Genetics of hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic recurrent inflammatory skin disease
affecting apocrine gland-bearing body areas such as axillae, groin and perianal
regions Characteristic for this disease are painful, inflammatory nodules and
sterile abscesses, followed by tissue fibrosis and sinus tract formation. HS
usually develops after puberty and the overall prevalence is estimated around
1% (1). Women are more frequently affected than men (female: male ratio, 3:1).
About 85-95% of the patients are active smokers (2). The exact pathogenesis of
HS is still unknown. The primary event is thought to be occlusion of the
terminal hair follicle caused by infundibular hyperkeratosis and hyperplasia of
the follicular epithelium. (3) Bacterial cultures from HS lesions are often
sterile or only grow commensal skin flora. (4) The diagnosis is made based on
the clinical presentation. Available treatments are limited, antibiotics,
retinoids, corticosteroids and cyclosporine can give temporarily relieve.
Radical excision with secondary wound healing is the therapy of first choice.
(5)

In approximately 40% of the patients, HS occurs in one or more family members.
(4) It is hypothesized that in some cases there is an autosomal dominant
inheritance with a variable penetrance. (6) To date, several genetic loci have
been identified which are associated with HS, but so far no causative genes
have been found. Mutations in the gamma-secretase gens (PSENEN, PSEN1 and
NCSTN) were identified in families with multiple family members suffering from
a special form of HS. However, how these mutations cause HS is still unknown.
(7)


1. Revuz JE, Canoui-Poitrine F, Wolkenstein P, Viallette C, Gabison G, Pouget
F, et al. Prevalence and factors associated with hidradenitis suppurativa:
results from two case-control studies. Journal of the American Academy of
Dermatology. Elsevier; 2008;59(4):596-601.
2. König A, Lehmann C, Rompel R, Happle R. Cigarette smoking as a triggering
factor of hidradenitis suppurativa. Dermatology. Karger Publishers;
1999;198(3):261-4.
3. Kurzen H, Kurokawa I, Jemec GBE, Emtestam L, Sellheyer K,
Giamarellos-Bourboulis EJ, et al. What causes hidradenitis suppurativa?
Experimental dermatology. Copenhagen: Munksgaard, c1992-; 2008;17(5):455-6.
4. Jemec G, Revuz J, Leyden J. Hidradenitis Suppurativa. 1st ed. Heidelberg,
Germany: Springer; 2006.
5. Ritz JP, Runkel N, Haier J, Buhr HJ. Extent of surgery and recurrence rate
of hidradenitis suppurativa. International journal of colorectal disease.
Springer; 1998;13(4):164-8.
6. Von der Werth JM, Williams HC, Raeburn JA. The clinical genetics of
hidradenitis suppurativa revisited. British Journal of Dermatology. Wiley
Online Library; 2000;142(5):947-53.
7. Wang B, Yang W, Wen W, Sun J, Su B, Liu B, et al. γ-secretase gene mutations
in familial acne inversa. Science. American Association for the Advancement of
Science; 2010;330(6007):1065.

To determine which gen defects are associated with hidradenitis suppurativa.

The collected blood and saliva are processed at the laboratory of Internal
Medicine of Erasmus MC. DNA will be disposed of after sequencing.
The skin collected from surgery will be examined on protein level to see if
possible genetic defects are expressed there. This is to verify the relevance
of the found genetic abnormalities.

From patients visiting the department of dermatology venous blood will be drawn
or saliva will be collected. Skin will also be collected from surgery.
The burden and risks for participation are minimal for the patients.