Elevated serum tumour necrosis factor-like weak inducer of apoptosis in alopecia areata: a possible marker of disease severity.

BACKGROUND: Alopecia areata (AA) is, an organ-specific autoimmune disease, characterized by an aberrant expression of cytokines of the T helper 1 type. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifactorial cytokine that exerts a role in the pathogenesis of inflammatory and autoimmune diseases, especially in cutaneous diseases. AIM: To estimate the serum level of TWEAK in AA and to correlate it with different parameters. METHODS: This case-control study enrolled 40 patients with AA and 50 clinically healthy volunteers matched for age and sex. A blood sample (5 mL) was extracted from each participant for analysis of serum TWEAK levels by ELISA. RESULTS: Levels of TWEAK were significantly higher in patients with AA (mean ± SD 213.7 ± 59.2 pg/mL, range 109.1-341.6 pg/mL) than in controls (95.97 ± 13.28 pg/mL, range 80.1-152.3 pg/mL) (P < 0.001). A significant positive correlation was found between serum TWEAK level and the Severity of Alopecia Tool (SALT) score (r = 0.56, P < 0.001). CONCLUSION: To our knowledge, this study highlights for the first time a possible link between higher serum TWEAK level and AA. Serum TWEAK level appears to reflect AA disease severity.

Toll-like receptor (TLR)7 expression in mycosis fungoides and psoriasis: a case-control study.

BACKGROUND: Toll-like receptors (TLRs) have been implicated in various dermatological diseases. TLR agonists have the capacity to potently activate the innate immune cells of patients with advanced, refractory, cutaneous T-cell lymphoma (CTCL). AIM: To detect TLR7 gene expression in mycosis fungoides (MF) (a neoplastic skin condition) and to compare it with psoriasis (an inflammatory skin condition) in an attempt to clarify the pathogenic role played by TLR7 in both conditions. METHODS: This case-control study enrolled 28 patients with MF: 30 patients with psoriasis, and 30 age- and sex-matched healthy controls (HCs). A 4-mm punch skin biopsy was obtained from lesional skin of patients and from normal skin of HCs for detection of TLR7 gene expression using real-time PCR. RESULTS: Mean TLR7 level in patients with MF (0.4 ± 0.23) was significantly lower than in patients with psoriasis (1.49 ± 0.46) and in HCs (1.22 ± 0.44) (P < 0.001), and mean TLR7 level in patients with psoriasis was significantly higher than in HCs (P < 0.03). Based on MF staging, 21.4% of patients had stage Ia, 28.6% had stage Ib, 28.6% had stage IIa and 21.4% had stage IIb disease. Comparing the TLR7 levels in relation to MF staging revealed the lowest mean value was in stage IIb and highest mean value in stage Ia, and this was significant (P < 0.001). CONCLUSION: Disturbed innate immunity might play a role in the pathogenesis of neoplastic and inflammatory skin conditions. TLR7 could be useful as a prognostic factor in MF.

Reduction in tissue plasmin: a new mechanism of action of narrowband ultraviolet B in psoriasis.

BACKGROUND: Plasmin (PL) is a potent inflammatory cell activator, and ultraviolet (UV)B has immunomodulatory effects on cutaneous inflammatory responses. There are no previous studies comparing the effect of narrowband (NB)-UVB on tissue PL levels in psoriasis. AIM: To estimate the possible role of PL in the pathogenesis of psoriasis, and to evaluate the effect of NB-UVB on tissue PL in psoriasis. METHODS: This case-control study enrolled 21 patients with psoriasis and 20 clinically healthy volunteers matched for age and sex. Patients underwent 24 sessions of NB-UVB radiation. Biopsy samples using a 4 mm punch were taken from all patients before and after treatment and from the controls for estimation of tissue PL level by ELISA. RESULTS: Tissue PL was significantly upregulated in psoriasis before treatment (mean ± SD 1.73 ± 1.23 ng/mg protein) compared with controls (0.21 ± 0.15 ng/mg protein) (P < 0.001). A statistically significant positive correlation (P = 0.02) was found between the tissue PL before treatment and the Psoriasis Area and Severity Index. Patients received 24 sessions of NB-UVB, with a mean cumulative dose of 23.25 ± 8.14 mJ/cm(2) . Tissue PL levels were reduced by a mean of 30.3% post-treatment compared with baseline (P < 0.001). The reduction in Pl levels was significantly correlated with the cumulative dose of NB-UVB, and with the percentage reduction in PASI (P < 0.001). CONCLUSIONS: Our study highlights the possible role played by tissue PL level in the pathogenesis of psoriasis. PL level appears to reflect disease severity, and is a possible marker of therapeutic efficacy of NB-UVB on psoriatic skin.

Kallin syndrome associated with vitiligo.

Kallin syndrome (KS) is a variant of epidermolysis bullosa simplex (EBS), which, in addition to the classic features of EBS, also presents with deafness, alopecia, hypodontia and nail dystrophy. We report the case of a 17-year-old boy who presented to our clinic with trauma-induced skin blistering, alopecia, deafness, dental caries, nail dystrophy and vitiliginous areas. The skin blisters had been appearing since birth, and healed without scarring. The vitiliginous areas were unrelated to the sites of the blisters. Electron microscopy of the skin blisters was diagnostic of EBS, and the depigmented lesions were similar to those of vitiligo. An association of vitiligo with EBS has not been reported previously. Multiple genetic findings have confirmed a role for keratin in regulating skin pigmentation. Apoptosis of melanosome-bearing keratinocytes may participate in the reduction of melanin density and result in depigmentation. Further studies on the defective proteins in KS may clarify the mechanism underlying the association with vitiligo.

Medical ethical standards in dermatology: an analytical study of knowledge, attitudes and practices.

BACKGROUND: Dermatology practice has not been ethically justified at all times. OBJECTIVE: The objective of the study was to find out dermatologists' knowledge about medical ethics, their attitudes towards regulatory measures and their practices, and to study the different factors influencing the knowledge, the attitude and the practices of dermatologists. METHODS: This is a cross-sectional comparative study conducted among 214 dermatologists, from five Academic Universities and from participants in two conferences. A 54 items structured anonymous questionnaire was designed to describe the demographical characteristics of the study group as well as their knowledge, attitude and practices regarding the medical ethics standards in clinical and research settings. Five scoring indices were estimated regarding knowledge, attitude and practice. Inferential statistics were used to test differences between groups as indicated. The Student's t-test and analysis of variance were carried out for quantitative variables. The chi-squared test was conducted for qualitative variables. The results were considered statistically significant at a P > 0.05. RESULTS: Analysis of the possible factors having impact on the overall scores revealed that the highest knowledge scores were among dermatologists who practice in an academic setting plus an additional place; however, this difference was statistically non-significant (P = 0.060). Female dermatologists showed a higher attitude score compared to males (P = 0.028). The highest significant attitude score (P = 0.019) regarding clinical practice was recorded among those practicing cosmetic dermatology. The different studied groups of dermatologists revealed a significant impact on the attitude score (P = 0.049), and the evidence-practice score (P < 0.001). CONCLUSION: Ethical practices will improve the quality and integrity of dermatology research.

The Pro12Ala polymorphism of the gene for peroxisome proliferator activated receptor-gamma is associated with a lower Global Acne Grading System score in patients with acne vulgaris.

BACKGROUND: Acne vulgaris is a multifactorial disease of the skin. Several studies have shown that sebocyte proliferation and/or lipogenesis, as well as inflammatory reactions, may be regulated by peroxisome proliferator-activated receptor (PPAR)γ-mediated pathways. AIM: To investigate whether the Pro12Ala polymorphism of the PPARγ gene might be associated with the risk of acne, and to assess the effect of this polymorphism on acne severity. METHODS: This case-control study enrolled 100 patients with acne and 100 apparently healthy subjects. The clinical grade of acne was assessed using the Global Acne Grading System. We used PCR to identify the presence of the Pro12Ala polymorphism in exon 2 of PPARγ. RESULTS: Our results revealed a statistically significant difference (P = 0.001) in the genotype distribution between patients and controls, with higher incidence of the Pro/Ala genotype in controls (51%) than in patients (28%). A statistically significant association (P < 0.001) between disease severity and genotype distribution was found, indicating that the Pro/Ala genotype is less prevalent in patients with severe acne. CONCLUSIONS: Our results suggest that that the Ala allele might be a protective factor against acne development or may attenuate acne severity.

Serum ferritin and vitamin d in female hair loss: do they play a role?

AIM: Evaluation of serum ferritin and vitamin D levels in females with chronic telogen effluvium (TE) or female pattern hair loss (FPHL), in order to validate their role in these common hair loss diseases. METHODS: Eighty females (18 to 45 years old) with hair loss, in the form of TE or FPHL, and 40 age-matched females with no hair loss were included in the study. Diagnosis was based upon clinical examination as well as trichogram and dermoscopy. Serum ferritin and vitamin D2 levels were determined for each participant. RESULTS: Serum ferritin levels in the TE (14.7 ± 22.1 µg/l) and FPHL (23.9 ± 38.5 µg/l) candidates were significantly lower than in controls (43.5 ± 20.4 µg/l). Serum vitamin D2 levels in females with TE (28.8 ± 10.5 nmol/l) and FPHL (29.1 ± 8.5 nmol/l) were significantly lower than in controls (118.2 ± 68.1 nmol/l; p < 0.001). These levels decreased with increased disease severity. Serum ferritin cut-off values for TE and FPHL were 27.5 and 29.4 µg/l, respectively, and those for vitamin D were 40.9 and 67.9 nmol/l. CONCLUSION: Low serum ferritin and vitamin D2 are associated with hair loss in females with TE and FPHL. Screening to establish these levels in cases of hair loss and supplementing with them when they are deficient may be beneficial in the treatment of disease.

The antioxidant role of paraoxonase 1 and vitamin E in three autoimmune diseases.

PURPOSE OF THE STUDY: To investigate the role of paraoxonase 1 (PON1) and vitamin E in the pathogenesis of some autoimmune diseases, and to correlate their levels with the disease activity. PROCEDURES: This randomized case control study was performed on 60 subjects: 45 patients [suffering from psoriasis, vitiligo and alopecia areata (AA) 15 patients each group] and 15 healthy controls. Venous blood and tissue biopsy were collected from each subject to estimate the levels of vitamin E and PON1. RESULTS: All patients showed significantly lower levels of both PON1 and vitamin E in tissue and serum than the controls (p < 0.001). CONCLUSION: An association between oxidative stress and pathogenesis of these autoimmune diseases is identified. Attenuation of oxidative stress might be a relevant therapeutic approach and it would be useful to recommend additional drugs with antioxidant effects in the treatment of these conditions.

DNA polymorphisms and tissue cyclooxygenase-2 expression in oral lichen planus: a case-control study.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disorder defined as a precancerous condition. Special attention has been paid to the expression of cyclooxygenase-2 (COX-2) and its potential role in development of oral squamous cell carcinoma. The identification of single nucleotide polymorphisms that affect gene function or expression and contribute to disease predisposition has become a major area of investigation toward understanding the mechanisms for cancer. OBJECTIVE: The objective of this study is to investigate the association between the COX-2 765G>C gene polymorphism, tissue COX-2 expression and the development of OLP as a chronic inflammatory condition. METHODS: This study was done on 50 patients with OLP and 50 healthy controls. COX-2 activity was assessed by measuring tissue prostaglandin E (PGE)2 levels by enzyme immunometric assay kit. COX-2 765G>C gene polymorphism was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by restricted fragment length polymorphism (RFLP). RESULTS: OLP patients showed statistically significant higher mean PGE2 than the control group. We did not observe any statistically significant differences in genotype distribution or allele frequency between the patients and the control group (P > 0.05). Odds ratio showed no statistically significant association between COX-2 765G>C polymorphism and lichen planus. CONCLUSION: The present evidence thus indicates that variation in the COX-2 gene is unlikely to be of relevance to the aetiology of OLP. As this is the first report concerning the COX-2 -765G>C gene polymorphism and the risk of OLP, additional studies with larger sample size will be required to confirm these findings.

Clinical study of nail changes in leprosy and comparison with nail changes in diabetic patients.

BACKGROUND: Nail changes in leprotic patients are not specific to leprosy, and may be observed in other peripheral neuropathies. Diabetes is one of the diseases that present with nail dystrophy secondary to peripheral neuropathy, vasculopathy, trauma and infections. Therefore, nail changes in diabetic neuropathy are expected to be very similar to that of leprosy. OBJECTIVES: To evaluate the frequency and pattern of nail changes in Egyptian leprotic patients with the different spectrums of the disease, and to compare nail changes in leprosy with those seen in patients with diabetic neuropathy. METHODS: The study included 115 leprosy patients and 60 patients with diabetic peripheral neuropathy. Nail examination was thoroughly carried out and various nail changes were recorded including the location of the involved nails (fingers, toes). RESULTS: Our study detected similar incidence of nail changes in both multibacillary (MB) (86%) and paucibacillary (PB) patients (86%). Flag sign (alternating horizontal bands of whitish and pinkish discoloration of the nail) observed in our study was not reported before. It was more commonly seen in MB patients (21%) than in PB patients (14%). Our results also revealed that the nail changes were more commonly seen in leprosy patients (86%) than in diabetic patients (68%). CONCLUSION: Nail changes in leprosy are multifactorial, and could be related to one or more of the following: neuropathy, endarteritis, trauma, drugs or superimposed infections. Nail changes in leprosy may be used as an additional clue that helps in the diagnosis.

Expression of cyclin D1 and p16 in psoriasis before and after phototherapy.

BACKGROUND: Psoriasis vulgaris (PV) is characterized by keratinocyte hyperproliferation. Altered expression of cell-cycle regulatory genes involved in the cyclin D1 / p16 INK4-pRb pathway may contribute to this epidermal hyperproliferation. AIM: To assess the expression of cyclin D1 and p16 in psoriasis, and to evaluate the effect of phototherapy on their expression. METHODS: The study population comprised 25 patients with PV and 10 healthy controls. Patients were treated with 24 sessions of either narrowband ultraviolet (UV) B or psoralen UVA. Skin biopsies were taken from the affected skin of each patient before and after treatment, and from the healthy controls, to examine cyclin D1 and p16 expression. RESULTS: Before phototherapy, the mean value of cyclin D1 concentration in patients was significantly greater than that in controls and the mean value of p16 concentration in patients was significantly lower than that in controls. Following treatment, we detected a significant decrease in cyclin D1 and a significant increase in p16. CONCLUSION: Cyclin D1 upregulation and p16 downregulation may play a role in the pathogenesis of psoriasis. Normalization of the levels of both parameters may be a mechanism by which phototherapy induces remission in psoriasis.

The use of sulfasalazine and pentoxifylline (low-cost antitumour necrosis factor drugs) as adjuvant therapy for the treatment of pemphigus vulgaris: a comparative study.

BACKGROUND: Pemphigus vulgaris (PV) represents a potentially life-threatening autoimmune blistering disease in which IgG autoantibodies are directed against cell-cell adhesion molecules. Tumour necrosis factor (TNF)-alpha has been suggested to have a possible role in the mechanism underlying acantholysis. OBJECTIVES: This comparative double-blinded study was carried out to estimate the use of both sulfasalazine (SSZ) and pentoxifylline (PTX) (low-cost anti-TNF drugs) as an adjuvant therapy for PV. METHODS: The study included 64 patients with PV: 42 patients received the full treatment regimen (with SSZ and PTX) and 22 patients followed the same regimen except they received placebo instead of PTX and SSZ. Five healthy subjects were included as controls. Serum samples were taken to measure TNF-alpha levels in the control group and before starting treatment in both the patient groups and this was repeated every 2 weeks for 8 weeks; a clinical assessment was made every week for all the patients. RESULTS: The serum level of TNF-alpha was statistically higher in both groups of patients than in the healthy individuals. There was a statistically significant decrease in the serum levels of TNF-alpha in patients in group 1 compared with those in group 2 at 6 and 8 weeks. There was also a significant clinical improvement in patients in group 1 compared with those in group 2. CONCLUSION: The use of PTX and SSZ as adjuvant therapy in the treatment of PV induced a faster and more significant decrease in the serum level of TNF-alpha, and this decrease was associated with rapid clinical improvement.