Clinical Case Summary

A 22-year-old female without comorbidities presented with epigastric and lower retroesternal chest pain, nausea and vomiting since 3 days that didn't response to oral medication. Patient denied dysphagia or odinophagia. Assessed in the emergency, treated with intravenous (IV) medications and discharged with prescription. Next day, the pain increased and vomited 15 times. Patient was admitted as a case of acute gastritis on intravenous proton pump inhibitors (PPIs) and metoclopramide. Routine laboratory and upper abdominal ultrasound done without significant findings only remarkable mild hyponatremia 134 (135-145).
Physical examination looked unwell. Vitally stable 105/75 mmHg. Afebrile (36.2). Malnourished. Weight 28.7 Height 145cms BMI 14.2. Mild epigastric tenderness.
Due to refractory symptoms despite IV medication. Endoscopy was done and showed round and serpiginous ulcers in the lower third of the esophagus with yellowish exudate suggestive of infectious esophagitis Cytomegalovirus vs Herpes. Normal aspect of stomach and duodenum. Histopathology confirmed herpes simplex esophagitis.
Under the suspicion of infectious esophagitis HIV serology came negative, CMV antibodies IgM negative IgG positive. Normal immunoelectrophoresis. No previous herpes viral infection. The only risk factor identified for the patient was the malnutrition, nevertheless vitamins and proteins were normal.
With histological confirmation after 48 hours of the endoscopy she was started on Acyclovir IV 5mg/kg every 8 hours with significant improvement in the next 48 hours. Patient discharged in stable condition after re-starting oral intake and completing the oral acyclovir 400 mg every 8 hours for 10 days. Patient responded well was assessed 7 days after discharge, free of symptoms and a weight gain of 1.3 kg.
Infectious esophagitis needs to be considered in immunocompetent host. Odynophagia/dysphagia can be absent. Endoscopy findings alone isn't sufficient to make a definitive diagnosis.

References

Endoscopy and histopathology.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, condition linked to a type 2 inflammatory response and frequently associated to other atopic conditions. EoE may presents either sporadically, or with aggregation of cases within a same family. Limited information has been provided on the differences in clinical characteristics and disease features between sporadic and familiar EoE, largely due to the lack of large patient cohorts.

Aims & Methods

To find differences in sporadic and familiar cases of EoE which may support distinct clinical management, a cross-sectional analysis of the multicenter EoE CONNECT registry was performed. Demographic and clinical from patients recruited at 42 hospitals in 4 European countries were extracted on March 28th, 2025. Information extracted included 1) age at diagnosis and diagnostic delay; 2) symptoms leading to diagnosis; 3) disease endoscopic and histologic features at diagnosis; and 4) atopic concomitances.

Results

	S-EoE	F-EoE
Age at diagnosis (n= 3,179) <18 years old	18.5%	30.6%
Inflammatory Score (n= 2,723)	1.62 ± 1.3	1.93 ± 1.32
Fibrosis Score (n=2,723)	1.04 ± 1.04	0.97 ± 1.08
Fibrosis (n=1,701)	58.6 %	62.8 %
EoE-Phenotype (n=3,017)
Inflammatory	75.9 %	79.6 %
Mixed	12.6 %	8.6 %
Stricturing	11.5 %	11.8 %

Overall, 4,053 patients (75.4 % males, mean age 33.3 ±15.2 years) were analyzed, including 3028 (74.7 %) sporadic (S-EoE), 714 (17.6%) without familiar data and 311 (7.7 %) familiar (F-EoE) cases including 89 families. Among the family forms, n= 76 families showed 2 affected members, n= 11 presented 3 members, and n= 2 with 4 members. In 85/89 families we identified the index case consisting in sons (13), parents (23), siblings (38), or other distant kinships.
The F-EoE forms were diagnosed at younger mean ± SD ages than S-EoE (29.8±15.6 vs. 33.7±15.1; p<0.001) and included a higher proportion of pediatric patients (considered as those below 18 at diagnosis; 30.6% vs. 18.5%; p<0.001)
Symptoms leading to EoE diagnosis were similar across study groups, with slightly higher presences of abdominal pain (as they included more pediatric cases; 7.7% vs. 4.5%; p=0.01) and chocking episodes (7.7% vs. 4.5%; p=0.01) among F-EoE.
Endoscopy presented more severe features according to EREFS among F-EoE (mean ± SD being 2.86 ± 1.66 vs. 2.64 ± 1.68; p=0.054) at the expense of both fibrotic and inflammatory features, despite only the later reach statistical significance (1.93 ± 1.32 vs. 1.62 ± 1.3; p<0.001). Esophageal biopsies exhibited higher mean ± SD peak eosinophil counts in F-EoE cases (57.11 ± 40.7 vs. 52.87 ± 37.97; p=0.04).
F-EoE were more allergic patients, as they presented a higher mean ± SD number of concomitant atopies (1.44 ± 1.25 vs. 1.25 ± 1.22; p=0.009) and all were more common among them, with conjunctivitis and hives reaching statistical significance (p=0.01 and p=0.002 respectively). Overall, a higher proportion of F-EoE had at least one atopy compared to S-EoE (69.4 % vs. 63.8%).

Conclusion

F-EoE seems to present more severely, with earlier onset, more inflammatory load in endoscopy and biopsies and higher concomitant allergic manifestations.

Introduction

Intestinal point-of-care ultrasound, as standardized by the International Bowel Ultrasound Group (IBUS), has emerged as a valuable tool for diagnosing, monitoring, and managing patients with Inflammatory Bowel Disease (IBD). While IBUS emphasizes a structured intestinal assessment, some European centers adopt a more comprehensive approach, combining intestinal ultrasound with a complete abdominal examination.
The Karolinska Centre for Digestive Health, a tertiary referral institution providing specialized care to approximately 4,500 patients with IBD, established a dedicated Gastrointestinal Ultrasound Unit in October 2023. This unit offers advanced diagnostic services to both hospitalized patients and those treated on an outpatient basis.

Aims & Methods

This retrospective study aimed to assess the prevalence of secondary extraintestinal findings in IBD patients undergoing comprehensive abdominal ultrasound between October 4, 2023, and March 4, 2025. All patients underwent ultrasound assessments that included both intestinal and abdominal imaging. Patients referred for indications unrelated to intestinal ultrasound (IUS), as well as those undergoing repeat examinations, were excluded from the analysis to ensure data consistency.
All examinations were performed by a single gastroenterologist with 25 years of ultrasound experience. In cases where secondary extraintestinal findings were identified, patients’ electronic medical records were reviewed to determine whether these findings represented new diagnoses or previously known conditions.

Results

The study included 348 patients with IBD, 201 (58%) females and 147 (42%) males, with a mean age of 42.4 years. Among these, 260 (75%) were referred internally by our IBD Outpatient Clinic, 47 (13%) by the Gastroenterology Ward, 33 (10%) by private outpatient clinics, and the remainder from other healthcare sites. IUS revealed evidence of intestinal inflammation in 144 patients (42%), while findings were normal in 204 patients (58%).
Furthermore, 150 patients presented with a total of 195 secondary extraintestinal findings, of which 113 (58%) represented newly identified pathologies. Among all secondary findings, the majority, 104 (53%), were related to the hepatobiliary system, including 33 newly diagnosed cases of hepatic steatosis and 17 new cases of cholecystolithiasis. One patient demonstrated ultrasound features suggestive of primary sclerosing cholangitis (PSC) and is currently undergoing further evaluation. Additional findings involved the reproductive system (29/15%), urinary system (15/7%), spleen (32/16%), and pancreas (5/2%). Various other intra-abdominal findings were also identified (37/18%). Notably, one patient presented with a suspicious mass in the right iliac fossa, and another demonstrated ultrasound findings suggestive of a prostatic tumor; both cases were referred for further oncologic evaluation. Additionally, three patients were newly diagnosed with intraductal papillary mucinous neoplasm (IPMN), which was subsequently confirmed via magnetic resonance imaging, and all were enrolled in the national IPMN surveillance protocol.

Conclusion

A considerable proportion of patients with IBD were found to have previously unknown extraintestinal abdominal pathologies, underscoring the essential role of comprehensive ultrasound examination that combines both intestinal and abdominal assessment. Fortunately, only a minority of these findings resulted in changes to patient management.

Disclosure

Francesca Bresso has acted as national and/or local principal investigator for clinical trials for Janssen, Ferring, and AbbVie. Charlotte Hedin served as a speaker and/or advisory board member for AstraZeneca, AbbVie, Dr. Falk Pharma and the Falk Foundation, Galapagos, Janssen, Pfizer, Ferring, Takeda, and Tillotts Pharma and received grant support from Tillotts Pharma and Takeda. Stephan L. Haas has served as a speaker for Takeda, Santax Medico, Tillotts Pharma, Johnson & Johnson, and Mediahuset. The rest of the authors have nothing to declare.

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.

Introduction

Tofacitinib, filgotinib, and upadacitinib, are Janus kinase inhibitors (iJAKs) approved for inflammatory bowel disease (IBD) treatment. Although no direct comparative studies exist, potential differences in efficacy and safety are attributed to in vitro-demonstrated affinity of each molecule for different JAK isoforms. JAK1 plays a crucial role in modulating cytokine-mediated immune responses, such as IL-6 and interferon, which are involved in inflammation and skin homeostasis. Its inhibition can promote conditions that may trigger acne.
Acne may be increased in iJAK-treated patients, meaning a clinical challenge for gastroenterologists.

Aims & Methods

A retrospective study was conducted at ten referral centers in Spain, including all IBD patients who had received iJAK therapy and had at least 3 months of follow-up. Demographic data, disease-related variables, and acne characteristics when appropriate, were collected. Univariate and multivariate logistic regressions were used to identify risk factors for acne; model discrimination was assessed by AUC.

Results

A total of 549 patients included: 258 (47%) were women; 354 (64%) had ulcerative colitis, 191 (35%) had Crohn’s disease and 1% had indeterminate colitis. Mean age was 41 years (IQR 30-52). 219 patients (40%) were treated with tofacitinib, 281 (51%) with upadacitinib, and 49 (9%) with filgotinib.
Ninety patients (16%) developed acne during iJAK treatment: 69% were mild, with only 4 severe cases (4%). Acne occurred early (median onset 42 days, IQR 7-122), predominantly on the face (56%), trunk (13%) or both (31%). Acne morphology included comedones (60%), papules (59%), pustules (39%), nodular-cystic (12%), scarring (9%); 48% showed more than one morphology.
Thirty-six patients received specific acne treatment: 89% topical (antiseptics, benzoyl peroxide, retinoids), 69% systemic (antibiotics, retinoids, antiandrogens), and 44% combined treatment. 83% of those patients responded to acne specific treatment, and only 8 patients (9% of those with acne; 1.5% overall) had to discontinue iJAK treatment, with acne resolving in all cases.
Acne developed in 26%, 6% and 6% of upadacitinib, tofacitinib and filgotinib treated patients respectively (p=0.001). Multivariate analysis showed that acne development was associated with upadacitinib (OR 10.28;IC95%=4,7–22,6; p<0,001) and history of acne (OR 3.52; IC95%=1,5–8,3; p=0,004), while older age (>35 years, OR 0.31; IC95% 0,11–0,83; p=0,02) and Crohn’s disease (OR 0.47; IC95% 0,25–0,90; p=0,02) showed to be protective. This model was reliable in predicting acne development (AUC 0.79). Additionally, univariate analysis showed high dose of iJAK was also associated with acne development, which could not be confirmed in multivariate analysis.

Conclusion

Acne occurred in a relevant proportion of iJAK-treated patients, was generally mild and manageable with dermatological care, and rarely required treatment discontinuation. Risk factors for iJAK-associated acne included use of upadacitinib (probably reflecting a greater affinity for JAK1) and history of acne, while older age and Crohn’s disease were protective.
Gastroenterologists should be aware of both likelihood and management of this specific adverse event when considering iJAK therapy.

Disclosure

Y G-L, MC, GB, ER, IB, DC, M B-dA, LM, I M-J, DG, IV have provided scientific advisory / participated in educational activities / received unrestricted research grants / received payments for lecturing from Johnson & Johnson, ​Takeda, Pfizer, Amgen, AbbVie, Lilly, AlfaSigma, Ferring, Gilead.