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.

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.

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.

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.

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.

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.

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.

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.

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.

Evaluation of clinicopathological and treatment characteristics of 80 patients with acquired perforating dermatosis.

Acquired perforating dermatosis (APD) is a group of a rare dermatological disorder characterized by elimination of dermal connective tissue through epidermis. We aimed to evaluate the characteristics of patients diagnosed with APD and to determine the differences in comorbidities according to subtypes of APD. A retrospective, observational, cross-sectional study was designed. Patients diagnosed with APD between January 2008 and January 2019 were reviewed. Eighty patients were included in the study. 61.2% (n = 49) of the patients were female and 38.8% (n = 31) were male with a mean age of 58.4 ± 12.5 years. 82.5% (n = 66) of the patients were diagnosed with reactive perforating collagenosis (RPC) and 17.5% (n = 14) of perforating folliculitis (PF). The most common concomitant disease was diabetes mellitus (82.5%). 5.0% of the patients had malignancy. The comorbidity rate in RPC group was higher than PF (P < .05). Topical steroid was the most frequently (90.0%) used treatment. Complete response was obtained 55.0% of patients. Exitus was observed in 23.8% (n = 19) of patients in a mean 17.6 ± 25.7 months follow-up period. APD may be associated with many diseases. Comorbidities are more frequent in RPC group. This situation warns us to evaluate patients with RPC in more detail for underlying diseases. High mortality rate related to the underlying systemic diseases suggests being careful in terms of mortality in patients diagnosed with APD.

Knowledge levels and concerns about oral isotretinoin treatment in the parents of adolescent acne patients.

Oral isotretinoin is frequently used in the treatment of young acne patients. However, knowledge levels and attitudes about this treatment have not been studied in the parents previously. We aimed to investigate the knowledge levels and concerns about oral isotretinoin in the parents of adolescent acne patients. We conducted a cross-sectional study on 136 parents of adolescent patients with moderate to very severe acne vulgaris who answered the questionnaire about oral isotretinoin treatment. Demographic data and acne characteristics were recorded. The parents' knowledge levels and concerns about the treatment process were asked by the questionnaire. Since 32 parents have never heard oral isotretinoin before, they were excluded from the study. Of the remaining 104 parents, 80.8% were female and 19.2% were male. Of the parents, 62.5% had some concerns about oral isotretinoin treatment and 34.6% had no idea whether the drug is suitable for the use of <18 years. 52.9% stated that they think the drug will damage the liver. The most known and worrying side effects were dry lips and vision problems, respectively. The knowledge levels about oral isotretinoin treatment and its side effects were low in the parents of adolescent acne patients, leading to prejudice to the drug.

Solitary noninfiltrating angiolipoma on the finger, an unusual localization.

Angiolipoma, a subtype of lipoma, is a benign adypocytic soft tissue tumor composed of mature adipose tissue and small vascular proliferations. This entity makes up 5-17% of all lipomas. The diagnosis is made by clinical and pathological examination, ultrasonography, and/or magnetic resonance imaging (MRI). It is generally an encapsulated tumor (noninfiltrative), but rarely has an infiltrative form. Angiolipoma mostly occurs on the trunk and extremities with male predominance. The forearm is the most frequent location for angiolipomas. It is very rarely seen on the fingers. Herein, we report a patient with solitary noninfiltrating angiolipoma on a finger. The patient was treated with surgical excision and no recurrence has been noted over one year of observation.

Comparison of topical clobetasol propionate 0.05% and topical tacrolimus 0.1% in the treatment of cutaneous lichen planus.

INTRODUCTION: The effectiveness of topical tacrolimus in the treatment of oral and genital lichen planus has been verified in many randomized studies; however, there are only few case reports in treatment of cutaneous lichen planus (CLP). AIM: We sought to compare the safety and efficacy of topical clobetasol propionate and tacrolimus ointment in the treatment of CLP. MATERIAL AND METHODS: Retrospective analysis of patient files was performed. We enrolled patients who were diagnosed with CLP and treated with topical tacrolimus 0.1% or topical clobetasol propionate 0.05%. Visual Analogue Scale (VAS) scores of pigmentation and pruritus, clinical response, laboratory data and adverse effects were obtained from medical records. RESULTS: A total of 27 patients were included in the clobetasol group and 23 patients in the tacrolimus group. Both groups showed an improvement in VAS scores regarding pruritus and pigmentation but a statistically significant difference was observed in the clobetasol group (p< 0.05). At week 12, a complete response was observed in 63% (n = 17) of the clobetasol and 26% (n = 6) of the tacrolimus group. CONCLUSIONS: In our study, both treatments were found effective in the treatment of CLP but clobetasol propionate was more effective. However tacrolimus may be preferred before topical corticosteroids for lesions on the face, neck, and intertriginous regions of the body, which are sensitive to the cutaneous adverse effects of topical corticosteroids. Our study may be one of the first studies to compare the effects of topical clobetasol and tacrolimus ointment in the management of CLP.

Assessment of quality of life in Turkish children with psoriasis and their caregivers.

BACKGROUND/OBJECTIVES: The effect of pediatric psoriasis on quality of life has been demonstrated, but data regarding its influence on caregiver quality of life are scarce. The objective was to investigate how psoriasis affects quality of life of children and their caregivers. METHODS: This multicenter study included 129 children with psoriasis and their caregivers, who were family members accompanying patients to the clinic. Patient quality of life was measured using the Child Dermatology Life Quality Index. Caregiver quality of life was assessed using Dermatological Family Impact Scale, a 15-item questionnaire validated for use in the Turkish language. RESULTS: Mean Child Dermatology Life Quality Index score was 7.6, indicating a moderate effect on patient quality of life. Symptoms and feelings were the most severely impaired domains of patient quality of life, and emotions was the most severely impaired domain of caregiver quality of life. Dermatological Family Impact Scale score was significantly correlated with Child Dermatology Life Quality Index (correlation coefficient [r] = .554, P < .001) and Psoriasis Area and Severity Index (r = .350, P < .001). Caregivers of patients receiving systemic agents or phototherapy had relative impairment of multiple domains of quality of life compared to caregivers of patients receiving topical treatment only. CONCLUSION: Psychosocial effect of pediatric psoriasis was shown to extend beyond the individual, highlighting the importance of addressing patient and caregiver quality of life concerns in an integrated approach.

Demodex mites in acne rosacea: reflectance confocal microscopic study.

BACKGROUND/OBJECTIVES: Demodex mite density is emphasised in the aetiopathogenesis of acne rosacea. Reflectance confocal microscopy (RCM) has been shown to be a good method for determining demodex mite density. The objective was to determine demodex mite density using RCM in acne rosacea patients and compare them with controls. METHODS: In all, 30 papulopustular rosacea (PPR) and 30 erythematotelangiectatic rosacea (ETR) totally 60 acne rosacea patients and 40 controls, were enrolled in the study. The right cheek was selected for imaging and RCM was used for scanning. Ten images of 1000 × 1000 µm (total 10 mm2 ) area were scanned from adjacent areas. The numbers of follicles, infested follicles and mites were counted. The mean numbers of mites per follicle and infested follicles were calculated and compared in the patients and control groups. RESULTS: The mean number of mites was 44.30 ± 23.22 in PPR, 14.57 ± 15.86 in ETR and 3.55 ± 6.48 in the control group (P < 0.001). The mean number of mites per follicle was 1.77 ± 0.90 in PPR, 0.57 ± 0.63 in ETR and 0.13 ± 0.23 in the control group (P < 0.001). The cut-off for the mean number of mites for determining mite infestation was 0.17 and above. CONCLUSIONS: Demodex mite density was markedly increased in both ETR and PPR patients. It is believed that the presence of demodex mites plays an important role in rosacea aetiopathogenesis. Demodex mite treatment may reduce the severity of the disease and slow its progressive nature.

Reflectance confocal microscopic evaluation of nonmelanocytic lip lesions.

Lips display various benign and malignant lesions. Considering their functional and cosmetic importance, noninvasive diagnostic methods are required. In vivo reflectance confocal microscopy (RCM) has already been reported to be useful in the evaluation of various skin lesions. The aim of this study was to define the RCM features of nonmelanocytic lip lesions, compare them with healthy lip, and demonstrate the applicability of RCM as a noninvasive diagnostic method for nonmelanocytic lip lesions. Sixty-seven patients with premalignant/malignant, inflammatory, and infectious lip lesions and twenty-one healthy volunteers were included in the study. Following clinical and RCM examination, histopathological confirmation was obtained in all lesions except herpes labialis, verrucae, and aphthae. RCM features of individual lesions and corresponding groups were evaluated and compared. Pleomorphism was the common feature of premalignant/malignant lesions. Dermal invasion of dyskeratotic keratinocytes was visualized in all squamous cell carcinoma lesions. Spongiosis and inflammatory cells were the common features of inflammatory lesions. Hypergranulosis and necrotic keratinocytes were highly specific for lichen planus. The most specific features for discoid lupus erythematosus were irregular pattern, follicular plugs, and perifollicular inflammatory cells. Virus-infected keratinocytes were visualized in herpes and verrucae. RCM features showed high sensitivity and specificity to detect nonmelanocytic lip lesions. Although the penetration is limited to the papillary dermis in nonmucosal skin, imaging down to the mid-dermis with satisfactory resolution was possible on the lips.

Intralymphatic nevus cells in benign nevi.

The histogenesis of nevus cell aggregates in lymph nodes lesion is controversial, and various hypotheses have been used to explain their origin. One of them is the transport of cells from cutaneous nevi or lesions to lymph nodes, called mechanical transport theory. We investigated in our cases of benign nevi to obtain evidence to substantiate this theory. A total of 369 benign cutaneous nevi were prospectively evaluated in excisional biopsy samples. Immunohistochemical stainings for CD31 and podoplanin (D2-40) were performed in the cases with intralymphatic nevus cell aggregate (ILNA), suspected for ILNA, and/or intralymphatic nevus cell protrusion. A total of 13 ILNAs were found in 10 patients. Six ILNA were verified with their histology as well as immunohistochemically with D2-40 and CD31. Protrusions of nevus cells inside the lymphatics (intralymphatic nevus cell protrusion) were seen in all cases of ILNA and also in 27 nevi where an ILNA was not observed. In most nevi, the perilymphatic orientation of nevus cells and their affinity to the lymphatics were observed. We suggested that ILNAs can be dislodged with local minor trauma and be carried inside the lymphatic vessel to the draining lymph node. Besides, whether ILNA or not, nevus cells could also move toward lymphatic spaces with mechanical effects due to their affinity to lymphatics and their localizations that are very close to the endothelium. Our findings might support the mechanical transport theory.