Treatment of chronic spontaneous urticaria with an inadequate response to H1-antihistamine

Abstract

Chronic spontaneous urticaria (CSU) is characterized by the sudden, continuous or intermittent appearance of pruritic wheals (hives), angioedema or both for 6 weeks or more, with no known specific trigger. The international EAACI/GA 2 LEN/EDF/WAO urticaria guideline advises standard-dose, second-generation H 1-antihistamines as first-line therapy. However, H 1-antihistamine treatment leads to absence of symptoms in fewer than 50% of patients. Updosing of second-generation H 1-antihistamines (up to fourfold) as recommended by the EAACI/GA 2 LEN/EDF/WAO urticaria guideline as second-line therapy can improve response, but many patients remain symptomatic. Definitions of response are often subjective and a consensus is needed regarding appropriate treatment targets. There is also an unmet need for biomarkers to assess CSU severity and activity and to predict treatment response. The EAACI/GA 2 LEN/EDF/WAO urticaria guideline recommends add-on omalizumab, ciclosporin A (CsA) or montelukast third line in patients with an inadequate response to high-dose H 1-antihistamines. Omalizumab is currently the only licensed systemic biologic for use in CSU. Both omalizumab and CsA are effective third-line CSU treatments; montelukast appears to have lower efficacy in this setting. Omalizumab carries a label warning for anaphylaxis, although no cases of anaphylaxis were reported in the phase III trials of omalizumab in CSU and it is generally well tolerated in patients with CSU. Omalizumab arguably has a better safety profile than CsA.

Doxepin in difficult‐to‐treat chronic urticaria: A retrospective, cross‐sectional study from Turkey

“…However, severe adverse reactions are mainly observed in patients with psychiatric disorders for which doxepin is prescribed in much higher doses than for CU. This helps explain the lack of significant adverse effects both in our study as well as in previous studies (Table 2) (Bernstein, 1982;Figueiredo et al, 1990;Ghose & Haldar, 1990;Goldsobel et al, 1986;Greene et al, 1985;Harto et al, 1985;Mukhopadhyay et al, 1995;Neittaanmäki et al, 1984). Although sedation and anticholinergic effects have been previously reported in several studies on CU, they are generally tolerated well by patients (Goldsobel et al, 1986;Harto et al, 1985), comparable to our results.…”

“…The management of CU patients with a poor response to antihistamines is challenging (Curto‐Barredo & Gimenez‐Arnau, ). Doxepin is an old tricyclic antidepressant (TCA) with high H1 and H2 histamine and muscarinic receptor blocking activities.…”

“…The management of CU patients with a poor response to antihistamines is challenging (Curto-Barredo & Gimenez-Arnau, 2019).…”

Combination therapy with omalizumab and an immune-suppressive agent for resistant chronic spontaneous urticaria - A real-life experience

“… 33 Data regarding methotrexate and azathioprine for CSU is scarce. 31 , 34 , 35 Although both are used as “steroid sparing” drugs for many autoimmune conditions, they are seldom recommended for CSU. In the current study, as described, only 2 patients that could not receive cyclosporine received these drugs.…”

Biomarcadores na Urticária Crónica Espontânea

“…1 Os AH2g são recomendados no tratamento da UCE, mas na prática 50% dos doentes, ou mais, não responde às doses recomendadas, nem mesmo com as doses mais elevadas recomendadas como segunda linha terapêutica. 13,[21][22][23] A ausência tão marcada de resposta pode resultar do facto de existirem outros mediadores libertados pelos mastócitos ou outras células também envolvidas na UCE. Nos infiltrados celulares das lesões dérmicas podem-se encontrar também basófilos, eosinófilos, neutrófilos e linfócitos, sendo estes casos ainda mais refratários aos anti-histamínicos.…”