Efficacy and safety of fumaric acid esters in patients with psoriasis on medication for comorbid conditions - a retrospective evaluation (FACTS).

BACKGROUND: Safety and efficacy of fumaric acid esters (FAE) in patients with psoriasis requiring treated comorbidit condition were investigated. PATIENTS AND METHODS: Data collected from 7 dermatology centers were used for a retrospective analysis of patients treated continuously with FAE for at least 6 weeks who required at least one medication for a comorbid condition. The records were analyzed at baseline and after 1, 3, 6, 12 and 24 months of therapy. Safety parameters were monitored and the severity of skin symptoms was assessed by 'Physician's Global Assessment' (PGA). RESULTS: A total of 69 patients with moderate to severe psoriasis and a mean duration of 27.4 months of continuous treatment were included in the study. In less than 5% were interactions between FAE and co-medications observed. Changes of hepatic, renal or hematological laboratory parameters were usually insignificant and required a modification of FAE treatment in less than 12% of the cases. The percentage of patients documented as markedly improved or clear was 61% after 6 months, 77% after 12 months, and 75% after 24 months of therapy. CONCLUSIONS: In patients with moderate to severe psoriasis on co-medications, FAE were effective and safe without any noteworthy drug interactions.

Combination of adalimumab with traditional systemic antipsoriatic drugs - a report of 39 cases.

BACKGROUND: Monotherapy with TNF-α inhibitors does not always produce a sufficient response in psoriasis patients. Combinations of TNF-α antagonists such as adalimumab with systemic antipsoriatic therapies such as methotrexate are not approved for use in psoriasis, and the published data are scarce. PATIENTS AND METHODS: The charts of 39 psoriasis patients from 6 dermatology departments were reviewed retrospectively. All patients were given adalimumbab with another systemic antipsoriatic drug. RESULTS: Combination therapy with methotrexate was most common (n = 32), followed by acitretin (n = 4) and cyclosporine (n = 3). Combination therapy with methotrexate lasted 10.8 ± 11.2 months (mean), with cyclosporine for 6.8 ± 3.3 months, and with acitretin 12.9 ± 12.4 months. Combinations were effective in the majority of patients: 30/39 (76.9 %) had a good (n = 9) or excellent (n = 21) response. Two patients had a moderate response and 7 patients had a poor response and were switched to another treatment. Overall, safety was very good. Eighteen patients experienced 24 adverse events; none was severe and/or required hospitalization. Of these, 10/24 adverse events were infections, most often infections of the upper respiratory tract (n = 5), bronchitis (n = 2), and influenza (n = 1). CONCLUSIONS: Combinations of adalimumab with traditional systemic antipsoriatic treatments offer a promising method for managing severe or recalcitrant psoriasis. More data are needed to determine the long-term safety and efficacy of these combinations.

A first prospective population-based analysis investigating the actual practice of melanoma diagnosis, treatment and follow-up.

AIM OF THE STUDY: To describe the current management of patients diagnosed with cutaneous melanoma and melanoma in situ in Germany and assess for adherence with the existing German guideline in a first prospective population-based analysis. METHODS: Prospective and longitudinal population-based study using online questionnaires. Registration by practitioners and hospitals was open for all patients diagnosed with melanoma between April and June 2008 in Germany. For data analysis, patients with melanoma stages 0-III (AJCC 2002) were included. RESULTS: Data from 1081 patients registered by 106 different centres were available for analysis. Male patients were significantly older than female patients (61.4 years versus 55.8years, p<0.0001) and presented with thicker primary tumours (1.62 mm [median 0.9 mm] versus 1.48 mm [median 0.8 mm], p=0.01). Excessive safety margin excisions were most often applied in melanoma in situ and in small centres. Insufficient excision margins (6.9%) were associated with head and neck localisation, geographical region and implementation of further staging procedures. Decision on sentinel lymph node biopsy complied with the German guideline in >85% of cases and was dependent on age and tumour localisation. Only 60% of patients received a complete lymph node dissection (CLND) after a positive SLNB, the rate of CLND was lowest in older patients. Adjuvant treatments were initiated in only 34% of patients formally qualifying for adjuvant treatment based on guideline recommendations. Approximately half of all staging procedures were done in no-risk/low-risk tumour patients. CONCLUSIONS: Management of melanoma in Germany did not show great dependency on centre size, geographical area or treating physician but rather on patient and tumour characteristics. The low rate of adjuvant treatment initiations reflects the need of treatment options in this patient group. Excessive initial staging procedures generate significant costs.

Protein expression of carcinoembryonic antigen cell adhesion molecules in benign and malignant melanocytic skin lesions.

Dysregulation of cell adhesion molecules is associated with progression of malignant melanoma. Immunohistologic study of benign nevi (BN), dysplastic nevi (DN), and primary superficial spreading melanoma (SSM) was performed for carcinoembryonic antigen (CEA) and CEA cell adhesion molecule-1 (CEACAM1) using monoclonal antibodies. We investigated BN (n = 42), DN (n = 22), thin SSM (n = 21), and thick SSM (n = 21). CEA expression in melanomas and DN was significantly increased compared with BN. CEA expression in thick SSM was significantly higher than in DN. Compared with BN, expression of CEACAM1 in melanomas was significantly increased. CEACAM1 expression in thick SSM was significantly increased compared with DN and thin SSM. Our data support the findings of previous studies indicating that cell adhesion molecules of the CEA family may have a role in the development and progression of cutaneous melanoma and potentially serve as prognostic markers.

Minichromosome maintenance proteins are useful adjuncts to differentiate between benign and malignant melanocytic skin lesions.

BACKGROUND: Markers identifying premalignant and malignant melanocytic skin lesions are needed. OBJECTIVE: We aimed to investigate the protein expression of minichromosome maintenance (MCM) proteins in melanocytic skin lesions with different malignant potential. METHODS: Paraffin-embedded sections of benign melanocytic nevi (BN, n = 37), dysplastic nevi (DN, n = 25), and primary superficial spreading (SSM, n = 58) were assessed. Immunohistochemistry was performed for Ki-67, MCM3, MCM4, and MCM7 antibodies. RESULTS: Ki-67 expression of SSM was significantly increased when compared to DN (P = .0001) and BN (P = .0015). Compared to BN and DN, expression of MCM3 was significantly increased in SSM (P < .0001 and P = .019, respectively). MCM3 expression of DN was significantly increased as compared to BN (P = .0067). There was a significant correlation between MCM3 expression and Breslow tumor thickness (r = 0.44, P = .019). In SSM, MCM4 expression was significantly increased when compared with DN (P < .0001) and BN (P = .0033). MCM4 immunoreactivity was significantly higher in DN than in BN (P = .016). Immunohistology of MCM7 did not reveal significant differences between the groups investigated (P = .48). However, immunoreactivity of MCM7 significantly correlated with Breslow tumor thickness and Clark level (r = 0.39, P = .023; r = 0.44, P = .010, respectively). LIMITATIONS: Limitations of our study include the absence of survival data, mRNA results, and functional studies. CONCLUSIONS: MCM3 as well as MCM4 are differentially expressed in BN, DN, and SSM. Hence, immunolabeling of MCM3 and MCM4 proteins appears to be a promising additive tool for distinguishing benign from malignant melanocytic skin lesions.

Differential expression of microtubule-associated protein 2 in melanocytic skin lesions.

Neoplastic melanocytes may exhibit certain differentiation characteristics of other neural-crest derivatives. We aimed to study the expression of microtubule-associated protein 2 (MAP-2) in different types of melanocytic skin lesions. Paraffin-embedded sections of 42 benign nevi (BN), 22 dysplastic nevi (DN), 45 superficial spreading melanomas (SSMs), and 15 subcutaneous melanoma metastases were immunohistologically assessed using the monoclonal mouse MAP-2ab antibody (Zytomed, Berlin, Germany). The percentage MAP-2 expression of DN and SSMs was significantly increased compared with BN. Moreover, subcutaneous melanoma metastases showed significantly decreased MAP-2 expression compared with DN and SSMs. In SSMs, MAP-2 expression significantly correlated with the Breslow vertical tumor thickness, Clark level, and stage of disease. We observed that MAP-2 is differentially expressed during the development and progression of benign and malignant melanocytic skin lesions. In contrast with the findings of previous studies, our data indicate that MAP-2 is a moderately positive predictor of the progression of SSMs.

Indoor tanning in North Rhine-Westphalia Germany: a self-reported survey.

BACKGROUND/AIMS: We examined the prevalence of indoor tanning in North Rhine-Westphalia and identified correlates of sunbed use. METHODS: During regular skin cancer screening campaigns 1242 subjects completed and returned a structured questionnaire on constitutional parameters and indoor tanning habits. RESULTS: The regular sunbed user rate (more than 10 exposures/year) was 15.4% (191/1242). Most sunbed users were under 29 years of age. The number of female sunbed users was greater than the number of male users. Respondents with secondary modern school qualification used sunbeds more infrequently than respondents with junior high school and high school qualifications. Respondents with skin type III and IV used sunbeds more frequently. Tanning and preparation for sunny holidays were the main reasons for sunbed use. The most frequently reported positive effects experienced by means of sunbed use were improved appearance and relaxation. Most respondents indicated that they hardly or never had sunburns following indoor tanning. Almost half of respondents consider radiation generated by sunbeds somewhat dangerous. CONCLUSIONS: Use of indoor tanning in North Rhine-Westphalia has increased and is significantly associated with female gender, younger age, high-level education, and skin type III and IV. The motivation for sunbed use and benefits experienced are mainly based on the perception of improved appearance due to tan and increased sense of well-being.

Bullous pemphigoid is a rare paraneoplastic syndrome in patients with renal cell carcinoma.

Renal cell carcinoma is associated with paraneoplastic syndromes in up to 40% of cases. Dermatological manifestations are rare. A case of a bullous pemphigoid as a paraneoplastic symptom was diagnosed in a 52-year-old patient with a partially sarcomatoid papillary renal cell carcinoma.

Impact of ultraviolet radiation on the expression of marker proteins of gap and adhesion junctions in human epidermis.

AIMS/BACKGROUND: We aimed to investigate the impact of ultraviolet B (UVB) as well as UVA1 on the epidermal expression of specific markers of gap and adhesion junctions. METHODS: Twelve healthy subjects were enrolled in the study. The back of the subjects was irradiated with three MED-UVB as well as three MED-UVA1. Twenty-four hours later, punch biopsies were taken from irradiated and non-irradiated skin. Immunohistochemical procedures were used for the detection of connexin 43, E-cadherin, involucrin, Ki-67 using specific antibodies. RESULTS: Staining intensity of connexin 43 in UVB-exposed skin was significantly increased when compared with non-exposed and UVA1-exposed sites. By contrast, staining intensity of E-cadherin in UVB-exposed skin was significantly decreased when compared with non-exposed and UVA1-exposed sites. Involucrin and Ki-67 staining of keratinocytes was significantly increased in UVB-exposed sites as compared with non-exposed and UVA1-irradiated sites. CONCLUSIONS: UVB significantly alters the epidermal expression of gap and adhesion junction proteins possibly indicating a role of these proteins in the regulation of UV-induced inflammation and development and progression of skin cancer.

Lipolysis of lipomas in patients with familial multiple lipomatosis: an ultrasonography-controlled trial.

BACKGROUND: Surgery of multiple lipomas, as in patients with familial multiple lipomatosis, is often limited by poor aesthetic outcome owing to extensive scarring. For this reason, phosphatidylcholine (PDC) has been widely used to treat areas of localized fat accumulation. However, no reports of lipoma therapy with intralesional application of PDC, that is, injection lipolysis, have been published to date. OBJECTIVE: To investigate whether injection lipolysis with PDC is an effective therapeutic option for patients with multiple lipomas. METHODS: Thirty lipomas in 10 patients were sonographically measured prior to treatment. Four injections at intervals of 6 to 8 weeks were done. Sonographic measurements of lipoma size were repeated before each injection. Side effects, a pain score using a visual analogue scale, and patient satisfaction were noted. In one lipoma, histologic changes after lipolysis are described. RESULTS: After four injections, a significant reduction in size of 45.8% was achieved. No complete elimination was seen in any lipoma. Histology showed a mild granulomatous septal panniculitis. Hematoma occurred in eight cases (27%). Four patients described pain on pressure for 3 days after injection. No severe side effects or systemic reactions were observed. CONCLUSION: Although surgery is the gold standard for lipoma therapy, injection lipolysis with PDC can also significantly reduce lipoma size. Complete elimination was not observed in any lipoma. Given that this was a short-term study, long-lasting therapeutic effects and possible recurrence of lipoma cannot be evaluated.

Pulsed high-dose corticosteroids combined with low-dose methotrexate in severe localized scleroderma.

OBJECTIVE: To evaluate the efficacy of pulsed high-dose corticosteroids combined with orally administered low-dose methotrexate therapy in patients with severe localized scleroderma (LS). DESIGN: A prospective, nonrandomized, open pilot study. SETTING: Dermatology department at a university hospital in Bochum, Germany. Patients Fifteen patients with histologically confirmed severe LS. Interventions Oral methotrexate (15 mg/wk) combined with pulsed intravenous methylprednisolone (1000 mg for 3 days monthly) for at least 6 months. MAIN OUTCOME MEASURES: Treatment outcome was evaluated by means of a clinical score, 20-MHz ultrasonography, and histopathologic analysis. Safety assessment included the monitoring of adverse effects and clinical laboratory parameters. RESULTS: One patient discontinued therapy. In most of the remaining 14 patients, significant elimination of all signs of active disease (inflammation) and remarkable softening of formerly affected sclerotic skin that resulted in a decrease of the mean +/- SD clinical score from 10.9 +/- 5.3 at the beginning to 5.5 +/- 2.5 at the end of therapy was observed (P < .001). Clinical improvement was confirmed by histologic and ultrasonographic assessments. No serious adverse effects were noted. CONCLUSIONS: These data suggest that pulsed high-dose corticosteroids combined with orally administered low-dose methotrexate therapy is beneficial and safe in the treatment of patients with LS. This treatment regimen should especially be considered for severe forms of LS in which conventional treatments have failed.

Pulsed intravenous immunoglobulin therapy in livedoid vasculitis: an open trial evaluating 9 consecutive patients.

BACKGROUND: Livedoid vasculitis (LV) usually presents with painful, slowly healing ulcerations of the lower limbs. The precise pathophysiology of this relatively rare disease remains obscure. Therapeutic strategies usually include rheologic, anti-inflammatory, or immunosuppressive agents. However, no continuing benefit has been reported in any of these modalities. Recently, encouraging case reports about the successful use of intravenous immunoglobulin (IVIg) in LV have been published. METHODS: We initiated an open single center trial to investigate the efficacy and safety of IVIg in LV. Nine patients with LV, 7 of whom were refractory to other treatment modalities, were included. Therapy with IVIg at a dose of 0.5 g/kg body weight per day over 2 or 3 consecutive days was performed monthly. Skin involvement before and after therapy was assessed by means of a clinical score. RESULTS: In all patients, significant regression of skin lesions was observed after therapy resulting in a decrease of the clinical score (including differential semiquantitative assessment of erythema, ulceration, and pain) from 6.5 +/- 1.7 at the beginning to 1.3 +/- 1.2 after therapy (P <.001). IVIg was well tolerated and therapy was finished in all patients. CONCLUSION: In all patients clinical evaluation revealed a marked improvement of erythema, pain, and healing of areas of active ulceration. Although this was an open non-controlled study, we propose that IVIg is a promising therapeutic option in LV refractory to other treatment modalities.

Immunohistochemical investigations and introduction of new therapeutic strategies in scleromyxoedema: case report.

BACKGROUND: Scleromyxoedema is a rare chronic skin disease of obscure origin, which may often be associated with severe internal co-morbidity. Even though different casuistic treatment modalities have been described, to date, curing still seems to be impossible. CASE PRESENTATION: We report a 44-year-old Caucasian female presenting with remarkable circumscribed, erythematous to skin-coloured, indurated skin eruptions at the forehead, arms, shoulders, legs and the gluteal region. Routine histology and Alcian blue labelling confirmed a massive deposition of acid mucopolysaccharides. Immunohistochemical investigations revealed proliferating fibroblasts and a discrete lymphocytic infiltration as well as increased dermal expression of MIB-1+ and anti-mastcell-tryptase+ cells. Bone marrow biopsies confirmed a monoclonal gammopathy of undetermined significance without morphological characteristics of plasmocytoma; immunofixation unveiled the presence of IgG-kappa paraproteins. CONCLUSIONS: Taking all data into account, our patient exhibited a complex form of lichen mxyoedematosus, which could most likely be linked a variant of scleromyxoedema. Experimental treatment with methotrexate resulted in a stabilisation of clinical symptoms but no improvement after five months of therapy. A subsequent therapeutic attempt by the use of medium-dose ultraviolet A1 cold-light photomonotherapy led to a further stabilisation of clinical symptoms, but could not induce a sustained amelioration of skin condition.

Metastatic cutaneous squamous cell carcinoma arising from a previous area of chronic hypertrophic lichen planus.

Malignant transformation of cutaneous lichen planus is a rare event. We report a 34 year old Caucasian male who presented with an exophytic tumor on the right foreleg. The tumor gradually developed within previous areas of histologically proven hypertrophic lichen planus that had existed for about 10 years. However, the current histological examination of the excised tumor revealed highly differentiated squamous cell carcinoma with a depth of tumor invasion of 10 mm. At that time, neither sentinel lymph node biopsy nor further imaging diagnostics revealed evidence for metastatic spreading. Nevertheless, five months after surgery inguinal lymph node metastases were detected. Initial chemotherapy and inguinal lymph node dissection were unable to stop the spread of the tumor. One year later, parailiacal lymph node metastases were detected by computed tomography. Further cycles of chemotherapy resulted in significant reduction of the parailiacal tumor masses. This report indicates that the long-standing hypertrophic form of lichen planus seems to have a considerable propensity for malignant transformation, even in young patients.