Opioid Withdrawal Misdiagnosed as a Crohn’s Flare Open Access

Opioid use disorder (OUD) affects over 2 million people in the USA [1] and is a predominant cause of decreasing life expectancy [2]. Although fentanyl is responsible for most deaths [3], prescription misuse significantly contributes to OUD, especially in people prescribed opioids for pain [4].

Diagnosing OUD and opioid withdrawal remains challenging, particularly in early stages and among non-intravenous drug users. The complexity is amplified in patients with other medical comorbidities, particularly gastrointestinal (GI) conditions such as inflammatory bowel disease (IBD), where overlapping symptoms can obscure the distinction between opioid withdrawal and an IBD flare. We present a case of a patient with Crohn’s disease (CD) with recurrent hospitalizations attributed to IBD flares versus urinary tract infections (UTIs), who was ultimately diagnosed with opioid withdrawal and started on medications for OUD (MOUD).

A 28-year-old Hispanic male with CD, anxiety, spina bifida requiring an appendicostomy, neurogenic bladder status post-Mitrofanoff procedure and bladder augmentation with bowel requiring intermittent catheterization, who presented to the hospital with severe left flank pain radiating to the suprapubic area, intermittent hematuria, nausea, vomiting, and non-bloody diarrhea. This was the patient’s first encounter in our healthcare system.

The patient initially established care with a private gastroenterologist in 2015 (we had no access to initial records) and who was no longer following this patient. Afterward, the patient established care at a private hospital system, where we obtained medical records via a health information exchange platform (Care Everywhere). Therefore, there was fragmented diagnostic history. From the data we could gather, the patient was initially diagnosed with small bowel CD in 2015 by his private gastroenterologist. At that time, he was experiencing 3–4 years of abdominal pain, vomiting, and cold sweats. In 5/2015, he had a capsule endoscopy that showed multiple aphthous ulcers in the small bowel. The patient was started on prednisone and mesalamine. In 2021, he developed acute pancreatitis secondary to mesalamine and was transitioned to adalimumab (ADA) (40 mg every other week). In 2022, he developed antibodies to ADA which led to his gastroenterologist to discontinue the medication. Based on limited records and patient history, it is unknown if a trough level was obtained or if the patient’s clinical condition worsened to support stopping the ADA, or if it was solely based on the presence of antibodies. He was off all therapies for 1 year prior to presentation at our hospital.

Since stopping treatment, the patient reported uncontrollable bloody diarrhea, intermittent hematuria, abdominal pain, 50-pound weight loss, and employment loss. During this time, he had 12 prior hospitalizations at an outside hospital where he was treated for “Crohn’s flares” and “recurrent UTIs,” requiring 13 prolonged courses of intravenous antibiotics and pain management with intravenous opioids. The patient was discharged with approximately 42.5 morphine milligram equivalents daily for 3–5 days after each admission.

In our emergency department, the patient was tachycardic to 110 and had generalized tenderness to palpation. Bloodwork was notable for a normal erythrocyte sedimentation rate and mildly elevated lactate to 3.8 mmol/L that normalized to 1.8 mmol/L on a 2-hour repeat. Laboratories were notable for iron deficiency anemia and otherwise unremarkable. The urinalysis showed hematuria, and a CT scan with contrast of his abdomen and pelvis did not show findings concerning for CD flare, gut edema, or kidney stones. Blood and urine cultures were collected. His urine toxicology report was negative for opioids. The patient had taken his last dose of oxycodone 2–5 days prior to arrival to the hospital, which explains the negative toxicology.

The patient was admitted, and urology was consulted given the patient’s history of recurrent UTIs. Given no clear signs of infection, antibiotics were held on admission. Urology recommended a GI consult given their concern that the patient’s urinary symptoms were related to a Crohn’s flare associated to his bladder being reconstructed with bowel. Hematuria was attributed to chronic diarrhea possibly leading to inflammation or micro trauma to the gut lining of reconstructed bladder. The GI consultant had a low concern for a Crohn’s flare given the patient’s normal C-reactive protein and CT but recommended a full workup as the patient had not undergone routine surveillance and was not on any CD treatment. Blood cultures, urine culture, an infectious enteric panel, and a stool sample for ova and parasites were negative. An upper endoscopy, colonoscopy, MRI enterography, and a capsule endoscopy were performed and revealed no evidence of a CD flare or other organic causes.

During the patient’s admission, consultant services and other staff members used stigmatizing language such as “drug-seeking behavior” despite the patient not requesting additional pain medications and dismissed the case after initial evaluation yielded no etiology. Within 48 h of admission, the patient’s symptoms improved, coinciding with opioid administration for pain management. Further chart review revealed that the patient had cycles of being diagnosed with Crohn’s flares and UTIs, after which he received antibiotics and opioids with improvement in symptoms and was discharged with recurrent opioid prescriptions. The patient’s symptoms recurred three to 5 days after his opioid prescriptions ended, prompting him to return repeatedly to the hospital, suggesting opioid withdrawal instead of a Crohn’s flare or UTI. Opioids were discontinued, leading to recurrence of symptoms within 24 h. The patient had never been counseled that his symptoms could be caused from opioids and was interested in starting treatment. He was discharged with an appointment at a buprenorphine clinic to start MOUD and was started on buprenorphine at 8 mg three times daily. Twelve months post-discharge, the patient’s symptoms are controlled and remains on MOUD. The patient regained 25 pounds, returned to work, and followed up with GI to resume treatment for his CD.

This report highlights the importance of a holistic diagnostic approach for patients with complex medical histories. Although the literature mentions similar presentations between CD and opioid withdrawal, there is a lack of documented cases discussing the complexity of reaching a final diagnosis when patients have both conditions. CD flares commonly present with symptoms of abdominal pain, diarrhea, nausea, and malaise, overlapping with many symptoms of opioid withdrawal [5]. Physicians must consider opioid withdrawal as a differential diagnosis when caring for patients with IBD, particularly in the absence of objective findings. This may provide earlier recognition of OUD, leading to expedited diagnosis and treatment and resource conservation. While there is no universally established minimum amount of opioids or morphine milligram equivalent required to develop OUD, the risk of developing OUD increases with higher doses and longer duration of opioid use [6], which was the case for this patient who was taking opioids for approximately 1 year. This is particularly important in IBD, where approximately 40% of patients experience chronic pain [7], many of whom are prescribed opioids despite no recommendation for their use in CD flares, thus increasing risk of OUD.

Additionally, the case provides insight into the initiation of MOUD and underscores the potential for clinical and psychological improvements with comprehensive treatment interventions. MOUD have repeatedly shown effectiveness not only by reducing opioid-related mortality [8] but also decreasing opioid use and withdrawals [9], decreasing HIV and hepatitis seroconversion [10, 11], and increasing employment [12]. Despite their effectiveness, only 22% of patients with OUD received MOUD in 2021 [13]. This discrepancy impacts both individuals with OUD and the healthcare system since patients with concurrent OUD and IBD are 47% more likely to have 30-day any-cause readmission rates [14].

Lastly, this case demonstrates persistent stigma regarding OUD among healthcare providers, despite heightened public awareness. This implicit bias decreases empathy from providers, decreases likelihood of MOUD prescription, and increases likelihood of suboptimal care [15]. It is imperative that gastroenterologists and hospitalists receive additional training on the impact of a stigmatizing approach to opioid use, especially given the overlapping symptoms between IBD and opioid withdrawal, and the impact it may have if untreated.

In conclusion, we reported a case of opioid withdrawal in a patient with CD that was originally thought to be either a Crohn’s flare or a UTI. It explains the initiation of MOUD and provides the evidence of their widespread effectiveness. This report also highlights the continued stigma regarding OUD in the medical community and the necessity of increased awareness and training of the use of nonstigmatizing language. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000546335).

Ethical approval is not required for this study in accordance with local or national guidelines at our institute. Written informed consent was obtained from the patient for publication of the details of their medical case.

The authors declare that there is no conflict of interest regarding the publication of this article.

No funding was received for this case report.

S.S. originated the idea for the case report and identified key discussion points. M.C.R. drafted the initial manuscript and S.S. and M.J.Y.W. provided an iterative review of the manuscript. All authors participated in interpreting the implications of the case report, contributed to the writing of the manuscript, provided critical feedback to the manuscript, and approved the final manuscript draft for submission.

Notice of prior presentation: This case has been accepted for poster presentation at the 2024 Florida Medical Association (FMA) Annual Meeting and the ACG’s 2024 Annual Scientific Meeting.

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further enquiries can be directed to the corresponding author.