Plasmacytoid dendritic cells are present in cutaneous dermatomyositis lesions in a pattern distinct from lupus erythematosus

Background:  Plasmacytoid dendritic cells (PDCs) are CD123-positive dendritic cells (DCs) capable of producing interferon-α (IFN). They are thought to play a role in anti-viral immunity and the pathogenesis of lupus erythematosus (LE). Given the histologic similarities between LE and dermatomyositis (DM), we evaluated the presence and distribution of PDCs in lesional skin of both diseases.
Methods:  Twenty-eight biopsies of DM and 27 biopsies of LE were labeled with antibodies to CD123 to identify PDCs. The presence and relative distribution of CD123+ cells was recorded.
Results:  PDCs are present in LE and DM, albeit in greater numbers in LE lesions. Interestingly, PDCs are preferentially located in the epidermis of DM, and are primarily located in the dermis of LE.
Conclusions:  Skin lesions of DM contain PDCs. Because PDCs are thought to participate in the pathogenesis of LE, this finding suggests that they may play a role in DM as well. The preferential epidermal localization of PDCs in DM suggests that their contribution to disease pathogenesis or maintenance in DM may be distinct from LE. Finally, although not pathognomonic, the different patterns of PDC localization in LE and DM may prove a helpful criterion for distinguishing between these two entities histologically.     

银屑病患者皮损和外周血中CD123+BDCA-2+ 浆细胞样树突细胞的表达

目的 探讨CD123+BDCA-2+浆细胞样树突细胞（PDC）在寻常性银屑病患者皮损和外周血中的表达及意义。方法 收集22例寻常性银屑病患者和15例健康人皮肤组织和外周血,免疫组化法检测患者皮损和健康人皮肤组织中PDC的表达水平,流式细胞仪检测外周血中PDC的比例。结果 免疫组化结果显示,银屑病皮损中PDC的表达水平为（10.1 ± 2.1）/mm2,健康对照组为（0.4 ± 0.6） /mm2,银屑病组显著高于健康对照组（t = 17.34,P < 0.01）。银屑病患者外周血中CD123+BDCA-2+PDC占外周血单一核细胞的比例为（0.17 ± 0.07）%,健康对照组为（0.33 ± 0.20）%,银屑病组显著低于健康对照组（t = 4.48,P < 0.01）。结论 PDC通过在皮损中重新分布,在银屑病外周血中下降,可能与银屑病的发生、发展相关。     

Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors

BACKGROUND: It has been proposed that the innate immune system plays a central role in driving the autoimmune T-cell cascade leading to psoriasis; however, there is no direct evidence for this. OBSERVATIONS: We observed aggravation and spreading of a psoriatic plaque when treated topically with the toll-like receptor (TLR) 7 agonist imiquimod. The exacerbation of psoriasis was accompanied by a massive induction of lesional type I interferon activity, detected by MxA expression after imiquimod therapy. Since imiquimod induces large amounts of type I interferon production from TLR7-expressing plasmacytoid dendritic cell precursors (PDCs), the natural interferon-producing cells of the peripheral blood, we asked whether PDCs are present in psoriatic skin. We identified high numbers of PDCs in psoriatic skin lesions (up to 16% of the total dermal infiltrate) based on their coexpression of BDCA2 and CD123. By contrast, PDCs were present at very low levels in atopic dermatitis and not detected in normal human skin. CONCLUSIONS: This study shows that psoriasis can be driven by the innate immune system through TLR ligation. Furthermore, our finding that large numbers of PDCs infiltrate psoriatic skin suggests a role of lesional PDCs as type I interferon-producing targets for the TLR7 agonist imiquimod.     

Expression of dipeptidyl-peptidase IV (CD26) on CD8+ T cells is significantly decreased in patients with psoriasis vulgaris and atopic dermatitis

T cells play a major role in inflammatory skin disorders such as psoriasis vulgaris and atopic dermatitis. They are both active on the level of cell-to-cell interaction and by the secretion of pro-inflammatory mediators. CD26 is a lymphocyte membrane-associated dipeptidyl peptidase IV (DPP IV), which is able to inactivate chemokines such as RANTES or eotaxin by cleaving dipeptides from the NH2-terminus of proteins. We investigated the expression of CD26 on CD4+ and CD8+ peripheral blood T cells in patients with psoriasis and atopic dermatitis. In addition PASI and SCORAD as a measure of disease severity were determined in each patient at the time of blood drawing. Thirty patients with psoriasis, 15 with atopic dermatitis and 17 age- and sex-matched healthy persons were investigated by two-colour flow cytometry using epitope-specific monoclonal antibodies. Our results revealed, that there is a significant decrease (P<0.05) of CD26 expression on CD8+ T cells in both psoriasis (7.7%+/-3.3, mean and SD, n=30) and atopic dermatitis patients (7.9%+/-3.7, mean and SD, n=15) compared to the control population (11.58%+/-5.0, mean and SD, n=17). However, there was no correlation to disease severity as determined by PASI and SCORAD, respectively. Since CD26 can be regarded as an anti-inflammatory principle the decreased expression in psoriasis and atopic dermatitis patients may lead to a dysbalance in favour of pro-inflammatory mediators in both clinical conditions.     

Mediation of systemic vascular hyperpermeability in severe psoriasis by circulating vascular endothelial growth factor

BACKGROUND: Severe forms of psoriasis can be complicated by systemic microvascular hyperpermeability. Vascular endothelial growth factor (VEGF) possesses potent vascular permeability activity. We suggest that VEGF enters the systemic circulation and acts on microvessels to mediate hyperpermeability. OBJECTIVES: To quantify renal microvascular permeability and circulating VEGF concentration in severe psoriasis, and to investigate the relationship between plasma VEGF concentration and skin and joint involvement. DESIGN: Inception cohort studies of patients with generalized pustular psoriasis and plaque psoriasis. SETTING: St John's Institute of Dermatology, London, England. PATIENTS: Twenty-two patients (15 men and 7 women) with moderate and severe psoriasis were recruited (age range, 29-77 years; mean age, 47 years); 5 had generalized pustular psoriasis, 2 had erythrodermic psoriasis, and 15 had moderate-severe plaque psoriasis. An age- and sex-matched control group of 17 individuals (10 men and 7 women) was recruited (age range, 29-69 years; mean age, 42 years). RESULTS: There was pathological proteinuria in patients with relapsing generalized pustular psoriasis, (4-fold increase in urinary protein excretion rate in relapse compared with remission). In patients with moderate and severe psoriasis, mean plasma VEGF concentration during relapse was approximately 2.5 times greater than during remission (mean VEGF(relapse) = 257 pg/mL; mean VEGF(remission) = 103 pg/mL; P<.01). There was a correlation between extent of skin involvement and plasma VEGF level (mean VEGF(severe psoriasis) = 365 pg/mL; mean VEGF(moderate psoriasis) = 149 pg/mL; P =.03). There was a correlation between presence of psoriatic arthritis and plasma VEGF level (mean relapse VEGF(arthritis) = 277 pg/mL; mean relapse VEGF(nonarthritis) = 103.5 pg/mL; P =.03). CONCLUSIONS: Generalized pustular psoriasis is accompanied by pathological proteinuria and elevated plasma VEGF levels. Plasma VEGF concentration is significantly elevated in patients with extensive skin and joint involvement and may act on renal microvasculature to induce hyperpermeability.     

Hypertrophic lupus erythematosus: the diagnostic utility of CD123 staining

CD123-positive plasmacytoid dendrocytes are prominent in the infiltrate of discoid lupus erythematosus (LE). We hypothesized that these cells would also be present in hypertrophic LE and would aid in the histopathologic distinction from squamous cell carcinoma (SCC) and hypertrophic actinic keratosis (AK). Five cases of hypertrophic LE and 10 cases each of SCC and hypertrophic AK were stained with CD123. A heavy band of CD123-positive cells was present at the epidermal-dermal junction in all cases of hypertrophic LE, and only single or rare scattered clusters of CD123-positive cells were seen in SCC and actinic keratoses. The pattern of CD123 staining can be a useful feature to distinguish hypertrophic LE from SCC and hypertrophic AK.     

Plaque psoriasis vs. atopic dermatitis and lichen planus: a comparison for lesional T-cell subsets, epidermal proliferation and differentiation

BACKGROUND: T-cell infiltration in plaque psoriasis has recently been an important subject of investigation. Interestingly, comparative analyses of the disease-specific composition of the lesional T-cell infiltrate in plaque psoriasis and other inflammatory dermatoses have only sparsely been performed. OBJECTIVES: To compare plaque psoriasis vs. atopic dermatitis and lichen ruber planus with respect to T-cell subsets, epidermal proliferation and keratinization. PATIENTS AND METHODS: Biopsies were taken from untreated lesional skin of patients, six with psoriasis, six with atopic dermatitis and six with lichen planus. T-cell subsets (CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+), an epidermal proliferation (Ki-67) and a keratinization marker (K10) were stained immunohistochemically and quantified using image analysis. RESULTS: The high number of CD8+ T cells (52 +/- 13 cells mm(-1)) found in the psoriatic epidermis was not found in the epidermis of atopic dermatitis (9 +/- 4), nor in the epidermis of lichen planus (34 +/- 10). The other T-cell subsets in the epidermis and dermis showed no statistically significant differences between psoriasis and atopic dermatitis. In contrast to the limited presence of CD4+, CD8+ and CD2+ in the psoriatic dermis (110 +/- 19, 27 +/- 9, 127 +/- 41, cells mm(-1), respectively), more impressive numbers of these cells were observed in the dermis of lichen planus (300 +/- 53, 144 +/- 38, 272 +/- 48, respectively). CD45RO+ memory effector T-cell counts were significantly higher in the epidermis of lichen planus (39 +/- 10) than in psoriasis (19 +/- 5). Psoriatic epidermis proved to have major keratinocyte hyperproliferation (247 +/- 26 cells mm(-1) lamina basalis), as compared with atopic dermatitis (134 +/- 15) and lichen planus (128 +/- 20). Furthermore, a marked decreased expression of keratin 10 was observed in psoriasis (41% of epidermal area) contrary to atopic dermatitis (70%). CONCLUSIONS: Psoriatic epidermis exhibits a pronounced CD8+ epidermotropism with accompanying epidermal hyperproliferation and abnormal keratinization, which changes are only minimally expressed in atopic dermatitis and lichen planus. In plaque psoriasis, substantially fewer activated CD4+ and CD8+ T cells in the dermis and less CD45RO+ T cells in the epidermis are present in comparison with lichen ruber planus.     

Risk factors for osteoporosis and bone status in postmenopausal women with psoriasis treated with UVB therapy

The aims of this study were to examine whether postmenopausal women with psoriasis who were exposed to regular ultraviolet light B (UVB) therapy had greater bone mineral density than women of similar age from the same region, and to estimate the influence of risk factors on bone status. A total of 35 randomly selected women, age (mean +/- SD) 69.3 +/- 6.29 years (age range 60-82 years), with active psoriasis, mean onset at 37.0 years (+/- 23.5 SD) were studied. The patients had been previously exposed to broadband or narrowband UVB. Age-matched, women (n = 2448) from G?teborg, examined at the Geriatric out-patient clinic during the years 2001 and 2002, were used as controls. Bone mineral density was examined by Dual-Energy X-ray Absorptiometry (Hologic Delphi A) at the hip and the lumbar spine. Medical history and lifestyle factors were assessed with a questionnaire. Postmenopausal women with psoriasis were found to have higher bone mineral density than age-matched controls. Higher body weight, physical activity and UVB exposure could explain this finding.     

UVB-induced leucocyte trafficking in the epidermis of photosensitive lupus erythematosus patients: normal depletion of Langerhans cells

BACKGROUND: The pathogenic mechanisms of UV-induced skin lesions of lupus erythematosus (LE) are unknown. In a recent study of pathogenic mechanisms of polymorphic light eruption (PLE), significantly more Langerhans cells (LCs) persisted in the epidermis after UVB overexposure than in healthy individuals. Interestingly, the same phenomenon was observed in one subacute cutaneous lupus erythematosus (SCLE) patient. It could therefore be hypothesized that both photodermatoses share a common pathogenic mechanism of photosensitivity. In the present study, we tested this hypothesis by investigating leucocyte trafficking in the initial phase of cutaneous LE after intense UVB exposure. METHODS: In 22 photosensitive LE patients (12 chronic discoid lupus erythematosus, seven systemic lupus erythematosus and three SCLE) and nine age/sex-matched controls, uninvolved buttock skin was exposed to six minimal erythemal dose (MED) UVB radiation. Subsequently, biopsies were taken after 24, 48 and 72 h, and one control biopsy was taken from unirradiated skin. Skin sections were stained for the presence of LCs, neutrophils and macrophages. Areal percentages of positively stained cells within the epidermis were quantified and compared between the patients and controls. RESULTS: A gradual decrease of epidermal LCs and a gradual increase of epidermal neutrophils and macrophages at several timepoints after six MED irradiation was observed equally in both LE patients and controls. CONCLUSION: Immunohistopathology of irradiated uninvolved skin of photosensitive LE patients did not reveal the same pathologic trafficking of LCs and neutrophils as described for PLE patients. We conclude that different mechanisms are operative in the pathogenesis of PLE and photosensitive LE.     

Antinuclear antibodies in patients with polymorphic light eruption: a long-term follow-up study

BACKGROUND: Previous studies have shown elevated titres of antinuclear antibodies (ANA) in 2.9-19% of patients with polymorphic light eruption (PLE). A diagnosis of lupus erythematosus (LE) was finally established in some of these ANA-positive patients. OBJECTIVES: To investigate whether the presence of ANA in patients with PLE merely represents an epiphenomenon or is associated with an increased risk of eventual progression to LE. METHODS: We identified 472 patients with PLE who had received prophylactic photo(chemo)therapy between 1986 and 2003 and were routinely tested for the presence of ANA. All ANA-positive (ANA titre of>or=1:80) patients were asked to attend for a follow-up examination comprising a medical history, complete skin inspection and a detailed laboratory analysis including ANA and antibodies against extractable nuclear antigens. RESULTS: Of all the patients, 55 (11.7%) were found to be ANA positive on one or several occasions, and three (0.6%) also had antibodies to SS-A/Ro. Thirty-nine (71%) of all ANA-positive patients including all Ro+ subjects were available for follow-up after a median follow-up period of 8 years (interquartile range 5-11.5). Twenty-five patients showed persistence of ANA positivity with a median titre of 1:160 (range 1:80-1:640), whereas in 14 patients ANA titres had returned to normal levels. None of the patients revealed additional clinical, histopathological or laboratory abnormalities suggestive of LE. CONCLUSIONS: After a median follow-up period of 8 years none of the ANA-positive patients developed LE. Our findings indicate that PLE is a benign disease without tendency to progress to LE.     

Beneficial effects of fumarate therapy in psoriasis vulgaris patients coincide with downregulation of type 1 cytokines

BACKGROUND: Fumarates have been shown to be effective in psoriasis vulgaris. OBJECTIVES: To find out whether successful therapy is associated with modulation of cytokines. METHODS: We determined interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 secretion capacities of peripheral blood mononuclear cells (PBMC) after phytohaemagglutinin stimulation, and IL-12p70 and IL-10 secretion capacities of PBMC after endotoxin stimulation in psoriasis vulgaris patients during treatment with fumarates. In a cohort study, 12 patients (five men, median age 50 years; seven women, median age 46 years) with psoriasis vulgaris were followed during 24 months of fumarate treatment. In addition, we followed 14 healthy controls (six men, median age 31 years; eight women, median age 29 years) without skin diseases during 12 months to investigate possible changes in the cytokine secretion capacity of PBMC as a result of seasonal changes. Disease activity in patients was determined by Psoriasis Area and Severity Index (PASI) score. Blood was collected for measurement by enzyme-linked immunosorbent assay of cytokine levels after stimulation of PBMC. RESULTS: Within 6 months of fumarate treatment, the mean +/- SD PASI score had decreased to 22 +/- 9% of its initial value. These beneficial effects coincided with lymphocytopenia and a significant (P < 0.05) downregulation of IFN-gamma expression by circulating blood cells, followed by a significant downregulation of IL-4 expression. Notably, production of the cytokine synthesis inhibitor IL-10 by PBMC was unchanged. CONCLUSIONS: The beneficial effects of fumarates may be attributed to their downregulatory action on type 1 cytokines.     

浆细胞样树突状细胞和TLR9及其mRNA在银屑病患者皮损中的表达

目的：探讨浆细胞样树突状细胞（Plasmacytoid dendritic cells,PDCs）和toll样受体9（TLR9）在银屑病发病中的表达状态。方法：采用免疫组织化学SP法和逆转录-聚合酶链反应（RT-PCR）方法检测了22例银屑病患者皮肤损害中PDCs和TLR9及其mRNA的表达。15例整形外科患者的皮肤作为正常对照。结果：免疫组化结果显示银屑病组皮损中PDCs、TLR9的表达明显增多,而在正常对照组没有表达;RT-PCR检测显示银屑病皮损中TLR9mRNA的表达明显高于正常对照组（P〈0.01）。结论：银屑病患者皮损中有PDCs浸润,TLR9及其mRNA的表达水平上调,可能与银屑病的发病相关。     

Patterns of skin manifestations and their relationships with CD4 counts among HIV/AIDS patients in Cameroon

BACKGROUND: Skin manifestations are common clinical features among HIV/AIDS-positive patients. Their frequencies, patterns and associated factors have been shown to vary from region to region. The present study is aimed at documenting skin manifestations and their relationships with CD4 cell counts among HIV/AIDS patients in Cameroon. METHODS: This study lasted for 16 months (from September 2001 to December 2002). After informed consent, data on skin disorders, HIV status, CD4 and viral load were obtained by physical examination and laboratory methods. RESULTS: Of the 384 subjects studied, 236 (61.5%) were females and 148 (38.5%) were males. Up to 264 (68.8%) patients presented with at least one type of skin problem. Generalized prurigo, oral candidiasis, herpes zoster, and vaginal candidiasis were the most common skin problems. Mean CD4 cell count (128 +/- 85 cells/mm(3)) and mean viral load (79,433 copies/mL) in patients with herpes zoster were higher (P < 0.001). Patients with oral candidiasis and vaginal candidiasis had significantly lower (109 +/- 127 cells/mm(3), P < 0.02) and higher (131 +/- 85 cells/mm(3), P < 0.05) mean CD4 cell counts, respectively. Prurigo was associated with higher mean viral load (31,623 +/- 20 copies/mL, P < 0.04). Viral lesions were associated with high mean CD4 cell count (123 +/- 83 cells/mm(3), P < 0.001). Kaposi's sarcoma and parasitic lesions (crusted scabies) were both, respectively, associated with lower mean CD4 cell counts [(78 +/- 66 cells/mm(3), P < 0.001) (6 +/- 0 cells/mm(3), P < 0.04)]. CONCLUSION: We conclude, first that skin problems are common in HIV-infected individuals in Cameroon and that patients with advanced stages of these problems have relatively very low mean CD4 cell counts. Second, that mucocutaneous disorders like vaginal candidiasis and herpes zoster occur early in HIV infection while Kaposi's sarcoma is common in advanced HIV infection.     

Epidermal CD8+ T cells reactive with group A streptococcal antigens in chronic plaque psoriasis

Chronic plaque psoriasis is a T cell mediated disease associated with group A streptococci (GAS). We have previously shown the presence of a psoriasis-specific dermal Th1 subset that recognizes GAS antigens. To assess whether GAS-reactive T cells are also present in lesional epidermis, fresh cell suspensions or T cell lines isolated from lesional epidermis of 33 psoriasis patients were stained for intracellular interferon-gamma after stimulation with GAS antigens. The patients were typed by PCR for HLA-DR7 and HLA-Cw6 expression. A subset of GAS-reactive CD8+ T cells (2.4% +/- 2.4) was found in 14/21 (67%) fresh cell suspensions. A smaller subset of GAS-reactive CD4+ T cells (0.9% +/- 0.9) was found in 13/21 (62%) fresh cell suspensions, which was expanded in the T cell lines. There was a significant inverse correlation between the proportions of GAS-reactive CD4+ and CD8+ T cells in the fresh suspensions (r = -0.48, P = 0.0277). The presence of GAS-reactive CD4+ or CD8+ T cells did not correlate with HLA-DR7 or HLA-Cw6 expression, respectively. This study has demonstrated GAS-reactive CD8+, and to a lesser extent CD4+, T cell subsets in psoriatic epidermis and provides further evidence that GAS antigens may play a role in the pathogenesis of chronic plaque psoriasis.     

Familial clustering of polymorphic light eruption in relatives of patients with lupus erythematosus: evidence of a shared pathogenesis

BACKGROUND: Abnormal photosensitivity is a common feature of many forms of lupus erythematosus (LE). OBJECTIVES: To examine the role of polymorphic light eruption (PLE) as a possible predisposing factor for cutaneous forms of LE. METHODS: Eighty-five patients with well-characterized subacute cutaneous LE (SCLE) and discoid LE (DLE) were recruited from outpatient clinics, and the prevalence of PLE determined by detailed interview and clinical examination. RESULTS: Symptoms consistent with PLE were reported in 61% and 55% of SCLE and DLE patients, respectively; this was significantly higher than the overall population prevalence of 13.6% (P < 0.001), giving a relative risk (RR) for PLE in SCLE patients of 3.37 (95% confidence interval, CI 2.46--4.28) and DLE patients of 3.11 (95% CI 2.31--3.91). PLE developed before the onset of LE in 61% of cases (median interval 12 years, range 1--40), concomitantly in 24%, and subsequently in a further 15% (median interval 3.5 years, range 1--25). To delineate the relationship between PLE and LE further, the prevalence of PLE was determined in 103 otherwise unaffected first-degree relatives of SCLE and DLE probands; we had previously demonstrated clustering of PLE in families, reflecting a strong genetic component. We found a significantly higher PLE prevalence in relatives of the LE probands than in the general population (P < 0.001), giving an RR for PLE of 2.29 (95% CI 1.55--3.03) and 2.61 (95% CI 1.32--3.89) for female and male relatives, respectively. CONCLUSIONS: The high prevalence of PLE in LE patients, together with clustering of PLE among first-degree relatives of SCLE and DLE probands, suggests that there may be a shared pathogenetic basis for PLE and cutaneous LE. We propose that predisposition to PLE may contribute to the LE phenotype in otherwise susceptible individuals.     

Serum levels of interleukin-18 and s-ICAM-1 in patients affected by psoriasis: preliminary considerations

OBJECTIVE: To find new aspects of the systemic involvement of the Immune System in psoriasis, we determined serum levels of interleukin-18 (IL-18) (Th1-inducing factor cytokine), CD30 (Th2 marker) and sICAM-1 (adhesion molecule). In addition we evaluated the correlation between these molecules and psoriasis area and severity index (PASI). BACKGROUND: Psoriasis is associated to an overexpression of Th1 cytokines and a relative underexpression of Th2 cytokines. IL-18 plays an important role in inducing Th1 response because it is a potent inductor of synthesis of IFN-gamma, TNF and other mediators. The two major sources of IL-18 are monocytes and macrophages but also human keratinocytes constitutively synthesized IL-18. SUBJECTS AND METHODS: We selected two groups of subjects: 16 healthy donors (HD) and 16 patients affected by psoriasis, matched for sex and age. Serum IL-18, CD30 and sICAM-1 levels were assayed by immunoenzymatic method with commercial kits. RESULTS: IL-18 and sICAM-1 levels in the patients were significantly higher than in the HDs (385.94 +/- 193.89 vs. 227.38 +/- 92.76 pg/mL, P = 0.005 and 445.00 +/- 152.67 vs. 317.88 +/- 107.20 ng/mL, P = 0.02, respectively). On the contrary, no significant difference was found between serum sCD30 levels of patients in respect to those of HDs. A significant correlation was found between serum IL-18 and PASI (Rho = 0.695, P = 0.0071), serum IL-18 and sICAM-1 (Rho = 0.543, P = 0.0356) and between sICAM-1 and PASI (Rho = 0.659, P = 0.0107).     

Associations of promoter region polymorphisms in the tumour necrosis factor-alpha gene and early-onset psoriasis vulgaris in a northern Polish population

BACKGROUND: Tumour necrosis factor (TNF)-alpha is considered to be an important mediator in the pathogenesis of psoriasis. Increased levels and activity of this cytokine have been observed in blood and skin of patients with psoriasis. As certain allelic variants of the TNF-alpha gene are associated with increased or decreased production of TNF-alpha, the disturbed cytokine balance may be under genetic control. OBJECTIVES: To investigate the potential association of TNF-alpha promoter alleles within subtypes of psoriasis compared with healthy controls in a northern Polish population. METHODS: We analysed 166 patients with psoriasis vulgaris (134 with type I and 32 with type II) and 65 healthy controls. The polymorphisms -238G/A and -308G/A in the promoter region of the TNF-alpha gene were typed using the amplification refractory mutation system-polymerase chain reaction method. RESULTS: We found that the TNF-alpha-308A allele frequency was significantly decreased among patients with early-onset psoriasis in comparison with control subjects (7.5% vs. 15.4%, P = 0.022), whereas in the same patients the frequency of the TNF-alpha-238A allele was significantly increased as compared with the controls (16.8% vs. 3.1%, P = 0.000017, odds ratio 8.79, 95% confidence interval 2.606-29.678). Patients with early-onset psoriasis with -238 genotype GA or AA were found more often among those with age at onset < 25 years in comparison with those with genotype GG (31.7% vs. 9.1%, P = 0.0312). We also found that the mean +/- SD age at onset among -238A carriers was significantly lower in comparison with that associated with the -238GG genotype (13.5 +/- 7.4 vs. 19.2 +/- 9.9 years, P = 0.0132). CONCLUSIONS: Our study confirming the association between -238 G/A TNF-alpha promoter polymorphism and early-onset psoriasis vulgaris in the northern Polish population suggests that the -238A variant may contribute not only to a predisposition to psoriasis vulgaris but also to the disease phenotype.     

The evaluation of the sociodemographic and clinical features of Turkish psoriasis patients

BACKGROUND: Psoriasis is a common, chronic and recurrent, inflammatory disease of the skin. With no sociodemographic psoriasis data available in Turkey, we decided to investigate the clinical features and distribution of this disease in our country. METHODS: The records of 329 patients with psoriasis were retrospectively reviewed. RESULTS: Psoriasis constituted 1.3% of the total dermatological disorders. Sixty-one per cent of the patients were female, and 39% were male. The mean age at onset of disease was 25 +/- 16 years in females, and 28 +/- 15 years in males. Family history was positive 30% of the patients. A positive family history was observed in 25% of the females and 37% of the males. 312 cases (95%) had psoriasis vulgaris, 17 cases (5%) had pustular psoriasis. Of the patients with psoriasis vulgaris, 212 (68%) had plaque, 73 (23%) guttate, 18 (6%) palmoplantar, 9 (3%) inverse type. The mean and median PASI score were 3.7 +/- 3.8 & 2.7 for females, 5.4 +/- 6.1 & 3.5 for males, respectively. 1.5% of patients had psoriatic arthropathy. Nail changes were seen in 54 (16%) of the cases. The various nail involvement types observed in descending frequency were: pitting (13%), subungual hyperkeratoses (7%), onycholysis (2%), discoloration (1.5%), oily spot (1%) and splinter hemorrhages (0.3%). CONCLUSIONS: The prevalence of psoriasis in Turkey is similar to numbers reported in South America and Germany. Females were predominant, and the mean age of onset was lower in women. Positive family history was more frequent in males. Plaque type psoriasis was the most common presentation. The difference between mean PASI scores of female and male patients was not statistically significant. Psoriatic arthritis was extremely rare in Turkish psoriasis patients. Pitting was the most common abnormality of the nails.     

The expression pattern of interferon-inducible proteins reflects the characteristic histological distribution of infiltrating immune cells in different cutaneous lupus erythematosus subsets

BACKGROUND: Plasmacytoid dendritic cells and type I interferons (IFNs) are supposed to play a central proinflammatory role in the pathogenesis of cutaneous lupus erythematosus (LE). The IFN-inducible chemokines CXCL9 and CXCL10 are involved in recruiting CXCR3+ effector lymphocytes from the peripheral blood into skin lesions of LE. We hypothesized that the expression pattern of IFN-inducible proteins reflects the characteristic distribution of the inflammatory infiltrate in different subsets of cutaneous LE. OBJECTIVES: To test this hypothesis in patients with LE. METHODS: Lesional skin biopsies taken from patients with different subsets of LE [chronic discoid LE (CDLE), n = 12; subacute cutaneous LE (SCLE), n = 5; LE tumidus (LET), n = 4; LE profundus (LEP), n = 6] were investigated by immunohistochemistry using monoclonal antibodies to the lymphocyte surface markers CD3, CD4, CD8, CD20 and CD68, the cytotoxic proteins Tia1 and granzyme B, the chemokine receptor CXCR3, the specifically type I IFN-inducible protein myxovirus protein A (MxA) and the chemokines CXCL9 and CXCL10. RESULTS: The expression pattern of MxA followed the distribution of the inflammatory infiltrate typically seen in the investigated cutaneous LE subsets. In CDLE and SCLE, expression was focused in the epidermis and upper dermis, while in LET a perivascular and in LEP a subcutaneous pattern was found. Similar findings were obtained for CXCL9 and CXCL10. CONCLUSIONS: Our results demonstrate a close morphological association between the expression pattern of IFN-inducible proteins and the distribution of CXCR3+ CD3+ lymphocytes in all investigated subsets of cutaneous LE. This supports the importance of an IFN-driven inflammation in this condition. Infiltrating lymphocytes carrying CXCL10 in their granules might amplify the lesional inflammation and be responsible for the chronic course of this disease.     

UVB therapy increases 25(OH) vitamin D syntheses in postmenopausal women with psoriasis

BACKGROUND: Vitamin D3 is produced in the epidermis by ultraviolet (UV) radiation (290-315 nm) of 7-dehydrocholesterol. A similar range of 290-320 nm (broadband UVB) has been successfully used for years to treat psoriasis. The aim of this study was to investigate whether UVB therapy was able to influence vitamin D synthesis in psoriasis patients. METHODS: Twenty-four postmenopausal, white Caucasian women, aged 69 +/- 5.9 (mean +/- SD), with active plaque psoriasis, were treated with broadband UVB two to three times per week for 8-12 weeks. The serum concentrations of calcidiol (25(OH)D3), calcitriol (1,25(OH)2D3), intact parathyroid hormone (PTH), thyroid hormones, osteocalcin, calcium and creatinine were measured before the first and after the last dose of radiation. Bone density was measured using Dual-Energy X-ray Absorptiometry (Hologic Delphi A) at the hip and lumbar spine. RESULTS: Serum levels of 25(OH)D3 increased from 36.8 +/- 17 ng/ml (mean +/- SD) to 59.6 +/- 18.7 ng/ml (P<0.001) after the UVB treatment period. Serum PTH decreased from 62.8 +/- 25.7 ng/l to 48.2 +/- 17.4 ng/l (P<0.001). Secondary hyperparathyroidism (PTH>65 ng/l) was revealed in seven patients (29%) in whom PTH values were suppressed by the UVB therapy. The serum levels of calcitriol, calcium, osteocalcin, thyroid hormones and creatinine were unaltered. CONCLUSION: UVB therapy in elderly psoriatic women improved psoriasis, increased serum 25(OH)D3 synthesis and reduced serum PTH concentrations.