Severe Chronic Skin Research Articles

Bioinspired Collagen Scaffold Loaded with bFGF-Overexpressing Human Mesenchymal Stromal Cells Accelerating Diabetic Skin Wound Healing via HIF-1 Signal Pathway Regulated Neovascularization.

The healing of severe chronic skin wounds in chronic diabetic patients is still a huge clinical challenge due to complex regeneration processes and control signals. Therefore, a single approach is difficult in obtaining satisfactory therapeutic efficacy for severe diabetic skin wounds. In this study, we adopted a composite strategy for diabetic skin wound healing. First, we fabricated a collagen-based biomimetic skin scaffold. The human basic fibroblast growth factor (bFGF) gene was electrically transduced into human umbilical cord mesenchymal stromal cells (UC-MSCs), and the stable bFGF-overexpressing UC-MSCs (bFGF-MSCs) clones were screened out. Then, an inspired collagen scaffold loaded with bFGF-MSCs was applied to treat full-thickness skin incision wounds in a streptozotocin-induced diabetic rat model. The mechanism of skin damage repair in diabetes mellitus was investigated using RNA-Seq and Western blot assays. The bioinspired collagen scaffold demonstrated good biocompatibility for skin-regeneration-associated cells such as human fibroblast (HFs) and endothelial cells (ECs). The bioinspired collagen scaffold loaded with bFGF-MSCs accelerated the diabetic full-thickness incision wound healing including cell proliferation enhancement, collagen deposition, and re-epithelialization, compared with other treatments. We also showed that the inspired skin scaffold could enhance the in vitro tube formation of ECs and the early angiogenesis process of the wound tissue in vivo. Further findings revealed enhanced angiogenic potential in ECs stimulated by bFGF-MSCs, evidenced by increased AKT phosphorylation and elevated HIF-1α and HIF-1β levels, indicating the activation of HIF-1 pathways in diabetic wound healing. Based on the superior biocompatibility and bioactivity, the novel bioinspired skin healing materials composed of the collagen scaffold and bFGF-MSCs will be promising for healing diabetic skin wounds and even other refractory tissue regenerations. The bioinspired collagen scaffold loaded with bFGF-MSCs could accelerate diabetic wound healing via neovascularization by activating HIF-1 pathways.

Unlocking the Potential of Herbal Therapies in the Management of Psoriasis: Prospects and Challenges

Background:: Psoriasis is a severe chronic skin disease with no permanent cure, caused by inherited, immunologic, and environmental factors, like trauma, medications, infection, humidity, and stress. It can have a devastating impact on people's lives and is often associated with systemic conditions, like arthritis. The exact cause of psoriasis remains unclear, but it involves the activation of cytokines, chemokines, and growth factors, playing a major role in Th1/Th17 regulation. Methods:: The PubMed and Google Scholar search engines were used to conduct the literature review. The search terms included "psoriasis and classification," "therapeutic strategies and psoriasis," "herbal medicine and psoriasis," and "herbal nanocarrier and psoriasis." An attempt was made to compile relevant material with a focus on only herbal treatments for psoriasis management. Results:: An extensive literature search showed that herbal treatments that constitute plant-based therapies have been largely utilized to treat infections. Natural medicines have been gaining tremendous momentum in the recent decade due to minimal side effects. Approximately 75-80% of the global population in developing countries consume natural remedies. Conclusion:: Psoriasis remains a severe chronic skin disease without a permanent cure, influenced by inherited, immunologic, and environmental factors. Herbal treatments show promise in managing psoriasis with minimal side effects, offering hope for improved quality of life. This report has highlighted the potential of plant-based therapies and their role in treating psoriasis.

Photogallery. Genodermatoses. Part II

Genodermatoses are a group of hereditary diseases primarily affecting the skin. To date, there are more than two hundred genetically determined dermatoses representing about 35% of all genetic diseases and 10% of all skin diseases. Genodermatoses can be caused by mutations in a single gene or the interaction of several genes and environmental factors. Hereditary diseases are characterized by a wide variety of phenotypic manifestations and the diagnostic complexity which represents a serious problem in modern dermatology.
 We present a gallery of hereditary dermatoses.
 Unna-Tost disease is a genodermatosis inherited in an autosomal dominant manner and characterized by diffuse excessive keratinization of the skin on the palms and soles, manifesting in the first to second year of life.
 Buschke-Fischer-Brauer punctate palmoplantar keratoderma is a late-developing focal dermatosis in which painful hyperkeratotic papules can occur when traumatized.
 Ehlers-Danlos syndrome is a condition demonstrating skin hyperextensibility and a number of typical symptoms of the skeletal and cardiovascular systems.
 Progeria manifests as premature skin aging, affecting the endocrine, skeletal, cardiovascular, and other systems of the body, as well as increasing the risk of developing malignant neoplasms of internal organs and skin.
 Congenital ichthyosiform erythroderma of Brocq is a severe chronic skin disease with autosomal recessive inheritance, which follows the pattern of lamellar ichthyosis but to a milder degree.
 X-linked ichthyosis, a hereditary "darkening" condition, occurs only in males and is characterized by impaired keratinization and the presence of gray-black scales on the skin.
 Lamellar ichthyosis is an autosomal recessive dermatosis characterized by generalized skin involvement.
 Netherton syndrome is a rare condition characterized by a combination of ichthyosis with structural anomalies of the hair shaft and atopy.

Outcome of Multiple Myeloma Patients Undergoing Allogeneic Stem Cell Transplant with Post-Transplant Cyclophosphamide - a Single Center Experience

Objective: The survival of multiple myeloma (MM) patients has improved significantly in the past decade with the development of new effective treatments including immunomodulators, monoclonal antibodies, and chimeric antigen receptor T cell (CAR-T) therapy. However, to date, none of the available treatments is curative for MM. In high-risk and relapsed patients, allogeneic stem cell transplant (allo-SCT) achieved long term survival in carefully selected MM patients. Here, we report our experience in MM patients who received allo-SCT at Thomas Jefferson University Hospital (TJUH). We aim to define the role of allo-SCT in the new era of MM treatment. Method: We retrospectively analyzed data of 57 MM patients who received allo-SCT at TJUH from 1996-2023. We used EZR software to analyze post-transplant outcomes including overall survival (OS) and disease-free survival (DFS) with Kaplan Meier method. Cumulative incidence (CI) calculated by EZR was used to determine relapse rate (RR) and non-relapse mortality (NRM). Median time to neutrophil and platelet engraftment was analyzed by Excel 2022. Results: The median age was 53 years old (range from 34-68 years old); 29 females and 28 males. Mean follow up time was 57.9 months (range from 0 to 253.6 months). Thirty-two patients received reduced intensity conditioning, 11 patients received myeloablative conditioning regimen, and 5 patients received non-myeloablative conditioning regimens. Thirty-one patients received matched related donor (MRD), 3 patients received matched unrelated donor (MUD), 21 patients received haploidentical (HI), and 2 patients received mismatched unrelated donor stem cell grafts. Time to neutrophil and platelet engraftment data was available for 33 and 29 patients, respectively. The median time to neutrophil engraftment was 12 days (range from 3-23 days). and the median time to platelet engraftment was 16 days (range from 6-51days). The 3-year and 5-year probabilities of OS were 53.2% (95% confidence interval is 38.7% to 65.7%) and 48.3% (95% confidence interval is 33.9% to 61.3%) respectively. The 3-year and 5-year probability of DFS were 37% (95% confidence interval is 21.6% to 52.5%) and 26.2% (95% confidence interval is 12.6% to 42%) respectively. Since 2009, most of the patients (33/36) in this study received post-transplant cyclophosphamide. Thus, we compared the OS for patients who received allo-SCT before 2009 and after 2009. The 5-years OS was 28.6% (95% confidence interval is 7.8% to 42.5%) and 62.7% (95% confidence interval is 43% to 77.2%) for patients who received allo-SCT before 2009 and after 2009 respectively (P=0.029). Among 43 patients with available relapse date data, the CI of relapse at 3 years was 36.9% (95% confidence interval 21.5%-52.4%) and the CI of NRM at 3 years was 26.1% (95% confidence interval 14%-39.9%). Thirty-five patients were evaluable for acute graft versus host disease (GVHD). Nine patients developed grade I-IV acute GVHD (25.7%) and 2 patients experienced grade III-IV acute GVHD (5.7%). Four out of 35 evaluable patients experienced chronic GVHD (11.4%): 2 patients had mild to moderate scleroderma, one patient had severe chronic skin GVHD and one had severe lung chronic GVHD. For 36 patients received allo-SCT after 2009, 3 died from relapse, 3 patients died from infection, 2 died from GVHD, 2 from unknown cause, one from brain bleeding, one from non-infectious pulmonary failure and one from acute heart failure. Conclusion: In MM patients with high-risk feature or relapsed/refractory disease, allo-SCT can be curative for approximately a third of the patients. Post-transplant cyclophosphamide coupled with contemporaneous MM treatments significantly increased the survival of allo-SCT MM patients in the modern era.

Adiponectin Contributes to the Inflammatory Milieu in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a severe chronic skin disease. Although the pathogenesis remains unclear, at the basis of HS there is an enhancement of the immune and inflammatory response together with a susceptibility to environmental factors. Cytokine dysregulation is crucial in HS severity and progression. The aim of this study was to analyze serum levels of different cytokines focusing on adiponectin concentration and its oligomers in HS patients compared to both obese and healthy subjects. The concentrations of adiponectin and cytokines were measured using enzyme-linked immunosorbent assay (ELISA); the oligomeric distribution of adiponectin (low molecular weight (LMW), medium molecular weight (MMW) and high molecular weight (HMW) oligomers)was evaluated through Western Blotting analysis. Total adiponectin is statistically higher in HS patients compared to matched controls and obese subjects. Interestingly, Adiponectin oligomerization state is altered in HS, with an increase of HMW oligomers. Serum levels of PDGF-BB, IL-1β, IL-5, Il-6, IL12, IL13, IL15, IL-17, GMCSF, INFγ, VEGF and MCP-1 are statistically higher while IL-1ra and RANTES levels are statistically lower in HS patients compared to healthy controls. Interestingly, adiponectin positively correlates with PDGF-BB, and IL-13. Our data confirmed that the complex network that links metabolism to immune homeostasis is dysregulated in HS and that adiponectin and its HMW oligomers are actively involved in this disease. In addition, the correlation between adiponectin and PDGF-BB, and IL-13 extends the role of this adipokine in modulation of the immune response, in particular regulating the innate immune system rather that the adaptive one. Further researches are needed to clarify the complex inflammatory milieu that characterizes HS syndrome.

Prenatal Diagnosis of Harlequin Ichthyosis: A Case Report

Abstract Harlequin ichthyosis is a severe autosomal recessive skin disorder. Most deaths occur within the first few days after birth, and the survivors still have severe chronic skin disease throughout their lives. Almost all cases were associated with a pathogenic variant of adenosine triphosphate binding cassette transporter, subfamily A, member 12 (ABCA12) gene. We described a case of HI diagnosed by ultrasound examination during the second-trimester and genetic diagnosis reveal two novel heterozygous ABCA12 mutations c.2563-2570delinsGGCAATT, p.(Leu855Glyfs∗13), and c.6116delT, p.(Met2039Argfs∗8) by the next-generation DNA sequencing, which further enriched our understanding of the pathogenic variation of ABCA12 gene.

Teledermatologic monitoring for chronic cutaneous autoimmune diseases with smartworking during COVID-19 emergency in a tertiary center in Italy.

Because of the coronavirus disease 2019 (COVID‐19) emergency, on March 9, 2020 Italy went in lock‐down imposing the closure of non‐urgent outpatient clinics devoted to care of chronic, severe, inflammatory skin diseases that require periodic follow‐up. In this emergency situation, due to the lack of a teledermatology platform and in order not to leave our vulnerable high‐need patients without proper follow‐up, we started a teledermatologic service in smartworking using phone calls and emails. The total number of patients scheduled was 195; in 12 cases, we were not able to talk to the patients. Remote monitoring was performed in 183 patients (126 moderate to severe psoriasis, 10 severe acne, 11 severe atopic dermatitis, 11 hidradenitis suppurativa, 9 blistering autoimmune diseases, and 16 other autoimmune skin diseases). During remote‐visits, several interventions were conducted: triage for COVID‐19 suspected symptoms, email check of clinical pictures and of laboratory examinations, advices for topical and systemic therapy continuation or discontinuation/switch and reschedule of next appointment. Only five patients required personal office visit (2.7%), reducing consistently the number of face‐to face visits. Our real‐life experience shows that remote monitoring was effective in preventing unnecessary worsening of severe chronic skin diseases and poor outcomes due to withdrawal of current therapy.

Care for children with severe chronic skin diseases

In this study, the care for children with a severe chronic skin disease in our national expert center of pediatric dermatology was evaluated. Patients and their parents were questioned by using existing questionnaires: 50 pediatric patients completed the modified "my positive health" questionnaire of Huber and 51 parents completed Pelentsov parental needs scale. Nineteen involved professionals answered a questionnaire with open boxes. Parents of children with a variety of chronic skin diseases and young adult patients were interviewed to find out what an optimal approach would look like according to them. Children with a severe chronic and/or congenital skin disorder score high on the "my positive health" questionnaire, indicating they are able to adapt and self-manage. Their highest median score was measured for the dimension "quality of life." Their parents expect improvement of "working with health care professionals," more specifically they want them to adopt a more holistic approach throughout the patient's life. Structured interviews showed they expect that a multidisciplinary team of care providers determine together with the patient and its family-in advance-which care is needed, at what time and by whom. The interviewed professionals indicated adoption of a holistic multidisciplinary approach as the single largest improvement to achieve better care.Conclusion: Although these children with a severe chronic and/or congenital skin disease were able to adapt and self-manage, they need a more personalized integrative multidisciplinary and systematic transmural approach covering all aspects of life during their lifetime. What is Known: • Severe skin disorders affect the child and its family in several ways. In our expert center, we try to optimize the care for these children through a multidisciplinary approach. What is New: • To our knowledge, no English publication describes the requirements for good care for pediatric patients with severe chronic skin disorders and how to optimize this care. We evaluated the health status of children with severe chronic skin disorders and the strengths and weaknesses of past and current care by questioning these children, their parents, adult patients, and involved professionals.

Higher response rates in patients with severe chronic skin graft-versus-host disease treated with extracorporeal photopheresis.

IntroductionDifferent forms of graft-versus-host disease (GVHD) remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The prognosis for steroid-refractory chronic GVHD (cGVHD) remains poor. Our aim was to evaluate extracorporeal photopheresis (ECP) treatment in cGVHD patients with different organ involvement to detect subgroups of patients with the best response.Material and methodsThirty-four patients who underwent HSCT and developed moderate (n = 7) or severe (n = 27) steroid-refractory or steroid-dependent cGVHD treated with ECP were included in the analysis. A matched cGVHD control patient group untreated with ECP was collected for comparison.ResultsCompared to the control group and the stable/progressive disease (SD/PD) patients, individuals with complete/partial remission have higher overall survival and lower transplant-related mortality. Furthermore, patients with complete and partial remission (CR/PR) had significantly higher levels of albumin and platelets after ECP treatment compared to patients with stable or progressive cGVHD (SD/PD). Corticosteroid treatment and other immunosuppressive agents could successfully be tapered in the CR/PR group compared to the SD/PD patients. In this study patients with skin cGVHD are those with the highest rate of CR/PR after ECP treatment.ConclusionsOur results suggest that ECP treatment is safe and effective for patients with predominantly skin, oral and liver cGVHD.

Access Pathway Delays and Burden of Disease for Patients with Severe Chronic Skin Conditions Requiring Systemic and Biologic Therapies at an Irish Dermatology Centre

Diseases that directly affect the skin are the fourth most frequent cause of all human illnesses. Despite this, skin diseases continue to receive little attention. Dermatology waiting times in Ireland are longer when compared to other health systems abroad. In this study we highlight a cohort of dermatological patients with inflammatory skin conditions, that require attention with regards to access to dermatological services. Aim of this study was to analyse our patient cohort currently taking biologic therapy to determine how they accessed the hospital system and the time course of transition to systemic and biologics therapy. This was a retrospective study with analysis of patients on biologic agents: etanercept, adalimumab, ustekinumab, infliximab and golimumab for chronic dermatoses from 2006-2012. We identified 157 patients on biologics between this period, with 114 of these patients currently on biologic therapy. Although 55% (62) were seen within 6 months of referral the mean wait from receipt of a GP referral letter to being seen in the outpatient was 11.6 months (range 0-87 months). This study shows that patients with severe inflammatory skin disease face significant delays in accessing the hospital system. This is partly due to inadequate infrastructure and staffing of Dermatology units.

Mycobacterial panniculitis caused byMycobacterium thermoresistibilein a cat

Case summaryA domestic shorthair cat was evaluated for chronic, bilateral, ulcerative dermatitis affecting the inguinal region and lateral aspects of both pelvic limbs. Histopathologic examination of skin biopsies collected throughout the course of disease revealed chronic pyogranulomatous ulcerative dermatitis. Aerobic bacterial skin cultures yielded growth of a methicillin-resistant Staphylococcus aureus and Corynebacterium amycolatum. Upon referral the clinical findings were suggestive of a non-tuberculous Mycobacterium species infection. Previously obtained skin cultures failed to yield growth of mycobacterial organisms. A deep skin biopsy was collected and submitted for mycobacterial culture. At 5 weeks of incubation Mycobacterium thermoresistibile was isolated. In previous reports, M thermoresistibile has been isolated after 2–4 days of incubation, suggesting that this strain may have been a slower growing variant, or other factors (such as prior antimicrobial therapy) inhibited rapid growth of this isolate. The cat was hospitalized for intravenous antibiotic therapy, surgical debridement of wounds, vacuum-assisted wound closure therapy and reconstruction procedures. The wounds were ultimately primarily closed and the cat was discharged to the owner after 50 days of hospitalization. Seven months after hospitalization, the ulcerative skin lesions had healed.Relevance and novel informationTo our knowledge, only two cases of M thermoresistibile panniculitis have been reported in cats. In the only detailed report of feline M thermoresistibile panniculitis, treatment was not attempted. The second case only reported detection of M thermoresistibile by PCR without a clinical description of the case. In our case report, severe chronic skin infection with M thermoresistibile was addressed using prolonged specific antibiotic therapy, surgical debridement and reconstructions, and treatment of secondary bacterial infections.

Quality of life and severity of skin changes in the dynamics of psoriasis.

IntroductionPsoriasis is a chronic skin disease with periods of recurrence and remission. The skin changes which are typical of this disease can have a considerable effect on the patient's psychological state, self-esteem and body image. It can also affect the patient's functioning in all areas of life and quality of life.AimThe present study characterized the patient needs to improve the quality of life in specified areas in patients depending on the severity of psoriatic changes.Material and methodsThe study was conducted in two stages on 100 patients aged from 18 to 66. A dermatological examination was conducted in stage one. Patients’ dermatological condition was assessed with the Psoriasis Area and Severity Index (PASI). Clinical and socio-economic information was collected in stage two using a questionnaire, a medical interview and a standardized questionnaire measuring quality of life, the WHOQOL-BREF.ResultsThe following factors had the greatest effect on the general quality of life and quality of health ratings in the studied sample: severity of psoriatic changes, duration of the most recent recurrence and sex. Severity of psoriatic changes had a negative effect on the patient's somatic, psychological, environmental and social functioning. Duration of the most recent recurrence had a negative effect on social functioning. Practical implications of this study allow dermatologists to determine the appropriate therapeutic intervention which improves the quality of life of these patients on the one hand, and will increase patient's involvement in the process of treatment on the other hand.ConclusionsQuality of life is more impaired by more severe chronic skin disease.

Involvement of necroptosis in the development of imiquimod-induced psoriasis-like dermatitis (BA3P.135)

Abstract Necroptosis is a form of programed cell death, in which receptor-interacting protein (RIP)1 and subsequent RIP3 kinase activation is a central pathway for its development. Necroptotic cells induce inflammation through the release of various cytokines or necrotic danger-associated molecular patterns. Recent reports indicated that mice with keratinocyte-specific necroptotic cell death exhibit severe chronic skin inflammation, which suggests the involvement of necroptosis in the pathogenesis of chronic skin inflammatory diseases, such as psoriasis. In this study, we investigated the involvement of necroptosis in the pathogenesis of psoriasis using an imiquimod (IMQ)-induced mouse psoriasis model. Daily application of IMQ to skin caused skin inflammation with psoriariform scaly erythema with epidermal and dermal thickening. In the skin, we detected positive signals of TUNEL both in the epidermis and dermis, suggesting the induction of programmed cell death in skin by IMQ application. In addition, RIP3 expression was significantly upregulated both in mRNA and protein level in the skin lesions. Administration of necrostatin-1, a specific inhibitor of RIP1 kinase, significantly reduced the severity of IMQ-induced psoriasis-like dermatitis. Immunohistochemical analysis revealed positive signals for RIP3 in the human psoriasis skin lesion. These results indicate the involvement of necroptosis in mouse psoriasis model, and suggest it's involvement in the pathogenesis of psoriasis.

Effect of Sho-Seiryu-To (XIAO-QING-LONG-TANG) on skin itching and peripheral eosinophil level in three elderly patients

Sho-Seiryu-To is known to be effective against allergic diseases, but its effect on skin itching has not been reported. We observed the effect of Sho-Seiryu-To on three elderly patients who, desoite using an anti-allergic drug, has severe chronic skin itching with peripheral eosinophilia. All three patients decreased their peripheral eosinophilia and improved their skin condition within eight weeks. We conclude that Sho-Seiryu-To could be capable of treating elderly patients with chronic skin itching and peripheral eosinophilia.

COMPLICATIONS OF INTENSIVE RADIATION THERAPY FOR CERVICAL CARCINOMA. WITH EMPHASIS ON SUPERVOLTAGE RADIATION AND SUPPLEMENTAL RADICAL PELVIC OPERATION

A comparison was made of the complications following conventional and telecobalt radiotherapy of 75 patients with cervical cancer. The most frequert complication of telecobalt therapy was subcutaneous lignification, which occurred in 24% of the patients. Other severe reactions were noted in bladder (5%), rectum (5%), and vagina (4%). Fracture of the femoral neck occurred in 5%, infection in 5%, and death (attributable to therapy) in 2%. No severe skin changes were noted below the 4000-r level, but 50% of patients receiving 4000 to 4999 r and 75% receiving 5000 r or more developed acute or severe chronic skin reactions. The changes are more likely to occur with high dosage increment, 500 to 800 r every fourth day, rather than with an increment of 300 r every second day. It is suggested that supervoltage radiation must be limited to the known tolerance of the exposed organs, including the subcutaneous tissue. At intensive dose levels the frequency and severity of complications precludes continuation of such therapeutic prograrns, such as additional radiation or radical operation for persistent cancer. A total lateral pelvic wall dosage of 5000 r, including intensive intracavitary radiation, is the suggested tentative limit above which complications increase markedly. (H.H.D.)