What is the differential diagnosis for a 50-year-old male on Ozempic (semaglutide) with acute onset of severe lower right abdominal pain, fever, and headache, following a large meal after injection?

Differential Diagnosis for Acute Right Lower Quadrant Abdominal Pain in Patient on Ozempic

The most critical diagnosis to rule out immediately is acute appendicitis, given the classic presentation of right lower quadrant pain with fever (101°F), pain with movement, and localized tenderness just above the beltline. 1

Primary Differential Diagnoses

Acute Appendicitis (Most Likely)

• Classic presentation: Migration of pain to right lower quadrant, fever, localized tenderness, and pain with movement are highly suggestive of appendicitis 1
• The 24-hour progression from diffuse abdominal pain to localized right lower quadrant pain follows the typical appendicitis pattern 1, 2
• Fever of 101°F with tachycardia (likely present) significantly increases probability of appendicitis 1
• Immediate action required: CT abdomen/pelvis with IV contrast is the diagnostic test of choice, with 94% sensitivity for appendicitis 1, 2

GLP-1 Receptor Agonist-Related Complications

• Acute pancreatitis: Semaglutide can cause acute pancreatitis, which presents with severe abdominal pain and may radiate or localize 3
• The rapid eating after prolonged fasting (9 hours post-injection) could trigger pancreatitis in a patient on GLP-1 agonist therapy 3
• Lipase level must be checked immediately to evaluate for pancreatitis 2
• Ileus or severe gastroparesis: GLP-1 agonists delay gastric emptying; rapid consumption of large meal could cause severe gastric distention and pain 3

Epiploic Appendagitis

• Often misdiagnosed as appendicitis: Presents with acute onset right lower quadrant pain, can cause fever, and is painful to palpation 4, 5
• More common in middle-aged adults (patient is 50 years old) 4, 5
• CT shows characteristic oval fat-density lesion with hyperattenuating ring sign 4, 5
• Critical distinction: This is managed conservatively, avoiding unnecessary surgery 4, 5

Acute Diverticulitis (Right-Sided)

• Less common in 50-year-old patients but possible 1, 2
• CT sensitivity >95% for detecting diverticulitis 1
• Would show bowel wall thickening and pericolonic inflammation on imaging 1

Cholecystitis with Atypical Presentation

• The 2-day history of GERD symptoms post-injection could represent biliary colic 1, 2
• GLP-1 agonists are associated with gallbladder and biliary tract diseases 3
• Pain can occasionally radiate to right lower quadrant 1

Critical Immediate Workup Required

Laboratory Tests (Stat)

• Complete blood count: Elevated WBC with left shift suggests appendicitis or other bacterial infection 1, 2
• Lipase: Essential to rule out pancreatitis given semaglutide use 2, 3
• C-reactive protein: Elevated in appendicitis and other inflammatory conditions 2
• Comprehensive metabolic panel: Assess renal function (GLP-1 agonists can cause acute kidney injury) and electrolytes 3
• Hepatobiliary markers: To evaluate for cholecystitis 2
• Urinalysis: Rule out urolithiasis or urinary tract infection 2

Imaging (Urgent)

• CT abdomen/pelvis with IV contrast is the single best test for this presentation with fever and localized right lower quadrant pain 1, 2
• CT will definitively diagnose or exclude appendicitis (94% sensitivity), epiploic appendagitis, pancreatitis, diverticulitis, and other serious pathology 1
• Plain radiographs have limited utility (only 49% sensitivity for obstruction, poor for detecting inflammatory processes) 1

Red Flags Requiring Immediate Intervention

This patient has multiple concerning features that mandate urgent evaluation:

• Fever ≥38°C (101°F) with localized abdominal pain indicates possible intra-abdominal infection requiring source control 1
• Pain lasting 24 hours with progression to localized right lower quadrant suggests evolving surgical pathology 1, 2
• Pain preventing sleep and requiring analgesics indicates severe pathology 1
• Pain with movement suggests peritoneal irritation 1

Clinical Pitfalls to Avoid

Do not delay imaging based on atypical features: The history of semaglutide use and rapid eating may distract from classic surgical emergencies like appendicitis 1

Do not assume GLP-1-related gastroparesis explains everything: While semaglutide causes gastrointestinal symptoms, fever and localized tenderness indicate infection or inflammation requiring different management 3

Do not rely on physical exam alone: In patients with fever and abdominal pain, imaging is essential as physical findings may be nonspecific 1

Tachycardia may be masked: If patient takes beta-blockers, absence of tachycardia does not rule out serious pathology 1

Management Algorithm

1. Immediate stabilization: IV access, fluid resuscitation, nothing by mouth 1
2. Stat laboratory tests: CBC, CRP, lipase, CMP, hepatobiliary markers, urinalysis 2
3. Urgent CT abdomen/pelvis with IV contrast (do not delay for oral contrast) 1
4. Surgical consultation: Given fever, localized tenderness, and 24-hour duration, surgical evaluation should occur simultaneously with imaging 1
5. Empiric antibiotics: If appendicitis suspected and patient shows signs of sepsis, start broad-spectrum antibiotics immediately after blood cultures 1

The combination of fever, localized right lower quadrant pain, and pain with movement in a 50-year-old male represents appendicitis until proven otherwise, regardless of semaglutide use. 1