Histology of hidradenitis suppurativa Gregor B. E. Jemec, MD, and Ulla Hansen, MD Copenhagen, Denmark

Background." Hidradenitis suppurativa is traditionally classified as a disease of the apocrine gland. However, different histologic descriptions exist. Objective: Our purpose was to describe prospectively the histopathologic characteristics of hidradenitis. Methods: We systematically described and classified 60 consecutive biopsy specimens from patients with hidradenitis and compared them with 33 specimens from clinically noninvolved regional controls. Results: A heterogeneous histologic picture was found. Apocfine glands were involved in a minority of the 60 specimens, 17 showed poral occlusion, 17 simple folliculitis without po- ral occlusion, 9 sinus tracts, 6 epithelial cyst, 5 abscess, 3 apocfinitis, 2 diffuse dermal inflammation, and 1 pyogenic granuloma and scarfing. Secondary involvement of apocrine glands was found in 12% of all specimens, and secondary involvement of eccrine glands was found in 25%. Sinus tracts were fotmd significantly more often in the presence of poral oc- clusion or epithelial cysts. Control specimens frequently revealed changes compatible with early stages of follicular involvement. Apocrine glands were observed significantly more of- ten in the axillae than in the groin. Conclusion: The clinical picture of hidradenitis suppurativa covers a broad histologic spec- trum. This may help explain the therapeutic problems posed by this disease. The disease ap- pears to be predominantly follicular, and apocrine glands appear to be primarily involved in only a minority of axillary lesions. (J Am Acad Dermatol 1996;34:994-9.)

In some studies hidradenitis is described as an in- flammation of the apocrine gland; other studies have suggested that it is a form of acne inversa and asso- ciated with the pilosebaceous unit rather than the apocrine gland. 1-5 This study was undertaken to

clarify its histologic features.

MATERIAL AND METHODS

A total of 93 biopsy specimens from patients with hidradenitis as well as from patients without any clinical evidence of hidradenitis were studied. Sixty specimens of hidradenitis were obtained from 36 patients (8 men and 28 women; mean age [SD], 33.2 years [9.5]; mean age of men [SD]: 39.6 years [10.6], of women: 31.4 years [8.5]). The sites of the lesions from which biopsy specimens were taken were axilla, 24; breast, 3; groin, 32; and but- tocks, 1. Control specimens were taken from patients re- quiting minor surgery in the axillae and from the axillae and groin of cadavers. A total of 33 specimens from 23

From the Department of Dermatology, Bispebjerg Hospital, and the Department of Pathology, Hvidovre Hospital, University of Copen- hagen.

Accepted for publication July 12, 1995. Reprint requests: Gregor Jemec, Strandvejen 97, 3tv, DK-2900

Hellerup, Denmark. Copyright © 1996 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/1/67775

994

persons (9 men, 14 women, mean age [SD]: 39 years [13.7]) were studied.

All specimens were fixed in formaldehyde 4% and embedded in paraffin. Sections were stained with hema- toxylin and eosin. Each slide was assigned a number and evaluated by both authors. Control specimens were viewed first to assess the normal regional histologic fea- tures, and lesional specimens were viewed without any information about the clinical presentation. The following features were described: parakeratosis, pilosebaceous unit, poral occlusion (lesional/paralesional), foUiculitis, inflammation of eccrine glands, inflammation of apocrine glands, sinus tracts, and fibrosis. Additional features were described if present. Parakeratosis, poral occlusion and folliculitis were graded 0, +, ++, and +++, and only spec- imens with ++ or +++ features were included (Fig. 1).

In the classification, the following definitions were ap- plied:

I. Poral occlusion/acne vulgaris: Infundibular hyper- keratosis in excess of that seen in control specimens. Changes range from pronounced hyperkeratosis without distortion of the general architecture (inflammation may be present) to pronounced inflmdibular hyperkeratosis with a milia-like appearance and a general distortion and distention of the pilosebaceous unit (inflammation is of- ten pronounced) (see Fig. 2).

2. Folliculitis: Infundibular hyperkeratosis not in ex-

Journal of the American Academy of Dermatology Volume 34, Nmnber 6 Jemec and Hansen 995

Poral occlusion ?

moderate/severe paralesional poral Yes, occlusion (n = 17)

Foll icul i t is wi thout poral occlusion ?

No t "~ !

Apocrinit is ?

No ~ "~ !

Eccrinitis ?

No ~ "~, !

Epithelial cyst ?

No ~ ~,~

1 Abscess ?

No ~ ~.

Yes, inflammation centered on follicles; possible concentric fibrosis; no paralesional poral occlusion; possible free hairs (n = 17)

Yes, isolated apocrine gland inflammation; intraepithelial and intraluminal (n=3)

Yes, isolated eccrine gland inflammation; intraepithelial and intraluminal (n =3)

Yes, lined with stratif ied epithelium; expansive growth (n= 6)

Yes, granulation = tissue (n 5)

Diffuse dermal inflammation ?

No ~ ~ . focal point found despite serial Yes, no

sections (n =2)

Sinus tracts ?

No ~ ~ .

1 Yes, uneven stratif ied epitherium; inf i l trat ive growth (n = 9)

Other: Pyogenic granuloma; fibrosis (n= 1)

Fig. 1. Hidradenitis suppurativa: Flow chart for classification of biopsy specimens (n = 60) according to dominant histologic feature. See "Material and Methods" section for definitions used. Specimens may display other features as secondary changes, n, Number of biopsy specimens in which the given feature was histologically dominant.

cess of that in control specimens. Inflammation originat- ing in a follicle, involving the follicular epithelium as well as lumen. The cellular infiltrate is dominated by neutro- phils and giant cells and often contains free hairs, but other cells may be present. Inflammation was classified as slight, moderate, or severe. Surrounding fibrosis is often present (Fig. 3).

3. Apocrinitis: Apocfinitis was present when apocrine glands showed cellular infiltrates primarily involving the gland and were surrounded by tissue without inflamma- tion. Inflammation must be at least intraepithelial and preferably intraluminal (Fig. 4).

4. Eccrinitis: Eccrinitis occurred when eccrine glands showed cellular infiltrates primarily involving the gland and were surrounded by tissue without inflammation. In- flammation must be at least intraepitheliaJ and preferably intraluminal.

5. Epidermal cyst: Space in the dermis or subcutis, lined with squamous epithelium of even thickness. The surrounding collagen/fat often appears concentric as a

sign of distention from expansive growth. Inflammation may or may not be present. The wall of the cyst may contain rudimentary skin appendages.

6. Abscess: A focus of acute inflammation surrounded by a pyogenic layer and granulation tissue.

7. Diffuse dermal inflammation: Diffuse dermal infil- tration without signs of a primary focus associated with the swuctures of epidermis or dermis. Appears with scar- ring of the tissue.

8. Sinus tract: Irregular space, often an elongated cav- ity in the dermis or subcutis lined by squamous epithelium of uneven thickness. The epithelium often extends into the surrounding dermis in a leaflike pattern. Surrounding collagen or fat does not appear compressed, suggesting irtffltrative rather than expansive growth. Inflammation may or may not be present.

Statistical methods

For contingency tables the chi-square test was used, except where any cell contained less than six patients or

Journal of the American Academy of Dermatology 996 Jemec and Hansen June 1996

Fig. 2. Moderate poral occlusion with distention of in- fundibulum.

specimens; in such cases Fisher' s exact test was used. For continuous data the t test was used, except when the SD of the two groups was different; in such cases Welch's alternate t test was used.

RESULTS

Examining specimens from clinically uninvolved skin formed the basis for assessing variation in nor- mal regional histologic features (Table I). A tentative diagnosis was made in eight control specimens: of minimal papillomatosis of the epidermis in three, perifollicular fibrosis in two, perifolliculitis in one, perivascular inflammation in one, and milia in one. Parakeratosis was present in two control and two le- sional specimens.

In the paralesional or lesional specimens a heter- ogeneous picture was found. In 17 moderate or se- vere paralesional specimens poral occlusion was found, suggesting the diagnosis of acne. Folliculitis without signs of poral occlusion was found in 17. Nine specimens showed sinus tracts as their main feature; six were diagnosed as epithelial cysts. Five

Fig. 3. Folliculitis without poral occlusion.

specimens showed flank abscess formation, apo- cfinitis was diagnosed in three, and two showed dif- fuse dermal inflammation of unknown origin in connection with widespread scarfing. Only one specimen fell outside the proposed classification by displaying a pyogenic granuloma and fibrosis.

The specimens often had additional features as can be seen in Table II. Intraglandular inflammation was found associated with dermal inflammatory foci in several: 7 of 57 showed secondary involvement of apocrine glands, and 15 of 60 showed secondary in- volvement of eccrine glands. Secondary involve- ment of apocrine or eccrine glands was not signifi- cantly greater in any of the groups. The diagnostic groupings of poral occlusion and epithelial cysts contained sinus tracts significantly more often (p = 0.04). There was no significant difference in the age or sex between different diagnostic groups.

DISCUSSION

Our results show that the majority of lesions clin- ically compatible with a diagnosis of hidradenitis suppurativa appear to be of follicular origin, and only a minority are without a follicular component. Fol-

Journal of the American Academy of Dermatology Volume 34, Number 6 Jemec and Hansen 997

licular lesions, lesions compatible with poral occlu- sion, or possible epithelial cysts account for some 67% of all lesions. Several other features are often present, but the dominant histologic feature is folli- cular involvement. Apocrinitis, originally suggested as the typical histologic appearance of hidradenitis, was the dominant histologic feature in only 5% of all lesions. This may result from the scarcity of apocrine glands in the genitofemoral area where lesions are often found (Table I). Secondary apocrine involve- ment in connection with poral occlusion was more common (12%; 7 of 57) but not as common as sec- ondary involvement of eccrine glands (25%; 15 of 60). This may be because of the greater number of eccrine glands in the specimens.

The remaining 28% of the lesions presented more obscure findings such as scarring, sinus tracts, and abscess formation. These appear to be more sugges- tive of later stages of disease.

Sinus tract formation has been considered the hallmark of hidradenitis and used to underline further the similarities between hidradenitis and other forms of acne. 4' 6, 7 It is not clear whether sinus tract formation is a general response pattern to any severe inflammation or a specific feature of hidrad- enitis. Sinus tracts were seen significantly more of- ten in the specimens in which the dominant feature was perilesional follicular occlusion (acne), suggest- hag these two diseases share a common pathogenic pathway.

Historically, the concept of hidradenitis suppura- tiva has caused considerable debate in dermatology. After the original clinical descriptions of the disease by Velpeau in 1832 and Vemeuil in 1864,1 subse- quent histologic studies showed the apocrine gland to be involved in producing characteristic lobular abscesses.2, 3, 8, 9 T h e c o n c e p t o f a p o c r i n e i n v o l v e -

m e n t , however, appears to have been developed only because of the presence of inflamed apocrine glands as a part of an often mixed histologic picture and be- cause of the overlapping location of hidradenitis and apocrine glands. On the basis of visualization of bacteria in the lesions, it was hypothesized that the disease was caused by staphylococci or streptococci entering the apocrine glands; a debate developed over the way bacteria reached the glands, z, 10, l~ Maintaining the central role of the apocrirle glands, some authors argued that the glands were the target of lymphatic or hematogenous spread of bacteria, whereas others argued that follicular involvement was necessary. Experimental studies by Shelley and

Table I. Histologic findings in control biopsy specimens*

Rating

Poral occlusion

Apocrine glands

Axilla Groin (No.) (No.)

Severe 0 0 Moderate 2 1 Slight 10 5 None 5 8

Many 14 1 Moderate 1 0 Few 1 1 None 1 12

*Histologic findings in clinically uninvolved skin of control biopsy specimens. Findings suggest apocrine glands are predominantly found in axillae, whereas genitofernoral regions contain very few or no apo- crine glands (many/moderate vs few/none;p < 0.0001; odds ratio: 97.5; 95% confidence interval 7.9-1203.8). A low degree of poral occlusion appears to be a common finding in clinically nomaal skin of regions studied.

C a h n 12 showed that follicular plugging could repro- duce lesions that were clinically and histologically compatible with hidradenitis; however, these results were not universally accepted, and the notion of pri- mary apocrine gland involvement therefore contin- ued.13, 14 More recently, specific studies of the fop licular orifice have found changes suggestive of fop licular plugging, thereby supporting the earlier experimental evidence. 4-6, 15 It has been speculated that follicular plugging can cause deep inflammation with associated or secondary intraglandular ab- scesses of the apocrine glands where these are present. 86 The current study found this histologic picture in 2 of 17 specimens (12%). If similar abscesses of the more prominent eccrine glands are considered, this histologic picture is found in ap- proximately 25% of specimens.

Local irritation of the skin from shaving, deodor- ants, and hyperhidrosis has been suggested as a pos- sible causal mechanism for hidradenitis. However, the absence of parakeratosis in our sample suggests that irritation of the skin surface is not a major fac- tor.

The life-time prevalence of hidradenitis has been estimated to be as high as 4% in women. 17 The study of control biopsy specimens suggests that low-grade poral occlusion is common in the regions where hidradenitis occurs, offering a possible explanation for the apparently high incidence of the disease. Control specimens also revealed that apocrine glands,

9 9 8 Jemec and Hansen Journal of the American Academy of Dermatology

June 1996

Fig. 4. Apocrine gland involvement classified as apocfinitis. Note predominantly intralu- minal infiltrate of polymorphonuclear leukocytes.

T a b l e I I . Histologic findings in classified lesional b iopsy specimens*

Classification Secondary fea~u-es

Poral occlusion (n = 17) t' t

Folliculitis without poral occlusion (n = 17)

Apocfinitis (n = 3)

Eccfinitis (n = 0) Epithelial cyst (n = 6)

Abscess (n = 5) Diffuse derma] inflarn-

marion (n = 2) Sinus tracts (n = 9)

Other (n = 1)

Two showed associated intraglandular abscesses in apocrine glands and four in the eccrine glands. One biopsy specimen showed an associated cyst; si- nus tracts were found in 16.

One showed associated intraglandular abscesses in apocwine glands and three in the eccfine glands. One biopsy specimen showed an associated cyst; si- nus tracts were seen in eight.

Associated eccfinitis was seen in two specimens, and sinus tracts were found in one.

This feature did not appear as a main finding in any biopsy specimen. One biopsy specimen showed associated eccfinitis, and one showed sinus

tracts. Associated apocrinitis and eccrinitis were each found in one specimen. Both specimens showed sinus tract formation and associated eccrine gland

abscesses; one showed an associated apocrine gland abscess. Two biopsy specimens showed associated intraglandular abscesses of eccfine

glands, and two showed intraglaaadular abscesses of apocrine glands. Pyogenic granuloma and fibrosis

*Histologic findings in biopsy specimens studied after their classification. Classified according to dominant histologic features, but presence (partial or secondary) of other features was also noted and is fisted for each of the major groups (e.g., of the 17 biopsies classified as poral occlusion, two showed apocrine gland involvement interpreted as secondary to poral occlusion). tParakeratosis was graded 0 (none), + (focal), ++ (extensive), and +++ (confluent); only biopsy specimens rated ++ or +++ are included. *Poral occlusion classified as 0, +, ++, or +++; only biopsy specimens rated ++ or +++ are included.

hitherto associated with hidradenitis, are rare in the

geni tofemoral area where hidradenitis appears. This

f inding supports the v iew that hidradenitis is not

pathogenet ical ly l inked with the presence o f apo- crine glands and that the observed apocrine involve-

men t is secondary.

REFERENCES 1. Vemeuil A. De l'hidrosad6nite phlegrnoneuse et des abc~s

sudoripares. Arch G6n M6d 1864;2:537-57. 2. Tachau P. Schweissdrtisenabscess der Erwachsenen. In:

Jadassohn J, Bloch B, Buschke A, et al, editors. Handbuch der Haut und Geschlechtskrankheiten; vol 9, part 2. Berlin: Julius Springer, 1934:375-88.

Journal of the American Academy of Dermatology Volume 34, Number 6 Jemec and Hansen 999

3. Brtmsting HA. Hidradenitis suppurativa: abscess of the apocfine sweat gland. Arch Dermatol Syphilol 1939;39: 108-20.

4. Plewig G, Steger M. Ache inversa (arias acne Iriad, tetrad or hidradenitis suppurativa). In: Marks R, Plewig G, editors. Ache and related disorders. London: M Dtmitz, 1988:345-57.

5. Yu CCW, Cook MG. Hidradenifis suppurativa: a disease of the follicular epithelium, rather than apocrine glands. Br J Dermatol 1990;122:763-9.

6. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 7th ed. Philadelphia: JB Lippincott, 1990:322.

7. Grosshans E, Bouffioux B, Toufik-Bellahcene M. Argu- ments en faveur de la nature folliculaire de la maladie de Vemeuil. Ann Dermatol Venerol 1991;118:207-9.

8. Sutton RL, Sutton RL Jr. Diseases of the skin. St Louis: CV Mosby, 1939:1444-6.

9. Ebling FJG. Apocrine glands in health and disorder. Int J Dermatol 1989;28:508-11.

10. Fehrman W. Zur Histologie und Pathogenese der Achsel- h6hienabszesse. Arch Dermatol Syphilis 1919; 127: 327-41.

11. Gans O. Zur Pathogenese der Achselh6hlenabszesse. Der- matol Wochenschr 1923;76:318-25.

12. Shelley WB, Cahn MM. The pathogenesis of hidradenitis suppurativa in man. Arch Dermatol 1955;72:562-5.

13. Benedek T. Hidradenitis suppurativa. Acta Derm Venereol (Stockh) 1957;37:(suppl 37):1-47.

14. Montgomery H. Dermatopathology; vol 1. New York: Hoeber, 1967:474-7.

15. Felding C, Moesgaard J, Clevin L, et al. Hair-follicle ob- stmction-hidradenitis suppurativa and pilonidal cyst: clin- ical features and histological picture. Ambulatory Surg 1995;3:3-6.

16. Fitzpatrick J. Inflammatory reactions of the sweat unit. In: Farmer ER, Hood AF, editors. Pathology of the skin. Nor- walk: Appleton & Lange, 1990:959-60.

17. Jemec GBE. The symptomatology of hidradenitis suppu- rativa in women. Br J Dermatol 1988;119:345-50.

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