Showing papers in "Journal of Dermatology in 2010"

Collagen-derived dipeptide, proline-hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts

Abstract: Orally ingested collagen undergoes degradation to small di- or tripeptides, which are detected in circulating blood 2 h after ingestion. The influence of collagen-derived peptides on dermal extracellular matrix components and cell proliferation was studied using cultured human dermal fibroblasts. Of the various collagenous peptides tested here, the dipeptide proline-hydroxyproline (Pro-Hyp) enhanced cell proliferation (1.5-fold) and hyaluronic acid synthesis (3.8-fold) at a dose of 200 nmol/mL. This was concomitant with a 2.3-fold elevation of hyaluronan synthase 2 (HAS2) mRNA levels. Small interfering RNA (siRNA)-mediated knockdown of the HAS2 gene in human dermal fibroblasts inhibited Pro-Hyp-induced HAS2 mRNA transcription and cell mitotic activity. Addition of genistein or H7, a protein kinase inhibitor, abolished the Pro-Hyp-induced HAS2 mRNA stimulation. Pro-Hyp elevated phosphorylation of signal transducer and activator of transcription 3 (STAT3) within a short time period (60 min). These results suggest that Pro-Hyp stimulates both cell mitotic activity and hyaluronic acid synthesis, which is mediated by activation of HAS2 transcription.

Autoantibody profiles in systemic sclerosis: predictive value for clinical evaluation and prognosis.

Abstract: Systemic sclerosis (SSc) is thought to be an autoimmune disease, as autoantibodies against a variety of extractable nuclear antigens can be detected in patient sera. Subgrouping patients based on the type of autoantibodies present can be useful in diagnosis and management. Anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (anti-topo I) are the classic autoantibodies associated with SSc. ACA are associated with limited cutaneous involvement and isolated pulmonary hypertension, whereas anti-topo I are associated with diffuse skin involvement and pulmonary fibrosis. ACA are predictors for a favorable prognosis, while anti-topo I are correlated with a poor prognosis and SSc-related mortality. Additionally, anti-RNA polymerase antibodies (anti-RNAP) are associated with diffuse cutaneous disease and renal involvement. Anti-nucleolar antibodies define multiple subgroups of patients with SSc. Of these, anti-Th/To antibodies (anti-Th/To) and anti-PM-Scl antibodies (anti-PM-Scl) are associated with limited cutaneous SSc (lSSc), whereas anti-U3RNP antibodies (anti-U3RNP) are associated with diffuse cutaneous SSc (dSSc). In addition, anti-Th/To and anti-U3RNP can be predictors for a less favorable prognosis with a higher frequency of organ involvement, such as pulmonary fibrosis, pulmonary hypertension and renal crisis. Other autoantibodies are less frequently reported: anti-Ku antibodies, anti-U1RNP antibodies, anti-human upstream-binding factor, and anti-U11/U12 antibodies. These antibodies are generally less specific to SSc, but also define clinically distinct patient subsets. Thus, characterization of autoantibodies in SSc together with knowledge of disease characteristics intrinsic to distinct patient populations is helpful for assessing the clinical presentation and prognosis of this disease, and for monitoring patients with SSc.

Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: efficacy and safety results from a Phase II/III randomized controlled study.

Abstract: Incidence of psoriasis vulgaris in Asians is estimated at 0.05-0.3%. Studies in North America and Europe demonstrated that adalimumab, a fully human, recombinant, immunoglobulin G(1) monoclonal antibody, was efficacious and well-tolerated in patients with chronic plaque psoriasis. This 24-week, placebo-controlled study evaluated the efficacy and safety of three different dosing regimens of adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis (n = 169). Patients were randomized to receive adalimumab 40 mg every other week (eow), adalimumab 80-mg loading dose at week 0 followed by adalimumab 40 mg eow starting at week 2, adalimumab 80 mg eow, or placebo eow given as s.c. injections. The primary efficacy endpoint was the percentage of patients achieving a 75% or greater improvement in Psoriasis Area and Severity Index (PASI 75) score at week 16. At week 16, PASI 75 response rates were significantly greater for all three adalimumab groups (40 mg eow: 57.9%, P < 0.001; 40 mg eow plus loading dose: 62.8%, P < 0.001; 80 mg eow: 81.0%, P < 0.001) versus placebo (4.3%). As early as week 4, the 40-mg eow plus loading dose and 80-mg eow groups achieved significantly greater PASI 75 response rates compared with placebo. Injection-site reactions and hepatic events occurred in greater percentages of adalimumab-treated patients compared with placebo. Adalimumab therapy demonstrated efficacy and safety at all three dosage regimens. Rapid response rate in patients receiving 40 mg eow plus loading dose supports using an 80-mg loading dose in the treatment of psoriasis.

Comorbidities associated with psoriasis: an experience from the Middle East.

Abstract: Recent studies suggest that psoriasis patients have higher rates of comorbidities. We sought to determine the prevalence of comorbidities and co-medications in our psoriasis patients. We conducted case-control study in 1835 patients with psoriasis vulgaris and age- and gender-matched cohort without psoriasis. Patients were examined for clinical characteristics of psoriasis, PASI scores, and data of age, sex, body mass index (BMI), smoking status, comorbidities, and co-medications were analysed for both patients and controls. We identified 1661 (92.8%) patients with mild to moderate psoriasis (PASI 10). Patients with psoriasis were more likely to be current smokers (51.34% vs 32.51% controls). Respective prevalence rates of risk factors in those with mild-moderate psoriasis, severe psoriasis, and controls were as follows: inflammatory arthritis (20%, 31% and 10.68%); coronary heart disease (4.1%, 8.35% and 1.42%); obesity (BM1) (32.5%, 41% and 17%); diabetes mellitus type II (37.4%, 41% and 16%); hypertension (32%, 40.3% and 11.55%); dyslipidemia (14.1%, 22.48% and 4.96%); metabolic syndrome (16%, 26.35% and 6.76%); chronic obstructive pulmonary disease (COPD) (5.36%, 6.98% and 4.03%); cancer (0.3%, 1.55% and 0.16%). They had a higher odds of inflammatory arthritis, coronary heart disease, obesity, diabetes mellitus II, hypertension, dyslipidemia, and metabolic syndrome. They were receiving significantly wider varieties of drugs. Which most commonly included antidiabetic drugs, antihypertensives, and hypolipidemic drugs.

Mechanisms of skin fibrosis in systemic sclerosis

Abstract: Systemic sclerosis (SSc) or scleroderma is an acquired disorder which typically results in fibrosis of the skin and internal organs. Skin fibrosis, the hallmark of this disease, is defined as excess deposition and accumulation of extracellular matrix, mainly type I collagen, in the dermis. Dermal fibroblasts isolated from lesional skin of SSc patients and cultured in vitro exhibit increased synthesis of collagen and decreased collagenase activity, consistent with the disease phenotype. This review focuses on the recent progress in the research for molecular mechanisms of skin fibrosis in SSc. The upregulated collagen production at transcriptional level in SSc fibroblasts involves various regulators including cytokines or transcription factors. Among them, transforming growth factor (TGF)-beta/Smad signaling is likely to play a key role in the pathogenesis of SSc, and the autocrine TGF-beta signaling hypothesis can explain intrinsic activation of collagen promoter in SSc fibroblasts. Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases might also contribute to the excess accumulation of collagen in the dermis.

Future treatments in systemic sclerosis

Abstract: Systemic sclerosis (SSc) is an autoimmune disorder with clinical manifestations resulting from immune activation, fibrosis development and damage of small blood vessels. Although there have been no established treatments for SSc, lots of new treatments targeting organ and pathogenesis are in the process of development. Transforming growth factor (TGF)-beta is a major cytokine involved in the pathogenesis of fibrosis in SSc. The blockade of cell surface molecules capable of activating latent TGF-beta, blockade of ligand by the pan-isoform-specific antibody, soluble TGF-beta receptors and a recombinant latency associated peptide, as well as inhibitors for ALK5 and Smad3 are the potential strategies to abolish the pathological activation of TGF-beta signaling in SSc fibroblasts. Besides TGF-beta, connective tissue growth factor (CTGF)/CCN2, platelet-derived growth factor (PDGF) and endothelin-1 are the candidates for the new therapeutic targets. As for immune dysfunction in SSc, i.v. immunoglobulin infusion, stem cell transplantation and B-cell depletion are potential new therapies under or awaiting a randomized, double-blind, placebo-controlled trial, although their efficacies are still controversial. Phosphodiesterase-5 inhibitors, endothelin receptor antagonists and inhibitors for serotonin signaling are the new therapeutic targets for Raynaud's phenomenon, digital ulceration and pulmonary arterial hypertension in SSc. Imatinib mesylate may be a novel new therapy for fibrosis and vasculopathy in SSc because it reverses the expression levels of Fli1, which is a transcription factor downregulated in SSc through an epigenetic mechanism and is likely to be involved in the development of fibrosis and vasculopathy in this disease. Potential therapeutic targets other than those described above are also reviewed.

Non-tuberculous mycobacterial infections of the skin: A retrospective study of 29 cases

Abstract: The incidence of infections caused by non-tuberculous mycobacteria has increased in recent years, due to a rise in dermatological procedures and a greater prevalence of immunosuppression in the general population. This study investigated the clinical and microbiological findings of non-tuberculous mycobacterial skin infections. The study population included 29 patients from whom non-tuberculous mycobacteria were cultured after isolation from skin biopsy materials, cutaneous abscesses or exudates. Clinical, microbiological and epidemiological data were collected from each patient. Eight patients were immunocompromised while 21 were not. Precipitating factors such as acupuncture, filler injection, surgical procedures and other traumatic events preceded infection in 13 (including 11 normal hosts and two immunocompromised hosts) of the 29 patients. Multiple skin lesions were present in eight patients (including three normal hosts and five immunocompromised hosts). In eight patients (including four immunocompromised hosts), symptoms were accompanied by tenosynovitis, osteomyelitis and myositis. Mycobacterium abscessus was isolated from nine patients, Mycobacterium fortuitum was isolated from nine patients, Mycobacterium chelonae was isolated from six patients, Mycobacterium marinum was isolated from two patients, a Mycobacterium avium complex member was isolated from two patients, and Mycobacterium haemophilum was isolated from one patient. Ten of the 24 cases caused by rapidly growing organisms (i.e. M. chelonae, M. abscessus and M. fortuitum groups) were precipitated by skin injuries such as acupuncture, filler infection and other medical procedures. Increases in skin medical procedures, including both acupuncture and esthetic interventions, explain the increasing incidence of these organisms. Immunocompromised patients tended to develop multiple skin lesions and deep tissue infections.

Epidermolysis bullosa acquisita: What's new?

Abstract: Type VII collagen is an adhesion molecule of the extracellular matrix in epithelial basement membranes, and the main constituent of anchoring fibrils at the dermal-epidermal junction (DEJ). Autoimmunity against this protein is causing the rare organ-specific epidermolysis bullosa acquisita (EBA). EBA is a rare acquired, heterogeneous, chronic blistering disease of skin disease of skin and mucous membranes characterized by subepidermal blisters and tissue-bound as well as circulating autoantibodies to the DEJ. EBA has several distinct clinical presentations with other subepidermal bullous diseases, such as mainly dystrophic epidermolysis bullosa or bullous pemphigoid. The circulating immunoglobulin G autoantibodies for EBA react with a 290-kDa dermal protein, type VII collagen, as detected by immunoblot analysis using dermal extracts. The pathogenicity of these autoantibodies has been demonstrated by experimental animal models, in which anti-type VII collagen antibodies injected into a mouse produced an EBA-like blistering disease in the animal. EBA cases often require high doses of systemic corticosteroids and a variety of immunosuppressants. Although treatment for EBA is frequently difficult and unsatisfactory, some therapeutic success has been reported with colchicine, dapsone, infliximab and i.v. immunoglobulin. In this review, we will focus on recent progress in our understanding of the clinical manifestations, the etiopathogenesis as well as the management of EBA.

Overview of epidermolysis bullosa.

Abstract: Epidermolysis bullosa (EB) is classified into major types - EB simplex (EBS), junctional EB (JEB) and dystrophic EB (DEB) - on the basis of the level of tissue separation within the cutaneous basement membrane zone. Recent advances in research on EB have led to the identification of 10 genes responsible for EB. The Japanese Ministry of Health, Labor and Welfare has designated JEB and DEB, but not EBS, as specified diseases. However, EBS has a lethal variant and should also be registered as a specified disease. In the Third Consensus Meeting on the Diagnosis and Classification of EB held in Vienna in 2007, it was recommended that Kindler syndrome should be classified as a subtype of EB. Corrective gene therapy is the most ideal therapy for EB, but much more research is required before it can be developed and used in clinical practice. Cell-based therapies using fibroblasts and bone marrow cells have recently attracted considerable attention.

Risk factors associated with having psoriatic arthritis in patients with cutaneous psoriasis.

Abstract: The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case-control study involving 400 psoriasis patients who attended the Psoriasis and Photo-medicine clinic in the National Skin Center of Singapore over a 1-year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self-administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49-169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33-4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.

From anti-p200 pemphigoid to anti-laminin γ1 pemphigoid

Abstract: Anti-laminin γ1 pemphigoid is an autoimmune subepidermal bullous disease first described in 1996, and has been distinct from previously known subepidermal blistering diseases, such as bullous pemphigoid and epidermolysis bullosa acquisita. Circulating autoantibodies of the patients do not react to any known autoantigen of the skin, but react to a 200-kDa molecule (p200) from dermal extracts. The identity of p200 was unmasked as laminin γ1, an extracellular matrix glycoprotein composing several forms of laminin heterotrimers. We renamed this disease from the previously used anti-p200 pemphigoid to anti-laminin γ1 pemphigoid, a new entity of an autoimmune bullous disease. In this decade, we have experienced over 70 cases of this disease. Although the number of the cases of anti-laminin γ1 pemphigoid is half as many as the number of definitely diagnosed cases of epidermolysis bullosa acquisita in the same duration, a considerable number of the cases could be clinically misdiagnosed as epidermolysis bullosa acquisita. Unveiling the pathogenicity and development of a useful diagnostic method is necessary for appropriate management of this new disease.

Acquired reactive perforating collagenosis : Current status

Abstract: Acquired reactive perforating collagenosis is a unique perforating dermatosis, characterized clinically by umbilicated hyperkeratotic papules or nodules and histologically by a focal hyperkeratosis in direct contact with transepidermal perforating dermal collagen. Several inflammatory or malignant systemic diseases may coexist with acquired reactive perforating collagenosis. The possible biochemical or immunological mechanisms of the systemic diseases, potentially responsible for the development and appearance of acquired reactive perforating collagenosis, are still under investigation. Several topical treatments, ultraviolet B phototherapy and allopurinol p.o. administration may be effective.

Animal model of systemic sclerosis.

Abstract: Scleroderma is a fibrotic condition characterized by immunological abnormalities, vascular injury and increased accumulation of extracellular matrix proteins in the skin. Although the etiology of scleroderma has not yet been fully elucidated, a growing body of evidence suggests that extracellular matrix overproduction by activated fibroblasts results from a complex interaction among endothelial cells, lymphocytes, macrophages and fibroblasts, through a number of mediators, such as cytokines, chemokines and growth factors. For a better understanding of the pathophysiology of scleroderma, animal models are important tools. These models reproduce several histological as well as biochemical aspects of human scleroderma, and we can learn a lot through animal studies. On the other hand, it must be emphasized that studying animal models cannot answer all the problems of human scleroderma. In this review, I introduce current insights into the pathogenesis and also recent updates of therapeutic approaches using several animal models of SSc, and discuss their contribution to our understanding of the pathogenesis of, and treatments for, human scleroderma.

Recent progress in studies of infantile hemangioma.

Abstract: A hallmark of infantile hemangioma, the most common tumor of infancy, is its dramatic growth after birth, by diffuse proliferation of immature endothelial cells, followed by spontaneous regression. The growth and involution of infantile hemangioma is quite different from other vascular anomalies, which do not regress and can occur at any time during life. Some hemangioma lesions can be extremely disfiguring and destructive to normal tissue and may even be life-threatening. Unfortunately, existing therapeutic approaches have limited success and significant adverse effects of some treatment modalities limit their use. Better understanding of the pathogenesis of hemangioma will enable the development of better therapeutic strategies. Herein, we review recent studies and new hypotheses on the pathogenesis of the tumor. Detailed mechanisms of activated vascular endothelial growth factor (VEGF) signaling in tumor cells, identification of their origin and characterization of multipotent stem cells that can give rise to infantile hemangioma are shedding new light on this intriguing vascular tumor.

Community‐based epidemiological study of psychosocial effects of acne in Japanese adolescents

Abstract: In this community-based cross-sectional study, 1443 Japanese adolescents aged 13-19 years participated from two schools in Kagawa Prefecture. Students completed a self-administered questionnaire to assess the prevalence of acne, knowledge about acne, self-management of acne and emotional well-being. A five-item version of the Mental Health Inventory (MHI) subscale of the Short Form 36 was used to assess psychological health and depression status. Among respondents, 859 (59.5%) said they had acne (51.6% of the boys and 64.8% of the girls). A majority (56.8%) of those who said they had acne also reported a family history of acne. Of the 555 female respondents with acne, 39.1% reported experiencing acne flares in temporal proximity to menstruation. Less than half (38.8%) of respondents with acne had sought or were seeking treatment. The three most common factors believed to trigger or exacerbate acne were stress, lack of sleep and sweat. The mean MHI score of 847 students with acne was significantly lower than 475 students without acne. The mean MHI score of female students with acne was significantly lower than male students with acne. Students with acne were also significantly more depressed than those without acne and female students were significantly more depressed than male students. Acne is a common problem for Japanese teenagers and causes personal and social difficulties. Our results suggest the necessity of educational programs in school or public to ensure that adolescents are aware of acne and to encourage young people to improve their mental health through better acne treatment.

Epidemiological survey of foot diseases in Japan: results of 30,000 foot checks by dermatologists

Abstract: There has been no epidemiological survey of foot diseases in Japan. In this study we determined the prevalence of foot diseases, especially tinea pedis (TP) and tinea unguium (TU) in Japan. We conducted a randomized survey of outpatients who visited a dermatologist during the third week of May in 1999, 2000 and 2006. The most frequently reported condition was "fungal infection" in 8737 (40.0%) of 21 820 patients in 1999/2000, and 3848 (49.4%) of 7783 patients in 2006. The patients who visited a dermatologist for reasons other than superficial fungal infection but were diagnosed with TP or TU comprised 18.6% of the study population in 2000 and 24.1% in 2006. Of the patients with TP or TU, 63.2% used topical medication only. This survey showed that often patients are not aware of fungal infections and that their treatment is sometimes insufficient. Dermatologists should actively examine and treat patients with TP and TU.

Temporal triangular alopecia and a review of 52 past cases

Abstract: Temporal triangular alopecia (TTA) is a circumscribed, non-cicatricial form of alopecia confined to the frontotemporal region. The patient, a 15-year-old boy, was noticed at birth to have an alopecial area, sized 1.5 cm x 2.5 cm, in the right temporal region. Microscopic examination revealed miniaturized hair follicles accompanied by differentiated sebaceous glands. We have provided a synopsis of the past 52 cases. Of the 53 cases of TTA including our case, more than half (55.8%) were detected in childhood between the ages of 2 and 9 years, while 36.5% were detected at birth and only 3.8% (only two cases) in adulthood. There were three familial cases. Several congenital diseases were associated with the condition, for example, phakomatosis pigmentovascularis, Down syndrome and Dandy-Walker malformation. This information suggests that TTA can be recognized as a hamartomatous mosaic disease.

Positive treatment effects of ustekinumab in psoriasis: Analysis of lesional and systemic parameters

Abstract: Ustekinumab, a human anti-interleukin (IL)-12/IL-23p40 monoclonal antibody has demonstrated significant efficacy in patients with moderate-to-severe psoriasis. Skin lesion biopsies, cell surface markers on peripheral blood lymphocytes, and ex vivo T-helper (Th)1/Th2 cytokine responses from peripheral blood mononuclear cells (PBMC) from patients receiving ustekinumab 45 or 90 mg, or placebo were evaluated at baseline and week 12. Inflammatory serum protein levels were measured at baseline, week 2 and week 12. At week 12, median epidermal thickness decreased from 312.1 to 132.7 μm, and median levels of cellular proliferation (Ki67) and T-cell infiltration (CD3) decreased by 84.3% and 70.7%, respectively, in the combined ustekinumab group (all P ≤ 0.002). Serum levels of tumor necrosis factor (TNF)-α, C-C motif ligand 27 (CCL27) and other inflammatory cytokines remained unchanged. Minimal variation in the percentage of T cells expressing cutaneous lymphocyte antigen (CLA) was observed following ustekinumab treatment, with no significant variation in the percentage of cells expressing CD45RA, CD45RO, CD25, human leukocyte antigen-DR (HLA-DR), and C-X-C motif receptor 3 (CXCR3). No apparent effect on the magnitude of Th1/Th2 responses to external stimuli in PBMC was observed following placebo or ustekinumab treatment. Ustekinumab improves histological psoriasis measures, with minimal impact on the systemic immune system.

Clinical course of guttate psoriasis: Long‐term follow‐up study

Abstract: Guttate psoriasis, known to have a better prognosis than other types of psoriasis, shows rapid involution and longer remission, but its clinical course has barely been studied. The aim of this study was to determine the clinical course and to compare the clinical and laboratory features of guttate psoriasis. This is a retrospective study of 26 patients with guttate psoriasis. The patients were divided into two groups; the good one with complete remission and long remission for at least 1 year (group A) and the poor one with incomplete remission and progression into chronic plaque psoriasis (group B). Among 36 patients, 22 patients (61.1%) were group A and 14 patients (38.9%) were group B. In group A, most of the skin lesions disappeared within 8 months. In group B, two patients without proper treatment progressed to plaque psoriasis. The onset age was younger and more frequent upper respiratory infection and high anti-streptolysin O (ASO) titer were found in group A, but family history of psoriasis was more common in group B. Patients had two distingushable clinical courses: rapid involuting course with long-term remission and chronic course without remission. There was a tendency toward younger age of onset with elevated ASO titer in patients with rapid involuting course.

New algorithm (KAWAKAMI algorithm) to diagnose primary cutaneous vasculitis

Abstract: Palpable purpura tends to indicate involvement of small vessel vasculitis in the upper dermis. Livedo racemosa, nodular lesion and skin ulceration are indicative of involvement of small to medium-sized vessel vasculitis in the lower dermis to subcutaneous fat. We set out to establish a new algorithm (KAWAKAMI algorithm) for primary cutaneous vasculitis based on the Chapel Hill Consensus Conference classification and our research results, and apply to the diagnosis. The first step is to measure serum antineutrophil cytoplasmic antibodies (ANCA) levels. If myeloperoxidase-ANCA is positive, Churg-Strauss syndrome or microscopic polyangiitis can be suspected, and if the patient is positive for proteinase 3-ANCA, Wegener's granulomatosis is most likely. Next, if cryoglobulin is positive, cryoglobulinemic vasculitis should be suspected. Third, if direct immunofluorescence of the skin biopsy specimen reveals immunoglobulin A deposition within the affected vessels, Henoch-Schonlein purpura is indicated. Finally, the presence of anti-phosphatidylserine-prothrombin complex antibodies and/or lupus anticoagulant and histopathological necrotizing vasculitis in the upper to middle dermis (leukocytoclastic vasculitis) indicates cutaneous leukocytoclastic angiitis, whereas if necrotizing vasculitis exists in the lower dermis and/or is associated with the subcutaneous fat, cutaneous polyarteritis nodosa is indicated. The KAWAKAMI algorithm may allow us to refine our earlier diagnostic strategies and allow for efficacious treatment of primary cutaneous vasculitis. In cutaneous polyarteritis nodosa, warfarin or clopidogrel therapies should be administrated, and in cases that have associated active inflammatory lesions, corticosteroids or mizoribine (mycophenolate mofetil) therapy should be added. We further propose prophylactic treatment of renal complications in patients with Henoch-Schonlein purpura.

Efficacy and safety of liposome-encapsulated 4-n-butylresorcinol 0.1% cream for the treatment of melasma: A randomized controlled split-face trial

Abstract: Melasma is an acquired pigmentary disorder that most commonly occurs in women of child-bearing age. Melasma is therapeutically challenging, and most commercially available hypopigmenting agents include tyrosinase inhibitors, which regulate the rate-limiting step of melanogenesis. 4-n-Butylresorcinol has received considerable attention as a novel hypopigmenting agent in the last 15 years because it has an inhibitory effect against tyrosinase and tyrosinase-related protein-1. However, the hypopigmenting effect of 4-n-butylresorcinol in human subjects has only been shown in a few studies. Liposome encapsulation is known to improve stabilization and enhance penetration of the product. Therefore, this study was conducted to evaluate the hypopigmenting efficacy and safety of liposome-encapsulated 4-n-butylresorcinol 0.1% cream in patients with melasma. This was a randomized, double-blind, vehicle-controlled and split-face comparison study. Twenty-three patients with a clinical diagnosis of melasma were included. 4-n-Butylresorcinol 0.1% cream or vehicle was applied to each side of the face twice daily for 8 weeks. Clinical and photographic evaluations, Mexameter measurements and assessment of patient satisfaction and side-effects were performed at baseline, 4 and 8 weeks. All subjects completed the study. Mexameter measurements demonstrated that the melanin index of the 4-n-butylresorcinol-treated side showed a significant decrease when compared with the vehicle-treated side after 8 weeks (P = 0.043). No adverse reactions were observed throughout the study. Subjectively, 4-n-butylresorcinol was considered to be efficacious in more than 60% of the patients after 8 weeks of treatment. In conclusion, liposome-encapsulated 4-n-butylresorcinol 0.1% cream was well tolerated and showed significant higher efficacy than vehicle alone for the treatment of melasma.

Anti-infliximab antibody status and its relation to clinical response in psoriatic patients: A pilot study.

Abstract: Although the mechanisms underlying the loss of response to infliximab are not completely understood, the formation of antibodies to infliximab (ATI) are thought to play a role. The aim of this study was to investigate the presence of ATI in psoriatic patients and to evaluate its relationship to the clinical response. Fifteen patients with psoriasis were treated with infliximab (5 mg/kg) every 8 weeks after an initial three-dose induction treatment. An enzyme linked immunosorbent assay kit was used for analyzing the presence of ATI in sera. Effectiveness assessments included the change in Psoriasis Area and Severity Index (PASI) compared with study entry. Five (33.3%) patients developed ATI. While 5.9 +/- 3.2 infliximab infusions achieved a fall in the PASI score from a mean of 20.4 +/- 8.3 to 5.3 +/- 2.4 in ATI-negative patients, these values changed from 23.3 +/- 11 to 10 +/- 4.9 after 9 +/- 5.2 infusions in ATI-positive patients. Our results suggested that ATI measured in psoriatic patients are of clinical importance. Therefore, monitoring for the induction of ATI and rescue strategies should be developed to avoid or to maintain a delay in ATI development.

Etoricoxib-induced toxic epidermal necrolysis: successful treatment with infliximab.

Abstract: Dear Editor, Toxic epidermal necrolysis (TEN) is usually the maximal form of a bullous drug reaction. Frequent elicitors are allopurinol, sulfonamides, carbamazepine, lamotrigine, phenytoin, barbiturates, sulfasalazine, nevirapine and oxicam-type non-steroidal anti-inflammatory drugs (NSAIDs). No therapeutic gold standard has yet been established for TEN. Immediate withdrawal of all potentially eliciting medications is important as an essential causal measure in TEN. In addition to supportive intensive therapy, adequate local treatment under sterile conditions is decisive in minimizing the risk of sepsis. Regular ophthalmological and urological control examinations promote early recognition or prevention of ocular synechiae and scarred urethra strictures. High-dose systemic glucocorticoids appear to have a favorable effect – if any at all – only in the first days of exanthema development, while later they increase the danger of sepsis. There have been individual reports of successful administration of the tumor necrosis factor (TNF)-a antibody infliximab in treating TEN. Etoricoxib (Arcoxia; MSD, Haar, Germany) is a highly-selective cyclooxygenase-2 inhibitor NSAID and is used in clinical practice mainly for the treatment of osteoarthritis, rheumatoid arthritis and pain. Only isolated case reports of serious cutaneous drug reactions, such as erythema exsudativum multiforme-like exanthema or acute generalized exanthematous pustulosis, have been published so far. We are reporting on the successful treatment with infliximab of a case of TEN following treatment with etoricoxib and wish in this connection to again point out the evident and rapid efficacy of TNF-a blockade. After 3 weeks of continuous p.o. administration of etoricoxib at a dose of 60 mg ⁄day for pain treatment of a herniated disk – with no concurrent medications – a 31-year-old man was hospitalized because

Cutaneous polyarteritis nodosa: A report of 16 cases with clinical and histopathological analysis and a review of the published work

Abstract: Sixteen cases of cutaneous polyarteritis nodosa referred to our Department from 1985 to 2003 were studied clinically and histopathologically. Laboratory data, treatments and clinical courses were also evaluated retrospectively. All cases had nodules and/or indurated erythemas on their lower extremities. All cases showed necrotizing vasculitis of small muscular arteries in the subcutaneous tissues and/or occlusion of those arteries histopathologically. Fifteen cases also had accumulation of plasma protein in vessels of the dermis and subcutaneous tissues. Laboratory data showed high activity of platelets and coagulation in some cases. Eleven cases had been effectively treated with non-steroidal anti-inflammatory drugs. Eight cases were observed for at least 5 years (the longest for approximately 19 years) and had good prognoses and no systemic involvement. Cutaneous polyarteritis nodosa seems to be a benign disease, and differs from systemic polyarteritis nodosa although their histopathological features are common. Cutaneous polyarteritis nodosa might involve local dysfunction of the circulation from the dermis to the subcutaneous area. A review of the published work shows that the cause(s) of most cases of cutaneous polyarteritis nodosa is unknown, that no controlled trials for treatment of cutaneous polyarteritis nodosa compared to polyarteritis nodosa have been reported, and that no definitively effective therapy for cutaneous polyarteritis nodosa has been established.

What's new in bullous pemphigoid.

Abstract: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. BP patients have autoantibodies against type XVII collagen (COL17, also called BP180 or BPAG2), a type II transmembrane protein that spans the lamina lucida and projects into the lamina densa of the epidermal basement membrane. The non-collagenous 16A domain of COL17 is considered to contain pathogenic epitopes of BP. The transfer of immunoglobulin (Ig)G from BP patients fails to cause blisters on mouse skin probably due to differences between humans and mice in the amino acid sequence of NC16A pathogenic epitope of COL17. Passive transfer of rabbit IgG antibodies against the murine homolog of human COL17 NC16A triggers immune reactions to COL17 in mice, including complement activation, mast cell degranulation and neutrophilic infiltration, resulting in dermal-epidermal separation. Recent studies using COL17-humanized mice that express human COL17 but lack murine COL17 were the first to demonstrate the pathogenicity of anti-COL17 human BP IgG autoantibodies in vivo. These new findings provide a greater understanding of BP pathomechanisms and facilitate the development of novel specific and efficient therapeutic strategies for BP.

Cutaneous Malassezia microbiota of healthy subjects differ by sex, body part and season.

Abstract: Malassezia is a component of normal cutaneous resident microbiota. The aim of this study was to quantitatively clarify the differences in cutaneous Malassezia microbiota in healthy subjects by sex, body part and season. Samples were collected from the forehead, cheek, upper chest and upper back of 20 healthy men and 20 healthy women (average age 32 years) in summer and winter by the swab method. Malassezia DNA was analyzed using a real-time PCR system. As a result, in sex, body parts and season, men, the upper trunk and summer showed the highest total numbers of cutaneous Malassezia species on average. There were also differences depending on the analytical method. The predominant species were M. restricta on the face of men, M. globosa and M. dermatis on the upper trunk of men, and M. globosa and M. sympodialis on the upper trunk of women. This study clarified that the cutaneous Malassezia microbiota of healthy subjects differed by sex, body part and season.

Pilomatrix carcinoma arising from pilomatricoma after 10‐year senescent period: Immunohistochemical analysis

Abstract: Pilomatrix carcinoma is a rare malignant counterpart of pilomatricoma. To our knowledge, only approximately 90 cases have been published in English literature. Pilomatrix carcinoma is locally aggressive and occasionally shows rapid progression infiltrating to the muscle, bone and vessels. We report a case of pilomatrix carcinoma that developed in a 38-year-old man and started to grow after a long stable period, relapsed for a short time and infiltrated into the muscle underneath. While the initial skin biopsy showed histopathological findings consistent with pilomatricoma, the recurrent tumor contained marked cellular atypia and an aggressive growth pattern. Although it is still controversial whether pilomatrix carcinoma arises de novo or through malignant transformation of a pilomatricoma, the present case might be caused by the latter process considering the patient's clinical course. beta-catenin is a downstream effecter in the canonical pathway of Wnt, acting as a signal for cell differentiation and proliferation. The characteristic nuclear staining pattern of beta-catenin in the basaloid tumor cells, which is usually observed in pilomatrix carcinoma, supported the diagnosis of pilomatrix carcinoma in the present case.

Pyoderma gangrenosum on the breast: A case presentation and review of the published work

Abstract: We present a case of pyoderma gangrenosum localized on the breast, without a preceding surgical intervention and associated systemic disorder. The ulcer had rapidly developed and covered a large portion of the breast. The patient responded well to systemic steroids and salicylazosulfapyridine and the ulcer completely healed with scarring after 3 months of treatment. Pyoderma gangrenosum rarely involves the breasts. A published work survey disclosed only 31 reported cases up to date. In most of these cases the lesions were related to previous surgical interventions, probably as the result of a pathergy phenomenon. The main differential diagnoses were skin and soft tissue infections including necrotizing fasciitis, and malignant neoplasms. Negative initial wound cultures and the relative sparing of nipple/areola complex helped to eliminate these disorders. Though an unusual site for pyoderma gangrenosum, lesions on the breast showed the characteristic clinical features of the disease. The types of associated disorders were also similar to those of the cases with classical pyoderma gangrenosum. As most of the lesions healed with significant scarring, early recognition and treatment of pyoderma gangrenosum located on the breast is important to prevent serious physical and psychological morbidity.

B lymphocytes: shedding new light on the pathogenesis of systemic sclerosis

Abstract: Systemic sclerosis (SSc) is a connective tissue disease characterized by autoimmunity and tissue fibrosis. In patients with SSc, there is a close association between the presence of specific autoantibodies and the development of clinical features. Although it is known that cytokines, including transforming growth factor-beta, can modulate the synthesis of extracellular matrix by fibroblasts, it is not clear how autoimmunity and tissue fibrosis are interrelated. Several recent lines of evidence indicate a potential role for B cells in the development of SSc. CD19 is a critical regulator of B-cell signaling thresholds, and B cells from SSc patients exhibit increased expression of CD19, a molecule that induces SSc-specific autoantibody production in transgenic mice. Both SSc patients and tight-skin mice, a genetic model of SSc, have intrinsic B-cell abnormalities characterized by chronic B-cell activation. Remarkably, CD19 loss or B-cell depletion using antimouse CD20 antibody suppresses the development of skin hyperplasia and autoimmunity in tight-skin mice. Additionally, a recent study revealed a possible beneficial effect of antihuman CD20 antibody (rituximab) therapy for SSc patients. As B cells have a variety of functions, further investigation into the pathogenic roles of B cells, as well as trials of B-cell-targeting therapies, may shed new light on the pathogenesis of SSc.

Childhood and adulthood traumatic experiences in patients with psoriasis.

Abstract: It is well known that several psychiatric disorders may be related to childhood psychological trauma. Recent studies have associated childhood exposure to trauma to some skin diseases. Our study aimed at exploring whether psoriasis is related to the reported positive and negative traumatic life events in different age intervals beginning from early childhood to adulthood. Furthermore, we investigated differences between psoriatics with early and late onset according to traumatic experiences in different age intervals. Also, we investigated the possible correlation of traumatic experiences with the disease severity. One hundred patients with psoriasis and 101 controls (patients with skin conditions considered to be "non-psychosomatic") were enrolled in the study. All participants completed a specific questionnaire measuring traumatic life experiences (Traumatic Antecedents Questionnaire, TAQ). The TAQ assesses positive personal experiences (competence and safety) and negative personal experiences (neglect, separation, secrets, emotional, physical and sexual abuse, trauma witnessing, other traumas and exposure to alcohol/drugs) from early childhood to adulthood. The severity of psoriasis was estimated according to the Psoriasis Area and Severity Index (PASI), a standardized measuring instrument. The amount of positive experiences did not differ significantly among groups, except for safety scores that were higher in controls compared with both psoriatic groups (early and late onset). On the other side, negative traumatic experiences appeared more frequently in patients with psoriasis during all developmental periods. We found no correlation between severity of psoriasis and traumatic experiences. The present study demonstrates an increased history of childhood and adulthood negative traumatic experiences in patients with psoriasis compared to the control group. Our findings suggest a relationship between retrospectively reported negative traumatic experiences and psoriasis.