COVID-19 severity and SARS-Cov-2 vaccine safety in pemphigus patients.

There are safety concerns in the treatment of pemphigus patients with immunosuppressants, particularly rituximab (RTX), in times of the COVID-19 pandemic. In the beginning, the reports were more pessimistic. However, few reports have recently pointed to manageable courses in this patient group. Therefore, we investigated the disease characteristics and demographic features of pemphigus patients in the period of the COVID-19 pandemic. We aimed to investigate the impact of immunosuppressants on the course of COVID-19 in pemphigus patients. Also, we tried to find out the rate of flares due to COVID-19 and SARS-Cov-2 vaccines. This multicenter study included 247 patients with pemphigus from three tertiary dermatology clinics with the specialized outpatient clinic for autoimmune blistering diseases. Patients were asked standardized questions in person or via telephone calls. Also, demographic data were collected from patients' files. Two hundred forty-four of 247 patients took the survey between August and September 2021. The data of three patients were obtained from the National Health System. We collected the data of all pemphigus patients who visited the clinics at least once in the past 3 years. Among 51 patients having COVID-19, 40 had a non-serious disease, whereas 11 required hospitalization. One patient died because of COVID-19 infection. The number of patients is limited, and data depends mainly on patients' statements. RTX treatment does not require additional safety cautions than other immunosuppressives.

A multicentre prospective analysis of the incidence of pemphigoid diseases in Turkey.

BACKGROUND: The differentiation between the pemphigoid diseases is essential for treatment and prognosis. In Turkey, data on the incidence of these diseases are insufficient. Our aim in this study is to determine the incidence, demographics and clinical characteristics associated with diseases of the pemphigoid group. METHODS: We prospectively analysed 295 patients with pemphigoid who visited dermatology clinics of tertiary referral hospitals in 12 different regions of Turkey within a year. The diagnosis was based on clinical, histopathological, direct immunofluorescence (DIF) and serological (multivariant enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence and mosaic-based BIOCHIP) examinations. Clinical and demographic findings, aetiological factors and concomitant diseases observed in the patients were recorded. RESULTS: A total of 295 (female/male ratio: 1.7/1) patients with pemphigoid were diagnosed in 1-year period. The overall incidence rate of pemphigoid diseases was found to be 3.55 cases per million-years. The ratio of pemphigoid group diseases to pemphigus group diseases was 1.6. The most common pemphigoid type was bullous pemphigoid (BP, 93.2%). The others were epidermolysis bullosa acquisita (3.1%), pemphigoid gestationis (2.4%), linear IgA disease (1%) and mucous membrane pemphigoid (0.3%). The most common (26.8%) possible trigger of the bullous pemphigoid was gliptin derivative drugs. The most common concomitant diseases with pemphigoid were cardiovascular (27.8%) and neurological diseases (23.7%). CONCLUSIONS: This study showed that the increased frequency of bullous pemphigoid reversed the pemphigoid/pemphigus ratio in Turkey. Further studies are warranted regarding the reasons for this increase.

Rituximab therapy in pediatric pemphigus patients: A retrospective analysis of five Turkish patients and review of the literature.

BACKGROUND/OBJECTIVES: There is inadequate knowledge regarding rituximab (RTX) administration in autoimmune bullous diseases (AIBDs), disease prevalence, clinical characteristics, and treatment outcomes within pediatric populations due to the rarity of AIBDs affecting the pediatric age group. The aim of this retrospective analysis was to evaluate the effectiveness, safety of RTX, and treatment outcomes in Turkish pediatric patients with pemphigus vulgaris (PV) and to review the literature. METHODS: Five patients under 18 years of age and diagnosed with PV received RTX treatment and were identified in four dermatology departments of Turkey. RESULTS: The mean age of the patients at the time of RTX therapy initiation was 15 years (range: 11-17 years), and the total duration of follow-up after RTX therapy was 42.6 months (range: 19-60 months). All patients showed a clinical response. At the last visit, complete remission off therapy was achieved in three patients. The remaining two patients achieved partial remission off therapy. No adverse events were observed. CONCLUSIONS: This retrospective case series of five pediatric patients showed that RTX treatment can be effective and safe for the treatment of recalcitrant PV in pediatric patients. With increasing evidence, RTX is a good treatment choice in adults and pediatric patients with pemphigus.

Psoriasis and the liver: problems, causes and course.

BACKGROUND/OBJECTIVES: Psoriasis patients have a higher risk of liver abnormalities such as non-alcoholic fatty liver disease (NAFLD), drug-induced hepatitis, alcoholic hepatitis and neutrophilic cholangitis, than the general population. Associated liver disease limits therapeutic options and necessitates careful monitoring. The aim of the study was to identify liver problems in psoriasis patients and to investigate the underlying causes as well as their course. METHODS: The files of 518 psoriasis patients were retrospectively reviewed. Among these, 393 patients with relevant laboratory data were analysed for liver enzymes and their relation to the known risk factors for liver disease (obesity, diabetes mellitus, alcohol consumption, hepatotoxic medications, dyslipidemia, psoriatic arthritis and infectious hepatitis). RESULTS: Among 393 patients, 24% and 0.8% developed liver enzyme abnormalities and cirrhosis, respectively. The most common factors associated with pathological liver enzymes were drugs (57%) and NAFLD (22%). Other rare causes were alcoholic hepatitis, viral hepatitis, neutrophilic cholangitis, autoimmune hepatitis and toxic hepatitis due to herbal therapy. Drug-induced liver enzyme abnormalities were reversible whereas in patients with NAFLD transaminases tended to fluctuate. One patient with herbal medicine-related cirrhosis died of sepsis. CONCLUSION: Liver enzyme abnormalities are common in psoriasis patients and are mostly associated with drugs and NAFLD. Although most cases can be managed by avoiding hepatotoxic medications and close follow up, severe consequences like cirrhosis may develop.

Assessment of arterial stiffness and cardiovascular hemodynamics by oscillometric method in psoriasis patients with normal cardiac functions.

Arterial stiffness is associated with increased cardiovascular risk. Pulse wave velocity (PWV) and augmentation index (AIx) are non-invasive markers for assessment of arterial stiffness. Increased arterial stiffness is associated with atherosclerosis in patients with psoriasis. Previous studies have shown that high neutrophil-to-lymphocyte ratio (NLR) predicts poor cardiovascular outcome. The aim of this study was to evaluate arterial stiffness and cardiovascular hemodynamics by oscillometric method in psoriasis patients with normal cardiac functions. Fifty consecutive patients with the diagnosis of psoriasis and 50 controls were included in the study. NLR was calculated as the ratio of neutrophil count to lymphocyte count. All patients underwent echocardiographic examination. Measurements of arterial stiffness were carried out using a Mobil-O-Graph arteriograph system. Fifty patients with psoriasis (26 male, mean age 43.3 ± 13.2 years) and 50 controls (33 male, mean age 45.0 ± 6.1 years) were included into the study. The distribution of cardiovascular risk factors was similar between the two groups, and NLR was significantly higher in patients with psoriasis (2.74 ± 1.78 versus 1.82 ± 0.52, p = 0.002). There was a weak correlation between NLR and PASI score without reaching statistical significance (r = 0.300, p = 0.060). While echocardiographic and hemodynamic parameters were comparable between psoriasis and control groups, heart rate was significantly higher in psoriasis group (81.5 ± 15.1 and 75.2 ± 11.8 beats/min, p = 0.021). Psoriasis patients had significantly higher AIx and PWV values as compared to controls (25.8 ± 13.1 versus 17.4 ± 12.3%, p = 0.001 and 6.78 ± 1.42 versus 6.18 ± 0.80 m/s, p = 0.011, respectively). AI and PWV were significantly associated with psoriasis when adjusted by heart rate (p = 0.005, odds ratio 1.04, 95% confidence interval 1.01-1.08 and p = 0.035, odds ratio 1.52, 95 % confidence interval 1.02-2.26, respectively). PWV significantly correlated with blood pressure, lipid levels, and several echocardiographic indices. AIx only correlated with left atrial diameter (r = 291, p = 0.040). Linear regression analysis was performed to find predictors of PWV. Central systolic blood pressure, left atrial diameter, and total cholesterol were independent predictors of PWV. PWV and AIx were significantly higher in patients with psoriasis. Assessment of arterial stiffness parameters may be useful for early detection of cardiovascular deterioration in psoriasis patients with normal cardiac functions. Novel inflammatory biomarkers such as NLR may elucidate the mechanism of vascular dysfunction in such patients.

Mesenchymal stem cells derived from human dental follicle modulate the aberrant immune response in atopic dermatitis.

Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder. The advancements in the understanding of AD immunological pathogenesis have caused the development of therapies that suppress the dysregulated immune response. We aimed to evaluate the immunomodulatory effect of dental stem cells (dental follicle-mesenchymal stem cells [DF-MSCs]) on AD patients. Materials & methods: We investigated the immunoregulatory potential of DF-MSCs on T cell response in AD and compared them with psoriasis and healthy individuals and the underlying mechanisms. Results: DF-MSCs significantly reduced Fas, FasL and TNFR II frequency in T cells, increased naive T cell population while reducing memory T cell, decreased inflammatory cytokine levels and promoted Tregs frequency in the AD population. Conclusion: These results imply that DF-MSCs are modulating inflammation through decreasing T cell apoptosis, inducing Treg expansion and stabilizing cytokine levels.

Lay abstract Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. There is no definite solution for the treatment of AD. We aimed to evaluate the immunomodulatory and immunosuppressive effect of dental stem cells (dental follicle-mesenchymal stem cell [DF-MSCs]) on AD. Materials & methods: We investigated the immunoregulatory potential of DF-MSCs on inflammatory response in AD and compared them with psoriasis and healthy individuals and the mechanism underlying it. Results: DF-MSCs significantly reduced apoptosis-related markers in immune cells, decreased inflammatory cytokine levels and promoted Treg frequency in the AD. Conclusion: Our findings provide basic evidence for the potential role of DF-MSCs as a cellular therapy option in the treatment of AD and shed light on future clinical studies.

Tumor necrosis factor-alpha inhibitors for the treatment of psoriasis patients with liver cirrhosis: A report of four cases with a literature review.

Patients with psoriasis are at an increased risk of developing liver disease due to various factors. The existing data regarding the treatment of psoriasis patients with associated liver cirrhosis is limited. We report four patients of psoriasis with liver cirrhosis who were treated with TNF-alpha inhibitors for a mean duration of 35.4 months. Two patients were treated with etanercept, one with adalimumab and one was treated with both infliximab and etanercept. Three patients tolerated the treatment well without any deterioration of liver disease whereas one died of progressive liver disease. Although large-scale, controlled studies are needed, this case series provides insights regarding the long-term safety of TNF-alpha inhibitors in patients with psoriasis and liver cirrhosis.

Epidemiology of Pemphigus in Turkey: One-year Prospective Study of 220 Cases.

Pemphigus is a group of rare and life-threatening autoimmune blistering diseases of the skin and mucous membranes. Although they occur worldwide, their incidence shows wide geographical variation, and prospective data on the epidemiology of pemphigus are very limited. Objective of this work is to evaluate the incidence and epidemiological and clinical features of patients with pemphigus in Turkey. All patients newly diagnosed with pemphigus between June 2013 and June 2014 were prospectively enrolled in 33 dermatology departments in 20 different provinces from all seven regions of Turkey. Disease parameters including demography and clinical findings were recorded. A total of 220 patients were diagnosed with pemphigus during the 1-year period, with an annual incidence of 4.7 per million people in Turkey. Patients were predominantly women, with a male to female ratio of 1:1.41. The mean age at onset was 48.9 years. Pemphigus vulgaris (PV) was the commonest clinical subtype (n=192; 87.3%), followed by pemphigus foliaceus (n=21; 9.6%). The most common clinical subtype of PV was the mucocutaneous type (n=83; 43.2%). The mean Pemphigus Disease Area Index was 28.14±22.21 (mean ± Standard Deviation). The incidence rate of pemphigus in Turkey is similar to the countries of South-East Europe, higher than those reported for the Central and Northern European countries and lower than the countries around the Mediterranean Sea and Iran. Pemphigus is more frequent in middle-aged people and is more common in women. The most frequent subtype was PV, with a 9-fold higher incidence than pemphigus foliaceus.

Growth arrest-specific 6 and cardiometabolic risk factors in patients with psoriasis.

OBJECTIVES: An increased risk for cardiovascular disease with psoriasis has been reported. Growth Arrest-Specific 6 (GAS6) amplifies pro-inflammatory endothelial cell activation via TAM receptors. However, it also inhibits inflammation by multiple mechanisms including phagocytosis. The objective of this study was to investigate whether plasma GAS6 levels are associated with conventional cardiometabolic (CM) risk factors in patients with psoriasis. METHODS: Forty patients diagnosed with psoriasis (22 male, mean age: 43.3 ± 13.8 years) and 40 age-/sex-matched healthy controls (22 male, mean age: 39.3 ± 8.9 years) were included in the study. CM risk factors (hypertension, hyperlipidemia, diabetes mellitus, and cigarette smoking) were identified. GAS6 levels were measured by ELISA. RESULTS: There were no significant differences between the plasma GAS6 levels of patients with psoriasis compared to the control group (6.6 ± 2.0 ng/mL, 7.6 ± 2.8 ng/mL, respectively, P > 0.05). However, GAS6 levels of patients with psoriasis having a smoking history (n = 11) were significantly lower than both patients with psoriasis who had no smoking history (n = 29) and controls (5.5 ± 1.7 ng/mL, 6.9 ± 1.9 ng/mL, 7.6 ± 2.8 ng/mL, respectively, P < 0.05). Similarly, psoriasis patients with at least one CM risk factor showed lower GAS6 levels compared to subjects without any CM risk factor (5.7 ± 1.7 ng/mL, 7.3 ± 2.0 ng/mL, P < 0.01). There was no correlation between the GAS6 level, disease duration or PASI score (r = 0.150, -0.150, and P = 0.310, 0.398, respectively). CONCLUSIONS: This pilot study provides the first evidence in humans for an association between low plasma GAS6 levels and conventional risk factors in psoriasis. Further large scale, prospective studies are needed to confirm these results.

The risk of tuberculosis in patients with psoriasis treated with anti-tumor necrosis factor agents.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) antagonist treatment is associated with 1.6 to 27 times higher risk of tuberculosis (TB). OBJECTIVE: To find TB incidence of psoriasis patients treated with TNF- α antagonists and define risk factors related with this condition in a country with moderately high risk of TB. METHODS: Three hundred seventy psoriasis patients treated by anti-TNF agents in four referral centers were included. The data on the characteristics of the patients, TB history, tuberculosis skin test results, anti-TNF agent type and exposure time, localization of TB, and isoniazide prophylaxis state were analyzed. RESULTS: Four patients (1.08%) developed TB, three pulmonary and one gastrointestinal, 2-23 months after initiating anti-TNF agents. Other than the patient with gastrointestinal TB, who was using methotrexate and corticosteroid concomitantly, none had contributing risk factors for TB. Two patients developed pulmonary TB in spite of chemoprophylaxis. Three patients with pulmonary TB completely recovered following antiTB treatment whereas patients with gastroinrestinal TB developed renal failure. LIMITATIONS: The major limitation of the study is the lack of a diseased control group, which enables us to compare the risk of psoriatics with that of patients having other inflammatory diseases. CONCLUSION: Tuberculosis is a rare but a severe complication of anti-TNF treatment and may develop in spite of chemoprophylaxis. The risk of TB in psoriasis patients in the present study is comparable to literature mostly based on rheumatology patients.