Treatment of Chronic Parastomal Ulceration with Silver Sulfadiazine and Hyaluronic Acid: Two Case Reports.

ABSTRACT: Skin complications in individuals with an ostomy are widely reported and can cause physical and emotional challenges in everyday life. Chronic parastomal skin complications can be difficult to heal and cause significant pain.Two patients presented to the stomal therapy clinic for treatment and were diagnosed with chronic parastomal skin ulceration. Following standard treatment of wound management, topical corticosteroid ointment, and appliance review, the ulcers either were not improving or had reoccurred. Treatment with a combination cream consisting of 0.2% hyaluronic acid and 1% silver sulfadiazine was initiated, and both patients demonstrated complete healing.Treatment of parastomal skin ulceration with dual-action cream 0.2% hyaluronic acid and 1% silver sulfadiazine was successful for these two patients, with a reduction in pain and purulent fluid noted throughout treatment, in addition to a reduced cost of treatment when compared with standard protocols.

Efficacy of plasma rich in growth factors for healing chronic skin ulcers: a systematic review of randomized controlled trials with meta-analysis.

BACKGROUND: Chronic skin ulceration is a serious pathological condition for which the adjuvant use of platelet-rich plasma (PRP) has been indicated. However, evidence for the use of PRP in patients with chronic skin ulcers remains insufficient due to a large heterogeneity in experimental designs, PRP composition, and preparation protocols. OBJECTIVE: To assess previously published reports of the clinical effect of plasma rich in growth factors (PRGF) on chronic skin wounds. METHODS: A comprehensive search of the PubMed, Cochrane Library, and Scopus databases was performed to identify randomized controlled trials (RCTs) assessing the effect of PRGF on chronic ulcer healing, with no limitation regarding publication date (up to September 1, 2022). Percentage area reduction and probability of complete healing in chronic ulcers, pain reduction, infection risk, and cost savings were analyzed. A meta-analysis was performed, and the overall evidence was qualified using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. RESULTS: A total of 113 studies were identified. After full-text screening, 5 RCTs met the inclusion criteria. The meta-analysis showed a significant effect of PRGF on both wound area reduction (mean difference, 56.90% [95% CI, 52.28-61.51], I² = 0%; P = .56) and on the probability of complete healing (RR, 7.07 [95% CI, 1.84-27.16], I² = 0%; P = .53) in chronic ulcers. The overall risk of bias rating was "some concerns," whereas the certainty of evidence was high for both outcomes. A qualitative analysis suggested that PRGF did not increase infection risk and was able to reduce wound pain. CONCLUSION: The use of PRGF significantly enhances wound area reduction and also the probability of complete healing in chronic ulcers. More studies are needed to assess the effect of PRGF on pain and infection, as well as its cost-effectiveness.

Olive Oil Shows Promise for Wound Healing of Ulcers.

In proper skin healing, inflammation will stop once the harmful microbes are removed. However, an excess and prolongation of inflammation can result in delayed healing. Thus, interventions that can limit the amount of inflammation can help promote wound healing. The use of olive oil in wound therapy has been of great interest. Herein, we will review studies that investigated the use of olive oil on diabetic foot ulcers, pressure ulcers, perineal ulcers, and chronic ulcers.

Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review.

Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of pityriasis lichenoides, characterized by sudden onset of generalized ulceronecrotic papules that rapidly coalesce into ulcers associated with high fever. Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common. Treatment is based on oral corticosteroids, immunosuppressive drugs such as methotrexate, and general supportive treatment. The present case describes a stepwise approach to a patient with Mucha-Habermann disease with insufficient response to methotrexate.

Long-Term Data on Efficacy and Safety of Selexipag for Digital Systemic Sclerosis Vasculopathy.

OBJECTIVE: Raynaud phenomenon (RP) and digital ulcers (DUs) are the main signs of digital vasculopathy in systemic sclerosis (SSc). Selexipag is an oral prostacyclin agonist approved for SSc-related pulmonary arterial hypertension. Following our previous preliminary short-course report, we herein present long-term data on selexipag safety and efficacy in the treatment of SSc digital vasculopathy. METHODS: Selexipag was administered to patients with SSc with severe digital vasculopathy refractory or with contraindication to all other vasoactive therapies. Each subject was assessed at baseline and after 3, 6, and 12 months. Clinical outcomes related to RP and DUs were evaluated along with modified Rodnan skin score of the fingers. Digital perfusion was assessed by laser speckle contrast analysis (LASCA). Nailfold videocapillaroscopy (NVC) was also performed. RESULTS: Eight patients with SSc (63% female, mean age 50.1 years) received selexipag. After 12 months of treatment, RP was reported to significantly decrease in the number of daily episodes and mean duration (P < 0.001 and P = 0.01, respectively). All patients achieved a complete healing of their DUs (P = 0.03) within 6 months. A progressive reduction of fingers skin score was observed (P = 0.03). No structural changes of capillaries were noted on NVC. Conversely, LASCA revealed an important increase in total digital perfusion (P = 0.004) despite seasonal variability. The safety profile was consistent with that reported in the literature. CONCLUSION: We observed a sustained efficacy of selexipag on SSc digital vasculopathy during 1 year of administration. Our promising results encourage the design of a new randomized controlled trial to evaluate the effect of selexipag on SSc digital vasculopathy.

Perianal Ulcers from Antihemorrhoidal Ointment: A Case Report and Literature Review.

ABSTRACT: Perianal ulcers (PAUs) related to antihemorrhoidal product use have been recently reported in the literature through a few case reports. However, other etiologies of PAU must be ruled out, including infectious disease, inflammatory disease, malignancy, pressure injuries, radiotherapy, and other topical drugs. In this report, the authors describe two cases of PAUs due to an antihemorrhoidal ointment. In case 1, a 68-year-old woman with a history of hemorrhoids presented with PAUs after using an antihemorrhoidal ointment for 2 months. The ulcers were assessed through a histopathologic study and treated with calcium alginate dressings, with complete re-epithelialization occurring after 2 months. In case 2, a 58-year-old woman with a history of hemorrhoids developed painful PAUs while using an antihemorrhoidal ointment for 2 months. No other probable cause was found, and the ulcers were treated by discontinuing the ointment. The ulcers showed marked improvement, and complete re-epithelialization occurred after 6 weeks without additional treatment.

Amyopathic Dermatomyositis Presenting with Digital Ulcerations: Case Report and Literature Review.

ABSTRACT: Clinically amyopathic dermatomyositis (CADM) is a rare subtype of dermatomyositis that presents with cutaneous features and no muscle involvement. This case report describes a 26-year-old woman with recurrent and multiple digital ulcerations coinciding with the start of winter each year. There was no evidence of myopathy, and antibody testing yielded negative results. A diagnosis of CADM was ultimately made based on clinicopathologic correlation. The patient's ulcers demonstrated excellent response to a combination therapy of hydroxychloroquine and potent topical and systemic steroids. Herein, the authors discuss the pathologic and immunologic characteristics of CADM.

Network Pharmacology Study on Herb Pair Bletilla striata-Galla chinensis in the Treatment of Chronic Skin Ulcers.

BACKGROUND: Herb pair Bletilla striata-Galla chinensis (BS-GC) is a classic combination of topical traditional Chinese medicine formulae in the treatment of chronic skin ulcers (CSUs). OBJECTIVE: The aim of this study is to explore the effective active ingredients of BS-GC, as well as the core targets and signal transduction pathways of its action on CSUs. METHODS: The ingredients of BS-GC were obtained from TCMSP and HERB databases. The targets of all active ingredients were retrieved from the SwissTargetPrediction database. The targets of CSUs were obtained from OMIM, GeneCards, Drugbank, and DisGeNET databases. A drug-disease target protein-protein interaction (PPI) network was constructed to select the most core targets, and an herb-ingredient-target network was built by utilizing Cytoscape 3.7.2. Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database (KEGG) analysis and verified the results of network pharmacology through molecular docking. RESULTS: A total of 40 active ingredients from the herb pair BS-GC were initially screened, and a total of 528 targets were retrieved. Meanwhile, the total number of CSU targets was 1032. Then, the number of common targets between BS-GC and CSUs was 107. The 13 core targets of herb pair BS-GC with CSUs were filtered out according to the PPI network, including AKT1, TNF, EGFR, BCL2, HIF1A, MMP-9, etc. The 5 main core active ingredients were 1-(4-Hydroxybenzyl)-2-methoxy-9,10-dihydrophenanthrene-4,7-diol, 1-(4- Hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol, physcion, dihydromyricetin, and myricetin. The main biological processes were inflammation, oxidative stress, and immune response, involving the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, NF-κB signaling pathway, and calcium signaling pathway. Molecular docking results showed good binding activity between the 5 main core active ingredients and 13 core targets. CONCLUSION: This study predicted the core targets and signal transduction pathways in the treatment of CSUs to provide a reference for further molecular mechanism research.

Effects of photodynamic therapy in patients with infected skin ulcers: A meta-analysis.

The purpose of the meta-analysis was to evaluate and compare the photodynamic therapy's effectiveness in treating infected skin wounds. The results of this meta-analysis were analysed, and the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated using dichotomous or contentious random- or fixed-effect models. For the current meta-analysis, 6 examinations spanning from 2013 to 2021 were included, encompassing 154 patients with infected skin wounds were the used studies' starting point. Photodynamic therapy had a significantly lower wound ulcer size (MD, -4.42; 95% CI, -7.56--1.28, p = 0.006), better tissue repair (MD, -8.62; 95% CI, -16.76--0.48, p = 0.04) and lower microbial cell viability (OR, 0.13; 95% CI, 0.04-0.42, p < 0.001) compared with red light exposure in subjects with infected skin wounds. The examined data revealed that photodynamic therapy had a significantly lower wound ulcer size, better tissue repair and lower microbial cell viability compared with red light exposure in subjects with infected skin wounds. However, given that all examinations had a small sample size, consideration should be given to their values.

Effect of photodynamic therapy with 5-aminolevulinic acid and EDTA-2Na against mixed infection of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

BACKGROUND: The increasing abundance of drug-resistant bacteria is a global threat. Photodynamic therapy is an entirely new, non-invasive method for treating infections caused by antibiotic-resistant strains. We previously described the bactericidal effect of photodynamic therapy on infections caused by a single type of bacterium. We showed that gram-positive and gram-negative bacteria could be killed with 5-aminolevulic acid and 410 nm light, respectively. However, clinically, mixed infections are common and difficult to treat. OBJECTIVE: We investigated the bactericidal effects of photodynamic therapy on mixed infections of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. METHODS: We compared bacterial growth with and without photodynamic therapy in vitro. Then, in vivo, we studied mixed infections in a mouse skin ulcer model. We evaluated the rates of ulcer area reduction and transitions to healing in treated and untreated mice. In addition, a comparison was made between PDT and existing topical drugs. RESULTS: We found that photodynamic therapy markedly reduced the growth of both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, in culture, and it reduced the skin ulcer areas in mice. PDT was also more effective than existing topical medicines. CONCLUSION: This study showed that photodynamic therapy had antibacterial effects against a mixed infection of gram-positive and gram-negative bacteria, and it promoted skin ulcer healing. These results suggested that photodynamic therapy could be effective in both single- and mixed-bacterial infections.

Features of apoptotic and proliferative processes in experimental infected radiation-induced skin ulcer under conditions of photodynamic therapy and the use of platelet-rich plasma.

OBJECTIVE: . Aim: The purpose of the study was to identify the features of apoptotic and proliferative processes in experimental Staphylococcus aureus-infected radiation skin ulcer under conditions of photodynamic therapy and the use of platelet-rich plasma. PATIENTS AND METHODS: Materials and Methods: An experimental study was conducted on 95 six-month-old male rats of the WAG population, which were divided into three groups. Group 1 included 25 animals that were simulated a radiation ulcer of the skin in the thigh area with subsequent application to its surface on the 7th day after irradiation with 0.2 ml of a suspension of the Staphylococcus aureus (ATCC 25923) reference strain (0.5 million microbial cells/cm2). Group 2 included 25 animals with Staphylococcus aureus-infected radiation skin ulcer, which were subjected to photodynamic therapy a day after infection. Group 3 included 45 animals with Staphylococcus aureus-infected radiation skin ulcers, which, 1 day after infection, received photodynamic therapy in the first half of the day, and in the second half of the day the periphery of the wound defect was injected with platelet-rich plasma. The material for the study was skin with underlying soft tissues from the area of radiation exposure. Histological, immunohistochemical, morphometric and statistical methods were used. RESULTS: Results: In cases of simultaneous use of photodynamic therapy and platelet-rich plasma, compared with photodynamic therapy alone, the processes ofapoptosis and proliferation were more balanced, active, with a shift in the proliferative-apoptotic ratio towards proliferation processes and met the needs of the regenerative process. From the 10th to the 22nd day of the experiment these processes increased, which indicated active healing processes, that, during survey microscopy on the 22nd day, were manifested by the complete filling of the wound cavity with granulation and connective tissues with the presence of an epithelial layer on the surface of the regenerate. From the 22nd to the 45th day of the experiment, a decrease in the rate of regeneration was recorded, as evidenced by a decrease in the intensity of apoptotic and proliferative processes. The intensity of the latter was sufficient, which led to the healing of Staphylococcus aureus-infected radiation skin ulcer on the 45th day with complete restoration of the original structure of the skin. CONCLUSION: Conclusions: Photodynamic therapy in combination with the use of platelet-rich plasma balancedly activates apoptotic and proliferative processes with a predominance of the latter in granulation and connective tissues filling the lumen of Staphylococcus aureus-infected radiation skin ulcer, which on the 45th day of the experiment leads to wound healing with complete restoration of the original structure of the skin.

Extensive and deep granulomatous ulcers as an atypical manifestation of cartilage-hair hypoplasia syndrome: A diagnostic and therapeutic challenge.

Cartilage hypoplasia syndrome is a primary immunodeficiency disease characterized by short stature, hypoplastic hair and a variable degree of immunodeficiency. Noninfectious cutaneous granulomas represent an uncommon yet well-recognized manifestation within the spectrum of primary immunodeficiency diseases. However, cutaneous granulomas as a manifestation of cartilage-hair hypoplasia syndrome, are extremely rare. We present a case of a middle-aged man with cartilage hypoplasia syndrome featuring cutaneous granulomas, manifesting as chronic, extensive and deep cutaneous ulcers. The patient was treated with anti-TNF-alpha adalimumab with partial improvement. Our case underscores the broad spectrum of clinical manifestations associated with cartilage hypoplasia syndrome and adds new evidence to the potential therapeutic efficacy of anti-TNF-alpha drugs in its treatment.

Treatment of myopathy and cutaneous ulcers in anti-MDA5-positive dermatomyositis with triple therapy.

Antimelanoma differentiation-associated protein 5 positive dermatomyositis (MDA5 DM) is a rare subtype of idiopathic inflammatory myopathy. There are limited data available regarding the cutaneous manifestations of MDA5 DM in the African American population. We presented the case of a male patient in his early 20s who presented with debilitating cutaneous ulceration and myopathy. Workup revealed interstitial lung disease (ILD) and positive MDA5 serology consistent with MDA5 DM. He made a remarkable recovery in terms of myopathy and cutaneous ulcerations with a multipronged regimen of prednisone, intravenous immunoglobulin and mycophenolate mofetil. However, there was a progression of ILD on this regimen which warranted use of rituximab.

Systematic literature review to inform the Portuguese recommendations for the management of Raynaud's phenomenon and digital ulcers in systemic sclerosis and other connective tissue diseases.

OBJECTIVE: To perform a systematic literature review (SLR) aimed at evaluating the efficacy and safety of pharmacological and non-pharmacological treatments for Raynaud's phenomenon (RP) and digital ulcers (DU) in patients with systemic sclerosis (SSc) and other connective tissue diseases (CTD), in order to inform the Portuguese recommendations for managing RP and DU in these patients. METHODS: A SLR was conducted until May 2022 to identify studies assessing the efficacy and safety of pharmacological and non-pharmacological interventions for RP and DU in SSc and other CTD. Eligible study designs included randomized controlled trials (RCTs), controlled clinical trials, and their extensions for assessing efficacy and safety of interventions. Observational studies with a comparator were included for evaluating the efficacy and safety of non-pharmacological interventions and safety of pharmacological interventions. The risk of bias of each study was assessed using standard tools. RESULTS: Out of 71 publications meeting the inclusion criteria, 59 evaluated pharmacological and 12 non-pharmacological interventions. We found moderate quality evidence supporting the efficacy of calcium channel blockers, phosphodiesterase-5 inhibitors, and intravenous prostacyclin analogues in reducing RP frequency, severity, and duration. Intravenous iloprost had a small to moderate effect size in improving DU healing. Phosphodiesterase-5 inhibitors were effective in reducing total DU count, new DU occurrence, and enhancing DU healing. Bosentan effectively prevented new DU in SSc patients. No new safety concerns were associated with these treatments. The studies on non-pharmacological interventions were, in general, of low quality, and had a small sample size. Warming measures decreased frequency and duration of RP attacks; laser therapy improved RP-related outcomes; local oxygen-ozone therapy improved RP outcomes as an add-on therapy; bone marrow mononuclear cell implantation improved DU-associated pain; periarterial sympathectomy and vascular bypass reduced DU number and finger amputation risk. CONCLUSION: The available evidence supports the efficacy and safety of pharmacological interventions, namely nifedipine, sildenafil, iloprost, and bosentan in treating RP and DU in patients with SSc and other CTD. Scarce and low-quality evidence does support the use of some non-pharmacological interventions but with only a modest effect size. This SLR underscores the limited availability of high-quality evidence for determining the optimal treatment.

Kodamaea ohmeri Leg Skin Ulcer Infection in an Immunocompetent Patient: A Case Report.

INTRODUCTION: Kodamaea ohmeri is an emerging fungus recognised as an important pathogen in immunocompromised hosts, responsible for life-threatening infections. CASE PRESENTATION: We describe a case of a 69-year-old immunocompetent man with a long history of leg skin ulcers infected by K. ohmeri. This is the first case of leg wounds infected by K. ohmeri in an immunocompetent patient. The infection was successfully treated with voriconazole 200 mg daily. CONCLUSION: Though rare, K. ohmeri should be considered in patients with skin ulcers that are poorly responsive to medical treatment, even if not immunocompromised.

Cutaneous ulceration in juvenile dermatomyositis with anti-melanoma differentiation-associated gene 5.

This report presents the case of an 11-year-old girl with juvenile dermatomyositis (JDM), anti-MDA5 antibodies and multiple skin ulcers. Treatment with traditional immunomodulators and tofacitinib resulted in healing of the skin ulcers and normalization of muscle enzyme markers. This case highlights the significance of recognizing the association between anti-MDA5 antibodies and cutaneous ulceration in JDM and supports the use of Janus kinase inhibitors as a management option.

The effect of calcium channel blockers on digital ulcers in systemic sclerosis: data from a prospective cohort study.

Digital ulcers (DU) are a common, severe vascular manifestation of systemic sclerosis (SSc) with few effective treatment options. Using data from the Australian Scleroderma Cohort Study (ASCS), we sought to evaluate the effect of calcium channel blockers (CCB) on the treatment and prevention of DU.Using data from 1953 participants, with a median of 4.34 years of follow-up, we used generalised estimating equations to evaluate the clinical characteristics associated with CCB use and ascertain the risk factors for the presence of DU at subsequent study visits. A time-dependent Cox-proportional hazard model was applied to evaluate the risk of future occurrence of DU with CCB use.Sixty-six percent of participants received CCB and patients with a history of DU were more likely to be prescribed a CCB (76.76% vs 53.70%, p < 0.01). CCB use was more frequent in patients with severe complications of DU including chronic DU (OR 1.47, p = 0.02), need for hospitalisation for iloprost (OR 1.30, p = 0.01) or antibiotics (OR 1.36, p = 0.04) and digital amputation (OR 1.48, p < 0.01). Use of CCB was more likely in patients who experienced DU at subsequent study visits (OR 1.32, p < 0.01) and was not associated with a decreased risk of the development of a first DU (HR 0.94, p = 0.65).CCB are frequently used in the management of SSc in the ASCS and their use is associated with severe peripheral vascular manifestations of SSc. However, our results suggest that CCB may not be effective in the healing or prevention of DU.