Chronic Autoimmune Urticaria

Introduction

Urticaria (hives) lasting six or more weeks is known as chronic urticaria. Though it is a benign disease, it significantly affects the quality of life. Chronic urticaria is of three types

• Physical urticaria.

• Chronic idiopathic urticaria.

• Urticaria vasculitis.

In several patients with chronic idiopathic urticaria, an autoimmune basis for the disease has been identified over the past few years. Therefore on eliminating physical urticaria and urticaria vasculitis from all chronic urticaria cases, 45 % of the remainder is chronic autoimmune urticaria, and 55 % is chronic idiopathic urticaria.

In autoimmune urticaria, the patient’s serum has autoantibodies against IgE that will activate the serum basophils and mast cells in the skin along with complement release. The gold standard diagnostic test for chronic autoimmune urticaria is detecting the autoantibodies to FceRI. In addition, the activation of mast cells and serum basophils and the release of histamines are precise to chronic autoimmune urticaria. The pathogenicity of the autoimmune condition is not well known. On intradermal injection, the antibodies cause whealing, and eliminating auto-antibodies will result in disease remission. The disorder is seen in all age groups. Immunomodulatory treatment is efficient for treatment-resistant and severely affected patients.

What Is Chronic Autoimmune Urticaria?

Chronic autoimmune urticaria is a type of chronic idiopathic urticaria. Several studies suggest that 30 % to 50 % of people with idiopathic urticaria have autoantibodies against the FceRI-high-affinity IgE receptors (35 % to 40 %) and IgE antibodies (five to ten percent). Autoantibodies are highly significant clinically for severely affected and treatment-resistant patients. Therefore, immunomodulatory treatments are considered to be highly effective for such patients.

What Is the Pathogenesis of Autoimmune Urticaria?

Generally, many non-immunological and immunological agents can activate the mast cells in the skin and serum. However, in chronic autoimmune urticaria, autoantibodies against the IgE high-affinity receptors, IgE antibodies, and complement C5a are significant. The autoantibodies activate the mast cells to secrete mediators like histamine, interleukin-1, protease, and tumor necrosis factor alpha. The mediators are cytokines that increase the expression of adhesion molecules in the post-capillary venules. In addition, the initially synthesized mediators like leukotrienes, cytokines, prostaglandins, and chemokines will recruit the leucocytes and eosinophils, which is the late-phase reaction.

The high-affinity receptor of the IgE antibody has four peptide chains.

• Intracellular alpha-1 chain.

• Intracellular alpha-2 chain.

• Intracellular beta chain.

• Alpha chain with an extracellular component: it bears the IgE binding site.

The binding site for autoantibodies is located on the extracellular component of the alpha chain. Binding in this site will result in basophil and mast cell activation with the release of proinflammatory mediators. In patients with an affinity of autoantibodies for the IgE, the autoantibodies will cross-link with the receptor-bound IgE and dimerize the IgE bound to the mast cells, evoking the release of histamines. The autoantibodies can be inactivated by lactic acid stripping. The process will remove the IgE from the basophils and mast cells.

What Is the Role of Compliments in the Pathology of Chronic Autoimmune Urticaria?

Several studies suggest a significant involvement of the classical complement pathways and C5a in the pathogenesis of chronic autoimmune urticaria. The activation of the complement pathway and release of the complement C5a will help in activating the cutaneous mast cells. C5a attracts neutrophils and eosinophils, which explains the increased accumulation of neutrophils and eosinophils in the skin lesions.

What Are the Diagnostic Tests for Chronic Autoimmune Urticaria?

It is often difficult to distinguish between different types of chronic urticarias clinically and microscopically. The autologous serum skin test can be used as a screening test. Some reports suggest that the microscopic features of a positive autologous serum skin test indicate an IgE-mediated late-phase reaction.

The test is considered to be a useful tool for filtering chronic idiopathic urticaria patients who have wheal-producing factors in their serum. However, the specificity in identifying the autoantibodies against the high-affinity IgE receptor is low. The demonstration makes the confirmation of the diagnosis of histamine-releasing activity in the serum. At its best, the autologous serum skin test is 80 % sensitive and specific.

What Is the Confirmatory in Vitro Test for Chronic Autoimmune Urticaria?

Several non-histamine-releasing autoantibodies against the high-affinity IgE receptors are also present in the serum of chronic autoimmune urticaria patients. In such patients, immunoassays have poor specificity. Therefore, one of the most efficient confirmatory tests for chronic autoimmune urticaria is the demonstration of histamine release from the basophils and mast cells. The gold standard for detecting the autoantibodies against the high-affinity IgE receptors is the functional in vitro donor basophil histamine release assay. Basophil histamine release assay is the most common commercial service available from the laboratories.

What Is the Histological Appearance of Chronic Autoimmune Urticaria?

Microscopically, the skin of patients affected by chronic autoimmune urticaria shows a late-phase reaction. The infiltrate is characterized by an accumulation of granulocytes as opposed to other types of chronic urticarias. However, apart from the granulocytes, the other cells in the infiltrate are similar in both cases. The serum tryptase and cytokines are elevated in the autoimmune condition.

What Are the Treatment Strategies for Chronic Autoimmune Urticaria?

Patients are treated with oral antihistamines. H1 antihistamine remains the gold standard of treatment for all types of chronic urticaria. A tapering dose of prednisolone for a short duration is given in cases of flare-ups. Some lifestyle changes should be implemented in all the cases of chronic urticaria. Avoiding stress, alcohol, overtiredness, non-steroidal anti-inflammatory drugs, and tight-fitting clothes should be avoided.

The drugs employed in treatment are

• Oral antihistamines.

• Leukotriene antagonists.

• Cyclosporine.

• Tacrolimus.

• Methotrexate.

• Hydroxychloroquine.

According to a recent report, biologics is a practical treatment approach for resistant chronic autoimmune urticarias. Omalizumab reduces the level of free IgE and high-affinity IgE receptors, eventually reducing their expression on basophils and mast cells. It is effective in lowering urticarial lesions.

Conclusion

Chronic autoimmune urticaria satisfies most of the criteria for autoimmune disease. However, the absence of autoantibodies in patients with autoimmune urticarial lesions remains a mystery. Therefore, more efficient and specific in vitro tests needs to be developed for detecting and confirming the diagnosis of the disease.