Lack of association between alopecia areata and visceral or hematopoietic cancers

Alopecia areata (AA) is a polygenic, patchy non-scarring hair loss presenting on the scalp and body, with drastic implications on patients’ quality of life.¹ The pathogenesis of AA remains elusive, though T-lymphocyte mediated inflammation and various environmental stressors play a role.¹ The association between AA and various autoimmune diseases, has been explored in several studies.¹ Most recently, studies found lower rates of non-melanoma skin cancers and a trend towards decreased melanoma among AA patients.^2,3 To our knowledge, no studies assessed the association between AA and systemic malignancy. The current popularity of Janus Kinase inhibitors for AA highlights the need to further investigate this association as they theoretically increase the risk of malignancy.⁴ This research letter represents a review of Cleveland Clinic Alopecia Registry specifically looking at all cancers present in patients diagnosed with AA, in an effort to add to the growing literature base characterizing this multifactorial disease.

A retrospective chart review of AA patients, with varying degrees of severity, was performed, from the Cleveland Clinic Alopecia registry in the period from 2005–2016 (n=636). A control group of age-matched patients diagnosed with seborrheic dermatitis (SD) without hair loss was randomly selected (n=215). Hair loss specialists assessed the control group for absence of hair loss to ensure validity. Data were collected on gender, age, and presence of visceral cancers. The inclusion criteria were diagnosis of AA or SD by a Cleveland Clinic dermatologist. The presence of systemic cancers in AA and control group was determined by manual chart review. Demographic and clinical variables were compared using t-test, χ² test and Fisher exact test. Significance was considered at an α=0.05.

In our study population of 636 AA patients, mean age was 39.72±18.91 with a female predominance (71.7%, Table 1). There was no calculable difference in cancer incidence between AA and the control group. Interestingly, thyroid cancers and leukemia were noted only in the AA group while lung cancers were present only in the control group, though these findings were not deemed statistically significant due to low number of patients. We hypothesized that the rates of systemic malignancy would be lower in AA secondary to the autoimmune nature of the disease. It is known that treatment of cancers with immune checkpoint inhibitors such as tumor necrosis factor-α, cytotoxic T-lymphocyte-associated protein-4, programmed cell death protein and ligand, can induce AA.⁵ Induction of AA was likely due to activation of the inflammatory response and exposure of hair follicle antigens leading to loss of immune privilege.⁵

Table 1.

Summary of demographic characteristics and cancers among alopecia areata patients and control group

Characteristic	Alopecia Areata (n=636, (%))	Control (n=215, (%))	P-value
Gender
Female	456 (71.7%)	159 (73.95%)	0.44
Male	184 (31.50%)	56 (26.05%)
Mean age±SD	39.72±18.91	39.93±17.59	0.1
Breast Cancer	11 (1.73%)	3 (1.4%)	0.73
Bladder	2 (0.31%)	1 (0.47%)	0.58
Lymphoma	2 (0.31%)	1 (0.47%)	0.58
Endometrial Cancer	1 (0.16%)	2 (0.93%)	0.17
Prostate	1 (0.54%)	1 (1.79%)	0.41
Colon	1 (0.16%)	1(0.47%)	0.44
Thyroid	1 (0.16%)	0 (0%)
Leukemia	1 (0.16%)	0 (0%)
Lung cancer	0 (0%)	2 (0.93%)

Our findings call for additional, larger studies to further validate the claim that AA does not affect the risk of developing systemic cancers. These findings could potentially aid in understanding risks associated with AA.

Strengths of our study are that our team consisted of a group of hair loss specialists. Furthermore, the centralized AA registry used was detailed and manually entered, ensuring that relevant data was obtained for all patients. The main limitation of this study is that the cancer incidence of the control group may differ from the general population.

ABBREVIATIONS

AA

Alopecia Areata

SD

Seborrheic Dermatitis