Cutaneous Inflammatory Diseases Research Articles

Elongated linear vessels simulating branching vessels and diffuse structureless orange areas as prominent dermoscopic features of diffuse flat facial and extrafacial granuloma faciale: A case series.

Dermoscopy can be an important help for the diagnosis of skin cancers and inflammatory cutaneous diseases. The list of the dermoscopic features reported in granuloma faciale is wide and includes vascular and non-vascular features. We report here three cases of diffuse flat facial and extrafacial granuloma faciale that exhibited elongated linear vessels simulating branching vessels and diffuse structureless orange areas. The differential diagnosis between flat-type granuloma faciale, basal cell carcinoma and cutaneous sarcoidosis can be extremely difficult, making histology mandatory before any treatment.

Effects on peripheral and central nervous system of key inflammatory intercellular signalling peptides and proteins in psoriasis.

Psoriasis is a chronic systemic inflammatory cutaneous disease. Where the immune system plays an important role in its pathogenesis, with key inflammatory intercellular signalling peptides and proteins including IL-17 and IL-23. The psychoneurological system also figures prominently in development of psoriasis. There is a high prevalence of comorbidity between psoriasis and mental health disorders such as depression, anxiety and mania. Patients with psoriasis often suffer from pathological pain in the lesions, and their neurological accidents could improve the lesions in innervated areas. The immune system and the psychoneurological system interact closely in the pathogenesis of psoriasis. Patients with psoriasis exhibit abnormal levels of neuropeptides both in circulating and localized lesion, acting as immunomodulators involved in the inflammatory response. Moreover, receptors for inflammatory factors are expressed in both peripheral and central nervous systems (CNSs), suggesting that nervous system can receive and be influenced by signals from immune system. Key inflammatory intercellular signalling peptides and proteins in psoriasis, such as IL-17 and IL-23, can be involved in sensory signalling and may affect synaptic plasticity and the blood-brain barrier of CNS through the circulation. This review provides an overview of the multiple effects on the peripheral and CNS under conditions of systemic inflammation in psoriasis, providing a framework and inspiration for in-depth studies of neuroimmunomodulation in psoriasis.

State of the Art on the Role of Staphylococcus aureus Extracellular Vesicles in the Pathogenesis of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic and relapsing inflammatory cutaneous disease. The role of host defense and microbial virulence factors in Staphylococcus aureus skin colonization, infection, and inflammation perpetuation in AD remains an area of current research focus. Extracellular vesicles (EV) mediate cell-to-cell communication by transporting and delivering bioactive molecules, such as nucleic acids, proteins, and enzymes, to recipient cells. Staphylococcus aureus spontaneously secretes extracellular vesicles (SA-derived EVs), which spread throughout the skin layers. Previous research has shown that SA-derived EVs from AD patients can trigger cytokine secretion in keratinocytes, shape the recruitment of neutrophils and monocytes, and induce inflammatory AD-type lesions in mouse models, in addition to their role as exogenous worsening factors for the disease. In this review article, we aim to examine the role of SA-derived EVs in AD physiopathology and its progression, highlighting the recent research in the field and exploring the potential crosstalk between the host and the microbiota.

From neglect to spotlight: the underappreciated role of B cells in cutaneous inflammatory diseases.

The skin, covering our entire body as its largest organ, manifests enormous complexities and a profound interplay of systemic and local responses. In this heterogeneous domain, B cells were considered strangers. Yet, recent studies have highlighted their existence in the skin and their distinct role in modulating cutaneous immunity across various immune contexts. Accumulating evidence is progressively shedding light on the significance of B cells in maintaining skin health and in skin disorders. Herein, we integrate current insights on the systemic and local contributions of B cells in three prevalent inflammatory skin conditions: Pemphigus Vulgaris (PV), Systemic Lupus Erythematosus (SLE), and Atopic Dermatitis (AD), underscoring the previously underappreciated importance of B cells within skin immunity. Moreover, we address the potential adverse effects of current treatments used for skin diseases, emphasizing their unintentional consequences on B cells. These comprehensive approaches may pave the way for innovative therapeutic strategies that effectively address the intricate nature of skin disorders.

Fluorescent In Situ Hybridization for the Detection of Intracellular Bacteria in Companion Animals.

FISH techniques have been applied for the visualization and identification of intracellular bacteria in companion animal species. Most frequently, these techniques have focused on the identification of adhesive-invasive Escherichia coli in gastrointestinal disease, although various other organisms have been identified in inflammatory or neoplastic gastrointestinal disease. Previous studies have investigated a potential role of Helicobacter spp. in inflammatory gastrointestinal and hepatic conditions. Other studies evaluating the role of infectious organisms in hepatopathies have received some attention with mixed results. FISH techniques using both eubacterial and species-specific probes have been applied in inflammatory cardiovascular, urinary, and cutaneous diseases to screen for intracellular bacteria. This review summarizes the results of these studies.

PNAd-expressing vessels characterize the dermis of CD3+ T-cell-mediated cutaneous diseases.

T-cell recruitment to skin tissues is essential for inflammation in different cutaneous diseases; however, the mechanisms by which these T cells access the skin remain unclear. High endothelial venules expressing peripheral node address in (PNAd), an L-selectin ligand, are located in secondary lymphoid organs and are responsible for increasing T-cell influx into the lymphoid tissues. They are also found in non-lymphoid tissues during inflammation. However, their presence in different common inflammatory cutaneous diseases and their correlation with T-cell infiltration remain unclear. Herein, we explored the mechanisms underlying the access of T cells to the skin by investigating the presence of PNAd-expressing vessels in different cutaneous diseases, and its correlation with T cells' presence. Skin sections of 43 patients with different diseases were subjected to immunohistochemical and immunofluorescence staining to examine the presence of PNAd-expressing vessels in the dermis. The correlation of the percentage of these vessels in the dermis of these patients with the severity/grade of CD3+ T-cell infiltration was assessed. PNAd-expressing vessels were commonly found in the skin of patients with different inflammatory diseases. A high percentage of these vessels in the dermis was associated with increased severity of CD3+ T-cell infiltration (P < 0.05). Additionally, CD3+ T cells were found both around the PNAd-expressing vessels and within the vessel lumen. PNAd-expressing vessels in cutaneous inflammatory diseases, characterized by CD3+ T-cell infiltration, could be a crucial entry point for T cells into the skin. Thus, selective targeting of these vessels could be beneficial in cutaneous inflammatory disease treatment.

Multi-Omics Approach to Improved Diagnosis and Treatment of Atopic Dermatitis and Psoriasis.

Psoriasis and atopic dermatitis fall within the category of cutaneous immune-mediated inflammatory diseases (IMIDs). The prevalence of IMIDs is increasing in industrialized societies, influenced by both environmental changes and a genetic predisposition. However, the exact immune factors driving these chronic, progressive diseases are not fully understood. By using multi-omics techniques in cutaneous IMIDs, it is expected to advance the understanding of skin biology, uncover the underlying mechanisms of skin conditions, and potentially devise precise and personalized approaches to diagnosis and treatment. We provide a narrative review of the current knowledge in genomics, epigenomics, and proteomics of atopic dermatitis and psoriasis. A literature search was performed for articles published until 30 November 2023. Although there is still much to uncover, recent evidence has already provided valuable insights, such as proteomic profiles that permit differentiating psoriasis from mycosis fungoides and β-defensin 2 correlation to PASI and its drop due to secukinumab first injection, among others.

Dermoscopy for Nurse Practitioners

ABSTRACT Dermoscopy refers to the examination of skin by use of a dermatoscope. These devices provide a practical, noninvasive, painless, and incredibly detailed view of the skin. When used in the hands of a trained clinician, dermoscopy significantly increases diagnostic accuracy. Although most known for its role in pigmented lesion assessment, dermoscopy use has expanded to include the evaluation of nonpigmented lesions, conditions of the hair (trichoscopy), infestations (entomodermatoscopy), nail disease (onychoscopy), and cutaneous inflammatory disease (inflammatoscopy). Studies suggest that dermoscopy is valuable as it increases sensitivity for skin cancer detection. This is especially important in the setting of melanoma as it accounts for most skin-cancer-related deaths. Overall, utilization enhances diagnosis, prompts treatment, reduces morbidity and mortality, and increases healthcare cost-effectiveness. This article is written with the intent to inform dermatology nurse practitioners about this innovation. It may additionally serve as a useful resource for other advanced care providers who perform cutaneous assessment. Examples of such clinicians may include, but are not limited to, urgent care providers, pediatricians, dentists, podiatrists, and primary care providers.

Antioxidant defense of children and adolescents with atopic dermatitis: Association with disease severity.

Atopic dermatitis (AD) is a relapsing, chronic cutaneous inflammatory disease with onset, in general, in early childhood. Chronic skin inflammation is associated with overproduction of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. Oxidative stress, an imbalance between the production of free radicals and antioxidant defense, results in tissue inflammation due to the upregulation of genes that encode inflammatory cytokines. This condition plays an important role in the pathogenesis of AD. To compare the antioxidant defense in children and adolescents with AD with that of healthy individuals and to verify the association of antioxidant defense with disease severity and nutritional status. Cross-sectional study that evaluated 48 children and adolescents with AD and 25 controls for nutritional assessment (body mass index z score [BMIZ] and height for age z score [HAZ]) and levels of vitamins A, C, E, and D, zinc (Zn), copper (Cu), antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]), high-sensitivity C-reactive protein (CRP) and interleukin 33 (IL-33). There was no significant difference in the comparison between AD and control groups for serum levels of vitamins (A, D, C, and E), copper, and antioxidant enzymes. Serum zinc levels were higher in the AD group (β = 24.20; 95% CI 13.95-34.91; P < 0.001) even after adjusting the BMIZ, HAZ, gender, IL-33, and CRP. Children and adolescents with moderate or severe AD compared to mild AD (SCORAD - 36.7±17.4 vs 11.8 ± 3.9; P < 0.001) had lower values of the vitamin E/total lipid ratio (3.68 [0.29;12.63] vs 5.92 [3.27;17.37]; P = 0.013). Children and adolescents with AD had higher concentrations OF elevated levels of zinc compared to controls, a fact not observed for other biomarkers of antioxidant defense. AD in moderate or severe forms presented lower concentrations of vitamin E, a potent antioxidant fat soluble.

Inhibitory effects of catalpol on DNCB-induced atopic dermatitis and IgE-mediated mast cells reaction

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation. Catalpol is an iridoids, possessing anti-inflammatory, antioxidant, and neuroprotective activities. It can be added to food as a dietary supplement. To evaluate the effects and mechanisms of catalpol on AD, both in vitro and in vivo studies were conducted. It was found that catalpol downregulated the phosphorylation of Lyn and Syk to inhibit various downstream pathways, including intracellular Ca2+ elevation, cytokines generation, and histamine release, which ultimately controlled mast cell (MCs) degranulation. The results showed that catalpol alleviated AD-like skin lesions and MC infiltration via regulation of pro-Th2 and Th2 cytokines in vivo. Furthermore, this compound reduced the levels of IgE in AD mice and improved allergic reactions in PCA mice. The results provided that catalpol was potentially developed as a dietary supplement to improve AD and other atopic diseases.

Iranian psoriasis registry: Research protocol and preliminary results of a pilot study.

Psoriasis as a common cutaneous inflammatory disease affect many aspects of patients' life. Disease registries render it possible to collect valuable data regarding a disease prevalence and burden as well as long-term observations concerning possible therapeutic regimens. This registry was designed for the ongoing systematic data collection on patients with psoriasis at two referral dermatology centers in Iran. The pilot phase of the registry was used to identify possible obstacles in the application and execution of systematic registration. A total of 281 patients were registered with the mean age of 42.02 years. The disease duration was 12.06 ± 10.90 years with the variety of clinical presentations. There was no significant difference between males and females in the age of disease onset (p = 0.53). Notably, 167 patients had children. Among them, 13 had children with psoriasis. The gender of the affected parent did not affect the possibility of psoriasis transmission to the child, and no significant difference was seen between the two sexes (P = 0.569). Regarding treatment, 99.4% of patients (n = 280) had used topical agents, 52.3% (n = 147) biologics, and 60.9% (n = 171) nonbiologic medications. Clinical trials report the efficacy and safety data regarding limited study populations in a restricted time window, and the results may differ from the general population. This highlights the importance of registry-based studies for collecting and analyzing longitudinal information. In terms of long-term disease complications such as malignancies, cardiovascular events, and serious adverse events, registry-based studies will help clinicians better recognize and manage each disease.

Can hydradenitis suppurativa be associated with inflammatory joint involvement? Report of a case series and review of the literature.

Dear Editor, Hidradenitis suppurativa (HS) or acne inversus, is a chronic inflammatory cutaneous disease with a significant negative impact on the patient's quality of life, from a psychological, social and occupational point of view. The disease mainly affects the female sex and occurs between puberty and 40 years of age. It is estimated that in Europe the prevalence of the disease in the general population is 1%.1 Recent studies have shown a high incidence of inflammatory arthritis, in particular spondyloarthritis, in patients with HS.2 In this report, we present 18 cases of patients with hidradenitis suppurativa, visited at the San Gallicano Dermatological Institute, who presented joint symptoms. [...]

Targeting dysbiosis in psoriasis, atopic dermatitis, and hidradenitis suppurativa: the gut-skin axis and microbiome-directed therapy

Emerging evidence highlights the gut-skin microbiota as a potential therapeutic target for the management of inflammatory-driven cutaneous diseases as well as the interconnection of the gut-skin microbiota in disease pathogenesis and progression. Although not fully understood, recent research has indicated that commensal microbiota and the interaction of the gut-skin axis play an important role in maintaining skin homeostasis. Dysbiosis and disruption of the skin-gut microbiome may lead to impaired skin barrier function, thus triggering downstream inflammatory responses involved in the development of inflammatory skin disorders, especially in atopic dermatitis, psoriasis, and hidradenitis suppurativa. The skin microbiome may also serve as adjunctive therapeutic modalities for treatment. Herein, we review the latest reports on the interrelationship between microbial dysbiosis and inflammatory cutaneous diseases as well as emerging microbiome-directed therapeutics in atopic dermatitis, psoriasis, and hidradenitis suppurativa.

Clinical Accuracy Of Dermatologists And Nondermatologists In The Diagnosis Of Dermatological Diseases.

To compare the clinical diagnostic accuracy of dermatologists and non- dermatologists in the diagnosis of dermatological diseases. The descriptive, cross-sectional study was conducted at the Dermatopathology department of a tertiary healthcare hospital in the Punjab province of Pakistan from January 1 to December 31, 2019, and comprised biopsy specimens of patients with diseases of the skin and subcutaneous tissue. The clinical diagnoses of general surgeons, otolaryngologists, dental/maxillofacial surgeons, plastic surgeons and gynaecologists were noted and compared with those of dermatologists in the light of histopathological findings. Data was analysed using SPSS 16. Of the 386 specimens submitted, 113(29.3%) were sent by dermatologists and 273(70.7%) by non-dermatologists. Clinical diagnostic accuracy of dermatologists 92(81.4%) compared to non-dermatologists 137(50.2%) (p<0.005). The dermatologists diagnosed significantly more cases belonging to inflammatory and miscellaneous cutaneous diseases category accurately than non-dermatologists (p<0.005). Similarly, the dermatologists diagnosed significantly more cases of neoplastic disorders accurately than the non-dermatologists (p= 0.018). There was no significant difference in the clinical diagnostic accuracy of dermatologists and non-dermatologists in cases of cystic lesions (p>0.05). In the neoplastic category, no significant difference was found in the clinical accuracy of dermatologists and plastic surgeons (p=0.347). The specialised skills of dermatologists could not be matched by any other group of physicians.

"Outside-to-inside," "inside-to-outside," and "intrinsic" endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations.

Permeability barrier disruption has been shown to induce immunological alterations (i.e., an "outside-to-inside" pathogenic mechanism). Conversely, several inflammatory and immunological mechanisms reportedly interrupt permeability barrier homeostasis (i.e., an "inside-to-outside" pathogenic mechanism). It is now widely recognized that alterations of even a single molecule in keratinocytes can lead to not only permeability barrier dysfunction but also to immunological alterations. Such a simultaneous, bidirectional functional change by keratinocytes is herein named an "intrinsic" pathogenic mechanism. Molecules and/or pathways involved in this mechanism could be important not only as factors in disease pathogenesis but also as potential therapeutic targets for inflammatory cutaneous diseases, such as atopic dermatitis, psoriasis, and prurigo nodularis. Elevation of skin surface pH following permeability barrier abrogation comprises one of the key pathogenic phenomena of the "outside-to-inside" mechanism. Not only type 2 cytokines (e.g., IL-4, IL-13, IL-31) but also type 1 (e.g. IFN-γ), and type 3 (e.g., IL-17, IL-22) as well as several other inflammatory factors (e.g. histamine) can disrupt permeability barrier homeostasis and are all considered part of the "inside-to-outside" mechanism. Finally, examples of molecules relevant to the "intrinsic" pathogenic mechanism include keratin 1, filaggrin, and peroxisome proliferator-activated receptor-α (PPARα).

Repressive Control of Keratinocyte Cytoplasmic Inflammatory Signaling.

The overactivity of keratinocyte cytoplasmic signaling contributes to several cutaneous inflammatory and immune pathologies. An important emerging complement to proteins responsible for this overactivity is signal repression brought about by several proteins and protein complexes with the native role of limiting inflammation. The signaling repression by these proteins distinguishes them from transmembrane receptors, kinases, and inflammasomes, which drive inflammation. For these proteins, defects or deficiencies, whether naturally arising or in experimentally engineered skin inflammation models, have clearly linked them to maintaining keratinocytes in a non-activated state or returning cells to a post-inflamed state after a signaling event. Thus, together, these proteins help to resolve acute inflammatory responses or limit the development of chronic cutaneous inflammatory disease. We present here an integrated set of demonstrated or potentially inflammation-repressive proteins or protein complexes (linear ubiquitin chain assembly complex [LUBAC], cylindromatosis lysine 63 deubiquitinase [CYLD], tumor necrosis factor alpha-induced protein 3-interacting protein 1 [TNIP1], A20, and OTULIN) for a comprehensive view of cytoplasmic signaling highlighting protein players repressing inflammation as the needed counterpoints to signal activators and amplifiers. Ebb and flow of players on both sides of this inflammation equation would be of physiological advantage to allow acute response to damage or pathogens and yet guard against chronic inflammatory disease. Further investigation of the players responsible for repressing cytoplasmic signaling would be foundational to developing new chemical-entity pharmacologics to stabilize or enhance their function when clinical intervention is needed to restore balance.

A Web-Based Instrument for Infantile Atopic Dermatitis Identification (Electronic Version of the Modified Child Eczema Questionnaire): Development and Implementation.

Atopic dermatitis (AD) is a chronic inflammatory cutaneous disease that affects 30.48% of young children; thus, there is a need for epidemiological studies in community settings. Web-based questionnaires (WBQs) are more convenient, time-saving, and efficient than traditional surveys, but the reliability of identifying AD through WBQs and whether AD can be identified without the attendance of doctors, especially in community or similar settings, remains unknown. This study aimed to develop and validate a web-based instrument for infantile AD identification (electronic version of the modified Child Eczema Questionnaire [eCEQ]) and to clarify the possibility of conducting WBQs to identify infantile AD without the attendance of doctors in a community-representative population. This study was divided into 2 phases. Phase 1 investigated 205 children younger than 2 years to develop and validate the eCEQ by comparison with the diagnoses of dermatologists. Phase 2 recruited 1375 children younger than 2 years to implement the eCEQ and verify the obtained prevalence by comparison with the previously published prevalence. In phase 1, a total of 195 questionnaires were analyzed from children with a median age of 8.8 (IQR 4.5-15.0) months. The identification values of the eCEQ according to the appropriate rules were acceptable (logic rule: sensitivity 89.2%, specificity 91.5%, positive predictive value 97.1%, and negative predictive value 72.9%; statistic rule: sensitivity 90.5%, specificity 89.4%, positive predictive value 96.4%, and negative predictive value 75%). In phase 2, a total of 837 questionnaires were analyzed from children with a median age of 8.4 (IQR 5.2-14.6) months. The prevalence of infantile AD obtained by the eCEQ (logic rule) was 31.9% (267/837), which was close to the published prevalence (30.48%). Based on the results of phase 2, only 20.2% (54/267) of the participants identified by the eCEQ had previously received a diagnosis from doctors. Additionally, among the participants who were not diagnosed by doctors but were identified by the eCEQ, only 6.1% (13/213) were actually aware of the possible presence of AD. Infantile AD can be identified without the attendance of doctors by using the eCEQ, which can be easily applied to community-based epidemiological studies and provide acceptable identification reliability. In addition, the eCEQ can also be applied to the field of public health to improve the health awareness of the general population.

JAK inhibitor: Introduction.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a key regulatory signaling system for cellular proliferation, differentiation, and apoptosis. In addition, JAK signaling pathway plays critical roles in orchestrating immune response through its interactions with the cytokine receptors and the transcriptions factors. Several key cytokines use JAK-STAT signaling proteins to transduce intra-cellular signals which are involved in the pathogenesis of autoimmune and inflammatory diseases such as in psoriatic disease (psoriasis, psoriatic arthritis), atopic dermatitis, alopecia areata, vitiligo, rheumatoid arthritis, ankylosing spondylitis, lupus erythematosus, Sjogren's syndrome, and other autoimmune diseases. In recent years, understandings of the molecular mechanisms of JAK-STAT pathway in the inflammatory proliferative cascades of autoimmune diseases has led to the development of JAK inhibitors and has opened a new dimension for the treatment of systemic and cutaneous inflammatory diseases. In this symposium we have provided a broad perspective on the use of Janus kinase inhibitors in cutaneous autoimmune diseases.

Role of VivaScope 2500ex vivo confocal microscopy in skin pathology: Advantages, limitations, and future prospects.

Vivascope 2500 ex vivo confocal microscopy (EVCM) is an emerging optical imaging device that allows nuclear level resolution of freshly excised tissues. EVCM provides, rapid real-time pathological examination in many subspecialties of pathology including skin, prostate, breast, liver, etc. In contrast to traditional time-consuming frozen sectioning and histological analysis. To evaluate the current state of EVCM utilization. This study highlights the advantages, limitations, and prospects of EVCM in skin pathology. Our findings demonstrate that EVCM is a promising adjunctive tool to assess margins in Mohs surgery and to provide rapid, accurate diagnosis of cutaneous tumors, infectious and inflammatory diseases. EVCM is a revolutionary device that can be used as an adjunct to paraffin-fixed, hematoxylin and eosin-stained slides and frozen sectioning. Additional refinements are required before EVCM can be used as an alternative to frozen sectioning or traditional tissue processing.

Pityriasis lichenoides presented with skin rash mimicking Urticaria: A case report.

Acute urticaria is urticaria with or without angioedema that is present for less than six weeks, while chronic urticaria is present for more than six weeks. Pityriasis lichenoides (PL) is a benign cutaneous inflammatory disease of unknown etiology. Acute PL typically resolves within a few weeks, while chronic PL lasts several months. The skin rash of PL may resemble the rash of other conditions, so the distinction is essential and depends on history and physical examination and is confirmed by skin biopsy. A 64-year-old gentleman presented with seven days history of generalized itchy skin (hives). Individual lesions last 24-48 hours and do not leave pigmentation or scarring. No systemic involvement. No specific triggers, with two previous similar episodes 30 years and 20 years ago. Levocetirizine, 5 mg tablet, was prescribed, and he was instructed to increase the dose to 4 tablets daily if needed. On reassessing the patient after ten days, he did not respond well. The rash was different from the initial one, with individual lesions lasting for five days or more, so he was referred to a dermatologist for a skin biopsy. Basic investigations were normal. Performing skin biopsy is needed to exclude other pathologies. Skin biopsy showed pathological changes of lichenoid dermatitis compatible with pityriasis lichenoides et varioliformis acuta (PLEVA). He has been treated with azithromycin 250 mg daily for three weeks with rapid and complete resolution without scaring. Urticarial rash may mimic the skin rash of other conditions. Detailed serial history and physical examination are warranted to exclude other diagnoses. Skin biopsy is needed when diagnosing conditions other than urticaria are suspected.