Introduction

Diverticular disease of the colon is one of the most common diseases in Western world. Despite in the natural history in most of cases diverticulosis remains asymptomatic or manifests with mild abdominal pain, complications may occur. Bleeding from diverticula is one of the most common complications and, despite it is usually a self-limiting event, it may lead to anemia or shock. Among the endoscopic interventions for active bleeding, direct or indirect clipping of the diverticulum is the most diffuse one. However, it has been hypothesized that endoscopic band ligation (EBL) may be more effective, since it may improve the chance to close the bleeding vessel, with a better outcome on long term. Therefore we performed a meta-analysis comparing clipping versus EBL for diverticular bleeding.

Aims & Methods

Literature search on main databases (PubMed, Web of science, SCOPUS, EMBASE) was performed in November 2022. Studies comparing clip versus EBL for acute diverticular bleeding were selected. We excluded case series, abstract and articles not written in English. The following outcomes were analysed: short term effectiveness, early rebleeding, tardive rebleeding and need for surgery or radiologic embolization. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculate according to Mantel-Haenszel method. Heterogeneity was estimated by I² statistic with chi square test, and, if present, a random effect model was used, otherwise a fixed one was adopted.

Results

Seven studies were selected, overall enrolling 2322 patients (979 in EBL and 1343 in clip groups). Immediate haemostasis was achieved in the EBL and clipping group respectively in the 96.8% and 96.5% (OR=0.94, 95% CI 0.59-4.19, p=0.79). Early rebleeding was observed more frequently in the clipping (25.0%) than in the EBL group (11.8%), with an OR=0.40 (95% CI 0.32-0.51, p<0.001). Similarly, tardive rebleeding was more common in the clipping arm (37.4%) than in the EBL (24.5%), OR=0.39, 95% CI 0.22-0.68, p=0.0001. Patients receiving clipping needed more frequently salvage surgery or embolization than EBL (1.48% versus 0.53%, OR=0.40, 95% CI 0.17-0.93, p=0.03).

Conclusion

Despite EBL and clip have similar effectiveness in achieving immediate haemostasis, EBL showed better effectiveness in maintaining it on longer interval times, with less probable need for major surgical/radiologic interventions.

Introduction

Type 1 AIP is the most common presentation of IgG4-related disease. Serum IgG4 levels are widely used in initial screening and diagnosis, with levels ≥135 mg/dL recommended as part of the diagnostic criteria. However, its diagnostic specificity is limited as it can be elevated in a broad spectrum of neoplastic, infectious, and autoimmune diseases. Histological diagnosis though definitive, remains challenging in real life clinical practice. In recent years, IgG4/IgG ratio has been proposed as a promising alternative serum biomarker.

Aims & Methods

We aimed to study the diagnostic utility of serum IgG4/IgG ratio compared to serum IgG4 alone in the diagnosis of Type 1 AIP. We identified a cohort of patients from 2015 to 2021 who had raised serum IgG4 levels in Tan Tock Seng Hospital, Singapore. Associations between serum IgG4 level and IgG4/IgG ratio were compared to confirmed AIP diagnosis and characteristic computed tomography (CT) and magnetic resonance imaging (MRI) features (diffuse pancreatic swelling, rim-like enhancement). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at IgG4/IgG thresholds of ≥15% and ≥20%.

Results

Our sample included a total of 60 patients with raised serum IgG4 levels. 21 patients had been diagnosed with Type 1 AIP, and 39 patients had not.
The majority of our patients had serum IgG4 ≥135 mg/dL (n=53, 88.3%). However, there was no significant association between the conventional serum IgG4 cut off of ≥135 mg/dL and the diagnosis of AIP (p = 0.687). In contrast, serum IgG4/IgG ratio demonstrated significantly higher values in patients with AIP compared to those without (median 23.2% vs 13.9%; p < 0.001). Analysis by logistic regression of IgG4/IgG ratio showed an acceptable performance with an area under the curve of 0.779, sensitivity of 92.3%, and specificity of 52.4%.

Variable	Type 1 AIP Present (n=21)	Type 1 AIP Absent (n=39)	Test Statistic	p-value
IgG4/IgG ratio	23.2 (24.0 ± 14.2)	13.9 (13.4 ± 4.5)	U = 184	<0.001
Serum IgG4 ≥135 mg/dL	18/21 (85.7%)	35/39 (89.7%)	Fisher's exact	0.687

We performed further analysis to determine a threshold for diagnostic utility of serum IgG4/IgG ratio. A ratio of ≥20% was strongly associated with AIP diagnosis (OR = 13.2, 95% CI: 3.08–56.5; p < 0.001), with high specificity (92.3%) and PPV (78.6%). Reducing the diagnostic threshold to ≥15% increased sensitivity to 76.2% (vs 52.4% at ≥20%) and improved NPV 84.4%, however this reduced specificity to 69.2%.

Subset analysis was performed among patients with Type 1 AIP (n=21) to evaluate for relationship between serum biomarkers and typical imaging findings (diffuse pancreatic swelling, rim-like enhancement). When stratified to a cut off of ≥135 mg/dL, the association between serum IgG4 levels with imaging findings trended towards positivity, but was not statistically significant (OR 3.14, p = 0.0553, φ 0.196). The IgG4/IgG ratio demonstrated a stronger association with typical imaging findings, although still not achieving statistical significance (OR = 1.065, p = 0.129). This subset analysis is likely limited by the small sample size.

Conclusion

This study demonstrates that serum IgG4/IgG ratio is a superior serological marker compared to serum IgG4 alone, particularly in the diagnosis of type 1 AIP. A threshold ratio of ≥20% demonstrated strong association with AIP diagnosis, with high specificity and PPV.
Our findings support the incorporation of IgG4/IgG ratio - particularly at a cut-off of 20% - as a valuable adjunct in diagnosis of suspected type 1 AIP, and we recommend further research in a larger cohort to validate this data.

References

1. Wallace ZS, Naden RP, Chari S, Choi HK, Della-Torre E, Dicaire JF, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Arthritis Rheumatol. 2020;72(1):7–19.
2. Umehara H, Okazaki K, Kawa S, Takahashi H, Yoshino T, Matsui S, et al. The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-related disease. Mod Rheumatol. 2021;31(3):529–33.
3. Lanzillotta M, Mancuso G, Della-Torre E. Advances in the diagnosis and management of IgG4-related disease. BMJ. 2020;369:m1067.
4. Uchida K, Okazaki K. Current status of type 1 (IgG4-related) autoimmune pancreatitis. J Gastroenterol. 2022;57(10):695–708.
5. Xia CS, Zhang S, Duan L, Zhao CW, Zhang F. Diagnostic performances of serum IgG4 concentration and IgG4/IgG ratio in IgG4-related disease. Clin Rheumatol. 2017;36(11):2769–74.

Introduction

Janus kinase (JAK) inhibitors have emerged as an important therapeutic class for the management of several immune-mediated conditions, including inflammatory bowel disease (IBD), but they are associated with several side effects. A renewed attention to the safety profile of this drug class has been driven by increasing reports of JAK inhibitor-induced acneiform eruptions seen in clinical trials and real-life practice.

Aims & Methods

We aimed to investigate the epidemiology, clinical characteristics, and treatment outcomes of this condition in patients with IBD. This was an international, multicenter, retrospective cohort study that consecutively enrolled patients with IBD who were treated with JAK inhibitors and subsequently developed acne. The primary objective was to evaluate the clinical characteristics of acne presentation. Secondary objectives included determining acne prevalence, assessing its impact on quality of life, and evaluating the effectiveness of treatments.

Results

Of the 2,183 JAK inhibitor-treated patients with IBD screened, 272 developed acne and were included in the study. The crude prevalence rates of acne were 15.9% for upadacitinib, 4.3% for tofacitinib, and 1.9% for filgotinib, with dose-dependent relationships observed for upadacitinib and tofacitinib. Acne predominantly affected patients aged 30–50 years, with most cases being mild to moderate in severity. Acneiform eruptions most frequently involved the face (89%), followed by the back (33%) and chest (27%). Lesion characteristics were documented in 159 patients; papules (82%), pustules (52%), and comedones (42%) were the most frequently reported. In contrast, nodules (19%) and cysts (18%) – features associated with more severe disease – were less commonly observed. Among the 213 patients with available time-to-onset data, the median time to acne onset following JAK inhibitor initiation was 47 days (IQR: 28–98 days). Patients with a previous history of acne vulgaris were significantly more likely to develop severe drug-induced acne (p<0.0001). Although corticosteroids are known to contribute to acne, our data did not demonstrate an association between concomitant steroid use and increased acne severity. There was also no difference in time to onset or resolution of acne between the steroid-treated and non-steroid treated groups. A third of patients reported a negative impact on psychosocial well-being, and 40% required pharmacological intervention. Topical therapies were required for 106 patients (39%), with 52 (49%) showing acne improvement or resolution. Systemic oral agents were required for 38 patients (14%), including 25 patients who did not respond or had a partial response to topical therapies. Antibiotics were prescribed to 29 patients (most commonly from the tetracycline class), leading to acne improvement or resolution in 14 patients (48%). Oral isotretinoin was required for 8 patients (3%) and was effective in all but one patient. Eighteen percent of patients who developed acne (2.2% of total cohort) required a JAK inhibitor dose reduction or discontinuation, although most did not have severe disease.

Conclusion

This study is the first to characterise this adverse event in JAK inhibitor-treated patients with IBD and presents the largest cohort of JAK inhibitor-induced acne cases to date across all immune-mediated diseases. JAK inhibitor-induced acne is a common adverse effect resulting in significant psychological burden. Early identification, proactive counselling, and timely interventions, such as dose reduction or referral to dermatology, are crucial in managing this side effect.