What is the differential diagnosis for a patient with hypertension, type 2 diabetes, obesity, and asthma presenting with nausea, vomiting, diarrhea, and fever?

Differential Diagnosis for Nausea, Vomiting, Diarrhea, and Fever

In a patient with hypertension, type 2 diabetes, obesity, and asthma presenting with nausea, vomiting, diarrhea, and fever, the differential diagnosis must prioritize infectious gastroenteritis, diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS), and medication-related causes, with immediate assessment for life-threatening complications including severe dehydration, electrolyte disturbances, and hyperglycemic crisis. 1, 2

Critical Life-Threatening Diagnoses to Exclude First

Hyperglycemic Emergencies

• DKA can present with nausea, vomiting, and abdominal pain in diabetic patients, and requires immediate laboratory evaluation including plasma glucose, arterial pH, serum bicarbonate, and ketones. 2
• The American Diabetes Association defines DKA by plasma glucose ≥250 mg/dL, arterial pH <7.30, serum bicarbonate <15 mEq/L, and positive ketones. 2
• HHS presents with plasma glucose ≥600 mg/dL, altered mental status or severe dehydration, and effective serum osmolality ≥320 mOsm/kg. 2
• Infection, including gastroenteritis, commonly precipitates both DKA and HHS, making this distinction critical in diabetic patients with GI symptoms and fever. 2

Severe Dehydration and Electrolyte Disorders

• Hyponatremia commonly presents with nausea, vomiting, weakness, and headache, and can progress to delirium, confusion, seizures, and death when sodium is <125 mEq/L. 3
• Intravenous rehydration with isotonic fluids (lactated Ringer's or normal saline) is required when there is severe dehydration, shock, or altered mental status. 1
• Hyperkalemia can present with gastrointestinal symptoms including nausea, vomiting, and diarrhea, along with cardiac dysrhythmias requiring immediate treatment. 4

Primary Infectious Causes

Acute Infectious Gastroenteritis

• Infectious diarrhea is the most common cause of acute nausea, vomiting, diarrhea, and fever, and should be the primary working diagnosis in this presentation. 1
• Stool work-up should include evaluation for blood, fecal leukocytes, C. difficile, Salmonella, E. coli, and Campylobacter in patients with fever or signs of inflammatory diarrhea. 1
• COVID-19 can present with nausea, vomiting, and diarrhea that predate respiratory symptoms, with up to 61% of outpatients experiencing GI symptoms. 1
• During evaluation, acute nausea, vomiting, or diarrhea with fever should prompt consideration of COVID-19 and appropriate testing, particularly if other risk factors or exposures are present. 1

Diabetes-Related Complications

Diabetic Diarrhea

• Idiopathic diabetic diarrhea occurs frequently in patients with poorly controlled diabetes who have evidence of peripheral and autonomic neuropathy. 5
• The diarrhea is typically painless, occurs day and night, may be associated with fecal incontinence, and often alternates with periods of normal bowel movements or constipation. 5
• Multiple mechanisms include autonomic neuropathy, bacterial overgrowth, and pancreatic exocrine insufficiency. 5

Diabetic Gastroparesis

• Gastroparesis affects 20-40% of diabetic patients and presents with nausea, vomiting, and early satiation. 6
• Hyperglycemia itself causes gastric dysmotility, making blood glucose control essential in evaluating GI symptoms in diabetic patients. 6

Medication-Related Causes

Antihypertensive and Diabetic Medications

• Multiple medications used for hypertension and diabetes can cause GI side effects including nausea, vomiting, and diarrhea. 6
• SGLT2 inhibitors can precipitate DKA with glucose <200 mg/dL (euglycemic DKA), particularly with dehydration, reduced food intake, or infection. 2

Asthma Medications

• Systemic corticosteroids used for asthma exacerbations can cause nausea, vomiting, and hyperglycemia. 1

Essential Initial Assessment

Immediate Clinical Evaluation

• Assess hemodynamic status including blood pressure, heart rate, orthostatic changes, temperature, and mental status to identify volume depletion, ongoing losses, infection, or shock. 1, 7
• Evaluate for signs of severe dehydration: poor skin turgor, hypotension, tachycardia, altered mental status, and decreased urine output. 1, 2
• Examine for abdominal distention, absent bowel sounds, peritoneal signs, or severe localized tenderness that would suggest bowel obstruction or other surgical emergencies. 7

Critical Laboratory Studies

• Obtain plasma glucose, complete metabolic panel with calculated anion gap, complete blood count, lactic acid, arterial blood gas (if glucose >250 mg/dL), and urinalysis with urine ketones. 2, 7
• Check serum and urine osmolality and sodium in urine if hyponatremia is present. 3
• Obtain stool studies for infectious pathogens if fever persists, bloody diarrhea develops, or severe symptoms continue beyond 48 hours. 1

Additional Differential Considerations

Gastrointestinal Structural Causes

• Peptic ulcer disease can present with nausea and vomiting, particularly in patients on multiple medications. 6
• Bowel obstruction presents with abdominal pain, nausea, vomiting, abdominal distention, and absent bowel sounds. 7, 6

Metabolic and Endocrine Disorders

• Adrenal insufficiency can present with nausea, vomiting, fever, hypotension, hyponatremia, and hyperkalemia. 1
• Thyroid storm (in undiagnosed hyperthyroidism) presents with fever, tachycardia, vomiting, diarrhea, and altered mental status. 1

Cardiovascular Causes

• Acute coronary syndrome can present atypically with nausea, vomiting, and diaphoresis, particularly in diabetic patients with autonomic neuropathy. 8

Common Pitfalls to Avoid

• Do not attribute all GI symptoms to simple gastroenteritis in diabetic patients without checking blood glucose and assessing for hyperglycemic crisis. 2
• Do not delay treatment for severe dehydration while pursuing diagnostic work-up; begin isotonic fluid resuscitation immediately if hemodynamically unstable. 1
• Avoid assuming viral gastroenteritis without considering bacterial pathogens, particularly if fever is prominent or symptoms persist beyond 48-72 hours. 1
• Do not overlook medication review, as polypharmacy in patients with multiple comorbidities frequently contributes to GI symptoms. 6
• Recognize that approximately 10% of patients can present with concurrent DKA and HHS features, requiring aggressive management of both conditions. 2