Evaluation of the Factors Influencing Mortality in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Multicenter Study of 166 Patients.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening acute mucocutaneous disorders usually triggered by drugs. In this study, we aimed to evaluate the factors affecting mortality in patients with SJS-TEN. METHODS: Our study is a retrospective cohort study, analyzing data collected from a total of 12 tertiary care centers between April 2012 and April 2022. RESULTS: The study included 59 males and 107 females, a total of 166 patients, with an average age of 50.91 ± 21.25 years. Disease classification was TEN in 50% of cases, SJS in 33.1%, and SJS-TEN overlap in 16.9%. The average SCORTEN within the first 24 h was 2.44 ± 1.42. Supportive care was provided to 99.4% of patients. The most commonly used systemic immunomodulatory treatments were systemic steroids (84.3%), IVIG (intravenous immunoglobulin) (49.3%), and cyclosporine (38.6%). Plasmapheresis was administered to five patients. While 66.3% of patients were discharged, 24.1% resulted in exitus. Our comparative analysis of survivors and deceased patients found no effect of systemic steroids, IVIG, and cyclosporine treatments on mortality. Univariate analysis revealed that the SCORTEN scores on days 1 and 3 as well as the rates of detachment at the onset and during follow-up were significantly higher in deceased patients compared to survivors. The rates of fever, positive blood cultures, and systemic antibiotic use were higher in deceased patients compared to survivors. The presence of comorbidities, diabetes, and malignancy were significantly more common in deceased patients. Multivariate regression analysis indicated that over SCORTEN 2, the mortality risk exponentially rose with each SCORTEN increment, culminating in an 84-fold increase in mortality at SCORTEN 5-6 (odds ratio [95% confidence interval]: 13.902-507.537, p < 0.001) compared to SCORTEN 0-1. Additionally, the utilization of plasmapheresis was associated with a 22-fold increase in mortality (odds ratio [95% confidence interval]: 1.96-247.2, p = 0.012). CONCLUSION: Our study found that a high SCORTEN score within the first 24 h and the use of plasmapheresis were related to increased mortality, while systemic steroids, IVIG, and cyclosporine treatments had no impact on mortality. We believe that data gathered from one of the most comprehensive studies which we conducted on SJS-TEN will enrich the literature, although additional research is warranted.

Analysis of clinical characteristics and factors affecting treatment responses in patients with pyoderma gangrenosum: a multicenter study of 239 patients☆.

BACKGROUND: Pyoderma Gangrenosum (PG) is a chronic disease characterized by recalcitrant skin ulcers. OBJECTIVE: We aimed to evaluate the demographic, clinical characteristics, treatments and factors affecting the treatment responses of patients with PG. METHODS: We performed a multicenter study of 12 tertiary care centers. We analyzed the data of the patients who were followed up with a diagnosis of PG between the years 2012‒2022 retrospectively. RESULTS: We included a total of 239 patients of whom 143 were female and 96 were male, with an average age of 54.2 ±â€¯17.4 years. The most common treatment was systemic steroids (n = 181, 75.7%). Among these patients, 50.8% (n = 92) used systemic steroids as the sole systemic agent, while 49.2% (n = 89) used at least one adjuvant immunosuppressive agent. The independent factors determined in regression analysis to influence response to systemic steroids positively were disease onset age ≥ 30-years, negative pathergy, absence of leukocytosis, negative wound culture, presence of a single lesion, and absence of upper extremity involvement. Biological agents were used in 18.4% (n = 44) of the patients in the present study. We also analyzed pathergy positive PG and early onset (onset age < 30) PG separately due to their distinct clinical features which were revealed during statistical analysis. STUDY LIMITATIONS: Retrospective nature of the present study. CONCLUSIONS: Analyses of the factors influencing treatment responses are addressed in this study. Also, we concluded that investigation for accompanying autoinflammatory diseases of pathergy positive PG and early onset PG is necessary and the patients in these two groups are more resistant to treatment, necessitating more complicated treatments.

Evaluation of Ocular and Systemic Oxidative Stress Markers in Ocular Rosacea Patients.

Purpose: To investigate oxidative stress markers in tears and serum of patients with ocular rosacea and to examine their association with both ocular surface parameters and cutaneous rosacea subtypes. Methods: This prospective study includes rosacea patients with ocular involvement and healthy controls. We performed ophthalmological examination of all participants and collected tear breakup time (TBUT), Schirmer, Meibomian gland dysfunction (MGD) and Ocular Surface Disease Index (OSDI) scores. We quantified the total antioxidant status (TAS), total oxidant status (TOS), and arylesterase (ARE) levels from tear and serum samples, and calculated the oxidative stress index (OSI). We also classified patients into phymatous, erythematotelangiectatic, papulopustular subtypes. Results: We included 90 ocular rosacea patients and 30 healthy controls. Oxidative stress (TOS, OSI) levels were significantly higher (P < 0.01) and antioxidant levels (TAS, ARE) were significantly lower (P < 0.01) in both tear and serum samples of ocular rosacea patients as compared to controls. We found a significant positive correlation between the tear and serum values regarding oxidative stress parameters (P < 0.05). Besides, OSI was negatively correlated with TBUT and positively correlated with MGD score (meiboscore) and OSDI (P < 0.05). The Schirmer score was not correlated with OSI. No difference was found between the cutaneous subtypes with respect to TAS, TOS, ARE, and OSI results. Conclusions: In this study, we identified oxidative stress markers in the serum and tears of ocular rosacea patients and showed their correlation with clinical signs of MGD, suggesting that oxidative stress contributes to ocular rosacea pathogenesis and that oxidative stress could be an indicator of MGD severity.

Investigation of the PD-1/PD-L1 Expression in the Lesional Skins of Patients With Psoriasis.

INTRODUCTION: Psoriasis is an immune-mediated, chronic and inflammatory disease whose pathogenesis is affected by the interactions of several immune cells and cytokines. PD-1 is an inhibitor receptor that is expressed to a large extent in T lymphocytes and responsible for regulating autoimmunity and self-tolerance. OBJECTIVES: In this study, we aimed to investigate the expression of PD-1/PD-L molecules in the lesioned skins of psoriasis patients. METHODS: The study included 30 psoriasis patients, and 15 healthy volunteers as the control group. Anti PD-1 and PD-L1 antibodies were applied to the skin biopsy samples that were collected from the patient and control groups. Cytoplasmic and membranous staining of PD-1 and PD-L1 were considered positive. The number of stained immune cells that was examined for each case. RESULTS: The percentage of the tissues with high PD-1 (+) and PDL-1 (+) immune cell counts were significantly higher in the psoriasis patients compared to healthy controls (P values = 0.004 and 0.002, respectively). A negative and statistically significant correlation was detected between PDL-1(+) immune cell numbers and PASI scores (P = 0.033, r=-0.57). CONCLUSIONS: In the lesioned skin samples of psoriasis patients, the PD-1 and PD-L1 expressions were significantly higher in immune cells than that in the skin samples of the healthy controls. This study was the first investigation of the expression of PD-1/PD-L molecules in the immune cells in found the lesioned skins of psoriasis patients.

Cutaneous findings in patients with chronic venous insufficiency.

BACKGROUND: Venous hypertension causes many different cutaneous findings such as varicosities, telangiectasia, edema, and pigmentation, dermatitis, and venous ulcers on the skin. OBJECTIVE: This study aims to investigate the cutaneous signs and symptoms of chronic venous insufficiency (CVI) and to examine their contribution to early diagnosis. METHODS: A total of 150 patients were included in the study who applied to the dermatology outpatient clinic and were diagnosed with skin disease related to CVI or had skin findings. Patient's age, gender, complaints, occupation, additional diseases, drug usage, history of prolonged standing and travel, smoking habit, number of pregnancies, history of varicose veins in the family, dermatological diagnosis/findings, and venous Doppler ultrasonography reports were examined retrospectively. RESULTS: 56% of patients were women. Mean age was 56.69 ± 13.6 years. Overall, 82.7% of total patients had at least one skin finding. The most frequent skin findings except varicose veins were insufficiency dermatitis accounted for 32.7% of patients, telangiectasia, and pigmentation which were comprised 25.3%, 19.3% of the total number of patients respectively. In addition to this, 48.7% of patients had itching problems and 32.7% had pain. Moreover, 46% of patients presented superficial vein insufficiency, while 8.7% had deep vein insufficiency. For 47.3% of patients, vein diameter dilation was observed and 11.3% suffered from perforating vein insufficiency. In terms of Clinical-Etiologic-Anatomic-Pathophysiologic (CEAP) classification, scores of 52% of the patients were C3 and lower, while scores of 48% of total patients were C4a and higher. CONCLUSIONS: Early diagnosis and treatment of chronic venous insufficiency could prevent further chronic processes such as venous ulceration which is an advanced CVI finding. Thus, assessing the early skin findings might be important to identify the underlying venous insufficiency disease.

Investigation of plasma thiol/disulfide balance in male patients with androgenetic alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is the most common cause of hair loss in men. In addition to genetic and hormonal factors, oxidative stress (OS) is suggested as a factor in the etiology. AIM: In this study, we aimed to investigate the presence of OS due to thiol disulfide balance deterioration in male patients with AGA. MATERIALS AND METHODS: A total of 45 male AGA patients and 42 healthy male controls were included in the study. Native thiol, disulfide, and total thiol levels were assessed through automated spectrophotometry. The relationship between total protein, albumin, native thiol, disulfide, and total thiol levels in addition to demographic and clinical characteristics of the patients were examined. RESULTS: The mean age of the patients was 32.6 ± 10 years, and the median AGA duration in the patients was 3 years. There was no statistically significant difference in terms of native thiol, disulfide, total thiol levels, disulfide/total thiol, disulfide/native thiol, and native thiol/total thiol ratios between AGA patients and controls. Native thiol and total thiol levels negatively correlated with age and AGA duration, while disulfide levels only correlated with age.Albumin and native thiol levels were significantly lower in patients with low vitamin D levels (p = 0.040 and p = 0.021, respectively); however, total thiol and native thiol/total thiol ratio values were significantly higher. CONCLUSION: According to this study, thiol disulfide homeostasis is in balance in male patients with AGA. In patients with emotional stress and vitamin D deficiency, the balance appears to be shifted in favor of oxidative stress.

Examination of androgenetic alopecia with serum biomarkers.

BACKGROUND: Androgenetic alopecia (AGA) is the most common type of hair loss and affects approximately 50% of the male population. AIMS: In the present study, to investigate microinflammation, perifollicular fibrosis, and oxidative stress in AGA cases, some serum biomarker levels were measured and evaluated. PATIENTS/METHODS: Serum samples were drawn from patients (n = 58) and control (n = 30) groups referring to Atatürk Training and Investigation Hospital Dermatology Outpatient clinic. In serum samples, NF-κB, TNF-α, TGF-ß1, thioredoxin, nitric oxide, TOS, TAS, and thiol disulfide homeostasis (native thiol, total thiol, disulfide) were measured and evaluated. RESULTS: In patients with AGA, NF-κB (P = .005), TNF-α (P = .008), TGF-ß1 (P = .028), thioredoxin (P = .004), nitric oxide (P < .001), and TOS (P < .001) serum levels were found to be significantly higher than those in control group, while TAS (P = .003), native thiol (P < .001), total thiol (P < .001), and disulfide (P < .001) serum levels were found to be significantly lower. CONCLUSIONS: According to the results of the present study, it was concluded that in that AGA androgens lead to oxidative stress by increasing free oxygen radicals, which accelerates hair loss by causing microinflammation and fibrosis. The recognition of the effect of androgens and associated factors on the hair follicle cycle is essential for the development of new and effective treatment methods.

A case of tinea incognito mimicking subcorneal pustular dermatosis.

An 89-year-old woman presented with plaque-like lesions, accompanied with pustules and desquamation on the back and front of the trunk for approximately one year. Long term use of potent topical corticosteroids was ineffective. Because of the chronicity of her condition, the diagnoses of subcorneal dermatosis or subcorneal pustular dermatosis type of IgA pemphigus were considered. However, fungal hyphae were observed in the potassium hydroxide examination. Therefore, we present this case since this clinical appearance of tinea incognito can also mimic various pustular dermatoses.

Dynamic Thiol/Disulfide Balance in Patients with Seborrheic Dermatitis: A Case-Control Study.

BACKGROUND: Seborrheic dermatitis is a chronic, inflammatory skin disease, in which many endogenous and exogenous factors play a role. Recent studies have shown that oxidative stress increases in these patients. The role of the dynamic thiol/disulfide homeostasis, an important component of the oxidative stress, in the pathogenesis of seborrheic dermatitis has not yet been investigated. OBJECTIVES: The objective was to investigate the relationship between the dynamic thiol/disulfide balance in the plasma of seborrheic dermatitis patients and disease severity. METHODS: In this case-control study, 70 seborrheic dermatitis patients and 61 age- and sex-matched healthy controls were included. Thiol/disulfide homeostasis was calculated from venous blood samples, and tests were performed by automated spectrophotometric method. The thiol/disulfide balance between the patient and control groups was compared. In addition, disease severity and other demographic characteristics and thiol/disulfide balance parameters were compared. RESULTS: Native and total thiols were significantly higher in the patient group than that in the control group (P < 0.001). Disulfide levels were nonsignificantly lower in the patient group than controls (P = 0.821). Patients' age and age at the onset of disease were found to have a negative correlation with native and total thiol levels. CONCLUSION: Higher levels of thiols in the serum may be responsible for the increased proliferation of seborrheic dermatitis lesions. To the best of the authors' knowledge, this is the first report on the correlation between thiol/disulfide homeostasis in patients with seborrheic dermatitis.

Thiol/disulfide homeostasis as a marker of oxidative stress in rosacea: a controlled spectrophotometric study.

BACKGROUND: Rosacea is the chronic inflammatory disease of the facial skin. Although its aetiology is not clear yet, inflammatory processes triggered by oxidative stress and oxidation of lipids have been suggested to play a role. While studies on the relationship between inflammation and oxidative stress are ongoing, thiol metabolism and its role in oxidative stress have also begun to be investigated. Thiols are among the key molecules of protein metabolism in the organism and they are the firstly consumed antioxidants in case of oxidative stress. Thiols regulate intracellular redox metabolism and protect keratinocytes against the results of oxidative alterations in the stratum corneum. There is a balance known as dynamic thiol/disulfide homeostasis between thiols and their oxidized forms; disulfides. AIM: This study aimed to determine the effects of oxidative stress on protein metabolism in rosacea patients by investigating thiol/disulfide homeostasis using a newly developed and fully automated method. Determination of plasma thiol levels provides important clues regarding the extent of free radical-mediated oxidation of proteins causing damage in rosacea. METHODS: The study included 50 rosacea patients who were diagnosed clinically or histopathologically with rosacea and 42 age- and gender-matched healthy controls. Plasma levels of native thiol, total thiol, and disulfide were determined. The following ratios were calculated: disulfide/native thiol ratio, disulfide/total thiol ratio, and native thiol/total thiol ratio. RESULTS: The mean age was 41.8 ± 10.5 in the rosacea patients (35 females) and 42.5 ± 10.3 years in the control group (33 females). The mean disulfide level was found to be significantly higher in the rosacea patients than in the control group (23.4 ± 5.5 µM/L and 17.3 ± 6.2µM/L, respectively; p < 0.001). The mean disulfide/native thiol ratio (0.055 ± 0.016 vs. 0.041 ± 0.017) and the mean disulfide/total thiol ratio (0.049 ± 0.012 vs.0.037 ± 0.013) were significantly higher and the mean native thiol/total thiol ratio (0.884 ± 0.118 vs. 0.923 ± 0.027) was significantly lower in the patients as compared with the controls (p < 0.05 for all). CONCLUSION: In rosacea patients, the thiol/disulfide balance was observed to shift towards disulfides, which could be considered an indicator of oxidative stress in rosacea.

Dynamic thiol/disulfide homeostasis in patients with lichen planus.

OBJECTIVE: Lichen planus (LP) is an autoimmune inflammatory disease of the mucocutaneous tissue, whose exact pathological course remains unclear. Abnormal thiol/disulfide homeostasis has been postulated to be responsible for a number of diseases predominated by chronic inflammation. To be able to contribute complicated and unclear pathogenesis of LP, we aimed to investigate dynamic thiol/disulfide homeostasis in patients with LP, using an original automated method developed by Erel and Neselioglu in this study. METHODS: The study group consisted of 81 unrelated patients with LP and 80 unrelated healthy controls with no LP lesions in their personal history or on clinical examination. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. RESULTS: Native thiol and total thiol levels were found as significantly higher in patients with LP than the control group (P = 0.026 and 0.035, respectively). There was no significant difference between the disulfide levels of the patients with LP and the control group. CONCLUSIONS: We provide evidence that that thiol/disulphide homeostasis impaired in favor of thiol levels in LP patients compared to the control group based on the data of our study. To the best of our knowledge, the present study is the first examination on the correlation between thiol and disulfide homeostasis in patients with LP.

The treatment of ingrown nail: Chemical matricectomy with NAOH versus wedge resection.

Ingrown nail is a common problem seen in the dermatology clinics. The aim of this study is to compare the wedge resection method and chemical matricectomy with NaOH in terms of operation time, postoperative pain severity, postoperative drainage, recurrence rates, recovery time, and the effects of these two methods on Dermatology Quality of Life Index. This study included 60 patients. About 42 nail edges of 30 patients were treated with NaOH for chemical matricectomy and wedge resection was performed for 33 nail edges of 30 patients. Operation time for chemical matricectomy and wedge resection was an average of 7.66 ± 3.65 and 19.25 ± 5.54 min (p < .001). Recovery time was an average of 17.27 ± 14.22 days for chemical matricectomy and an average of 28.85 ± 17.03 days for wedge resection (p = .004). Recurrence was detected in 5.4% of the nail edges treated with chemical matricectomy and 3.6% of the nail edges treated with wedge resection (p = 1.000). Absence of differences for the recurrence rates between wedge resection method and chemical matricectomy method with NaOH shows that effectiveness of these approaches are similar. It seems that quite short operation and recovery times in the chemical matricectomy are the main advantage of the method.

Plasma Thiol Levels are Associated with Disease Severity in Nonsegmental Vitiligo.

BACKGROUND: Vitiligo is a depigmenting cutaneous disorder with complex pathogenesis. Thiol compounds are well-known organic structures that play a major role in melanogenesis. AIM: The aim of this study was to determine the association between plasma thiol level and disease severity in patients with nonsegmental vitiligo. METHODS: A total of 73 patients with nonsegmental vitiligo (57 generalized and 16 localized type) and age- and sex-matched 69 healthy controls were enrolled in the study. Plasma levels of native thiols, disulfides, and total thiols were measured by a novel and automated assay. Disease severity of vitiligo was assessed with Vitiligo Area Scoring Index (VASI) score. The extent, stage, and spread of vitiligo of patients were evaluated according to the Vitiligo European Task Force (VETF) system. RESULTS: The native and total thiol levels of vitiligo patients were higher than those of healthy control group (P≤0.001 and 0.001, respectively). The median VASI score of patients was 0.7 (0.02-28.30). Univariate analyses showed that plasma native thiol levels, VETF spread score, disease duration, and vitiligo type significantly correlated with VASI scores (r=0.237, P=0.043; r=0.458, P<0.001; and P<0.001, respectively). Stepwise multivariate analysis revealed that disease duration (ß=0.017; P=0.005) and spread score (ß=1.301; P=0.001) were found statistically significant as independent factors on VASI score. CONCLUSION: Although plasma native thiol level significantly correlated with VASI scores of patients, it is not a predictive factor for vitiligo severity.

Receptor for advanced glycation end products is overexpressed in psoriatic plaques independent of disease severity.

BACKGROUND: Enhanced expression and excitation of the receptor for advanced glycation end products is considered to play a role in the regulation of many pro-inflammatory genes involved in the pathogenesis of psoriasis. AIM: We investigated the expression of receptor for advanced glycation end product in various cell types, in lesional and peri-lesional skin of patients with psoriasis, and its correlation with disease severity. METHODS: Paraffin-embedded punch biopsy tissue taken from psoriatic plaques and peri-lesional normal appearing skin tissue of twenty patients with psoriasis, and normal skin samples of eleven healthy participants, were enrolled in the study. The sections were stained immunohistochemically with anti-receptor for advanced glycation end product antibody. The intensity of receptor for advanced glycation end product expression was assessed semi-quantitatively on epidermal cells, microvascular endothelium, dermal fibroblasts and inflammatory cells. They were graded as follows: 0 (no staining), 1 (weak), 2 (moderate) and 3 (strong) intensity. RESULTS: Receptor for advanced glycation end product expression on epidermis, microvascular endothelium, inflammatory cells and fibroblasts in the psoriatic plaques was more intense than perilesional and normal tissue (all P < 0.05). It did not correlate with disease severity. LIMITATIONS: The main limitation of our study is that this was a semi-quantitative assessment, detected immunohistochemically in skin biopsies. CONCLUSION: Receptor for advanced glycation end product expression may have an important role in psoriasis pathogenesis, independent of disease severity.

Expression of the receptor for advanced glycation end products in acquired reactive perforating collagenosis.

BACKGROUND: Acquired reactive perforating collagenosis (ARPC) is a rare skin disorder characterized by transepidermal elimination of dermal collagen. There is little data regarding the pathogenesis of ARPC. The receptor for advanced glycation end products (RAGE) is a multiligand transmembrane receptor that plays an important role in inflammatory responses and may be involved in the pathogenesis of ARPC. AIM: To explore the expression of RAGE in ARPC. METHODS: Paraffin-embedded punch biopsy specimens of 41 patients with ARPC and of 11 healthy controls with normal skin were obtained from the Department Of Pathology. Clinical data of all patients were reviewed from the medical files. All specimens were stained immunohistochemically with antibody to RAGE (Anti-RAGE). The intensity of RAGE expression was assessed semi-quantitatively on epidermal cells, microvascular endothelium, dermal fibroblasts and inflammatory cells and graded as 0 (no staining), 1 (weak), 2 (moderate) and 3 (strong). The patients were divided into diabetic and nondiabetic groups for analysis. RESULTS: RAGE expression in microvascular endothelium, inflammatory cells and fibroblasts of patients with ARPC was more intense than normal tissues of healthy participants (P values are 0.005, 0.017 and P > 0.05). LIMITATIONS: Our method of assessment of RAGE expression was semi-quantitative. CONCLUSION: We observed an overexpression of RAGE in lesional samples of patients with ARPC which was independent of the presence of diabetes.