Autoimmune Skin Disease Research Articles

The Role of Non-Neuronal Acetylcholine in the Autoimmune Blistering Disease Pemphigus Vulgaris

The importance of acetylcholine (ACh) in keratinocyte adhesion and acantholysis has been investigated over the last three decades, particularly in the pathophysiology of autoimmune blistering dermatoses. Pemphigus vulgaris (PV) is an autoimmune blistering skin disease where autoantibody-mediated suprabasilar intraepidermal splitting causes flaccid blisters and non-healing erosions of the oral mucosa and sometimes also of the skin. Historically, acantholysis in PV was thought to be driven by anti-desmoglein (Dsg) antibodies. Herein, we describe the role of autoantibodies against keratinocyte muscarinic and nicotinic acetylcholine receptors, as well as the annexin-like molecule pemphaxin that also binds ACh, in the immunopathogenesis of PV. The identification of targets in this disease is important, as they may lead to novel diagnostic and therapeutic options in the future for this potentially deadly disease.

A review of JAK and IL-23 inhibitors to treat vitiligo.

Vitiligo is an autoimmune skin disorder resulting in the depigmentation of skin characterised by patches of varying sizes and shapes. A common disorder of pigmentation that affects 0.5%-2% of the global population. Despite its well-understood autoimmune pathogenesis, the targets for effective cytokine intervention remain unclear. Current first-line treatments include oral or topical corticosteroids, calcineurin inhibitors and phototherapy. These treatments are limited, have varying efficacies, and are associated with significant adverse events or can be time-consuming. Therefore, biologics should be explored as a potential treatment for vitiligo. There are currently limited data for the use of JAK and IL-23 inhibitors for vitiligo. A total of 25 studies were identified in the review. There is promising evidence regarding the use of JAK and IL-23 inhibitors for the treatment of vitiligo.

Granzyme B in Autoimmune Skin Disease.

Autoimmune diseases often present with cutaneous symptoms that contribute to dysfunction, disfigurement, and in many cases, reduced quality-of-life. Unfortunately, treatment options for many autoimmune skin diseases are limited. Local and systemic corticosteroids remain the current standard-of-care but are associated with significant adverse effects. Hence, there is an unmet need for novel therapies that block molecular drivers of disease in a local and/or targeted manner. Granzyme B (GzmB) is a serine protease with known cytotoxic activity and emerging extracellular functions, including the cleavage of cell-cell junctions, basement membranes, cell receptors, and other structural proteins. While minimal to absent in healthy skin, GzmB is markedly elevated in alopecia areata, interface dermatitis, pemphigoid disease, psoriasis, systemic sclerosis, and vitiligo. This review will discuss the role of GzmB in immunity, blistering, apoptosis, and barrier dysfunction in the context of autoimmune skin disease. GzmB plays a causal role in the development of pemphigoid disease and carries diagnostic and prognostic significance in cutaneous lupus erythematosus, vitiligo, and alopecia areata. Taken together, these data support GzmB as a promising therapeutic target for autoimmune skin diseases impacted by impaired barrier function, inflammation, and/or blistering.

Potential effects of shift work on skin autoimmune diseases.

Shift work is associated with systemic chronic inflammation, impaired host and tumor defense and dysregulated immune responses to harmless antigens such as allergens or auto-antigens. Thus, shift workers are at higher risk to develop a systemic autoimmune disease and circadian disruption with sleep impairment seem to be the key underlying mechanisms. Presumably, disturbances of the sleep-wake cycle also drive skin-specific autoimmune diseases, but epidemiological and experimental evidence so far is scarce. This review summarizes the effects of shift work, circadian misalignment, poor sleep, and the effect of potential hormonal mediators such as stress mediators or melatonin on skin barrier functions and on innate and adaptive skin immunity. Human studies as well as animal models were considered. We will also address advantages and potential pitfalls in animal models of shift work, and possible confounders that could drive skin autoimmune diseases in shift workers such as adverse lifestyle habits and psychosocial influences. Finally, we will outline feasible countermeasures that may reduce the risk of systemic and skin autoimmunity in shift workers, as well as treatment options and highlight outstanding questions that should be addressed in future studies.

The Dermatologic Care Needs of a Rural Community in South Florida.

For patients in rural areas, primary care is often their only access to healthcare services, and skin concerns are among the most common diseases seen in these settings. This study aims to investigate the most common skin conditions, management trends and patterns of referral to dermatology in a rural and underserved community in South Florida. A retrospective chart review was conducted using medical records from the C.L. Brumback Primary Care Clinic in Belle Glade, FL. The most common skin conditions were fungal infections, unspecified dermatitis, pruritus, skin cancer concern, alopecia, and autoimmune skin disorders. The most frequent management strategy was medication prescription followed by specialist referral. Of the 21 percent of patients referred to a specialist, 55 percent of these were to dermatology. The most common diagnoses referred to dermatology were atopic dermatitis and alopecia. Only 20 percent of these patients reported attending their follow-up appointment, and the average distance to referral was 21 miles. Belle Glade is unique in its need for and access to dermatologic care. The lack of access to specialists in rural communities is a public health issue that more studies and outreach initiatives should address.

B-cell depletion in the treatment of pemphigus: two clinical cases and literature review

Pemphigus presents a group of chronic autoimmune bullous skin disorders with well-known clinical signs, which pathophysiology is mediated by antibodies to various epidermal self-antigens. For a long time, the only therapeutic option for this disease was the lifelong use of non-selective immunosuppressive agents limited by high rate of severe adverse reactions. The article presents two clinical cases of rituximab use (a targeted agent leading to B-cell depletion) in patients with pemphigus (vulgaris and foliaceous) who were previously resistant to high-dose steroid therapy. Treatment with rituximab lead to response and allowed to decrease the prednisone dose in both cases. These results confirm that rituximab can be successfully used in pemphigus as adjuvant therapy if conventional agents for this dermatosis are ineffective.

CircVAPA contributes to hyper-proliferation and inflammation of keratinocytes through miR-125b-5p/sirt6 axis in psoriasis.

Psoriasis is an autoimmune skin disease with abnormal keratinocyte hyperproliferation. The important roles of circular RNAs (circRNAs) in various inflammatory diseases have been revealed. The present study aimed to investigate the roles of circVAPA and its molecular mechanisms in psoriasis. Quantitative real-time polymerase chain reaction was performed to measure the RNA expression. Enzyme-linked immunosorbent assays were employed to examine the production of inflammatory factors. Cell-counting kit-8, EDU and flow cytometry assay were conducted to examine the cell viability, proliferation and apoptosis respectively. Dual-luciferase reporter assay and ribonucleoprotein immunoprecipitation (RIP) were conducted to verify the target relationship between miR-125b-5p and circVAPA or Sirt6. Herein our findings showed increased expression of circVAPA and Sirt6 and decreased level of miR-125b-5p in psoriatic lesional tissues and M5-stimulated keratinocytes. Mechanistically, circVAPA knockdown significantly suppressed the promotion of M5 on cell viability, proliferation, and inflammation of HaCaT cells. circVAPA was verified to interact with miR-125b-5p, while inhibition of miR-125b-5p counteracted circVAPA knockdown-mediated effects in M5-stimulated HaCaT cells. Sirt6 was confirmed as a target of miR-125b-5p, and miR-125b-5p overexpression inhibited cell growth and inflammation partly by targeting Sirt6 in M5-stimulated HaCaT cells. Moreover, circVAPA was featured as a competing endogenous RNA by directly sponging miR-125b-5p to up-regulate the expression of Sirt6. CircVAPA participate in the progression of psoriasis through miR-125b-5p/sirt6 axis by regulating proliferation and inflammation of keratinocytes, highlighting a potential therapeutic target for psoriasis.

Celastrol inhibits store operated calcium entry and suppresses psoriasis.

Introduction: Psoriasis is an inflammatory autoimmune skin disease that is hard to cure and prone to relapse. Currently available global immunosuppressive agents for psoriasis may cause severe side effects, thus it is crucial to identify new therapeutic reagents and druggable signaling pathways for psoriasis. Methods: To check the effects of SOCE inhibitors on psoriasis, we used animal models, biochemical approaches, together with various imaging techniques, including calcium, confocal and FRET imaging. Results and discussion: Store operated calcium (Ca2+) entry (SOCE), mediated by STIM1 and Orai1, is crucial for the function of keratinocytes and immune cells, the two major players in psoriasis. Here we showed that a natural compound celastrol is a novel SOCE inhibitor, and it ameliorated the skin lesion and reduced PASI scores in imiquimod-induced psoriasis-like mice. Celastrol dose- and time-dependently inhibited SOCE in HEK cells and HaCaT cells, a keratinocyte cell line. Mechanistically, celastrol inhibited SOCE via its actions both on STIM1 and Orai1. It inhibited Ca2+ entry through constitutively-active Orai1 mutants independent of STIM1. Rather than blocking the conformational switch and oligomerization of STIM1 during SOCE activation, celastrol diminished the transition from oligomerized STIM1 into aggregates, thus locking STIM1 in a partially active state. As a result, it abolished the functional coupling between STIM1 and Orai1, diminishing SOCE signals. Overall, our findings identified a new SOCE inhibitor celastrol that suppresses psoriasis, suggesting that SOCE pathway may serve as a new druggable target for treating psoriasis.

Integrative medicine (East Asian herbal medicine combined with conventional medicine) for psoriasis: A protocol for systematic review and meta-analysis.

Psoriasis is a chronic, inflammatory, autoimmune skin disease. The aim of this review is to systematically evaluate the efficacy and safety of integrative medicine (East Asian herbal medicine combined with conventional medicine) used to treat inflammatory skin lesions of psoriasis. A comprehensive literature search will be conducted in 3 English databases (PubMed, Cochrane Library, and Embase), 4 Korean databases (Korean Studies Information Service System, Research Information Service System, Oriental Medicine Advanced Searching Integrated System, and Korea Citation Index), 2 Chinese databases (Chinese National Knowledge Infrastructure Database and Wanfang data), and 1 Japanese database (Citation Information by National Institute of Informatics) for randomized controlled trials from their inception until July 29, 2021. Statistical analysis will be performed using R version 4.1.2 and the R studio program using the default settings of the "meta" and "metafor" packages. The primary outcome will be an improvement in the psoriasis area severity index. All outcomes will be analyzed using a random-effects model to produce more statistically conservative results. If heterogeneity is detected in the study, the cause will be identified through sensitivity, meta-regression, and subgroup analyses. Methodological quality will be assessed independently using the revised tool for the risk of bias in randomized trials, version 2.0. The overall quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation pro framework. This study will review all available trials on the same subject and arrive at a more statistically robust conclusion based on a sufficient sample size of participants and additional analysis using data mining techniques will be performed on intervention prescription information in clinical studies collected according to rigorous criteria. We believe that this study will provide useful knowledge on managing inflammatory skin lesions of psoriasis vulgaris using integrative medicine using East Asian herbal medicine.

Deregulated phenotype of autoreactive Th17 and Treg clone cells in pemphigus vulgaris after in-vitro treatment with desmoglein antigen (Dsg-3)

The loss of balance between regulatory T (Treg) and T helper 17 (Th17) causes loss of tolerance against desmoglein (Dsg)-3 leading to pemphigus vulgaris (PV), an autoimmune bullous skin disorder associated with autoantibodies against Dsg-3. We aimed to elucidate the complex relationship of Th17 and Treg cells, their molecules, and the underlying mechanism in the development of PV disease. Using cytokine secretion assays, Th17 and Treg cells were sorted by FACS Aria-III within Dsg-3-responsive PBMC population and homogeneous T cell clones were generated in-vitro. Different cell surface molecules like CD25, GITR, CD122, CD152, CD45RO, IL-23R, STAT3, STAT5, CD127, HLA-DR, CCR4, CCR5, CCR6 and CCR7 were studied. The functional response of Th17 and Treg cells were elucidated by measuring the levels of various cytokines released by IL-10 and IL-17 T cells. The mRNA expression of transcription factors (FoxP3 and RORγt) was also analyzed. IL-17 secreting (Th17) cells with phenotype CD4+IL-17+ were greatly increased and IL-10 secreting (Treg) cells with phenotype CD4+IL-10+ were reduced in PV cases than healthy controls. The qPCR analysis showing high expression of retinoic acid receptor-related orphan receptor gamma (RORγt) mRNA in comparison to forkhead box P3 (FoxP3) mRNA confirmed the development of pro-inflammatory Th17 response in PV. Further, the cytokine profile of pro-inflammatory and anti-inflammatory cytokines suggested defective suppressive functions in Treg cells with high inflammatory response. Our findings indicate that autoantigen Dsg-3 specifically allows the proliferation of IL-17 secreting T cells though has a negative effect on IL-10 secreting T cells leading to dysregulation of immunity in PV patients. This antagonistic relationship between Dsg-3-specific Th17 and Treg cells may be critical for the onset and persistence of inflammation in PV cases.

Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation.

Psoriasis is a chronic autoimmune inflammatory skin disorder characterized by epidermal hyperplasia and aberrant immune response. In addition to aberrant cytokine production, psoriasis is associated with activation of the Akt/mTOR pathway. mTOR/S6K1 regulates T-lymphocyte activation and migration, keratinocytes proliferation and is upregulated in psoriatic lesions. Several drugs that target Th1/Th17 cytokines or their receptors have been approved for treating psoriasis in humans with variable results necessitating improved therapies. Fisetin, a natural dietary polyphenol with anti-oxidant and anti-proliferative properties, covalently binds mTOR/S6K1. The effects of fisetin on psoriasis and its underlying mechanisms have not been clearly defined. Here, we evaluated the immunomodulatory effects of fisetin on Th1/Th17-cytokine-activated adult human epidermal keratinocytes (HEKa) and anti-CD3/CD28-stimulated inflammatory CD4+ T cells and compared these activities with those of rapamycin (an mTOR inhibitor). Transcriptomic analysis of HEKa revealed 12,713 differentially expressed genes (DEGs) in the fisetin-treated group compared to 7,374 DEGs in the rapamycin-treated group, both individually compared to a cytokine treated group. Gene ontology analysis revealed enriched functional groups related to PI3K/Akt/mTOR signaling pathways, psoriasis, and epidermal development. Using in silico molecular modeling, we observed a high binding affinity of fisetin to IL-17A. In vitro, fisetin significantly inhibited mTOR activity, increased the expression of autophagy markers LC3A/B and Atg5 in HEKa cells and suppressed the secretion of IL-17A by activated CD4+ T lymphocytes or T lymphocytes co-cultured with HEKa. Topical administration of fisetin in an imiquimod (IMQ)-induced mouse psoriasis model exhibited a better effect than rapamycin in reducing psoriasis-like inflammation and Akt/mTOR phosphorylation and promoting keratinocyte differentiation and autophagy in mice skin lesions. Fisetin also significantly inhibited T-lymphocytes and F4/80+ macrophage infiltration into skin. We conclude that fisetin potently inhibits IL-17A and the Akt/mTOR pathway and promotes keratinocyte differentiation and autophagy to alleviate IMQ-induced psoriasis-like disease in mice. Altogether, our findings suggest fisetin as a potential treatment for psoriasis and possibly other inflammatory skin diseases.

Matrix remodeling associated 7 proteins promote cutaneous wound healing through vimentin in coordinating fibroblast functions

Wound healing depends largely on the remodeling of the extracellular matrix around and reorganization of tissue-resident cells. Matrix remodeling associated 7 (MXRA7) is a member of the matrix remodeling-associated gene family and is involved in matrix remodeling-associated processes, such as inflammatory neovascularization, liver injury, and autoimmune skin disease. To investigate whether and how MXRA7 participate in cutaneous wound healing, an ear-punching model was utilized in wild-type (WT) and MXRA7-deficient mice, and the dermal fibroblasts from these mice were further studied in vitro. Results showed that the MXRA7 deficiency impaired the wound healing process in mice. Quantitative PCR indicated that lack of MXRA7 impaired the expression of several extracellular matrix genes (e.g., MMP-2) and inhibited signaling pathways (e.g., STAT3) in healing ear tissues. In in vitro culture system, migration, contraction, or proliferation of fibroblasts was impaired upon MXRA7 deficiency. Pull-down and mass spectrum assay revealed that vimentin was among the proteins that bound MXRA7 proteins in cells, and further investigations indicate MXRA7 was an autocrine factor in fibroblasts that involved vimentin in certain ways, such as JNK and STAT3/STAT5 signaling pathways in our study. In conclusion, MXRA7 proteins promote wound healing through vimentin in coordinating fibroblast functions.

The Potentials of Herbal Plant against the Psoriasis

Chronic autoimmune skin disease termed psoriasis is characterised by excessive keratinocyte multiplication, scaly plaques, severe inflammation, and erythema. T lymphocytes, leukocytes, vascular endothelium, and epidermal keratinocytes also contribute in the pathogenesis of psoriasis. Increased leukocyte recruitment and increased levels of cytokines, growth factors, and genetic factors like interleukin (IL)-1, IL-6, IL-17, IL-22, IL-23, tumour necrosis factor (TNF), interferon (IFN), transforming growth factor (TGF), toll-like receptor (TLR)-2, signal transducer and activator of transcription (STAT-3), 15-lipoxygenase (LOX)-2. The most important aspects impacting the treatment of psoriasis are coiled-coil alpha-helical rod protein 1 (CCHCR1), steroidogenic acute regulatory protein (StAR), and vitamin D receptor (VDR). Various synthetic medicinal drugs have also been known to have the side effect of psoriasis. Due to their safety and accessibility, herbal medications may indicate the potential as effective anti-psoriatic agents.
 Keywords: Psoriasis, Herbal Drug, Silybum marianum, Thespesia populnea, Mahonia aquifolium

Human Regulatory T Cells: Understanding the Role of Tregs in Select Autoimmune Skin Diseases and Post-Transplant Nonmelanoma Skin Cancers.

Regulatory T cells (Tregs) play an important role in maintaining immune tolerance and homeostasis by modulating how the immune system is activated. Several studies have documented the critical role of Tregs in suppressing the functions of effector T cells and antigen-presenting cells. Under certain conditions, Tregs can lose their suppressive capability, leading to a compromised immune system. For example, mutations in the Treg transcription factor, Forkhead box P3 (FOXP3), can drive the development of autoimmune diseases in multiple organs within the body. Furthermore, mutations leading to a reduction in the numbers of Tregs or a change in their function facilitate autoimmunity, whereas an overabundance can inhibit anti-tumor and anti-pathogen immunity. This review discusses the characteristics of Tregs and their mechanism of action in select autoimmune skin diseases, transplantation, and skin cancer. We also examine the potential of Tregs-based cellular therapies in autoimmunity.

Review of an Anti-CD20 Monoclonal Antibody for the Treatment of Autoimmune Diseases of the Skin.

Biologic therapies targeting B-cells are emerging as an effective strategy to treat a variety of immune-mediated diseases. One of the most studied B-cell-targeted therapies is rituximab, an anti-CD20 monoclonal antibody that exemplifies B-cell depletion therapy and has served as the prototype for other anti-CD20 monoclonal antibodies and the development of biosimilars. While there are multiple studies on the use of rituximab in dermatology, a comprehensive review of rituximab therapy in autoimmune skin conditions is lacking. In this literature review, we summarize indications, treatment efficacy, and safety of rituximab among common autoimmune diseases of the skin: pemphigus vulgaris, cutaneous lupus erythematous, dermatomyositis, systemic sclerosis, thyroid dermopathy, autoimmune pemphigoid diseases, and cutaneous vasculitis diseases. Existing data on rituximab support the approach of rituximab, biosimilars, and newer B-cell-targeting therapies in immune-mediated cutaneous diseases. Overall, rituximab, which targets CD20, provides an effective alternative or concomitant option to traditional immunosuppressants in the management of various autoimmune diseases of the skin. Further studies are necessary to expand the understanding and possible utility of B-cell-targeted therapies among autoimmune skin diseases.

Novel Synergistic Approach: Tazarotene-Calcipotriol-Loaded-PVA/PVP-Nanofibers Incorporated in Hydrogel Film for Management and Treatment of Psoriasis.

Psoriasis is an autoimmune skin disease that generally affects 1%-3% of the total population globally. Effective treatment of psoriasis is limited because of numerous factors, such as ineffective drug delivery and efficacy following conventional pharmaceutical treatments. Nanofibers are widely being used as nanocarriers for effective treatment because of their multifunctional and distinctive properties, including a greater surface area, higher volume ratio, increased elasticity and improved stiffness and resistance to traction, favorable biodegradability, high permeability, and sufficient oxygen supply, which help maintain the moisture content of the skin and improve the bioavailability of the drugs. Similar to the extracellular matrix, nanofibers have a regeneration capacity, promoting cell growth, adhesion, and proliferation, and also have a more controlled release pattern compared with that of other conventional therapies at the psoriatic site. To ensure improved drug targeting and better antipsoriatic efficacy, this study formulated and evaluated a tazarotene (TZT)-calcipotriol (CPT)-loaded nanofiber and carbopol-based hydrogel film. The nanofiber was prepared using electrospinning with a polyvinyl alcohol/polyvinylpyrrolidone (PVA/PVP) K-90 polymeric blend that was later incorporated into a carbopol base to form hydrogel films. The prepared nanofibers were biochemically evaluated and in vitro and in vivo characterized. The mean diameters of the optimized formulation, i.e., TZT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-PVA/PVP-NF) and TZT-CPT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-CPT-PVA/PVP-NF) were 244.67 ± 58.11 and 252.31 ± 35.50 nm, respectively, as determined by scanning electron microscopy, and their tensile strength ranged from 14.02 ± 0.54 to 22.50 ± 0.03 MPa. X-ray diffraction revealed an increase in the amorphous nature of the nanofibers. The biodegradability studies of prepared nanofiber formulations, irrespective of their composition, showed that these completely biodegraded within 2 weeks of their application. The TZT-CPT-PVA/PVP-NF nanofibers exhibited 95.68% ± 0.03% drug release at the end of 72 h, indicating a controlled release pattern and following Higuchi release kinetics as a best-fit model. MTT assay, antioxidant and lipid profile tests, splenomegaly assessment, and weight fluctuation were all performed in the in vitro as well as in vivo studies. We found that the TZT-CPT-PVA/PVP-NF-based hydrogel film has high potential for antipsoriatic activity in imiquimod-induced Wistar rats in comparison with that of TT-PVA/PVP-NF nanofibers.

Autoimmune blistering skin diseases triggered by COVID-19 vaccinations: An Australian case series.

Autoimmune blistering skin diseases (AIBD) can be induced or flared by a multitude of sources, however, there have been some reports suggesting that this occurrence is due to COVID-19 vaccinations. At a single academic blistering disease centre in Sydney, Australia, a retrospective review was conducted, identifying 59 patients with AIBD seen between February 2021 and November 2022. Secondary to recent COVID-19 vaccination, four patients had induction of bullous pemphigoid, three patients had a flare of pre-existing bullous pemphigoid, one patient had induction of pemphigus, and two patients had a flare of pre-existing pemphigus vulgaris. This adds to our understanding of the role of vaccinations in the activity of AIBD.

Lisinopril prevents bullous pemphigoid induced by dipeptidyl peptidase 4 inhibitors via the Mas receptor pathway.

Recent studies have suggested that dipeptidyl peptidase 4 (DPP4) inhibitors increase the risk of development of bullous pemphigoid (BP), which is the most common autoimmune blistering skin disease; however, the associated mechanisms remain unclear, and thus far, no therapeutic targets responsible for drug-induced BP have been identified. Therefore, we used clinical data mining to identify candidate drugs that can suppress DPP4 inhibitor-associated BP, and we experimentally examined the underlying molecular mechanisms using human peripheral blood mononuclear cells (hPBMCs). A search of the US Food and Drug Administration Adverse Event Reporting System and the IBM® MarketScan® Research databases indicated that DPP4 inhibitors increased the risk of BP, and that the concomitant use of lisinopril, an angiotensin-converting enzyme inhibitor, significantly decreased the incidence of BP in patients receiving DPP4 inhibitors. Additionally, in vitro experiments with hPBMCs showed that DPP4 inhibitors upregulated mRNA expression of MMP9 and ACE2, which are responsible for the pathophysiology of BP in monocytes/macrophages. Furthermore, lisinopril and Mas receptor (MasR) inhibitors suppressed DPP4 inhibitor-induced upregulation of MMP9. These findings suggest that the modulation of the renin-angiotensin system, especially the angiotensin1-7/MasR axis, is a therapeutic target in DPP4 inhibitor-associated BP.

Antiproliferative and Anti-Inflammatory Activities of Deprungsith Formulation and Its Bioactive Compounds Against Mild Psoriasis and Potential of Metabolic Herb-Drug Interactions.

Psoriasis is an incurable, chronic and auto-immune skin disorder with a global prevalence rate of approximately 2-3%. The study investigated the antipsoriasis activities of Deprungsith formulation and its bioactive components and their potential for inhibitory activities on human cytochrome P450 (CYP450). HaCaT and peripheral blood mononuclear cells (PBMCs) from healthy volunteers (n = 9) and psoriasis patients (n = 10) were exposed to Deprungsith formulation (Thai traditional medicine for psoriasis consisting of 16 plants), ethyl p-methoxycinnamate (EPMC), ligustilide and cyclosporin for 24 and 48 h. The antiproliferative, cell apoptosis and cell cycle arrest activities were evaluated using MTT assay and flow cytometry, respectively. The pro-inflammatory cytokine mRNA expression levels were measured using real-time polymerase chain reaction (RT-PCR). The CYP450 inhibitory effect was investigated using a bioluminescent-based CYP450 assay. Deprungsith formulation and the bioactive compounds inhibited HaCaT cells and PBMCs with weak to moderate potencies. EPMC and ligustilide combination produced an additive effect. Most substances arrested cell transition at sub-G1 and S phases, leading to early and late apoptosis induction. With prolonged exposure (48 h), all test substances decreased PBMCs necrosis. The mRNA expression of all pro-inflammatory cytokines was downregulated. Deprungsith formulation, EPMC, ligustilide and ferulic acid inhibited CYP1A2, CYP2C9, CYP2D6 and CYP3A4 activities with weak to moderate potencies. Deprungsith formulation and bioactive components induced cell apoptosis by inhibiting cell transition at specific cell cycle phases, which was correlated with the mRNA downregulation of interleukin (IL-6, IL-12p19, IL-23) and tumor necrosis factor (TNF-α). There is a low risk of potential adverse drug reactions and toxicity due to CYP450 interaction when Deprungsith formulation is concurrently administered with modern medicines.

Primary biliary cholangitis—cause or association with psoriasis: a case report

Primary biliary cholangitis is a chronic progressive cholestatic granulomatous and destructive inflammatory lesion of small intralobular and septal bile ducts that primarily affects women. The exact etiology of this disease has not yet been elucidated; however, it is believed to be the result of a combination of environmental triggers in genetically predisposed individuals. It can manifest itself simultaneously with, before, or after the onset of psoriasis and other skin autoimmune diseases. Standard treatment is ursodeoxycholic acid. A 65-year-old patient presenting with elevated hepatic laboratory findings that had persisted for several years and normal abdominal ultrasound was additionally diagnosed with primary biliary cholangitis after 2 years on a biological drug for psoriasis. She did not have other symptoms except elevated liver tests. The skin showed a strong response to biological therapy and treatment with ursodeoxycholic acid prompted lowering of liver enzymes. The skin was clear all throughout the treatment. This article emphasizes the importance of additional diagnostic workups in patients with psoriasis and elevated hepatic laboratory findings.