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Background: Epidermal Growth Factor Receptor (EGFR) antibodies are innovative anti-cancer drugs prolonging survival in metastatic colocrectal cancer. However, due to adverse drug reactions, patients develop acneform skin toxicities. We hypothesized that the skin reaction leads to a decline in general (QOL) and dermatological health related quality of life (HQOL). Furthermore, we aimed at evaluating predictors for QOL and HQOL to improve individual adjustment of therapy. Methods: 40 outpatients with metastatic colocrectal cancer were involved in this study. According to their KRAS status, patients were allocated to 2 groups: The CTCX group (n = 20; KRAS wild-type) was treated with the EGFR-antibody Cetuximab plus chemotherapy, the CT group (n = 20; KRAS mutation) was receiving chemotherapy only. Psychological assessment consisted of questionaires to evaluate QOL and HQOL, depression, coping-styles, health beliefs and the patient´s personality. Results: Between the two groups, no significanct difference in QOL was found, QOL remained stable over the course of treatment. Yet, the severity of the skin reactions had a significant influence on HQOL. Internal health beliefs and high compliance were found to be protective factors, while passive coping strategies, depression and the personality trait neuroticism were identified as risk factors. Discussion: Interdisciplinary cooperation between medical professionals and psycho-oncologists is strongly recommended to encourage patients to embark on and to retain EGFR-antibody therapy. If risk factors are present, psycho-oncological therapy should focus on the minimization of depression and on the development of active coping strategies.

Background Primary cutaneous B-cell lymphomas (PCBCL) are subdivided into the aggressive form, primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT) and two subtypes of indolent behaviour (primary cutaneous follicle centre lymphoma and primary cutaneous marginal zone B-cell lymphoma). The difference in clinical behaviour can be explained by the tumour cell itself, or the lymphoma microenvironment including the antitumour immune response. Objectives To investigate the presence of regulatory T cells (Treg), CD4+CD25+FOXP3+, in the microenvironment of PCBCL in correlation with clinical outcome. Methods Tumour specimens of 55 consecutive cases of PCBCL were blinded and analysed for FOXP3, CD4 and CD25 expression by immunohistochemistry. Confocal images were taken with a Leica SP5. Statistical analyses were performed to determine significance. The test was considered significant when P Results The CD4 and FOXP3 expression as well as the CD4/FOXP3 ratio were significantly increased in PCBCL of indolent behaviour in contrast to PCLBCL, LT (P=0.0002 for CD4, P Conclusion High numbers of Treg in the lymphoma microenvironment correlate with a better prognosis in PCBCL. In PCLBCL, LT the presence of FOXP3+ tumour cells is beneficial for prognosis suggesting that FOXP3 expression of PCLBCL, LT tumour cells might serve as a tumour suppressor.

Summary Background Cutaneous T-cell lymphoma (CTCL) is a slowly progressive malignancy for which there is no cure. Therefore, accurate prediction of prognosis is important for the conduct of clinical trials and for counselling of individuals. Objectives To improve prediction of survival in patients with CTCL. Methods Prognostic factors including tumour–node–metastasis (TNM) criteria and the CTCL Severity Index (CTCL-SI) were analysed using a Weibull model for multivariate analysis in a sample of 62 patients with classical CTCL (mycosis fungoides and Sezary syndrome). The Brier score was used to quantify the quality of individual prediction. Results Estimated 5-year survival rate (SR5) differed according to TNM stage: stage IA, 100% (95% confidence interval 70–100%); IB–III, 86% (73–100%); IVA, 54% (32–91%); IVB, 0% (0–52%). In a multivariate analysis, two independent prognostic factors were identified: lymph node (P = 0·036) and blood involvement (P = 0·015). A probability of survival model showed correlation of CTCL-SI with survival in patients with CTCL-SI > 20 according to the following formula: SR5 = 124–2 × (CTCL-SI)%. Calibration of SR5 against CTCL-SI-independent CTCL subsets revealed underestimation of Sezary syndrome. When CTCL-SI parameters were adjusted accordingly, the probability of survival model did not change significantly, while SR5 values became adequate. In addition, CTCL-SI was shown to be superior to TNM by 30% regarding individual predictive power. Conclusions Probability of survival in CTCL can be accurately predicted by a CTCL-SI-based survival rate formula. Careful monitoring of lymph node and blood compartments and quantification by CTCL-SI are reliable tools for follow-up of patients with CTCL and allow progression-adjusted prediction of prognosis.

Background: The c-myb oncogene is a transcription factor that regulates proliferation, differentiation and apoptosis of haematopoietic cells and activated T cells by binding to promoter sequences of such genes as c-myc or bcl-2 that are expressed in cutaneous T-cell lymphoma (CTCL). Objective: Our study was performed in order to evaluate c-myb expression as a quantitative parameter for differential diagnosis in leukaemic and non-leukaemic variants of CTCL. Methods: c-myb expression was analysed in lesional skin and in the peripheral blood of 21 patients with mycosis fungoides (MF), 15 patients with Sézary syndrome (SS) and 15 patients with inflammatory skin diseases using immunohistochemistry and semiquantitative as well as quantitative RT-PCR. Results: Immunohistochemistry confirmed expression of c-myb in the lesional skin of the majority of CTCL patients with a tendency towards higher expression in SS (1.86 ± 0.5) versus MF (1.2 ± 0.7) while c-myb was absent from the lesional skin of patients with inflammatory skin diseases. c-myb was overexpressed in the peripheral blood in all SS patients (100% SS vs. 35.7% MF) at a high expression level (51,335.31 ± 31,960.32 AU in SS vs. 1,226.35 ± 1,258.29 AU in MF using semiquantitative RT-PCR, and 5.72 × 10–2 ± 2.27 × 10–2 in SS vs. 0.91 × 10–2 ± 1.18 × 10–2 in MF vs. 0.24 × 10–2 ± 0.11 × 10–2 in inflammatory skin disease using quantitative RT-PCR). CD4+ cells from the peripheral blood of SS patients and cell lines in vitro showed the highest c-myb expression levels upon quantitative RT-PCR (23.27 × 10–2 and 10.78 × 10–2 ± 7.24 × 10–2). Conclusion: Overexpression of c-myb in skin lesions of both non-leukaemic and leukaemic CTCL independent of the stage of the disease indicates that it acts early in disease development. Nevertheless, if positive, c-myb expression in lesional skin is a clear-cut diagnostic marker for CTCL as compared to inflammatory skin diseases. High-level expression of c-myb in the peripheral blood as assessed by quantitative RT-PCR constitutes an additional diagnostic parameter for SS and may be especially useful in cases in which morphological determination of Sézary cells or FACS analysis of CD7 and CD26 remain inconclusive.

Background: Jessner’s lymphocytic infiltration of the skin (JLIS) is a clinically and histologically distinct disease entity. Conflicting results have been reported concerning its differentiation from cutaneous lupus erythematosus and polymorphous light eruption, its relationship to palpable migratory arciform erythema and its classification as a B-cell or a CD4+ T-cell lymphoproliferative disease. Objective: Our study was performed in order to re-evaluate JLIS clinically and by immunohistochemical and molecular analyses. Methods: Stringent inclusion/exclusion criteria were used to collect a cohort of 34 patients with JLIS that did not overlap with lupus erythematosus or polymorphous light eruption. Clinical data were analysed, and immunohistochemical and molecular studies were performed including TCR-γ PCR GeneScan software analysis of tissue and peripheral blood samples. Results: In the majority of the patients, the lesions consisted only of papules and plaques while in 12% annular lesions were also seen. The lesions were found on the face (38%), on the trunk and arms (50%) or at both sites (12%). Immunohistochemical analyses revealed a clear predominance of T cells in all patients, and of CD8+ T cells in 77% of the patients. As judged by TCR-γ PCR GeneScan analysis, 98 and 79% of the tissue and peripheral blood samples, respectively, showed a polyclonal T-cell population; identical T-cell clones were not detected concomitantly in both the skin and the peripheral blood of the same patient. Conclusions: JLIS occurs at 2 major predilection sites, that is the face and trunk. Therefore introduction of palpable migratory arciform erythema as a separate entity is not justified. The lymphoid infiltrates are dominated immunohistochemically by CD8+ T cells that do not show clonality on molecular analysis. Thus, JLIS represents a characteristic CD8+ polyclonal reactive skin condition.

Background: Although several immunological abnormalities have been demonstrated in Behçet’s disease (BD), the exact mechanism of the inflammatory changes occurring is still unknown. Antigen-presenting cells, such as mononuclear phagocytes, play a major role in the regulation of immune-mediated as well as of non-specific inflammation. Objective: To investigate the serum activity of patients with BD on antigen and chemokine expression of human macrophages in vitro. Methods: Serum of 15 patients (8 women, 7 men; mean age 33 ± 10 years) with BD was incubated with cultured macrophages isolated from peripheral blood of healthy volunteers. Macrophages maintained in patients’ serum, fetal calf serum with/without dexamethasone and interleukin (IL)-4 or γ-interferon were investigated for alternative macrophage-activation-associated CC-chemokine 1 (AMAC-1) and IL-8 mRNA expression by Northern blotting. In addition, cytocentrifuge macrophage preparations were stained with monoclonal antibodies against proteins indicating alternative (anti-inflammatory) macrophage activation, such as MS-1 high-molecular-weight protein (MS-1-HMWP), RM3/1 antigen (CD163) and 25F9, as well as classical (pro-inflammatory) macrophage activation, such as CD11c, class I receptor binding the Fc part of IgG (FcγRI: CD64) and class III receptor binding the Fc part of IgG (FcγRIII: CD16). Results: Macrophages treated with patients’ serum showed neither AMAC-1 expression nor staining with monoclonal antibodies for MS-1-HMWP, CD163 or 25F9. Concomitant treatment with IL-4/dexamethasone up-regulated significantly the expression of CD163. In contrast, IL-8 mRNA expression and staining for CD11c and CD64 were strongly positive after treatment with serum of patients with BD. CD64 positivity and IL-8 mRNA expression were more prominent in patients with active BD than in patients with inactive disease. Conclusion: Taken together, our results indicate that serum of patients with BD induces classical (pro-inflammatory) activation of human peripheral blood macrophages in vitro. Our findings suggest that serum factor(s) may be responsible for inflammatory changes in BD.

Primary cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of neoplasms characterized by skin-homing malignant T-lymphocytes. In contrast to primary extracutaneous (nodal) lymphomas, CTCL is characterized by a prolonged clinical course with a different clinical behavior and outcome. Disease progression, however, involves the recirculation compartments, i.e. lymph nodes and peripheral blood, and may finally spread to the visceral organs. Advances in T-cell receptor gene rearrangement techniques support the clinical diagnosis in early stages of CTCL by improved sensitivity and specificity of molecular diagnosis. The pathogenesis of CTCL is characterized by an altered immune biology and the accumulation of genetic mutations during disease progression. Although there is an initial response to standard therapy, including photochemotherapy, interferons, and retinoids, all patients will eventually relapse, and therefore treatment of CTCL continues to be palliative. New therapeutic drugs including bexarotene, DAB(389)IL-2 and IL-12 have demonstrated clinical responses; and new experimental therapeutic directions, e.g. stem cell transplantation and vaccination strategies may be applied with the intention to cure.

Objective: To evaluate, in the context of a randomized study, the ‘Sole Si Sole No GISED’ project, the effectiveness of an educational intervention to improve sun protection behaviour in schoolchildren. Methods: A large number of primary schools (classes II and III) in Italy were randomized to an educational intervention or control group: The intervention was conducted by trained teachers using ad hoc developed materials. Attitudes toward sun exposure and behaviour while in the sun were assessed at baseline and 1 year after concluding the educational intervention. In a subgroup of children, melanocytic naevi were counted on the upper limbs at the same intervals. The pilot phase of the study was started in 2001. Results: During the pilot phase, a total of 4,233 children was recruited. Of these, 2,116 were randomized to the active intervention and 2,117 to the control group. No difference for any of the study variables was documented between the 2 groups at baseline. About 20% of the children reported intense sun exposure during the year preceding the study. About 88% of the children reported adequate modalities of sun protection. Sunscreens were commonly used. A total of 508 children (12%) reported a history of sunburns in the year preceding the start of the study. Melanocytic naevi were counted in a total of 1,503 children (852 in the experimental and 651 in the control group). No differences in terms of skin, hair and eye colours were documented between the experimental and the control groups. The mean naevus count at baseline was 9.6 (median 7) in the experimental group and 10.1 (median 8) in the control group. Conclusion: About 50% of the total expected number of children was recruited during the pilot phase of the study. Randomization proved to be an excellent modality to select 2 samples similar for all the important study variables examined. A history of sunburns was reported less frequently than expected. The ‘Sole Si Sole No GISED programme’ is one of the few examples of a controlled evaluation of the effectiveness of an educational intervention in Italy.

The sentinel lymph node is a reliable indicator for a lymphogenous metastasis of malignant tumors. Its operative removal followed by histological examination enables an exact staging of the nodal status. Micrometastases can be detected at a very early time of tumor dissemination and high-risk patients can be selected for further operative and/or medicamentous therapeutic modalities. A close cooperation of surgeon, pathologist and nuclear medicine physician is necessary for optimum results. Preoperative identification must be performed by dynamic lymphoscintigraphy after peritumoral injection of a radiotracer. For the surgical removal of the SLN a combined approach by gamma-probe guidance and blue-dye is the procedure of choice. Complete cutting of the SLN and immunohistochemical stainings facilitate the detection of the often tiny micrometastases. By the described technique the identification and extirpation of the SLN succeded in nearly 100% of the more than 400 patients. During a 6-year follow-up only one patient with a negative SLN developed a lymph-node recurrence. This corresponds to a false-negative rate of less than 0.3%. However, it is not sure in which tumors a SLNE is indicated. We recommend the SLNE in all new diagnosed melanoma patients in clinical stages Ib to IIIa and other high-risk skin malignancies. The detection of tumor cells in the SLN is an indication for a radical lymph node dissection, but there is also no consensus concerning this point. Nevertheless studies have to show whether the removal of the SLN is more than a very sensitive diagnostic method or whether patients will profit from this early knowledge of metastases. Hitherto no influence on overall survival can be shown.

Lymphocytes do not just act as immunological effector cells, but also play an important role in the regulation of the immune response. They are able to induce or suppress inflammatory reactions and this balancing function is reflected in the well-known Th1/Th2 concept. Lymphocytes depend on antigen presenting cells (APC) for induction of differentiation and specific activation mediated by antigen capture, processing and presentation. Thus, APC represent a link between innate and acquired immunity. In parallel to the Th1/Th2 dichotomy, APC may be subdivided into (a) pro-inflammatory, classically activated APC such as mature dendritic cells and IFN-gamma-activated effector macrophages, and (b) into anti-inflammatory, alternatively activated APC such as IL-10-activated immature dendritic cells and IL-4-induced suppressor macrophages. Alternatively activated APC may mediate induction and maintenance of tolerance towards allergens and environmental substances, control the course of inflammatory reactions, and participate in healing processes by enhancing angiogenesis. Malignant tumors and certain infectious agents may misuse alternatively activated APC for their purposes, thereby requiring counter-action by Th1 lymphocytes and classically activated APC. The concept of alternative activation thus confirms the important role of APC in maintaining the balance between induction and suppression of both inflammation and immunity and it opens new perspectives for the development of specific immunotherapeutic approaches.

Classic variants of cutaneous borreliosis are erythema chronicum migrans (ECM), lymphadenosis benigna cutis (LBC) and acrodermatitis chronica atrophicans (ACA). Other dermatoses have been reported in the literature as possibly linked to borreliosis. A 59-year old female patient was seen in the late phases of cutaneous borreliosis with histologically confirmed ACA. In addition, prominent livedo racemosa was seen on the legs, also showing tissue changes similar to those of ACA. Borrelia burgdorferi infection was serologically confirmed by the presence of anti-IgM and anti-IgG antibodies. The clinical spectrum of late cutaneous borreliosis should be enlarged to include livedo racemosa.

Infolge der Seltenheit der Erkrankung sind die therapeutischen Strategien nicht sehr gut abgesichert, insbesondere ist die adjuvante Behandlung der drainierenden Lymphabflusswege und des Primartumors Gegenstand anhaltender Kontroversen.

Radiation-induced acne is a rare, clinically and pathogenetically ill-defined acneiform dermatosis with special features that may occur in irradiated skin areas especially after high doses of deeply penetrating radiation. We report on a patient with an oropharyngeal carcinoma who developed severe radiation-induced acne including comedones and cysts as well as few inflammatory papules and pustules in a skin area irradiated with up to 63 gray of a 6 MeV photon beam. Acnegenic drugs may precipitate the disease; our patient was on longterm therapy with carbamazepine whose acnegenic potency is less well documented than that of testosterone or glucocorticoids. Treatment of radiation-induced acne is comedolytic; topical retinoids are especially valuable.

A case report of recurrent angiolymphoid hyperplasia with eosinophilia (ALHE) in an otherwise healthy 20-year-old female with manifestation of the disease limited to the left arm and hand is presented together with brief evaluation of the literature as well as the features distinguishing ALHE and Kimura's disease. Immunohistochemical investigations support the hypothesis that ALHE represents a reactive inflammatory lesion rather than a benign vascular neoplasm. A viral cause of ALHE (e.g., HHV8 or Epstein-Barr virus (EBV)) could not be demonstrated. The recurrent nature of the disease is shown by this case, which also demonstrates the need for frequent medical and surgical management.

We describe a patient with follicular mycosis fungoides (MF), a rare folliculotropic variant of cutaneous T-cell lymphoma (CTCL). Follicular involvement in CTCL usually presents clinically as alopecia mucinosa associated histologically with follicular mucinosis. Follicular MF differs from alopecia mucinosa/follicular mucinosis associated with MF with regard to its clinical presentation, histology and, presumably, prognosis. Our patient presented with the characteristic findings of follicular MF, i.e. infiltrated plaques showing numerous enlarged, comedo-like follicular infundibula; histology was dominated by exclusive folliculotropism of atypical lymphocytes sometimes forming follicular Pautrier's microabscesses, and by lack of epidermotropism and follicular mucinosis. Despite photochemotherapy and treatment with oral retinoids and interferon alpha, the patient's follicular MF rapidly developed into a progressive CTCL with large tumorous lesions, but responded to electron beam therapy. The course of our patient's disease confirms the notion that follicular MF may be associated with a worse prognosis than classical MF. However, electron beam irradiation induced remission of follicular MF that was maintained by a combination therapy consisting of extracorporeal photopheresis and interferon alfa.

A 76-year-old female patient developed severe manifestations of a kaposi-like acroangiodermatitis (so-called Mali's disease) due to chronic venous insufficiency of the lower extremities. The patient presented with large areas of confluent, violaceous or brown-black papules on both lower legs. Histologically, proliferation of thick-walled capillaries was seen in the upper dermis consisting of fully differentiated endothelial cells, as shown by immunohistochemistry. In contrast to true Kaposi's sarcoma, human-herpes-virus-8 DNA could not be detected by polymerase-chain-reaction in this condition. We review the diagnostic criteria used to distinguish between acroangiodermatitis, also called pseudo-Kaposi's sarcoma, and the true Kaposi's sarcoma.

Background: Chronic cutaneous graft-versus-host disease (GvHD) can arise as a late complication after allogeneic bone marrow transplantation. Patients with extensive disease to date require intensive early and long-term immunosuppression; however, treatment is often insufficient. Since the beneficial effects of phototherapy for chronic cutaneous GvHD are well known, extracorporeal photoimmunotherapy (ECP) was also tried with some success for a few single patients with this disease. Objective: The long-term effect of ECP was evaluated in 4 patients with therapy-resistant severe chronic cutaneous GvHD after allogeneic bone marrow transplantation. Methods: Four patients were treated with monthly sessions of ECP over a period of 16–40 months. Disease severity was assessed by a semiquantitative score adapted from the literature including extent of skin area involved, rigidity of the skin, involvement of joints and immunosuppressive drug consumption. Results: In all patients, a favorable response was observed after 6–12 treatment cycles. One patient had a complete response, 2 patients had a partial response, and 1 patient had a minor response after treatment. In 2 patients, immunosuppressive medication started before initiating ECP could be reduced or completely withdrawn under ECP. Peripheral blood lymphocyte immunophenotyping revealed reduction of CD3+ CD4+ T cells in 3 patients and of elevated CD3+ CD8+ and CD57+ CD8+ T cell subsets in 2 patients. Conclusion: ECP is effective in treating severe chronic cutaneous GvHD. ECP possibly exerts its effects by reducing the number of CD8+ suppressor/cytotoxic T cells, the presumptive effector cells of GvHD. ECP is well tolerated with essentially no side effects and allows reducing the dosage of immunosuppressive agents.

Schnitzler's syndrome is a distinct disease entity characterized by the association of chronic urticaria, intermittent fever, arthralgia, elevated erythrocyte sedimentation rate and IgM macroglobulinaemia. We report a patient with the same symptoms, but a monoclonal IgG instead of IgM gammopathy. Histological examination of the urticarial lesions showed signs of mild leucocytoclastic vasculitis. Except for the different class of the monoclonal immunoglobulin, the clinical symptoms, laboratory findings and histology in this patient were identical with those in classical Schnitzler's syndrome. IgG and IgM paraproteins may be equivalent with regard to the putative pathophysiology of the disease process in Schnitzler's syndrome. We therefore suggest that the spectrum of Schnitzler's syndrome is expanded to include patients with chronic urticaria and monoclonal IgG gammopathy, as a closely related variant.

We compared the immunological functions of interferon-gamma (IFN-gamma)-induced, classically activated macrophages (caM phi) and of interleukin-4 (IL-4)- and glucocorticoid-induced, alternatively activated macrophages (aaM phi) in a human co-culture system in vitro. Proliferation of peripheral blood leucocytes (PBL) or CD4+ T cells mediated by optimal doses of phytohaemagglutinin (PHA) or concanavalin A (Con A) was only marginally influenced by caM phi, but was strongly inhibited by aaM phi. The degree of lymphocyte proliferation sustained in the presence of caM phi was gradually reduced in a dose-dependent fashion by the addition of aaM phi. Flow cytometric analysis revealed that expression of costimulatory molecules such as CD11a, CD40, CD54, CD58, CD80 and CD86 did not vary significantly between caM phi and aaM phi and was low for CD58, CD80 and CD86. As shown by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, IL-10 was expressed in caM phi, aaM phi and control macrophages; the level of expression of IL-10 was slightly enhanced in aaM phi. Neither neutralizing anti-IL-10 antibodies, indomethacin nor NG-monomethyl-L-arginine (NMMLA) was able to reverse aaM phi-mediated inhibition of lymphocyte proliferation. Of several agents interfering with various second messenger pathways, cAMP and the Ca(2+)-ionophore A23187 inhibited differentiation of cultured human monocytes into phenotypically mature aaM phi expressing MS-1 high molecular weight protein (MS-1-HMWP) and RM 3/1 antigen, and prevented the suppressive action of aaM phi on lymphocyte proliferation. In conclusion, these results who that aaM phi actively inhibit mitogen-mediated proliferation of PBL and CD4+ T cells independently of the expression of costimulatory molecules and of IL-10, NO or prostaglandin synthesis, and that inhibition of phenotypic differentiation of aaM phi is paralleled by a lack of functional maturation. Thus, fully matured aaM phi may be functional in down-regulating CD4+ T-cell-mediated immune reactions by an as yet unknown mechanism.

Mutations in genes encoding for proteins along the RAS-RAF-MEK-ERK pathway have been detected in a variety of tumor entities, including malignant melanoma, thyroid, colonic and ovarian carcinomas, and some sarcomas. Thus, a number of inhibitors of this pathway have been developed, whose antitumor potential is currently being assessed in different clinical trials. Up to now one drug of this category (vemurafenib) has been approved by the FDA and the European Commission for late-stage melanoma. Although these new targeted anticancer therapies are generally considered to be safe and well tolerated, certain toxicities have been attributed to them, with cutaneous side effects being perhaps the most frequent amongst them. Based on results of clinical trials and on case series, a distinct profile of cutaneous toxicity has been observed, which is similar to that of EGFR and multikinase inhibitors. As exanthema, palmar-plantar erythrodysesthesia syndrome, hyperkeratosis, xerosis, pruritus, photosensitivity, and paronychia, can be controlled in most cases with common conservative modalities, special attention should be given to the early detection of epithelial skin tumors (mainly keratoakanthomas) that can be induced during therapy with these agents. This report reviews all current published data on cutaneous side effects of RAS-RAF-MEK-ERK pathway inhibitors, and attempts to provide the clinician with clear hints for their management.

Primary cutaneous B-cell lymphomas (PCBCL) are subdivided into the aggressive form, primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT) and two subtypes of indolent behaviour (primary cutaneous follicle centre lymphoma and primary cutaneous marginal zone B-cell lymphoma). The difference in clinical behaviour can be explained by the tumour cell itself, or the lymphoma microenvironment including the antitumour immune response.To investigate the presence of regulatory T cells (Treg), CD4+CD25+FOXP3+, in the microenvironment of PCBCL in correlation with clinical outcome.Tumour specimens of 55 consecutive cases of PCBCL were blinded and analysed for FOXP3, CD4 and CD25 expression by immunohistochemistry. Confocal images were taken with a Leica SP5. Statistical analyses were performed to determine significance. The test was considered significant when P0.05.The CD4 and FOXP3 expression as well as the CD4/FOXP3 ratio were significantly increased in PCBCL of indolent behaviour in contrast to PCLBCL, LT (P=0.0002 for CD4, P0.0001 for FOXP3 and P=0.0345 for FOXP3/CD4 ratio). CD25 expression did not differ in the three groups (P=0.9414). Within the group of patients with PCLBCL, LT we identified a subgroup with FOXP3+ tumour cells as demonstrated by CD20/FOXP3 double stainings. Patients with FOXP3+ PCLBCL, LT tumour cells showed a better prognosis on Kaplan-Meier analysis.High numbers of Treg in the lymphoma microenvironment correlate with a better prognosis in PCBCL. In PCLBCL, LT the presence of FOXP3+ tumour cells is beneficial for prognosis suggesting that FOXP3 expression of PCLBCL, LT tumour cells might serve as a tumour suppressor.

Patient preferences for psoriasis treatments can impact treatment satisfaction and adherence and may therefore influence clinical outcome.To assess the impact of treatment experience (satisfaction with current treatment, number of prior visits, disease duration, number of preceding therapies and currently prescribed treatment modalities) on treatment preferences.A computer-based conjoint analysis experiment was conducted to analyse preferences of patients with moderate or severe psoriasis (n = 163) treated at a German University Medical Center for outcome (probability, magnitude and duration of benefit; probability, severity and reversibility of side effects) and process attributes (location, frequency, duration, delivery method, individual cost) of psoriasis treatments. Relative importance scores (RIS) were calculated for each attribute and compared using anova, post hoc test and multivariate regression analysis.Participants with longer disease duration attached significantly greater importance to duration of benefit (β = 0.206, P = 0.018), whereas participants on oral therapy were more concerned about magnitude of benefit by trend (β = 0.218, P = 0.058). Participants receiving injectables not only set higher value to probability of benefit (RIS = 32.80 vs. 21.89, P = 0.025) but also to treatment location (RIS = 44.74 vs. 23.03, P = 0.011), delivery method (RIS = 43.75 vs. 19.29, P = 0.019), treatment frequency (RIS = 31.24 vs. 16.89, P = 0.005) and duration (RIS = 32.54 vs. 16.57, P = 0.003) when compared with others. Treatment satisfaction was significantly higher in participants on infusions or injections compared with those on phototherapy and mere topical therapy.Treatment preferences may change over time course and with treatment experience. Participants on injectables attach great importance to efficiency and convenience of therapies, and are highly satisfied with their treatment.

Objective. Cellular adhesion and differentiation molecules (CAMs) may play a role in the recruitment and retention of inflammatory cells into rheumatoid arthritis synovial tissue (RA ST). In order to determine if certain CAMs are up-regulated in RA ST compared with normal ST, we studied the distribution of intercellular adhesion molecules (ICAMs) 1, 2, and 3 in ST. We also studied the MS-1 antigen since it is preferentially expressed on discontinuous endothelia, such as those found in RA ST; MS-1 is also expressed differentially upon cytokine activation of cells in vitro or in pathologic conditions in situ. Thus, we postulated a possible similarity between MS-1 and ICAM-1 expression in inflamed ST. Methods. Immunohistochemical analysis was used to determine the distribution of ICAMs and MS-1 in ST from 10 patients with RA, 10 with osteoarthritis (OA), and 4 normal individuals. Results. ICAM-1 expression was found on significantly more RA ST endothelial cells compared with normal cells, as well as on RA ST macrophages and lining cells. ICAM-2, also found on endothelial cells, showed no differential staining pattern. ICAM-3 was present on RA ST macrophages and lining cells as well as on some RA and OA endothelial cells. The MS-1 antigen was present on most RA and OA ST endothelia, lining cells, and macrophages. ICAM-1 expression and MS-1 expression in the lining layer were positively correlated in both RA and OA. Conclusion. ICAM-1, while found mainly on endothelial cells, is up-regulated on RA ST macrophages and lining cells, suggesting a role for these cells in the infiltration and tissue damage seen in the RA ST. ICAM-3, which is present mainly on normal resting leukocytes but not on normal endothelium, is expressed by some diseased ST leukocytes and endothelial cells. MS-1 is also found on the RA ST specialized, fenestrated endothelium, on macrophages, and in the lining layer. These results suggest that the differential expression of ICAMs and MS-1 in RA ST compared with normal ST might play a special role in the pathogenesis of RA.

Although the incidence of tumors of the lips is low, they are the most common oral tumors and their therapy is often challenging for the surgeon. Depending on the extent of resected lip tissue, various surgical procedures are performed for reconstruction. They all follow the goal to combine complete tumor resection with maximal functional and aesthetic restoration. Surgical procedures are classified regarding the direction of tissue mobilization into one-, two- and three-dimensional techniques. Even though more than two hundred different techniques have been described, only a small number are used on a regular basis. To select the appropriate procedure for the individual patient the exact anatomic location and size of the defect have to be taken into consideration. Treatment algorithms may guide the surgeon to a suitable reconstructive procedure for each case. Complications may occur more often due to the size and the site of the procedure. Final functional and aesthetic results are usually satisfying.

Scleromyxedema is a rare chronic cutaneous mucinosis usually associated with a monoclonal gammopathy and underlying systemic disease. The etiology of the disease is not known. There are no standard treatments and response to various therapeutic modalities varies. We report a case of refractory scleromyxedema in a 63-year-old man with a biclonal IgG and IgM λ-gammopathy. The patient was successfully managed with intravenous immunoglobulin.

A 71-year-old woman presented with an asymptomatic growing dermal tumor on her thumb. Clinical picture, ultrasound, laboratory investigations and histology were consistent with the diagnosis of gouty tophus. Pathogenesis, risk factors and therapy of tophaceous gout are discussed.

The reconstruction of deep facial wounds in oncological surgery is challenging. Especially for elderly multimorbid patients, a rapid procedure with acceptable aesthetic and reliable functional outcome is required. Recently, a new single layer skin substitute was developed. Integra® dermal regeneration template single layer (IDRT-SL) allows one-stage surgery in combination with split thickness skin grafting. However, no study has yet analysed the efficiency of IDRT-SL treatment.To evaluate applicability and efficiency of the IDRT-SL treatment in combination with split thickness skin grafting for a one-step closure of deep facial surgical wounds in elderly multimorbid patients.This prospective study analysed the functional and aesthetic outcome after reconstruction with an IDRT-SL template and an immediate split thickness skin graft in the face (80±3 years;3 concomitant diseases).Nine tumours, four basal cell carcinoma, two lentigo maligna, one spinal cell carcinoma, one lentigo maligna melanoma and one Bowen carcinoma were resected. Five defects were located on the nose and four on the cheek. The mean defect size was 11±3 cm2. All but one graft were taken completely without any complication. One patient suffered from a partial graft loss (30%). All defects showed significant shrinkage of 61±4%.One-stage reconstruction with a combination of IDRT-SL and split thickness skin grafting is an elegant, easy and rapid method to treat deep skin defects. The take rates, functional and early cosmetic outcome are promising. This new method should be considered for selected cases of elderly multimorbid patients with deep facial wounds.

Skin substitutes are a growing market since technical advancements have allowed a substantial progress in treating extensive defects of the skin. A variety of skin substitutes with different properties and thus resulting different indications is offered on the market. Important benefits of skin substitutes are their ready availability in almost any quantity and the predictable product properties concerning implantation, incorporation, resorption and long-term outcome. Although, most skin substitutes still need skin grafts at a later date which is disadvantageous. Nevertheless dermal substitutes have reduced the need for thick skin grafts allowing the donor site and the patient to heal faster with fewer surgeries. The use of skin substitutes in dermatologic surgery is widespread and new fields of application are emerging. The variety of artificial skin has definitely changed the reconstructive ladder helping to cover larger defects with less time and effort which is an important issue especially in elderly and multimorbid patients. In the last years a growing number of studies in the literature report the use of artificial skin substitutes to secure a rapid reconstruction with reliable cosmetic and functional results after oncological resections. Furthermore, skin substitutes are used to cover chronic wounds like diabetic foot ulcers or venous leg ulcers to promote healing. Congenital diseases like giant hairy nevi, aplasia cutis congenital or epidermolysis bullosa are conditions in children where skin substitutes play a role. But even in tissue augmentation or in cosmetic surgery skin substitutes come into vogue. The latest advance are cultured autologous or allogenic substitutes some even in combination with alloplastic material. Besides of medical questions that arise from the use of these materials in reconstructive surgery legal and economic aspects have to be taken into account. This article is giving an overview over the most common skin substitutes and their use in dermatosurgery.

Cranial fasciitis is a rare variation of nodular fasciitis that occurs in the region of the capillitium. We report on a 29-year-old patient who presented with a 2-month history of a tumor progressively increasing in size located on the occiput. Histological examination revealed a tumor, consisting of tightly packed spindle-shaped cells with underlying myxoid stroma, which extended from the dermis to the subcutis. Actin and vimentin were detected by immunohistochemistry. We established a diagnosis of cranial fasciitis and excised the tumor. Especially when a child or young adult presents with a tumor in the skull area, consideration should be given to cranial fasciitis in the differential diagnosis to avoid unnecessary and possibly very invasive treatment approaches.

Cutaneous T-cell lymphoma (CTCL) is an extra-nodal non-Hodgkin lymphoma of mature T cells. These tumor cells home to and persist in the skin, producing a broad spectrum of clinical entities. Recent results of basic research on tumor biology and tumor immunology as well as molecular genetics of cutaneous T-cell lymphoma have fostered the development of new therapeutic approaches. Several clinical trials testing these targeted therapies have shown encouraging results. This article provides an overview of recent research developments and therapeutic strategies for cutaneous T-cell lymphoma.

Caterpillar dermatitis or lepidopterism (Lepidoptera = butterflies) is a toxic-irritant, or rarely allergic, reaction triggered by the release of histamine, thaumetopoein and other kinins from the hairs of butterflies and caterpillars. In Central Europe, the two main causes of caterpillar dermatitis are the oak and pine processionary caterpillar. In addition to cutaneous reactions, patients may develop conjunctivitis, bronchitis and even anaphylactic reactions. We describe the cutaneous aspects of caterpillar dermatitis based on two case reports.

Mitomycin C is an alkylating chemotherapeutic agent which is instilled intravesically to prevent recurrence of superficial bladder carcinomas. After several cycles of mitomycin C, our patient developed a pruritic genital dermatitis and palmar desquamation. Following exclusion of a fungal infection, we performed patch tests using the standard series, the major basic ointment ingredients, disinfectants, and mitomycin C in concentrations of 0.001 to 0.1%; the resulting diagnosis was allergic contact dermatitis due to delayed-type hypersensitivity to mitomycin C. The skin rash rapidly resolved with application of topical steroids, and the intravesical chemotherapy was changed to doxorubicin. Eczematous skin reactions are quite common side effects after intravesical instillation of mitomycin C. In the majority of cases, they are caused by delayed-type hypersensitivity reactions, presumably elicited by hematogenous spread of the allergen, and not by irritation. The sensitization most likely occurs via the bladder mucosa. In order to differentiate between allergic and toxic contact dermatitis, patch tests with the above-mentioned mitomycin C concentrations are useful. In cases of mild allergic contact dermatitis the intravesical chemotherapy might be continued with concomitant topical steroids.

Pine wood is one of the most used raw products in furniture manufacturing in Europe. High concentrations of colophony and turpentine can be extracted from pine resins. A 45-year-old woman developed a contact dermatitis of the face and hands due to a sensitization to colophony and turpentine after she had bought untreated pine chairs. The increased use of untreated pine in the furniture industry might result in an increase of colophony and turpentine-induced contact allergies. Therefore, the slogan "untreated=harmless" should be considered critically in such cases.

The idiopathic hypereosinophilic syndrome is a rare systemic disease characterized by blood and tissue eosinophilia of unknown etiology, in which multiple organs may be affected. In hypereosinophilic dermatitis the only affected organ besides the blood is the skin.We present a series of seven patients with hypereosinophilic dermatitis who were treated in our hospital between 2002 and 2003.All patients initially showed characteristic, therapy-resistant, polymorphic skin lesions, presenting with a combination of erythematous, pruritic and urticarial papules and plaques. All had blood eosinophilia without evidence of allergic, parasitic or other causes. The histology showed tissue eosinophilia only in half of the cases; the other histological findings were non-specific. We observed a good response to therapy with systemic corticosteroids, dapsone and light therapy, applied as UVA-1 irradiation or as shower photochemotherapy.The diagnosis "hypereosinophilic dermatitis" should be based primarily on the characteristic clinical picture together with "idiopathic" peripheral eosinophilia, whereas the histological findings are not always indicative. Because of the multiplicity of possible differential diagnoses and the often non-revealing histology, we assume that the diagnosis "hypereosinophilic dermatitis" is often overlooked.

The c-myb oncogene is a transcription factor that regulates proliferation, differentiation and apoptosis of haematopoietic cells and activated T cells by binding to promoter sequences of such genes as c-myc or bcl-2 that are expressed in cutaneous T-cell lymphoma (CTCL).Our study was performed in order to evaluate c-myb expression as a quantitative parameter for differential diagnosis in leukaemic and non-leukaemic variants of CTCL.c-myb expression was analysed in lesional skin and in the peripheral blood of 21 patients with mycosis fungoides (MF), 15 patients with Sézary syndrome (SS) and 15 patients with inflammatory skin diseases using immunohistochemistry and semiquantitative as well as quantitative RT-PCR.Immunohistochemistry confirmed expression of c-myb in the lesional skin of the majority of CTCL patients with a tendency towards higher expression in SS (1.86 +/- 0.5) versus MF (1.2 +/- 0.7) while c-myb was absent from the lesional skin of patients with inflammatory skin diseases. c-myb was overexpressed in the peripheral blood in all SS patients (100% SS vs. 35.7% MF) at a high expression level (51,335.31 +/- 31,960.32 AU in SS vs. 1,226.35 +/- 1,258.29 AU in MF using semiquantitative RT-PCR, and 5.72 x 10(-2) +/- 2.27 x 10(-2) in SS vs. 0.91 x 10(-2) +/- 1.18 x 10(-2) in MF vs. 0.24 x 10(-2) +/- 0.11 x 10(-2) in inflammatory skin disease using quantitative RT-PCR). CD4+ cells from the peripheral blood of SS patients and cell lines in vitro showed the highest c-myb expression levels upon quantitative RT-PCR (23.27 x 10(-2) and 10.78 x 10(-2) +/- 7.24 x 10(-2)).Overexpression of c-myb in skin lesions of both non-leukaemic and leukaemic CTCL independent of the stage of the disease indicates that it acts early in disease development. Nevertheless, if positive, c-myb expression in lesional skin is a clear-cut diagnostic marker for CTCL as compared to inflammatory skin diseases. High-level expression of c-myb in the peripheral blood as assessed by quantitative RT-PCR constitutes an additional diagnostic parameter for SS and may be especially useful in cases in which morphological determination of Sézary cells or FACS analysis of CD7 and CD26 remain inconclusive.