Urticária Crónica - Do Diagnóstico ao Tratamento
Resumo
Cerca de 20 % da população sofre pelo menos um episódio de urticária e 0,5 a 1 % sofre de urticária crónica, com uma duração média entre 1 e 5 anos e uma maior incidência em mulheres entre os 20 e os 40 anos. Dada a publicação, em 2014, de recomendações europeias para a sua orientação diagnóstica e terapêutica, os autores fazem uma revisão dos vários aspetos da urticária crónica. A urticária crónica, resultante da libertação de mediadores pró-inflamatórios do mastócito, caracteriza- se pelo aparecimento diário ou quase diário, de lesões cutâneas maculopapulares, eritematosas, pruriginosas e/ou angioedema, que persistem por um período superior a 6 semanas. Classifica-se em urticária crónica espontânea ou indutível, sendo aconselhável a realização de exames complementares de acordo com a história clínica. O tratamento é sintomático, baseado em evidência, sendo a 1ª linha os anti-histamínicos H1 de 2ª geração, que podem ser aumentados até 4x a dose aprovada e numa 3ª linha, fármacos como o omalizumab ou a ciclosporina. Dado o impacto negativo na qualidade de vida e os custos que esta patologia crónica acarreta, é de extrema importância alertar os clínicos para a necessidade de diagnóstico e tratamento correcto precoces e, se necessário, referenciação atempada para centros especializados, tendo sempre como objetivo o controlo completo dos sintomas, da forma mais segura possível.
Downloads
Referências
Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, et al. The EAACI/GA(2) LEN/EDF/
WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and
update. Allergy. 2014; 69:868-87.
Gimenez-Arnau AM, Grattan C, Zuberbier T, Toubi E. An individualized diagnostic approach based on guidelines
for chronic urticaria (CU). J Eur Acad Dermatol Venereol. 2015; 29:3-11.
Toubi E, Kessel A, Avshovich N, Bamberger E, Sabo E, Nusem D, et al. Clinical and laboratory parameters in
predicting chronic urticaria duration: a prospective study of 139 patients. Allergy. 2004; 59:869-73.
Maurer M, Weller K, Bindslev-Jensen C, Gimenez-Arnau A, Bousquet PJ, Bousquet J, et al. Unmet clinical needs
in chronic spontaneous urticaria. A GA(2)LEN task force report. Allergy. 2011; 66:317-30.
Magerl M, Borzova E, Gimenez-Arnau A, Grattan CE, Lawlor F, Mathelier-Fusade P, et al. The definition and
diagnostic testing of physical and cholinergic urticarias-EAACI/GA2LEN/EDF/UNEV consensus panel recommendations. Allergy. 2009; 64:1715-21.
Kozel MMA, Mekkes JR, Bossuyt PM, Bos JD. Natural course of physical and chronic urticaria and angioedema
in 220 patients. J Am Acad Dermatol. 2001; 45:387-91.
Delong LK, Culler SD, Saini SS, Beck LA, Chen SC. Annual direct and indirect health care costs of chronic idiopathic urticaria. Arch Dermatol. 2008; 144:35-9.
Maurer M, Ortonne JP, Zuberbier T. Chronic urticaria: a patient survey on quality-of-life, treatment usage and
doctor-patient relation. Allergy. 2009 ;64:581-8.
Zuberbier T, Maurer M. Omalizumab for the treatment of chronic urticaria. Expert Rev Clin Immunol. 2015;
:171-80.
ODonnell BF, Lawlor F, Simpson J, Morgan M, Greaves MW. The impact of chronic urticaria on the quality of life.
Br J Dermatol. 1997; 136:197-201.
Ferrer M. Immunological events in chronic spontaneous urticaria. Clin Transl Allergy. 2015;5:30.
Kay AB, Ying S, Ardelean E, Mlynek A, Kita H, Clark P, et al. Elevations in vascular markers and eosinophils
in chronic spontaneous urticarial weals with low-level persistence in uninvolved skin. Br J Dermatol. 2014;
:505-11.
Kay AB, Ying S, Ardelean E, Mlynek A, Kita H, Clark P, et al. Calcitonin gene-related peptide and vascular endothelial growth factor are expressed in lesional but not uninvolved skin in chronic spontaneous urticaria. Clin
Exp Allergy. 2014; 44:1053-60.
Kay AB, Clark P, Maurer M, Ying S. Elevations in T-helper-2-initiating cytokines (interleukin-33, interleukin-25
and thymic stromal lymphopoietin) in lesional skin from chronic spontaneous ('idiopathic') urticaria. Br J Dermatol.
; 172:1294-302.
Asero R, Tedeschi A, Marzano AV, Cugno M. Chronic spontaneous urticaria: immune system, blood coagulation,
and more. Expert Rev Clin Immunol. 2016; 12:229-31.
Atwa MA, Emara AS, Youssef N, Bayoumy NM. Serum concentration of IL-17, IL-23 and TNF-alpha among
patients with chronic spontaneous urticaria: association with disease activity and autologous serum skin test. J Eur
Acad Dermatol Venereol. 2014;28:469-74.
Konstantinou GN, Asero R, Ferrer M, Knol EF, Maurer M, Raap U, et al. EAACI taskforce position paper: evidence
for autoimmune urticaria and proposal for defining diagnostic criteria. Allergy. 2013; 68:27-36.
Saini SS. Basophil responsiveness in chronic urticaria. Curr Allergy Asthma Rep. 2009; 9:286-90.
Hide M, Francis DM, Grattan CEH, Hakimi J, Kochan JP, Greaves MW. Autoantibodies against the high-affinity ige
receptor as a cause of histamine-release in chronic urticaria. New Engl J Med. 1993; 328:1599-604.
Altrichter S, Peter HJ, Pisarevskaja D, Metz M, Martus P, Maurer M. IgE mediated autoallergy against thyroid
peroxidase-a novel pathomechanism of chronic spontaneous urticaria? PLoS One. 2011; 6:e14794.
Hatada Y, Kashiwakura J, Hayama K, Fujisawa D, Sasaki-Sakamoto T, Terui T, et al. Significantly high levels
of anti-dsdna immunoglobulin e in sera and the ability of dsdna to induce the degranulation of basophils from
chronic urticaria patients. Intl Arch Allergy Immunol. 2013; 161:154-8.
Losol P, Yoo HS, Park HS. Molecular genetic mechanisms of chronic urticaria. Allergy Asthma Immunol Res. 2014; 6:13-21.
Wu CH, Ardern-Jones MR, Eren E, Venter C. An observational study of the diagnosis and management of chronic
urticaria in the UK. Int Arch Allergy Immunol. 2015; 167:1-8.
Celen OM, Kutlubay Z, Aydemir EH. Usefulness of the autologous serum test for the diagnosis of chronic idiopathic urticaria. Ann Dermatol. 2014; 26:592-7.
Hipolito AC. Diagnóstico de urticária crónica autoimune-Estudo de activação dos basófilos por citometria de
fluxo. [consultado Jan 206] Disponível em: http://repositorio.ul.pt/.../18102_ulsd_dep.17630_Tese_de_mestrado.
www.biblioteca.fm.ul.pt. 2009.
Christensen CU, Vestergaard C, Hoffmann HJ. Activation markers CD63 and CD203c are upregulated in chronic
urticaria. Allergy. 2014 ; 69:581.
Asero R. D-dimer: A biomarker for antihistamine-resistant chronic urticaria. J Allergy Clin Immunol. 2013 ;
:983-6.
Marzano AV, Tavecchio S, Venturini M, Sala R, Calzavara-Pinton P, Gattorno M. Urticarial vasculitis and urticarial
autoinflammatory syndromes. G Ital Dermatol Venereol. 2015 ; 150:41-50.
Venzor J, Lee WL, Huston DP. Urticarial vasculitis. Clinical Reviews in Allergy Immunol. 2002; 23:201-16.
de Koning HD, Bodar EJ, van der Meer JWM, Simon A. Schnitzler syndrome: Beyond the case reports: Review
and follow-up of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum. 2007;
:137-48.
Berkun Y, Eisenstein EM. Diagnostic criteria of familial Mediterranean fever. Autoimmun Rev. 2014; 13:388-90.
Yu JR, Leslie KS. Cryopyrin-associated periodic syndrome: an update on diagnosis and treatment response.
Curr Allergy Asthma Rep. 2011; 11:12-20.
Weller K, Ardelean E, Scholz E, Martus P, Zuberbier T, Maurer M. Can on-demand non-sedating antihistamines
improve urticaria symptoms? A double-blind, randomized, single-dose study. Acta Derm Venereol. 2013 27;
:168-74.
Sharma M, Bennett C, Carter B, Cohen SN. H1-antihistamines for chronic spontaneous urticaria: An abridged
Cochrane Systematic Review. J Am Acad Dermatol. 2015; 73:710-6.
Church MK, Maurer M, Simons FER, Bindslev-Jensen C, van Cauwenberge P, Bousquet J, et al. Risk of first-generation H-1-antihistamines: a GA2LEN position paper. Allergy. 2010; 65:459-66.
Staevska M, Gugutkova M, Lazarova C, Kralimarkova T, Dimitrov V, Zuberbier T, et al. Night-time sedating
H1 -antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria:
a randomized controlled trial. Br J Dermatol. 2014; 171:148-54.
Simons FER, Silver NA, Gu XC, Simons KJ. Clinical pharmacology of H-1-antihistamines in the skin. J Allergy Clinical Immunol. 2002; 110:777-83.
de Silva NL, Damayanthi H, Rajapakse AC, Rodrigo C, Rajapakse S. Leukotriene receptor antagonists for chronic
urticaria: a systematic review. Allergy Asthma Clin Immunol. 2014; 10:24.
Di Gioacchino M, Di Stefano F, Cavallucci E, Verna N, Ramondo S, Paolini F, et al. Treatment of chronic idiopathic
urticaria and positive autologous serum skin test with cyclosporine: Clinical and immunological evaluation. Allergy
Asthma Proc. 2003; 24:285-90.
Grattan CE, O'Donnell BF, Francis DM, Niimi N, Barlow RJ, Seed PT, et al. Randomized double-blind study of
cyclosporin in chronic 'idiopathic' urticaria. Br J Dermatol. 2000; 143:365-72.
Kessel A, Toubi E. Low-dose cyclosporine is a good option for severe chronic urticaria. J Allergy Clin Immunol.
; 123:970.
Vena GA, Cassano N, Colombo D, Peruzzi E, Pigatto P. Cyclosporine in chronic idiopathic urticaria: a double-
-blind, randomized, placebo-controlled trial. J Am Acad Dermatol. 2006; 55:705-9.
Kaplan A, Ledford D, Ashby M, Canvin J, Zazzali JL, Conner E, et al. Omalizumab in patients with symptomatic
chronic idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol. 2013; 132:101-9.
Maurer M, Rosen K, Hsieh HJ, Saini S, Grattan C, Gimenez-Arnau A, et al. Omalizumab for the treatment
of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013; 368:924-35.
Saini SS, Bindslev-Jensen C, Maurer M, Grob JJ, Baskan EB, Bradley MS, et al. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on h-1 antihistamines: a randomized, placebo-controlled study. J Invest Dermatol. 2015; 135:67-75.
Silva PM, Costa AC, Mendes A, Barbosa MP. Long-term efficacy of omalizumab in seven patients with treatment-
-resistant chronic spontaneous urticaria. Allergol Immunopathol. 2015;43:168-73.
Silva PM, Costa AC, Mendes A, Barbosa MP. Eficácia do tratamento com omalizumab na urticária crónica espontânea resistente à terapêutica habitual combinada.
Metz M, Ohanyan T, Church MK, Maurer M. Retreatment with omalizumab results in rapid remission in chronic
spontaneous and inducible urticaria. JAMA Dermatol. 2014;150:288-90.
Metz M, Ohanyan T, Church MK, Maurer M. Omalizumab is an effective and rapidly acting therapy in difficult-
to-treat chronic urticaria: a retrospective clinical analysis. J Dermatol Sci. 2014; 73:57-62.
Lang DM. Omalizumab is efficacious for management of recalcitrant, antihistamine-resistant chronic urticaria.
Drugs Today. 2015 ; 51:367-74.
Urgert MC, van den Elzen MT, Knulst AC, Fedorowicz Z, van Zuuren EJ. Omalizumab in patients with chronic
spontaneous urticaria: a systematic review and GRADE assessment. Br J Dermatol. 2015; 173:404-15.
Mitchell S, Balp MM, Samuel M, McBride D, Maurer M. Systematic review of treatments for chronic spontaneous
urticaria with inadequate response to licensed first-line treatments. Int J Dermatol.2015; 54:1088-104.
Savic S, Marsland A, McKay D, Ardern-Jones MR, Leslie T, Somenzi O, et al. Retrospective case note review of chronic spontaneous urticaria outcomes and adverse effects in patients treated with omalizumab or ciclosporin in UK
secondary care. Allergy Asthma Clin Immunol. 2015;11:21.
Asero R, Tedeschi A. Usefulness of a short course of oral prednisone in antihistamine-resistant chronic urticaria: a retrospective analysis. J Investig Allergol Clin Immunol. 2010; 20:386-90.
Sackesen C, Sekerel BE, Orhan F, Kocabas CN, Tuncer A, Adalioglu G. The etiology of different forms of urticaria in childhood. Pediatr Dermatol. 2004; 21:102-8.
Fitzsimons R, van der Poel LA, Thornhill W, du Toit G, Shah N, Brough HA. Antihistamine use in children. Arch
Dis Childhood-Educ Pract Ed. 2015; 100:122-31.
Ahmed SF, Tucker P, Mushtaq T, Wallace AM, Williams DM, Hughes IA. Short-term effects on linear growth
and bone turnover in children randomized to receive prednisolone or dexamethasone. Clin Endocrinol. 2002;
:185-91.
Doshi DR, Weinberger MM. Experience with cyclosporine in children with chronic idiopathic urticaria. Pediatr Dermatol. 2009; 26:409-13.
Neverman L, Weinberger M. Treatment of chronic urticaria in children with antihistamines and cyclosporine. J
Allergy ClinImmunol Pract. 2014; 2:434-8.
Asero R, Casalone R, Iemoli E. Extraordinary response to omalizumab in a child with severe chronic
urticaria. Eur Ann Allergy Clin Immunol. 2014; 46: 41-2.
Netchiporouk E, Nguyen CH, Thuraisingham T, Jafarian F, Maurer M, Ben-Shoshan M. Management of pediatric
chronic spontaneous and physical urticaria patients with omalizumab: case series. Pediatr Allergy Immunol.
;26:585-8.
Hilbert J, Moritzen V, Parks A, Radwanski E, Perentesis G, Symchowicz S, et al. The Pharmacokinetics of loratadine in normal geriatric volunteers. J Int Med Res. 1988;16:50-60.
Asero R, Tedeschi A, Cugno M. Treatment of refractory chronic urticaria: current and future therapeutic options.
Am J ClinDermatol, 2013; 14:481-8.
Lawlor F. Urticaria and angioedema in pregnancy and lactation. Immunol Allergy Clin North Am. 2014;
:149-56.
Maurer M, Church MK, Goncalo M, Sussman G, Sanchez-Borges M. Management and treatment of chronic
urticaria (CU). J Eur Acad Dermatol Venereol. 2015;29:16-32.
Mcgee DC. Steroid use during pregnancy. J Perinat Neonatal Nurs. 2002; 16:26-39.
Koren G, Sarkar M, Einarson A. Safety of using montelukast during pregnancy. Can Fam Physician. 2010;
:881-2.
Clift DE, Thorn RJ, Passarelli EA, Kapoor M, LoPiccolo MK, Richendrfer HA, et al. Effects of embryonic cyclosporine exposures on brain development and behavior. Behav Brain Res. 2015; 282:117-24.
Namazy J, Cabana MD, Scheuerle AE, Thorp JM, Chen H, Carrigan G, et al. The Xolair Pregnancy Registry (EXPECT): The safety of omalizumab use during pregnancy. J Allergy Clinical Immunol. 2015 ; 135:407-12.
Kaplan AP, Joseph K, Maykut RJ, Geba GP, Zeldin RK. Treatment of chronic autoimmune urticaria with omalizumab. J Allergy ClinImmunol. 2008; 122:569-73.
Maurer M, Altrichter S, Bieber T, Biedermann T, Brautigam M, Seyfried S, et al. Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase. J Allergy Clin Immunol. 2011; 128:202-9.
Saini S, Rosen KE, Hsieh HJ, Wong DA, Conner E, Kaplan A, et al. A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine-refractory chronic idiopathic urticaria.
J Allergy Clin Immunol. 2011; 128:567-73.
Labrador-Horrillo M, Valero A, Velasco M, Jauregui I, Sastre J, Bartra J, et al. Efficacy of omalizumab in chronic
spontaneous urticaria refractory to conventional therapy: analysis of 110 patients in real-life practice. Expert Opin
Biol Therap. 2013; 13:1225-8.
Altman MC, Naimi DR. Omalizumab for chronic urticaria. New Engl J Med. 2013; 368:2528-30.
Sussman G, Hebert J, Barron C, Bian J, Caron-Guay RM, Laflamme S, et al. Real-life experiences with omalizumab for the treatment of chronic urticaria. Ann Allergy Asthma Immunol. 2014; 112:170-4.
Toubi E, Blant A, Kessel A, Golan TD. Low-dose cyclosporin A in the treatment of severe chronic idiopathic urticaria. Allergy. 1997; 52:312-6.
Inaloz HS, Ozturk S, Akcali C, Kirtak N, Tarakcioglu M. Low-dose and short-term cyclosporine treatment in
patients with chronic idiopathic urticaria: A clinical and immunological evaluation. J Dermatol. 2008; 35:276-
Loria MP, Dambra PP, D'Oronzio L, Nettis E, Pannofino A, Cavallo E, et al. Cyclosporin A in patients affected
by Chronic Idiopathic Urticaria: A therapeutic alternative. Immunopharmacol Immunotoxicol. 2001; 23:205-13.
Kessel A, Toubi E. Cyclosporine-A in severe chronic urticaria: the option for long-term therapy. Allergy. 2010;
:1478-82.
Nettis E, Colanardi MC, Paradiso MT, Ferrannini A. Desloratadine in combination with montelukast in the
treatment of chronic urticaria: a randomized, double-blind, placebo-controlled study. Clin Exp Allergy. 2004;
:1401-7.
Kosnik M, Subic T. Add-on montelukast in antihistamine-resistant chronic idiopathic urticaria. Respir Med. 2011;
:S84-S8.
Lynch N, Khan S. Efficacy of montelukast in chronic idiopathic urticaria. Clin Exp Allergy. 2011; 41:1836.
Todos os artigos desta revista são de acesso aberto sob a licença internacional Creative Commons Attribution-NonCommercial 4.0 (CC BY-NC 4.0).