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.

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.

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.

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.

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.

Cutaneous alternariosis in a renal transplant recipient: a case report and literature review.

Organ transplant recipients under immunosuppressive therapy have a highly increased risk of acquiring unusual opportunistic infections. Diagnosis of the etiology of infection may be difficult in clinical manifestations, which need further histological and biological investigations. We recently treated a male renal transplant recipient with a cutaneous phaeohyphomycosis due to Alternaria species. The diagnosis was based on microscopy and culture of the skin lesions. Treatment with oral itraconazole for 5 weeks was ineffective, then clinical improvement was achieved by combination of amphotericin B wet-packing and systemic antifungal therapy with oral voriconazole. Alternaria species are ubiquitous plant-inhabiting saprobes, which are increasingly associated with opportunistic phaeohyphomycosis in immunocompromised individuals. To the best of our knowledge, this is the second case report noting sporotrichoid pattern as the manifestation of cutaneous alternariosis. In this context, we reviewed recent renal-transplant-related cutaneous alternariosis reported in the English-language literature during 1995 to 2011 to summarize its clinical features and outcomes, and to guide clinicians in the care of kidney transplant patients with cutaneous alternariosis.

Herpes zoster-associated severity and duration of pain, health-related quality of life, and healthcare utilization in Taiwan: a prospective observational study.

BACKGROUND: To assess the severity and duration of herpes zoster (HZ)-associated pain (ZAP) and its impact on quality of life (QoL) and healthcare utilization (HCRU) from a patient perspective in routine care in Taiwan. METHODS: A prospective, observational, single-cohort study was conducted in five centers across Taiwan. Patients were recruited at different time points during their HZ episode and were followed for ≤180 days. ZAP was assessed with the Initial Zoster Impact Questionnaire and the Zoster Brief Pain Inventory, QoL with the EQ-5D, and HCRU with a simple questionnaire. RESULTS: A total of 150 patients were included with a mean age of 64.9 years and mean time since rash onset of 18.8 days. Prodromal pain was experienced by 64.7% of patients, of whom 91.8% reported moderate-to-severe pain. At enrollment, 98.0% of patients experienced ZAP. Mean ± SD worst pain score decreased from 5.95 ± 3.09 at enrollment to 2.65 ± 2.98 at 30 days and 0.28 ± 0.83 at 180 days. Postherpetic neuralgia was observed in 20.7% of patients. Mean ± SD EQ-5D score significantly decreased (P < 0.001) from 0.91 ± 0.16 before rash onset to 0.67 ± 0.18 after rash onset, showing significant QoL deterioration up to 60 days. The impact of HZ on QoL and pain severity was similar across age groups. Significant HCRU was observed including visits to the doctor (83.3% of patients), specialist (30.7%), emergency department (24.7%), physiotherapist (23.3%), and hospitalizations (20.7%). CONCLUSION: Severe morbidity and significant HCRU are associated with HZ in Taiwan, supporting the need for early intervention and preventive strategies to reduce the HZ-associated burden of illness.

Bowen's disease with features resembling myrmecia wart.

We report the clinical and pathological findings of two cases of Bowen's disease (BD) with features resembling myrmecia wart, and tried to find evidence of human papillomavirus (HPV) infection in such lesions by immunohistological staining, genotyping systems, polymerase chain reaction (PCR) and electron microscopy. Both cases manifested unique barnacle-like hyperkeratotic nodules or plaques clinically, and microscopically proliferation of atypical keratinocytes involving the entire thickness of the epidermis, hypergranulosis with eosinophilic and/or basophilic inclusion bodies, features that mimicked myrmecia wart. Electron microscopy revealed myrmecia inclusion-like large intranuclear and cytoplasmic electron-dense bodies. Immunohistological staining with anti-HPV antibody, genotyping systems for HPV infection and specific PCR designed to detect HPV-1 L1 sequences failed to detect evidence of HPV infection. P16(INK4a) was overexpressed in the atypical keratinocytes of both cases. This finding suggests that the pathogenesis of these two BD may involve certain unknown or undetectable HPV, or reflect disturbances of the Rb signaling pathway unrelated to HPV infection. The unique "myrmecioid" clinicopathological features in our cases suggest that this type of lesion may be a new variant of BD.

Early intervention with high-dose steroid pulse therapy prolongs disease-free interval of severe alopecia areata: a retrospective study.

BACKGROUND: Spontaneous recovery of severe alopecia areata is rare and the condition is difficult to treat. OBJECTIVE: The aim of this study is to investigate and compare the effects and safety of steroid pulse therapy between oral and intravenous administrations between 1999 and 2010 at the Department of Dermatology, National Cheng Kung University Hospital. METHODS: Data were retrospectively retrieved. A satisfactory response was defined as more than 75% hair regrowth in the balding area. RESULTS: A total of 85 patients with more than 50% hair loss were identified and treated, with an overall satisfactory response rate of 51.8%. The mean follow-up time was 37.6 months, with a relapse rate of 22.7%. Patients with alopecia areata (hereafter, AA) of recent onset within one year showed higher response rates (p<0.001) and lower relapse rates compared to patients with AA persisting for more than 1 year. Further, even in patients with alopecia totalis, alopecia universalis or ophiasis type, early treatment resulted in a satisfactory response rate of 47% among the treated patients. In general, oral therapy was as effective and well-tolerated as intravenous therapy. CONCLUSION: The response rate is determined by disease severity and time of intervention, not by the administration form of steroid pulse therapy. Oral steroid pulse therapy can be considered as the first-line treatment for patients with severe AA of recent onset within one year.

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.

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.

A novel splice mutation in the ATP2C1 gene in a woman with concomitant psoriasis vulgaris and disseminated Hailey-Hailey disease.

Concurrent psoriasis vulgaris and Hailey-Hailey disease is very rare. The clinical and pathologic findings of widespread Hailey-Hailey disease in a 48-year-old woman with pre-existing generalized psoriasis vulgaris were described. In our patient, the vesicular eruption of Hailey-Hailey disease was obscured clinically by the psoriatic lesions. The diagnosis of both diseases was confirmed pathologically. The patient had a total of five skin biopsies performed over the neck, flank area, back, pubic area, and a finger. Acantholytic dyskeratosis, changes suggestive of Hailey-Hailey disease, were found in four specimens, psoriasis in two specimens, and both diseases in one specimen. The diagnosis of Hailey-Hailey disease was further confirmed by detecting a novel splice mutation (832G>A) in the ATP2C1 gene. Our case illustrated that diagnosis of disseminated Hailey-Hailey disease may easily be missed in a patient with a pre-existing generalized pruritic eruption, such as psoriasis. The appearance of eczematous vesicular eruption or eroded intertrigo-like lesions in a patient with pre-existing generalized eruption should raise a suspicion of Hailey-Hailey disease.

Evanescent and persistent pruritic eruptions of adult-onset still disease: a clinical and pathologic study of 36 patients.

OBJECTIVE: Persistent pruritic eruptions (PPE) are common among our patients with adult-onset Still disease (AOSD). We aimed to characterize the clinicopathologic features of the AOSD-associated evanescent and persistent rashes. METHODS: We reviewed the clinicopathologic features of the skin lesions from all AOSD cases diagnosed in our hospital during 1988 to 2009. The diagnoses were based on Yamaguchi criteria for AOSD. RESULTS: Altogether, there were 36 patients (6 men and 30 women) with age of onset ranging from 17 to 67 years (average 35.7 years). Evanescent rash was recorded in 31 patients (86%) and PPEs in 28 (78%). PPEs usually appeared at the disease onset and manifested as widespread, pruritic, erythematous urticarial or violaceous to brownish flat-topped (lichenoid) papules and plaques over the trunk, neck, face, and extensor sides of the extremities. PPEs were classified clinically as urticarial papules (n = 21), lichenoid papules (n = 18), prominent linear and dermographism-like (n = 11), dermatomyositis-like (n = 7), prurigo pigmentosa-like (n = 4), and lichen amyloidosis-like (n = 2). The clinical activity score was 5.78 ± 1.11 (range 4 to 8) for the series and 6.57 ± 0.98 and 5.57 ± 1.07, respectively, for the groups with and without dermatomyositis-like PPE (P = 0.0314). Five patients died, 3 of them with dermatomyositis-like PPE. Histopathologically, the evanescent rash (8 specimens) showed a superficial perivascular infiltrate of lymphocytes and neutrophils, whereas the PPEs (32 specimens) revealed solitary or cluster necrotic keratinocytes in the superficial epidermis with infiltration of lymphocytes and neutrophils in the upper and mid dermis. CONCLUSIONS: PPEs were very common among our patients with AOSD. Recognition of the characteristic clinical and pathologic features of PPE can facilitate diagnosis of AOSD. Therefore, biopsy of atypical eruptions in AOSD patients is recommended because it is likely that the highly distinctive histopathologic features will allow these eruptions to be readily classified.