Ilya Petrou, MD

Atopic dermatitis (AD) is a common dermatologic condition often associated with a variety of different comorbidities which can prove challenging to manage and can further negatively impact the quality of life of patients far beyond their cutaneous eczematous symptoms. A recent study found that patients with AD have an increased prevalence of infertility, underscoring the need for appropriate consultation and treatment management in this patient population.

“In recent years, studies have demonstrated associations between AD and extracutaneous medical conditions, including a comorbidity linkage between atopy and infertility, revealing that atopic women had fewer children than non-atopic women,” wrote Amir Horev, MD, Pediatric Dermatology Service, Soroka University Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel, and head author of the study.

Estimated to affect approximately 10% adults and 30% of children world-wide, AD or atopic eczema is a chronically relapsing inflammatory skin condition associated with various morphology, distribution, and disease severity and course. Still having an unclear pathophysiology, AD appears to be the result of both genetic and environmental factors that induce skin barrier dysfunction, cutaneous and systemic dysregulation, and skin microbiota dysbiosis, leading to the typical clinical picture of AD.

Some of the most common causes of infertility include ovulatory disorders, endometriosis, pelvic adhesions, tubal abnormalities, hyperprolactinemia, sperm count, morphology, and function disorders. Nevertheless, infertility remains unexplained after standard medical investigation in approximately 30-40 percent of cases. According to the study authors, infertility and AD share common pathophysiological factors and mechanisms and therefore may also have an epidemiologic association.

“The etiologies of these comorbid conditions are complex and are likely multifactorial, involving epidermal structure abnormalities and dysfunction of barrier elements. Similarly, barrier dysfunctions are closely related to the development of infertility, as barrier function is needed for maintaining the immune privilege functions of several sites along the reproductive system,” the study authors wrote.

Horev and fellow colleagues recently performed a retrospective cohort study to evaluate the prevalence of infertility in patients with AD as well as investigate the association between AD and infertility in a real-life setting in a broad community-based population. 

Using the Clalit Health Services (CHS) medical database (the second largest healthcare organization provider world-wide), the researchers conducted a search between 2002 and 2018 and identified 127,150 patients with dermatologist diagnosis-confirmed diagnosis of AD and 127,071 comparison enrollees in the gender and age-matched control group to be included in the final evaluation. Study participants were subdivided according to age into adults and children, and further subdivided according to their AD severity which was classified either as mild or moderate to severe according to AD-related drug use and healthcare utilization services.

The researchers found that AD was associated with a higher prevalence of infertility in the general population compared to controls (1.4 and 1.1 percent, respectively). Data showed that the prevalence of infertility, per 1,000 patient-years, was increased in patients with AD compared to that of the control group (2.17 and 1.7, respectively). The researchers also found that regardless of the severity of symptoms whether mild or moderate to severe, AD was a key risk factor for infertility in both male and female subjects.

“Given that AD is an inflammatory disorder, and as other inflammatory disorders such as rheumatoid arthritis and asthma have been associated with infertility, it is reasonable to hypothesize that systemic inflammation related to AD may account for, at least in some part, some cases of infertility,” the study authors wrote.

, Bláfoss et al. investigated the impact of female asthma and atopy on fertility and found that there was a clear trend toward an association between female atopy and a reduction of fertility; hence, higher rates of atopic women require fertility treatments.

The results of the current study offer further epidemiological evidence on the significant association between AD and infertility and suggests that infertility may be an additional manifestation of the characteristically cutaneous disease. According to the study authors, further research should be performed to help better evaluate the impact of AD management in the setting of infertility and vice versa.

“Our study demonstrated a subtle, yet significant higher risk of infertility in the AD population; however, this observation has imperative and meaningful clinical applications from a public health perspective. Information regarding improvement in symptoms or recovery of patients with AD and the possible effect on infertility could not be drawn, and further prospective studies are warranted to address this issue,” the study authors wrote.

1. Horev A, Shalom G, Weintraub AY, Freud T, Cohen AD. Atopic dermatitis and infertility: a nationwide retrospective cohort study. Dermatology.2022;238(2):313-319. doi: 10.1159/000515600. Epub 2021 Apr 21.

2. Bláfoss J, Hansen AV, Malchau Lauesegaard SS, Ali Z, Ulrik CS. Female asthma and atopy – impact on fertility: a systematic review. J Asthma Allergy. 2019 Jul;12(12):205–11.

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A recent study showed that patients with atopic dermatitis have a higher prevalence of infertility, highlighting the need for clinicians to be wary of this increased risk and improve the care and management of this patient population.

Atopic dermatitis and infertility

Challenging to treat in the general patient population, hidradenitis suppurativa (HS) can cause serious, even lethal, complications for pregnant patients. Results of a recent study

 found that pregnant patients with HS have an increased risk of obstetric and pregnancy complications, including lower odds of a live birth, which underscores the need to proactively manage this disease. HS is characterized by recurrent painful nodules, abscesses, draining dermal fistula tracts, and scarring with a predilection for intertriginous sites such as the axillae, groin, gluteal, and submammary regions. It can significantly affect a patient’s quality of life. Associated comorbidities in more severe cases include metabolic syndrome, follicular occlusion disorders, inflammatory bowel diseases such as Crohn's disease, and spondyloarthropathy.

Lyons et al state that HS disproportionally affects women of childbearing age.

Nevertheless, although the effect of pregnancy on the clinical course of HS has been evaluated in the literature, there is a dearth of research on the effect of HS on pregnancy outcomes.

“Similar to the increased risks of pregnancy seen in female patients with psoriasis, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and other inflammatory diseases, pregnant patients with HS also can have a higher rate of pregnancy complications,” said Joslyn Sciacca Kirby, MD, MS, MEd, an associate professor in the Department of Dermatology at Penn State College of Medicine, Pennsylvania State University in Hershey. “There is an opportunity here for us as dermatologists to think about all our patients holistically. Although they might not be pregnant at the visit, it might be something they are thinking about, and more information could help them.”

FEWER LIVE BIRTHS, MORE CESAREAN DELIVERIES

Kirby and colleagues recently conducted a study

 investigating the maternal and obstetric outcomes and treatment utilization among women with HS. The researchers used the IBM MarketScan Commercial Claims and Encounters Database to identify a cohort of 998 pregnant women with HS and a cohort of 5065 age-matched pregnant women without HS. Retrospective analysis data on diagnoses, procedures, and medications were analyzed.

Pregnancies were assigned to 1 of 6 types: live birth, ectopic/molar pregnancy, elective termination, spontaneous abortion, unspecified abortion, and stillbirth. Only women with live births were evaluated for pregnancy complications, which included vaginal and cesarean delivery and treatments. The most common comorbidities represented in both the HS and non-HS cohorts were overweight/obesity, anxiety, and depression.

Compared with women without HS, the inves- tigators found that pregnant women with HS had significantly lower odds of having live childbirth (odds ratio [OR], 0.45; 95% CI, 0.39-0.51) and significantly higher odds of having elective terminations (OR, 2.51; 95% CI, 2.13-2.96), cesarean deliveries (OR, 1.28; 95% CI, 1.06-1.55), or gestational hypertension (OR, 1.44; 95% CI, 1.12-1.84).2

After adjusting for confounders, data showed higher odds for having cesarean delivery, which significantly diverges from another recent retrospective cohort study2 performed by Lyons et al. However, results showing preeclampsia/eclampsia and gestational hypertension were proportionally higher in women with HS echoed similar data from the Lyons study.

A flaring of HS symptoms is likely to occur in pregnant patients, according to Kirby. She advised clinicians to watch for these flares but also to make their pregnant patients aware of symptoms such as itchy or painful bumps found mostly in the armpits, groin, under the breasts, or in the anal and genital areas that could indicate a pending eruption. She recommended physicians also discuss with pregnant patients with HS disease and symptom control management during the postpartum period.

Hormone dysfunctions are thought to play a role in the underlying pathogenesis, development, and chronicity of HS, given the association of the disease with hormonal acne, polycystic ovarian syndrome, and fluctuations in HS disease severity associated with the menstrual cycle.

“There is an old rule for pregnancy and what to expect from skin conditions stating that [approximately] one-third of patients get better, one-third stay the same, and one-third get worse,” Kirby said. “This is also partially true for HS patients in that it seems that HS may improve in one-third of women who get pregnant. However, of the remaining two-thirds of patients, there are more who may worsen than stay the same.”

Investigators also found that pregnant women with HS had higher usage of topical and oral antibiotics and a higher prevalence of cutaneous surgeries during pregnancy compared with pregnant women without HS. According to Kirby, this finding reflects the fact that patients with HS commonly are prescribed multiple medications and may require a higher rate of procedures and/or surgeries to manage the disease.

Decisions on HS treatment become more complex in the context of pregnancy. Kirby said she asks patients to tell her as soon as they know they are pregnant so that they can work together to develop the optimal pregnancy and postpartum treatment regimen.

That may mean switching therapies. For example, she pointed out that therapies such as systemic retinoids, finasteride, and spironolactone that are used in managing HS are contraindicated in pregnancy, and many medications have safety profiles that are not clearly defined yet.

Kirby recommended consideration of a multidisciplinary management approach for pregnant patients with HS, underscoring the importance of dermatologists and obstetrical providers collaborating on a patient’s care throughout the pregnancy. Working with a team can be particularly beneficial for patients with HS because therapy management can require a different dynamic in each trimester, she added.

“Sometimes we will alter the therapy with some medications such as the biologics during the third trimester because many agents can cross the placenta into the baby,” she said. “This reinforces the need to communicate with the obstetrician and to work with the patient and help them understand the implications of continuing the medication through the third trimester.”

Pregnancy in patients with acne offers the same kind of challenge as with those with HS because they share a similar etiological background, Kirby noted. She said that, fortunately, there are different classes of topical and oral antibiotics as well as topical antiseptics that can be used safely. In her view, that list includes metformin for milder cases of HS and biologics, especially tumor necrosis factor inhibitors, for more severe disease.

“Hidradenitis suppurativa can get worse when associated with pregnancy and it is important to continue to manage the disease both medically and, when necessary, with surgical procedures with the guidance of both the dermatologist and obstetrician,” she said. “Heightened attention of care for these patients can help us better control the disease and significantly improve patients’ quality of life.”

Kirby is a consultant and speaker for AbbVie, receives honoraria for participating on an advisory board for AbbVie, and receives honoraria as a consultant for ChemoCentryx, Incyte, Janssen, Novartis, and UCB.

This article was originally published by our sister publication Dermatology Times.

Sakya SM, Hallan DR, Maczuga SA, Kirby JS. Outcomes of pregnancy and childbirth in women with hidradenitis suppurativa. J Am Acad Dermatol. 2022;86(1):61-67. doi:10.1016/j.jaad.2021.05.059

Lyons AB, Peacock A, McKenzie SA, et al. Retrospective cohort study of preg- nancy outcomes in hidradenitis suppurativa. Br J Dermatol. 2020;183(5):945- 947. doi:10.1111/bjd.19155

This painful skin disease may lower the odds of live birth and trigger comorbidities.

Ilya Petrou, MD

Articles

Atopic dermatitis and infertility

Hidradenitis suppurativa in pregnancy