Lymphocyte-predominant lesional inflammatory infiltrates of the skin are associated with mucosal-dominant phenotype in pemphigus.

INTRODUCTION: Pemphigus is a potentially life-threatening autoimmune blistering disease. To date, studies assessing the association of histopathology with clinical phenotype are lacking. We sought to evaluate the main histopathologic findings and, also, the potential links between cutaneous inflammatory infiltrates and clinical characteristics in pemphigus. METHODS: We conducted a retrospective cohort study in patients diagnosed with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) in a referral center for autoimmune blistering diseases. RESULTS: A total of 124 patients were included in the study (97 had PV and 27 had PF). On biopsy specimens, PV was more frequently associated with the "row of tombstones" feature (36.1% vs. 11.1%, p = 0.013), and PF was associated with acanthosis (44.4% vs. 23.7%, p = 0.034). Acantholysis was found in the upper half of the epidermis in PF (96.3% vs. 5.15%, p < 0.001), as opposed to the lower half in PV (75.2% vs. 0%, p = 0.002). Patients with lymphocyte-predominant inflammatory infiltrates in lesional skin specimens presented with a higher frequency of the mucosal-dominant phenotype (25.5% vs. 9.1%, p = 0.014), higher-density cellular infiltrate (100% vs. 41.6%, p < 0.001), and more frequent acantholytic cells (42.6% vs. 23.4%, p = 0.025). Neutrophil-predominant infiltrates in specimens from lesional skin were linked to a milder disease based on median Pemphigus Disease Area Index (38.9% vs. 13.2%, p = 0.036) and Autoimmune Bullous Skin Disorder Intensity Score (20.2 vs. 36.3, p = 0.019), while eosinophil-predominant inflammatory infiltrates were more often associated with eosinophilic spongiosis (100% vs. 23.1%, p = 0.014). CONCLUSIONS: Lymphocyte-predominant infiltrates in lesional skin specimens of pemphigus patients predict a mucosal-dominant phenotype, while neutrophil-predominant infiltrates are associated with a milder disease.

Challenges and pitfalls between lichen planus pemphigoides and bullous lichen planus.

Lichen planus pemphigoides (LPP) and bullous lichen planus (BLP) are rare dermatoses, which are characterised by blisters and lichenoid lesions. Their clinical presentation is heterogenous, displaying overlapping features or mimicking other dermatological diseases. Therefore, diagnosis can often be challenging, requiring a thorough dermatological examination along with distinctive histological and immunopathological characteristics. Lichenoid degeneration of the basal epidermis exposes various antigens of the dermal-epidermal junction in LPP, resulting in the breakdown of immune tolerance, hence, the production of autoantibodies against type XVII collagen. Conversely, no pathogenic autoantibodies are detected in BLP. However, some cases of mucosal lichen planus might display immunopathological features suggestive of autoimmune blistering diseases. Therefore, a better understanding of the pathophysiology of these two distinct dermatoses is imperative. The aim of this review was to provide a summary of the current knowledge on the clinical hallmarks, diagnosis and available therapeutic options in LPP and BLP.

Phenotypic and genetic spectrum of incontinentia pigmenti - a large case series.

BACKGROUND AND OBJECTIVES: Incontinentia pigmenti is a rare X-linked dominantly inherited systemic disease affecting primarily the skin but also other neuroectodermal tissues such as teeth, hair, eyes, and the central nervous system. PATIENTS AND METHODS: This multicenter case series study was conducted at three European departments of Dermatology including 30 patients with incontinentia pigmenti. Twenty patients were evaluated clinically and genetically, another ten only genetically. RESULTS: The study included 28 females and two males with a median age of three years. Cutaneous manifestations were present in all 20 patients with clinical data. Stage I was observed in 90 % of those patients. Stage IV was observed as early as one year of age. Dental (81 %), hair (78 %) and neurological anomalies (53 %) were more frequent than previously reported. Fourteen skin biopsies showed typical features of the corresponding stage. Genetic testing of 24 patients revealed the common exon 4-10 deletion in 14 cases and seven other pathogenic variants, including three unpublished mutations. In another three cases, no genetic alterations were found. CONCLUSIONS: In this study, the phenotype ranged from only subtle cutaneous involvement to severe multisystemic disorders. Extracutaneous involvement should be evaluated at the time of diagnosis and in regular intervals, as some manifestations may develop over time.

Phänotypisches und genetisches Spektrum von Incontinentia pigmenti - eine große Fallserie.

HINTERGRUND: Incontinentia pigmenti ist eine seltene X-chromosomal dominant vererbte Systemerkrankung, die vor allem die Haut, aber auch andere neuroektodermale Gewebe wie Zähne, Haare, Augen und das zentrale Nervensystem betrifft. PATIENTEN UND METHODIK: Diese multizentrische Fallserienstudie wurde an drei europäischen Hautkliniken durchgeführt und umfasste 30 Patienten mit Incontinentia pigmenti. Zwanzig Patienten wurden klinisch und genetisch untersucht, weitere zehn nur genetisch. ERGEBNISSE: Die Studie umfasste 28 Frauen und zwei Männer mit einem medianen Alter von drei Jahren. Kutane Manifestationen zeigten sich bei allen 20 Patienten mit klinischen Daten. Stadium I wurde in 90 % dieser Patienten beobachtet. Stadium IV wurde bereits im Alter von einem Jahr beobachtet. Zahn- (81 %), Haar- (78 %) und neurologische Anomalien (53 %) waren häufiger als in bisherigen Berichten. Vierzehn Hautbiopsien zeigten typische Merkmale des entsprechenden Stadiums. Genetische Tests wurden bei 24 Patienten durchgeführt, von denen 14 die häufige Exon 4-10-Deletion und sieben andere pathogene Varianten aufwiesen, darunter drei unveröffentlichte Mutationen. In drei weiteren Fällen wurden keine genetischen Veränderungen gefunden. SCHLUSSFOLGERUNGEN: In dieser Studie reichte der Phänotyp von lediglich subtil ausgeprägter Hautbeteiligung bis hin zu schweren Multisystemerkrankungen. Die extrakutane Beteiligung sollte zum Zeitpunkt der Diagnose und in regelmäßigen Abständen evaluiert werden, da sich einige Manifestationen erst mit der Zeit entwickeln. SUMMARY: Background and objectives Incontinentia pigmenti is a rare X-linked dominantly inherited systemic disease affecting primarily the skin but also other neuroectodermal tissues such as teeth, hair, eyes, and the central nervous system. Patients and methods This multicenter case series study was conducted at three European departments of Dermatology including 30 patients with incontinentia pigmenti. Twenty patients were evaluated clinically and genetically, another ten only genetically. Results The study included 28 females and two males with a median age of three years. Cutaneous manifestations were present in all 20 patients with clinical data. Stage I was observed in 90 % of those patients. Stage IV was observed as early as one year of age. Dental (81 %), hair (78 %) and neurological anomalies (53 %) were more frequent than previously reported. Fourteen skin biopsies showed typical features of the corresponding stage. Genetic testing of 24 patients revealed the common exon 4-10 deletion in 14 cases and seven other pathogenic variants, including three unpublished mutations. In another three cases, no genetic alterations were found. Conclusions In this study, the phenotype ranged from only subtle cutaneous involvement to severe multisystemic disorders. Extracutaneous involvement should be evaluated at the time of diagnosis and in regular intervals, as some manifestations may develop over time.

A novel IKBKG mutation in a patient with incontinentia pigmenti and features of hepatic ciliopathy.

We describe a new mutation in exon 4 of IKBKG, encoding nuclear factor-kappa B in a patient with incontinentia pigmenti. The patient had a severe cholestatic liver disease with features of a ciliopathy and underwent liver transplantation. We cannot establish a link between incontinentia pigmenti, a very rare disease, and hepatic ciliopathy, but we suggest that hepatic evaluation should be considered in patients with incontinentia pigmenti.

Diffuse cutaneous bullous mastocytosis with IgM deposits at dermo-epidermal junction.

Cutaneous mastocytosis is a disease characterized by the infiltration and proliferation of mast cells in the skin. In children, the most common form of presentation is urticaria pigmentosa, while the diffuse cutaneous bullous mastocytosis is one of the rarest subtypes seen. The aim of this paper is to present a case of diffuse bullous mastocytosis with detection of IgM deposits at dermo-epidermal junction using direct immunofluorescence (DIF) microscopy. The diagnosis of diffuse bullous mastocytosis is a challenge, and DIF microscopy is necessary in order to exclude an autoimmune bullous disorder. However, IgM deposits at dermo-epidermal junction can be nonspecific, being found in a variety of skin disorders. A 6-month-old girl presented with bullous lesions and erosions on the scalp and the trunk. During hospitalization, further bullous lesions appeared, along with generalized erythrodermia. Skin biopsy revealed aspects of urticaria pigmentosa. Taking into account the clinical findings, the case was enclosed as bullous mastocytosis. Treatment included the avoidance of trigger factors, and administration of antihistamines along with a short-term course of systemic steroids. The evolution was favorable, with remission of the existing lesions and without occurrence of new ones.

An overview of cutaneous squamous cell carcinoma imaging diagnosis methods.

Cutaneous squamous cell carcinoma, a type of non-melanoma skin cancer, is a form of keratinocyte carcinoma that stands as one of the most prevalent cancers, exhibiting a rising frequency. This review provides an overview of the latest literature on imaging methods for diagnosing squamous cell carcinoma (SCC) and actinic keratosis (AK). It discusses the diagnostic criteria, advantages, and disadvantages of various techniques such as dermatoscopy, skin ultrasound (US), in vivo and ex-vivo reflectance confocal microscopy (RCM), and line-field confocal optical coherence tomography (LC-OCT). These methods offer benefits including non-invasiveness, rapidity, comprehensive lesion imaging, and enhanced sensitivity, but face challenges like high costs and the need for specialized expertise. Despite obstacles, the use of these innovative techniques is expected to increase with ongoing technological advancements, improving diagnosis and treatment planning for keratinocyte carcinomas. Standardizing LC-OCT imaging algorithms for AK, Bowen's disease, and SCC remains an area for further research.

Preoperative bimodal imaging evaluation in finding histological correlations of in situ, superficial spreading and nodular melanoma.

Background: The aim of this study is to correlate the diagnostic criteria described in dermoscopy, ultrasonography (US), and histology of the most common types of cutaneous melanoma (CM). Methods: We conducted a prospective study including 40 CM cases, which were analyzed by dermoscopy using the Delta 30 dermatoscope and Vidix 4.0 videodermoscope, by ultrasound (US) using a high-resolution 20 MHz linear probe, along with histopathological analysis. Results: The study involved 40 patients with histopathologically confirmed CM, comprising 10 nodular melanomas (NM), 21 superficial spreading melanomas (SSM), and nine in situ melanomas (MIS). US measurements of tumor thickness exhibited strong correlations with the histopathological Breslow index (BI), particularly in the NM and SSM groups. A notable correlation was observed between the presence of ulceration in histopathology and ultrasonography. Dermoscopic analysis revealed significant associations between specific features and CM types. For instance, the presence of an atypical network, irregular globules, irregular dots, prominent skin margins, angulated lines/polygons, dotted and short linear vessels, and negative network correlated with a median BI ≤ 0.5 mm. Conversely, the presence of blue-white veil, atypical vessels, blue-black color, and milky red color were associated with a median BI ≥ 2.3 mm. Furthermore, regression observed in histopathology correlated with regression identified in dermoscopy, we also found statistical correlations between the presence of vascularization at US with the high Clark level, and the presence of prominent skin markings at dermoscopy. The presence of histopathological regression was more frequently associated with tumors that had precise margins, absent vascularization and with those that did not have ulceration on US. The high mitotic rate was associated with tumors that presented imprecise margins, increased vascularization and US detectable ulceration. Conclusion: Innovative CM diagnosis using non-invasive methods like dermoscopy and ultrasound may enhance accuracy and treatment guidance by assessing lesion characteristics.

Imaging Approach in the Diagnostics and Evaluation of the Psoriasis Plaque: A Preliminary Study and Literature Review.

(1) Background: the aim of the study was to demonstrate its usefulness in the field of imaging evaluation of plaque morphology in psoriasis vulgaris, with an emphasis on the use of confocal microscopy and other advanced skin-imaging techniques. (2) Methods: we conducted a prospective study over two years (July 2022-April 2024), on patients diagnosed with moderate or severe psoriasis vulgaris, treated in the dermatology department of our institution. We selected 30 patients, of whom 15 became eligible according to the inclusion and the exclusion criteria. A total of 60 psoriasis plaques were analyzed by dermatoscopy using a Delta 30 dermatoscope and Vidix 4.0 videodermoscope (VD), by cutaneous ultrasound (US) using a high-resolution 20 MHz linear probe, and by confocal microscopy, along with histopathological analysis. (3) Results: the study included fifteen patients with vulgar psoriasis, diagnosed histopathologically, of whom six were women and nine were men, with an average age of 55. Between two and six plaques per patient were selected and a total of sixty psoriasis plaques were analyzed by non-invasive imaging techniques. Twelve lesions were analyzed with ex vivo fluorescence confocal microscopy (FCM), compared to histology. US showed that the hyperechoic band and the lack of damage to the subcutaneous tissue were the most common criteria. The epidermis and dermis were found to be thicker in the area of psoriasis plaques compared to healthy skin. Dermatoscopy showed that the specific aspect of psoriasis plaques localized on the limbs and trunk was a lesion with an erythematous background, with dotted vessels with regular distribution on the surface and covered by white scales with diffuse distribution. The presence of bushy vessels with medium condensation was the most frequently identified pattern on VD. Good correlations were identified between the histological criteria and those obtained through confocal microscopy. (4) Conclusions: the assessment and monitoring of patients with psoriasis vulgaris can be conducted in a more complete and all-encompassing manner by incorporating dermatoscopy, ultrasonography, and confocal microscopy in clinical practice.

Is Mir-205 a possible biomarker for evaluating treatment response in psoriasis?

Psoriasis is a chronic skin disease that affects a significant number of patients and can severely impair quality of life. Although the diagnosis is normally clinical, paraclinical determination can occasionally be useful either in differential diagnosis or in evaluating the inflammatory response to treatment. MicroRNAs (miRNAs) are small non-coding parts of the RNA family that regulate gene expression and may have an important role as biomarkers in evaluating treatment response. The dysregulation of miRNAs has been well studied in other diseases, especially in oncology, but their role in chronic skin conditions such as psoriasis is still not fully understood. This study aims to evaluate the levels of three miRNAs (miR-155, miR-210, and miR-205) in patients with psoriasis, treated either systemically or topically, compared to a control group, and to assess the possible relationship between miRNA levels and systemic therapy. Our findings show a constant dysregulation of miR-205 in patients with psoriasis, with significantly higher levels compared to the control group, which can be explained as conferring a protective effect to treated patients. Further studies are needed in order to fully understand the role of miRNAs in the physiopathology of psoriasis and even, potentially, to provide more targeted genetic therapies in the future.

Epidemiological Characteristics of Inherited Epidermolysis Bullosa in an Eastern European Population.

Background/Objectives: Epidermolysis bullosa (EB) is a hereditary condition characterized by skin and mucosal fragility, with various degrees of severity. This study's objectives are to obtain updated epidemiological data that will help identify the specific types and subtypes of EB, determine the case distribution in Romania, and establish the incidence and prevalence of the condition. Methods: This population-based observational study included Romanian patients and collected data from 2012 to 2024. The following information was recorded: date of birth, status (deceased or alive), date of death (if applicable/available), sex, county, and city of residence, EB type and subtype if available, diagnosis (clinical and/or immunofluorescence mapping, transmission electron microscopy, genetic molecular analysis), affected genes, inheritance, and affected family members. Results: The study included a total of 152 patients. The point prevalence (the proportion of the population with a condition at a specific point in time) and the incidence of EB in Romania were 6.77 per million population and 24.23 per million live births, respectively. EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), Kindler EB (KEB), and not otherwise specified EB, as well as EB (NOS), were the main types of the condition identified in 21%, 3%, 63%, 2%, and 11% of the total cases. The point prevalence and incidence for the same time intervals were 1.58 and 5.28 in EBS, 0.10 and 1.76 in JEB, 4.72 and 12.34 in DEB, 0.16 and 0 in KEB, and 0.21 and 4.85 in EB (NOS). Conclusions: The study provides updated epidemiological data for Romania and underlines the necessity for accurate diagnosis, facilitated by access to genetic molecular testing and better reporting systems.

Blood-Count-Derived Inflammatory Markers as Predictors of Response to Biologics and Small-Molecule Inhibitors in Psoriasis: A Multicenter Study.

Background: Psoriasis is an immune-mediated chronic disorder associated with various comorbidities. Even though biologics and small-molecule inhibitors are the mainstay treatment for moderate-to-severe psoriasis, there is no current consensus regarding which agent should be used for a specific type of patient. This paper aims to test the reliability of blood-count-derived inflammatory markers in assessing treatment response to biologics and small-molecule inhibitors in psoriasis. Material and Methods: Bio-naïve adult patients diagnosed with chronic plaque psoriasis fulfilling the inclusion criteria were enrolled. They were divided into study subgroups based on treatment of choice, and blood-count-derived inflammatory markers were analyzed at baseline, three-month, six-month, and at twelve-month visits. Results: A total of 240 patients were included. The highest number of patients underwent treatment with ixekizumab. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-monocyte ratio (PMR), monocyte-to-lymphocyte ratio (MLR), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), and aggregate index of systemic inflammation (AISI) all varied significantly (p < 0.005) between the four visits. The psoriasis area severity index (PASI) score correlated with PLR, d-NLR, and SII, while the psoriasis scalp severity index (PSSI) score correlated with AISI and SIRI. More than half of patients reached the target goal of PASI90 at the six-month visit. A total of 77 patients were super-responders, with the highest number undergoing treatment with ixekizumab. Higher baseline values of d-NLR and SIRI are independent predictors of the super-responder status. Conclusions: Blood-count-derived inflammatory markers can serve as indicators of treatment response to biologics in psoriasis, while d-NLR and SIRI were independent predictors of super-responders in our study.

Ultrasound in non-tumoral pathology of the skin.

Skin ultrasound (US) is a relatively new imaging technique, for which interest has grown significantly in the last decade. Properties such as mobility, real-time imaging and lack of irradiation or sedation, have made it a useful tool in completing the clinical examination. The use of probes of different frequencies has managed to improve the US technique, offering the possibility of obtaining high quality images. Thus, by using high-frequency and ultra-high frequency US, subclinical information can be obtained with a wide applicability in dermatological pathology. In this paper we aim to discuss the main uses of skin US in non-tumoral pathology (inflammatory and autoimmune pathology).

Advancements in Basal Cell Carcinoma Diagnosis: Non-Invasive Imaging and Multimodal Approach.

(1) Background: The aim of this study was to correlate the diagnostic criteria described in dermatoscopy, ultrasonography (US), ex vivo confocal microscopy, and histology to the most common subtypes of basal cell carcinoma (BCC). (2) Methods: We conducted a prospective study including 46 BCC cases, which were analyzed with dermatoscopy using the Delta 30 dermatoscope and Vidix 4.0 videodermoscope, with US using a high-resolution 20 MHz linear probe, with confocal microscopy, along with histopathological analysis. (3) Results: This study categorized BCC by histological subtype, with nodular being the most common (84.8%) and various other subtypes represented. US measurements of tumor thickness correlated strongly with the histopathological depth of invasion index (DI). Dermatoscopy analysis revealed significant associations between specific features and BCC subtypes. The DI was directly related to arborized vessels but inversely related to short, fine telangiectasias, maple-leaf-like areas, and spoke-wheel areas. The presence of ulceration was directly related to the DI. Confocal microscopy images exhibited several characteristics, including fluorescence, nuclear crowding, peripheral palisading, clefting, increased nuclear-cytoplasmic (N/C) ratio, and a "cauliflower-like" appearance. (4) Conclusion: The advanced detection of BCC through imagistic techniques like dermatoscopy, confocal microscopy, and ultrasound improves the diagnosis and may offer valuable insights for treatment in the future by evaluating lesion characteristics.

The Psoriasis Disability Index in Romanian Psoriasis Patients during COVID-19 Pandemic: Contribution of Clinical and Psychological Variables.

BACKGROUND: Psoriasis is one of the most frequent chronic inflammatory skin diseases and has a negative impact on the interpersonal relationship and psychosocial well-being. The aims of this study were to examine the effects of intensity of pruritus on quality of life and depression, to investigate the relationship between anger, self-esteem, and depression, and to compare patients with early and late onset of psoriasis. As our study was carried out during the COVID-19 pandemic, we aimed also to investigate the safety concerns and anxiety related to COVID-19 in psoriasis patients. METHODS: This cross-sectional study included 137 patients diagnosed with plaque psoriasis. The patients were classified as early-onset (age < 30 years) and late-onset psoriasis (age ≥ 30 years). Duration of disease, pruritus scores, and socio-demographic characteristics were recorded. Measures included the State-Trait Anger Expression Inventory (STAXI), Rosenberg Self-Esteem Scale, Beck Depression Inventory (BDI-II), Psoriasis Disability Index (PDI), and Fear and anxiety in relationship with COVID-19 Scale were used for determining anger, anger expression style, self-esteem, depression, anxiety, and quality of life. RESULTS: The psoriasis patients had a lower score for self-esteem than the normative data from the Romanian general population. The average scores for state anger and trait anger are similar to the normative data from the Romanian general population, but the scores for anger-in and anger-out are higher. Patients with early onset had higher depression scores and lower quality of life. Self-esteem correlates negatively with depression, anger, severity of disability due to psoriasis, number of affected areas, and duration of disease. Lower level of self-esteem led to increased anger. CONCLUSIONS: Reduced self-esteem, increased anger levels, and depression are present in psoriasis patients. The effective treatment of psoriasis must, therefore, consist of a multidisciplinary approach, in which the personalized treatment of the skin condition is as important as the adjuvant therapies that reduce the patients' stress level.

Survival and prognostic factors in bullous pemphigoid: A retrospective cohort study.

Background Bullous pemphigoid is the most common subepidermal autoimmune blistering disease. Till now, the reported prognostic factors in bullous pemphigoid vary considerably. Aims The purpose of this study was to determine the overall survival rate and prognostic factors in bullous pemphigoid. Methods We conducted a retrospective cohort study on newly diagnosed bullous pemphigoid patients between July 2001 and November 2019 in a referral unit for autoimmune blistering skin diseases in Romania. Results One hundred forty-eight patients were included in the study. The Kaplan-Meier overall survival rates at 1, 3, 5 and 10 years were respectively 74.2% (95% confidence interval, 67.5-81.6%), 53.4% (45.7-62.2%), 43.6% (35.9-53%) and 31.3% (23.5-41.7%). The median follow-up among survivors was 48 months (interquartile range: 11-150). Ninety (60.8%) patients died during the follow-up period; of them, 38 (42.2%) had active disease at the time of death. Advanced age, neurological diseases, valvular heart disease, malignancies, use of statins, skin infections and extensive cutaneous involvement were linked to poorer outcomes, while the use of topical corticosteroids was associated with increased overall survival. Limitations This study lacks a control cohort to validate the obtained results. It was conducted in a retrospective manner in a single centre. In addition, indirect immunofluorescence microscopy was not performed in all patients. Conclusion Beyond ageing and neurological comorbidities, the prognosis of bullous pemphigoid patients was significantly influenced by the presence of skin infections, valvular heart disease, use of statins and extensive cutaneous involvement. Topical corticosteroid treatment was associated with increased survival in these patients.

The relevance of complement in pemphigoid diseases: A critical appraisal.

Pemphigoid diseases are autoimmune chronic inflammatory skin diseases, which are characterized by blistering of the skin and/or mucous membranes, and circulating and tissue-bound autoantibodies. The well-established pathomechanisms comprise autoantibodies targeting various structural proteins located at the dermal-epidermal junction, leading to complement factor binding and activation. Several effector cells are thus attracted and activated, which in turn inflict characteristic tissue damage and subepidermal blistering. Moreover, the detection of linear complement deposits in the skin is a diagnostic hallmark of all pemphigoid diseases. However, recent studies showed that blistering might also occur independently of complement. This review reassesses the importance of complement in pemphigoid diseases based on current research by contrasting and contextualizing data from in vitro, murine and human studies.

Romanian experience in child celiac disease diagnosis.

Last consensus in celiac disease in 2008 conducted under the aegis of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition jointly with North American Society of Pediatric Gastroenterology, Hepatology and Nutrition reveals the following: "celiac disease is a chronic immune-mediated enteropathy characterized by sensitization to gluten. That can affect any organ or system, with a wide range of clinical manifestations of variable severity". Thus, in recent years, clinical picture of celiac disease has changed the old paradigm--bowel disease with villous atrophy and malnutrition, being replaced with the new paradigm--multi-organ autoimmune disease, affecting many organs and systems throughout but with more less specific symptoms, which undiagnosed leads to delayed diagnosis, at a late-onset disease and long-term major complications as the risk of cancer. According to this consensus "the serological diagnosis of celiac disease is based on high sensitivity and specificity tests", but in line with changing clinical features of celiac disease, its diagnosis has undergone significant changes in recent years. These changes in the diagnosis of celiac disease, we have decided to analyze them.

MicroRNAs in pemphigus and pemphigoid diseases.

Autoimmune blistering diseases are a heterogenous group of dermatological disorders characterized by blisters and erosions of the skin and/or mucous membranes induced by autoantibodies against structural proteins of the desmosome or the dermal-epidermal adhesion complex including the hemidesmosome. They consist of the two major disease groups, pemphigus and pemphigoid diseases (PPDs). The diagnosis is based on clinical findings, histopathology, direct immunofluorescence, and detection of circulating autoantibodies. The pathogenesis is not fully elucidated, prognostic factors are lacking, and to date, there is no cure for PPDs. MicroRNAs (miRNAs) represent small, non-coding RNAs that play a pivotal role in the posttranscriptional regulation of gene expression. Their dysfunction was highlighted to play a significant role in the pathogenesis of various diseases. Even though a link between miRNAs and autoimmune blistering diseases had been suggested, the research of their involvement in the pathogenesis of PPDs is still in its infancy. miRNAs hold promise for uncovering new layers in the pathogenesis of PPDs, in order to improve diagnosis and also to develop potential therapeutic options. In the current article, we provide an overview regarding current knowledge of miRNAs in terms of complex pathogenesis of PPDs, and, also, their potential role as biomarkers, predictive factors and therapeutic targets.

Novel concepts in psoriasis: histopathology and markers related to modern treatment approaches.

Psoriasis is a chronic autoimmune disease affecting over 2% of the worldwide population. From an anatomopathological point of view, psoriasis is characterized by immune cells infiltration, epidermal hyperproliferation, and abnormal keratinocyte differentiation. Understanding the pathogenesis of psoriasis will allow clinicians to manage this complex disease. Under these conditions, the application of effective treatments requires a thorough knowledge of all the pathogenetic mechanisms that lead to psoriasis. Numerous immunopathological pathways play crucial roles in the development of new therapies, such as biological therapies, which have been a breakthrough in psoriasis's treatment. Pharmacogenetics is an essential factor in the patient's response to treatment. One important pathway targeted by modern treatments is the interleukin (IL)-23∕T-helper (Th)17 axis. Like IL-17 inhibitors, IL-23 blockers are a very effective therapy for this autoimmune disease. It is considered that micro-ribonucleic acids (microRNAs) are the starting point for any autoimmune disease. Studying certain microRNA (miR) involved in the inflammatory pathway in psoriasis can find direct targets to future treatments that can even be more specific than actual biological therapies. As such, miR-210 has proven to be up-regulated in psoriasis, also leading to the up-regulation of the Th1∕Th17 axis. On the other hand, miR-187 was found to be down-regulated, influencing the outcome of psoriasis by increasing the proliferation of IL-6 stimulated keratinocytes and consecutively generating epidermal thickening. In this review, we are aiming to do an up-to-date briefing of psoriasis histopathology and pharmacogenetic factors that are considered for the accurate evaluation of treatment response.