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.

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.

Acral lesions of vitiligo: why are they resistant to photochemotherapy?

BACKGROUND: Acral lesions of vitiligo are usually resistant to conventional lines of treatment as well as surgical interventions. OBJECTIVE: To clarify causes underlying resistance of acral lesions to pigmentation in vitiligo by studying some of the factors associated with mechanisms of repigmentation following photochemotherapy. METHODS: The study included twenty patients with active vitiligo. Skin biopsies were taken from lesional and perilesional skin of areas expected to respond (trunk and proximal limb) and skin of acral areas, before and after PUVA therapy. Sections were stained with H and E, Melan-A, MHCII, CD1a, SCF and c-kit protein. RESULTS: Before treatment acral areas showed significantly lower hair follicle density, melanocyte density, Langerhans cell (LC) density, epidermal MHCII expression, lesional SCF expression and perilesional c-kit expression. Following treatment with PUVA in both non-responsive acral and repigmenting non-acral lesions identical immunohistochemical changes in the form of significant decrease in LC density, epidermal MHC-II and SCF expression were observed. CONCLUSION: The surprisingly similar histochemical changes in response to PUVA in acral and non-acral lesions did not manifest with clinical repigmentation except in non-acral ones. Factors such as inherent lower melanocyte density, lower melanocyte stem cell reservoirs and/or lower baseline epidermal stem cell factor may be considered as possible play makers in this respect.

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.

Narrow band UVB (311 nm), psoralen UVB (311 nm) and PUVA therapy in the treatment of early-stage mycosis fungoides: a right-left comparative study.

BACKGROUND: Psoralen ultraviolet A (PUVA) is a widely used first-line therapy for treatment of early cutaneous T-cell lymphoma. Narrow band UVB (UVB-NB) (311 nm) has been recently introduced as another effective line of treatment. It is postulated that the efficacy of UVB-NB could be enhanced by addition of psoralen. AIM: The aim of the present work was to compare the clinical and histopathologic efficacy of PUVA and UVB-NB in the treatment of early-stage MF (stages IA, IB and IIA), and to evaluate whether psoralen adds to the efficacy of UVB-NB or not. PATIENTS AND METHODS: Twenty patients (stage IA, IB or IIA) were divided into two equal groups: group I received UVB-NB on the right body half vs. PUVA on the left side of the body for 48 sessions, and group II received PUVB-NB on the right side of the body vs. PUVA on the left side for 36 sessions. The sessions were administered three times weekly. RESULTS: In group I, almost equal results were obtained on both sides, i.e., UVB-NB and PUVA were equally effective in the treatment of early stages of MF, both clinically and histopathologically. In group II, PUVB-NB was found to be as effective as conventional PUVA in the treatment of early-stage mycosis fungoides, also on both clinical and histopathological grounds. CONCLUSION: UVB-NB phototherapy should be included among the initial therapeutic options of mycosis fungoides in view of its efficacy, convenience, and likelihood of fewer long-term adverse effects. Addition of psoralen does not seem to enhance its therapeutic efficacy.