[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 54.197.142.219. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Download PDF
Table 1. Demographic Characteristics of 12 720 Patients With Chronic Urticaria
Table 1. Demographic Characteristics of 12 720 Patients With Chronic Urticaria
Table 2. Standardized Incidence Ratios (SIRs) of Overall Cancer Occurrence in Chronic Urticariaa
Table 2. Standardized Incidence Ratios (SIRs) of Overall Cancer Occurrence in Chronic Urticariaa
Table 3. Standardized Incidence Ratios (SIRs) of Hematologic Cancers in Chronic Urticariaa
Table 3. Standardized Incidence Ratios (SIRs) of Hematologic Cancers in Chronic Urticariaa
Table 4. Standard Incidence Ratios (SIRs) of Specific Types of Hematologic Malignant Tumors in Chronic Urticariaa
Table 4. Standard Incidence Ratios (SIRs) of Specific Types of Hematologic Malignant Tumors in Chronic Urticariaa
Table 5. Standard Incidence Ratios (SIRs) of Nonhematologic Cancers in Chronic Urticariaa
Table 5. Standard Incidence Ratios (SIRs) of Nonhematologic Cancers in Chronic Urticariaa
1.
van der Valk PG, Moret G, Kiemeney LA. The natural history of chronic urticaria and angioedema in patients visiting a tertiary referral centre.  Br J Dermatol. 2002;146(1):110-113PubMedArticle
2.
Lindel öf B, Sigurgeirsson B, Wahlgren CF, Eklund G. Chronic urticaria and cancer: an epidemiological study of 1155 patients.  Br J Dermatol. 1990;123(4):453-456PubMedArticle
3.
Deacock SJ. An approach to the patient with urticaria.  Clin Exp Immunol. 2008;153(2):151-161PubMedArticle
4.
Kulthanan K, Cheepsomsong M, Jiamton S. Urticarial vasculitis: etiologies and clinical course.  Asian Pac J Allergy Immunol. 2009;27(2-3):95-102PubMed
5.
Shah D, Rowbottom AW, Thomas CL, Cumber P, Chowdhury MM. Hypocomplementaemic urticarial vasculitis associated with non-Hodgkin lymphoma and treatment with intravenous immunoglobulin.  Br J Dermatol. 2007;157(2):392-393PubMedArticle
6.
Lin CC, Lai MS, Syu CY, Chang SC, Tseng FY. Accuracy of diabetes diagnosis in health insurance claims data in Taiwan.  J Formos Med Assoc. 2005;104(3):157-163PubMed
7.
Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML. Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan.  Pharmacoepidemiol Drug Saf. 2011;20(3):236-242PubMedArticle
8.
Wu CY, Kuo KN, Wu MS, Chen YJ, Wang CB, Lin JT. Early Helicobacter pylori eradication decreases risk of gastric cancer in patients with peptic ulcer disease [published online ahead of print August 5, 2009].  Gastroenterology. 2009;137(5):1641-1648, e1-e2PubMedArticleArticle
9.
Chen YJ, Wu CY, Huang YL, Wang CB, Shen JL, Chang YT. Cancer risks of dermatomyositis and polymyositis: a nationwide cohort study in Taiwan [published online ahead of print April 16, 2010].  Arthritis Res Ther. 2010;12(2):R70PubMedArticleArticle
10.
Wu CY, Wu CH, Wu MS,  et al.  A nationwide population-based cohort study shows reduced hospitalization for peptic ulcer disease associated with H pylori eradication and proton pump inhibitor use.  Clin Gastroenterol Hepatol. 2009;7(4):427-431PubMedArticle
11.
Wu CY, Wu MS, Kuo KN, Wang CB, Chen YJ, Lin JT. Effective reduction of gastric cancer risk with regular use of nonsteroidal anti-inflammatory drugs in Helicobacter pylori –infected patients.  J Clin Oncol. 2010;28(18):2952-2957PubMedArticle
12.
Huang YL, Chen YJ, Lin MW,  et al.  Malignancies associated with dermatomyositis and polymyositis in Taiwan: a nationwide population-based study.  Br J Dermatol. 2009;161(4):854-860PubMedArticle
13.
Chen YJ, Chang YT, Wang CB, Wu CY. Malignancy in systemic lupus erythematosus: a nationwide cohort study in Taiwan.  Am J Med. 2010;123(12):1150.e1-1150.e6PubMedArticleArticle
14.
Chen YJ, Chang YT, Wang CB, Wu CY. The risk of cancer in rheumatoid arthritis patients: a nationwide cohort study in Taiwan.  Arthritis Rheum. 2010;63(2):352-358Article
15.
Breslow NE, Day NE. Statistical methods in cancer research, II: the design and analysis of cohort studies.  IARC Sci Publ. 1987;(82):1-406PubMed
16.
Greaves MW. Chronic urticaria.  N Engl J Med. 1995;332(26):1767-1772PubMedArticle
17.
Clore LS Jr, Stafford CT. Chronic urticaria as a presenting sign of hairy cell leukemia.  Allergy Asthma Proc. 1999;20(1):51-55PubMedArticle
18.
Alonso R, Cister ó-Bah íma A, Enrique E, Besses C. Chronic urticaria associated with chronic myelomonocytic leukemia.  J Investig Allergol Clin Immunol. 2000;10(6):380-381PubMed
19.
Lipsker D, Cribier B, Maloisel F, Heid E, Grosshans E. Chronic urticaria and IgA myeloma.  Acta Derm Venereol. 1998;78(5):395PubMedArticle
20.
Mowad CM, Mowad JJ, Cirigliano MD. Testicular cancer presenting as urticaria.  Cutis. 1998;61(3):147-148PubMed
21.
Reinhold U, Bruske T, Schupp G. Paraneoplastic urticaria in a patient with ovarian carcinoma.  J Am Acad Dermatol. 1996;35(6):988-989PubMedArticle
22.
Hills EA. Adenocarcinoma of the bronchus with Cushing's syndrome, carcinoid syndrome, neuromyopathy and urticaria.  Br J Dis Chest. 1968;62(2):88-92PubMedArticle
23.
Campanelli A, Prins C, Saurat JH. Chronic urticaria revealing a colonic adenocarcinoma.  J Am Acad Dermatol. 2005;52(6):1105PubMedArticleArticle
24.
Manganoni AM, Tucci G, Venturini M, Farisoglio C, Baronchelli C, Calzavara Pinton PG. Chronic urticaria associated with thyroid carcinoma: report of 4 cases.  J Investig Allergol Clin Immunol. 2007;17(3):192-195PubMed
25.
Weller K, Altrichter S, Ardelean E,  et al.  Chronic urticaria: prevalence, course, prognostic factors and impact.  Hautarzt. 2010;61(9):750-757PubMedArticle
26.
Lim W, Shumak KH, Reis M,  et al.  Malignant evolution of Schnitzler's syndrome —chronic urticaria and IgM monoclonal gammopathy: report of a new case and review of the literature.  Leuk Lymphoma. 2002;43(1):181-186PubMedArticle
27.
Puddu P, Cianchini G, Girardelli CR, Colonna L, Gatti S, de Pita O. Schnitzler's syndrome: report of a new case and a review of the literature.  Clin Exp Rheumatol. 1997;15(1):91-95PubMed
28.
Peterlana D, Puccetti A, Tinazzi E, Simeoni S, Lunardi C. Schnitzler's syndrome treated successfully with intravenous pulse cyclophosphamide.  Scand J Rheumatol. 2005;34(4):328-330PubMedArticle
29.
Rizzi R, Curci P, Rinaldi E,  et al.  Schnitzler's syndrome: monoclonal gammopathy associated with chronic urticaria.  Acta Haematol. 2008;120(1):1-4PubMedArticle
30.
Greaves MW, Tan KT. Chronic urticaria: recent advances.  Clin Rev Allergy Immunol. 2007;33(1-2):134-143PubMedArticle
31.
Champion RH. Urticaria: then and now.  Br J Dermatol. 1988;119(4):427-436PubMedArticle
32.
Farell AM, Sabroe RA, Bunker CB. Urticarial vasculitis associated with polycythaemia rubra vera.  Clin Exp Dermatol. 1996;21(4):302-304PubMedArticle
33.
Highet AS. Urticarial vasculitis and IgA myeloma.  Br J Dermatol. 1980;102(3):355-357PubMedArticle
34.
Blanco R, Martinez-Taboada VM, Gonzalez-Vela C, Rodriguez-Valverde V. Urticarial vasculitis as clinical presentation of megakaryocytic leukemia.  J Clin Rheumatol. 1996;2(6):366PubMedArticle
35.
Calvo-Romero JM. Diffuse large B cell lymphoma in a patient with hypocomplementemic urticarial vasculitis.  J Postgrad Med. 2003;49(3):252-253PubMed
36.
Bernatsky S, Joseph L, Boivin JF,  et al.  The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case-cohort study.  Ann Rheum Dis. 2008;67(1):74-79PubMedArticle
Evidence-Based Dermatology: Study
Jan 2012

Cancer Risk in Patients With Chronic UrticariaA Population-Based Cohort Study

Author Affiliations

Author Affiliations: Department of Dermatology (Dr Chen) and Faculty of Medicine (Dr Wu), National Yang-Ming University, Taipei; Division of Gastroenterology (Drs Wu and Chang and Ms Chen) and Department of Dermatology (Drs Chen and Shen), Taichung Veterans General Hospital, and Department of Life Sciences, National Chung-Hsing University (Dr Wu), Taichung; Department of Public Health, College of Public Health, China Medical University, Taichung (Dr Shen); and Department of Dermatology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei (Dr Chang), Taiwan.

Arch Dermatol. 2012;148(1):103-108. doi:10.1001/archdermatol.2011.682
Abstract

Objective To investigate the relative risk of cancer among patients with chronic urticaria in the Taiwanese population.

Design Retrospective population-based cohort study.

Setting The National Health Insurance Research Database of Taiwan from January 1, 1996, through December 31, 2008.

Participants A total of 12  720 patients with chronic urticaria, with long-term antihistamine use and no history of malignant tumors, autoimmune diseases, atopy, or allergic diseases.

Main Outcome Measure Relative cancer risk calculated by standardized incidence ratios.

Results There were 704 cancers among chronic urticaria patients. An increased risk of cancer (standardized incidence ratio, 2.2; 95% CI, 2.0-2.3), especially hematologic malignant tumor (4.1; 3.1-5.4), was observed. The relative risk of cancer varied by age and was highest among those aged 20 to 39 years in comparison with the general population. Most cancer cases were detected within the first year of diagnosis. The risk of non-Hodgkin lymphoma was greatest (standardized incidence ratio, 4.4; 95% CI, 3.0-6.1) among the hematologic cancers.

Conclusions Patients with chronic urticaria are at increased risk of cancer, especially hematologic malignant tumors. Further studies are needed to delineate the associations.

Chronic urticaria is a common and frustrating disorder, characterized by a diverse and heterogeneous presentation. The pathogenic mechanisms of chronic urticaria remain elusive. Chronic urticaria is defined as urticaria that persists for more than 6 weeks with daily or nearly daily symptoms. More than 50% of patients continue to experience chronic urticaria 10 years after initial diagnosis,1 and most of these patients need long-term treatment. In contrast to acute urticaria, there is no evidence of an exogenous allergen as a cause of this disorder. On the basis of different clinical presentations, chronic urticaria can be classified as ordinary urticaria, physical urticaria, angioedema, contact urticaria, or urticarial vasculitis.

Although there have been case reports of urticaria associated with malignant tumor, a study of more than 1000 patients showed no association between chronic urticaria and malignant tumor.2 Urticarial vasculitis sometimes occurs in patients with lymphoproliferative disease, such as mixed cryoglobulinemia and IgM gammopathy.3 Urticarial vasculitis with IgM gammopathy or Schnitzler syndrome has been associated with a higher frequency of hematologic malignant tumors.4,5 Only limited epidemiologic information is available about the exact extent of the association between chronic urticaria and cancer. Our aim was to evaluate the relative risk of cancer occurrence among chronic urticaria patients who have received long-term antihistamine treatment by means of a nationwide population-based database of Taiwan.

METHODS
DATA SOURCES

This study was based on data from the National Health Insurance Research Database (NHIRD) released by the National Health Research Institute. Taiwan began its National Health Insurance program in 1995 to finance health care for all of its residents. There are presently more than 23 million enrollees in the program, representing approximately 99% of Taiwan's population. The NHIRD contains registration files and original claims data for reimbursements for all enrollees, making it one of the largest and most complete nationwide population-based health care services data sets in the world. In this database, the diagnostic codes of the patients, in the format of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), were established by the board-certified physicians in the corresponding specialties. The accuracy of diagnosis of major diseases in the NHIRD, such as diabetes mellitus and stroke, has been validated,6,7 and this database has been used extensively in many epidemiologic studies in Taiwan.812 Personal information, including family history, lifestyle, and habits such as smoking and alcohol use, was not available from the NHIRD.

STUDY PATIENTS

This retrospective population-based cohort study made use of data from the Longitudinal Health Insurance Database 2000, a subset of the NHIRD that contains all the original claims data from 1  000  000 individuals randomly sampled from the Registry of NHIRD in 2000. A total of 17  206 patients with a diagnosis of urticaria (ICD-9-CM code 708) who had received long-term antihistamines (ie, use of antihistamine for a total of 6 months during 2 years) were identified. The antihistamines included second- and third-generation antihistamines, such as cetirizine hydrochloride, desloratadine, fexofenadine hydrochloride, levocetirizine dihydrochloride, loratadine, and traditional sedating antihistamines. To minimize the possible effect of personal allergy history on cancer occurrence, patients with coexisting atopic dermatitis (ICD-9-CM code 691.8, diagnosed by dermatologists, pediatricians, or immune-rheumatologists), asthma (ICD-9-CM code 493, diagnosed by internists or immune-rheumatologists), or allergic rhinitis (ICD-9-CM code 477, diagnosed by immune-rheumatologists or otolaryngologists), who may need long-term antihistamine treatment, were excluded. Patients with a history of malignant tumors or with coexisting rheumatoid arthritis (ICD-9-CM code 714), systemic lupus erythematosus (ICD-9-CM code 710.0), or Sjogren syndrome (ICD-9-CM code 710.2) were also excluded. The diagnoses of coexisting autoimmune diseases were based on the records from the registry of Catastrophic Illness Patient Database, which includes only those meeting the diagnostic criteria of diseases, as described previously.13,14 Finally, a total of 12  720 chronic urticaria patients were enrolled as the study cohort. All study patients were included between January 1, 1996, and December 31, 2006, and followed up until December 31, 2008, to ensure that each patient was observed for at least 2 years.

WAIVER OF REVIEW

The data set used in this study consisted of deidentified secondary data released to the public for research purposes. Therefore, the institutional review board of Taichung Veterans General Hospital waived a review of this study.

IDENTIFICATION OF CANCER CASES

We identified the diagnoses of cancers in the study cohort by linking to the records of the Catastrophic Illness Patient Database. To apply for a cancer catastrophic illness certificate, one must provide cytologic or pathologic reports or evidence, such as additional laboratory and imaging studies, that support the diagnosis of cancer, including tumor marker surveys, radiographs, bone scans, computed tomography scans, or magnetic resonance imaging scans. At least 2 oncologists carefully examine the medical records, laboratory information, and results of imaging studies. Only those patients who meet the criteria of diagnoses are issued certificates. We excluded those with in situ malignant tumors because in situ malignant diseases do not qualify for a catastrophic illness certificate. The diagnostic codes of malignant tumors were defined as those from 140 to 208.91 in the ICD-9-CM format. We categorized these cancer cases into hematologic cancers and nonhematologic cancers. Hematologic cancers were subcategorized into leukemias (coded 204-208) and lymphomas (including non-Hodgkin lymphoma [coded 200 or 202-203] and Hodgkin lymphoma [coded 201]), according to the methods of the Cancer Registry in Taiwan.

STATISTICAL ANALYSIS

All study subjects were followed up until a first-time diagnosis of cancer, the end of follow-up in the medical records, or the end of 2008. We examined the association between chronic urticaria and specific cancer types using standardized incidence ratios (SIRs). Standardized incidence ratios were calculated as the number of cancer cases among chronic urticaria patients divided by the expected number of cancer cases according to national age-specific, sex-specific, and period-specific cancer rates. The CIs are based on the Byar approximation of the exact Poisson distribution, which is extremely accurate even for small numbers.15

Yearly reports of cancer rates were obtained from the Taiwan National Cancer Registry. Hospitals with greater than 50-bed capacity that provide outpatient and inpatient cancer care participate in reporting all newly diagnosed malignant neoplasia to the registry. Cancer incidence data appear each year in a special bulletin and in an annual registry report published by the Ministry of Health. Analyses and observed trends are published in annual reports. The registry also provides a database of cancer-related data for various research efforts. We adopted the 2003 Cancer Registry Report of Taiwan as a standard.

To assess the effect of age on the relative risk of malignant tumors, we analyzed the relative risk among patients younger than 20, those aged 20 to 39, 40 to 59, and 60 to 79, and those 80 years or older at diagnosis of chronic urticaria. Analysis was also performed to determine whether the association of malignant tumors varied according to the length of time after diagnosis of chronic urticaria. We divided follow-up times into 6 periods: less than 1 year, 1 to less than 2 years, 2 to less than 4 years, 4 to less than 6 years, 6 to less than 8 years, and 8 years or more.

The SAS statistical package, version 9.1 (SAS Institute, Inc), and the Stata statistical package, version 9.1 (StataCorp), were used to perform analyses of the data in this study.

RESULTS
DEMOGRAPHIC DATA

The age and sex distribution of study subjects are presented in Table 1. Among 12  720 study patients, 10  720 (84.3%) received systemic corticosteroids, with a median duration of 10 days per year (mean [interquartile range], 30.7 [3.4-29.6] days per year). There were 186 patients (1.5%) receiving other immunosuppressants, including methotrexate sodium, cyclosporine, and azathioprine sodium, with a median duration of 28 days per year (mean [interquartile range], 98.1 [6.5-120.6] days per year).

OVERALL CANCER RISK ANALYSIS

During the observation period of 69  305 person-years, 704 cancers were identified after the diagnosis of chronic urticaria. The incidence was 1016 cases per 100  000 person-years. An increased overall cancer risk in chronic urticaria was observed (SIR, 2.2; 95% CI, 2.0-2.3). Female and male patients showed similar risks of developing cancer (Table 2). After we excluded the 186 patients who received immunosuppressants other than antihistamines or corticosteroids, the risk of malignant tumor remained elevated (SIR, 2.2; 95% CI, 2.0-2.4).

The relative risk of cancer was greatest among young and middle-aged patients with chronic urticaria (Table 2). Malignant diseases in chronic urticaria were mostly detected in the first year following diagnosis (SIR, 4.3; 95% CI, 3.8-4.9). The risk ratios gradually decreased over time (Table 2). After 8 years of follow-up, the SIR of malignant tumors in chronic urticaria remained elevated (SIR, 1.5; 95% CI, 1.0-2.2).

ASSOCIATION OF HEMATOLOGIC CANCERS WITH CHRONIC URTICARIA

Among all malignant diseases, there were 58 hematologic malignant tumors (8.2%), including 35 cases of non-Hodgkin lymphoma, 1 case of Hodgkin lymphoma, and 22 cases of leukemia. A significantly elevated risk for hematologic malignant tumors in chronic urticaria was observed (SIR, 4.1; 95% CI, 3.1-5.4) (Table 3). The risk of cancer varied by age. Young patients ( <20 years) were at greatest relative risk for hematologic cancers compared with the age-matched general population (Table 3).

The risks for hematologic cancers were highest following the first year of diagnosis (SIR, 16.5; 95% CI, 11.4-23.2). The relative risk of hematologic cancer remained elevated after long-term observation (Table 3).

Ten occurrences of malignant tumors were observed in those younger than 20 years. Among them were 7 lymphohematopoietic cancers (5 acute or chronic lymphocytic leukemias and 2 leukemias of monocytic cells or unspecified cell types). Of the 3 remaining malignant diseases, 2 were brain tumors and 1 was a tumor of ovarian origin. In regard to specific cancer types, the risk of non-Hodgkin lymphoma (including other lymphosarcoma, reticulosarcoma, multiple myeloma, and other immunoproliferative neoplasms) was greatest (SIR, 4.4; 95% CI, 3.0-6.1), followed by leukemia (3.7; 2.3-5.6) (Table 4).

ASSOCIATION OF NONHEMATOLOGIC CANCERS WITH CHRONIC URTICARIA

An increased risk of various nonhematologic malignant tumors (SIR, 2.1; 95% CI, 1.9-2.3) was also observed in chronic urticaria patients (Table 5). The most significantly associated cancers were those originating from the brain, retroperitoneum, vulva, and kidney.

COMMENT

Various causes of urticaria, including food, infection, and drugs, have been reported. However, the cause is unknown in more than 80% of cases.16 The association of malignant tumor and chronic urticaria remains controversial. Several cases of malignant tumors have been reported in association with urticaria, including leukemias and lymphomas,17,18 myeloma,19 testicular cancer,20 ovarian carcinoma,21 lung cancer,22 colon cancer,23 and thyroid carcinoma.24 Nevertheless, 1 population-based study showed no associations between chronic urticaria and malignant tumor.2 Our study provided nationwide population-based evidence that chronic urticaria patients may be at increased risk of cancer occurrence, especially hematologic cancers.

A point prevalence of 0.5% to 1% of chronic urticaria in the general population has been reported.25 However, to our knowledge, no epidemiologic data regarding chronic urticaria have been published in Taiwan. We identified 3357 patients with chronic urticaria in 2000, with an estimated prevalence of 0.4% (data not shown). This is comparable with reports from other countries. A comprehensive prospective surveillance for chronic urticaria in Taiwan is needed for further studies.

A link between chronic urticaria and hematologic malignant tumor has rarely been reported. Schnitzler syndrome is defined as chronic urticaria and monoclonal gammopathy, in combination with at least 2 of the following features: fever, arthralgia or arthritis, bone pain, hepatomegaly and/or splenomegaly, palpable lymph node, elevated erythrocyte sedimentation rate, and leukocytosis. Rarely, patients progress to develop lymphoplasmacytic neoplasia, particularly Waldenstrom macroglobulinemia.26 Most of these patients present with gammopathy and hematologic disorder in their 40s to 60s after 4 to 9 years of chronic urticaria.2729

To our knowledge, no previous studies have examined the effect of age at onset of chronic urticaria on cancer occurrence. Our study demonstrated that younger patients (aged <40 years) tend to have the greatest risk of cancer development, especially for hematologic cancers. These results suggest that thorough and periodic assessment may be needed in younger patients.

An association of hematologic malignant tumors in urticarial vasculitis has been described. Urticarial vasculitis, comprising approximately 2% of chronic urticaria,30,31 often presents clinically as persistent urticaria lesions and microscopically as leukocytoclastic vasculitis. Multisystem involvement in urticarial vasculitis, such as severe angioedema, arthritis, and pulmonary involvement, has been frequently described. Various neoplastic conditions have been reported to be associated with hypocomplementemic urticarial vasculitis, such as polycythemia rubra vera,32 IgA myeloma,33 megakaryocytic leukemia,34 and non-Hodgkin lymphoma.5,35 However, the diagnosis of urticarial vasculitis is sometimes underinvestigated by physicians, and there is no specific diagnostic code for urticarial vasculitis in the ICD-9 coding system.

This study demonstrated associations of cancers of various origins with chronic urticaria. Significant elevated risks of cancers originating from the brain, retroperitoneum, vulva, and kidney were observed. At present, it is not known whether the coexistence of chronic urticaria and various malignant tumors is merely a coincidence or whether there are shared etiologic factors. In some case reports, removal of the tumor leads to prompt resolution of urticarial lesions,17,18,21,23,24 suggesting a pathogenetic relationship between these diseases. The SIRs of most cancers were very modest and the case numbers were small for certain tumor types, which limited subset analyses. Further studies are needed to address these relationships.

The effect of medications commonly used for chronic urticaria on cancer development has not been explored in detail. To our knowledge, no studies have reported an association between corticosteroid use and cancer development in other autoimmune diseases, such as systemic lupus erythematosus.36 Long-term use of common immunosuppressants, except cyclophosphamide, does not increase the cancer risk in systemic lupus erythematosus.36 An association between cancer and chronic urticaria remained unchanged in our study after we excluded patients receiving long-term immunosuppressants other than corticosteroids. This implied that the effect of corticosteroid-sparing immunosuppressants is not strong in regard to cancer risk in chronic urticaria patients.

There are 3 main limitations to our study. First, we did not have personal patient information, such as family history of cancer, lifestyle, body mass index, or smoking and alcohol use. There was also no information regarding signs or symptoms, other than urticaria, or laboratory abnormalities that would suggest the need for an evaluation for cancer. Second, to diminish the likelihood of a misdiagnosis of common urticaria based on the administrative database, we used additional pharmaceutical information (long-term use of oral antihistamines) to select our case patients. Thus, the prevalence of chronic urticaria may have been underestimated. Third, we were not able to separate out possible cases of urticarial vasculitis from cases of common chronic urticaria because of the lack of a distinct diagnostic code for urticarial vasculitis. Because internal malignant tumors have been reported more frequently in patients with vasculitis, this may have distorted the findings.

Our study provides some valuable information. We demonstrated a possible link between cancer and chronic urticaria on the basis of a nationwide database in Taiwan. Most cancers were detected within 1 year of diagnosis. The possible association between cancer and chronic urticaria deserves further study.

Back to top
Article Information

Correspondence: Yun-Ting Chang, MD, PhD, Department of Dermatology, Taipei Veterans General Hospital and National Yang-Ming University, No. 201, Sec 2, Shih-Pai Rd, Taipei 112, Taiwan (ytchang@vghtpe.gov.tw).

Submitted for Publication: February 23, 2011; final revision received September 9, 2011; accepted September 22, 2011.

Author Contributions: Drs Chen and Wu contributed equally to this study. Drs Chen, Wu, and Chang had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Y.-J. Chen, Wu, and Chang. Acquisition of data: Y.-J. Chen, Wu, Shen, T.-T. Chen, and Chang. Analysis and interpretation of data: Y.-J. Chen, Wu, and Chang. Drafting of the manuscript: Y.-J. Chen. Critical revision of the manuscript for important intellectual content: Y.-J. Chen, Wu, Shen, T.-T. Chen, and Chang. Statistical analysis: Y.-J. Chen and T.-T. Chen. Obtained funding: Y.-J. Chen, Wu, and Shen. Administrative, technical, and material support: Y.-J. Chen, Wu, and Shen. Study supervision: Wu and Chang.

Financial Disclosure: None reported.

Funding/Support: This study was partly supported by grants TCVGH-996801B and TCVGH-996802C from Taichung Veterans General Hospital.

Disclaimer: This study is based in part on data from the NHIRD provided by the Bureau of National Health Insurance, Department of Health, and managed by the National Health Research Institute. The interpretations and conclusions contained herein do not represent those of the Bureau of National Health Insurance, Department of Health, or the National Health Research Institute.

References
1.
van der Valk PG, Moret G, Kiemeney LA. The natural history of chronic urticaria and angioedema in patients visiting a tertiary referral centre.  Br J Dermatol. 2002;146(1):110-113PubMedArticle
2.
Lindel öf B, Sigurgeirsson B, Wahlgren CF, Eklund G. Chronic urticaria and cancer: an epidemiological study of 1155 patients.  Br J Dermatol. 1990;123(4):453-456PubMedArticle
3.
Deacock SJ. An approach to the patient with urticaria.  Clin Exp Immunol. 2008;153(2):151-161PubMedArticle
4.
Kulthanan K, Cheepsomsong M, Jiamton S. Urticarial vasculitis: etiologies and clinical course.  Asian Pac J Allergy Immunol. 2009;27(2-3):95-102PubMed
5.
Shah D, Rowbottom AW, Thomas CL, Cumber P, Chowdhury MM. Hypocomplementaemic urticarial vasculitis associated with non-Hodgkin lymphoma and treatment with intravenous immunoglobulin.  Br J Dermatol. 2007;157(2):392-393PubMedArticle
6.
Lin CC, Lai MS, Syu CY, Chang SC, Tseng FY. Accuracy of diabetes diagnosis in health insurance claims data in Taiwan.  J Formos Med Assoc. 2005;104(3):157-163PubMed
7.
Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML. Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan.  Pharmacoepidemiol Drug Saf. 2011;20(3):236-242PubMedArticle
8.
Wu CY, Kuo KN, Wu MS, Chen YJ, Wang CB, Lin JT. Early Helicobacter pylori eradication decreases risk of gastric cancer in patients with peptic ulcer disease [published online ahead of print August 5, 2009].  Gastroenterology. 2009;137(5):1641-1648, e1-e2PubMedArticleArticle
9.
Chen YJ, Wu CY, Huang YL, Wang CB, Shen JL, Chang YT. Cancer risks of dermatomyositis and polymyositis: a nationwide cohort study in Taiwan [published online ahead of print April 16, 2010].  Arthritis Res Ther. 2010;12(2):R70PubMedArticleArticle
10.
Wu CY, Wu CH, Wu MS,  et al.  A nationwide population-based cohort study shows reduced hospitalization for peptic ulcer disease associated with H pylori eradication and proton pump inhibitor use.  Clin Gastroenterol Hepatol. 2009;7(4):427-431PubMedArticle
11.
Wu CY, Wu MS, Kuo KN, Wang CB, Chen YJ, Lin JT. Effective reduction of gastric cancer risk with regular use of nonsteroidal anti-inflammatory drugs in Helicobacter pylori –infected patients.  J Clin Oncol. 2010;28(18):2952-2957PubMedArticle
12.
Huang YL, Chen YJ, Lin MW,  et al.  Malignancies associated with dermatomyositis and polymyositis in Taiwan: a nationwide population-based study.  Br J Dermatol. 2009;161(4):854-860PubMedArticle
13.
Chen YJ, Chang YT, Wang CB, Wu CY. Malignancy in systemic lupus erythematosus: a nationwide cohort study in Taiwan.  Am J Med. 2010;123(12):1150.e1-1150.e6PubMedArticleArticle
14.
Chen YJ, Chang YT, Wang CB, Wu CY. The risk of cancer in rheumatoid arthritis patients: a nationwide cohort study in Taiwan.  Arthritis Rheum. 2010;63(2):352-358Article
15.
Breslow NE, Day NE. Statistical methods in cancer research, II: the design and analysis of cohort studies.  IARC Sci Publ. 1987;(82):1-406PubMed
16.
Greaves MW. Chronic urticaria.  N Engl J Med. 1995;332(26):1767-1772PubMedArticle
17.
Clore LS Jr, Stafford CT. Chronic urticaria as a presenting sign of hairy cell leukemia.  Allergy Asthma Proc. 1999;20(1):51-55PubMedArticle
18.
Alonso R, Cister ó-Bah íma A, Enrique E, Besses C. Chronic urticaria associated with chronic myelomonocytic leukemia.  J Investig Allergol Clin Immunol. 2000;10(6):380-381PubMed
19.
Lipsker D, Cribier B, Maloisel F, Heid E, Grosshans E. Chronic urticaria and IgA myeloma.  Acta Derm Venereol. 1998;78(5):395PubMedArticle
20.
Mowad CM, Mowad JJ, Cirigliano MD. Testicular cancer presenting as urticaria.  Cutis. 1998;61(3):147-148PubMed
21.
Reinhold U, Bruske T, Schupp G. Paraneoplastic urticaria in a patient with ovarian carcinoma.  J Am Acad Dermatol. 1996;35(6):988-989PubMedArticle
22.
Hills EA. Adenocarcinoma of the bronchus with Cushing's syndrome, carcinoid syndrome, neuromyopathy and urticaria.  Br J Dis Chest. 1968;62(2):88-92PubMedArticle
23.
Campanelli A, Prins C, Saurat JH. Chronic urticaria revealing a colonic adenocarcinoma.  J Am Acad Dermatol. 2005;52(6):1105PubMedArticleArticle
24.
Manganoni AM, Tucci G, Venturini M, Farisoglio C, Baronchelli C, Calzavara Pinton PG. Chronic urticaria associated with thyroid carcinoma: report of 4 cases.  J Investig Allergol Clin Immunol. 2007;17(3):192-195PubMed
25.
Weller K, Altrichter S, Ardelean E,  et al.  Chronic urticaria: prevalence, course, prognostic factors and impact.  Hautarzt. 2010;61(9):750-757PubMedArticle
26.
Lim W, Shumak KH, Reis M,  et al.  Malignant evolution of Schnitzler's syndrome —chronic urticaria and IgM monoclonal gammopathy: report of a new case and review of the literature.  Leuk Lymphoma. 2002;43(1):181-186PubMedArticle
27.
Puddu P, Cianchini G, Girardelli CR, Colonna L, Gatti S, de Pita O. Schnitzler's syndrome: report of a new case and a review of the literature.  Clin Exp Rheumatol. 1997;15(1):91-95PubMed
28.
Peterlana D, Puccetti A, Tinazzi E, Simeoni S, Lunardi C. Schnitzler's syndrome treated successfully with intravenous pulse cyclophosphamide.  Scand J Rheumatol. 2005;34(4):328-330PubMedArticle
29.
Rizzi R, Curci P, Rinaldi E,  et al.  Schnitzler's syndrome: monoclonal gammopathy associated with chronic urticaria.  Acta Haematol. 2008;120(1):1-4PubMedArticle
30.
Greaves MW, Tan KT. Chronic urticaria: recent advances.  Clin Rev Allergy Immunol. 2007;33(1-2):134-143PubMedArticle
31.
Champion RH. Urticaria: then and now.  Br J Dermatol. 1988;119(4):427-436PubMedArticle
32.
Farell AM, Sabroe RA, Bunker CB. Urticarial vasculitis associated with polycythaemia rubra vera.  Clin Exp Dermatol. 1996;21(4):302-304PubMedArticle
33.
Highet AS. Urticarial vasculitis and IgA myeloma.  Br J Dermatol. 1980;102(3):355-357PubMedArticle
34.
Blanco R, Martinez-Taboada VM, Gonzalez-Vela C, Rodriguez-Valverde V. Urticarial vasculitis as clinical presentation of megakaryocytic leukemia.  J Clin Rheumatol. 1996;2(6):366PubMedArticle
35.
Calvo-Romero JM. Diffuse large B cell lymphoma in a patient with hypocomplementemic urticarial vasculitis.  J Postgrad Med. 2003;49(3):252-253PubMed
36.
Bernatsky S, Joseph L, Boivin JF,  et al.  The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case-cohort study.  Ann Rheum Dis. 2008;67(1):74-79PubMedArticle
×