HIDRADENITIS SUPPURATIVA: A Case Series of Eight PatientsSummaryIntroduction: Hidradenitis suppurativa (HS) is a persistent, inflammatory and recurrent disease of the hair follicles which, in time, results in ugly scars. Earlier it was thought that the basis of the diseases is the inflammation and obstruction of a sweat gland channel. Now, it is a cutaneous pathologic condition that involves skin containing apocrine sweat glands. The cause of the obstruction is the follicular keratinization disorder or impaired due to the hydration of keratin. Then a bacterial colonization begins with S. epidermidis, Staphylococcus epidermidis, Escherichia coli, Klebsiella, Proteus, Streptococcus, anaerobic bacteria, although negative cultures are common. Case Series: This paper presents the cases of 8 patients operated on in the past 3 years. We point to a possibility of an oversight in making the diagnosis, as well as an under-estimate in the treatment. Together with surgical methods, we also present other therapeutic possibilities from the existing literature. This is retrospective analysis of the surgical findings. The treatment was multidisciplinary buth the surgical excision has been the only option which provides a healing without recurrences so far. In our series the excision can be done to the fascia or to leave a thin layer of adipose tissue. Reconstruction can be done by healing per secundam, by autologous skin or artificial graft, or by narrowing of the wound with a skin portion. Our results acquired by stage, secondary stitches and rotation portions were satisfying. Conclusion In advanced disease only a surgery can lead to healing. We performed late surgery because the patients occurred in the late stages by Hurley. The operative management is a wide excision in all our patients. Reconstruction was performed: in 3 patients with rotation flap, in 4 patients the wound healing per secundam and in one with primary suture. Our patients did not suffer recurrence of the primary disease. The disease was combined in one cases with perianal fistula.Keywords: hidradenitis suppurativa, hair follicles, apocrine sweat gland, surgical excision.IntroductionWhen hidradenitis suppurativa (HS) is mentioned, most surgeons think that they know what, when and how to treat. Is that really true? The fact is that there are too many cases when the diagnosis was oversighted [1]. Actually, it is a common dermatological and surgical problem.Hidradenitis suppurativa is a chronic, recidivous, inflammatory and painful process in the follicles of hair and near sweat gland. It is characterized by a thickening of the affected skin together with knots and sinuses and development of ugly scars [2]. Topologically, it primarily affects the skin of the folds i.e. the skin of the armpits, groin, genitals and perianal region. The disease was precisely defined on the Second International HS Research symposium in San Francisco in March, 2009. [3]. The synonyms for the disease are acnae inverse, Verneuils disease and follicular hyperkeratosis [4].The objective of the study was to show a little series of patients with pictures and definitive results of the surgical procedure. We point to a possibility of an oversight in making the diagnosis, as well as an under-estimate in the treatment. Together with surgical methods, we also present other therapeutic possibilities from the existing literature.Case reports:In the three-year period between 2011 and 2013, 8 patients diagnosed with hidradenitis suppurativa were operated on in the regional Department of Surgery. All the patients were male. The localizations in 7 of the patients were the perianal and gluteal region. One patient had changes both in the inguinum and pubis. The age of the patients ranged from 30 to 73 years, the average being 42 years. Through a retrospective analysis of the surgical findings of all 8 patients, together with an interview (after median time of 1 year, and with 2 of them after a shorter period of time), we gathered the data about the treatment methods applied before the surgery, about the length of the treatment, then, the quality of life before the surgery, especially related to the disease, and, finally, the level of satisfaction after the surgery, both in the functional and aesthetic aspect. The diagnosis was made in all 8 patients by inspection (Figure 1 and 2). We had a differential-diagnostic dilemma about 2 patients whether a perianal fistula was present, which proved true in one case intraoperatively. The average length of the treatment before the surgery ranged from 7 to 35 years, the average being 15 years. They were treated with antibiotics, disinfectants and occasional incisions. Most frequently used antibiotics were orally given cephalosporins together with an iodine preparation and symptomatic, often multiple incisions in cases of the appearance of suppuration. The incisions were done under a local anaesthesia. Before the arrival to the Colorectal ward of the Department of Surgery, just one patient had an accurately made diagnosis. Two of them were treated with the diagnosis of fistulous sinus pilonidalis, 3 as pyodermia, and 1 as perianal arborized fistula. They all had a chronic inflammation of the affected region with a continuous spillage. Before the indication was set, the disease had been treated by different specialists (a gynaecologist, a general medicine specialist, a dermatologist, a surgeon, an occupational health specialist) as a typical recurrent skin suppuration. The patients had been treated with various antibiotics, dermatological mixtures, occasional incisions, disinfectants and ointments. During that time, scars and channels (sinuses) had multiplied leaving ugly skin deformities. All the patients who were surgically treated were at the 3rd stage, according to Hurley. Seven patients were operated on under the general anaesthesia by the same team, and one under the peridural anaesthesia.. A wide surgical excision was applied to all of the patients (Figure 3 and 4). The excision to the fascia was performed in 5 cases and the excision near the fascia with leaving a layer of fat tissue in 3. The injection of methylene-blue into the sinuses was not done. None of the cases included the covering of the tissue defect by a skin graft. The skin defect was narrowed by rotating portions and Z plastic on 3 patients (Figure 5 and 6). A larger part of the postoperative wound healed per secundam. (Figure 7 and 8) We did both pre-operative and post-operative interviews with the patients. The interviews included the following questions: 1. How long did the treatment before the suggested operation last? 2. Were they satisfied with the previous treatment? 3. How do they evaluate the influence of the disease on their everyday life? 4. Were they satisfied with the results of the operation both in the functional and aesthetic senses? All the answers are descriptive, except the ones about the length of the previous treatment, which is mentioned above. We did not use formal interviews such as Dermatology Life Quality Index (DLQI), Skindex or VQ-Dermato.All of the patients showed the dissatisfaction with the previous treatment. The main reasons referred to the functional difficulties: secretion and occasional pain. They disturbed their everyday life and working ability. One of the patients had antidepressive sances, among other things, because of the gluteal change spillage. The quality of life stands in direct correlation with the activity of the changes and the seriousness of the disease. None of them suffered the HS reccurence, except the patient with the perianal fistula (outer opening 10 cm from the anus). The fistula was diagnosed during the operation. All but one patient were operated in the prone position, slightly bent on the operating table. The length of the hospital treatment was between 7 and 14 days or until granulation started to develop, and the total treatment with ambulance bandaging lasted over 2 months, all the way to the complete forming of a stable scar and to a partial epithelizing.During the postoperative interviews, all operated patients showed functional satisfaction, even the one with the fistula reccurence. But the youngest and unmarried patient expressed an aesthetic dissatisfaction. It points to the psycho-social importance of the disease[5]. DiscussionNo increase of the HS patients has been noticed in the last decades, but it is sure that many essays on the disease have been published in the past 10 years [6]. Although HS is not that rare, both the oversights in its diagnosis and the under-estimation in its treatment are quite frequent. The duration of the disease until the surgery is between 7 and 19 years [3]. As for our patients, the average time elapsed up to the operation was 15 years. All our patients (except one who was 73) ranged from 15 to 40 years of age, the same as in most of the published works. All our patients was male contrary to the statistics found in the literatureIs it a rare disease or not? By the European criteria, a rare disease is the one with the frequency smaller than 5 in 10.000 cases and the American criteria recognize the frequency. less than 1 in 1250 people [7]. The European literature quotes the disease frequency of 1 4 % [8, 9]. Some American sources mention the frequency of only 0.053 %, which is a greatly underestimated prevalence [10]. The most abundant data are given by Naldi L. in his analysis of 9 studies which mention the frequency ranging from 4 in 100 to 1 in 3000. He explains such a discrepancy by methodological differences. Nevertheless, he comes to a conclusion that the value of 1 % is the most precise for many European countries [11]. Most authors quote 2 to 5 times greater frequency in women and the ages affected by the disease ranging from puberty to 40 years of age [1, 12]. The pathogenesis is unknown. It is common knowledge that hyperkeratotic production occurs in the hair follicle and leads to the occlusion of the output channel. Thus created cystoid formation grows into a small abscess by the intrafollicular bacteria multiplication. The inner follicular pressure increases and causes the rupture of the cystoid formation and the creation of a tract in the surrounding subcutaneous tissues fistulisation (Figure 8). The healing and recurrence of the inflammation lead to the hardening and thickening of the tissue, as well as to the development of the chronic infection with the skin maceration [13]. But the right question is what initiates these processes? Etiological causes are: genetic factors - family predisposition with the frequency of 30-40 % [14], overweight, smoking, changed cutaneo-immunological response and hormone stimulation. The presence and multiplying of bacteria together with a frequent mechanical skin irritation (friction) bring about the development and aggravation of the disease [15]. We think that is cause of dessease of our patients. Thorough anamnesis and close inspection are all we need to diagnose the disease. The localization and characteristic changes clearly point to HS. A biopsy may be performed only if a combined disease is suspected [3]. The differential diagnosis takes into consideration infected acne, furunculosis, cat scratch disease, cellulitis, cutaneous blastomycosis, epidermoid cyst, erysipelas, granuloma inguinale and lymphogranuloma venereum [16]. It may co-exist with the following diseases: perianal fistula, sinus pilonidalis, Crohns disease, irritable colon syndrome, Downs syndrome, some forms of arthritis, Graves disease, Hashimotos thyroiditis and Sjgrens syndrome [13]. HS shares the same immunological etiology with some of these diseases. Certain syndromes, in which HS is a part of the clinical picture, are precisely defined, for example, PAPASH pyogenic arthritis, pyodermia gangrenosum, acne and hidradenitis suppurativa. PASH, PAPA and others have been noted earlier, too. They are believed to be the consequences of gene mutation [17]. One our patient was reccurence of perianal fistula. Preoperative physical examination may find internal opening in about 75% and transanal ultrasound (TUS) with 95% [30].HS can also be the cause of the squamous-cellular carcinoma (SCC) especially in the perianal region [18]. According to the data quoted by Nassif A. and Jemec GBE., the SCC development frequency in the HS field ranges from 1.7 to 3.2 % (according to Li M., Hunt MJ. And Commens CA., 1997), and a cancer develops after approximately 23 years of suffering from one of the diseases belonging to the group of the follicular occlusion syndrome which also includes HS (according to Gur E. et al., 1997). According to the morphological criterion set by Hurley in 1989, the HS classification has 3 stadiums:1. Isolated knots (a blind boil)2. Forming of fibroses and fistulous (sinus) channels not connected into a unique area3. Confluent fistulae, knots and hypertrophic scars. [19]The treatment mostly depends on the disease stadium: mild, medium and heavy forms which correlate with Hurleys morphological picture. Even a few death cases have been recorded due to HS.According to Hurley, our patients were classified in stage 3. The HS patients quality of life is always seriously decreased, especially in the stages of the disease which are graver and more spread on the skin. Regarding the most frequently affected age group, the disease can cause both psychological and physical disorder of the patients sex life. In any case, both the social life and the professional ability of the patients are disturbed. That makes the social support and psychological treatment necessary.The basic principle in the management of HS for stage 3 and some patients at stage 2 is that an early and thorough surgical excision gives the best results. The treatment includes: a local treatment: disinfectants, light (photodynamic), laser treatment, local antibiotics and other solutions (which were not used extensively); a pharmacological and medicamentous treatment: immunosupressives and immunomodulators, TNF alpha inhibitors, antibiotics, oral retinoids and anti-androgens (we do not have that medication); a surgical treatment: deroofing, wide excision; - operations at 2 times, skin grafts and other aesthetic operations like temporery solution; a radiological treatment an external radiation (which was not used); and a psychological treatment.A radical surgery can be delayed in the first stadium. As for the later stadiums, it is best to have a surgical intervention as soon as possible, as our experience shows. Generally, the operation can be delayed during the first stadium. The shaving of the region and administering of antibiotics according to the antibiogram are recommended instead, as well as the local treatment of rinsing with antibiotic and disinfecting solutions. The most common isolated causes of an infection are: Staphilococcus aureus (51 %), then, Escherischia colli, Streptococcus, anaerobes [17]. Various antibiotics are given like our expirience : clindamycin 300 mg twice-daily and rifampicin 300 mg twice-daily for at least 3 months, , cephalosporin, tetracycline, and others. At recent time, the photodynamic therapy has been used, as well as the laser therapy for the 1st and 2nd stadiums [17]. Unfortunately, we do not have that experience. The change of lifestyle in terms of a weight loss and giving up smoking affects the treatment results in some patients. Because of the high percentage of the relapsing, it is necessary to psychologically prepare a patient to a long-lasting and, finally, surgical treatment [19].According to Hurley, the surgical treatment is applied in the 2nd and 3rd stadiums. It can be performed alone or in the combination with a medication treatment. For stage 1 and part of stage 2, we suggested giving up smoking and the reduction of body weight, as well as the topical treatment with clindamycin, Resorcinol and Intralesional triamcinolone in small doses of 25 mg. According to the available literature, it can be said that the medications used in the treatment are: immunomodulatory medications (anakinra, cinakinumab, ustekunimab improves condition in 2/3 of the HS patients and is also used in psoriasis, azathioprine, tacrolimus, thalidomide) [7], anti-inflammatory TNF-inhibitors (infliximab, etanercept, adalimumab), immunosupressors (prednisone), dapson (has partial antibiotic and partial immune-regulating effects), antiandrogens and acitretin. They have good effects when the disease is of the autoimmune genesis. We did not use such treatment because all our patients were in the 3rd stadium of the disease.Our patients surgical therapy was always a wide excision of the changes in the gluteal region: to the fascia in 5 cases (one of them with several different excisions of the affected cutaneous and subcutaneous areas) and with the removal of the most part of the subcutaneous, fat tissue except a thin layer above the fascia i.e. almost to the fascia in the other 3 cases. Most authors agree that the surgical treatment has no alternative in other types of treatments if we want to come to a definite solution of the problem [21, 22, 23, 24]. A dilemma is whether to perform the excision to the fascia or almost to the fascia until the granulation begins [25].After the excision of the affected region, the following is possible: 1. Leaving the wound to heal per secundam, 2. Healing per secundam with a partial closing of some of the portions, 3. Delayed grafting with an autologous skin portion in its full thickness [25], and 4. Delayed grafting with an artificial graft [26]. The choice depends on the size of a defect, risk of a recidive, risk of an infection and expected aesthetic result. The healing per secundam and partial narrowing of the excised area by skin portions, Z plastic, etc have the smallest percentage of recidive and infection but the longest treatment and poorest aesthetic result [26]. The grafting with skin in its full thickness gives good results, but has a higher percentage of infection [27]. More and more authors advocate the grafting with an artificial skin graft. However, considering the graft thickness and aesthetic aspect, it is not recommended to do the excision to the fascia, but more moderately [28].We did not perform the surgical procedure of cutting and opening the sinus tracts with the removal of their surface parts (deroofing) and we think it is a palliative measure with a high percentage of relapsing [28]. It is good for the ambulance dealing with multiple suppurations. We used simple and multiple incisions as a temporary procedure. Recently, many advised the use of X-rays and laser before the final operation (neodymium: yttrium-aluminium-garnet laser with a 3 month application, or carbon dioxide laser). The logical goal was to dry the affected area by the application of the outer radiation in the amount of 3-8 Gy in several fractions. A study dating from the year 2000 cites radical withdrawal of the changes in 1/3 of 231 cases [24].ConclusionHidradenitis suppurativa is not a rare disease. The choice of the treatment methods is wide. It is sure that keeping records of the patients improves the treatment as they do in the Scandinavian countries with the so-called HISREG [29] method of case registration. We did not use a radical surgical treatment for the early stages. When we speak of the advanced disease, only a surgery can lead to healing. The affected regions are characteristic. The affected region in all our patients was the gluteal region. When scars and sinus fistulae appear, an early operation prevents the creation of more serious aesthetic consequences. The operative management is a wide excision without compromise and with one of the described ways of the operative wound closing. Recurrences on some parts of the operated area are possible even after the surgery. In that case, a re-excision is performed. Our patients did not suffer recurrences of the primary disease. The disease may be combined with other diseases such as: fistulae, pilonidal sinus, immunosuppressive states, or within the mentioned syndromes. References:1. Shah N. Hidradenitis Suppurativa: A Treatment Challenge. Am Fam Physician 2005;72:1547-52.2. Revuz JE, Canoui-Poitrine F, Wolkenstein P. et al. J Am Acad Dermatol 2008:59: 596601.3. Danby FW, Margesson LJ. Hidradenitis Suppurativa. Dermatol Clin 2010;28:77993.4. Al Aboud K, Al Aboud A. The fading eponym of Verneuils disease. Our Dermatol Online 2013;4:128-9.5. Matusiak L, Bieniek A, Szepietowski JC. Hidradenitis suppurativa markedly decreasesquality of life and professional activity (to the editor). J Am Acad Dermatol 2010;62:707.6. Sung S, Kimball AB. Counterpoint: Analysis of patient claims data to determine the prevalence of hidradenitis suppurativa in the United States (letter to editor). J am acad dermatol 2013;70:818.7. Deckers I, van der Zee H, Prens E. Epidemiology of Hidradenitis Suppurativa: Prevalence, Pathogenesis, and Factors Associated with the Development of HS. Curr Derm Rep 2013; DOI 10.1007/s13671-013-0064-8.8. Van der Zee HH, Laman JD, Boer J, Prens EP. Hidradenitis suppurativa: viewpoint on clinical phenotyping, pathogenesis and novel treatments. Experimental Dermatology, 2012, 21,7359.9. Cosmatos I, Matcho A, Weinstein R, Montgomery MO, Stang P. Analysis of patient claims data to determine the prevalence of hidradenitis suppurativa in the United States. J Am Acad Dermatol. 2013;69:819.10. Naldi L. Epidemilogy. In: Gebec, Revus, Leyden (eds): Hidradenitis suppurativa. Springer-Verlag Berlin Heidelberg 2006:58-64. 11. Jemec GB. The symptomatology of hidradenitis suppurativa in women. Br J Dermatol 1988;119: 34550.12. Yazdanyar, S., Jemec, G.B., 2010. Hidradenitis suppurativa: a review of cause and treatment. Curr. Opin. Infect. Dis. 24,11823.13. Von der Werth J, Wood P, Irvine AD, McLean WHI. Genetics of Hidradenitis Suppurativa. In: Hidroedenitis suppurativa. Springer-Verlag Berlin Heidelberg 2006:70-83.14. Nazary M, Van der Zee HH, Prens EP, Folkerts G, Boer J. Pathogenesis and pharmacotherapy of hidradenitis suppurativa. Eur J Pharmacol 2011;672:18.15. http://emedicine.medscape.com/article/762444-clinical#showall16. Marzano AV, Trevisan V, Gattorno M, Ceccherini I, De Simone C, Crosti C. Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa (PAPASH): A New Autoinflammatory Syndrome Associated With a Novel Mutation of the PSTPIP1 Gene. JAMA Dermatol. 2013;149:762-4.17. Lavogiez C, Delaporte E, Darras-Vercambre S, De Lassalle EM, Castillo C, Mirabel X, Laurent F, Patenotre P, Gheit T, Talmant JC, Beylot-Barry M, Martinot V, Piette F, Aubin F, Mortier L. Clinicopathological Study of 13 Cases of Squamous Cell Carcinoma Complicating Hidradenitis Suppurativa. Dermatology 2010;220:14753.18. Collier F, Smith R, Morton CA. Diagnosis and management of hidradenitis suppurativa. BMJ 2013;346:1-6.19. Sartorius K, Lapins J, Emtestam L. Et al. Br J Dermatol 2003;149:2113.20. Bilali S, Todi V, Lila A, Bilali V, Habibaj J. Surgical treatment of chronic hidradenitis suppurativa in the gluteal and perianal regions. ACI 2010;LIX:91-5.21. Jemec GBE. Hidradenitis suppurativa. N Engl J Med 2012;366:158-64.22. Alharbi Z, Kauczok J, Pallua N. A review of wide surgical excision of hidradenitis suppurativa. BMC Dermatology 2012,12:9.23. Bocchini SF, Habr-Gama A, Kiss DR, Imperiale AR, Araujo SEA. Gluteal and Perianal Hidradenitis Suppurativa - Surgical Treatment by Wide Excision. Dis Colon Rectum 2003; 46:9449.24. Yamadhita Y, Hashimoto I, Matsuo S, Abe Y, Ishida S, Nakanishi H. Two-Stage Surgery for Hidradenitis Suppurativa: Staged Artificial Dermis and Skin Grafting. Dermatol Surg 2013;16.25. Hosnuter M, Tosun Z, Savac I. Surgical therapy for uncontrolled chronic hidradenitis suppurativa. Eur J Plast Surg 2002;25:116.26. Endo Y, Tamura A, Ishicawa O, Miyachi Y. Perianal hidradenitis suppurativa: early surgical treatment gives good results in chronic or recurrent cases. British Journal of Dermatology; 139:90610.27. Van der Zee HH, Prens EP, Boer J. Deroofing: A tissue-saving surgical technique for the treatment of mild to moderate hidradenitis suppurativa lesions. J Am Acad Dermatol. 2010;63(3):475-80.28. Ingvarsson G, Dufour DN, Killasli H. Et al. Development of a Clinical Scandinavian Registry for Hidradenitis Suppurativa: HISREG. Acta Derm Venereol 2013;93:35078.29. Ozkavukcu E, Haliloglu N, Erden A. Frequencies of perianal fistula types using two classification systems. Jpn J Radiol 2011;29:293300.

Figure 1-2.: Hidradenitis suppurativa grade III

Figure 3-4: Wide excision affected tissues

Figure 5-6: Primary reconstruction

Figure 7 8: Secondary stitches of the postoperative wound

Kratak sadrajUvod Hidroadenitis suppurativa je uporno, zapaljenjsko, rekurento, oboljenje folikula korena dlake koje se lako prenosi na znojne lezde i vremenom dovodi do runih oiljaka. Kroz rad prikazujemo 8 operisanih bolesnika u zadnje 3 godine. Mogunost previda u postavljanju dijagnoze kao i potcenjivanje u leenju je prisutno. Uz operativne metode prikazujemo i pregled drugih terapijskih mogunosti iz literature kroz metod retrospektivne analize operativnih podataka i intervjua sa bolesnicima. Zadnjih godina je otkriveno mnogo podataka o etiologiji bolesti. Leenje je multidisciplinarno, ali hirurka ekscizija je, kao to prikazuju nai rezultati, jedina opcija koja obezbeuje izleenje bez recidiva. Ekscizija se moe izvesti do fascije ili uz ostavljanje tankog sloja masnog tkiva (bolje prihvatanje transplantanta ili renja), a rekonstrukcija moe biti zaceljenjem per secundam, autolognim konim ili arteficijalnim graftom, ili suenjem rane konim renjem. Nai rezultati etapnim, sekundarnim avovima i rotacionim renjevima su zadovoljavajui na osnovu pregleda bolesnika i postoperativnog intervjua..Zakljuak Kad govorimo o uznapredovalom stadijumu bolesti samo hirurgija obezbeuje izleenje. Operativno leenje je iroka ekscizija to smo primenjivali sa nekim od prikazanih metoda zatvaranja rane. Mogui su recidivi, a tada se praktikuje re-ekscizija. Nai bolesnici nisu imali recidive primarne bolesti. HS moe biti udruena sa perianalnim fistulama, pilonidalnim sinusom, imunosupresivnim stanjima i drugim sindromima. Mi smo imali 1 sluaj udruen sa fistulom. Kljune rei: hidradenitis suppurativa, znojna lezda, hirurka ekscizija, folikul dlake

ABBREVIATIONS: HS hidradenitis suppurativaDLQI - Dermatology Life Quality IndexPAPASH pyogenic arthritis, pyodermia gangrenosum, acne and hidradenitis suppurativa.TUS transanal ultrasoundSCC squqmous cellular carcinomaTNF tumor necrosing factor