Updated evidence-based (S2e) European Dermatology Forum guideline on topical corticosteroids in pregnancy.

BACKGROUND: Topical corticosteroids may be needed for treating skin conditions in pregnancy. Nevertheless, only limited data on the fetal effects of topical corticosteroids are available. OBJECTIVE: To update an evidence-based guideline on the safe use of topical corticosteroids in pregnancy. METHODS: A guideline subcommittee of the European Dermatology Forum updated the guideline by adding and appraising new evidence. RESULTS: The current best evidence from 14 observational studies with 1 601 515 study subjects found no significant associations between maternal use of topical corticosteroids of any potency and some adverse pregnancy outcomes including mode of delivery, birth defect, preterm delivery and fetal death. However, maternal use of potent/very potent topical corticosteroids, especially in large amounts, is associated with an increase in the risk of low birthweight. CONCLUSION: Mild/moderate topical corticosteroids should be preferred to potent/very potent ones in pregnancy. The well-known topical side-effects of corticosteroids on the mother's side need to be considered as well.

[ASSOCIATION OF SKIN PHOTOTYPE AND UV EXPOSURE WITH EXPRESSION OF HER RECEPTORS, Ki67 AND p53 IN PATIENTS WITH CUTANEOUS SQUAMOUS CELL CARCINOMA].

An increase in the incidence of cancer, in particular skin cancer, has been observed in the last few decades. Skin cancer represents a significant public health problem in Croatia and worldwide. Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor arising in epidermal keratinocytes. Together with basal cell carcinoma it belongs to non-melanoma skin cancers, which are the most common cancers in humans. The lifetime risk of cSCC development in Caucasian population is nowadays estimated to about 15%, which makes it double compared to 20 years ago. The most probable causes are increased ultraviolet light (UV) exposure (exposure to artificial UV sources in suntan parlors, spending more time outdoors, changes in fashion, as well as ozone holes), and longer life expectancy. In its etiopathogenesis, important risk factors include genetic factors, fair-skin phototype, UV exposure, chronic degenerative and inflammatory conditions, chemical factors, oncogenic viruses, immunosuppression, ionizing radiation, as well as habitual risk factors. Human epidermal growth factor receptor (HER) family is involved in the control of multiple signal pathways. Their dysregulation is associated with development of many cancers such as breast carcinoma, non-small cell lung carcinoma, ovarian carcinoma, carcinoma of pancreas, head and neck carcinoma, as well as glioblastoma. The objective of our investigation was to establish if there is association of the skin phototype and UV exposure with the expression of HER receptors, Ki67 and p53 in patients with cSCC. Study group included 101 cSCC patients. Inclusion criteria were age >50, both sexes, histopathologically confirmed cSCC, no previous therapy, specimens sufficient for immunohistochemistry, and complete clinical data collected by a questionnaire. Material obtained by excisional biopsy was completely histopathologically evaluated and additional tissue slices were immunohistochemically analyzed. Statistical analysis of the sample included non-parametrical statistical methods and statistical reviews. Analysis was done using R statistical package. Statistical significance was set at p<0.05. The following skin phototypes (according to Fitzpatrick) were present in our study: 54 (53.47%) patients with phototype II and 47 (46.53%) patients with phototype III. The majority of patients (n=93; 92.08%) were exposed to increased UV radiation during lifetime. Forty (39.60%) patients had three or more sunburns during childhood. Study results showed a signifi cantly higher expression of EGFR receptors, Ki67 and protein p53 in patients with light skin phototype that had been exposed to increased UV light during lifetime or had acquired 3 or more sunburns in childhood, suggesting that UV exposure led to the induction of EGFR, Ki67 and protein p53, and consequently to development of cSCC.

Guidelines for treatment of atopic eczema (atopic dermatitis) part I.

The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune-suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.

Guidelines for treatment of atopic eczema (atopic dermatitis) Part II.

The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune-suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.

Evidence-based (S3) guideline on topical corticosteroids in pregnancy.

Women with skin conditions may need topical corticosteroids during pregnancy. However, little is known about the effects of topical corticosteroids on the fetus. A guideline subcommittee of the European Dermatology Forum was organized to develop an evidence-based guideline on the use of topical corticosteroids in pregnancy (http://www.euroderm.org/edf/images/stories/guidelines/EDF-Guideline-on-Steroids-in-Pregnancy.pdf). The evidence from a Cochrane Review suggested that the major possible adverse effects on the fetus of topical corticosteroids were orofacial clefts when used preconceptionally and in the first trimester of pregnancy, and fetal growth restriction when very potent topical corticosteroids were used during pregnancy. To obtain robust evidence, a large population-based cohort study (on 84,133 pregnant women from the U.K. General Practice Research Database) was performed, which found a significant association of fetal growth restriction with maternal exposure to potent/very potent topical corticosteroids, but not with mild/moderate topical corticosteroids. No associations of maternal exposure to topical corticosteroids of any potency with orofacial cleft, preterm delivery and fetal death were found. Moreover, another recent Danish cohort study did not support a causal association between topical corticosteroid and orofacial cleft. The current best evidence suggests that mild/moderate topical corticosteroids are preferred to potent/very potent ones in pregnancy, because of the associated risk of fetal growth restriction with the latter.

Contact allergy to corticosteroids and Malassezia furfur in seborrhoeic dermatitis patients.

BACKGROUND: Seborrhoeic dermatitis (SD) is a chronic skin disease, requiring long-term treatment, which might promote sensitization. Malassezia furfur (Mf) plays an important role in seborrhoeic dermatitis. Objectives The aim of this study was to determine the frequency of contact sensitivity in SD patients. PATIENTS AND METHODS: A total of 100 patients and 20 healthy controls (HC) were investigated: 50 suffering from SD with no previous local corticosteroid treatment (SDN), 50 SD patients treated with local corticosteroids (SDC). Mycological examination for Mf was performed. All patients were patch tested with the baseline standard, corticosteroid series, with 12 commercial corticosteroid preparations frequently used in Croatia; and also with Mf. RESULTS: Malassezia furfur was found in 44 (88%) SDN, 37 (74%) SDC, and in 4 (20%) HC; patch test reaction to Mf was positive in one SDN and in three SDC. Positive patch tests to standard allergens were observed in 17 (34%) SDN, 33 (66%) SDC and 2 (10%) HC. Patch tests to the corticosteroid series revealed positive reactions in 4 SDC and to commercial corticosteroids in seven patients, i.e. 2 SD and 5 SDC. CONCLUSIONS: Patch tests to the baseline series and to both individual corticosteroid and commercial corticosteroid preparations should be performed in SD patients with persistent dermatitis, as contact-allergic reactions may complicate their dermatitis. Sensitization to Mf was found to be infrequent.

A case of lichen ruber planus in a patient with familial multiple sclerosis.

Multiple sclerosis and lichen ruber planus are clinically and histologically distinct complex disorders of putative autoimmune aetiology that are fairly commonly observed in isolation but rarely found in combination. Only two previous reports have described lichen skin disorders in association with multiple sclerosis. The present report describes the case of a 51-year-old Caucasian woman exhibiting both familial multiple sclerosis and lichen ruber planus. This combination may have occurred by chance or it might imply that these disorders share common mechanisms in their pathogenesis.

Interest of the association retinaldehyde/glycolic acid in adult acne.

BACKGROUND: Topical retinoids have been successfully used in the treatment of acne vulgaris but may induce irritation when used twice daily. The association of retinaldehyde (RAL) with glycolic acid (GA) have complementary activities, which could be of interest for adult women with acne because of a better tolerance/efficacy ratio. The aim of this study was to evaluate the tolerance and the efficiency of RAL (0.1%)/GA (6%) in adult women with acne when used alone or in combination with their usual acne products except retinoids. METHODS: Three hundred ninety-seven women with acne (aged between 30 and 40 years old) were included in this open multicentric study. They had to apply cream containing RAL/GA for 90 days without stopping their previous acne treatment (except topical retinoids). The tolerance was the main criteria and the second one is the efficacy, which was assessed by counting inflammatory and retentional lesions after 30 and 90 days of treatment. RESULTS: Used alone or in association with other anti-acne treatments, RAL/GA was considered to be highly tolerated. A significant decrease in both inflammatory and retentional lesions between day 0 and day 90 indicates that RAL/GA can be used as monotherapy for mild acne or could potentate the efficiency of other anti-acne products used at the same time by patients suffering from moderate acne. Complaints about side-effects were rare. The subjective evaluation of the preparation's efficacy by investigators and patients was strongly favourable. CONCLUSION: These data show that a combination of RAL 0.1% and GA 6% may be used in association with other topical anti-acne treatments with an excellent tolerance.

Serum eosinophil cationic protein in children with atopic dermatitis.

BACKGROUND: Eosinophil cationic protein (ECP) is a cytotoxic agent secreted by activated eosinophils during allergic and inflammatory processes. The aim of the study was to determine the ECP level, absolute and relative eosinophil count and IgE antibodies in children with atopic dermatitis (AD) compared with those of nonatopic children, and to assess the correlation of these laboratory parameters with the clinical severity of AD. METHODS: This prospective study comprised 70 children. There were 49 children with AD aged 3-36 months, and the control group comprised 21 children with a negative personal and family history for atopic diseases. Detailed history, serum ECP levels (UniCAP FEIA), relative and absolute eosinophil counts and total serum IgE antibodies were determined in both groups. In the children with AD, skin involvement was measured by the SCORAD index. RESULTS: The calculated SCORAD index was between 16 and 83. IgE antibodies, relative and absolute eosinophil counts showed a significantly wider range of values and a statistically higher median (P < 0.001) in the patients with AD compared with the control group. These laboratory parameters did not correlate with the severity of AD. The serum ECP median level, in the children with AD, was 16.2 microg/L (range 3.01-65.30) compared with 5.92 microg/L (range 2.76-21.90) in the control group. Correlation of the total SCORAD index and the serum ECP levels was negative, weak (r = -0.065) and statistically not significant (P > 0.05). The same was found for the correlation of serum ECP and intensity of skin changes (r = -0.095) and serum ECP and subjective symptoms (r = -0.045). The correlation was positive, but weak and statistically not significant for the serum ECP and extent of the skin lesions (r = 0.079, P > 0.05). CONCLUSION: Elevated levels of ECP, relative and absolute eosinophil counts, as well as IgE antibodies were determined in the patients with AD. As these laboratory findings did not correlate with the severity of AD, they can be considered only as additional methods in the evaluation of patients with AD.

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report.

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Perifolliculitis capitis abscedens et suffodiens.

Perifolliculitis capitis abscedens et suffodiens (PCAS) is rare chronic, suppurative and inflammatory scalp disease. Its aetiology and pathogenesis is not completely understood. The treatment is usually difficult and often disappointing. We report a case of 29-year-old male who presented with tender, fluctuant nodules and abscesses, with draining pus and patchy alopecia on his scalp for 3 years. A skin biopsy from scalp lesions revealed features that are characteristic of perifolliculitis. Initially, the patient was treated with periodic incision and drainage of the scalp abscesses. The answer was very poor. When admitted to our department, isotretinoin was started at daily dose of 30 mg, because initially his cholesterol and triglyceride levels were mildly increased. When dose was reduced to 10 mg the levels of cholesterol and triglyceride remained normal. A response to treatment was excellent and rapid. The treatment of PCAS represents usually difficulties and frustration for both the patient and the physician. A long course of isotretinoin can be considered as one of the most effective treatment for PCAS.

Pemphigus vulgaris: a review of treatment over a 19-year period.

BACKGROUND: Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes with a high mortality if left untreated. OBJECTIVE: We present a retrospective analysis of 159 patients with pemphigus vulgaris and pemphigus vegetans who were admitted to the Department of Dermatology and Venereology, Zagreb University Hospital Center (Zagreb, Croatia) from 1980 to 1998. RESULTS: Female to male ratio was approximately 2:1. The mean age was 53 years. During the war years in Croatia (1991-95) we noticed a low incidence of pemphigus vulgaris, and from 1996 to 1998 the incidence almost doubled. Diagnosis was based on histopathology [showing typical pemphigus vulgaris changes in 156 (98%) patients], indirect immunofluorescence [positive in 122 (77%) patients], direct immunofluorescence [positive in 141 (89%) patients], and blister smear cytology (Tzanck test) [positive in 115 (72%) patients]. High dosages of prednisone (100-150 mg) were given to 129 patients, which was combined with azathioprine. Patients with refractory pemphigus vulgaris were treated with intramuscular gold (14 patients) and plasmapheresis (five patients). All patients were treated with local ointments. The prolonged use of high doses of corticosteroids and immunosuppressants caused several complications, in particular, steroid diabetes (37 patients), skin infections (26 patients), arterial hypertension (23 patients), cardiorespiratory diseases (22 patients), sepsis (nine patients), etc. During the hospital treatment, 14 patients died, 10 during 1980-89 and only four during the 1990-98 period. The main causes of death were cardiorespiratory failure (six patients) and sepsis (five patients). CONCLUSIONS: Although pemphigus vulgaris is still a life-threatening disease, today it can be successfully treated with a combination of immunosuppressive agents. Early diagnosis and treatment of pemphigus vulgaris allow a better prognosis with lower mortality rates.

A randomized, double-blind, parallel-group, duration-finding study of oral terbinafine and open-label, high-dose griseofulvin in children with tinea capitis due to Microsporum species.

BACKGROUND: Tinea capitis, a common clinical pattern of dermatophyte infection in children is becoming a public health hazard in some countries. Several studies have reported terbinafine to be a safe and well-tolerated fungicidal drug for the treatment of this infection. However, the optimal treatment duration for its use in the treatment of tinea capitis caused by Microsporum species has not yet been determined. OBJECTIVE: (i) To establish the optimal duration for terbinafine treatment to bring about complete cure of tinea capitis due to Microsporum infection in a large paediatric population, and (ii) to obtain information on the maximum therapeutic effect of the existing therapy. PATIENTS AND METHODS: This parallel-group, double-blind, multicentre study was conducted in Europe and South America. Patients were randomized to one of four oral terbinafine treatment arms (6, 8, 10 or 12 weeks treatment) or to an open label, 12-week, high-dose griseofulvin (20 mg x kg(-1) x day(-1)) arm at a 1 : 1 : 1 : 1 : 1 ratio. All patients were followed up for 4 weeks after the end of the treatment phase. RESULTS: In this group of 134 intention-to-treat patients, effective treatment was observed at the end of study in 62% of patients treated with terbinafine for 6 weeks and in 63% treated for 8 weeks. Mycological cure was obtained in 59% and 57%, respectively, and clinical cure in 76% and 80%. In the griseofulvin group, effective treatment was 88%, mycological cure was 76% and clinical cure 96%. However, these high rates were believed to be due to the high dosage of this drug and the prolonged course of treatment. Complete cure was observed at the end of study in 62% patients treated with terbinafine for 6 weeks, in 60% treated for 8 weeks and in 84% patients treated with griseofulvin for 12 weeks. CONCLUSIONS: Although there was no statistical trend between the duration of terbinafine treatment within the groups for complete cure at the end of study, there was a positive correlation between the daily dose of terbinafine (mg x kg(-1)) and complete cure. Terbinafine therapy for 6 weeks could represent an alternative to griseofulvin for the treatment of Microsporum tinea capitis. However, further clinical trials are required in order to optimize the dose regimen to allow higher cure rates to be reached.

Sepsis as an unusual event in dyskeratosis follicularis.

Dyskeratosis follicularis is a genetic disorder characterized by pathogenetic changes of keratinization. We report on a severe case of the disease with an unusual manifestation involving Staphylococcal sepsis. The patient was treated systemically with infusions, oral antibiotics, and retinoids. Antiseptics, keratolytic ointments, and creams were given topically to promote epithelization. His condition improved dramatically after 14 days of treatment. All erosions of the trunk, extremities, neck, and head had epithelized. We suspect that extreme sun exposure and neglect of care on genetically susceptible sites triggered the sepsis.

Tinea incognito caused by trichophyton mentagrophytes -- a case report.

A case of widespread tinea due to Trichophyton mentagrophytes is described. A healthy 75-year-old woman presented with 134 typical tinea corporis and faciei lesions previously treated with topical steroids. The diagnosis was based on direct mycologic examination and culture. The treatment with oral administration of terbinafine for four weeks and topical application of clotrimazole resulted in complete clinical resolution of the lesions