Franjo Gruber

Roles of stress, stress perception and trait-anxiety in the onset and course of alopecia areata

Clinical observations suggest that the nervous system, including psychological factors, can influence the onset and course of alopecia areata (AA). The aim of this study was to determine whether stressful life events, stress perception, and trait‐anxiety are risk factors in the onset and course of AA. A group of 45 patients diagnosed with AA and a group of 45 healthy controls were participants in the study. The patients with AA were divided into two subgroups: patients with a first episode of AA and patients with recidivism of the disease. All participants completed questionnaires addressing sociodemographic, clinical and psychological aspects of their disorder. The frequency and types of stressful life events experienced over the previous six months were recorded. Lemyre and Tessiers Mesure de Stress Psychologique was used to measure emotional, cognitive, behavioral, and physiological aspects of distress. Anxiety was evaluated by the Spielbergs Trait Anxiety Inventory. The subgroups of AA and the control group, using the same numbers of subjects matched for age and sex, education level, marital and employment status, were statistically compared. The number of patients with four stressful life events over the previous 6 months was significantly higher in the group of AA patients with recidivism of disease compared to the control group (P=0.004). There were no differences among the other groups with respect to the frequency of life events. Examination of the relationships between the two groups regarding anxiety, as well as perceived distress, revealed that the groups differed significantly with respect to psychosocial variables studied. A significantly higher degree of trait‐anxiety and perceived distress were observed among patients in both AA subgroups (first onset and recidivism of AA) than in the healthy control group. The highest scores for anxiety and stress perception among examined groups were obtained in the group with recidivism of AA (33.42 ± 12.71 and 90.32 ± 50.74, respectively). Trait‐anxiety and stress perception constitutes risk factors that may influence the onset and exacerbation of AA. The present study does not provide evidence of a significant role of stress in the onset of AA. Life events may play an important role in triggering of some episodes.

p53 protein expression and cell proliferation in non-neoplastic and neoplastic proliferative skin diseases.

Aims and background The p53 protein is essential for the regulation of cell proliferation and its aberrant accumulation is usually seen in malignant tumors but also occurs in squamous epithelium of inflammatory skin diseases characterized by hyperproliferation. The aim of this study is to elucidate the role of the p53 tumor suppressor protein in the pathogenesis of different hyperproliferative, non-malignant and malignant skin diseases, and to determine the association between p53 overexpression and cell proliferation. We also investigated the influence of aging on p53 and Ki-67 protein expression. Methods One hundred and fifty skin specimens divided into 30 samples each of normal skin (NS), psoriatic skin (PS), keratoacanthomas (KA), basal cell carcinomas (BCC), and squamous cell carcinomas (SCC) were examined immunohistochemically to assess p53 and Ki-67 protein expression. Results p53 immunostaining of NS, PS, KA, BCC and SCC was detected in 39.0%, 46.7%, 66.7%, 80% and 86.7% of cases, respectively. Median values and ranges of p53 protein expression were as follows: 0.0% (range, 0.0–1.8%) in NS, 0.0% (range, 0.0–6.5%) in PS, 9.2% (range, 0.0–24.0%) in KA, 19.3% (range, 0.0–48.1%) in BCC and 30.1% (range, 0.0–68.1%) in SCC. p53- and Ki-67-positive cells were present in basal (NS) and suprabasal layers (PS), and not only in cancer nests of KA, BCC and SCC but also in dysplastic and even morphologically normal epidermis adjoining cancers. The positivity of p53 and Ki-67 proteins differed significantly among the groups, with no differences in p53 expression between NS and PS and in Ki-67 expression between PS and KA. Within all groups there was a significant correlation between p53 and Ki-67 expression. Lesion location and patient age, with the exception of location in PS and age in BCC, were significantly related to p53 and Ki-67 expression in all groups. Conclusions Our findings suggest that p53 overexpression occurs mainly in neoplastic skin lesions, although it may also occur in squamous epithelium of inflammatory skin diseases such as PS, as well as in normal skin epithelium. It is associated with cell proliferation in normal as well as altered epithelium. p53 protein overexpression is an age-related process and significantly associated with sun exposure, especially in NS and PS but also in KA and SCC. Our findings suggest that Ki-67 rate and p53 protein expression reflect the degree of malignancy in the examined cutaneous neoplasms.

Acne vulgaris: myths and misconceptions among patients and family physicians

The objective of the study was to evaluate the health beliefs and knowledge about acne among acne patients and family physicians. A total of 100 patients referred to a dermatologist for management of acne vulgaris and 120 family physicians completed questionnaires. The questionnaires consisted of questions about health beliefs, the natural course of the disease, the causes of acne, and a set of questions about the knowledge of acne therapy. Acne was considered as a trivial and transitory condition by 52% of the acne patients and 44% of the family physicians. The overall score of correct answers pertaining to the causes of acne among the acne patients and family physicians was 11 and 15%, respectively. The percentage of correct answers regarding the natural course of the disease was 6% for both subsets of subjects. Acne was believed to be curable by 96% of acne patients. Most patients (66%) believed that acne would improve immediately after the first treatment. The knowledge of isotretinoin teratogenecity was reasonable among family physicians (55% correct answers), but it was much lower for other side effects (9%). The overall score of correct answers regarding antibiotic therapy among family physicians was only 21%. Impact of the disease was underestimated by family physicians and also by acne patients. Overall knowledge pertaining to the causes, natural course and therapy was very low. Myths and misconceptions still exist among patients but also among family physicians.

Treatment of early syphilis with azithromycin

Abstract An open, noncomparative study was performed to establish the efficacy of azithromycin in the treatment of early syphilis. Sixteen patients were treated with oral azithromycin: 1g the first day and then 500 mg for the following 8 days. Two patients were excluded from the study, leaving 14 patients for the evaluation of the efficacy. Venereal Disease Research Laboratory (VDRL) negativity was observed in 3 out of 6 patients treated for primary syphilis after 3 months and in all patients after 6 months. Two of 8 patients treated for manifest or early latent secondary syphilis had VDRL negativity after 3 months and 4 patients after 6 months.This study demonstrates that azithromycin is effective in the treatment of early syphilis. Two patients experienced gastrointestinal side effects which did not require treatment interruption.

Perforin expression is upregulated in the epidermis of psoriatic lesions.

Background  There are currently very few data regarding the role of cell‐mediated cytotoxicity in psoriasis. Both cytotoxic T lymphocytes and natural killer (NK) cells mediate cytotoxicity reactions, mainly by two distinct pathways, the perforin/granzyme and the Fas/Fas ligand pathway.

Analysis of HLA Antigens in Croatian Patients with Psoriasis

In common with most autoimmune diseases, psoriasis is associated with some HLA antigens. We studied the distribution of HLA antigens in Croatian patients with psoriasis: 108 patients were divided into groups according to family history and age of disease onset. HLA antigens were analyzed serologically and HLA-C alleles were analyzed using polymerase chain reaction. We found significant increases in HLA-A2, -B17, -B37 and -B13 antigens and highly significant increases in HLA-Cw*0602 and DR7 antigens in psoriatic patients compared with controls. Patients with type I psoriasis (early onset, positive family history) showed highly significant associations with Cw*0602 [p < 0.00001; relative risk (RR) = 14.45] and DR7 (p < 0.00001; RR = 15.09) antigens. Patients with type II psoriasis (late onset, no family history) had a significant association with Cw*03 antigen (p = 0.008; RR = 0.17). In conclusion, HLA-B13, -B17, Cw*0602 and -DR7 antigens are associated with a significant risk of psoriasis in the Croatian population and the Cw*0602 allele has the strongest association, especially for type I psoriasis.

Perforin expression in peripheral blood lymphocytes and skin-infiltrating cells in patients with lichen planus

Background  Current evidence suggests that lichen planus is a T‐cell‐mediated autoimmune disease in which cytotoxic mechanisms have been poorly investigated.

Postcoital fixed drug eruption in a man sensitive to trimethoprim‐sulphamethoxazole

We describe a 34‐year‐old patient with a probable fixed drug eruption caused by trimethoprim‐sulphameth‐oxazole, having developed the eruption after sexual intercourse with his wife, who was taking the drug. The patient was known to be allergic to trimethoprim‐sulphamethoxazole by history, and the lesion then recurred at the same site when the drug was administered orally to his wife. To the best of our knowledge, this is the first report describing postcoital fixed drug eruption. Physicians should thus be aware of unusual and atypical forms of fixed drug eruption.

Delayed onset of warts over tattoo mark provoked by sunburn

Multiple warts in a 32‐year‐old‐man are reported that developed after tattooing and remaining exclusively confined to that area. The tattooing was done 2.5 years earlier by a professional tattoo artist. It was previously a lesion‐free tattoo, but when damaged by sunburn developed multiple skin warts. The ability of a latent virus to induce warts after cutaneous ultraviolet exposure was discussed.

The role of perforin-mediated apoptosis in lichen planus lesions

Lichen planus is recognized as a T-cell-mediated disease. Histologically, it is characterized by the formation of colloid bodies representing apoptotic keratinocytes. The apoptotic process mediated by CD8+ cytotoxic T lymphocytes (CTLs) and NK cells mainly involves two distinct pathways: the perforin/granzyme pathway and the Fas/FasL pathway. So far, little is known regarding the role of perforin-mediated apoptosis in lichen planus. In the present study, the expression and distribution of perforin, T and NK cell subsets in the epidermis and dermis of lesional and nonlesional lichen planus skin were studied. Skin biopsy specimens from lesional and nonlesional skin of ten patients with lichen planus and eight healthy persons were analysed by immunohistochemistry. Significant accumulation of T cells, particularly of CD4+ and CD8+ subsets, was found in both epidermis and dermis of lichen planus lesions compared with nonlesional and healthy skin. There were no significant differences in the incidence of NK cells (CD16+ and CD56+) between lesional, nonlesional and healthy skin. Perforin expression was significantly upregulated in the epidermis of lichen planus lesions. In conclusion, accumulation of perforin+ cells in the epidermis of lichen planus lesions suggest a potential role of perforin in the apoptosis of basal keratinocytes.