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Successful Treatment of Recalcitrant Chronic
Idiopathic Urticaria With Sulfasalazine
Laura Y. McGirt, MD; Kavitha Vasagar, MS; Laura M. Gober, MD; Sarbjit S. Saini, MD; Lisa A. Beck, MD Background: Antihistamines are the standard treat-
who required systemic steroids to control their urti- ment for chronic idiopathic urticaria (CIU). For pa- caria, all were able to reduce or discontinue steroid use tients whose urticaria is unresponsive to antihista- during sulfasalazine therapy. Although 7 patients (37%) mines, the treatment options are limited. During the had adverse effects (eg, nausea, headache, mild or tran- previous decade, there have been several case reports dem- sient leukopenia, and transaminitis) that were thought onstrating success with sulfasalazine therapy. In this ar- to be caused by the use of sulfasalazine, they all kept tak- ticle, we present a case series evaluating sulfasalazine therapy for antihistamine-unresponsive CIU.
Conclusions: This case series demonstrates that sul-
Observations: Nineteen patients with antihistamine-
fasalazine can be a successful and safe treatment option unresponsive CIU were treated with sulfasalazine be- for patients with CIU who have not responded ad- tween 2002 and 2005. During sulfasalazine therapy, 14 equately to treatment with antihistamines. Sulfasala- patients (74%) reported significant improvement, 4 pa- zine was steroid sparing in all subjects who were steroid tients (21%) reported minimal improvement but were not satisfied with their symptom relief, and 1 patient (5%)reported a worsening of symptoms. Of the 13 patients CHRONICIDIOPATHICURTI- beinganinfectiousorautoimmuneori-
thought to play a role in the development of CIU, but definitive proof is still lack- ing. For example, Helicobacter pylori has least 6 weeks, without an obvious cause.
been extensively studied as a possible caus- The wheals usually resolve in less than 24 ative agent, specifically in reference to its ability to cause formation of autoantibod- ies through the immunogenicity of its cell acute or chronic urticaria at some point in envelope.8 Currently, there is conflicting evidence in the literature as to an associa- mately 0.5% lifetime prevalence of CIU in tion between the eradication of H pylori such as Candida albicans and Malessezia furfur, have also been implicated.13,14 ies that have found that approximately 30% 90% of cases.5,6 The discomfort and nega- Author Affiliations:
chronic urticaria, as well as the elusive pathogenesis and the lack of satisfactory the ␣ chain of the high-affinity IgE recep- tor found on mast cells, basophils, and an- pies, can be very frustrating for patients and tigen-presenting cells have been isolated health care providers. It has also been es- from the serum of patients with CIU.18-20 timated that the disability suffered by those is also supported by the association of CIU Dr Beck is now with theDepartment of Dermatology, tify the pathogenesis of this disease, with 12% to 19% of patients with CIU,21-23 with (REPRINTED) ARCH DERMATOL/ VOL 142, OCT 2006 2006 American Medical Association. All rights reserved.
of patients with CIU have thyroid autoantibodies com- and antimicrosomal and antithyroglobin antibodies, was per- pared with 6% of the general population.23,24 formed. A punch biopsy of an urticarial wheal was performed Currently, antihistamines, which generally work by to rule out other diagnoses such as urticarial vasculitis and to alleviating the symptoms rather than enacting a cure, are further characterize the urticaria as lymphocyte or neutrophil the standard treatment for CIU.25,26 With the recent ad- predominant. Patients were counseled on the potential ad-verse effects of sulfasalazine, including headache, photosensi- vent of nonsedating or minimally sedating H1 receptor tivity, gastrointestinal distress, liver and kidney abnormali- antagonists, some patients with CIU have found relief from ties, leukopenia, and reversible oligospermia. The sulfasalazine symptoms without the adverse effect of excessive drowsi- therapy was started at a dosage of 500 mg/d and increased by ness. Unfortunately, there are those whose urticaria does 500 mg each week until a satisfactory clinical response was not respond to treatment with antihistamines, with some achieved or until a daily dose of 2 to 4 g/d was reached. Dur- studies reporting a 5% to 12% failure rate with fexofena- ing dose escalation, blood work was repeated weekly and then dine hydrochloride therapy.27,28 For those individuals, H every 3 months after the final dosage had been reached.
receptor antagonists, leukotriene antagonists, and sys- Based on subjective reports, the patients were categorized temic corticosteroids have also been used, with varying into the following groups: significant or nonsignificant im- degrees of success.29,30 The potential role of an autoim- provement, no change, or worse with the use of sulfasalazine.
Patients with significant improvement had at least a 50% re- mune mechanism in at least some cases of CIU has led duction of their urticaria according to a subjective report of re- to the use of alternative therapies focusing on immuno- sponse using either a symptom severity scale from 1 to 10 or a modulation. For example, recent randomized trials have report of symptom frequency. One of patients with significant demonstrated the efficacy of cyclosporine.31,32 There have improvement was classified as such based on the statement in also been smaller, uncontrolled studies indicating a po- his medical record that during sulfasalazine therapy his urti- tential benefit from dapsone33 and hydroxychloro- caria was “minimally symptomatic.” Nonsignificant improve- quine,34 and additional case reports have shown prom- ment included those who noted a minimal decrease in urti- ise with other medications such as methotrexate35,36 and caria but were not satisfied enough to continue taking cyclophosphamide.37 Despite these advances, many per- sulfasalazine. Anyone not classified as having significant im- sons still suffer from therapy-resistant CIU. There is a provement was considered a treatment failure. Patients gener-ally had a clinical response to sulfasalazine within 2 to 4 weeks need for further investigation of immunoregulatory agents but required a full 8-week course before being classified as a with more benign adverse effect profiles that can effec- tively reduce or eradicate the symptoms of urticaria anddecrease the need for systemic steroids.
Over the last decade, there have been sporadic case REVIEW OF THE LITERATURE
reports demonstrating successful alleviation of symp-toms with the use of sulfasalazine.38-40 We present a re- A computer search of the MEDLINE database (http://www.ncbi view of the literature and a retrospective review of our .nlm.nih.gov/entrez/query.fcgi) was performed, as was a re- own institutional experience with sulfasalazine for the view of the reference section of each primary source. All cases treatment of recalcitrant CIU. In 2 patients taking sul- of chronic urticaria that were treated with sulfasalazine and de- fasalazine, we also noted a functional change in the his- scribed in the English-language medical literature between the tamine-releasing capabilities of their basophils before and years of 1966 and 2005 were identified.
after sulfasalazine treatment, a finding that coincided withclinical improvement (data not shown).
Nineteen patients from the Johns Hopkins Bayview Medi-cal Center were diagnosed as having CIU and started sul-fasalazine therapy between the years of 2002 and 2005.
RETROSPECTIVE CHART REVIEW
Fifteen patients (79%) were female, and the mean ± SDage was 39 ± 3 years. The mean ± SD duration of CIU We performed a retrospective medical chart review of 19 pa- symptoms before the initiation of sulfasalazine therapy tients diagnosed with CIU and subsequently treated with sul- was 81 ± 25 months, with a median of 60 months. The fasalazine at Johns Hopkins Bayview Medical Center, Balti-more, Md, from 2002 to 2005. The study was approved by the dosage ranged from 0.5 to 4 g/d, with a mean ± SD dose institutional review board at the Johns Hopkins Medical Insti- of 2 ± 0.16 g/d. Fourteen patients (74%) had a history of tutions, Baltimore. The diagnosis of CIU was based on clinical angioedema, and of the 16 patients with thyroid stud- history and physical examination and was supported by skin ies, 6 (38%) had evidence of thyroid autoimmunity biopsy findings in 17 cases (89%). The remaining 2 patients (Table 1). All 19 patients had tried at least 2 different
did not have any biopsy data on record and were diagnosed as antihistamines (including sedating and nonsedating). Ac- having CIU solely on their disease presentation. The follow- cording to the patients’ reports, they had taken as much ing information was obtained: disease duration, history of an- antihistamine as they could tolerate (in terms of adverse gioedema, presence of thyroid autoantibodies (antimicro- effects) and still did not have adequate control of their somal and antithyroglobin), thyroid function, dosage of sulfasalazine therapy, subjective clinical response to sulfasala-zine therapy, adverse effects during sulfasalazine therapy, thera- Fourteen patients (74%) reported significant improve- pies for CIU used before and after sulfasalazine therapy, and ment with the use of sulfasalazine. Four patients (21%) skin biopsy findings. Before the initiation of sulfasalazine therapy, reported nonsignificant improvement, and 1 patient (5%) baseline blood work, including kidney and liver function tests, felt that the urticaria worsened during sulfasalazine a complete blood cell count, and determination of thyrotropin therapy (Table 2). The average maximum dosage of
(REPRINTED) ARCH DERMATOL/ VOL 142, OCT 2006 2006 American Medical Association. All rights reserved.
Table 1. Individual Patient Demographics and Response to Sulfasalazine Therapy
Duration of
% Symptom
Previous
Systemic
Systemic
Duration
Sulfasalazine
Reduction or
Steroids Before
Steroids During
Response to
Sulfasalazine
Therapy,
Subjective
Antihistamine
Sulfasalazine
Sulfasalazine
Sulfasalazine
Sulfasalazine
Dose, g/d
(180 mg/d),hydroxyzine HCl(75 mg nightly) (180 mg/d), cetirizineHCl (10 mg twice daily),hydroxyzine HCl(50 mg nightly) (4 mg 3 times daily),cetirizine HCl(10 mg/d) Abbreviations: approx, approximately; CIU, chronic idiopathic urticaria; ellipses, not applicable; HCl, hydrochloride.
(REPRINTED) ARCH DERMATOL/ VOL 142, OCT 2006 2006 American Medical Association. All rights reserved.
the urticaria was seen in all patients after they took the Table 2. Clinical Response to and Adverse Effects
sulfasalazine for anywhere from a few days to multiple Associated With Sulfasalzine Therapy
weeks. The dosage of sulfasalazine therapy required forresponse ranged from 2 to 4 g/d, with a mean of 3.2 g/d.
Variable
All subjects were able to stop using corticosteroids but did require a maintenance dose of sulfasalazine (2-3 g/d). The urticaria flared in 3 patients who attempted dose reduc- tion below their maintenance dose. The mean follow-up period was 9 months. No adverse effects were reported, and 50% of the patients were reported to have undergone routine blood work during the treatment. Two patients also received folate supplementation (1 mg/d) during treat- ment. In summary, these patients were reported to have Adverse effects due to sulfasalazine therapy complete clearance of their urticaria, were able to stop (eg, headache, gastrointestinal complaints, leukopenia,and transaminitis) (n = 19) taking systemic steroids, and had no reported adverse sulfasalazine therapy was 1.8 g/d for those with signifi- cant improvement and 2.6 g/d for those who failed treat-ment. Treatment failure was not associated with sex, eth- Sulfasalazine is composed of a sulfapyridine covalently nicity, duration of CIU symptoms, characteristics of the linked to 5-aminosalicylic acid. The sulfa moiety is known cellular infiltrate in the biopsy specimen, history of an- to have antimicrobial properties, whereas the salicylate com- gioedema, thyrotropin level, presence of antimicro- ponent acts as an anti-inflammatory agent. Despite our somal or antithyroglobin antibodies, or previous ste- knowledge of the structure and activity of sulfasalazine, we have a poor understanding of how it produces therapeutic Thirteen patients required intermittent or long-term effects in disease. It has been used most extensively in the daily treatment with systemic steroids before initiation treatment of inflammatory bowel disease (ie, Crohn dis- of sulfasalazine therapy for control of their urticaria. Of ease and ulcerative colitis), and it also been used to treat those patients, 9 did not require any steroid use during rheumatoid arthritis, psoriasis, ankylosing spondylitis, and treatment with sulfasalazine, and the other 4 were able to reduce their dose of steroids 3- to 4-fold. One patient We are reporting our use of sulfasalazine over the pre- classified as a treatment failure did require steroids dur- vious 3 years to treat 19 patients with CIU that was not ing sulfasalazine therapy, whereas she had not required adequately controlled with standard therapy. We classi- fied 14 patients (74%) as having significant improve- Six patients have been able to completely stop taking ment with sulfasalazine therapy, and 6 of the patients were all other urticaria medication, including antihistamines able to stop taking all other medication for CIU. Five pa- and systemic steroids. Two of the aforementioned pa- tients (26%) were not satisfied with sulfasalazine and were tients have tapered off sulfasalazine, and another has re- considered treatment failures despite the fact that 4 of duced her dosage of sulfasalazine by 50%, all without a them did experience minimal improvement in symp- recurrence of urticarial symptoms. Sulfasalzine therapy toms. We also found that all 13 patients who had previ- was tapered in the 3 others, and they developed in- ously required systemic steroids for CIU control were able creased urticaria, requiring a reinitiation of or an in- to completely stop or reduce their steroid intake during Adverse effects attributed to sulfasalazine use were re- It is also worth noting that the patients in our study ported by 7 patients (37%). They ranged from mild head- had different demographics from those of previously de- ache and gastrointestinal discomfort to mild leukopenia scribed CIU populations. Our cohort had a greater female- (white blood cell count, 3.7ϫ103/µL and 4.2ϫ103/µL) in male ratio (4:1 vs 2:1)4 and an increase in thyroid auto- 2 patients and elevated liver enzyme levels (aspartate ami- immunity (38% vs 14%-27%).23,24 Although we were notransferase/alanine aminotransferase, 54/75 IU/L) in unable to perform quality-of-life measurements owing to 1 patient. All of these patients were able to continue the the retrospective nature of this study, it is likely that our use of sulfasalazine, and the cases of leukopenia and el- cohort represents a more severe form of the disease. All evated liver enzyme levels resolved spontaneously or with patients seen in clinic were referred for recalcitrant CIU, as their urticaria had been inadequately controlled by an- There have been a few small case reports in the litera- tihistamines and other standard therapies. Also, more than ture citing successful treatment of CIU with sulfasalazine half of the patients (68%) had required systemic ste- in 6 subjects (5 men and 1 woman; mean age, 39.6 years).
roids, and the mean CIU duration before the initiation Three subjects were diagnosed as having CIU and 3 as hav- of sulfasalazine therapy was 81 months. It is possible that ing pressure-induced urticaria.38-40 All 6 subjects had been being female and having evidence of thyroid autoimmu- diagnosed as having urticaria that was refractory to stan- nity may be associated with a more severe form of CIU, dard antihistamine treatment, and all required treatment as both females and thyroid autoimmunity were over- with systemic steroids for control. Complete resolution of (REPRINTED) ARCH DERMATOL/ VOL 142, OCT 2006 2006 American Medical Association. All rights reserved.
Our follow-up period ranged from a few months to 3 CIU may help to elucidate the mechanism of action ex- years, and because of that we have extremely variable lon- erted by sulfasalazine. Overall, there has not been enough gitudinal data on our patients. We do know that 6 pa- evidence to firmly establish a causal relationship be- tients with significant improvement were able to taper tween any infectious agent and CIU,47 but if there were their sulfasalazine dosage. Two of the 6 patients were able such a relationship, sulfasalazine might be able to re- to stop taking all other urticaria medications and then duce the urticaria, at least in part, through its antimicro- successfully tapered off sulfasalazine therapy and have bial properties. Interestingly, sulfasalazine has also been been urticaria free for anywhere from 3 to 13 months.
effective in the treatment of other autoimmune diseases Another 2 were able to taper off sulfasalazine and all other such as rheumatoid arthritis and inflammatory bowel dis- urticaria medication for 4 to 12 months but then devel- ease. While we do not know whether our patients have oped a recurrence. The last 2 patients tapered their dos- an autoimmune basis for their urticaria, it is possible that age of sulfasalazine therapy from 2 g/d to 1 g/d, and 1 sulfasalazine therapy is combating the autoimmune pro- developed a mild increase in urticaria.
The dosage of sulfasalazine therapy for various in- In addition to a potential autoimmune component flammatory conditions has ranged widely from 2 to 6 g/d.
and/or infectious pathogenesis, basophils and mast cells We initially set our maximum dose at 4 g/d, but after we are thought to play a role in CIU. A recent publication treated a number of patients, it became apparent that those reports a difference in the FcεRI-signaling molecules in without improvement at 2 g/d rarely improved at higher basophils and mast cells of patients with CIU that may doses. Also, adverse effects have been reported to occur be critical for development of urticaria.48 In the 1990s, with greater frequency at higher doses, so we rarely pre- Lee and Kim49 demonstrated reduced histamine release scribe a dose higher than 2 g/d. Of the patients who re- in the peritoneal mast cells of rats, when treated with sul- sponded, most started to see an improvement after a few fasalazine. Similar studies on human mast cells and ba- weeks, although some required closer to 1 month for any sophils found the opposite, ie, that sulfasalazine en- hanced IgE-induced histamine release.50,51 Interestingly, Seven patients (37%) reported adverse effects from the the metabolite of sulfasalazine, 5-aminosalicylic acid, use of sulfasalazine, including gastrointestinal discom- caused a reduction of IgE-induced release of histamine fort, nausea, and mild headache, as well as leukopenia and in human basophils and mast cells.50 Although it is un- elevated liver enzyme levels. These complications have been clear how this alteration in basophil and mast cell func- reported previously, and all of the patients were able to con- tion affects the presentation of CIU, we believe that it is tinue taking sulfasalazine, although some reduced their dose possible that the clinical improvement seen with sul- from 2 g/d to 1.5 g/d. Also, the abnormal liver enzyme lev- fasalazine therapy may be associated with a distinct phe- els and leukopenia had resolved on follow-up testing. Be- notypic change in the histamine-releasing capabilities of cause of the adverse effect profile of sulfasalazine and the laboratory monitoring required, we do not suggest it as a Chronic idiopathic urticaria continues to be a frus- first-line agent for CIU. Instead, we believe that sulfasala- trating disease for many patients. Therefore, we must look zine therapy is most beneficial when antihistamines and for new treatments and evaluate potential causes of this other common medications with a more benign adverse disease. In summary, we believe that the findings we re- effect profile (eg, H2-receptor antagonists and leukotriene port suggest that sulfasalazine therapy can be an effec- antagonists) do not adequately control symptoms. Based tive and safe treatment for patients with recalcitrant CIU.
on the current risk-benefit profile, it is reasonable to try Its ability to improve symptoms in the majority of our sulfasalazine therapy instead of treatment with medica- patients and to greatly reduce systemic steroid use indi- tions such as systemic steroids or cyclosporine. Because of cates that it should be considered when standard thera- concerns about prescribing sulfasalazine for patients re- pies fail. We also believe that our initial results warrant ported to be sulfa allergic, 1 patient (not included in our further studies to better elucidate the efficacy of sul- data set) was started on olsalazine therapy (maximum dose, fasalazine in the treatment of CIU and to help clarify the 1.5 g/d). Of note, she also experienced significant improve- mechanism of action of sulfasalazine in patients with CIU.
We are aware that the retrospective nature of our case Accepted for Publication: March 31, 2006.
series does introduce certain biases, as we are relying on Correspondence: Lisa A. Beck, MD, Department of Der-
the patient record as the sole source of information. We matology, University of Rochester, 601 Elmwood Ave, were not able to have any objective measurement of PO Box 697, Rochester, NY 14642 (lisa_beck@URMC change in disease during sulfasalazine therapy, and we were not able to standardize follow-up for all patients.
Author Contributions: Dr Beck had full access to all the
Despite these problems, we do believe that the steroid- data in the study and takes responsibility for the integ- sparing effects and the impressive reduction in urticaria rity of the data and the accuracy of the data analysis. Study that the majority of our patients with fairly severe and concept and design: McGirt and Beck. Acquisition of data: long-standing, recalcitrant CIU experienced indicate that McGirt, Vasagar, Gober, Saini, and Beck. Analysis and in- sulfasalazine threapy should be considered for patients terpretation of data: McGirt, Vasagar, Gober, Saini, and with CIU that does not respond adequately to antihista- Beck. Drafting of the manuscript: McGirt, Saini, and Beck.
Critical revision of the manuscript for important intellec- It is not clear how sulfasalazine is able to reduce and tual content: McGirt, Saini, and Beck. Statistical analysis: even resolve CIU, but looking at the proposed causes of McGirt and Beck. Obtained funding: Saini and Beck. Ad- (REPRINTED) ARCH DERMATOL/ VOL 142, OCT 2006 2006 American Medical Association. All rights reserved.
ministrative, technical, and material support: McGirt. Study edema with thyroid autoimmunity: a study of 90 patients. J Allergy Clin Immunol.
25. Kaplan AP. Chronic urticaria—new concepts regarding pathogenesis and treatment.
Financial Disclosure: None reported.
Curr Allergy Asthma Rep. 2002;2:263-264.
Funding/Support: This study was supported in part by
26. Stanaland BE. Treatment of patients with chronic idiopathic urticaria. Clin Rev grants AI50024 (Dr Beck) and AI01564 (Dr Saini) from Allergy Immunol. 2002;23:233-241.
the National Institutes of Health, Bethesda, Md.
27. Kulthanan K, Gritiyarangsan P, Sitakalin C, et al. Multicenter study of the effi- cacy and safety of fexofenadine 60 mg twice daily in 108 Thai patients with chronicidiopathic urticaria. J Med Assoc Thai. 2001;84:153-159.
28. Vena GA, Cassano N, Filieri M, Filotico R, D’Argento V, Coviello C. Fexofenadine in chronic idiopathic urticaria: a clinical and immunohistochemical evaluation.
1. Swinney B. The atopic factor in urticaria. South Med J. 1941;34:855-858.
Int J Immunopathol Pharmacol. 2002;15:217-224.
2. Sheldon JM, Mathews KP, Lovell RG. The vexing urticaria problem: present con- 29. Sanada S, Tanaka T, Kameyoshi Y, Hide M. The effectiveness of montelukast for cepts of etiology and management. J Allergy. 1954;25:525-560.
the treatment of anti-histamine-resistant chronic urticaria. Arch Dermatol Res.
3. Greaves MW. Chronic idiopathic urticaria. Curr Opin Allergy Clin Immunol. 2003; 30. Kaplan AP. Chronic urticaria: pathogenesis and treatment. J Allergy Clin Immunol.
4. Sibbald RG, Cheema AS, Lozinski A, Tarlo S. Chronic urticaria: evaluation of the role of physical, immunologic, and other contributory factors. Int J Dermatol.
31. Grattan CE, O’Donnell BF, Francis DM, et al. Randomized double-blind study of cy- closporin in chronic “idiopathic” urticaria. Br J Dermatol. 2000;143:365-372.
5. Sabroe RA, Seed PT, Francis DM, Barr RM, Black AK, Greaves MW. Chronic id- 32. Di Gioacchino M, Di Stefano F, Cavallucci E, et al. Treatment of chronic idio- iopathic urticaria: comparison of the clinical features of patients with and with- pathic urticaria and positive autologous serum skin test with cyclosporine: out anti-FcepsilonRI or anti-IgE autoantibodies. J Am Acad Dermatol. 1999; clinical and immunological evaluation. Allergy Asthma Proc. 2003;24: 6. Champion RH, Roberts SO, Carpenter RG, Roger JH. Urticaria and angio- 33. Cassano N, D’Argento V, Filotico R, Vena GA. Low-dose dapsone in chronic id- oedema: a review of 554 patients. Br J Dermatol. 1969;81:588-597.
iopathic urticaria: preliminary results of an open study. Acta Derm Venereol. 2005; 7. O’Donnell 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.
34. Reeves GE, Boyle MJ, Bonfield J, Dobson P, Loewenthal M. Impact of hydroxy- 8. Greaves MW. Chronic Idiopathic urticaria and H pylori: not directly causative but chloroquine therapy on chronic urticaria: chronic autoimmune urticaria study and could there be a link? ACI Int. 2001;13:23-26.
evaluation. Intern Med J. 2004;34:182-186.
9. Federman DG, Kirsner RS, Moriarty JP, Concato J. The effect of antibiotic therapy 35. Gach JE, Sabroe RA, Greaves MW, Black AK. Methotrexate-responsive for patients infected with Helicobacter pylori who have chronic urticaria. J Am chronic idiopathic urticaria: a report of two cases. Br J Dermatol. 2001;145: Acad Dermatol. 2003;49:861-864.
10. Gaig P, Garcia-Ortega P, Enrique E, Papo M, Quer JC, Richard C. Efficacy of the 36. Weiner MJ. Methotrexate in corticosteroid-resistant urticaria. Ann Intern Med.
eradication of Helicobacter pylori infection in patients with chronic urticaria: a placebo-controlled double blind study. Allergol Immunopathol (Madr). 2002; 37. Bernstein JA, Garramone SM, Lower EG. Successful treatment of autoimmune chronic idiopathic urticaria with intravenous cyclophosphamide. Ann Allergy Asthma 11. Hook-Nikanne J, Varjonen E, Harvima RJ, Kosunen TU. Is Helicobacter pylori in- fection associated with chronic urticaria? Acta Derm Venereol. 2000;80:425-426.
38. Jaffer AM. Sulfasalazine in the treatment of corticosteroid-dependent chronic id- 12. Moreira A, Rodrigues J, Delgado L, Fonseca J, Vaz M. Is Helicobacter pylori in- iopathic urticaria. J Allergy Clin Immunol. 1991;88:964-965.
fection associated with chronic idiopathic urticaria? Allergol Immunopathol (Madr).
39. Hartmann K, Hani N, Hinrichs R, Hunzelmann N, Scharffetter-Kochanek K. Suc- cessful sulfasalazine treatment of severe chronic idiopathic urticaria associated 13. Serrano H. Hypersensitivity to “Candida albicans” and other fungi in patients with with pressure urticaria. Acta Derm Venereol. 2001;81:71.
chronic urticaria [in Spanish]. Allergol Immunopathol (Madr). 1975;3:289-298.
40. Engler RJ, Squire E, Benson P. Chronic sulfasalazine therapy in the treatment of 14. Tang XP, Zeng K, Chen GH, Bi LY, Fan LZ, Shao CF. Study of the association of delayed pressure urticaria and angioedema. Ann Allergy Asthma Immunol. 1995; Malassezia furfur with chronic urticaria among the ship crews [in Chinese]. Di Yi Jun Yi Da Xue Xue Bao. 2003;23:870-872.
41. Dougados M, Boumier P, Amor B. Sulphasalazine in ankylosing spondylitis: a 15. Fiebiger E, Maurer D, Holub H, et al. Serum IgG autoantibodies directed against double blind controlled study in 60 patients. Br Med J (Clin Res Ed). 1986; the alpha chain of Fc epsilon RI: a selective marker and pathogenetic factor for a distinct subset of chronic urticaria patients? J Clin Invest. 1995;96:2606-2612.
42. Willoughby CP, Cowan RE, Gould SR, Machell RJ, Stewart JB. Double-blind com- 16. Tong LJ, Balakrishnan G, Kochan JP, Kinet JP, Kaplan AP. Assessment of auto- immunity in patients with chronic urticaria. J Allergy Clin Immunol. 1997;99: parison of olsalazine and sulphasalazine in active ulcerative colitis. Scand J Gas- troenterol Suppl. 1988;148:40-44.
17. Zweiman B, Valenzano M, Atkins PC. Modulation of serum histamine releasing ac- 43. Pinals RS, Kaplan SB, Lawson JG, Hepburn B. Sulfasalazine in rheumatoid arthri- tivity in chronic idiopathic urticaria. Immunopharmacology. 1998;39:225-234.
tis: a double-blind, placebo-controlled trial. Arthritis Rheum. 1986;29:1427-1434.
18. Niimi N, Francis DM, Kermani F, et al. Dermal mast cell activation by autoanti- 44. Summers RW, Switz DM, Sessions JT Jr, et al. National Cooperative Crohn’s Dis- bodies against the high affinity IgE receptor in chronic urticaria. J Invest Dermatol.
ease Study: results of drug treatment. Gastroenterology. 1979;77:847-869.
45. Gupta AK, Ellis CN, Siegel MT, et al. Sulfasalazine improves psoriasis: a double- 19. Hide M, Francis DM, Grattan CE, Hakimi J, Kochan JP, Greaves MW. Autoanti- blind analysis. Arch Dermatol. 1990;126:487-493.
bodies against the high-affinity IgE receptor as a cause of histamine release in 46. Dougados M, vam der Linden S, Leirisalo-Repo M, et al. Sulfasalazine in the treat- chronic urticaria. N Engl J Med. 1993;328:1599-1604.
ment of spondylarthropathy: a randomized, multicenter, double-blind, placebo- 20. Grattan CE. Histamine-releasing autoantibodies in chronic urticaria. Skin Pharmacol.
controlled study. Arthritis Rheum. 1995;38:618-627.
47. Kozel MM, Sabroe RA. Chronic urticaria: aetiology, management and current and 21. Kandeel AA, Zeid M, Helm T, Lillie MA, Donahue E, Ambrus JL Jr. Evaluation of future treatment options. Drugs. 2004;64:2515-2536.
chronic urticaria in patients with Hashimoto thyroiditis. J Clin Immunol. 2001; 48. Vonakis BM, Saini SS. Basophils and mast cells in chronic idiopathic urticaria.
Curr Allergy Asthma Rep. 2005;5:270-276.
22. Turktas I, Gokcora N, Demirsoy S, Cakir N, Onal E. The association of chronic 49. Lee EH, Kim HM. Inhibition of anaphylaxis by sulfasalazine in rats. Pharmacology.
urticaria and angioedema with autoimmune thyroiditis. Int J Dermatol. 1997; 50. Fox CC, Moore WC, Lichtenstein LM. Modulation of mediator release from hu- 23. Zauli D, Grassi A, Ballardini G, Contestabile S, Zucchini S, Bianchi FB. Thyroid man intestinal mast cells by sulfasalazine and 5-aminosalicylic acid. Dig Dis Sci.
autoimmunity in chronic idiopathic urticaria: implications for therapy. Am J Clin 51. Barrett KE, Tashof TL, Metcalfe DD. Inhibition of IgE-mediated mast cell de- 24. Leznoff A, Sussman GL. Syndrome of idiopathic chronic urticaria and angio- granulation by sulphasalazine. Eur J Pharmacol. 1985;107:279-281.
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