Chronic urticaria can be caused by cancer and resolves with its cure

Dear Editor, We read with great interest the letter of Larenas-Linnemann et al concerning chronic urticaria (CU) caused by malignancy and healed after antineoplastic treatment. We agree with the authors that the link between CU and cancer is unclear. In our experience, the occurrence of CU in patients with neoplastic diseases is very rare. Herein, we report data from a retrospective evaluation of consecutive patients with CU who were referred to Dermatology Unit of the University of Naples Federico II from January 2008 to December 2016. The study was approved by Ethical Committee. A total of 1493 patients (697 males, 46.7%, and 796 females, 53.3%; mean age 48.3 18.1 years) were enrolled. They all signed an informed consent. According to the EAACI/GALEN/EDF/ WAO guidelines, in all patients, complete blood count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were performed. Furthermore, based on the medical history, 182 (12.2%) patients were screened with thyroid function tests [including thyroid-stimulating hormone (TSH), free thyroxine (fT) 4 and 3, antithyroglobulin Ab, antithyroperoxidase Ab], 178 (11.9%) with chest Xray, 102 (6.8%) with abdominal ultrasound, 92 (6.2%) with prostate specific antigen, 91 (6.1%) with stool test, 83 (5.7%) with mammography, and 65 (4.5%) with lymphonodular ultrasound. Only in 1 of 1493 (0,007%) patients, we found CU most likely associated with cancer. It was a 62-year-old woman with CU lasting 4 months and unresponsive to antihistamines, used up to quadruple dose. The patient referred temporary and incomplete improvement after treatment with oral prednisone. Because of weight loss in the last 2 months, laboratory workup (including fT3, fT4, TSH, antinuclear antibodies and abdominal ultrasound, other than blood count, ESR, CRP) was normal. On the other hand, chest X-ray showed a large atelectasis of the upper lobe of the right lung and an elevation of homolateral hemidiaphragm, due to a hilar mass. Lung computed tomography scan and biopsy confirmed the diagnosis of small cell cancer. Chemotherapy was started and CU disappeared after the first session of treatment. At the present time, the patient is in remission from cancer and is free from hives. About one quarter of malignancies found linked with CU are papillary carcinomas of thyroid. Moreover, hematologic, gastrointestinal, breast, testicle, prostate, ovarian, or brain malignancies have been sporadically reported. CU has been associated with cancer of the lung in 4 cases, in 1 case only with small cell carcinoma. In agreement with Larenas-Linnemann et al, cancer-associated CU seems to have some peculiar characteristics: (i) patients are resistant to antihistamine treatment, while only oral corticosteroids lead to temporary improvement; (ii) the mean duration of CU is 2-8 months before detection of malignancy; (iii) CU resolves in few weeks after the start of chemotherapy; and (iv) the recurrence of urticaria may be the expression of cancer relapse. Malignancy might induce immune dysregulation and hormonal abnormality with subsequent complement activation or alteration in the coagulation pathways, both related to CU. We believe that the effect of medications commonly used for CU is not remarkable on cancer development, as antihistamines do not seem to have oncogenic activity and the CU duration is relatively short before the discovery of the malignancy. We would like to thank Larenas-Linnemann et al for their contribution to literature with such an excellent paper. The cases reported in the literature are anecdotal; instead, our data cover a large cohort of 1493 consecutive CU patients and seem to confirm the rarity of the association (0.007% of our patients). Notwithstanding, a careful medical history should be taken in all patients with antihistamineresistant CU, as cutaneous disease may sometimes be the only clinical expression of malignancy. Therefore, in these cases an appropriate diagnostic course should be performed according to clinical features.