Newer Insights on Hidradenitis Suppurativa.pptx

Hidradenitis suppurativa (HS) is an inflammatory disorder that is characterized by chronic deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in the axilla, inguinal area, submammary folds, and perianal area. This disfiguring condition is accompanied by pain, embarrassment, and a significantly decreased quality of life. Although the mechanism of HS has not been entirely elucidated, lesion formation is believed to center around follicular hyperkeratosis within the pilosebaceous-apocrine unit. Recent research has provided new insight into the role of cytokines in the pathogenesis of HS, helping close some existing knowledge gaps in the development of this condition.

1. HIDRADENITIS SUPPURATIVA Dr. MOHNISH SEKAR

2. INTRODUCTION C hronic inflammatory skin condition with lesions including deep-seated nodules and abscesses, draining tracts and fibrotic scars . M ost commonly  areas rich in apocrine glands such as axillary, groin, perianal, perineal and inframammary locations . Negative psychosocial impact  associated pain, sensitive locations, drainage, odor and scarring.

3. EPIDEMIOLOGY AGE  The average age of sufferers is 24.2 years (― 12 years). SEX  Women are more frequently affected than men in a ratio of 2.7 :1 ASSOCIATED DISEASES  Follicular occlusion tetrad - Acne conglobata , dissecting cellulitis of the scalp and pilonidal sinus can coexist with HS.

4. OTHER INFLAMMATORY CONDITIONS GENODERMATOSES CROHNS DISEASE KERATOSIS ICTHYOSIS DEAFNESS OSTEITIS PACHYONYCHIA CONGENITA PYOGENIC ARTHRITIS STEATOCYSTOMA MULTIPLEX PYODERMA GANGRENOSUM DOWLING DEGOS DISEASE ACNE CONGLOBATA SUPPURATIVE HIDRADENITIS PERIPHERAL ULCERATIVE KERATITIS SYNOVITIS HLA B27 ASSOCIATED INFLAMMATORY SPONDYLO ARTHROPATHY OF AXIAL AND APPENDICULAR JOINTS HYPEROSTOSIS

5. Pathophysiology P rimary defect  O cclusion and subsequent inflammation of the hair follicle. Bacterial infection and colonization  secondary pathogenic factor. Infundibular hyperkeratosis  follicular dilatation/cyst formation  follicular rupture with subsequent inflammation  fistula formation by epidermal strands. Other factors  altered expression of antimicrobial peptides, abnormal secretion of apocrine glands , abnormal invaginations of the epidermis leading to sinus tract formation and deficient numbers of sebaceous glands.

6. Follicular hyperkeratinization and occlusion  rupture of pilosebaceous units, releasing bacteria within the dermis and triggering a local inflammatory response and cause chronic inflammation. S taphylococcus epidermidis and S.aureus    most prevalent species. Other common species  polymicrobial anaerobic microflora , streptococcus species, actinomycetes and Cutibacterium acnes. Genetics  Autosomal pattern of inheritance can be found. Loss‐of‐function mutations in the γ‐ secretase genes Nicastrin , Presenilin‐1 and Presenilin enhancer‐2. Environmental factors  Smoking, obesity , m echanical irritation and shear forces.

7. Melnik and Plewig  A n auto-inflammatory disease characterized by dysregulation of the gamma- secretase /Notch pathway. Appropriate Notch signaling  maintaining the inner and outer root sheath of the hair follicle and skin appendages. Deficiency in the Notch signaling pathway  conversion of hair follicles to keratin-enriched epidermal cysts, compromises apocrine gland homoeostasis and leads to the stimulation of toll-like receptor (TLR)-mediated innate immunity, supporting and maintaining chronic inflammation.  Altered TLRs(toll like receptors) signaling on macrophages and dendritic cells ( DCs) produces increased amounts of pro inflammatory cytokines such as tumor necrosis factor (TNF)- α, interleukin (IL)-1 β and IL-17  activation of DCs which secrete IL-23 promoting Th17 cell polarization.

8. CLINICAL FEATURES Essential criteria for diagnosis (San Francisco modification of the Dessau criteria): 1.Typical lesions: Deep‐seated painful nodules, abscesses, draining sinuses, bridged scars and paired or multiheaded open pseudocomedones 2.Typical topography: Axillae, groin, perineal and perianal region, buttocks,infra ‐ and intermammary folds 3.Recurrence of lesions

9. History P ainful subcutaneous nodules or abscesses that persist for a mean duration of 7–15 days. Spontaneous regression , partial regression or progression to abscess formation with the rupture and release of purulent malodorous discharges.

10. Multiple inflamed nodules and draining sinuses in mons pubis Non‐draining sinus, recognized by the palpable oblong shape. Classical axillary abscess as seen in HS

11. PRESENTATION Inflamed and non‐inflamed dermal and subcutaneous nodules , On palpation  rounded (as opposed to ‘pointing’) abscesses and draining or non‐draining sinus tracts. Scarring is typically bridged or ‘rope‐like’, it can be hypertrophic or atrophic , producing depressions especially on the buttocks and may be associated with contractures. Pseudo- ( secondary) comedones are often seen, typically paired, polyporous and grouped Associated lesions  follicular papules and pustules, pyogenic granulomas at sinus tract openings and indurated plaques. Epidermoid cysts are seen in some patients on external genitalia, the face and the thorax.

12. Follicular pattern involving the buttocks. Tombstone comedones in the axilla

13. Nodules and sinus tracts involving the buttocks Follicular pattern involving the genito ‐femoral area showing non‐active disease.

14. Clinical variants 1.Classical variant : S carring lesions in the axillae and under the breasts and often includes lesions in the ano ‐genital area . 2.Second variant: Additional involvement of the ears, chest, back or legs, with pilonidal sinuses, comedones , severe acne and a family history of HS . 3. T hird variant: Gluteal involvement, papules and folliculitis.

15. Differential diagnosis Common abscess Carbuncles Furunculosis Infected Bartholin’s gland Inflamed epidermal cysts Pilonidal cyst Scrofuloderma Actinomycosis Lymphogranuloma venereum

16. Classification and severity assessment There are several scoring systems for the assessment of disease severity of HS Hurley staging HS Physician’s Global Assessment (PGA ), T he M odified Sartorius score (MSS), HS Severity Index (HSSI ).

17. HURLEY STAGING SYSTEM STAGE 1 Recurrent abscess formation without sinus tracts and cicatrization . STAGE 2 Recurrent abscesses with widely separated sinus tracts and cicatrization STAGE 3 Multiple interconnected abscesses, sinus tracts and cicatrization diffusely involving an entire region. DISADVANTAGES  Although the system is fast and easy, Hurley classification is not suitable for monitoring the efficacy of therapeutic interventions in clinical trials, since the classification is not quantitative.

18. Hurley stage I disease of the genito ‐femoral area showing a solitary nodule . Notice the normal‐looking surrounding skin and perilesional halo of discoloration indicating a recent episode of inflammation. Hurley stage II disease of the genito ‐femoral area. (a) Hurley stage II is a broad category which may involve more severe disease as shown here. (b) Inactive,mild disease. (c) Severe, active, multifocal disease. Notice the areas of normal‐looking skin separating the lesions .

19. Hurley stage III disease. (a) Non‐draining, confluent, chronic lesions involving the entire axilla. (b) Active draining lesions in the axilla.

20.   The Modified Sartorius Score (MSS) This is a more detailed and dynamic classification system, based on the counting of individual nodules and fistulas within seven anatomical regions. The system which was developed by Sartorius et al and later modified, is the first disease-specific instrument for dynamically measuring clinical severity of HS. Calculating MSS requires measuring the longest distance between two lesions of the same type within each anatomical region and applying predetermined weights to specific types of lesion characteristics . Disadvantages The system is time consuming and sometimes difficult to interpret; consequently, MSS is not optimal for evaluating inflammatory manifestations in clinical practice or trials.

21. The Modified Sartorius Score For Evaluation Of Disease Severity

22.   HS Physician’s Global Assessment (PGA) HS-PGA is relatively easy to use and is frequently used to measure clinical improvement in clinical trials of medical treatments. It classifies HS severity by counting the number of abscesses, fistulas, inflammatory and non inflammatory nodules in all skin areas. The system describes six disease stages, I ncreasing in severity on a scale from 1 to 6 (from stage 1: clear, non inflammatory nodules to stage 6: severe, >5 abscesses or draining fistulas ). However , a serious limitation of HS-PGA is that patients could experience clinically important improvement but not gain a meaningful reduction in their HS-PGA score, as patients in the most severe category may show marked heterogeneity

23.   HS-specific severity index This score incorporates categorical objective and subjective parameters. Body surface area involved , Number of skin lesions , pain severity (determined through a visual analog scale), and drainage ( determined by the number of dressing changes/working hours). HSSI score ≥13 indicate severe disease S cores between 8 and 12  moderate disease S cores between 0 and 7  mild disease .

24. Complications and co‐morbidities Superinfection  a curable complication and should be suspected when flares are preceded by stinging pain or associated with the development of pustules and other superficial lesions STRUCTURAL COMPLICATIONS:  L ymphedema  S crotal elephantiasis  Crohns disease  S quamous cell carcinoma

25. OTHER COMPLICATIONS:  Anaemia (multifactorial)  Hypoalbuminaemia ,  Hypergammaglobulinaemia Amyloidosis Sacral bacterial osteomyelitis Depression.

26. Investigations Microbiology  ( swabs, purulent exudate and tissue) HPE  refractory or atypical cases. Imaging (both ultrasound and magnetic resonance imaging). Routine blood investigation C‐reactive protein

27. MANAGEMENT Treatment  determined by disease severity and its individual subjective impact . The degree of HS clinical involvement is usually ascertained according to the three-stage Hurley system

28. Adjuvant treatment  Patients should be encouraged and supported to lose weight.  Tobacco abstinence  Recommended to wear loose fitting clothes ANALGESICS:  NSAIDS  PARACETAMOL  CENTRALLY ACTING ANALGESICS (TRAMADOL)

29. Topical and Intralesional therapy Clindamycin lotion 0.1%  superficial lesions (folliculitis, papules, and pustules ) but has poor efficacy in deep lesions (nodules and abscess) T opical resorcinol 15%  localized , recalcitrant lesions provides improved disease control A ntiseptics such as chlorhexidine washes or benzoyl peroxide can be used to prevent secondary infections Intralesional triamcinolone(10 mg/mL) (0.2-2.0 mL), into inflamed HS lesions  demonstrated significant reductions in physician-assessed erythema, edema and suppuration.

30. Systemic treatments Clindamycin–rifampicin  In widespread Hurley stage I or mild stage II disease, the combined use of systemic clindamycin and systemic rifampicin (300 mg of clindamycin b.i.d . given in combination with rifampicin [600 mg daily given as either 1 or 2 doses] for 10 weeks. Rifampicin– moxifloxacin –metronidazole Rifampicin 10 mg/kg once daily or 300mg twice daily, moxifloxacin 400 mg daily, and metronidazole 500 mg t.i.d . for 6 weeks ( to avoid neurotoxicity) followed by rifampicin– moxifloxacin therapy has been shown to be effective Tetracycline 500 mg BD with topical clindamycin Minocycline 100mg daily for 6 months and colchicine 0.5mg twice daily for 9 months Doxycycline 100 mg twice daily was used in combination with adalimumab or placebo but it was not independently linked to better outcomes.

31. Dapsone (50mg daily upto 200mg daily can be considered) Treatment for at least 3 months is recommended and long-term maintenance may sustain response. Reserved as third-line treatment in Hurley stage I or II disease . Ertapenem  1 g daily intravenously for 6 weeks was able to decrease the median Sartorius score from 49.5 to 19.0

32. HORMONAL THERAPIES IN HS Androgens influence HS, as evidenced by the effects of pregnancy and menstrual cycles for many patients M onotherapy in females with mild-to-moderate HS or as adjunctive agents for more severe disease. Patients reporting HS flares around menses or with features of PCOS may more likely benefit Only RCT of hormonal therapy compared ethinyl estradiol/ noregestrol with ethinyl estradiol and cyproterone acetate Spironolactone 100 - 150 mg daily Metformin , 500 mg 2 to 3 times daily  significant improvement in Sartorius score

33. RETINOIDS IN HS Isotretinoin monotherapy, 0.5 to 1 mg/kg/d x 4 to 10 months Acitretin 0.5-0.6 mg/kg/ d,x 3-12 months Contraindicated in women with reproductive potential 2 nd & 3 rd line of treatment or in patients with severe concomitant acne

34. SYSTEMIC IMMUNOSUPPRESSANTS A vailable limited evidence does not support the use of methotrexate or azathioprine in the treatment of HS . Cyclosporine 3-5mg/kg  considered in patients with recalcitrant moderate-to-severe HS who have failed or are not candidates for standard therapy . Prednisolone pulses or multiweek tapers as rescue therapy for flares or to bridge to other long-term therapy Effect  rapid and substantial, but side effects limit prolonged use

35. BIOLOGICS IN HS Adalimumab FDA approved 160mg SC on day 1(given in day 1 or split over 2 consecutive days) then 80mg SC 2 weeks later Maintenance  40mg SC weekly or 80mg every other week  Infliximab (5 mg/kg) administered intravenously over a period of 2 hours on day 0, 2, 6, and then regularly every 8 weeks  Expert experience suggests that titration to doses of 10 mg/kg every 4 to 8 weeks may be necessary for optimal control Anakinra  100 mg daily, may be effective for HS .

36. Ustekinumab , 45 to 90 mg administered every 12 weeks , Dose ranging studies of biologics  needed to determine the optimal dosage for management .

37. HS IN pregnancy Topical antibiotics such as clindamycin (1 %), metronidazole (0.75%), and erythromycin (2%) can be applied to active HS lesions twice daily until resolution. Combination therapy  O ral clindamycin and rifampin  first-line for moderate-to severe HS. Clindamycin  pregnancy category B drug and safe during pregnancy and lactation. Rifampin  pregnancy category C drug and is excreted into breast milk and has no adverse effects. Rifampin induces the cytochrome P450 system and contributes to numerous drug-drug interactions, 10-week course of 600 mg clindamycin and 600 mg rifampin daily  pregnant or nursing patients with moderate-to-severe HS.

38. Dapsone safe for use during lactation. 50mg as starting dose and increasing as per clinically for 3 months L ate-line therapy for HS Screening for glucose-6-phosphate dehydrogenase deficiency. H uman placenta most permeable to maternal IgG antibodies in the 3rd trimester M onoclonal antibody based therapy be stopped in the third trimester to avoid placental transfer.

39. Metformin  500 mg to 1500 mg daily over 3 weeks reduced clinical severity and improved quality of life over a course of 24 weeks. Excreted minimally into the breast milk and has not been shown to adversely affect breastfed infants Azathioprine  safely used for other indications during pregnancy and lactation. R easonable option for the management of severe HS during pregnancy.

40. HS IN PEDIATRIC AGE GROUP Pediatric onset of hs  mostly associated with comorbid conditions such as :  Concomitant adrenal hyperplasia,  Obesity  Precocious puberty,  Down syndrome and diabetes. 1 ST LINE THERAPY  Topical and oral antibiotics Hair removal laser, intralesional corticosteroids, hormonal therapies and TNF- α Inhibitors for recalcitrant cases There are currently no treatment guidelines for hs in pediatric age group.

41. Experimental therapies Zinc gluconate (90 mg/day)  maintenance therapy or in combination with other therapies. Other treatments reported to be effective  I.M immunoglobulin and botulinum toxin. Surgery Several lesion‐directed therapies  useful in the management of HS. Incision and drainage  Classical incision and drainage is useful only when frank fluctuating abscesses appear.

42. Localized surgery  Single lesions can be surgically excised. Ablative lasers and electrosurgery  CO2 laser evaporation provides a method whereby all visibly affected tissue can be vaporized using a scanner in a manner akin to macroscopic Mohs ’ surgery. Extensive surgery  In severe disease when entire sites are involved with multiple interconnecting sinus tracts, the only curative method is excision of the entire area involved. For extensive ano ‐genital disease, multidisciplinary collaboration with plastic surgery and, where a temporary colostomy may be required, with colorectal surgery .

43. Non‐ablative lasers/intense pulsed light  Hair removal using light‐based therapies appears to have a beneficial effect in HS  M onthly treatments with both ( Nd:YAG ) laser as well as intense pulsed light  Significant improvement Radiotherapy  It is considered for recalcitrant disease.  Total doses of up to 12 Gy have been administered as single doses of 0.5–1.0 Gy given 4–12 times

44. CONCLUSION HS  chronic inflammatory skin disease that can have a debilitating effect on a patient’s social activities, work activities , and overall quality of life due to frequent disease relapses with painful and foul smelling lesions. It is multifactorial , with interplay between multiple genetic, immunological, behavioral, and endocrine factors playing a key role in its development . Prompt treatment is required to reduce and limit burden

45. References Ballard K, Shuman VL. Hidradenitis Suppurativa . [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Rundle, CW, Price, KN, Hogeling , M., Hsiao, JL, & Shi, VY. Recent advances in hidradenitis suppurativa in pediatrics.  Dermatology Online Journal , 2020. Alikhan A, Sayed C, Alavi A, Alhusayen R, Brassard A, Burkhart C, Crowell K, Eisen DB, Gottlieb AB, Hamzavi I, Hazen PG, Jaleel T, Kimball AB, Kirby J, Lowes MA, Micheletti R, Miller A, Naik HB, Orgill D, Poulin Y. North American clinical management guidelines for hidradenitis suppurativa : A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol . 2019 Jul;81(1):76-90 . Magalhães RF, Rivitti -Machado MC, Duarte GV, et al. Consensus on the treatment of hidradenitis suppurativa - Brazilian Society of Dermatology.  An Bras Dermatol . 2019;94(2 Suppl  1):7-19 . Scuderi N, Monfrecola A, Dessy LA, Fabbrocini G, Megna M, Monfrecola G. Medical and Surgical Treatment of Hidradenitis Suppurativa : A Review. Skin Appendage Disord . 2017 May;3(2): 95-110 Napolitano M, Megna M, Timoshchuk EA, et al. Hidradenitis suppurativa : from pathogenesis to diagnosis and treatment.  Clin Cosmet Investig Dermatol . 2017;10:105-115. Published 2017 Apr 19 . Perng P, Zampella JG, Okoye GA. Management of hidradenitis suppurativa in pregnancy. J Am Acad Dermatol . 2017 May;76(5):979-989.

46. Blok JL, Li K, Brodmerkel C, Horvátovich P, Jonkman MF, Horváth B. Ustekinumab in hidradenitis suppurativa : clinical results and a search for potential biomarkers in serum. Br J Dermatol . 2016 Apr;174(4):839-46. Kimball AB, Kerdel F, Adams D, Mrowietz U, Gelfand JM, Gniadecki R, Prens EP, Schlessinger J, Zouboulis CC, van der Zee HH, Rosenfeld M, Mulani P, Gu Y, Paulson S, Okun M, Jemec GB. Adalimumab for the treatment of moderate to severe Hidradenitis suppurativa : a parallel randomized trial. Ann Intern Med. 2012 Dec 18;157(12):846-55 . Desai N , van der Zee HH. Hidradenitis Suppurativa In: Breathnach S, Cox N, Griffiths C, editor. Rook’s textbook of dermatology.9 th edn . Blackwell publishing Ltd ; John Wiley and sotus ; 2016; 92.1-92.11 Zouboulis C.C& Tsatsou F. Disorders of the Apocrine Sweat Glands In: Kang S, editor. Fitzpatrick’s Dermatology, 9 th edn . Mc-Graw Hill Education; 2019. p.953-959 McMichael A, Curtis R.A, Sanchez G.D and Kelly P. Folliculitis and Other Follicular Disorders In: Bolognia JL, editor. Dermatology, 4 th edn . Elsevier Inc.; 2018. p.583-585.

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