FormalPara Key Summary Points

Hidradenitis suppurativa (HS) is a chronic skin condition that can have a profound negative impact on patients’ quality of life. Although most prevalent among people in their twenties and thirties, HS can present in adolescence or late adulthood.

There is currently a lack of population-specific treatment guidelines for HS in children, pregnant and breastfeeding women, and the elderly.

Management of HS in the pediatric population is largely modeled after adult guidelines and includes treatments such as topical agents, systemic antibiotics, hormonal and metabolic therapies, supplements, retinoids, biologics, small molecule inhibitors, and procedures.

Although some HS medications should be avoided during pregnancy and lactation, there are medical and procedural treatment modalities that can be safely or cautiously used in these patients.

Treatment of HS in the elderly should take into consideration the patient’s overall health, comorbidities, potential drug–drug interactions, and goals of care.

Introduction

Hidradenitis suppurativa (HS) is a chronic, inflammatory disorder characterized by recurrent and painful nodules, abscesses, tunnels, and scarring that typically involve intertriginous areas [1]. Prevalence of HS is reported to be 0.1% in the USA [2] but is likely more common given frequent underdiagnosis and misdiagnosis of this condition. Due to its chronic and debilitating nature, HS can profoundly negatively impact multiple aspects of a patient’s life. Patients with HS experience higher rates of unemployment, disability, pain, substance use, and mental health disparities [1, 3]. Timely diagnosis and intervention are critical in minimizing the burden of disease. Therefore, it is important that clinicians are prepared to diagnose and manage HS in all stages of life. Although HS has been found to be most prevalent among people in their twenties and thirties, up to 50% of patients with HS show symptoms between the ages of 10 and 21 years [4], emphasizing the need for improved early diagnosis of HS in the pediatric population. For a subset of patients, symptoms may manifest in late adulthood. Patients with HS have been found to have a lower life expectancy and higher all-cause mortality; chronic systemic inflammation may play a role [5,6,7]. Aggressive control of disease is essential, and consequences of untreated HS must be carefully weighed against risks of therapeutic interventions. There is a paucity of data on optimal management of HS in children, pregnant and breastfeeding women, and the elderly. This review discusses HS treatment strategies for the aforementioned special populations. Treatment strategies discussed are based on extrapolation from general HS literature as well as population-specific efficacy data wherever available. HS-specific drug safety data regarding use in these special populations is currently limited, thus safety conclusions also leverage existing literature regarding individual treatments used in these special populations for conditions other than HS. Herein, we aim to update clinicians on a practical approach to management of HS in these patients.

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

HS in Children

HS affects approximately 28 out of 100,000 children and adolescents in the USA. When broken down, HS is quite rare under the age of 10 years and uncommon between ages 10 and 14 years. Of pediatric patients with HS, 72.4% are between the ages of 15 and 17 years [8], though underdiagnosis of HS in younger patients may skew prevalence data. Clinical presentation of HS in children can vary, leading to misdiagnosis and undertreatment of symptoms. Pediatric patients may present with subtle findings such as comedones, papules, pustules, and isolated cysts or abscesses [9]. As such, early disease is often misdiagnosed as acne, folliculitis, or infection. The chronic and recurrent nature of the skin lesions and their tendency to appear in intertriginous regions can help steer clinicians toward a diagnosis of HS. Average time from symptom onset to HS diagnosis is 2.5 years in the pediatric population [9], and up to 7 years in adults [10]. This lag time may contribute to worsening of symptoms and subsequent formation of irreversible skin damage. Clinicians should also assess for co-morbidities including psychiatric conditions (i.e. depression and anxiety), metabolic conditions (i.e. obesity, diabetes), polycystic ovarian syndrome, acne, atopic disease, asthma, and Crohn’s disease [11, 12]. Importantly, it is recommended to screen all patients with Down syndrome for HS given the increased risk of HS in this patient population [13].

Management of HS in the pediatric population is largely modeled after treatment guidelines for adults. There are currently no pediatric-specific HS treatment guidelines, and most systemic treatments are used off label in children, highlighting the need for further work in this area. Commonly utilized medications are listed in Table 1.

Table 1 Agents used in pediatric hidradenitis suppurativa
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Approach to pediatric dosing can be challenging and has historically been determined by using one of the following methods: (1) age-based categories, (2) weight-based dosing, (3) use of body surface area, and (4) an allometric scaling method where physiological function is related to body size [14]. The Pediatric Pharmacy Advocacy group recommends that weight-based dosing be utilized in patients under the age of 18 years who are less than 40 kg. Weight-based dosing should also be used in patients ≥ 40 kg, unless standard recommend adult dosing is surpassed [15]. Over 70% of pediatric patients with HS are 15–17 years of age [8], and thus are likely to require adult dosing for many medications. Of note, there is rising incidence of childhood obesity that can further complicate pediatric medication dosing, as it has been postulated that obese individuals may have decreased hepatic clearance and larger volume of distribution for lipophilic medications. Collaboration with a clinical pharmacist and pharmacokinetic analysis may be considered for overweight children to ensure safe and therapeutic dosing [15].

Topical Agents

Topical treatments may be considered first-line in milder disease states. Antiseptic washes such as chlorhexidine or benzoyl peroxide can be recommended for use in affected areas to help decrease bacterial load [12, 16]. Clindamycin 1% is the topical antibiotic of choice and can be used once to twice daily to active areas [17]. Resorcinol, a compounded topical keratolytic agent, may also be utilized as spot treatment twice daily to active lesions in pediatric patients with HS on the basis of promising efficacy in adults [18, 19].

Systemic Antibiotics

Systemic antibiotics may be utilized to address acute flares or as a bridge to more sustainable long-term therapeutics across all Hurley stages. Limited literature suggests that response rate to systemic antibiotics among pediatric patients is high [20]. Tetracyclines, such as doxycycline, can be utilized in patients over 8 years of age. They are generally not recommended in children under 8 years due to concerns for dental staining; however, more recent studies suggest that this age limit should be reconsidered if there may be substantial benefit to doxycycline use [21]. The combination of oral clindamycin and rifampin has been shown to be clinically effective in treating HS in pediatric populations [22]. Other systemic antibiotics that can be considered include trimethoprim-sulfamethoxazole, azithromycin, erythromycin, and metronidazole. Dapsone has been shown to improve disease in 9 out of 24 adults with HS, hypothetically due to its anti-inflammatory effects, but data on its use in pediatric patients with HS are limited [23]. Similarly, ertapenem, an intravenous beta-lactam antibiotic, has been efficacious as rescue treatment of adult HS, with little data on pediatric patients’ response [24].

Hormonal, Metabolic, and Supplement Therapies

Hormones likely play a role in HS pathogenesis, given onset of HS commonly occurs after puberty and for women; HS symptoms often flare with menses [25]. Modulating hormonal factors in adolescent patients, especially those undergoing puberty, can be helpful in managing HS symptoms across all severity levels. Finasteride, a 5-alpha reductase inhibitor, has been shown to reduce the frequency and severity of HS flares in female children in a few cases [26]. It is generally recommended to avoid finasteride use in males until after puberty. For post-menarche females over the age of 14 years, a combined oral contraceptive pill (OCP) or spironolactone may be used [27,28,29,30]. Pediatric female patients of childbearing age who are sexually active should undergo contraceptive counseling and adjunctive OCP if on finasteride or spironolactone, as these agents should be avoided during pregnancy. Metformin can be considered in pediatric patients with HS with milder disease or as an adjunct agent, particularly in patients with concomitant metabolic conditions such as obesity, type II diabetes mellitus, or insulin resistance. Several studies report improvement of pediatric HS on metformin, and a systemic review found metformin use to be relatively safe for managing obesity in children [20, 31, 32]. Additionally, oral zinc supplementation (90 mg/day) can be a useful and safe adjunctive therapy [33]. Low-dose copper should be co-administered, as zinc may deplete copper stores [34].

Retinoids

Consistent data suggesting efficacy of retinoids for HS is lacking; thus, they are only recommended as second- or third-line agents to consider for HS. Oral retinoids are best considered in patients with HS who have widespread comedones, a scarring folliculitis phenotype [35], or concomitant nodulocystic acne. Although the efficacy of isotretinoin has been inconsistent, younger age has been found to be associated with an improved response to isotretinoin [1, 36]. Two case reports suggest improvement of HS with acitretin use in adolescent boys with HS [37, 38].

Biologics

Adalimumab, a tumor necrosis factor (TNF) alpha inhibitor, is currently the only Food and Drug Administration (FDA)-approved biologic for pediatric HS in patients 12 years and older with moderate-to-severe disease. Secukinumab is an IL-17 inhibitor currently FDA-approved for treatment of moderate-to-severe HS in adults; however, it is approved for pediatric psoriatic arthritis down to the age of 2 years of age. Thus, it is reasonable to discuss secukinumab as a first- or second-line off-label treatment for pediatric HS on the basis of efficacy in adult clinical trials [39]. Dosing is weight dependent and typically lower than standard adult dosing. Infliximab, an intravenous TNF-alpha inhibitor, can be considered for severe or recalcitrant disease and is currently approved for treatment of Crohn’s disease and ulcerative colitis in patients aged 6 years and older. Several case studies demonstrate complete resolution or improvement of HS symptoms in adolescent patients while on infliximab therapy [40, 41]. A case series of 12 pediatric patients studied the efficacy of adalimumab, infliximab, and anakinra (an IL-1 antagonist) in treating HS. Results showed that 6 out of 7 patients who trialed infliximab, 4 out of 7 who trialed adalimumab, and the single patient who trialed anakinra achieved HS clinical response (HiSCR) after at least 4 months of treatment [41]. Ustekinumab, an anti-IL-12/IL-23 monoclonal antibody, is also recommended as a second-line agent in the North American Management Guidelines for HS [16]. One study of biologic use in children found that two patients treated with ustekinumab achieved complete resolution of HS symptoms without relapse within less than 12 months of therapy [42]. Ustekinumab is approved down to the age of 6 years for pediatric psoriasis and psoriatic arthritis. Anakinra, currently FDA-approved for treatment of IL-1 receptor antagonist deficiency, achieved HiSCR in a 15-year-old patient who had previously failed adalimumab and infliximab [41]. Although data on anakinra use for HS specifically in pediatric patients are limited, IL-1 inhibition may be considered as an alternative to those who have failed TNF and IL-17 inhibition.

Small Molecule Inhibitors

Oral small molecule inhibitors may be considered, especially for children who are unable to tolerate biologic injections. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, has been shown to improve HS abscess and nodule count in adults [43]. Although apremilast does not currently have an FDA indication for use in children, no new safety signals were identified when studied in pediatric patients with plaque psoriasis [44]. Upadacitinib, a Janus kinase (JAK) 1 inhibitor, is FDA-approved for atopic dermatitis in children down to the age of 12 years and phase 3 adult HS trials are currently underway [45, 46].

Procedures for HS

Surgical management of HS should be considered when patients present with HS flares or persistent HS lesions despite medical management. Surgical interventions can be implemented in conjunction with medical management, but patients’ age, tolerance for in-office procedures, and parental comfort should be considered. A systematic review of procedural treatments across 81 pediatric HS had showed favorable response. Reported procedures included as incision and drainage (I&D), deroofing, excisions, photodynamic therapy, botulinum toxin, laser treatments, hyperbaric oxygen, negative pressure wound therapy, and cryoinsufflation [47]. I&D can be performed to relieve acutely painful abscesses [18, 48]. Intralesional steroid injections have been found to be effective in treating acutely painful nodular lesions in patients with HS; strategies such as dilution with lidocaine 1% or application of topical lidocaine with distraction techniques should be implemented to help decrease anxiety regarding injections [12]. Surgical deroofing, excisions, and laser therapy have also been used for pediatric patients [18, 49].

HS in Pregnancy

HS disproportionately affects women of childbearing age [50, 51]. Thus, clinicians must be familiar with treatment options for HS that are considered compatible with pregnancy and breastfeeding. There appears to be considerable variability in HS disease activity during pregnancy. Although some patients may see improvement of their HS, most patients may experience unchanged or worsening disease activity during pregnancy and in the post-partum period [52, 53]. Furthermore, women with HS have been found to be at higher risk of adverse maternal, and pregnancy-related and neonatal outcomes, such as preterm birth or gestational hypertension, with HS being an independent risk factor for spontaneous abortion, gestational diabetes and cesarean section [54]. Women with HS have also been found to have lower likelihood of live birth and higher odds of elective termination [55]. Therefore, it is crucial that patients maintain regular follow-up appointments with both their dermatologist and obstetrician throughout their pregnancy. Prospective, large-scale studies are needed to determine the impact of HS treatments on pregnancy outcomes.

The FDA previously categorized medications into A, B, C, D, and X, with A signifying adequate human studies showing no risk to fetus and X defined as positive evidence of human fetal risk [56]. The pregnancy letter categories were recently replaced by the Pregnancy and Lactation Labeling Rule in 2015, as many providers found the letter classification to be confusing and overly simplistic; however, they are included in this review for historical reference. HS medications that are considered compatible, can be used with caution, or contraindicated in pregnancy are listed in Table 2.

Table 2 Agents used for hidradenitis suppurativa and their compatibility during pregnancy and breastfeeding
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Topical Agents

Antiseptic washes such as chlorhexidine wash and benzoyl peroxide wash are generally considered to be safe during pregnancy [57, 58]. Topical clindamycin 1% (Category B) can safely be recommended for pregnant women to treat active HS lesions [58].

Systemic Antibiotics

Systemic antibiotics for HS that are commonly prescribed by HS experts and generally considered safe to use during pregnancy include clindamycin (B), cephalexin (B), cefdinir (B), amoxicillin/clavulanate (B), and metronidazole (B) [59, 60]. Amoxicillin should be restricted to use in the second and third trimesters only due to potential risk of cleft lip and palate with exposure during the first trimester [61]. Although clindamycin is typically used in combination with rifampin, clindamycin monotherapy may have similar efficacy to combo therapy and thus is a reasonable treatment consideration [62].

Rifampin (C), dapsone (C), moxifloxacin (C), and ertapenem (B) should be used with caution during pregnancy. Rifampin should be considered on a case by case basis due to teratogenicity in animal studies and few reports of maternal and infant postnatal hemorrhage when used in the weeks preceding delivery and induction [63]. Tuberculosis consensus guidelines suggest that rifampin can be administered during pregnancy, thus clinicians may exercise use with caution when potential benefits outweigh risks [64]. Dapsone has not been associated with risk of congenital defects; however, cases of dose-related neonatal hemolysis [65] and hyperbilirubinemia [66] have been reported. While it is acceptable to use during pregnancy, it should be discontinued at least a month before birth to avoid kernicterus [66]. Moxifloxacin, a fluoroquinolone, has not been associated with a statistically significant increased risk of adverse pregnancy outcomes [67, 68]. Although there is limited human data, animal studies suggest increased risk of quinolone-induced arthropathy [69]. Intravenous ertapenem can be considered as rescue therapy for severe, recalcitrant HS [24]. Human safety data regarding ertapenem use during pregnancy are limited; however, animal studies suggest no developmental toxicity with fetal exposure of the drug. Mice exposed to drug in utero were found to have slight decreased fetal weight and decreased average number of ossified vertebrae [70]. Ertapenem may be used cautiously in scenarios where the clinical benefits outweigh risks.

Metabolic and Supplement Therapies

Metformin (B) can be utilized as adjunct therapy for HS in pregnant patients, especially in those with gestational diabetes. It is generally considered compatible with pregnancy, and two meta-analyses have not shown associated congenital abnormalities when taken during the first trimester [71, 72]. Zinc gluconate has also been shown to have therapeutic effects on HS, and is generally safe to use during pregnancy, although safety data is limited. Patients should be supplemented with low dose copper as excess zinc can deplete copper stores [34].

Biologics

Biologic safety data for treating of HS during pregnancy are limited, but many biologics have been tested in pregnant patients for other inflammatory conditions such as psoriasis and inflammatory bowel disease. Adalimumab (B) and infliximab (B) have not been associated with significant pregnancy or neonatal complications [73]. There is general consensus that adalimumab and infliximab are considered safe during the first two trimesters of pregnancy, and that, with the increased transfer of IgG antibodies across the placenta at the beginning of the third trimester, a discussion should be had regarding continuation versus discontinuation [74]. Risk of fetal drug exposure versus the potential for uncontrolled disease with medication discontinuation must be taken into consideration. If TNF-inhibition is continued through delivery, live vaccines should be avoided for at least the first 6 months of the newborn’s life [75]. Certolizumab (B), a pegylated anti-TNF-alpha agent, is considered safe to use throughout pregnancy due to limited transfer of the medication across the placenta [76]. HS-specific safety and efficacy data for certolizumab is lacking and is currently limited to a few case reports [77,78,79].

There is currently a lack of safety data to recommend use of IL-17 agents such as secukinumab (B) during pregnancy. The Novartis Global Safety Database did not identify increased risk of spontaneous abortion, congenital malformation, or safety signals among 238 exposures, though only 153 outcomes were known. Pregnancy outcome data, especially with drug exposure during the second and third trimesters, are further limited, as a vast majority of patients discontinued secukinumab during their first trimester [80]. Ustekinumab (B), an IL-12/23 antagonist, has limited data in pregnancy as well. Data from the Pregnancy Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) registry did not identify increased risk of spontaneous abortion or congenital malformations across 47 exposures. [81, 82]. Due to overall limited safety data, it is recommended that secukinumab and ustekinumab be considered only if a patient has failed or has a contraindication to TNF-alpha inhibition.

Small Molecule Inhibitors

There is limited human data on apremilast use in pregnancy. In animals, apremilast exposure during pregnancy has been associated with embryo-fetal death [83]. It is also recommended to avoid use of JAK inhibitors during pregnancy due to teratogenicity reported in animal studies [84].

Procedural Management

Major surgical procedures requiring sedation should be deferred until after delivery. However, in-office procedures including intralesional steroids and those that utilize local anesthesia are safe to perform during pregnancy. These procedures include local excision, incision and drainage, and de-roofing of sinus tracts. Local anesthesia is achieved with lidocaine (B) and is generally considered safe to use in pregnant individuals [85].

HS in Breastfeeding

Breastfeeding mothers with HS face unique challenges to both management of symptoms and safety of their child. Many patients experience postpartum flares, posing additional difficulties for these patients during a demanding time. Pain associated with HS, safety concerns regarding medications entering breastmilk, and concerns about their child coming into contact with HS can all impact a patient’s decision to breastfeed [86]. Clinicians should be familiar with the safety profile of HS therapies during lactation to minimize disruption of breastfeeding (Table 2).

Special Considerations for HS Treatment

Most medications safe to use in pregnancy are considered compatible during breastfeeding. Clindamycin is excreted into breast milk in small quantities and thus can be considered during breastfeeding; there is a small potential to disturb the gut microbiome in infants [87, 88]. Metronidazole can present in high concentrations in breast milk and should be discontinued 12–24 h prior to breastfeeding [89]. Rifampin is excreted into breast milk but has no adverse effects on infants. Therefore, it is safe to use in breastfeeding mothers with a similar caution with regards to its impact on the CYP-450 system [90]. Metformin is minimally excreted in breast milk and is generally safe to use in breastfeeding patients with HS [91]. Zinc does not enter breast milk; thus, it can be safely used [92].

Adalimumab and infliximab are both excreted in breast milk in negligible concentrations and are not well-absorbed through the gut; there have been no reported adverse effects on breastfeeding infants for either medication. Therefore, they are generally considered safe to prescribe during lactation [93]. Safety data on secukinumab and ustekinumab in breastfeeding are limited, but detection of these drugs in breast milk is expected to be low to minimal [94,95,96]. Apremilast and JAK inhibition should be avoided during lactation due to lack of human data [97].

HS in the Elderly

Geriatric HS is defined as the presence of active disease beyond the age of 65 years. The term “HS tarda” has been proposed and can be further subdivided in those with late onset and those with earlier onset and persistence into older age. The literature suggests a prevalence of 0.2% for late-onset HS and 0.8% for persistent HS in elderly individuals [98]. As in the adult population, elderly females are more commonly affected than elderly males. However, there was a higher proportion of males within the elderly HS population compared with the adult HS population (35.9% versus 22.8%) [98]. Overall, the female to male predominance is less in the older population compared with the adult population [99].

Literature suggests that HS can present more severely in elderly patients than their younger counterparts, and perhaps independent of overall disease duration [100,101,102]. Larger studies are needed to investigate for potential differences in clinical characteristics among those with late onset versus persistent HS. Elderly patients with HS are more likely to present with multiple comorbidities including hypertension, dyslipidemia, diabetes mellitus, cardiac disease, renal disease, hepatic abnormalities, obesity, and tobacco use [98, 103, 104]. Thus, considering comorbidities is an important aspect of selecting appropriate therapies for older patients with HS.

Special Considerations for HS Treatment

Treatment of HS in the elderly population should take into consideration the overall health of the patient, as well as comorbidities, medications, and goals of care.

The topical therapies discussed in above sections are also standard of care for elderly patients with milder HS or as adjunct therapies [100, 103]. Choosing an optimal systemic antibiotic agent is contingent upon careful medication review to ensure no medication interactions, given polypharmacy is common in elderly patients [105]. Rifampin, for example, can decrease bioavailability of drugs metabolized by the cytochrome P-450 system, such as warfarin, digoxin, amiodarone, statins, β-blockers, and sulfonylureas [106].

Although there is no documentation on the efficacy of finasteride on older patients with HS, finasteride has been shown to be safe in postmenopausal women (those without a menstrual cycle for 12 consecutive months) and older men, and it may be an appropriate adjuvant therapy for HS in elderly patients. Metformin is also an option for patients with metabolic comorbidities to achieve control of both insulin resistance and HS [107]. If prescribing spironolactone to an elderly female patient, potassium levels should be closely monitored, especially in the setting of renal impairment [108]. Other medications requiring dose adjustment for patients with renal impairment include rifampin, trimethoprim-sulfamethoxazole, cephalexin, ciprofloxacin, amoxicillin-clavulanate, dapsone, ertapenem, metformin, and spironolactone [109]. Tetracyclines, azithromycin, rifampin, metformin, and acitretin should be avoided in those with severe hepatic impairment [110]. According to the American Geriatrics Society 2023 Beers Criteria, trimethoprim-sulfamethoxazole, ciprofloxacin, spironolactone, systemic estrogens, non-steroidal anti-inflammatory drugs(NSAIDs), gabapentin, and opioids should be used with caution or avoided in the elderly [111].

Biologics including adalimumab, infliximab, secukinumab, and golimumab have been implemented as treatments for HS in the elderly [103]. TNF-inhibitors should be avoided in patients with a past medical history of class III or IV congestive heart failure [112]. There is currently limited evidence to guide clinicians on use of biologics in those with a history of malignancy. According to the joint American Academy of Dermatitis (AAD)-National Psoriasis Foundation (NPF) psoriasis guidelines, TNF-inhibitors are typically contraindicated in individuals with history of lymphoreticular malignancy but can be considered in patients with a history of solid tumor malignancy who have failed other therapies [112]. The AAD-NPF psoriasis guidelines do not list history of lymphoreticular or solid organ malignancy as relative or absolute contraindications to IL-17 inhibition [112]. A retrospective study of 42 psoriasis patients with a history of prior malignancy found no increased likelihood of malignancy recurrence with IL-17 inhibition [113]. Biologic use in patients with a history of malignancy should be discussed with the patient’s oncologist, when possible, prior to initiation.

In-office procedures can be safely utilized for elderly patients as in the aforementioned populations. Procedures requiring general anesthesia should be considered on a case-by-case basis and require a multidisciplinary approach and thorough pre-operative evaluation. Elderly individuals are at increased risk of perioperative complications due to reductions in physiologic reserve, functional status, and coexisting diseases [114]. Thus, benefits and risks should be weighed, and use of in-office procedures should be implemented when feasible. Post-operative use of NSAIDs and opioids should be limited whenever feasible [111].

Conclusion

HS is an oftentimes debilitating disease for patients across different stages of life. However, certain demographic groups present with distinct management challenges that require additional considerations, particularly around medication safety. More research is needed to guide optimization of HS care for pediatric, pregnant, breastfeeding, and elderly patients, as HS data specific to these populations remains limited.