Chronic urticaria (CU) is a persistent skin condition defined by the recurrent appearance of wheals, or hives, which last for six weeks or longer. These raised, itchy, red or skin-colored welts affect approximately 0.5–2% of the population at some point in their lives. The hives may appear and fade repeatedly, sometimes persisting for months or even years. While rare, there is a documented association between chronic hives and an underlying systemic disease. This discussion explores the specific malignancies that can manifest with chronic hives and the clinical signs that warrant a deeper investigation.
The Relationship Between Chronic Hives and Cancer
The vast majority of chronic hives cases are benign, often classified as chronic spontaneous urticaria where no external cause is identified. In up to 90% of cases, the underlying cause of chronic urticaria is never precisely determined, or it is linked to autoimmune processes. Routine cancer screening is generally not recommended unless a patient presents with specific concerning symptoms.
The appearance of chronic hives as a manifestation of an internal tumor is described as a paraneoplastic syndrome. These syndromes are clinical symptoms caused by substances, such as hormones or immune system molecules, released by tumor cells, rather than direct tumor invasion. In these rare instances, the chronic urticaria is a distant effect of the tumor, often preceding the cancer diagnosis by several months.
Some large population-based studies have indicated a slightly elevated risk of cancer, especially during the first year following a chronic urticaria diagnosis. This suggests that the persistent skin reaction may be an early, subtle signal of a developing malignancy. Therefore, the possibility of a paraneoplastic cause is considered by physicians when other common etiologies have been ruled out.
Specific Malignancies Linked to Chronic Urticaria
The cancers most frequently associated with chronic urticaria fall primarily into the category of hematologic malignancies, or blood cancers. These diseases affect the blood, bone marrow, and lymph nodes, and they account for the strongest statistical association with chronic hives. Non-Hodgkin lymphoma represents the most studied link, showing a significantly higher incidence ratio in patients with chronic urticaria in some large cohort studies.
Other blood cancers, including various forms of leukemia and myeloproliferative disorders, have also been reported where chronic hives were an early or preceding symptom. The hives in these patients are sometimes particularly resistant to standard antihistamine treatments, which can be an important diagnostic clue.
Chronic hives have also been documented in association with a range of solid tumors, although this link is less frequent than with blood cancers. Case reports have described urticaria preceding the diagnosis of lung adenocarcinoma. Other solid tumors occasionally reported include cancers of the breast, colon, prostate, and ovary.
The mechanism often involves the tumor releasing substances that activate mast cells, the immune cells responsible for releasing histamine and causing hives. The chronic hives often resolve entirely once the underlying malignancy is successfully treated with chemotherapy or surgical resection, supporting the paraneoplastic nature of the hives in these rare cases.
Clinical Indicators Suggesting a Malignant Origin
Physicians look for specific systemic signs and symptoms, often referred to as “red flags,” to help differentiate common chronic hives from those that might be linked to a malignancy. One significant indicator is the presence of systemic symptoms that accompany the hives, known as B symptoms in the context of lymphoma. These symptoms include unexplained persistent fever, drenching night sweats, and significant unintentional weight loss.
Another important clue is the physical examination finding of enlarged lymph nodes, or lymphadenopathy, which is not typically seen with benign chronic urticaria. Persistent joint pain, known as arthralgia, or chronic fatigue also raise suspicion for a systemic disease process. These associated symptoms suggest that the immune reaction causing the hives is part of a broader body-wide disorder.
Laboratory abnormalities detected in routine blood work can provide further evidence suggesting a deeper issue. These may include unexplained anemia or a high white blood cell count. Elevations in inflammatory markers such as C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) are also considered abnormal findings that warrant a more extensive evaluation.
The clinical characteristics of the hives themselves can also be suggestive, especially if the wheals are severely refractory to standard treatment. Chronic urticaria that fails to respond to high doses of antihistamines or requires frequent courses of oral corticosteroids suggests a more complex underlying mechanism. Hives that last longer than 24 hours in the same spot, sometimes leaving a bruise, may indicate urticarial vasculitis, which has a stronger association with lymphoproliferative disorders.
Common Non-Malignant Causes of Chronic Hives
The vast majority of chronic hives are not related to cancer, with many cases being classified as idiopathic, meaning the cause remains unknown. A substantial portion of these idiopathic cases are now understood to have an autoimmune basis, where the body’s immune system mistakenly attacks its own skin cells. This involves autoantibodies that activate mast cells, leading to the release of histamine and the formation of wheals.
Chronic infections are another common non-malignant cause that can trigger or exacerbate chronic hives. These include bacterial infections such as Helicobacter pylori or various chronic viral infections. Treating the underlying infection often leads to a significant improvement or complete resolution of the skin symptoms.
Chronic urticaria is frequently associated with other autoimmune and endocrine conditions, most notably autoimmune thyroid disease. Patients with conditions like Hashimoto’s thyroiditis or Graves’ disease have a higher incidence of chronic hives. Systemic diseases such as lupus and rheumatoid arthritis can also occasionally manifest with chronic urticaria.
Physical urticaria represents a distinct category where the hives are triggered by an external stimulus like cold, heat, pressure, or exercise. These types of hives are generally easily identifiable and are not linked to internal malignancy. The high prevalence of these benign causes reinforces that chronic hives should first be investigated for common triggers before considering a rare cancer association.