Evaluation of the Quality of Life and the Demographic and Clinical Characteristics of Patients With Pemphigus With Oral Mucosal Involvement: A Multicenter Observational Study.

INTRODUCTION: Pemphigus vulgaris (PV) is an autoimmune disease primarily affecting the oral mucosa. OBJECTIVES: This study aimed to determine the demographic, clinical and treatment characteristics of PV patients with oral mucosal involvement and to assess the impact on their quality of life. METHODS: We conducted a prospective observational study among 106 patients diagnosed with PV and presenting oral mucosal involvement. Demographic data, clinical and treatment characteristics, and quality of life questionnaires were recorded. RESULTS: The study included 106 patients, 55 (51.89%) were male and there was a predominance of the mucocutaneous subtype in 83 individuals (78.38%). Oral mucosa was the initial site of manifestation in 44 patients (41.51%). Bilateral buccal mucosa was the most frequently affected site. The predominant symptom reported was a burning sensation, noted in 91 patients (85.85%). Oral mucosal examination revealed erosions in 85.85% of the patients. Systemic steroids were the most commonly administered treatment, and rituximab was used in 18 patients (16.98%). A positive and significant correlation was found between pemphigus severity and Oral Health Impact Profile-14, Dermatology Life Quality Index and Dermatological Quality of Life Scale scores (P < 0.05). The presence of superficial ulcers, flaccid bullae, lesion diameter ≥1 cm, and >10 lesions were factors that markedly diminished quality of life. Complete response to treatment was noted in all patients administered rituximab. CONCLUSIONS: The most common area of involvement was bilateral buccal mucosa, and the severity of PV closely correlated with a decline in quality of life measures. These results highlight the need for careful clinical oversight of PV, taking into account its effects on patients quality of life.

Dermatoscopic Characteristics, Lesional Capillaroscopic Features, and Histopathological Correlation of Small Plaque Parapsoriasis and Mycosis Fungoides.

INTRODUCTION: Dermatoscopy is a frequently used non-invasive diagnostic procedure. OBJECTIVES: Considering that mycosis fungoides (MF) mimics parapsoriasis clinically in early stages, we aim to determine the dermatoscopic criteria and the histopathological correlations in patients with MF and small plaque parapsoriasis (SPP). METHODS: This prospective study involved 28 patients with clinical and histopathological diagnoses of MF and 31 patients with SPP. Videodermoscopy and USB capillaroscope were used to evaluate the patients vessels at ×200 magnification. Vascularity was evaluated through microvascular density (MVD) scoring involving CD34 antibody staining. RESULTS: Fifty-nine patients were included in this study. The scores corresponding to the presence of short linear vessels, linear-curved vessels, branching linear vessels, and non- structured orange-colored areas were significantly higher in the MF patients than in the SPP patients (P < 0.05). The highest MVD (P = 0.01) scores were also higher in the MF patients than in the SPP patients. CONCLUSIONS: The SPP and early-stage MF patients differed in their MVD scores, and the findings correlated with the dermatoscopy and lesional capillaroscopy findings. Differentiating features between SPP and MF were thus identified.

Interstitial Granulomatous Dermatitis and Palisaded Neutrophilic Granulomatous Dermatitis: Retrospective Clinicopathological Analysis of 16 Cases.

INTRODUCTION: Reactive granulomatous dermatitis (RGD) is a new entity, which is highly associated with systemic disorders. There is scarce data regarding interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic granulomatous dermatitis (PNGD). OBJECTIVES: We aimed to evaluate clinical and histopathological characteristics of IGD and PNGD as unified entities under the term of RGD. METHODS: Observational, retrospective, single-center study of patients diagnosed with IGD and PNGD between 2012 and 2021 were included in the study. RESULTS: Of 16 patients (14 females and 2 males) with RGD, 13 had IGD and 3 had PNGD with a mean age of 62.5 years. The most common clinical presentation was plaques 37.5% (N=6), followed by patches 25% (N=4). The most common localization of involvement was lower extremity 75% (N=12), followed by trunk and upper extremity. Multiple localization of involvement was determined in 75% (N=12) of patients. None of the patients had rope sign. Associated comorbidities such as autoimmune diseases and malignancies were detected in 68.7% (N=11) of patients. In majority of biopsies (87.5%; N=14), there were lymphohistiocytic cell infiltration. Other accompanying cells were scarce neutrophils 31.2% (N=5) and eosinophils 31.2% (N=5). All of the biopsies had interstitially located lymphohistiocytic cell infiltration surrounding with swollen and degenerated collagen. Palisaded pattern was determined in 18.7% (N=3) of patients and floating sign was seen in 18.7% (N=3) of biopsies. CONCLUSIONS: RGD is a rare entity and most patients with RGD had associated disorders such as autoimmunity or malignancy. There is overlapping between IGD and PNGD, therefore supporting the usage of umbrella term as reactive granulomatous dermatitis is compatible with the literature.

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.

Clinical and Histopathological Evaluation of Forty-one Cases of Pediatric Granuloma Annulare.

INTRODUCTION: Granuloma annulare (GA) is a non-infectious granulomatous disease that can affect children and adults. Although many studies have been conducted in adult GA patients, the literature on pediatric GA cases is limited. OBJECTIVES: Therefore, this study aimed to examine the demographic, clinical, and pathological features of pediatric GA cases. METHODS: This study was performed retrospectively in a single-center tertiary dermatology hospital. Demographic characteristics and clinical and histopathological features were recorded. RESULTS: Forty-one participants were included in this study, of which 66% were females. The mean age was 3.8 ± 2.6 years, and the mean lesion duration was 7.5 ± 10.3 months. The involvement of 78% of the patients was localized, and the remaining 22% was generalized. Asthma (30%) was the most common comorbid disease. Histopathological examination was performed on 21 patients, and the infiltrate pattern was interstitial in 71% of the cases and palisadic in 29%. Generalized distribution, trunk involvement, and concomitant disease tended to be higher in patients with an interstitial pattern than in those with a palisadic pattern. CONCLUSIONS: Atopy and asthma should be questioned in pediatric GA cases. There are differences between involvement, distribution, concomitant disease, and histopathological patterns, which may indicate differences in pathogenesis.

Evaluation of serum vascular endothelial growth factor level and findings of nailfold capillaroscopy by dermatoscope in the differential diagnosis of palmoplantar psoriasis and palmoplantar eczema.

OBJECT: This study aimed to evaluate VEGF level, capillaroscopic findings, and these features for differential diagnosis of palmoplantar psoriasis and eczema patients. METHODS: This comparative cross-sectional study included 40 patients clinical and histopathologically diagnosed with eczema or psoriasis (20 psoriasis and 20 eczema) and 30 patients of similar age and gender without inflammatory disease in the control group. Serum samples of patients were collected and analyzed for VEGF by enzyme-linked immunosorbent assay (ELISA) and at the same time, we applied capillaroscopy with computerized dermatoscopy qualitatively and semiquantitatively. RESULTS: In the qualitative evaluation, a decrease in capillary density and a significant increase of the avascular area was in palmoplantar plaque psoriasis (PPP) and palmoplantar eczema (PPE) patients compared to the control group. In the semiquantitative evaluation, the mean score decreased capillary density was significantly higher in PPE than in the PPP and control groups (p < 0.001). Minor morphological change (tortuous, crossed and enlarged capillary) scores were significantly higher in patients with PPE compared to PPP and control groups (p = 0.011). Major morphological change (mega, meandering, branching, bushy, bizarre, and disorganized polymorphic capillary) score was significantly higher in patients with PPP than PPE and the control group (p < 0.001). Major morphological change and m-PPPASI scores were correlated in PPP patients (p < 0.05). Disorganized capillaries in PPP patients were significantly higher than in the PPE and control groups (p < 0.001). There was no significant correlation between serum VEGF value and clinical severity and capillaroscopy findings of the patients. CONCLUSION: Significant morphological changes were detected between PPP, PPE, and control groups in the qualitative and semi-quantitative evaluation of capillaroscopic findings. In the differential diagnosis of PPP and PPE, major morphological change, especially the presence of disorganized polymorphic capillaries, was considered an important finding in the capillaroscopic evaluation. These capillaroscopic findings may be helpful to discriminate eczema and psoriasis. However, there was no significant relationship between serum VEGF level and the patients' capillaroscopic findings and clinical severity.

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.

Association between intervertebral disc degeneration and Behçet's disease.

Behçet's disease (BD) is a chronic systemic vasculitis with a wide range of clinical findings. It has both autoinflammatory and autoimmune features and manifests with recurrent inflammatory attacks involving the innate immune system. Recently, autoinflammation has started to take place in the pathogenesis of intervertebral disc degeneration. The aim of this study is to evaluate the relationship between intervertebral disc degeneration and BD. We evaluated patients with BD who suffered neck or low back pain in the last 1 year. Eighty four patients underwent musculoskeletal system examination with MRI imaging of the cervical and lumbar vertebrae, and serum levels of IL6, IL8, and TNF-α were determined. The mean age was 47.7 ± 11.5 (range 20-68) years. Cervical and/or lumbar herniation was detected in the MRI imaging of 65 (77.3%) out of 84 patients. The mean IL8 levels of the group with pain and disc herniation and the group with pain and bulging were statistically significantly higher than the other groups (p = 0.007; p = 0.045, respectively). Chronic inflammation in BD may cause disc degeneration and radicular pain to begin and progress earlier in patients.

Palisaded Encapsulated (Solitary Circumscribed) Neuroma: A Review of 30 Cases.

Background. Solitary circumscribed neuroma (SCN), also known as palisaded encapsulated neuroma (PEN), is a benign neural tumor. It may be mistaken as either schwannoma or neurofibroma in pathology practice. In this study, we aimed to define clinicopathologic and immunohistochemical features and discuss its differential diagnosis. Materials and Methods. The histopathological features of 30 cases of SCN/PEN were reviewed. The presence of intralesional axons, Schwann, and perineural cell distributions were investigated by performing neuronal immunomarkers. Results. Twelve cases were females, and 18 cases were males. The mean age was 48 years. Lesions were mostly located on the face (27/30). Histologically, 18 had a lobular pattern, 9 were plexiform, 2 fungating, and 1 multilobular. Although the majority of cases were well circumscribed, capsular integrity was at least focally disrupted (73%). Verocay body was noted only in 6 cases (20%). One case showed excessive hyperkeratosis, forming a keratin horn. Adipocytic change was detected in another case. The lesions consisted of S100-positive Schwann cell proliferation and were partially surrounded by perineural cells highlighted by EMA or Claudin-1. The amount of intralesional axons revealed by neurofilament immunostaining was variable. Conclusion. SCN/PEN is a relatively common lesion, and usually seen as an asymptomatic papule on the face of elderly patients. A circumscribed lesion composed of bundles of bland-looking spindle cells thought to be of neural origin is seen in the dermis. Pathologists should be aware of the existence of plexiform and multilobular PEN/SCN variants, to avoid misdiagnosis of plexiform neurofibroma or schwannoma.

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.

The reflectance confocal microscopy in diagnosis of recurrent basal cell carcinoma.

BACKGROUND: Reflectance confocal microscopy (RCM) is very valuable, non-invasive diagnostic tool in the diagnosis of basal cell carcinoma (BCC). Objective: We aimed to demonstrate the positive predictive value (PPV), negative predictive value, sensitivity and specificity of RCM and dermoscopic features in recurrent BCC. METHODS: The 152 entire lesion sites in 128 patients with BCC were evaluated by clinical examination, dermoscopy and RCM imaging techniques. Biopsy was performed from 46 lesions if there was at least one of the clinical findings or at least one of the diagnostic criteria of BCC with dermoscopy or RCM examination. Histopathological examination was considered as a gold standard for the diagnosis of recurrence BCC. RESULTS: Recurrence was observed in 29 cases (63%). In the dermoscopic examination, arborizing telangiectasia and blue-grey globules were found to be statistically significantly correlated with BCC recurrence (p<0.05). The specificity and PPV of nucleated corneocytes in the stratum corneum and polarisation of elongated nuclei in the epidermis was 100%. PPV of streaming of aggregated tumour cells and variable refractile stroma was 92% with RCM examination. CONCLUSION: RCM is a diagnostic tool with a high PPV, sensitivity and specificity for the diagnosis of recurrence of BCC lesions.

Intravascular/Intralymphatic Histiocytosis: A Report of 3 Cases.

Intravascular/intralymphatic histiocytosis (IV/ILH) is a rare, reactive cutaneous condition, with uncertain pathogenesis. It may be associated with various inflammatory and neoplastic diseases. Although the clinical presentation is various, the biopsies reveal dilated vessels, mostly lymphatics, containing aggregates of histiocytes within their lumina. We described 3 cases of IV/ILH with different clinical presentations. In the first case, the patient presented with lymphedema in the genital region without any underlying disease. However, the second and third cases had reticular erythematous skin lesions. The second case had common variable immunodeficiency disease, rheumatoid arthritis, inflammatory bowel disease, and a history of a lymphoproliferative lesion. The third case had metal prostheses at both his right and left knees. In all these 3 cases, histopathologic and immunohistochemical findings were similar to each other and to those cases reported in the literature. In addition, the third case was admixed with reactive angioendotheliomatosis. In the second case, the endothelium of the ectatic vessels expressed CD31 and CD34, but not D2-40/podoplanin, pointing out that these vessels were blood vessels rather than lymphatics, differing from the other 2 cases. In conclusion, we believe, the most convincing statement about IV/ILH is that it is not a distinct clinicopathologic entity, but a histopathologic feature found as a part of a constellation of inflammatory changes or many other conditions.

Necrotic ulcer: a manifestation of leukemia cutis.

A 71-year-old man presented to our dermatological clinic with a 3-month history of a wound on his leg. He complained of weakness for the past few months. On his dermatological examination he had a 3x3-cm necrotic ulcer on his left tibia (Figure 1). On physical examination, there was 1 x 1-cm axillary lymphadenopathy. There was no other lymph node enlargement, hepatosplenomegaly, or gingival hypertrophy. Peripheral blood results showed 2.4x103/mm3 leukocytes (normal range 4-11 x 103/mm3) with 66% neutrophils. The hemoglobin value was 10.1 g/dL (13-18 g/dL), and the platelet count was 63x103/mm3 (150-440 x 103/mm3). No blasts were detected in a peripheral blood smear. His lactate dehydrogenase level was 567 U/L (240-480 U/L). All other results of blood chemistry were within normal limits. Punch biopsy of the skin lesion showed ulceration and dense dermal acute and chronic inflammation. There was a superficial and deep perivascular and periadnexal infiltrate of neoplastic cells composed of relatively abundant eosinophilic cytoplasm and large nuclei with blastic chromatin and occasional small nucleoli (Figure 2). Mitotic figures were prominent. Immunohistochemical stains were performed, and the neoplastic cells were CD3, CD20, CD138, and S100 protein negative. Myeloperoxidase and CD68 were positive. The histopathological findings were consistent with leukemic infiltration. Examination of bone marrow biopsy revealed that the blastic cells constituted more than 20% of the bone marrow cellularity. Cytogenetic analysis of bone marrow aspiration with fluorescence in situ hybridization was negative for inversion 16, t(8;21) and t(15;7). Histochemical stains for myeloperoxidase, sudan black, periodic acid-Schiff, and alpha naphthyl acetate were also negative. Blastic cells were DR, CD13, CD117, and CD34 positive and CD5, CD7, CD10, CD14, CD19, CD20, CD33, CD41, CD56, CD64, and CD79 negative according to flow cytometry immunophenotyping. Blastic cells were 35% in the bone marrow. Based on the findings of bone marrow examination, the patient was diagnosed as having acute myeloblastic leukeamia (AML) with minimal differentiation (subtype MO) according to French-American-British and World Health Organization classification. The examination of abdominal ultrasonography and thorocic and abominal computed tomography revealed no metastases. The patient was treated with chemotherapy that consisted of cytarabin and daunorubicin. After chemotherapy, the lesion regressed. One month after chemotherapy, the patient presented to the hospital with a complaint of fever. He was diagnosed with febrile neutropenia. He died of cardiac failure 12 months after appearance of skin infiltration.

Turkish version of Skindex-29.

BACKGROUND: There is a clear need for a useable measure of health-related quality-of-life (HRQoL) for dermatology patients. Most of the existing dermatology-specific measures were developed for the English language, and these measures should be adapted for use in other cultures. OBJECTIVE: To adapt Skindex-29 (one of the most widely recognized dermatology-specific quality-of-life indices) for the Turkish cultural setting. PATIENTS AND METHODS: Forward and backward translations were carried out, and for doubtful items the process was repeated until a satisfactory agreement with the original version of Skindex-29 was achieved. The intermediate Turkish version was administered to a group of 20 randomly selected Turkish adults with and without skin conditions. The final Turkish version of the Skindex-29 was administered to 456 patients attending Osmangazi University Dermatology outpatient clinics. Reliability, construct and content validity were assessed. RESULTS: The instrument was internally consistent, with Cronbach's alpha-coefficients of 0.94, 0.76, 0.88, and 0.92 for entire questionnaire, symptom, emotional, and functional scales, respectively. The Turkish Skindex-29 demonstrated construct and content validity. CONCLUSION: Our evaluation of the Skindex-29 indicates that the instrument is a comprehensible, useable, reliable and valid measure of quality-of-life for Turkish dermatologic patients.