Divergent in situ expression of IL-31 and IL-31RA between bullous pemphigoid and pemphigus vulgaris.

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two major autoimmune blistering skin diseases. Unlike PV, BP is accompanied by intense pruritus, suggesting possible involvement of the pruritogenic cytokine IL-31. However, the underlying mechanisms of the clinical difference between BP and PV in terms of pruritus are not fully understood. To compare the expression levels of IL-31 and its receptor IL-31RA in the lesional skin, including peripheral nerves in BP and PV patients, immunohistochemical staining for IL-31 and IL-31RA was performed in skin samples of BP and PV patients and healthy controls (HC). The IL-31RA-expressing area in epidermis and peripheral nerves was analysed using ImageJ and the percentage of positive cells for IL-31/IL-31RA in dermal infiltrating cells was manually quantified. Quantitative analyses revealed that IL-31/IL-31RA expressions in the epidermis and dermal infiltrate were significantly increased in BP compared to PV and HC. The difference between BP and PV became more obvious when advanced bullous lesions were compared. Peripheral nerves in BP lesions presented significantly higher IL-31RA expression compared to PV lesions. In conclusion, we found significantly augmented expressions of IL-31/IL-31RA in BP lesions, including peripheral nerves, in comparison to PV. These results suggest a possible contribution of IL-31/IL-31RA signalling to the difference between BP and PV in the facilitation of pruritus and local skin inflammation, raising the possibility of therapeutic targeting of the IL-31/IL-31RA pathway in BP patients.

Systemic disease in leukocytoclastic vasculitis: a focus on direct immunofluorescence findings

Abstract Background Direct immunofluorescence (DIF) panels are usually ordered for clinically suspected cutaneous vasculitis, but their positivity rate is variable, and their prognostic significance is not clear to date. Objective The study aims to investigate the systemic involvement rate in leukocytoclastic vasculitis (LCV) patients and the potential clinical and laboratory associations with systemic involvement, including DIF findings. Methods A retrospective study of patients with histopathologically proven cutaneous LCV examined in the dermatology department between 2013 and 2017 was performed. Results Of the 81 patients (mean age, 50.6 years), 42 (52%) were male. The mean time between the appearance of skin lesions and biopsy was 23.1 days, ranging from 2 to 180 days. DIF showed overall positivity of 90.1%, and C3 was the most frequent immunoreactant (82.7%). Any kind of extracutaneous involvement was present in 47 (58%) of patients, with renal involvement being the most frequent (53.1%), followed by articular (18.5%) and gastrointestinal (11.1%) involvement. The presence of renal disease was associated with the detection of IgG in the lesional skin (p = 0.017), and with the absence of IgM in the lesional skin (p = 0.032). There was a significant association between C3 deposition and joint involvement (p = 0.05). Study limitations This is a single-center study with a retrospective design. Conclusion DIF seems to be a useful ancillary diagnostic tool in the evaluation of cutaneous vasculitis, but the relationship between DIF findings and systemic involvement needs to be further elucidated due to contradictory data in the current literature.

Systemic disease in leukocytoclastic vasculitis: a focus on direct immunofluorescence findings.

BACKGROUND: Direct immunofluorescence (DIF) panels are usually ordered for clinically suspected cutaneous vasculitis, but their positivity rate is variable, and their prognostic significance is not clear to date. OBJECTIVE: The study aims to investigate the systemic involvement rate in leukocytoclastic vasculitis (LCV) patients and the potential clinical and laboratory associations with systemic involvement, including DIF findings. METHODS: A retrospective study of patients with histopathologically proven cutaneous LCV examined in the dermatology department between 2013 and 2017 was performed. RESULTS: Of the 81 patients (mean age, 50.6 years), 42 (52%) were male. The mean time between the appearance of skin lesions and biopsy was 23.1 days, ranging from 2 to 180 days. DIF showed overall positivity of 90.1%, and C3 was the most frequent immunoreactant (82.7%). Any kind of extracutaneous involvement was present in 47 (58%) of patients, with renal involvement being the most frequent (53.1%), followed by articular (18.5%) and gastrointestinal (11.1%) involvement. The presence of renal disease was associated with the detection of IgG in the lesional skin (p = 0.017), and with the absence of IgM in the lesional skin (p = 0.032). There was a significant association between C3 deposition and joint involvement (p = 0.05). STUDY LIMITATIONS: This is a single-center study with a retrospective design. CONCLUSION: DIF seems to be a useful ancillary diagnostic tool in the evaluation of cutaneous vasculitis, but the relationship between DIF findings and systemic involvement needs to be further elucidated due to contradictory data in the current literature.

Patient Use of Complementary and Alternative Medicine for Psoriasis Vulgaris and Factors Believed to Trigger the Disease: a Multicenter Cross-Sectional Study With 1621 Patients.

Introduction: Due to the chronic recurrent nature of psoriasis vulgaris (PV) and lack of definitive treatment for the disease, patients often resort to alternative treatments. Physicians seem to have low awareness of this issue. Objectives: To elicit the perceptions of 1,621 PV patients on complementary and alternative medicine (CAM) and examine factors reported to worsen PV. Methods: The patients sociodemographic characteristics, Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI), disease duration, and severity were recorded, and the patients CAM use was questioned in detail. The patients were also asked about factors that worsened PV and their experiences with a gluten-free diet. Results: Of the patients, 56.51% had used CAM. The mean age, illness duration, PASI scores and DLQI of those using CAM were significantly higher. CAM use was significantly higher in those with facial, genital involvement, and arthralgia/arthritis. The patients mostly referred to CAM when PV became severe (46.4%). Of the CAM users, 45.52% used herbal topicals. The physicians of 67.03% did not inquire whether they used CAM. Of the participants, 37.73% considered that stress worsened their disease. Gluten-free diet did not affect PV symptoms in 52.22%. Conclusions: Patients CAM use is often overlooked by dermatologists. Our results showed that more than half the patients used CAM and did not share this information with their physicians. Therefore, the awareness of physicians should be increased and patients should be asked about the use of CAM and directed to the appropriate medical treatment options by physicians.

Bullous Pemphigoid Associated with Dipeptidyl Peptidase 4 Inhibitors for the Treatment of Type 2 Diabetes: A Multicenter Study in Istanbul.

Objectives: Recent studies have revealed an association between dipeptidyl peptidase 4 inhibitors (DPP4i) and development of bullous pemphigoid (BP). The main aim of our study is to evaluate the association between DPP4i treatment and BP development. The secondary endpoints were to evaluate clinical characteristics and biochemical parameters of the DPP4i associated BP cases and determine the differences of DPP4i associated BP disease than non-DPP4i associated BP cases. Methods: We designed a retrospective case-control study, comparing type 2 diabetic 58 BP cases to 75 type 2 diabetic controls. Data were collected from three dermatological departments in Istanbul/Turkey, from November 1, 2008, to January 1, 2019. Medical records of each patient's demographic, clinical characteristics, drugs used, and laboratory data were reviewed. Results: There was no statistical difference in age and gender between the patient and control group. The most common prescribed oral antidiabetic for both groups was metformin. The most commonly prescribed DPP4i was vildagliptin. Fourteen (24.1%) out of 58 diabetic patients with BP were using vildagliptin, 12 (20.7%) out of 58 diabetic BP patients were using linagliptin, 6 (10.3%) out of 58 diabetic BP patients were using sitagliptin, and 1 (1.7%) out of 58 diabetic BP patients were using saxagliptin. There was no significant difference between the two groups regarding the DPP4 is use (using DPPi at the time of diagnosis and not). Both groups had similar clinical characteristics, localizations, disease severity, comorbidities, treatment responses, and biochemical parameters. BP patients using DPP4i had statistically less mucosal involvement than BP patients not using DPP4i (p=0.044). Conclusion: Even though there was no difference between two groups, when BP develops in diabetic patients, DPP4 is should be questioned and with cooperation with clinician's consideration of change may be planned.

Habits of Using Social Media and the Internet in Psoriasis Patients.

Introduction: Psoriasis significantly affects the patients quality of life, which often leads patients to seek online information about this disease. Objectives: To explore the habits of patients with psoriasis related to their use of social media (SM) and the internet to obtain information about their disease. Methods: 1,520 patients completed the survey and the Dermatology Life Quality Index (DLQI) questionnaire. The Psoriasis Area Severity Index scores (PASI) and clinical data of the patients were recorded by their physicians. Results: Of the 1,114 patients that reported using SM and internet, 48.38% regularly and 31.14% sometimes resorted to obtain information about psoriasis. The use of SM and internet for psoriasis was statistically significantly higher among young people (P = 0.000), those with university or higher education (P = 0.009), higher DLQI (P = 0.000) and PASI (P = 0.011) scores, facial (P = 0.050), scalp (P = 0.032), hand (P = 0.048), genital (P = 0.001) and inverse (P = 0.000) involvement, and arthralgia/arthritis (P = 0.006). The participants mostly used the Google (86%) and Facebook (41%). More than half of the participants (62.8%) expected dermatologists to inform society that psoriasis is not contagious. Conclusions: Internet and SM being widely available and offering substantial information to be easily accessed make it very attractive for patients to use these platforms to investigate diseases, including psoriasis. If what is presented on SM conflicts with what the physician says, patients mostly trust the latter, but at the same time, they tend not to share the results of their online inquiries with their physicians.

Is cutaneous microbiota a player in disease pathogenesis? Comparison of cutaneous microbiota in psoriasis and seborrheic dermatitis with scalp involvement.

Background Knowledge about cutaneous microbiota in psoriasis vulgaris and seborrheic dermatitis is limited, and a comparison of microbiota in the two diseases was not yet previously undertaken. Aims/Objectives This study aimed to compare the scalp lesional and non-lesional microbiota in psoriasis vulgaris and seborrheic dermatitis with that in a healthy control group. Methods Fifty samples were taken with sterile swabs from patients' and controls' scalps, and 16S rRNA gene sequencing analyses were performed. Results Alpha and beta diversity analyses showed that bacterial load and diversity were significantly increased in psoriasis vulgaris and seborrheic dermatitis lesions compared to the controls. As phyla, Actinobacteria decreased and Firmicutes increased, while as genera, Propionibacterium decreased; Staphylococcus, Streptococcus, Aquabacterium, Neisseria and Azospirillum increased in lesions of both diseases. Specifically, Mycobacterium, Finegoldia, Haemophilus and Ezakiella increased in psoriasis vulgaris and Enhydrobacter, Micromonospora and Leptotrichia increased in seborrheic dermatitis lesions. Mycobacterium, Ezakiella and Peptoniphilus density were higher in psoriasis vulgaris compared to seborrheic dermatitis lesions. The bacterial diversity and load values of non-lesional scalp in psoriasis vulgaris and seborrheic dermatitis lay between those of lesional areas and controls. Limitations The small sample size is the main limitation of this study. Conclusion Higher bacterial diversity was detected in lesions of both psoriasis and seborrheic dermatitis compared to the controls, but similar alterations were observed when the two diseases were compared. Although these differences could be a result rather than a cause of the two diseases, there is a need to analyze all members of the microbiota and microbiota-host interactions.

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.

IL-36α and IL-36γ expressions in the differential diagnosis of palmoplantar psoriasis and palmoplantar eczema: A retrospective histopathologic and immunohistochemical study.

BACKGROUND: Diagnosing hyperkeratotic lesions on the palms and soles is often challenging for both clinicians and pathologists. Interleukin (IL)-36 cytokines play an important role in the pathogenesis of psoriasis. METHODS: We retrospectively re-evaluated hematoxylin-eosin-stained biopsy specimens of 30 patients with clinically diagnosed palmoplantar psoriasis (PP) and 30 patients with palmoplantar eczema (PE), and then performed IL-36α and IL-36γ immunohistochemistry. RESULTS: Among the histopathologic features, thinning of the rete ridges and vertical alternation of parakeratosis and orthokeratosis had the highest positive predictive value (PPV) in diagnosing PP (72.7% and 69.3%, respectively). Immunohistochemically, patients with PP predominantly showed diffuse or focal strong expression with IL-36α and IL-36γ staining in the upper layers of the epidermis (86.7% and 83.3%, respectively). The comparison of the mean IL-36α and IL-36γ expression scores significantly differed between PP and PE (P < .001). Among all histopathologic and immunohistochemical features, diffuse strong expression of IL-36α and IL-36γ staining had the highest PPVs in favor of a diagnosis of PP (75% and 76.7%, respectively). CONCLUSIONS: Our data suggest that IL-36α and IL-36γ immunohistochemistry can be used in the differential diagnosis of PP and PE.

Solitary Subungual Orf.

Orf-ecthyma contagiosum-is an endemic cutaneous disease caused by parapoxvirus that is transmitted via direct contact with contagious animals. The lesions are located frequently on the hands and fingers. Subungual presentation of orf is very rare. We report a case of solitary subungual orf. Suspicious subungual nodular lesions may be cases of orf, especially in endemic areas. Orf disease should be considered in the differential diagnosis of subungual nodular lesions to avoid unnecessary surgical interventions.

Plasma matrix metalloproteinase-9 level change with omalizumab treatment in chronic spontaneous urticaria.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an enzyme that contributes to inflammation and tissue remodelling. In chronic urticaria, increased plasma levels of MMP-9 and its correlation with disease severity have been shown in several studies, suggesting that MMP-9 could be used to evaluate the effects of new treatments. We aimed to compare MMP-9 levels in chronic urticaria patients with those of healthy patients. Then we planned to investigate the changes in plasma MMP-9 levels with chronic urticaria treatment, the role of this enzyme in demonstrating the efficacy of treatment, and its correlation with C-reactive protein (CRP). METHODS: Forty-one patients with chronic urticaria who were scheduled for omalizumab treatment and 41 sex- and age-matched healthy volunteers were included in the study. In the patient group, before treatment and at the end of the 12th week, the urticaria activity score used for 7 consecutive days (UAS7) was calculated, and the MMP-9 and CRP levels were measured. Plasma MMP-9 levels were measured from venous blood in the control group. RESULTS: The plasma MMP-9 levels of the patients before treatment were significantly higher than those of the control group (P < .01). In the patient group, there was no significant relationship between the UAS7 score and the MMP-9 and CRP levels before treatment. The UAS7 values were 28 ± 7 before omalizumab treatment and 5 ± 6 at the end of the 12th week (P < .0001). The post-treatment MMP-9 levels (1818 ± 297 pg/mL) were higher compared with the pre-treatment values (1617 ± 380) (P < .05). The post-treatment CRP levels of the patients (2.41 ± 2.17 mg/L) were lower than their pre-treatment CRP levels (8.20 ± 19.70) (P < .05). CONCLUSION: MMP-9 levels were not associated with the severity of disease, and MMP-9 levels were not decreased with treatment response. Therefore, MMP-9 cannot be used as a parameter of disease activity in chronic urticaria or to evaluate the efficacy of new treatments.

COVID-19 induced telogen effluvium.

COVID-19 is a febrile, infectious illness that has previously been associated with telogen effluvium (TE). However, to date, no study has been conducted to determine the incidence of TE in those who have had COVID-19. To assess the frequency of TE in post-COVID-19 patients and the correlation between the development of TE and the severity of COVID-19, to understand whether emotional stress or medications are responsible for the development of TE. Totally 204 patients with a history of SARS-CoV-2 infection in the last 3 months were included in the study. The diagnosis of TE was made by history of excessive hair shedding, hair pull test, diffuse or bitemporal thinning, and absence of anisotrichosis in trichoscopy. Patients who did not have any TE cause other than COVID-19 and whose hair loss started after COVID-19 were considered as "COVID-19 associated TE (CATE)." We found TE in 75 (36.7%) cases and androgenetic alopecia (AGA) in 85 (41.7%) cases. CATE was present in 27.9% of cases and developed on average 53.76 (± 23.772) days after COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) positivity. The proportion of patients with CATE was numerically higher in hospitalized patients compared to outpatients (31.7% vs. 24.3%; p = 0.238); and significantly higher in women compared to men (42.3% vs. 6.2%; p < 0.001), in patients with hypertension compared to those without hypertension (40.4% vs. 23.1%; p = 0.014), and in patients who had respiratory symptoms compared to those who had not (31.7% vs. 14.0%; p = 0.021). The patients with and without CATE were similar in terms of stress level and usage of COVID-19 medications. Patients with AGA had a higher rate of hospitalization (69.4% vs. 35.3%; p < 0.001) and a higher incidence of fever (69.4% vs. 54.6%; p = 0.033) during COVID-19, compared to those without. TE developed in approximately one-quarter of people who have had COVID-19, and our study is the first to detect it. The time to onset of CATE, which was 7-8 weeks after the SARS-CoV-2 RT-PCR positivity, was not much different from post-infectious TE. Patients with severe COVID-19 seem to be more prone to develop TE. The presence of AGA is associated with a more severe COVID-19. During the pandemic, clinicians should consider a previous SARS-CoV-2 infection in patients presenting with hair loss.

Has the COVID-19 pandemic changed attitudes and behaviors concerning cosmetic care and procedures among patients presenting to the dermatology outpatient clinic? A multicenter study with 1437 participants.

BACKGROUND: The rate of cosmetic procedures and use of skincare products is considered to be affected during the pandemic period; however, this has not been investigated yet. OBJECTIVE: To determine whether the ongoing pandemic has changed people's habits related to skincare products and cosmetic procedures. METHODS: We conducted a multicenter survey study covering both private and public hospitals. Sociodemographic characteristics and clinical diagnoses of the patients were noted by dermatologists. A survey was used to determine the type and application areas of skincare products and cosmetic procedures before and during the pandemic, whether the patients were concerned about being infected, and any change in the make-up habits of female patients. RESULTS: Of the 1437 patients, 86.7% presented to the hospital due to dermatological complaints and 13.3% for cosmetic procedures. The rate of those that did not use skincare products was 0.05% before and 0.06% during the pandemic. Of the participants, 43.2% had undergone cosmetic procedures before and 38.1% during the pandemic. For both periods, the most frequent cosmetic procedure applied was laser epilation, followed by skincare treatment and chemical peeling. While undergoing these procedures, 34.9% of the patients were concerned about contracting coronavirus. CONCLUSION: There was no significant difference in the use of skincare products and cosmetic procedures before and during the pandemic. The majority of the patients continued to undergo these procedures despite their fear of being infected. This shows that during the pandemic period, patients are concerned with their appearance and continue to undergo cosmetic procedures and pay attention to their skincare.

Effect of the varicella vaccination implementation on the development of herpes zoster in children and adolescents.

Herpes zoster (HZ) is an infectious disease caused by latent varicella-zoster virus reactivation. There are conflicting reports on the varicella vaccine's effect on the incidence of HZ in children and adolescents. This study aimed to determine the impact of the single dose of varicella vaccination on HZ prevalence during childhood and adolescence. The study included children and adolescents aged <18 years who presented to the dermatology outpatient clinic between 2005 and 2019 and were diagnosed with HZ. Considering that the universal vaccination program started to be implemented in Turkey in 2013, non-vaccinated cases in the prevaccination period, vaccinated cases in the postvaccination period, and non-vaccinated patients in the postvaccination period were compared in terms of HZ prevalence and demographic features. After the initiation of the varicella vaccination program, the prevalence of HZ was found to decrease by 24.7% in all. The HZ prevalence was significantly reduced in vaccinated children, while the rate of decrease in non-vaccinated children was low (58.6% and 16.4%, respectively). The median age of the non-vaccinated cases in the postvaccination period (10 [min 0.5-max 17] years) was significantly higher compared to the other groups (p < 0.001). The number of cases aged <2 years was the highest in the vaccinated group (p < 0.001). Administration of a single dose of varicella vaccine was insufficient to decrease the prevalence of HZ <18 years of age. In the post-vaccination period, the frequency of HZ in unvaccinated cases increased in adolescence. In vaccinated children, HZ seems to develop at an earlier age.

Tissue eosinophil levels as a marker of disease severity in bullous pemphigoid.

BACKGROUND: Eosinophils play an important role in bullous pemphigoid (BP) pathogenesis. Although tissue infiltration with eosinophils has been known for a long time, there is a lack of knowledge about the relationship between tissue eosinophil levels and disease severity and clinical characteristics of the patients. METHODS: Fifty-nine patients diagnosed with BP between January 2008 and December 2018 were reviewed. Haematoxylin-Eosin (H&E)-stained preparations were re-evaluated in terms of tissue eosinophil levels. For disease severity, Bullous Pemphigoid Disease Area Index (BPDAI) was used. The relationship between tissue eosinophil levels and disease severity and clinical features were evaluated. RESULTS: Erosion/blister and urticaria/erythema BPDAI scores were higher in the group with high tissue eosinophil level than the group with low tissue eosinophil level. Tissue and peripheral blood eosinophil count were correlated with total urticaria/erythema BPDAI scores. There was no correlation between blood and tissue eosinophil count. The mortality rate was 64.7% vs 44.0% in the high vs low tissue eosinophil groups. Tissue eosinophil levels were high in patients with BP accompanying neurological disease. CONCLUSIONS: Tissue eosinophil count and peripheral blood eosinophil count were correlated with disease severity in BP. Tissue eosinophil levels were also high in patients with BP accompanying neurological disease.

Carotid intima-media thickness and serum proinflammatory cytokine levels in rosacea patients without cardiovascular risk factors.

There is a growing body of evidence linking rosacea to various systemic disorders, even though data regarding the association between rosacea and cardiovascular diseases are presently controversial. We sought to investigate the potential association of rosacea with subclinical atherosclerosis and serum proinflammatory/proatherogenic markers. This study included 44 patients with rosacea and 44 age-matched and sex-matched healthy control subjects. Patients with traditional cardiovascular risk factors or a history of cardiovascular events were excluded. Demographic, clinical, and laboratory data, including serum interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) levels were assessed. Carotid intima-media thickness (CIMT) and carotid plaques were measured by carotid ultrasonography. Serum IL-1ß (P < .001), IL-6 (P < .001), TNF-α (P < .001), and hs-CRP (P < .001) levels were significantly higher in the patient group compared with the control group. Mean CIMT values did not differ significantly between the patient group and control group (P > .05). Patients with moderate to severe rosacea had a significantly greater CIMT than those with mild rosacea (P = .047). Rosacea patients with eye involvement had a significantly greater CIMT than those without eye involvement (P = .008). There was no significant correlation between CIMT values and inflammation parameters. As conclusion, in the absence of other traditional cardiovascular risk factors, rosacea does not seem to affect mean CIMT value. However, specific subgroups such as patients with moderate to severe disease or with eye involvement are associated with increased subclinical atherosclerosis and may require additional attention for cardiovascular disease prevention.