Janus kinase inhibitors in atopic dermatitis: an umbrella review of meta-analyses.

Background: Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent. Methods: Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE). Results: Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]). Conclusion: Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).

Validation of the Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE): a new clinician reported outcome measure of CHE severity.

The Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE) is a novel Clinician-Reported Outcome measure that allows investigators to assess cross-sectional CHE global disease severity using clinical characteristics of erythema, scaling, lichenification/hyperkeratosis, vesiculation, oedema, and fissures as guidelines for overall severity assessment. This study aimed to evaluate the psychometric properties of the IGA-CHE for use as an outcome measure in CHE clinical trials and clinical practice. Psychometric analyses were performed using data from a sample of 280 patients with moderate to severe CHE from a phase 3 trial of delgocitinib cream, pooled across treatment groups. Test-retest reliability results were moderate to strong with kappa coefficients ranging from 0.63 to 0.76. Correlations with measures assessing related concepts were moderate or strong (range 0.65-0.72) and exceeded a priori hypotheses, providing evidence of convergent validity. Known-groups validity was supported by statistically significant differences between severity groups (< 0.001). Within-group effect sizes were consistently larger for improved groups compared to stable groups, providing evidence of ability to detect change. Anchor-based analyses generated within-subject meaningful change estimates ranging from - 0.8 to - 2.3. A correlation weighted average suggested a single value of - 1.7 in change from baseline. These findings provide evidence the IGA-CHE scale has strong reliability, construct validity, and ability to detect change, supporting its use as an endpoint in CHE clinical trials and clinical practice. Based on the evidence, 2-level changes in IGA-CHE score are considered a conservative meaningful change threshold; however, findings also indicate 1-level change in IGA-CHE scores reflects a clinically meaningful improvement for patients.Clinical trial registration: NCT04871711.

Autoantibodies in rheumatoid arthritis - rheumatoid factor, anticitrullinated protein antibodies and beyond.

PURPOSE OF REVIEW: RA is characterized by the presence of autoantibodies among which rheumatoid factors (RFs) and antimodified protein antibodies (AMPA) are serological hallmarks of the disease. In recent years, several novel insights into the biology, immunogenetics and clinical relevance of these autoantibodies have been obtained, which deserve to be discussed in more detail. RECENT FINDINGS: RFs from RA patients seem to target distinct epitopes which appear to be quite specific for RA. Determination of immunoglobulin A (IgA) isotypes of RF and anticitrullinated protein antibodies (ACPA) may provide prognostic information because their presence is associated with reduced therapeutic responses to TNF inhibitors. Furthermore, IgA levels are increased in RA patients and IgA immune complexes are more potent than immunoglobulin G (IgG) complexes in inducing NET formation. Concerning AMPAs, investigations on variable domain glycosylation (VDG) revealed effects on antigen binding and activation of autoreactive B cells. Studies on pathogenetic involvement of ACPA suggest Janus-faced roles: on the one hand, ACPA may be involved in joint destruction and pain perception while on the other hand protective anti-inflammatory effects may be attributed to a subset of ACPAs. SUMMARY: The autoimmune response in RA is extremely complex and still far from being fully understood. Antibodies are not only valuable diagnostic biomarkers but also seem to play pivotal roles in the pathophysiology of RA.

INDIVIDUAL ARTICLE: Sarecycline Improves Acne Severity, Symptoms, and Psychosocial Burden in Non-nodular Acne Vulgaris: PROSES Study.

BACKGROUND: Patient-reported outcomes (PROs) are emerging as a fundamental component of disease impact assessment in acne vulgaris (AV), complementing clinician-reported outcomes. No data is available on PROs for patients with AV using sarecycline in real-world settings. METHODS: A single-arm, prospective cohort study that included patients ≥9 years old diagnosed with moderate or severe non-nodular AV was implemented as part of routine care in clinical practices (N=30). Patients received oral sarecycline (60 mg, 100 mg, or 150 mg) for 12 weeks, as part of usual care. The primary endpoint was Acne Symptom and Impact Scale (ASIS) responses from patients (≥12 years) and caregivers (for patients 9-11 years) at week 12 and change from baseline (CFB). Investigator’s Global Assessment (IGA) of AV severity and adverse events (AEs) were also recorded. RESULTS: A total of 253 patients with AV completed the study (adults: 60.1%, females: 77.6%). ASIS mean scores significantly decreased (P <.0001) at week 12 for: signs (mean CFB ± standard deviation [SD]: –0.8 ± 0.7), impact (–1.0 ± 1.0), emotional impact (–1.2 ± 1.1), and social impact (0.6 ± 1.1). Significant reductions in AV severity (P <.0001) were reported by patients and caregivers. The IGA success rate was 58.9% and physician satisfaction with treatment outcomes was 88.1%. A total of 31 (10.3%) patients reported ≥1 AE during the study. CONCLUSIONS: Patients with moderate-to-severe AV receiving acne management with an oral antibiotic for 12 weeks experienced a significant improvement in AV-related symptoms and psychosocial burden. J Drugs Dermatol. 2024;23:1(Suppl 1):s12-18.

A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and Future.

The clinical association of purpura, arthralgia, and arthritis was first described in 1837 in a publication by Johann Lukas Schönlein, a German physician. In 1874, Eduard Henoch, a student of Schönlein, reported cases of children with purpura, abdominal pain, bloody diarrhea, and joint pain. IgA vasculitis, or Henoch-Schönlein purpura, is a systemic hypersensitivity vasculitis caused by the deposition of immune complexes in small blood vessels, including the renal glomeruli and mesangium. In the skin, the presentation is with non-thrombocytopenic purpura or urticaria. Worldwide, IgA nephropathy is the most common cause of primary glomerulonephritis. Detection of IgA deposition in small blood vessels and the renal glomeruli is diagnostic in most cases. This article aims to review the history, current classification, epidemiology, presentation, and diagnosis of IgA vasculitis and nephropathy, disease associations or trigger factors, including infections, vaccines, and therapeutic agents, and highlights some future approaches to improve diagnosis and clinical management.

Pharmacological effects of biologically synthesized ginsenoside CK-rich preparation (AceCK40) on the colitis symptoms in DSS-induced Caco-2 cells and C57BL mice.

BACKGROUND: Despite the notable pharmacological potential of natural ginsenosides, their industrial application is hindered by low oral bioavailability. Recent research centers on the production of less-glycosylated minor ginsenosides. PURPOSE: This study aimed to explore the effect of a biologically synthesized ginsenoside CK-rich minor ginsenoside complex (AceCK40), on ameliorating colitis using DSS-induced colitis models in vitro and in vivo. METHODS: The ginsenoside composition of AceCK40 was determined by HPLC-ELSD and UHPLC-MS/MS analyses. In vitro colitis model was established using dextran sodium sulfate (DSS)-induced Caco-2 intestinal epithelial model. For in vivo experiments, DSS-induced severe colitis mouse model was established. RESULTS: In DSS-stimulated Caco-2 cells, AceCK40 downregulated mitogen-activated protein kinase (MAPK) activation (p < 0.05), inhibited monocyte chemoattractant protein-1 (MCP-1) production (p < 0.05), and enhanced MUC2 expression (p < 0.05), mediated via signaling pathway regulation. Daily AceCK40 administration at doses of 10 and 30 mg/kg/day was well tolerated by DSS-induced severe colitis mice. These doses led to significant alleviation of disease activity index score (> 36.0% decrease, p < 0.05), increased luminal immunoglobulin (Ig)G (> 37.6% increase, p < 0.001) and IgA (> 33.8% increase, p < 0.001), lowered interleukin (IL)-6 (> 65.7% decrease, p < 0.01) and MCP-1 (> 116.2% decrease, p < 0.05), as well as elevated serum IgA (> 51.4% increase, p < 0.001) and lowered serum IL-6 (112.3% decrease at 30 mg/kg, p < 0.001). Hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining revealed that DSS-mediated thickening of the muscular externa, extensive submucosal edema, crypt distortion, and decreased mucin droplets were significantly alleviated by AceCK40 administration. Additionally, daily administration of AceCK40 led to significant recovery of colonic tight junctions damaged by DSS through the elevation in the expression of adhesion molecules, including occludin, E-cadherin, and N-cadherin. CONCLUSION: This study presents the initial evidence elucidating the anti-colitis effects of AceCK40 and its underlying mechanism of action through sequential in vitro and in vivo systems employing DSS stimulation. Our findings provide valuable fundamental data for the utilization of AceCK40 in the development of novel anti-colitis candidates.

The effect of enterocin A/P dipeptide on growth performance, glutathione-peroxidase activity, IgA secretion and jejunal morphology in rabbits after experimental methicillin-resistant Staphylococcus epidermidis P3Tr2a Infection.

The increasing frequency of methicillin-resistant (MR) staphylococci in humans and animals need special attention for their difficult treatment and zoonotic character, therefore novel antimicrobial compounds on a natural base against antibiotic-resistant bacteria are requested. Currently, bacteriocins/enterocins present a new promising way to overcome this problem, both in prevention and treatment. Therefore, the preventive and medicinal effect of dipeptide enterocin EntA/P was evaluated against MR Staphylococcus epidermidis SEP3/Tr2a strain in a rabbit model, testing their influence on growth performance, glutathione-peroxidase (GPx) enzyme activity, phagocytic activity (PA), secretory (s)IgA, and jejunal morphometry (JM). Eighty-eight rabbits (aged 35 days, meat line M91, both sexes) were divided into experimental groups S (SEP3/Tr2a strain; 1.0 × 105 CFU/mL; dose 500µL/animal/day for 7 days, between days 14 and 21 to simulate the pathogen attack), E (EntA/P; 50 µL/animal/day, 25,600 AU/mL in two intervals, for preventive effect between days 0 and 14; for medicinal effect between days 28 and 42), E + S (EntA/P + SEP3/Tr2a; preventive effect; SEP3/Tr2a + EntA/P; medicinal effect) and control group (C; without additives). Higher body weight was recorded in all experimental groups (p < 0.001) compared to control data. The negative influence/attack of the SEP3Tra2 strain on the intestinal immunity and environment was reflected as decreased GPx activity, worse JM parameters and higher sIgA concentration in infected rabbits. These results suggest the promising preventive use of EntA/P to improve the immunity and growth of rabbits, as well as its therapeutic potential and protective role against staphylococcal infections in rabbit breeding.

Efficacy of a multitargeted, salicylic acid-based dermocosmetic cream compared to benzoyl peroxide 5% in Acne vulgaris: Results from a randomized study.

INTRODUCTION: Acne vulgaris (acne) is characterized by both inflammatory and non-inflammatory lesions. Benzoyl peroxide (BPO) 5% is approved to treat acne but may cause skin irritation and/or contact allergy. OBJECTIVES: To compare the benefit in acne of a multitargeted dermocosmetic cream containing salicylic acid, lipohydroxy acid, niacinamide, 2-oleamido-1,3-octadecanediol, piroctone olamine, zinc, Aqua posae filiformis, and thermal spring water (DC-Eff) to BPO 5% gel. MATERIALS AND METHODS: 150 Caucasian subjects (50% female) aged between 18 and 40 years, with mild to moderate acne according to the GEA (Global Evaluation of Acne) grading system were randomized into two parallel groups (DC-Eff or BPO to be applied twice daily for 56 days). IGA (investigator global assessment), GEA, lesion count, clinical signs and symptoms, and subject assessment were evaluated at baseline, and after 28 and 56 days (D28 and D56) of treatment. RESULTS: The responder analyses of the IGA and GEA scores showed that 62.2% and 47.3%, respectively, in the DC-Eff, compared with 50.0% and 36.5%, respectively, in the BPO, had improved by at least one point at D56. Inflammatory, non-inflammatory, and total lesion counts significantly (p < 0.0001) decreased with both products from baseline, with no between-group difference. Subjects considered that their skin was smoother and that DC-Eff was easy to apply. DC-Eff was better tolerated than BPO. CONCLUSIONS: DC-Eff applied twice daily is as beneficial as BPO in improving mild-to-moderate acne. DC-Eff was better tolerated than BPO and highly appreciated.

Alitretinoin as a Treatment Modality for Ichthyosis in Women of Childbearing Age: A Case Series and Review of the Literature.

BACKGROUND: Acitretin, a synthetic vitamin A derivative, is the most studied and widely used oral retinoid for ichthyoses. Its major disadvantage is the need for contraceptive measures during 3 years after discontinuation. An alternative is needed for women of childbearing age. With alitretinoin, another retinoid, pregnancy is considered safe 1 month after discontinuation. OBJECTIVES: The aim of this study was to provide evidence for alitretinoin as an alternative for acitretin for ichthyosis in women of childbearing age. Our experience is shared in a case series combined with an overview of the current literature. METHODS: Nine women of childbearing age (19-31 years, median 21) with different subtypes of ichthyosis (autosomal recessive congenital ichthyosis, (superficial) epidermolytic ichthyosis, erythrokeratoderma variabilis, and epidermolytic epidermal nevi, a mosaic form of epidermolytic ichthyosis) were included and treated with 30 mg alitretinoin during 2-28 months. Severity was measured by Ichthyosis Area Severity Index (IASI) and Investigator Global Assessment (IGA). A literature search in Pubmed using the Mesh terms "alitretinoin," "skin diseases, genetic" and "ichthyosis" was performed. RESULTS: Significant reduction in the mean scores of IGA, IASI-erythema, IASI-scaling, and IASI-total was seen. Seven patients are still being treated, 1 patient stopped to become pregnant, 1 patient discontinued due to financial reasons. Observed side effects were reversible headache (n = 6), asteatotic eczema (n = 1), "not feeling well" temporarily (n = 1), and easier blistering of the feet (n = 1). The literature search resulted in six case reports and case series about alitretinoin in ichthyosis and ichthyosis syndromes with in total 29 patients. The vast majority of articles (21/29) reported significant improvement or even complete remission of skin symptoms. However, validated outcome measures to support these results were lacking. Side effects (n = 16) were relatively mild, except for benign intracranial hypertension (n = 1) and autoimmune hypothyroidism (n = 1). CONCLUSION: Our study shows, with validated outcome measures, that alitretinoin is effective to mitigate the symptoms of ichthyosis in women of childbearing age and a suitable alternative to acitretin.

Effectiveness and safety of baricitinib in patients with moderate-to-severe refractory alopecia areata in real world: An open-label, single-center study.

PURPOSE: Baricitinib is a small-molecular drug that selectively inhibits the Janus Kinase (JAK) 1 and 2. However, it showed various efficiency and safety in treating moderate-to-severe alopecia areata (AA). This study was to describe the real-world effectiveness of baricitinib in treating moderate-to-severe refractory AA. METHODS: Patients who were affected by moderate-to-severe AA and reported no shrinkage in the alopecia area after 6 months of conventional treatment were enrolled in the retrospective study. The patients were treated with baricitinib orally for at least 24 weeks. The severity of alopecia was evaluated at the end of 4, 12, and 24 weeks of treatment. RESULTS: The 32 patients included 23 females and nine males, with a median duration of AA of 14.5 months. Among them, 28 patients received baricitinib 2 mg per day for 24 weeks while the other four patients increased the daily dose from 2 to 4 mg after the first 12 weeks due to the unobvious hair restoration. SALT value showed a significant decrease from baseline at week 12 and 24 (64.45 [44.68-100.00] vs. 26.80 [13.40-62.32], p < 0.0001 and 64.45 [44.68-100] vs. 9.40 [4.85-34.95], p < 0.0001). After 24 weeks of treatment, 50% of patients had an improvement of ≥2 points in IGA scores from the baseline, and IGA scores of 68.75% of patients were less than 2. CONCLUSION: This 24-week research showed that baricitinib had favorable clinical efficacy and safety in treating moderate-to-severe AA, which is worthy of attention and expectation.

IgA Vasculitis as a Potential Complication of Fourth-Line Chemotherapy with Tegafur/Gimeracil/Oteracil (S-1) in Advanced Non-Small Cell Lung Cancer: A Case Report.

BACKGROUND Immunoglobulin A (IgA) vasculitis is a systemic vasculitis that involves the small vessels. It is mainly characterized by skin symptoms such as purpura, arthritis/arthralgia, abdominal symptoms, and nephropathy, which are caused by IgA adherence to the vessel walls. Herein, we report the case of an advanced non-small cell lung cancer (NSCLC) and a purpuric skin rash of the legs that developed during fourth-line chemotherapy with tegafur/gimeracil/oteracil (S-1). CASE REPORT A 68-year-old man diagnosed with NSCLC 2 years ago was undergoing S-1 as fourth-line chemotherapy when he developed purpura and edema on the lower extremities. Biopsy renal specimens were consistent with IgA vasculitis. Considering his medical history, both IgA vasculitis induced by S-1 and a paraneoplastic syndrome were considered, although the exact cause could not be identified. Subsequently, chemotherapy was discontinued because of his deteriorating general condition, and he received optimal supportive care. The purpura spontaneously disappeared; however, his ascites and renal function deteriorated. Systemic steroids improved renal function, but the ascites did not resolve. One month after being diagnosed with IgA vasculitis, the patient died due to deterioration of his general condition. CONCLUSIONS This case emphasizes the occurrence of IgA vasculitis during lung cancer treatment and its potential impact on the disease course of lung cancer. Moreover, the possible causes of IgA vasculitis in this case were paraneoplastic syndrome or S-1 adverse effects, but further case series are needed to gain a more comprehensive understanding. Refractory, steroid-unresponsive ascites may occur as an abdominal manifestation of IgA vasculitis.

Inhibition of excessive autophagy alleviates renal injury and inflammation in a rat model of immunoglobulin A nephropathy.

The pathogenesis of immunoglobulin A nephropathy (IgAN) is closely related to immunity and inflammation. The clinical process of IgAN varies greatly, making the assessment of prognosis challenging and limiting progress on effective treatment measures. Autophagy is an important pathway for the development of IgAN. However, the role of autophagy in IgAN is complex, and the consequences of autophagy may change during disease progression. In the present study, we evaluated the dynamic changes in autophagy during IgAN. Specifically, we examined autophagy in the kidney of a rat model of IgAN at different time points. We found that autophagy was markedly and persistently induced in IgAN rats, and the expression level of inflammation was also persistently elevated. The autophagy enhancer rapamycin and autophagy inhibitor 3-methyladenine were used in this study, and the results showed that 3-methyladenine can alleviate renal injury and inflammation in IgAN rats. Our study provides further evidence for autophagy as a therapeutic target for IgAN.

Leuconostoc mesenteroides subsp. strain NTM048 ameliorated nasal symptoms in patients with Japan cedar pollinosis: Randomized, double-blind, and placebo-controlled trial.

BACKGROUND: Lactobacillales including L mesenteroides have beneficial effects on human health, including improvement of psychological status and alleviation of allergic rhinitis. In mice, L mesenteroides subsp. strain NTM048 (NTM048) increased intestinal s-IgA. In humans, however, the effects of NTM048 on s-IgA secretion have been unclear. STUDY: This 16-week trial was performed using a double-blind, placebo-controlled, parallel group design. We aimed to establish whether Leuconostoc mesenteroides subsp. strain NTM048 increases the secretion of s-IgA in saliva. Forty healthy adults and forty patients with Japanese cedar pollinosis were recruited. Participants took either 2 test capsules including NTM048 (1010 CFU/day), or 2 placebo capsules per day, for 16 weeks. They were asked to collect their saliva and answered POMS2, a questionnaire about psychological status. The patients also answered questions about nasal symptoms. Blood samples were collected from the patients with Japanese Cedar pollinosis. Stool samples were collected at the start and on the last day of the trial. RESULTS: All subjects completed the trial. It was conducted during the season when Japanese cedar pollen is most scattered. Serum concentration of Japanese cedar pollen-specific IgE was > 2.0 UA/mL in patients with Japanese cedar pollinosis. The amount of s-IgA in saliva was not increased by NTM048 in overall subjects, and Japanese cedar pollen-specific IgE was not changed by NTM048 in patients with Japanese cedar pollinosis. The symptom of nasal blockage was improved by NTM048 12 weeks after the start of trial. post hoc analysis indicated a positive correlation between improving psychological status and the increase in occupation ratio of lactobacillus including NTM048. CONCLUSION: The amount of s-IgA in saliva was not increased by NTM048, but nasal blockage was improved by it. Psychological status might be improved if dosage of NTM048 is raised to the degree that NTM048 might be increased in the intestinal tract.

Safety and Efficacy of Oral Hydroxychloroquine in the Treatment of Ophthalmic Disease Associated with Sjögren's Syndrome.

Background: Dry eye disease is common among patients with primary Sjögren's syndrome (pSS). Hydroxychloroquine (HCQ), known for its immunomodulatory effects and minimal adverse effects, has emerged as a pivotal treatment option for pSS. Nonetheless, conflicting evidence exists regarding the therapeutic efficacy of HCQ in managing dry eye disease associated with pSS. Objectives: To evaluate the safety and efficacy of oral hydroxychloroquine in treating dry eye disease associated with pSS. Methods: A prospective randomized controlled study was conducted, enrolling pSS patients with moderate to severe dry eye disease. Participants were randomly assigned to an oral HCQ group and an observation group. Various scales (ESSDAI, ESSPRI, OSDI, and SPEED questionnaire score), dry eye-related tests (OSS score, TBUT, and Schirmer test I), ophthalmology-specific tests (BCVA, SD-OCT RT, field of view, latency and amplitudes for multifocal ERG ring 1 and ring 2), whole body protein levels (serum IgA, IgG, and IgM), and blood glucose were assessed before and after 12 months of treatment. Results: Pairwise comparison of the observed indicator baseline revealed no statistical significance (P > .05). After 12 months, the HCQ group exhibited notable improvements in ESSPRI, serum IgA, and Schirmer test I results compared to the control group (P < .05). Both groups demonstrated significant improvements in BCVA, OSDI, SPEED scores, and dry eye-associated examinations compared to baseline (P < .05). Serum IgG and IgM levels decreased in the HCQ group after 12 months of treatment, but without statistical significance (P > .05). None cases of HCQ retinopathy were reported during follow-up. Conclusions: Oral HCQ was demonstrated safety and efficacy in managing pSS-related dry eye disease. Treatment with Oral HCQ markedly reduced the ESSPRI score, improve patients' systemic dryness symptoms, and greatly decreased blood IgA levels. Combined with topical cyclosporin, HCQ improved Schirmer test I scores and alleviated ocular surface inflammation and dry eye signs and symptoms.

A Prospective Randomized Controlled Pilot Study to Assess the Response and Tolerability of Cold Atmospheric Plasma for Rosacea.

INTRODUCTION: Rosacea is a common, facial, chronic inflammatory skin disease. Due to its complex pathogenesis, adequate therapy of rosacea can be challenging. An innovative recent therapeutic tool is cold atmospheric plasma (CAP), which is already established in the treatment of chronic wounds and promising in different other skin diseases. METHODS: In a split-face pilot study we investigated dielectric-barrier-discharged CAP in erythemato-telangiectatic (ETR) and/or papulopustular rosacea (PPR). CAP treatment was applied on lesional skin of a randomized side once daily (90 s/area) for 6 weeks. The other untreated side served as control. Co-primary endpoints were ≥1 improvement of the Investigator Global Assessment (IGA) score on the treated side compared to control and a decline of the Dermatology Life Quality Index (DLQI) after 6 weeks. Secondary endpoints included inflammatory lesion count (papules and pustules), skin redness intensity and erythema size. Adverse events (AEs) were recorded constantly. Additionally, participants were weekly assessed for symptoms, skin condition, trigger factors, skin care, treatment success, and local tolerance parameters. All p values were calculated using the Wilcoxon signed-rank test. RESULTS: Twelve subjects (ETR, n = 3; ETR and PPR, n = 9) completed the study. DLQI was significantly improved after 6 weeks (p = 0.007). On the CAP-treated side, lesions (p = 0.007) and erythema size (p = 0.041) were significantly reduced compared to the control. IGA (p = 0.2) and skin redness intensity (p = 0.5) did not differ significantly between control and CAP-treated side. No serious AEs occurred and treatment was well tolerated. CONCLUSION: CAP is a promising new treatment of rosacea, especially for PPR.

[Immunoglobulin A vasculitis (IgAV)]. / Immunglobulin-A-Vaskulitis (IgAV).

IgA vasculitis (IgAV) is an immune complex-mediated vasculitis characterized by IgA1-dominant immune deposits in small vessels. It is the most common systemic vasculitis in childhood with a mostly uncomplicated and self-limiting course. Adults are less affected but the course is frequently more complicated and more frequently accompanied by renal involvement. IgAV characteristically manifests itself on the skin with palpable purpura and in joints, the kidneys and the gastrointestinal tract. In cases of incomplete or atypical symptoms a differential diagnostic work-up is required. A number of triggers have been suggested, especially infections and drugs. Disease management is tailored to organ manifestations and the severity of the symptoms. For children, optimized supportive care and targeted symptom relief are usually sufficient. Management of renal and gastrointestinal manifestations follows recommendations for ANCA-associated vasculitis and IgA nephropathy. Treatment options include glucocorticoids and immunosuppressive agents with varying and mostly insufficient evidence.

Clinical features, treatment and outcome of pediatric patients with severe cutaneous manifestations in IgA vasculitis: Multicenter international study.

OBJECTIVE: IgA vasculitis (IgAV) (formerly Henoch-Schönlein Purpura, HSP) rarely causes severe skin lesions in children. The purpose of the research was to determine whether severe skin manifestations were associated with a more severe disease course. METHODS: Severe cutaneous manifestations were defined as presence of hemorrhagic vesicles, bullae, ulcerations and/or necroses. Data were collected retrospectively from 12 international tertiary university medical centers. RESULTS: A total of 64 patients with the most severe skin changes in IgAV/HSP and median (Q1, Q3) age of 8.08 (5.08, 11.92) years at the disease onset were compared with 596 IgAV/HSP patients without these manfiestations and median (Q1, Q3) age of 6.33 (4.50, 8.92) years. The patients with severe cutaneous manifestations were older in comparison to other patients with IgAV/HSP (p<0.001), they developed nephritis more frequently (40.6% vs. 20.6%, p = 0.001) with worse outcome of renal disease (p = 0.001). This group of patients also had higher frequencies of severe gastrointestinal complications like hematochezia, massive bleeding and/or intussusception (29.3% vs. 14.8%, p<0.001). d-dimer concentrations were significantly higher in these patients (4.60 mg/L vs. 2.72 mg/L, p = 0.003) and they had more frequent need for treatment with systemic glucocorticoids (84.4% vs. 37.2%, p<0.001) in comparison with the control group. Further multivariate analysis showed that severe cutaneous changes were associated with higher risk of developing nephritis [OR=3.1 (95%CI 1.04-9.21), p = 0.042] and severe gastrointestinal complications [OR=3.65 (95%CI 1.08-12.37), p = 0.038]. CONCLUSION: Patients with IgAV/HSP and severe skin manifestations had a more severe clinical course and more frequently required glucocorticoids compared to classic IgAV/HSP patients.

Efficacy of metformin vs. doxycycline in treating acne vulgaris: An assessor-blinded, add-on, randomized, controlled clinical trial.

INTRODUCTION: Insulin-like growth factor 1 (IGF-1) plays a role in the pathogenesis of acne vulgaris. Metformin can reduce IGF-1 levels and insulin resistance, so it may be useful in treating acne. OBJECTIVE: This study compared the efficacy of metformin and doxycycline in treating patients with acne vulgaris. METHODS: In this assessor-blind, add-on, randomized controlled clinical trial, we enrolled 40 patients with moderate acne vulgaris aged 15-40 and randomly divided them into two groups. For two months, the first group received doxycycline 100 mg capsules daily, and the second received metformin 500 mg tablets twice daily. The patients in both groups were adminitered to apply a fingertip (fourth finger) of 5% benzoyl peroxide gel (Pangel®) topically every night over the lesions, and to wash it off after 30 min. Patients were evaluated using the Global Acne Grading System (GAGS) score, Investigator Global Assessment for Acne (IGA) score, Cardiff Acne Disability Index (CADI), Total Acne Lesion Count (TLC), and the number of inflammatory and noninflammatory lesions. RESULTS: By the end of the study, the GAGS, IGA, CADI, and TLC scores and the number of inflammatory and noninflammatory lesions decreased significantly in both groups (p < 0.001), with no significant difference between the two groups (p > 0.05). CONCLUSION: This trial indicates equal efficacy of doxycycline and metformin in reducing acne vulgaris severity, with doxycycline performing better in reducing lesions of the inflammatory type. Confirmatory or equivalence clinical trials should be performed to confirm our results.

Successful Treatment of Prurigo Nodularis by Dupilumab: Report of 24 Patients.

BACKGROUND: Prurigo nodularis (PN) is a chronic pruritic skin disease which is difficult to treat. Current treatment options often lead to limited clinical benefit or severe side effects. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of dupilumab in the treatment of PN in adults. METHOD: This study is a retrospective cohort study. Twenty-four adult patients with PN were included and treated with dupilumab. The primary outcomes were the mean reduction in the Investigator's Global Assessment (IGA) score and pruritus numeric rating scale (p-NRS) score. Outcomes were assessed at baseline, week 4, week 16, and week 36. RESULTS: The study included 24 patients, of whom 9 (37.5%) were male, and the mean (SD) age of the enrolled patients was 49.88 ± 16.71 years. At the end of the 16-week treatment, the mean p-NRS score decreased from 7.50 ± 2.21 to 1.41 ± 0.91 (p < 0.001), sleeplessness numeric rating scale (s-NRS) score declined from 5.33 ± 3.29 to 0.18 ± 0.59 (p < 0.001), and Dermatology Life Quality Index (DLQI) score decreased from 13.32 ± 4.88 to 0.91 ± 0.81 (p < 0.001). Fourteen (63.6%) of 22 patients achieved IGA 0/1 and 21 (95.5%) patients achieved IGA activity 0/1. Among 14 patients who achieved IGA 0/1, 10 had an elevated serum IgE level, and patients with a high serum IgE level showed a more remarkable reduction in IGA (r = 0.52, p = 0.03). Patients with AD responded faster than those without AD (3.76 ± 1.71 weeks vs. 6.40 ± 1.67 weeks, p = 0.01). Adverse events were recorded in 4/24 (16.6%) patients, with conjunctivitis being the most frequent. CONCLUSION: This study demonstrated that dupilumab is effective and safe for PN and could be a potential therapeutic option.

Antibody diversity in IVIG: Therapeutic opportunities for novel immunotherapeutic drugs.

Significant progress has been made in the elucidation of human antibody repertoires. Furthermore, non-canonical functions of antibodies have been identified that reach beyond classical functions linked to protection from pathogens. Polyclonal immunoglobulin preparations such as IVIG and SCIG represent the IgG repertoire of the donor population and will likely remain the cornerstone of antibody replacement therapy in immunodeficiencies. However, novel evidence suggests that pooled IgA might promote orthobiotic microbial colonization in gut dysbiosis linked to mucosal IgA immunodeficiency. Plasma-derived polyclonal IgG and IgA exhibit immunoregulatory effects by a diversity of different mechanisms, which have inspired the development of novel drugs. Here we highlight recent insights into IgG and IgA repertoires and discuss potential implications for polyclonal immunoglobulin therapy and inspired drugs.