Letter: Human papilloma virus and molluscum contagiosum lesions related to infliximab therapy for psoriasis: a case series.

INTRODUCTION: Biological therapy for psoriasis exerts its action via an immunomodulatory and eventually immunosuppressive mode. Immunosuppression is linked to HPV flares. Our purpose is to investigate a possible relationship between infliximab therapy for psoriasis and human papilloma virus and molluscum (HPV/MC) infections. METHODS: We report a case series of three patients with psoriasis on infliximab, who developed HPV/MC lesions following their treatment. RESULTS: Our patients developed HPV/MC lesions within a few months after the initiation of infliximab infusions for psoriasis. DISCUSSION: Immunosuppresion is related to HPV/MC flares. Biological therapy and in particular infliximab treatment acts by immunomodulation and eventually a degree of immunosuppression. CONCLUSIONS: Anti-TNF treatment could be associated with HPV and/or MC flares. For this reason, we suggest the consideration of obtaining a routine cervical PAP smear before the commencement and during treatment with anti-TNF agents for psoriasis.

The role of inflammatory markers in assessing disease severity and response to treatment in patients with psoriasis treated with etanercept.

BACKGROUND: Psoriasis is a chronic, systemic, inflammatory disease. Inflammatory markers are used in clinical practice to detect acute inflammation, and as markers of treatment response. Etanercept blocks tumour necrosis factor (TNF)-α, which plays a central role in the psoriatic inflammation process. AIM: To reveal any possible association between disease severity [measured by Psoriasis Area and Severity Index (PASI)] and the inflammatory burden (measured by a group of inflammatory markers), before and after etanercept treatment. METHODS: In total, 41 patients with psoriasis vulgaris, eligible for biological treatment with etanercept, were enrolled in the study. A set of inflammatory markers was measured, including levels of white blood cells and neutrophils, fibrinogen, ferritin, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), haptoglobin, ceruloplasmin and α1-antitrypsin, before and after 12 weeks of etanercept 50 mg twice weekly. RESULTS: All markers were reduced after treatment (P < 0.001). PASI correlated with fibrinogen and hs-CRP. Of the 41 patients, 19 (46.3%) achieved reduction of 75% in PASI (PASI75). An increase in hs-CRP and ESR difference (values before minus values after treatment) was related to higher likelihood of achieving PASI75. CONCLUSIONS: Inflammatory markers, particularly hs-CRP and to a lesser extent, fibrinogen and ESR, can be used to assist in assessing disease severity and response to treatment in patients with psoriasis. A combination of selected inflammatory factors (which we term the Index of Psoriasis Inflammation) in combination with PASI might reflect inflammatory status in psoriasis more accurately than each one separately.

Pimecrolimus 1% cream in non-specific inflammatory recurrent balanitis.

BACKGROUND: Non-specific balanitis is a common inflammatory dermatosis with frequent relapses and considerable impact on male sexual life. OBJECTIVE: To evaluate the efficacy and safety of pimecrolimus 1% cream in recurrent non-specific balanitis. METHODS: Twenty-six patients with recurrent flares of non-specific balanitis were randomly assigned to 1 group applying pimecrolimus cream 1% and 1 group applying placebo on the glans twice daily for 7 days. The patients were assessed on day 14. They were instructed to continue applying the agent whenever symptoms initialized for the following 90 days and take account of the cumulative days with symptoms. RESULTS: Seven out of the 11 (63.6%) patients in the pimecrolimus group and 1 out of 11 (9%) in the control group were free of all symptoms and lesions after 14 days, 3 (27.3%) in both groups reported improvement, while 1 (9.1%) in the pimecrolimus and 7 (63.6%) in the control group remained unaffected. (chi(2) = 9.0, d.f. = 2, p = 0.011). Days with symptoms during the 90-day follow-up period were 7.50 +/- 3.02 for the pimecrolimus and 17.62 +/- 4.40 for the control group (p = 0.000064). CONCLUSIONS: Pimecrolimus 1% cream is promising in relieving symptoms and signs of non-specific balanitis during flares and controlling the disease during long-term follow-up.

Raised beta-endorphin serum levels in children with atopic dermatitis and pruritus.

Atopic dermatitis (AD) is a pruritic cutaneous inflammatory condition. As pruritus and pain are very close symptoms, we determined the beta-endorphin serum concentrations in 21 atopic children with pruritus (group A) and 20 children with healed AD without pruritus (group B). Twenty-five healthy school children were the control group. The beta-endorphin serum concentrations (14.95 +/- 2.75 pmol/l) in group A were statistically (P < 0.001) elevated in our patients compared to controls (8.85 +/- 2.39 pmol/l) whereas these in group B were not elevated (9.4 +/- 2.46 pmol/l). We suggest that the elevated beta-endorphin concentrations in atopic patients with pruritus confirm the hypothesis that there is an increased activity of their opioid system and that an opioid antagonist might block itching which is their major clinical symptom.

The corticotrophin releasing factor test: a valuable and rapid procedure for the differential diagnosis of hirsutism.

Plasma concentrations of adrenocorticotrophic hormone, cortisol, 17-hydroxyprogesterone, testosterone, delta 4-androstenedione and dehydroepiandrosterone sulphate were determined in 10 regularly menstruating hirsute women 0, 15, 30, 60, 90 and 120 min after intravenous injection of 100 micrograms corticotrophin releasing factor. The baseline concentrations of adrenocorticotrophic hormone, cortisol, progesterone and dehydroepiandrosterone sulphate were within the normal range, whereas the mean delta 4-androstenedione and testosterone concentrations were mildly elevated. The administration of corticotrophin releasing factor induced a rapid and significant increase in plasma concentrations of adrenocorticotrophic hormone, cortisol, 17-hydroxyprogesterone and delta 4-androstenedione after 60 min, whereas dehydroepiandrosterone sulphate and testosterone concentrations were not significantly elevated. These findings suggest that the corticotrophin releasing factor test can readily be used as an out-patient procedure to exclude adrenal hirsutism.

Pyoderma gangrenosum of the penis: a potentially dramatic skin disease.

We report the case of a 17-year-old boy who presented with penile ulceration and a urethral fistula that had failed to heal after plastic reconstructions with skin grafts. The patient had a history of pathergy, because the initial lesion was an ulcer that deteriorated and led to the development of the fistula after surgical interventions for its repair. On the basis of the patient's history and normal laboratory evaluation findings, the diagnosis of penile pyoderma gangrenosum was made, and the patient began corticosteroids and cyclosporine. Four months after treatment initiation, the penile area was free of inflammation and ulceration.

Poikiloderma of Civatte: a histopathological and ultrastructural study.

BACKGROUND: Poikiloderma of the face and neck (Civatte) has not been studied in depth for decades, especially as far as the histopathology is concerned. MATERIAL AND METHODS: We studied 50 consecutive patients with poikiloderma of Civatte (PC). Their evaluation included: history, physical examination, lesional skin biopsy and histological examination of sections stained with hematoxylin-eosin, PAS, Fontana-Masson, acid orcein Giemsa for elastic fibers and toluidine blue for mast cells. In 10 randomly selected subjects, a second skin biopsy was performed and specimens were examined under the electron microscope. RESULTS: There were 34 females (68%) and 16 males. The mean age at diagnosis was 47.8 years for females and 61.7 years for males. Histological examination revealed an atrophic (62%), flattened (84%) epidermis with hyperkeratosis (92%) and occasional follicular plugging (34%). In some cases, mild hydropic degeneration of the basal cell layer was evident (46%). Melanin was irregularly distributed in the lower epidermis (94%), and melanophages were often present in the dermis (92%). The most prominent and constant feature (100%) was solar elastosis of the papillary dermis. The blood vessels were almost invariably dilated (96%) with a mild perivascular lymphohistiocytic infiltrate (78%), sometimes with plasmacytes (56%). At the ultrastructural level, the epidermis showed only minor changes. The dermoepidermal junction was intact. The most constant findings were swelling and disruption of the collagen fibers as well as focal degeneration of the collagen bundles. Occasionally, several vacuolar spaces were found just under the basal lamina. Melanin-laden macrophages scattered in the dermis were also detected. CONCLUSIONS: PC shows distinct histological and ultrastructural features, supporting the theory that it represents a separate entity. The histology of PC is characteristic but not pathognomonic. On this basis, the differential diagnosis from Riehl's melanosis, poikiloderma atrophicans et vasculare and other acquired poikilodermas can be made. Ultrastructural findings were consistent with the histological findings. Changes of the dermal connective tissue (solar elastosis) predominated, providing morphological evidence for the role of ultraviolet radiation in the pathogenesis of PC.

Coping with acne: beliefs and perceptions in a sample of secondary school Greek pupils.

BACKGROUND: Information on the understanding of acne in adolescents has only occasionally been reported in the medical literature. OBJECTIVE: To evaluate the perceptions of Greek high school students regarding acne causation, exacerbating factors, sources of information, and effect on their daily life and school performance. PATIENTS AND METHODS: Three-hundred and forty-seven students (aged 13-18) of four Athenian high schools completed a self-reported questionnaire. RESULTS: Self-reported acne was present in 59.2% (187/316). Popular sources of information were parents (31.6%), dermatologists (26.7%), magazines and television (17.5%), pharmacists (16.2%), friends (5.3%), beauticians (1.6%) and other doctors (1.1%). Fifty-two per cent considered the information received as inadequate. Reported causal or exacerbating acne factors included: diet (62.3%), hormones (55.1%), poor hygiene (42.4%), stress (31.9%), infection (14.9%) and genetics (5.7%). Reported ameliorating factors included frequent washing (80.7%), sunbathing (38.6%) and adequate hours of sleep (32%). These notions did not differ among pupils with and without acne or among pupils receiving information from different sources (P < 0.05 in all comparisons). Smoking habits, school performance, hours of sleep, sleep disturbances and self-assessment of stress status were not statistically significantly different between pupils with and without acne. Among pupils with acne 48.6% believed that acne was compromising interpersonal relations while 64.4% believed that acne was compromising their self-image. Fifteen per cent of adolescents reported pruritus associated with their acne lesions. CONCLUSION: Beliefs of Greek adolescents about acne were shown to be similar to those of pupils in other developed countries.

Tacrolimus ointment 0.1% in pityriasis alba: an open-label, randomized, placebo-controlled study.

BACKGROUND: Pityriasis alba (PA) is a frequent reason for dermatological consultation because of its chronic course, tendency to relapse and aesthetic impact. OBJECTIVES: In view of its strong association with atopic dermatitis, the objective of this open-label study was to assess the efficacy and safety of tacrolimus ointment in the treatment of PA compared with the efficacy of moisturizers. PATIENTS/METHODS: The study population consisted of 60 individuals of phototype III or IV according to Fitzpatrick's classification, aged 6-21 years. Patients were randomly assigned to one of two groups. Subjects in group A were instructed to apply tacrolimus ointment 0.1% twice daily, 12 h apart, on all hypopigmented macules. Standard moisturizers with SPF 20 sunscreen were used on all lesions applied at least 30 min apart from the tacrolimus ointment. Subjects in group B used solely the same moisturizers with sunscreen. Hypopigmented areas were evaluated at baseline and weeks 0, 3, 6 and 9 by investigators for scaling, hypopigmentation and pruritus on a scale of 0-3. Patient satisfaction was also recorded on a scale of 0-3. All adverse effects were recorded. RESULTS: A statistically significant improvement through time, in hypopigmentation, pruritus and scaling was observed in both groups during the course of 9 weeks. Hypopigmentation resolved from a baseline score of 2.38+/-0.64 to 1.15+/-0.54 at week 3, 0.46+/-0.51 at week 6 and 0.00+/-0.00 at week 9 for the group applying tacrolimus ointment 0.1%. The difference in improvement between the two groups was statistically significant on all three assessments for hypopigmentation (P<0.001), and for pruritus on week 6 and 9 assessments (P<0.05). Three patients (11.5%) in the tacrolimus group reported a mild transient sensation of burning. All patients in the tacrolimus group reported they were completely satisfied or just satisfied with the treatment compared with only 50% of patients using the placebo. CONCLUSIONS: Tacrolimus ointment 0.1% appears to be an effective and safe treatment for PA.

Oral inosiplex in the treatment of cervical condylomata acuminata: a randomised placebo-controlled trial.

Conventional therapies for human papillomavirus infection aim to remove clinically apparent lesions, while latent infection may remain, representing a threat for transmission and carcinogenesis. The use of a systemic agent may more effectively control the virus. We conducted a randomised placebo-controlled study to investigate the efficacy and safety of oral inociplex in the treatment of cervical condylomata acuminata (CA) that had been resistant to conventional therapies. Thirty-eight white European women, aged 20-43 years, with genital warts of the cervix, refractory to at least one conventional therapy, were randomly assigned to receive either inosiplex, 50 mg/kg daily peros for 12 weeks (group 1), or placebo (group 2). Of the 17 evaluable group 1 women, 4 responded to the treatment completely, 7 responded partially and 6 did not respond. Of the 19 group 2 women, none responded to the treatment completely, 3 responded partially and 16 did not respond. The therapeutic difference between women receiving active and placebo therapy was statistically significant (chi(2)= 6.69, P < 0.01) and remained significant when an intention-to-treat analysis was performed (chi(2)= 7.69, P < 0.01). None of the complete responders experienced recurrence during the 12-month follow up. Adverse effects were mild and resolved upon completion of therapy. Compared with placebo, inosiplex showed considerable efficacy with insignificant and reversible adverse effects and without recurrences. Inosiplex may represent an efficacious and safe alternative systemic form of therapy for cervical genital warts.

Poikiloderma of Civatte: a clinical and epidemiological study.

BACKGROUND: Although a common dermatosis, idiopathic poikiloderma of the face and neck has not been studied in depth for decades. OBJECTIVES: To reassess the clinical and epidemiological characteristics of poikiloderma of Civatte (PC). MATERIAL AND METHODS: Fifty consecutive patients with PC. Evaluation included history taking and physical examination. Epidemiological and clinical parameters were recorded and analysed. The literature from 1923 until today, was reviewed thoroughly. RESULTS: The frequency of PC among dermatologic patients was estimated to be 1.4%. There were 34 females (68%) and 16 males in the present study. The mean age at diagnosis was 47.8 years for females and 61.7 years for males. The majority (88%) had skin phototype II or III. Among females, 26 were at their peri-menopausal stage, including three cases of iatrogenic menopause. Four patients reported that other blood-related family members also had PC. The v and the sides of the neck and the upper chest were most often affected in a symmetric distribution. The face (preauricular and parotid region) was involved in 19 patients (38%). The erythemato-telangiectatic clinical type predominated (58%), followed by the mixed (22%) and the pigmented type (20%). Almost half of the patients (46%) were symptomatic (itching, burning and 'flushing'). The mean duration from onset to diagnosis was 6.2 years according to the patients' report. The course was usually slowly progressive (82%) and irreversible. CONCLUSIONS: PC shows characteristic features, supporting the theory that it represents a distinct entity. It is rather common in Greece. Although menopausal women predominated in our cohort, men were not uncommonly affected and were diagnosed at an older age. Based on the predominating clinical feature, PC can be classified into three clinical forms. Symmetry and sparing of the anatomically shaded areas of the neck are highly characteristic for PC. Face involvement was not as common and as severe as it had been considered in the past. Recognition of clinical type is important for the selection of the most appropriate treatment, which, despite the advent of novel modalities, remains problematic.

Immunophenotypic analysis of the p53 gene in non-melanoma skin cancer and correlation with apoptosis and cell proliferation.

BACKGROUND: Sunlight precipitates a series of genetic events that lead to the development of skin cancers such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The p53 tumour suppressor gene, which plays a pivotal role in cell division and apoptosis, is frequently found mutated in sunlight-induced skin tumours. OBJECTIVE: To investigate the immunoreactivity of the p53 gene in non-melanoma skin cancers and to correlate its expression with apoptotic and cell proliferation markers. METHODS: We analysed 35 non-melanoma tumours including 19 BCCs and 16 SCCs from sun-exposed skin areas. p53 protein expression was studied immunohistochemically using the DO7 monoclonal antibody against wild-type and mutant p53 forms. The percentage of p53-immunopositive nuclei was measured by image analysis. Cell proliferation and apoptosis were also assessed by image analysis following Ki-67 immunostaining and application of the TUNEL method on paraffin sections, respectively. RESULTS: The percentage of p53-expressing cells varied from 3.5 to 90 in BCCs (median value 54.4%) and from 3.7 to 94 in SCCs (median value 40.3%). The mean value of Ki-67-positive cells was comparable in both groups of tumours with a mean value of 40.6% in BCCs and 34.6% in SCCs. Conversely, the TUNEL assay showed sporadic staining of apoptotic cells within the tumours with a mean value of 1.12% in BCCs and 1.8% in SCCs. p53 protein expression was correlated positively with cell proliferation (r = 0.75, P = 0.000001) and negatively with apoptosis (r = -0.23, P = 0.05). CONCLUSION: p53 immunoreactivity was high in the majority of the skin carcinomas examined and correlated positively with cell proliferation and negatively with apoptosis. The p53 protein overexpression appears to be related to an inactivated protein resulting from mutations of the p53 gene or other unclear molecular mechanisms.

Dinitrochlorobenzene treatment of condylomata acuminata.

Fifteen patients with treatment-resistant condylomata acuminata have been treated by application of Dinitrochlorobenzene (DNCB). The agent was applied weekly as a 0.5 or 1% solution in acetone for a period of 6 to 8 weeks. Patients were sensitised 15 days before the onset of treatment by applying a 2% DNCB solution on the right arm in a quantity of 0.15 ml. In one patient treatment had to be stopped because of local irritation and one discontinued treatment. In the other 13 patients all lesions cleared completely. Patients were followed up for a year and no recurrence has appeared as yet. DNCB seems to be useful agent for treatment-resistant condylomata acuminata and justifies further clinical trials.

Parameters of cell-mediated immunity in recurrent herpes simplex.

Cell-mediated immunity was studied by a leukocyte migration inhibition assay, tuberculin, and a DNCB skin test in 32 patients with recurrent herpes simplex infection and in 34 healthy individuals who served as controls. Migration inhibition was found to be significantly reduced in patients who had suffered from recurrences for more than 1 year as compared to the controls. DNCB and tuberculin sensitivity were also found to be impaired in the group with infections of long duration. The data presented suggest a functional defect in cell-mediated immunity in individuals suffering from recurrent herpes simplex which could be responsible for the relapses.

Hormonal status in postmenopausal androgenetic alopecia.

The development of androgenetic alopecia is thought to be caused by increased androgen action on hair follicles with menopause. Testosterone, estradiol and sex hormone binding globulin (SHBG) serum levels were determined in ten postmenopausal women with androgenetic alopecia and in ten sex and age matched healthy controls. No statistically significant differences were found in the hormone levels between the patients and the controls. These findings suggest that a genetically determined functional alteration of androgen receptors and/or a metabolic disturbance may exist in the hair follicle keratinocytes in androgenetic alopecia.