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In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.

Background: Psoriatic arthritis (PsA) results from joint destruction by osteoclasts. Promising efficacy of TNF-α blockage indicates its important role in osteoclastogenesis of PsA. WNT ligands actively regulate osteoclastogenesis. We investigated how WNT ligands activate osteoclasts amid the TNF-α milieu in PsA. Methods: We first profiled the expression of WNT ligands in CD14+ monocyte-derived osteoclasts (MDOC) from 3 PsA patients and 3 healthy controls (HC) and then validated the candidate WNT ligands in 32 PsA patients and 16 HC. Through RNA interference against WNT ligands in MDOC, we determined the mechanisms by which TNF-α exerts its effects on osteclastogenesis or chemotaxis. Results: The results showed numbers of CD68+WNT5A+ osteoclasts are increased in PsA joints. WNT5A was selectively upregulated by TNF-α in MDOC from PsA patients. However, direct osteoclastogenesis effect (RANK expression) by TNF-αwas not inhibited by WNT5A siRNA. Instead, CXCL1, CXCL16, and MCP-1 was selectively increased in supernatants of MDOC from PsA patients. RNA interference against WNT5A abolished the increased MCP-1 from MDOC and THP-1-cell-derived osteoclasts. The increased migration of osteoclast precursors (OCP) induced by supernatant from PsA MDOC was abolished by MCP-1 neutralizing antibody. WNT5A and MCP-1 expressions were decreased in MDOC from PsA patients treated by biologics against TNF-a but not IL-17. Conclusion: We conclude TNF-α recruits OCP by WNT5A-mediated MCP-1 production but not directly activates osteoclastogenesis in PsA.

Background/Objectives: Plaque psoriasis is a debilitating condition that significantly affects patient well-being. Limited data are available regarding the effect of psoriasis and treatment on health-related quality of life (HRQoL) and work ability among Taiwanese patients.To document and compare HRQoL, treatment satisfaction, and work disability among Taiwanese patients with current and past moderate-to-severe plaque psoriasis. Methods: This was a multicenter, non-interventional, cross-sectional study of adult patients with moderate-to-severe plaque psoriasis. During a single clinic visit, each patient was assessed for body surface area (BSA) involvement, Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI), Euro Quality of Life-5 Dimensions (EQ-5D), 10-level satisfaction scale for psoriasis treatment, and Working Productivity and Activity Impairment (WPAI). Multivariate regression was used to identify factors associated with HRQoL and work disability. Results: A total of 305 patients were included within the analysis. The mean PASI score was 11.83, and the mean BSA involvement was 20.90%. The mean EQ-5D score was 65.68 and the mean DLQI score was 12.55. Fewer than half of patients (45.68%) indicated they were satisfied with the standard therapy they were currently receiving. Among employed patients, the mean reduction in on-the-job effectiveness was 32.09% and the mean reduction in overall productivity was 33.48%. The regression analysis indicated that patients with more severe psoriasis defined by PASI scores show a greater impact in quality of life and impairment in work disability; and that patients who were satisfied with current standard treatment had a better quality of life. Conclusion: The effect of psoriasis on HRQoL among patients with psoriasis in Taiwan is substantial, with fewer than half of patients reporting satisfaction with therapeutic options. Keywords: DLQI, EQ-5D, Health-related quality of life, Psoriasis, WPAI

Psoriatic arthritis (PsA) is a destructive joint disease mediated by osteoclasts. MicroRNAs (miRNAs) regulate several important pathways in osteoclastogenesis. We profiled the expression of miRNAs in CD14+ monocytes from PsA patients and investigated how candidate microRNAs regulate the pathophysiology in osteoclastogenesis. The RNA from circulatory CD14+ monocytes was isolated from PsA patients, psoriasis patients without arthritis (PsO), and healthy controls (HCs). The miRNAs were initially profiled by next-generation sequencing (NGS). The candidate miRNAs revealed by NGS were validated by PCR in 40 PsA patients, 40 PsO patients, and 40 HCs. The osteoclast differentiation and its functional resorption activity were measured with or without RNA interference against the candidate miRNA. The microRNA-941 was selectively upregulated in CD14+ monocytes from PsA patients. Osteoclast development and resorption ability were increased in CD14+ monocytes from PsA patients. Inhibition of miR-941 abrogated the osteoclast development and function while increased the expression of WNT16. After successful treatment, the increased miR-941 expression in CD14+ monocytes from PsA patients was revoked. The expression of miR-941 in CD14+ monocytes is associated with PsA disease activity. MiR-941 enhances osteoclastogenesis in PsA via WNT16 repression. The miR-941 could be a potential biomarker and treatment target for PsA.

Background Deep cutaneous fungal infections, including subcutaneous mycoses and systemic fungal infection with cutaneous involvement, cause significant morbidity and mortality in light of increasing immunocompromised patients and global warming. Although a few studies reviewed deep fungal infections in temperate regions, a relevant study in tropical regions is lacking. We evaluated features of deep cutaneous fungal infections in southern Taiwan among the tropical regions. Methods We retrospectively reviewed all histopathological specimens with deep cutaneous fungal infections in a single referral center from 2001 to 2014 and successfully identified 23 cases. Medical chart review revealed patient demographic data, clinical presentation, underlying disease, microbiological culture reports, and treatment outcomes. Results The average patient age was 52 years. Fourteen cases had primary subcutaneous mycoses, and nine had systemic mycoses. Fifteen patients were immunocompromised, including hematological malignancies. Acquired immune deficiency syndrome (AIDS) and long-term steroid use were most commonly associated with deep fungal infections. The positive culture growth rate was 63%. Fonsecaea sp. was most frequently identified by tissue culture. Aspergillosis, mucormycosis, and disseminated cryptococcosis were particularly fatal. Conclusions Diabetes and long-term steroid use appear as major risk factors for advanced mycoses in this region. Rapid diagnosis with skin biopsy and tissue culture along with appropriate treatment of deep cutaneous fungal infection are necessary.

In psoriatic arthritis (PsA), progressive bone destruction is mediated by monocyte-derived osteoclasts. MicroRNAs (miRNAs) regulate many pathophysiological processes, however, their function in PsA patient monocytes has not been examined. This study aims to address whether specific miRNAs in CD14+ monocytes and monocyte-derived osteoclasts cause active osteoclastogenesis in PsA patients. Candidate miRNAs related to monocyte activation (miR-146a-5p, miR-146b-5p and miR-155-5p) were measured in circulatory CD14+ monocytes collected from 34 PsA patients, 17 psoriasis without arthritis (PsO) patients, and 34 normal controls (NCs). CD14+ monocytes were cultured with media containing TNF-&alpha, and RANKL to differentiate into osteoclasts. Osteoclast differentiation and bone resorption were measured by TRAP immunostaining and dentin slice resorption, respectively. The results showed that the miR-146a-5p expression was higher in PsA patient-derived CD14+ monocytes compared to PsO and NCs. Activation and bone resorption were selectively enhanced in osteoclasts from PsA patients, but both were abrogated by RNA interference against miR-146a-5p. More importantly, after clinical improvement using biologics, the increased miR-146a-5p expression in CD14+ monocytes from PsA patients was selectively abolished, and associated with blood CRP level. Our findings indicate that miR-146a-5p expression in CD14+ monocytes derived from PsA patients correlates with clinical efficacy, and induction of osteoclast activation and bone resorption.

For the past decades, although the rash at the bacillus Calmette-Guerin (BCG) inoculation site has been recognized as a diagnostic clue in Kawasaki disease, the present study is the first known one attempting to characterize BCG inoculation by dermatoscopy in Kawasaki disease and correlate the grade of BCG reaction with systemic involvement. Thirty-four patients diagnosed with Kawasaki disease by pediatric specialists were enrolled. We performed detailed history taking, laboratory examination, physical examination and dermatoscopy examinations. Based on the BCG reaction pattern by dermatoscopy, we were able to characterize three patterns: (A) Bull's eye pattern in 18 patients; (B) faint homogenous erythema in nine; and (C) central white patch in seven. Patients from group A exhibited the highest elevation of blood aspartate aminotransferase levels (P < 0.05). Notably, three patients from group A had a significantly dilated coronary artery despite i.v. immunoglobulin injection. We concluded that the bull's eye dermatoscopy sign is not only a useful diagnostic clue but also a severity biomarker in patients with Kawasaki disease.

Psoriasis is associated with atherosclerosis, in which circulating microparticles play an important role. In severe psoriasis, there was an increase of endothelial- and platelet- microparticles which could be decreased by anti-TNFα. However, whether anti-IL-12/23 treatment would decrease the level of microparticles remains unknown. Our study showed that, despite the clinical improvement of psoriasis after IL-12/13 blockage, the increased levels of circulating CD41a and CD31 microparticles were unchanged after anti-IL-12/23. This result suggested that anti-IL12/23 treatment may not alter the development of cardiovascular disease in patients with psoriasis.

Abnormal skin melanin homeostasis results in refractory pigmentary diseases. Melanogenesis is influenced by gene regulation, ultraviolet radiation, and host epigenetic responses. Steroid receptor RNA activator (SRA), a long noncoding RNA, is known to regulate steroidogenesis and tumorigenesis. However, how SRA contributes to melanogenesis remains unknown. Using RNA interference against SRA in B16 and A375 melanoma cells, we observed increased pigmentation and increased expression of TRP1 and TRP2 at transcriptional and translational levels only in B16 cells. The constitutive phosphorylation of p38 in B16-shCtrl cells was inhibited in cells with knocked down SRAi. Moreover, the melanin content of control B16 cells was increased by SB202190, a p38 inhibitor. Furthermore, reduced p38 phosphorylation, enhanced TRP1 expression, and hypermelanosis were observed in A375 cells with RNA interference. These results indicate that SRA-p38-TRP1 axis has a regulatory role in melanin homeostasis and that SRA might be a potential therapeutic target for treating pigmentary diseases.

Melanoma metastasis signals dismal prognosis even with current checkpoint inhibitors. Long noncoding RNAs (lncRNAs) regulate dynamic metastasis in several cancers, including melanoma. We became interested in a lncRNA, steroid receptor RNA activator (SRA), because it is the first lncRNA also encoding a conserved protein, SRAP, and it regulates progression of prostate and breast cancers. We investigated how SRA mediates melanoma proliferation, migration, invasion, epithelial-mesenchymal transformation (EMT), and metastasis by RNA interference. The expression of SRAP was measured in melanoma tissue and in human and mouse B16 melanoma cells by immunofluorescence and PCR. The results showed that SRA knockdown decreased B16 cell and A375 cell proliferation and inhibited B16 cell migration significantly. Transwell analysis revealed that CCL21-mediated invasion was abolished in SRA-deficient B16 cells. In parallel, p38 dephosphorylation and reciprocal phosphorylation of B-Raf and mitogen-activated protein kinase kinase 1/2 were present in B16-SRA inhibited cells. The induction of EMT markers, β-catenin and N-cadherin, by CCL21 was reduced in B16-SRA inhibited cells, suggesting that SRA promotes the EMT process. In vivo experimental metastasis showed that B16-SRA inhibited cells formed significantly fewer tumor nodules in the lungs grossly and microscopically. In summary, our results showed that SRA expression is increased in melanoma tissue and that SRA mediates p38 activation, cell invasion, and proliferation and regulates EMT and distant metastasis.

BACKGROUND. Cytotoxic T lymphocyte–mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. METHODS. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. RESULTS. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%–62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. CONCLUSIONS. The anti–TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01276314","term_id":"NCT01276314"}}NCT01276314. FUNDING. Ministry of Science and Technology of Taiwan.

TRP channels are expressed in various cells in skin. As an organ system to border the host and environment, many nonneuronal cells, including epidermal keratinocytes and melanocytes, express several TRP channels functionally distinct from sensory processing. TRPV1 and TRPV3 in keratinocytes of the epidermis and hair apparatus inhibit proliferation, induce terminal differentiation, induce apoptosis, and promote inflammation. Activation of TRPV4, 6, and TRPA1 promotes regeneration of the severed skin barriers. TRPA1 also enhances responses in contact hypersensitivity. TRPCs in keratinocytes regulate epidermal differentiation. In human diseases with pertubered epidermal differentiation, the expression of TRPCs are altered. TRPMs, which contribute to melanin production in melanocytes, serve as significant prognosis markers in patients with metastatic melanoma. In summary, not only act in sensory processing, TRP channels also contribute to epidermal differentiation, proliferation, barrier integration, skin regeneration, and immune responses. In diseases with aberrant TRP channels, TRP channels might be good therapeutic targets.

Background Psoriasis is a systemic inflammatory disease with dramatic responses to TNF-α inhibitors. TNF-α is mainly produced by macrophages. However, how macrophage polarization contributes to psoriasis remains unknown. Objective We aimed to investigate the molecular mechanisms of macrophage polarization in psoriasis. Methods 8 patients with moderate to severe psoriasis (Male/Female: 4/4, average age: 47.9 years old) and 8 healthy controls (Male/Female: 4/4, average age: 49.3 years old) were recruited. Their peripheral CD14+ monocytes were isolated with magnetic beads and then were differentiated into macrophages. The differential macrophage polarization was compared among normal controls, psoriatic patients before and after TNF-α inhibitors. The U937 cells were used to investigate the mechanisms by which TNF-α altered the macrophage polarization. Results The ratio of M1 to M2a macrophage polarization was higher in psoriatic patients comparing with that in controls. The decreasing M1/M2a ratio was parallel to decreasing PASI severity score after adalimumab treatment. Consistently, TNF-α blockage decreased M1/M2a ratio in U937 cells. The induction of STAT1 and IRF-1 in polarized U937 M1 cells was inhibited by TNF-α inhibitor. However, STAT1 and/or IRF-1 interference could not resume M1 polarization. In skin, the increased M1 and M2 infiltration in lesions returned to baseline after successful treatment with TNF-α inhibitor. Conclusions Increased M1 polarization is associated with higher disease severity in psoriasis, resuming to baseline after successful treatment by TNF-α inhibitors. TNF-α blockage inhibits M1 polarization through STAT1- and IRF-1-independent pathways. Macrophage polarization may contribute to disease progression in psoriasis.

Background Protothecosis is an uncommon infection caused by the achlorophyllic algae found more commonly in tropical areas. Only a limited number of cases have been reported. Objective We aimed to evaluate the clinicopathological features and treatment outcomes of cutaneous protothecosis. Methods We retrospectively identified 20 pathology-confirmed cases of cutaneous protothecosis based on skin biopsies in two tertiary medical centres in Taiwan from 1997 to 2015. Results The age of the patients at the time of diagnosis ranged from 48 to 85 years (mean age of 74 years). All lesions developed on the limbs. Twelve (60%) patients had adrenal insufficiency, but no patients had active malignancy at diagnosis. Interestingly, four (20%) patients had concurrent scabies infestation. Clinically, most lesions were erythematous plaques studded with punctate ulcers. Microscopically, the most common finding was granulomatous inflammation. Nineteen (95%) cases were successfully treated with itraconazole for 14-148 days with only one case of recurrence. Concomitant scabies should be suspected if pruritus is recalcitrant despite itraconazole treatment. Conclusion Despite its rarity, cutaneous protothecosis has become more significant due to an increased prevalence of immunocompromised individuals. Steroid overuse or iatrogenic adrenal insufficiency predisposes individuals to high-risk infections. Neglecting the disease leads to a chronic and incurable state. Protothecosis should be suspected in chronic eczematous and ulcerative plaques on the limbs refractory to conventional antibacterial and antiviral treatments, especially in patients with adrenal insufficiency. Clinical suspicion should be confirmed by skin biopsies, and confirmed cases can be successfully treated with itraconazole.

Background: Psoriasis has been reported to impact patients' health-related quality of life. Limited data are available on patients' perception of this disease and the importance of clear/almost clear skin as a treatment goal in Taiwan. Objectives: A clear about Psoriasis worldwide survey was conducted among patients with moderate-to-severe psoriasis to assess patients' perspective on the impact of psoriasis on their personal and professional lives, treatment satisfaction, and the importance of achieving clear/almost clear skin. Here, we report the data for the Taiwanese patient population. Methods: A 20-min survey consisting of multiple choice questions and validated scales to assess disease severity and patient' quality of life was conducted between October 2015 and March 2016. Patients (age ≥18 years) with medically diagnosed moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] score ≥10 or PASI >5 to

A murine repeated protein-patch model has been established to study epicutaneous sensitization in atopic dermatitis. This model has shown a predominant Th2 and a weak Th1 response in both BALB/c and C57BL/6 mice. However, Th responses induced in the repeated model are not consistent with the generally accepted theory that BALB/c and C57BL/6 mice are Th2 and Th1 prone and are representatives of human atopy and non-atopy, respectively. In this study, a single protein-patch model was established, which showed in addition to the Th2 response, a remarkable Th1 response in C57BL/6 mice, but not in BALB/c mice. Moreover, using muLangerin-DTR mice, we demonstrated that dermal dendritic cells, but not Langerhans cells, are critical in single epicutaneous sensitization in both strains of mice.

Background and Study Aims. The association betweenHelicobacter pylori(H. pylori) and chronic spontaneous urticaria (CSU) remains controversial. This study explored the role ofH. pyloriin CSU among different virulent genotypes patients.Patients and Methods. Patients infected byH. pyloriwere sorted into two groups as group A (with CSU) and group B (without CSU). The tissue materials were taken via endoscopy for polymerase chain reaction study to determine virulence factors.AfterH. pylorieradication therapy, the eradication rate and response of urticaria were evaluated by using C13-UBT and a three-point scale (complete remission, partial remission, or no improvement).Results. The results were comparable between patients of groups A and B in terms ofH. pyloriinfection rates and eradication rate. Longitudinal follow-up of 23.5 months showed complete remission of urticaria in 63.6% but no improvement in 36.4% of the patients afterH. pylorieradication.H. pyloriinfected patients with different virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin gene A signal region and middle region have similar remission rates for CSU.Conclusions. Current study suggests thatH. pylorimay play a role in the development and disease course of CSU but may be irrelevant to different virulent genotypes.

Background.In Asians, most basal cell carcinomas (BCCs) are pigmented with clear borders. The consensus of 4 mm surgical margin for BCC largely depends on studies in nonpigmented BCCs in Caucasians. However, little is known about recurrences of pigmented BCCs with a narrower surgical margin. We aimed to investigate 5-year recurrence of BCCs, either pigmented or nonpigmented, in Taiwanese with 3 mm surgical margin.Materials and Methods.143 patients with BCC (M/F = 66/77, average 64 years) were confirmed pathologically from 2002 to 2013. Based on the pathological margin (>1 mm, ≤1 mm, and involved), patients were categorized into the complete excision group (n=77), histology with close proximity group (n=43), and unclear surgical margin group (n=23).Results.Among 143 cases, 105 were pigmented. With standard 3 mm excision, there were 7 recurrences, with 6 of them from nonpigmented BCC group. Logistic regression showed that pigmentation was associated with lower recurrence. Interestingly, 5-year recurrence of completely excised and histology with close proximity BCC (0/77 versus 1/43) was not different statistically.Conclusions.A 3 mm surgical margin is adequate for pigmented BCC. A “wait and see” approach rather than further wide excision is appropriate for BCC with

Ustekinumab has been evaluated in Caucasian patients with psoriasis, but no studies have been conducted in Asian patients.To assess the efficacy and safety of ustekinumab in Taiwanese and Korean patients with moderate-to-severe psoriasis.In this 36-week, multicenter, double-blind, placebo-controlled study, 121 patients with moderate-to-severe psoriasis were randomized (1:1) to receive subcutaneous injections of ustekinumab 45mg at weeks 0, 4, 16 or placebo at weeks 0, 4 and ustekinumab 45mg at weeks 12, 16. Efficacy endpoints at week 12 included the proportion of patients achieving at least 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75; primary endpoint), proportion of patients with Physician's Global Assessment (PGA) of cleared or minimal, and change from baseline in Dermatology Life Quality Index (DLQI).At week 12, the proportion of patients achieving PASI 75 was 67.2% and 5.0% in the ustekinumab 45mg and placebo groups, respectively (p0.001). PGA of cleared or minimal was achieved by 70.5% (ustekinumab) and 8.3% (placebo; p0.001), and median DLQI changes were -11.0 and 0.0, respectively (p0.001). Efficacy was maintained through week 28 in ustekinumab-treated patients. Adverse event (AE) profiles at week 12 were similar between the ustekinumab and placebo groups: 65.6% and 70.0%, respectively, had at least one reported AE. Through week 36, no disproportionate increase in AEs was observed, with the exception of abnormal hepatic function, which was related to concomitant isoniazid treatment for latent tuberculosis. Injection-site reactions were rare and mild. No deaths, malignancies, or cardiovascular events were reported.Treatment with subcutaneous ustekinumab 45mg offers a favorable benefit/risk profile for Taiwanese and Korean patients with moderate-to-severe psoriasis. The efficacy and safety profile is consistent with the global phase III studies of ustekinumab in psoriasis.

Psoriasis is a chronic inflammatory skin disease with a profound effect on quality of life and psychosocial stress. The relationship between clinical improvement and psycho-social impact after treatment is complex. The objective of this study was to compare changes in quality of life and psychosocial distress, and overall cost-effectiveness, in patients with psoriasis receiving the modified Goeckerman regimen (UV irradiation and coal tar) with those receiving conventional treatment. Patients with moderate/severe psoriasis receiving the Goeckerman regimen were followed from admission to discharge. Clinical severity, was evaluated weekly using the Psoriasis Area and Severity Index (PASI). Psoriasis Disability Index (PDI) and Hospital Anxiety and Depression Scale (HADS) questionnaires were applied at admission and one month after discharge. Thirty-six patients with psoriasis receiving conventional treatment and 48 patients receiving the Goeckerman regimen were recruited to the study. The mean PASI score in the Goeckerman group decreased from 27.1 to 6.9 and PDI scores decreased from 25.3 to 13.8. HADS scores for anxiety and depression decreased significantly from 9.8 to 6.3 and 9.1 to 6.8, respectively. In comparison with conventional therapy, the modified Goeckerman regime showed similar clinical efficacy, with additional benefits in improving overall quality of life and psychosocial distress in patients with moderate/severe psoriasis, and more cost-effectiveness.

daily for 1 week), pulse therapy with methylprednisolone (1000 mg/day for 3 days) and rituximab (100 mg/week for 2 weeks) were initially used for correcting the coagulopathy. Prednisolone (1 mg/kg/day) and cyclophosphamide (100 mg/ day) were prescribed as maintenance therapy. The coagulatory disorder improved after 2 months of treatment associated with reduction of factor VIII inhibitor to 35 Bethesda units/mL with concomitant improvement of ecchymosis (Figure 3). A subsequent reduction in the factor VIII inhibitor level was observed and it was 3 Bethesda units/mL after 3 months of follow-up.

Drug-induced pseudolymphoma syndrome is a rare form of adverse cutaneous drug reaction. Its clinical and histological presentation may mimic mycosis fungoides, which sometimes leads to misdiagnosis and unnecessary treatments. We describe the case of a 65-year-old man with a generalized pruritic and confluent maculopapular eruption. His history of skin lesions was concordant with medication and resolved after discontinuation. However, microscopic examination showed characteristic features of mycosis fungoides, including Pautrier-like microabscesses and cerebriform nuclei of atypical lymphocytes. The immunohistochemical study showed CD4/CD8 infiltrate ratio to be 1 in the epidermis. The histopathological result of a second skin biopsy was compatible with drug eruption. This experience demonstrates that combining clinical history, histological and immunohistochemical findings is crucial for a definite diagnosis of PLS.

OBJECTIVE To present data on cancer distribution in renal-transplant recipients in Chinese people, as in Western studies renal-transplant recipients are reportedly at greater risk of malignancies, especially skin cancer, but there is limited information in Chinese people. PATIENTS AND METHODS Using the data of a cancer registry, we compared a hospital-based cohort of 283 renal-transplant recipients between 1981 and 2002 with the general population in Taiwan, to identify the incidence and risk factors of cancer. RESULTS The cumulative period of observation was 22 582.93 person-months. Twenty-five patients (8.83%) developed malignancies after renal transplantation; the standardized incidence ratio was 4.6 (95% confidence interval 2.84-6.48). Bladder and renal cancers were commonest, and the cumulative incidence rate (CIR) was 4.59%. The second most frequent type was hepatoma, where the CIR was 1.77%. The third was malignant tumour of the skin, with a CIR of 1.41%; these comprised three Kaposi's sarcoma and one malignant lymphoma, with no incidence of squamous or basocellular skin cancer. CONCLUSION Compared with Western countries, the distribution pattern of cancer after kidney transplantation was different, with no squamous or basocellular skin cancers, and a very high incidence of kidney and urinary tract cancer.

Acne is a common disease in adolescence with female preponderance. It could cause poor self-esteem and social phobia. Previous studies based on questionnaires from several thousands of adolescents showed that acne is associated with major depression and suicide. However, the gender- and age-specific risk of depression and suicide in patients with acne remain largely unknown. Using a database from the National Health Insurance, which included 98% of the population of Taiwan in 2006, we identified patients of acne, major depression, and suicide based on ICD-9-CM codes. Totally 47111 patients with acne were identified (16568 males and 30543 females) from 1 million subjects. The youths of 7–12 years had the highest prevalence of acne (14.39%). Major depression was more common in those with acne (0.77%) than controls (0.56% ,P< 0.0001) regardless of gender. Multiple logistic regression showed an increased risk of major depression in women without acne (OR = 1.85, 95% CI 1.75–1.96). The risk is additive in women with acne (OR = 2.78, 95% CI 2.43–3.17). Similar additive risk of suicide was noticed in women with acne. In conclusion, acne and gender, independently and jointly, are associated with major depression and suicide. Special medical support should be warranted in females with acne for the risk of major depression and suicide.

Background: The effective therapy for uremic pruritus remains a clinical challenge, and the factors affecting the pruritus before and after parathyroidectomy have not been defined. Study Design: Thirty-seven patients were operated on for secondary hyperparathyroidism. Their ages ranged from 14 to 73 years, and the duration of dialysis from 12 to as long as 168 months. Indications for surgery were skin itch in 22 patients and other reasons in 15 patients. Serum levels of calcium, phosphorus, intact PTH (i-PTH), and alkaline phosphatase were checked at two different intervals—before surgery and 1 week after operation. Immunohistochemical stain of mast cells, antihuman macrophage (CD68), antihuman dendritic reticulum cell (CD35), and i-PTH (IHPTH) were performed on skin specimens. Skin samples were prepared into tissue homogenates and analyzed for concentrations of interleukin-2 (Il-2) and tumor necrosis factor-α (TNF-α). Il-2 and TNF-α were measured by sandwich enzyme-linked immunosorbent assay. The extent of pruritus was evaluated on a visual analog scale (VAS) ranging from 0 to 10 and a behavior rating scale (BRS) ranging from 0 to 5, at a preoperative stage and 1 week after operation. Results: Serum levels of calcium, phosphorus, the product of calcium and phosphorous (Ca × P), alkaline phosphatase, and i-PTH changed significantly after parathyroidectomy. The VAS decreased from 5.4 ± 3.2 to 1.8 ± 1.5 (p Conclusions: Pruritus in patients with secondary hyperparathyroidism can be reduced by parathyroidectomy. Apparently, high-level Ca × P is the only factor that seems to affect the postoperative extent of pruritus.

The immune function of peripheral mononuclear cells (MNC) in patients with endemic arsenic-induced Bowen's disease (BD) was investigated. Many cytokines and immune-related factors were determined in the present study. Interleukin-1beta and TNF-alpha production was used as an indicator of monocyte/macrophage function. II-2 and sIL-2R production was used as an indicator of lymphocyte activation. The release of sCD4 and sCD8 was used as an indicator of activation of respective T-cell subpopulations. Production of IFN-gamma and IL-2 reflected the cellular effector function of helper T-cells type 1. In vivo cell-mediated immunity was also assessed by estimation of the percentage of T-cells in peripheral blood MNC and the nonspecific delayed-type hypersensitivity (DTH) response to 2,4-dinitrochlorobenzene (DNCB). Both assays revealed depressed cell-mediated immunity in BD. Compared with healthy controls, spontaneous and PHA-induced IFN-gamma and TNF-alpha production was significantly decreased in BD whereas spontaneous release of IL-2, sCD4 and sCD8 was significantly increased. Although PHA stimulation increased IL-2 release, the expression of IL-2R alpha and beta chains and the release of sIL-2R were not proportionately increased in BD. In addition, IL-2-mediated [3H]-thymidine incorporation by MNC in patients with BD was significantly decreased. These findings suggest that the defective cell-mediated immune function in BD is due to impairment of membrane IL-2R expression in lymphocytes after stimulation.

Glucagonoma syndrome encompasses necrolytic migratory erythema (NME), hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, angular cheilitis, steatorrhea, diarrhea, venous thrombosis, and neuropsychiatric disturbance. Of all the symptoms, NME is a rare skin disorder which is pathognomonic for glucagonoma. We present a 61-year-old woman diagnosed initially as pancreatic head adenocarcinoma with liver metastasis prior to the skin eruption. From the dermatologic finding and other clues, glucagonoma was diagnosed finally.

Prurigo pigmentosa is a rare inflammatory dermatosis of unknown etiology. It is characterized by a recurrent pruritic rash and net like pigmentation. Most of the reported cases have been from Japan; however, here we report on several cases from Taiwan.This was a single hospital-based retrospective study conducted in a tertiary medical center in Southern Taiwan, recruiting 14 patients with a clinical diagnosis of prurigo pigmentosa between January 1, 2000 and December 31, 2007. Clinical information was collected and reviewed, and skin biopsies were performed for all cases.Of the 14 cases, 11 exhibited clinical and histopathological correlation with prurigo pigmentosa and were enrolled in our study. The age of the patients at diagnosis ranged from 16 to 30 years (mean, 22.3) with female predominance (female: male ratio, 8:3). Patient lesions were primarily distributed symmetrically over the chest and back area and they responded well to doxycycline treatment. The biopsy specimens of all patients showed nonspecific lymphocytic infiltration; folliculitis was noted in 7 specimens and both superficial and deep perivascular lymphocytic infiltration was found in 8 specimens.Although far more prevalent in Japan, prurigo pigmentosa can be seen in Taiwan. In our study, patients were predominantly young females who had been initially diagnosed as having eczema. Therefore, young females who present with intractable eczema distributed symmetrically over the trunk should prompt physicians to consider prurigo pigmentosa.

Leprosy has long been in Taiwan, but it has never been eradicated. Incidental cases are easily overlooked nowadays because most younger dermatologists are unfamiliar with this disease.We review and analyze 13 cases diagnosed as leprosy at the Department of Dermatology, Chang Gung Memorial Hospital at Kaohsiung from 1988 to 2004, all of which were histopathologically proven.The ages of the 13 recruited patients ranged from 31 to 73 (mean, 58.6) years, without a gender preference (male: female, 7:6). Two male patients were under 40 years old; one was a foreign worker from Thailand and the other was a local person in Penghu working as the chief officer on a fishing boat. The most-common clinical subtype was lepromatous leprosy (5/13), followed by borderline lepromatous leprosy, borderline tuberculoid leprosy, and tuberculoid leprosy (each 2/13), and then borderline leprosy and indeterminate leprosy (each 1/13). The initial clinical impression before the histopathological diagnosis included granuloma annulare, generalized eczema, lymphoma, syphilis, papular urticaria, cutaneous tuberculous infection, Sweet's syndrome, erythema annulare centrifugum, and hematoma. Most of these patients only received irregular treatment after the diagnosis was made and were soon lost to follow-up.With increasing numbers of foreign workers and immigrants living in Taiwan in recent years, leprosy seems to have become a challenging diagnosis for younger dermatologists. Dermatologists should keep this ancient disease in mind and not overlook it. Because of the necessity of prolonged medication, complete treatment and long-term follow-up of leprosy cases will remain a major problem in public health.

To investigate the disease characteristics of sarcoidosis in southern Taiwan, and to investigate diagnostic methods.We retrospectively reviewed the medical records of all patients diagnosed with sarcoidosis at Chang Gung Memorial Hospital, Kaohsiung, from March 1988 to February 2002.A total of 12 patients (3 men, 9 women), with a mean age of 44.5 years, and a diagnosis of sarcoidosis by positive histology and either a typical chest roentgenogram or clinical presentation were included. All 12 patients had intrathoracic involvement (hilar or mediastinal lymph nodes, 12; lungs, 5), eight had skin involvement, and two had extrathoracic lymph node involvement. The most frequent biopsy specimens were from the skin (n = 10), followed by the intrathoracic lymph nodes (n = 4), lungs (n = 2), and extrathoracic lymph nodes (n = 2). Four patients had positive biopsies from two organs. Our data showed an older age distribution and a greater female predominance of the disease compared with Western countries. A higher rate of intrathoracic and skin involvement was also found, but the reason for this was not clear.Greater awareness of possible skin involvement may enable chest physicians and clinical practitioners to suspect this condition earlier. A histologic diagnosis from skin biopsy should then be made, rather than using more invasive procedures.

Importance The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. Objective To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. Design, Setting, and Participants Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. Main Outcomes and Measures Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. Results The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 ( CYP2C9*3 ) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P =1.1 × 10 −17 ). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z =8.58; P CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. Conclusions and Relevance This study identified CYP2C variants, including CYP2C9*3 , known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

A 40-year-old woman presented with a 10-year history of multiple subcutaneous nodules on the lower extremities. The first subcutaneous nodule occurred on the left shin, and over the last year, had increased in number and spread to the proximal extremities. The general condition of the patient was otherwise healthy, except that she was diagnosed with descending colon cancer and underwent surgery 2 years ago. A physical examination revealed mobile, firm, subcutaneous and asymptomatic nodules symmetrically distributed over the bilateral shins. The size of these nodules ranged from 2 mm to 4 mm in diameter; the number of the nodules was more than 20 (Figure 1). One subcutaneous nodule was taken from the right shin for histological examination. The epidermis and dermis were unremarkable. There were well-demarcated, round-shaped nodules encapsulated by fibrous tissue (Figure 2). Lipo membranous fat necrosis appeared to be associated with focal calcification in the center of the nodule (Figure 3). The skin lesions persisted during a 6-month follow-up.