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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.

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: 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.

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.

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.

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.

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.

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.

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.

There is a wide variety of topical or surgical treatment options for molluscum contagiosum (MC). However, treatment in young or anxious children is difficult, time-consuming and often painful. We studied the topical efficacy and tolerance of imiquimod, a topical immune-response modifier, which stimulates the production of interferon-alpha and other cytokines in children with MC. In an open-label, follow-up trial, imiquimod 5% cream was applied three times a week for 16 weeks to 15 children aged 4-11 years with multiple MC. Nine of 13 children (69%) who completed treatment responded. Two patients (15%) showed a complete remission, and seven (54%) had a partial response, with a remarkable reduction of the MC lesions. Four children (31%) showed stable or progressive disease. In three children (23%) with partial remission, the number of mollusca were considerably reduced, thus avoiding surgical treatment. In general, the treatment was well-tolerated, without systemic side-effects. Local side-effects included erythema (85%), itching (75%), burning sensations (23%) and pain (11%). Three children (23%) discontinued treatment because of local side-effects. The results of this study suggest that imiquimod 5% cream is a useful new treatment option for MC in children, especially in severe cases. The dosing schedule and length of treatment requires further evaluation.

We report on a 74-year-old female patient with a primary cutaneous CD20+, diffuse large cell B-cell lymphoma of the lower leg resembling a chronic non-healing leg ulcer. There was no evidence of systemic involvement on computed tomography (CT) scans of the chest, abdomen and pelvis; a slightly enlarged lymph node in the right groin showed dermatopathic lymphadenopathy on histology and immunohistochemistry. Involvement of the bone marrow and peripheral blood was ruled out by punch biopsy and fluorescent activated cell sorter (FACS) analysis of the blood, respectively. Therapeutic anti-CD20 monoclonal antibody rituximab was given at 375 mg m(-2) i.v. once weekly for 7 weeks, without adverse effects, resulting in a minor improvement in the centre of the ulcerated tumour. Unfortunately, the response was not maintained, and after 7 weeks of treatment the patient started to develop new tumour lesions at the border of the ulcer. Local radiotherapy was started and combined photon and electron beam irradiation induced complete remission of the B-cell lymphoma.

Severe generalized nodular and bullous mastocytosis of the xanthelasmoid type is described in a 7-month-old boy. Reddish to yellowish-brown xanthelasmoid papules and nodules first developed in the inguinal region a few weeks after birth and then progressively spread to cover nearly the entire body surface. There was severe pruritus and recurrent episodes of blistering. The diagnosis of cutaneous mastocytosis of the xanthelasmoid type with subepidermal bullae was confirmed by skin biopsies showing solid and deeply penetrating infiltrates of metachromatic mast cells under light and electron microscopy. Systemic involvement of other organs, however, was excluded by bone scintigraphy, abdominal ultrasound, bone marrow aspiration and echocardiography. The extensive skin involvement was reflected in highly elevated urinary levels of histamine (263.4 microg L(-1)) and its metabolite N-methylimidazole acetic acid (20.8 mg L(-1)). The patient was systematically well and received only symptomatic treatment. Over a period of 1 year, the condition gradually improved, and the skin lesions began to flatten and regress.

Facial palsy and orofacial swelling in childhood represent a challenge in differential diagnosis for paediatricians and dermatologists. One possible entity, Melkersson-Rosenthal syndrome (MRS), is a rarity in childhood. We describe a 9-year-old girl with the diagnosis of MRS who had episodic swelling of the upper lip and complete peripheral facial palsy, associated with herpes and recurrent bacterial infections. Therapeutic options for MRS in childhood are limited. Our patient benefited from a 2-month course of prednisolone 1 mg kg(-1) daily. We review previously published cases of MRS in childhood, and discuss the differential diagnosis of orofacial swelling and facial palsy as well as treatment options in children.

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.

An otherwise healthy 24-year-old woman presented with persistent asymptomatic skin-coloured papular lesions on her trunk which had appeared over 18 months, gradually increasing in number, size and the extent of the skin surface area involved. Physical examination revealed multiple flesh - to whitish - coloured papules, 2 to 5 mm in diameter, located on her neck, anterior chest wall, axillae and upper abdomen (Fig. 1). The lesions were smooth, painless on palpation and not grouped. Laboratory investigations only showed normal results. Histopathological examination of a papular lesion from the upper abdomen revealed a cystic structure in the mid-dermis lined by four to five layers of squamous epithelium with a discrete granular layer. Laminated keratinous material and multiple transversely or obliquely cut vellus hairs were present within the cyst, while sebaceous elements were lacking in the vicinity or within the cyst wall (Fig. 2a, b). Polaroscopic examination demonstrated double refractile vellus hairs in the cyst.

Glomangiomas are benign tumors arising from neuromyoarterial cells surrounding cutaneous arteriovenous anastomoses that serve as temperature regulators. They exist as solitary or multiple types, occurring sporadically or in a familial pattern, the latter of which is rare.We describe a 4-generation pedigree of familial cutaneous glomangioma, in addition to the 3 other well-documented pedigrees reported in the literature to date, and we clarify ways in which to distinguish the different types of glomus tumors.Nodular skin lesions of 4 affected family members were analyzed by histologic, immunohistologic, and electron microscopic methods. To elucidate the gene defect in this family, we searched for a linkage to a candidate locus on chromosome 11q23 previously identified in paragangliomas, one form of glomus tumor, in 16 family members of 4 generations by using polymorphic markers.The diagnosis of disseminated cutaneous glomangiomas was confirmed histologically in 4 family members of 3 different generations. Glomangiomas were transmitted in an autosomal dominant pattern via the paternal line. Genetic linkage analysis of the affected family members excluded linkage to chromosome 11q23.An autosomal dominant pattern of inheritance has been described for glomus tumors of the paraganglioma type originating from the APUD cell system, the underlying genetic defect of which has been mapped to chromosome 11q23. In contrast, we show that the genetic defect in disseminated cutaneous glomus tumors of the glomangioma type deriving from smooth muscle cells or pericytes is not linked to chromosome 11. Thus we suggest that the common term glomus tumor, used for both paragangliomas and glomangiomas in the current literature, is misleading and should be avoided because these tumors have different histologic derivation and genetic origin.

Inflammatory skin diseases such as allergic contact dermatitis, atopic dermatitis, and psoriasis are together the most frequent dermatoses and are of great medical and economic significance. Despite impressive progress in recent years, the immune pathogenesis of these diseases is not yet fully understood. In particular, it remains an open question which anti-inflammatory mechanisms can be activated to prevent development of such abnormal immune reactions in the still healthy organism, and how these anti-inflammatory processes may be enhanced and instrumentalized for treatment of these disease states.

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.

Perforating disorders represent a heterogenous group of dermatoses characterized by transepithelial elimination of dermal structures. Primary perforating disorders should be distinguished from secondary perforating disorders in which perforation with transepithelial elimination is a rare component of a variety of dermatoses. The primary perforating disorders are hyperkeratosis follicularis et parafollicularis in cutem penetrans (Kyrle's disease), elastosis perforans serpiginosa and perforating folliculitis. Acquired reactive perforating dermatosis (also known as acquired reactive perforating collagenosis) together with the hereditary variant of the reactive perforating collagenosis represent further examples of the primary perforating disorders. We report on 84 year old and 96 year old female patients with an acquired perforating dermatosis. Both of the patients additionally showed diabetes and hyperuricemia. Oral administration of allopurinol (100 mg daily) led to a healing of the disseminated skin lesions in 1-2 weeks. After a follow-up period of 6 months, both patients were in complete remission. On one hand, these results prove again the existence and the severity of this disease, and on the other hand suggest an immunomodulating or differentiation-promoting action in addition to the uricostatic effect of allopurinol.

Between 1982 and 1995, over 700 HIV-infected patients with different skin diseases were registered at the Department of Dermatology, Benjamin Franklin Medical Center, The Free University of Berlin. Thirty-six of them (approximately 5%) were diagnosed as having psoriasis. This is clearly a higher prevalence of psoriasis than in the general population (1-2%). If psoriasis lesions are not clinically seen before diagnosis of HIV infection, the disease will preferentially (approximately 80% of these cases) appear during the late stages of the infection (CD4/CD8 ratio0.4). Six of the 36 patients with HIV-related psoriasis (= 16%) were found to have severe disease, showing an exsudative clinical picture. In this paper we report in detail on two representative cases from this group of patients. Histological examination also revealed exsudative changes in HIV-infected patients with clinically moderate psoriasis. Immunohistochemically, HIV-related psoriasis showed a moderately decreased number of infiltrating T-cells, in contrast to psoriatic skin from non-infected patients. A marked difference was the reduced expression of the lymphocyte antigen OPD-4 in HIV-related psoriasis. Routine antipsoriatic treatment modalities in combination with systemic retinoids and phototherapy (SUP/PUVA) were successful in the treatment of severe exsudative psoriasis in HIV patients, but the course of the disease was prolonged and exacerbation was more frequent. HIV-related psoriasis was found not to influence the underlying HIV infection.

We describe clinically and histologically typical eccrine hidrocystomas on the eyelids and forehead of a 60-year-old woman which were successfully treated with topical atropine. Concomitantly the patient had long-standing Parkinson's disease with typical facial seborrhea and hyperhidrosis. In this report, we review the literature about eccrine hidrocystomas and discuss the question of a causal relationship with Parkinson's disease in our patient.

Superior vena cava syndrome (VCSS) develops because of a progressive reduction of venous return from the head, neck and the upper extremities. The presenting sign of this relatively rare condition is often a rapidly developing, often massive facial edema. As a consequence, such the patients are often seen initially by a dermatologist. Other clinical characteristics may include cyanotic facial erythema, dilatation of the neck veins, and a prominent venous pattern n the anterior chest. Today, primary lung cancers and other mediastinal tumours represent the most common cause of VCSS, which may take a slowly progressive or a more fulminant course. In these cases, the disease develops rapidly and becomes life-threatening, requiring intensive medial diagnosis and care. We describe three patients with superior vena cava syndrome due to a) bronchogenic carcinoma, b) bihilar sarcoidosis and c) metastasizing malignant melanoma. Since recognition of VCSS broadens the diagnostic spectrum of the dermatologist, an overview on its diagnostic and therapeutic implications is given based on our cases and the literature.

In this paper we present two patients with T-cell lymphomas, who presented with unique skin lesions, but later developed extracutaneous involvement. The first patient showed marked edematous infiltration of the trunk and legs as well as grouped, umbilicated red-to-blue papules limited to the body folds. The second patient had lesions reminiscent of poikiloderma vascular atrophicans, with erythema, teleangiectasia, hypo- and hyperpigmentation, and bizarre scarring, followed by development of papules and nodules. The first patient also had marked leukocytosis and lymph node enlargement. Histology, immunohistology, and immunophenotyping revealed an unclassifiable CD8+, alpha, beta +, CD10+ cutaneous T cell lymphoma with leukemic involvement. Unclassifiable cutaneous T-cell lymphoma was also diagnosed in the second patient: it was associated with a monoclonal proliferation of T-cell receptor V gamma 9, delta + large granular T lymphocytes and finally developed into frank, acute pre-T lymphatic leukemia.

Besides the classical forms of cutaneous T-cell lymphoma (C-CTCL), such as mycosis fungoides and Sézary's syndrome, unique variants may be encountered. The classification of these rare cutaneous T cell lymphomas is problematic and controversial. Newer classifications of lymphoma in general, such as the Revised European-American Lymphoma (REAL) Classification, emphasize well-established clinico-pathological entities. It seems appropriate to attempt to bring greater clarity to the classification of cutaneous T-cell lymphomas using the same principles. In this review, we list and characterize the rare variants of cutaneous T-cell lymphoma, such as (1) clinical, histological and immunological variants of mycosis fungoides; (2) progressive cutaneous T-cell lymphoma (P-CTCL) including transformed classical cutaneous T-cell lymphoma (TC-CTCL) and primary progressive cutaneous T-cell lymphoma (PP-CTCL); (3) angiocentric and angioimmunoblastic cutaneous T-cell lymphomas; (4) large cell anaplastic, CD30+ cutaneous T-cell lymphoma; (5) HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL); (6) cutaneous manifestations of primary extracutaneous T-cell neoplasias; (7) unclassifiable cutaneous T-cell lymphoma.

Rat monoclonal antibody MS-44B was raised against the dendritic human melanoma cell line SK-Mel 25 and detects highly dendritic cells and endothelial cells in various human organs. Among the cells recognized are dendritic cells in lymphoid organs, such as lymph node, tonsil and spleen, dendritic cells in skin, lung and lamina propria, (astro-)glial cells in the central nervous system and mesangial cells in the kidney. In peripheral lymph nodes (and less consistently in visceral lymph nodes), MS-44B reactive cells are found predominantly in the paracortical area and in the region of the marginal sinus; in tonsils these dendritic cells are concentrated at the outer rim of the follicle, while their distribution in the white pulp of the spleen is less well defined. In skin, both dermal and epidermal dendritic cells are stained. In the dermis just beneath the dermal-epidermal border, dendritic cells may be found with their processes protruding into the epidermal basal layer. MS-44B reactive epidermal dendritic cells send their processes in a horizontal direction or into the upper epidermal cell layers. MS-44B reactive epidermal dendritic cells are neither Langerhans cells, since they lack HLA-DR antigens and CD1, nor Merkel cells, since they lack cytokeratin expression. They rather seem to constitute a subpopulation of epidermal melanocytes that are low in tyrosinase expression and do not populate the melanocyte area of the hair bulb. With regard to the endothelium, monoclonal antibody MS-44B reveals marked heterogeneity in that it preferentially stains the endothelium of large and medium-sized arterial vessels, while capillary and venous endothelia are less well stained.(ABSTRACT TRUNCATED AT 250 WORDS)