This case series was conducted in a private mixed pediatric/adult practice allergy clinic in Vancouver, British Columbia, Canada. Patient charts were reviewed if the patient had a confirmed diagnosis of HAE based on prior abnormally low C1 inhibitor functional testing on at least two separate occasions, and either confirmatory genetic testing showing a pathologic mutation in SERPING1 or a family history of HAE. Individuals with other forms of angioedema such as acquired angioedema, ACE-inhibitor associated angioedema or hereditary angioedema with normal C1 inhibitor were excluded. Malignancy and immune disorder diagnoses were based on either patient reported history of condition or based on details provided in other medical subspecialty consultation letters (e.g. rheumatology, oncology). Malignancy included any form of malignant cells in any body system (including dysplasia). Immune disorders were defined as conditions involving dysfunction of the immune system including autoimmune diseases and primary immunodeficiencies.
49 charts of patients with HAE were reviewed and we identified six patients with a documented diagnosis of malignancy and six patients with a documented diagnosis of an immune disorder. A variety of malignant conditions were identified including two patients with breast cancer, one with melanoma, one with pancreatic cancer, one with renal cancer, and one with cervical dysplasia. All those with a diagnosis of malignancy were age 50 or greater at the time of diagnosis, with the exception of one patient who was diagnosed with cervical dysplasia in her early 40s (Table 1). All individuals with a malignancy diagnosis either had a strong family history of HAE or genetic testing that confirmed a diagnosis of HAE, as opposed to a diagnosis of malignancy associated AAE. Three of these patients were diagnosed with malignancy prior to being diagnosed with HAE.
Table 1
Details of HAE patients with Malignancy Diagnosis
Patient Number | Age at Time of Study | Sex | Age of HAE Diagnosis | Details of HAE Diagnosis | Type of Malignancy | Age of Malignancy Diagnosis | Extent of Malignancy and Treatment |
Patient 1 | 57 | F | 41 | Multiple family members with HAE on paternal side | Breast | 54 | Invasive ductal carcinoma - ER/PR+, HER2 equivocal, treated with surgery and post-menopausal state |
Patient 2 | 58 | M | 12 | 8 family members with HAE | Melanoma | 56 | Stage 3 with unknown primary, treated with surgery and chemotherapy |
Patient 3 | 70 | F | 66 | Sister, father and daughter with HAE | Pancreatic | 70 | Metastatic, passed away shortly after diagnosis |
Patient 4 | 46 | F | 42 | Mother and maternal aunt with HAE | Cervical dysplasia (ASC-H, prior HSIL) | Early 40s, prior to HAE diagnosis | Localized, treated with Hysterectomy. Currently being investigated for bladder cancer. |
Patient 5 | 58 | F | 56 | Brother and nephew with HAE | Breast | 50 | Treated with mastectomy and tamoxifen for five years |
Patient 6 | 74 | F | 73 | Mutation in SERPING1, suspected family history (currently being investigated) | Renal | 62 | Metastatic, treated with nephrectomy, immunotherapy, and localized radiation |
ER: estrogen receptor, PR: progesterone receptor, HER2: Herceptin receptor, ASC-H: atypical squamous cells, HSIL: high-grade squamous intraepithelial lesion |
Six patients reported a diagnosis of an immune disorder including two patients with ulcerative colitis, two patients with rheumatoid arthritis, one patient with Sjogren’s syndrome, and one patient with hypothyroidism and chronic spontaneous urticaria (CSU). The youngest patient identified with an immune disorder was Patient 8, who indicated that she was diagnosed with ulcerative colitis at age 19 (Table 2). The age of diagnosis of the immune disorder was not available for any of the other patients, however at the time of our data collection, three patients were aged 18–49 and three patients were aged 50 or older. Both patients with ulcerative colitis (Patient 8 and Patient 11), required management with biologic therapy. No patients were identified with a primary immunodeficiency.
Table 2
Details of HAE Patients with Immune Disorder Diagnosis
Patient Number | Age at Time of Study | Sex | Immune Disorder | Other Details & Treatment |
Patient 7 | 41 | F | Rheumatoid Arthritis | Managed with hydroxychloroquine and methotrexate |
Patient 8 | 31 | F | Ulcerative Colitis | Managed with infliximab |
Patient 9 | 90 | F | Sjogren’s Syndrome | |
Patient 10 | 42 | F | Hypothyroidism and CSU | |
Patient 11 | 64 | M | Ulcerative Colitis | Managed with ustekinumab |
Patient 12 | 67 | M | Rheumatoid Arthritis | Also, history of renal transplant due to ESRD secondary to type 2 DM, immunosuppressed with MMF, tacrolimus and prednisone |
CSU: chronic spontaneous urticaria, ESRD: end-stage renal disease, DM: diabetes mellitus, MMF, mycophenolate mofetil |