Women Physically or Emotionally Abused in Childhood Face Significantly Increased Risk of Lupus

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WOMEN PHYSICALLY OR EMOTIONALLY ABUSED IN CHILDHOOD FACE SIGNIFICANTLY INCREASED RISK OF LUPUS

Newswise — CHICAGO – Women who experienced physical or emotional abuse in childhood have a significantly increased risk of developing systemic lupus erythematosus (SLE) as adults, according to new research findings presented this week at the 2018 ACR/ARHP Annual Meeting (Abstract #2807).

SLE, also called lupus, is a chronic disease that causes systemic inflammation that affects multiple organs. Lupus flares vary from mild to serious. Most patients have times when the disease is active, followed by times when the disease is mostly quiet, which is called remission. Lupus is far more common in women than men.

Past research shows associations between post-traumatic stress disorder and an increased risk of developing lupus, and that individuals who experience adverse childhood events have higher risk of hospitalization for an autoimmune disease in adulthood. Researchers at Brigham and Women’s Hospital/Harvard Medical School and the Harvard T.H. Chan School of Public Health in Boston examined the connections between experiencing childhood maltreatment and lupus risk.

“In prior work, exposure to stress and stress-related disorders, notably post-traumatic stress disorder, has been associated with increased risk of subsequently developing autoimmune diseases, including lupus,” said Candace H. Feldman, MD, ScD, Assistant Professor, Harvard Medical School, and the study’s lead author. “Exposure to adverse childhood experiences has specifically been associated with higher levels of inflammation, as well as with changes in immune function.”

The researchers gathered data on 67,434 women participating in the Nurses’ Health Study II, a longitudinal cohort of female, U.S.-based nurses who enrolled in 1989 and completed health questionnaires every 2 years. The researchers used validated questionnaire-based measures to assess the level of childhood physical abuse, emotional maltreatment and sexual abuse experienced by study participants. All questionnaires were administered in 2001 and most women completed them (75 percent response rate).

Exposure to physical and emotional abuse was assessed using the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire (CTQ), in which participants were asked to indicate whether and how often, as a child (<=age 11), they had experienced physical abuse from a family member, or yelling, screaming or insulting remarks from a family member. Responses were scored as never (0), rarely (1), sometimes (2), often (3) or very often true (4), summed, the mean was determined, and divided into quartiles to assess a dose-response relationship between CTQ score and SLE incidence. The researchers also conducted a secondary analysis examining physical assault using questions from the Conflict Tactics Scale (CTS). Responses to questions about recalled incidents of physical abuse, ranging from disciplinary spanking to choking or burning, were recorded, including the type of abuse and frequency. Answers were summed and divided into these categories: none, mild, moderate and severe abuse.

Sexual abuse was assessed using the Sexual Maltreatment Scale of the Parent-Child Conflicts Tactics Scale, and participants were asked to recall incidents of forced sexual activity by either adults or older children, including during their childhood or adolescence. Responses were scored as no abuse (0), mild abuse (1-2), moderate abuse (3-4), and severe sexual abuse (>4). These categories were examined separately, and then the moderate and severe categories were combined due to small sample sizes, Dr. Feldman said.

The researchers defined new lupus cases through 2015 through self-report of physician diagnoses, confirmed by medical record review by two rheumatologists. All cases had >=4 1997 ACR SLE Classification Criteria. The researchers used multivariable Cox regression models to evaluate the association between childhood abuse and risk of developing lupus. They accounted for potential confounders (e.g. parental socioeconomic status) as well as lifestyle and reproductive factors (e.g. smoking, body mass index (BMI), age at menarche).

There were 93 cases of lupus that developed among the 67,434 women. Women were on average 34.6 years old in 1989 and were followed for more than 24 years. After taking account of age and race, the researchers found that exposure to the highest vs. the lowest physical and emotional abuse levels was associated with a more than twofold greater risk of developing lupus. Exposure to moderate or high levels of physical assault was associated with 1.70 times higher risk of lupus compared to no exposure to assault. Adjusting for potential confounders as well as lifestyle and reproductive factors only modestly attenuated these associations. The data did not reveal a statistically significant association between sexual abuse and lupus risk.

“The study’s findings suggest that the effects of exposure to physical and emotional abuse during childhood may be more far-reaching than previously appreciated,” said Dr. Feldman. “Women with higher exposure to childhood maltreatment had a higher risk of developing lupus years later in adulthood. Exposure to abusive symptoms is surprisingly prevalent. The strong association observed between childhood abuse and lupus risk suggests the need for further research to understand biological and behavioral changes triggered by stress combined with other environmental exposures. In addition, physicians should consider screening their patients for experiences of childhood abuse and trauma.”

Limitations in the study included a potential for recall bias. Participants were asked in 2001 to report any childhood abuse. The researchers conducted sensitivity analyses which were fully prospective, and excluded any lupus cases that occurred prior to 2001. Even taking this potential bias into account, the association between physical and emotional abuse and lupus risk persisted, they found. Generalizability was another potential limitation, as the cohort was mostly Caucasian and comprised of female nurses, and may not be generalizable to men or people in other racial or ethnic groups, Dr. Feldman said.

This research was supported by the National Institutes of Health.

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Abstract #: 2807

Association of Exposure to Childhood Abuse with Incident Systemic Lupus Erythematosus in a Longitudinal Cohort of Women

Candace H. Feldman¹, Susan Malspeis¹, Cianna Leatherwood¹, Laura Kubzansky², Karen Costenbader¹ and Andrea Roberts², ¹Brigham and Women's Hospital, Boston, MA, ²Harvard T.H. Chan School of Public Health, Boston, MA

Background/Purpose: Prior studies demonstrated associations between post-traumatic stress disorder and increased risk of incident SLE and between childhood trauma and increased risk of hospitalization for autoimmune disease during adulthood. Severe stressors may alter immune function and result in increased inflammation and cytokine release, thereby increasing risk of SLE. We examined if childhood abuse is associated with increased risk of incident SLE.

Methods: Data are from the Nurses’ Health Study II, a longitudinal cohort of female U.S.-based nurses enrolled in 1989 followed with biennial questionnaires. To measure childhood physical and emotional maltreatment, we used the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire (CTQ), for sexual abuse, the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scales (CTS-SA), and for childhood physical assault, the Physical Assault Scale of the Conflict Tactics Scales (CTS-PA), all administered in 2001 with 75% response rate (68,505/91,268). Higher scores indicate more frequent abuse. We defined incident SLE through 2015 by self-report, confirmed by medical record review with >4 SLE ACR criteria. We excluded 1,071 women with missing childhood abuse exposure data or with self-reported, unconfirmed connective tissue disease. Multivariable Cox regression models evaluated the association (hazard ratio [HR] and 95% CI) between childhood abuse and incident SLE. We examined whether biennially assessed risk factors (e.g. smoking, BMI, alcohol use, oral contraceptive use) and potential confounders (e.g. age, race, median household income, parental education) accounted for increased SLE risk among those with vs. without childhood abuse exposure.

Results: Among 67,434 women, with a mean age of 34.6 (SD 4.8) in 1989, with >24 years of follow-up, there were 93 incident SLE cases. In age and race-adjusted models, exposure to the highest vs. lowest physical and emotional maltreatment was associated with >2-fold greater risk of SLE (HR 2.21 (95% CI 1.29-3.80)). Exposure to moderate and high levels of physical assault was associated with 1.70 (95% CI 1.08-2.68) times higher risk of SLE vs. no exposure. We did not find statistically significant associations between sexual abuse and SLE risk. After additionally accounting for potential lifestyle, reproductive and socioeconomic factors in separate models, HRs were only slightly attenuated (Table).

Conclusion: In this longitudinal cohort, we observed significantly increased risk of incident SLE among women who experienced childhood physical and emotional abuse compared with women who had not. Our findings suggest that exposure to extreme childhood stress and adversity may contribute to SLE development. Further studies are needed to investigate the role of timing and of the socioenvironmental context of abuse exposures and potential underlying mechanisms.

Disclosures: C. H. Feldman, None, S. Malspeis, None, C. Leatherwood, None L. Kubzansky, None, K. Costenbader, None, A. Roberts, None