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 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.

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.

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.

Detection and typing of human papillomaviruses by means of polymerase chain reaction and fragment length polymorphism in male genital lesions.

We investigated the distribution of genital human papillomaviruses (HPVs) among 171 consenting men of which four were involved twice in this study. The DNA was obtained from 7 normal tissues and 168 genital lesions of which 115 were diagnosed as condylomata acuminata, 17 as condylomata plana and 36 as HPV-associated lesions (papules, lichen-like lesions, etc.). The DNA samples were analysed for the presence and type of HPV DNA (HPV type 6, 11, 16, 18, 31 or 33) by means of polymerase chain reaction (PCR). Out of 175 specimens tested, 140 (80%) were HPV positive and 35 (20%) HPV negative. There were 81.43% (114 out of 140) typed HPVs, while 18.57% (26 out of 140) remained untyped. Most samples were HPV 6/11 positive (92 out of 114, 80.7%). Restriction fragment length polymorphism (RFLP) of HPV 6/11 PCR products in 89.13% (82 out of 92) and 10.87% (10 out of 92) specimens corresponded to HPV 6 and HPV 11, respectively. The frequency of other HPVs was low, i.e. there were 4.57% (8 out of 175), 1.71% (3 out of 75) and 0.57% (1 out of 175) HPV type 16, 18 and 33, respectively. There were 10 out of 175 (5.71%) cases of multiple HPV infections, of which 6 out of 10 were cases with HPV 6 and other HPV types. This raises the total prevalence of HPV type 6 to 50.29% (88 out of 175) in the study-population. The clinical diagnosis condylomata acuminata was preferentially associated with low-risk HPVs (types 6 and 11), while other lesions, especially condylomata plana, with high-risk HPVs (types 16, 18, 31 and 33) and untyped HPVs. The male population, indeed, represents a reservoir of HPV infection and directly influences cervical cancerogenesis.

Langerhans cells in the immunopathology of contact allergic dermatitis.

The functional morphology, topography and frequency of Langerhans cells (LCs), which are significant factors in the pathogenesis of contact allergic dermatitis (CAD), were studied by histoenzymatic methods (adenosine triphosphatase (ATP-ase), acid phosphatase (AF) and alpha naphtylacetate esterase (ANAE), immunohistochemical methods (indirect immunoperoxidase (IPO) with the monoclonal antibody OKT 6), and the peroxidase-antiperoxidase (PAP) method with the polyclonal S-100 antibody in skin biopsies of 24 patients with CAD, as well in skin biopsies in experimental models in guinea pigs. The results confirmed the significant role of LCs in the pathogenesis of contact allergic dermatitis.

Prostaglandins in dermatology.

Prostaglandins, local hormones, are produced by almost every tissue and organ in the body (except for erythrocytes). They are active at the site of their production or next to the cells that secrete them. Prostaglandins play an important biological role, because they are involved in many physiological and pathological processes. Some of their effects are still unknown. They are involved in inflammatory process of the skin. They have been implicated as possible mediators of contact allergic dermatitis and among others, act in immune response. The use of prostaglandin in dermatology is still experimental. In the near future, they might be use in therapy for systemic scleroderma, aberration of extremity circulation with ulcers, vasculitis, etc. An overview is provided of prostaglandins in dermatology.

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

Are respiratory allergic diseases related to atopic dermatitis?

The difference of test results between patients with "pure" atopic dermatitis (AD) and "mixed" AD (with concomitant respiratory allergy, RA) was investigated in 30 AD patients. The results showed the onset of disease that mostly occur in the early infancy [15 (50%) patients had developed the disease under the age of 2-2/10 in "pure" AD, and 13/20 in "mixed" AD]. Twenty (66.6%) of them had a history of RA ("mixed" AD) whereas the remaining 10 (33.3%) had "pure" AD. Seventeen (56.6%) AD patients had one concomitant allergic disease, while 3 (10%) patients had two comorbid conditions (AR and AB) each. Family history was positive for atopy in 22 (73.3%) AD patients [in 14 (46.6%) patients in a first-degree relative]. Twenty-four (80%) patients had positive prick test [9/10 (90%) in "pure" AD and 15/20 (75%) in "mixed" AD], mostly for house dust (20). Positive scratch test was observed in 16 (53.3%) patients [4/10 in "pure" AD, and 12/20 in "mixed" AD]. Nineteen (63.3%) AD patients showed positive patch test reaction [5/10 in "pure" AD, and 14/20 in "mixed" AD]. AD patients had higher serum IgE (21/30) than non-atopic ones but similar in "pure" AD, and "mixed" AD [7/10 (70%) in "pure" AD, and 14/20 (70%) in "mixed" AD]. Determination of CD23 marker on B-lymphocytes showed normal values in 24, and increased values in six patients [2/10 in "pure" AD, and 4/20 in "mixed" AD]. The values of CD21 were decreased in 16 AD patients [6/10 in "pure" AD, and 10/20 in "mixed" AD]. HLA-DR expression was normal in almost all patients. There were no statistically significant differences (p < 0.05) between the "pure" AD and "mixed" AD patient groups, except for the age at onset, which was younger in the group of patients with concomitant RA. Accordingly, study results pointed to the association between AD and RA.

Contact hypersensitivity in atopic dermatitis.

From January 1990 to December 1994, a total of 84 patients (56 men and 28 women) with atopic dermatitis (AD) were referred to our Clinic for patch testing. The European standard series of allergens was applied to all subjects together with any additional series indicated in the case history. Sensitization to at least one of the allergens was found in 57.1% of individuals with AD. Positive reactions were more frequently determined in adults than in children with AD. Women and men were equally positive in epicutaneous testing. The commonest sensitizer was nickel sulfate (discriminative in 28.6%). Adult patients with atopic dermatitis significantly differed from patients with chronic urticaria or healthy controls in patch test positive results. Our findings suggest that allergic contact dermatitis is more common in patients with AD than generally assumed and that patch testing is a practicable and clinically worthwhile procedure for determining allergic contact dermatitis in patients with AD.

Values of complement, T- and B-lymphocytes and immune complexes in patients with skin allergies.

The aim of this pilot study was to determine the values of total complement, C3 and C4 fractions, C1-esterase inhibitor, T- and B-lymphocytes, and immune complexes in our patients with skin allergic disease. The purpose was to investigate the probability of type III hypersensitivity reaction in the development and onset of skin allergies. The values of these parameters were determined in ten patients with atopic dermatitis and ten patients with chronic allergic urticaria. Results showed most of the study subjects with atopic dermatitis (7/10) to have increased CH50 values, a finding not observed in the patients with chronic allergic urticaria (2/10) and healthy controls (0/10). No major changes in other parameteres were found in any of the patient groups. A statistically significant difference (p < 0.05) was found among the three groups in CH50 and C4 values.

Neomycin--a frequent contact allergen.

The incidence of allergic contact dermatitis from neomycin evaluated in relation to 1381 verified cases of allergic contact dermatitis showed a progressive increase (5.00, 7.69, 10.18%) over a three-year period (1990-1992). Sensitivity to neomycin was investigated with special reference to possible cross-reactions between neomycin and the allergens that are commonly used in the manufacture of cosmetic products. Contact sensitivity to neomycin was found to be present with the other diagnoses, such as atopic dermatitis, seborrhoeic dermatitis, hypostasic dermatitis and psoriasis vulgaris.

Contact allergy and psoriasis.

The study was conducted over a two-year period and included 48 psoriatic patients with palmar and plantar lesions and 61 psoriatic patients without palmar and plantar lesions who served as controls. The objective was to establish the incidence of contact sensitization and its importance as the causative factor in palmar and plantar psoriasis. The most frequent contact allergens were: nickel sulphate, mercapto mix, balsam of Peru, potassium dichromate, mercury mix and fragrance mix. Patch tests were positive in 41.7% psoriatics with palmar-plantar psoriasis and in only 6.6% of psoriatics without palmar-plantar involvement. The study showed an increased incidence of contact allergy in patients with palmar-plantar psoriasis.

[Routine immunologic tests in atopic dermatitis]. / Rutinski imunoloski testovi u atopijskom dermatitisu.

The study comprised 100 examinees with atopic dermatitis and 50 examinees with chronic urticaria (adult patients and children), as well as 50 examinees in a control group. The parameters for monitoring included laboratory findings; values of eosinophiles, total lymphocytes, T and B lymphocytes, serum immunoglobulin (IgG, IgA, IgM) total IgE and specific IgE; results of cutaneous tests: prick and intradermal test to inhalative and nutritive allergens, scratch test to preservatives and additives, and epicutaneous (patch) test to contact allergens. In detection and monitoring of patients with atopic dermatitis, several methods were applied with different diagnostic success. The values of total number of lymphocytes and T and B lymphocytes were mainly within the normal limits, therefore these were not good diagnostic parameters. Eosinophiles were mainly higher and were useful in determination of AD. Mainly normal values of IgE, IgA and IgM were found by radial immunodiffusion, but the ELISA method, as well as the RIST method, showed high values of total IgE. Of the applied skin tests, the most important was intradermal test which gave most of the positive results in the patients with atopic dermatitis (97.7%), then followed scratch test (83.3%), patch test (64.3%), and finally epicutaneous test (57.1%).

[The mastocytosis syndrome]. / Sindrom mastocitoze.

A female patient with the history and clinical signs suggesting cutaneous and systemic mastocytosis is reported. The diagnosis of cutaneous mastocytosis was confirmed by the Darier's sign as well as by histologic analysis of the skin. An X-ray film of the bones showed an infiltration of the mast cells into the skeletal system what was also cytologically and histologically proven. The patient was treated only symptomatically because of the benign course of the disease. A current literature data on mastocytosis syndrome are discussed.