Phenotypic analysis of circulating T-cell subset and its association with burden of skin disease in patients with chronic actinic dermatitis: a hematologic and clinicopathologic study of 20 subjects.

BACKGROUND: Chronic actinic dermatitis (CAD) is a recurrent photosensitive dermatitis that occurs predominantly on sun-exposed areas with unknown etiology. In severe cases, it may present with erythroderma, which is clinicopathologically analogous to cutaneous T-cell lymphoma. Typically, inflammatory infiltrates in the skin lesions are mainly CD8+ reactive T cells. However, hematologic characteristics of CAD have not been fully elucidated. METHODS: Twenty patients with CAD ranging in age from 45 to 86 years (median, 64), including 17 males and three females (M/F ratio, 5.7), were examined. All patients were phototested for UV light. In addition, seven of the 20 patients with extensive eruption were also tested for visible light. All biopsy specimens were obtained from the CAD eruptions (n = 25 lesions). Histopathologic and immunohistochemical studies were performed. Furthermore, flow cytometric analysis was performed to determine the CD4/8 ratio using peripheral blood mononuclear cells of 13 of the 20 patients. RESULTS: In 11 of the 20 patients (55%), the eruption was localized to sun-exposed areas. Skin-infiltrating T cells were CD8-dominant in the CAD eruption. Three patients (15%) showed erythroderma with a reduced CD4/8 ratio (median, 0.7) of peripheral mononuclear cells. As for treatment, eight of the 20 patients (40%) required oral cyclosporine in addition to topical therapies. Subsequently, the reduced CD4/8 ratio was normalized after treatment in two of the three patients with erythroderma. CONCLUSIONS: We considered that there appeared to be a relationship between the reduced CD4/8 ratio of circulating T cells (hematologic burden) and the affected area (skin burden).

Predictors of Beagley-Gibson skin cast grade in older adults.

BACKGROUND AND PURPOSE: The Beagley-Gibson (BG) grading system utilizes microtopographical skin changes to generate an individualized, objective estimate of cumulative, lifetime ultraviolet radiation (UVR) exposure. However, predictors of BG grade are ill-defined, particularly in older populations. The aim of this cross-sectional study was to describe the factors associated with skin damage as measured by the BG method in 835 community-dwelling older adults. METHODS: Study participants aged 53-83 years had silicone casts taken from the dorsum of both hands and graded by the BG method. Lifetime sun exposure, skin phenotypic traits and smoking status were assessed by questionnaire. 25-hydroxyvitamin D and melanin density were measured using radioimmunoassay and spectrophotometry, respectively. Ordered logistic regression was used to compute a single odds ratio (OR) by taking BG grade as the outcome variable. RESULTS: Higher 25-hydroxyvitamin D was associated with increasing BG grade (OR = 1.39, P = 0.02) in adjusted analysis. Age (OR = 1.14, P < 0.001), occupational sun exposure (OR = 1.62, P < 0.001), ability to tan (OR = 1.40, P < 0.001), melanin density (OR=0.79, P = 0.001), lifetime leisure time sun exposure (OR = 1.21, P = 0.004), current smoking (OR = 1.82, P = 0.007), propensity to sunburn (OR = 1.18, P = 0.016), and waist-hip ratio (OR = 1.10, P = 0.02) were independent predictors of BG grade. Hair colour, number of sunburns, body mass index and gender were not independent predictors of BG grade. CONCLUSIONS: Beagley-Gibson skin cast grade is a biologically relevant marker of UVR exposure in older adults influenced by both intrinsic and extrinsic factors.

Correlation of serum IgE levels and clinical manifestations in patients with actinic prurigo.

BACKGROUND: Actinic prurigo is an idiopathic photodermatosis, the pathophysiology of which has been hypothesized to involve subtype IV type b (Th2) hypersensitive response, whereby IL4, IL5, and IL13 are secreted and mediate the production of B cells, IgE, and IgG4. OBJECTIVES: To examine the association of serum IgE levels and the clinical severity of injuries. METHODS: This case-control study comprised patients with a clinical and histopathological diagnosis of actinic prurigo, as well as clinically healthy subjects, from whom 3cc of peripheral blood was taken for immunoassay. Cases were classified by lesion severity as mild, moderate, and severe. Descriptive statistics were analyzed, and chi-square test was performed. RESULTS: We included 21 actinic prurigo patients and 21 subjects without disease; 11 patients with actinic prurigo had elevated serum IgE levels, and 10 had low serum levels. Six actinic prurigo (AP) patients with elevated serum levels of IgE had moderate injuries, 4 had severe injuries, and 1 had minor injuries. Eight out of 10 patients with normal IgE levels presented with minor injuries in the clinical evaluation. The 21 controls did not have increased serum IgE levels. CONCLUSIONS: Elevated IgE levels are associated with moderate to severe clinical lesions, suggesting that actinic prurigo entails a type IV subtype b hypersensitivity response in which Th2 cells predominate.

Correlation of serum IgE levels and clinical manifestations in patients with actinic prurigo

Abstract BACKGROUND: Actinic prurigo is an idiopathic photodermatosis, the pathophysiology of which has been hypothesized to involve subtype IV type b (Th2) hypersensitive response, whereby IL4, IL5, and IL13 are secreted and mediate the production of B cells, IgE, and IgG4. OBJECTIVES: To examine the association of serum IgE levels and the clinical severity of injuries. METHODS: This case-control study comprised patients with a clinical and histopathological diagnosis of actinic prurigo, as well as clinically healthy subjects, from whom 3cc of peripheral blood was taken for immunoassay. Cases were classified by lesion severity as mild, moderate, and severe. Descriptive statistics were analyzed, and chi-square test was performed. RESULTS: We included 21 actinic prurigo patients and 21 subjects without disease; 11 patients with actinic prurigo had elevated serum IgE levels, and 10 had low serum levels. Six actinic prurigo (AP) patients with elevated serum levels of IgE had moderate injuries, 4 had severe injuries, and 1 had minor injuries. Eight out of 10 patients with normal IgE levels presented with minor injuries in the clinical evaluation. The 21 controls did not have increased serum IgE levels. CONCLUSIONS: Elevated IgE levels are associated with moderate to severe clinical lesions, suggesting that actinic prurigo entails a type IV subtype b hypersensitivity response in which Th2 cells predominate.

A multicenter photoprovocation study to identify potential biomarkers by global peptide profiling in cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) is an inflammatory autoimmune skin disease in which abnormal photosensitivity is an important pathogenetic factor but is difficult to predict, creating a challenge in determining treatment efficacy. Although photosensitivity in CLE patients may change over time, photoprovocation testing with ultraviolet (UV) A and UVB irradiation can be a helpful tool to explore differences between responders and nonresponders during photoprovocation. To identify biomarkers that could substitute for the clinical endpoint lesion development, we performed a global peptidomics profiling analysis of CLE subjects in a controlled photoprovocation study. Plasma and skin biopsy samples were collected before and after UV-irradiation from 13 healthy volunteers and 47 CLE subjects. Twenty-two of the 47 CLE subjects developed skin lesions. The samples were analyzed using a label-free quantitative peptidomics workflow combined with univariate and multivariate statistical analyses. The primary finding was identification of a specific plasma peptide signature separating responders versus nonresponders at baseline. The peptide signature consisted of beta 2-microglobulin (B2MG), human beta-defensin-1, and peptides derived from CD99, polymeric immunoglobulin receptor, and immunoglobulin kappa light chains. In skin, elevated B2MG levels correlated with lesion formation. Our results show that the peptidome is a rich source of potential biomarkers for predicting photosensitivity in CLE.

Sunlight exposure behaviour and vitamin D status in photosensitive patients: longitudinal comparative study with healthy individuals at U.K. latitude.

BACKGROUND: Low vitamin D status is prevalent in wintertime in populations at northerly latitudes. Photosensitive patients are advised to practise sun avoidance, but their sunlight exposure levels, photoprotective measures and resulting vitamin D status are unknown. OBJECTIVES: To examine seasonal vitamin D status in photosensitive patients relative to healthy individuals and to assess quantitatively behavioural and demographic contributors. METHODS: This was a longitudinal prospective cohort study (53·5°N) examining year-round 25-hydroxyvitamin D [25(OH)D] levels, sun-exposure behaviour and oral vitamin D intake in photosensitive patients diagnosed at a photoinvestigation unit (n = 53), compared with concurrently assessed healthy adults (n = 109). RESULTS: Photosensitive patients achieved seasonal 25(OH)D variation, but insufficient (< 20 ng mL(-1); 50 nmol L(-1)) and even deficient (< 10 ng mL(-1); 25 nmol L(-1)) levels occurred at the summer peak in 47% and 9% of patients, respectively, rising to 73% and 32% at the winter trough. Adjusting for demographic factors, the mean values were lower than for healthy volunteers by 18% [95% confidence interval (CI) 4-29] in summer (P = 0·02) and 25% (95% CI 7-39) in winter (P = 0·01). Behavioural factors explained 25(OH)D differences between cohorts. Patients demonstrated lower weekend ultraviolet B doses (P < 0·001), smaller skin surface area exposure (P = 0·004) and greater sunscreen use (P < 0·001), while average oral vitamin D intake was low in both groups (photosensitive: 2·94 µg per day). Supplementation and summer surface area exposure predicted summer peak and winter trough 25(OH)D levels. A 1 µg per day increment in supplementary vitamin D raised summer and winter 25(OH)D by 5% (95% CI 3-7) and 9% (95% CI 5-12), respectively (both P < 0·001). CONCLUSIONS: Photosensitive patients are, through their photoprotective measures, at high risk of year-round low vitamin D status. Guidance on oral measures should target this patient group and their physicians.

Prevalence of photosensitivity in chronic hepatitis C virus patients and its relation to serum and urinary porphyrins.

BACKGROUND & AIMS: HCV is a major cause of chronic liver disease in Egypt. The aim was to study the prevalence of photosensitivity among asymptomatic HCV-infected patients and its possible relation to porphyrins levels and whether it can be considered an alarm for early diagnosis of the disease, which is the most important goal in the management. METHODS: This study included 100 accidentally discovered HCV positive cases and 100 HCV negative healthy controls. All patients and controls were subjected to: Detailed history and clinical examination, dermatological examination including evaluation of reaction to solar exposure, measurement of serum AST, ALT, albumin, bilirubin, serum and urinary porphyrins levels. RESULTS: The prevalence of photosensitivity among HCV-positive cases (33%) was significantly higher compared to 10% in the control group. Serum porphyrins were positive in 46 cases (46%), twenty-three cases (23%) had positive urinary porphyrins, while only four controls (4%) showed positive serum porphyrins and one (1%) showed positive urinary porphyrins, the difference was statistically significant. Cases with photosensitivity showed significantly higher prevalence of serum and urinary porphyrins existence as well as serum porphyrins levels. Levels of viraemia showed statistically significant relation to levels of porphyrins. CONCLUSION: Asymptomatic chronic HCV infection cases showed significantly high prevalence of photosensitivity, which is related to the associated disturbance of porphyrins metabolism. Photosensitivity can thus be considered an early marker of HCV infection. Patients discovered to have recently acquired photosensitivity should be screened for HCV infection especially in endemic areas like Egypt.

Impaired secondary oxidant deactivation capacity and enhanced oxidative stress in serum from alveld affected lambs.

Alveld is a hepatogenous photosensitivity disorder in lambs. The aim of the study was to investigate if alveld affected lambs had a reduced capacity to handle oxidative stress induced from either endogenous and/or exogenous photosensitizers. Serum samples from alveld lambs (n=33) were compared to serum samples from control lambs (n=31) and exposed to a controlled amount of singlet oxygen ((1)O2). The sera from alveld lambs were found to have an impaired ability to deactivate reactive oxygen species (ROS) compared to control sera. A higher degree of initial hemolysis and a higher concentration of the exogenous photosensitizer phytoporphyrin (PP) were detected in alveld sera compared to the controls. The action spectrum for the formation of (1)O2 indicated that PP as well as the endogenous compound protoporphyrin IX (PP IX) may act as in vivo photosensitizers. A relatively high level of iron was detected in pooled serum from alveld lambs that showed a high degree of hemolysis. It was concluded that alveld photosensitivity is likely to be initiated by a photodynamic reaction involving PP and possibly also PP IX followed by a light-independent reaction involving hemoglobin-related products and catalysis by the Fenton reaction.

Elevated protoporphyrin in patients with skin cancer receiving taxane chemotherapy.

BACKGROUND: Docetaxel and paclitaxel are both taxanes used for treatment of various malignant tumors. Only two case reports have described photohypersensitivity induced by docetaxel and paclitaxel in association with porphyrin aberrations. OBJECTIVES: To examine whether aberrations in the biosynthesis of porphyrins and photohypersensitivity occur among patients receiving taxanes. MATERIALS & METHODS: We examined porphyrin aberrations and photohypersensitivity in 8 patients with skin cancers who received docetaxel or paclitaxel chemotherapy in our department. RESULTS: Aberrations in erythrocyte protoporphyrin were detected in 4 patients, while no such aberration was detected in the control group. Photohypersensitivity to Ultraviolet B (UVB) was detected in 2 patients; one was related to an elevated synthesis of protoporphyrin but the other was not. Photohypersensitivity to Ultraviolet A (UVA) or visible light was not detected. CONCLUSION: Docetaxel and paclitaxel chemotherapy seemed to induce aberrations in porphyrin biosynthesis, although an elevated synthesis of porphyrin did not necessarily cause photohypersensitivity.

Genetic study in a Singaporean patient with erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disorder of haem biosynthesis resulting from a partial decrease in ferrochelatase (FECH) activity which leads to the excessive accumulation of protoporphyrin in blood, erythrocytes and tissues. Cutaneous manifestations of photosensitivity usually appear in early infancy upon the first sun exposures. This normally requires the co-inheritance of a common hypomorphic FECH allele and a deleterious FECH mutation. Here, we report the first Singaporean Chinese patient with EPP characterized at the molecular level.

Seasonal variation in the activity of systemic lupus erythematosus.

OBJECTIVE: To determine whether there is any seasonal variation in the activity of systemic lupus erythematosus (SLE) overall and by individual organs. METHODS: The study group comprised 2102 patients with SLE who were followed in a prospective longitudinal cohort study. In this cohort, 92.3% of the patients were women. The mean ± SD age of the patients was 47.9 ± 13.9 years, 56.3% were white, 37.1% were African American, and 3.1% were Asian. Global disease activity was recorded by the Safety of Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the physician's global assessment. Activity of each organ was also recorded using SLEDAI terms and a visual analog scale (VAS; 0 to 3). RESULTS: There was significant seasonal variation in photosensitive rash (p < 0.0001), which was more frequent in the spring and summer months (p < 0.0001). There was significantly more arthritis activity in spring and summer, as measured by both SELENA-SLEDAI (p = 0.0057) and the joint VAS (p = 0.0047). A decrease in renal activity was found in the summer months compared to the rest of the year (p = 0.0397). Serositis recorded by VAS had higher activity from August to October (p = 0.0392). Anti-dsDNA levels were significantly higher during October and November (p < 0.0001). There was significant seasonal variation in antiphospholipid antibody levels (p < 0.0001) and lupus anticoagulant (p = 0.0003). We found a significant variation in activity through the year in global disease activity as measured by SELENA-SLEDAI (p = 0.048). CONCLUSION: In the Hopkins Lupus Cohort, skin and joint activity is increased during the spring and summer, but other organs have different patterns. These seasonal variations likely reflect environmental factors that influence disease activity, including ultraviolet light and infections.

Reduced serum concentrations of 25-hydroxy vitamin D in Egyptian patients with systemic lupus erythematosus: relation to disease activity.

BACKGROUND: Recently, vitamin D deficiency has been implicated as a potential environmental factor triggering some autoimmune disorders, including systemic lupus erythematosus (SLE)). In addition, patients with SLE, especially those with increased disease activity, were suggested to have decreased vitamin D level, suggesting that vitamin D might play a role in regulating autoantibody production. MATERIAL/METHODS: To assess 25 hydroxy vitamin D [25(OH)D] status in Egyptian patients with SLE and its relation to disease activity. Clinical evaluation and assay of serum 25(OH)D, total calcium, phosphorous, alkaline phosphatase (ALP) and parathyroid hormone (PTH) were done on 60 SLE patients in comparison to 60 matched-healthy subjects. Serum 25(OH)D levels <30 and 10 ng/ml were defined as vitamin D insufficiency and deficiency, respectively. RESULTS: Serum 25(OH)D was significantly lower in patients than in controls (26.33 ± 12.05 vs. 42.66 ± 9.20 respectively, p < 0.0001), with 13.30% and 60% being deficient and insufficient, respectively. Serum 25(OH)D levels were lower with increased disease activity (p = 0.03) and frequency of photosensitivity(p = 0.02) and photoprotection (p = 0.002). Systemic lupus erythematosus disease activity index (SLEDAI) score (OR: 2.72, 95% CI: 1.42-5.18, P = 0.002), photosensitivity (OR: 3.6, 95% CI: 1.9-6.8, P < 0.01) and photoprotection (OR: 6.7, 95% CI: 2.9-8.8, P < 0.001) were significant predictors of 25(OH)D level among SLE cases. CONCLUSIONS: Low vitamin D status is prevalent in Egyptian SLE patients despite plentiful exposure to sunlight throughout the year, and its level is negatively correlated to disease activity. Future studies looking at a potential role of vitamin D in the pathophysiology and treatment of SLE are warranted.

Erythropoietic protoporphyria in Sweden: demographic, clinical, biochemical and genetic characteristics.

OBJECTIVE: To investigate the demographic, clinical, biochemical and genotypic features of patients with erythropoietic protoporphyria (EPP) in a Swedish cohort. DESIGN: Cross-sectional questionnaire, biochemical and genetic study. SETTING: Sweden. SUBJECTS: Fifty-one Swedish individuals known in 2008 to have EPP confirmed by molecular diagnosis. There were no exclusion criteria; all patients were included in the demographic and genetic study. A total of 92% participants completed the questionnaire study and 82% the biochemical study. RESULTS: The prevalence of EPP was 1 : 180,000. Nine novel ferrochelatase gene mutations were found. The most commonly reported age at onset of symptoms was the first year of life and the mean age at diagnosis was 22 years. Painful photosensitivity was the main symptom. Exogenous factors other than sunlight were frequently reported to cause cutaneous symptoms. One in five patients reported a positive effect of beta-carotene therapy. A marked impact of EPP on quality of life was reported. Women had a significantly lower mean erythrocyte protoporphyrin concentration than men. Of all participants, 84% had insufficient vitamin D concentrations, 44% had below normal serum ferritin or transferrin saturation levels and red cell abnormalities were common. CONCLUSIONS: The notably delayed diagnosis suggests the need for an increased awareness of EPP. Disturbed erythropoiesis, biochemical signs of iron deficiency and low vitamin D levels are frequent findings in this disease. New and better treatments are needed as current treatment options for symptom amelioration are limited. Vitamin D supplementation should be considered.

Detection of singlet oxygen in blood serum samples of clinically healthy lambs and lambs suffering from alveld disease.

Alveld is a disease in lambs of domestic sheep (Ovis aries L.), characterized by a combination of photosensitivity and liver damage. Generation of singlet oxygen play a major role in phototoxicity reactions. The compound phylloerythrin (phytoporphyrin) is so far assumed to be the main photodynamic agent in hepatogenous photosensitivity diseases in sheep. Phylloerythrin is a potent photosensitizer and an efficient source of singlet oxygen. The compound accumulates in the peripheral circualtion upon liver damage. Liver dysfunction is also likely to cause an increase in the blood level of bilirubin. Formation of singlet oxygen by bilirubin is reported. In the present work the photosensitizing potential of serum has been measured and related to the bilirubin- and phylloerythrin levels in lambs suffering from alveld and in clinically healthy controls. The singlet oxygen level of the serum was taken as a measure of the photosensitizing potential. The observed singlet oxygen values in serum from alveld lambs were significantly higher than the corresponding values observed in clinically healthy control lambs. This indicates that the serum of the alveld lambs contains an elevated concentration of photosensitizer. The singlet oxygen level was not correlated to the concentration of bilirubin or phylloerythrin. The results indicate that the photosensitizing mechanism is quite complex and may involve other sensitizer(s) than phylloerythrin.

European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus.

OBJECTIVE: To determine whether genetic substructure in European-derived populations is associated with specific manifestations of systemic lupus erythematosus (SLE), including mucocutaneous phenotypes, autoantibody production, and renal disease. METHODS: SLE patients of European descent (n=1,754) from 8 case collections were genotyped for >1,400 ancestry informative markers that define a north-south gradient of European substructure. Using the Structure program, each SLE patient was characterized in terms of percent Northern (versus percent Southern) European ancestry based on these genetic markers. Nonparametric methods, including tests for trend, were used to identify associations between Northern European ancestry and specific SLE manifestations. RESULTS: In multivariate analyses, increasing levels of Northern European ancestry were significantly associated with photosensitivity (Ptrend=0.0021, odds ratio for highest quartile of Northern European ancestry versus lowest quartile [ORhigh-low] 1.64, 95% confidence interval [95% CI] 1.13-2.35) and discoid rash (Ptrend=0.014, ORhigh-low 1.93, 95% CI 0.98-3.83). In contrast, increasing levels of Northern European ancestry had a protective effect against the production of anticardiolipin autoantibodies (Ptrend=1.6x10(-4), ORhigh-low 0.46, 95% CI 0.30-0.69) and anti-double-stranded DNA autoantibodies (Ptrend=0.017, ORhigh-low 0.67, 95% CI 0.46-0.96). CONCLUSION: This study demonstrates that specific SLE manifestations vary according to Northern versus Southern European ancestry. Thus, genetic ancestry may contribute to the clinical heterogeneity and variation in disease outcomes among SLE patients of European descent. Moreover, these results suggest that genetic studies of SLE subphenotypes will need to carefully address issues of population substructure based on genetic ancestry.

Sun-induced life-threatening lupus nephritis.

Photosensitivity is a widely known characteristic of both cutaneous and systemic lupus erythematosus (LE). However, sun-induced organ involvement is rarely reported in LE. We describe a 34-year-old woman who had been in complete remission of systemic LE for more than 8 years without treatment. After sunbathing, she developed acute sunburn followed by cutaneous LE in sun-exposed areas. Six weeks later, a lupus nephritis was diagnosed and high serum levels of antidouble-stranded (ds) DNA and anti-Ro/SSA antibodies were detected. Treatment with systemic cyclophosphamide and prednisolone led to septicemia requiring assisted ventilation for more than 2 weeks and repeated hemodialysis. Clinical remission was achieved 3 months later by the use of prednisolone and mycophenolate mofetile. Meanwhile, mild proteinuria persisted, anti-dsDNA antibodies normalized. We hypothesize that the sunburn-induced keratinocyte necrosis/apoptosis exposed intracellular antigens as trigger for the generation of autoantibodies that finally mediated immune-complex nephritis. The patient highlights the impact of UV light not only on skin but also on internal organ involvement in LE.