Does molecular scarring in psoriasis exist? A review of the literature.

Plaque psoriasis is a chronic inflammatory dermatosis characterized by a tendency to recur in the same locations after discontinuation of treatment. The implementation of therapy with drugs targeting cytokines like interleukin (IL) 17A (IL-17A) and IL-23 has revolutionized the treatment of psoriasis and enabled the achievement of skin without lesions. However, despite the clinical resolution of psoriatic eruptions, cells that maintain the local memory of the disease remain in the dermis and epidermis, constituting a kind of molecular scar. The cells responsible for maintaining memory in the skin of patients and influencing the rapid relapse of the disease after the triggering factor are primarily tissue resident memory T cells (TRM), but it seems that regulatory T lymphocytes (Treg), dendritic cells (DC), and Langerhans cells (LC) may also play an important role in this process. We reviewed the literature to explain the concept of molecular scarring in psoriasis, and to assess the effect of various therapies on immune memory.

Substantivity of mouth-rinse formulations containing cetylpyridinium chloride and O-cymen-5-ol: a randomized-crossover trial.

BACKGROUND: The efficacy of mouth-rinses strongly depends upon their substantivity. The use of natural and non-toxic products that avoid secondary effects is gaining interest in preventive dentistry. The purpose of this study was to evaluate the substantivity of two formulations of mouth-washing solutions based on cetylpyridinium (CPC) and O-cymen-5-ol. METHODS: This was a randomized, double-blind, crossover trial conducted at the Faculty of Medicine and Health Sciences of the University of Barcelona. Bacterial re-colonization was followed by live/dead (SYTOTM9 + propidium iodide) bacterial staining and measured by confocal laser scanning microscopy and fluorometry. Unstimulated saliva samples were collected from 16 healthy individuals at baseline saliva and then, at 15 min, 30 min and 1, 2, 3, and 4 h after the following mouth-rinses: (i) a single, 1-min mouth-rinse with 15 ml of placebo (negative control); (ii) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) ; (iii) a single, 1-min mouth-rinse with 15 ml of O-cymen-5-ol (0.09%); (iv) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) + O-cymen-5-ol (0.09%). RESULTS: Proportion of dead bacteria was significantly higher for all mouthrinses during the first 15 min compared to baseline (CPC = 48.0 ± 13.9; 95% CI 40.98-56.99; p < 0.001, O-cymen-5-ol = 79.8 ± 21.0; 95% CI 67.71-91.90; p < 0.05, CPC + O-cymen-5-ol = 49.4 ± 14; 95% CI 40.98-56.99; p < 0.001 by fluorometry and 54.8 ± 23.0; 95% CI 41.50-68.06; p < 0.001, 76.3 ± 17.1; 95% CI 66.36-86.14; p < 0.001, 47.4 ± 11.9; 95% CI 40.49-54.30; p < 0.001 by confocal laser scanning microscopy, respectively). Nevertheless, after 4 h, CPC + O-cymen-5-ol was the only one that obtained significant values as measured by the two quantification methods used (80.3 ± 22.8; 95% CI 67.15-93.50; p < 0.05 and 81.4 ± 13.8; 95% CI 73.45-89.43; p < 0.05). The combined use of CPC + O-cymen-5-ol increased the substantivity of the mouthrinse with respect to mouthrinses prepared with either of the two active products alone. CONCLUSION: The synergistic interaction of CPC and O-cymen-5-ol prolongs their substantivity. The resulting formulation may be as effective as other antimicrobials, such as triclosan or chlorhexidine, but without their undesirable secondary effects. Thus, mouthrinsing products based on Combinations of CPC and O-cymen-5-ol may replace in the near future Triclosan and Chlorhexidine-based mouthrinses.

Aseptic Abscess Syndrome in Rheumatoid Arthritis Patient.

Aseptic abscess syndrome (AAS) is a rare, potentially life-threatening disorder, with numerous features of neutrophilic dermatoses. The main symptoms include aseptic abscess-like collections in internal organs (spleen, liver, lungs), lack of microbes (bacteria, viruses, or parasites) after an exhaustive search, ineffectiveness of antibiotics, and high sensitivity to corticosteroid therapy. AAS is characterized by the development of deep, inflammatory abscesses and systemic symptoms (weight loss, abdominal pain, fever, and leukocytosis). They may be associated with inflammatory bowel disease (IBD) and autoimmune diseases. The patient in this study is a 67-year-old man, suffering from rheumatoid arthritis (RA), with numerous purulent abscesses in the mediastinum, within the subcutaneous tissue above the extension surfaces of the joints, and on the dorsum of the hands. The lesions are accompanied by bone destruction. The patient was treated with prednisone 40 mg and adalimumab, which resulted in a quick reduction of inflammatory markers and clinical improvement, as well as the healing and absorption of abscesses. Despite COVID-19 infection, treatment with remdesivir, prednisone, and adalimumab was continued, with the complete resolution of the lesions. AAS is difficult to recognize, so practitioners have to be aware of this condition, especially in patients with RA.

The effect of therapy on TRM in psoriatic lesions.

Introduction: The course of psoriasis is associated with recurrence of the lesions at the same location despite effective treatment. It is due to the presence of TRM (tissue-resident memory cells) in the seemingly healthy skin, which may initiate an inflammatory cascade. Aim: The assessment of TRM in psoriatic lesions prior to and after 12 weeks of systemic therapy with methotrexate (MTX) or secukinumab (SEC) or ixekizumab (IXE) or adalimumab (ADA). Material and methods: TRM markers (CD4, CD8, CD103, CD69, CD49, CXCR6) and the tissue expression of cytokines (IL-17, IL-22) in the psoriatic lesions obtained from 13 patients compared to 10 healthy skin samples were evaluated with immunohistochemistry. Biopsy specimens were collected three times from the same psoriatic plaque before and after 4 and 12 weeks of therapy. Results: The expression of TRM markers in the lesions decreased at three time points (W0, W4, W12), revealing the diminished intensity of fluorescence over time with each therapy. The most rapid response was observed with anti-IL-17 therapy at W4 of treatment, while with MTX and ADA at W12. Conclusions: The decreased expression of TRM markers occurring predominantly in the lesional dermis and not in the epidermis over 12 weeks of observation may be due to the poorer penetration of systemic drugs to the epidermis, or the process of psoriatic lesion regression in the epidermis is secondary to the reduction of inflammation in the skin, or TRM in the epidermis may be more resistant to therapy.

D-chiro-inositol as a treatment in plaque psoriasis: A randomized placebo-controlled clinical trial.

Cyclitols are widely available natural sugars which do not exert toxic effects. Their anti-inflammatory and antioxidant properties may be used in the treatment of psoriasis. The aim of this placebo-controlled, double-blind study was to evaluate the clinical effects of D-chiro-inositol (DCI) in mild plaque psoriasis (46 psoriatic patients and 10 healthy volunteers). Three stable psoriatic plaques were selected for evaluation in every patient. Different samples were applied on each lesion twice a day: vehiculum without an active agent, containing 1% DCI and 0.25% DCI. The lesions were assessed using the PSI, VAS scale, and the objective measurement of hydration, transepidermal water loss (TEWL), elasticity, and thickness (DermaLab Combo) at 0, 3, and 6 weeks. PSI and VAS were improved in all groups without significant statistical differences. 1% DCI sample presented the highest statistically significant increase in the hydration of 50%, but it was still significantly lower than in healthy controls. TEWL increased for 1% DCI, which was a statistically significant difference compared to 0.25% DCI and still higher than in controls. An improvement in elasticity was observed in all lesions-it was statistically significant for 1% DCI. The thickness of the lesion decreased for 1% DCI, but the change was not statistically significant. Subepidermal low-echogenic band showed a decreasing tendency in all groups, but it was not statistically significant. Favorable 1% DCI sample results indicate that it may be used as an adjuvant to the local treatment of psoriasis.

The Role of Chemokines in Psoriasis-An Overview.

By participating in both the recruitment and activation of T lymphocytes, macrophages and neutrophils at the site of psoriatic inflammation, chemokines play an important role in the pathogenesis of psoriasis and, crucially, may be one indicator of the response to the systemic treatment of the disease. As a result of their major involvement in both physiological and pathological processes, both chemokines and their receptors have been identified as possible therapeutic targets. Due to their presence in the inflammatory process, they play a role in the pathogenesis of diseases that often coexist with psoriasis, such as atherosclerosis and psoriatic arthritis. Chemokines, cytokines and adhesion molecules may be biological markers of disease severity in psoriasis. However, the mechanism of inflammation in psoriasis is too complex to select only one marker to monitor the disease process and improvement after treatment. The aim of this review was to summarize previous reports on the role of chemokines in the pathogenesis of psoriasis, its treatment and comorbidities.

Immunological Memory of Psoriatic Lesions.

The natural course of psoriasis is the appearance of new lesions in the place of previous ones, which disappeared after a successful therapy. Recent studies of psoriasis etiopathogenesis showed that after psoriatic plaques have disappeared, in healthy skin we can still find a trace of inflammation in the form of tissue resident memory cells (TRM). They are originally responsible for protection against viral and bacterial infections in non-lymphatic tissues. In psoriatic inflammation, they are characterized by heterogeneity depending on their origin. CD8+ T cells TRM are abundantly present in psoriatic epidermis, while CD4+ TRM preferentially populate the dermis. In psoriasis, epidermal CD8+ TRM cells express CLA, CCR6, CD103 and IL-23R antigen and produce IL-17A during ex vivo stimulation. However, CD4+ CD103+ TRM can also colonize the epidermis and produce IL-22 during stimulation. Besides T cells, Th22 and epidermal DCs proved that epidermal cells in healed skin were still present and functioning after several years of disease remission. It explains the clinical phenomenon of the tendency of psoriatic lesions to relapse in the same location and it allows to develop new therapeutic strategies in the future.

Efficacy and tolerability of a depigmenting gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that targets the biological processes regulating skin melanogenesis.

BACKGROUND: The diverse causes of hyperpigmentation and complex nature of melanogenesis make it a challenge to manage. Current approaches either fail to deliver effective pigmentation control or have undesirable safety profiles that preclude their long-term use. AIMS: To evaluate the capacity of a cosmetic gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that was designed to target the biological processes regulating skin melanogenesis to attenuate melanin production in vitro and reduce hyperpigmentation clinically. METHODS: Capacity to reduce melanin production in vitro was determined in melanocyte-containing reconstructed human epidermis (RHEm). Clinical efficacy and skin tolerability following twice daily application were assessed in 35 subjects with slight to moderate facial hyperpigmentation by instrumental (VISIA®-CR, Mexameter®) and clinical (mMASI, clinical score, IGA for hyperpigmentation) evaluation on D14, D28, D56, and D84. Maintenance of pigmentation control was followed up 1 month after cessation of treatment on D112. RESULTS: In RHEm in vitro, melanin production was reduced by 50.0% from baseline (D0) on D14 (p < 0.001) and by 67.0% on D21 (p < 0.001). Clinical reductions from baseline in brown spots count (-9.0%; p < 0.05), brown spots area (-16.7%; p < 0.001), and the melanin index (-11.4%; p < 0.001) were observed within 14 days of use. Statistically significant improvements in all clinical parameters were achieved by D28. By the end of treatment on D84, the number and surface area of brown spots were reduced by 28.4% and 40.3% compared to D0, respectively (p < 0.001, both), the melanin index was reduced by 31.1% (p < 0.001), mMASI was reduced by 63.0% (p < 0.001), and skin luminosity was increased by 79.0% (p < 0.001). IGA was reduced from 2.3 on D0 to 1.3 on D84 (p < 0.001). Improvements to all these parameters were maintained until D112, 1 month after termination of treatment. The product also demonstrated very good skin tolerability. CONCLUSION: A gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, and hydroxy acids, designed to target the biological processes regulating skin melanogenesis, demonstrates rapid, robust, and sustained pigmentation control in this cohort.

Natural Retinol Analogs Potentiate the Effects of Retinal on Aged and Photodamaged Skin: Results from In Vitro to Clinical Studies.

INTRODUCTION: Plants are a source of natural ingredients with retinol-like properties that can deliver anti-aging benefits without the side effects typically associated with retinoid use. We hypothesized that by combining two such analogs, bakuchiol (BAK) and Vigna aconitifolia extract (VAE), with the potent retinoid retinal (RAL), the anti-photoaging potential of RAL could be enhanced without compromising its skin irritation profile. The purpose of this study was to demonstrate that BAK and VAE potentiate the anti-photoaging activity of RAL. METHODS: Gene expression profiling of full-thickness reconstructed skin was first used to examine the impact of BAK or VAE in combination with RAL on skin biology. Next, the irritative potential of this combination, and its capacity to reverse key signs of photoaging in an ex vivo model was assessed. Finally, a proof-of-concept open label clinical study was performed to evaluate the anti-photoaging capacity and skin compatibility of a cosmetic formulation (tri-retinoid complex; 3RC) containing this complex in combination with other well characterized anti-photoaging ingredients. RESULTS: In vitro profiling suggested that combining 0.1% RAL with BAK or VAE potentiates the effect of RAL on keratinocyte differentiation and skin barrier function without affecting its skin irritation profile. When formulated with other anti-photoaging ingredients, such as niacinamide and melatonin, 3RC reversed ultraviolet radiation-induced deficits in structural components of the dermal extracellular matrix, including hyaluronic acid and collagen. In vivo, it led to a reversal of clinical signs of age and photodamage, with statistically significant improvement to skin firmness (+5.6%), skin elasticity (+13.9%), wrinkle count (-43.2%), and skin tone homogeneity (+7.0%), observed within 28 days of once nightly use. Notably, the number of crow's feet wrinkles was reduced in 100% of subjects. Furthermore, 3RC was very well tolerated. CONCLUSION: These data suggest that 3RC is a highly effective and well-tolerated treatment for photoaging.

Surgical Treatment of Vitiligo.

Vitiligo is described as a dermatological condition characterized by pigmentation disorders in both the skin and mucous membranes. Clinically, this disease is characterized by the presence of well-defined white areas of various shapes and sizes, which are a manifestation of a reduced number of melanocytes. Due to the fact that vitiligo can be a significant cosmetic problem for patients, a number of methods are currently available to help fight for a better skin appearance. If all the available non-invasive procedures turn out to be ineffective, surgery can help, which is a very good alternative in the case of difficult-to-treat but stable changes. Both the development of new techniques and modifications to the already available treatment of cell and tissue transplantation give hope to numerous patients around the world. The effectiveness of a particular method is determined by its appropriate selection depending on the lesions undergoing therapy. Each form of surgical intervention has its advantages and disadvantages, which, along with the location or size of the treated hypopigmentation area, should be analyzed by a doctor and discussed with their patient. This article is an overview of the currently available methods of surgical treatment of vitiligo and a comparison of their pros and cons.

Changes in Tumor Necrosis Factor α (TNFα) and Peptidyl Arginine Deiminase 4 (PAD-4) Levels in Serum of General Treated Psoriatic Patients.

Psoriasis is an autoimmune disease in which the disturbed dependencies between lymphocytes, dendritic cells, keratinocytes and neutrophils play the most important role. One of them is the overproduction of neutrophil extracellular traps (NETs). The release of NETs can be induced by pathogens, as well as antibodies and immune complexes, cytokines and chemokines, including TNFα. The first step of the NET creation is the activation of peptidyl arginine deiminase 4 (PAD-4). PAD-4 seems to be responsible for citrullination of histones and chromatin decondensation, but the data on PAD-4 in NETs is inconclusive. Thus, the current study aimed to determine PAD-4 and TNFα levels in the serum of psoriatic patients by ELISA and observe the response of these factors to systemic (anti-17a, anti-TNFα and methotrexate) therapies. Increased levels of both PAD-4 and its main stimulus factor TNFα in pre-treatment patients have been reported along with the concentrations of proteins correlated with disease severity (PASI, BSA). Before treatment, the irregularities in the case of anti-nuclear antibodies level (ANA) were also observed. All of the applied therapies led to a decrease in PAD-4 and TNFα levels after 12 weeks. The most significant changes, both in protein concentrations as well as in scale scores, were noted with anti-TNFα therapy (adalimumab and infliximab). This phenomenon may be associated with the inhibition of TNFα production at different stages of psoriasis development, including NET creation. The obtained data suggest the participation of PAD-4 in the activation of neutrophils to produce NETs in psoriasis, which may create opportunities for modern therapies with PAD inhibitors. However, further exploration of gene and protein expression in psoriatic skin is needed.

The Effect of the Long-Term Calcipotriol/Betamethasone Dipropionate Local Therapy on Tissue Resident Memory Cells Markers in Psoriatic Eruptions.

BACKGROUND: The natural course of psoriasis is characterized by the long-term persistence of lesions and a predilection for relapse in the same area. It is caused by the inherence of TRM (tissue resident memory T cells) in apparently healthy skin. These cells are able to initiate an inflammatory cascade and induce relapse of the disease. These cells are characterized by high resistance to damaging factors and apoptosis, which determines their longevity. AIM: The aim of our study was to evaluate the presence of TRM in psoriatic plaques before, during and after 12 weeks of therapy in patients treated with topical calcipotriol and betamethasone dipropionate (Cal/BD) foam. METHODS: TRM markers (CD4, CD8, CD103, CD69, CD49, CXCR6) and tissue expression of cytokines (IL-17A, IL-22) in the lesional psoriatic skin from 10 patients compared to 10 healthy skin samples were estimated by immunohistochemistry. Biopsy samples from the area of the same psoriatic plaque were collected three times: before the initiation of therapy, 4 and 12 weeks after its initiation. RESULTS: The presence of TRM markers in the epidermis and dermis of psoriatic lesions was significantly higher when compared to the skin of control group patients. A reduction in the expression of the characteristic TRM markers (CD8, CD4, CD103, CD69, CXCR6, IL-17A and IL-22) was observed in the epidermis on week 12 of therapy, while a depletion in the expression of TRM in the dermis was demonstrated only in CD4 and IL-22. CONCLUSIONS: Topical treatment with Cal/BD foam significantly decreased the expression of TRM markers mainly in the epidermis, and to a lesser extent in the dermis, during the 12-week observation period. It probably results from a worse penetration of the drug into the dermis and the effect of the preparation mainly on the epidermis. The persistence of a high expression of TRM markers in the dermis may result in the rapid recurrence of lesions after discontinuation of topical treatment.

Assessment of the Tissue Resident Memory Cells in Lesional Skin of Patients with Psoriasis and in Healthy Skin of Healthy Volunteers.

BACKGROUND: In the course of plaque psoriasis, tissue resident memory cells (TRM) are responsible for the phenomenon of "immune memory" of lesions, i.e., the appearance of recurrences of lesions in the same location, as well as Koebner phenomenon. We present results determining the location and amount of TRM in psoriatic lesions in patients suffering from plaque psoriasis, as well as an analysis of the relationship between TRM markers expression and the duration and severity of the disease. METHODS: TRM markers (CD4, CD8, CD103, CD69, CD49, CXCR6) and tissue expression of cytokines (IL-17, IL-22) in the lesional psoriatic skin of 32 patients compared with 10 healthy skin samples were evaluated by immunohistochemistry. RESULTS: The presence of TRM markers in both the epidermis and skin with psoriatic eruptions was demonstrated in much higher amounts compared with the skin of healthy volunteers. A significant positive relationship was demonstrated between the expression of TRM markers in patients with plaque psoriasis and the duration of skin lesions. There was no relationship between the amount of TRM and the severity of plaque psoriasis. CONCLUSIONS: A thorough understanding of the mechanisms responsible for the development and relapse of plaque psoriasis may contribute to the implementation of more effective therapies.

The Correction of Facial Morphea Lesions by Hyaluronic Acid: A Case Series and Literature Review.

INTRODUCTION: The aim of the study is to assess the long-term safety and efficacy of hyaluronic acid (HA) administration in correction of facial morphea lesions and to review the literature on the subject. Morphea is a chronic inflammatory disease of the connective tissue which may lead to serious deformations. The lesions located on the face particularly affect patients' quality of life and self-esteem; thus, there is a demand for safe and effective methods of treatment. CASE PRESENTATION: The paper presents three female patients aged 16, 17 and 70 with facial morphea lesions who had HA preparation Juvéderm® Voluma or Volux, Vycross® technology, Allergan, injected. One of the patients had additionally fractional ablative CO2 laser (FAL) therapy. DISCUSSION: The literature provides reports on successful use of HA, polymethylmethacrylate and poly-L-lactic acid for the correction of facial defects in localized scleroderma. HA is a natural component of the extracellular matrix and it therefore minimizes the probability of immunogenicity. The application technique also plays an important role. On the other hand, FAL therapy leads to the degradation of the abnormal collagen and the induction of normal collagen synthesis. CONCLUSIONS: HA injection and combination of HA application with FAL are minimally invasive, effective and safe therapeutic options for patients suffering from morphea.