Hidradenitis Suppurativa in the Pediatric Population

Key Points

Question

What are the clinical features of pediatric patients presenting with hidradenitis suppurativa (HS)?

Findings

In this international, multicenter, cross-sectional study including 481 pediatric patients with HS, the median (interquartile range) disease duration at the time of diagnosis was 2.5 (1-5) years, and at first assessment 23 (48%) patients already had scarring; comorbidities and complications were seen in 406 (85%) and 378 (79%) patients, respectively.

Meaning

The study findings suggest that there is a delay in diagnosing pediatric HS, a condition poorly characterized in children, that is associated with comorbidities and complications in pediatric patients.

This cross-sectional study examines the demographics, clinical features, treatment, associated comorbidities, and outcomes in a large cohort of pediatric patients with hidradenitis suppurativa.

Abstract

Importance

Hidradenitis suppurativa (HS) in pediatric patients has been understudied. Increased awareness and recognition of HS prevalence in children demand efforts to better understand this condition.

Objective

To describe the demographics, clinical features, treatment, associated comorbidities, and outcomes in a large cohort of pediatric patients with HS.

Design, Setting, and Participants

International, multicenter, retrospective medical record review of pediatric patients (aged 1-18 years) with a clinical diagnosis of HS carried out in 10 dermatology clinics across the US, Canada, Israel, Australia, and Italy from January 1996 to January 2017.

Main Outcomes and Measures

Patient demographics, clinical features, severity, associated comorbidities, and treatments in pediatric patients with HS.

Results

This cross-sectional study included 481 patients diagnosed with HS. Overall, 386 (80%) were girls. The mean (SD) age of disease onset was 12.5 (2.9) years, and the mean (SD) age at diagnosis was 14.4 (3.5) years. Family history of HS was present in 111 of 271 (41%) patients. First signs/symptoms reported at disease onset were cyst/abscess in 229 of 481 (48%), pain/tenderness in 118 of 481 (25%), and papules/pustules in 117 of 481 (24%). At initial dermatologic assessment, 233 of 481 (48%) patients already had evidence of skin scarring. Disease severity (Hurley staging) was documented in 288 of 481 (60%) patients (47% stage 1, 45% stage 2 and 8% stage 3). Comorbid conditions were reported in 406 of 481 (85%) patients, the most common being obesity (263/406 [65%]) and acne vulgaris (118/406 [29%]). Complications occurred in 378 of 481 (79%) patients, the most common of which were scars or contractures (301/378 [80%]).

Conclusions and Relevance

The findings of this study indicate that there is a gap in recognizing and diagnosing pediatric HS. Pediatric patients with HS are likely to present with other comorbidities. Prospective observational and interventional studies are needed to better understand clinical course and optimal treatments for pediatric HS.

Introduction

Hidradenitis suppurativa (HS) is a long-term, inflammatory, recurring, and debilitating disorder of the hair follicles. It usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, such as the axillae, inguinal folds, and perianal area.¹ Previous studies reported that the mean age of onset of HS was between 20 to 24 years.¹ More recently, it has been shown that HS has a bimodal age of onset, with the first peak in the late teens and a second peak in the mid 40s, and that for classic HS the mean age at diagnosis is later in male than female patients (19.7 years vs 16.8 years, respectively).²

Although accurate HS prevalence estimates are difficult to ascertain owing to misdiagnosis and diagnostic delay, HS is more common than we originally understood.^3,4 In 2018, Ingram et al⁵ reported an estimated prevalence of 0.77% across all age groups in a Western population. Data specific to pediatric patients is lacking; however, it has been estimated that less than 2% of people with HS had disease onset before age 11 years, a phenomenon observed more commonly in boys than in girls.^6,7 It has been recently reported that HS prevalence is higher among African American girls aged 15 to 17 years.⁶

Overall, there is limited literature addressing HS in the pediatric population. Deckers et al⁸ reported that a positive family history of HS is associated with more widespread disease in children, but not necessarily more severe disease. Growing evidence links HS with a significant effect on quality of life, lifestyle, and self-esteem.⁹ Multiple comorbidities have been associated with HS, but these have not been well characterized in children with this diagnosis. Tiri et al¹⁰ reported that pediatric patients with HS experience somatic and psychiatric comorbidities (34% and 16%, respectively). Medical treatment of HS in children is particularly challenging owing to lack of clinical research and limited data on long-term outcomes in pediatric populations with HS.^11,12 This descriptive study provides a foundation for our understanding of the clinical characteristics, comorbidities, and complications in pediatric-onset HS.

Methods

An international multicenter retrospective medical chart review was conducted in collaboration with the Pediatric Dermatology Research Alliance (PeDRA). Medical records from 10 academic institutions (US, 6; Canada, 1; Israel, 1; Australia, 1; Italy, 1) ranging from January 1996 to January 2017 were reviewed. Approval from ethics committees at each participating institution was obtained. Informed consent was waived because only deidentified data were collected.

Patients between ages 1 to 18 years were included if they had a clinical diagnosis of HS established by their dermatology assessments at participating sites. Patients included met diagnostic criteria based on medical record review if they had characteristic lesions or locations (axillae, groin, buttocks, and inframammary or intermammary areas) on physical examination, and evidence of chronicity and recurrence of disease in a 6-month period.¹³ Hurley staging was used to determine severity (stage 1: presence of abscesses, no sinus tracts, no cicatrization; stage 2: recurrent abscesses with tract formation and cicatrization; stage 3: diffuse or near-diffuse involvement or multiple interconnected tracts and abscess). Patients were excluded if diagnostic criteria were not met.

The primary objective was to describe demographic characteristics, clinical features, severity, comorbidities, and treatments used in patients with pediatric-onset HS. Investigators at each institution were asked to complete a consensus-derived electronic case report form capturing all available pertinent electronic medical health record data for each patient meeting eligibility criteria. The lead institution (Hospital for Sick Children in Toronto, Canada) provided training on data collection. All data was entered into a secure Research Data Capture (REDCap) database hosted by the Hospital for Sick Children in Toronto, Canada. Data were cleaned at the lead institution, and clarification was requested from participating sites if discrepancies arose.

Descriptive statistics were used to characterize the study population. Categorical variables were summarized with counts and proportions. Continuous variables were summarized with mean (SD) or median (interquartile range) as appropriate. Statistical analyses were performed using version 9.4 of the SAS system for Windows (2002-2012; SAS Institute, Inc).

Results

Patient Characteristics

A total of 481 pediatric patients were diagnosed with HS. Most pediatric patients were girls (386/481, 80%). The mean (SD) age of HS onset by patient report was 12.5 (2.9) years, and the mean (SD) age at diagnosis was 14.4 (3.5) years. The median (interquartile range) disease duration at the time of diagnosis was 2.5 (1-5) years. Other patient characteristics and clinical features are summarized in Table 1.

Table 1. Demographic and Clinical Features of 481 Pediatric Patients With Hidradenitis Suppurativa^a.

Variables	No. (%)
Demographic features
Age, mean (SD), y
At onset	12.5 (2.9)
At diagnosis	14.4 (3.5)
Female sex	386 (80)
BMI
Normal (18.5-24.9)	77 (20)
No.	388
Overweight (25.0-29.9)	62 (16)
No.	388
Obese (>30.0)	249 (64)
No.	388
Family history of hidradenitis suppurativa	111 (41)
No.	271
Disease duration, mean (SD), y	3.4 (2.9)
Clinical features
Hurley stage	288 (60)
No.	288
1	135 (47)
2	129 (45)
3	24 (8)
Affected body areas, No.
1-2	251 (52)
3-4	172 (36)
5-6	44 (9)
>6	14 (3)
Bilateral involvement	410 (85)
Axilla(e)	359 (75)
Inguinal fold(s)	224 (47)
Inner thigh(s)	86 (18)
Inframammary fold(s)	76 (16)
Perianal	38 (8)
Buttock(s)	28 (6)
Mons pubis	24 (5)
Intermammary	15 (3)
Chest	15 (3)
Neck	9 (2)
Labia	9 (2)
Type of lesion
Cyst/abscess	238 (49)
Papule/pustule	235 (49)
Scars	233 (48)
Double-headed comedone	111 (23)
Nodule	96 (20)
Purulent discharge	86 (18)
Fistula/sinus tract/tunnel	49 (10)
Ulcer/erosion	31 (6)
Granulation tissue	10 (2)
Associated symptoms
Pain/tenderness	313 (65)
Drainage	208 (43)
Malodor	25 (5)
Pruritus	22 (5)
Fever	2 (0.4)

^aN = 481 unless otherwise indicated.

Abbreviation: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).

Hidradenitis suppurativa was the referring diagnosis in 152 of 393 (39%) patients, followed by cysts/abscesses in 105 of 393 (27%), acne in 46 of 393 (12%), growth/bumps in 36 of 393 (9%), folliculitis/furunculosis in 32 of 393 (8%), and unknown diagnosis in 30 of 393 (8%) patients. Patients were most commonly referred by pediatricians (184/411 [45%]), family physicians (73/411 [18%]), self-referred (45/411 [11%]), surgeons (35/411 [9%]), emergency medicine physicians (21/411 [5%]), or other subspecialists (53/411 [13%]).

Family history of HS in first-degree relatives was present in 111 of 271 (41%) patients. Of 369 patients, 186 (50%) had a first-degree relative with at least 1 comorbidity. The most common comorbidities reported in first-degree relatives were type 2 diabetes in 109 of 186 (59%), hypertension in 82 of 186 (44%), and dyslipidemia in 29 of 186 (16%).

Overall, the first sign or symptom reported by patients at disease onset was cyst/abscess in 229 (48%), pain/tenderness in 481 (25%), and papules/pustules in 117 (24%). In contrast, during the first dermatological assessment, 233 (48%) patients were found to have scarring, and the most common symptom reported by patients was tenderness or pain in 313 patients (65%). Bilateral distribution of skin lesions was observed in 410 (87%) patients and most patients, 251 (52%), had only 1 to 2 body sites affected. Other patient characteristics and symptoms reported during the first assessment are summarized in Table 1.

Comorbidities were reported in in 406 of 481 (84%) patients, the most common being obesity in 263 of 406 (65%), acne vulgaris in 118 of 406 (29%), and overweight in 55 of 406 (14%). Other comorbidities are summarized in Table 2. The percentage of patients self-reported or reported to have obesity or overweight by their family was similar to that calculated using their height and weight obtained during the first assessment (65% and 14% vs 64% and 16%, respectively). Of note, when body mass index (BMI) was calculated, 77 of 388 (20%) patients had normal weight.

Table 2. Family-Reported Comorbidities in Patients With Pediatric Hidradenitis Suppurativa.

Comorbidities	No. (%)
No.	406
Obesity	263 (65)
Acne vulgaris	118 (29)
Overweight	55 (14)
Endocrine abnormalities	53 (13)
Diabetes type 2	21 (5)
PCOS	20 (5)
Hypothyroidism	8 (2)
Diabetes type 1	3 (1)
Adrenal hyperplasia	1 (0.2)
Premature adrenarche	1 (0.2)
Menstrual irregularities (dysmenorrhea/metrorrhagia)	25 (5)
Down syndrome	23 (6)
Asthma	17 (4)
Hyperlipidemia	15 (4)
Anxiety/depression disorder	11 (3)
Eczema	11 (3)
ADHD	9 (2)
Hypertension	8 (2)
IBD	6 (1)
Acne conglobata	5 (1)
Dissecting cellulitis	5 (1)
Pyoderma gangrenosum	1 (0.2)

Abbreviations: ADHD, attention deficit hyperactivity disorder; IBD, inflammatory bowel disease; PCOS, polycystic ovary syndrome.

Bacterial skin swab cultures were performed in 119 of 481 (25%) patients and an organism was identified in 30 of 119 (25%) culture results. Normal flora was reported in 15 of 30 (50%) cultures, whereas the remaining cultures had positive results for methicillin-sensitive Staphylococcus aureus (MSSA; 9/30 [30%]), methicillin-resistant Staphylococcus aureus (MRSA; 4/30 [13%]), Staphylococcus lugdunensis (1/30 [3%]), and Enterococcus species (1/30 [3%]).

The most common treatments used are summarized in Table 3. Topical treatment was used in 421 of 481 (88%) patients, the most common being clindamycin and benzoyl peroxide in 315 of 421 (75%) and 252 of 421 (60%), respectively. Systemic antibiotics were used in 379 of 481 (79%) patients, the most common of which was doxycycline in 183 of 379 (48%). Other interventions like psychological and nutritional support were reported in a minority of patients (20/481 [4%] and 12/481 [2%], respectively).

Table 3. Treatments Used in 481 Patients With Pediatric Hidradenitis Suppurativa.

Treatment	Value, No. (%)
Topical treatment	421 (88)
Clindamycin	315 (75)
Antiseptic wash: benzoyl peroxide	252 (60)
Benzoyl peroxide	176 (42)
Antiseptic wash: chlorhexidine	126 (30)
Topical retinoid	105 (25)
Antiseptic wash: triclosan	22 (5)
Mupirocin	22 (5)
Silver sulfadiazine	10 (2)
Dapsone	8 (2)
Gentamycin	6 (1)
Fusidic acid	6 (1)
Clobetasol	5 (1)
Systemic antibiotics	379 (79)
Doxycycline	183 (48)
Clindamycin	86 (23)
Rifampicin	29(8)
Trimethoprim-sulfamethoxazole	19 (5)
Cephalexin	19 (5)
Erythromycin	9 (2)
Lyimecycline	6 (2)
Amoxicillin	5 (1)
Ciprofloxacin	5 (1)
Amoxicillin-clavulanic acid	4 (1)
Clarithromycin	4 (1)
Dicloxacillin	3 (0.7)
Cefadroxil	2 (0.5)
Metronidazole	2 (0.5)
Tetracycline	2 (0.5)
Moxifloxacin	1 (0.2)
Other treatments
Laser treatment	65 (14)
Hormonal therapy	50 (10)
Zinc supplementation	44 (9)
Surgical treatment	33 (7)
Systemic retinoid	28 (6)
Psychological support	20 (4)
Biologics	17 (4)
Nutritional support (dietician)	12 (2)

Of 481 patients, visits to the emergency department due to HS were reported in 101 (22%), and hospitalizations due to HS were reported in 37 (8%). Follow-up information was available in 328 of 481 (68%) patients; of those, 47 of 328 (14%) reported remission on therapy, 158 of 328 (48%) had improvement with minimal flares, 106 of 328 (32%) had persistent flares despite treatment, and 17 of 328 (5%) reported worsening on treatment. Complications occurred in 378 of 481 (79%) patients, with the most common being scarring and contractures in 301 of 378 (80%) patients. Other complications included psychological distress in 38 (10%), restricted movement in 16 (4%), fistulas/tunnels in 12 (3%), obstructed lymph drainage in 8 (2%), and anemia in 3 (1%) of 378 patients.

Discussion

To our knowledge, this study comprises the largest series of patients with pediatric HS and describes important characteristics of this patient population. We found that in pediatric patients, by the time of dermatologic diagnosis, there was already irreversible damage observed on physical examination. More than half of pediatric patients had Hurley stage 2 or 3 disease at initial presentation (129/288 [45%] and 24/288 [8%], respectively), and 378 of 481 [79%] patients had complications due to their disease, most commonly scarring and contractures (301/378 [80%]). Most pediatric patients with HS (406/481 [85%]) presented with comorbidities, most commonly obesity. Although follow-up records were not available for all patients, most patients reported improvement with minimal flares (158/328 [48%]) or persistent flares despite treatment (106/328 [32%]), illustrating the long-term nature of this disease.

Previous studies examining pediatric HS have identified that female sex, positive family history, and individuals with presence of follicular occlusion tetrad had higher risk of early-onset HS.¹⁴ Similar to previous reports, this study showed a female predominance, with comparable female-to-male ratio to that reported in the literature (4:1 vs 4:1, 3.6:1 and 3.8:1).^6,15

We found a difference between the mean age at disease onset (12.5 years) and mean age at diagnosis (14.4 years), suggesting a clinically meaningful diagnostic gap of nearly 2 years. In adults, an average of up to 7.2 years between symptom onset and HS diagnosis has been reported, as well as a high frequency of undiagnosed and misdiagnosed cases.^16,17 In either case, this significant interval highlights the importance of raising awareness of HS among other health care professionals, patients, and families.

Delayed diagnosis of HS is likely to result in undertreatment and, as a consequence, disease progression and increased disability.¹⁸ We found that the signs and symptoms at disease onset are quite different than those on physical examination during diagnosis of disease, with 233 of 481 (48%) patients already presenting with scarring at the time of diagnosis. Scarring and contractures were also the most common complication reported in our cohort. Early recognition and treatment of disease might modify this outcome and deserves further evaluation.

Genetic susceptibility appears to be an important contributor to HS. An association between HS and Down syndrome has also been suggested,¹⁹ and we found 23 patients with Down syndrome in this study. Variations in NCSTN, PSEN1, and PSENEN genes have been identified in some families with HS, and affected individuals tend to have a more severe phenotype.²⁰ Approximately 40% of patients with adult onset HS have an affected first-degree family member with the disease,²¹ and patients with early-onset HS (onset prior to age 13 years) may be more likely to have a family history of the disease.²² In our study, 111 of 271 (41%) patients reported a positive family history of HS, which was lower than the 37 of 66 (56%) patients with early onset HS (defined as onset before the thirteenth birthday) reported by Deckers et al.⁸

Multiple studies^{17,23,24,25,26} indicate that patients with adult-onset HS have an increased incidence of comorbidities, including acne, polycystic ovary syndrome, Crohn disease, diabetes, obesity, insulin resistance, dyslipidemia, hyperglycemia, and hypertension. Limited literature has been published reporting pediatric HS comorbidities, so we opted to be inclusive of all comorbid conditions reported in the these patients, and recognize that some might be simply concurrent. Compared with adults with HS, children with HS have been found to have more hormonal imbalances.²⁷ In this study we found that 406 of 481 (84%) patients had at least 1 comorbidity, most commonly obesity (263/406 [65%]), acne (118/406 [29%]), overweight (55/406 [14%]), and endocrine abnormalities (53/406 [13%]). The proportion of patients in our cohort with obesity is comparable to the prevalence of obesity among pediatric patients with HS reported by Balgobind et al²⁸ of 69%. Although some authors suggest that early-onset HS is indicative of precocious puberty,^7,29,30 we found only 1 patient with premature adrenarche and 1 with adrenal hyperplasia. The most common endocrinologic abnormalities observed were type 2 diabetes mellitus (21/406 [5%]) and polycystic ovary syndrome (20/406 [5%]). Tiri et al¹⁰ reported that 16% of children and adolescents with HS had at least 1 psychiatric comorbidity, but this association was lower in our cohort. Early recognition and treatment of comorbidities in pediatric-onset HS is vital to minimize long-term effects.

Treatment of HS in our cohort was varied. Antibiotics were commonly used to treat patients, but dosing and type of antibiotics varied widely, making it challenging to draw conclusions or recommendations regarding treatment. At the time that our data were collected, there were no Food and Drug Administration-approved treatments for HS, and that has changed. The approval of adalimumab for the treatment of HS in patients aged 12 years or older could change outcomes in the near future. Of note, nutritional and psychological support were provided in a minority of patients, despite most being obese or overweight and dealing with a long-term, relapsing disease. Further studies are needed to explore effective treatments and interventions for pediatric HS.

The link between bacteria and HS also deserves further study. Although prevailing thought has been that HS lesions are aseptic, recent research looking at the microbiome and HS shows lesions are resoundingly not aseptic.^19,31,32 A recent report found a higher incidence of cutaneous infections in children and adults with HS compared with controls.³³ In this study, only 47 of 328 (25%) patients had bacterial cultures performed, and an organism was identified in 30 of 119 (25%) cultures. Half of the identified organisms were normal skin flora. This suggests that traditional skin swabs might not be useful in these patients and that alternative approaches are needed to characterize perturbations in the microbiome in pediatric patients with HS.³⁴

Only a minority of patients reported remission of disease while on therapy (47/328 [14%]), highlighting the long-term nature of HS. Most patients reported improvement with minimal flares or persistent flares despite treatment and 17 of 328 (5%) reported worsening of disease on treatment. The natural history of pediatric patients with HS and outcomes in this patient population need to be further explored.

Limitations

Limitations of this study include its retrospective nature, cross-sectional design, and incomplete data for some variables. Not all patients had categorization of disease severity using Hurley stage, and we did not use any other severity scale system to determine disease severity retrospectively. We did not capture temporal relationships between the diagnosis of HS and other diagnoses or clinical care time points, or the order of treatments or length of use. Referral bias should also be recognized because participating sites were tertiary centers and their patients may not be representative of the true spectrum of HS severity in pediatric patients, limiting the generalizability of the results. Nevertheless, our multi-institutional collaboration allows us to report a large number of patients, and our findings provide insights into clinical treatment practices that can guide future prospective studies.

Conclusions

Pediatric HS is underrecognized, and there is a significant gap in diagnosis after symptom onset, as suggested by the large proportion of patients who present with scarring at diagnosis. Patients with pediatric HS are likely to present with other comorbidities and have complications from their disease. There is variation in treatment and management of pediatric HS. Further studies are needed to identify distinct characteristics of patients with pediatric-onset HS to guide effective counseling and treatment.