Urticaria consists of pruritic skin lesions of a wheal-and-flare reaction: a localized intra-dermal oedema (wheal) that is surrounded by erythema. Individual hives can last from 30 minutes up to 36 hours.
Urticaria is classified as acute or chronic based on duration of symptoms.1
Acute urticaria – urticaria clearing within 6 weeks. This type of urticaria is the result of an allergic reaction to food, medications or infection.
Chronic urticaria – urticaria persisting for more than 6 weeks. This type has an incidence of 0.5% in the general population.1 It is further divided into two categories: autoimmune and idiopathic. Chronic autoimmune urticaria accounts for 45% of cases, and chronic idiopathic urticaria is seen in the other 55% of cases.
Physical urticaria and urticarial vasculitis are not considered to be chronic urticaria.
The mainstay of urticaria treatment is antihistamines. Patients with chronic urticaria have to take antihistamines for longer periods. In some patients, antihistamines are not able to control symptoms effectively. Evaluation of chronic urticaria to rule out autoimmune cause is not practised routinely. However, if autoantibodies are found, immunosuppressive therapy can be useful.
Materials and methods
Sixty patients with chronic urticaria, consulted over a 2-year period, were evaluated. Patients presenting with urticarial wheals daily for a period of more than 6 weeks were selected. The average duration of symptoms was 6 months. One patient had the symptoms for 15 years. Five patients had symptoms for a period of more than 3 years. These patients were on antihistamines regularly or intermittently.
Evaluation of case history and physical examination were used to rule out physical urticaria and urticarial vasculitis. Complete blood count, a thyroid function test and an evaluation of antithyroid antibody prevalence were advised. An autologous serum skin test was not performed for logistical reasons.
Patients positive for antithyroid antibodies were given immunosuppressive therapy (methotrexate, 15 mg per week) as well as antihistamines [levocetrizine (Xyzal®, UCB Pharma Ltd., Mumbai, India) 5 mg].
Out of 60 patients, 24 were male and 36 were female (Figure 1).
The majority of the patients were between 20 and 40 years of age (46 in total) and the rest were more than 40 years of age (14 in total) (Figure 2).
Complete blood count was normal, but basophil depletion was seen in all samples. Seventeen patients were positive for antithyroid antibodies, of which 10 were positive for antimicrosomal antibodies and the remaining seven were positive for both antimicrosomal and antithyroglobulin antibodies. Two patients were diagnosed with subclinical hypothyroidism.
Patients positive for antithyroid antibodies were prescribed methotrexate tablets (7.5 mg per week) for 4 weeks. After 4 weeks the dose was increased to 15 mg per week. Regular monitoring of complete blood count, liver function and renal function was carried out. After 12 weeks of treatment, patients reported dissipation of itchy wheals more consistently than with antihistamines alone.
After 6 months of treatment with methotrexate, repeat titres of antithyroid antibodies were carried out. There was a significant decline in antithyroid antibody levels.
Clinically these patients could discontinue antihistamines. Five patients showed recurrence of symptoms 3 months after discontinuation of treatment, but the symptoms were mild and easily controlled with antihistamines.
Autoimmune urticaria accounts for 45% of chronic urticaria cases.2 It is characterized by the formation of autoantibodies that trigger activation of mast cells in the skin. Anti-IgE and antiFcεRI autoantibodies are specific antibodies seen in sera from these patients. An association between autoimmune urticaria and autoimmune thyroid disease has also been observed. Hence, antithyroid antibodies have been detected in 12–29% of patients with autoimmune urticaria in various studies.3–6
For the most part, these antibodies are not associated with abnormal thyroid function.
The effects of replacement treatment for hypothyroidism on clinical symptoms of urticaria are still controversial. Leznoff et al.7 reported that l-thyroxine therapy improved clinical symptoms of chronic urticaria. Some studies confirmed this observation, while other authors failed to find any influence of l-thyroxine on the course of urticaria.8–10
The combination of immunosuppressive therapy and antihistamines is said to be beneficial for autoimmune urticaria patients. Ciclosporin (Sandimmun®/Neoral®, Novartis Pharmaceuticals, Surrey, UK), tacrolimus (Pangraf®, Panacea Biotec Ltd., New Delhi, India), methotrexate and intravenous immunoglobulins have all been used to treat chronic autoimmune urticaria.
Methotrexate is used in our patients because it is comparatively well tolerated, economical and easy to monitor for adverse effects.
The use of methotrexate in these patients resulted in the dissipation of all symptoms, which was followed by the reduction of antihistamine dosage with subsequent discontinuation of treatment in some patients. Five patients showed recurrence of symptoms 3 months after discontinuation of treatment, but the symptoms were mild and easily controlled with antihistamines.
Chronic urticaria is a very disturbing condition which impacts on quality of life. Antihistamines, alone or in combination with mast cell stabilizers, are not able to control the symptoms in many patients. Autoimmune cause is attributed to around 45% of chronic urticaria cases. Screening for antithyroid antibodies is useful, as they have been detected in 12–29% of patients with autoimmune urticaria. Immunosuppressive therapy in these patients controls progression of the disease and significantly reduces symptoms leading to an improved quality of life.