Methotrexate vs. ciclosporin in psoriasis: effectiveness, quality of life and safety. A randomized controlled trial.

BACKGROUND: When this study was initiated, no previous studies comparing methotrexate and ciclosporin for moderate to severe plaque psoriasis had been performed. OBJECTIVES: To compare the effectiveness, quality of life and side-effects of methotrexate and ciclosporin treatments in a context reflecting normal clinical practice. METHODS: Eighty-four patients with moderate to severe plaque psoriasis were randomized to treatment with methotrexate or ciclosporin for 12 weeks. The primary outcome was the Psoriasis Area and Severity Index (PASI). The secondary outcome was quality of life, measured by the Dermatology Life Quality Index (DLQI) and the 36-item Short Form Health Survey (SF-36). A visual analogue scale (VAS) was used for patients' assessment. RESULTS: Sixty-eight patients started treatment and were included in the analysis. Dropout before initiation of treatment was higher in the ciclosporin group. Mean PASI change from baseline at 12 weeks was 58% in the methotrexate group and 72% in the ciclosporin group, showing ciclosporin to be more effective than methotrexate. Improvement of the VAS score was higher in the ciclosporin group. The methotrexate group showed a greater improvement in the subscale Physical Functioning of the SF-36. No significant difference between the groups was found for DLQI. CONCLUSIONS: Treatment with methotrexate or ciclosporin for chronic plaque psoriasis brings satisfactory disease control, improved quality of life and tolerable side-effects. A statistically significant difference in effectiveness between treatment groups was recorded, showing ciclosporin to be more effective than methotrexate in a short-term perspective.

Seborrhoeic dermatitis and Pityrosporum (Malassezia) folliculitis: characterization of inflammatory cells and mediators in the skin by immunohistochemistry.

BACKGROUND: The fact that Pityrosporum ovale plays a part in seborrhoeic dermatitis is well established but the mechanism of this relationship has not been established. OBJECTIVES: To compare the number and type of inflammatory cells and mediators in skin biopsies from normal and lesional skin from the trunk and scalp in patients with seborrhoeic dermatitis, Pityrosporum (Malassezia) folliculitis and in normal skin from healthy controls. METHODS: The skin biopsies were stained using the labelled Streptavidin-biotin METHOD: The following markers were studied: CD4, CD8, CD68, HLA-DR, NK1, CD16, C1q, C3c, IgG, CD54 (ICAM-1), interleukin (IL) -1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, tumour necrosis factor-alpha and interferon-gamma. RESULTS: HLA-DR+ cells were seen in the highest number, and were higher in lesional skin compared with normal skin from both patients and healthy volunteers. ICAM-1 expression was also increased in lesional skin. C1q and the interleukins showed an increased cellular and intercellular staining in patients compared with healthy controls and the intercellular staining was often more intense in lesions compared with non-lesional skin. Staining was often more intense when Malassezia (Pityrosporum ovale) yeast cells were present. CONCLUSIONS: An increase in NK1+ and CD16+ cells in combination with complement activation indicates that an irritant non-immunogenic stimulation of the immune system is important. The result with the interleukins showed both an increase in the production of inflammatory interleukins as well as in the regulatory interleukins for both TH1 and TH2 cells. Similarities to the immune response described for Candida albicans infections indicate the role of Malassezia in the skin response in seborrhoeic dermatitis and Pityrosporum folliculitis.

Cell-mediated immunity to Malassezia furfur in patients with seborrhoeic dermatitis and pityriasis versicolor.

The lymphocyte transformation response to Malassezia furfur, Candida albicans, phytohaemagglutinin, concanavlin A and tuberculin purified protein derivative of 12 patients with pityriasis versicolor, 15 patients with seborrhoeic dermatitis and matched controls, was studied. Patients with pityriasis versicolor showed a significantly lower response to M. furfur than patients with seborrhoeic dermatitis and controls.

PCR detection of Epstein-Barr virus, herpes simplex virus and human papillomavirus from the anal mucosa in HIV-seropositive and HIV-seronegative homosexual men.

This study aimed to examine the prevalence of the Epstein-Barr virus (EBV), herpes simplex virus (HSV) and human papillomavirus (HPV) in the anal and oral mucosa of homosexual men with and without HIV infection and to correlate these findings to CD4+ count and anal cytology. Anal and oral cell samples from 20 HIV-infected and 14 non-infected homosexual men attending the STD clinic at Sahlgrenska University Hospital, Goteborg were examined for EBV, HSV and HPV by the polymerase chain reaction (PCR) technique. Proctoscopy was performed in all patients and swabs for cytology were taken. EBV was demonstrated in 32% (6/19) of anal cell samples from the HIV-positive group but in none from 13 HIV-negative men. Asymptomatic shedding of HSV type 2 from the anus was detected in 3 of 19 HIV-positive men, all with low CD4+ counts and abnormal cytology. No patient in the HIV-negative group shed HSV from the anus. HPV was demonstrated in 16 of 17 anal cell samples in the HIV-infected group and in 7 of 13 HIV-negative men. More than one HPV type was detected in 7 HIV-infected men. Five (29%) of 17 HIV-positive patients exhibited abnormal cytology whereas none did so in the HIV-negative group. Those with abnormal cytology all had CD4+ counts below 0.35 and were infected with multiple HPV types including HPV 16/18. In conclusion, our results demonstrate an enhanced expression of HPV as well as EBV from the anus in HTV-infected homosexual men. In this small number of patients EBV was not related to low CD4+ count or to abnormal cytology.

Quantitative cultures of Candida from mouthwash fluid in HIV-infected patients: a longitudinal study.

The density of Candida colonization in mouthwash fluid of 59 HIV-seropositive patients and 21 controls was determined. No significant difference in colony-forming units was found. No correlation was found between the colonizing density of Candida albicans and the CD4 count among the patients. Twenty-seven of the HIV-seropositive patients were followed for almost 3 years. No difference was found between the number of Candida albicans colony-forming units at the first and second time of sampling. Vaccination with HIV IIIB GP 160 vaccine did not have any influence on the prevalence of Candida albicans.

Seborrhoeic dermatitis and Pityrosporum yeasts.

The connection between P. ovale and seborrhoeic dermatitis has been clearly demonstrated in a number of treatment studies but we still do not know how P. ovale induces skin lesions. An enhanced growth of P. ovale cannot be the cause, because a number of studies with quantitative determinations of P. ovale have not been able to show any difference in the number of yeast cells between patients and healthy controls. The number of P. ovale is probably only important for the individuals who are susceptible to seborrhoeic dermatitis. An abnormal immune response to P. ovale could be another explanation. Sohnle et al. have shown that P. ovale can activate complement by both the classical and the alternative pathway. A defective cell-mediated immunity to P. ovale in patients with seborrhoeic dermatitis has been demonstrated by Wikler et al. In patients with AIDS, who are known to have a diminished T-cell function, a high incidence of seborrhoeic dermatitis has been found. Activation of the alternative complement pathway by P. ovale, which does not require T-cell function, could be an explanation for the inflammatory response. I also believe that the skin lipids are important in the pathogenesis. An improvement of seborrhoeic dermatitis has been demonstrated after treatment with drugs that reduce the sebum excretion. Pityrosporum has lipase activity and may generate free fatty acids, which could also contribute to the inflammatory response. There are a number of factors which are probably important in the pathogenesis of seborrhoeic dermatitis, that is, the number of P. ovale, P. ovale lipase activity, skin lipids, immune function, heredity, atmospheric humidity and emotional state. A reduction in the number of P. ovale in patients suffering from seborrhoeic dermatitis and being treated with antimycotic treatment is, at the present state of knowledge, the best way to treat the disease.

Polymerase chain reaction for monitoring human papillomavirus contamination of medical personnel during treatment of genital warts with CO2 laser and electrocoagulation.

Genital warts and intraepithelial neoplasia caused by infection with human papillomavirus are usually treated with CO2 laser or electrocoagulation. In this study, contamination of personnel and operating theatres with human papillomavirus DNA during treatment sessions was investigated. Samples were taken from the nostrils, nasolabial folds and conjunctiva of the operating physician before and after operating sessions and from Petri dishes left open in the operating theatres. Human papillomavirus DNA was demonstrated by the polymerase chain reaction technique. The results show that there is a risk of contamination of the operator by human papillomavirus DNA, detectable with the polymerase chain reaction technique, during both CO2 laser and electrocoagulation treatment.

Pityrosporum ovale culture from the forehead of healthy children.

One hundred and thirty-eight children aged between 2 months and 15 years were investigated to determine the prevalence and quantity of the yeast Pityrosporum ovale. Samples were taken from the forehead and cultured on a medium containing cow's milk, glycerol, glycerol monostearate and Tween 60 as the lipid source. Eighty-seven per cent of all children were positive in the qualitative culture. The largest number of colonies of P. ovale was found among children aged 2-23 months and among children older than 9 years.

Adherence of Malassezia furfur to human stratum corneum cells in vitro: a study of healthy individuals and patients with seborrhoeic dermatitis.

The role of Malassezia furfur adherence to human stratum corneum cells in vitro was studied. The adherence assay was performed with one strain of M. furfur and stratum corneum cells from 30 healthy individuals and from 28 patients with seborrhoeic dermatitis. Stratum corneum cells from patients with seborrhoeic dermatitis contained significantly lower numbers of adherent M. furfur cells than cells from healthy individuals. No correlation was found with sex or age. The adherence assay was also performed with stratum corneum cells from one healthy individual and M. furfur strains from 15 patients with seborrhoeic dermatitis and 13 healthy controls. Malassezia furfur strains from patients with seborrhoeic dermatitis showed the same in vitro capacity for adherence to stratum corneum cells as strains from healthy individuals. This in vitro study does not indicate that M. furfur adherence to human stratum corneum cells is of importance in the pathogenesis of seborrhoeic dermatitis.

An improved method for quantitative culture of Malassezia furfur.

Quantitative culture of Malassezia furfur from clinically healthy skin in 25 individuals was performed with two different methods using contact plates. The best results were obtained when a glucose peptone yeast extract medium, with the addition of milk, Tween-60, glycerol and glycerol monostearate was used. Different techniques for incubation and the reproducibility of this method were evaluated. Incubation can be done in a plastic bag at 32 or 37 degrees C. This new method is simple, the colonies are easy to identify and the counts are high and reliable.

The in vivo effect of UVB radiation on skin bacteria in patients with atopic dermatitis.

Fourteen patients suffering from atopic dermatitis under treatment with UVB radiation were subjected to aerobic bacterial cultures in order to investigate whether this ultraviolet waveband has any in vivo germicidal effects, and, if so, whether there is a correlation with clinical improvement. Treatments were given 3 times a week for 8 weeks. Bacterial samples were collected before, midway and after the termination of therapy. On the latter two occasions, cultures were performed 30 min and 24 h post-UVB irradiation. The main bacteria found were Staphylococcus epidermidis and S. aureus. S. aureus carriage was found in 12 patients in lesional, dermatitic skin, and in 11 patients in clinically non-lesional skin. UVB radiation was found to have an antimicrobial effect primarily concerning S. aureus. Bacterial counts of this organism in lesional skin were decreased from a mean of 1.3 x 10(3) to 1.2 x 10(1) bacteria per cm2 skin at the 8-week 30-min count (p less than 0.01) and 7.5 x 10(1) at the 8-week 24-h count (p less than 0.05). The treatment yielded a statistically significant clinical improvement.

An immunological study in patients with seborrhoeic dermatitis.

The humoral and cellular immune-status was studied in 30 patients with seborrhoeic dermatitis. Increased frequencies of natural killer cells were found in 46% of patients. Furthermore, subnormal mitogen stimulation responses were demonstrated in 13 patients, whereas two individuals were found to have very high numbers of activated T lymphocytes in peripheral blood. Higher-than-normal total serum IgG and IgA was observed in 14 and 11 patients, respectively. For nine of 12 patients with skin lesions, dermal perivascular cell infiltrates were seen. The majority of the infiltrating cells reacted with anti-CD4 antibodies. HLA-DR-expressing keratinocytes were found in two biopsies. The study suggests that patients with seborrhoeic dermatitis may have depressed T-cell function. This could have a bearing on their susceptibility to the Pityrosporum ovale-associated dermatitis. The very high frequencies of activated T cells observed in the peripheral blood of two otherwise healthy seborrhoeic individuals suggests that intermittent systemic immune activation may occur. Seborrhoeic dermatitis is a common skin disease. It can be diagnosed by its characteristic red to yellow-brown lesions covered with greasy scales distributed in areas with a high number of sebaceous glands, such as the scalp, face and upper trunk. There is an association between seborrhoeic dermatitis and the lipophilic yeast Pityrosporum ovale but its exact aetiological role is not known. The yeast is a member of the normal cutaneous flora but also the aetiological agent of pityriasis versicolor and Pityrosporum folliculitis. P. ovale can activate complement via the direct and alternative pathways. This may play some part in the induction of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

The evaluation of various methods and antigens for the detection of antibodies against Pityrosporum ovale in patients with seborrhoeic dermatitis.

Sera from 10 patients with seborrhoeic dermatitis and from 10 age-matched healthy individuals were examined for IgG activity against Pityrosporum ovale. The IgG activity was analysed using the following techniques: an enzyme-linked immunosorbent assay (ELISA) against whole P. ovale cells, purified cell-wall carbohydrate or protein extract, an indirect slide-immunofluorescence assay and fluorescence-activated flow cytometry using the whole organism as antigen. The ELISA method using the protein antigen was the only technique that showed a significant difference between patients and controls; a lower antibody response was found in the seborrhoeic dermatitis patients compared to healthy controls.

Seborrhoeic dermatitis and Pityrosporum ovale: cultural, immunological and clinical studies.

Seborrhoeic dermatitis is a common skin disease mainly affecting the scalp and face. The etiology of seborrhoeic dermatitis is unknown but a connection with the lipophilic yeast Pityrosporum ovale has been found in a number of treatment studies. P. ovale belongs to the normal cutaneous flora but is also an opportunistic pathogen. The purpose of these studies was to examine how the density of P. ovale changes with age, to determine the number of P. ovale in seborrhoeic dermatitis compared to controls, to study the immunological functions in patients with seborrhoeic dermatitis, to evaluate different methods of detecting antibodies against P. ovale and to describe how the patients experience their disease. The number of P. ovale on clinically normal skin decreases with increasing age. In patients with seborrhoeic dermatitis, the number of P. ovale in lesional skin was not increased compared to healthy skin in the patients or in healthy controls. A reduction of the skin surface lipids was seen in elderly healthy individuals. The lipid content on the skin in patients with seborrhoeic dermatitis was higher than in controls (p = 0.0001). Serum IgG antibodies against P. ovale measured with indirect immunofluorescence decreased parallel to increasing age in healthy individuals and no difference was found between patients with seborrhoeic dermatitis and healthy controls. ELISA with a P. ovale protein extract was the only method that demonstrated a difference in immune response between patients and controls when this method was compared with four other assays (p = 0.03). Immunological screening was done in 30 patients with seborrhoeic dermatitis. No major abnormalities in the humoral and local immune system were found but T-cell and NK-cell aberrations were found in several patients with seborrhoeic dermatitis. One-third of the patients had low lymphocyte stimulations with Concanavalin-A and phytohaemagglutinin and almost half of the patients had high frequencies of circulating natural killer-cells. In a questionnaire answered by 431 patients with seborrhoeic dermatitis, we found indications that hereditary, the season, mental stress and the work environment influence the disease. The investigations suggest that the number of P. ovale in seborrhoeic dermatitis is of minor importance. How each individual reacts to P. ovale and the amount of skin surface lipids are probably of greater importance in the development of seborrhoeic dermatitis.

The role of Pityrosporum ovale in seborrheic dermatitis.

This paper discusses the relation between the lipophilic dimorphic yeast Pityrosporum ovale and seborrheic dermatitis. A review of studies concerning the microbiology in seborrheic dermatitis and immune reactions to P ovale are given. In our own studies with quantitative cultures, no significant difference was found in the number of P ovale in patients compared with controls, or between healthy and lesional skin in the patient group. IgG serum antibodies against P ovale cells estimated with indirect immunofluorescence did not show any difference between patients and controls, but a significant difference was found when a P ovale protein extract and ELISA were used. Immunological investigation on serum samples were done on 30 patients with seborrheic dermatitis. Defects were found in their T-cell function. The number of P ovale is of importance in those individuals who are susceptible to seborrheic dermatitis and the development of the disease depends on the way their immune system reacts to the antigens derived from P ovale.

Immune reactions to Pityrosporum ovale in adult patients with atopic and seborrheic dermatitis.

Pityrosporum ovale is a lipophilic yeast commonly present in the seborrheic areas of the skin of adults. Fifty-five young adult patients with atopic dermatitis, 19 patients with seborrheic dermatitis, and 19 healthy control subjects were examined for immune reactions to P. ovale, including tests for specific IgE antibodies (prick test, histamine release), IgG antibodies and epicutaneous testing. IgE antibodies against P. ovale were found in two thirds of the patients with atopic dermatitis and were more frequent in patients with lesions predominantly in the seborrheic areas. In addition, some atopic patients had positive reactions to epicutaneous tests, which suggest that delayed allergic reactions to P. ovale may also be important. In patients with seborrheic dermatitis, no evidence of immediate or delayed hypersensitivity to P. ovale was found. IgG antibody levels were low in all groups.

Seborrhoeic dermatitis and Pityrosporum ovale: a cultural and immunological study.

Seborrhoeic dermatitis is associated with Pityrosporum ovale, but the exact role of the organism is not clarified. In order to study this connection we have investigated 30 patients with seborrhoeic dermatitis with quantitative culture for P. ovale, serum IgG antibodies against P. ovale and lipid measurements. We compared the patients with 60 healthy individuals and found no significant difference in the number of P. ovale or serum antibodies. The lipid content on the skin was significantly higher in the patient group (p = 0.0001). There was no difference in the number of P. ovale in lesions compared to healthy skin in the patient group. This study support our theory that an abnormal reaction in the skin to P. ovale causes the inflammation and the number of P. ovale is of minor importance.