Necrotising fasciitis – Patofizjologia i mechanizm

Necrotising fasciitis
Patofizjologia i mechanizm

Martwicze zapalenie powięzi (necrotising fasciitis) to szybkopostępująca, zagrażająca życiu infekcja tkanek miękkich, charakteryzująca się martwicą powięzi i tkanki podskórnej, z prędkością rozprzestrzeniania się nawet 2,5 cm/godz. Etiologia obejmuje głównie zakażenia polimikrobialne (typ I, 70-80%) z udziałem bakterii tlenowych i beztlenowych, oraz monomikrobialne (typ II, 20-30%) najczęściej wywołane przez Streptococcus pyogenes i Staphylococcus aureus (w tym MRSA). Patogeneza opiera się na wniknięciu bakterii przez przerwanie ciągłości skóry, rozprzestrzenianiu się infekcji wzdłuż powięzi, uwalnianiu toksyn i enzymów bakteryjnych, zakrzepicy naczyń oraz masowej proliferacji limfocytów T indukowanej przez superantygeny, co prowadzi do zespołu toksycznego wstrząsu, sepsy i niewydolności wielonarządowej. Charakterystyczne czynniki wirulencji to białko M, egzotoksyny pirogenne SPE A, B, C oraz leukocydyna Pantona-Valentine’a (PVL) w przypadku S. aureus. Czynniki ryzyka obejmują cukrzycę, immunosupresję, marskość wątroby, choroby naczyń obwodowych, podeszły wiek, urazy, zabiegi chirurgiczne oraz stosowanie NLPZ i steroidów.

Patogeneza martwiczego zapalenia powięzi

Martwicze zapalenie powięzi (necrotising fasciitis) to rzadka, lecz groźna infekcja tkanek miękkich charakteryzująca się szybko postępującym zapaleniem i martwicą powięzi oraz tkanki podskórnej. Proces chorobowy przebiega wzdłuż płaszczyzny powięziowej, która ma słabe unaczynienie, co sprzyja szybkiemu rozprzestrzenianiu się infekcji. W około 80% przypadków jest to bezpośredni skutek zakażenia bakteryjnego wprowadzonego przez przerwanie ciągłości skóry¹. Zakażenie może również powstać w wyniku krwiopochodnego rozsiewu bakterii lub bezpośredniego rozprzestrzeniania się z perforowanego narządu wewnętrznego¹.

Czynniki etiologiczne

W zależności od czynnika etiologicznego, martwicze zapalenie powięzi dzieli się na kilka typów:

Typ I – zakażenie polimikrobialne (mieszane), stanowiące 70-80% przypadków, obejmujące tlenowe i beztlenowe bakterie. Występuje najczęściej w okolicach jamy brzusznej lub krocza¹. Dokładny mechanizm patogenezy typu I nie jest w pełni poznany, ale wiadomo, że różne gatunki bakterii działają synergistycznie, wzmacniając rozprzestrzenianie się infekcji¹.
Typ II – zakażenie monomikrobialne, stanowiące 20-30% przypadków, najczęściej spowodowane przez Streptococcus pyogenes (paciorkowiec grupy A) samodzielnie lub w połączeniu z gronkowcem (Staphylococcus aureus). Dotyczy głównie kończyn². Metycylinooporny Staphylococcus aureus (MRSA) stanowi do jednej trzeciej zakażeń typu II³.
Typ III – wywoływany przez organizmy morskie, głównie Vibrio vulnificus, bakterię występującą w wodzie słonej, która może wywoływać martwicze zapalenie powięzi po wniknięciu do organizmu przez przerwanie ciągłości skóry⁴.
Typ IV – najrzadszy typ (poniżej 1% przypadków), spowodowany głównie przez grzyby Candida albicans⁵.

Historycznie, paciorkowce grupy A beta-hemolizujące (GABS) były identyfikowane jako główna przyczyna tego zakażenia. Jednak w ostatnich dziesięcioleciach badacze odkryli, że martwicze zapalenie powięzi jest zwykle polimikrobialne, a nie monomikrobialne¹. Bakterie beztlenowe są obecne w większości martwiczych zakażeń tkanek miękkich, zwykle w połączeniu z tlenowymi organizmami Gram-ujemnymi².

Mechanizm patogenezy

Mechanizm patogenezy martwiczego zapalenia powięzi obejmuje kilka etapów:

Wniknięcie bakterii – bakterie wnikają do organizmu przez przerwanie ciągłości skóry (uraz, ukąszenie, ukłucie, operacja) lub rzadziej drogą krwiopochodną¹.
Rozprzestrzenianie się zakażenia – organizmy rozprzestrzeniają się z tkanki podskórnej wzdłuż powierzchownych i głębokich płaszczyzn powięziowych, prawdopodobnie ułatwiane przez enzymy bakteryjne i toksyny¹.
Uwalnianie toksyn i enzymów – bakterie uwalniają różnorodne proteazy i enzymy, które uszkadzają tkanki gospodarza. Te enzymy proteolityczne są regulowane przez wiele procesów transkrypcyjnych i potranslacyjnych¹.
Zakrzepica naczyń – bakterie i ich toksyny powodują zakrzepicę w naczyniach krwionośnych, co prowadzi do niedokrwienia i martwicy tkanek¹. Większość małych i średnich naczyń krwionośnych ulega zakrzepicy¹.
Martwica tkanek – postępujące niedokrwienie prowadzi do martwicy powięzi powierzchownej, powięzi głębokiej, tkanki tłuszczowej podskórnej, nerwów, tętnic i żył¹.
Reakcja ogólnoustrojowa – toksyny bakteryjne wchłaniane do krwiobiegu mogą prowadzić do zespołu toksycznego wstrząsu, sepsy i niewydolności wielonarządowej¹.

Procesy te zachodzą szybko – martwicze zapalenie powięzi postępuje z prędkością nawet 2,5 cm (1 cal) na godzinę¹, co podkreśla pilną potrzebę wczesnej interwencji chirurgicznej.

Czynniki wirulencji bakterii

Bakterie powodujące martwicze zapalenie powięzi posiadają szereg czynników wirulencji, które przyczyniają się do ich zjadliwości i zdolności do wywoływania ciężkiego zakażenia.

Paciorkowce grupy A (Streptococcus pyogenes)

Streptococcus pyogenes (GAS) posiada liczne czynniki wirulencji, które odgrywają kluczową rolę w patogenezie martwiczego zapalenia powięzi typu II:

Białko M – powierzchniowe białko, które hamuje fagocytozę bakterii przez neutrofile i makrofagi, pozwalając im na uniknięcie mechanizmów obronnych gospodarza. Białko M zidentyfikowano jako silny induktor zapalenia, odpowiedzialny za ciężkość martwiczego zapalenia powięzi¹. Szczególnie typy M1, M3, M12 i M28 są często związane z martwiczym zapaleniem powięzi¹.
Otoczka polisacharydowa – utrudnia fagocytozę bakterii przez komórki układu odpornościowego¹.
Streptokokowe egzotoksyny pirogenne (SPE) A, B i C – są bezpośrednio toksyczne i są zwykle wytwarzane przez szczepy powodujące martwicze zapalenie powięzi².
Superantygeny – stymulują masową proliferację limfocytów T i kaskadowe uwalnianie cytokin, aktywując proces zapalny. Ten mechanizm prowadzi do zespołu szoku toksycznego i może przyczyniać się do ciężkiego przebiegu systemowego².
Enzymy hydrolityczne – hialuronidaza, streptokinaza, streptolizyny i inne enzymy degradujące tkanki gospodarza i ułatwiające rozprzestrzenianie się bakterii¹.

Zmienność genetyczna paciorkowców odgrywa również istotną rolę w ich zjadliwości. Pojedyncze zmiany nukleotydowe są najczęstszą przyczyną naturalnej zmienności genetycznej wśród członków tego samego gatunku³. Badania wykazały, że mutacje punktowe w genomie GAS mogą znacząco zmieniać jego zjadliwość, wpływając na ekspresję kluczowych czynników wirulencji, takich jak proteaza SpeB¹.

Staphylococcus aureus

Staphylococcus aureus, w tym szczepy MRSA, również posiadają czynniki wirulencji przyczyniające się do rozwoju martwiczego zapalenia powięzi:

Leukocydyna Pantona-Valentine’a (PVL) – toksyna produkowana przez niektóre szczepy S. aureus, która może powodować ciężkie zapalenie mięśni towarzyszące martwiczemu zapaleniu powięzi¹.
Szczepy USA 300 CA-MRSA – najczęściej izolowane szczepy z przypadków martwiczego zapalenia powięzi wywołanego przez S. aureus, które wyrażają leukocydynę Pantona-Valentine’a i inne cechy zjadliwości¹.

Jednak konkretne role tych toksyn i patogeneza ciężkich zakażeń skóry i tkanek miękkich wywoływanych przez gronkowce pozostają niejasne².

Zakażenia polimikrobialne

W przypadku zakażeń polimikrobialnych (typ I), bakterie tlenowe i beztlenowe działają synergistycznie, wzmacniając proces chorobowy:

Bakterie tlenowe – zużywają tlen w środowisku, tworząc warunki beztlenowe sprzyjające wzrostowi bakterii beztlenowych. Końcowymi produktami tlenowego metabolizmu są dwutlenek węgla i woda⁴.
Bakterie beztlenowe – wytwarzają wodór, azot i siarkowodór, które niszczą kwas hialuronowy, umożliwiając rozprzestrzenianie się infekcji².
Osłabiona funkcja neutrofili – fagocyty wielojądrzaste (PMN) wykazują zmniejszoną funkcję w warunkach hipoksycznych ran, co sprzyja wzrostowi fakultatywnych organizmów tlenowych³.

Interakcja między różnymi szczepami bakterii w zakażeniach polimikrobialnych może modulować zjadliwość i odpowiedź immunologiczną, jak widać w mieszanych zakażeniach szczepami Aeromonas hydrophila².

Patofizjologia martwiczego zapalenia powięzi

Martwicze zapalenie powięzi charakteryzuje się szeroko rozprzestrzenioną martwicą tkanki podskórnej i powięzi⁴. Proces ten przebiega w kilku fazach:

Faza początkowa

Zakażenie zaczyna się w powięzi powierzchownej. Enzymy i białka uwalniane przez odpowiedzialne mikroorganizmy powodują martwicę warstw powięziowych³. Poziome rozprzestrzenianie się infekcji może nie być klinicznie widoczne na powierzchni skóry, co może opóźnić diagnozę⁴.

Bakterie produkują enzymy, takie jak hialuronidaza, które trawią powięzię². Wytwarzają również superantygeny, które prowadzą do zespołu toksycznego wstrząsu paciorkowcowego³.

Progresja zakażenia

Infekcja rozprzestrzenia się następnie pionowo w górę do skóry i w dół do głębszych struktur⁵. Zakrzepica zamyka tętnice i żyły, prowadząc do niedokrwienia i martwicy tkanek⁶.

Histologiczne kryteria diagnostyczne opisane przez Stamenkovic i Lew (1984) obejmują: martwicę powięzi powierzchownej, infiltrację wielojądrową skóry właściwej i powięzi, zakrzepy włóknikowe tętnic i żył przebiegających przez powięzię, zapalenie naczyń z martwicą włóknikową ścian tętniczych i żylnych, obecność mikroorganizmów w zniszczonej powięzi i skórze właściwej oraz brak zajęcia mięśni⁴.

Zmiany naczyniowe

Zakażenie tkanki podskórnej prowadzi do zakrzepicy żylnej podskórnej i infiltracji komórek zapalnych z tworzeniem ropni, a następnie do niedokrwienia tętniczego z powodu zapalenia błony wewnętrznej naczyń¹. Powoduje to krytyczne niedokrwienie skóry, z tworzeniem pęcherzy².

Następstwem jest martwica skóry i zgorzel kolikwacyjna³. Na tym etapie ból zmniejsza się w wyniku zniszczenia powierzchownych nerwów skórnych⁴.

Zmiany kliniczne

Początkowo skóra, która wydaje się niezmieniona, przechodzi w rumieniową, czerwono-purpurową do niebiesko-szarej barwę². W ciągu 24-48 godzin skóra może stać się ciemna, rozwija się niedokrwienie skóry, tworzą się pęcherze wypełnione płynem o barwie słomkowej, które stopniowo ciemnieją z powodu płynu krwotocznego¹.

Przebarwienie skóry wskazuje na zakrzepicę małych naczyń w brodawkach skóry. Dotknięte tkanki stopniowo ciemnieją od czerwonego do fioletowego, niebieskiego i czarnego. Gdy pojawia się zgorzel, skóra staje się znieczulona, ponieważ powierzchowne nerwy obumierają¹.

Zmiany stają się ostro odgraniczone. Kiedy skóra złuszcza się, tworzy się martwiczny strup, przypominający oparzenie trzeciego stopnia².

Objawy ogólnoustrojowe

Zaawansowane stadia zakażenia charakteryzują się objawami ogólnoustrojowymi, takimi jak gorączka, tachykardia i sepsa². Może wystąpić zespół odpowiedzi zapalnej (SIRS), który może postępować do niewydolności wielonarządowej¹.

W martwiczym zapaleniu powięzi typu II, spowodowanym przez paciorkowce grupy A, masowa proliferacja limfocytów T i uwalnianie cytokin mogą występować z powodu działania białka M paciorkowca hemolizującego grupy A. To filamentowe białko ma właściwości antyfagocytarne i jest ważnym czynnikiem zjadliwości, ponieważ może wytwarzać wiele egzotoksyn ropnych, które działają jak superantygeny².

Czynniki ryzyka i predysponujące

Martwicze zapalenie powięzi może wystąpić u osób zdrowych, jednak istnieją czynniki zwiększające ryzyko zachorowania:

Choroby współistniejące

Cukrzyca – pacjenci z cukrzycą wykazują upośledzenie gojenia się ran skórnych i zwiększoną podatność na zakażenia, co może wpływać na przebieg zakażeń tkanek miękkich¹.
Stany immunosupresji – w tym nowotwory, leczenie immunosupresyjne, zakażenie HIV¹.
Marskość wątroby – zwiększa podatność na zakażenia bakteryjne¹.
Choroby naczyń obwodowych – powodują gorsze ukrwienie tkanek².
Podeszły wiek – związany z wyższą śmiertelnością³.

Czynniki lokalne

Urazy – nawet drobne urazy mogą stanowić wrota zakażenia².
Zabiegi chirurgiczne – mogą stanowić wrota zakażenia¹.
Ukąszenia owadów lub zwierząt – umożliwiają wniknięcie bakterii¹.
Zakażenia skórne – mogą prowadzić do głębszego zakażenia tkanek¹.
Choroby infekcyjne górnych dróg oddechowych lub ostre/przewlekłe bakteryjne zapalenie zatok – mogą prowadzić do martwiczego zapalenia powięzi oczodołu².

Leki i substancje

Niesteroidowe leki przeciwzapalne (NLPZ) – mogą zwiększać ryzyko martwiczego zapalenia powięzi poprzez upośledzenie odpowiedzi immunologicznej lub maskowanie objawów wtórnego zakażenia, prowadząc do opóźnionej diagnozy i leczenia¹. Mechanizm, w którym NLPZ zwiększają ryzyko martwiczego zapalenia powięzi, może być związany z hamowaniem odpowiedzi immunologicznej lub maskowaniem objawów wczesnej infekcji².
Steroidy – terapia kortykosteroidami została wykazana jako czynnik predysponujący².
Dapagliflozyna – rzadkie, ale poważne bakteryjne zakażenie powodujące uszkodzenie tkanki pod skórą (martwicze zapalenie powięzi) w okolicy między odbytem a narządami płciowymi (krocze) obserwowano u kobiet i mężczyzn z cukrzycą przyjmujących dapagliflozynę¹.

Leczenie martwiczego zapalenia powięzi

Leczenie martwiczego zapalenia powięzi jest wielokierunkowe i wymaga szybkiego wdrożenia, aby zmniejszyć śmiertelność, która wynosi od 20 do 80%⁴.

Leczenie chirurgiczne

Podstawą leczenia martwiczego zapalenia powięzi jest wczesne i agresywne chirurgiczne usunięcie martwiczych tkanek (debridement). Nie należy tracić czasu na wezwanie konsultacji chirurgicznej. Im wcześniej przeprowadzona zostanie operacja, tym lepszy wynik⁵. Wcześniejsza operacja może pomóc zminimalizować utratę tkanki i wyeliminować potrzebę amputacji kończyny z zgorzelą⁶.

W złożonych przypadkach może być konieczne powtórzenie chirurgicznego oczyszczenia w ramach operacji drugiego spojrzenia. Konieczne jest usunięcie wszystkich niezdrowych lub martwiczych tkanek, ponieważ czas i zakres pierwszego oczyszczenia są najważniejszymi czynnikami decydującymi o zmniejszeniu śmiertelności. Opóźnienia w chirurgicznym oczyszczeniu, usunięciu martwicy i fasciotomii (12 godzin) mogą prowadzić do piorunującego martwiczego zapalenia powięzi i wyższej śmiertelności¹.

Zwykle konieczne jest kilkakrotne oczyszczanie chirurgiczne – średnio 3,8 zabiegów na pacjenta¹. 24-godzinne opóźnienie w leczeniu zwiększa śmiertelność o 18%².

Antybiotykoterapia

Antybiotykoterapia jest ważnym uzupełnieniem kontroli źródła zakażenia i może zapobiec progresji wstrząsu septycznego, gdy jest stosowana wcześnie³. Terapia antybiotykowa opiera się na wynikach barwienia metodą Grama. Po potwierdzeniu, że etiologią jest paciorkowiec grupy A, zalecane leczenie to wysokie dawki penicyliny i klindamycyny (która hamuje produkcję toksyn)³.

W przypadku zakażeń polimikrobialnych (typ I) zalecane są antybiotyki o szerokim spektrum działania, takie jak glikopeptydy lub linezolid z antybiotykami o szerokim spektrum działania, takimi jak karbapenemy lub piperacylina/tazobaktam¹.

Dodanie klindamycyny jest dobrze poparte – szczególnie w przypadku paciorkowców grupy A, gdzie hamuje ona bakteryjną syntezę endotoksyny⁵.

Terapie wspomagające

Terapia tlenem hiperbarycznym (HBOT) – może być skuteczna w przypadku małych ran, ale nie ma dowodów, że ta terapia poprawia gojenie lub przedłuża życie w przypadku dużych ran⁷. HBOT może poprawiać przeżycie pacjentów, zmniejszając liczbę chirurgicznych oczyszczeń i potencjalnie zakres rekonstrukcji poprzez hamowanie systemowej odpowiedzi zapalnej i poprawę aktywności leukocytów. Ponadto może ułatwiać transport niektórych antybiotyków, takich jak aminoglikozydy¹. Jest uważana za cenną w poprawie gojenia i zapobieganiu dalszemu uszkodzeniu tkanek poprzez zwiększenie ciśnienia cząstkowego tlenu w zakażonych tkankach miękkich¹. Może być mniej skuteczna w zakażeniach tlenowych².
Dożylne immunoglobuliny (IVIG) – wykazano, że są korzystne u pacjentów z martwiczym zapaleniem powięzi wywołanym przez paciorkowca grupy A, które postępowało do zespołu wstrząsu toksycznego². Badacze powiązali skuteczność IVIG w martwiczym zapaleniu powięzi z jego zdolnością do zmniejszania ogólnoustrojowej odpowiedzi zapalnej poprzez ukierunkowanie na egzotoksyny³. Mechanizm działania IVIG u osób z martwiczym zapaleniem powięzi nie jest w pełni zrozumiany. Eksperci zdrowotni uważają, że IVIG może działać poprzez: neutralizację toksyn bakteryjnych, zapobieganie nieprawidłowo szybkiemu namnażaniu się określonych komórek odpornościowych, zmniejszanie stanu zapalnego¹.

Mimo obiecujących wyników w badaniach kazuistycznych, kilka wyzwań nadal ogranicza stosowanie IVIG w martwiczym zapaleniu powięzi. Badacze muszą jeszcze określić: najbardziej skuteczny czynnik IVIG, czas terapii, dawkę, czas trwania leczenia².

Nowe odkrycia w patogenezie

Najnowsze badania nad patogenezą martwiczego zapalenia powięzi przyniosły interesujące odkrycia, które mogą wpłynąć na przyszłe podejście do diagnostyki i leczenia:

Defekty genetyczne

Nowe fińskie badanie sugeruje, że martwicze zapalenie powięzi, zagrażające życiu zapalenie tkanki łącznej prowadzące do martwicy tkanek, może być spowodowane defektem genetycznym¹. Badanie to analizowało mechanizm, w jaki defekt genetyczny powoduje nadmierną i gwałtowną odpowiedź zapalną².

U pacjentów łagodny uraz, operacja lub zakażenie wywołały niekontrolowaną reakcję zapalną prowadzącą do ciężkiego głębokiego zapalenia tkanki³. Badacze znaleźli aktywujący zapalenie defekt w genie NFKB1 u trzech fińskich i trzech zagranicznych pacjentów pediatrycznych i dorosłych z ciężkim zapaleniem powięzi⁴.

Dzięki nowym technikom edycji genów byli w stanie zidentyfikować charakter odpowiedzi zapalnej i mechanizmy, za pomocą których defekt genetyczny powoduje silną odpowiedź zapalną⁵.

Mutacje genetyczne bakterii

Badania wykazały, że pojedyncze mutacje nukleotydowe w genomie paciorkowca grupy A mogą znacząco zmieniać jego zjadliwość, wpływając na ekspresję kluczowych czynników zjadliwości, takich jak proteaza SpeB³.

Stwierdzono, że funkcja dzikiego typu mtsR jest wymagana, aby paciorkowiec grupy A powodował martwicze zapalenie powięzi u myszy i naczelnych innych niż ludzie³.

Ponadto interakcja między różnymi szczepami bakterii w zakażeniach polimikrobialnych może modulować zjadliwość i odpowiedź immunologiczną, jak obserwowano w mieszanych zakażeniach szczepami Aeromonas hydrophila⁴.

Znaczenie wczesnej diagnozy

Pomimo rozszerzonego zrozumienia patofizjologii sepsy, współczesnych wyrafinowanych metod diagnostycznych i nowoczesnych zaawansowanych antybiotyków, chirurgiczne oczyszczenie pozostaje podstawą leczenia martwiczego zapalenia powięzi¹.

Badania kliniczne na temat tej rzadkiej i śmiertelnej choroby brakuje dowodów wysokiej jakości, podkreślając konieczność współpracy wieloośrodkowej w tym wysiłku naukowym².

Złotym standardem diagnozy jest eksploracja operacyjna. Chirurgiczne badanie jest jedynym sposobem, aby definitywnie ustalić diagnozę i odróżnić martwicze zapalenie powięzi od innych jednostek chorobowych¹.

Typ martwiczego zapalenia powięzi	Czynniki etiologiczne	Charakterystyka	Główne czynniki wirulencji
Typ I (70-80% przypadków)	Zakażenie polimikrobialne – mieszane bakterie tlenowe i beztlenowe	Wolniejszy przebieg, ewoluuje przez 2-4 dni, najczęściej w okolicach jamy brzusznej lub krocza	Synergistyczne działanie różnych gatunków bakterii, wytwarzanie gazów (wodór, azot, siarkowodór)
Typ II (20-30% przypadków)	Streptococcus pyogenes (samodzielnie lub z S. aureus)	Bardziej podstępny początek, ale szybsza progresja, głównie kończyny	Białko M, superantygeny, egzotoksyny pirogenne (SPE A, B, C)
Typ III (rzadkie)	Vibrio vulnificus, organizmy morskie, Clostridium	Związane z ekspozycją na wodę morską, często po urazach u rybaków	Toksyny, enzymy proteolityczne
Typ IV (poniżej 1% przypadków)	Głównie Candida albicans	Zakażenia grzybicze, związane z immunosupresją	Enzymy hydrolityczne, inwazja tkanek

Podsumowanie patogenezy

Martwicze zapalenie powięzi to ciężkie, zagrażające życiu zakażenie tkanek miękkich, charakteryzujące się szybko postępującym zapaleniem i martwicą powięzi i tkanki podskórnej¹. Patogeneza tej choroby jest złożona i obejmuje interakcję między czynnikami bakteryjnymi a odpowiedzią gospodarza³.

Kluczowe aspekty patogenezy martwiczego zapalenia powięzi obejmują:

Wniknięcie bakterii przez przerwanie ciągłości skóry lub rzadziej drogą krwiopochodną¹.
Wytwarzanie przez bakterie toksyn powodujących śmierć tkanek².
Rozprzestrzenianie się zakażenia wzdłuż płaszczyzn powięziowych, ułatwiane przez enzymy bakteryjne⁵.
Zakrzepica naczyń mikrokrążenia powięzi powierzchownej prowadząca do wtórnej zgorzeli skóry¹.
Masowa proliferacja limfocytów T i uwalnianie cytokin w odpowiedzi na superantygeny bakteryjne⁴.
Progresja do ogólnoustrojowego zespołu odpowiedzi zapalnej (SIRS), sepsy i niewydolności wielonarządowej⁵.

Wczesna diagnoza i interwencja chirurgiczna są kluczowe dla poprawy wyników leczenia. Opóźnione rozpoznanie i leczenie są związane z wyższą śmiertelnością i powikłaniami, w tym wstrząsem septycznym, niewydolnością wielonarządową, utratą kończyny, ciężkim bliznowaceniem i śmiercią⁸².

Kolejne rozdziały

Zapraszamy do dalszego czytania naszego leksykonu.

Wybierz kolejny rozdział z menu poniżej, aby otworzyć nową podstronę kompedium wiedzy i uzyskać szczegółowe informację o leku, substancji lub chorobie.

Materiały źródłowe

#1 Necrotizing Fasciitis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK430756/
Necrotizing fasciitis is a subset of aggressive skin and soft tissue infections that cause muscle fascia and subcutaneous tissue necrosis. The infection typically travels along the fascial plane, which has a poor blood supply. The infectious process can rapidly spread, causing infection of the fascia and perifascial planes and secondary infection of the overlying and underlying skin, soft tissue, and muscle. […] Necrotizing fasciitis is typically an acute process that occurs rapidly over several days. In approximately 80% of cases, it is a direct sequela of bacterial infection introduced through a break in the skins integrity. […] The infection rapidly transits the muscle fascia. After several days, the overlying skin, which initially appears unaffected, will transition to an erythematous, reddish-purple to bluish-gray hue.
#1 Pitfalls in Diagnosing Necrotizing Fasciitis | PSNet
https://psnet.ahrq.gov/web-mm/pitfalls-diagnosing-necrotizing-fasciitis
Necrotizing fasciitis is a peculiar condition in which the skin manifestations apparent to the patient or health care provider lag behind the disease progression under the skin. Understanding the pathophysiology enables the clinician to appreciate the insidious progression of NF despite the paucity of skin signs. […] Microbial invasion of the subcutaneous tissues occurs either through external trauma (often seen in fishermen who have injuries from marine organisms), direct spread from a perforated viscus, or from a hematogenous source. […] Historically, group Abeta-hemolytic streptococcus has been identified as the major cause of this infection. During the last two decades, scientists have reported that the pathogenesis of necrotizing fasciitis is usually polymicrobial (type 1 NF) rather than monomicrobial (type 2 NF).
#1 Necrotizing fasciitis – Wikipedia
https://en.wikipedia.org/wiki/Necrotizing_fasciitis
Type I infection: This is the most common type of infection, and accounts for 70 to 80% of cases. It is caused by a mixture of bacterial types, usually in abdominal or groin areas. […] In polymicrobial (mixed) infections, Group A Streptococcus (S. pyogenes) is the most commonly found bacterium, followed by S. aureus. However, when the infection is caused solely by S. pyogenes and/or S. aureus, it is classified as a Type II infection. […] Type II infection: This infection accounts for 20 to 30% of cases, mainly involving the extremities. This involves Streptococcus pyogenes, alone or in combination with staphylococcal infections. Methicillin-resistant Staphylococcus aureus (MRSA) is involved in up to a third of Type II infections. […] Type III infection: Vibrio vulnificus is a bacterium found in saltwater. It occasionally causes NF after entering the body through a break in the skin. One in three patients with a V. vulnificus infection develop necrotizing fasciitis. […] Type IV infection: This type of NF accounts for less than 1% of cases. It is mostly caused by the Candida albicans fungus. Risk factors include age and immunodeficiency.
#1 Necrotizing fasciitis pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Necrotizing_fasciitis_pathophysiology
The pathogenesis of necrotizing fasciitis is the result of bacterial and host factors. […] The exact pathogenesis of type 1 necrotizing fasciitis is not fully understood. It is thought that type 1 NF is caused by polymicrobial species that work synergistically to enhance the spread of infection. […] Group A streptococcus is the most common causative agent of type 2 NF. The pathogenesis of type 2 NF is the result of the following process: Inhibition of phagocytosis of bacteria by hyaluronic acid capsule and M protein. Adherence of bacteria to host cell through adherence factors such as M protein, protein F and lipoteichoic acid. Release of exotoxins (streptococcal pyogenic exotoxins and superantigen) into blood produce massive proliferation of T cells and cascading release of cytokines activating inflammatory process. […] The massive release of cytokines result in systemic inflammatory response syndrome resulting in shock, organ failure, depression of myocardial function and immune suppression.
#1 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
Necrotizing fasciitis is characterized by widespread necrosis of the subcutaneous tissue and the fascia. […] Although the pathogenesis of necrotizing fasciitis is still open to speculation, the rapid and destructive clinical course of necrotizing fasciitis is thought to be due to multibacterial symbiosis and synergy. […] Historically, group A beta-hemolytic Streptococcus (GABS) has been identified as a major cause of this infection. […] During the last few decades, researchers have found that necrotizing fasciitis is usually polymicrobial rather than monomicrobial. […] Anaerobic bacteria are present in most necrotizing soft-tissue infections, usually in combination with aerobic gram-negative organisms. […] Facultative aerobic organisms grow because polymorphonuclear neutrophils (PMNs) exhibit decreased function under hypoxic wound conditions.
#1 Necrotizing Fasciitis: Analysis of the Clinical, Microbiological Pattern, and Factors Associated with Mortality
https://clinmedjournals.org/articles/ijsrp/international-journal-of-surgery-research-and-practice-ijsrp-9-142.php?jid=ijsrp
Necrotizing fasciitis is a life-threatening rapidly progressing bacterial infection associated with necrotic changes of the superficial fascia, subcutaneous tissue, and the deep fascia. […] The precise pathogenesis of necrotizing fasciitis is not entirely developed. Inoculation of microbes can occur through minor trauma, snake or insect bite, or surgical incisions. Under favorable environmental conditions like immunocompromised states, renal failure, liver failure, and diabetes mellitus, the organisms multiply to cause the disease process. […] The aggressive course of necrotizing fasciitis could lead to considerable morbidity and mortality. Acidosis and hypoalbuminemia were found to be factors strongly associated with high mortality. Other possible factors include truncal location (from the neck to the pelvic region) and leukocytosis.
#1 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
Carbon dioxide and water are the end products of aerobic metabolism. […] In necrotizing fasciitis, group A hemolytic streptococci and Staphylococcus aureus, alone or in synergism, are frequently the initiating infecting bacteria. […] Organisms spread from the subcutaneous tissue along the superficial and deep fascial planes, presumably facilitated by bacterial enzymes and toxins. […] Important bacterial factors include surface protein expression and toxin production. […] Streptococcal pyrogenic exotoxins (SPEs) A, B, and C are directly toxic and tend to be produced by strains causing necrotizing fasciitis. […] The poor prognosis associated with necrotizing fasciitis has been linked to infection with certain streptococcal strains. […] Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species.
#1 Molecular pathogenesis of necrotizing fasciitis – PubMed
https://pubmed.ncbi.nlm.nih.gov/19737105/
Necrotizing fasciitis, also known as the flesh-eating disease, is a severe invasive infection associated with very high rates of human morbidity and mortality. […] Herein, we review recent discoveries bearing on the molecular pathogenesis of GAS necrotizing fasciitis. […] Importantly, the integration of new technologies and the development of human-relevant animal models have markedly expanded our understanding of the key pathogen-host interactions underlying GAS necrotizing fasciitis. […] For example, we now know that GAS organisms secrete a variety of proteases that disrupt host tissue and that these proteolytic enzymes are regulated by multiple transcriptional and posttranslational processes. […] This pathogenesis knowledge will be crucial to supporting downstream efforts that seek to develop novel vaccines and therapeutic agents for this serious human infection.
#1 Necrotising fasciitis
https://dermnetnz.org/topics/necrotising-fasciitis
Necrotising fasciitis is a very serious bacterial infection of the soft tissue and fascia. The bacteria multiply and release toxins and enzymes that result in thrombosis in the blood vessels. The result is the destruction of the soft tissues and fascia. […] The infection starts in the superficial fascia. Enzymes and proteins released by the responsible micro-organisms cause necrosis of fascial layers. Horizontal spread of infection may not be clinically apparent on the skin surface and hence diagnosis may be delayed. The infection then spreads vertically up into the skin and down into deeper structures. Thrombosis occludes the arteries and veins leading to ischaemia and necrosis of the tissues. […] Streptococci produce M proteins, which initiate an inflammatory response with the release of numerous cytokines (IL-1, IL-6, TNF). Exotoxins, which destroy neutrophils allowing bacterial growth and destroying tissues. […] Aerobic and anaerobic bacteria produce hydrogen, nitrogen, and hydrogen sulfide gases that destroy hyaluronic acid enabling the spread of infection.
#1 Necrotizing Fasciitis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK430756/
Advanced stages of the infection are characterized by systemic symptoms such as fever, tachycardia, and sepsis. […] Anaerobic bacteria mixed with aerobic organisms are commonly found in most soft tissue infections. […] The majority of small and medium-sized blood vessels will be thrombosed. […] The treatment of necrotizing fasciitis is surgery, and no time should be wasted calling for a surgical consult. The earlier the surgery is undertaken, the better the outcome. […] The earlier the surgery may help minimize tissue loss and eliminate the need for amputation of a gangrenous extremity. […] Hyperbaric oxygen therapy may be effective for small wounds, but there is no evidence that this therapy improves healing or prolongs life for large wounds. […] Necrotizing fasciitis is a serious life-threatening infection with mortality rates ranging from 20 to 80%. Poor prognosis has been linked to certain streptococcal strains, advanced age, uncontrolled diabetes, state of immunosuppression, and delayed surgery. […] The complications that can manifest with necrotizing fasciitis are as follows: multiorgan failure, septic shock, loss of extremity, severe scarring, toxic shock, and death.
#1 Necrotizing fasciitis pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Necrotizing_fasciitis_pathophysiology
The pathophysiology of necrotizing fasciitis is common to all types, but the speed of development and associated clinical features differs depending on the causative organisms. Following transmission, the bacteria uses the entry site to invade the fascial planes which causes the wide spread necrosis of superficial fascia, deep fascia, subcutaneous fat, nerves, arteries, and veins. […] The pathogenesis of necrotizing fasciitis is the result of bacterial and host factors. The exact pathogenesis of type 1 necrotizing fasciitis is not fully understood but polymicrobial species work synergistically to enhance the spread of infection. Group A streptococcus is the most common causative agent of type 2 necrotizing fasciitis. Bacterial virulence factors, exotoxins, superantigens and host immune system plays a major role in the pathogenesis of type II necrotizing fasciitis.
#1 necrotizing fasciitis | Calgary Guide
https://calgaryguide.ucalgary.ca/necrotizing-fasciitis-pathogenesis-and-clinical-findings/necrotizing-fasciitis/
Sepsis […] Blood clots in vessels […] Tissue ischemia in epidermis, dermis, subcutaneous fat, muscle fascia, and/or muscle […] Bacteria releases toxins which are taken up into the bloodstream […] Immune cells produce inflammatory cytokines […] Circulating toxins activate T cells, over-activating the systemic immune response […] Toxic Shock syndrome […] Tissue hypoxia anaerobic metabolism […] Poor perfusion of lungs impairs gas exchange […] Compartment syndrome […] Amputation
#1 Necrotizing fasciitis: A challenging obstetric emergency
https://www.ginekologiaipoloznictwo.com/articles/necrotizing-fasciitis-a-challenging-obstetric-emergency-103184.html
NF is a rare progressive infection that primarily affects subcutaneous fascia, but rapidly may spread to the rectal sheath and skin. Known for her vigorous spread to the surrounding tissues, with initial unspecific symptoms, prompt surgical intervention of the necrotic tissue is recommended to prevent fulminant deterioration to septic shock, multi-organ failure and death respectively. […] Bacterial overgrowth is supported by compromise in skin or mucosal integrity, hyperglycemia and systemic immunosuppression. Tissue necrosis and spread of causative agents, is facilitated by their enzymes and toxins. […] Progression of tissue necrosis is as fast as 1 inch per hour. […] The correlation between histopathologic findings of debrided tissue in patients with NF and the clinical outcome was adopted as a prognostic tool.
#1 Multidisciplinary management of periocular necrotising fasciitis: a series of 11 patients | Eye
https://www.nature.com/articles/eye2011241
The streptococcal M protein has been identified as a potent inducer of inflammation and seems to be responsible for the severity of necrotising fasciitis. Other bacteria have also been implicated in the pathogenesis of necrotising fasciitis like Escherichia coli, Kleibsella pneumoniae, and Moraxella. […] Thrombosis of the microcirculatory vessels of superficial fascia leads to secondary gangrene of the skin and forms the basis for the pathogenesis of this condition. Periocular necrotising fasciitis can have devastating complications. Central retinal artery occlusion with loss of vision and exenteration for deep orbital involvement, has been reported. Early surgical intervention reduces morbidity and mortality significantly; left untreated, the mortality ranges between 30-70%. […] The key to successful management of necrotising fasciitis is early diagnosis and intervention. The use of hyperbaric oxygen and intravenous immunoglobulin have been recommended by some researchers, but are more useful as adjuncts to broad-spectrum intravenous antibiotic therapy and early debridement.
#1 Necrotizing Fasciitis | Johns Hopkins ABX Guide
https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540378/all/Necrotizing_Fasciitis
Some classify necrotizing fasciitis (NF) into Type I and Type II. […] Group A Streptococcus (GAS, S. pyogenes, Type II) is thought to be the most common cause. […] Certain streptococcal strains are seen more frequently in NF, most commonly those that contain M protein types 1, 3, 12, and 28 (elaborating pyrogenic exotoxin A). […] Some also use Type III, designating NF due to clostridial causing gas gangrene. […] Clostridia perfringens is the most common; see module for details. […] Other pathogens that may cause NF include other Streptococcal species, Staphylococcus aureus, Vibrio vulnificus, Aeromonas spp., Klebsiella spp., Pseudomonas aeruginosa, and a host of occasional bacterial pathogens implicated, including Candida and Mucor spp. also rarely described.
#1 Necrotizing fasciitis | Description, Cause, Symptoms, & Treatment | Britannica
https://www.britannica.com/science/necrotizing-fasciitis
necrotizing fasciitis, rapidly spreading infection of the underlying skin and adipose (fat) layers caused by a variety of pathogenic bacteria, principally Streptococcus pyogenes, also known as the group A streptococcus. […] The bacteria that cause necrotizing fasciitis usually enter the body through the mucous membranes or breaks in the skin. […] The group A streptococci produce a variety of so-called virulence factors that permit them to evade the defense mechanisms of the host and thus cause disease. These factors include polysaccharide capsules and M proteins that impede phagocytosis, enzymes that degrade host tissues, and toxins that overstimulate the immune system, causing fever and shock.
#1 Necrotising soft tissue infections | Deranged Physiology
https://derangedphysiology.com/main/required-reading/sepsis-and-infections/Chapter-341/necrotising-soft-tissue-infections
S.pyogenes produces enzymes such as hyaluronidase, which digest the fascia. […] It also produces superantigen toxins, which lead to streptococcal toxic shock syndrome. […] The histologic criteria for diagnosis as described by Stamenkovic and Lew (1984) were as follows: necrosis of the superficial fascia, polymorphonuclear infiltration of the dermis and fascia, fibrinous thrombi of arteries and veins coursing through the fascia, angiitis with fibrinoid necrosis of arterial and venous walls, presence of microorganisms within the destroyed fascia and dermis, and an absence of muscle involvement. […] The addition of clindamycin is well supported – particularly with Group A streptococci, where it inhibits the bacterial synthesis of endotoxin. […] The already-mentioned retrospective audit from Victoria had also suggested that people with severe soft tissue infections benefit from IVIg irrespective of whether they have toxic shock syndrome or not.
#1 What Is Necrotizing Fasciitis (Flesh-Eating Bacteria)? – Consensus: AI Search Engine for Research
https://consensus.app/home/blog/what-is-necrotizing-fasciitis-flesh-eating-bacteria/
Necrotizing fasciitis is primarily caused by Group A Streptococcus (GAS), a versatile pathogen responsible for a range of diseases from mild pharyngitis to life-threatening infections like NF. GAS secretes a variety of proteases that disrupt host tissues, regulated by multiple transcriptional and posttranslational processes. […] Recent studies have shown that single-nucleotide mutations in the GAS genome can significantly alter its virulence, affecting the expression of key virulence factors like SpeB protease. Moreover, the interaction between different bacterial strains in polymicrobial infections can modulate the virulence and immune response, as seen in mixed infections with Aeromonas hydrophila strains.
#1 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
It was found that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. […] Severe myositis accompanying septic necrotizing fasciitis may be caused by a Panton-Valentine leukocidinpositive S aureus strain. […] Although necrotizing fasciitis most frequently develops after trauma that compromises skin integrity, it may rarely develop in a healthy person after minor trauma such as an isolated shoulder sprain that occurred without a break in skin barrier.
#1 Necrotizing Fasciitis (Synergistic Necrotizing Cellulitis, Fournierâs Gangrene, Hemolytic Streptococcal gangrene, Meleneyâs ulcer, suppurative fasciitis, Ludwigâs angina) – Dermatology Advisor
https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/necrotizing-fasciitis-synergistic-necrotizing-cellulitis-fourniers-gangrene-hemolytic-streptococcal-gangrene-meleneys-ulcer-suppurative-fasciitis-ludwigs-angina/
Type 2 necrotizing fasciitis due to group A beta-hemolytic streptococcal infection is associated with strains expressing particular streptococcal M proteins. In the United States, these are most commonly Type 1 and 3 but also Types 12 and 28. Strains also produce soluble exotoxins A and B. Some of these toxins act as superantigens that stimulate T-cells to produce large amounts of cytokines such as TNF, and this cytokine storm may also contribute to the severe systemic manifestations of the disease. […] The specific virulence factors contributing to staphylococcal necrotizing fasciitis remain poorly characterized. Strains isolated from these infections have most commonly been USA 300 CAMRSA strains that express the Panton-Valentine leukocidin and other virulence traits, but the specific roles of these toxins and the pathogenesis of these severe staphylococcal skin and soft tissue infection remains uncertain.
#1 Cervical Necrotizing Fasciitis in Adults: A Life-Threatening Emergency in Oral and Maxillofacial Surgery
https://www.mdpi.com/2673-4095/5/3/42
NF is characterized by the rapidly progressive necrosis of the superficial fascia and overlying subcutaneous tissue. […] The infection of subcutaneous tissue leads to subdermal venous thrombosis and inflammatory cell infiltration with abscess formation, followed by arterial compromise due to endarteritis obliterans. […] This causes critical skin ischemia, with blisters or bullae formation. […] Necrosis of the skin and coliquative gangrene follow. […] At this point, pain is reduced, secondary to the destruction of superficial cutaneous nerves.
#1 Clinical Guidance for Type II Necrotizing Fasciitis | Group A Strep | CDC
https://www.cdc.gov/group-a-strep/hcp/clinical-guidance/necrotizing-fasciitis.html
Necrotizing fasciitis may also occur as a superinfection complicating varicella lesions. […] Corticosteroid therapy has been shown to be a predisposing factor. […] While rare, when necrotizing fasciitis occurs it frequently happens after trauma or surgery. […] Necrotizing fasciitis can affect any part of the body, but most commonly affects extremities, particularly the legs. […] The patient’s pain is usually out of proportion to the signs of the local skin infection. […] Treating healthcare providers may underestimate the extent of tissue infected due to spread within the subcutaneous tissue that spares the overlying skin and absence of lymphadenitis and lymphangitis. […] Within 24 to 48 hours, overlying skin may turn dusky, cutaneous ischemia develops, bullae form and fill with straw-colored fluid, and bullae progressively turn dark due to hemorrhagic fluid.
#1 Clinical Guidance for Type II Necrotizing Fasciitis | Group A Strep | CDC
https://www.cdc.gov/group-a-strep/hcp/clinical-guidance/necrotizing-fasciitis.html
Skin discoloration indicates small vessels in the dermal papilla have thrombosed. Affected tissues progressively darken from red to purple to blue to black. As gangrene sets in, skin becomes anesthetized as superficial nerves die. […] Indications of advance disease include anesthesia, bullae, crepitus, ecchymosis, and necrosis. […] The lesions become sharply demarcated. As skin sloughs, a necrotic eschar forms, resembling a third-degree burn. […] Primary treatment of necrotizing fasciitis is early and aggressive surgical exploration and debridement of necrotic tissue. […] Antibiotic therapy is based upon Gram stain findings. Once group A strep is confirmed to be the etiology, recommended treatment is high-dose penicillin and clindamycin (interferes with toxin production). […] Amputations are a common complication of necrotizing fasciitis. […] In the most recent 5 years, the mortality rate of streptococcal necrotizing fasciitis has been around 13 to 18%. It increases with age of the person affected and the presence of streptococcal toxic shock syndrome.
#1 The Diagnosis And Management Of Necrotising Fasciitis : Virtual Library
https://resources.wfsahq.org/atotw/the-diagnosis-and-management-of-necrotising-fasciitis-anaesthesia-tutorial-of-the-week-298/
Massive T cell proliferation and cytokine release can occur in type II NF via the effects due to the M protein of group A -haemolytic streptococcus (GAS). This filamentous protein has anti-phagocytic properties and is an important virulence determinant as it can produce multiple pyogenic exotoxins that act as super-antigens. These cause a systemic inflammatory response syndrome (SIRS) which may progress to multi-organ failure. […] NF is a surgical emergency and warrants immediate surgical referral. Evidence has shown that when treatment is based on just antimicrobial therapy and support, mortality approaches 100%. Surgery is a vital means of source control. […] Antibiotics are a vital adjunct to source control and may prevent the progression of septic shock when used early. […] Hyperbaric oxygen (HBO) is thought to increase the bactericidal effects of neutrophils since at low oxygen tensions killing mechanisms reliant on oxygen free radicals are less effective. HBO alone is also thought to be bactericidal for certain anaerobes, including Clostridium Perfringens as it switches off -toxin production. […] The role of IVIG and HBO in the treatment of NF remains unclear due to the lack of randomized controlled trials. However if available, these therapies should be considered when surgical debridement, antibiotics and general supportive measures have proved unsuccessful.
#1 Necrotizing fasciitis in patients with diabetes mellitus: clinical characteristics and risk factors for mortality | BMC Infectious Diseases | Full Text
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-015-1144-0
Necrotizing fasciitis (NF) is a rapidly progressive and life-threatening infection. This study aimed to investigate the clinical characteristics and mortality-associated factors in diabetic patients. […] Diabetic patients exhibit impaired cutaneous wound healing and increased susceptibility to infection, which may affect the course of soft-tissue infections. […] The infection most commonly involved the lower limbs, followed by the trunk, and the upper limbs. […] The elevated serum potassium level on admission may reflect acute renal impairment. […] Bacteraemia frequently causes sepsis, which is the typical cause of death in NF patients. […] Diabetes is a disorder that adversely affects the immune system, thus representing a common underlying disease in NF patients. […] The present study further emphasized the importance of recognizing monomicrobial NF caused by Klebsiella pneumoniae as a common entity of NF in diabetic patients. […] Bacteraemia on admission is significant risk factor for mortality in NF patients with diabetes.
#1 PlasticSurgerySHO – Necrotising Fasciitis
https://www.plasticsurgerysho.co.uk/infection/necrotising-fasciitis
Life-threatening infection that spreads rapidly along fascial planes and subcutaneous tissue with mortality of around 53%. […] Could be due to trauma, bite, scratch, sting, recent surgery, or haematogenous spread with no known focus of infection. […] Can be young fit individuals, however immunocompromise predisposes individuals (history of diabetes, elderly, steroids, HIV). […] Patients require early and radical surgical debridement.
#1 Clinical Guidance for Type II Necrotizing Fasciitis | Group A Strep | CDC
https://www.cdc.gov/group-a-strep/hcp/clinical-guidance/necrotizing-fasciitis.html
Necrotizing fasciitis is a rapidly progressive infection that destroys deep soft tissues. […] Multiple species of bacteria can cause necrotizing fasciitis. This page focuses on type II necrotizing fasciitis, which is also known as Hemolytic streptococcal gangrene and Streptococcal necrotizing fasciitis. […] It’s characterized by the isolation of Streptococcus pyogenes (group A strep bacteria) with or without other bacterial species. Staphylococcus aureus is the most common species found in co-infection cases. […] Some streptococcal strains may be more likely to cause necrotizing fasciitis. Commonly involved strains, such as those containing M protein types 1, 3, 12, and 28, typically produce pyrogenic exotoxin A1. […] Certain systemic or local immunocompromising conditions increase the risk of getting necrotizing fasciitis, including cancer, cirrhosis, diabetes mellitus, and peripheral vascular disease.
#1 Necrotizing Fasciitis: Pearls & Pitfalls – emDocs
https://www.emdocs.net/necrotizing-fasciitis-pearls-pitfalls/
Necrotizing soft tissue infections (NSTI) include necrotizing forms of cellulitis, fasciitis, and myositis. NSTIâs are rare but deadly deep soft tissue infections associated with tissue destruction, systemic toxicity, and high morbidity and mortality. The estimated mortality rate of necrotizing fasciitis is estimated to be between 25-35%. […] Infection requires inoculation with the bacteria, which typically occurs via a break in the epithelial or mucosal surface secondary to trauma, IV drug use, insect or animal bites, or surgery. However, it has also been reported without any known trauma in up to 17% of cases. […] Necrotizing fasciitis (NF) is a necrotizing soft tissue infection of muscular fascia in which the muscle tissue below is frequently spared. Infection spreads quickly along the fascia due to poor blood supply. The skin findings seen on exam are secondary to vasculitis and thrombosis of the perforating blood vessels, which produces tissue ischemia, erythema, and cutaneous anesthesia.
#1 Periorbital Necrotizing Fasciitis – EyeWiki
https://eyewiki.org/Periorbital_Necrotizing_Fasciitis
Necrotizing fasciitis is a rare and severe soft tissue infection characterized by cutaneous gangrene, suppurative fasciitis, and vascular thrombosis. Periorbital necrotizing fasciitis is a rapidly progressive, highly destructive microbial infection involving the skin, subcutaneous and deep soft tissue, and muscle of the periorbital tissues. […] Periorbital necrotizing fasciitis is an invasive, synergistic, polymicrobial soft tissue infection. The disease is usually preceded by trauma in patients that have pre-disposing systemic risk factors, most commonly diabetes and alcoholism. […] The most common inciting factor for periorbital necrotizing fasciitis is penetrating or surgical trauma. Sometimes the injury may be so trivial that the patient is not able to recall it. Other risk factors include upper respiratory illness, acute or chronic bacterial sinusitis, recent ocular or periocular infection, or systemic infection.
#1 MEDSAFE
https://medsafe.govt.nz/profs/PUarticles/necf.htm
For some time published case reports and case series have described cases of necrotising fasciitis (NF) in patients who have recently used an NSAID, and an association has been postulated. […] The mechanism by which NSAIDs increase the risk of NF may be by impairment of the immune response, or by masking of the symptoms of secondary infection, leading to delayed diagnosis and treatment. […] Whether this effect is due to masking of symptoms of early NF by NSAIDs, or whether the frequent use of NSAIDs for nonspecific musculo-skeletal symptoms plays a role in the pathogenesis of NF, has not been clarified. […] Although, the underlying mechanism of the association of NSAIDs and increased severity of streptococcal infections has not been defined, some indications that NSAIDs may alter the biological response to infection have been identified in in vitro studies.
#1 Dapagliflozin: Uses, Dosage, Side Effects, Warnings – Drugs.com
https://www.drugs.com/dapagliflozin.html
A rare but serious bacterial infection that causes damage to the tissue under the skin (necrotizing fasciitis) in the area between and around the anus and genitals (perineum). Necrotizing fasciitis of the perineum has happened in women and men with diabetes mellitus who take dapagliflozin. Necrotizing fasciitis of the perineum may lead to hospitalization, may require multiple surgeries, and may lead to death. Seek medical attention immediately if you have fever or you are feeling very weak, tired, or uncomfortable (malaise) and you develop any of the following symptoms in the area between and around the anus and genitals: […] pain or tenderness […] swelling […] redness of skin (erythema)
#1
https://journals.lww.com/prsgo/fulltext/2024/01000/practical_review_of_necrotizing_fasciitis_.23.aspx
Necrotizing fasciitis (NF) is a rapidly progressing soft tissue infection that aggressively spreads along fascial layers and subcutaneous tissues. Common sites of infection include the extremities, abdomen, and perineum. NF can be idiopathic or secondary (after trauma, chronic wounds, or skin abrasions). Diagnosis can often be challenging and is primarily diagnosed based on clinical presentation. NF has a mortality rate of 8.7%76%, underscoring the need for timely and accurate diagnosis and prompt medical and surgical treatment. This practical review will focus on the basic tenets of NF, including classification, comorbidities related to NF, clinical presentation and diagnosis, and nonsurgical and surgical management principles. […] The mainstay of treatment for NF consists of emergency surgical debridement of the infected tissue. Surgical management is especially indicated in NF with systemic inflammatory response syndrome or multiorgan failure, associated with a mortality rate of 70%. Moreover, surgery is mandatory for a patient experiencing severe pain with erythema, ecchymosis, blisters, or bullae. Surgery reduces bioburden by inhibiting the spread along the fascial planes. To minimize the risk of scarring and promote better wound healing, incisions are initially made parallel to the Langer lines. Incisions perpendicular with Langer lines can be made to keep the wound open and to allow further drainage and removal of necrotic tissue, except in cases of abdominal wall or retroperitoneal space involvement. Close ongoing surveillance over surgical wounds and tissue viability is required for the next 24 hours. In complex cases, repeat surgical debridement can be beneficial as a second-look operation. It is imperative to remove all nonviable or necrotic tissue, as the timing and the extent of the first debridement are the most important determining factors in mitigating the mortality rate. Delays in surgical debridement, necrosectomy, and fasciotomy (12 hours) may result in fulminant NF and higher mortality.
#1 Perineal Necrotising Fasciitis | British Journal of Medical Practitioners
https://www.bjmp.org/content/perineal-necrotising-fasciitis
A 24 hour delay in treatment has been shown to increase mortality by 18% and further surgery is usually indicated with an average of 3.8 debridements needed overall. Surgical treatment should be instigated in conjunction with broad spectrum intravenous antibiotics and intensive care. The antibiotics selected should be effective against gram-positive, gram negative and anaerobic organisms.
#1 Necrotising Fasciitis: Clinical Evaluation and Treatment Results of 18 Patients – Mediterranean Journal of Infection Microbes and Antimicrobials
https://www.mjima.org/articles/necrotising-fasciitis-clinical-evaluation-and-treatment-results-of-18-patients/doi/mjima.galenos.2019.2019.9
For empirical antibiotic therapy, regimens such as glycopeptides or linezolid with broad-spectrum antibiotics such as carbapenems or piperacillin/tazobactam are recommended; clindamycin in combination with penicillin is recommended for monomicrobial NF caused by group A streptococci. […] The effective use of LRINEC score in our study resulted in proper management of our patients. […] The amount of aggressive debridement is not defined in the literature. […] The importance of early diagnosis and aggressive treatment has been discussed in the literature. […] We believe that the disease was controlled earlier in our patients since the necessary initial debridement for NF spread was performed appropriately by the orthopedics and traumatology department in conjunction with the departments of cardiovascular surgery, general surgery, and obstetrics. […] NF is a rare and complicated soft tissue infection with high mortality rates and is considered one of the infectious disease emergencies. […] The most important factor in diagnosis is clinical suspicion.
#1
https://journals.lww.com/prsgo/fulltext/2024/01000/practical_review_of_necrotizing_fasciitis_.23.aspx
Hyperbaric oxygen (HBO) and Intravenous immunoglobulin (IVIG) have been suggested as adjunct treatments for NF. Research indicates that HBO improves patient survival while decreasing the number of surgical debridements and potentially the extent of reconstruction by inhibiting the systemic inflammatory response system and improving leukocyte activity. Moreover, it can facilitate the transport of some antibiotics, such as aminoglycosides. IVIG has been shown to be beneficial in patients with GAS NF that progressed into toxic shock syndrome. Researchers have linked the efficacy of IVIG in NF to its ability to reduce a systemic inflammatory response by targeting the exotoxins.
#1 Improvement in mortality with hyperbaric oxygen therapy in cervical necrotising fasciitis: a systematic review of the literature – Tseros – Australian Journal of Otolaryngology
https://www.theajo.com/article/view/4571/html
The mainstay of treatment of CNF includes early and aggressive surgical debridement with broad spectrum antibiotic therapy. […] HBOT is considered to be valuable in improving healing and preventing further tissue damage through the increase in the partial pressure of oxygen within infected soft tissues. […] This allows for continued cellular metabolism, increases fibroblast proliferation and maturation, promotes neutrophilic phagocytosis, inhibits the proliferation of anaerobic bacteria, and is thought to increase the protective immunological effects of oxygen free radicals. […] The findings of this systematic review suggest that there is an improvement in mortality in patients who have undergone HBOT for CNF. […] As a result, we recommend that HBOT may be a useful adjunct to urgent surgical debridement and antibiotic therapy in patients with CNF. […] This treatment may be less efficacious in aerobic infections.
#1 IVIG for Toxic Necrotizing Fasciitis: What the Evidence Says – AmeriPharmaÂ® Specialty Care
https://ameripharmaspecialty.com/ivig/ivig-for-toxic-necrotizing-fasciitis-what-the-evidence-says/
Necrotizing fasciitis is a rare, aggressive bacterial infection. Delayed treatment may result in multiple organ failure and death. […] Necrotizing fasciitis causes death (necrosis) of the fascia and tissues beneath your skin. The fascia is a thin layer of connective tissue that surrounds your muscles, bones, and organs. […] Necrotizing fasciitis affects about four in one million Americans each year. It can occur when a bacterium or several bacteria enter the body and produce toxins. These toxins limit blood supply to tissues and damage cells, causing pus-filled lesions. […] If the toxins reach your bloodstream, it may result in toxic shock. […] How IVIG benefits people with necrotizing fasciitis isnât fully understood. Health experts believe IVIG may work by: Neutralizing the bacterial toxins, Preventing abnormally rapid multiplication of certain immune cells, Reducing inflammation. […] Despite promising results in case studies, several challenges still limit IVIG use for necrotizing fasciitis. Researchers have yet to determine: The most effective IVIG agent, The timing of therapy, The dose, The duration of treatment.
#1 Necrotizing fasciitis not always caused by bacteria but by a combination of tissue damage and a gene defect | HUS
https://www.hus.fi/en/newsroom/necrotizing-fasciitis-not-always-caused-bacteria-combination-tissue-damage-and-gene-defect
A new Finnish-led study suggests that necrotizing fasciitis, a life-threatening inflammation of connective tissue that leads to tissue necrosis, may be caused by a gene defect. […] The study investigated the mechanism of how a gene defect causes an excessive and violent inflammatory response. […] In patients, mild injury, surgery or infection had triggered an uncontrolled inflammatory reaction leading to severe deep tissue inflammation. […] Researchers have found an inflammation-activating defect in the NFKB1 gene in three Finnish and three foreign pediatric and adult patients with severe fasciitis. […] With new gene-editing techniques, we were able to identify the nature of the inflammatory response and the mechanisms by which a gene defect causes a strong inflammatory response.
#1 Necrotising Fasciitis | SpringerLink
https://link.springer.com/10.1007/978-3-642-34746-7_73?fromPaywallRec=true
Despite the expanded understanding on the pathophysiology of sepsis, the contemporary sophisticated diagnostic methods, and the modern advanced antibiotics, surgical debridement remains the cornerstone of treatment of necrotising fasciitis. […] Clinical research on this rare and lethal disease lacks of high-level evidence, highlighting the necessity of multicentre collaboration on this scientific effort. […] Young LM, Price CS. Community-acquired methicillin-resistant Staphylococcus aureus emerging as an important cause of necrotizing fasciitis. […] Wong CH, Khin LW, Heng KS, et al. The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. […] Liu YM, Chi CY, Ho MW, et al. Microbiology and factors affecting mortality in necrotizing fasciitis.
#1 Necrotizing Fasciitis: Pearls & Pitfalls – emDocs
https://www.emdocs.net/necrotizing-fasciitis-pearls-pitfalls/
Patients may not show signs of severe systemic illness until the disease progresses. In fact, NF is misdiagnosed as cellulitis in up to three quarters of the time. […] The gold standard for diagnosis is operative exploration. Surgical exploration is the only way to definitively establish the diagnosis and distinguish necrotizing fasciitis from other entities.
#1 Necrotising Fasciitis: Clinical Evaluation and Treatment Results of 18 Patients – Mediterranean Journal of Infection Microbes and Antimicrobials
https://www.mjima.org/articles/necrotising-fasciitis-clinical-evaluation-and-treatment-results-of-18-patients/doi/mjima.galenos.2019.2019.9
Necrotizing fasciitis (NF) is a complicated and rapidly spreading soft tissue infection that affects the superficial fascia, skin, and subcutaneous tissue. […] If not treated properly, the resulting tissue necrosis spreads quickly and causes sepsis, leading to toxic shock syndrome and multiple organ failure, and ultimately ending in death. […] Inflammation and necrosis of the subcutaneous adipose tissue and deep fascia with muscle sparing are characteristic features of the disease. […] The clinical signs of NF may not be distinguishable from cellulitis and erysipelas in the early stage. […] Early diagnosis is life-saving in NF patients. […] The treatment of NF involves intravenous administration of empirical broad-spectrum antibiotics and emergency surgical debridement. […] The aim of surgical intervention is to eliminate all necrotic tissues, including muscle, fascia, and skin.
#1 Necrotizing fasciitis – Wikipedia
https://en.wikipedia.org/wiki/Necrotizing_fasciitis
Bacterial infection is by far the most common cause of necrotizing fasciitis. Despite being called a „flesh-eating disease”, bacteria do not eat human tissue. Rather, they release toxins that cause tissue death. Typically, the infection enters the body through a break in the skin such as a cut or burn. […] NSAIDs may increase the rates of necrotizing infections by impairing the body’s immune response. NSAIDs inhibit the production of prostaglandins responsible for fever, inflammation, and pain. In theory, it also prevents white blood cells from migrating to infected areas, thus increasing the risk of soft-tissue infections. […] Necrotizing fasciitis is divided into four classes by the type of bacteria causing the infection. This classification system was first described by Giuliano and his colleagues in 1977.
#2 Necrotizing fasciitis – Wikipedia
https://en.wikipedia.org/wiki/Necrotizing_fasciitis
Type I infection: This is the most common type of infection, and accounts for 70 to 80% of cases. It is caused by a mixture of bacterial types, usually in abdominal or groin areas. […] In polymicrobial (mixed) infections, Group A Streptococcus (S. pyogenes) is the most commonly found bacterium, followed by S. aureus. However, when the infection is caused solely by S. pyogenes and/or S. aureus, it is classified as a Type II infection. […] Type II infection: This infection accounts for 20 to 30% of cases, mainly involving the extremities. This involves Streptococcus pyogenes, alone or in combination with staphylococcal infections. Methicillin-resistant Staphylococcus aureus (MRSA) is involved in up to a third of Type II infections. […] Type III infection: Vibrio vulnificus is a bacterium found in saltwater. It occasionally causes NF after entering the body through a break in the skin. One in three patients with a V. vulnificus infection develop necrotizing fasciitis. […] Type IV infection: This type of NF accounts for less than 1% of cases. It is mostly caused by the Candida albicans fungus. Risk factors include age and immunodeficiency.
#2 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
Necrotizing fasciitis is characterized by widespread necrosis of the subcutaneous tissue and the fascia. […] Although the pathogenesis of necrotizing fasciitis is still open to speculation, the rapid and destructive clinical course of necrotizing fasciitis is thought to be due to multibacterial symbiosis and synergy. […] Historically, group A beta-hemolytic Streptococcus (GABS) has been identified as a major cause of this infection. […] During the last few decades, researchers have found that necrotizing fasciitis is usually polymicrobial rather than monomicrobial. […] Anaerobic bacteria are present in most necrotizing soft-tissue infections, usually in combination with aerobic gram-negative organisms. […] Facultative aerobic organisms grow because polymorphonuclear neutrophils (PMNs) exhibit decreased function under hypoxic wound conditions.
#2 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
Carbon dioxide and water are the end products of aerobic metabolism. […] In necrotizing fasciitis, group A hemolytic streptococci and Staphylococcus aureus, alone or in synergism, are frequently the initiating infecting bacteria. […] Organisms spread from the subcutaneous tissue along the superficial and deep fascial planes, presumably facilitated by bacterial enzymes and toxins. […] Important bacterial factors include surface protein expression and toxin production. […] Streptococcal pyrogenic exotoxins (SPEs) A, B, and C are directly toxic and tend to be produced by strains causing necrotizing fasciitis. […] The poor prognosis associated with necrotizing fasciitis has been linked to infection with certain streptococcal strains. […] Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species.
#2 Necrotizing fasciitis pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Necrotizing_fasciitis_pathophysiology
The pathogenesis of necrotizing fasciitis is the result of bacterial and host factors. […] The exact pathogenesis of type 1 necrotizing fasciitis is not fully understood. It is thought that type 1 NF is caused by polymicrobial species that work synergistically to enhance the spread of infection. […] Group A streptococcus is the most common causative agent of type 2 NF. The pathogenesis of type 2 NF is the result of the following process: Inhibition of phagocytosis of bacteria by hyaluronic acid capsule and M protein. Adherence of bacteria to host cell through adherence factors such as M protein, protein F and lipoteichoic acid. Release of exotoxins (streptococcal pyogenic exotoxins and superantigen) into blood produce massive proliferation of T cells and cascading release of cytokines activating inflammatory process. […] The massive release of cytokines result in systemic inflammatory response syndrome resulting in shock, organ failure, depression of myocardial function and immune suppression.
#2 Necrotizing Fasciitis (Synergistic Necrotizing Cellulitis, Fournierâs Gangrene, Hemolytic Streptococcal gangrene, Meleneyâs ulcer, suppurative fasciitis, Ludwigâs angina) – Dermatology Advisor
https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/necrotizing-fasciitis-synergistic-necrotizing-cellulitis-fourniers-gangrene-hemolytic-streptococcal-gangrene-meleneys-ulcer-suppurative-fasciitis-ludwigs-angina/
Type 2 necrotizing fasciitis due to group A beta-hemolytic streptococcal infection is associated with strains expressing particular streptococcal M proteins. In the United States, these are most commonly Type 1 and 3 but also Types 12 and 28. Strains also produce soluble exotoxins A and B. Some of these toxins act as superantigens that stimulate T-cells to produce large amounts of cytokines such as TNF, and this cytokine storm may also contribute to the severe systemic manifestations of the disease. […] The specific virulence factors contributing to staphylococcal necrotizing fasciitis remain poorly characterized. Strains isolated from these infections have most commonly been USA 300 CAMRSA strains that express the Panton-Valentine leukocidin and other virulence traits, but the specific roles of these toxins and the pathogenesis of these severe staphylococcal skin and soft tissue infection remains uncertain.
#2 Necrotising fasciitis
https://dermnetnz.org/topics/necrotising-fasciitis
Necrotising fasciitis is a very serious bacterial infection of the soft tissue and fascia. The bacteria multiply and release toxins and enzymes that result in thrombosis in the blood vessels. The result is the destruction of the soft tissues and fascia. […] The infection starts in the superficial fascia. Enzymes and proteins released by the responsible micro-organisms cause necrosis of fascial layers. Horizontal spread of infection may not be clinically apparent on the skin surface and hence diagnosis may be delayed. The infection then spreads vertically up into the skin and down into deeper structures. Thrombosis occludes the arteries and veins leading to ischaemia and necrosis of the tissues. […] Streptococci produce M proteins, which initiate an inflammatory response with the release of numerous cytokines (IL-1, IL-6, TNF). Exotoxins, which destroy neutrophils allowing bacterial growth and destroying tissues. […] Aerobic and anaerobic bacteria produce hydrogen, nitrogen, and hydrogen sulfide gases that destroy hyaluronic acid enabling the spread of infection.
#2 What Is Necrotizing Fasciitis (Flesh-Eating Bacteria)? – Consensus: AI Search Engine for Research
https://consensus.app/home/blog/what-is-necrotizing-fasciitis-flesh-eating-bacteria/
Necrotizing fasciitis is primarily caused by Group A Streptococcus (GAS), a versatile pathogen responsible for a range of diseases from mild pharyngitis to life-threatening infections like NF. GAS secretes a variety of proteases that disrupt host tissues, regulated by multiple transcriptional and posttranslational processes. […] Recent studies have shown that single-nucleotide mutations in the GAS genome can significantly alter its virulence, affecting the expression of key virulence factors like SpeB protease. Moreover, the interaction between different bacterial strains in polymicrobial infections can modulate the virulence and immune response, as seen in mixed infections with Aeromonas hydrophila strains.
#2 Necrotising soft tissue infections | Deranged Physiology
https://derangedphysiology.com/main/required-reading/sepsis-and-infections/Chapter-341/necrotising-soft-tissue-infections
S.pyogenes produces enzymes such as hyaluronidase, which digest the fascia. […] It also produces superantigen toxins, which lead to streptococcal toxic shock syndrome. […] The histologic criteria for diagnosis as described by Stamenkovic and Lew (1984) were as follows: necrosis of the superficial fascia, polymorphonuclear infiltration of the dermis and fascia, fibrinous thrombi of arteries and veins coursing through the fascia, angiitis with fibrinoid necrosis of arterial and venous walls, presence of microorganisms within the destroyed fascia and dermis, and an absence of muscle involvement. […] The addition of clindamycin is well supported – particularly with Group A streptococci, where it inhibits the bacterial synthesis of endotoxin. […] The already-mentioned retrospective audit from Victoria had also suggested that people with severe soft tissue infections benefit from IVIg irrespective of whether they have toxic shock syndrome or not.
#2 Cervical Necrotizing Fasciitis in Adults: A Life-Threatening Emergency in Oral and Maxillofacial Surgery
https://www.mdpi.com/2673-4095/5/3/42
NF is characterized by the rapidly progressive necrosis of the superficial fascia and overlying subcutaneous tissue. […] The infection of subcutaneous tissue leads to subdermal venous thrombosis and inflammatory cell infiltration with abscess formation, followed by arterial compromise due to endarteritis obliterans. […] This causes critical skin ischemia, with blisters or bullae formation. […] Necrosis of the skin and coliquative gangrene follow. […] At this point, pain is reduced, secondary to the destruction of superficial cutaneous nerves.
#2 Necrotizing Fasciitis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK430756/
Necrotizing fasciitis is a subset of aggressive skin and soft tissue infections that cause muscle fascia and subcutaneous tissue necrosis. The infection typically travels along the fascial plane, which has a poor blood supply. The infectious process can rapidly spread, causing infection of the fascia and perifascial planes and secondary infection of the overlying and underlying skin, soft tissue, and muscle. […] Necrotizing fasciitis is typically an acute process that occurs rapidly over several days. In approximately 80% of cases, it is a direct sequela of bacterial infection introduced through a break in the skins integrity. […] The infection rapidly transits the muscle fascia. After several days, the overlying skin, which initially appears unaffected, will transition to an erythematous, reddish-purple to bluish-gray hue.
#2 Clinical Guidance for Type II Necrotizing Fasciitis | Group A Strep | CDC
https://www.cdc.gov/group-a-strep/hcp/clinical-guidance/necrotizing-fasciitis.html
Skin discoloration indicates small vessels in the dermal papilla have thrombosed. Affected tissues progressively darken from red to purple to blue to black. As gangrene sets in, skin becomes anesthetized as superficial nerves die. […] Indications of advance disease include anesthesia, bullae, crepitus, ecchymosis, and necrosis. […] The lesions become sharply demarcated. As skin sloughs, a necrotic eschar forms, resembling a third-degree burn. […] Primary treatment of necrotizing fasciitis is early and aggressive surgical exploration and debridement of necrotic tissue. […] Antibiotic therapy is based upon Gram stain findings. Once group A strep is confirmed to be the etiology, recommended treatment is high-dose penicillin and clindamycin (interferes with toxin production). […] Amputations are a common complication of necrotizing fasciitis. […] In the most recent 5 years, the mortality rate of streptococcal necrotizing fasciitis has been around 13 to 18%. It increases with age of the person affected and the presence of streptococcal toxic shock syndrome.
#2 Necrotizing Fasciitis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK430756/
Advanced stages of the infection are characterized by systemic symptoms such as fever, tachycardia, and sepsis. […] Anaerobic bacteria mixed with aerobic organisms are commonly found in most soft tissue infections. […] The majority of small and medium-sized blood vessels will be thrombosed. […] The treatment of necrotizing fasciitis is surgery, and no time should be wasted calling for a surgical consult. The earlier the surgery is undertaken, the better the outcome. […] The earlier the surgery may help minimize tissue loss and eliminate the need for amputation of a gangrenous extremity. […] Hyperbaric oxygen therapy may be effective for small wounds, but there is no evidence that this therapy improves healing or prolongs life for large wounds. […] Necrotizing fasciitis is a serious life-threatening infection with mortality rates ranging from 20 to 80%. Poor prognosis has been linked to certain streptococcal strains, advanced age, uncontrolled diabetes, state of immunosuppression, and delayed surgery. […] The complications that can manifest with necrotizing fasciitis are as follows: multiorgan failure, septic shock, loss of extremity, severe scarring, toxic shock, and death.
#2 The Diagnosis And Management Of Necrotising Fasciitis : Virtual Library
https://resources.wfsahq.org/atotw/the-diagnosis-and-management-of-necrotising-fasciitis-anaesthesia-tutorial-of-the-week-298/
Massive T cell proliferation and cytokine release can occur in type II NF via the effects due to the M protein of group A -haemolytic streptococcus (GAS). This filamentous protein has anti-phagocytic properties and is an important virulence determinant as it can produce multiple pyogenic exotoxins that act as super-antigens. These cause a systemic inflammatory response syndrome (SIRS) which may progress to multi-organ failure. […] NF is a surgical emergency and warrants immediate surgical referral. Evidence has shown that when treatment is based on just antimicrobial therapy and support, mortality approaches 100%. Surgery is a vital means of source control. […] Antibiotics are a vital adjunct to source control and may prevent the progression of septic shock when used early. […] Hyperbaric oxygen (HBO) is thought to increase the bactericidal effects of neutrophils since at low oxygen tensions killing mechanisms reliant on oxygen free radicals are less effective. HBO alone is also thought to be bactericidal for certain anaerobes, including Clostridium Perfringens as it switches off -toxin production. […] The role of IVIG and HBO in the treatment of NF remains unclear due to the lack of randomized controlled trials. However if available, these therapies should be considered when surgical debridement, antibiotics and general supportive measures have proved unsuccessful.
#2 Clinical Guidance for Type II Necrotizing Fasciitis | Group A Strep | CDC
https://www.cdc.gov/group-a-strep/hcp/clinical-guidance/necrotizing-fasciitis.html
Necrotizing fasciitis is a rapidly progressive infection that destroys deep soft tissues. […] Multiple species of bacteria can cause necrotizing fasciitis. This page focuses on type II necrotizing fasciitis, which is also known as Hemolytic streptococcal gangrene and Streptococcal necrotizing fasciitis. […] It’s characterized by the isolation of Streptococcus pyogenes (group A strep bacteria) with or without other bacterial species. Staphylococcus aureus is the most common species found in co-infection cases. […] Some streptococcal strains may be more likely to cause necrotizing fasciitis. Commonly involved strains, such as those containing M protein types 1, 3, 12, and 28, typically produce pyrogenic exotoxin A1. […] Certain systemic or local immunocompromising conditions increase the risk of getting necrotizing fasciitis, including cancer, cirrhosis, diabetes mellitus, and peripheral vascular disease.
#2 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
It was found that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. […] Severe myositis accompanying septic necrotizing fasciitis may be caused by a Panton-Valentine leukocidinpositive S aureus strain. […] Although necrotizing fasciitis most frequently develops after trauma that compromises skin integrity, it may rarely develop in a healthy person after minor trauma such as an isolated shoulder sprain that occurred without a break in skin barrier.
#2 Periorbital Necrotizing Fasciitis – EyeWiki
https://eyewiki.org/Periorbital_Necrotizing_Fasciitis
Necrotizing fasciitis is a rare and severe soft tissue infection characterized by cutaneous gangrene, suppurative fasciitis, and vascular thrombosis. Periorbital necrotizing fasciitis is a rapidly progressive, highly destructive microbial infection involving the skin, subcutaneous and deep soft tissue, and muscle of the periorbital tissues. […] Periorbital necrotizing fasciitis is an invasive, synergistic, polymicrobial soft tissue infection. The disease is usually preceded by trauma in patients that have pre-disposing systemic risk factors, most commonly diabetes and alcoholism. […] The most common inciting factor for periorbital necrotizing fasciitis is penetrating or surgical trauma. Sometimes the injury may be so trivial that the patient is not able to recall it. Other risk factors include upper respiratory illness, acute or chronic bacterial sinusitis, recent ocular or periocular infection, or systemic infection.
#2 MEDSAFE
https://medsafe.govt.nz/profs/PUarticles/necf.htm
For some time published case reports and case series have described cases of necrotising fasciitis (NF) in patients who have recently used an NSAID, and an association has been postulated. […] The mechanism by which NSAIDs increase the risk of NF may be by impairment of the immune response, or by masking of the symptoms of secondary infection, leading to delayed diagnosis and treatment. […] Whether this effect is due to masking of symptoms of early NF by NSAIDs, or whether the frequent use of NSAIDs for nonspecific musculo-skeletal symptoms plays a role in the pathogenesis of NF, has not been clarified. […] Although, the underlying mechanism of the association of NSAIDs and increased severity of streptococcal infections has not been defined, some indications that NSAIDs may alter the biological response to infection have been identified in in vitro studies.
#2 Clinical Guidance for Type II Necrotizing Fasciitis | Group A Strep | CDC
https://www.cdc.gov/group-a-strep/hcp/clinical-guidance/necrotizing-fasciitis.html
Necrotizing fasciitis may also occur as a superinfection complicating varicella lesions. […] Corticosteroid therapy has been shown to be a predisposing factor. […] While rare, when necrotizing fasciitis occurs it frequently happens after trauma or surgery. […] Necrotizing fasciitis can affect any part of the body, but most commonly affects extremities, particularly the legs. […] The patient’s pain is usually out of proportion to the signs of the local skin infection. […] Treating healthcare providers may underestimate the extent of tissue infected due to spread within the subcutaneous tissue that spares the overlying skin and absence of lymphadenitis and lymphangitis. […] Within 24 to 48 hours, overlying skin may turn dusky, cutaneous ischemia develops, bullae form and fill with straw-colored fluid, and bullae progressively turn dark due to hemorrhagic fluid.
#2 Perineal Necrotising Fasciitis | British Journal of Medical Practitioners
https://www.bjmp.org/content/perineal-necrotising-fasciitis
A 24 hour delay in treatment has been shown to increase mortality by 18% and further surgery is usually indicated with an average of 3.8 debridements needed overall. Surgical treatment should be instigated in conjunction with broad spectrum intravenous antibiotics and intensive care. The antibiotics selected should be effective against gram-positive, gram negative and anaerobic organisms.
#2 Improvement in mortality with hyperbaric oxygen therapy in cervical necrotising fasciitis: a systematic review of the literature – Tseros – Australian Journal of Otolaryngology
https://www.theajo.com/article/view/4571/html
The mainstay of treatment of CNF includes early and aggressive surgical debridement with broad spectrum antibiotic therapy. […] HBOT is considered to be valuable in improving healing and preventing further tissue damage through the increase in the partial pressure of oxygen within infected soft tissues. […] This allows for continued cellular metabolism, increases fibroblast proliferation and maturation, promotes neutrophilic phagocytosis, inhibits the proliferation of anaerobic bacteria, and is thought to increase the protective immunological effects of oxygen free radicals. […] The findings of this systematic review suggest that there is an improvement in mortality in patients who have undergone HBOT for CNF. […] As a result, we recommend that HBOT may be a useful adjunct to urgent surgical debridement and antibiotic therapy in patients with CNF. […] This treatment may be less efficacious in aerobic infections.
#2
https://journals.lww.com/prsgo/fulltext/2024/01000/practical_review_of_necrotizing_fasciitis_.23.aspx
Hyperbaric oxygen (HBO) and Intravenous immunoglobulin (IVIG) have been suggested as adjunct treatments for NF. Research indicates that HBO improves patient survival while decreasing the number of surgical debridements and potentially the extent of reconstruction by inhibiting the systemic inflammatory response system and improving leukocyte activity. Moreover, it can facilitate the transport of some antibiotics, such as aminoglycosides. IVIG has been shown to be beneficial in patients with GAS NF that progressed into toxic shock syndrome. Researchers have linked the efficacy of IVIG in NF to its ability to reduce a systemic inflammatory response by targeting the exotoxins.
#2 IVIG for Toxic Necrotizing Fasciitis: What the Evidence Says – AmeriPharmaÂ® Specialty Care
https://ameripharmaspecialty.com/ivig/ivig-for-toxic-necrotizing-fasciitis-what-the-evidence-says/
Necrotizing fasciitis is a rare, aggressive bacterial infection. Delayed treatment may result in multiple organ failure and death. […] Necrotizing fasciitis causes death (necrosis) of the fascia and tissues beneath your skin. The fascia is a thin layer of connective tissue that surrounds your muscles, bones, and organs. […] Necrotizing fasciitis affects about four in one million Americans each year. It can occur when a bacterium or several bacteria enter the body and produce toxins. These toxins limit blood supply to tissues and damage cells, causing pus-filled lesions. […] If the toxins reach your bloodstream, it may result in toxic shock. […] How IVIG benefits people with necrotizing fasciitis isnât fully understood. Health experts believe IVIG may work by: Neutralizing the bacterial toxins, Preventing abnormally rapid multiplication of certain immune cells, Reducing inflammation. […] Despite promising results in case studies, several challenges still limit IVIG use for necrotizing fasciitis. Researchers have yet to determine: The most effective IVIG agent, The timing of therapy, The dose, The duration of treatment.
#2 Necrotizing fasciitis not always caused by bacteria but by a combination of tissue damage and a gene defect | HUS
https://www.hus.fi/en/newsroom/necrotizing-fasciitis-not-always-caused-bacteria-combination-tissue-damage-and-gene-defect
A new Finnish-led study suggests that necrotizing fasciitis, a life-threatening inflammation of connective tissue that leads to tissue necrosis, may be caused by a gene defect. […] The study investigated the mechanism of how a gene defect causes an excessive and violent inflammatory response. […] In patients, mild injury, surgery or infection had triggered an uncontrolled inflammatory reaction leading to severe deep tissue inflammation. […] Researchers have found an inflammation-activating defect in the NFKB1 gene in three Finnish and three foreign pediatric and adult patients with severe fasciitis. […] With new gene-editing techniques, we were able to identify the nature of the inflammatory response and the mechanisms by which a gene defect causes a strong inflammatory response.
#2 Necrotising Fasciitis | SpringerLink
https://link.springer.com/10.1007/978-3-642-34746-7_73?fromPaywallRec=true
Despite the expanded understanding on the pathophysiology of sepsis, the contemporary sophisticated diagnostic methods, and the modern advanced antibiotics, surgical debridement remains the cornerstone of treatment of necrotising fasciitis. […] Clinical research on this rare and lethal disease lacks of high-level evidence, highlighting the necessity of multicentre collaboration on this scientific effort. […] Young LM, Price CS. Community-acquired methicillin-resistant Staphylococcus aureus emerging as an important cause of necrotizing fasciitis. […] Wong CH, Khin LW, Heng KS, et al. The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. […] Liu YM, Chi CY, Ho MW, et al. Microbiology and factors affecting mortality in necrotizing fasciitis.
#2 Necrotizing fasciitis – Wikipedia
https://en.wikipedia.org/wiki/Necrotizing_fasciitis
Bacterial infection is by far the most common cause of necrotizing fasciitis. Despite being called a „flesh-eating disease”, bacteria do not eat human tissue. Rather, they release toxins that cause tissue death. Typically, the infection enters the body through a break in the skin such as a cut or burn. […] NSAIDs may increase the rates of necrotizing infections by impairing the body’s immune response. NSAIDs inhibit the production of prostaglandins responsible for fever, inflammation, and pain. In theory, it also prevents white blood cells from migrating to infected areas, thus increasing the risk of soft-tissue infections. […] Necrotizing fasciitis is divided into four classes by the type of bacteria causing the infection. This classification system was first described by Giuliano and his colleagues in 1977.
#2 Multidisciplinary management of periocular necrotising fasciitis: a series of 11 patients | Eye
https://www.nature.com/articles/eye2011241
The streptococcal M protein has been identified as a potent inducer of inflammation and seems to be responsible for the severity of necrotising fasciitis. Other bacteria have also been implicated in the pathogenesis of necrotising fasciitis like Escherichia coli, Kleibsella pneumoniae, and Moraxella. […] Thrombosis of the microcirculatory vessels of superficial fascia leads to secondary gangrene of the skin and forms the basis for the pathogenesis of this condition. Periocular necrotising fasciitis can have devastating complications. Central retinal artery occlusion with loss of vision and exenteration for deep orbital involvement, has been reported. Early surgical intervention reduces morbidity and mortality significantly; left untreated, the mortality ranges between 30-70%. […] The key to successful management of necrotising fasciitis is early diagnosis and intervention. The use of hyperbaric oxygen and intravenous immunoglobulin have been recommended by some researchers, but are more useful as adjuncts to broad-spectrum intravenous antibiotic therapy and early debridement.
#3 Necrotizing fasciitis – Wikipedia
https://en.wikipedia.org/wiki/Necrotizing_fasciitis
Type I infection: This is the most common type of infection, and accounts for 70 to 80% of cases. It is caused by a mixture of bacterial types, usually in abdominal or groin areas. […] In polymicrobial (mixed) infections, Group A Streptococcus (S. pyogenes) is the most commonly found bacterium, followed by S. aureus. However, when the infection is caused solely by S. pyogenes and/or S. aureus, it is classified as a Type II infection. […] Type II infection: This infection accounts for 20 to 30% of cases, mainly involving the extremities. This involves Streptococcus pyogenes, alone or in combination with staphylococcal infections. Methicillin-resistant Staphylococcus aureus (MRSA) is involved in up to a third of Type II infections. […] Type III infection: Vibrio vulnificus is a bacterium found in saltwater. It occasionally causes NF after entering the body through a break in the skin. One in three patients with a V. vulnificus infection develop necrotizing fasciitis. […] Type IV infection: This type of NF accounts for less than 1% of cases. It is mostly caused by the Candida albicans fungus. Risk factors include age and immunodeficiency.
#3 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
Carbon dioxide and water are the end products of aerobic metabolism. […] In necrotizing fasciitis, group A hemolytic streptococci and Staphylococcus aureus, alone or in synergism, are frequently the initiating infecting bacteria. […] Organisms spread from the subcutaneous tissue along the superficial and deep fascial planes, presumably facilitated by bacterial enzymes and toxins. […] Important bacterial factors include surface protein expression and toxin production. […] Streptococcal pyrogenic exotoxins (SPEs) A, B, and C are directly toxic and tend to be produced by strains causing necrotizing fasciitis. […] The poor prognosis associated with necrotizing fasciitis has been linked to infection with certain streptococcal strains. […] Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species.
#3 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
Necrotizing fasciitis is characterized by widespread necrosis of the subcutaneous tissue and the fascia. […] Although the pathogenesis of necrotizing fasciitis is still open to speculation, the rapid and destructive clinical course of necrotizing fasciitis is thought to be due to multibacterial symbiosis and synergy. […] Historically, group A beta-hemolytic Streptococcus (GABS) has been identified as a major cause of this infection. […] During the last few decades, researchers have found that necrotizing fasciitis is usually polymicrobial rather than monomicrobial. […] Anaerobic bacteria are present in most necrotizing soft-tissue infections, usually in combination with aerobic gram-negative organisms. […] Facultative aerobic organisms grow because polymorphonuclear neutrophils (PMNs) exhibit decreased function under hypoxic wound conditions.
#3 Necrotising fasciitis
https://dermnetnz.org/topics/necrotising-fasciitis
Necrotising fasciitis is a very serious bacterial infection of the soft tissue and fascia. The bacteria multiply and release toxins and enzymes that result in thrombosis in the blood vessels. The result is the destruction of the soft tissues and fascia. […] The infection starts in the superficial fascia. Enzymes and proteins released by the responsible micro-organisms cause necrosis of fascial layers. Horizontal spread of infection may not be clinically apparent on the skin surface and hence diagnosis may be delayed. The infection then spreads vertically up into the skin and down into deeper structures. Thrombosis occludes the arteries and veins leading to ischaemia and necrosis of the tissues. […] Streptococci produce M proteins, which initiate an inflammatory response with the release of numerous cytokines (IL-1, IL-6, TNF). Exotoxins, which destroy neutrophils allowing bacterial growth and destroying tissues. […] Aerobic and anaerobic bacteria produce hydrogen, nitrogen, and hydrogen sulfide gases that destroy hyaluronic acid enabling the spread of infection.
#3 Necrotising soft tissue infections | Deranged Physiology
https://derangedphysiology.com/main/required-reading/sepsis-and-infections/Chapter-341/necrotising-soft-tissue-infections
S.pyogenes produces enzymes such as hyaluronidase, which digest the fascia. […] It also produces superantigen toxins, which lead to streptococcal toxic shock syndrome. […] The histologic criteria for diagnosis as described by Stamenkovic and Lew (1984) were as follows: necrosis of the superficial fascia, polymorphonuclear infiltration of the dermis and fascia, fibrinous thrombi of arteries and veins coursing through the fascia, angiitis with fibrinoid necrosis of arterial and venous walls, presence of microorganisms within the destroyed fascia and dermis, and an absence of muscle involvement. […] The addition of clindamycin is well supported – particularly with Group A streptococci, where it inhibits the bacterial synthesis of endotoxin. […] The already-mentioned retrospective audit from Victoria had also suggested that people with severe soft tissue infections benefit from IVIg irrespective of whether they have toxic shock syndrome or not.
#3 Cervical Necrotizing Fasciitis in Adults: A Life-Threatening Emergency in Oral and Maxillofacial Surgery
https://www.mdpi.com/2673-4095/5/3/42
NF is characterized by the rapidly progressive necrosis of the superficial fascia and overlying subcutaneous tissue. […] The infection of subcutaneous tissue leads to subdermal venous thrombosis and inflammatory cell infiltration with abscess formation, followed by arterial compromise due to endarteritis obliterans. […] This causes critical skin ischemia, with blisters or bullae formation. […] Necrosis of the skin and coliquative gangrene follow. […] At this point, pain is reduced, secondary to the destruction of superficial cutaneous nerves.
#3 Necrotizing Fasciitis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK430756/
Advanced stages of the infection are characterized by systemic symptoms such as fever, tachycardia, and sepsis. […] Anaerobic bacteria mixed with aerobic organisms are commonly found in most soft tissue infections. […] The majority of small and medium-sized blood vessels will be thrombosed. […] The treatment of necrotizing fasciitis is surgery, and no time should be wasted calling for a surgical consult. The earlier the surgery is undertaken, the better the outcome. […] The earlier the surgery may help minimize tissue loss and eliminate the need for amputation of a gangrenous extremity. […] Hyperbaric oxygen therapy may be effective for small wounds, but there is no evidence that this therapy improves healing or prolongs life for large wounds. […] Necrotizing fasciitis is a serious life-threatening infection with mortality rates ranging from 20 to 80%. Poor prognosis has been linked to certain streptococcal strains, advanced age, uncontrolled diabetes, state of immunosuppression, and delayed surgery. […] The complications that can manifest with necrotizing fasciitis are as follows: multiorgan failure, septic shock, loss of extremity, severe scarring, toxic shock, and death.
#3 The Diagnosis And Management Of Necrotising Fasciitis : Virtual Library
https://resources.wfsahq.org/atotw/the-diagnosis-and-management-of-necrotising-fasciitis-anaesthesia-tutorial-of-the-week-298/
Massive T cell proliferation and cytokine release can occur in type II NF via the effects due to the M protein of group A -haemolytic streptococcus (GAS). This filamentous protein has anti-phagocytic properties and is an important virulence determinant as it can produce multiple pyogenic exotoxins that act as super-antigens. These cause a systemic inflammatory response syndrome (SIRS) which may progress to multi-organ failure. […] NF is a surgical emergency and warrants immediate surgical referral. Evidence has shown that when treatment is based on just antimicrobial therapy and support, mortality approaches 100%. Surgery is a vital means of source control. […] Antibiotics are a vital adjunct to source control and may prevent the progression of septic shock when used early. […] Hyperbaric oxygen (HBO) is thought to increase the bactericidal effects of neutrophils since at low oxygen tensions killing mechanisms reliant on oxygen free radicals are less effective. HBO alone is also thought to be bactericidal for certain anaerobes, including Clostridium Perfringens as it switches off -toxin production. […] The role of IVIG and HBO in the treatment of NF remains unclear due to the lack of randomized controlled trials. However if available, these therapies should be considered when surgical debridement, antibiotics and general supportive measures have proved unsuccessful.
#3 Clinical Guidance for Type II Necrotizing Fasciitis | Group A Strep | CDC
https://www.cdc.gov/group-a-strep/hcp/clinical-guidance/necrotizing-fasciitis.html
Skin discoloration indicates small vessels in the dermal papilla have thrombosed. Affected tissues progressively darken from red to purple to blue to black. As gangrene sets in, skin becomes anesthetized as superficial nerves die. […] Indications of advance disease include anesthesia, bullae, crepitus, ecchymosis, and necrosis. […] The lesions become sharply demarcated. As skin sloughs, a necrotic eschar forms, resembling a third-degree burn. […] Primary treatment of necrotizing fasciitis is early and aggressive surgical exploration and debridement of necrotic tissue. […] Antibiotic therapy is based upon Gram stain findings. Once group A strep is confirmed to be the etiology, recommended treatment is high-dose penicillin and clindamycin (interferes with toxin production). […] Amputations are a common complication of necrotizing fasciitis. […] In the most recent 5 years, the mortality rate of streptococcal necrotizing fasciitis has been around 13 to 18%. It increases with age of the person affected and the presence of streptococcal toxic shock syndrome.
#3
https://journals.lww.com/prsgo/fulltext/2024/01000/practical_review_of_necrotizing_fasciitis_.23.aspx
Hyperbaric oxygen (HBO) and Intravenous immunoglobulin (IVIG) have been suggested as adjunct treatments for NF. Research indicates that HBO improves patient survival while decreasing the number of surgical debridements and potentially the extent of reconstruction by inhibiting the systemic inflammatory response system and improving leukocyte activity. Moreover, it can facilitate the transport of some antibiotics, such as aminoglycosides. IVIG has been shown to be beneficial in patients with GAS NF that progressed into toxic shock syndrome. Researchers have linked the efficacy of IVIG in NF to its ability to reduce a systemic inflammatory response by targeting the exotoxins.
#3 Necrotizing fasciitis not always caused by bacteria but by a combination of tissue damage and a gene defect | HUS
https://www.hus.fi/en/newsroom/necrotizing-fasciitis-not-always-caused-bacteria-combination-tissue-damage-and-gene-defect
A new Finnish-led study suggests that necrotizing fasciitis, a life-threatening inflammation of connective tissue that leads to tissue necrosis, may be caused by a gene defect. […] The study investigated the mechanism of how a gene defect causes an excessive and violent inflammatory response. […] In patients, mild injury, surgery or infection had triggered an uncontrolled inflammatory reaction leading to severe deep tissue inflammation. […] Researchers have found an inflammation-activating defect in the NFKB1 gene in three Finnish and three foreign pediatric and adult patients with severe fasciitis. […] With new gene-editing techniques, we were able to identify the nature of the inflammatory response and the mechanisms by which a gene defect causes a strong inflammatory response.
#3 What Is Necrotizing Fasciitis (Flesh-Eating Bacteria)? – Consensus: AI Search Engine for Research
https://consensus.app/home/blog/what-is-necrotizing-fasciitis-flesh-eating-bacteria/
Necrotizing fasciitis is primarily caused by Group A Streptococcus (GAS), a versatile pathogen responsible for a range of diseases from mild pharyngitis to life-threatening infections like NF. GAS secretes a variety of proteases that disrupt host tissues, regulated by multiple transcriptional and posttranslational processes. […] Recent studies have shown that single-nucleotide mutations in the GAS genome can significantly alter its virulence, affecting the expression of key virulence factors like SpeB protease. Moreover, the interaction between different bacterial strains in polymicrobial infections can modulate the virulence and immune response, as seen in mixed infections with Aeromonas hydrophila strains.
#3 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
It was found that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. […] Severe myositis accompanying septic necrotizing fasciitis may be caused by a Panton-Valentine leukocidinpositive S aureus strain. […] Although necrotizing fasciitis most frequently develops after trauma that compromises skin integrity, it may rarely develop in a healthy person after minor trauma such as an isolated shoulder sprain that occurred without a break in skin barrier.
#3 Necrotizing fasciitis pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Necrotizing_fasciitis_pathophysiology
The pathogenesis of necrotizing fasciitis is the result of bacterial and host factors. […] The exact pathogenesis of type 1 necrotizing fasciitis is not fully understood. It is thought that type 1 NF is caused by polymicrobial species that work synergistically to enhance the spread of infection. […] Group A streptococcus is the most common causative agent of type 2 NF. The pathogenesis of type 2 NF is the result of the following process: Inhibition of phagocytosis of bacteria by hyaluronic acid capsule and M protein. Adherence of bacteria to host cell through adherence factors such as M protein, protein F and lipoteichoic acid. Release of exotoxins (streptococcal pyogenic exotoxins and superantigen) into blood produce massive proliferation of T cells and cascading release of cytokines activating inflammatory process. […] The massive release of cytokines result in systemic inflammatory response syndrome resulting in shock, organ failure, depression of myocardial function and immune suppression.
#4 Necrotizing fasciitis – Wikipedia
https://en.wikipedia.org/wiki/Necrotizing_fasciitis
Type I infection: This is the most common type of infection, and accounts for 70 to 80% of cases. It is caused by a mixture of bacterial types, usually in abdominal or groin areas. […] In polymicrobial (mixed) infections, Group A Streptococcus (S. pyogenes) is the most commonly found bacterium, followed by S. aureus. However, when the infection is caused solely by S. pyogenes and/or S. aureus, it is classified as a Type II infection. […] Type II infection: This infection accounts for 20 to 30% of cases, mainly involving the extremities. This involves Streptococcus pyogenes, alone or in combination with staphylococcal infections. Methicillin-resistant Staphylococcus aureus (MRSA) is involved in up to a third of Type II infections. […] Type III infection: Vibrio vulnificus is a bacterium found in saltwater. It occasionally causes NF after entering the body through a break in the skin. One in three patients with a V. vulnificus infection develop necrotizing fasciitis. […] Type IV infection: This type of NF accounts for less than 1% of cases. It is mostly caused by the Candida albicans fungus. Risk factors include age and immunodeficiency.
#4 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
Carbon dioxide and water are the end products of aerobic metabolism. […] In necrotizing fasciitis, group A hemolytic streptococci and Staphylococcus aureus, alone or in synergism, are frequently the initiating infecting bacteria. […] Organisms spread from the subcutaneous tissue along the superficial and deep fascial planes, presumably facilitated by bacterial enzymes and toxins. […] Important bacterial factors include surface protein expression and toxin production. […] Streptococcal pyrogenic exotoxins (SPEs) A, B, and C are directly toxic and tend to be produced by strains causing necrotizing fasciitis. […] The poor prognosis associated with necrotizing fasciitis has been linked to infection with certain streptococcal strains. […] Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species.
#4 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
Necrotizing fasciitis is characterized by widespread necrosis of the subcutaneous tissue and the fascia. […] Although the pathogenesis of necrotizing fasciitis is still open to speculation, the rapid and destructive clinical course of necrotizing fasciitis is thought to be due to multibacterial symbiosis and synergy. […] Historically, group A beta-hemolytic Streptococcus (GABS) has been identified as a major cause of this infection. […] During the last few decades, researchers have found that necrotizing fasciitis is usually polymicrobial rather than monomicrobial. […] Anaerobic bacteria are present in most necrotizing soft-tissue infections, usually in combination with aerobic gram-negative organisms. […] Facultative aerobic organisms grow because polymorphonuclear neutrophils (PMNs) exhibit decreased function under hypoxic wound conditions.
#4 Necrotising fasciitis
https://dermnetnz.org/topics/necrotising-fasciitis
Necrotising fasciitis is a very serious bacterial infection of the soft tissue and fascia. The bacteria multiply and release toxins and enzymes that result in thrombosis in the blood vessels. The result is the destruction of the soft tissues and fascia. […] The infection starts in the superficial fascia. Enzymes and proteins released by the responsible micro-organisms cause necrosis of fascial layers. Horizontal spread of infection may not be clinically apparent on the skin surface and hence diagnosis may be delayed. The infection then spreads vertically up into the skin and down into deeper structures. Thrombosis occludes the arteries and veins leading to ischaemia and necrosis of the tissues. […] Streptococci produce M proteins, which initiate an inflammatory response with the release of numerous cytokines (IL-1, IL-6, TNF). Exotoxins, which destroy neutrophils allowing bacterial growth and destroying tissues. […] Aerobic and anaerobic bacteria produce hydrogen, nitrogen, and hydrogen sulfide gases that destroy hyaluronic acid enabling the spread of infection.
#4 Necrotising soft tissue infections | Deranged Physiology
https://derangedphysiology.com/main/required-reading/sepsis-and-infections/Chapter-341/necrotising-soft-tissue-infections
S.pyogenes produces enzymes such as hyaluronidase, which digest the fascia. […] It also produces superantigen toxins, which lead to streptococcal toxic shock syndrome. […] The histologic criteria for diagnosis as described by Stamenkovic and Lew (1984) were as follows: necrosis of the superficial fascia, polymorphonuclear infiltration of the dermis and fascia, fibrinous thrombi of arteries and veins coursing through the fascia, angiitis with fibrinoid necrosis of arterial and venous walls, presence of microorganisms within the destroyed fascia and dermis, and an absence of muscle involvement. […] The addition of clindamycin is well supported – particularly with Group A streptococci, where it inhibits the bacterial synthesis of endotoxin. […] The already-mentioned retrospective audit from Victoria had also suggested that people with severe soft tissue infections benefit from IVIg irrespective of whether they have toxic shock syndrome or not.
#4 Cervical Necrotizing Fasciitis in Adults: A Life-Threatening Emergency in Oral and Maxillofacial Surgery
https://www.mdpi.com/2673-4095/5/3/42
NF is characterized by the rapidly progressive necrosis of the superficial fascia and overlying subcutaneous tissue. […] The infection of subcutaneous tissue leads to subdermal venous thrombosis and inflammatory cell infiltration with abscess formation, followed by arterial compromise due to endarteritis obliterans. […] This causes critical skin ischemia, with blisters or bullae formation. […] Necrosis of the skin and coliquative gangrene follow. […] At this point, pain is reduced, secondary to the destruction of superficial cutaneous nerves.
#4 Necrotizing Fasciitis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK430756/
Advanced stages of the infection are characterized by systemic symptoms such as fever, tachycardia, and sepsis. […] Anaerobic bacteria mixed with aerobic organisms are commonly found in most soft tissue infections. […] The majority of small and medium-sized blood vessels will be thrombosed. […] The treatment of necrotizing fasciitis is surgery, and no time should be wasted calling for a surgical consult. The earlier the surgery is undertaken, the better the outcome. […] The earlier the surgery may help minimize tissue loss and eliminate the need for amputation of a gangrenous extremity. […] Hyperbaric oxygen therapy may be effective for small wounds, but there is no evidence that this therapy improves healing or prolongs life for large wounds. […] Necrotizing fasciitis is a serious life-threatening infection with mortality rates ranging from 20 to 80%. Poor prognosis has been linked to certain streptococcal strains, advanced age, uncontrolled diabetes, state of immunosuppression, and delayed surgery. […] The complications that can manifest with necrotizing fasciitis are as follows: multiorgan failure, septic shock, loss of extremity, severe scarring, toxic shock, and death.
#4 Necrotizing fasciitis not always caused by bacteria but by a combination of tissue damage and a gene defect | HUS
https://www.hus.fi/en/newsroom/necrotizing-fasciitis-not-always-caused-bacteria-combination-tissue-damage-and-gene-defect
A new Finnish-led study suggests that necrotizing fasciitis, a life-threatening inflammation of connective tissue that leads to tissue necrosis, may be caused by a gene defect. […] The study investigated the mechanism of how a gene defect causes an excessive and violent inflammatory response. […] In patients, mild injury, surgery or infection had triggered an uncontrolled inflammatory reaction leading to severe deep tissue inflammation. […] Researchers have found an inflammation-activating defect in the NFKB1 gene in three Finnish and three foreign pediatric and adult patients with severe fasciitis. […] With new gene-editing techniques, we were able to identify the nature of the inflammatory response and the mechanisms by which a gene defect causes a strong inflammatory response.
#4 What Is Necrotizing Fasciitis (Flesh-Eating Bacteria)? – Consensus: AI Search Engine for Research
https://consensus.app/home/blog/what-is-necrotizing-fasciitis-flesh-eating-bacteria/
Necrotizing fasciitis is primarily caused by Group A Streptococcus (GAS), a versatile pathogen responsible for a range of diseases from mild pharyngitis to life-threatening infections like NF. GAS secretes a variety of proteases that disrupt host tissues, regulated by multiple transcriptional and posttranslational processes. […] Recent studies have shown that single-nucleotide mutations in the GAS genome can significantly alter its virulence, affecting the expression of key virulence factors like SpeB protease. Moreover, the interaction between different bacterial strains in polymicrobial infections can modulate the virulence and immune response, as seen in mixed infections with Aeromonas hydrophila strains.
#4 The Diagnosis And Management Of Necrotising Fasciitis : Virtual Library
https://resources.wfsahq.org/atotw/the-diagnosis-and-management-of-necrotising-fasciitis-anaesthesia-tutorial-of-the-week-298/
Massive T cell proliferation and cytokine release can occur in type II NF via the effects due to the M protein of group A -haemolytic streptococcus (GAS). This filamentous protein has anti-phagocytic properties and is an important virulence determinant as it can produce multiple pyogenic exotoxins that act as super-antigens. These cause a systemic inflammatory response syndrome (SIRS) which may progress to multi-organ failure. […] NF is a surgical emergency and warrants immediate surgical referral. Evidence has shown that when treatment is based on just antimicrobial therapy and support, mortality approaches 100%. Surgery is a vital means of source control. […] Antibiotics are a vital adjunct to source control and may prevent the progression of septic shock when used early. […] Hyperbaric oxygen (HBO) is thought to increase the bactericidal effects of neutrophils since at low oxygen tensions killing mechanisms reliant on oxygen free radicals are less effective. HBO alone is also thought to be bactericidal for certain anaerobes, including Clostridium Perfringens as it switches off -toxin production. […] The role of IVIG and HBO in the treatment of NF remains unclear due to the lack of randomized controlled trials. However if available, these therapies should be considered when surgical debridement, antibiotics and general supportive measures have proved unsuccessful.
#5 Necrotizing fasciitis – Wikipedia
https://en.wikipedia.org/wiki/Necrotizing_fasciitis
Type I infection: This is the most common type of infection, and accounts for 70 to 80% of cases. It is caused by a mixture of bacterial types, usually in abdominal or groin areas. […] In polymicrobial (mixed) infections, Group A Streptococcus (S. pyogenes) is the most commonly found bacterium, followed by S. aureus. However, when the infection is caused solely by S. pyogenes and/or S. aureus, it is classified as a Type II infection. […] Type II infection: This infection accounts for 20 to 30% of cases, mainly involving the extremities. This involves Streptococcus pyogenes, alone or in combination with staphylococcal infections. Methicillin-resistant Staphylococcus aureus (MRSA) is involved in up to a third of Type II infections. […] Type III infection: Vibrio vulnificus is a bacterium found in saltwater. It occasionally causes NF after entering the body through a break in the skin. One in three patients with a V. vulnificus infection develop necrotizing fasciitis. […] Type IV infection: This type of NF accounts for less than 1% of cases. It is mostly caused by the Candida albicans fungus. Risk factors include age and immunodeficiency.
#5 Necrotising fasciitis
https://dermnetnz.org/topics/necrotising-fasciitis
Necrotising fasciitis is a very serious bacterial infection of the soft tissue and fascia. The bacteria multiply and release toxins and enzymes that result in thrombosis in the blood vessels. The result is the destruction of the soft tissues and fascia. […] The infection starts in the superficial fascia. Enzymes and proteins released by the responsible micro-organisms cause necrosis of fascial layers. Horizontal spread of infection may not be clinically apparent on the skin surface and hence diagnosis may be delayed. The infection then spreads vertically up into the skin and down into deeper structures. Thrombosis occludes the arteries and veins leading to ischaemia and necrosis of the tissues. […] Streptococci produce M proteins, which initiate an inflammatory response with the release of numerous cytokines (IL-1, IL-6, TNF). Exotoxins, which destroy neutrophils allowing bacterial growth and destroying tissues. […] Aerobic and anaerobic bacteria produce hydrogen, nitrogen, and hydrogen sulfide gases that destroy hyaluronic acid enabling the spread of infection.
#5 Necrotizing Fasciitis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK430756/
Advanced stages of the infection are characterized by systemic symptoms such as fever, tachycardia, and sepsis. […] Anaerobic bacteria mixed with aerobic organisms are commonly found in most soft tissue infections. […] The majority of small and medium-sized blood vessels will be thrombosed. […] The treatment of necrotizing fasciitis is surgery, and no time should be wasted calling for a surgical consult. The earlier the surgery is undertaken, the better the outcome. […] The earlier the surgery may help minimize tissue loss and eliminate the need for amputation of a gangrenous extremity. […] Hyperbaric oxygen therapy may be effective for small wounds, but there is no evidence that this therapy improves healing or prolongs life for large wounds. […] Necrotizing fasciitis is a serious life-threatening infection with mortality rates ranging from 20 to 80%. Poor prognosis has been linked to certain streptococcal strains, advanced age, uncontrolled diabetes, state of immunosuppression, and delayed surgery. […] The complications that can manifest with necrotizing fasciitis are as follows: multiorgan failure, septic shock, loss of extremity, severe scarring, toxic shock, and death.
#5 Necrotising soft tissue infections | Deranged Physiology
https://derangedphysiology.com/main/required-reading/sepsis-and-infections/Chapter-341/necrotising-soft-tissue-infections
S.pyogenes produces enzymes such as hyaluronidase, which digest the fascia. […] It also produces superantigen toxins, which lead to streptococcal toxic shock syndrome. […] The histologic criteria for diagnosis as described by Stamenkovic and Lew (1984) were as follows: necrosis of the superficial fascia, polymorphonuclear infiltration of the dermis and fascia, fibrinous thrombi of arteries and veins coursing through the fascia, angiitis with fibrinoid necrosis of arterial and venous walls, presence of microorganisms within the destroyed fascia and dermis, and an absence of muscle involvement. […] The addition of clindamycin is well supported – particularly with Group A streptococci, where it inhibits the bacterial synthesis of endotoxin. […] The already-mentioned retrospective audit from Victoria had also suggested that people with severe soft tissue infections benefit from IVIg irrespective of whether they have toxic shock syndrome or not.
#5 Necrotizing fasciitis not always caused by bacteria but by a combination of tissue damage and a gene defect | HUS
https://www.hus.fi/en/newsroom/necrotizing-fasciitis-not-always-caused-bacteria-combination-tissue-damage-and-gene-defect
A new Finnish-led study suggests that necrotizing fasciitis, a life-threatening inflammation of connective tissue that leads to tissue necrosis, may be caused by a gene defect. […] The study investigated the mechanism of how a gene defect causes an excessive and violent inflammatory response. […] In patients, mild injury, surgery or infection had triggered an uncontrolled inflammatory reaction leading to severe deep tissue inflammation. […] Researchers have found an inflammation-activating defect in the NFKB1 gene in three Finnish and three foreign pediatric and adult patients with severe fasciitis. […] With new gene-editing techniques, we were able to identify the nature of the inflammatory response and the mechanisms by which a gene defect causes a strong inflammatory response.
#5 Necrotizing Fasciitis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/784690-overview
Carbon dioxide and water are the end products of aerobic metabolism. […] In necrotizing fasciitis, group A hemolytic streptococci and Staphylococcus aureus, alone or in synergism, are frequently the initiating infecting bacteria. […] Organisms spread from the subcutaneous tissue along the superficial and deep fascial planes, presumably facilitated by bacterial enzymes and toxins. […] Important bacterial factors include surface protein expression and toxin production. […] Streptococcal pyrogenic exotoxins (SPEs) A, B, and C are directly toxic and tend to be produced by strains causing necrotizing fasciitis. […] The poor prognosis associated with necrotizing fasciitis has been linked to infection with certain streptococcal strains. […] Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species.
#5 The Diagnosis And Management Of Necrotising Fasciitis : Virtual Library
https://resources.wfsahq.org/atotw/the-diagnosis-and-management-of-necrotising-fasciitis-anaesthesia-tutorial-of-the-week-298/
Massive T cell proliferation and cytokine release can occur in type II NF via the effects due to the M protein of group A -haemolytic streptococcus (GAS). This filamentous protein has anti-phagocytic properties and is an important virulence determinant as it can produce multiple pyogenic exotoxins that act as super-antigens. These cause a systemic inflammatory response syndrome (SIRS) which may progress to multi-organ failure. […] NF is a surgical emergency and warrants immediate surgical referral. Evidence has shown that when treatment is based on just antimicrobial therapy and support, mortality approaches 100%. Surgery is a vital means of source control. […] Antibiotics are a vital adjunct to source control and may prevent the progression of septic shock when used early. […] Hyperbaric oxygen (HBO) is thought to increase the bactericidal effects of neutrophils since at low oxygen tensions killing mechanisms reliant on oxygen free radicals are less effective. HBO alone is also thought to be bactericidal for certain anaerobes, including Clostridium Perfringens as it switches off -toxin production. […] The role of IVIG and HBO in the treatment of NF remains unclear due to the lack of randomized controlled trials. However if available, these therapies should be considered when surgical debridement, antibiotics and general supportive measures have proved unsuccessful.
#6 Necrotising fasciitis
https://dermnetnz.org/topics/necrotising-fasciitis
Necrotising fasciitis is a very serious bacterial infection of the soft tissue and fascia. The bacteria multiply and release toxins and enzymes that result in thrombosis in the blood vessels. The result is the destruction of the soft tissues and fascia. […] The infection starts in the superficial fascia. Enzymes and proteins released by the responsible micro-organisms cause necrosis of fascial layers. Horizontal spread of infection may not be clinically apparent on the skin surface and hence diagnosis may be delayed. The infection then spreads vertically up into the skin and down into deeper structures. Thrombosis occludes the arteries and veins leading to ischaemia and necrosis of the tissues. […] Streptococci produce M proteins, which initiate an inflammatory response with the release of numerous cytokines (IL-1, IL-6, TNF). Exotoxins, which destroy neutrophils allowing bacterial growth and destroying tissues. […] Aerobic and anaerobic bacteria produce hydrogen, nitrogen, and hydrogen sulfide gases that destroy hyaluronic acid enabling the spread of infection.
#6 Necrotizing Fasciitis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK430756/
Advanced stages of the infection are characterized by systemic symptoms such as fever, tachycardia, and sepsis. […] Anaerobic bacteria mixed with aerobic organisms are commonly found in most soft tissue infections. […] The majority of small and medium-sized blood vessels will be thrombosed. […] The treatment of necrotizing fasciitis is surgery, and no time should be wasted calling for a surgical consult. The earlier the surgery is undertaken, the better the outcome. […] The earlier the surgery may help minimize tissue loss and eliminate the need for amputation of a gangrenous extremity. […] Hyperbaric oxygen therapy may be effective for small wounds, but there is no evidence that this therapy improves healing or prolongs life for large wounds. […] Necrotizing fasciitis is a serious life-threatening infection with mortality rates ranging from 20 to 80%. Poor prognosis has been linked to certain streptococcal strains, advanced age, uncontrolled diabetes, state of immunosuppression, and delayed surgery. […] The complications that can manifest with necrotizing fasciitis are as follows: multiorgan failure, septic shock, loss of extremity, severe scarring, toxic shock, and death.
#7 Necrotizing Fasciitis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK430756/
Advanced stages of the infection are characterized by systemic symptoms such as fever, tachycardia, and sepsis. […] Anaerobic bacteria mixed with aerobic organisms are commonly found in most soft tissue infections. […] The majority of small and medium-sized blood vessels will be thrombosed. […] The treatment of necrotizing fasciitis is surgery, and no time should be wasted calling for a surgical consult. The earlier the surgery is undertaken, the better the outcome. […] The earlier the surgery may help minimize tissue loss and eliminate the need for amputation of a gangrenous extremity. […] Hyperbaric oxygen therapy may be effective for small wounds, but there is no evidence that this therapy improves healing or prolongs life for large wounds. […] Necrotizing fasciitis is a serious life-threatening infection with mortality rates ranging from 20 to 80%. Poor prognosis has been linked to certain streptococcal strains, advanced age, uncontrolled diabetes, state of immunosuppression, and delayed surgery. […] The complications that can manifest with necrotizing fasciitis are as follows: multiorgan failure, septic shock, loss of extremity, severe scarring, toxic shock, and death.
#8 Necrotizing Fasciitis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK430756/
Advanced stages of the infection are characterized by systemic symptoms such as fever, tachycardia, and sepsis. […] Anaerobic bacteria mixed with aerobic organisms are commonly found in most soft tissue infections. […] The majority of small and medium-sized blood vessels will be thrombosed. […] The treatment of necrotizing fasciitis is surgery, and no time should be wasted calling for a surgical consult. The earlier the surgery is undertaken, the better the outcome. […] The earlier the surgery may help minimize tissue loss and eliminate the need for amputation of a gangrenous extremity. […] Hyperbaric oxygen therapy may be effective for small wounds, but there is no evidence that this therapy improves healing or prolongs life for large wounds. […] Necrotizing fasciitis is a serious life-threatening infection with mortality rates ranging from 20 to 80%. Poor prognosis has been linked to certain streptococcal strains, advanced age, uncontrolled diabetes, state of immunosuppression, and delayed surgery. […] The complications that can manifest with necrotizing fasciitis are as follows: multiorgan failure, septic shock, loss of extremity, severe scarring, toxic shock, and death.