depend on hormonal stimuli. The skin is not a common location, as most cases of endometriosis involve pelvic sites, such as the ovaries, peritoneum and bowel. However, the most common extrapelvic site affected is the abdominal wall and this location of the disease is frequently associated with obstetric and gynecologic surgery. Here we report a case of skin endometriosis emerged as a painful subcutaneous nodule located near to the left side of an obstetrical surgery procedure scar. The patient affected was a woman in her reproductive age, with a history of right ovary endometriotic cyst laparoscopically removed and histologically confirmed as a primary endometriosis. Dermatologists should be aware of this condition in any woman with a painful lump located in the proximity of a pelvic surgery-induced scar. Its non-specific clinical appearance may confuse the clinician and may delay the diagnosis and management.

Management of psoriasis in children (Review).

Psoriasis is a common long-lasting, inflammatory disease that mainly affects the skin. The incidence of this condition has increased significantly over time and at this point, it affects approximately 1% of children. Psoriasis can appear at any age, including childhood and adolescence, with a higher frequency in girls, an earlier onset being associated with severe psoriasis. The pathology is the result of the interaction between genetics and trigger factors such as infections, stress, diet, obesity, and chemical irritants. Paradoxically, tumor necrosis factor (TNF)-α inhibitors (infliximab, adalimumab) may induce psoriasis in children. Psoriasis is a long-term condition with periods of exacerbation; thus, the quality of life can be affected and patients should receive psychosocial support. Although most children have mild disease and topical treatment is efficient, some cases are challenging to treat. The aim of this review was to provide an overview of the current knowledge concerning the epidemiology, etiology, pathogenesis, clinical features, comorbidities, and treatment of psoriasis in children and also to emphasize the need for a multidisciplinary approach to this complex pathology.

In Vivo Reflectance Confocal Microscopy-Diagnostic Criteria for Actinic Cheilitis and Squamous Cell Carcinoma of the Lip.

Actinic cheilitis (AC) is one of the most frequent pathologies to affect the lips. Studies show that the most commonplace oral malignancy, squamous cell carcinoma (SCC), often emerges from AC lesions. Invasive diagnostic techniques performed on the lips carry a high risk of complications, but reflectance confocal microscopy (RCM), a non-invasive skin imaging technique, may change the current diagnostic pathway. This retrospective study was aimed at consolidating the RCM diagnostic criteria for AC and lip SCC. The study was conducted in two tertiary care centers in Bucharest, Romania. We included adults with histopathologically confirmed AC and SCC who also underwent RCM examination. Of the twelve lesions included in the study, four were AC and eight were SCC. An atypical honeycomb pattern and the presence of target cells in the epidermis were RCM features associated with AC. SCC was typified by the presence of complete disruption of the epidermal architecture and dermal inflammatory infiltrates. The mean blood vessel diameter in SCC was 18.55 µm larger than that in AC (p = 0.006) and there was no significant difference (p = 0.64) in blood vessel density, as measured by RCM, between SCC and AC. These data confirm that RCM can be useful for the in vivo distinction between AC and lip SCC.

Acquired angioedema induced by angiotensin-converting enzyme inhibitors - experience of a hospital-based allergy center.

Angiotensin-converting enzyme inhibitors (ACEIs) represent an important group of pharmacological compounds, largely prescribed for more than 30 years. They have been extensively evaluated in clinical trials, demonstrating significant reduction of morbidity and mortality of patients with cardiovascular diseases, mainly high blood pressure, myocardial infarction, heart failure and stroke. Besides their beneficial effects and a general good safety profile, it was proven that ACEIs might also induce adverse effects in some patients, most notably angioedema (AE) and chronic cough. The occurrence rate of adverse events induced by ACEIs is low, but the number of suffering patients is relatively high, since ACEIs is one of the most frequently prescribed medication worldwide. The aim of our study was to evaluate clinical pattern, risk factors and general management of ACEI-induced angioedema in a cohort of patients addressed for allergist evaluation in one university hospital in Romania, during a period of 32 months. It was found that ACEI-induced angioedema (ACEI-AE) represented more than half of the total number of patients addressed for angioedema without urticaria, with variable clinical and time-patterns. Most of the patients were referred by general practitioners (GPs) with diagnosis of urticaria or other skin allergy and continued to take ACEIs for months and years after onset of angioedema. We concluded that the awareness of acquired, non-allergic angioedema induced by ACEI therapy in medical practice is still low and there is a need for improved knowledge and interdisciplinary collaboration in this field.

Role of osteodensitometry in osteoporosis and osteopenia in psoriatic arthritis.

Dual-energy X-ray Absorptiometry (DEXA) determines the mineral contents for the spine, the proximal femur and the entire body. A group of 36 patients with psoriatic arthritis were chosen, with different types of arthropathy, from the total 82 patients with psoriatic arthritis in the study group, for which bone mineral density (BMD) was measured, using the DEXA technique. The chosen study group comprised 12 men, 12 premenopausal women and 12 menopausal women, with psoriatic joint damage and a group of 36 healthy individuals, divided based on the same criteria: Men, premenopausal and menopausal women. This study did not emphasize an association between the patient type and the presented bone demineralization type (χ2 (2)=4.473, P=0.107) in men. In premenopausal women, there was a significant association between the patient type and the presented bone demineralization type (χ2 (2)=8.778, P=0.012), as the female patients with psoriatic arthritis presented total and partial demineralization to a larger degree, compared with healthy individuals. In menopausal women, this study did not highlight an association between the patient type and the presented bone demineralization type (χ2 (2)=4.523, P=0.104). Bone demineralization was significant in all three patient groups, both total and partial, in patients with psoriatic arthritis compared with healthy patients. Bone demineralization manifested as osteopenia, with T-scores ranging from -2.5 to -1, and not as osteoporosis. Determining B MD by DEXA technique revealed osteopenia to a higher degree within the group of patients with psoriatic arthritis compared with the healthy patients, as well as the absence of osteoporosis in psoriatic arthritis.

Implications of self-esteem in the quality of life in patients with psoriasis.

Skin has an integrative role in daily life, being a communication organ between the patient and the world. Skin affection in psoriasis has consequences on the patient's self-esteem, with direct implications on the quality of life. This study focused on the impairment of self-esteem in a group of 110 patients: Patients with severe cutaneous and psoriasis arthritis and patients with mild types of psoriasis, using the Rosenberg Self-Esteem Scale. Patients with severe cutaneous and psoriasis arthritis have a lower self-esteem compared with patients with mild psoriasis. The statistical data of two groups regarding the degree of education (secondary and higher education), in the male patients with severe cutaneous and psoriasis arthritis with higher education showed a lower self-esteem, compared with male patients with severe cutaneous and psoriasis arthritis with secondary education. In mild forms of psoriasis, the self-esteem of women and men is relatively equal, but below the general population average. Male patients with psoriasis arthritis have a much lower self-esteem compared with that of women, looking at life prospects more negatively. Psoriasis has a major impact on self-esteem, which correlates with quality of life in patients with psoriasis arthritis, depending on the skin condition that creates a major visual impact in society.

Mite allergy and atopic dermatitis: Is there a clear link? (Review).

Atopic dermatitis (AD) represents a widespread chronic skin disease associated with different atopic disorders and allergies. These associations, similar to overall AD pathophysiology, are entangled, multifactorial and they are yet to be clarified. IgE and non IgE mediated pathomechanisms appear to be implicated in AD. Allergens constitute key aspects in AD pathogenesis, as they may serve as trigger factors. This review emphasizes mainly house dust mites (HDM), as they are likely the most relevant airborne allergen for AD. Here we review in a concise form the mite allergens, the role of molecular diagnosis and the treatment strategies for HDM. Strategies of avoiding allergens, with a few exceptions, are not enough to control children's AD; recent studies show HDM avoidance procedures in diagnosed AD are insufficient. Regardless, some guidelines acknowledge the benefit of mattress and pillow covers in patients with dust mite sensitization that are unresponsive to optimal AD management. Most clinical trials investigating allergen-specific immunotherapy (AIT) as a potential treatment for AD were done with adult patients; a scarce number of studies looked into the efficacy of AIT as a treatment option in children suffering from AD, with conflicting data among them. One of the most feasible of these studies showed significant improvement of AD outcomes only in the mild/moderate group, but not in the severe group. Uncontrolled studies are hard to interpret, considering the natural history of remitting and relapsing of AD, in many of the patients, without clinical interventions. More AIT studies, especially pediatric studies, are required in order to either prove the reproducibility of positive results or to deny its effectiveness.

Cytomegalovirus seroprevalence in pregnant women in the western region of Romania: A large-scale study.

Cytomegalovirus (CMV) infection is the most common congenital infection worldwide, and remains a significant cause of the neurological deficiency and sensory deafness in developed countries. Maternal primary infection, reactivation or reinfection during pregnancy may lead to fetal infection and congenital CMV syndrome. The purpose of this study was to analyze the CMV seroprevalence according to demographic features of pregnant women in western Romania as well as the evolution of CMV immunity in two time intervals. IgG anti-CMV antibodies were tested in sera of 8,951 pregnant women during two successive intervals: 2008-2010 (n=1466) and 2015-2018 (n=7485). The CMV seroprevalence in women of reproductive age decreased from 94.6 to 91.80% in the last decade. The seroprevalence was higher in women from rural areas compared with those from urban areas. These results show that the western region of Romania has a low-risk profile for primary CMV infection during pregnancy due to a large number of seropositive women. However, this risk has increased in the last ten years, from 5.4 to 8.2%, which may show the need to implement a national screening program.