What is the differential diagnosis for a patient with colonic strictures, pyloric antral strictures, and imaging/endoscopy findings suggestive of Inflammatory Bowel Disease (IBD), bulky ovaries, ascites, myositis of the bilateral iliopsoas and lateral compartment of the leg, and a positive Cancer Antigen (CA) 19.9?

Differential Diagnosis

This patient presents with a complex multisystem inflammatory syndrome that extends well beyond typical IBD, requiring immediate consideration of IgG4-related disease, malignancy (particularly ovarian with peritoneal carcinomatosis), tuberculosis despite negative QuantiFERON, and systemic vasculitis as primary diagnostic considerations.

Primary Diagnostic Considerations

IgG4-Related Disease

• IgG4-related disease is the leading diagnosis given the constellation of gastrointestinal strictures (both colonic and gastric), myositis, and ovarian involvement with ascites 1
• This condition characteristically causes tumefactive lesions and strictures in multiple organs simultaneously, including the GI tract, retroperitoneum (explaining iliopsoas myositis), and can involve ovaries 1
• Elevated CA 19-9 is frequently seen in IgG4-related disease affecting the pancreaticobiliary system and can occur with other organ involvement 1
• Diagnosis requires serum IgG4 levels >135 mg/dL and tissue biopsy showing >10 IgG4-positive plasma cells per high-power field with IgG4/IgG ratio >40% 1

Ovarian Malignancy with Peritoneal Carcinomatosis

• Bulky ovaries with ascites and elevated CA 19-9 strongly suggest ovarian cancer with peritoneal spread 2
• Peritoneal carcinomatosis can cause colonic strictures through serosal involvement and mimic IBD endoscopically 1
• Gastric involvement (pyloric antral strictures) occurs with peritoneal metastases, particularly from ovarian primary tumors 2
• Urgent gynecologic oncology consultation with CA-125, pelvic MRI, and diagnostic paracentesis with cytology is mandatory 2

Intestinal Tuberculosis

• Despite negative QuantiFERON, intestinal TB remains in the differential given the stricturing disease pattern 3
• QuantiFERON has 70-80% sensitivity; false negatives occur with immunosuppression, disseminated disease, and in 20-30% of culture-proven TB cases 3
• Ileocecal involvement with strictures, patulous ileocecal valve, and transverse ulcers favor TB over Crohn's disease 3
• Obtain AFB cultures from endoscopic biopsies, PCR for Mycobacterium tuberculosis from tissue, and consider empiric anti-TB therapy if clinical suspicion remains high 3, 1

Systemic Vasculitis

• Myositis (bilateral iliopsoas and leg compartments) combined with GI involvement suggests medium-vessel vasculitis such as polyarteritis nodosa 1, 4
• Mesenteric vasculitis causes intestinal ischemia leading to strictures that can mimic IBD 1
• Check ANCA panel, complement levels (C3, C4), cryoglobulins, and hepatitis B/C serology 4
• Muscle biopsy from affected areas may show vasculitic changes 4

Secondary Considerations

Crohn's Disease with Extraintestinal Manifestations

• While endoscopy suggests IBD, the extensive extraintestinal involvement (myositis, ovarian masses) is atypical for standard Crohn's disease 5, 6
• Crohn's can cause discontinuous lesions and strictures, but bilateral iliopsosis myositis is not a recognized extraintestinal manifestation 5, 4
• Ovarian involvement is exceptionally rare in IBD and should prompt investigation for alternative diagnoses 6, 4

Lymphoma

• IBD patients have increased lymphoma risk, particularly with immunosuppressive therapy 2
• Gastrointestinal lymphoma can cause strictures, bulky masses (explaining ovarian appearance), and systemic symptoms 2
• Elevated CA 19-9 can occur with lymphoma 2
• PET-CT scan is essential to evaluate for lymphoproliferative disease 2

Critical Diagnostic Workup

Immediate Laboratory Studies

• Serum IgG4 level (most important single test given clinical presentation) 1
• CA-125, CEA, AFP in addition to CA 19-9 2
• Complete autoimmune panel: ANA, ANCA (PR3 and MPO), anti-dsDNA, complement levels 4
• Repeat inflammatory markers: ESR, CRP, complete blood count with differential 3
• Serum protein electrophoresis to exclude paraproteinemia 4

Tissue Diagnosis Required

• Repeat endoscopic biopsies with specific request for IgG4 immunostaining, AFB cultures, TB PCR, and lymphoma markers (CD20, CD3, CD5) 3
• Muscle biopsy from affected iliopsoas or leg compartment for histology, vasculitis assessment, and cultures 4
• Image-guided biopsy of ovarian mass if accessible 2
• Diagnostic paracentesis with cytology, cell count, albumin, LDH, and cultures 2

Advanced Imaging

• PET-CT to assess metabolic activity in all affected sites and identify occult malignancy or lymphoma 2
• Contrast-enhanced MRI of abdomen/pelvis already obtained; review for characteristic IgG4 findings (sausage-shaped pancreas, retroperitoneal fibrosis) 1
• Consider whole-body MRI if systemic vasculitis suspected 4

Critical Pitfalls to Avoid

• Do not assume this is straightforward IBD despite endoscopic appearance suggesting inflammatory bowel disease; the multisystem involvement demands broader investigation 3, 1
• Do not dismiss TB based solely on negative QuantiFERON; obtain tissue for AFB culture and TB PCR, which have higher sensitivity in GI tuberculosis 3, 1
• Do not delay gynecologic oncology evaluation given the combination of bulky ovaries, ascites, and elevated tumor marker 2
• Do not start immunosuppressive therapy until malignancy and infection are definitively excluded, as this could be catastrophic 1, 2
• Recognize that CA 19-9 elevation is non-specific and occurs in IgG4 disease, malignancy, and inflammatory conditions 1, 2