S2k guidelines on diagnosis and treatment of linear IgA dermatosis initiated by the European Academy of Dermatology and Venereology.

INTRODUCTION: Linear IgA dermatosis (LAD) is a rare subepidermal autoimmune bullous disease (AIBD) defined by predominant or exclusive immune deposits of immunoglobulin A at the basement membrane zone of skin or mucous membranes. This disorder is a rare, clinically and immunologically heterogeneous disease occurring both in children and in adults. The aim of this project is to present the main clinical features of LAD, to propose a diagnostic algorithm and provide management guidelines based primarily on experts' opinion because of the lack of large methodologically sound clinical studies. METHODS: These guidelines were initiated by the European Academy of Dermatology and Venereology (EADV) Task Force Autoimmune Bullous Diseases (AIBD). To achieve a broad consensus for these S2k consensus-based guidelines, a total of 29 experts from different countries, both European and non-European, including dermatologists, paediatric dermatologists and paediatricians were invited. All members of the guidelines committee agreed to develop consensus-based (S2k) guidelines. Prior to a first virtual consensus meeting, each of the invited authors elaborated a section of the present guidelines focusing on a selected topic, based on the relevant literature. All drafts were circulated among members of the writing group, and recommendations were discussed and voted during two hybrid consensus meetings. RESULTS: The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD. CONCLUSION: These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD.

Infectious Disease Screening Prior to Systemic Immunomodulatory Therapy in Hidradenitis Suppurativa: Consensus Guidelines from the Asia-Pacific Hidradenitis Suppurativa Foundation.

BACKGROUND: Current infectious disease screening recommendations for hidradenitis suppurativa (HS) are adopted from recommendations in chronic plaque psoriasis. No HS-specific guidelines for infectious disease screening prior to immunomodulatory therapy have been developed. OBJECTIVES: To establish an expert Delphi consensus of recommendations regarding infectious disease screening prior to systemic immunomodulatory therapy in HS. METHODS: Participants were identified via recent publications in the field and were sent a questionnaire regarding infectious diseases encountered in the setting of HS, and opinions regarding infectious disease screening prior to various systemic immunomodulatory therapies. All questions were informed by a systematic literature review regarding infections exacerbated or precipitated by immunomodulatory therapy. Questionnaire responses were followed by round-table discussion with a core group of 8 experts followed by a final round of questionnaires resulting in achievement of consensus. RESULTS: 44 expert HS physicians from 12 countries on 5 continents participated in the development of the expert consensus recommendations. Consensus recommendations include screening for hepatitis B, hepatitis C and tuberculosis in all individuals with HS prior to therapy. All immunomodulatory therapies (biologic and systemic immunosuppressant therapy) should be preceded by infectious disease screening including patient and location specific considerations for endemic local diseases and high-risk activities and occupations. Clinical assessment has a significant role in determining the need for laboratory screening in the setting of many uncommon or tropical diseases such as leprosy, leishmaniasis and strongyloidiasis. CONCLUSIONS: The presented consensus recommendations are the first specifically developed for pre-treatment infectious disease screening in Hidradenitis Suppurativa.

Teledermatology in an emergency department: benefits and gaps.

BACKGROUND: Teledermatology has provided new avenues through which dermatologists can provide healthcare. Teledermatology was introduced to the Emergency Department (ED) to enable immediate dermatological consult. We aimed to assess the impact of teledermatology on the management of dermatological conditions by emergency medicine physicians and subsequent health resource utilization. METHODS: We conducted a retrospective review of teledermatology referrals from the ED of our tertiary hospital in Singapore from June 2015 to December 2019. The dermatological conditions, the triaging and treatment recommendations were analyzed. Follow-up plans were recorded. RESULTS: Between June 2015 and December 2019, 147 patients were referred from the ED via teledermatology; 11 (7.5%) were admitted, and 136 (92.5%) were recommended to be discharged with a dermatological diagnosis and management plan. If required, a follow-up appointment in the dermatology specialist clinic was arranged. Of the 136 patients who were discharged, 129 (94.9%) patients were provided with outpatient appointment in the dermatology clinic, out of which 110 patients returned for follow-up. 90 (81.8%) patients retained the initial teledermatology diagnoses and 20 (18.2%) patients had their teledermatology diagnoses revised after in-person review. CONCLUSIONS: Teledermatology allows for more efficient triaging of patients with dermatological conditions. Reliability between teledermatology and clinic-based examination is good. Patients may be managed mainly in the outpatient setting with appropriate specialty-directed treatment, return advice, and appropriately-triaged follow-up outpatient appointment.

Dermatologists' Perceptions of the Use of Teledermatology in Managing Hidradenitis Suppurativa: Survey Study.

BACKGROUND: The field of teledermatology has expanded tremendously and has been used for conditions including hidradenitis suppurativa (HS). However, due to the sensitive location of lesions, HS may be considered less suitable for teledermatology. OBJECTIVE: We sought to assess dermatologists' experiences and perceptions toward using teledermatology for HS relative to atopic dermatitis (AD) as a comparison. METHODS: A survey was disseminated electronically to practicing dermatologists in the Asia-Pacific region between February and June 2022. Differences in attitudes and perceptions between HS and AD were compared using random-effects ordered logistic regression, controlling for demographics. RESULTS: A total of 100 responses were obtained comprising of 76 (81.7%) dermatologists and 17 (18.3%) dermatology trainees; 62.6% (62/98) of physicians were uncomfortable with using teledermatology for HS. Multivariable regression confirmed increased perceived challenges with managing HS using teledermatology compared to AD. These challenges include the need for photography of hard-to-reach or sensitive areas (odds ratio [OR] 4.71, 95% CI 2.44-9.07; P<.001), difficulties in accurate assessment of severity (OR 2.66, 95%CI 1.48-4.79; P=.001), and inability to palpate lesions (OR 2.27, 95% CI 1.23-4.18; P=.009). CONCLUSIONS: This study confirms the relative reluctance of dermatologists to use teledermatology for HS and complements existing data showing mixed levels of willingness from patients. The use of teledermatology for HS may need to be optimized to overcome these challenges, including increasing security features, selection of patients with milder or limited diseases, and selecting patients with an established and strong doctor-patient relationship.

Understanding Discordant Perceptions of Disease Severity Between Physicians and Patients With Eczema and Psoriasis Using Structural Equation Modeling.

Importance: Patients and physicians often have differing opinions on the patient's disease severity. This phenomenon, termed discordant severity grading (DSG), hinders the patient-physician relationship and is a source of frustration. Objective: To test and validate a model explaining the cognitive, behavioral, and disease factors associated with DSG. Design, Setting, and Participants: A qualitative study was first performed to derive a theoretical model. In this subsequent prospective cross-sectional quantitative study, the qualitatively derived theoretical model was validated using structural equation modeling (SEM). Recruitment was conducted between October 2021 and September 2022. This was a multicenter study in 3 Singapore outpatient tertiary dermatological centers. Dermatology patients and their attending physicians were recruited by convenience sampling. Patients were aged 18 to 99 years with psoriasis or eczema of at least 3 months' duration and recruited only once. The data were analyzed between October 2022 to May 2023. Main Outcomes and Measures: The outcome was the difference between global disease severity (0-10 numerical rating scale with a higher score indicating greater severity) as independently scored by the patient and the dermatologist. Positive discordance was defined as patient-graded severity more than 2 points higher (graded more severely) than physicians, and negative discordance if more than 2 points lower than physicians. Confirmatory factor analysis followed by SEM was used to assess the associations between preidentified patient, physician, and disease factors with the difference in severity grading. Results: Of the 1053 patients (mean [SD] age, 43.5 [17.5] years), a total of 579 (55.0%) patients were male, 802 (76.2%) had eczema, and 251 (23.8%) had psoriasis. Of 44 physicians recruited, 20 (45.5%) were male, 24 (54.5%) were aged between 31 and 40 years, 20 were senior residents or fellows, and 14 were consultants or attending physicians. The median (IQR) number of patients recruited per physician was 5 (2-18) patients. Of 1053 patient-physician pairs, 487 pairs (46.3%) demonstrated discordance (positive, 447 [42.4%]; negative, 40 [3.8%]). Agreement between patient and physician rating was poor (intraclass correlation, 0.27). The SEM analyses showed that positive discordance was associated with higher symptom expression (standardized coefficient B = 0.12; P = .02) and greater quality-of-life impairment (B = 0.31; P < .001), but not patient or physician demographics. A higher quality-of-life impairment was in turn associated with lower resilience and stability (B = -0.23; P < .001), increased negative social comparisons (B = 0.45; P < .001), lower self-efficacy (B = -0.11; P = .02), increased disease cyclicity (B = 0.47; P < .001), and greater expectation of chronicity (B = 0.18; P < .001). The model was well-fitted (Tucker-Lewis: 0.94; Root Mean Square Error of Approximation: 0.034). Conclusions and Relevance: This cross-sectional study identified various modifiable contributory factors to DSG, increased understanding of the phenomenon, and set a framework for targeted interventions to bridge this discordance.

Knowledge, attitudes, and perceptions of hidradenitis suppurativa among young adults in Singapore.

Background: The prevalence of hidradenitis suppurativa (HS) is 0.00033% to 4.10% globally. Few epidemiological studies derive from Asia, with social stigmatization postulated to result in under-diagnosis. Objective: This study aimed to assess the self-reported prevalence of HS, and the knowledge, attitudes, and perceptions towards HS among Singaporean young-adults. Methods: A cross-sectional study (n = 158) was conducted by anonymous online questionnaire. The association between demographic factors and risk of potentially undiagnosed HS was evaluated using multivariable logistic regression. Differences between attitude-perception scores by demographic factors and knowledge of HS were tested using two-sample t-tests. Results: The prevalence of diagnosed and potentially undiagnosed HS was 0.63% and 8.9%, respectively. Non-Chinese had significantly higher social attitude-perception scores than Chinese (P = .029). Females had significantly higher social (P = .048) as well as economic and work (P = .037) attitude-perception scores than males. Those with knowledge of HS had significantly higher attitude-perception scores for interpersonal (P = .031) and social (P = .0052) subsections. Limitations: Small sample size, low frequency of HS cases, and self-reported prevalence may not generalize to the broader population in Singapore. Conclusion: Our results suggest a potential underdiagnosis of HS. Non-Chinese stigmatize HS less than Chinese, and females less than males. Individuals with knowledge of HS might be more open to interpersonal and social interactions with HS sufferers.

S2k guidelines on the management of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.

Malignancy-associated generalised exfoliative dermatitis: A retrospective study in a single-centre Asian cohort.

BACKGROUND: Erythroderma is an inflammatory skin condition that causes extensive erythema and skin scaling amounting ≥90% of the body surface area. This retrospective cohort study describes the prevalence of malignancy-associated erythroderma in a single centre where there was concerted effort to systematically offer malignancy screens to all adult erythroderma patients above the age of 65 years. METHODS: Clinical charts were reviewed for all adult inpatients and outpatients with erythroderma who attended the National University Hospital (NUH) from 1 July 2019 to 31 December 2021. Data collected included patient demographics, clinical findings, laboratory investigations, disease-specific investigations such as endoscopic procedures and biopsies, follow-up duration and mortality data. RESULTS: Seventy-four patients were analysed. The median age of the patients was 73 years old (interquartile range: 59-81 years old). An underlying dermatosis was the most common cause of erythroderma-63 patients having atopic dermatitis/asteatotic eczema or psoriasis. Three patients had erythroderma from drug eruptions, and 1 patient had chronic actinic dermatitis. Four patients had associated malignancies (5.4%). Half of our patients completed further evaluation for malignancy (52.7%). The rest had either declined or were eventually unable to complete the investigations. There was a higher prevalence of associated malignancy (7.8%) in elderly patients above 65 years old. CONCLUSION: When compared to existing literature, our cohort reflects a higher observed occurrence of malignancy in association with erythroderma. As delays in evaluation for underlying malignancy could result in potentially deleterious outcomes, it is prudent to consider systematic screening for malignancy in high-risk populations such as elderly erythroderma patients.

Case Report of a Novel Association between Anti-p200 Pemphigoid and Acquired Haemophilia A.

Anti-p200 pemphigoid is an uncommon subepidermal autoimmune bullous disease that, unlike many other autoimmune bullous diseases, has not previously been associated with hematological diseases. The diagnosis of anti-p200 pemphigoid in a patient with congruent clinical features requires the demonstration of subepidermal blistering, with linear deposition of immunoglobulin (Ig) G and/or C3 at the dermoepidermal junction on direct immunofluorescence, and a floor-binding pattern on indirect immunofluorescence. In addition, the detection of antibodies against p200 antigen via immunoblotting is ideal but not readily accessible in many facilities, leading to a potential under-recognition and under-diagnosis of this condition. In this case report, we describe a 53-year-old gentleman with recently diagnosed acquired hemophilia A who developed a concurrent vesiculobullous eruption and was evaluated to have anti-p200 pemphigoid. Both of his conditions were controlled with immunosuppression via prednisolone and cyclophosphamide. While we acknowledge the contemporaneous occurrence of both diseases in this patient may be a mere coincidence, it is important to recognize the possibility of this association given the potential clinical significance. Whether the activity of one disease parallels the other will require further evaluation.

The psychosocial burden of hidradenitis suppurativa in Singapore.

Background: Hidradenitis suppurativa (HS) is a chronic debilitating inflammatory skin disorder known to result in significant psychological symptoms and impaired quality of life. However, most of these studies are limited to western countries, with limited data from other sociocultural regions. Objective: To understand the psychosocial burden of HS in the Asian context, by exploring the correlation between objective disease measures with psychosocial health and work productivity. Methods: A prospective single-center questionnaire study was conducted. A total of 45 patients with HS completed a questionnaire and examination by a dermatologist. Results: Higher objective disease severity scores (Hurley, physician global assessment, International Hidradenitis Suppurative Severity, and modified Sartorius) correlated with poorer quality of life (Dermatology Life Quality Index and Patient Global Assessment), increased anxiety and depression (hospital anxiety and depression scale) and at-work productivity loss. There was no significant correlation between objective disease severity and other domains Work productivity and activity impairment score or self-esteem (Rosenburg Self-Esteem Scale). Limitations: The main limitation of our study is the small sample size, assessment at a single time point, and lack of control cohort. Conclusion: Our findings demonstrate the impact of HS on a patient's psychosocial well-being and emphasize the importance of treating patients from a holistic standpoint.

Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus-2 infection: a systematic review.

Introduction: We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity. Methods: We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded. Results: 169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum. Conclusion: Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.

Understanding the systemic burden of disease in hidradenitis suppurativa from plasma lipidomic analysis.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin condition that is often considered a systemic disease due to its association with metabolic comorbidity. OBJECTIVE: In this study, we aimed to identify differences in plasma lipidomic profiles between HS patients and control subjects. METHODS: HS patients were recruited from a tertiary dermatological centre and demographic and comorbidity matched controls from the general population. A targeted lipidomic approach was performed to characterize over 700 lipid species representing 35 lipid classes/sub-classes. Linear regression models adjusted for confounding factors were used to compare the plasma lipidomic profiles of HS patients to controls. Ordinal regression models were used to study the association of lipids with disease activity and severity scores. RESULTS: 60 HS patients and 73 control subjects were recruited. Differential levels (p < 0.05) of 32 lipid species in HS patients compared to controls were observed, including a decrease in the long chain base d19:1 containing ceramides, and elevation of hydroxyeicosatetraenoic acid (HETE) and dihydroxyeicosatrienoic acid (DHET) oxylipins. These lipids along with several other molecules showed associations with Hurley, HS-PGA and disease activity scores. CONCLUSION: This study found mild changes in plasma lipidomic profiles, consistent with previous studies showing attenuated metabolomic changes in plasma as opposed to lesional skin. However, a number of lipid species were associated with increasing activity and severity of the disease. Further, the significant lipid species within the same class showed consistent trends of increase or decrease in HS as compared to controls.