Special Issue:
Challenges and Opportunities in Psoriasis
Hamza Malick, BS
Texas A&M College of Medicine, Dallas, Texas
Seo Won Cho, BS
Texas A&M College of Medicine, Dallas, Texas
Kyle C. Lauck, MD
Baylor University Medical Center, Dallas, Texas
Aaisha Firdaus, MBBS
Katihar Medical College & Hospital, Katihar, Bihar, India
Dario Kivelevitch
Texas A&M College of Medicine, Dallas, Texas; Baylor University Medical Center, Dallas, Texas
Abstract
Psoriasis, a chronic immune-mediated skin disorder impacting millions globally, is increasingly recognized for its links to various disease processes. As our understanding of immune dysregulation in psoriasis progresses, acknowledging the pivotal role of dysregulated T-cells in the pathogenic development of the persistent inflammatory state becomes crucial. This immune dysregulation and the resulting prevalent inflammatory state have raised concerns about psoriasis potentially serving as a significant comorbidity in cancer development among patients. To contribute to this discussion, we conducted a global retrospective cohort study with propensity score matching (PSM) using the TriNetX Analytics platform. The study aimed to investigate whether patients diagnosed with psoriasis face an elevated risk in the development of cutaneous malignancies, encompassing both melanoma and non-melanoma skin cancers. Our findings confirmed a noteworthy concern, revealing a significantly increased risk of developing cutaneous neoplasms in individuals with psoriasis. In conclusion, our study underscores the importance of heightened awareness and the necessity for routine skin cancer screenings in this unique patient population. The observed association between psoriasis and an increased risk of cutaneous neoplasms highlights the need for proactive medical interventions and emphasizes the potential impact of psoriasis as a comorbidity in the context of cancer development.
Imre Lázár
Semmelweis University, Institute of Behavioral Sciences, Medical Humanities Research Group, Budapest; Károli Gáspár University of Reformed Church, Institute of Social and Communication Sciences, Budapest
Abstract
Psoriasis is a common immune-mediated inflammatory disease that can often be associated with psychiatric problems such as depression and anxiety. Although psychiatric disorders were initially considered secondary, the high prevalence suggests that common pathophysiological mechanisms may be involved in the development of psoriasis and psychiatric disorders. The shared neuroendocrine and immune mediators weave a web of networks with bidirectional pathways. Biopsychosocial patterns of psoriasis include psychological and behavioral consequences influencing personal social networks, psychological dispositions, and brain-skin psychoimmunological network patterns, which sums in a network of networks. The pathodynamics of other organ diseases like diabetes, liver diseases, internal organ tumors, and latent long-term inflammatory processes (chronic tonsillitis, prostatitis, abscesses and inflammations in the gums, chronic sinusitis) influence psoriasis. Vice versa, psoriasis might cause a pathological impact on other organ systems via networked connections, like arthritis or psychological dispositions. Treatment of psoriasis needs networking through the cooperation of dermatology, rheumatology, and psychiatry and by combining different therapies.
Rachel de lima Grynszpan, MD, MSc
Federal University of Rio de Janeiro, Medical Clinics Department, Post-graduation Course, Sector of Dermatology, Rio de Janeiro, Brazil
Maria da Gloria Carvalho Barreiros, MSc
Federal University of Rio de Janeiro, Medical Clinics Department, Post-graduation Course, Sector of Dermatology, Rio de Janeiro, Brazil
Marilene do Nascimento Paixão
Federal University of Rio de Janeiro, Medical Clinics Department, Post-graduation Course, Sector of Dermatology, Rio de Janeiro, Brazil
Felipe Aguinaga, MD
Federal University of Rio de Janeiro, Medical Clinics Department, Post-graduation Course, Sector of Dermatology, Rio de Janeiro, Brazil
Danielle Carvalho Quintella, MD, PhD
State University of Rio de Janeiro, Medical Specialties Department, Post-graduation Course, Sector of Dermatology, Rio de Janeiro, Brazil
Marcia Ramos-e-Silva, MD, PhD
Federal University of Rio de Janeiro, Medical Clinics Department, Post-graduation Course, Sector of Dermatology, Rio de Janeiro, Brazil
Sueli Carneiro, MD, PhD
Federal University of Rio de Janeiro, Medical Clinics Department, Post-graduation Course, Sector of Dermatology, Rio de Janeiro, Brazil
Abstract
Background: Epidemiological studies indicate that onychomycosis may affect up to 79% of psoriatic patients. Onychomycosis in psoriatic patients is more commonly caused by yeasts comparing with non-psoriatic. There are different methods for diagnosing onychomycosis that could be used separated or together.
Objectives: To compare the histopathological findings (nail clipping) with Direct Mycological Examination (DME) and mycological culture on patients with psoriasis and nail psoriasis.
Methods: Eighty-three finger nails of 12 patients with the diagnosis of nail psoriasis were analyzed. None were under topical therapy or the nails. Samples for clipping, Direct Mycological Examination and mycological culture were collected. The proportions were analyzed using the chi-square test. The comparison of Direct Mycological Examination, mycological culture and clipping results were analyzed through sensitivity, specificity, positive and negative predictive value. Spss® 22 software was used for the analysis.
Results: Direct Mycological Examination x mycological culture: Direct Mycological Examination and mycological culture show agreement regarding their negative test. Of the 51 negative mycological culture exams, 5 were positive on Direct Mycological Examination and of the 51 negatives on Direct Mycological Examination, 5 were positive on mycological culture (p<0,0000). Therefore, Direct Mycological Examination and mycological culture are reliable and complementary methods on diagnosis of onychomycosis. Clipping x mycological culture: in the 51 negative mycological culture tests, were found 30 positive clipping tests (61.2%). Of the 34 negatives clipping, 13 were considered positive on mycological culture (38,2%) (p=0,96). Clipping x Direct Mycological Examination + mycological culture: Of the 56 negative results Direct Mycological Examination +mycological culture, 32 were positive on clipping (57,1%). Of the 34 negatives clipping, 10 were considered positive on Direct Mycological Examination + mycological culture (37%) (p: 0,613). This means that nail clipping “rescues” negative results from mycological culture. In Direct Mycological Examination there was a predominance of blastoconidia. No septae hyphae were detected. In mycological culture, the most prevalente fungi was Candida. There was no dermatophyte growth.
Conclusion: Nail clipping was positive more than half of the negative samples for mycological culture, and can be considered a great diagnostic aid, complementary to Direct Mycological Examination and mycological culture. These results are consistent with some previous reports, Candida was the fungus with higher frequency on the psoriatic nails, however, the role of these fungi is controversial (contamination x colonization x infection).
Shahir Mazaheri
Department of Neurology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Yazdan Heshmati
Department of Neurology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Mohsen Vazifehdaryazd
Department of Neurology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Mojtaba Khazaei
Department of Neurology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Masoud Ghiasian
Department of Neurology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Ashkan Rasouli-Saravani
Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Mehrdad Hajilooi
Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Ghasem Solgi
Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Psoriasis Research Centre, Hamadan University of Medical Sciences, Hamadan, Iran
Abstract
Backgrounds: Environmental factors such as bacterial infections, as well as genetic factors—in particular the human leukocyte antigen (HLA) alleles—have been implicated in the etiology of multiple sclerosis (MS). This study aims to explore the relationship between Helicobacter pylori infection, HLA alleles, and disease severity in Iranian MS patients.
Methods: The study population comprised 125 MS patients and 153 ethnically matched healthy controls. Stool antigen test was used to detect H. pylori, and the expanded disability status scale (EDSS) scores were assessed in the patients. HLA-DRB1 and DQB1 alleles and haplotypes were determined in both the patients and the controls. The relationships between H pylori infection, HLA alleles, and EDSS were also analyzed.
Results: HLA-DRB1*15 and DQB1*06 alleles families and the DRB1*15~DQB1*06 haplotype were significantly more frequent in MS patients, whereas HLA-DRB1*14 and DRB1*14~DQB1*05 haplotype were less frequent. Of the 125 MS patients, 38 were diagnosed with active H. pylori infection. We found lower frequencies of HLA-DRB1*15 (P = .08) and DRB1*16 (P = .05) alleles and a higher frequency of DQB1*02 (P = .06) in the H. pylori-positive patients. HLA-DRB1*07 was more prevalent in patients with EDSS≤3.0 (P = .06). More severe MS cases (EDSS>3.0) were linked to H pylori positivity (P = .02), disease chronicity (P = .001), receiving non-steroidal anti-inflammatory drugs (P = .02), and female gender (P = .05).
Conclusion: These preliminary findings suggest a link between H. pylori infection and the severity of MS H. pylori-positive patients regardless of the type of HLA carriage.
Herbert B. Allen, MD
Professor and Chair Emeritus Drexel University, College of Medicine Adjunct Professor of Dermatology Eastern Virginia Medical School Clinical Professor Geriatrics and Gerontology Rowan School of Osteopathic Medicine
Rachel A. Allen, BA
Jefferson Medical School
Kiertana Kannan, BS
Drexel Medical School
Lucy Fransko
Abstract
This will be an overview of our studies on biofilms and the diseases with which they are associated. Where possible, it will include the microbes that create these biofilms, their locations in the body, and their impact on the innate and adaptive immune systems. It will include all the diseases which we have recently classified as eczema in addition to those previously considered as such. It will also include psoriasis, tinea versicolor, leprosy, tertiary Lyme disease and Alzheimer’s disease, the deposition diseases (arteriosclerosis, gout pretibial myxedema), the necrobiotic granulomas (granuloma annulare, rheumatoid nodules, and necrobiosis lipoidica), molluscum contagiosum and squamous cell carcinoma in situ in pigmented transplant patients. Consequently, many chronic skin and systemic diseases have been shown to be biofilm diseases. This implies that these disorders have a large, often determinative microbiological component. Where known, the mechanism whereby these biofilms interact with the immune system will be discussed.
Devika Dua
Rheumatology Department, University Hospitals Coventry and Warwickshire NHS Trust Coventry, UK
Nicola Gullick
Rheumatology Department, University Hospitals Coventry and Warwickshire NHS Trust Coventry, UK; Warwick Medical School, University of Warwick, Coventry, UK
Catherine Tonks
Rheumatology Department, University Hospitals Coventry and Warwickshire NHS Trust Coventry, UK
Keir Young
Rheumatology Department, University Hospitals Coventry and Warwickshire NHS Trust Coventry, UK
Tim Blake
Rheumatology Department, University Hospitals Coventry and Warwickshire NHS Trust Coventry, UK; Warwick Medical School, University of Warwick, Coventry, UK
Abstract
Introduction: Axial Spondyloarthritis is a complex and heterogenousisorder. The disease varies significantly leading to a diverse spectrum of management choices. We analysed retrospective clinical data from our centre to identify factors associated with multiple biologic switches. We used clustering analysis, an unsupervised machine learning algorithm, and multivariate logistic regression.
Aim: To identify factors associated with a higher frequency of biologic switches in axial spondyloarthropathy patients in a real-world clinical setting.
Materials and Methods: Data were collected retrospectively from the consultations of 166 patients receiving biologic treatment for axial spondyloarthropathy at our centre from 2003 until 2021. Feature selection included: demographics; body mass index; clinical phenotype (axial involvement; peripheral arthritis; enthesitis; uveitis; psoriasis; inflammatory bowel disease); HLA-B27 positivity; radiographic disease; chronic widespread pain diagnosis; disease activity measures (baseline and aggregate scores over disease course) – Bath Ankylosing Spondylitis Disease Activity Index; Spinal pain Visual Analogue Score; Bath Ankylosing Spondylitis Functional Index; C-reactive protein; time to start biologic from diagnosis; number of biologics and mode of action. Clustering analysis included two additional variables: – response to Tumour Necrosis Factor inhibitors and Interleukin-17 inhibitors. Patients were defined as high biologic switchers if they received three or more biologics (not including non-medical switches to biosimilar agents). Multi-variate logistic regression was performed using MNLogit algorithm and clustering analysis using the k-means algorithm (Anaconda Distribution 2.7).
Results: Clustering partitioned our dataset into three clusters: Low Disease Burden (LDB), High Disease Burden 1(HDB1) and High Disease Burden 2(HDB2). The LDB cluster showed good response to treatment, lower disease activity scores and fewer treatment switches. HDB clusters had higher disease activity scores; however, the HDB1 patients had significantly fewer biologic switches. Common features of the HDB1 cluster were female sex, HLA-B27 negativity, less radiographic disease, and more chronic widespread pain diagnosis. Multivariate logistic regression showed that HLA-B27 positivity and higher disease activity scores were positively associated with more biologic switches, whereas time to start biologic and a diagnosis of chronic widespread pain were negatively associated.
Conclusion: HLA-B27 positivity, male sex, higher radiographic burden, higher disease activity scores and early biologic requirement were associated with more biologic switches. Females with axial spondyloarthropathy, HLA-B27 negativity and lower radiographic disease burden had significantly fewer biologic switches despite higher disease activity scores and were more likely to have accompanying chronic widespread pain. Despite advances in treatment, patients with high symptom burden pose a challenge in clinical practice. Consideration should be given to objective and holistic assessment of symptoms and treating other associated conditions, as necessary.
Mukund Tinguria
Department of Pathology and Laboratory Medicine Brantford General Hospital 200 Terrace Hill Street Brantford, Ontario Postal Code – N3R 1G9 Canada
Abstract
Celiac disease (CD) is an immune mediated disorder characterised by intolerance to glutens in certain grains like whet, barley, and rye. The exposure to gliadin protein component in the susceptible individuals leads to an inflammatory reaction damaging small bowel mucosa with progressive disappearance of intestinal villi. The damaged intestinal mucosa leads to malabsorption. The usual symptoms of celiac disease include diarrhea, steatorrhea, weight loss, fatigue, and abdominal pain. Diagnosis is based on clinical features, duodenal biopsy, elevated levels of anti-gliadin antibodies and response to gluten free diet. Contrary to common belief, celiac disease is a protein systemic disease rather than merely a pure digestive alteration. Celiac disease is closely associated with genes that code HLA -II antigens mainly of DQ2 and DQ8 classes, production of disease specific antibodies (i.e., endomysial antibodies), multiorgan involvement, comorbidity with other autoimmune diseases (shared autoimmunity), familial aggregation, and immune system dysregulation.
The clinical presentation of celiac disease can be variable. In mild form, patients can be almost asymptomatic whereas in the most severe form, the patients are at increased risk of life-threatening complications. Celiac disease has a well-known association with other autoimmune diseases such as autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), diabetes mellitus, autoimmune thyroid diseases, skin diseases such as dermatitis herpetiformis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, psoriasis, sarcoidosis, immune thrombocytopenic purpura, and pancreatitis. In addition, celiac disease may be associated with rare but potentially serious complications such as, collagenous sprue, ulcerative jejunoileitis, refractory celiac disease (RCD), enteropathy associated T-cell lymphoma, small bowel adenocarcinoma (SBA), hyposplenism, and cavitating mesenteric lymph node syndrome (CMLNS). The present article describes clinicopathologic features of these rare but serious complications of celiac disease.
Thanet Pongcharoensuk
Phramongkutklao hospital
Chutika Srisuttiyakorn
Phramongkutklao hospital
Abstract
Erythroderma is a medical condition characterized by inflammation involving skin over 90% of the body’s surface area. This condition can result in high mortality rate and many systemic complications including fluid and electrolyte imbalance, infections, thermoregulatory disturbance and high output cardiac failure. In Thailand, limited data have been reported in the literature.
This study aims to investigate epidemiologic, clinical and histologic data relevant to etiologies of erythroderma among adults.
We performed a retrospective study among all patients acquiring erythroderma, aged above 16 years and visiting at the Division of Dermatology, Department of Internal Medicine, Phramongkutklao Hospital, Thailand from January 2015 to December 2019. The following data were recorded: personal data, medical history, clinical manifestations, histopathologic results, possible etiologies, laboratory profiles, treatment methods and outcomes.
During the 5-year study, 35 patients with erythroderma were collected. Men outnumbered women 6:1 (30 men and 5 women). The age of these patients ranged from 18-90 with mean age of 66.4 years. Idiopathic was the predominant etiology with 20/35 cases (57.1%), followed by drug eruption (17.1%). Herbal medicine (33.3%) and spironolactone (33.3%) were the most implicated drugs. Pre-existing skin diseases were observed including psoriasis (17.1%), pityriasis rubra pilaris (2.8%) and malignancy associated erythroderma (2.8%). Epidermal spongiosis was the most common histological feature observed in all etiologies (85.7%), (p=0.029). Complete clearance was obtained in 15/35 (42.8%). Death 2/35 (5.6%) occurred in one patient with drug reaction and one patient with pemphigus vulgaris associated erythroderma complicated with sepsis.
Although data are limited, erythroderma remains a serious condition effecting quality of life of patients. Our study demonstrated further epidemiology, etiologies and clinicopathologic information of erythroderma among Thai patients.
Daliya Banerjee
Nirogy Therapeutics
Abstract
RORyt/y driven type-17 “pro-inflammatory “gene expression profile has been implicated in the pathogenesis of several human immune-mediated diseases and remains a compelling target for therapeutic intervention. However, several challenges, from both drug discovery and biology standpoint, have made it intractable. While biologics targeting IL-23, IL-17, IL-17R, and other cytokines in the ROR pathway have demonstrated clinical efficacy in psoriasis, ankylosing spondylitis, etc., it has been challenging to extend the utility of these therapeutics beyond a handful of autoimmune diseases, especially in atopic or rheumatic diseases. This review summarizes the complexities in defining the pathogenicity of the human type-17 pathway and underscores the need for targeting a phenotypically heterogeneous and therapeutically relevant pathogenic cell subset marked by CD161.
