Taiwanese Dermatological Association (TDA) consensus recommendations for the definition, classification, diagnosis, and management of hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disease characterized by painful, recurrent, inflamed lesions most commonly occurring in the axillary, inguinal, and anogenital regions. HS can inflict immense physical and psychological impact on patients who suffer from this distressing disease. Management of HS generally requires combining various medical and procedural treatment modalities; however, the disease is often recalcitrant to conventional treatments. In light of recent evidence supporting the effectiveness of biologic agents in the treatment of HS, the Taiwanese Dermatological Association established an expert panel of nine dermatologists to develop consensus statements aimed to provide up-to-date evidence-based guidance in optimizing HS patient management in Taiwan. The recommendations described in the statements were summarized in a management algorithm in terms of general care, topical treatment, systemic treatment, and procedural treatment.

Plectin Missense Mutation p.Leu319Pro in the Pathogenesis of Autosomal Recessive Epidermolysis Bullosa Simplex.

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Scleritis and anterior uveitis may herald the development of an epibulbar tumor in patients with extranodal Rosai-Dorfman disease: a case report.

BACKGROUND: Rosai-Dorfman disease is a rare non-Langerhans cell histiocytosis. Ocular involvement is even rarer, mostly involving the orbit and eyelids, although marginal corneal ulcers, uveitis, and epibulbar masses have also been reported, and is characterized by multiple recurrences. However, the disease course and optimal treatment strategies remain undetermined, in light of the rarity of this disease. CASE PRESENTATION: We reported a 36-year-old male patient with the extranodal form of Rosai-Dorfman disease, presenting with scleritis and anterior uveitis in the left eye, who experienced subsequent development of an epibulbar tumor in the same eye. The patient was also complicated by a relapsing facial nodule on the right cheek. After the pathological diagnosis of Rosai-Dorfman disease was obtained, the patient underwent surgical excision of the epibulbar tumor and the facial nodule, accompanied by systemic immunosuppression therapy. At the last follow-up, the patient was asymptomatic without signs of recurrence. CONCLUSIONS: This report highlights the progression of ocular manifestations of Rosai-Dorfman disease and emphasizes the importance of systemic therapy.

High prevalence of anal human papillomavirus infection and associated risky behaviors in men infected with human immunodeficiency virus in Taiwan.

A cross-sectional study was conducted to investigate the prevalence, types, and risk factors associated with anal HPV infection among HIV-infected men in outpatient clinics at an AIDS designated hospital in Taiwan. Anal swabs were collect and PCR (polymerase chain reaction) was used to analyze the types of anal HPV infection. HPV DNA was detected in 74.2% of the 198 participants, including high-risk types (40.4%), low-risk types (18.2%) and multiple-types (6%). The most common types were HPV 16 (13.1%), 6 (10.4%), 11 (7.1%) and 18 (6.1%). The significant risk factor for being infected with any type or a high-risk type of HPV was having sexual partners (>3) in the preceding 6 months. Low-risk type of anal HPV infection was associated with a history of anal lesions. Our findings support the need for regular follow-up of all HIV/HPV coinfected patients and their partners to allow early detection of anal intraepithelial neoplasia.

Pneumocystis jirovecii pneumonia in systemic lupus erythematosus from southern Taiwan.

BACKGROUND: Opportunistic infection has been documented in systemic lupus erythematosus with special attention paid to Pneumocystis jirovecii because of the significant morbidity and high mortality. OBJECTIVES: The limited large-scale investigations covering P. jirovecii pneumonia (PCP) in systemic lupus erythematosus following biologics or immunosuppressants therapy prompted us to perform this study in southern Taiwan. METHODS: A retrospective study was completed in 858 hospitalized lupus patients from January 2000 to December 2011. The definite diagnosis of PCP was made by the laboratory detection of Pneumocystis organisms together with consistent clinical and radiological manifestations of PCP. Positive polymerase chain reaction results of sputum samples were not regarded as infection in this study, unless P. jirovecii was the sole pathogen found and pulmonary manifestations resolved following antibiotics for PCP treatment alone. RESULTS: The laboratory identification of Pneumocystis organisms depended on lung biopsy in 2 cases and bronchoalveolar lavage in 3 patients. Five cases, 2 women and 3 men aged 30 to 50 years (41.8 ± 8.8 years), were identified with a 0.6% incidence. None received chemoprophylactics against P. jirovecii infection. All had lupus nephritis and lymphopenia with low CD4 T-cell counts. Prior usages of higher daily prednisolone dosages and concomitant biologics or immunosuppressants were observed in all patients. Pneumocystis jirovecii pneumonia contributed to a high mortality rate (60%). CONCLUSIONS: We report the rare occurrence but high mortality of PCP infection in this study. A consensus guideline addressing prophylactic antibiotics against Pneumocystis organisms in highest-risk lupus patients on biologics or immunosuppressants could be helpful in guiding their management.

Mutational analysis of epidermolysis bullosa in Taiwan by whole-exome sequencing complemented by RNA sequencing: a series of 77 patients.

BACKGROUND: Epidermolysis bullosa (EB) is a heterogeneous group of hereditary skin diseases characterized by skin fragility. Primary data on Taiwanese population remain scarce. METHODS: We gathered clinical information from EB patients at National Cheng Kung University Hospital from January, 2012, to June, 2021. Diagnostic tests including transmission electron microscopy, immunofluorescence studies, and whole-exome sequencing (WES) were performed. The pathogenicity of novel splice-site mutations was determined through reverse transcriptase-PCR of skin mRNA followed by Sanger and/or RNA sequencing. RESULTS: Seventy-seven EB patients from 45 families were included: 19 EB simplex, six junctional EB, and 52 dystrophic EB. Pathogenic variants were identified in 37 of 38 families (97.4%), in which WES was used as a first-line tool for mutational analysis; RNA sequencing determined pathogenic variants in the remaining one family. A total of 60 mutations in EB-related genes were identified, including 22 novel mutations. The mutations involved KRT5, KRT14, PLEC, COL17A1, LAMB3, LAMA3, ITGB4, and COL7A1. Over one-quarter of DEB patients had EB pruriginosa. CONCLUSIONS: The distinct clinical presentation and molecular pathology of EB in Taiwan expand our understanding of this disorder. WES was an effective first-line diagnostic tool for identifying EB-associated variants. RNA sequencing complemented WES when multiple potentially pathogenic splice-site mutations were found.

Naevus anaemicus-like hypopigmented macules in dyskeratosis congenita.

In the present paper we report on a Taiwanese case of X-linked recessive dyskeratosis congenita (DC), confirmed by detection of a 214 C→T mutation in the DKC1 gene, and provide a detailed description of mottled pigmentary changes of the skin, specifically numerous small, whitish macules dispersed against a background of diffuse, finely reticulated hyperpigmentation. The hypopigmented macules showed no discernible erythema upon rubbing or the local application of heat. The naevus anaemicus-like macules may be a relatively common but under-recognized feature in DC. More studies are required to determine the incidence and histopathology of these macules.

Early-life or lifetime sun exposure, sun reaction, and the risk of squamous cell carcinoma in an Asian population.

BACKGROUND: It has been widely accepted that sun exposure is a risk factor of squamous cell carcinoma (SCC) among fair-skinned populations. However, sun exposure and sun reaction have not been explored in Asians and no gender-specific data were available. METHOD: In a case-control study, 176 incident skin cancer cases were recruited from National Cheng-Kung University Medical Center from 1996 to 1999. Controls included 216 age-, gender-, and residency-matched subjects from the southwestern Taiwan. A questionnaire was administered to collect information on life style and other risk factors. Logistic regression analysis was performed to evaluate the association between sun exposure or sun reaction and the risk of SCC by gender. RESULTS: Early-age (age 15 to 24) and lifetime sun exposure were significantly associated with increased risk of SCC in a dose-response pattern [odds ratio (OR) = 1.49-3.08, trend p = 0.009 and 0.0007, respectively]. After stratified by gender, the third tertile of early-age sun exposure was significantly associated with the SCC risk among men (OR = 3.08). The second and third tertiles of lifetime sun exposure was significantly associated with SCC risk among women (OR = 3.78 and 4.53, respectively). Skin reaction after 2-h sun exposure during childhood and adolescence was not significantly associated with the risk of SCC. CONCLUSIONS: Lifetime sun exposure was more related to SCC risk in women, while early-age sun exposure was more relevant to men's SCC risk. This may be attributable to different lifestyle between men and women.

Real-world efficacy of biological agents in moderate-to-severe plaque psoriasis: An analysis of 75 patients in Taiwan.

BACKGROUND: Real-world clinical data on psoriasis patients receiving different biological agents is needed, especially in Asian populations. OBJECTIVES: Our aim is to compare and analyze the efficacy and safety profile of four biological agents (etanercept, adalimumab, ustekinumab and secukinumab) in a real-world setting in Taiwan. METHODS: We retrospectively analyzed the clinical data of all patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index (PASI) ≥ 10) who received etanercept, adalimumab, ustekinumab or secukinumab between January 2011 and December 2018 in a tertiary hospital in Taiwan. RESULTS: A total of 119 treatment episodes in 75 patients were included in this study. Ustekinumab was used in 49 treatment episodes, followed by secukinumab in 46 treatment episodes, adalimumab in 14 treatment episodes and etanercept in 10 treatment episodes. The proportion of the biologic-naïve was highest in etanercept (100%) and lowest in secukinumab (23.9%). The PASI-75, -90 and -100 were the highest in secukinumab (91.3%, 82.6%, 41.3%, respectively), followed by ustekinumab (79.6%, 44.9%, 16.3%), adalimumab (64.3%, 28.6%, 7.1%) and etanercept (50.0%, 30.0%, 0%). The rate of adverse events that required treatment was highest for secukinumab (15.2%), followed by adalimumab (14.3%), ustekinumab (8.2%), and etanercept (0%), including 4 cases of infections, 2 cases of cardiovascular diseases and 4 cases of cancers. CONCLUSIONS: This real world data showed differential efficacy and safety of the four biological agents.

PTPN11 mutations in LEOPARD syndrome: report of four cases in Taiwan.

BACKGROUND/PURPOSE: LEOPARD syndrome (LS) is a rare, autosomal dominant disorder. The typical clinical presentation includes multiple lentigines and cardiac defects. Mutation analysis of the PTPN11 gene is feasible. We report four cases of LS, which were confirmed by molecular genetic study. METHODS: The clinical features and mutations of the four patients were summarized. RESULTS: The diagnosis of all four patients was made when lentigines appeared during childhood. Three cases had hypertrophic cardiomyopathy. No electrocardiographic conduction abnormality was noted in any of the cases. Three patients had hypertelorism and three had short stature. Two patients, identical twins, presented with the atypical phenotype of tongue protrusion and hepatosplenomegaly at birth. Twin B had mild mental retardation. Case 4 had moderate hearing impairment. Point mutation of the PTPN11 gene was found in all patients. CONCLUSION: LS has typical skin manifestations. All patients should undergo a comprehensive examination, especially echocardiography and electrocardiography. The diagnosis can be confirmed by genetic study.

Giant café-au-lait macule in neurofibromatosis 1: a type 2 segmental manifestation of neurofibromatosis 1?

Type 2 segmental manifestation of autosomal dominant dermatoses refers to pronounced segmental lesions superimposed on the ordinary nonsegmental phenotype, indicating loss of heterozygosity occurring at an early stage of embryogenesis. We describe a 20-year-old Taiwanese woman with typical lesions of neurofibromatosis type 1 (NF1) in the form of characteristic café-au-lait spots, neurofibromas, axillary freckling and Lisch nodules. In addition, a giant garment-like or "bathing-trunk" café-au-lait macule involved the lower half of the trunk, the buttocks, and parts of the thighs, being superimposed on the ordinary smaller spots of NF1. This large café-au-lait macule may be best explained as an example of type 2 segmental NF1. A novel mutation (3009delG) in exon 23 was also identified in this patient, which has not yet been described in sporadic and familial NF1.

Case report of Schöpf-Schulz-Passarge syndrome resulting from a missense mutation, p.Arg104Cys, in WNT10A.

Schöpf-Schulz-Passarge syndrome (SSPS) is a rare ectodermal dysplasia characterized by cysts of the eyelids, hypodontia, hypotrichosis, palmoplantar keratosis and onychodystrophy, and it is not common in Asia according to the published work. This autosomal recessive disorder was believed to result from mutations in the WNT10A gene. We report a 54-year-old Taiwanese man with SSPS resulted from a homozygous mutation (p.Arg104Cys) in WNT10A. This mutation has not been reported in odonto-onycho-dermal dysplasia but was demonstrated to link with dental abnormalities. This report implies the significance of WNT10A gene mutation in ectodermal dysplasia and highlights the clinical features of SSPS.

Mutation analyses of COL7A1 gene in three Taiwanese patients with severe recessive dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa (DEB) is a hereditary mechanobullous disorder characterized by fragility of the skin and mucous membranes caused by abnormal anchoring fibrils. Both dominant and recessive DEB are caused by mutations in COL7A1, the gene encoding type VII collagen, the major component of anchoring fibrils. We performed mutation analysis of COL7A1 in three patients with recessive DEB. The diagnosis of DEB was based on the characteristic clinical features and confirmed histopathologically. All 118 exons and flanking intron boundaries of COL7A1 were amplified. Four novel mutations (3373insGG, 7769delG, E1535X, G2061E) and two potential splicing mutations were detected. The first three of these mutations resulted in premature termination codons, while G2061E caused a glycine substitution mutation in the triple-helical domain. This is the first report of mutation analyses of the COL7A1 gene in Taiwanese pedigrees with recessive DEB. Each patient had a heterozygous premature termination codon mutation combined with either a glycine substitution mutation in the critical triple-helical collagenous domain or a potential splicing mutation. These genotypes correlate well with the severe clinical phenotype of recessive DEB.

WOX1 is essential for UVB irradiation-induced apoptosis and down-regulated via translational blockade in UVB-induced cutaneous squamous cell carcinoma in vivo.

PURPOSE: We investigated the role of candidate tumor suppressor and proapoptotic WOX1 (also named WWOX, FOR, or WWOXv1) in UVB-induced apoptosis and formation of cutaneous squamous cell carcinomas (SCC). EXPERIMENTAL DESIGN: Expression of WOX1 and family proteins (WWOX) in human primary cutaneous SCCs was examined by immunohistochemistry, in situ hybridization, and reverse transcription-PCR. UVB irradiation-induced WOX1 activation (Tyr33 phosphorylation and nuclear translocation), apoptosis, and cutaneous SCC formation were examined both in vitro and in vivo. RESULTS: Up-regulation of human WOX1, isoform WOX2, and Tyr33 phosphorylation occurred during normal keratinocyte differentiation before cornification and death. Interestingly, significant reduction of these proteins and Tyr33 phosphorylation was observed in nonmetastatic and metastatic cutaneous SCCs (P < 0.001), but without down-regulation of WWOX mRNA (P > 0.05 versus normal controls), indicating a translational blockade of WWOX mRNA to protein. During acute exposure of hairless mice to UVB, WOX1 was up-regulated and activated in epidermal cells in 24 hours. In parallel with the clinical findings in humans, chronic UVB-treated mice developed cutaneous SCCs in 3 months, with significant reduction of WOX1 and Tyr33 phosphorylation and, again, without down-regulation of WWOX mRNA. Human SCC-25 and HaCaT cells were transfected with small interfering RNA-targeting WOX1 and shown to resist UVB-induced WOX1 expression, activation, and apoptosis. CONCLUSIONS: WOX1 is essential for UVB-induced apoptosis and likely to be involved in the terminal differentiation of normal keratinocytes. During UVB-induced cutaneous SCC, epidermal cells have apparently prevented the apoptotic pressure from overexpressed WOX1 by shutting down the translation machinery for WWOX mRNA.