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This article aims to present current COVID-19 vaccination considerations for patients on immunotherapeutics for the management of immune-mediated dermatological diseases and summarize the recommendations relevant to clinical practice in Taiwan. These Taiwan Dermatological Association (TDA) recommendations are intended to be dynamic in nature and serve as an interim guide to optimize patient care at this current juncture. It is expected that our clinical practice would continually evolve and be informed by new evidence that emerges in this pandemic.

Background: Plasmacytoid dendritic cells (pDCs) are implicated in the reactivation of human herpesvirus 6 (HHV-6) in drug reaction with eosinophilia and systemic symptoms (DRESS). Objectives: We aimed at identifying the alterations of circulating pDCs, basophils, and myeloid dendritic cells (mDCs) during the active stage of drug eruptions and the relationship between pDC alteration and HHV-6 reactivation in DRESS patients. Methods: Nine DRESS patients and twelve patients of other drug eruptions (ODE, including five cases of maculopapular eruptions (MPEs), five cases of Stevens–Johnson syndrome, and two cases of fixed drug eruption) were prospectively recruited. Blood samples were collected weekly for 2 consecutive weeks for flow cytometry of pDC, basophil, mDC, and detection of HHV-6 reactivation by serum anti-HHV-6 immunoglobulin G, or whole blood HHV-6 viral DNA by quantitative polymerase chain reaction. Results: The HHV-6 reactivation was exclusively seen in DRESS, and the pDC levels decreased in DRESS compared with ODE (P = 0.002) and (MPE, P = 0.021), with the timing of such decrease preceding HHV-6 reactivation. Conclusion: The decrease of pDC levels is significantly more common in DRESS patients and occurs before HHV-6 reactivation. The chronological sequence implies that the decrease of pDC may be crucial in the pathogenesis of viral reactivation.

Background: Atopic dermatitis (AD) is a prevalent skin disease in Asia. Attitudes and practice vary among the Asian cities. Objectives: This study aimed to survey similarities and differences in dermatologists' attitudes and practice in Asian cities. Methods: A questionnaire survey was sent to 118 dermatologists in Singapore, Malaysia, Thailand, Taiwan, and Hong Kong. Results: About 30.8% of respondents from Taiwan and 44.4% of respondents from Hong Kong saw most of their patients presenting with severe AD. This is significantly higher than respondents from Singapore, Malaysia, and Thailand (4%–12%). Majority of the respondents would use topical corticosteroids in infants and children with AD. About 55.6% of the respondents from Hong Kong used topical calcineurin inhibitors in AD, which is a significantly lower than the other countries. Top 3 most prescribed antibiotics in infected AD were cephalexin, cloxacillin, and amoxicillin/clavulanic acid combination. Most respondents used oral corticosteroids in severe AD. Many respondents from Singapore and Malaysia use cyclosporin (70%–92%), azathioprine (80%–100%), and methotrexate (72%–75%). Fewer respondents from Thailand, Taiwan, and Hong Kong used cyclosporin (22.2%–59%), azathioprine (0%–66.7%), and methotrexate (8%–25.6%). A large majority of respondents from Singapore, Taiwan, and Malaysia use phototherapy in management of AD (90%–100%). About 24% of respondents from Thailand and 33.3% of respondents from Hong Kong use phototherapy in AD. Conclusion: Compared to the previous study, there is improvement in the proportion of dermatologists in Asia using topical calcineurin inhibitors and phototherapy. This may signify better access to these treatment modalities throughout the region. Educational programs that allow a patient-centered approach should be recommended as an adjunct to medical therapy. The management of AD among Asians requires a holistic approach while considering accessibility and cultural differences.

Atopic dermatitis (AD) is generally considered a T-helper type 2-dominated disease. Adult AD is often more severe and less manageable by topical therapies and may require systemic immunosuppressants that bear notable side effects and organ toxicities. There is an unmet need for safe and effective long-term therapy in this population. Dupilumab, a fully human monoclonal antibody, dually inhibits interleukin (IL) IL-4 and IL-13 signaling and has demonstrated promising efficacy and acceptable safety profile in several Phase III trials, followed by recent Food and Drug Administration approval for the treatment of moderate-to-severe AD in adults whose disease is inadequately controlled with topical therapies. Dupilumab may also serve as a new treatment option when other systemic medications have failed or are inadvisable. Nevertheless, long-term safety data beyond 1 year and comparison with the existing therapies remain to be investigated. Other emerging agents targeting pruritogenic proteins, chronic inflammation, and epidermal hyperplasia are under vigorous clinical development. In particular, nemolizumab, blocking IL-31-mediated pruritus, has been reported in Phase II trials to provide symptom relief by interrupting the itch-scratch cycle. Accompanied by thorough characterization of different phenotype and endotype subsets, the era of precision medicine could bring new prospects in the optimal treatment of AD.

A 40-year-old female presented with rapid-onset generalized erythematous eruption with pustules agminated over the flexural areas and the flanks for 2 days. In skin histopathology, extensive subcorneal pustules, spongiosis and neutrophilic exocytosis, papillary dermal edema, and perivascular and interstitial mixed-cell infiltrates were observed. No psoriasis history but irregular intake of numerous kinds of Chinese herbal medications and the last-modified regimen including Radix Aucklandiae 14 days before the onset of pustular eruption were unveiled. Patch test showed positive result with only Radix Aucklandiae. Thus, acute generalized exanthematous pustulosis induced by Radix Aucklandiae was diagnosed.

Acrylates are esters of acrylic acid, which are potent sensitizers that can cause occupational allergic contact dermatitis (ACD) in dental personnel. More recently, an increasing number of cases of both occupational and non-occupational ACD in beauty industry are observed. Here we present three cases of ACD to acrylate and its derivatives in both nail beauticians and do-it-yourself gel nail users due to exposure to nail cosmetics presenting with chronic hand eczema with severe pulpitis and even nail dystrophy with patch-test-confirmed diagnosis. Chemical analysis of commercial nail cosmetic products has been done in one of the patients and successfully identified 2-hydroxypropyl acrylate as the contact allergen. Keywords: Acrylic acid, Acrylate, Allergic contact dermatitis (ACD), Methacrylate, Nail cosmetic products

Background/Objective: There is a rising awareness of drug reaction with eosinophilia and systemic symptoms (DRESS) due to its possible morbidity and mortality. Early diagnosis of DRESS is crucial for administering timely treatment; however, prompt diagnosis based on its early presentation can be quite problematic due to its clinical resemblance to common maculopapular eruptions (MPE). Methods: A retrospective cohort study of patient data from September 2010 to June 2016 was conducted to compare the clinical presentations of DRESS and MPE validated by the RegiSCAR scoring system. The demographic data, clinical presentations, and histopathological patterns were reviewed. Results: Fifty-eight patients with DRESS and 29 patients with MPE were included. The mean age at diagnosis of DRESS was 47 years (range: 2–82 years), and female patients predominated by a ratio of 2.2:1. The three most common culprit medications for DRESS were allopurinol, sulfasalazine, and trimethoprim/sulfamethoxazole. The most significant differences between the DRESS and MPE groups were the presence of fever, peripheral blood eosinophilia and atypical lymphocytosis, characteristic skin lesions, abnormal liver functions, and prolonged resolution of skin lesions for more than 15 days in the DRESS patients. The most common histologic features in the DRESS patients were coexistent eczematous, interface dermatitis, and vascular damage patterns, or interface dermatitis alone. The concurrence of fever, peripheral blood eosinophilia, and abnormal liver function within three days of visiting a medical facility were more common in cases of DRESS than of MPE (24.1% vs. 0%, P = 0.004). Conclusion: Although DRESS and MPE look similar, especially in the early stage of DRESS, the concurrence of fever, peripheral blood eosinophilia, and abnormal liver functions within three days of visiting a medical facility might aid in the early diagnosis of DRESS.

Background/Objectives: Accumulating evidence has shown that omalizumab is an effective and safe treatment for chronic spontaneous urticaria (CSU), but there is little information regarding the use of omalizumab to treat CSU in Taiwan. Reports on clinical experiences with using omalizumab for CSU for more than 6 months are also lacking. Methods: A retrospective review of medical records of consecutive CSU patients receiving omalizumab treatment in the Urticaria Special Clinic of one tertiary referral center in Taiwan was conducted. We analyzed clinical features of the patients, treatment efficacy and safety, and also long-term outcomes after omalizumab treatment. An Urticaria Activity Score over 7 days (UAS7) was recorded at each visit. Results: A total of 17 CSU patients were identified (11 females and 6 males, age range: 21–83 years) with a baseline mean UAS7 of 29.8 ± 8.9 despite antihistamine treatment. All patients were treated with at least 3 doses of monthly subcutaneous injections of omalizumab. Fifteen patients achieved a UAS7 of 6 or less after 3 doses of monthly omalizumab injections. Seven of those 15 patients received an additional 1 to 3 doses and all ended up with a UAS7 of less than 2 at the 24-week follow-up. A sustained response to maintenance treatment after 24 weeks was observed in 5 patients with individual tailoring of treatment duration and dosing interval. Conclusion: Omalizumab is an effective and safe treatment for antihistamine refractory CSU. Maintenance therapy with individual tailoring of the treatment duration and interval is possible.

Background/Objective: Since 2005, there has been a significant increase in contact allergy to methylisothiazolinon (MI)/methylchloroisothiazolinone (MCI) incidences in European countries, but there has been no documented large-scale studies of such incidences in Taiwan. Methods: From 1987 to 2015, a total of 2590 patients received patch testing in our Contact Dermatitis Clinic. Analyzed were patients with positive reactions to MI/MCI (Kathon CG) in patch testing and with suspected allergy to MI/MCI. Results: Among the total 2590 patients, 2388 received patch testing during 1987–2005, while 202 received patch testing during 2006–2015. Because Kathon CG was not routinely patch tested for all patients from 1987 to 2005, the incidence of contact allergy to MI/MCI was thus corrected to 3/145 (2.1%) for this time period. After 2005, there were 11 patients (11/202, 5.4%) who showed positive reactions to MI/MCI. Amongst the 14 patients who showed positive reactions to MI/MCI, 12 of them were females (85.7%). The majority of the lesions was located on the hands (10 patients, 71.4%), along with the face (3 patients, 21.4%). Interestingly, 6 patients (42.9%) who showed positive reactions to MI/MCI were associated with contact allergy to essential oils, and five of them were aromatherapists. Conclusion: According to our study, the incidence of MI/MCI contact allergy in a referral center in Taiwan was 5.4%. A trend of increasing incidence of contact allergy to MI/MCI was noted after 2005, which is consistent with the findings in Europe. Allergic contact dermatitis to MI/MCI should be suspected in patients who have eczema on the hands and face, especially those who are aromatherapists.

Background/Objective: This report describes the 2014 consensus of the Taiwanese Dermatological Association (TDA) regarding the treatment of atopic dermatitis (AD). The TDA consensus is distributed to practices throughout Taiwan to provide recommendations for therapeutic approaches for AD patients to improve their quality of life. Methods: The information in the consensus was agreed upon by a panel of national experts at TDA AD consensus meetings held on March 16, May 4, and June 29, 2014. The consensus was in part based on the 2013 Asia–Pacific AD guidelines and the guidelines of the American Academy of Dermatology, with modification to reflect the clinical practice in Taiwan. Results: The amendments were drafted after scientific discussions focused on the quality of evidence, risk, and benefits; all the consensus contents were voted on by the participating dermatologists, with approval by at least 75% for inclusion. Conclusion: The consensus provides a comprehensive overview of treatment for AD, with some local and cultural considerations for practitioners in Taiwan, especially the use of wet dressings/wraps, systemic immunomodulatory agents, and complementary therapies.

Background/objective: Contact dermatitis to topical medicaments is commonly encountered in daily practice of dermatologists. The incidence and ranking of common allergens in topical medicaments may vary depending on local prescription and self-medication behavior. The objective of this study is to investigate the clinical features and common allergens of contact dermatitis to topical medicaments in Taiwan. Methods: From 1978 to 2005, a total of 3717 patients had been patch tested in our Contact Dermatitis Clinic. Any case with suspected contact allergy to topical medicaments receiving patch testing was included in this study. Results: During this period, a total of 608 patients were included and 603 of them completed the patch tests. Of the 603 patch-tested patients, 397 (66%) were positive for at least one antigen, and all patch tests were negative in 206 (34%). Patients with positive patch testing were characterized by younger age and location on the limbs and skin folds, while sex and atopy were not different among the two groups. A total of 1076 positive reactions to identifiable medicaments or main ingredients were recorded in 397 patients with positive patch testing. Among these positive reactions, 701/1076 counts (65%) were read as relevant. Traditional herbal medicaments (50%), antiseptics (21%), vehicle ingredients (9%), antibiotics (8%), corticosteroids (2%), anesthetics (2%), and nonsteroidal anti-inflammatory drugs (1%) were the most common sensitizers in this study, and the common concomitant allergens were fragrance (52%) and metal (20%). Conclusion: The results emphasized the special cultural consideration in Taiwanese patients with contact dermatitis to topical medicaments.

Background: Chronic actinic dermatitis (CAD) is an idiopathic photosensitive dermatosis induced by ultraviolet B (UVB), sometimes ultraviolet A (UVA), and occasionally visible light. Diagnosis is suggested by the clinical findings, typically a chronic eczematous rash on the sun exposed areas, and confirmed by phototesting, which demonstrates the abnormal photosensitivity. The aim of this study was to determine the characteristics of CAD in Taiwanese patients. Methods: We retrospectively reviewed the clinical and photobiological features of all patients diagnosed as having CAD at our institute from 2002 to 2012. Results: A total of 15 patients with CAD were identified. The mean age at diagnosis was 58.6 years (range, 28–82 years). All the patients were males. The face, neck, forearms, and dorsal hands were most commonly involved. Eight patients (53.3%) had decreased minimal erythema dose (MED) to both UVB and UVA; six patients (40.0%) had decreased MED to only UVB; one patient (6.7%) had decreased MED to only UVA. All were managed with photoprotection and topical corticosteroids. Four patients received azathioprine (50 mg twice a day to every other day) and one received prednisolone (10 mg per day to every other day). Conclusion: In Taiwan, CAD affects elderly men more commonly. The most common phototest results were decreased MED to both UVB and UVA, followed by to UVB alone. All patients were managed with photoprotection and topical corticosteroids, and some also required systemic agents, in particular azathioprine.

Background: Azathioprine is used as an immunosuppressant and corticosteroid-sparing agent for the treatment of several cutaneous diseases. The mutation of thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) has been reported to result in the accumulation of toxic thiopurine metabolites and to increase the adverse effects during azathioprine treatment. In the Chinese population, TPMT∗3C and ITPA C94A polymorphisms have been documented. Methods: Genotyping was performed for TPMT and ITPA polymorphisms in 92 unrelated healthy volunteers and in 74 dermatology patients (46 with adverse effects and 28 without adverse effects) during azathioprine treatment. Results: Two functional polymorphisms, TPMT∗3C and ITPA C94A, were detected. After analysis, ITPA C94A showed weak association with nausea/vomiting induced by azathioprine. Furthermore, we revealed that the ITPA 94 A allele was most common in patients with nausea/vomiting and developing slow-appearing adverse effects (67%), followed by patients with nausea/vomiting but not developing slow-appearing adverse effects (50%) and patients without nausea/vomiting but developing slow-appearing adverse effects (25%). Conclusion: Adverse reaction to azathioprine cannot be predicted by TPMT polymorphism. However, genetic testing of ITPA polymorphism may be more important for the prediction of nausea/vomiting in Taiwanese. Currently, regular blood tests and clinical vigilance remain most important in preventing severe drug reactions during clinical use of azathioprine.

Background/Objectives: Paraneoplastic pemphigus (PNP) is a rare mucocutaneous disease with a high mortality rate. It is defined by polymorphic mucocutaneous manifestations, particular histological features, characteristic results of direct and indirect immunofluorescence examinations, presences of specific autoantibodies, and associations with underlying neoplasms. However, currently, there is no existing study regarding the characteristics of PNP patients in Taiwan. In this study, we report a case series and try to determine the specific presentations of PNP patients in Taiwan. Materials and methods: PNP patients treated in a referral center in northern Taiwan from 1998 to 2012 were retrospectively recruited. The clinical manifestations, histopathological features, findings of direct and indirect immunofluorescence, results of immunoblotting, and all relevant clinical information were collected. Results: Eleven patients were identified with an average age of 62 years. Polymorphic mucocutaneous manifestations were observed in almost all patients. The most common presentation was pemphigus-like lesions, followed by lichen planus-like lesions. All patients had recalcitrant oral mucosal lesions. Five and four patients had genital and eye involvements, respectively. The mostly associated neoplasm is Castleman’s disease, followed by malignant thymoma. Acantholysis is the mostly observed histological features, followed by lichenoid dermatitis and interface dermatitis. Depositions of immunoglobulins or complements on the surface of keratinocytes or along basement membrane zone were found in eight and seven patients, respectively. Respiratory symptoms presented in eight patients. Despite intensive treatments, seven patients expired. Conclusion: PNP in Taiwanese patients has a high association with Castleman’s disease or malignant thymoma. Complete laboratory examinations and thorough investigations for occult neoplasms are mandatory to establish a diagnosis in patients with clinical suspicions of PNP.

Sarcoidal alopecia is a subtype of plaque-forming cutaneous sarcoidosis that may resemble discoid lupus erythematosus (DLE). Because the clinical appearance of the two lesions is similar, the correct diagnosis may be missed. The systemic involvement and progressive nature of sarcoidosis, make it important to differentiate sarcoidal alopecia from DLE, so that proper treatment can be initiated and potential long-term sequelae avoided. We present the case of a 57-year-old Taiwanese woman with sarcoidal alopecia of the scalp that mimicked DLE.

Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) involves a unique and severe adverse drug reaction. Patients present with fever, rash, lymphadenopathy, hematological abnormalities, systemic illness, and may suffer from prolonged courses. Although the precise pathogenesis of DRESS/DIHS is not fully understood, it is widely considered to be an immunological reaction to a drug or drug metabolites. In this review article, we discuss the historical aspects of nosology, variable clinical and histopathological features, advantages and disadvantages of using an international Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) and Japanese DIHS criteria, pathogenesis, treatment, and long-term sequelae of DRESS/DIHS. Early recognition of this syndrome, withdrawal of suspected culprit drugs, and adequate supportive care are mainstays of improving patient prognosis and reducing morbidities and mortality. Moreover, some DRESS/DIHS patients may develop long-term sequelae, especially autoimmune diseases and end organ failure. Physicians should be aware of these possibilities in patients after DRESS/DIHS and cautiously follow-up symptoms and laboratory tests for early detection of these sequelae.

Seventeen case series investigating the effects of omalizumab on patients with atopic dermatitis included patients whose pretreatment serum IgE was above 700 IU/ml, the upper inclusion limit specified in the product label. In all, 107 patients received omalizumab at doses of ≤375 mg every 2 weeks, which is recommended for patients with IgE

Background/Objective: Fixed drug eruption (FDE) is a dermatosis characterized by recurrent patches or plaques at exactly the same sites with each administration of the causative drug. Vesicles or bullae may sometimes be found, and generalized bullous fixed drug eruption (GBFDE) may be confused with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). This study aimed to investigate the clinical and pathologic features of FDE in Taiwan. Methods: A retrospective analysis evaluated patients with FDE in a referral center in Taiwan covering a period of 11 years. Clinical data, suspected etiologies, and pathology/patch test results were collected. We also compared the GBFDE cases with SJS/TEN overlap or TEN cases to find differentiating clues. Results: There were 39 FDE patients, including nine GBFDE cases. The most frequent causative drugs were non-steroidal anti-inflammatory drugs (five cases, 12.8%) and antibiotics (four cases, 10.3%). Extremities other than the hands (71.8%) were the most frequently affected sites, followed by the trunk (51.3%), mucosa (38.5%), and hands (33.3%). The average age of FDE patients was 52.2 years (median, 56 years; range, 4–86 years). Patients with GBFDE were significantly older than non-GBFDE patients (69.1±19.7 vs. 47.2±23.6, p=0.0124) and the trunk was more likely to be involved in GBFDE cases (88.9% vs. 40.0%, p=0.0197). GBFDE cases also showed tendency to have more mucosal involvement (66.7% vs. 30.0%, p=0.0631). Although similar to SJS/TEN, GBFDE cases had fewer constitutional symptoms, less mucosal involvement but had previous episodes. Histopathologically, the presence of more than two aggregated dyskeratotic keratinocytes (fire flag sign) in the epidermis was more frequently observed in SJS/TEN, whereas GBFDE had superficial and deep dermal infiltration of eosinophils and melanophages. Conclusion: FDE is one of the specialized cutaneous drug reactions and GBFDE should be kept in mind and differentiated from SJS/TEN.

Background: Epidermal growth factor receptor antagonists, such as gefitinib, erlotinib, and cetuximab, have been used in treating carcinomas. The efficacies have been proposed to correlate with skin reactions, but the most important predictive indicator is still unknown. Our aim was to investigate the types of skin toxicities and to analyze the major therapeutic predictive indicators in Taiwan. Methods: A retrospective analysis was used to study 68 patients with advanced non-small-cell lung cancer receiving gefitinib. Results: Acneiform eruption (41.2%), xerosis (38.2%), pruritus (26.5%), and paronychia (16.2%) composed most of the skin reactions. The univariate analysis revealed paronychia as the most substantial survival predictive indicator (p=0.0427). In the multivariate analysis, older patients with paronychia had better prognosis (p=0.0050). Women tended to develop paronychia (p=0.1098). Xerosis positively correlated with paronychia (p=0.0082). Conclusion: Paronychia is the most indicative survival predictive factor among the skin manifestations, and it correlates with age, gender, and xerosis. Elucidation of the relationship between cutaneous reactions can provide information on the epidermal growth factor receptor signaling mechanism of skin.

Background: Linear immunoglobulin A bullous dermatosis (LABD) is a rare autoimmune subepidermal bullous disease. It is defined by continuous linear deposition of IgA in the basement membrane zone on direct immunofluorescence microscopy. The clinical presentations of LABD may mimic other diseases, and data in Taiwanese populations are still lacking. The current study aims to examine LABD status in Taiwan. Methods: We reviewed the database at our institute from 1995 to 2008. The gold standard for the diagnosis of LABD is based on continuous linear depositions of IgA in the basement membrane zone on direct immunofluorescence. Results: A total of 16 LABD patients were identified. Mean age at diagnosis was 55 years, and most (> 80%) occurred after the fourth decade. The trunk was most commonly involved (76%). However, in contrast to previous reports, the mucosal involvement was rare in our series (18%). Initial impressions were dermatitis herpetiformis in 8 patients (50%), bullous pemphigoid in 4 patients (25%), and vasculitis, varicella, and pemphigus vulgaris in the remaining 4 patients (25%). Four patients reported a history of drug ingestion shortly before the onset of the disease, and all recovered after discontinuing the offending drugs. One of them had griseofulvin-associated LABD, a case not reported previously. The other three drugs were rifampin, vancomycin and gemcitabine. Among the various regimens, dapsone (100 mg) twice a day achieved the best treatment response in the five treated patients. Conclusion: The rare and diverse presentations of LABD highlight the importance of our study results in aiding clinical diagnosis and planning treatment strategies.