Hoda Rasheed

Interleukin 17, Interleukin 22 and FoxP3 expression in tissue and serum of non-segmental vitiligo: A case- controlled study on eighty-four patients

BACKGROUND Skewing of responses towards T helper (Th) 17 and away from T regulatory cells (T-regs) has been suggested to be partially involved in autoimmune diseases like vitiligo. AIMS Clarify the possible role and relationship between Th17 and T-regs in vitiligo by measuring tissue, systemic levels of interleukin (IL)-17, IL-22 and Forkhead box P3. PATIENTS AND METHODS 84 non-segmental vitiligo patients and 80 controls were included. Vitiligo Area Scoring Index, Vitiligo Disease Activity and stress score were determined. Skin biopsies underwent immunohistochemical staining for IL-17, IL-22 and FoxP3 and their systemic levels were determined by ELISA and quantitative real time PCR. RESULTS Mean area % of +ve immunostaining and serum levels of IL-17 (34.12 ± 5.12, 23.62 ± 8.17 pg/mL) and IL-22 (48.63 ± 19.23, 43.53 ± 11.95 pg/mL) were significantly higher in patients compared to controls (15.33 ± 4.19, 12.83 ± 3.29 pg/mL) (13.44 ± 3.82, 9.92 ± 4.7 pg/mL) (P<0.001). Mean area % of +ve immunostaining and peripheral blood levels of FoxP3 were significantly lower in patients (2.67 ± 0.54, 0.574 ± 0.32) compared to controls (7.12 ± 0.18, 1.48 ± 0.49) (P<0.001). In patients, a positive correlation between IL-17 and IL-22 was detected (r = 0.671, P<0.001), each showing negative correlation with FoxP3 (r = -0.548, P<0.001), (r = -0.382, P<0.001). VASI, VIDA and stress score correlated positively with IL-17, IL-22 and negatively with FoxP3. CONCLUSION Th17 and T-regs are intertwined in the complexity of vitiligo giving hope of treatment through adjuvant therapies controlling the delicate balance between them.

Oral propranolol: an effective, safe treatment for infantile hemangiomas

Infantile hemangiomas (IH) are the most common childhood tumors. In 2008, Labreze reported the serendipitous effect of oral propranolol on hemangioma and since then it has overshadowed the use of other therapeutic modalities in the treatment of IH. The aim of this prospective, clinical study was to assess the efficacy and safety profile of oral propranolol at a fixed dose of 2 mgkg(-1) in the treatment of 30 patients with problematic IH. Propranolol treatment continued for a duration of 2-14 months where 60% of the patients (n=18) showed a final excellent response with complete resolution of the lesion (P<0.001). 20% (n=6) showed a good response with more than 50% reduction in the size of the IH. 16.6% showed a fair response (n=5) with less than 50% reduction in the size of the IH. Only one patient (3.3%) was resistant to treatment. Five patients (17.24%) showed evidence of rebound growth after cessation of therapy and responded well to re-treatment.We did not face any side effects related to the oral propranolol. In conclusion, propranolol therapy at a fixed dose of 2 mgkg(-1), given in three equally divided doses, is a very safe and effective regimen in the treatment of IH.

Propranolol and infantile hemangiomas: Different routes of administration, a randomized clinical trial

UNLABELLED Oral propranolol has become the treatment of choice of infantile hemangiomas (IH)s. However, the safety of systemic propranolol is questioned. Topical therapy with 1% propranolol has been reported to be safe and effective. Intralesional (IL) administration may possibly allow safe delivery of higher drug dosages. AIM To assess the efficacy and safety of two locally administered routes of propranolol (topical and IL), in comparison with its systemic oral use in the treatment of IHs. PATIENTS AND METHODS 45 patients with IHs were randomly divided into 3 groups, A, B and C (n = 15 in each), receiving oral propranolol, 2 mg/kg/day, topical propranolol 1% ointment twice daily, IL propranolol, 1 mg of propranolol hydrochloride in 1 ml of injection once weekly, respectively. Follow up was done for 6 months after treatment was stopped. RESULTS Excellent response was achieved in 9 patients in group A (60%), 3 in group B (20%) and 2 in group C (13.3%), (P value : 0.04). As regards safety, all 3 modalities proved safe with no major side effects apart from 1 patient in group A and 3 in group C who dropped out due to pain or inconvenience of therapy. CONCLUSIONS Further work is needed to establish clear guidelines and reach best formulations. Nevertheless, in properly selected patients with IHs, we recommend the usage of oral propranolol. Topically administered propranolol could be considered in patients at risk of potential side effects from oral administration. As IL application did not offer any more benefits, it could not be recommended.

Immunohistochemical study of the expression of matrix metalloproteinase-9 in skin lesions of mycosis fungoides.

Matrix metalloproteinase-9 (MMP-9) has been correlated with poor clinical outcome in various malignancies and is associated with enhanced tumor growth and dissemination through its role in angiogenesis. This study was carried out to review the immunohistological staining of MMP-9 in skin lesions of different stages of mycosis fungoides (MF). The study was carried on 22 patients with MF and 10 healthy controls. Immunohistochemical staining using MMP-9 monoclonal anti-human antibodies was performed to determine the intensity of expression and distribution pattern of MMP-9 in MF lesions and in normal control skin. The general intensity of expression of MMP-9 was found to be significantly higher in cases with MF than in controls, and it increased in direct proportion to the increase in disease severity, being greatest in the tumor stages. A significantly greater number of blood vessels were found in cases with MF when compared with controls, and the MMP-9 expression by endothelial cells was significantly higher in endothelial cells within tumor cell aggregates than in endothelial cells outside the tumor cell aggregates. This study raises the possibility that MMP-9 may play an important role in the development of MF lesions, and its significantly higher expression in tumor stages may point to a possible role in disease progression. Further studies are needed to validate these findings and to assess the possible therapeutic role of drugs targeting MMP-9 in the treatment of MF.

Sulfasalazine and pentoxifylline in psoriasis: A possible safe alternative

Abstract Background: Conventional therapy of extensive psoriasis is effective but has complications. Biologics are safer but expensive. Objective: To assess the efficacy of sulfasalazine and pentoxifylline, which have TNF antagonizing and anti-proliferative action in the treatment of psoriasis. Methods: In this randomized controlled trial, 32 patients with extensive psoriasis were divided into four groups: group A received sulfasalazine; group B received pentoxifylline; group C received both drugs; and group D received methotrexate. The Psoriasis Area and Severity Index (PASI) score was done at weeks 0, 2, 4, 6 and 8. Results: A significant reduction in PASI score occurred in groups C and D (p = 0.043 and 0.018, respectively). A significantly higher percentage of PASI score reduction occurred in group D compared with groups A, B and C (p = 0.006, 0.003 and 0.030, respectively). An excellent response occurred in one patient (14.3%) in group D. A very good response occurred in two patients (22.2%) in group C, and in five patients (71.4%) in group D. A moderate response occurred in three patients (37.5%) in group A, one patient (12.5%) in group B, and one patient (14.3%) in group D. Conclusion: Although incomparable to methotrexate, combined sulfasalazine and pentoxifylline produced a good response in cases of extensive psoriasis. Multicentre studies are needed to validate these results.

Propranolol versus captopril in the treatment of infantile hemangioma (IH): A randomized controlled trial

BACKGROUND Renin-angiotensin system components have been demonstrated in the biology of infantile hemangioma (IH). Captopril, an angiotensin-converting enzyme inhibitor, is proposed as a therapeutic alternative to oral propranolol. OBJECTIVES We sought to compare the benefit of propranolol and captopril in the treatment of IH, and to assess angiotensin-converting enzyme gene polymorphism in patients with IH and in control subjects. METHODS Thirty patients with IH and 35 healthy control subjects were enrolled in this study. Patients were randomly assigned to treatment with either propranolol or captopril. Assessment was done clinically and by measurement of serum vascular endothelial growth factor and angiotensin II in patients and control subjects. Angiotensin-converting enzyme gene polymorphism was also studied. RESULTS Clinical improvement was significantly better and faster in the patients treated with propranolol. Both groups showed reduced vascular endothelial growth factor and angiotensin II levels posttreatment, with a significantly higher percentage reduction in the propranolol-treated group. Cardiac side effects were reported only in the captopril-treated group. Baseline vascular endothelial growth factor level was significantly higher, and baseline angiotensin II level was significantly lower, in patients than control subjects. LIMITATIONS We studied a relatively small number of patients and control subjects. CONCLUSION Propranolol shows greater benefit than captopril in the treatment of IH.

Expression of sirtuins 1, 6, tumor necrosis factor, and interferon-γ in psoriatic patients

Sirtuins (SIRT) have been regarded as culprits in the pathogenesis of various diseases. Their exact role has not been explained. This study aimed to assess the expression of SIRT1, SIRT6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in psoriatic patients. Thirty psoriatic patients and 22 controls were enrolled. Clinical examination and Psoriasis Area and Severity Index (PASI) were obtained. Two skin biopsies (lesional, peri-lesional) and one from controls were obtained. Tissue levels of SIRT1, SIRT6, TNF-α, and IFN-γ were measured using ELISA. SIRT1 was significantly lower in lesional skin with gradual increase in perilesional followed by control skin (P <0.001). SIRT6, TNF-α, and IFN-γ were significantly higher in lesional than perilesional and control skin (P <0.001). Significant positive correlations were found between SIRT1 and TNF-α, IFN-γ and between SIRT6 and TNF-α in peri-lesional skin. SIRT1 and SIRT6 are potentially involved in the pathogenesis of psoriasis. Modulating their action could offer a novel therapy for such disease.

Serum Vitamin D and Vitamin D Receptor Gene Polymorphism in Mycosis Fungoides Patients: A Case Control Study

Background Vitamin D has been considered a key player in various malignancies including cutaneous cancers. To date, mycosis fungoides (MF) has been the least studied in relation to vitamin D. Furthermore, the vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) have not been tackled before in the context of MF, despite their incrimination in numerous diseases. Aim of study To assess the role of vitamin D in MF by measuring its serum level, and studying VDR SNPs (TaqI, BsmI, FokI) in different stages of MF. Patients and Methods 48 patients with various stages of MF, and 45 healthy controls were included. Complete history, full clinical examination and a five mm punch skin biopsy were performed to all recruited patients. Venous blood samples were withdrawn from both patients and controls to determine the serum vitamin D level and VDR gene polymorphisms. Results Serum vitamin D level was significantly lower in patients (5.3–33.7 nmol/L)] compared to controls (8.3–90.1 nmol/L)] (P<0.001). A significant difference was observed between patients and controls regarding the FokI polymorphism only, being higher in patients (P = 0.039). Also Vitamin D serum levels differed significantly in patients with FokI genotypes (P = 0.014). No significant correlations were detected between any of the studied parameters and the demographic and clinical data of the included subjects. Conclusion Depressed vitamin D and FokI polymorphism are potentially involved in the context of MF. VDR gene polymorphisms warrant further larger scale investigations to detect the exact genes involved in the pathogenesis of such an enigmatic disease.

CXCL-10 and Interleukin-6 are Reliable Serum Markers for Vitiligo Activity: A Multicenter Cross-Sectional Study.

This cross‐sectional multicenter study aimed to evaluate serum CXCL‐10, as an activity marker for vitiligo, and compare it with other putative serum and tissue markers. Serum CXCL‐10 was compared to interferon gamma (IFN‐γ), interleukin 6 (IL‐6), and IL‐17 using ELISA in 55 non‐segmental vitiligo patients (30 active and 25 stable) and 30 healthy controls. Marginal skin biopsy was taken for immunohistochemical evaluation of CD8+T cells and CXCL‐10+ve cells. Serum levels of CXCL‐10, IL‐17, and IL‐6 were elevated in all vitiligo patients compared to controls (p < .05). All investigated serum markers were higher in active versus stable vitiligo. Tissue expression of CXCL‐10+ve cells and CD8+ve T cells was stronger in vitiligo patients compared to controls, and tissue CXCL‐10+ve cell expression was stronger in active versus stable cases. Positive correlations were noted between the different serum and tissue markers. CXCL‐10 was the most specific, whereas IL‐6 was the most sensitive serum marker to distinguish active from stable disease.