Evaluation of OVOL1 and Filaggrin immunohistochemical expression and clinical relevance in psoriasis.

BACKGROUND: Psoriasis is a disease of overactive immune system. OVOL1 and Filaggrin have been associated with many inflammatory skin lesions. To the best of our knowledge, the correlation between OVOL1 and Filaggrin in psoriasis was not previously investigated. This work aims to search the immunohistochemical expression and correlation between OVOL1 and Filaggrin in psoriasis. MATERIALS AND METHODS: Slides cut from paraffin blocks of 30 psoriasis cases and 30 control subjects were stained with OVOL1 and Filaggrin. Clinicopathological data were correlated with the results of staining. RESULTS: OVOL1 and Filaggrin expression in epidermis showed a significant gradual reduction from normal skin to peri-lesional and psoriasis biopsies (P < 0.001). In contrast, psoriasis dermis showed a significant overexpression of OVOL1 in inflammatory cells in relation to peri-lesional biopsies (P < 0.002). OVOL1 demonstrated a significant direct correlation with Filaggrin expression in psoriasis (r = 0.568, P < 0.004). OVOL1 and Filaggrin expression in psoriasis skin epidermis demonstrated a statistically significant negative correlation with PASI score. CONCLUSION: OVOL1 and Filaggrin might be involved in psoriasis-associated inflammation and skin hyperproliferation. OVOL1 might have a protective barrier function in the skin and could be used to stratify progressive disease. Filaggrin may play a role in progression of psoriasis. OVOL1 inhibition could be considered in suppression of Filaggrin function. OVOL1 agonists may be beneficial in psoriasis treatment.

Mitochondrial DNA copy number as a diagnostic marker and indicator of degree of severity in alopecia areata.

Alopecia areata (AA) is a disorder with several etiologies. The evidence suggests that the absolute copy number of mitochondrial deoxyribonucleic acid (mtDNA), as well as proportion of mutated mtDNA copies, determines disease onset. This study aims to quantify the relative index of the mtDNA copy number in patients with AA and healthy controls and correlate the results with the existing clinical information. This case-control study included 50 patients with AA and 50 age- and sex-coordinated healthy persons as controls. The severity of AA was weighed using the Severity of Alopecia Tool and Kavak's classification. The relative index of the mtDNA copy number was measured by real-time qPCR. Significant statistical difference was observed between cases and controls regarding mean mtDNA copy number, p < .001. There was significant positive correlation with SALT score (p = â€…0.001). A cutoff value of >1.619 N/µL could significantly diagnose AA cases (p < .001), and a cutoff value of > 1.36 N/µL could discriminate mild AA cases from those with moderate AA (p = â€…0.007). The relative index of mtDNA copy number is significantly elevated in AA cases and could be helpful in diagnosing and evaluating AA severity.

Nucleotide binding and oligomerization domain 2 in psoriasis: a clinical and immunohistochemical study.

Psoriasis is a chronic immune-mediated inflammatory disease, affecting about 2 to 3% of the population worldwide. Nucleotide-binding and oligomerization domain 2-like receptor has been implicated in the pathogenesis of different inflammatory diseases. The current work aims to investigate the expression of nucleotide-binding and oligomerization domain 2-like receptor in psoriatic skin through an immunohistochemical study. This cross-sectional case-control study included 20 patients with chronic plaque psoriasis and 20 age- and sex-matched normal subjects as controls. Psoriasis severity was assessed through the use of Psoriasis Area Severity Index (PASI) score. Skin biopsies were taken under local anesthesia from cases and from matched sites of controls. Expression of nucleotide-binding and oligomerization domain 2 in epidermis of studied cases and controls showed positive epidermal expression of nucleotide-binding and oligomerization domain 2 in all cases (100%) versus 6 (30%) controls with a significant increase (χ2 = 21.54, P˂0.001). Moreover, dermal expression of nucleotide-binding and oligomerization domain 2 was higher in psoriatic skin lesion (95%) compared to controls (15%) with a significant difference (χ2 = 25.86, P˂0.001). We concluded that nucleotide-binding and oligomerization domain 2 may be implicated in psoriasis pathogenesis being higher in cases in comparison to controls.

Immunohistochemical expression of cornulin in lesional and perilesional skin of plaque psoriasis.

BACKGROUND: Psoriasis is an immune-related disease with dermal inflammation and epidermal hyperplasia. Cornulin has a significant role in keratinocyte proliferation and stimulates inflammation in psoriasis. AIM OF THE WORK: This work aims to evaluate Cornulin expression values in lesional and perilesional psoriatic skin compared with the control group's skin through immunohistochemistry. METHODS: This case-control study included 30 cases with plaque psoriasis and another 30 as controls. Patient samples were collected, and immunohistochemical staining of Cornulin was conducted. RESULTS: In the epidermis, there was a stepwise pattern of significant Cornulin overexpression in keratinocytes starting from controls (34.00 ± 23.65) to lesional (62.59 ± 23.93) passing through perilesional skin (36.52 ± 18.49) (p < 0.001). Moreover, there was also a stepwise pattern of the significance of Cornulin starting from 4 in controls (13.3% for both) to 28 lesional cases (93.3%) and 18 (60.0%) passing through 17 perilesional skin cases (56.7%) and 5 (16.7%) (p < 0.001 for both) for inflammatory cells and adnexa, respectively. A significant relationship between lesional epidermal Cornulin's strong intensity and a higher H-score and both hyperkeratosis and parakeratosis was found (p = 0.008 for both intensity and 0.028 for both H-scores). CONCLUSION: Cornulin might be implicated in keratinocyte hyperproliferation and inflammation in plaque psoriasis and may be valuable as therapeutic target.

CD93 has a crucial role in pathogenesis of psoriasis.

BACKGROUND: Psoriasis is a chronic, immune-related disorder; inflammation, higher rate of epidermal proliferation, and angiogenesis are the main pathognomonic features. Cluster of differentiation 93 (CD93), an angiogenic element, plays a role in cell adhesion regulation and has a putative function in inflammation. OBJECTIVE: To assess CD93 immunohistochemical expression in psoriatic skin and the association of CD93 single nucleotide polymorphisms (SNPs) rs2749817 to disease pathogenesis and severity. METHODS: This case-control study was done on 50 patients with psoriasis vulgaris beside 50 age- and sex-matched healthy controls. Assessment of psoriasis severity was done by Psoriasis Area and Severity Index (PASI) score. 3 mm punch skin biopsies were taken from every participant, and hematoxylin and eosin staining and immunohistochemical staining for CD93 antibody were done. Assessment of CD93 rs2749817 gene polymorphism by the TaqMan allelic discrimination assay technique (real-time PCR) was done. RESULTS: Immunohistochemical expression of CD93 showed membrano-cytoplasmic localization in both endothelial and inflammatory cells of cases and controls with significant more positivity in dermal endothelial and inflammatory cells of cases than controls (p = 0.001 and 0.014 respectively). Strong intensity was present in 18 of cases endothelial cells and 24 inflammatory cells with absence in controls (p =  0.001 for both) with significantly higher H-score and higher percent of positive cells (p  =  0.001 for both). The TC genotype was lower in patients compared to control (p-value = 0.006) and CC genotype which was present only in cases (p-value = 0.021). CONCLUSION: Cluster of differentiation 93 has an essential role in psoriasis and an encouraging future therapy for psoriasis.

The clinical and pathological effectiveness of microneedling and topical 5-fluorouracil in vitiligo treatment: An association with matrix metalloproteinase 2 immunohistochemical expression.

BACKGROUND: The current therapies for vitiligo require long duration with often disappointing outcomes. 5-Fluorouracil (5-FU) is a chemotherapeutic agent approved for topical use in the treatment of several dermatologic conditions. Matrix metalloproteinase 2 (MMP2) is synthesized by keratinocytes during the epidermal remodeling process and has been found to help in melanocyte migration. AIM: To investigate the efficacy and safety of flexible microneedling followed by application of 5-FU in vitiligo treatment and to evaluate the immunohistochemical expression of MMP2 in involved skin in vitiligo patients before and after treatment. METHODS: Twenty patients presented with vitiligo were planned to receive one session every 2 weeks for 12 weeks of microneedling followed by 5-FU application. Clinical response to therapy was evaluated by VASI score. Pre- and post-treatment biopsies were taken from vitiliginous patches for MMP2 immunostaining. RESULTS: Fifteen patients (75%) responded to therapy with observed side effects such as pain, erythema, and hyperpigmentation of margins. The clinical response was more in young patients and those who have short disease duration. MMP2 was significantly increased in post-treatment biopsy compared with the pretreatment one. CONCLUSIONS: 5-Fluorouracil application after microneedling is effective in the treatment of vitiligo with 75% response, 60% patient satisfaction, and tolerable side effects. The improvement in vitiligo patients by microneedling and 5-fluorouracil could be due to upregulation of MMP2 in affected vitiligo specimens.

Expression of Transient Receptor Potential Channel of Melastatin number 8 (TRPM8) in Non- Melanoma Skin Cancer: A Clinical and Immunohistochemical study.

Transient Receptor Potential Channel of Melastatin number 8 (TRPM8) is abnormally expressed in many cancers as lung, however little is known about TRPM8 expression in non-melanoma skin cancer (NMSC) including cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). This work aimed to study TRPM8 expression in NMSC. It included 100 skin biopsies (50 normal skin as control group, 15 BCC and 35 SCC). Immunohistochemical staining for TRPM8 was done and results were correlated with clinicopathological characters. There was significant higher TRPM8 H-score in NMSC than control skin. On comparing SCC cases to control, there was significant positive TRPM8 expression, strong intensity, diffuse pattern, cytoplasmic and nucleo-cytoplasmic localization and higher range of H-score in SCC. In contrast, BCC showed significant lower TRPM8 positive expression when compared to control skin. Higher TRPM8 H-score in SCC showed significant positive correlation with large tumor size and poor tumor differentiation.TRPM8 may be implicated in pathogenesis of NMSC. Its association with bad prognostic characters; potentiates its role as prognostic biomarker and open new chances for therapeutic intervention in NMSC. TRPM8 antagonists may share in decreasing tumor growth and progression and may serve as potential target for tumor immunotherapy.

Role of CYR61 in psoriatic lesional and perilesional skin: A clinical and immunohistochemical study.

BACKGROUND: Psoriasis is considered as an immune-mediated disorder with significant epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (CYR61), known as CCN family member 1 (CCN1), plays an important role in cell proliferation and neovascularization which may trigger psoriasis development. AIMS: This study aimed to assess the immunostaining of CYR61 in psoriatic skin (lesional and perilesional) compared to control skin. PATIENTS/METHODS: This is a case-control study. The Psoriasis Area and Severity Index (PASI) was used to evaluate disease severity. A punch biopsy was taken from psoriatic skin lesions (30), perilesional (30) skin, and matched site of controls (20). The pathological and immunostaining assessments of CYR61 were conducted. RESULTS: There was a significant gradual progressive overexpression of CYR61 in keratinocytes from control skin to perilesional and lesional psoriatic skin (P = .00). Moreover, lesional psoriatic skin showed overexpression of CYR61 in inflammatory cells in the dermis than controls. CYR61 expression (lesional epidermis) revealed a significant positive correlation with the PASI score (r = .63; P = .00). There was a significant relationship between intensity and H-core of CYR61 in the lesional psoriatic epidermis with joint affection. CONCLUSION: CYR61 may trigger epidermal hyperplasia and potentiate inflammatory infiltration in psoriasis vulgaris patients, and therapies targeting CYR61 may be effective in the management of psoriasis vulgaris.

Tissue expression of IL-17A and FOXP3 in acne vulgaris patients.

BACKGROUND/OBJECTIVES: CD4+  T helper (Th) cells through its pro-inflammatory cell type, interleukin-17 (IL-17)-generating cells and its anti-inflammatory category forkhead box P3-positive (FOXP3+ ) regulatory T (Treg) cells, play a vital role in the immune balance in inflammatory disorders. Therefore, assessment of both IL-17 and FOXP3 in acne vulgaris (AV), a chronic inflammatory disease of the pilosebaceous unit, could be of value in understanding AV pathogenesis. This study aimed to investigate the immunohistochemical expression of IL-17A and FOXP3 in acne vulgaris lesions versus normal skin. METHODS: Forty-five AV patients and 25 controls were included in this case-control study. Biopsies from participants were analyzed for IL-17A and FOXP3 immunohistochemical profiles using IL-17A and FOXP3 polyclonal antibodies. RESULTS: Compared to controls, AV patients exhibited a significant increase of IL-17A percent of expression in epidermis (P ≤ .001), in lymphocytes in papillary dermis (P ≤ .001), and in perifollicular lymphocytic inflammatory infiltrate in AV lesions. Also, there was a significant elevation in FOXP3 percent of expression in epidermis (P = .049) and in lymphocytes in papillary dermis (P ≤ .027) in acne patients than control. A significant positive correlation between IL-17A expression in papillary lymphocytes and in epidermal keratinocyte was observed (r = .537, P = .001). In acne vulgaris patients, the associations between IL-17A and FOXP3 expressions could not reach level of significance. CONCLUSIONS: There was an up-regulation of IL-17A and FOXP3 in acne vulgaris development, but with independent roles. Moreover, targeting of IL-17A and FOXP3 may open the door for development of new therapeutic agents in acne vulgaris treatment.

Relationship Between sCD163 and mCD163 and Their Implication in the Detection and Typing of Leprosy.

BACKGROUND: Leprosy is a chronic contagious disease caused by Mycobacterium lepraea. CD163 is a monocyte trans-membrane glycoprotein receptor (mCD163) that sheds from the cell surface and circulates as a soluble (serum) form (sCD163). Changes in the mCD163 and sCD163 levels could mirror the categorization of inflammatory procedure, demonstrating a possible use of CD163 as a diagnostic indicator of inflammation. OBJECTIVE: To investigate the possible role of CD163 (sCD163 and mCD163) in leprosy pathogenesis and to assess whether CD163 is a helpful inflammatory marker of leprosy development and typing. PATIENTS AND METHODS: This case control study included 70 leprosy patients and 30 healthy controls. Leprosy patients were classified according to the Madrid criteria (1953) into: tuberculoid leprosy (TT), border-line leprosy (BL), and lepromatous leprosy (LL). For all participants, complete blood count (CBC), serum CD163 using ELISA and monocytes positive for CD163 using flow cytometry were done. RESULTS: Leprosy patients had significantly low WBCs and platelet counts (p<0.001) and had significantly higher sCD163 (p=0.025) and mCD163 (p=0.042) that were highest in LL followed by BL, then TT patients (p<0.001). There was a significant positive correlation between mCD163 and sCD163 levels in leprosy patients (r=0.896, p<0.001). ROC analysis revealed a significant role of serum sCD163 and of mCD163 positive monocytes in the detection (p<0.001) and typing of leprosy (p=0.002 and p<0.001, respectively). CONCLUSION: Both sCD163 and mCD163 positive monocytes may have an active role in leprosy pathogenesis. They could be potential biomarkers for leprosy detection and typing.

Protein tyrosine phosphatase nonreceptor type 22 gene polymorphism in alopecia areata: Does it have an association with disease severity?

BACKGROUND: Alopecia areata is a condition involving hair loss from certain or all areas of the body. It has been considered as an immune-mediated disease, characterized by the infiltration of CD4+ and CD8+ lymphocytes in the hair follicles. AIM OF THE STUDY: The study aimed to assess whether protein tyrosine phosphatase nonreceptor type 22 gene single nucleotide polymorphism 1858C/T has any relationship with alopecia areata in Egyptian patients and whether it is associated with disease severity or not. SUBJECTS AND METHODS: Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) C1858T gene polymorphism was identified using polymerase chain reaction-restriction fragment length polymorphism analysis technique in 60 patients suffering from alopecia areata and 30 age- and sex-matched healthy controls. Disease severity was assessed using SALT score. RESULTS: CT and TT genotypes were significantly higher in the patients' group (P = .005), OR = 4.38 95% CI [1.48-12.96], with significant statistical predominance of T allele in patients, P = .003, OR = 3.86, 95% CI [1.52-9.77]. There was also a positive significant relationship between protein tyrosine phosphatase nonreceptor type 22 genotype CT and SALT score. CONCLUSION: PTPN22 1858T allele is associated with the development and severity of alopecia areata in Egyptians.

Smad7 in psoriasis vulgaris patients: A clinical and immunohistochemical study.

BACKGROUND: Psoriasis is an inflammatory disease that is mostly immune-derived. It causes proliferation of skin cells, forming plaques. Psoriasis etiology is unknown. It might be multifactorial. AIMS: This work aimed to study Smad7 expression in psoriasis vulgaris patients in comparison with normal skin. PATIENTS/METHODS: Thirty patients with psoriasis vulgaris in comparison with 20 age- and sex-matched seemingly healthy individuals were selected. We used psoriasis area and severity index (PASI) to evaluate psoriasis severity. Skin biopsies were prepared from skin lesions (30), perilesions (30) and control (20) groups for histopathological and immunostaining evaluation of Smad7. RESULTS: Smad7 was progressively upregulated in proliferating keratinocytes from controls (58.18 ± 30.93) to perilesional (106 ± 38.93) and lesional (156.33 ± 62.01) skin (P < .001). Also, dermal inflammatory cells showed upregulation of Smad7 expression from control skin (40 ± 28.28) to skin lesions (137.33 ± 73.86) (P < .010). Smad7 expression showed a positive significant correlation with psoriasis severity (r = .452; P < .012). CONCLUSION: Smad7 may be involved in increased keratinocyte proliferation as well as skin inflammation in psoriasis vulgaris patients.

Plexin-B2 in psoriasis; a clinical and immunohistochemical study.

Psoriasis is an inflammatory, immune-mediated disease. Plexins are transmembrane proteins that are involved in immune system regulation and inflammation. This work aimed to investigate the immunohistochemical expression of Plexin-B2 in plaque psoriasis in both lesional and perilesional skin. This case-control study included 30 patients with psoriasis vulgaris in comparison with 20 age- and sex-matched apparently healthy persons. We used the Psoriasis Area and Severity Index (PASI) score to evaluate psoriasis severity. Biopsies from 30 lesional, 30 perilesional, and 20 control-skin patients were subjected to histopathological and immunohistochemical evaluations of Plexin-B2. There was significant stepwise overexpression of Plexin-B2 in proliferating keratinocytes from controls (66 ± 31.02) to perilesional (116 ± 41.95) and lesional (159.7 ± 63.05) skin (P < .001). Also, Plexin-B2 showed significant overexpression in dermal inflammatory cells of lesional psoriatic skin (153.67 ± 72.71) when compared to controls skin (25.71 ± 11.34) (P < .001). There was a significant positive correlation between Plexin-B2 expression and psoriasis severity (r = 0.557; P < .001). Plexin-B2 could promote skin inflammation, as well as keratinocyte proliferation in psoriasis vulgaris; therefore, it may be used as a targeted therapy for psoriasis treatment.

Immunohistochemical study of janus kinase 1/signal transducer and activator of transcription 3 in psoriasis vulgaris.

Background: Human JAKs are responsible for generating docking sites for human SSTAT phosphorylation. The role of JAKs in psoriasis pathogenesis has not been clearly explained. Aim: To investigate the role of JAK1 in psoriasis pathogenesis and to assess if this role is mediated through STAT3 or not, through evaluation of their immunohistochemical expression in the skin of psoriatic patients. Methods: This case-control study was carried out on 26 patients presenting with psoriasis vulgaris versus 26 age- and sex-matched apparently healthy volunteers. Psoriasis Area and Severity Index (PASI) scores were used to evaluate psoriasis severity. From all controls and cases (lesional and perilesional), skin biopsies were taken for histopathological and immunohistochemical JAK1 and STAT3 evaluation. Results: There was significant stepwise upregulation of JAK1 from controls to perilesional to lesional psoriatic skin of the patient group in both epidermis and dermis (P≤0.001 for both). Dermal JAK1 H-score was significantly associated with psoriasis severity (P=0.01). STAT3 was significantly overexpressed in lesional psoriatic skin over nonlesional skin (P<0.001). There were significant positive correlations between lesional H-scores for STAT3 and Psoriasis Area and Severity Index scores in epidermis (r=0.63, P<0.001), and in dermis (r=0.47, P=0.04). There was a significant positive correlation between JAK1 and STAT3 expression in epidermal lesional psoriatic skin (r=0.44, P=0.03). Conclusion: JAK1 has a proinflammatory effect in psoriasis pathogenesis, which could be mediated through increasing STAT3 expression in psoriasis. JAK1 and STAT3 tissue expression could be markers of psoriasis severity. JAK1 may be used as a target for immunotherapy in psoriasis-management programs.

Aquaporin 3 and E-Cadherin Expression in Perilesional Vitiligo Skin.

INTRODUCTION: Vitiligo is a common dermatologic disorder with debated aetiology. Most studies focused on role of melanocytes and few investigated the role of keratinocytes in pathogenesis of the disease. AIM: To investigate the keratinocyte adhesion in perilesional vitiligo skin through the immunolocalization of Aquaporin-3 (AQP3) and E-cadherin. SETTING AND DESIGN: Sixty five subjects were selected. These included 40 cases with vitiligo and 25 age and gender-matched healthy subjects as a control group. MATERIALS AND METHODS: Skin biopsies were taken from perilesional skin of cases and from site-matched areas of control subjects. The expression of AQP3 and E-cadherin was evaluated by immunohistochemical techniques. STATISTICAL ANALYSIS: Results were statistically analysed using IBM personal computer and the statistical package SPSS version 11. Fisher-exact and Chi-square tests were used to study the association between two qualitative variables. Mann-Whitney test was used for comparison between quantitative variables not normally distributed. Spearman's correlation coefficient was used to assess correlation between two quantitative variables. The p≤0.05 was considered significant. RESULTS: Regarding AQP3 expression, strong intensity, diffuse distribution, higher percent of expression and higher H-score (p<0.001 for all) were significantly associated with control skin compared with perilesional skin in follicular and inter-follicular epidermis. Regarding E-cadherin expression, moderate intensity, higher percent of expression and higher H- score (p<0.001 for all) were significantly associated with control skin compared with perilesional skin in follicular and inter-follicular epidermis. No significant association was found between E-cadherin and AQP3 H-scores or percent of expression and clinical data of selected cases. No significant correlation was detected between E-cadherin and AQP3 H-scores or percent of expression and age of cases, disease duration or Vitiligo Disease Activity (VIDA) score. CONCLUSION: The following sequence of events can be suggested for vitiligo pathogenesis, based on findings in perilesional skin: AQP3 is downregulated by a primary unknown factor and this will lead to down regulation of its downstream molecules, mainly phosphatidylinositol 3-kinase, E-cadherin and catenins, which is followed by defective keratinocyte adhesion and decreased release of keratinocyte-derived growth factors. Subsequently a secondary event, physical trauma, oxidative stress or autoantibodies, may lead to exfoliation of keratinocytes and pigmented cells.

Idiopathic acquired true leukonychia totalis.

Idiopathic acquired true leukonychia totalis is a rare nail disorder not associated with other abnormalities. We present a case in a 12-year-old Egyptian boy.

Isolated oral Kaposi sarcoma in an HIV-negative patient: a case report.

BACKGROUND: Kaposi sarcoma is a well-known vascular tumor first described by Moriz Kaposi in 1872. Oral involvement is seen as an AIDS-related malignant neoplasm but is rarely described in HIV-negative and non-immunosuppressed individuals. CASE: We report a case of oral Kaposi sarcoma in a 75-year-old, HIV-negative woman. Diagnosis was achieved according to clinical, histopathological and positive polymerase chain reaction for human herpes virus 8. The tumor was surgically excised and no recurrence was detected in the following 6 months. CONCLUSION: Oral Kaposi sarcoma is rare in HIV-negative patients and is associated with HHV-8 infection. Lesions are usually solitary and can be treated surgically. It should be included in the differential diagnoses of oral lesions that are clinically suspicious and resistant to therapy.