Table 1.

Summary table.

PT #	Initial presentation	Diagnostic evaluations	Subsequent diagnosis	Medical therapies attempted	Surgical procedures	Ultimate diagnosis and plan
Cases with a current presumptive diagnosis of CD, despite lack of evidence of luminal CD:
Continuing on biologic therapy
(1) 34M	Abdominal pain, diagnosed with sigmoid diverticulitis	Colonoscopy + bx CT MRI MRE EUA	Refractory perianal fistula with abscess	Biologics, aminosalicylates, and immunomodulators: Infliximab x16mo (continuing) Ustekinumab x10mo Tacrolimus Azathioprine Non-CD medical therapies: Metronidazole Ciprofloxacin Amoxicillin-Clavulanic acid	I&D Seton	Outcome: Active perianal fistula Diagnosis: Isolated perianal disease in the setting of presumed CD Timeline: 13 years after initial presentation Treatment Plan: Chronic tx with chronic, cyclical abx (Ciprofloxacin or Amoxicillin-Clavulanic acid) CD-directed therapy (Azathioprine + Infliximab; will consider Upadacitinib once approved by the FDA) Planning for surgical f/u
(2) 24F	Perianal pain, diagnosed as perianal abscess with fistula; also presented with rheumatologic symptoms	Colonoscopy + bx MRI EUA	Refractory perianal abscess; inflammatory arthropathy	Biologics, aminosalicylates, and immunomodulators: Adalimumab x46mo Infliximab x12mo (continuing) Azathioprine Non-CD medical therapies: Ciprofloxacin Metronidazole	I&D Seton	Outcome: Active perianal fistula Diagnosis: Presumed CD with perianal disease and inflammatory arthropathy Timeline: 9 years after initial presentation Treatment Plan: CD-directed therapy (Infliximab + Azathioprine) Planning for surgical f/u
(3) 50F	Diarrhea and rectal ulcers, presumed to have CD; also presented with rheumatologic symptoms	Colonoscopy + bx (including ileal and rectal bx) CT MRI EUA	Refractory perianal fistula with abscess	Biologics, aminosalicylates, and immunomodulators: Infliximab x39mo (continuing) Non-CD medical therapies: Colchicine Prednisone	I&D Seton Perineal debridement Fistulotomy	Outcome: Active perianal fistula Diagnosis: Presumed CD with perianal disease Timeline: 5 years after initial presentation Treatment Plan: CD-directed therapy (Infliximab)
(4) 21F	Ischiorectal abscess and posterior anal fissure, diagnosed with isolated perianal CD	Colonoscopy + bx (including ileal and rectal bx) MRI EUA Fecal calprotectin (within normal limits)	Isolated perianal CD	Biologics, aminosalicylates, and immunomodulators: Infliximab x16mo (continuing) Mercaptopurine Non-CD medical therapies: Ciprofloxacin Metronidazole	I&D Seton Transanal advancement flap Penrose drain placement Foley catheter placed into perianal abscess cavity Diverting colostomy	Outcome: Active perianal fistula Diagnosis: Presumed isolated perianal CD and lymphocytic colitis Timeline: 6 years after initial presentation Treatment Plan: CD-directed therapy (Infliximab + Mercaptopurine)
(5) 34F	Abdominal pain, constipation, and hematochezia, given presumptive diagnosis of unspecified IBD	Colonoscopy + bx (including ileal and rectal bx) US MRI MRE EUA Fecal calprotectin (mild elevation)	Refractory perianal fistula with abscess	Biologics, aminosalicylates, and immunomodulators: Ustekinumab x9mo (continuing) Mesalamine Non-CD medical therapies: Trimethoprim-Sulfamethoxazole	I&D Seton	Outcome: Active perianal fistula Diagnosis: Presumed unspecified IBD with refractory perianal disease Timeline: 4.5 years after initial presentation Treatment Plan: CD-directed therapy (Ustekinumab)
(6) 16F	Isolated perianal fistula with abscess, presumed to have isolated perianal CD; family history of Crohn’s disease	Colonoscopy + bx (including ileal and rectal bx) MRI EUA Fecal calprotectin (elevated)	Isolated perianal CD	Biologics, aminosalicylates, and immunomodulators: Infliximab x64mo (continuing) Non-CD medical therapies: Ciprofloxacin Metronidazole	I&D Seton	Outcome: Active perianal fistula Diagnosis: Presumed isolated perianal CD Timeline: 5.5 years after initial presentation Treatment Plan: CD-directed therapy (Infliximab)
(7) 36M	Chronic diarrhea, abdominal pain, and isolated perianal fistula with abscess presumed to have isolated perianal CD; also presented with spondyloarthropathy.	EGD Colonoscopy + bx MRE EUA	Isolated perianal CD	Biologics, aminosalicylates, and immunomodulators: Infliximab x16mo Ustekinumab x32mo (continuing) Azathioprine Non-CD medical therapies: Ciprofloxacin	I&D Seton Diverting loop ileostomy LIFT Stem cell injections	Outcome: Active perianal fistula Diagnosis: Presumed isolated perianal CD Timeline: 18 years after initial presentation Treatment Plan: CD-directed therapy (Ustekinumab with stem cell injections)
(8) 43M	Perianal fullness and pain, with episodes of drainage, diagnosed with recurrent perianal fistula	Colonoscopy + bx MRI EUA	Isolated perianal CD	Biologics, aminosalicylates, and immunomodulators: Infliximab x44mo (continuing) Non-CD medical therapies: Ciprofloxacin	I&D Seton	Outcome: Active perianal fistula Diagnosis: Presumed isolated perianal CD Timeline: 5 years after initial presentation Treatment Plan: CD-directed therapy (Infliximab) Planning for surgical f/u
(9) 30F	Pilonidal cyst with anal fistula	EGD Colonoscopy + bx (including ileal and rectal bx) MRI Fecal calprotectin (mild elevation)	Complex, recurrent perianal fistula	Biologics, aminosalicylates, and immunomodulators: Infliximab x17mo Mercaptopurine Adalimumab x50mo (continuing) Non-CD medical therapies: Ciprofloxacin Metronidazole Amoxicillin-Clavulanic acid Budesonide	I&D Seton Cystectomy Fistulotomy	Outcome: Fistula symptom remission Diagnosis: Presumed chronic fistulizing perianal CD; in steroid-free clinical and biochemical remission Timeline: 9 years after initial presentation Treatment Plan: CD-directed therapy (Adalimumab)
(10) 27M	Perianal abscess in the setting of long history of anal fissures; family history of Crohn’s disease	Colonoscopy + bx (including ileal and rectal bx) MRI MRE	Isolated perianal CD	Biologics, aminosalicylates, and immunomodulators: Infliximab x24mo Mercaptopurine x6mo	I&D Seton Sphincterotomy	Outcome: Fistula closure (clinical closure) Diagnosis: Presumed isolated perianal CD; no recurrence of fistula or fissure Timeline: 2.5 years after initial presentation Treatment Plan: CD-directed therapy (Infliximab)
(11) 41F	Perianal fistula in the setting of long history of abdominal pain and alternating diarrhea and constipation; family history of Crohn’s disease	EGD Capsule Flexible sigmoidoscopy Colonoscopy + bx (including rectal bx) CTE EUA	Unclear dx	Biologics, aminosalicylates, and immunomodulators: Adalimumab x1mo (continuing) Non-CD medical therapies: Undefined abx	I&D Seton	Outcome: Active perianal fistula Diagnosis: Presumed isolated perianal CD; continues to develop recurrent fistulas Timeline: 1 year after initial presentation Treatment Plan: CD-directed therapy (adalimumab) Undefined abx
(12) 28F	Perianal fistula with abscess developed after birth of first child, had previous history of recurrent abscesses; diagnosed with presumed isolated perianal CD	Colonoscopy + bx (including ileal and rectal bx) MRI MRE CT EUA Fecal calprotectin (within normal limits)	Still considering as isolated perianal CD despite lack of luminal disease and normal fecal calprotectin	Biologics, aminosalicylates, and immunomodulators: Adalimumab x7mo Infliximab x41mo (continuing) Azathioprine Non-CD medical therapies: Amoxicillin-clavulanic acid	I&D Seton Mallinckrodt drain Fistulotomy x2	Outcome: Fistula symptom remission Diagnosis: Presumed isolated perianal CD; MRI shows healing of fistula Timeline: 7 years after initial presentation Treatment Plan: CD-directed therapy (Infliximab), planning to discontinue with close monitoring in the near future given MRI showing healing
Cases with no current presumptive diagnosis of CD
Continuing on biologic therapy
(13) 69M	Recurrent diverticulitis with perianal abscess and fistula	EGD Colonoscopy + bx (including ileal and rectal bx) CT CTE MRI MRE Fecal calprotectin (elevated)	Ileitis with recurrent perianal disease	Biologics, aminosalicylates, and immunomodulators: Adalimumab x11mo (continuing)	I&D Seton LIFT	Outcome: Active perianal fistula Diagnosis: Ileitis with recurrent perianal disease, no luminal CD Timeline: 13 years after initial presentation Treatment Plan: CD-directed therapy (Adalimumab) MRE pending
(14) 30F	Perianal fistula; family history of Crohn’s disease	EGD Colonoscopy + bx (including ileal and rectal bx) MRI Fecal calprotectin (within normal limits)	Ileitis with recurrent perianal abscess	Biologics, aminosalicylates, and immunomodulators: Adalimumab x52mo (continuing)	I&D FMT	Outcome: Fistula symptom remission Diagnosis: Ileitis with recurrent perianal abscess, no luminal CD, complicated by recurrent Clostridioides difficile; clinically in symptom remission Timeline: 8 years after initial presentation Treatment Plan: CD-directed therapy (Adalimumab) FMT
(15) 18F	Perianal pain found to have perianal fistula w/ abscess, no other GI symptoms; some intermittent rheumatologic sx	EGD Colonoscopy + bx (including ileal and rectal bx) Flexible sigmoidoscopy CT MRI MRE EUA Fecal calprotectin (within normal limits)	Unclear dx	Biologics, aminosalicylates, and immunomodulators: Infliximab x53mo Non-CD medical therapies: Amoxicillin Hyperbaric oxygen	I&D Seton Mushroom drain Fistulotomy	Outcome: Fistula symptom remission Diagnosis: Isolated perianal disease Timeline: 5.5 years after initial presentation Treatment Plan: CD-directed therapy (Infliximab)
Trialed but no longer on biologic therapy
(16) 39F	Painful perianal mass, presumed to be an abscess or hemorrhoids	Flexible sigmoidoscopy Colonoscopy + bx (including rectal bx) MRI EUA	Refractory perirectal and rectovaginal fistula with abscess (diagnosed following childbirth via cesarean section, not vaginal delivery)	Biologics, aminosalicylates, and immunomodulators: Adalimumab x9mo Methotrexate Non-CD medical therapies: Ciprofloxacin Metronidazole Amoxicillin-Clavulanic acid Prednisone	I&D Seton Fistulectomy + sphincterotomy Diverting sigmoid colostomy Fistulotomy	Outcome: Active perianal fistula Diagnosis: Do not suspect CD; nonhealing cryptoglandular anal fistula c/b surgery Timeline: 3 years after initial presentation Treatment Plan: Discontinued CD therapy given lack of clinical improvement; off all medical tx Planning for surgical f/u with consideration of transperitoneal repair vs clinical trial of stem cell injection
Never trialed on biologic therapy
(17) 43M	Painful perianal mass, presumed to be a rectal abscess	Colonoscopy + bx MRI EUA	Refractory perianal abscess	Non-CD medical therapies: Amoxicillin-Clavulanic acid	I&D	Outcome: Fistula symptom remission Diagnosis: Isolated cryptoglandular abscess with proctitis and internal hemorrhoids Timeline: 2.5 years after initial presentation Treatment Plan: No need for chronic antibiotics; off all medical tx Sitz baths and Preparation H as needed If symptoms worsen will plan for surgical f/u
(18) 28F	Perianal abscess and fistula in ano in the setting of lifelong diarrheal illness and known lymphocytic colitis, concern for CD; family history of ulcerative colitis	Colonoscopy + bx (including ileal and rectal bx) CT MRI EUA Fecal calprotectin (mild elevation)	Microscopic colitis with refractory perianal fistula with abscess	Biologics, aminosalicylates, and immunomodulators: Balsalazide Mesalamine Non-CD medical therapies: Amitriptyline Bismuth Subsalicylate Budesonide CBD oil	I&D Seton Collagen plug placement Fibrin glue Fistulotomy Cystoscopy + laser lithotripsy Stem cell injection	Outcome: Active perianal fistula Diagnosis: Microscopic colitis Timeline: 13 years after initial presentation Treatment Plan: Continuing mesenchymal stem cell injections as part of clinical trial
(19) 32M	Perianal fistula with drainage; family history of ulcerative colitis	EGD Colonoscopy + bx (including ileal and rectal bx) VCE MRE EUA Fecal lactoferrin (mild elevation)	Refractory perianal fistula with abscess	Biologics, aminosalicylates, and immunomodulators: Methotrexate Non-CD medical therapies: Budesonide	I&D Seton Fistulotomy Advancement flap procedure LIFT	Outcome: Active perianal fistula Diagnosis: Refractory perianal dz Timeline: 12 years after initial presentation Treatment Plan: Budesonide taper with plan to start CD-directed therapy (anti-TNF combination therapy) Patient was unfortunately lost to follow-up
(20) 35F	IBS, rectal pain and perianal drainage	EGD Flexible sigmoidoscopy Colonoscopy + bx (including ileal and rectal bx) VCE MRI EUA Fecal calprotectin (within normal limits)	Complex perianal fistula	Biologics, aminosalicylates, and immunomodulators: Methotrexate Non-CD medical therapies: Ciprofloxacin Metronidazole Budesonide	I&D Seton Endorectal advancement flap Fistulotomy	Outcome: Fistula closure (clinical closure) Diagnosis: Isolated perianal disease; status post successful surgery with closure of fistula Timeline: 11 years after initial presentation Treatment Plan: Not on treatment
(21) 59F	Pilonidal cyst, found to have 2 draining perianal fistulas; family history of Crohn’s disease	Capsule Flexible sigmoidoscopy Colonoscopy + bx (including rectal bx) MRI EUA	Isolated perianal CD	Biologics, aminosalicylates, and immunomodulators: Mercaptopurine x6-9mo	I&D Fistulotomy	Outcome: Fistula closure (clinical + radiologic closure) Diagnosis: Cryptoglandular fistula, no luminal CD; no further drainage, fistulas closed Timeline: 1.5 years after initial presentation Treatment Plan: Not on treatment
(22) 44M	Recurrent rectal abscess	Colonoscopy + bx (including ileal and rectal bx) CT MRI MRE EUA Fecal calprotectin (elevated)	Unclear dx	Non-CD medical therapies: Ciprofloxacin Metronidazole	I&D Seton Endoanal advancement flap	Outcome: Fistula closure (clinical and radiologic closure) Diagnosis: Cryptoglandular fistula, no luminal CD; abscess resolved w/o fistula Timeline: 1 year after initial presentation Treatment Plan: Not on treatment
(23) 22M	Perirectal abscess	Colonoscopy + bx MRI EUA	Unclear dx	Non-CD medical therapies: Undefined abx	I&D	Outcome: Fistula closure (clinical closure) Diagnosis: Cryptoglandular fistula, no luminal CD; abscess resolved w/o fistula Timeline: 1 year after initial presentation Treatment Plan: Not on treatment
(24) 28F	Perianal abscess in the setting of abdominal pain and intermittent diarrhea	Colonoscopy + bx (including ileal and rectal bx) MRI EUA	Unclear dx	Non-CD medical therapies: Undefined abx	I&D Fistulotomy + marsupialization	Outcome: Active perianal fistula Diagnosis: Cryptoglandular fistula, no luminal CD; persistent fistula Timeline: 1 year after initial presentation Treatment Plan: Undefined abx

Abbreviations: Bx, biopsies; C/B, complicated by; CD, Crohn’s disease; EUA, exam under anesthesia; F, female; FMT, fecal microbiota transplantation; F/U, follow-up; I&D, incision and drainage; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; LIFT, ligation of the intersphincteric fistula tract; M, male; MRE, magnetic resonance elastography; MRI, magnetic resonance imaging; TNF, tumor necrosis factor; VCE, video capsule endoscopy.