From PsO to PsA: the role of TRM and Tregs in psoriatic disease, a systematic review of the literature.

Introduction: Psoriasis (PsO) is a chronic skin condition driven by immune mediators like TNFα, INFγ, IL-17, and IL-23. Psoriatic arthritis (PsA) can develop in PsO patients. Although psoriatic lesions may apparently resolve with therapy, subclinical cutaneous inflammation may persist. The role of tissue-resident memory T-cells (TRM), and regulatory T cells (Tregs) that also contribute to chronic inflammation are being explored in this context. This systematic review explores TRM and Tregs in psoriatic disease (PsD) and its progression. Methods: A systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed using Pubmed® and Web of Science™ databases on June 3rd 2023, using patient/population, intervention, comparison, and outcomes (PICO) criteria limited to the English language. Results: A total of 62 reports were identified and included. In PsO, chronic inflammation is driven by cytokines including IL-17 and IL-23, and cellular mediators such as CD8+ and CD4+ T cells. TRM contributes to local inflammation, while Tregs may be dysfunctional in psoriatic skin lesions. Secukinumab and guselkumab, which target IL-17A and the IL-23p19 subunit, respectively, have different effects on CD8+ TRM and Tregs during PsO treatment. Inhibition of IL-23 may provide better long-term results due to its impact on the Treg to CD8+ TRM ratio. IL-23 may contribute to inflammation persisting even after treatment. In PsA, subclinical enthesitis is perceived as an early occurence, and Th17 cells are involved in this pathogenic process. Recent EULAR guidelines highlight the importance of early diagnosis and treatment to intercept PsA. In PsA, CD8+ TRM cells are present in synovial fluid and Tregs are reduced in peripheral blood. The progression from PsO to PsA is marked by a shift in immune profiles, with specific T-cells subsets playing key roles in perpetuating inflammation. Early intervention targeting TRM cells may hold promising, but clinical studies are limited. Ongoing studies such as IVEPSA and PAMPA aim to improve our knowledge regarding PsA interception in high-risk PsO patients, emphasizing the need for further research in this area. Conclusion: Early intervention is crucial for PsO patients at high risk of PsA; T cells, particularly type 17 helper T cells, and CD8+ cells are key in the progression from PsO-to-PsA. Early targeting of TRM in PsD shows promise but more research is needed.

Real-world clinical, psychosocial and economic burden of atopic dermatitis: Results from a multicountry study.

BACKGROUND: Atopic dermatitis (AD), a relapsing, inflammatory skin disease, is associated with pruritus that can negatively affect patients' quality of life. Understanding the burden of AD is critical for informing and tailoring treatment and disease management to improve patient outcomes. This study characterized global treatment patterns and the clinical, psychosocial and economic burden of moderate-to-severe AD. METHODS: MEASURE-AD was a cross-sectional 28-country study in patients with physician-confirmed moderate-to-severe AD who were either receiving or eligible for systemic therapy for AD. Patients ≥12 years were enrolled between December 2019 and December 2020 while attending routine office or clinic visit. Primary outcomes included Worst Pruritus Numeric Rating Scale (WP-NRS; range: 0-10) and Dermatology Life Quality Index (DLQI; range: 0-30) and Children's DLQI (CDLQI; range: 0-30). Secondary outcomes included physician- and patient-reported clinical, psychosocial and economic burden. RESULTS: Of the 1591 patients enrolled, 1558 (1434 adults and 124 adolescents) fulfilled all patient selection criteria and were included in this analysis. Almost all patients (98.4%) in the total population were using AD medications and more than half (56%) were receiving systemic medication (15% systemic monotherapy). The most used systemic therapies were dupilumab (56.3%), systemic glucocorticoids (18.1%) and methotrexate (16.2%). Mean WP-NRS was 5.3 in the total population, and most patients (≥55%) reported moderate-to-severe pruritus (WP-NRS ≥4). Mean DLQI was 10.8 and mean CDLQI was 9.6. Secondary endpoints demonstrated substantial clinical, psychosocial, and economic burden of disease. Subgroup analysis demonstrated that patients receiving systemic therapy had lower disease burden than those not taking systemic medications. CONCLUSIONS: While systemic therapy lowers overall disease burden, patients with moderate-to-severe AD continue to have substantial multidimensional disease burden and uncontrolled disease. Overall, there is a need for effective disease management, including effective treatments that improve patients' psychosocial outcomes and reduce the economic burden of AD.

Bruton's tyrosine kinase inhibition-An emerging therapeutic strategy in immune-mediated dermatological conditions.

Bruton's tyrosine kinase (BTK), a member of the Tec kinase family, is critically involved in a range of immunological pathways. The clinical application of BTK inhibitors for B-cell malignancies has proven successful, and there is strong rationale for the potential benefits of BTK inhibitors in some autoimmune and allergic conditions, including immune-mediated dermatological diseases. However, the established risk-to-benefit profile of "first-generation" BTK inhibitors cannot be extrapolated to these emerging, non-oncological, indications. "Next-generation" BTK inhibitors such as remibrutinib and fenebrutinib entered clinical development for chronic spontaneous urticaria (CSU); rilzabrutinib and tirabrutinib are being studied as potential treatments for pemphigus. Promising data from early-phase clinical trials in CSU suggest potential for these agents to achieve strong pathway inhibition, which may translate into measurable clinical benefits, as well as other effects such as the disruption of autoantibody production. BTK inhibitors may help to overcome some of the shortcomings of monoclonal antibody treatments for immune-mediated dermatological conditions such as CSU, pemphigus, and systemic lupus erythematosus. In addition, the use of BTK inhibitors may improve understanding of the pathophysiological roles of mast cells, basophils, and B cells in such conditions.

Beyond striae cutis: A case report on how physical skin complaints unveiled end-of-life total experience.

BACKGROUND: End-of-life is a unique and multidimensional experience, and physical complaints can reveal other areas of distress. METHOD: A case report of a woman with terminal cancer with painful and deforming skin striae cared by a multidisciplinary team. RESULTS: After initially treating her physical pain, other end-of-life psychosocial, spiritual, and existential aspects could be addressed. SIGNIFICANCE OF RESULTS: Physical distress can unveil other essential areas of end-of-life experience when multidisciplinary teams caring for the terminally ill patients use holistic approaches.

Plantar keratoderma climatericum: Successful improvement with a topical estriol cream.

Keratoderma climatericum affects menopausal women, and the diagnosis relies on typical clinical findings and exclusion of other potential causes of acquired keratoderma. Although its pathophysiology is still unknown, there has been speculation about its relation to hormonal dysregulation (possibly a local estrogen deficiency) since the 1930s. A female patient with long-lasting keratoderma climatericum was initially prescribed a topical 50% urea ointment and clobetasol propionate 0.05% ointment, with just a slight improvement after 2 months of daily use. The patient was started on topical estriol 0.125 mg/g vaginal cream applied on the plantar surface after her daily shower and application of the same topical 50% urea ointment and clobetasol propionate 0.05% ointment on alternate nights. There was a marked improvement under this regimen with total and fast control of the pruritus. At 6-month follow-up the patient retained total symptomatic control and was just applying the estriol cream and the 50% urea containing ointment. We report a case of a difficult to treat plantar keratoderma that markedly improved after adding a daily topical application of a vaginal cream containing estriol 0.125 mg/g. Trials that determine the efficacy and safety of topical estrogens for keratoderma climatericum are warranted.

Rapidly involuting congenital hemangioma

Abstract: Rapidly involuting congenital hemangioma is a rare vascular tumor that generally has a good prognosis. The authors describe a case of a newborn girl with a left cervical vascular lesion. Image exams were performed, and the lesion slowly decreased, leaving redundant skin. Considering all of the findings, a final diagnosis of a rapidly involuting congenital hemangiomas was suspected.

Secondary Skin Plasmacytomas.

A 78-year old man was diagnosed in 2006 with IgAκ multiple myeloma (MM) (stage III-A). The patient was referred to our dermatology department in 2012 for evaluation of erythematous skin nodules on the anterior right aspect of the thorax; the skin lesions were noted during hospitalization for multiple bone fractures. He was on fourth-line chemotherapy (with vincristine/adriamycin/dexamethasone) because of constant disease progression. The patient was unaware of the skin lesions' evolution over time and did not recall when they had first appeared. He had no pain, itching, or spontaneous bleeding.

Rapidly involuting congenital hemangioma.

Rapidly involuting congenital hemangioma is a rare vascular tumor that generally has a good prognosis. The authors describe a case of a newborn girl with a left cervical vascular lesion. Image exams were performed, and the lesion slowly decreased, leaving redundant skin. Considering all of the findings, a final diagnosis of a rapidly involuting congenital hemangiomas was suspected.

De novo HIV infection diagnoses in a Department of Dermatology and Venereology in Lisbon, Portugal.

Background Portugal has the highest prevalence rate of HIV infection in Western Europe. The proportion of patients with a late diagnosis, carried out in full-blown AIDS stage, remains high. Skin and mucous membrane manifestations are not rare in these patients. Objective A demographic, clinical, and laboratorial characterization of patients with de novo HIV infection diagnosis made in the Department of Dermatology and Venereology of a central hospital in Lisbon, Portugal. Methods Retrospective review of medical records of adult patients newly diagnosed with HIV infection (reactive immunoassay for antibodies to HIV-1/HIV-2 or HIV p24 antigen) in the Dermatology and Venereology Department of a Portuguese central hospital in the period between January 2005 and December 2013. Results During the study period, 97 new cases were diagnosed, 70 men and 27 women. The median age at diagnosis was 36 years. Of the total, 50 cases were diagnosed with a concomitant sexually transmitted infection (STI), more frequently syphilis and ano-genital HPV infection. The remaining 47 patients were diagnosed with other dermatological conditions such as prurigo nodularis, psoriasis, and Kaposi's sarcoma. The duration of complaints that lead to medical attention ranged from <1 week to 8 years, being significantly lower in patients diagnosed with a concomitant STI ( p < 0.01). Basal viral load was also lower in this group of patients ( p < 0.05). Of all the new diagnosed cases, 80% of patients are currently retained in care. Conclusion This study grants a descriptive overview of de novo HIV infection diagnoses performed by dermatovenereologists in a central hospital in Lisbon, Portugal. As in the past, the importance of Dermato-Venereology for HIV infection diagnosis remains present in daily clinical practice.

IgA vasculitis (formerly Henoch-Schönlein purpura) in an adult with systemic lupus erythematosus.

We report a case of a 65-year-old man with systemic lupus erythematosus (SLE) and antiphospholipid syndrome, presenting palpable purpuric lesions, necrotic blisters and swelling ankles, after a previous tracheobronchitis episode. Laboratory data were remarkable for mild proteinuria and imaging studies were normal. A skin biopsy showed IgA deposits on superficial dermal capillaries and IgA vasculitis (IgAV) (former Henoch-Schönlein purpura) was assumed. The patient was treated with colchicine, deflazacort and azathioprine, but as a regression in the purpuric lesions was noted, a decline in renal function was detected. A kidney biopsy revealed mesangial proliferation with IgA deposition and IgAV nephritis was considered. Immunosuppressive treatment was adjusted, with progressive normalisation of renal function and disappearance of proteinuria over a monthly follow-up; after 6 months, total remission was achieved. To the best of our knowledge, this is the first reported case of IgAV in an adult patient with SLE.

Imatinib: a novel treatment approach for generalized morphea.

BACKGROUND: Morphea is a rare chronic inflammatory disease that involves skin and subcutaneous tissues, causing skin sclerosis. Generalized morphea is characterized by extensive cutaneous involvement and poor response to therapy. Although the pathophysiology for morphea is not completely understood, abnormal signaling through the platelet-derived growth factor and transforming growth factor beta axes seems to play a major role in the inflammatory response and sclerotic process. Imatinib, a tyrosine kinase inhibitor, interferes with both transforming growth factor beta and platelet-derived growth factor signaling pathways. Recent studies proved imatinib's efficacy in the prevention and regression of fibrosis associated with systemic sclerosis, nephrogenic sclerosis, and bleomycin-related fibrosis. OBSERVATIONS: We present the case of a 50-year-old Caucasian man with a generalized morphea diagnosed 10 years ago, with multiple ulcers, who was treated with imatinib over the course of 12 months. At the end of the treatment, most of the skin ulcerations had healed, and cutaneous thickness was reduced as demonstrated by skin biopsy and ultrasound evaluation. The patient also experienced an improvement in articular mobility, sustained by a 20° increase in left knee extension. CONCLUSIONS: Although controlled studies are necessary to access the antifibrotic effect of imatinib in morphea, the present report shows its potential role in the treatment of this condition.