What I Don’t Want to See: Catastrophic Antiphospholipid Syndrome

SA Kahn et al. NEJM 2023; 388: 358-368. Case 3-2023: A 16-Year-Old Girl with Abdominal Pain and Bloody Diarrhea

This case report of a girl presenting with abdominal pain and diarrhea identifies a rare etiology, catastrophic antiphospholipid syndrome (CAPS). CAPS can result in ischemic colitis. This patient underwent a colonoscopy which was normal in rectum but then became abnormal in the sigmoid colon:

“CAPS is thought to result from the binding of antiphospholipid antibodies to cell surfaces, which activates endothelial cells, monocytes, and platelets and leads to inflammation, complement activation, and thrombosis. The formation of thrombi in patients with antiphospholipid antibodies is thought to be a multihit process.7 The presence of antiphospholipid antibodies in the blood is the first event, but the antibodies typically do not cause disease until another event occurs.”

Management of antiphospholipid antibodies: “Thrombotic disease manifestations are important in guiding therapy. For patients with antiphospholipid antibodies and no history of clotting, anticoagulation for primary thromboprophylaxis is generally not recommended…For patients with antiphospholipid antibodies and a history of unprovoked thrombosis (e.g., patients with APS), long-term thromboprophylaxis is recommended…For patients with more severe presentations — such as this patient, who had CAPS with thrombosis in multiple organs — treatment is more aggressive and involves targeting multiple steps within the CAPS cascade.”

From ChatGPT

My take: This 16 yo had a severe presentation and the case is a reminder that there are multiple reasons besides IBD for a teenager to have bloody diarrhea and abdominal pain.

Related blog posts:

Favorite Posts 2022

Thank you to those who have helped me this past year with this blog –colleagues, friends and family. Wishing all of you a good 2023. Here are some of my favorite posts from this past year:





Health Policy:


Improving Natural History of Pediatric Crohn’s Disease with Biologic Therapy -Two Studies

D Ley et al. Clin Gastroenterol Hepatol 2022; 20: 2588-2597. Open Access! New Therapeutic Strategies Have Changed the Natural History of Pediatric Crohn’s Disease: A Two-Decade Population-Based Study

This retrospective study dating back to 1988 examined 1007 patients diagnosed with CD who were followed up for a median duration of 8.8 years.

Key findings:

  • The risk for intestinal resection at 5 years decreased significantly over time (P1, 35%; P2, 31%; and P3, 22%; P = .0003. This decrease in resections coincided with increased use of immunosuppressive (IS) and anti-TNF therapy: IS and anti-TNF exposure rate at 5 years increased from 33.9% (in P1) to 76.5% (in P3) and from 0% (in P1) to 50.5% (in P3).
  • The risk for progression from inflammatory to stricturing behavior decreased significantly over time (P1, 27%; P2, 28%; and P3, 20%)

LE Targownik et al. Clin Gastroenterol Hepatol 2022; 20: 2607-2618. Earlier Anti-TNF Initiation Leads to Long-term Lower Health Care Utilization in Crohn’s Disease but Not in Ulcerative Colitis

Methods: The authors “used health administrative data from Manitoba, Canada to identify all persons with a new diagnosis of inflammatory bowel disease (IBD) between 2001 and 2018 who received tumor necrosis factor antagonists (anti-TNF) therapy and had at least 1 year of post anti-TNF initiation follow-up.”

Key findings:

  • Among 742 persons with CD, early anti-TNF initiators had fewer IBD-specific and overall hospitalizations over the 5 years following the start of therapy
  • Incidence of resective surgery was also lower in earlier anti-TNF initiators with CD if the first year following initiation was excluded from the analysis.
  • In 318 cases of UC, there was no impact of the timing of anti-TNF therapy on the rates of hospitalization and surgery.

My take: These two studies show that use of biologic therapy is associated with better outcomes in Crohn’s disease including fewer intestinal resections and fewer hospitalizations. It appears that earlier use may alter the natural history in part by reducing the likelihood of stricturing disease. Interestingly, the RISK study showed a reduction in penetrating disease with early use of biologics but not a reduction in stricturing disease (Related blog post: CCFA: Updates in Inflammatory Bowel Disease 2017 (part 3))

IBD Updates: Dietary Patterns and Disease Activity, Ustekinumab in SUSTAIN study, INSPECT Study for Perianal Fistulas

BN Limketkai et al. Inflamm Bowel Dis 2022; 28: 1627-1636. Open Access! Dietary Patterns and Their Association With Symptoms Activity in Inflammatory Bowel Diseases. This retrospective study with dietary surveys of 691 participants found the following:

  • Compared with WD1 (typical Western Diet), PB2 (Plant-based diet 2) was associated with lower odds of active symptoms for CD (odds ratio [OR], 0.32
  • PB1 (Plant-based diet 1) was associated with lower odds of active symptoms for participants with UC (OR, 0.45; 95% CI, 0.23-0.90) but not for participants with CD (OR, 0.95

Diet PB1 (“Plant-based Diet 1”) was characterized by much higher intake of fruits, vegetables, plant-based proteins, and cooked grains than most other dietary clusters. There was low water intake in favor of juices and other beverages. There was otherwise average intake of added fats and oils, sugars, seafood, and dairy products, and modest intake of meats, eggs, mixed grains, and breads.

Diet PB2 (“Plant-based Diet 2”) was characterized by high intake of fruits, vegetables, plant proteins, and cooked grains and low intake of animal proteins (especially red and cured meats), added fats, sweetened beverages, sweet bakery products, other desserts, eggs, and breads. There was also a reduction of other beverages in favor of water. There was otherwise an average intake of seafood and dairy products.

M Chaparro et al. Inflamm Bowel Dis 2022; 28: 1725-1736. Open Access! Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study In this retrospective study, 97% of the 463 patients had received prior biological therapy.

  • At week 16, 56% had remission, 70% had response
  • 26.1% required dose escalation or intensification
  • After a median follow-up of 15 months, 356 (77%) patients continued treatment.
  • Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation.
  • Neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk

J Panes et al. Inflamm Bowel Dis 2022; 28: 1737-1745. Open Access! INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn’s Disease Treated in the ADMIRE-CD Trial

Background: The current chart review study evaluated the longer-term effectiveness and safety of darvadstrocel (expanded allogeneic adipose-derived mesenchymal stem cells).; n=43 treated patient and n=46 controls.

Key findings:

  • At 52, 104, and 156 weeks posttreatment, clinical remission was observed in 29 (67.4%) of 43, 23 (53.5%) of 43, and 23 (53.5%) of 43 darvadstrocel-treated patients, compared with 24 (52.2%) of 46, 20 (43.5%) of 46, and 21 (45.7%) of 46 control subjects, respectively.

Selected Slides from NASPGHAN 2022 Postgraduate Course (Part 2)

See previous post for lecturers

Oral small molecultes in IBD. Anne Griffiths, MD
Judith Kelsen, Very early onset IBD
VEO Evaluation
VEO Treatments
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Jeremy Adler and Treat to Target for IBD
Timothy Sentongo and Growth and Nutrition Issues in the NICU
Maureen Leonard and Gluten-Related Disorders Update
Maureen Leonard and Gluten-Related Disorders Update
Maureen Leonard and Gluten-Related Disorders Update
Maureen Leonard and Gluten-Related Disorders Update
Rachel Rosen and Esophageal Motor Disorders
Katja Kovacic and Functional Nausea
This study was 20 yrs ago -we can do better today

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Safety of Preoperative Tumor Necrosis Factor  Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal Surgery

BL Cohen et al. Gastroenterol; 2022; 163: 204-221. Prospective Cohort Study to Investigate the Safety of Preoperative Tumor Necrosis Factor Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal Surgery

Key finding:

  • Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort. Any infection (18.1% vs 20.2%, P = .469) and SSI (12.0% vs 12.6%, P = .889) rates were similar in patients currently exposed to TNFis and those unexposed.

IBD -Briefly Noted: Intestinal U/S and Anxiety/Depression Not Worsening Pediatric IBD Activity

EA van Wassenaer et al. Inflamm Bowel Dis 2022; 28: 783-787. Open Access PDF: Intestinal Ultrasound in Pediatric Inflammatory Bowel Disease: Promising, but Work in Progress

Key points from this review:

  • Research has shown that IUS has the potential to be a valuable additional point-of-care tool to guide treatment choice and to monitor and predict treatment response, although evidence of its accuracy and value in clinical practice is still limited
  • The utility may be operator-dependent as well

My take: Due to low upfront costs, IUS would be appealing adjunct to current monitoring. However, one could envision IUS leading to more downstream studies (& costs), especially if its sensitivity and specificity are not very high.

EJ Brenner et al. Inflamm Bowel Dis 2022; 28: 728-733. Anxiety and Depressive Symptoms Are Not Associated With Future Pediatric Crohn’s Disease Activity

In this internet-based cohort of 9-17 yr olds (n=159, 96% white), the authors found no association between baseline PROMIS Pediatric anxiety score and subsequent sCDAI (change in sCDAI for 3-point change in PROMIS Pediatric −0.89; 95% CI −4.81 to 3.03). This study is in contrast to studies in adults which have shown a bidirectional relationship between anxiety/depression and IBD activity.

My take: It is difficult to know with certainty whether anxiety/depression may trigger IBD activity; more studies are needed. Treatment of mental health is important regardless of its effects on IBD activity.

Related blog posts:

“We Can’t Wait” App

CCFA: We Can’t Wait: New app helps inflammatory bowel disease patients find available restrooms nearby

An excerpt: “The Crohn’s & Colitis Foundation…launched the We Can’t Wait app, which provides an interactive map that allows users to find a restroom near them across the U.S.  Driven by crowd-sourced submissions and major retail and restaurant partners that contributed their restroom location data, the app empowers IBD patients – and all users – with a tool to find restrooms more easily, both in emergency and everyday situations. The app is free and available for download now.  

Related blog post: When you gotta go…looking for a clean bathroom

Can You Give Ustekinumab Subcutaneously After IV Reaction?

J Sunny et al. JPGN Reports: May 2022 – Volume 3 – Issue 2 – p e205 Open Access: Hypersensitivity Reaction to Ustekinumab in Pediatric and Young Adult Inflammatory Bowel Disease Patients: A Case Series

This is a case series of six pediatric patients and young adults who developed hypersensitivity reactions during intravenous infusion with ustekinumab (UST).

Key findings:

  • Hypersensitivity reactions during intravenous (IV) induction dose of UST, ranging from mild allergic reactions to anaphylaxis, with no antibodies detected in the two who had testing
  • Reactions occurred 0-30 minutes after start of infusion
  • Management was with methylprednisolone in 5 of 6 patients, diphendyramine in 3 of 6, and epinephrine in 1. One patient was managed with IV diphenhydramine alone.
  • Four of six continued with UST subcutaneously without reactions. ***Change of formulation of UST from IV to subcutaneous was done in a controlled hospital-based setting. The other two 33% were switched to another biologic due to physician preference and were never exposed to the subcutaneous formulation
  • Although the exact pathogenesis of this infusion reaction remains unknown, it has been attributed to EDTA

My take: It appears that patients with UST hypersensitivity reactions can be changed to SC formulation. The authors recommend to trial a subcutaneous dose of UST in a controlled setting; in addition, they suggest testing with skin prick testing or specific IgE levels to EDTA done by allergy and immunology.

Related blog posts:

Sandia Mountain, near Albuquerque

Good News for Fans of Gluten

EW Lopes et al. Clin Gastroenterol Hepatol 2022; 20: 303-313.Open Access: Dietary Gluten Intake Is Not Associated With Risk of Inflammatory Bowel Disease in US Adults Without Celiac Disease

Key finding: In 3 large adult US prospective cohorts (n=208,280), gluten intake was not associated with risk of CD or UC in 5,115,265 person-years of follow-up evaluation.

My take (from authors): These ” findings are reassuring at a time when consumption of gluten has been increasingly perceived as a trigger for chronic gastrointestinal diseases.”

Related blog posts:

Chattahoochee River, Atlanta