Misdiagnosis of Diverticulitis After a Prior Diagnosis of Irritable Bowel Syndrome (IBS)

George F. Longstreth, MD; Carrie Wong, MD; Qiaoling Chen, MS

J Am Board Fam Med. 2020;33(4):549-560.

Abstract and Introduction

Abstract

Introduction: Irritable bowel syndrome (IBS) and diverticulitis share clinical features. Misdiagnosed diverticulitis can cause unnecessary antibiotic therapy. Among IBS and non-IBS patients, we compared outpatient, clinically diagnosed (no computed tomography) diverticulitis rates. Among primary-care, diverticulitis-diagnosed IBS patients, we assessed imaged diverticulosis and probable misdiagnosed diverticulitis.

Methods: Among 3836-patient IBS and 67,827-patient non-IBS cohorts identified from 2000 to 2002, we retrospectively compared the frequency of outpatient, clinically diagnosed, antibiotic-treated diverticulitis from 2003 to endpoints of December 31, 2017, disenrollment, or death. In IBS patients, we reviewed records of initial, primary care-managed episodes for misdiagnosis.

Results: In 3836 clinically diagnosed IBS and 63,991 non-IBS cohorts, followup (median [interquartile range]) was 12.4 (3.9 to 15.0) years versus 10.2 (3.0 to 15.0) years, respectively (P < .001). The incidence rate/1000 patient-years (95% CI) of diagnosed diverticulitis was 14.0 (12.1 to 16.3) and 4.2 (4.0 to 4.5), respectively, (crude incidence rate ratio, 3.3 [2.8–3.9]; P < .001). Of examined features, the diagnosis of IBS was most strongly associated with clinically diagnosed diverticulitis (adjusted incidence rate ratio [95% CI]; 2.64 [2.21–3.15], P < .001). Of initial diverticulitis diagnoses in 189 IBS patients, objective evidence-based diagnosis revision or exclusion occurred in 12 (6.3%), including 6 hospitalized; 29 (15.3%) had colon imaging before and/or afterward without diverticulosis reported; 143 (75.1%) had image-documented diverticulosis; and 6 (3.2%) had no imaging.

Conclusions: Outpatient, clinically diagnosed, antibiotic-treated diverticulitis was increased 3-fold in IBS patients. Primary care clinical misdiagnosis of initial episodes occurred in 1 of 5 patients, but additional misdiagnosis due to misattribution of IBS pain to diverticulitis is suggested.

Introduction

Irritable bowel syndrome (IBS), a common functional disorder, is clinically diagnosed by typical symptoms and exclusion of organic disease, usually by limited testing. It is characterized by recurrent abdominal pain and disordered bowel habits.^[1] Colonic diverticulosis is also common, but only a minority of patients with it develop acute diverticulitis.^[2,3] Abdominal pain is the most common gastrointestinal symptom prompting outpatient visits,^[4] and diverticulitis is often diagnosed in outpatients.^[5,6] Abdominal pain varies from mild to severe in both IBS^[7] and diverticulitis, and abdominal tenderness is found with both disorders.^[1,7–9] Furthermore, many patients with diverticulitis report constipation or diarrhea.^[8,10,11] These shared clinical features, the frequent absence of fever and leukocytosis,^[8] and common uncertainty about whether a patient has diverticulosis promote confusion of IBS with diverticulitis.^[11,12] Outpatients diagnosed with diverticulitis are often treated with antibiotics, so misdiagnosis can result in unnecessary antibiotic therapy.

In a retrospective long-term cohort study, we aimed to 1) compare health examinees with and without IBS regarding the frequency of outpatient clinically diagnosed (no computed tomography), antibiotic-treated diverticulitis and assess associated patient features; and 2) assess imaging reports of diverticulosis, a prerequisite for diverticulitis, and documented misdiagnosis among IBS patients who had an initial primary care diagnosis of diverticulitis.

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Abstract and Introduction
Methods
Results
Discussion
Appendix
References

Table 1. Baseline Demographic, Medical, and Surgical Features in 67,827 Examinees with and without IBS (2000–2002)
Feature	IBS (n = 3836)	No IBS (n = 63,991)	P Value
Demographic
Age, mean + SD, y	54.3 + 14.1	51.0 + 15.1	<.001
Sex, n (%)			<.001
Male	1139 (29.7)	35,015 (54.7)
Female	2697 (70.3)	28,976 (45.3)
Race/ethnicity, n (%)			<.001
White	3026 (78.9)	41,215 (64.4)
Asian	124 (3.2)	5656 (8.8)
Black	142 (3.7)	3801 (5.9)
Hispanic	399 (10.4)	10,280 (16.1)
American Indian	11 (0.3)	177 (0.3)
Pacific Islander	22 (0.6)	786 (1.2)
Multiple categories	112 (2.9)	2076 (3.2)
Education, n (%)			<.001
Some high school	201 (5.2)	4518 (7.1)
Some college	1993 (52.0)	32,307 (50.5)
College and above	1642 (42.8)	27,166 (42.5)
Medical history, n (%)
Charlson Comorbidity Index			<.001
0	3334 (86.9)	57,712 (90.2)
1 to 2	480 (12.5)	5931 (9.3)
3 or more	22 (0.6)	348 (0.5)
Anxious	1469 (38.3)	12,856 (20.1)	<.001
Worried about being ill	1053 (27.5)	10,363 (16.2)	<.001
Depression	1005 (26.2)	7545 (11.8)	<.001
Frequent headaches	1149 (30.0)	10,555 (16.5)	<.001
Smoking			<.001
Never	2173 (56.6)	36,105 (56.4)
Past	1361 (35.5)	21,650 (33.8)
Current	302 (7.9)	6236 (9.7)
Alcohol			<.001
Daily	286 (7.5)	5651 (8.8)
Never, hardly ever	2321 (60.5)	35,085 (54.8)
Less than daily	1229 (32.0)	23,255 (36.3)
Vegetarianism	135 (3.5)	995 (3.1)	.166
Verbal or physical abuse	791 (20.6)	6659 (10.4)	<.001
Sexual abuse	599 (15.6)	4421 (6.9)	<.001
Diabetes	185 (4.8)	3088 (4.8)	.993
Fibromyalgia	309 (8.1)	698 (1.1)	<.001
Hypertension	1244 (32.4)	16,887 (26.4)	<.001
Painful intercourse*	411 (15.2)	2681 (9.3)	<.001
Chronic pelvic pain*	164 (6.1)	627 (2.2)	<.001
Painful urination*	111 (4.1)	610 (2.1)	<.001
Frequent urination*	1034 (38.3)	6902 (23.8)	<.001
Irregular periods*	383 (14.2)	4259 (14.7)	.485
Painful periods*	260 (9.6)	2902 (10.0)	.535
Surgical history, n (%)
Cholecystectomy	487 (12.7)	2617 (4.1)	<.001
Appendectomy	837 (21.8)	7731 (12.1)	<.001
Hysterectomy*	920 (34.1)	5206 (18.0)	<.001
Back surgery	174 (4.5)	1926 (3.0)	<.001
Coronary artery surgery	118 (3.1)	1691 (2.6)	.105
Peptic ulcer surgery	19 (0.5)	235 (0.4)	.207

IBS, irritable bowel syndrome; SD, standard deviation.
*Results from women only.

Table 2. Patient Features Associated with Clinically Diagnosed Diverticulitis in 1959 Examinees, 290 with IBS and 1669 Without IBS, During Followup (2003 to 2017)
Feature	Adjusted IRR	95% CI	P Value
Irritable bowel syndrome	2.64	2.21 to 3.15	<.001
Age, y	1.02	1.01 to 1.02	<.001
Race/ethnicity			<.001
White		Reference
Asian/Pacific Islander	0.62	0.49 to 0.79	<.001
Black	0.73	0.54 to 1.00	.047
Hispanic	1.53	1.29 to 1.83	<.001
Other	1.04	0.75 to 1.18	.817
Frequent headaches	1.46	1.25 to 1.70	<.001
Smoking			.028
Never		Reference
Past	1.17	0.96 to 1.48	.106
Current	1.16	1.03 to 1.31	.012
Vegetarianism	0.65	0.45 to 0.93	.020
Diabetes	0.69	0.53 to 0.91	.007
Hypertension	1.35	1.19 to 1.54	<.001
Cholecystectomy	1.47	1.18 to 1.85	.001
Back surgery	1.41	1.09 to 1.81	.009

IRR, incidence rate ratio; IBS, irritable bowel syndrome; CI, confidence interval.

Table 3. Twelve Patients with Irritable Bowel Syndrome Whose Diagnosis of Diverticulitis Was Subsequently Revised or Excluded (2003 to 2017)
Case # Age Sex	Presenting Features and Therapy of Clinically Diagnosed Diverticulitis	Prior Colon Imaging	Later Events, Revised Diagnosis, Therapy and Outcome
1 6 F	Abdominal pain, diarrhea ×3 weeks, generalized abdominal tenderness. T 36.6°C, Long-term cephalexin usage for cystitis. Leukocytes 7900/mm³. Ciprofloxacin/metronidazole.	Barium enema 8 years before—diverticulosis	Hospitalized 2 days later, diarrhea and weakness. CT—no diverticulitis, C. difficile toxin–positive colitis, acute renal failure. Vancomycin—recovered. IBS symptoms during 4.3-year followup.
2 90 F	Diarrhea, mild LLQ pain ×1 week. Took amoxicillin or cephalexin daily in cycles until 10 weeks before, then took vancomycin for unproven C. Difficile infection until 2 weeks before. T 36.8°C, LLQ tenderness. Leukocytes 11,600/mm³. Ciprofloxacin/metronidazole.	CT 0.4 years before, barium enema 8.3 years before—diverticulosis	Hospitalized 2 weeks later, severe bloody diarrhea. CT—sigmoid/descending colon wall thickening. Flexible sigmoidoscopy—severe pseudomembranous colitis.C. difficile toxin–positive. Vancomycin—recovered. Recurrent antibiotic-induced C. difficile diarrhea before death from heart failure 4.7 years later.
3 77 F	Low abdominal pain ×2 days. T 36.9°C, LLQ tenderness. Leukocytes 9900/mm³. Amoxicillin/metronidazole.	Barium enema 6 years before—diverticulosis	Urinalysis—urinary tract infection. Therapy changed: Ciprofloxacin/metronidazole later the same day—recovered. Diverticulitis diagnosed clinically again 4.1 year later. IBS symptoms during 11-year followup.
4 81 F	Low abdominal pain ×1 day. T 37.4°C, low abdominal tenderness. Leukocytes 12,700/mm3. Ciprofloxacin/metronidazole	CT 0.3 year before, colonoscopy 0.4 year before, barium enema 11 years before—diverticulosis	Urinalysis—urinary tract infection. Therapy changed: Amoxicillin clavulanate 6 days later—recovered. Diverticulitis diagnosed clinically again 0.2 year later. Died from cancer 2.6 years later.
5 48 M	LLQ pain, urgency, bloody stool ×4 days. T 37.1°C, LLQ tenderness. Leukocytes 8400/mm³. Ciprofloxacin/metronidazole.	None	CT 2 days later—sigmoid wall thickening without diverticulosis. Symptoms persisted. Colonoscopy 3.5 months later—colitis. Drug therapy-refractory. Proctocolectomy (Crohn's disease) 2.6 years later. Stable during 10.8-year followup.
6 36 F	Abdominal pain, diarrhea ×3 weeks. T 36.3°C, low abdominal tenderness. Leukocyte count not done. Ciprofloxacin/metronidazole.	None	Flexible sigmoidoscopy 6 days later—Crohn's disease. Erythema nodosum, arthritis 8 days later. Drug therapy—did well during 2.4-year followup.
7 89 F	"LLQ pain" ×3 days, history of cholecystitis. T 37.5°C, "LLQ tenderness." On penicillin for dental disease. Leukocytes 8600/mm³. Metronidazole added.	Colonoscopy 2.1 year before, CT 2.4 years before—diverticulosis.	Hospitalized 12 hours later, pain worse. Surgeon noted mid-abdominal pain, epigastric tenderness. Ultrasound—gallstones, gallbladder wall thickened—cholecystitis. Amoxicillin clavulanate—recovered. Occasional low abdominal pain until death from pneumonia 2.5 years later.
8 77 M	Left abdominal pain ×1 day, history of metastatic ileal carcinoid and 2 episodes small bowel obstruction. T 36.8°C, left abdominal tenderness. Leukocytes 6700/mm³. Ciprofloxacin/metronidazole.	CT 1.2 years before, colonoscopy 7.2 years before—no diverticulosis.	Hospitalized 1 day later, pain worse, CT—small bowel obstruction. Resolved. Death from carcinoid 2.3 years later.
9 81 F	Low abdominal pain, diarrhea ×10 days. T 36.7°C, low abdominal tenderness. Leukocyte count not done. Ciprofloxacin.	Barium enema 9.5 years before—no diverticulosis	Hospitalized 5 days later, pain worse. CT—sigmoid volvulus. Colonoscopic detorsion—recovered. No visits for abdominal pain until death from cancer 1.7 years later.
10 50 F	LLQ pain ×1 day. T 36.4°C, LLQ tenderness. Leukocytes 9800/mm³. Ciprofloxacin/metronidazole.	Flexible sigmoidoscopy 1.4 years before, colonoscopy 0.8 years before—no diverticulosis.	To ED 2 days later, pain persistent. CT—4.6-cm left ovarian cyst. Oophorectomy (cystadenoma) 6 weeks later. No visits for abdominal pain during 4-year followup.
11 67 M	Mid-abdominal pain, ×1 day.T 37.1°C, "LLQ tenderness." Leukocytes 15,300/mm³. Ciprofloxacin/metronidazole	Colonoscopy 0.7 years before—diverticulosis	Hospitalized 13 days later, pain persisted, worsened. Severe RUQ tenderness. Leukocytes 18,300/mm³. CT—gallstones, gallbladder wall thickened with surrounding edema. Lipase, liver tests increased. Cholecystitis, pancreatitis. Cholecystectomy (chronic cholecystitis with focal gangrene)—recovered. Occasional IBS symptoms during 7.2-year followup.
12 86 F	Presenting history, examination, temp data unavailable. Leukocyte count not done. Ciprofloxacin/metronidazole	None	To ED 3 days later due to vomiting, bloating after starting antibiotics. CT—diverticulosis without diverticulitis. Drug-induced symptoms. Antibiotics stopped. Recovered. Many visits for IBS symptoms, depression, anxiety and 3 more nondiagnostic CTs done for abdominal pain before general decline and death 7.2 years later.

CT, computed tomography; ED, emergency department; F, female; M, male; IBS, irritable bowel syndrome; LLQ, left lower quadrant; RUQ, right upper quadrant; T, temperature.
Revised Diagnoses in Bold.