What is the diagnosis and treatment for a patient experiencing flushing in the cheeks, feeling disoriented, loss of memory, tingling in the lower legs and feet, and sensations in the arms and back?

Differential Diagnosis and Management of Acute Multi-System Symptoms

Immediate Priority: Rule Out Life-Threatening Conditions

This symptom constellation—flushing, altered mental status, memory loss, and peripheral paresthesias—requires immediate exclusion of anaphylaxis, stroke/TIA, and mast cell activation syndrome before considering other diagnoses. 1, 2

First-Line Assessment: Anaphylaxis Evaluation

• Anaphylaxis is highly likely if: acute onset with skin involvement (flushing) plus either respiratory compromise OR two or more organ systems involved (neurological symptoms with flushing qualifies) 1, 2
• Administer epinephrine 0.3 mg intramuscularly into mid-outer thigh immediately if anaphylaxis criteria are met—do not delay for laboratory confirmation 1
• Obtain serum tryptase 15 minutes to 3 hours after symptom onset, but normal levels do NOT rule out anaphylaxis 1, 2
• Look for additional anaphylaxis features: urticaria, angioedema, pruritus, tachycardia, hypotension, wheezing, or gastrointestinal symptoms 2, 3

Second Priority: Stroke/TIA Assessment

• Patients with acute onset neurological symptoms (disorientation, memory loss, sensory changes) require urgent stroke evaluation 2
• This patient has multiple concerning features: altered mental status ("feels out of it"), memory loss, and bilateral sensory symptoms in extremities and back 2
• Perform immediate brain CT or preferably MRI with T1, T2, and FLAIR-weighted images 2
• CT angiography should assess both extracranial and intracranial circulation ('aortic arch-to-vertex') 2
• Obtain ECG to assess for atrial fibrillation or other arrhythmias that could cause embolic stroke 2

Third Priority: Mast Cell Activation Syndrome (MCAS)

• MCAS presents with episodic flushing plus two or more organ systems involved concurrently (cardiovascular, dermatologic, respiratory, gastrointestinal, or neurological) 2
• Neurological manifestations include: dizziness, lightheadedness, confusion, altered mental status, and restlessness 2
• Obtain urinary N-methylhistamine, 11β-PGF2α, and LTE4 during symptomatic episodes 2
• Serum tryptase should be >baseline × 1.2 + 2 ng/mL during acute episodes 2
• Common triggers include: hot water, alcohol, drugs, stress, exercise, hormonal fluctuations, infection, and physical stimuli 2

Secondary Differential Diagnoses

Diabetic Neuropathy with Autonomic Dysfunction

• Distal symmetric polyneuropathy causes tingling in lower legs and feet, with possible sensory changes in arms and back 2
• Autonomic neuropathy can cause flushing, heat intolerance, and altered mental status from blood pressure dysregulation 2
• Screen with: temperature sensation, pinprick sensation, vibration perception (128-Hz tuning fork), pressure sensation (10-g monofilament), and ankle reflexes 2
• Obtain fasting glucose, HbA1c, and assess for postural hypotension 2

Medication-Induced Flushing with Neurological Effects

• SSRIs (like escitalopram), niacin, calcium channel blockers, nitrates, ACE inhibitors, and vancomycin commonly cause flushing 3, 4
• Review all current medications, including recent additions or dose changes 3
• Prostacyclins (epoprostenol, treprostinil, iloprost) cause prominent flushing 4
• Consider serotonin syndrome if patient takes SSRIs: altered mental status, autonomic instability, and neuromuscular changes 4

Carcinoid Syndrome and Pheochromocytoma

• Carcinoid syndrome causes episodic flushing, diarrhea, and neurological symptoms from serotonin release 3
• Measure serum serotonin and 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA) 3
• Pheochromocytoma causes flushing, headache, palpitations, and altered mental status from catecholamine surges 3
• Measure plasma-free metanephrine and urinary vanillylmandelic acid 3

Panic Attack with Somatic Manifestations

• Panic attacks have sudden onset with trembling, dizziness, de-realization, paresthesias, and hot flushes 2
• However, memory loss and persistent disorientation are atypical for panic attacks alone 2
• Consider panic disorder only after excluding organic causes 2

Diagnostic Algorithm

1. Immediate (within minutes): Assess for anaphylaxis criteria and administer epinephrine if present 1
2. Urgent (within 1 hour): Obtain vital signs, ECG, capillary glucose, complete blood count, electrolytes, renal function 2
3. Urgent (within 2-4 hours): Brain CT/MRI with vascular imaging if neurological symptoms persist 2
4. Same day: Serum tryptase (if within 3 hours of symptom onset), comprehensive metabolic panel 2, 1
5. Within 24-48 hours: Urinary mast cell mediators (if MCAS suspected), diabetic neuropathy screening, medication review 2
6. Within 1 week: Carcinoid and pheochromocytoma workup if symptoms persist without alternative explanation 3

Critical Pitfalls to Avoid

• Do not delay epinephrine if anaphylaxis criteria are met while waiting for tryptase results 1
• Do not attribute all symptoms to anxiety without excluding stroke, especially with acute memory loss and altered mental status 2
• Do not rely solely on loss of consciousness to determine stroke severity—memory impairment and sensory symptoms alone warrant urgent evaluation 2
• Do not overlook medication-induced causes, which are far more common than neoplastic etiologies 3, 4
• Do not dismiss bilateral sensory symptoms as "atypical"—they can represent spinal cord pathology, diabetic neuropathy, or systemic processes 2

Initial Management Pending Diagnosis

• Ensure hemodynamic stability and continuous monitoring if altered mental status persists 2
• Avoid beta-blockers if MCAS suspected, as they may worsen symptoms 2
• Consider H1 and H2 antihistamines (diphenhydramine and famotidine) if mast cell activation suspected 2
• Optimize glucose control if diabetic neuropathy identified 2
• Discontinue or adjust potentially causative medications after consultation 3, 4