Why do I have hives despite Cetirizine, with normal tests?

Question

Hello doctor,

I have been experiencing chronic urticaria for the past six months, with daily itchy welts mostly on my arms and legs, sometimes on the face. I took antihistamines like Cetirizine, but the effect wears off quickly. Allergy testing did not reveal any specific triggers.

My CBC and liver function tests came back normal, and I do not have a thyroid disorder. So, can you give your suggestions on the following:

Could this be autoimmune urticaria?
Should I ask my doctor about Omalizumab or another advanced treatment if antihistamines are not working well anymore?
Also, could stress or diet be contributing even though I have not noticed a consistent pattern?

Please help.

Answer 1

Hello,

Welcome to icliniq.com.

I understand your concern.

Thank you for getting in touch. I completely understand how frustrating and exhausting it can be to deal with chronic urticaria daily, especially when standard antihistamines stop working effectively over time.

Based on your description, daily itchy welts without a clear allergic trigger, normal blood tests, and no thyroid issues, it is very likely that you are experiencing chronic spontaneous urticaria, possibly with an autoimmune basis. In these cases, the immune system may be inappropriately activating mast cells, even in the absence of any external allergen.

The possible causes can be chronic spontaneous urticaria, possibly autoimmune-mediated. I suggest you get the following investigations:

Autologous serum skin test (ASST) to check for autoimmune urticaria.
ANA (antinuclear antibody test) to rule out autoimmune diseases.
ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein) are used to detect any underlying inflammation.
Serum tryptase, especially if symptoms are severe or involve angioedema.

Differential diagnoses to consider are:

Chronic spontaneous (idiopathic) urticaria.
Autoimmune urticaria.
Physical urticaria (triggered by cold, pressure, or heat).
Drug-induced urticaria.
Urticarial vasculitis (if lesions are painful or last more than 24 hours).

The probable diagnosis is chronic spontaneous urticaria, likely autoimmune. The treatment plan includes:

Continue taking nonsedating antihistamines (such as Cetirizine or Fexofenadine). These can be taken at up to four times the usual dose under medical supervision.
If symptoms persist, consider adding a leukotriene receptor antagonist like Montelukast.
For cases unresponsive to the above, Omalizumab (an anti-IgE injection) is a highly effective third-line option.
Your allergist or dermatologist can advise further. During flares, a short course of oral corticosteroids (like Prednisolone) may help, though they are not suitable for long-term use.
Avoid common triggers such as NSAIDs (non-steroidal anti-inflammatory drugs
Avoid known aggravating factors like tight clothing, extreme temperatures, and alcohol.

Discuss with your healthcare provider about starting Omalizumab or similar biologics if antihistamines no longer provide relief. Keep a record of any changes in symptom patterns, duration of flare-ups, or new symptoms like fever or joint pain. Some preventive measures you can take are:

Maintain a daily symptom and food diary. Patterns may emerge over time, even if they are not obvious right now.
Manage emotional stress, which can worsen symptoms.
Try to take a low-histamine diet temporarily. This means avoiding foods like fermented products, aged cheeses, processed meats, and alcohol.

Feel free to share any recent test results or updates on your symptoms. I would be glad to help you navigate the next steps.

I hope this helps.

Thank you.