ABSTRACT
There is evidence that the concomitance of psoriasis and obesity may originate from the interplay between multiple genetic pathways and involve gene−gene interactions. The aim of this study was to compare the genetic background related to obesity among psoriatic patients versus healthy controls by means of a Genome-Wide Association Study (GWAS). A total of 972 psoriatic patients and a total of 5878 healthy donors were enrolled in this study. DNA samples were genotyped for over 500,000 single nucleotide polymorphisms (SNPs) using Infinium CoreExome BeadChips (Illumina, San Diego, CA, USA). Statistical analysis identified eleven signals (p < 1 × 10−5) associated with BMI across the study groups and revealed a varying effect size in each sub-cohort. Seven of the alternative alleles (rs1558902 in the FTO gene, rs696574 in the CALCRL gene, as well as rs10968110, rs4551082, rs4609724, rs9320269, and rs2338833,) are associated with increased BMI among all psoriatic patients and four (rs1556519 in the ITLN2 gene, rs12972098 in the AC003006.7 gene, rs12676670 in the PAG1 gene, and rs1321529) are associated with lower BMI. The results of our study may lead to further insights into the understanding of the pathogenesis of obesity among psoriatic patients.
Subject(s)
Genome-Wide Association Study , Psoriasis , Adaptor Proteins, Signal Transducing/genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Body Mass Index , Genetic Predisposition to Disease , Genotype , Humans , Lectins/genetics , Membrane Proteins/genetics , Obesity/genetics , Overweight/genetics , Polymorphism, Single Nucleotide , Psoriasis/geneticsABSTRACT
OBJECTIVE: Pruritus is an important symptom frequently accompanying various inflammatory skin conditions and some recent data indicated that it may be associated with autoimmune connective tissue diseases. The aim of this study was to assess the frequency and clinical presentation of itch in CLE. METHODS: A multinational, prospective, cross-sectional study was performed to assess the prevalence, intensity and clinical characteristic of pruritus in various subtypes of CLE. A total of 153 patients with active CLE lesions were included. Their age ranged between 17 and 82 years (mean 49.8 ± 15.4 years), and 115 patients (75.2%) were women. The disease activity and damage were assessed according to the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Pruritus severity was assessed with Numeric Rating Scale (NRS) and the 12-Item Pruritus Severity Scale. Dermatology Life Quality Index and EQ-5D questionnaire were used to measure quality of life. RESULTS: Pruritus was present in 116 (76.8%) of patients of whom half had NRS scoring equal or above 4 points indicating moderate or severe pruritus. Most commonly itch was localized on the scalp, face (excluding ears and nose) and arms (40.5%, 36.2%, 31.9%, respectively). Sensations connected with pruritus were most frequently described as burning, tingling and like ants crawling feeling, but 31.9% patients described it as "pure itch". More than half of patients reported that pruritus was present every day, and it was most frequent during the evenings. The pruritus scoring and the CLASI activity score were significantly correlated (r = 0.42, p = 0.0001), while no correlation was found with the CLASI damage score (p = 0.16). Both the maximum and average itch intensity were correlated with systemic lupus erythematosus (SLE) activity measured with the Systemic Lupus Erythematosus Disease Activity Index. CONCLUSIONS: Pruritus is a common, but frequently overlooked symptom of CLE. Its intensity correlates with the activity of CLE, but not with the skin damage. In more than a half of patients it occurs on a daily basis. The correlation between the intensity of pruritus and the activity of the skin lesions and the systemic involvement indicate that pruritus could be an individual indicator of both SLE and CLE activity.
Subject(s)
Lupus Erythematosus, Cutaneous , Pruritus , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Lupus Erythematosus, Cutaneous/complications , Lupus Erythematosus, Cutaneous/epidemiology , Male , Middle Aged , Prospective Studies , Pruritus/diagnosis , Pruritus/epidemiology , Pruritus/etiology , Quality of Life , Severity of Illness Index , Young AdultABSTRACT
Generalized pustular psoriasis (GPP) is a severe, relapsing, immune-mediated disease characterized by the presence of multiple sterile pustules all over the body. The exact pathomechanisms behind GPP remain elusive, although increased interest in the genetic basis and immunological disturbances have provided some revealing insights into the underlying signaling pathways and their mutual interaction. The genetic background of GPP has been thoroughly investigated over the past few years. The conducted studies have identified genetic variants that predispose to pustular forms of psoriasis. The loss-of-function mutation of the interleukin 36 receptor antagonist gene, along with rare gain-of-function mutations in the gene that encodes the keratinocyte signaling molecule (CARD14), are examples of the uncovered abnormalities. Interleukin 36 (IL-36), along with neutrophils, is now considered a central cytokine in GPP pathogenesis, with IL-36 signaling providing a link between innate and adaptive immune responses. More recently, a new concept of inflammation, caused by a predominantly genetically determined abnormal activation of innate immune response and leading to inflammatory keratinization, has arisen. GPP is currently considered a representative of this novel group of skin conditions, called autoinflammatory keratinization diseases. As no therapeutic agents have been approved for GPP to date in the United States and Europe, the novel anti-IL-36R antibodies are particularly promising and may revolutionize management of the disease.
Subject(s)
Psoriasis/immunology , Adaptive Immunity , Antibodies, Monoclonal/therapeutic use , Humans , Immunity, Innate , Psoriasis/genetics , Psoriasis/therapyABSTRACT
Prior to the introduction of antiretroviral therapy, the concomitant occurrence of sarcoidosis and human immunodeficiency virus (HIV) was extremely rare. Today, an increased prevalence of sarcoidosis as a result of immune reconstitution syndrome (IRIS) is observed in HIV patients. A 37-year-old male patient that was co-infected with HIV and hepatitis C had a 6month history of gradually progressive asymptomatic periorbital erythematous plaques and papules. Routine clinical examinations were normal. Skin punch biopsy taken from the upper portion of the right cheek showed several non-caseating dermal granulomas with multinucleated giant cells, enabling unequivocal histological diagnosis. Based on the clinical picture and histological findings, the patient was diagnosed with cutaneous sarcoidosis. This case study underlines the change in possible rheumatological and dermatological comorbities in HIV-positive patients treated with highly active antiretroviral therapy. Therefore, physicians treating HIV infections should be familiar with the definition of IRIS.
Subject(s)
Granuloma/complications , HIV Infections/complications , Hepatitis C/complications , Sarcoidosis/diagnosis , Adult , Antiretroviral Therapy, Highly Active/methods , Glucocorticoids/administration & dosage , Granuloma/diagnosis , Granuloma/drug therapy , HIV Infections/drug therapy , HIV Infections/immunology , Humans , Immune Reconstitution Inflammatory Syndrome , Male , Sarcoidosis/complications , Sarcoidosis/drug therapyABSTRACT
Psoriasis is a multifactorial disease in which genetic, environmental and epigenetic factors regulating gene expression play a key role. In the "genomic era", genome-wide association studies together with target genotyping platforms performed in different ethnic populations have found more than 50 genetic susceptible markers associated with the risk of psoriasis which have been identified so far. Up till now, the strongest association with the risk of the disease has been proved for HLA-C*06 gene. The majority of other psoriasis risk SNPs are situated near the genes encoding molecules involved in adaptive and innate immunity, and skin barrier function. Many contemporary studies indicate that the epigenetic changes: histone modification, promoter methylations, long non-coding and micro-RNA hyperexpression are considered as factors contributing to psoriasis pathogenesis as they regulate abnormal keratinocyte differentiation and proliferation, aberrant keratinocytes - inflammatory cells communication, neoangiogenesis and chronic inflammation. The circulating miRNAs detected in the blood may become specific markers in the diagnosis, prognosis and response to the treatment of the disease. The inhibition of expression in selected miRNAs may be a new promising therapy option for patients with psoriasis.
ABSTRACT
Psoriasis is a systemic disease that is strictly connected with metabolic disorders (insulin resistance, atherogenic dyslipidemia, arterial hypertension, and cardiovascular diseases). It occurs more often in patients with a more severe course of the disease. Obesity is specially an independent risk factor and it is associated with a worse treatment outcome because of the high inflammatory activity of visceral fatty tissue and the production of inflammatory mediators involved in the development of both psoriasis and metabolic disorders. However, in psoriasis the activation of the Th17/IL-17 and the abnormalities in the Th17/Treg balance axis are observed, but this pathomechanism does not fully explain the frequent occurrence of metabolic disorders. Therefore, there is a need to look for better biomarkers in the diagnosis, prognosis and monitoring of concomitant disorders and therapeutic effects in psoriasis. In addition, the education on the use of a proper diet as a prophylaxis for the development of the above disorders is an important element of holistic care for a patient with psoriasis. Diet may affect gene expression due to epigenetic modification which encompasses interactions of environment, nutrition and diseases. Patients with psoriasis should be advised to adopt proper diet and dietician support.
ABSTRACT
Psoriasis is a common, chronic, inflammatory, immune-mediated skin disease affecting about 2% of the world's population. According to current knowledge, psoriasis is a complex disease that involves various genes and environmental factors, such as stress, injuries, infections and certain medications. The chronic inflammation of psoriasis lesions develops upon epidermal infiltration, activation, and expansion of type 1 and type 17 Th cells. Despite the enormous progress in understanding the mechanisms that cause psoriasis, the target cells and antigens that drive pathogenic T cell responses in psoriatic lesions are still unproven and the autoimmune basis of psoriasis still remains hypothetical. However, since the identification of the Th17 cell subset, the IL-23/Th17 immune axis has been considered a key driver of psoriatic inflammation, which has led to the development of biologic agents that target crucial elements of this pathway. Here we present the current understanding of various aspects in psoriasis pathogenesis.
ABSTRACT
Psoriatic arthritis (PsA) is a chronic, progressive, inflammatory arthropathy associated with psoriasis as well as a complex pathogenesis. Genetic and environmental factors trigger the development of the immune-mediated auto-inflammatory response in different sites: skin, bone marrow, entheses and synovial tissues. Studies of the last two decades have changed the view of PsA from a mild, non-progressive arthritis to an inflammatory systemic disease with serious health consequences, not only associated with joint dysfunction, but also with an increased risk of cardiovascular disease and socioeconomic consequences with significantly reduced quality of life. The joint damage starts early in the course of the disease, thus early recognition and treatment with modern biological treatments, which may modify the natural history and slow down progression of this debilitating disease, is essential for the patient long-term outcome.
ABSTRACT
Rheumatoid neutrophilic dermatitis is a rare extra-articular manifestation of rheumatoid arthritis, both seropositive and seronegative for rheumatoid factor. The condition most often presents as symmetric erythematous papules, nodules, plaques, and urticaria-like lesions in patients with severe, long-lasting rheumatoid arthritis. We report a case of a 65-year-old man with well-controlled rheumatoid arthritis, who developed rheumatoid neutrophilic dermatitis on the right lower leg. The biopsy of skin lesions revealed an intense, neutrophilic dermal infiltrate, microabscesses, and leukocytoclasis without vasculitis. The patient responded well to pulses of intravenous methylprednisolone. We present this patient due to the rarity of the disease and atypical unilateral manifestation involving the flexural surfaces of the lower leg.
ABSTRACT
A number of rheumatic disorders may appear as paraneoplastic syndromes, the most common being dermatomyositis or polymyositis. Systemic sclerosis is associated with a slightly increased risk of cancer, although its direct association with malignancies is controversial. We describe a case of a 57-year-old male with rectal adenocarcinoma and systemic sclerosis. Close temporal relationship between the initial presentation and parallel course of both conditions, as well as atypically rapid progression of systemic sclerosis symptoms, were observed in the reported case. The strict relation between these two conditions suggested that systemic sclerosis was a paraneoplastic syndrome rather than a concomitant morbidity in the presented patient. Current literature on systemic sclerosis coexisting with colorectal tumours is very limited, especially in the paraneoplastic setting.
ABSTRACT
INTRODUCTION: Due to a wide array of dermatologic manifestations, assessment of disease severity in cutaneous lupus erythematosus (CLE) remains challenging. Given a need for some standardization in this field, we conducted a worldwide questionnaire-based study among physicians experienced in CLE management. AIM: We asked about CLE assessment, their prophylactic measures advised to patients, and treatment recommendations. MATERIAL AND METHODS: A total of 83 completed questionnaires were received. Participating physicians recommended assessing disease severity at each patient's visit (39.1%), monthly (4.9%) or at least every third month (17.3%). Almost half of the responding physicians (47.0%) waited 2-3 months before identifying a specific treatment option as not effective. RESULTS: The vast part of the participants informed their patients about of the risks of sun exposure and advised adequate preventive measures. Smoking was less frequently a matter of discussion between physicians and their patients. Recommendations for the timing of CLE severity assessment likely depends on disease severity and the type of therapeutic intervention. CONCLUSIONS: Proper patient education about effective prophylactic measures should be included during routine CLE patient consultations.
ABSTRACT
INTRODUCTION: Lupus erythematosus (LE) shows a wide variety of clinical manifestations, skin involvement being one of the most important. AIM: To analyze the clinical presentation of cutaneous variants of lupus erythematosus in terms of skin lesion spectrum and extracutaneous involvement. MATERIAL AND METHODS: A total of 64 patients with cutaneous LE (CLE) were included. The study was based on the "Core Set Questionnaire" developed by the European Society of Cutaneous Lupus Erythematosus (EUSCLE). Clinical severity of skin lesions was evaluated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). All results were subjected to statistical analysis. RESULTS: Fifteen (23.4%) patients had an acute CLE (ACLE), 26 (40.6%) subacute CLE (SCLE) and 21 (32.8%) chronic CLE (CCLE). Two (3.2%) individuals only demonstrated urticarial vasculitis as a cutaneous manifestation of LE and these patients were excluded. Patients with ACLE were characterized by the earliest onset of the disease (mean age of 31.9 ±15.0 years; p < 0.001). On average, 4.8 ±1.8 criteria of systemic LE were found in the ACLE group compared to 2.7 ±1.3 criteria in SCLE and 2.5 ±1.5 criteria in CCLE (p < 0.001). The highest activity of skin lesions according to CLASI was found in the SCLE group (p = 0.002). On the other hand, the most severe skin damage was observed in CCLE (p < 0.01). CONCLUSIONS: Each variant of CLE differs significantly from the others in respect of various aspects of clinical manifestations. Due to a number of different variants of LE skin lesions, a unified classification of CLE still remains a challenge.
Subject(s)
Blood Vessels/pathology , Collagen Diseases/complications , Skin Diseases, Vascular/complications , Skin/blood supply , Telangiectasis/etiology , Adult , Aged , Asymptomatic Diseases , Biopsy , Collagen Diseases/pathology , Dermoscopy , Disease Progression , Female , Humans , Male , Skin Diseases, Vascular/pathology , Telangiectasis/pathology , Time FactorsABSTRACT
The present multi-center, long-term, real-life study made an attempt to assess the efficacy of risankizumab in the treatment of moderate-to-severe plaque psoriasis. The study comprised 185 patients from 10 Polish dermatologic departments undergoing risankizumab treatment. The disease severity was measured using the Psoriasis Area and Severity Index (PASI) before the start of the risankizumab treatment and next at the defined timepoints, i.e., 4, 16, 28, 40, 52 and 96 weeks of treatment. The percentage of patients achieving PASI90 and PASI100 responses as well as the PASI percentage decrease at the defined timepoints were calculated, and correlations with clinical characteristics and therapeutic effect were analyzed. The number of patients evaluated at the defined timepoints was: 136, 145, 100, 93, 62, and 22 at 4, 16, 28, 40, 52 and 96 weeks of treatment, respectively. At 4, 16, 28, 40, 52 and 96 weeks, the PASI90 response was achieved in 13.2%, 81.4%, 87.0%, 86.0%, 88.7% and 81.8% of patients, whereas the PASI100 response was achieved in 2.9%, 53.1%, 67.0%, 68.8%, 71.0% and 68.2% of patients, respectively. Our study revealed a significant negative correlation between a decrease in the PASI and the presence of psoriatic arthritis as well as the patient's age and duration of psoriasis at several timepoints throughout the observation period.
ABSTRACT
The epidemiology of psoriasis has not been widely assessed in Polish population so far. This study aimed to investigate psoriasis epidemiological situation by evaluating disease course and severity, management, comorbidities, environmental factors, and knowledge about this disorder among psoriatic patients in Poland. A cross-sectional cohort population-based study enrolled 1080 psoriatic patients and 1200 controls. The mean age of psoriasis onset was 27.6 years; 78.24% had type I psoriasis. Positive family history of psoriasis was reported in 44.81% of patients, whereas itch was reported in vast majority of patients (83.33%). Based on PASI score moderate psoriasis was the most common in studied group (mean 12.63 ± 9.33, range 0−67.2). The DLQI score (12.01 ± 7.41, range 0−30.0) indicated a very large effect of psoriasis on the quality of life. Hypertension was the most prevalent comorbidity (33.80%), followed by obesity (16.85%) and dyslipidemia (11.85%). Stress was the foremost cause of disease exacerbation (66.20%); however, infections (44.07%) and seasonal changes (45.09%) had also an impact on the course of psoriasis. Psoriatic patients were more often smokers (37.59%) vs. general population (27.50%; p < 0.0001). In conclusion, epidemiological studies help clinicians in better disease and patient understanding, which may translate into better management and patient compliance.
ABSTRACT
The global pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging. Various cutaneous manifestations have been observed in patients with SARS-CoV-2 infection, yet exacerbations of psoriasis have been reported sporadically. Acrodermatitis continua of Hallopeau (ACH) is an uncommon, sterile pustular dermatosis involving one or more digits. In some rare cases, ACH may evolve into generalized pustular psoriasis (GPP), which is a severe, and potentially life-threatening, form of psoriasis that manifests itself with widespread eruptions of pustules. We describe the first case of a patient in whom ACH abruptly progressed into GPP during COVID-19. A combination of infliximab and acitretin was used allowing swift clinical improvement.
ABSTRACT
Pyoderma gangrenosum (PG) is an uncommon, serious, ulcerating skin disease of uncertain etiology. It manifests as a noninfectious, progressive necrosis of the skin characterized by sterile neutrophilic infiltrates. It seems to be a disorder of the immune system. PG is associated with certain underlying conditions in at least 50% of cases. Therefore, it is important to look carefully for comorbidities in every patient with PG and treat them adequately to improve the prognosis. Here, we demonstrate a 35-year-old man diagnosed with multifocal PG and hemophagocytic lymphohistiocytosis (HLH) with fatal outcome, despite combined, long-term, intensive dermatological and hematological treatment with high doses of steroids, cyclosporin, intravenous immunoglobulins (IVIG), HLH-2004 protocol with intravenously administered etoposide, and anakinra. This case is presented owing to the extremely rare coexistence of PG and HLH and the related diagnostic and therapeutic difficulties. It is also worth underlying that the diagnosis of HLH should perhaps be considered in the presence of a high percentage of double-negative T lymphocytes (DNTs) in flow cytometry, after excluding the diagnosis of lymphoma and leukemia. In this article we have also performed and present the critical literature review of local and systemic options in the management of PG lesions based on a detailed search of the PubMed database.
ABSTRACT
OBJECTIVE: The aim of the study was to evaluate QoL in patients suffering from morphea. Material and Methods. Sixty-five patients with morphea were recruited into this cross-sectional, prospective parallel study. QoL among adult patients was assessed with the Dermatology Life Quality Index (DLQI) and Euro-QoL-5D questionnaire; patients aged <17 years used the Children's Dermatology Life Quality Index (CDLQI). The severity of morphea was assessed using the Localized Scleroderma Cutaneous Assessment Tool. The results of QoL and its association with disease severity were compared between patients with various morphea subtypes. RESULTS: The mean DLQI scoring was 3.8 ± 4.1 points and the CDLQI was 2.3 ± 3.0. The mean value of Visual Analogue Scale thermometer (EQ VAS) was 66.9 ± 17.5 points. The disease activity of morphea based on mLoSSI correlated significantly with QoL impairment according to the DLQI (R = 0.41, p = 0.001). No significant correlation was observed between morphea-induced damage and QoL (p = 0.99). CONCLUSIONS: Evaluation of QoL in patients with morphea is still challenging due to lack of good assessment tools dedicated specifically for morphea patients. In general, QoL in morphea patients is significantly correlated with the disease activity, but not with disease-induced skin damage.