What is the differential diagnosis for a patient presenting with fever, rash, vomiting, and abdominal pain?

Differential Diagnosis for Fever, Rash, Vomiting, and Abdominal Pain

Immediate Life-Threatening Conditions to Rule Out First

Meningococcemia must be excluded immediately, as abdominal pain can be the initial presenting symptom before the characteristic purpuric rash develops, and delayed diagnosis significantly increases mortality. 1

• Meningococcemia can present with fever and abdominal pain for 24 hours before purpuric lesions appear on the extremities, progressing rapidly to septic shock 1
• Acute mesenteric ischemia should be considered if pain is out of proportion to physical examination findings, particularly with cardiovascular risk factors 2
• Perforated viscus requires immediate surgical evaluation if abdominal rigidity or peritoneal signs are present 2

Infectious Etiologies

Bacterial Infections

• Typhlitis (neutropenic enterocolitis) presents with right lower quadrant pain, fever, vomiting, and diarrhea in immunocompromised patients; contrast-enhanced CT shows thickening of the ascending colonic wall 3
• Clostridium difficile colitis should be considered with watery diarrhea, fever, and abdominal pain 3
• Mesenteric adenitis can present with fever, abdominal pain, and vomiting, sometimes discovered during exploratory laparotomy 1

Viral and Parasitic Infections

• COVID-19 can present with gastrointestinal symptoms (diarrhea 4.5-36.6%, nausea/vomiting 3.7-17.3%, abdominal pain 0.4-6.9%) along with fever, though rash is less commonly reported 4
• Hookworm infection causes transient pruritic maculopapular rash followed weeks later by nausea, vomiting, diarrhea, and abdominal pain 5
• Trichinellosis presents with upper abdominal pain, fever, vomiting, diarrhea, followed by severe myalgia and urticarial rash after consuming undercooked pork 5

Autoinflammatory Syndromes

• Familial Mediterranean Fever (FMF) presents with recurrent episodes of fever, severe abdominal pain mimicking acute abdomen, and vomiting; consider in patients of Mediterranean descent 6
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) causes migratory rash, periorbital edema, abdominal pain, and myalgia during episodic attacks 5
• Mevalonate Kinase Deficiency (MKD) presents with periodic fever attacks lasting 4-6 days, urticarial or maculopapular rash, severe abdominal pain with vomiting and diarrhea 5

Common Surgical and Medical Conditions

• Acute appendicitis accounts for approximately one-third of emergency department presentations with acute abdominal pain 2
• Acute cholecystitis occurs in 9-11% of acute abdominal pain cases 2
• Small bowel obstruction presents in 4-5% of cases with colicky pain, vomiting, and abdominal distension 7, 2
• Acute pancreatitis can present with fever, abdominal pain, vomiting, and elevated pancreatic enzymes 6

Critical Diagnostic Approach

Immediate Assessment

• Check hemodynamic stability immediately: assess for tachycardia, hypotension, fever, or signs of shock indicating potential bowel ischemia, perforation, or sepsis 7
• Examine for peritoneal signs (guarding, rebound tenderness, rigidity) suggesting perforation or ischemia requiring urgent surgical consultation 7
• Document the character and distribution of the rash: purpuric lesions suggest meningococcemia 1, urticarial or maculopapular rash suggests autoinflammatory syndromes or parasitic infections 5

Essential Laboratory Testing

• Complete blood count: leukocytosis >14,000 suggests infection, ischemia, or inflammation; marked elevation indicates potential bowel ischemia 7
• Metabolic panel with lactate: low bicarbonate, elevated lactate, and elevated pH indicate intestinal ischemia 7
• Inflammatory markers (ESR, CRP, serum amyloid A) during symptomatic episodes for autoinflammatory syndromes 5
• Blood cultures if sepsis is suspected 3, 1
• Stool studies including concentrated microscopy for parasites and C. difficile testing 5, 3

Imaging Strategy

• CT abdomen and pelvis with IV contrast is the preferred initial study for diffuse or nonlocalized abdominal pain, changing diagnosis in 49% of cases and management in 42% of patients 7
• CT is mandatory in immunocompromised patients to differentiate typhlitis from other intra-abdominal pathologies 3
• Ultrasonography for right upper quadrant pain if cholecystitis is suspected 7

Critical Pitfalls to Avoid

• Do not delay imaging based on clinical impression alone, as CT changes diagnosis in approximately 50% of cases with nonspecific pain 7
• Do not rely on normal laboratory values in elderly or immunocompromised patients, as many serious infections present with normal white blood cell counts 7, 2, 3
• Do not dismiss the possibility of meningococcemia if purpuric rash has not yet appeared, as abdominal symptoms can precede the rash by 24 hours 1
• Do not overlook autoinflammatory syndromes in patients with recurrent episodes, particularly those of Mediterranean or Turkish descent 6