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Keywords:

  • chronic urticaria;
  • leukotriene receptor antagonists;
  • leukotrienes;
  • montelukast;
  • therapy;
  • zafirlukast

Some patients with chronic idiopathic urticaria (CIU) do not respond to antihistamines and require long-term steroid administration or even cyclosporin to control their disease. Recently, several studies reported good results with antileukotriene drugs in CIU (1–4); however, a prospective investigation aiming to detect which patients are more likely to benefit from antileukotriene treatment has not been carried out yet.

Twelve consecutive patients with unremitting, steroid-dependent urticaria were studied. Clinical features and results of the main laboratory investigations are shown in Table 1. Montelukast 10 mg once a day (n=5) or zafirlukast 20 mg twice a day (n=7) was started. The usual therapies were not changed at the start of the scheduled 3-week treatment period, but patients were left free to reduce or withdraw antihistamine treatment in the case of a remission of the disease. Patients recorded both the severity of urticaria and the drugs used, and were followed up weekly. The primary end point of the study was an adequate control of the disease, defined as absence or marked reduction of pruritus and urticaria without the need for systemic steroid therapy.

Table 1.  Clinical features of patients studied
Patient no.Sex/age (years)DD (mo)NSAID intoleranceASSTHRAThyroid autoimmunityLRA usedOutcome
  1. DD (mo): disease duration (months); ASST: autologous serum skin test results; LRA: leukotriene receptor antagonist (M: montelukast; Z: zafirlukast); HRA: histamine-release assay (positive if >5%); NV: not evaluable due to severe dermatographism (ID test with saline positive); ND: not done.

1F/59160YesPosNDNegMRemission
2M/4730YesNegNDNegZUnchanged
3F/5924YesPos9.5%NegMRemission
4F/3780YesNDNDNegZUnchanged
5F/21150YesPosNDNegM/ZNot tolerated
6F/26150YesPosNDNegZRemission
7M/6116NoPosNegativePosZRemission
8F/7970NoPosNDNegZRemission
9M/2224NoPosNegativeNegZUnchanged
10M/623NoPosNDNegZUnchanged
11M/2696NoNENDNegMUnchanged
12F/6248NoNeg6%NegMRemission

One patient was excluded because of intolerance of both montelukast and zafirlukast (severe headache). Six of the remaining 11 patients (55%) responded to zafirlukast (n=3) or montelukast (n=3) (Table 1). In these subjects, leukotriene receptor antagonists (LRA) induced a nearly total remission of the disease: four could easily control their urticaria with cetirizine 10 mg every other day, and two could discontinue antihistamine treatment altogether. The effect of LRA was already appreciable after some days of treatment. Responders have now been followed up for 6–24 months; they are still taking LRA and are all still in remission. No clinical feature or specific “marker” (sex, age, duration of the disease, NSAID intolerance, autologous serum skin test [ASST] result, thyroid autoimmunity, or histamine-releasing activity of serum) was associated with the response to LRA (Table 1).

Leukotrienes might well play a central pathogenic role in some patients with CIU. Their injection into human skin produces a wheal and flare reaction (5), and, on a molar basis, they are 100 times more potent than histamine; moreover, serum from some patients with CIU, particularly those positive on ASST, induces both histamine release and de novo production of sulfidoleukotrienes in human basophils (6).

Interestingly, in one study (3), one nonresponder to LRA showed a complete response to the lipoxygenase inhibitor, zileuton, suggesting a possible pathogenic role for LTB4, a substance that enhances cutaneous microvascular permeability by a not yet identified neutrophil-derived mediator (7). Because zileuton is not available in Italy, we could not confirm these observations.

This study suggests that, in view of their good tolerability and low cost, LRA should be tried in all patients with unremitting, steroid-dependent chronic urticaria before more challenging therapies, such as IVIG or cyclosporin, are considered.

Acknowledgments

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  2. Acknowledgments
  3. References

We thank Mr Enos Venturini and Ms Sonia Minisini for technical assistance.

References

  1. Top of page
  2. Acknowledgments
  3. References