Primary cutaneous alveolar rhabdomyosarcoma in an adolescent - A challenging diagnosis.

Primary cutaneous alveolar rhabdomyosarcoma is an extremely rare and highly aggressive soft tissue sarcoma that predominantly arises on the extremities and perineum of adolescents and young adults. Dermatologists should be aware of these tumors in order to promptly make the diagnosis and initiate treatment.

Analysis of the Prevalence of Mental Disorders in Psoriasis: The Relevance of Psychiatric Assessment in Dermatology.

BACKGROUND: The boundary between Dermatology and Psychiatry has increasing recognition. Psoriasis is a common psychophysiological skin disease with a major impact on patient's quality of life and a paradigmatic example of a pathology in that boundary. Studies are needed to exactly point out the prevalence of specific psychopathology and mental disorders associated with psoriasis. This work intends to analyse the prevalence of psychopathology and psychiatric comorbidities in patients with psoriasis. METHODS: A systematic review of the literature was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the "5S" model proposed by Haynes. From all the papers retrieved by this search, a total of 34 papers met the inclusion criteria and were then deeply analysed. RESULTS: The most prevalent mental disorders in these patients are sleep disorders (average prevalence: 62.0%), sexual dysfunction (45.6%), personality (35.0%), anxiety (30.4%), adjustment (29.0%), depressive (27.6%) and substance-related and addictive disorders (24.8%). Other mental disorders have been less described, namely somatic symptoms and related disorders, schizophrenia and other psychoses, bipolar disorder and eating disorders. CONCLUSIONS: This updated research shows that the prevalence of psychiatric conditions in psoriasis may range from 24% to 90%. The study of the mind-skin connection in psoriasis may improve the knowledge about psoriasis and its psychiatric comorbidities. The link between psoriasis and associated mental disorders is frequently forgotten or not considered in the clinical practice. Psychiatric disorders in patients with psoriasis may be underdiagnosed. These patients would really benefit from psychiatric assessment, with therapeutic relevance.

Systemic drugs inducing non-immediate cutaneous adverse reactions and contact sensitizers evoke similar responses in THP-1 cells.

Contact sensitizers induce phenotypic and functional changes in dendritic cells (DC) that enhance their antigen-presenting capacity and, ultimately, modulate the T cell response. To evaluate if there is a similar effect of drugs causing T-cell-mediated cutaneous adverse drug reactions (CADR), we studied the in vitro effect of drugs on THP-1 cells, a cell line widely used to evaluate the early molecular and cellular events triggered by contact sensitizers. The effect of allopurinol, oxypurinol, ampicillin, amoxicillin, carbamazepine and sodium valproate, at EC30 concentrations, was evaluated on p38 MAPK activation, by Western Blot, and on the expression of genes coding for DC maturation markers, pro-inflammatory cytokine/chemokines and hemeoxygenase 1 (HMOX1), by real-time RT-PCR. Results were compared with lipopolysaccharide (LPS), a DC maturation stimulus, and the strong contact sensitizer, 1-fluoro-2,4-dinitrobenzene (DNFB). All drugs studied significantly upregulated HMOX1 gene transcription and all, except the anticonvulsants, also upregulated IL8. Allopurinol and oxypurinol showed the most intense effect, in a magnitude similar to DNFB and superior to betalactams. Transcription of CD40, IL12B and CXCL10 genes by drugs was more irregular. Moreover, like DNFB, all drugs activated p38 MAPK, although significantly only for oxypurinol. Like contact sensitizers, drugs that cause non-immediate CADR activate THP-1 cells in vitro, using different signalling pathways and affecting gene transcription with an intensity that may reflect the frequency and severity of the CADR they cause. Direct activation of antigen-presenting DC by systemic drugs may be an important early step in the pathophysiology of non-immediate CADR.

Epidemiology of Psoriasis in Portugal: A Population-Based Study.

INTRODUCTION: Psoriasis is a common, chronic, and inflammatory skin disorder with a high personal, social and economic burden and important implications for healthcare systems. The aim of this study was to provide an epidemiological characterization of individuals with psoriasis in Portugal. MATERIAL AND METHODS: A large observational, cross-sectional, nationwide, population-based survey study developed by the Portuguese Psoriasis Group of the Portuguese Society of Dermatology and Venereology (GPP-SPDV). A structured questionnaire was designed and applied by experienced interviewers to a random, representative sample of Portuguese individuals with psoriasis and/or psoriatic arthritis. Patients were considered to have psoriasis if they replied positively to one of the following questions: "Does any physician have ever diagnosed you with psoriasis?" or "Do you have a skin disorder characterized by scaling, reddish skin lesions located in the elbows/knees/scalp?". RESULTS: A total of 6381 individuals were interviewed, of which 283 met the criteria for psoriasis, corresponding to a prevalence rate of 4.4% (95% CI 3.95 - 4.98). Out of the participants that met psoriasis criteria, 24% had suggestive signs/symptoms but did not have a clinical diagnosis established and were not being monitored by a physician. Although more than 70% of participants had active disease (scaling, erythema, or pruritus) and one third had joint symptoms, only 12% were on systemic treatment. Fifty percent of participants with psoriasis (n = 139) had relevant comorbidities (most frequently depression/anxiety and cardiometabolic diseases). Sixteen percent of participants with psoriasis (n = 46) reported that psoriasis interfered with their daily activities (median impact of 5 in a 0 - 10 scale) and 12% mentioned the disease had an impact in their sexual life (median impact of 5 in a 0 - 10 scale). CONCLUSION: The results of this study suggest that the prevalence rate of psoriasis is likely to be high in Portugal, and several gaps exist at different levels of healthcare delivery to these patients, from diagnosis to treatment. This study provides important data for the future planning of interventions targeting the improvement of psoriasis care in Portugal.

Verruciform xanthoma: report of two cases.

Verruciform xanthoma (VX) is an uncommon benign condition of unknown etiology, which frequently affects the oral mucosa in adults. Other less common locations include the anogenital region and the skin. VX typically presents as an asymptomatic plaque showing a verrucous appearance. Histological examination is essential for the diagnosis and shows verrucous hyperplasia of the epidermis and xanthoma cells limited to the dermal papillae. We present herein two cases of VX and discuss the histopathological findings and possible correlation with a postulated etio-pathogenesis.

Signal transduction profile of chemical sensitisers in dendritic cells: an endpoint to be included in a cell-based in vitro alternative approach to hazard identification?

The development of non-animal testing methods for the assessment of skin sensitisation potential is an urgent challenge within the framework of existing and forthcoming legislation. Efforts have been made to replace current animal tests, but so far no alternative methods have been developed. It is widely recognised that alternatives to animal testing cannot be accomplished with a single approach, but rather will require the integration of results obtained from different in vitro and in silico assays. The argument subjacent to the development of in vitro dendritic cell (DC)-based assays is that sensitiser-induced changes in the DC phenotype can be differentiated from those induced by irritants. This assumption is derived from the unique capacity of DC to convert environmental signals encountered at the skin into a receptor expression pattern (MHC class II molecules, co-stimulatory molecules, chemokine receptors) and a soluble mediator release profile that will stimulate T lymphocytes. Since signal transduction cascades precede changes in surface marker expression and cytokine/chemokine secretion, these phenotypic modifications are a consequence of a signal transduction profile that is specifically triggered by sensitisers and not by irritants. A limited number of studies have addressed this subject and the present review attempts to summarise and highlight all of the signalling pathways modulated by skin sensitisers and irritants. Furthermore, we conclude this review by focusing on the most promising strategies suitable for inclusion into a cell-based in vitro alternative approach to hazard identification.

Pruritus, Allergy and Autoimmunity: Paving the Way for an Integrated Understanding of Psychodermatological Diseases?

Pruritus is a key symptom in allergology and dermatology, contributing to the global and huge impact on quality of life related to skin disorders, both those which are not related to a primary dermatosis (illness) and those which are linked with primary skin lesions (disease). This is particularly evident within psychophysiological dermatoses, a group of psychodermatological diseases where there is a primary dermatosis, where psychological stress plays a role, and where pruritus may represent a major and shared symptom. The etiopathogenesis of pruritus in those disorders sheds light on the link among psychopathological features, psychological stress and the subtle interface between allergic and autoimmune mechanisms, where mast cells play a pivotal role. Allergy has long been recognised as an altered reactivity to exogenous antigens (allergens), defined as an immediate hypersensitivity mediated by immunoglobulin E (IgE). In turn, the immunological understanding of atopy is related to an immediate hypersensitivity reaction to environmental antigens involving T-helper 2 (Th2) responses and the IgE production. Mast cells are major cells in the early phase of allergy, releasing the mediators involved in the symptoms associated with the allergic disease, including pruritus, when the allergen cross-links with IgE, whose mechanisms can be observed in acute urticaria and atopy. Some allergic reactions may persist and allergy may eventually lead to autoimmunity, with the development of a T-helper 1 (Th1) and then IgE-independent inflammation. For instance, in chronic spontaneous urticaria, the mast cell activation may include autoimmune mechanisms, where autoantibodies against the extracellular α subunit of the high-affinity IgE receptor (FcεRIα) and to IgE are observed, with the involvement of Th1 lymphocytes and the production of interferon-γ (INF-γ). The role of autoimmunity is also suggested in the etiopathogenesis of other psychophysiological dermatoses, namely psoriasis, atopic dermatitis and alopecia areata. In the latter, for example, mast cells were reported to be linked with the loss of immune privilege and they are the key cells involved in the experience of pruritus, whose intensity was reported to precede and be correlated with the onset of the hair loss. Furthermore, considering that the role of hair and skin is wide, from psychosocial aspects (communication and social interaction) to vital functions (such as, temperature control), it is straightforward that they are central in our interactions and synchronization with others and the world; thereby, we may admit that the psychophysiological dermatoses could represent a loss of such synchronization. Furthermore, they are often linked with psychopathology which strongly connects with the concept of desynchronization, namely, sleep disorders and depressive symptoms, the clinical expression of a dysfunction in the interplay among mast cells, pineal gland and melatonin, thus the circadian rhythm, as well as their connection with the hypothalamic corticotrophin-releasing hormone (CRH), well-known for its key role in stress response. Moreover, increasing evidence has supported the existence of cutaneous equivalents for these mechanisms, connecting with those central pathways. Thereby, taking all these concepts into consideration, this review intends to look into the updated evidence on the shared biological mechanisms between allergy and autoimmunity, underlining pruritus as a core element, then revisiting the key role of mast cells and discussing the connection with melatonin and immune-inflammatory pathways in the physiopathology of psychophysiological dermatoses, thus paving the way for the understanding of their psychosomatic correlates and a comprehensive psychodermatological approach.

Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS).

BACKGROUND: In some patterns of cutaneous adverse drug reactions, and depending on the culprit drug, patch testing has been helpful in confirming its cause. Its value in Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has not been established in a large cohort of patients. OBJECTIVE: The aim of the present study is to evaluate the safety and usefulness of patch testing in DRESS. PATIENTS/METHODS: Between January 1998 and December 2008, we studied 56 patients with DRESS induced by antiepileptic agents in 33 patients (59%), allopurinol in 19 (34%) and sulfasalazine, cotrimoxazole, tenoxicam, and amoxicillin in 1 patient each (7%). RESULTS: A positive patch test reaction was observed in 18 patients (32.1%), of which 17 were with antiepileptics and 1 with tenoxicam. In the antiepileptic group, carbamazepine alone was responsible for 13 of 17 positive reactions (76.5%). Patch tests with allopurinol and its metabolite were negative in all cases attributed to this drug. CONCLUSIONS: In this study, patch testing was a safe and useful method in confirming the culprit drug in DRESS induced by antiepileptic drugs, whereas it had no value in DRESS induced by allopurinol. The pathogenesis of DRESS is not yet entirely clarified, but positive patch tests suggest a drug-dependent delayed hypersensitivity mechanism.

Photoallergic contact dermatitis from benzydamine presenting mainly as lip dermatitis.

BACKGROUND: Benzydamine, a non-steroidal anti-inflammatory drug (NSAID) in use for more than four decades, has been reported to cause photosensitivity. OBJECTIVES: To study the results of photopatch testing to benzydamine and the clinical features of the dermatitis during a 3-year period (2006-2008). PATIENTS AND METHODS: During this period, 74 patients with photodermatoses were photopatch tested with an extended baseline series of allergens including benzydamine and in suspicious cases, with drugs that contain it. Test sites were irradiated on D2 with 5 J/cm(2) and readings were performed on D2 and D4. RESULTS: Ten patients (six females/four males), aged 21-84 years (mean 64.9) had a positive photopatch test to benzydamine [1-5% petrolatum (pet.) from Bial-Aristegui] and to drugs that contain it (Tantum verde oral solution and Momen gel). Nine patients had lower lip cheilitis and one lichenified eczema on photo-exposed sites. CONCLUSION: Photosensitivity from both topical and systemic benzydamine has been occasionally described, mainly in southern Spain. Despite its widespread use and its known photosensitizing capacity, photoallergic contact dermatitis from benzydamine is probably underdiagnosed as the clinical presentation of mainly the lip and chin is not typical of photoallergic contact dermatitis and benzydamine is not part of most photoallergen series.

Allergic contact dermatitis to shoes induced by dimethylfumarate: A new allergen imported from China.

BACKGROUND: In the last two years several cases of severe contact dermatitis related to newly acquired sofas and armchairs originating from China have been published. The responsible allergen is dimethylfumarate (DMF), an extremely potent sensitizer and irritant found in sachets inside the furniture. Recently, cases of contact dermatitis related to shoes and riding helmets have also been described. METHODS: We evaluated two patients with allergic contact dermatitis related to shoes manufactured in China that were contaminated by dimethylfumarate found in sachets placed inside the shoeboxes. RESULTS: Patch tests with DMF extracted from the sachets inside the shoeboxes showed positive reactions. Postitive reactions were also obtained using small fragments of the shoes and tissue of the "MouldProof" sachet. The patients were instructed to avoid the suspected shoes and were treated with topical corticosteroids. CONCLUSIONS: Contact dermatitis induced by dimethylfumarate should be suspected in appropriate cases. It is important to remember that this allergen is not included in most series for patch testing.

Unilateral progressive osseous heteroplasia.

A 50-year-old male patient presented with firm subcutaneous nodules and plaques with a gritty texture, unilaterally affecting the left side of the trunk and the left limbs. These lesions had had a progressive course since early childhood and caused functional impairment. There was no family history of similar disorders. No phospho-calcium metabolism abnormalities were observed. Biopsies of the affected areas demonstrated osteoma cutis. Analysis of DNA showed no mutation of the GNAS gene. The clinical features were consistent with progressive osseous heteroplasia, atypically presented in a unilateral form, probably revealing a mosaic distribution.

Photopatch testing with an extended series of photoallergens: a 5-year study.

OBJECTIVE: We conducted a retrospective study (2003-07) evaluating the results of photopatch tests (PPTs) performed with an extended series with the objective of determining the main photoallergens in our region and whether they would be detected by a recently recommended baseline PPT series. MATERIALS AND METHODS: 83 patients (58 females/25 males, mean age 54.8 years) were tested with a photoallergen series, and among these, 30 were also tested with a non-steroidal anti-inflammatory drug (NSAID) series, irradiated at D2 with 5 J/cm(2) ultraviolet A (UVA). RESULTS: Thirty-six of 83 patients (43.3%) had at least one positive reaction, with 21 (25.3%) reacting in the photoallergen series. The main relevant reactions were as follows: 10 to ultraviolet filters (benzophenone-3 and benzophenone-4, 3 patients each), 7 to promethazine, and 2 to chlorpromazine. Twenty of 30 patients tested (70%) had a relevant positive PPT to an NSAID, 9 to piroxicam because of systemic photosensitivity, 8 to benzydamine from a topical gel or oral solution, and 2 to ketoprofen. CONCLUSIONS: Our results are discordant with most recently published studies because of the particularities of the population studied and to regional prescribing habits. Therefore, apart from the recommended baseline series of photoallergens, other substances must be tested according to regional peculiarities.

Cutaneous pseudallescheria boydii infection in a renal transplant patient: A case report.

We describe the case of a 59-year-old male renal transplant recipient who presented with a 1 month history of nodular, erythematous, and crusted lesions on the anterior surface of the left leg. There was no history of trauma. The patient had no systemic signs or symptoms. A skin biopsy revealed evidence of a deep fungal infection, with septate and branching hyphae amongst the dermal inflammatory infiltrate, but the culture was negative. Initial treatment with itraconazole proved ineffective and new lesions appeared. New tissue samples were obtained for culture, allowing the isolation of Pseudallescheria boydii. The patient underwent surgical excision of the lesions combined with voriconazole 400 mg/day for 2 months. After this period no new lesions appeared and the patient has remained without recurrence after 2 years of follow-up. Pseudallescheria boydii is an opportunistic fungus that can cause systemic infection mainly in immunocompromised patients that manifests as pulmonary, osteoarticular, ocular, vascular, cutaneous or central nervous system disease. Resistance to therapy can occur with infection progression and high mortality. Treatment with the combination of an antifungal agent, mainly voriconazole, and surgery, when feasible, probably provide the best results in cutaneous infections.

A remarkable case of cutaneous metastatic breast carcinoma.

We describe a 50-year-old woman with a 5-month history of multiple asymptomatic papulonodular lesions on the left chest area. Biopsy was consistent with cutaneous metastases from a ductal breast carcinoma. No distant metastatic lesions were detected. The patient was referred to the Gynecologic Oncology Department. Treatment included chemotherapy, radiotherapy and surgery. At present the patient is well with no signs of recurrence. This case reports a clinically remarkable cutaneous metastatic breast carcinoma.

Scrofuloderma: A Diagnosis to Bear in Mind in the Western World.

The incidence of tuberculosis has been increasing worldwide. Contrarily, a recent decrease in Portugal has been reported. Cutaneous tuberculosis comprises a low percentage of all cases. We report a 70-year-old female with a 2-month-history of painful, nodular, suppurative lesions in the groin area, bilaterally. Previous history was remarkable for Human Immunodeficiency Virus infection and stage-IIIB cervical cancer. A skin biopsy, stained with periodic acid-Schiff and Fite's stain, polymerase chain reaction on purulent discharge and mycobacterial culture of the skin were performed, leading to the diagnosis of scrofuloderma. Tuberculostatic therapy was initiated and complete response was observed. This case depicts an uncommon variant of tuberculosis, highlighting the need for awareness of the cutaneous variants of tuberculosis that, although rare, can still present in the clinic today.

A incidência de tuberculose tem vindo a aumentar globalmente. Em Portugal, porém, esta incidência diminuiu na última década. A tuberculose cutânea representa uma pequena percentagem de todos os casos. Apresenta-se o caso de uma mulher de 70 anos com nódulos supurativos da região inguinal bilateralmente, dolorosos, evoluindo há 2 meses. Como antecedentes relevantes, apresentava infeção por vírus da imunodeficiência humana e carcinoma do colo do útero, estadio IIIB. Foram realizadas biópsia cutânea (coloração pelo ácido periódico de Shiff e coloração de Fite), pesquisa de micobactérias por polymerase chain reaction e estudo microbiológico por cultura, tendo sido estabelecido o diagnóstico de escrofuloderma. Iniciou terapêutiva tuberculostática com resposta favorável. Este artigo realça a importância do reconhecimento das formas cutâneas de tuberculose e a necessidade de manter um elevado índice de suspeição, sobretudo em pacientes imunodeprimidos.

Elephantiasis nostras verrucosa in the setting of lymphoedema tarda and neurofibromatosis type 1.

Elephantiasis nostras verrucosa (ENV) comprises an uncommon skin disease characterised by dermal fibrosis with hyperkeratotic, verrucous and papillomatous lesions that usually occur after chronic lymphoedema. We describe the case of a 56-year-old-man with neurofibromatosis type 1, no known surgical history, no chronic medication and no travel history, presenting with worsening non-pitting oedema and impressive foul-smelling mossy plaques and cobblestone-like nodules in both legs and feet, especially on the right, compatible with the diagnosis of ENV.

A new scalp formulation of calcipotriene plus betamethasone compared with its active ingredients and the vehicle in the treatment of scalp psoriasis: a randomized, double-blind, controlled trial.

BACKGROUND: New topical treatments in scalp psoriasis are needed because many current topical treatments are disliked by patients and associated with poor compliance. OBJECTIVE: To compare the efficacy and safety of once-daily, two-compound scalp formulation containing calcipotriene plus betamethasone dipropionate with the individual components in the same vehicle and the vehicle alone. METHODS: In this 8-week, multicenter, randomized, double-blind study, patients with scalp psoriasis were randomized to treatment with the two-compound scalp formulation (calcipotriene 50 microg/g plus betamethasone 0.5 mg/g, as dipropionate) (n = 541), betamethasone 0.5 mg/g (as dipropionate) in the same vehicle (n = 556), calcipotriene 50 microg/g in the same vehicle (n = 272), or vehicle alone (n = 136). RESULTS: More patients achieved "absent" or "very mild" disease at week 8 with the two-compound scalp formulation (71.2%) compared with betamethasone dipropionate in the same vehicle (64.0%, p = .011), calcipotriene in the same vehicle (36.8%, p < .0001), or the vehicle (22.8%, p < .0001). LIMITATIONS: Efficacy of the active comparators in the study has not been established in relation to calcipotriene and betamethasone formulations available for clinical use. CONCLUSION: Calcipotriene plus betamethasone dipropionate scalp formulation was more effective than either of the individual components or the vehicle alone.

Differential modulation of CXCR4 and CD40 protein levels by skin sensitizers and irritants in the FSDC cell line.

The development of non-animal methods for skin sensitization testing is an urgent challenge. Some of the most promising in vitro approaches are based on the analysis of phenotypical and functional modifications induced by sensitizers in dendritic cell models. In this work, we evaluated, for the first time, a fetal skin-derived dendritic cell line (FSDC) as a model to discriminate between sensitizers and irritants, through analysis of their effects on CD40 and CXCR4 protein expression. The chemicals concentrations were chosen based on a slight cytotoxicity effect (up to 15%). Protein levels were evaluated by Western blot and immunocytochemistry, after stimulation with the skin sensitizers 2,4-dinitrofluorobenzene (DNFB), 1,4-phenylenediamine (PPD) and nickel sulphate (NiSO(4)), the non-sensitizer 2,4-dichloronitrobenzene (DCNB), and the irritants sodium dodecyl sulphate (SDS) and benzalkonium chloride (BC). All sensitizers tested increased CD40 and CXCR4 levels. In contrast, irritants decreased both proteins levels, with a more pronounced effect on CXCR4. In agreement with these results, dendritic cells derived from human peripheral blood monocytes-derived dendritic cells (MoDC) showed a similar response pattern to the skin sensitizer and irritant tested, PPD and SDS, respectively. In conclusion, evaluation of CD40 and CXCR4 proteins in chemical-treated FSDC may represent a useful tool in a future in vitro test for sensitizing assessment.