Unveiling the impact of psoriasis on liver health: does methotrexate play a villainous role?

Psoriasis might bring about an increased risk of liver diseases like nonalcoholic fatty liver disease and fibrosis. The impact of methotrexate on liver function is still a cause for concern, because of the studies suggesting an increased risk of liver damage and others finding no association. The focus of this study was the liver functions in psoriatic patients investigating the impact of long-term use of methotrexate on liver in psoriasis. A retrospective investigation including 140 patients with psoriasis receiving methotrexate treatment for at least 6 months and a control group consisted of 105 healthy ones was conducted. Liver function tests (AST, ALT, PLT) were assessed, and the association of baseline PASI with FIB-4 and APRI values was investigated. Additionally, FIB-4 and APRI values at baseline, 3rd, and 6th months of methotrexate treatment for psoriasis were compared. Compared with the controls, psoriatic patients exhibited significantly higher FIB-4 scores (p = 0.004). A moderate and significant correlation was observed between baseline PASI score and baseline FIB-4 score in psoriatic patients (p < 0.001, rho = 0.626). Long-term methotrexate use had no effect on APRI or FIB-4 (p = 0.104 and p = 0.475, respectively). Psoriatic patients face an elevated risk of liver fibrosis. Long-term methotrexate use does not adversely affect liver function in psoriatic patients. Noninvasive tools like APRI and FIB-4 scores can be employed to evaluate the risk of liver disease in these patients.

Analysis of factors influencing target PASI responses and side effects of methotrexate monotherapy in plaque psoriasis: a multicenter study of 1521 patients.

Methotrexate (MTX) is commonly used as first-line systemic treatment agent in psoriasis. We aimed to evaluate the clinical characteristics and treatment responses of patients with psoriasis undergoing MTX monotherapy. Data from adult patients with plaque psoriasis who received MTX monotherapy for at least 3 months between April 2012 and April 2022 were retrospectively evaluated in 19 tertiary care centers. Our study included 722 female and 799 male patients, a total of 1521 participants. The average age of the patients was 44.3 ± 15.5 years. Mode of treatment was oral in 20.4% of patients while in 79.4% it was subcutaneous. The median treatment duration was 8 months (IQR = 5-15). The median weekly dose was 15 mg (IQR = 11-15). 1448 (95.2%) patients were taking folic acid supplementation. At week 12, 16.3% of the patients achieved PASI (Psoriasis Area and Severity Index) 90 response while at week 24, 37.3% achieved it. Logistic regression analysis for week 12 identified the following independent factors affecting PASI 90 achievement positively: median weekly MTX dose ≤ 15 mg (P = 0.011), subcutaneous administration (P = 0.005), no prior systemic treatment (< 0.001) and folic acid use (0.021). In logistic regression analysis for week 24; median weekly MTX dose ≤ 15 mg (P = 0.001), baseline PASI ≥ 10 (P < 0.001), no prior systemic treatment (P < 0.004), folic acid use (P = 0.001) and absence of comorbidities (P = 0.009) were determined as independent factors affecting the achievement of PASI 90. Adverse effects were observed in 38.8% of the patients, with nausea/vomiting (23.9%) and transaminase elevation (13%) being the most common. The most common reasons for interruptions (15.3%) and discontinuations (27.1%) of the treatment were patient related individual factors. The use of MTX as the first systemic treatment agent, at doses ≤ 15 mg/week and concurrent folic acid application are positive predictive factors for achieving the target PASI response both at weeks 12 and 24. In our study, which is one of the most comprehensive studies on MTX treatment in psoriasis, we observed that MTX is an effective and safe treatment option.

Case report: Drug-induced vitiligo during treatment with BRAF/MEK inhibitors in a patient with metastatic conjunctival melanoma.

INTRODUCTION: Autoimmune side effects can be detected during the use of BRAF/MEK inhibitor. Although its frequency, mechanism and importance are not known exactly, there are cases reported in the literature. CASE REPORT: We report a case of drug-induced vitiligo in a patient with metastatic conjunctival malignant melanoma who was treated with BRAF/MEK inhibition therapy. MANAGEMENT AND OUTCOME: In the case, vitiligo was controlled with topical treatments. Follow-up process of the patient has been continuing with no progression on month 12 of the current treatment. DISCUSSION: Although ICI-related autoimmune side effects and vitiligo have been described more frequently, vitiligo may also occur secondary to BRAK/MEK inhibition. This case also points out that cutaneous toxicity is manageable with no delay in treatment thanks to collaboration of dermatologists and oncologists.

Serum zinc-alpha-2 glycoprotein and insulin levels and their correlation with metabolic syndrome in patients with rosacea.

BACKGROUND: Metabolic syndrome and insulin resistance may accompany rosacea. Zinc-alpha-2 glycoprotein (ZAG) is an adipokine involved in lipid, glucose, and insulin metabolism and might be associated with metabolic syndrome and insulin resistance. AIMS: To investigate the serum ZAG levels, presence of metabolic syndrome, insulin resistance, and the correlation between ZAG levels, rosacea severity, and metabolic syndrome in patients with rosacea. PATIENTS/METHODS: Seventy-nine patients with rosacea and 80 healthy volunteers were included. Anthropometric and demographic features, personal and family histories, clinical data, the subtype, severity, and duration of rosacea were recorded. Metabolic syndrome, insulin resistance, and dyslipidemia were evaluated in both groups. Fasting blood sugar, lipid panel, C-reactive protein, sedimentation rate, insulin, and serum ZAG levels were investigated. RESULTS: Frequency of metabolic syndrome, systolic and diastolic blood pressures, and C-reactive protein levels were significantly higher in the rosacea group (p < 0.001 and p = 0.001, respectively). Frequency of dyslipidemia and insulin resistance did not significantly differ between the groups (p = 0.175 and 0.694, respectively). The mean serum ZAG levels were lower in the rosacea group, but no significant difference was evident. In rosacea patients with metabolic syndrome, serum ZAG levels were significantly lower (p = 0.043); however, serum ZAG levels, insulin, and the homeostasis model assessment-estimated insulin resistance values were significantly higher (p = 0.168, 0.013 and 0.001, respectively). CONCLUSION: Metabolic syndrome, high blood pressure, and high C-reactive protein levels were associated with rosacea indicating chronic systemic inflammation. ZAG levels were associated with metabolic syndrome in patients with rosacea but not associated with rosacea subtype and disease severity.

The effect of COVID-19 on development of hair and nail disorders: a Turkish multicenter, controlled study.

BACKGROUND: A broad spectrum of skin diseases, including hair and nails, can be directly or indirectly triggered by COVID-19. It is aimed to examine the type and frequency of hair and nail disorders after COVID-19 infection. METHODS: This is a multicenter study conducted on consecutive 2171 post-COVID-19 patients. Patients who developed hair and nail disorders and did not develop hair and nail disorders were recruited as subject and control groups. The type and frequency of hair and nail disorders were examined. RESULTS: The rate of the previous admission in hospital due to COVID-19 was statistically significantly more common in patients who developed hair loss after getting infected with COVID-19 (P < 0.001). Telogen effluvium (85%) was the most common hair loss type followed by worsening of androgenetic alopecia (7%) after COVID-19 infection. The mean stress scores during and after getting infected with COVID-19 were 6.88 ± 2.77 and 3.64 ± 3.04, respectively, in the hair loss group and were 5.77 ± 3.18 and 2.81 ± 2.84, respectively, in the control group (P < 0.001, P < 0.001). The frequency of recurrent COVID-19 was statistically significantly higher in men with severe androgenetic alopecia (Grades 4-7 HNS) (P = 0.012; Odds ratio: 2.931 [1.222-7.027]). The most common nail disorders were leukonychia, onycholysis, Beau's lines, onychomadesis, and onychoschisis, respectively. The symptoms of COVID-19 were statistically significantly more common in patients having nail disorders after getting infected with COVID-19 when compared to the control group (P < 0.05). CONCLUSION: The development of both nail and hair disorders after COVID-19 seems to be related to a history of severe COVID-19.

Cutaneous reactions after COVID-19 vaccination in Turkey: A multicenter study.

OBJECTIVES: In this study covering all of Turkey, we aimed to define cutaneous and systemic adverse reactions in our patient population after COVID-19 vaccination with the Sinovac/CoronaVac (inactivated SARS-CoV-2) and Pfizer/BioNTech (BNT162b2) vaccines. METHODS: This prospective, cross-sectional study included individuals presenting to the dermatology or emergency outpatient clinics of a total of 19 centers after having been vaccinated with the COVID-19 vaccines. Systemic, local injection site, and non-local cutaneous reactions after vaccination were identified, and their rates were determined. RESULTS: Of the 2290 individuals vaccinated between April 15 and July 15, 2021, 2097 (91.6%) received the CoronaVac vaccine and 183 (8%) BioNTech. Systemic reactions were observed at a rate of 31.0% after the first CoronaVac dose, 31.1% after the second CoronaVac dose, 46.4% after the first BioNTech dose, and 46.2% after the second BioNTech dose. Local injection site reactions were detected at a rate of 35.6% after the first CoronaVac dose, 35.7% after the second CoronaVac dose, 86.9% after the first BioNTech dose, and 94.1% after the second BioNTech dose. A total of 133 non-local cutaneous reactions were identified after the CoronaVac vaccine (2.9% after the first dose and 3.5% after the second dose), with the most common being urticaria/angioedema, pityriasis rosea, herpes zoster, and maculopapular rash. After BioNTech, 39 non-local cutaneous reactions were observed to have developed (24.8% after the first dose and 5% after the second dose), and the most common were herpes zoster, delayed large local reaction, pityriasis rosea, and urticaria/angioedema in order of frequency. Existing autoimmune diseases were triggered in 2.1% of the patients vaccinated with CoronaVac and 8.2% of those vaccinated with BioNTech. CONCLUSIONS: There are no comprehensive data on cutaneous adverse reactions specific to the CoronaVac vaccine. We determined the frequency of adverse reactions from the dermatologist's point of view after CoronaVac and BioNTech vaccination and identified a wide spectrum of non-local cutaneous reactions. Our data show that CoronaVac is associated with less harmful reactions while BioNTech may result in more serious reactions, such as herpes zoster, anaphylaxis, and triggering of autoimmunity. However, most of these reactions were self-limiting or required little therapeutic intervention.

Cochlear Histopathologic Findings in Patients With Systemic Lupus Erythematosus: A Human Temporal Bone Study.

HYPOTHESIS: We hypothesized that, in archived human temporal bone samples from patients with systemic lupus erythematosus (SLE), a pathologic condition exists in the stria vascularis and cochlear hair cells. BACKGROUND: Sensorineural hearing loss is a common feature in SLE patients. However, the pathophysiologic mechanism of cochlear dysfunction is unclear. METHODS: We examined 15 temporal bone samples from 8 SLE patients, along with 17 samples from 10 age-matched healthy control patients. The samples were serially sectioned in the horizontal plane and stained with hematoxylin and eosin. We determined the area of the stria vascularis in a midmodiolar section of each cochlear turn. Then, we made cytocochleograms and calculated the percentage of missing inner and outer hair cells. RESULTS: The area of the stria vascularis in our SLE group was significantly smaller than in our control group. The number of remaining inner hair cells in our SLE group was smaller than in our control group; however, the difference did not reach statistical significance. The loss of outer hair cells in our SLE group was significantly higher than in our control group. There was a tendency toward a positive correlation between the loss of cochlear hair cells and the duration of SLE. CONCLUSION: The stria vascularis and cochlear hair cells are affected in SLE patients. Our findings could provide the histopathologic basis for the cochlear dysfunction, including sensorineural hearing loss, experienced by SLE patients.

Stria vascularis and cochlear hair cell changes in syphilis: A human temporal bone study.

OBJECTIVE: To observe any changes in stria vascularis and cochlear hair cells in patients with syphilis. MATERIALS AND METHODS: We examined 13 human temporal bone samples from 8 patients with syphilis (our syphilis group), as well as 12 histopathologically normal samples from 9 age-matched patients without syphilis (our control group). We compared, between the two groups, the mean area of the stria vascularis (measured with conventional light microscopy connected to a personal computer) and the mean percentage of cochlear hair cell loss (obtained from cytocochleograms). RESULTS: In our syphilis group, only 1 (7.7%) of the 13 samples had precipitate in the endolymphatic or perilymphatic spaces; 8 (61.5%) of the samples revealed the presence of endolymphatic hydrops (4 cochlear, 4 saccular). The mean area of the stria vascularis did not significantly differ, in any turn of the cochlea, between the 2 groups (P>0.1). However, we did find significant differences between the 2 groups in the mean percentage of outer hair cells in the apical turn (P<0.026) and in the mean percentage of inner hair cells in the basal (P=0.001), middle (P=0.004), and apical (P=0.018) turns. In 7 samples in our syphilis group, we observed either complete loss of the organ of Corti or a flattened organ of Corti without any cells in addition to the absence of both outer and inner hair cells. CONCLUSION: In this study, syphilis led either to complete loss of the organ of Corti or to significant loss of cochlear hair cells, in addition to cochleosaccular hydrops. But the area of the stria vascularis did not change.

Histopathologic ear findings of syphilis: a temporal bone study.

To the best of our knowledge, histopathologic studies of syphilitic ears have generally focused on hydropic changes; so far, no such studies have investigated peripheral vestibular otopathology using differential interference contrast microscopy, in patients with syphilis. For this study, we examined 13 human temporal bone samples from 8 patients with a history of syphilis. Using conventional light microscopy, we performed qualitative histopathologic assessment. In addition, using differential interference contrast microscopy, we performed type I and type II vestibular hair cell counts on each vestibular sense organ with minimal autolysis; in which the neuroepithelium was oriented perpendicular to the plane of section. We then compared vestibular hair cell densities (cells per 0.01 mm² surface area) in the syphilis group vs. the control group. In the syphilis group, we observed precipitate in the endolymphatic or perilymphatic spaces in 1 (7.7 %) of the samples and endolymphatic hydrops in eight (61.5 %) of the samples. Hydrops involved the cochlea (four samples) and/or saccule (four samples). In addition, the syphilis group experienced a significant loss of type II vestibular hair cells in the maculae of the utricle and saccule, and in the cristae of the lateral and posterior semicircular canals, as compared with the control group (P < 0.05).

Histopathologic Findings in Peripheral Vestibular System From Patients With Systemic Lupus Erythematosus: A Human Temporal Bone Study.

HYPOTHESIS: We hypothesized that a pathologic condition exists in vestibular hair cells in human temporal bones from patients with systemic lupus erythematosus (SLE). BACKGROUND: A significant association between sensorineural hearing loss and autoimmune disease has been reported. Patients with SLE also frequently have vestibular symptoms whose pathophysiologic mechanism is unclear. METHODS: We examined 15 temporal bone samples from 8 patients with SLE, along with 21 samples from 17 age-matched healthy control patients. The samples were serially sectioned in the horizontal plane and stained with hematoxylin and eosin. Using differential interference contrast microscopy, we counted the number of type I and type II hair cells in the saccular macula, the utricular macula, and the cristae of the three semicircular canals; then, we calculated the hair cell density (cells per 0.01 mm). RESULTS: The mean density of type I hair cells in our SLE group was significantly lower than in our control group in the saccular macula, in the utricular macula, and in the superior, lateral, and posterior semicircular canals. But in all five vestibular sensory epithelia, the mean density of type II hair cells did not significantly differ between our two groups. In our SLE group, the mean density of vestibular hair cells did not significantly correlate with the patient's age at death or with the duration of SLE. CONCLUSION: Type I hair cells in peripheral vestibular organs are affected in patients with SLE. Our findings could provide a pathologic basis for the difficulty with balance experienced by patients with SLE.

A family of Bart-Pumphrey syndrome.

Bart-Pumphrey syndrome (BPS) is an autosomal-dominant disorder characterized by hearing loss, leukonychia, knuckle pads and palmoplantar keratoderma. Two mutations in the extracellular domain of GBJ2 are resposible for this syndrome. To date, less than 10 case reports or clinical series about BPS have been published in the literature. Hearing loss and knuckle pads are the more commonly seen findings of this syndrome. Three generations and six family members with variable findings of knuckle pads, leukonychia, hearing loss and palmoplantar hyperkeratosis were presented in this report. We want to emphasize that dermatogists must be alert during the evaluation of these findings because some findings of this disorder may be vague or absent.