Current evidence in the pathogenesis of hidradenitis suppurativa

Hidradenitis suppurativa (HS) kronična je upalna bolest pilosebacealne jedinice koja svojim recidivirajućim tijekom, bolnošću, pojavom sekreta neugodnog mirisa i estetskim nedostatcima uvelike smanjuje kvalitetu života oboljelih osoba. Vrhunac svoje pojavnosti najčešće doseže u ranim dvadesetim i/ili tridesetim godinama života. Etiopatogeneza bolesti još uvijek nije do kraja razjašnjena, no zna se da je riječ o multifaktorijalnoj bolesti u čijem nastanku ključnu ulogu ima neadekvatan imunološki odgovor tkiva u kombinaciji s rizičnim čimbenicima, poput prekomjerne tjelesne težine, pušenja, mehaničke iritacije te genetskih čimbenika. Okluzija folikula rezultira njegovom dilatacijom, rupturom i izlaskom folikularnog sadržaja u dermis. Stanični debris, bakterije i sebum potiču upalne stanice, mahom makrofage i neutrofile, na pojačanu sintezu i lučenje matriks metaloproteinaza, antimikrobnih peptida i brojnih citokina među kojima se, svojom ulogom, najviše ističu TNF-α i IL-17. Kliničkom slikom HS dominiraju subkutani bolni čvorovi koji progrediraju do dubokih apscesa, drenažnih sinusa te hipertrofičnih ožiljaka i kontraktura u intertriginoznim predjelima. Dijagnoza se postavlja klinički, na temelju anamneze, karakterističnih kožnih lezija te njihove topografije. Sukladno europskim smjernicama, liječenje HS može biti medikamentozno, kirurško, lasersko te kombinacija navedenih modaliteta. Oblik primijenjene terapije ovisi o težini kliničke slike odnosno stupnju zahvaćenosti kože te bolesnikovim komorbiditetitma. Cilj ovog diplomskog rada je prikazati najnovije spoznaje o etiopatogenezi HS kroz prikaz kaskade autoinflamatornih reakcija, aktiviranih različitim signalnim putevima, koje se manifestiraju u obliku kronične upalne kožne bolesti.Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the pilosebaceous unit which, by its recurrent course, pain, unpleasant odour and aesthetic deficiencies, dramatically reduces patient's quality of life. It most often reaches its peak incidence in the early twenties or thirties. The etiopathogenesis of disease has not yet been fully elucidated. Still, it is known that it is multifactorial disease in which inadequate tissue immune response, in combination with risk factors including overweight, smoking, mechanical irritation and genetic factors, plays a key role. Follicle occlusion results in dilatation, rupture and release of follicular content into the dermis. Cellular debris, bacteria and sebum stimulate inflammatory cells, mostly macrophages and neutrophils, to enhanced synthesis and secretion of matrix metalloproteinases, antimicrobial peptides and numerous cytokines, among which, by their role, TNF-α and IL-17 stand out the most. Clinical picture of HS is characterized by painful subcutaneous nodules that progress to deep abscesses, drainage sinuses, and hypertrophic scars and contractures in the intertriginous areas. Diagnosis is made clinically, based on the case history, characteristic skin lesions and their topography. According to European guidelines, the treatment of HS can be medicamentous, surgical, laser and a combination of these treatment modalities. The form of used therapy depends on the severity of the clinical picture, the degree of skin involvement and the patient's comorbidities. Aim of this thesis is to present current evidence in the pathogenesis of HS through the cascade of autoinflammatory reactions, activated by signaling pathways, which manifests in the form of chronic inflammatory skin disease