- •Vulvodynia may be due to immune dysregulation given its association with other immune conditions.
- •The risk of vulvodynia is greater with increasing numbers of unique immune related conditions.
- •Being born preterm, small for gestational age, or low birth weight may increase vulvodynia risk.
Vulvodynia, impacts up to 8% of women by age 40, and is hypothesized to manifest through an altered immune-inflammatory response. To test this hypothesis, we identified all women born in Sweden between 1973 and 1996 diagnosed with localized provoked vulvodynia (N76.3) and/or vaginismus (N94.2 or F52.5) between 2001 and 2018. We matched each case to two women from the same birth year with no vulvar pain ICD codes. As a proxy for immune dysfunction, we used Swedish Registry data to capture 1) immunodeficiencies, 2) single organ and multiorgan autoimmune conditions, 3) allergy and atopies, and 4) malignancies involving immune cells across the life course. Women with vulvodynia, vaginismus or both were more likely to experience immune deficiencies (OR 1.8, 95% CI, 1.2–2.8), single organ (OR 1.4, 95% CI, 1.2–1.6) and/or multi-organ (OR 1.6, 95% CI, 1.3–1.9) immune disorders, and allergy/atopy conditions (OR 1.7, 95% CI, 1.6–1.8) compared to controls. We observed greater risk with increasing numbers of unique immune related conditions (1 code: OR = 1.6, 95% CI, 1.5–1.7; 2 codes: OR = 2.4, 95% CI, 2.1–2.9; 3 or more codes: OR = 2.9, 1.6–5.4). These findings suggest that women with vulvodynia may have a more compromised immune system either at birth or at points across the life course than women with no vulvar pain history.
Women with vulvodynia are substantially more likely to experience a spectrum of immune related conditions across the life course. These findings lend support to the hypothesis that chronic inflammation initiates the hyperinnervation that causes the debilitating pain in women with vulvodynia.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to The Journal of Pain
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Emerging evidence of macrophage contribution to hyperinnervation and nociceptor sensitization in vulvodynia.Front Mol Neurosci. 2019; 12: 186
- Hyperinnervation and mast cell activation may be used as histopathologic diagnostic criteria for vulvar vestibulitis.Gynecol Obstet Invest. 2004; 58: 171-178
- Psoriasin, a novel anti-Candida albicans adhesin.J Mol Med (Berl). 2018; 96: 537-545
- Mast cells: Versatile gatekeepers of pain.Mol Immunol. 2015; 63: 38-44
- Mechanisms and therapeutic relevance of neuro-immune communication.Immunity. 2017; 46: 927-942
- The Swedish medical birth register during five decades: Documentation of the content and quality of the register.Eur J Epidemiol. 2023; 38: 109-120
- Repeated vulvovaginal fungal infections cause persistent pain in a mouse model of vulvodynia.Sci Transl Med. 2011; 3: 101ra91
- Is socioeconomic status associated with utilization of health care services in a single-payer universal health care system?.Int J Equity Health. 2014; 13 (115-1)
- Site-specific mesenchymal control of inflammatory pain to yeast challenge in vulvodynia-afflicted and pain-free women.Pain. 2015; 156: 386-396
- Recurrent yeast infections and vulvodynia: Can we believe associations based on self-reported data?.J Womens Health (Larchmt). 2017; 26: 1069-1076
- Allergic reactions and risk of vulvodynia.Ann Epidemiol. 2009; 19: 771-777
- Prevalence of symptoms consistent with a diagnosis of vulvodynia: Population-based estimates from 2 geographic regions.Am J Obstet Gynecol. 2014; 210: 40.e1-40.e8
- A population-based assessment of chronic unexplained vulvar pain: Have we underestimated the prevalence of vulvodynia?.J Am Med Womens Assoc. 1972; 58 (2003): 82-88
- Preterm birth and sustained inflammation: Consequences for the neonate.Semin Immunopathol. 2020; 42: 451-468
- Neuro-immune crosstalk and allergic inflammation.J Clin Investigation. 2019; 129: 1475-1482
- Nordic health registry-based research: A review of health care systems and key registries.Clin Epidemiol. 2021; 13: 533-554
- External review and validation of the Swedish national inpatient register.BMC Public Health. 2011; 11 (450-450)
- Reproduction and mode of delivery in women with vaginismus or localised provoked vestibulodynia: A Swedish register-based study.BJOG. 2015; 122: 329-334
- Early life health in women with provoked vestibulodynia and/or vaginismus.J Womens Health (Larchmt). 2021; 30: 799-806
- Urogenital infections in relation to the occurrence of vulvodynia.J Reprod Med. 2009; 54: 385-392
- Nociceptor sensory neuron-immune interactions in pain and inflammation.Trends Immunol. 2017; 38: 5-19
- Mast cell infiltrates in vulvodynia represent secondary and idiopathic mast cell hyperplasias.APMIS. 2015; 123: 452-456
- Activation of vestibule-associated lymphoid tissue in localized provoked vulvodynia.Am J Obstet Gynecol. 2015; 212: 476.e1-476.e8
- Immune activation enhances epithelial nerve growth in provoked vestibulodynia.Am J Obstet Gynecol. 2016; 215: 768.e1-768.e8
- Characterizing differences in thymic function in women with and without vulvodynia: A community-based study.J Low Genit Tract Dis. 2021; 25: 296-302
- Cytokine profiles of women with vulvodynia: Identification of a panel of pro-inflammatory molecular targets.Eur J Obstet Gynecol Reprod Biol. 2018; 226: 66-70
Published online: March 18, 2023
Accepted: March 11, 2023
Received in revised form: March 7, 2023
Received: November 8, 2022
Publication stageIn Press Journal Pre-Proof
All authors declare no conflicts of interest.
The research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Grant R21-HD099533.
© 2023 by United States Association for the Study of Pain, Inc.