Chronic spontaneous urticaria, despite its cause being unknown, is linked to a higher prevalence of autoimmune diseases, and is often worsened by triggers like stress, infections, certain foods, or nonsteroidal anti-inflammatory drugs.

Mast cells release proteases, histamine, cytokines, and arachidonic acid metabolites, causing swelling, redness, and itching.

Basic laboratory tests, such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and possibly a complete blood count (CBC) with differential, are critical for detecting signs of systemic inflammation and ruling out autoinflammatory conditions as well as urticarial vasculitis with systemic involvement.

A therapeutic approach should be implemented in three steps, according to current guidelines: (1) taking a second-generation antihistamine once daily; (2) increasing the second-generation antihistamine's daily dose up to four times; and (3) pursuing off-label therapy with cyclosporine A or montelukast or add-on therapy with omalizumab, which is an approved treatment option for CSU.

[10] Many patients with chronic spontaneous urticaria report that certain triggers, like stress, infections, certain foods, or nonsteroidal anti-inflammatory drug consumption, cause their disease to worsen.

[10] Researchers found that patients with systemic lupus erythematosus, rheumatoid arthritis, thyroid issues, celiac disease, Sjögren syndrome, and type 1 diabetes had higher rates of these conditions than those with chronic urticaria in a study involving a database of 13,000 patients compared to 10,000 control subjects.

[12] The majority of patients with chronic spontaneous urticaria frequently linked multiple triggers to flare-ups.

[13] However, the suspected trigger does not always result in symptoms, so patients frequently subject themselves to needless limitations and lifestyle modifications.

These cells release proteases, histamine, and cytokines along with platelet-activating factors and other metabolites of arachidonic acid.

[7] These mediators cause swelling, redness, and itching by stimulating sensory nerve endings, increasing vascular permeability, and inducing vasodilatation.

[20] T-cell expression of IL-4, IL-5, and IFN-g is evident in the lesion cytokine profile, indicating a mixed TH1/TH2 response.

[21] The dermis of lesion skin contains epithelial-derived cytokines that support the TH2 profile, such as IL-33, IL-25, and thymic stromal lymphopoietin, as well as the vasoactive agents calcitonin gene-related peptide and vascular endothelial growth factor.

Because chronic as well as recurrent infections are known to cause urticaria, only differential blood counts and CRP or ESR are advised if no symptom-inducing factor can be found.

[37] Basic laboratory tests, which include inflammatory markers C-reactive protein (CRP) as well as erythrocyte sedimentation rate (ESR) and possibly complete blood count (CBC) with differential, are crucial to detect signs of systemic inflammation and rule out autoinflammatory conditions as well as UV with systemic involvement.

[39] Here, the doctor should closely examine the patient's history, age at symptom onset, duration of attacks, presence of abdominal angioedema episodes, use of concurrent medications (particularly ACE inhibitor intake), lack of response to antihistamines or corticosteroids, and prodromal symptoms.

[16] According to current guidelines, a therapeutic approach should be implemented in three steps: (1) taking a second-generation antihistamine once daily; (2) increasing the daily dose of the second-generation antihistamine up to four times; and (3) pursuing off-label therapy with cyclosporine A or montelukast or add-on therapy with omalizumab, which is an approved treatment option for CSU.

[44] Despite having nearly as good of an efficacy as omalizumab, cyclosporine is regarded as third line because it carries a much higher risk of side effects.

[45] Long-term use of corticosteroids is not advised because the side effects increase with dosage and duration and eventually result in greater disability than CSU.