International Consensus Definition and Diagnostic Criteria for Generalized Pustular Psoriasis From the International Psoriasis Council.

Importance: Generalized pustular psoriasis (GPP) lacks internationally accepted definitions and diagnostic criteria, impeding timely diagnosis and treatment and hindering cross-regional clinical and epidemiological study comparisons. Objective: To develop an international consensus definition and diagnostic criteria for GPP using the modified Delphi method. Evidence Review: The rarity of GPP presents a challenge in acquiring comprehensive published clinical data necessary for developing standardized definition and criteria. Instead of relying on a literature search, 43 statements that comprehensively addressed the fundamental aspects of the definitions and diagnostic criteria for GPP were formulated based on expert reviews of 64 challenging GPP cases. These statements were presented to a panel of 33 global GPP experts for voting, discussion, and refinements in 2 virtual consensus meetings. Consensus during voting was defined as at least 80% agreement; the definition and diagnostic criteria were accepted by all panelists after voting and in-depth discussion. Findings: In the first and second modified Delphi round, 30 (91%) and 25 (76%) experts participated. In the initial Delphi round, consensus was achieved for 53% of the statements, leading to the approval of 23 statements that were utilized to develop the proposed definitions and diagnostic criteria for GPP. During the second Delphi round, the final definition established was, "Generalized Pustular Psoriasis is a systemic inflammatory disease characterized by cutaneous erythema and macroscopically visible sterile pustules." It can occur with or without systemic symptoms, other psoriasis types, and laboratory abnormalities. GPP may manifest as an acute form with widespread pustules or a subacute variant with an annular phenotype. The identified essential criterion was, "Macroscopically visible sterile pustules on erythematous base and not restricted to the acral region or within psoriatic plaques." Conclusions and Relevance: The achievement of international consensus on the definition and diagnostic criteria for GPP underscores the importance of collaboration, innovative methodology, and expert engagement to address rare diseases. Although further validation is needed, these criteria can serve as a reference point for clinicians, researchers, and patients, which may contribute to more accurate diagnosis and improved management of GPP.

A biomechanical assessment of tissue-engineered polymer neo-uteri after orthotopic implantation.

OBJECTIVE: To assess the in vivo biomechanical maturation of tissue-engineered neo-uteri that have previously supported live births in a rabbit model. DESIGN: Nonclinical animal study. SETTING: University-based research laboratory. ANIMALS: Eighteen adult female rabbits. INTERVENTION: Biodegradable poly-DL-lactide-co-glycolide-coated polyglycolic acid scaffolds seeded with autologous uterine-derived endometrial and myometrial cells. Nonseeded scaffolds and seeded, tissue-engineered neo-uteri were implanted into one uterine horn of rabbits for 1, 3, or 6 months, excised, and biomechanically assessed in comparison to native uterine tissue. MAIN OUTCOME MEASURES: Tensile stress-relaxation testing, strain-to-failure testing, and viscoelastic modeling. RESULTS: By evaluating the biomechanical data with several viscoelastic models, it was revealed that tissue-engineered uteri were more mechanically robust than nonseeded scaffolds. For example, the 10% instantaneous stress of the tissue-engineered neo-uteri was 2.1 times higher than the nonseeded scaffolds at the 1-month time point, 1.6 times higher at the 3-month time point, and 1.5 times higher at the 6-month time point. Additionally, as the duration of implantation increased, the engineered constructs became more mechanically robust (e.g., 10% instantaneous stress of the tissue-engineered neo-uteri increased from 22 kPa at 1 month to 42 kPa at 6 months). Compared with native tissue values, tissue-engineered neo-uteri achieved or surpassed native tissue values by the 6-month time point. CONCLUSION: The present study evaluated the mechanical characteristics of novel tissue-engineered neo-uteri that have previously been reported to support live births in the rabbit model. We demonstrate that the biomechanics of these implants closely resemble those of native tissue, giving further credence to their development as a clinical solution to uterine factor infertility.

Manually prepared lamellae for Descemet stripping endothelial keratoplasty (Pachy-DSEK): comparison of four dissection depths / Lamelas manualmente dissecadas para transplante endotelial de córnea (Pachy-DSEK): comparação entre quatro profundidades de dissecção

ABSTRACT Purpose: This study aimed to compare four depths of manual dissection for the preparation of Descemet stripping endothelial keratoplasty lamellae. Methods: Eye bank corneas were randomized into four groups according to dissection depths: Pachy-100 (incision depth = central corneal thickness-safety margin of 100 µm), Pachy-50 (safety margin of 50 µm), Pachy-0 (no safety margin), and Pachy+50 (incision depth = central corneal thickness + 50 µm). All endothelial lamellae were prepared using a standardized method of manual dissection (Pachy-DSEK). The central, paracentral (3.0-mm zone), and peripheral (6.0-mm zone) lamella thicknesses and incision depths were measured by optical coherence tomography. The 3.0-mm and 6.0-mm zone central-to-peripheral thickness ratios were calculated. Results: Endothelial perforation occurred only in the Pachy+50 group (n=3, 30%). Central lamella's thickness in Pachy-100, Pachy-50, Pachy-0, and Pachy+50 groups measured 185 ± 42 µm, 122 ± 29 µm, 114 ± 29 µm, and 58 ± 31 µm, respectively (p<0.001). The overall 3.0- and 6.0-mm C/P ratios were 0.97 ± 0.06 and 0.92 ± 0.14, respectively. Preoperative donor characteristics were not correlated with most thickness outcomes. The planned incision depth correlated significantly with most lamella's thickness parameters (p<0.001). The overall thickness of the lamella negatively correlated with the planned incision depth (p<0.001, r=-0.580). The best outcome was found in the Pachy-0 group, as 75% of the lamellae measured <130 µm and there was no endothelial perforation. Conclusions: By using a standardized method of dissection, most manually prepared lamellae presented a planar shape. Setting the incision depth to the central corneal thickness did not result in endothelial perforation and a high percentage of ultrathin lamellae was achieved.

RESUMO Objetivo: Comparar quatro profundidades de dissecção manual usadas no preparo de lamelas para transplante endotelial. Métodos: Córneas humanas de treinamento disponibilizadas foram randomizadas em quatro grupos: Pachy-100 (profundidade de incisão = espessura corneana central - margem de segurança de 100 µm), Pachy-50 (margem de segurança de 50 µm), Pachy-0 (sem margem de segurança) e Pachy+50 (profundidade de incisão = espessura corneana central + 50 µm). Todas as lamelas foram dissecadas através um método padronizado e já publicado (Pachy-DSEK). As espessuras das lamelas (centro, zona de 3,0mm e zona de 6,0mm) foram medidas com tomografia de coerência óptica. A razão de espessura centro-periferia foi calculada aos 3,0 e 6,0 mm de diâmetro. Resultados: Perfuração endotelial ocorreu apenas no grupo Pachy+50 (n=3, 30%). A espessura central da lamela nos grupos Pachy-100, Pachy-50, Pachy-0 e Pachy+50 foi de 185 ± 42 µm, 122 ± 29 µm, 114 ± 29 µm, e 58 ± 31 µm, respectivamente (p<0,001). As razões C/P aos 3,0 e 6,0 mm foram de 0,97 ± 0,06 e 0,92 ± 0,14, respectivamente. Os parâmetros de características do doador não se correlacionaram com os resultados de espessura de lamela. A profundidade planejada de incisão se correlacionou com a maioria dos parâmetros de espessura de lamela (p<0,001). A espessura de lamela se correlacionou negativamente com a profundidade planejada da incisão (p<0.001, r=-0,580). O melhor resultado foi observado no grupo Pachy-0, em que 75% das lamelas mediram abaixo de 130 µm e não houve perfuração endotelial. Conclusão: Através de um método padronizado de dissecção, a maioria das lamelas endoteliais apresentou uma configuração planar. O planejamento de profundidade de incisão igual à espessura corneana central resultou em alta porcentagem de lamelas ultrafinas sem ocorrência de perfuração.

Cumulative life course impairment in patients with dermatological diseases, with a focus on psoriasis.

The concept of "Cumulative Life Course Impairment" (CLCI) characterizes the set of factors harmful to the lives of patients resulting from the stigma and physical and psychological impairment associated with different chronic diseases, which can accumulate irreversibly over the course of patients lives. The sum of these factors often makes it impossible for these individuals to enjoy their lives fully, intensely and adequately. On the other hand, CLCI also incorporates coping strategies, including external factors and personality characteristics, which may act as modulating or protective factors of vulnerability to the CLCI. Although psoriasis is the most studied dermatological disease in relation to its impact on quality of life and CLCI, several other chronic inflammatory diseases such as atopic dermatitis, hidradenitis suppurativa, and alopecia areata have also been evaluated in relation to the magnitude of the damage to patients lives.

Navigating the Multidimensional Impact of Living with Hidradenitis Suppurativa: An In-Depth Netnographic Study on Social Media Platforms.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic skin condition causing considerable distress. It impacts mobility, social interaction, and quality of life. In Brazil, there is a notable gap in epidemiological data and patient experiences regarding HS. METHODS: This study, spanning 2019 to 2022, employed netnography to probe the experiences of Brazilian patients with HS. This approach gleans insights from online interactions, offering a direct view into patients' lives. RESULTS: Notably, the data illuminated the challenges patients face, such as difficulties in obtaining a diagnosis and the complexities involved in managing a chronic, and often debilitating, condition. Furthermore, patients' experiences with various treatments, encompassing antibiotics, biologic agents, lifestyle alterations, surgical procedures, and alternative remedies, were also examined. CONCLUSION: By undertaking a longitudinal analysis of patient interactions, the study aimed to offer a richer understanding of HS, from its diagnosis to its treatment. It underscores the necessity for a more patient-centered approach when managing this condition. We hope that this enhanced understanding can facilitate better care for those affected by HS.

Requirements for Brazilian Outpatient Centers of Excellence in Hidradenitis Suppurativa: Consensus Co-Creative Study.

Background: Hidradenitis suppurativa (HS) is a chronic skin condition. Its complexity and impact on patients highlight the need for multidisciplinary care that can address the physical, psychological, and social aspects. Centers of excellence can ideally provide the necessary infrastructure, resources, and expertise to effectively treat HS. However, there are still no consolidated models of centers of excellence in HS, and establishing their foundations is an intricate research challenge. Purposely, design and co-creation as innovation techniques are helpful approaches to this type of research. Methods: In this study, we conducted a co-creation with consensus among HS specialists to propose the criteria and requirements to establish outpatient centers of excellence of HS in Brazil. We followed a linear process with mixed methods in 6 stages. Results: The process resulted in 10 categories for establishing outpatient centers, including their respective requirements, rationale, and classification. The categories include onboarding and welcoming; infrastructure and procedures; infusion therapy; flows and referrals; staffing; disease management; metrics during diagnosis; metrics during treatment; awareness and advocacy; research and education. Discussion: The idealized outpatient centers can play a role in the complete multidisciplinary treatment for HS and advancing the science of healthcare services by providing a focus for research, training, and translation of findings into practice.

Mohs micrographic surgery in rare cutaneous tumors: a retrospective study at a Brazilian tertiary university hospital

Abstract Background Mohs micrographic surgery is an established technique in the treatment of cutaneous neoplasms. It offers higher cure rates and the main indications are non-melanoma malignant skin tumors. Few studies have been performed on the treatment of rare tumors through this technique. Objective To study rare skin tumors and rare variants of basal cell carcinoma and squamous cell carcinoma submitted to Mohs micrographic surgery in a tertiary service in relation to frequency, disease-free evolution, and applicability of this surgical procedure for this group of tumors. Methods This was a retrospective observational study including rare skin tumors and less common variants of basal cell carcinoma and squamous cell carcinoma treated using Mohs micrographic surgery, between October 2008 and April 2021. Results During the study period, 437 tumors were treated using Mohs micrographic surgery, and 22 (5%) rare skin tumors were selected. The tumors comprised three dermatofibrosarcomas protuberans, two atypical fibroxanthomas, two spiradenomas, two hypercellular fibrohistiocytomas, one primary cutaneous adenocarcinoma, one trichoblastoma, one porocarcinoma, one chondroid syringoma, one cutaneous angiosarcoma, one Merkel cell carcinoma, and one sebaceous carcinoma. Six other cases of rare basal cell carcinoma variants with trichoepitheliomatous differentiation, metatypical basal cell carcinoma, and clear cell squamous cell carcinoma were included. There were no cases of recurrence after an average of six years of follow-up. Study limitations This is a retrospective study on rare neoplasms carried out in a single referral center, and this surgical technique isn't widely available in the public service. Conclusion This retrospective case series showed that Mohs micrographic surgery is an appropriate treatment for rare skin tumors. They corresponded to 5% of the tumors treated by the technique during a 12-year-period, with no recurrences identified.

Mohs micrographic surgery in rare cutaneous tumors: a retrospective study at a Brazilian tertiary university hospital.

BACKGROUND: Mohs micrographic surgery is an established technique in the treatment of cutaneous neoplasms. It offers higher cure rates and the main indications are non-melanoma malignant skin tumors. Few studies have been performed on the treatment of rare tumors through this technique. OBJECTIVE: To study rare skin tumors and rare variants of basal cell carcinoma and squamous cell carcinoma submitted to Mohs micrographic surgery in a tertiary service in relation to frequency, disease-free evolution, and applicability of this surgical procedure for this group of tumors. METHODS: This was a retrospective observational study including rare skin tumors and less common variants of basal cell carcinoma and squamous cell carcinoma treated using Mohs micrographic surgery, between October 2008 and April 2021. RESULTS: During the study period, 437 tumors were treated using Mohs micrographic surgery, and 22 (5%) rare skin tumors were selected. The tumors comprised three dermatofibrosarcomas protuberans, two atypical fibroxanthomas, two spiradenomas, two hypercellular fibrohistiocytomas, one primary cutaneous adenocarcinoma, one trichoblastoma, one porocarcinoma, one chondroid syringoma, one cutaneous angiosarcoma, one Merkel cell carcinoma, and one sebaceous carcinoma. Six other cases of rare basal cell carcinoma variants with trichoepitheliomatous differentiation, metatypical basal cell carcinoma, and clear cell squamous cell carcinoma were included. There were no cases of recurrence after an average of six years of follow-up. STUDY LIMITATIONS: This is a retrospective study on rare neoplasms carried out in a single referral center, and this surgical technique isn't widely available in the public service. CONCLUSION: This retrospective case series showed that Mohs micrographic surgery is an appropriate treatment for rare skin tumors. They corresponded to 5% of the tumors treated by the technique during a 12-year-period, with no recurrences identified.

Manually prepared lamellae for Descemet stripping endothelial keratoplasty (Pachy-DSEK): comparison of four dissection depths.

PURPOSE: This study aimed to compare four depths of manual dissection for the preparation of Descemet stripping endothelial keratoplasty lamellae. METHODS: Eye bank corneas were randomized into four groups according to dissection depths: Pachy-100 (incision depth = central corneal thickness-safety margin of 100 µm), Pachy-50 (safety margin of 50 µm), Pachy-0 (no safety margin), and Pachy+50 (incision depth = central corneal thickness + 50 µm). All endothelial lamellae were prepared using a standardized method of manual dissection (Pachy-DSEK). The central, paracentral (3.0-mm zone), and peripheral (6.0-mm zone) lamella thicknesses and incision depths were measured by optical coherence tomography. The 3.0-mm and 6.0-mm zone central-to-peripheral thickness ratios were calculated. RESULTS: Endothelial perforation occurred only in the Pachy+50 group (n=3, 30%). Central lamella's thickness in Pachy-100, Pachy-50, Pachy-0, and Pachy+50 groups measured 185 ± 42 µm, 122 ± 29 µm, 114 ± 29 µm, and 58 ± 31 µm, respectively (p<0.001). The overall 3.0- and 6.0-mm C/P ratios were 0.97 ± 0.06 and 0.92 ± 0.14, respectively. Preoperative donor characteristics were not correlated with most thickness outcomes. The planned incision depth correlated significantly with most lamella's thickness parameters (p<0.001). The overall thickness of the lamella negatively correlated with the planned incision depth (p<0.001, r=-0.580). The best outcome was found in the Pachy-0 group, as 75% of the lamellae measured <130 µm and there was no endothelial perforation. CONCLUSIONS: By using a standardized method of dissection, most manually prepared lamellae presented a planar shape. Setting the incision depth to the central corneal thickness did not result in endothelial perforation and a high percentage of ultrathin lamellae was achieved.

Clinical Specialty Setting as Determinant of Management of Psoriatic Arthritis: A Cross-Sectional Brazilian Study.

OBJECTIVE: The aim of this study was to examine the effect of clinical specialty setting on the management of psoriatic arthritis (PsA) as well as disease activity/burden in Brazil. METHODS: This study is a post hoc analysis of the Brazilian population in a cross-sectional, observational study conducted in 17 countries. Patients were 18 years or older with suspected or confirmed PsA attending routine visits at participating sites. Primary end points were time from symptom onset to PsA diagnosis, from diagnosis to first conventional systemic disease-modifying antirheumatic drug (DMARD) or first biologic DMARD, and from first conventional systemic DMARD to first biologic DMARD. Potential associations were assessed using the Student t test or the Mann-Whitney U nonparametric test. Normality was tested using the Shapiro-Wilk and Kolmogorov-Smirnov tests. For qualitative variables, the χ2 test was adopted. RESULTS: Patients (n = 130) visited dermatology (n = 75) or rheumatology (n = 55) sites. All primary end points were similar between the 2 settings; however, dermatology patients had significantly greater enthesitis counts (2.1 vs 0.6; p = 0.002), absenteeism at work (Work Productivity and Activity Impairment, 19.7% vs 5.2%; p = 0.03), and pain (Health Assessment Questionnaire-Disability Index pain scale, 1.39 vs 1.01; p = 0.032), as well as worse quality of life related to psoriasis (Dermatology Life Quality Index total score, 8.5 vs 5.0; p = 0.019) and mental health (12-item Short-Form Health Survey, version 2.0 subscale, 42.4 vs 47.4; p = 0.029). CONCLUSIONS: In Brazil, PsA disease burden and disease activity were influenced by clinical specialty. Irrespective of setting, patients experienced a delay in being diagnosed with PsA, reinforcing the need for collaborative management of PsA by rheumatologists and dermatologists for better outcomes in these patients.

Immunophenotypic profile of macrophages in generalized pustular psoriasis and deficiency of the interleukin-36 receptor antagonist.

M2 macrophages are copious in generalized pustular psoriasis (GPP). M2 macrophages seem to acquire new skills and share common characteristics in GPP. HAM56 may play a role in attracting immature neutrophils to the inflammatory environment in GPP.

Immunobiologicals in dermatology.

Immunobiologicals are a reality in current clinical practice and have increasingly gained space in the inflammatory disease scenario, especially in dermatology, with approved drugs for psoriasis, atopic dermatitis, and hidradenitis suppurativa, in addition to many others undergoing study. It is important for dermatologists to have knowledge of the medications approved in Brazil, for the best management of dermatoses, in addition to the fact that they represent hope for improvement in patients with chronic diseases.

Therapies for hidradenitis suppurativa: a systematic review with a focus on Brazil.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a significant negative impact on the quality of life of patients. METHODS: We conducted a systematic review to assess current treatment for HS, with a special focus on therapies approved or used in Brazil. We used the PICO framework to improve the research process. The systematic review was reported in line with the PRISMA statement checklist. The search was conducted with clinical questions on two global databases (PubMed (MEDLINE) and Google Scholar) and three databases especially selected to retrieve Brazilian outcomes (BVS, SCIELO and REDALYC). RESULTS: Overall, 4640 articles were screened, 182 articles were analysed and 70 were used in a thematic qualitative analysis. Of these, 12 articles were from Brazil. The evidence-based literature was largely limited to case reports, case series, observational studies and expert opinion. Topical therapy, lifestyle interventions and oral antibiotics appeared as effective measures for mild HS. However, moderate-to-severe HS remains refractory to conventional treatments. CONCLUSION: Some biologic agents, such as adalimumab, infliximab, ustekinumab and secukinumab, have been shown to be effective in the management of moderate-to-severe HS that failed conventional treatment and demonstrated a good tolerability and safety profile.

Generalized pustular psoriasis (von Zumbusch)

Abstract Generalized pustular psoriasis (von Zumbusch) is a rare and acute eruption characterized by multiple sterile pustules over an erythematous and edematous background, eventually associated with psoriasis vulgaris. Classically, it manifests as a potentially severe systemic picture and demands prompt diagnosis and intervention. The duration of each flare-up and intervals between the pustular episodes is extremely variable. Recently, genetic abnormalities have been identified mainly in the familial and early variants of this disease. The therapeutic arsenal is limited; however, new drugs being evaluated aim to control both pustular flare-ups and disease recurrences.

Intrastromal corneal ring segments followed by PRK for postkeratoplasty high astigmatism: prospective study.

PURPOSE: To evaluate refractive and topographic results of the association of intrastromal corneal ring segments (ICRS) with photorefractive keratectomy (PRK) for the correction of high (>6.0 diopters [D]) postkeratoplasty astigmatism (PKA). SETTING: University of São Paulo, São Paulo, Brazil. DESIGN: Prospective interventional study. METHODS: Postpenetrating keratoplasty patients, intolerant to contact lens fitting, and with corneal astigmatism higher than 6.0 D were treated by the combination of ICRS and PRK from January 2017 to June 2019. First, patients underwent femtosecond laser-assisted ICRS implantation to reduce and regularize corneal astigmatism, and 3 months later, submitted to PRK for the residual astigmatism. Outcomes were obtained 12 months after PRK. RESULTS: The study comprised 30 eyes of 29 patients. Mean uncorrected distance visual acuity (logMAR) changed from 1.16 ± 0.37 in the preoperative to 0.69 ± 0.40 after ICRS ( P < .0001) and to 0.34 ± 0.29 12 months after PRK ( P < .0001). Mean spherical equivalent decreased from -5.19 ± 4.81 D in the preoperative to -3.38 ± 4.51 D after ICRS ( P < .0001) and to -2.30 ± 2.84 D after PRK ( P = .132). Mean topographic astigmatism decreased from 7.88 ± 2.13 D in the preoperative to 5.47 ± 2.29 D after ICRS ( P < .0001) and to 4.12 ± 2.93 D after PRK ( P = .003). Mean refractive astigmatism decreased from 7.10 ± 1.13 D in the preoperative to 4.61 ± 1.61 D after ICRS ( P < .0001) and to 2.58 ± 1.49 D after PRK ( P < .0001). After PRK, the mean correction index (CI) for corneal astigmatism was 0.77 ± 0.36. The ICRS/PRK combination resulted in a higher CI than ICRS only, both for corneal and refractive astigmatism. 2 eyes (8%) presented clinically significant opacification. Other complications were endothelial rejection (n = 1, 4%), infectious keratitis (n = 1, 4%), and ICRS extrusion after corneal melting (n = 1, 4%). CONCLUSIONS: The association of ICRS and PRK was effective for treating high PKA. This strategy improved visual acuity, spherical equivalent, topographic and refractive astigmatism and resulted in a high CI. Safety questions remain open and must be balanced against benefits.

Generalized pustular psoriasis (von Zumbusch).

Generalized pustular psoriasis (von Zumbusch) is a rare and acute eruption characterized by multiple sterile pustules over an erythematous and edematous background, eventually associated with psoriasis vulgaris. Classically, it manifests as a potentially severe systemic picture and demands prompt diagnosis and intervention. The duration of each flare-up and intervals between the pustular episodes is extremely variable. Recently, genetic abnormalities have been identified mainly in the familial and early variants of this disease. The therapeutic arsenal is limited; however, new drugs being evaluated aim to control both pustular flare-ups and disease recurrences.

Immunobiologicals in dermatology

Abstract Immunobiologicals are a reality in current clinical practice and have increasingly gained space in the inflammatory disease scenario, especially in dermatology, with approved drugs for psoriasis, atopic dermatitis, and hidradenitis suppurativa, in addition to many others undergoing study. It is important for dermatologists to have knowledge of the medications approved in Brazil, for the best management of dermatoses, in addition to the fact that they represent hope for improvement in patients with chronic diseases.