Boosting wound healing in diabetic rats: The role of nicotinamide riboside and resveratrol in UPR modulation and pyroptosis inhibition.

BACKGROUND: Diabetes-related skin ulcers provide a substantial therapeutic issue, sometimes leading to amputation, needing immediate practical treatments for efficient wound care. While the exact mechanisms are unknown, pyroptosis and deregulation of the unfolded protein response (UPR) are known to exacerbate inflammation. Nicotinamide Riboside (NR) and Resveratrol (RV), which are known for their Nicotinamide adenine dinucleotide (NAD+) boosting and anti-inflammatory properties, are being studied as potential treatments. The purpose of this study was to shed light on the underlying molecular mechanisms and explore the medical application of NR and RV in diabetic wound healing. METHODS: 54 male Sprague-Dawley rats divided into control, diabetic (DM), Gel Base, DM-NR, DM-RV, and DM-NR + RV. Rats were orally administered 50 mg/kg/day of RV and 300 mg/kg/day of NR for 5 weeks. Following diabetes induction, their wounds were topically treated with 5 % NR and RV gel for 15 days. The wound closure rate, body weight, and serum lipid profiles were examined. Gene expression study evaluated UPR and pyroptosis-related genes (BIP, PERK, ATF6, IRE1α, sXBP1, CHOP, NLRP3, caspase-1, NFκB, and IL1-ß) in wound tissues, alongside histological assessment of cellular changes. RESULTS: NR and RV treatments greatly enhanced wound healing. Molecular investigation demonstrated UPR and pyroptosis marker modifications, suggesting UPR balance and anti-inflammatory effects. Histological investigation demonstrated decreased inflammation and increased re-epithelialization. The combination of NR and RV therapy had better results than either treatment alone. CONCLUSION: This study shows that NR and RV have therapeutic promise in treating diabetic wounds by addressing UPR dysregulation, and pyroptosis. The combination therapy is a viable strategy to improving the healing process, providing a multimodal intervention for diabetic skin ulcers. These findings pave the way for additional investigation and possible therapeutic applications, giving hope for better outcomes in diabetic wound care.

Trichoscopic findings in children and adults with alopecia areata: A comparative study.

BACKGROUND: Alopecia areata is a chronic and relapsing condition that affects individuals of all age groups. Dermoscopy is a popular and non-invasive method for diagnosing alopecia areata. This study aimed to analyze dermoscopic findings and their relationship with age, gender, appearance, and clinical signs in children and adults. METHODS: This retrospective cross-sectional study was conducted on 124 children and adults diagnosed with alopecia areata who were referred to a Hospital in Iran between 2021 and 2022. After reaching the calculated sample size, trichoscopic findings were examined and the results were recorded. Data analysis was performed by a statistician and presented in relevant tables. RESULTS: The participants in the study comprised 53.2% female children, 46.8% male children, 27.42% adult males, and 72.58% adult females. The median age in the pediatric group was 10 years, while it was 27 years in the adult group. Yellow dots were significantly less observed in children than in adults (29% vs. 48.4%), while exclamation mark hairs were significantly more common in children than adults (38.7% vs. 21%). No significant differences were found in the frequency of other trichoscopic features between children and adults. Specifically, black dots, broken hairs, short vellus hairs, pigtail hairs, and empty follicular openings were observed in 38.7%, 40.3%, 32.3%, 11.3%, and 75.8% of children, respectively, and in 35.5%, 32.3%, 21%, 46.8%, and 12.9% of adults, respectively. CONCLUSION: The most common trichoscopic findings in alopecia areata in children are empty follicular openings and broken hairs, while exclamation mark hairs are more common in children than adults. In contrast, yellow dots are less frequently observed in children compared to adults. This distinct difference between children's and adults' dermoscopic findings highlights the critical need for age-specific considerations in AA evaluations.

Is skin autofluorescence a novel non-invasive marker in diabetes? A systematic review and meta-analysis of case-control studies.

Background: The advanced glycation end product (AGE) is produced from the nonenzymatic reaction between glucose and macromolecules by aging. Accumulation of AGE causes functional and structural changes in body proteins that lead to impairment of tissue protein functions. We aimed to validate AGE measurement by skin autofluorescence (SAF) in diabetes mellitus (DM) compared to the nondiabetes population. Materials and Methods: We searched the PubMed, Cochrane, and Scopus databases from their inception till September 18, 2022, for casecontrol studies measuring AGE by SAF. Nonhuman studies, as well as review articles, study proposals, editorials, case reports, or congress posters, were excluded. We used a random effects model to assess the standard mean difference (MD) of age, body mass index (BMI), HbA1c, and SAF between diabetes and nondiabetes individuals. Results: Higher SAF in DM patients indicated more accumulation of AGE compared with the nondiabetic population. Furthermore, HbA1c was considerably higher in DM patients. The MD of age, male gender, and BMI were significantly different between the DM individuals, compared with nondiabetic subjects, which can lead to altered SAF level and AGE production. There was a remarkable heterogeneity between diabetes and nondiabetes when measuring age, gender, and BMI, as well as HbA1c and SAF level. Conclusion: This study could not confirm the validity of SAF as a surrogate marker in diabetes patients. Interestingly, metabolic load and high BMI can increase SAF, considerably. Altogether, SAF could be helpful in the future as a marker for metabolic syndrome or diabetes.

Lichenoid mycosis fungoides: Report of a case with lichen planus-like histopathologic features.

Key Clinical Message: Mycosis fungoides is a diagnostic challenge. Herein, we report a case with marked lichenoid features in pathology assessments. After several biopsies and clinicopathologic correlation, the diagnosis of lichenoid mycosis fungoides was made. Abstract: Mycosis fungoides (MF) is a great imitator and mimicks other dermatoses clinically and histopathologically. We report a 61-year-old patient with 5-year history of generalized violaceous patches and plaques. His biopsy revealed a marked lichenoid band-like infiltrate of inflammatory cells along the basal layer with basal layer vacuolar changes; the diagnosis of lichen planus was first made histopathologically. Several biopsy specimens, clinicopathologic correlation, and immunohistochemistry findings confirmed the diagnosis of lichenoid MF. Awareness of peculiar histopathologic findings of MF is essential to avoid a potential misdiagnosis. When in doubt, multiple biopsies with other diagnostic methods should be employed.

Combination therapy for management of pemphigus patients with unexpected therapeutic response to rituximab: A report of five cases.

Key Clinical Message: The immunosuppressant agents should be considered earlier in the course of treatment with rituximab, possibly after the unfavorable response at first cycle of treatment, especially in male patients and those with high BMI. Abstract: Rituximab (RTX) has recently been proposed as an alternative first-line therapy for pemphigus patients. However, there are some rare reports of worsening of pemphigus following RTX therapy in the literature. This study aimed to evaluate the efficacy and safety of using a combination treatment of mycophenolate mofetil or dapsone and methotrexate in case of nonresponse, exacerbation or development of allergic reactions following rituximab therapy in pemphigus patients. In this case series, archive files of pemphigus patient in a tertiary care hospital from 2016 to 2021 who were treated with rituximab were reviewed and those with failure in treatment process including nonresponsiveness, exacerbation or development of allergic reactions to rituximab were identified and assessed. The study includes five patients out of 1245 RTX-treated patients, who did not respond to RTX (one patient) or experienced an exacerbation of disease (two patients) or development of allergic reactions (two patients). Male patients with high BMI (BMI > 25) whose response to rituximab was not good at first cycle and happened to receive rituximab later in the course of disease, had highest number of relapses and benefited the most from this combination immunosuppressive treatment as an alternative for repeating rituximab cycles. The lower risk of relapse and a better chance of remission might indicate the efficacy of adjuvant immunosuppressant therapy in patients with no-response, exacerbation, or allergic reaction to rituximab. These therapeutic effects were better observed in patients who received lower doses of rituximab which could suggest that the immunosuppressant agents should be considered earlier in the course of the disease, possibly after the first failed trial of rituximab therapy.

Two cases of neglected leishmaniasis with marked facial disfigurement: A diagnostic conundrum.

Key Clinical Message: There is a need to pay more attention to cutaneous leishmaniasis in endemic regions which may mimic other dermatoses and treatment should be initiated with a strong clinical suspicion even without any histopathologic or PCR confirmation to avoid disfigurement or development of secondary malignancy. Abstract: Leishmaniasis is a vector-borne disease with a variety of Clinical manifestations. Cutaneous leishmaniasis (CL) is the most common form of disease and can mimic other dermatoses. We describe two unusual cases of chronic leishmaniasis that remained undiagnosed for many years and led to superimposition of squamous cell carcinoma (SCC) on lesions of one patient. These reports showed that the leishmaniasis should be borne in mind by clinicians when encountering any infiltrated lesion in patients from endemic regions and treatment should be initiated with a strong clinical suspicion even without any histopathologic or PCR confirmation to avoid disfigurement or development of secondary malignancy.

Cutaneous manifestations in patients with end-stage renal disease on hemodialysis.

Background: End-stage renal disease (ESRD) is a serious chronic disease that affects many organ systems. Skin manifestations that are commonly seen in ESRD can significantly impair the quality of life in these patients. Early recognition and management of mucocutaneous disorders can improve quality of life and decrease morbidity. This study aimed to evaluate the skin manifestations in ESRD patients undergoing hemodialysis. Methods: In this cross-sectional study 150 patients undergoing hemodialysis in the Nephrology Department of Shahid-Beheshti Hospital in Babol were enrolled. The demographic and clinical data were assessed. Analysis was done by SPSS 22 and significance level was under 0.05. Results: The mean duration of hemodialysis was 8.7 months. The most common skin findings in patients include xerosis 84.7%, pallor 82.7%, pruritus 67.3%, hyperpigmentation 40%, purpura 28%. Skin infections were detected in 36% of patients (fungal 28%, bacterial 10.7%, and viral 5.3%). Nail, hair and mucosal changes were observed among 65.3%, 38% and 17.3% of patients respectively. No significant correlation was detected between skin findings and duration of dialysis. Conclusion: The findings of the present study showed that skin manifestations are highly prevalent among patients with ESRD. Prompt diagnosis and management of the dermatological disorders may improve the quality of life in the affected patients.

A case report of esophageal cancer in a patient with pemphigus vulgaris: A coincidence or something beyond that?

BACKGROUND: Pemphigus is a group of rare but serious autoimmune blistering disorders, affecting skin and mucus membrane. Different reports have been published in respect to the coexistence of pemphigus with neoplasms, especially lympho-proliferative ones. CASE: Here, we have reported a patient previously diagnosed with pemphigus vulgaris (PV) who developed esophageal squamous cell carcinoma (SCC). CONCLUSION: Dyspepsia and dysphagia in patients with PV might not be merely due to pemphigus erosions or simply an adverse effect of systemic corticosteroid such as irritant or candidal esophagitis and should raise the suspicion of more serious conditions in case of resistant symptoms without appropriate response to treatment.

COVID outcome in pemphigus: Does rituximab make pemphigus patients susceptible to more severe COVID-19?

BACKGROUND: The COVID-19 pandemic has raised some concerns regarding the management of chronic skin diseases, especially in patients on immunosuppressive therapy including patients with pemphigus vulgaris (PV). Literature review reveals conflicting results about the effect of monoclonal antibodies such as rituximab on clinical outcome of COVID-19. OBJECTIVES: To assess the reciprocal interaction of COVID-19 and pemphigus and the effect of rituximab on prognosis of COVID-19 in patients. METHODS: We set up a retrospective study on adult patients with a confirmed diagnosis of pemphigus vulgaris and a history of COVID-19 with or without symptoms during 2020. RESULTS: Thirty-six adults with pemphigus vulgaris and SARS-CoV-2 infection were included. The SARS-CoV-2 infection was confirmed with positive RT-PCR test results in 31 cases (86.1%) and suspected in the 5 others (13.9%). Gender, total dose of rituximab, number of rituximab cycles, and involvement of head and neck were not associated to duration of COVID-19 symptoms (p values: 0.32, 0.23, 0.84, and 0.51, respectively), severity of disease (hospitalization) (p values: 0.46, 0.39, 0.23, and 0.72, respectively), or the percentage of lung involvement on CT scan (p values: 0.07, 0.36, 0.38, and 0.09, respectively). Regarding the impact of COVID-19 on pemphigus, the majority of patients did not experience any changes in their pemphigus regarding clinical phenotype (100%) or severity (83.3%), but PV was worsened in 6 (16.9%) patients which was controlled with increasing the prednisolone dosage. CONCLUSION: Rituximab appears to be safe with no increased risk of severe form of COVID-19 in patients with pemphigus vulgaris.

The impact of the COVID-19 pandemic on the diagnosis and treatment of skin cancers, a mini review.

BACKGROUND: The SARS-Cov-2 pandemic has caused dermatologists around the world to adapt their practice in the aim of protecting patients with special clinical conditions such as those having skin cancers or premalignant conditions and some diagnostic or therapeutic programs would be suspended due to being infected to SARS-CoV-2. We focused the existing data in this regard through searching on PubMed, Google Scholar, and Scopus and tried to summarize recommendations for treating this group of patients in COVID era to provide a practical guide for clinicians. RECENT FINDINGS: The number of diagnosed skin cancers dropped significantly since the beginning of the pandemic, specially in the peaks of various variants of the SARS-CoV-2 infection. The new guidelines allowed even a 3-month delay in excision and recommended surgery for non-melanoma growing skin cancers. CONCLUSION: Dermatologists should perform a careful, individualized risk-benefit assessment for their patients and consider some changes in routine protocols such as having a delayed diagnostic or therapeutic intervention.

A Comprehensive Review on HIV-Associated Dermatologic Manifestations: From Epidemiology to Clinical Management.

Dermatological disorders are among the most prevalent manifestations of HIV infection/acquired immunodeficiency syndrome (AIDS). In this review, we aimed to characterize the various dermatologic presentations among HIV-infected patients with a detailed categorization of the mucocutaneous signs and symptoms, their etiopathogenic factors, and clinical management. In fact, cutaneous manifestations of HIV are quite various, ranging from AIDS-specific skin eruptions (xerosis, pruritic papular eruptions, eosinophilic folliculitis, and acne), opportunistic infections (herpes simplex, molluscum contagiosum, cutaneous leishmaniasis, bacillary angiomatosis, disseminated histoplasmosis, disseminated cryptococcosis, and zoster) to AIDS-related malignancies (Kaposi's sarcoma, lymphoma, and nonmelanoma skin cancers) and antiretroviral therapy (ART)-associated drug eruptions. We tried to classify HIV-related cutaneous presentations which can help clinicians for a better understanding of the various specific and nonspecific features of AIDS-associated cutaneous manifestations and management of the condition.

Striae gravidarum treatment: evaluating non-ablating fractional laser (NAFL) efficacy and safety.

BACKGROUND: Striae gravidarum (SG) is a common pregnancy-related dermatologic problem, for which finding an effective treatment remains a challenge. AIM: To evaluate the safety and efficacy of 1540 nm non-ablative fractional laser (Star lux 500) in the treatment of SG in Iranian women and peruse the relationship between clinical improvement rate and patient characteristics as well as clinical features of striae. METHOD: A prospective before-after study was conducted on 50 patients with SG who received three monthly sessions of 1540 nm non-ablative fractional laser and were followed for 2 months after the last treatment session. Clinical changes were measured using both provider-rated outcome through before/after pictures represented by final clinical score (from 0 to 5) and patient-reported outcome (patient global assessment or PGA). RESULTS: Over the course of the study both final clinical score and PGA increased significantly from week 4 to week 20 (P value: <0.001 and 0.048, respectively). Only modest adverse effects including erythema, edema and hyperpigmentation were noted. CONCLUSION: In conclusion, patients with SG of different type (rubra/alba) or maturity may somehow benefit from treatment with NAFL experiencing minimal transient side effects.Therefore, NAFL may be considered a safe and partially effective treatment option for stretch mark of patients with SG.

Isotretinoin and timing of procedural interventions: Clinical implications and practical points.

BACKGROUND: For decades, the notion that elective surgeries and cutaneous procedures should be postponed for 6-12 months in patients on, or recently administered with isotretinoin, has been widely accepted. However, some recent studies showed the need for a change in this regard. METHOD: Here, we reviewed the existing data in this regard through searching on PubMed, Google Scholar, and Scopus. All of the relevant papers published in English, until October, 2022, which we could access to their full-texts, were included. RESULTS: We found some recommendations made by plastic surgeons, dermatologists, ENT surgeons, ophthalmologists, orthopedic surgeons, and dentists regarding the correct timing of procedural interventions in patients on, or recently administered with isotretinoin and tried to summarize them to provide a practical guide for clinicians. CONCLUSION: Physicians may discuss with patients regarding the known risk of abnormal wound healing in the setting of systemic isotretinoin treatment and suggest that, when possible, surgical procedures be postponed until the activity of the retinoids has time to subside. It is even more important regarding patients with darker skin phototypes to follow an even more strict guideline.

Reliability and validity of the Persian version of psoriatic arthritis screening questionnaire.

Background: The Early Arthritis for Psoriatic Patients (EARP) questionnaire is a fast and simple way to screen psoriatic arthritis. This study was carried out to investigate the diagnostic accuracy of the Persian version of the Early Arthritis for Psoriatic Patients (P-EARP) questionnaire. Methods: A total of 100 psoriasis patients responded to the questionnaire after the translation procedure (translation, back translation). After determining the validity of the questionnaire, the diagnostic accuracy of the P-EARP questionnaire was assessed using the ROC curve (receiver operating characteristic curve). Internal and external reliability of the questionnaire were also evaluated by statistical tests. Results: In assessing the reliability of the questionnaire using test-retest, correlation coefficient (r=0.994, p <0.001) and Cronbach's alpha (α = 0.85) were obtained. The P-EARP questionnaire had a sensitivity and specificity of 90.48% and 96.55% in ROC analysis, respectively, and cutoff point 3 was regarded as the cutoff point of the P-EARP questionnaire like the original version of the questionnaire (EARP). Conclusion: The results of this study showed that the P-EARP questionnaire had high sensitivity and specificity for the identification of psoriatic arthritis. The P-EARP questionnaire is an appropriate screening tool for the identification of psoriatic arthritis in the dermatology clinics.