Factors influencing the outcomes of dermatoses during the COVID-19 outbreak in China: a retrospective study.

Background: The coronavirus disease 2019 (COVID-19) pandemic subverted people's lives and potentially affected the management and prognosis of pre-existing dermatoses. The study aims to identify factors influencing the outcomes of dermatoses during a rapid and widespread Omicron outbreak in China following the adjustment of the COVID-19 policy. Materials and methods: This retrospective observational study involved outpatients visiting the dermatology department at a tertiary referral hospital in Beijing, China between December 2022 and February 2023. Demographics, COVID-19 characteristics, treatment modalities, and dermatosis outcomes were subjected to statistical analysis. Results: The odds ratio (OR) for vitiligo aggravation during COVID-19 was 0.497 [95% confidence interval (CI): 0.254-0.973, p = 0.038] compared to total patients with various dermatoses. Psoriasis patients with a maximum body temperature (Tmax) over 38.6°C during COVID-19 were 2.833 times more likely to experience dermatosis aggravation (OR: 2.833 [1.029-7.803], p = 0.041). Moreover, autoimmune bullous disease (AIBD) patients receiving biologics treatment exhibited a reduced likelihood of aggravation during the COVID-19 outbreak (OR: 0 [0-0.531], p = 0.011). Conclusion: Vitiligo exhibits lower aggravation rates during COVID-19 than other dermatoses. A higher body temperature during COVID-19 infection can increase the risk of psoriasis aggravation. Biologics treatment reduces the risk of AIBD aggravation during the COVID-19 outbreak.

Anti-interleukin 4 receptor α antibody for the treatment of Chinese bullous pemphigoid patients with diverse comorbidities and a 1-year follow-up: a monocentric real-world study.

Background: Bullous pemphigoid (BP) is a common subepidermal bullous disorder that lacks adequate treatment alternatives. Dupilumab, an anti-interleukin (IL) 4 receptor α antibody blocking Th2 molecules IL-4 and 13, has been used off-label and shown to be effective in refractory BP cases. Methods: BP patients with various disease severities and comorbidities were included in this case series. All patients received dupilumab alone or in combination with immunosuppressants in a real-world setting. Complete remission (CR) was defined as the absence of pruritus symptoms and previous BP eruptions, with only hyperpigmentation patches and without newly occurring lesions for at least 4 weeks. Disease relapse was classified as the appearance of three or more new lesions within 1 month or at least one large urticarial or eczematous lesion that did not resolve within a week. Findings: Ten individuals were enrolled in this case series. Pruritus symptoms and BP eruptions improved significantly in nine patients (90%). Seven patients (70%) attained CR, including all mild-to-moderate (100%) cases and three of six (50%) severe BP cases. At the dupilumab monotherapy stage, eosinophilia was observed in two severe cases. One patient out of seven (14.3%) relapsed after 1 year of follow-up after CR. Conclusion: Treatment of BP with diverse comorbidities with anti-IL-4 receptor α antibody provides further credentials to a prospective randomized study. More impressive efficacy and safety profiles were observed in patients with mild-to-moderate disease after 1 year of follow-up. Eosinophilia may occur in patients receiving dupilumab monotherapy.

Severe acute respiratory syndrome coronavirus 2 infection in patients with autoimmune bullous diseases in China.

Patients with autoimmune bullous diseases (AIBDs) are considered to be immunocompromised and, consequently, they may be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and have poorer outcomes. However, the risk and repercussions of SARS-CoV-2 infection in patients with AIBDs have not been fully understood. Therefore, we aimed to investigate the risk factors of SARS-CoV-2 infection and the impact of SARS-CoV-2 on patients with AIBDs. From December 2022 to January 2023, all patients with AIBDs who visited our clinic were enrolled in this study. Meanwhile, web-based questionnaires and telesurveys were used as supplements. Information about patients' demographics, comorbidities, SARS-CoV-2 infection, and vaccination, as well as AIBD status and treatments were collected and analyzed. The diagnosis of SARS-CoV-2 infection was based on a positive polymerase chain reaction test, and/or an antigen test, or the presence of typical symptoms in conjunction with an epidemiological history. Finally, 95 patients with AIBDs were enrolled, including 47 cases of pemphigus and 48 cases of pemphigoid cases, and 73 had symptoms consistent with coronavirus disease 2019. Common symptoms after SARS-CoV-2 infection were fever (80.8%), fatigue (75.0%), cough (71.2%), muscle/joint pain (49.3%), and sore throat (45.2%). No significant differences were found between SARS-CoV-2-infected and asymptomatic patients. Patients who had hypertension (p = 0.034), hyperlipidemia (p = 0.017), or more than two comorbidities (p = 0.011) were more likely to develop pneumonia after infection. Patients with pemphigus who did not achieve disease control (p = 0.045) or had an oral corticosteroid dose ≥15 mg/day (p = 0.024) and patients with pemphigoid with a disease duration ≥2 years (p = 0.037) were more prone to AIBDs aggravation. In conclusion, patients with AIBDs are generally susceptible to SARS-CoV-2 infection. Individuals with newly diagnosed AIBDs, uncontrolled disease, and a higher corticosteroid dose are more susceptible to disease exacerbation.

Expression of Thymic Stromal Lymphopoietin in Immune-Related Dermatoses.

Thymic stromal lymphopoietin (TSLP), long known to be involved in Th2 response, is also implicated in multiple inflammatory dermatoses and cancers. The purpose of this study was to improve our understanding of the expression of TSLP in the skin of those dermatoses. Lesional specimens of representative immune-related dermatoses, including lichen planus (LP), discoid lupus erythematosus (DLE), eczema, bullous pemphigoid (BP), psoriasis vulgaris (PsV), sarcoidosis, and mycosis fungoides (MF), were retrospectively collected and analyzed by immunohistochemistry. Morphologically, TSLP was extensively expressed in the epidermis of each dermatosis, but the expression was weak in specimens of DLE. In a semiquantitative analysis, TSLP was significantly expressed in the epidermis in LP, BP, eczema, PsV, sarcoidosis, and MF. TSLP expression was higher in the stratum spinosum in LP, eczema, BP, PsV, and MF and higher in the stratum basale in sarcoidosis and PsV. Moreover, we found positive TSLP staining in the dermal infiltrating inflammatory cells of BP, PsV, and sarcoidosis. Our observation of TSLP in different inflammatory dermatoses might provide a novel understanding of TSLP in the mechanism of diseases with distinctly different immune response patterns and suggest a potential novel therapeutic target of those diseases.

Coexistence of Anti-p200 Pemphigoid and Psoriasis: A Systematic Review.

Background: A close association between psoriasis and anti-p200 pemphigoid has been demonstrated by numerous studies. However, the clinical characteristics of patients suffering from these two entities have not yet been well-elucidated. Objective: This study aimed to review the case reports and case series, summarizing clinical features and therapeutic strategies in patients suffering from anti-p200 pemphigoid and psoriasis. Methods: A systematic review was conducted by searching PubMed, EMBASE, and Web of Science databases for studies published in English involving patients with psoriasis and anti-p200 pemphigoid on 6 September 2021. All case reports and case series reporting patients diagnosed with anti-p200 pemphigoid and psoriasis were included in this systematic review. Results: A total of 21 eligible studies comprising 26 anti-p200 pemphigoid patients with preceding psoriasis were included in the qualitative synthesis. The average age at blisters eruption was 62.5 years, and the mean duration between the two entities was 15.6 years. Twenty-four percent of patients developed bullous lesions during UV therapy. Clinical manifestation of bullae and/or vesicles was recorded in all patients, and the trunk (94.7%) was most frequently involved, with only 15.8% reporting mucosal involvement. Epitope spreading was detected by immunoblotting in 33.3% of patients. All the patients reached completed remission during the course of disease, with 36.8% experiencing at least one relapse. Monotherapy of prednisolone was the leading therapeutic approach (n=6, 31.6%) required for disease control, but 5 (83.3%) of them suffered from blister recurrence after tapering or ceasing corticosteroid. Conclusion: Most of the clinical aspects of patients with anti-p200 pemphigoid and psoriasis were similar to what was demonstrated in previous articles on anti-p200 pemphigoid. Nevertheless, compared with other anti-p200 pemphigoid cases without psoriasis, a clinical manifestation pattern with more frequent involvement of the trunk and less mucosal involvement was illustrated in those with psoriasis. Generally, monotherapy is sufficient for a complete remission for such patients. However, one or more relapses have been recorded in a considerable portion of patients, especially those prescribed with prednisolone. It reminded us to be more cautious during a tapering of medication.

Efficacy and safety of tetracyclines for pemphigoid: a systematic review and meta-analysis.

The aim of this review was to evaluate the efficacy and safety of tetracyclines for treatment of pemphigoid. We searched PubMed, EMBASE, Ovid, Web of Science, and the Cochrane Library for studies involving pemphigoid patients treated with tetracyclines published in English before 29 February 2020. References of included studies were also screened to widen the scope of the literature search. Data regarding predefined clinical outcomes of 341 patients from 77 studies were extracted and analyzed. A meta-analysis was conducted on the basis of 4 studies including 2 randomized controlled trials and 2 comparative studies. The patients had a mean age of 74.60 ± 13.18 years, 45.4% were males, and 54.6% were females. There were 185 patients with mild-to-moderate and 143 patients with severe disease. The average initial doses were 1.62 ± 0.39 g/day for tetracycline, 0.20 ± 0.01 g/day for doxycycline, and 0.11 ± 0.05 g/day for minocycline. The average time on tetracyclines was 3.74 ± 5.99 months, and 261 (81.3%) patients reported partial or complete remission. Relapses occurred in 72 (28.3%) cases. Adverse effects were experienced by 130 (41.9%) patients. The pooled ORs for short-term effectiveness, relapse, adverse effects, and 1-year survival in patients treated with oral tetracyclines vs. systemic corticosteroids were 0.40 (95% CI, 0.22-0.76), 0.69 (95% CI, 0.44-1.10), 0.47 (95% CI, 0.27-0.82) and 2.02 (95% CI, 1.16-3.50), respectively. Compared to doxycycline and minocycline, tetracycline was significantly associated with better treatment outcomes and fewer adverse effects (p < 0.05). This review revealed tetracyclines' efficacy and safety in pemphigoid treatment and may offer support for clinical use of tetracyclines in pemphigoid.

Case report: Successful treatment of non-bullous lichen planus pemphigoides with dupilumab.

Lichen planus pemphigoides (LPP) is a rare autoimmune bullous disease, characterized by the coexistence of lichen planus and subepidermal bullae. However, the minority of LPP patients present with papules rather than vesicles or blisters, which is defined as non-bullous LPP. The diagnosis of LPP relies on manifestations, histopathology, serological assay, and direct immunofluorescence of linear disposition of IgG and/or C3 at the basement membrane zone. Up to now, no standard therapeutic strategies have been proposed for the treatment of LPP. Herein, we describe an uncommon non-bullous LPP patient with widespread papules and erythema, probably induced by vaccination. During hospitalization, he had a poor response to the conventional treatment of topical and systemic corticosteroids, and his condition was finally alleviated by the addition of dupilumab. For LPP patients with a traditional medication failure, or who were not suitable for a higher dose of corticosteroids, a combination with dupilumab could be an alternative option.

[Clinical Analysis of Eight Cases of Pemphigus with High Titers of Anti-desmoglein Antibodies in Remission].

Objective To investigate the clinical manifestations,diagnosis,treatment,and laboratory examination characteristics of 8 pemphigus patients with high titers of anti-desmoglein antibodies in remission. Methods A retrospective study was conducted for the pemphigus patients diagnosed and treated in the department of dermatology from January 2013 to September 2020.The patients should have the serum anti-desmoglein antibodies ≥150 U/ml in remission or the antibody levels dropped less than 20%(calculated based on the maximum detection limit of 150 U/ml)of their initial ones detected before treatment,and the clinical and laboratory data of patients eligible for the inclusion criteria were collected. Results Among the 134 pemphigus patients with available follow-up data during this period,a total of 8 patients met the criteria,with the follow-up period of 21-85 months and the remission duration of 18-70 months.They all received less than or equal to 10 mg/d prednisone and had high titers of anti-desmoglein antibodies.At their first visit,the number of patients with positive anti-desmoglein 1/desmoglein 3 antibodies was 7.Two patients still had high titers of anti-desmoglein 1 antibodies 19 months and 21 months after they achieved remission,and 5 patients had high titers of anti-desmoglein 3 antibodies in 18-70 months.There was one patient showing high titers of both antibodies,especially for anti-desmoglein 1 antibodies.This patient relapsed after 19 months' remission while other patients were still in clinical remission. Conclusions Some pemphigus patients showed persistent high titers of anti-desmoglein antibodies in remission.Anti-desmoglein 3 antibodies were more common to keep positive,while high titer of anti-desmoglein 1 antibodies was less observed.The high titer of anti-desmoglein 1 antibodies had a correlation with recurrence.For the pemphigus patients with long-term clinical remission but high antibody titer,the dosages of corticosteroids should be adjusted carefully according to their actual clinical manifestations and the positive antibody type.For the patients with high titer of anti-desmoglein 1 antibodies,the dosage reduction of corticosteroids should be appropriately slower.

Thymic Stromal Lymphopoietin Is Implicated in the Pathogenesis of Bullous Pemphigoid by Dendritic Cells.

OBJECTIVES: Both thymic stromal lymphopoietin (TSLP) and dendritic cells (DCs) are involved in many autoimmune diseases, but the potential roles of TSLP and DCs in bullous pemphigoid (BP) have not been clarified. We sought to explore the contributions of TSLP and DCs in patients with BP. METHODS: TSLP levels in sera and blister fluids were measured by enzyme-linked immunosorbent assay. The TSLP expression in the BP lesional skin was detected by immunohistochemical staining. Infiltration of DCs, marked by DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), and its relationship with TSLP and TSLP receptors was evaluated by immunofluorescence staining. RESULTS: We found that TSLP levels in sera and in blister fluids of patients with BP were higher compared to the control groups. In patients with BP, TSLP levels in sera correlated with TSLP levels in blisters. The expression of TSLP in the BP lesional skin was higher compared to the healthy controls' skin. Greater numbers of TSLP-positive cells were observed in the epidermis of patients with BP compared to the healthy controls. Greater numbers of DC-SIGN-positive cells were present in the BP lesional skin compared to the skin of controls. The expression of TSLP was highly upregulated in DC-SIGN-positive cells, and most DC-SIGN-positive cells expressed TSLP receptors. CONCLUSIONS: We conclude that TSLP may activate DC-SIGN-positive DCs directly, which may be involved in the pathogenesis of BP.

Esters of Glucose-2-Phosphate: Occurrence and Chemistry.

Phosphodiesters of glucose-2-phosphate (G2P) are found only in few natural compounds such as agrocinopine D and agrocin 84. Agrocinopine D is a G2P phosphodiester produced by plants infected by Agrobacterium fabrum C58 and recognized by the bacterial periplasmic binding protein AccA for being transported into the bacteria before cleavage by the phosphodiesterase AccF, releasing G2P, which promotes virulence by binding the repressor protein AccR. The G2P amide agrocin 84 is a natural antibiotic produced by the non-pathogenic Agrobacterium radiobacter K84 strain used as a biocontrol agent by competing with Agrobacterium fabrum C58. G2P esters are also found in irregular glycogen structures. The rare glucopyranosyl-2-phophoryl moiety found in agrocin 84 is the key structural signature enabling its action as a natural antibiotic. Likewise, G2P and G2P esters can also dupe the Agrobacterium agrocinopine catabolism cascade. Such observations illustrate the importance of G2P esters on which we have recently focused our interest. After a brief review of the reported phosphorylation coupling methods and the choice of carbohydrate building blocks used in G2P chemistry, a flexible access to glucose-2-phosphate esters using the phosphoramidite route is proposed.

Treatment of bullous pemphigoid in Chinese patients with Tripterygium wilfordii Hook F.

Tripterygium wilfordii Hook F (TwHF) is a traditional Chinese herb used in many medicinal applications, but the treatment of bullous pemphigoid (BP) with TwHF has never been reported. The aim of this study was to evaluate the efficacy and safety of TwHF in BP patients. A retrospective study was performed from January 2015 to September 2019 in the Department of Dermatology, Peking Union Medical College Hospital. A total of 10 patients with mild to moderate BP and treated with TwHF were enrolled in the study with 10 mild or moderate BP patients treated with systemic glucocorticoid randomly selected as controls. In the TwHF group, a major response was seen in seven patients, a minor response in one and no response was seen in two patients. In the glucocorticoid group, a major response was seen in nine patients and a minor response in one patient. Two patients experienced treatment failure. The time to disease control in the TwHF group (34 ± 11 days) was longer as compared to the glucocorticoid group (18 ± 8 days, P < .05). Ten patients relapsed during the follow-up period. The adverse events in the TwHF group were lower than those in the glucocorticoid group (13 vs 19). Low-dose TwHF may be effective and safe for treating mild and moderate BP.

[Clinical and Laboratory Features of 6 Cases of Pemphigoid Nodularis].

Objective To investigate the clinical manifestations and laboratory characteristics of 6 cases of pemphigoid nodularis (PN). Method The clinical and laboratory data of 6 patients with PN admitted to the Department of Dermatology,Peking Union Medical College Hospital from January 2016 to August 2019 were retrospectively analyzed. Results PN mainly occurred in middle-aged and elderly people,with an average age of (58±16) years. Eosinophils were elevated in 4 patients. Immunoglobulin E (IgE) level was (530±672) kU/L in five patients. Direct immunofluorescence showed IgG and/or C3 deposition on basal membrane zone. Indirect immunofluorescence showed positive IgG anti-basement membrane zone,with a titer of 1:40-1:320. Enzyme-linked immunosorbent assay showed the anti-BP180 antibodies were positive [24-85 U/ml,average(43±26) U/ml] in 5 patients. None of the patients had neurological disorders. One patient was lost to follow-up. The disease recurred in 3 of 5 patients during the follow-up,and two patients still received maintenance corticosteroids. Conclusions PN mainly occurs in middle-aged and elderly individuals. It is featured by elevated eosinophils and total IgE and relatively low anti-BP180 antibody titers. Recurrence is common but PN is less likely to be associated with neurological diseases.

Synthesis of a non-natural glucose-2-phosphate ester able to dupe the acc system of Agrobacterium fabrum.

The first non-natural derivative of the rare d-glucose-2-phosphate (G2P), namely glucose-2-(O-lactic acid phosphate) (G2LP), has been synthesized. When used as sole carbon source, G2LP enables bacterial growth of the plant pathogenic strain Agrobacterium fabrum C58 (formerly referred to as Agrobacterium tumefaciens). X-ray crystallography and affinity measurements investigations reveal that G2LP binds the periplasmic binding protein (PBP) AccA similarly to the natural compounds and with the same affinity. Moreover, enzymatic assays show that it is able to serve as substrate of the phosphodiesterase AccF. The properties found for G2LP demonstrate that the very unusual glucose-2-phosphoryl residue, present in G2LP, can be used as structural feature for designing non-natural systems fully compatible with the Acc cascade of A. fabrum.

Influence of the d/l configuration of N-acyl-homoserine lactones (AHLs) and analogues on their Lux-R dependent quorum sensing activity.

Whereas l-3-oxo-hexanoyl homoserine lactone (OHHL) is the active enantiomer of the of LuxR-regulated quorum sensing (QS) autoinducer, its d isomer is implicitly considered as inactive. The present work aims to clarify this l-specificity and investigate whether it extends to some analogues in the acyl homoserine lactone (AHL) family. For this purpose, OHHL and a series of AHL analogs were synthesized in racemic and enantiomerically pure d and l forms and their ability to induce or attenuate bioluminescence in the LuxR-dependent QS system was evaluated. In this study, l-isomers are confirmed as either the only, or as the most active, enantiomers. However, in several cases, especially for the natural ligand of LuxR (OHHL) and the very similar AHL agonist analogue 2, the d-isomer cannot be considered as totally inactive on QS. Molecular modelling suggests that when the lactone moiety of the d-isomer is able to twist, enabling the lactone carbonyl group and the amide function to interact with the key residues in the binding site, then the d-isomer can exhibit some activity.

Three novel Cu6S6 cluster-based coordination compounds: synthesis, framework modulation and the sensing of small molecules and Fe(3+) ions.

Three novel Cu6S6 cluster-based coordination compounds formulated as [Cu(mpymt)3]2 (1), {(CuBr4)[Cu(mpymt)6]}n (2), and {(CuI6)[Cu(mpymt)6]}n (3) (Hmpymt = 4-methylpyrimidine-2-thione), have been synthesized under solvothermal conditions and characterized by elemental analysis, infrared (IR) spectroscopy, thermal gravimetric analysis, powder X-ray diffraction and single-crystal X-ray diffraction. Structural analysis reveals that compound 1 shows a distorted octahedral core of six copper atoms (Cu6S6) constructed from four α and two ß type N[double bond, length as m-dash]C-SH parts from six mpymt(-) anions. Compound 2 displays an interesting 3D framework constructed from Cu6S6 and Cu4Br4 Cu(i) clusters simultaneously, interestingly, six mpymt(-) with α type N[double bond, length as m-dash]C-SH parts are involved in the formation of Cu6S6. Compound 3 displays an infinite 1D framework constructed from Cu6S6 and Cu6I6 Cu(i) clusters, notably, four α and two ß type N[double bond, length as m-dash]C-SH parts are involved in the formation of the Cu6S6 cluster, however, only mpymt(-) ligands containing α type N[double bond, length as m-dash]C-SH parts form the bridged Cu6I6 cluster. The experimental results reveal that halogen ions finely modulate the structural features of compounds 1-3. The fluorescent properties of compounds 1-3 in the solid state and in various solvent emulsions were investigated in detail, the results of which indicate that compounds 1-3 are all highly sensitive naked eye colorimetric sensors for NB, 2-NT and Fe(3+) (NB = nitrobenzene and 2-NT = 2-nitrotoluene).

A Pyranose-2-Phosphate Motif Is Responsible for Both Antibiotic Import and Quorum-Sensing Regulation in Agrobacterium tumefaciens.

Periplasmic binding proteins (PBPs) in association with ABC transporters select and import a wide variety of ligands into bacterial cytoplasm. They can also take up toxic molecules, as observed in the case of the phytopathogen Agrobacterium tumefaciens strain C58. This organism contains a PBP called AccA that mediates the import of the antibiotic agrocin 84, as well as the opine agrocinopine A that acts as both a nutrient and a signalling molecule for the dissemination of virulence genes through quorum-sensing. Here, we characterized the binding mode of AccA using purified agrocin 84 and synthetic agrocinopine A by X-ray crystallography at very high resolution and performed affinity measurements. Structural and affinity analyses revealed that AccA recognizes an uncommon and specific motif, a pyranose-2-phosphate moiety which is present in both imported molecules via the L-arabinopyranose moiety in agrocinopine A and the D-glucopyranose moiety in agrocin 84. We hypothesized that AccA is a gateway allowing the import of any compound possessing a pyranose-2-phosphate motif at one end. This was structurally and functionally confirmed by experiments using four synthetic compounds: agrocinopine 3'-O-benzoate, L-arabinose-2-isopropylphosphate, L-arabinose-2-phosphate and D-glucose-2-phosphate. By combining affinity measurements and in vivo assays, we demonstrated that both L-arabinose-2-phosphate and D-glucose-2-phosphate, which are the AccF mediated degradation products of agrocinopine A and agrocin 84 respectively, interact with the master transcriptional regulator AccR and activate the quorum-sensing signal synthesis and Ti plasmid transfer in A. tumefaciens C58. Our findings shed light on the role of agrocinopine and antibiotic agrocin 84 on quorum-sensing regulation in A. tumefaciens and reveal how the PBP AccA acts as vehicle for the importation of both molecules by means of a key-recognition motif. It also opens future possibilities for the rational design of antibiotic and anti-virulence compounds against A. tumefaciens or other pathogens possessing similar PBPs.

Rapid microparticle patterning by enhanced dielectrophoresis effect on a double-layer electrode substrate.

We present a feasible dielectrophoresis (DEP) approach for rapid patterning of microparticles on a reusable double-layer electrode substrate in microfluidics. Simulation analysis demonstrated that the DEP force was dramatically enhanced by the induced electric field on top interdigitated electrodes. By adjusting electric field intensity through the bottom electrodes on thin glass substrate (100 µm), polystyrene particles (10 µm) were effectively patterned by top electrodes within several seconds (<5 s). The particle average velocity can reach a maximum value of about 20.0±3.0 µm/s at 1 MHz with the strongest DEP force of 1.68 pN. This approach implements integration of functional electrodes into one substrate and avoids direct electrical connection to biological objects, providing a potential lab-on-chip system for biological applications.