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Acne inversaReview Article 189
Daniela Meixner, Sylke Schneider, Markus Krause, Wolfram SterryDepartment of Dermatology, Venereology and Allergy, Charité, Berlin, Germany JDDG; 2008 • 6:189–196 Submitted: 11.10.2006 Accepted: 30.5.2007 Acne inversa is a chronic inflammatory skin disease featuring cutaneous and • hidradenitis suppurativa subcutaneous nodular inflammation, fistula formation and discharge of foul- • apocrine acne smelling secretions.The disease can lead to functional impairment and psycho- • pyodermia fistulans sinifica logical problems.There is inflammation of the terminal hair follicles in intertrig- • follicular retention tetrad inous regions, especially perianal, axillary and inguinal areas. Less often there issubmammary, periumbilical, retroauricular or nuchal involvement.
Without treatment the disease is chronic and progressive. The causes of acneinversa are multifactorial and pathogenesis is still not well understood. Besidesa positive family history, obesity and cigarette smoking are trigger factors. Earlydiagnosis and therapy of acne inversa saves the patient years of suffering.
The most effective treatment is undoubtedly the radical wide excision of theaffected areas. Local measures such as radiotherapy, photodynamic therapyand cryotherapy have provided little benefit; the same is true for systemicantibiotic treatment or hormonal therapy with anti-androgens. TNF-alphaantagonists seem to have a promising influence on the disease. Further studiesinvestigating the effect of these substances on acne inversa are warranted.
1 Historical background
with acne conglobata and perifolliculitis neous nodular inflammation, fistulas The Paris surgeon Velpeau described an capitis abscendens et suffodiens (dissect- and discharge of a foul-smelling secre- unusual inflammatory process with for- ing cellulitis of the scalp) as acne triad.
tion and capable of causing severe phys- mation of superficial axillary, submam- For the first time, it was discussed that ical and mental impairment.
mary and perianal abscesses in 1839 .
the pathogenetic mechanism of acne Pathogenetically, it is an inflammation His colleague Verneuil, also working in vulgaris and acne inversa are similar. of terminal hair follicles manifesting in Paris, coined the term "hidrosadénite Plewig and Kligman added another enti- intertriginous skin at perianal, inguinal phlegmoneuse" 15 years later . This ty to acne triad, pilonidal sinus . In and axillary sites. In addition to familial name reflects the former pathogenetic 1989 Plewig and Steger introduced the occurrence, smoking and obesity are model of acne inversa, which considered term acne inversa which is in use today, contributing factors to the disease.
inflammation of sweat glands as the indicating a follicular source of the dis- Treatment of choice is the radical exci- cause of the disease. This concept was ease  and replacing older terms such sion of affected regions.
followed by a variety of authors for many as Verneuil disease, hidradenitis suppu- decades. In 1922 Schiefferdecker suspected rativa, apocrine acne and pyoderma fis- a pathogenic association between acne tulans sinifica (Table 1).
The exact prevalence of acne inversa is inversa and apocrine sweat glands .
unknown and has been estimated at In 1956 Pillsbury et al.  postulated 2 Definition
0.3 % . Jemec et al.  report a point follicular occlusion as cause of acne Acne inversa is a chronic inflammatory prevalence of 4.1 % in a collective of inversa, which they grouped together skin disease with cutaneous and subcuta- young adults. The average age of these The Authors • Journal compilation Blackwell Verlag, Berlin • JDDG • 1610-0379/2008/0603-0189 JDDG 3˙2008 (Band 6)
The course of the disease, onset only after Table 1: Historical view.
puberty, improvement after menopauseand during pregnancy all suggest an influence of sexual hormones. Most First description of the disease patients with acne inversa have normalandrogen levels . Case reports do exist of successful therapy with anti-andro- Acne triad (hidradenitis suppurativa, perifolliculitis capitis abscendens et suffodiens) 4.2.2 Genetic factors Plewig/Kligman  Acne tetrad (acne triad + pilonidal sinus) Acne inversa often occurs in a familial Plewig/Steger  fashion, so that genetic factors probablyplay a role. The first study on a possiblehereditary pattern was performed by patients was 42 years for men and smoking has a positive effect on the Fitzsimmons et al. in 1984. Three fami- 39 years for women. course of the disease but prospective lies with 21 family members affected by In a study from 1996 Jemec found a studies are lacking. Obesity is probably acne inversa were examined. In one of clear predominance of women. He stud- not directly involved in the development the three families studied, family mem- ied the incidence of acne inversa in a col- of acne inversa, but maceration and bers in three generations were affected, lective of 507 patients. Anogenital occlusion in the body folds lead to follic- in the other two families; two genera- lesions are significantly more frequent in ular hyperkeratosis and thus worsen the tions each with acne inversa were report- women than in men (odds ratio 4.6), while axillary lesions were equally dis- In 45 % of patients with acne inversa One year later the authors expanded tributed among the genders . Further, sweating and heat; in 35 %, stress and their study and examined 26 patients Jemec et al. studied the prevalence of exhaustion; and in 16 %, wearing tight with acne inversa and their families.
acne inversa in an unselected collective clothing leads to deterioration of the dis- Information on family history could be of 793 randomly selected individuals; 3 ease . A variety of factors is blamed obtained from 23 patients. Among 14 women and 3 men with acne inversa with a causal relationship in the patho- patients a total of 37 further affected were found . A higher proportion of genesis of acne inversa. Included is use of family members were found. In nine women was confirmed by Barth et al. He deodorants and depilatory products or families the patients were the only clear- observed 10 men and 36 women who shaving of the involved sites. In a retro- ly affected family member . were admitted as inpatients for surgical spective study done by Morgan et al.
In 2000 the working group of Werth et treatment of acne inversa . comparing 40 patients with acne inversa al. studied the reproducibility of the The disease is quite rare before puberty with 40 healthy subjects, no significant autosomal dominant inheritance postu- . In the fifth decade of life, the inci- difference regarding the factors men- lated by Fitzsimmons et al. using the dence decreases. In women, the disease tioned above could be found . We same study group as then. Here, 14 sur- can continue into menopause, new man- assume that these factors at most play a viving persons and their families were ifestations after menopause are rarities. secondary role in the development and examined. Of these, 7 had stated a posi- aggravation of acne inversa. tive family history in the previous study, two, on the other hand, had stated a 4.1 Exogenic factors 4.2 Endogenous factors negative or only possible family history.
The exact etiology of acne inversa is not 4.2.1 Hormonal factors In the patient collective with a positive known. Smoking is without doubt asso- Essential for the pathogenesis of acne family history, 27 % of first-degree rela- ciated with the development of acne inversa is the effect of androgens in the tives were affected by the disease.
inversa. A series of studies has confirmed formation of terminal heir follicles in the Additionally, seven newly affected per- a significantly larger proportion of axillae and anogenital regions, as acne sons, who were not yet affected in the smokers in patient collectives with acne inversa is primarily an inflammatory dis- previous study, were found. An analysis inversa in comparison to control groups.
ease of terminal heir follicles and not, as of the pedigrees  shows that the dis- The proportion of patients with acne presumed in the past, a disease of apoc- ease is transmitted through several gener- inversa who smoke regularly is reported rine glands. This is also exemplified by ations of a family with acne inversa and at 84–89 % compared to the proportion the fact that terminal hair follicles on the affects both genders.
in control groups between 23–46 % scalp are not connected with apocrine . The pathogenetic mechanism by glands, but clinical manifestations such 4.3 Microbiologic data which smoking leads to acne inversa is as perifolliculitis capitis abscedens et suf- The role of bacterial colonization and/or unknown. Smoking induces chemotaxis fodiens (dissecting cellulitis of the scalp) infection in the pathogenesis of acne in neutrophilic granulocytes. This mech- do occur. This no longer can develop in inversa is discussed controversially. For a anism possibly plays a role in the etiolo- the face of androgenetic alopecia. With long time it was presumed that contami- gy of palmoplantar pustulosis  and the onset of puberty, the secretion of nation or infection by specific microor- may be involved in the development of androgens begins and thus the enlarge- ganisms belong to the triggering factors acne inversa. We presume that stopping ment of hair follicles. of the disease . Lapins et al. described JDDG 3˙2008 (Band 6)
the presence of Staphylococcus aureus and seen. Pressure can cause secretion of pus, development of squamous cell carcino- coagulase-negative streptococci . In sebum or a foul-smelling secretion. At a ma on the basis of chronic inflamma- a retrospective review of data, Brook and later point in time the disease is charac- tion. A series of case reports exists in the Frazer studied the microbiologic spec- terized by numerous scarred areas as the literature, but they do not allow for an trum of 17 samples from axillary lesions result of burned out inflammatory estimation of the incidence of malignant of patients with acne inversa. A total lesions (Figure 2).
tumors in acne inversa. Usually long- of 42 cultures were performed. The term presence of acne inversa for about most common aerobic organisms were 5.2 Clinical spectrum 20 years is a prerequisite for the develop- Staphylococcus aureus, Streptococcus pyo- Clinical forms of manifestation of acne ment of squamous cell carcinoma .
genes and Pseudomonas aeruginosa. The inversa are diverse. In addition to typical Men are predominantly affected. most common anaerobes found were clinical presentations in the above-men- peptostreptococci, Prevotella and tioned sites of predilection, acne 5.3.4 Chronic lymphedema fusobacteria . Highet et al. found keloidalis nuchae, folliculitis abscedens In the course of the disease recurrent Streptococcus milleri in three cases of severe et suffodiens (dissecting cellulitis of the infections, for example with streptococ- acne inversa in the anogenital region.
scalp) as well as the rarely observed cutis ci, as well as the formation of elephanti- This is a bacterium often found in the vertices gyrate-like acne inversa belong asis-like swellings mainly in the genital gastrointestinal tract and the female gen- to the broad spectrum of clinical presen- region can occur .
ital tract and is presumed to correlate tations. The latter is a form of scalp with disease activity of acne inversa .
involvement with folds resembling sulci 5.3.5 Anemia It is unclear at present if bacterial colo- and gyri of the brain, sinus tracks and Due to chronic inflammation anemia nization and infection are primarily or discharge of secretion .
has been reported in patients with acne secondarily included in the developmen- inversa .
tal process of acne inversa. Obviously, a 5.3 Complications very heterogenous spectrum of pathogens 5.3.1 Reduced mobility 5.4 Disease burden exists, so that the development of advanced Healing of areas affected by acne inversa Subjectively patients complain about stages of the disease is not bound to the with scarring can lead to contractures limited mobility and pain. In severe presence of a specific pathogen.
and greatly limit the mobility of the cases the patients are in reduced general limbs. This is especially true for axillary health. Due to feelings of shame, the dis- 5 Clinical features
manifestations of the disease.
ease causes a great mental burden result- 5.1 Course ing in social withdrawal. In a study by Clinical manifestations in early stages of 5.3.2 Fistulas Werth a distinctly reduced quality of life the disease include giant comedones and Anogenital disease is frequently accompa- in patients with acne inversa was meas- firm palpable nodules. In the further nied by anal, rectal or urethral fistulas .
ured using the Dermatology Life course these can coalesce deeply and Quality Index (DLQI). A total of 114 form large abscesses and sinus tracts 5.3.3 Development of malignant tumors patients, 16 men and 98 women, were (Figure 1). Additionally, darkly colored, The most severe complication of acne examined. The DLQI score correlated infiltrated inflammatory plaques are inversa of the anogenital region is the significantly with the number of inflam-matory lesions. In comparison topatients affected by other skin diseases,the quality of life of patients with acneinversa was lowest with an averageDLQI score of 8.9 . 6 Histology
Published studies on histopathologic
changes have contributed greatly to
understanding the disease acne inversa.
Plewig and Steger view the hyperkerato-
sis of the follicular infundibulum with
subsequent bacterial superinfection and
rupture of the follicle (Figure 3) and the
resulting inflammation of connective tis-
sue (Figure 4) as primary events.
Histologically, the apocrine and eccrine
sweat glands are not involved primarily,
but secondarily . Yu et al. examined
12 histological samples of patients with
acne inversa and found cysts and sinus
tracts lined by epithelium in the dermis
Figure 1: Axillary lesions of acne inversa with sinus
Figure 2: Axillary lesions of acne inversa with dermal
in 10. About one-half of the sinus tracts JDDG 3˙2008 (Band 6)
contained free hair shafts. In about one-third of the samples inflammation of theapocrine sweat glands with simultaneousinflammation of the eccrine sweat glandsand hair follicles was found . In astudy by Jemec et al. the majority ofsamples (44 of 51) revealed occlusion ofthe tracts and cysts and follicles. Primaryinflammation of apocrine glands was notseen . Boer and Weltervreden werealso able to demonstrate a primaryinflammation of the follicular infundibu-lum and secondary involvement of apoc-rine sweat glands (Table 2) . On the other hand, inflammation of thehair follicle without involvement of theassociated apocrine sweat glands is oftenseen . The inflammatory reaction is Figure 3: Rupture of hair follicle with inflammatory cell infiltrate.
quite mixed consisting of an unspecificlymphohistiocytic infiltrate, plasma cells,mononuclear cells and neutrophilicgranulocytes. Histological features are quite unequivo-cal and allow making differential diag-noses which are clinically difficult andrule out entities such as furunculosis,irritated sebaceous gland retention cysts,perianal Crohn disease or multiple sweatgland abscesses.
7 Differential diagnoses/associated
In initial stages of acne inversa differen-
tial diagnosis includes furuncles and car-
buncles caused by staphylococci and
streptococci. At the initial visit other
pathogen-induced diseases such as deep
fungal infections, actinomycosis and
Figure 4: Granulomatous inflammation with foreign body giant cells.
sporotrichosis should be excluded. In thegroin or anogenital region, lymphogran- Table 2: Dermatohistological view.
uloma venereum and granulomainguinale are additional considerations.
Further differential diagnoses are granu- Initial hyperkeratosis of the follicular lomatous diseases such as tuberculosis cutis colliquativa or cutaneous fistulas in Bacterial superinfection and follicle rupture Crohn disease (Table 3). Plewig et al.  Granulomatous inflammatory reaction of the Clinical differentiation from Crohn dis- connective tissue ease can be particularly difficult, as in Apocrine and eccrine sweat glands secondarily 5 % of all cases of Crohn disease perianal lesions are the initial manifestation .
In a study by Church et al. 38 % of patients Cysts and sinus tracts lined with epithelium, with acne inversa examined had simultane- in part with hair shafts ous Crohn disease (n = 61 patients). The Inflammation of apocrine sweat glands only diagnosis of Crohn disease preceded acne if eccrine sweat glands and hair follicles are inverse by 3.5 years on average .
Primary inflammation of the follicular 8 Treatment
8.1 Surgical treatment Apocrine sweat glands secondarily involved Treatment method of choice is the totalexcision of affected skin areas. JDDG 3˙2008 (Band 6)
the extent of surgery . This was con- Table 3: Differentiation points.
firmed in a study by Ritz et al. Here, thelong-term results of three differing surgi- Differential diagnoses
cal procedures were followed over up to72 months postoperatively. The compar- Follicular nodule, Bacteriologic identifi- ison revealed a recurrence rate of 100 % rapid enlargement, cation of Staphylococ- in patients treated with incision and fluctuation and possi- drainage, a recurrence rate of 42.8 % in Diagnosis is made patients treated with narrow excision of the lesions as well as a recurrence rate of27 % in patients with wide excision of Inflammatory lesions Identification with lesions in healthy tissue . Deep fungal infection direct microscopy and For axillary lesions postoperative diffi- follicular abscesses culties are slight, but the recurrence rate Histologic identifica- is higher for primary wound closure than mandibular region, for secondary intention healing . Gram stain, anaerobic Varying statements on the extent of exci- sion, which correlates with recurrencerates, exist. The tissue block to be excised Histologic identifica- should include not only lateral but also tion of cigar-like yeast deep safety margins. Often subcutaneous cells in the PAS stain, Although the healing process is more nodes occurring on the Culture at 37 °C (yeast rapid with a split-thickness graft, patients arms, spread along colonies) and at 25 °C usually prefer healing by secondary lymphatic vasculature (colonies of hyphal intention. Advantages of secondary intention healing are a shorter hospitalstay, more rapid return to work as well asless limitation of mobility immediately Occurrence in endemic after surgery . Initially, primary regions (East Africa, In our clinic radical excision of affected papule, after 2–3 areas with secondary conditioning of the weeks lymph node Direct identification wound or split-thickness grafting after with FITC labeled adequate granulation to prevent scar strictures with the resulting limitation of Livid rope-like adherent antibodies, PCR, cul- mobility are standard (Figures 5–9). In swelling in the groin ture on McCoy cell patients with mild acne inversa who line (inclusion bodies) have only few inflammatory nodules andfistulas in a small area, we perform exci- Direct identification of sion and primary wound closure with Papules in the genital pathogen in a tissue adapting sutures. We do not perform biopsy, Giemsa stain Granuloma inguinale surgery on more than two extensively affected sites in one session. Antibiotic Culture on McCoy therapy is administered only in case of postoperative bacterial wound infection Diascopy: "apple jelly"- or preoperatively only in particularly Often clavicular, colored infiltrate; severe and active acne inversa.
Tuberculosis cutis submandibular and cervical location 8.2 Conservative treatment Clinical features similar Treatment of choice for acne inversa is Cutaneous manifesta- Often perianal or to acne inversa, no without doubt the surgical procedure tions of Crohn disease periorificial location described above. Due to the extent ofthis procedure and the incurrent signifi-cant surgical trauma, there has been a Unfortunately only few studies on surgical submammary 50 % . Here, pseudo- continual search for conservative treat- results and recurrence rates of acne inversa recurrences must be differentiated from after surgical treatment exist. The largest true recurrences. The former is the new A small study on cryotherapy exists.
study which we are aware of reports the manifestation of acne inversa in an untreat- Here, marked improvement could be following recurrence rates 3–72 months ed hairy border area of the surgical field.
realized in 8 of 10 patients. In addition after radical surgical excision: axillary 3 %, It was shown that the recurrence rate to considerable pain, in almost each case perianal 0 %, inguinal and perineal 37 %, after surgery correlated primarily with complications such as infection and/or JDDG 3˙2008 (Band 6)
Figure 7: Axillary nodular inflammation of acne inversa preoperative.
Figure 5: Axillary lesions of acne inversa before surgi-
Figure 8: Axillary lesions of acne inversa during operation.
Figure 6: Axillary lesions of acne inversa after skin graft.
ulceration were observed. No data onrecurrence rates were provided .
On the basis of knowledge on inductionof acne inversa by androgens , sub-stances with antiandrogenic propertieswere therapeutically tried. In a double-blind randomized study published in1986 treatment with ethinyl estradiol/cyproterone acetate and ethinyl estradi-ol/ norgestrel showed improvement in18 of 24 women treated over a follow-upperiod of 18 months .
The administration of 5-␣–reductasetype II inhibitors for therapy of benign Figure 9: Axillary lesions of acne inversa after primary wound closure and insertion of an elasic strap.
JDDG 3˙2008 (Band 6)
prostate hyperplasia as well as male study (follow-up 4–6 months) on androgenetic alopecia suggested use for isotretinoin, these positive effects could Velpeau A. Aissele. In: Bechet Jeune Z: acne inversa as well. In an open trial at a not on the whole be documented . Dictionnaire de medecine, on Reper- dose of 5 mg daily a positive effect was Great hope in the development of con- toire Générale des Sciences Medicals observed in six of seven patients treated servative treatment modalities have been sous le Rapport Theorique et Pratique.
(follow-up 8–24 months) . raised by the introduction of TNF␣ The important role of bacterial contami- antagonists. TNF␣ as a proinflammato- Verneuil AS. Etudes sur les tumeurs de nation and infection especially for signs ry cytokine plays a key role in the devel- la peau et quelques maladies de glandes and symptoms of the disease such as odor, opment of severe, chronic inflammatory sudoripares. Arch Gen Med 1854; 94: inflammation and suppuration particular- reactions. Based on positive results in ly in advanced stages of the disease sug- treating Crohn disease with infliximab, Schiefferdecker B. Die Hautdrüsen der gests primary or additional antibiotic ther- the first case report of successful admin- Menschen und der Säugetiere, ihre hi- apy. A retrospective evaluation of 14 istration of this monoclonal chimeric stologische und rassenanatomische Be- patients with long-term antibiotic therapy IgG TNF␣ antibody for acne inversa deutung sowie die muscularis sexualis.
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doses of 5 mg/kg body weight adminis- Pillsbury DM, Shelley WB, Kligmann In 10 patients complete healing occurred tered as a short infusion with up to 3 AM. Bacterial infections of the skin. In: . Case reports on the administration repetitions (week 0, 2, 6). In the first Pillsbury DM: Dermatoloy. 1st edn.
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JDDG 3˙2008 (Band 6)
Issue 7 - autumn 2012 Cannon Hil Anglican Col ege magazine providing the right the chairman environment for for thought also inside:the noblest of professions the art of role model ing PSA gains momentum Pax et Bonum Issue 07 - Autumn 12