Idiopathic guttate hypomelanosis: an electron microscopy study.

BACKGROUND: Few published data, concerning the electron microscopy findings of idiopathic guttate hypomelanosis have been published so far. OBJECTIVES: To reveal the electron microscopic findings of idiopathic guttate hypomelanosis and their aetiopathogenetic associations. METHODS: Punch biopsy specimens from four patients with idiopathic guttate hypomelanosis, after being properly processed, were observed under the electron microscope. RESULTS: In the epidermis, melanocytes and melanosomes were normal in structure. In some areas, there was a reduced uptake of melanosomes by the keratinocytes. In the dermis, fibroblasts were structurally normal. Also, most elastic and collagen fibres were normal, but there were focal elastotic changes. CONCLUSIONS: No significant structural abnormality of the melanocytes was observed, but rather a functional defect in the transfer of melanosomes from the melanocytes to the keratinocytes.

Long-term efficacy and safety of infliximab maintenance therapy in patients with plaque-type psoriasis in real-world practice.

BACKGROUND: Tumour necrosis factor-α inhibitors, including infliximab (IFX), can improve disease control of plaque-type psoriasis. OBJECTIVES: The Real-World Assessment of Long-Term Infliximab Therapy for Psoriasis (REALITY) study evaluated the efficacy and safety of maintenance IFX therapy in typical clinical settings. METHODS: In this prospective, observational, open-label, multicentre study in patients with plaque-type psoriasis, IFX 5 mg kg was infused at weeks 0, 2 and 6, and every 8 weeks thereafter during a 50-week treatment phase. The primary outcome was ≥ 75% Psoriasis Area and Severity Index (PASI) improvement from baseline to week 50. Patients with ≥ 25% PASI improvement from baseline to the end of the treatment phase were potentially eligible to enter a 48-week extended treatment phase. Response maintenance and other efficacy measures were evaluated. Adverse events (AEs) were collected. RESULTS: In total 660 patients enrolled. Of 521 efficacy-evaluable treatment phase patients (66% male, mean age 46·5 years, mean PASI 18·1), 56·8% achieved PASI 75 at the end of the treatment phase. Response was maintained at week 50 by 64·7% (205/317) of patients who achieved PASI 75 at week 14. During extended treatment, 66·3% (112/169) of patients attained PASI 75 at week 98; response was maintained at week 98 by 71·6% (101/141) of those who achieved PASI 75 at week 50. IFX was generally well tolerated. During treatment, 7·6% (50/659) of patients had serious AEs. During extended treatment, 4·1% (eight of 193) of patients had serious AEs. CONCLUSIONS: PASI 75 response was achieved by 56·8% and 66·3% of patients at weeks 50 and 98, respectively. The AE pattern was consistent with previous reports.

Immune response to hepatitis A vaccination in HIV-infected men in Greece.

HIV-infected patients are at increased risk for acquiring hepatitis A virus (HAV) infection. We evaluated the seroconversion rate (anti-HAV antibodies ≥ 20 mIU/ml) and the geometric mean antibody titres (GMTs) in a group of 351 HIV infected men, who had received two doses of a hepatitis A vaccine. We analysed blood samples collected at one, six, 12 and 18 months following the administration of the second dose of the vaccine. The seroconversion rate one month after the second dose of the vaccine was 74.4% (260/351). At month 18 after the end of vaccination, 56.1% of the subjects remained seropositive. GMTs were 315, 203, 153 and 126 mIU/ml at months 1, 6, 12, and 18, respectively. Logistic regression revealed that the CD4 count is the only factor affecting response to vaccination (P = 0.019). A higher response rate and higher GMTs were observed in patients with CD4 counts ≥ 500 cells/mm(3) (76.6%) than in patients with CD4 counts 200-499 cells/mm(3). In conclusion, even in patients with near-normal CD4 counts, the response to the hepatitis A vaccine is impaired.

Therapeutic combination of radiofrequency surgical dissection and oral acitretin in the management of perianal Buschke-Lowenstein tumour: a case report.

Giant condyloma acuminatum (GCA), or Buschke-Löwenstein tumour (BLT), is a rare large tumour of the anogenital area. It is caused by human papillomavirus genotypes 6 and 11, and it is characterized by aggressive local invasion and frequent recurrences after treatment. Treatment of choice is radical excision, although chemotherapy and radiation are also used in special cases. We report a case of a young man with anogenital GCA, presenting with a large perianal mass and pain during defaecation. The patient was treated by surgical removal of almost the entirety of the mass, using radiofrequency surgical dissection. The concurrent use of oral acitretin for the treatment of erythrodermic psoriasis led to elimination of the remaining disease. The patient remains free of disease 26 months after the end of treatment.

Advances in Merkel cell carcinoma pathogenesis and management: a recently discovered virus, a new international consensus staging system and new diagnostic codes.

Merkel cell carcinoma is a rare but aggressive neuroendocrine carcinoma of the skin with a rising incidence and a high mortality rate. It occurs primarily in sun-exposed skin of older individuals. It is characterized by a high rate of local recurrence, regional lymph node metastases and distant metastases, occurring even after prompt treatment. Many controversies exist regarding its pathogenesis and optimal management. The discovery of Merkel cell polyomavirus has been a major breakthrough in understanding the aetiology of the disease. A recently adopted new international consensus staging system in combination with new international diagnostic codes are expected to facilitate future clinical trials and improve the management of patients. According to recent (2010) guidelines, most patients should be managed with a combination of surgery and radiotherapy.

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.

Acne-associated syndromes: models for better understanding of acne pathogenesis.

Acne, one of the most common skin disorders, is also a cardinal component of many systemic diseases or syndromes. Their association illustrates the nature of these diseases and is indicative of the pathogenesis of acne. Congenital adrenal hyperplasia (CAH) and seborrhoea-acne-hirsutism-androgenetic alopecia (SAHA) syndrome highlight the role of androgen steroids, while polycystic ovary (PCO) and hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndromes indicate insulin resistance in acne. Apert syndrome with increased fibroblast growth factor receptor 2 (FGFR2) signalling results in follicular hyperkeratinization and sebaceous gland hypertrophy in acne. Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) and pyogenic arthritis-pyoderma gangrenosum-acne (PAPA) syndromes highlight the attributes of inflammation to acne formation. Advances in the understanding of the manifestation and molecular mechanisms of these syndromes will help to clarify acne pathogenesis and develop novel therapeutic modalities.

Atopic patients with genital warts have a more protracted clinical course and a greater probability of recurrences.

The factors predicting an unfavourable response of genital warts to treatment have not been determined. The disease characteristics were recorded for 390 patients with genital warts and treated by cryotherapy. The time to achieve clearance was recorded. A personal and family history of asthma, hay fever or eczema, as well as a personal history of common warts and number of recurrences was obtained by telephone four to five years after the clinical visits. In multiple regression analysis, the number of lesions (P < 0.001), extent of the disease (P = 0.003) and personal history of atopy (P = 0.001) were found to influence the time until response to treatment. Similar results were obtained for family history of atopy. The number of sexual partners (P = 0.007), extent of the disease (P = 0.009) and personal history of atopy (P < 0.001) were the main factors influencing the probability of recurrence in multiple logistic regression. The results for family history of atopy were again similar. The study concludes that atopy is a major factor influencing the time frame of the therapeutic response and the probability of recurrence in patients with genital warts.

Sequential treatment with biologics: switching from efalizumab to etanercept in 35 patients with high-need psoriasis.

BACKGROUND: Use of biological agents has been shown to be an efficacious approach in psoriasis, when traditional treatments fail. However, there are limited data on the effectiveness and safety of switching from one biological agent to another. OBJECTIVES: We aimed to evaluate the effectiveness and safety of etanercept as a sequential treatment in patients previously treated with efalizumab, and to evaluate different transition strategies from efalizumab to etanercept. METHODS: We present a retrospective study in patients with high-need plaque psoriasis who were unable to continue efalizumab and were immediately switched to etanercept. RESULTS: We included 35 patients during a 4.5-year period. At 24 weeks of etanercept therapy, 57% of patients had a PASI reduction of 75%, suggesting that alternating between biological agents is feasible. We used three different switching approaches: (i) etanercept in combination with cyclosporine as bridge therapy, (ii) etanercept in combination with methotrexate as bridge therapy, (iii) etanercept monotherapy. Combination therapy was efficacious in all patients, including eight patients with rebound phenomenon with efalizumab. Etanercept was discontinued in two patients as a result of serious adverse events that consisted of an oral squamous cell carcinoma and a diffuse B-cell-non-Hodgkin lymphoma. CONCLUSIONS: In our experience, it seems that etanercept alone may not be sufficient when transitioning from efalizumab in high-need patients with severe worsening or rebound of psoriasis. In such patients, combination of etanercept with cyclosporine or methotrexate is a more effective approach. Non-response to efalizumab did not preclude clinical response after switching to etanercept.

Pimecrolimus cream 1% for the treatment of papulopustular eruption related to epidermal growth factor receptor inhibitors: a case series and a literature review of therapeutic approaches.

BACKGROUND: Cutaneous side effects of epidermal growth factor receptor inhibitors (EGFRIs) are very frequent and well known. The aim of our study was to investigate the efficacy and safety of pimecrolimus 1% cream in the treatment of papulopustular eruption caused by EGFRIs and to review the relevant literature on therapeutic approaches. METHODS: Twenty cancer patients being treated with EGFRIs were included in the study. Nine of the patients showed grade 1 and 11 showed grade 2 papulopustular eruption. All patients were treated with pimecrolimus 1% cream, which was applied twice daily. Patients with grade 2 eruption also received systemic minocycline 100 mg/day. RESULTS: All patients with grade 1 eruption responded to treatment, with 4/9 experiencing complete resolution of the lesions 2 weeks after the initiation of treatment. Five out of 11 patients with grade 2 eruption had more than 50% improvement in erythema and pustules, and 1 had complete resolution of the skin lesions. Two patients did not respond to treatment but were significantly improved after substitution of pimecrolimus 1% cream with metronidazole 1% cream. No side effects were recorded. CONCLUSIONS: Our case series shows that pimecrolimus cream may be an effective and safe approach in the management of papulopustular eruption related to EGFRIs.

CHILD syndrome: the NSDHL gene and its role in CHILD syndrome, a rare hereditary disorder.

BACKGROUND: CHILD syndrome, a rare hereditary disorder of keratinization (MIM 308050, 300275), is the acronym proposed by Happle to name a rare entity, characterized by congenital hemidysplasia, icthyosiform nevus and limb defects, ranging from digital hypoplasia to icthyosiform nevus and ipsilateral limb defects, ranging from digital hypoplasia to complete amelia. PATIENTS AND METHODS: A 9-month-old female infant presented with skin and limb defects involving the right side of her body. Clinical and laboratory evaluation was performed, including DNA sequence analysis of the NSDHL gene. RESULTS: Our patient presented with some of the typical clinical characteristics of CHILD syndrome, i.e. two large erythematous plaques with sharp borders, covered with yellow, wax-like scaling, on the right axilla and on the right groin, dysplastic right hand and alopecia of the right occipital area. The diagnosis was confirmed by DNA screening analysis, that detected a missense mutation c.314C-->T;p-A105V, in the coding region of the NSDHL gene (exon4) of our patient. CONCLUSIONS: This is the first report of CHILD syndrome ever reported in Greece. We suggest that the diagnosis of the syndrome is important for patient information and genetic counselling.

Infliximab for the treatment of psoriasis in Greece: 4 years of clinical experience at a single centre.

BACKGROUND: Infliximab, a chimeric monoclonal antibody, has been shown to be effective for moderate to severe psoriasis. Clinical experience with long-term infliximab therapy for psoriasis is accumulating, and it is therefore important to share our experience with its use in real-life clinical practice. OBJECTIVES: To report our experience with infliximab (Remicade; Schering Plough, Kenilworth, NJ, U.S.A.) for the treatment of moderate to severe plaque psoriasis (and/or arthritis) from a single clinic in Greece. PATIENTS AND METHODS: Between August 2004 and March 2008, 62 patients presenting to our clinic with moderate to severe psoriasis were treated with infliximab. Disease phenotype, clinical course, disease severity and adverse events were assessed throughout the treatment period. RESULTS: Infliximab resulted in a reduction of median Psoriasis Area and Severity Index (PASI) of 70% at week 6 and 84.4% at week 14. Nineteen patients who have completed 1 year on infliximab treatment experienced sustained efficacy with a median PASI improvement of 92.16% and a Physician's Global Assessment (PGA) of 'clear' or 'almost clear', while nine patients have reached approximately 20 months of continuous therapy. All patients with psoriatic arthritis showed marked improvement in their clinical symptoms following the first infusion. Eight patients (12.9%) experienced adverse events that required discontinuation of treatment. There were no statistically significant differences in PASI and Dermatology Life Quality Index (DLQI) scores between patients with arthritis and those with only skin lesions, or between those who received methotrexate, either from the beginning or during infliximab therapy, and those who did not receive methotrexate at all. Selected patients of interest are discussed. CONCLUSIONS: The above data confirm previous reports that treatment with infliximab is an efficacious and safe option for patients with moderate to severe plaque psoriasis (and/or arthritis). Long-term follow-up, continued pharmacovigilance, and controlled comparative studies will be required to fully evaluate its use in the treatment of psoriasis.

Clinical characteristics and course of CD8+ cytotoxic variant of mycosis fungoides: a case series of seven patients.

BACKGROUND: Fewer than 5% of cases of mycosis fungoides (MF) present with a cytotoxic/suppressor CD8+ phenotype which, despite immunophenotypic similarities with CD8+ aggressive lymphomas, is regarded as a phenotypic variant of MF. Poikilodermatous MF showing a CD8+ phenotype has been reported to have a nonaggressive clinical behaviour and a good response to psoralen plus ultraviolet A treatment. OBJECTIVES: To perform a retrospective study of CD8+ MF cases diagnosed in the skin lymphoma clinic of Andreas Sygros Hospital. METHODS: We analysed the clinical characteristics, the immunophenotypic and molecular indices, as well as the clinical course of these patients. RESULTS: Seven cases of CD8+ MF (6.5% of all cases of cutaneous T-cell lymphoma) were diagnosed during 2002-2007. One of seven patients had stage IA, five stage IB and one stage IIB disease. Clinical characteristics were variable: four of seven patients presented with poikilodermatous plaques (in one of them lesions of lymphomatoid papulosis with CD8+ phenotype coexisted), one patient with classic MF, one with plantar MF and one with follicular MF. The time period between disease onset and diagnosis was long for most patients (up to 33 years). All patients received the recommended treatment according to TNM staging. Five of seven patients had complete remission, one partial response and one stable disease. CONCLUSIONS: Special clinical characteristics, such as hyperpigmentation and poikiloderma, are often noted in CD8+ MF cases. In our series CD8+ MF presented with a long-standing disease and indolent course suggesting that CD8+ cytotoxic immunophenotype may represent a marker of mild biological behaviour.

Prognostic factors for the response to treatment in males with genital warts.

BACKGROUND: Factors predicting an unfavourable course of genital warts to treatment have not been determined. MATERIALS AND METHODS: Behavioural and baseline disease characteristics were recorded from 246 males with anogenital warts. Urethral swabs were obtained and examined using the Hybrid Capture 2 Microplate assay. Patients were treated for their anogenital warts with cryotherapy, imiquimod cream 5% or podophyllotoxin. They were followed up every 3 months for 1 year. RESULTS: Patients with a negative or low-risk initial test tended to respond earlier to treatment than those with a high/intermediate-risk human papillomavirus (HPV) or with a dual infection (P = 0.028). The response rate was unrelated (P > 0.05) to the duration, number and anatomical location of the lesions and to the patient's age and sexual orientation, and only marginally to the initial extent of the lesion (P = 0.046). However, the type of treatment predicted a favourable response (P < or = 0.001), with patients who received both imiquimod and crotherapy responding worse. Considering all factors simultaneously in logistic regression, only the type of treatment and extent of the disease were found to influence the response rate. CONCLUSION: The type of treatment and extent of the disease were the only factors found critical for patients' response.