What is the diagnosis and treatment plan for a patient with a 3-year history of chronic diarrhea, recently worsened to include nocturnal diarrhea and nasal regurgitation, who experiences palpitations, stomach upset, nausea, and dizziness, and has pitting edema in bilateral lower legs, while following a strict carnivore diet and having a reaction to reintroducing plant foods?

Urgent Gastroenterology Referral Required for Suspected Autonomic Dysfunction with Severe Organic Disease

This patient requires urgent gastroenterology referral within 2-4 weeks and comprehensive workup including colonoscopy with biopsies, as nocturnal diarrhea awakening from sleep is a red flag symptom with high specificity for organic disease, and the constellation of autonomic symptoms (palpitations, orthostatic dizziness, nasal regurgitation, fecal incontinence during sleep) suggests a serious underlying disorder requiring immediate investigation. 1

Critical Red Flags Demanding Urgent Evaluation

This patient presents with multiple alarm features that essentially rule out functional disorders:

• Nocturnal diarrhea awakening from sleep is the most specific red flag for organic disease and mandates urgent investigation 2, 1
• Fecal incontinence during sleep indicates severe disease burden requiring immediate evaluation 1
• Progressive worsening over 3 years despite strict dietary modification suggests advancing organic pathology 1
• Nasal regurgitation during sleep may indicate autonomic dysfunction or severe motility disorder 1
• Palpitations upon awakening before diarrhea episodes combined with orthostatic dizziness and symptoms when lying flat suggest autonomic nervous system involvement 2, 1
• Bilateral pitting edema raises concern for protein-losing enteropathy, malabsorption, or cardiac involvement 2

Immediate First-Line Laboratory Tests

Order the following tests before gastroenterology referral:

• Complete blood count to assess for anemia from iron, B12, or folate deficiency 1, 3
• C-reactive protein or erythrocyte sedimentation rate for inflammatory markers with high specificity for organic disease 1, 3
• Anti-tissue transglutaminase IgA with total IgA for celiac disease screening (mandatory despite carnivore diet, as this could explain malabsorption and neurologic symptoms) 1, 3
• Comprehensive metabolic panel to assess electrolyte disturbances and albumin (low albumin could explain edema) 1, 3
• Thyroid function tests to exclude hyperthyroidism 1, 3
• Fasting glucose or hemoglobin A1c to screen for diabetes with autonomic neuropathy 4
• Iron studies, vitamin B12, and folate 1

Essential Stool Tests

• Fecal calprotectin to distinguish inflammatory from non-inflammatory causes (elevated levels indicate inflammatory bowel disease or microscopic colitis) 1, 3
• Stool culture and ova/cysts/parasites to exclude chronic infections like giardiasis 1, 3
• Fecal immunochemical test (FIT) for occult blood 1
• Laxative screen to exclude factitious diarrhea 1

Mandatory Colonoscopy with Biopsies—Critical Pitfall to Avoid

Full colonoscopy with biopsies from both right and left colon is mandatory, even if the mucosa appears completely normal. 1, 3

Common Critical Errors to Avoid:

• Do NOT perform flexible sigmoidoscopy alone—full colonoscopy is required 1
• Do NOT skip colonic biopsies even with normal-appearing mucosa—microscopic colitis accounts for 15% of chronic diarrhea cases in adults and has entirely normal endoscopic appearance but shows characteristic histologic changes only on biopsy 1
• Do NOT rely on CT imaging alone—it is inadequate for detecting microscopic colitis, early inflammatory bowel disease, or subtle mucosal abnormalities 1

Priority Differential Diagnoses

Given the autonomic symptoms and severe presentation, prioritize:

Primary Considerations:

• Autonomic neuropathy (diabetic or idiopathic) causing gastroparesis with nasal regurgitation, orthostatic hypotension, and diarrhea from bile acid malabsorption or bacterial overgrowth 2, 4
• Microscopic colitis (collagenous or lymphocytic colitis)—common in adults, requires histologic diagnosis 1, 3
• Inflammatory bowel disease (Crohn's disease or ulcerative colitis) 1, 3
• Celiac disease—most common small bowel enteropathy in Western populations 1, 4, 3
• Bile acid diarrhea—typically occurs after meals, responds to cholestyramine 1, 4, 3
• Small bowel bacterial overgrowth 1, 3
• Endocrine disorders (hyperthyroidism, diabetes with autonomic neuropathy, Addison's disease) 1, 4
• Pancreatic insufficiency 1, 4
• Protein-losing enteropathy (to explain edema) 2

The Carnivore Diet and Rash Reaction:

The patient's strict carnivore diet and reaction to plant foods (red, itchy rash) could represent:

• Mast cell activation syndrome or histamine intolerance (which can cause diarrhea, flushing, palpitations, and rash) 5
• Food protein-induced enterocolitis syndrome 5
• Eosinophilic gastroenteritis 5

However, the carnivore diet may also be masking celiac disease by eliminating gluten, making serologic testing essential before dietary changes 1, 3.

Referral Timeline and Next Steps

• Urgent gastroenterology referral within 2-4 weeks given alarm features 1, 3
• Colonoscopy with biopsies should be scheduled as soon as possible through gastroenterology 1, 3
• If initial workup is unrevealing, proceed to upper endoscopy with duodenal biopsies and specialized testing (antroduodenal manometry for gastroparesis, autonomic function testing) within 4-6 weeks 2, 1

Symptomatic Management While Awaiting Workup

Do NOT use loperamide in this patient given the severe presentation, alarm features, and risk of masking serious pathology 6. Loperamide is contraindicated when organic disease has not been excluded and should never be used in patients with bloody diarrhea, high fever, or severe systemic symptoms 6, 7.

Instead:

• Maintain hydration with oral rehydration solutions 2, 7
• Continue carnivore diet temporarily until workup is complete, as dietary changes could interfere with diagnostic testing 1
• Address orthostatic symptoms with increased fluid and salt intake, compression stockings for edema 2
• Monitor for worsening symptoms requiring emergency evaluation (severe dehydration, hemodynamic instability, severe abdominal pain) 2, 7

Treatment After Diagnosis

Treatment must be specifically tailored to the underlying pathophysiology once identified 1:

• Celiac disease: strict lifelong gluten-free diet 1, 3
• Microscopic colitis: budesonide 1, 3
• Bile acid diarrhea: cholestyramine or bile acid sequestrants 1, 4, 3
• Inflammatory bowel disease: disease-specific immunosuppressive therapy 1
• Autonomic neuropathy: multidisciplinary approach with endocrinology, neurology, and gastroenterology 2
• Bacterial overgrowth: empirical trial of antibiotics 3

Why Functional Disorders Are Unlikely

Rome IV criteria have only 52-74% specificity and do not reliably exclude IBD, microscopic colitis, or bile acid diarrhea. 2, 3 This patient's presentation is inconsistent with functional disorders because:

• Nocturnal diarrhea essentially rules out irritable bowel syndrome 2, 1, 5, 8, 9
• Progressive worsening over 3 years with fecal incontinence indicates organic disease 1
• Autonomic symptoms (palpitations, orthostatic dizziness, nasal regurgitation) suggest systemic pathology 2, 1
• Bilateral pitting edema is not a feature of functional disorders 2