PORTLAND, ORE. – The recurrent boils, abscesses, and nodules of the chronic inflammatory skin condition hidradenitis suppurativa (HS) may improve during pregnancy for a subset of women, but for many, pregnancy does not change the disease course and may worsen symptoms.
In addition, HS appears to be a risk factor for adverse pregnancy and maternal outcomes.
“This is relevant, because in the United States, HS disproportionately impacts women compared with men by a ratio of about 3:1,” Jennifer Hsiao, MD, said at the annual meeting of the Pacific Dermatologic Association.
Dr. Jennifer Hsiao
“Also, the highest prevalence of HS is among people in their 20s and 30s, so in their practice, clinicians will encounter female patients with HS who are either pregnant or actively thinking about getting pregnant,” she said.
During a wide-ranging presentation, Dr. Hsiao of the department of dermatology at the University of Southern California, Los Angeles, described the impact of pregnancy on HS, identified appropriate treatment options for this population of patients, and discussed HS comorbidities that may be exacerbated during pregnancy.
She began by noting that levels of progesterone and estrogen both rise during pregnancy. Progesterone is known to suppress development and function of Th1 and Th17 T cells, but the effect of estrogen on inflammation is less well known. At the same time, serum levels of interleukin (IL)-1 receptor antagonist and soluble TNF-alpha receptor both increase during pregnancy.
“This would lead to serum IL-1 and TNF-alpha falling, sort of like the way that we give anti–IL-1 and TNF blockers as HS treatments,” she explained. “So, presumably that might be helpful during HS in pregnancy. On the flip side, pregnancy weight gain can exacerbate HS, with increased friction between skin folds. In addition, just having more adipocytes can promote secretion of proinflammatory cytokines like TNF-alpha.”
To better understand the effect of pregnancy on patients with HS, Dr. Hsiao and colleagues conducted a systematic review and meta-analysis on the topic published in Dermatology. They included eight studies in which a total of 672 patients self-reported their HS disease course during pregnancy and 164 self-reported whether they had a postpartum HS flare or not. On pooled analyses, HS improved in 24% of patients but worsened in 20%. In addition, 60% of patients experienced a postpartum flare.
“So, at this point in time, based on the literature, it would be fair to tell your patient that during pregnancy, HS has a mixed response,” Dr. Hsiao said. “About 25% may have improvement, but for the rest, HS symptoms may be unchanged or even worsen. That’s why it’s so important to be in contact with your pregnant patients, because not only may they have to stay on treatment, but they might also have to escalate [their treatment] during pregnancy.”
Lifestyle modifications to discuss with pregnant HS patients include appropriate weight gain during pregnancy, smoking cessation, and avoidance of tight-fitting clothing, “since friction can make things worse,” she said. Topical antibiotics safe to use during pregnancy for patients with mild HS include clindamycin 1%, erythromycin 2%, and metronidazole 0.75% applied twice per day to active lesions, she continued.
As for systemic therapies, some data exist to support the use of metformin 500 mg once daily, titrating up to twice or – if needed and tolerated – three times daily for patients with mild to moderate HS, she said, referencing a paper published in the Journal of the European Academy of Dermatology and Venereology.
Zinc gluconate is another potential option. Of 22 nonpregnant HS patients with Hurley stage I-II disease who were treated with zinc gluconate 90 mg daily, 8 had a complete remission of HS and 14 had partial remission, according to a report in Dermatology.
“Zinc supplementation of up to 50 mg daily has shown no effect on neonatal or maternal outcomes at birth based on existing medical literature,” Dr. Hsiao added.
Among antibiotics, injections of intralesional Kenalog 5-10 mg/mL have been shown to decrease pain and inflammation in acute HS lesions and are unlikely to pose significant risks during pregnancy, but a course of systemic antibiotics may be warranted in moderate to severe disease, she said. These include, but are not limited to, clindamycin, erythromycin base, cephalexin, or metronidazole.
“In addition, some of my HS colleagues and I will also use other antibiotics such as Augmentin [amoxicillin/clavulanate] or cefdinir for HS and these are also generally considered safe to use in pregnancy,” she said. “Caution is advised with using rifampin, dapsone, and moxifloxacin during pregnancy.”
As for biologic agents, the first-line option is adalimumab, which is currently the only Food and Drug Administration–approved treatment for HS.
“There is also good efficacy data for infliximab,” she said. “Etanercept has less placental transfer than adalimumab or infliximab so it’s safer to use in pregnancy, but it has inconsistent data for efficacy in HS, so I would generally avoid using it to treat HS and reach for adalimumab or infliximab instead.”
Data on TNF-alpha inhibitors from the GI and rheumatology literature have demonstrated that there is minimal placental transport of maternal antibodies during the first two trimesters of pregnancy.
“It’s at the beginning of the third trimester that the placental transfer of antibodies picks up,” she said. “At that point in time, you can have a discussion with the patient: do you want to stay on treatment and treat through, or do you want to consider being taken off the medication? I think this is a discussion that needs to be had, because let’s say you peel off adalimumab or infliximab and they have severe HS flares. I’m not sure that leads to a better outcome. I usually treat through for my pregnant patients.”
To better understand clinician practice patterns on the management of HS in pregnancy, Dr. Hsiao and Erin Collier, MD, MPH, of University of California, Los Angeles, and colleagues distributed an online survey to HS specialists in North America. They reported the findings in the International Journal of Women’s Dermatology.
Of the 49 respondents, 36 (73%) directed an HS specialty clinic and 29 (59%) reported having prescribed or continued a biologic agent in a pregnant HS patient. The top three biologics prescribed were adalimumab (90%), infliximab (41%), and certolizumab pegol (34%). Dr. Hsiao noted that certolizumab pegol is a pegylated anti-TNF, so it lacks an Fc region on the medication.
“This means that it cannot be actively transported by the neonatal Fc receptor on the placenta, thus resulting in minimal placental transmission,” she said. “The main issue is that there is little data on its efficacy in HS, but it’s a reasonable option to consider in a pregnant patient, especially in a patient with severe HS who asks, ‘what’s the safest biologic that I can go on?’ But you’d have to discuss with the patient that in terms of efficacy data, there is much less in the literature compared to adalimumab or infliximab.”
Breastfeeding while on anti–TNF-alpha biologics is considered safe. “There are minimal amounts of medication in breast milk,” she said. “If any gets through, infant gastric digestion is thought to take care of the rest. Of note, babies born to mothers who are continually treated with biologic agents should not be given live vaccinations for 6 months after birth.”
In a single-center study, Dr. Hsiao and colleagues retrospectively examined pregnancy complications, pregnancy outcomes, and neonatal outcomes in patients with HS. The study population included 202 pregnancies in 127 HS patients. Of 134 babies born to mothers with HS, 74% were breastfed and 24% were bottle-fed, and presence of HS lesions on the breast was significantly associated with not breastfeeding.
“So, when we see these patients, if moms decide to breastfeed and they have lesions on the breast, it would be helpful to discuss expectations and perhaps treat HS breast lesions early, so the breastfeeding process may go more smoothly for them after they deliver,” said Dr. Hsiao, who is one of the editors of the textbook “A Comprehensive Guide to Hidradenitis Suppurativa” (Elsevier, 2021). Safety-related resources that she recommends for clinicians include Mother to Baby and the Drugs and Lactation Database (LactMed).
Dr. Hsiao concluded her presentation by spotlighting the influence of pregnancy on HS comorbidities. Patients with HS already have a higher prevalence of depression and anxiety compared to controls. “Pregnancy can exacerbate underlying mood disorders in patients,” she said. “That’s why monitoring the patient’s mood and coordinating mental health care with the patient’s primary care physician and ob.gyn. is important.”
In addition, pregnancy-related changes in body mass index, blood pressure, lipid metabolism, and glucose tolerance trend toward changes seen in metabolic syndrome, she said, and HS patients are already at higher risk of metabolic syndrome compared with the general population.
HS may also compromise a patient’s ability to have a healthy pregnancy. Dr. Hsiao worked with Amit Garg, MD, and colleagues on a study that drew from the IBM MarketScan Commercial Claims Database to evaluate adverse pregnancy and maternal outcomes in women with HS between Jan. 1, 2011, and Sept. 30, 2015.
After the researchers adjusted for age, race, smoking status, and other comorbidities, they found that HS pregnancies were independently associated with spontaneous abortion (odds ratio, 1.20), gestational diabetes (OR, 1.26), and cesarean section (OR, 1.09). The findings were published in the Journal of the American Academy of Dermatology.
A separate study that used the same database found comparable results, also published in the Journal of the American Academy of Dermatology. “What I say to patients right now is, ‘there are many women with HS who have healthy pregnancies and deliver healthy babies, but HS could be a risk factor for a higher-risk pregnancy.’ It’s important that these patients are established with an ob.gyn. and are closely monitored to make sure that we optimize their care and give them the best outcome possible for mom and baby.”
Dr. Hsiao disclosed that she is on the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as an advisor for Novartis, UCB, and Boehringer Ingelheim and as a speaker and advisor for AbbVie.