Early Onset Hs

Clinical dermatology

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Concise report

Early-onset hidradenitis suppurativa R. A. Palmer and M. Keefe Department of Dermatology, Royal South Hants Hospital, Southampton, UK

Summary

A 9-year-old girl developed hidradenitis suppurativa 3 months after the first signs of adrenarche. Such a close temporal relationship is consistent with the hypothesis that the disease is androgen dependent. Less than 2% of patients have onset of the disease before the age of 11 years. The exceptionally early age of onset in our patient may be partly explained by the fact that she had an early puberty.

Report An 11-year-old girl presented to the dermatology department complaining of boils in the groin. She was otherwise well. She started to develop axillary hair and apocrine odour at the age of 9 years 0 months, boils in the inguinal areas at 9 years 3 months, and menarche at 10 years 5 months. Her mother and maternal grandmother gave a history consistent with hidradenitis suppurativa. At the time of presentation she was on the 97th centile for height and 85th for weight. Her body mass index was 19.0 kg/m2. Breast and pubic hair development were Tanner stage 4. Examination of the inguinal areas (Fig. 1) showed closed comedones, open comedones, red nodules and atrophic scars, consistent with hidradenitis suppurativa. Results of endocrinological investigations are shown in Table 1. The free androgen index (the testosterone concentration divided by the sex-hormone binding globulin concentration) was 0.02 (within the normal range). Fasting glucose, fasting insulin, lymphocyte subsets, serum immunoglobulins, and a short Synacthen test with measurement of cortisol and

Correspondence: R. Palmer, Department of Dermatology, Royal South Hants Hospital, Southampton, SO14 0YG, UK. Tel.: 144 7979 695798. Fax: 144 2380 825353. E-mail: [email protected] Accepted for publication 25 April 2001

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17-hydroxyprogesterone (for congenital adrenal hyperplasia), were within normal limits. A bacterial swab grew only coliforms. A small study of hidradenitis suppurativa suggested that HLA A1 and B8 predispose to more severe disease;1 our patient does not have these antigens. Before menarche, ovarian androgens are produced in negligible amounts, and it is the zona reticularis of the adrenal cortex that produces the only significant quantities of androgens. The principal adrenal androgens are dehydroepiandrosterone and androstenedione. Levels of these are low in early childhood, but as they rise they promote growth and axillary and pubic hair 2 this is called adrenarche. In girls, pubic hair typically appears at age 11. Menarche is caused by increasing serum concentrations of gonadotrophins and usually occurs later, between 11 and 13 years of age. The growth of apocrine glands and onset of secretion begin at puberty. The clinical features and investigations of our patient are consistent with an early puberty which is physiological not pathological. She had early adrenarche and menarche. She developed hidradenitis suppurativa 3 months after the first signs of adrenarche and before menarche. It is rare for hidradenitis suppurativa to occur so young. The disease has been reported in an infant with congenital adrenal hyperplasia,2 in an obese 7 years and 8 month-old girl after benign premature adrenarche,3 and in an obese 8-year-old prepubertal girl.4 We reviewed five studies1,5±8 which reported the age of

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Early-onset hidradenitis suppurativa

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R. A. Palmer and M. Keefe

Figure 1 Right inguinal region.

onset in a total of 225 females and 50 males. The data in these studies were presented in a comparable manner, and therefore it is valid to combine the data, giving the frequency distribution for the age of onset of hidradenitis suppurativa shown in Fig. 2. Only 2% of patients had onset of the condition before the age of 11 years. These studies were conducted among patients referred to secondary care and therefore probably select for patients with relatively severe disease. Disease severity may be positively associated with early age at onset, and therefore the true percentage is likely to be lower than 2%. The peak age at onset among females was 11± 20 years and among males was 21±30 years. One explanation for this age distribution is that the disease is androgen-dependent. The earlier onset in females may partly reflect earlier puberty, even though most patients have a delay between puberty and the onset of the condition. Pre-menstrual and menstrual exacerbations are common.5,7 Some reports

describe a tendency to improve in pregnancy, and subsequently relapse after childbirth.5 Hidradenitis suppurativa may be exacerbated by those oral contraceptives that contain a relatively androgenic progestogen, or a high progestogen to oestrogen ratio.9 In some women the disease can be controlled with ethinyloestradiol plus cyproterone acetate.10 A comparison can be made with other diseases of the skin adnexae; hirsutism and acne vulgaris are both androgen-dependent. Rarely hidradenitis suppurativa occurs in neonates and infants, but subsequently resolves later in infancy. This may reflect the relatively hyperandrogenaemic state during this period. However, if the disease is dependent on androgens, then it is surprising that it is more common among women than among men, and the relationship has therefore been questioned.11 The serum androgen levels of our patient are not abnormally high. This is consistent with most studies,

Table 1 Endocrinological investigations.

Result Androstenedione (nmol/L) Dehydroepiandrosterone sulphate (mmol/L) Testosterone (nmol/L) Sex-hormone binding globulin (nmol/L) Free androgen index Luteinizing hormone day 4 (IU/L) Follicle stimulating hormone day 4 (IU/L) Oestradiol day 4 (pmol/L)

Pre-puberty NR

3.9 2.6 0.9 53.3 0.02 2.3 5.3 , 73.4

Adult NR

0.4±3.3

0.8±11.9

0.3±1.5 , 2.0 55±120

3.6±9.9 0.3±2.5 30±90 , 0.06 0.8±12 0.8±11.5 110±180

, 2.0 , 2.0 40±90

NR, Normal range.

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Acknowledgements We are grateful for the contributions of J. H. Barth (Institute of Pathology, Leeds General Infirmary), P. Betts (Department of Paediatrics, Southampton University Hospitals Trust), P. S. Friedmann, C. Morgan and I. Pearson (all at the Department of Dermatology, Southampton University Hospitals Trust).

References

Figure 2 Age of onset of hidradenitis suppurativa in 275 patients.

which have generally found a higher median concentration of androgens among patients compared with controls, but which have nevertheless found that the majority of patients have androgen concentrations within the normal range.5,6 This situation is analogous to that found in acne vulgaris and hirsutism. Therefore androgens may be exerting most of their effect via an exaggerated end-organ response to relatively normal androgen levels. The mechanism of this is not known, but could involve, for example, increased activity of 5alpha-1 reductase. Most apocrine glands open into the upper part of follicles, above the sebaceous gland. The initiating event in hidradenitis suppurativa is probably keratinous plugging of the follicular infundibulum in apocrinebearing skin.12 This is consistent with the inclusion of the condition in the follicular occlusion triad, with acne conglobata and perifolliculitis capitis. Androgen receptors are present in pilosebaceous duct keratinocytes and may allow androgens to promote hypercornification. Keratinous plugging causes rupture of follicles, inflammation and infection, and apocrine glands become secondarily involved. The family history of our patient suggests a genetic predisposition. It would be consistent with the familial form of hidradenitis suppurativa with autosomal dominant inheritance that has been proposed.13 In conclusion, we hypothesize that the rise in serum androgens at puberty precipitated hidradenitis suppurativa in our patient, who was genetically predisposed to the condition. Partly because she had an early puberty she developed the disease at an exceptionally early age.

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1 O'Loughlin S, Woods R, Kirke PN, Shanahan F, Byrne A, Drury MI. Hidradenitis suppurativa. Arch Dermatol 1988; 124: 1043±6. 2 Jourdain JC, Le Lorier B, Mourier C, Ploussard JP, Roussel F. Virilisation par deficit en 21-hydroxylase et hyperplasie sudorale axillaire (in French). Ann Dermatol Venereol 1988; 115: 1136±8. 3 Lewis F, Messenger AG, Wales JKH. Hidradenitis suppurativa as a presenting feature of premature adrenarche. Br J Dermatol 1993; 129: 447±8. 4 Mengesha YM, Holcombe TC, Hansen RC. Prepubertal hidradenitis suppurativa: two case reports and review of the literature. Pediatr Dermatol 1999; 16: 292±6. 5 Mortimer PS, Dawber RPR, Gales MA, Moore RA. Mediation of hidradenitis suppurativa by androgens. Br Med J 1986; 292: 245±8. 6 Harrison BJ, Read GF, Hughes LE. Endocrine basis for the clinical presentation of hidradenitis suppurativa. Br J Surg 1988; 75: 972±5. 7 Jemec GBE. The symptomatology of hidradenitis suppurativa in women. Br J Dermatol 1988; 119: 345±50. 8 Boer J, Weltevreden EF. Hidradenitis suppurativa or acne inversa. A clinicopathological study of early lesions. Br J Dermatol 1996; 135: 721±5. 9 Stellon AJ, Wakeling M. Hidradenitis suppurativa associated with use of oral contraceptives. Br Med J 1989; 298: 28±9. 10 Mortimer PS, Dawber RPR, Gales MA, Moore RA. A double-blind controlled cross-over trial of cyproterone acetate in females with hidradenitis suppurativa. Br J Derm 1986; 115: 263±8. 11 Barth JH, Layton AM, Cunliffe WJ. Endocrine factors in pre- and postmenopausal women with hidradenitis suppurativa. Br J Dermatol 1996; 134: 1057±9. 12 Attanoos RL, Appleton MAC, Douglas-Jones AG. The pathogenesis of hidradenitis suppurativa: a closer look at apocrine and apoeccrine glands. Br J Dermatol 1995; 133: 254±8. 13 Von der Werth JM, Williams HC, Raeburn JA. The clinical genetics of hidradenitis suppurativa revisited. Br J Dermatol 2000; 142: 947±53.

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