This is a complex presentation, but here are some possible causes and areas to investigate based on the history provided:

1. Allergic or Hypersensitivity Reaction

• While angioedema is often linked to an allergic trigger, her IgE levels are normal, and there is no clear trigger. It’s worth noting that angioedema without urticaria (hives) can sometimes occur without an obvious cause.
• Hereditary or acquired angioedema should still be considered even with a normal C1 inhibitor, as some forms may involve functional defects.
• Non-allergic hypersensitivity: Rare forms of angioedema can be triggered by other medications or environmental factors not classically associated with allergy.

2. Infectious Causes

• Mycoplasma, strep, or other common infectious agents seem ruled out.
• Consider rarer infections (e.g., parasitic infections like trichinosis, toxoplasmosis, or Lyme disease) depending on exposure history.

3. Autoimmune/Inflammatory Disorders

• Elevated CRP with normal ESR may indicate localized inflammation or a more acute phase of inflammation.
• Conditions like lupus pernio (a cutaneous manifestation of sarcoidosis) or orbital inflammatory syndrome should be evaluated by an ophthalmologist or rheumatologist.
• Vasculitis: Though rare, some vasculitides can present with isolated swelling.

4. Renal or Endocrine Issues

• If she has any subtle renal symptoms (e.g., hematuria, proteinuria), nephrotic syndrome or other renal disorders may present with periorbital edema.
• Hypothyroidism is less likely given a normal TSH, but subclinical forms are worth considering.

5. Idiopathic Angioedema

• If all other causes are ruled out, this may be idiopathic recurrent angioedema. It may respond to medications like antihistamines, corticosteroids, or prophylactic treatments like montelukast.

Suggestions for Next Steps:

1. Allergist Appointment:
• Further allergy testing, including drug-induced hypersensitivity evaluation.
• Testing for mast cell disorders if symptoms continue or worsen.
2. Rheumatology or Immunology Consult:
• Investigate autoimmune causes, including ANA, complement levels, and additional inflammatory markers.
3. Ophthalmology Referral:
• To assess for orbital cellulitis, inflammatory orbitopathy, or rare tumors.
4. Consider Imaging (MRI or CT of the orbits):
• To rule out structural abnormalities or deep-seated infections.
5. Dietary and Environmental Review:
• Continue monitoring for any possible triggers, even subtle ones (e.g., airborne allergens, dust mites).

If symptoms persist or worsen, escalation to a multi-disciplinary team approach (e.g., involving immunology, rheumatology, and ophthalmology) may provide the most comprehensive evaluation.