MICROBIOLOGICAL BASIS FOR EFFECTIVE ANTIBIOTIC THERAPY OF HIDRADENITIS SUPPURATIVA/ACNE INVERSA
UDC 616-08-035
MICROBIOLOGICAL BASIS FOR EFFECTIVE ANTIBIOTIC THERAPY
OF HIDRADENITIS SUPPURATIVA/ACNE INVERSA
K. Robakidze, MD, PhD, Full Professor, Department of Dermatology and Venereology
Caucasus International University
(380092, Georgia, Tbilisi, St. Chargali, 73)
National Health Center named after Academician O. Gudushauri
(0186, Georgia, Tbilisi, Lubliana Street, 18/20)
E-mail: kakhaberrobakidze@mail.ru
I. Buchukuri, MD, PhD, Full Professor, Department of Dermatology and Venereology
Petre Shotadze Tbilisi Medical Academy
(Georgia, Tbilisi, Ketevan Tsamebuli Avenue, №51/2)
Department of Dermatology, MediClubGeorgia,
(0160, Georgia, Tbilisi, Tashkent Str. 22A)
- mail: irma_buchukuri@yahoo.com
https://orcid.org/0000-0002-6576-9131
T. Mgeliashvili, MD, PhD, Assistant Professor, Department of General Surgery
Tbilisi State Medical University
(380092, Georgia, Tbilisi, Vazha Pshavela Avenue, 33)
National Health Center named after Academician O. Gudushauri
(0186, Georgia, Tbilisi, Lubliana Street, 18/20)
E-mail: Teimuraz.mgeliashvili@mail.com
L. Grigolia, MD, PhD, Full Professor at the Department of Dentistry
Caucasus International University
(380092, Georgia, Tbilisi, St. Chargali, 73)
E-mail: lela.grigolia@ciu.edu.ge
Abstract. The article is devoted to one of the acute problems of dermatology – hidradenitis suppurativa/acne inversa. Based on literary sources, it discusses in detail the etiology, pathogenesis, clinical manifestations, diagnosis and modern methods of treatment of the disease. Attention is focused on the main method of treatment of the disease - antibiotic therapy. A long-term retrospective analysis has established that empirical antibiotic therapy with clindamycin does not guarantee unconditional clinical effectiveness. Antibiotic therapy in (HS/AI) should be individualized and based on preliminary microbiological studies.
Keywords: Hidradenitis suppurativa/acne inversa, empirical antibiotic therapy, clindamycin, etiological agent, antibiotic resistance.
Introduction
Hidradenitis suparativa/acne inversa (HS/AI) is a condition previously known as follicular occlusion syndrome. This term was coined by D.M. Pillsburry, W.B. Shelley, and A.M. Kligman in 1956 [33]. According to various sources, the prevalence of the disease worldwide ranges from 1% to 4%. Women are three times more likely to develop HS/AI than men [38, 55]. For a long time, the condition was described as a triad: acne conglobata and acne inversa, hidradenitis suparativa, and folliculitis inversa, or perifolliculitis capitis [47]. It was only in 1975 that a fourth component, the pilonidal cyst, was described [33].
The etiology and pathogenesis remain poorly understood, so modern medicine is unable to provide a universal treatment protocol for such patients. The underlying pathogenesis of the disease is hair follicle occlusion, which in 30–40% of cases is caused by a genetic predisposition to acne [48], hyperkeratinization, and the formation of lymphohistiocytic inflammation with a granulomatous reaction. Inflammation in the apocrine glands, accompanied by inflammation around the eccrine glands, hair follicles, and epithelial-lined structures, has been observed in only a small proportion of cases [52]. Follicular occlusion leads to stretching and rupture of the follicles, releasing their contents into the surrounding dermis. This facilitates the migration of neutrophils and lymphocytes to the site of inflammation [16, 30, 54], forming an inflammatory infiltrate followed by scar tissue formation [17]. It is generally accepted that bacteria do not influence the development of the disease, but secondary bacterial infection maintains the inflammatory process and promotes recurrence [43]. Pathological examination at early stages reveals follicular occlusion with or without inflammation, follicular cysts, decreased sebaceous gland volume, hyperplasia, and neutrophilic abscesses [52]. In severe cases, B cells and plasma cells are found in pseudofollicles, abscesses, and sinuses, surrounded by a chronic inflammatory infiltrate, with the presence of histiocytes and giant cells, as well as a large amount of granulation tissue [49]. GS/AI typically debuts after puberty with small, red, firm papules or, less commonly, pustules that gradually increase in size and merge with surrounding tissue. Gradually, the dermatosis transforms into a chronic, recurring inflammatory process with false-comedones, painful papules located in the deep layers of the skin, a tendency to form abscesses that merge into sinuses, and resolution with scarring [38, 47, 48, 55]. In women, the disease often develops in the breast fold, in the perineal area, and in men, in the anal area [11, 30]. The contents of the lesions are not evacuated, but remain intradermally as rounded subcutaneous formations [46, 50]. As skin symptoms worsen, systemic symptoms are added. Patients complain of pain, burning, profuse sweating, weakness, and, in severe cases, an inability to walk or sit, as well as an unpleasant odor. This condition can persist for a long time, and, importantly, there is no positive response to antibiotic therapy [24, 37]. To make a diagnosis, three mandatory criteria must be present [9]: Lesions: in the initial stages of the disease - deep painful nodes, abscesses, draining sinuses, scars; Localization: axillary, inguinal, anal areas, perineal area, abdominal area; Chronic course with the presence of relapses.
Treatment of HS/AI requires a comprehensive approach that should include both non-drug and drug-based solutions. It is essential to consider the patient's lifestyle and unhealthy habits. Weight control and smoking cessation play a crucial role in achieving successful treatment. V.S. Melnik and S.S. Zouboulis published observational results demonstrating that women with HS/AI exhibit high sensitivity to androgens [32], and therefore, androgen-containing medications should be excluded from therapy [6]. Patients should be reminded of three important facts. First, nicotine has been shown to influence the formation of follicular occlusion, leading to a more severe form of the disease in smokers [41]. Second, mechanical trauma to the lesions by the patients themselves can worsen the process, leading to deeper infection [8]. Thirdly, a direct correlation has been established between metabolic syndrome and the severity of HS/AI, so all overweight patients are advised to lose weight [41]. Due to the frequent combination of HS/AI with Crohn's disease and/or localization in the perianal region, the patient should be examined by a gastroenterologist and proctologist [46]. When choosing a treatment strategy for HS/AI, practicing physicians are advised to use the classification of this disease developed by H.J. Hurley in 1989 [32]. Other classifications exist (Sartorius score, the Hidradenitis Suppurativa Severity Index, Physician Global Assessment), but they are mainly used in clinical research studies [54].
According to the Hurley classification, three stages of the disease are distinguished:
Stage I – the presence of one or more isolated abscesses without scars or sinuses. Stage II – the presence of recurrent abscesses localized in more than one anatomical region. Sinus tracts form.
Stage III – the presence of extensive abscesses with multiple interconnected sinuses, leading to scarring. Treatment tactics depend on the stage of the pathological process. In stages I–II, topical treatment may be sufficient, while stage III disease is considered an indication for biological therapy [1, 19, 51]. According to the current literature, first-line treatment options include antibiotics and steroids, along with surgical drainage of purulent cavities. According to the European S1 guideline for the treatment of hidradenitis suppurativa/acne inverse, clindamycin is the only antibiotic recommended for topical use [54]. In the presence of multiple lesions and frequent exacerbations, systemic tetracyclines may be considered [25]. An alternative may be a triple regimen of rifampicin (10 mg/kg once daily), moxifloxacin (400 mg once daily), and metronidazole (500 mg three times daily) for 12 weeks, with metronidazole discontinued after 6 weeks. Patients with stage II–III HS/AI who have multiple active lesions should be immediately prescribed systemic clindamycin and rifampin (300 mg 2 times a day) [14, 15, 20]. Good results are observed with the use of 15% resorcinol as an exfoliant 2 times a day [3]. Some authors suggest the combined use of metronidazole 400 mg 2 times a day and clindamycin 600 mg 3 times a day intravenously for 2 weeks [44]. Corticosteroid drugs are also an integral part of the treatment of this complex disease [7, 36]. Since there are observations confirming the relationship between GS/AI and increased sensitivity to androgens [32], the administration of antiandrogens (cyproterone acetate, estrogens, finasteride) is justified [27, 42]. There are fewer publications regarding other drugs, in particular cytostatics, but in a number of cases successful therapy with cyclosporine has been noted [2, 18, 40]. In the modern literature, there is no consensus on the use of methotrexate in the treatment of HS/AI. In an early study conducted in 2002 by G.B. Jemec [26], methotrexate was used as monotherapy for a period of 6 weeks to 6 months. However, despite the lack of effect of methotrexate, some researchers argue that its addition in low doses to therapy with biological drugs is necessary in order to prevent the neutralization of autoantibodies, which prevents the development of secondary resistance to biological therapy [5]. The appointment of methotrexate is also justified in the presence of concomitant rheumatological diseases in patients with HS/AI [9]. Later studies conducted by P. Kozub et al. [29] demonstrated that methotrexate is ineffective either as monotherapy or in combination with infliximab. The authors have shown that methotrexate does not increase the clinical efficacy of infliximab [12, 13]. Modern studies also confirm the low efficacy of isotretinoin: approximately 60% of patients did not respond to treatment, and 13% experienced relapses [4, 10].
A more modern drug from the retinoid class, alitretinoin at a dose of 10 mg/day for 2 months followed by a maintenance dose of 20 mg, according to data [39], caused a stable remission in most patients. Surgical intervention is an important part of the management of such patients and is used at stages II–III of the disease. It is important not only to open the inflammatory elements, but also to drain them and excise the diverticula, which are usually located deeper than the main inflammatory focus [31]. There are practical recommendations for the use of lasers in HS/AI: carbon dioxide laser [21], NG:Yag laser [45], IPL [23], but there are not enough observations yet to draw final conclusions. As for biological therapy, anti-TNFα monoclonal antibodies - infliximab and adalimumab are indicated for patients with stage III of HS/AI [54]. Adalimumab was first used in 3 patients by A.A. Navarini and R.M. Trueb in 2010. All patients had previously received isotretinoin in combination with an antibiotic, without effect. The use of adalimumab helped to eliminate clinical symptoms and subjective sensations. However, after discontinuation of biological therapy, clinical manifestations began to return, and the patients were prescribed a repeat course of biological therapy [22, 28, 34, 35]. The literature contains evidence of the effectiveness of infliximab in a 30-year-old patient with a previous ineffective course of therapy with rifampicin 300 mg/day, prednisolone 50 mg/day and isotretinoin 30 mg/day [51]. Positive results have also been demonstrated with treatment with other biological drugs - etanercept and ustekinumab [1, 19].
Thus, as the analysis of literary sources has shown, despite long-term studies, hidradenitis suppurativa/acne inversa still remains an urgent problem of modern dermatology. The contradictory content of the literary sources available to us is an infallible confirmation of the fact that the etiology, pathogenesis, methods of diagnosis and effective treatment of the disease under study have not been finally established.
Most researchers agree that antibiotic therapy plays a crucial role in the treatment of the disease; clindamycin is considered to be the most effective antibiotic.
Considering the above, the aim of the study was to evaluate the microbiological basis of the clinical efficacy of clindamycin in hidradenitis suppurativa/acne inversa. To achieve this goal, our study aimed to isolate the pathogenic strain from a sick person and study its sensitivity to clindamycin. We have not studied the species or intraspecific identification of the isolated strains and their sensitivity to other groups of antibiotics at this stage of the study. The study was retrospective in nature and covered the years 2015-2025. 780 strains of various species isolated from individuals with hidradenitis suppurativa/acne inversa were studied. 59.23% of the strains tested (462 strains) exhibited resistance to clindamycin. We found the trend of increasing resistance during the study period particularly noteworthy: there was a slight trend of increasing resistance between individual years, although the difference in resistance prevalence rates at the baseline and follow-up stages of the study was statistically confirmed.
Therefore, our studies have shown that empirical antibiotic therapy for hidradenitis suppurativa/acne inversa should not be performed unconditionally with clindamycin alone. Effective antibiotic therapy should always be based on the results of preliminary microbiological studies.
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REFERENCES
1. Adams D.R., Yankura J.A., Fogelberg A.C., Anderson B.E. Treatment of hidradenitis suppurativa with etanercept injection. Arch Dermatol. 2010;146(5):501–504. DOI: 10.1001/archdermatol.2010.72.
2. Anderson M.D., Zauli S., Bettoli V. et al. Cyclosporine treatment of severe Hidradenitis suppurativa-A case series. J Dermatolog Treat. 2016;27(3):247–250. DOI: 10.3109/09546634.2015.1088128.
3. Boer J., Jemec G.B. Resorcinol peels as a possible self-treatment of painful nodules in hidradenitis suppurativa. Clin Exp Dermatol. 2010;35(1):36–40. DOI: 10.1111/j.1365-2230.2009.03377.x.
4. Boer J., van Gemert M.J. Long-term results of isotretinoin in the treatment of 68 patients with hidradenitis suppurativa. J Am Acad Dermatol. 1999;40(1):73–76. DOI: 10.1016/s0190-9622(99)70530-x.
5. Brunasso A.M., Massone C. Treatment of hidradenitis suppurativa with tumour necrosis factor-alpha inhibitors: An update on infliximab. Acta Derm Venereol. 2011;91(1):70–71. DOI: 10.2340/00015555-0989.
6. Danby F.W. Turning acne on/off via mTORC1. Exp Dermatol. 2013;22(7):505–506. DOI: 10.1111/exd.12180.
7. Danto J.L. Preliminary studies of the effect of hydrocortisone on hidradenitis suppurativa. J Invest Dermatol. 1958;31(6):299–300. DOI: 10.1038/jid.1958.124.
8. De Winter K., van der Zee H.H., Prens E.P. Is mechanical stress an important pathogenic factor in hidradenitis suppurativa? Exp Dermatol. 2012;21(3):176–177. DOI: 10.1111/j.1600-0625.2012.01443.x.
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Материал поступил в редакцию 10.05.26
МИКРОБИОЛОГИЧЕСКИЕ ОСНОВЫ ЭФФЕКТИВНОЙ АНТИБИОТИКОТЕРАПИИ HIDRADENITIS SUPPURATIVA/ACNE INVERSA
К. Робакидзе, доктор медицинских наук, профессор кафедры дерматологии и венерологии
Кавказский международный университет
(380092, Грузия, Тбилиси, ул. Чаргали 73)
Национальный Центр Здравоохранения имени Академика О. Гудушаури
(0186, Грузия, Тбилиси, ул. Лублиана, 18/20)
E-mail: kakhaberrobakidze@mail.ru
И. Бучукури, доктор медицинских наук, профессор кафедры дерматологии и венерологии
Тбилисская медицинская академия им. Петре Шотадзе
(Грузия, Тбилиси, Проспект Кетеван Цамебули, №51/2)
Отделение дерматологии, MediClubGeorgia
(0160, Грузия, Тбилиси, ул. Ташкент А, 22)
E-mail: mail: irma_buchukuri@yahoo.com
https://orcid.org/0000-0002-6576-9131
Т. Мгелиашвили, кандидат медицинских наук, доцент кафедры общей хирургии
Тбилисский государственный медицинский университет
(380092, Грузия, Тбилиси, Проспект Важа Пшавела, 33
Национальный Центр Здравоохранения имени Академика О. Гудушаури
(0186, Грузия, Тбилиси, ул. Лублиана, 18/20)
E-mail: Teimuraz.mgeliashvili@mail.com
Л. Григолия, кандидат медицинских наук, профессор кафедры стоматологии
Кавказский международный университет
(380092, Грузия, Тбилиси, ул. Чаргали 73)
E-mail: lela.grigolia@ciu.edu.ge
Аннотация. Статья посвящена одной из острых проблем дерматологии – Hidradenitis suppurativa/acne inversa. На основе литературных источников подробно рассматриваются этиология, патогенез, клинические проявления, диагностика и современные методы лечения заболевания. Особое внимание уделяется основному методу лечения – антибиотикотерапии. Долгосрочный ретроспективный анализ показал, что эмпирическая антибиотикотерапия клиндамицином не гарантирует безусловной клинической эффективности. Антибиотикотерапия при Hidradenitis suppurativa/acne inversa должна быть индивидуализирована и основываться на предварительных микробиологических исследованиях.
Ключевые слова: Hidradenitis suppurativa/acne inversa, эмпирическая антибиотикотерапия, клиндамицин, этиологический агент, антибиотикорезистентность.