Cholesterol sulphate levels in the hair and nails of patients with recessive X-linked ichthyosis

Cholesterol sulphate (CS) has been suggested as an intercellular glue for corneocyte-corneocyte cohesion from studies on patients with recessive X-linked ichthyosis (RXLI). Pathological stratum corneum of RXLI patients was found to show a significant elevation of CS. In the present study hair and nails, unaffected keratinized tissues in RXLI patients, were examined for CS levels. The results demonstrated significantly elevated CS levels in both tissues in RXLI patients (P less than 0.001). In particular the mean CS level in the hair of RXLI patients was five times greater than normal. The present study suggests that hair is a useful material for the diagnosis of RXLI.     

Simplified method of determination of serum cholesterol sulfate by reverse phase thin-layer chromatography

A new method for determination of cholesterol sulfate (CS) and dehydroepiandrosterone sulfate (DHEAS) from 1 ml serum by reverse phase thin-layer chromatography (TLC) is described. The method comprises an isolation step of sulfated steroids by means of octadecylsilane-bonded (C18) reverse phase column chromatography, a solvolysis step for desulfation of sulfated steroids, and a C18 TLC step for measurement on a photodensitometer. This method is much simpler and more rapid than the methods previously reported, since neither a radioisotope is needed, nor any steps of saponification, derivatization, tedious scraping from a TLC plate, and time-consuming conventional column chromatography are not required. The present method allowed us to distinguish recessive X-linked ichthyosis (RXLI) very easily from ichthyosis vulgaris (IV) by the size and gradation of clearly visible blue chromogen derived from CS on a TLC plate in RXLI. By photodensitometer scanning, the CS levels in patients with RXLI were about 10 times higher than those of patients with IV and healthy subjects, whereas the DHEAS level was normal in the RXLI patients. The present simplified method proved to be useful in diagnosis of RXLI.     

Simplified determination of serum cholesterol sulfate by gas-liquid chromatography combined with cyclohexylsilane-bonded phase column purification

Summary A new gas-liquid chromatographic (GLC) determination of cholesterol sulfate (CS) and dehydroepiandrosterone sulfate (DHEAS) for a biochemical diagnosis of recessive X-linked ichthyosis (RXLI) is described. Although the GLC method for determination of CS is known to be more sensitive than the thin layer chromatographic (TLC) method, the former method has not been widely employed because of its complicated pre-purification steps. The present method allows us to measure the serum levels of CS and DHEAS without tedious purification steps such as multiple conventional column chromatography and preparative thin layer chromatography. Sulfated steroids are rapidly purified with a commercially available mini disposable cyclohexylsilane-bonded phase (CH) column, CH BOND ELUT, and the purified steroids after desulfation are converted to water-resistant tert-butyldimethylsilyl ether derivatives for the GLC analysis on dual 2 m glass columns packed with 2% XE-60 on Chromosorb W.By the present method, serum CS concentrations in RXLI patients were shown to be about 10 times higher than those in patients with ichthyosis vulgaris, carriers of RXLI, and healthy subjects. This method is more suitable not only for a biochemical diagnosis of RXLI but also for studies on the metabolism of sulfated steroids than the previous time-consuming GLC methods.     

Metabolic alterations of DHEA and cholesterol sulphates in the hair of patients with acne measured by liquid chromatography–mass spectrometry

Please cite this paper as: Metabolic alterations of DHEA and cholesterol sulphates in the hair of patients with acne measured by liquid chromatography–mass spectrometry. Experimental Dermatology 2010; 19 : 694–696. Abstract: As the hormonal levels in scalp hair reflects the condition of skin appendage, the level of dehydroepiandrosterone‐3‐sulphate (DHEAS) and cholesterol sulphate (CS) was evaluated in scalp hair obtained from patients with acne. The hair samples were extracted by alkaline solution and were analysed by liquid chromatography–mass spectrometry coupled to column switching system. The levels of DHEAS in scalp hair of women with acne were higher (P < 0.001) than controls, while the levels of CS in scalp hair of women and men with acne were higher (P < 0.001) than both control subjects. Increased hair levels of both DHEAS and CS could indicate acne development because of its direct action or stimulatory effect on local enzyme activity. It may be also helpful to understand the pathogenesis of acne based on follicular retention hyperkeratosis and increased sebum production of both steroid sulphates.     

Oral zinc sulphate therapy in acne vulgaris: a double-blind trial

The effect of zinc sulphate and placebo was compared in a double-blind trial in 56 patients suffering from acne vulgaris. Serum vitamin A levels were studied in all, before and at the end of therapy, 29 patients received zinc sulphate 600 mg daily and 27 patients received placebo. Patients on placebo showed no improvement. After 12 weeks of treatment with zinc sulphate, 17 patients (58%) showed significant improvement. There was a statistically significant decrease in the number of papules, infiltrates and cysts. In zinc-treated cases there was statistically significant increase in serum vitamin A levels, while no change was found in the placebo group.     

鱼鳞病患者鳞屑、皮肤和血液的胆固醇和胆固醇硫酸酯分析

目的：探讨脂质与鳞屑性疾病的关系。方法：用气相质谱方法对性联隐性鱼鳞病（ＲＸＬＩ）、寻常性鱼鳞病（ＩＶ）各５例和５例正常对照组的鳞屑、表皮、真皮和血液中的胆固醇硫酸酯（ＣＳ）和胆固醇（ＣＨ）进行了定量分析。结果：鳞屑中ＲＸＬＩ组ＣＳ含量显著高于ＩＶ和正常对照组，ＣＨ和ＣＨ／ＣＳ显著低于其他二组。在表皮、真皮和血液中，ＲＸＬＩ组ＣＳ含量显著增高，而ＣＨ含量无明显变化，ＣＨ／ＣＳ下降。结论：ＲＸＬＩ的鳞屑产生与ＣＳ积聚及ＣＨ／ＣＳ下降有关，而ＩＶ的发病则与ＣＳ和ＣＨ无关。     

Serum vascular endothelial growth factor A levels reflect itch severity in mycosis fungoides and Sézary syndrome

Angiogenesis is an important step to support progression of malignancies, including mycosis fungoides (MF) and Sézary syndrome (SS). Vascular endothelial growth factor (VEGF)‐A, a key player in angiogenesis, is secreted by tumor cells of MF/SS and its expression levels in lesional skin correlated with disease severity. In this study, we examined serum VEGF‐A levels in MF/SS patients. Serum VEGF‐A levels were elevated in patients with erythrodermic MF/SS and the levels decreased after treatment. Importantly, serum VEGF‐A levels positively correlated with markers for pruritus. We also found that VEGF‐A upregulated mRNA expression of thymic stromal lymphopoietin by keratinocytes. Taken together, our study suggests that VEGF‐A can promote progression and pruritus in MF/SS. Inhibition of VEGF‐A signaling can be a therapeutic strategy for patients with erythrodermic MF/SS.     

Oral zinc sulphate therapy for acne vulgaris.

A double-blind controlled clinical trial was performed to evaluate the effect of oral zinc sulphate, 0.6 g daily, on acne vulgaris. Twenty patients received zinc sulphate tablets and 19 were given placebo tablets. Thirteen of the zinc group and 12 of the placebo group received their medication throughout a 12-week period, while the remaining patients were treated for 4 or 8 weeks. In all patients the numbers or papular and pustular acne lesions on the face and the back were significantly reduced, while larger infiltrates remained practically unaltered during the trial, which was performed from March through May 1975. No statistically significant difference in the improvement of the groups was demonstrable. Pretreatment serum zinc values, which were normal in all patients, rose significantly in the zinc group as well as in the control group, but the increase in the former was significantly higher. The negative therapeutical results might be attributable to the limited number of patients or related to the zinc dosage. Furthermore, the results might have been influenced by the unexplained rise in serum zinc values in the control group. A possible weak beneficial effect of zinc might also have been camouflaged by the seasonal variation in the severity of acne which was noted in this study.     

Increased interleukin‐36γ expression in skin and sera of patients with atopic dermatitis and mycosis fungoides/Sézary syndrome

Interleukin (IL)‐36γ is expressed by keratinocytes and functions as a key initiator of inflammation in the skin. IL‐36γ expression is enhanced by tumor necrosis factor‐α and IL‐17A, having a strong association with psoriasis. In this study, we examined the role of IL‐36γ in atopic dermatitis (AD) and mycosis fungoides (MF)/Sézary syndrome (SS). Serum levels of IL‐36γ in AD patients and MF/SS patients were elevated compared with those of healthy controls. Importantly, serum IL‐36γ levels in AD patients positively correlated with Eczema Area and Severity Index and those of MF/SS patients positively correlated with serum soluble IL‐2 receptor levels. IL‐36γ mRNA levels in AD skin and MF/SS skin were significantly higher than those of normal skin. IL‐36γ mRNA levels in MF/SS skin positively correlated with IL‐17A mRNA levels. Immunohistochemical staining revealed that IL‐36γ was highly expressed in keratinocytes in lesional skin of AD and MF/SS. Taken together, our study demonstrated that IL‐36γ expression was increased in sera and skin of patients with AD and MF/SS as was reported in psoriatic patients.     

Local absorption of zinc from wounds treated with different concentrations of zinc sulphate.

In the present study it was shown in rats that zinc is absorbed from excisional wounds treated with zinc sulphate. Systemic toxic effects were observed in the group treated with 20% zinc sulphate. Local toxic effects were seen in wounds treated with 0.2%, 2% and 20% zinc sulphate. An inhibitory effect of zinc on the migration of granulocytes was suggested on the basis of microscopic observation. In the operated groups which were not treated with zinc and the group treated with 0.02% zinc sulphate a decline was observed in the concentration of zinc in serum. The zinc concentration in serum increased in proportion to the zinc sulphate concentration (0.2%, 2% and 20%) applied to the wounds, while the copper concentration decreased in the groups treated with 2% and 20% zinc sulphate. In all operated groups an increase in zinc and copper concentrations was observed in liver. This was most pronounced in groups treated with higher concentrations of zinc sulphate (0.2%, 2% and 20%). The groups treated with higher concentrations of zinc sulphate also had higher pancreas zinc concentrations than the remaining groups.     

Sweet's syndrome: retrospective study of clinical and histologic features of 44 cases from a tertiary care center

Background Sweet’s syndrome (SS) is an uncommon disorder characterized by the abrupt onset of erythematous papules and plaques that histologically exhibit diffuse dermal neutrophilic infiltrate and edema. There are usually associated constitutional symptoms such as fever, neutrophilia, elevated serum inflammatory markers, and associated disorders. The aim of this study was to assess the clinical and histologic features of all patients diagnosed with SS at our institution between 1971 and 2008 and to compare their findings with those published in the literature. Methods Retrospective review of 44 cases of SS diagnosed at the American University of Beirut ‐ Medical Center between 1971 and 2008. Data collected included clinical (age, gender, morphology and distribution of lesions, associated symptoms and disorders, therapy) and histologic features, as well as laboratory abnormalities. Results Most of our patients showed the typical clinical, histologic, and laboratory abnormalities characteristic of SS. Of our 44 patients, 33 (75%) had classic SS while 11 (25%) had an underlying malignant disorder. Of all patients, 7 (16%) were in the pediatric age group, five (11%) had the neutrophilic dermatosis of the dorsal hands variant of SS and two (5%) had subcutaneous SS. Most patients were treated with a tapering dose of systemic corticosteroids with a good response. Conclusion The clinical and histologic findings of the 44 SS patients in our study are generally comparable to those published in the literature, with some differences.     

Oral zinc sulphate in the treatment of recalcitrant viral warts: randomized placebo-controlled clinical trial

BACKGROUND: Viral warts are common dermatological diseases; although the rate of spontaneous recovery is high, it usually takes a long time, and some patients might not show this spontaneous healing. Zinc has an important effect on the immune system and it has been used as an immunomodulator to treat a variety of skin disorders. OBJECTIVE: To assess whether oral zinc was effective in treating viral warts of patients evaluated between May 1999 and April 2000. PATIENTS AND METHODS: This was a placebo-controlled clinical trial. Eighty patients with viral warts (common, plantar and plane) were all resistant to all forms of treatment. Each patient had > 15 warts. Forty patients were treated by oral zinc sulphate at a dose of 10 mg kg(-1) daily up to 600 mg day(-1) and followed-up for resolution of their warts and for any evidence of recurrence for 2-6 months. Another 40 patients were given a placebo oral treatment in the form of glucose, and followed-up for the same period. RESULTS: Only 23 patients of the first group (zinc treated) and 20 patients of the second group (placebo treated) completed the study. In all patients the serum level of zinc was low. In the zinc-treated group, the overall response was complete clearance of warts observed in 20 patients (86.9%) after 2 months of treatment. Fourteen patients (60.9%) showed complete disappearance of their warts after 1 month. Three patients (13.3%) failed to respond to the treatment after 2 months of therapy. The response to treatment was directly related to the increment in serum zinc level. No patient of the placebo-treated group showed any response. CONCLUSIONS: We conclude that zinc sulphate at a dose of 10 mg kg(-1) daily seems to be a highly efficacious therapeutic option for recalcitrant viral warts and proved to be safe with few adverse effects.     

Elevated serum granulocyte colony-stimulating factor levels in patients with active phase of sweet syndrome and patients with active behcet disease: implication in neutrophil apoptosis dysfunction

BACKGROUND: Sweet syndrome (SS), an acute inflammatory disease, has clinical and laboratory features similar to those of Beh?et disease (BD). Serum levels of granulocyte colony-stimulating factor (G-CSF) are elevated in patients with SS, and exogenous administration of G-CSF has repeatedly been implicated in the causation of SS. Granulocyte colony-stimulating factor is a hematopoietic growth factor that regulates the production and differentiation of neutrophils. OBJECTIVES: To clarify the role of elevated serum G-CSF levels in patients with active SS and active BD compared with those with inactive SS or BD and healthy controls. To then analyze neutrophil apoptosis in the active state of SS and BD; and to also investigate the influence of autologous serum on neutrophil apoptosis. METHODS: Serum G-CSF was examined in 5 patients with active SS, 7 with inactive SS, 7 with active BD, 9 with inactive BD, and 5 healthy controls by means of an enzyme immunoassay kit. We measured apoptotic cells in the neutrophil fraction of peripheral blood collections in patients with active diseases and controls by means of flow cytometry. RESULTS: Serum G-CSF level was significantly higher in patients with active SS than in those with inactive SS. The difference in serum G-CSF levels among patients with active and inactive BD was also significant. Serum G-CSF level was significantly higher in patients with active SS than in those with active BD. Neutrophil apoptosis was significantly higher in patients with active SS than healthy controls. This increased apoptosis rate was also seen in patients with active BD. The increased rate of neutrophil apoptosis was significantly suppressed when the neutrophils were cultured for 18 hours in the presence of autologous active SS serum. Similarly, neutrophil apoptosis was suppressed in the presence of autologous serum in patients with active BD, but not significantly so. CONCLUSIONS: These findings indicate that increased production of G-CSF in patients with SS and BD may play an important role in the manifestation of these disorders. Given the suppression of neutrophil apoptosis in the active state in the presence of the influence of autologous serum, which includes elevated G-CSF level, we propose that serum G-CSF plays a significant role in the suppression of neutrophil apoptosis. Furthermore, G-CSF-induced suppression of neutrophil apoptosis appears to be deeply involved in the pathogenesis of SS and BD.     

Palmoplantar keratoderma with an unusual composition of stratum corneum and serum sterol derivatives: a new entity?

Summary Little is known about the aetiology and pathogenesis of the different types of inherited and acquired palmoplantar keratodermas. We describe a condition of painful palmoplantar keratoderma with an altered stratum corneum lipid pattern which may be responsible for the excessive cornilication. Plantar stratum corneum lipids were analysed by quantitative thin-layer chromatography. Serum lipids, and the activities and gene loci of the enzymes serum steroid sulphatase and arylsulphatase C were also determined. Examination revealed that both the stratum corneum and the serum cholesterol sulphate (CS) content were significantly elevated in comparison with the stratum corneum cholesterol ester content. The cholesterol content was unchanged compared with controls. Serum activities of steroid sulphatase and arylsulphatase C were decreased, but not to the extent found in recessive X-linked ichthyosis. Their gene loci did not show any deletions.
This unique distribution of stratum corneum sterol derivatives, reflected by the elevated serum CS concentration, may contribute to the altered structural and functional properlies of intercellular lipid lamellae within the stratum corneum of this type of keratoderma.     

Hyperprolactinemia and hypophyseal hypothyroidism as cofactors in hirsutism and androgen-induced alopecia in women

A more comprehensive hormonal diagnosis than has previously been performed shows that androgen-dependent diseases of hair growth are due to more varied hormonal disturbances than elevated androgen serum levels alone. In 46 female patients with androgenic hair loss and 27 patients with hirsutism, the levels of the androgens testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulphate and 17-hydroxyprogesterone and of sex hormone-binding globulin, cortisol, oestradiol and the hypophyseal hormones follicle-stimulating hormone and luteinizing hormone were determined and compared with the hormone levels of 27 female patients without endocrine disorders. Of the androgens, only androstenedione showed a slightly significant elevation in hirsutism. Cortisol was elevated significantly in androgenic hair loss, and with a low degree of significance in hirsutism. In view of the complex hormonal interactions of thyroxin, prolactin and androgens and thyroid hormones the thyrotropin-releasing hormone (TRH)-stimulation test was performed in 38 female patients with androgenic hair loss and 27 with hirsutism, and the results were compared with those recorded in 45 female control persons. The test is based on feedback mechanisms between hypothalamic TRH and hypophyseal TSH and prolactin and peripheral thyroid hormones. Baseline concentrations of TSH prior to stimulation were significantly elevated in hirsutism, while in androgenic hair loss both baseline and stimulated TSH levels were significantly elevated; thus, hypothyroidism is a significant finding in both clinical pictures. In the case of prolactin, both baseline and stimulated levels were highly significantly elevated in hirsutism, while in androgenic hair loss the stimulated levels were significantly elevated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased serum immunoglobulin levels are common in mycosis fungoides and Sézary syndrome

BACKGROUND: Patients with cutaneous T-cell lymphoma (CTCL; mycosis fungoides [MF] and Sézary syndrome [SS]) acquire immunodeficiency and opportunistic infections. OBJECTIVE: We attempted to determine whether abnormalities of humoral immunoglobulin levels are present. METHODS: A retrospective analysis of serum immunoglobulin levels in patients with CTCL at baseline evaluation at a cancer center was compared to levels in patients with leukemias and levels in healthy control subjects. RESULTS: A total of 254 of 650 patients with CTCL evaluated between 1987 and 2001 had baseline quantitative immunoglobulin levels. Mean IgG, IgA, and IgM levels were similar among all MF/SS patients versus controls. The percentages of MF/SS patients with elevated levels of each immunoglobulin class were higher than percentages in healthy controls, and elevated IgA levels occurred among late versus early patients (P =.043). CONCLUSION: High immunoglobulin levels are more frequent in patients with MF and SS than in healthy controls, patients with chronic lymphocytic leukemia, and patients with hairy cell leukemia. High IgA levels are more frequent in late stage MF/SS.     

ELEVATED LEVELS OF CHEMOTAXIS INHIBITORY ACTIVITY IN SERA OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

An inhibitory activity against neutrophil chemotactic factors was found in normal human serum. Elevated levels of this chemotaxis inhibitory activity were demonstrated in sera of patients with systemic lupus erythematosus (SLE). The physico-chemical characteristics of this chemotaxis inhibitory substance(s) in SLE serum were almost identical to those of the inhibitory substance(s) in normal human serum; both the inhibitory substances were heat labile, soluble in 45% saturated ammonium sulphate, worked directly on chemotactic factor and affected various chemotactic factors. A study using Sephadex G- 100 chromatography showed that the molecular sizes of both inhibitory substances were almost identical. No correlation was found between the levels of the chemotaxis inhibitory activity in SLE sera and other clinical parameters including erythrocyte sedimentation rate, and serum concentration of either the third component of complement (C3) or the fourth component of complement (C4). Specimens from patients with the following diseases failed to demonstrate elevated levels of chemotaxis inhibitory activities; rheumatoid arthritis, urticaria, psoriasis vulgaris, atopic dermatitis and discoid lupus erythematosus (DLE).     

Psoriatic arthritis treated with oral zinc sulphate

Twenty-four patients suffering from psoriatic arthritis participated in a double blind cross-over trial of peroral zinc sulphate versus placebo (Trial I). Eleven patients continued an open trial of peroral zinc sulphate for an additional 24 weeks (Trial II). Remission was assessed by the disappearance of symptoms (overall condition, morning stiffness, functional capacity of the joints and joint pains), and signs (mobility and swelling of the joints). Reduction of joint pains as well as increase of mobility and decrease of swelling of several joints were observed. The clinical signs of reduced inflammation were accompanied biochemically by reduction of serum immunoglobulins and an increase of serum albumin. The need for analgesics was diminished. Severe side-effects and changes in the psoriatic skin involvement were not seen. Oral zinc sulphate seems to be valuable in the treatment of psoriatic arthritis.     

Carrier identification in steroid sulphatase deficiency and recessive X-linked ichthyosis

Steroid sulphatase (STS) activity was measured with tritiated dehydroepiandrosterone sulphate (DHEAS) and oestrone sulphate (OES) in leucocytes as well as in skin fibroblasts from 31 women who were presumed to be carriers of STS deficiency and recessive X-linked ichthyosis. Overall, 30 of the 31 women (96.8%) could be identified as heterozygotes in at least one of the four assay systems used, i.e. on the basis of having an STS activity below the 2.5 percentile calculated for normal control females. In the individual assay systems, the highest carrier detection rate was achieved with OES in leucocytes (96.2%), followed by DHEAS in leucocytes (80.8%), whereas a more pronounced overlap was present in the fibroblast systems. In leucocytes as well as in fibroblasts, the STS activity determined with DHEAS was positively correlated with the STS activity determined with OES (p less than 0.001) suggesting that a single sulphatase is responsible for the hydrolysis of both steroid sulphates.     

Pituitary function and DHEA-S in male acne and DHEA-S, prolactin and cortisol before and after oral contraceptive treatment in female acne

Pituitary function (TRH-LHRH stimulation test) was investigated in male acne patients and serum levels of dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and other biochemical parameters were investigated in male acne patients and in female acne patients before and after treatment with an oral contraceptive. The TRH-LHRH stimulation test was performed with 15 male patients suffering from severe cystic acne and 7 healthy volunteers. Basal and stimulated prolactin, LH and FSH levels were statistically similar in the patients and control groups. However, the stimulated LH levels of the patients were 60% higher than those in controls. SHBG levels were significantly) higher in the patient group compared to those in the control group. Thirty-three female acne patients were randomly divided into two groups and treated for six months with an oral contraceptive containing 0.030 mg ethinylestradiol (EE) plus 0.150 mg levonorgestrel or 0.150 mg levonorgestrel. After six months' treatment a 30% decrease in DHEA-S levels were observed in the desogestrel/EE group and a 15% decrease in the levonorgestrel/EE group; the difference was not statistically significant. At the same time serum total cortisol increased by 75-100% and free testosterone fell by 30-40% in both groups, whereas SHBG elevated 250% in the desogestrel/EE group and 30% in the levonorgestrel/EE group. Acne improved significantly in both groups, desogestrel/EE showing greater improvement. A decrease in SHBG and increase in DHEA-S levels appear to be the most common hormonal changes in acne. Oral contraceptive treatment induces an increase in SHBG and decrease in DHEA-S and also improves acne.