View source for Gangrene

{{Short description|Type of tissue death by ischemia}}
{{Other uses}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox medical condition
| name            = Gangrene
| synonyms        = Gangrenous necrosis
| image           = GangreneFoot.JPG
| alt             =
| caption         = Dry gangrene affecting the toes as a result of [[peripheral artery disease]]
| field           = [[Infectious disease (medical specialty)|Infectious disease]], [[surgery]], [[podiatry]]
| symptoms        = Change in skin color to red or black, numbness, pain, skin breakdown, coolness<ref name="NHS2015Sym" />
| complications   = [[Sepsis]], [[amputation]]<ref name="NHS2015Sym" /><ref name="Pt2014" />
| onset           =
| duration        =
| types           = [[dry gangrene|Dry]], [[wet gangrene|wet]], [[gas gangrene|gas]], [[internal gangrene (disambiguation)|internal]]<!--intentional link to DAB page-->, [[necrotizing fasciitis]]<ref name="NHS2015Cau" />
| causes          =
| risks           = [[Diabetes]], [[peripheral arterial disease]], [[smoking]], [[major trauma]], [[alcoholism]], [[Plague (disease)|plague]], [[HIV/AIDS]], [[frostbite]], [[Raynaud's syndrome]]<ref name="NHS2015Cau" /><ref name="NHS2015Over" />
| diagnosis       = Based on symptom, with medical imaging used to identify the underlying cause.
| differential    =
| prevention      =
| treatment       = Depends on underlying cause<ref name="NHS2015Tx" />
| medication      =
| prognosis       = Variable
| frequency       = Unknown<ref name="Pt2014" />
| deaths          =
}}
[[File:Gangrene toes (1).jpg|thumb|Gangrenous toes in a diabetic]]<!-- Definition and symptoms -->
'''Gangrene''' is a type of [[necrosis|tissue death]] caused by a [[ischemia|lack of blood supply]].<ref name=NHS2015Over>{{cite web | title = Gangrene | date = 13 October 2015 | url = https://www.nhs.uk/conditions/gangrene/ | website = NHS | access-date = 12 December 2017 }}</ref> Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness.<ref name="NHS2015Sym" /> The feet and hands are most commonly affected.<ref name=NHS2015Sym>{{cite web | title = Gangrene Symptoms | date = 13 October 2015 | url = https://www.nhs.uk/conditions/gangrene/symptoms/ | website = NHS | access-date = 12 December 2017 }}</ref> If the gangrene is caused by an infectious agent, it may present with a [[fever]] or [[sepsis]].<ref name="NHS2015Sym" />

<!-- Cause and diagnosis -->
Risk factors include [[diabetes]], [[peripheral arterial disease]], [[smoking]], [[major trauma]], [[alcoholism]], [[HIV/AIDS]], [[frostbite]], [[influenza]], [[dengue fever]], [[malaria]], [[chickenpox]], [[Plague (disease)|plague]], [[hypernatremia]], [[radiation injuries]], [[meningococcal disease]], [[Group B streptococcal infection]] and [[Raynaud's syndrome]].<ref name=NHS2015Cau>{{cite web | title = Gangrene Causes | date = 13 October 2015 | url = https://www.nhs.uk/conditions/gangrene/causes/ | website = NHS | access-date = 12 December 2017 }}</ref><ref name="NHS2015Over" /> It can be classified as [[dry gangrene]], [[wet gangrene]], [[gas gangrene]], [[internal gangrene (disambiguation)|internal gangrene]]<!--intentional link to DAB page-->, and [[necrotizing fasciitis]].<ref name="NHS2015Cau" /> The diagnosis of gangrene is based on symptoms and supported by tests such as [[medical imaging]].<ref>{{cite web | title = Gangrene Diagnosis | date = 13 October 2015 | url = https://www.nhs.uk/conditions/gangrene/diagnosis/ | website = NHS | access-date = 12 December 2017 }}</ref>

<!-- Treatment -->
Treatment may involve surgery to remove the dead tissue, [[antibiotics]] to treat any infection, and efforts to address the underlying cause.<ref name="NHS2015Tx" /> Surgical efforts may include [[debridement]], [[amputation]], or the use of [[maggot therapy]].<ref name="NHS2015Tx" /> Efforts to treat the underlying cause may include [[bypass surgery]] or [[angioplasty]].<ref name=NHS2015Tx>{{cite web | title = Gangrene Treatment | url = https://www.nhs.uk/conditions/gangrene/treatment/ | website = NHS | access-date = 12 December 2017 }}</ref> In certain cases, [[hyperbaric oxygen therapy]] may be useful.<ref name="NHS2015Tx" /> How commonly the condition occurs is unknown.<ref name=Pt2014>{{cite web | title = Gangrene | date = 12 March 2014 | url = https://patient.info/doctor/gangrene | website = patient.info | access-date = 12 December 2017 }}</ref>

== Etymology ==
The [[etymology]] of gangrene derives from the [[Latin]] word {{lang|la|gangraena}} and from the [[Greek language|Greek]] ''gangraina'' (γάγγραινα), which means "[[putrefaction]] of tissues".<ref>Liddell & Scott's Lexicon, Oxford University Press, 1963 edition</ref>

==Signs and symptoms==
[[File:Plate II Mortification (gangrene), Robert Carswell 1830s Wellcome L0074380.jpg|upright=1.3|alt=Four drawn illustrations on a page, including (top left) a foot with black toes, (top right) a limb with holes in the skin showing yellowed matter beneath, (centre right) the end of a foot with blackened stubs where the toes once were, and (bottom) a foot that is wrinkled and dark, with prominent veins and purple toes.|thumb|An illustration showing four different stages of gangrene, including one (Fig. 4 top right) caused by an obstacle to the return of the venous blood due to heart disease.]]
Symptoms may include a change in skin color to red or black, numbness, pain, skin breakdown, and coolness.<ref name="NHS2015Sym" /> The feet and hands are most commonly involved.<ref name="NHS2015Sym" />

== Causes ==
Gangrene is caused by a critically insufficient blood supply (e.g., [[peripheral vascular disease]]) or infection.<ref name="NHS2015Cau" /><ref>{{cite journal | vauthors = Gardner AW, Afaq A | title = Management of lower extremity peripheral arterial disease | journal = Journal of Cardiopulmonary Rehabilitation and Prevention | volume = 28 | issue = 6 | pages = 349–357 | date = November–December 2008 | pmid = 19008688 | pmc = 2743684 | doi = 10.1097/HCR.0b013e31818c3b96 }}</ref><ref name="Yang_2015">{{cite journal | vauthors = Yang Z, Hu J, Qu Y, Sun F, Leng X, Li H, Zhan S | title = Interventions for treating gas gangrene | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 12 | article-number = CD010577 | date = December 2015 | pmid = 26631369 | pmc = 8652263 | doi = 10.1002/14651858.CD010577.pub2 }}</ref> It is associated with [[diabetes]]<ref>{{cite journal | vauthors = Korzon-Burakowska A, Dziemidok P | title = Diabetic foot - the need for comprehensive multidisciplinary approach | journal = Annals of Agricultural and Environmental Medicine | volume = 18 | issue = 2 | pages = 314–317 | date = December 2011 | pmid = 22216805 }}</ref> and long-term tobacco smoking.<ref name="NHS2015Over" /><ref name="NHS2015Cau" />

===Dry gangrene===
Dry gangrene is a form of [[coagulative necrosis]] that develops in [[ischemia|ischemic]] [[tissue (biology)|tissue]], where the blood supply is inadequate to keep tissue viable. It is not a disease itself, but a symptom of other diseases.<ref>{{cite book | vauthors = Smith T | title = Gangrene Management: Today and Tomorrow | date = 2015 | publisher = Hayle Medical }}{{page needed|date=March 2019}}</ref> The term ''dry'' is used only when referring to a limb or to the gut (in other locations, this same type of necrosis is called an infarction, such as [[myocardial infarction]]).<ref>{{cite book | vauthors = Cross S | title = Underwood's Pathology: A Clinical Approach | page = 124 | date = 2018 | publisher = Elsevier Health Sciences | isbn = 978-0-7020-7210-9 | edition = 7th | url = https://books.google.com/books?id=1jtRDwAAQBAJ | access-date = 8 April 2020 }}</ref> Dry gangrene is often due to [[peripheral artery disease]], but can be due to [[acute limb ischemia]]. As a result, people with atherosclerosis, high cholesterol, diabetes and smokers commonly have dry gangrene.<ref name="Al_Wahbi_2018" /> The limited oxygen in the ischemic limb limits [[putrefaction]] and bacteria fail to survive. The affected part is dry, shrunken, and dark reddish-black. The line of separation usually brings about complete separation, with eventual falling off of the gangrenous tissue if it is not removed surgically, a process called [[autoamputation]].<ref name="Al_Wahbi_2018">{{cite journal | vauthors = Al Wahbi A | title = Autoamputation of diabetic toe with dry gangrene: a myth or a fact? | journal = Diabetes, Metabolic Syndrome and Obesity | volume = 11 | pages = 255–264 | date = 2018-06-01 | pmid = 29910628 | pmc = 5987754 | doi = 10.2147/DMSO.S164199 | doi-access = free }}</ref>

Dry gangrene is the result of chronic [[ischemia]] without [[infection]]. If ischemia is detected early, when [[ischemic wound]]s rather than gangrene are present, the process can be treated by [[revascularization]] (via vascular bypass or angioplasty).<ref>{{cite journal | vauthors = Aiello A, Anichini R, Brocco E, Caravaggi C, Chiavetta A, Cioni R, Da Ros R, De Feo ME, Ferraresi R, Florio F, Gargiulo M, Galzerano G, Gandini R, Giurato L, Graziani L, Mancini L, Manzi M, Modugno P, Setacci C, Uccioli L | title = Treatment of peripheral arterial disease in diabetes: a consensus of the Italian Societies of Diabetes (SID, AMD), Radiology (SIRM) and Vascular Endovascular Surgery (SICVE) | journal = Nutrition, Metabolism, and Cardiovascular Diseases | volume = 24 | issue = 4 | pages = 355–369 | date = April 2014 | pmid = 24486336 | doi = 10.1016/j.numecd.2013.12.007 | doi-access = free }}</ref> However, once gangrene has developed, the affected tissues are not salvageable.<ref>{{cite journal | vauthors = Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FG, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L, Olin JW, Patel RA, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME | title = 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines | journal = Circulation | volume = 135 | issue = 12 | pages = e726–e779 | date = March 2017 | pmid = 27840333 | pmc = 5477786 | doi = 10.1161/CIR.0000000000000471 }}</ref> Because dry gangrene is not accompanied by infection, it is not as [[wikt:emergent|emergent]] as gas gangrene or wet gangrene, both of which have a risk of sepsis. Over time, dry gangrene may develop into wet gangrene if an infection develops in the dead tissues.<ref>{{cite book | vauthors = Nather A | title = The diabetic foot | date = 2013 | publisher = World Scientific }}</ref>

[[Diabetes mellitus]] is a risk factor for peripheral vascular disease, thus for dry gangrene, but also a risk factor for wet gangrene, particularly in patients with poorly controlled blood sugar levels, as elevated serum glucose creates a favorable environment for bacterial infection.<ref>{{cite journal | vauthors = Vayvada H, Demirdover C, Menderes A, Karaca C | title = Necrotising fasciitis in the central part of the body: diagnosis, management and review of the literature | journal = International Wound Journal | volume = 10 | issue = 4 | pages = 466–472 | date = August 2013 | pmid = 22694053 | pmc = 7950796 | doi = 10.1111/j.1742-481x.2012.01006.x | s2cid = 5693425 }}</ref>

===Wet gangrene===
[[File:Wet gangrene of the foot.jpg|thumb|Wet gangrene of the foot.]]
Wet, or infected, gangrene is characterized by thriving bacteria and has a poor [[prognosis]] (compared to dry gangrene) due to sepsis resulting from the free communication between infected fluid and circulatory fluid. In wet gangrene, the tissue is infected by [[Putrefying bacteria|saprogenic]] microorganisms (''[[Clostridium perfringens]]'' or ''[[Bacillus fusiformis]]'', for example), which cause tissue to swell and emit a foul odor. Wet gangrene usually develops rapidly due to blockage of venous (mainly) or arterial blood flow.<ref name="Al_Wahbi_2018" /> The affected part is saturated with stagnant blood, which promotes the rapid growth of bacteria. The toxic products formed by bacteria are absorbed, causing systemic manifestation of sepsis and finally death. The affected part is edematous, soft, putrid, rotten, and dark.{{citation needed|date=February 2021}}

Because of the high mortality associated with infected gangrene (about 80% without treatment and 20% with treatment), an emergency salvage amputation, such as a [[guillotine amputation]], is often needed to limit systemic effects of the infection.<ref name="CochAmp" /> Such an amputation can be converted to a formal amputation, such as a [[below knee amputation|below- or above-knee amputation]].<ref name=CochAmp>{{cite journal | vauthors = Tisi PV, Than MM | title = Type of incision for below knee amputation | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 4 | article-number = CD003749 | date = April 2014 | pmid = 24715679 | pmc = 7154343 | doi = 10.1002/14651858.CD003749.pub3 }}</ref>

===Gas gangrene===
{{Main|Gas gangrene}}
Gas gangrene is a bacterial infection that produces gas within tissues. It can be caused by ''[[Clostridium]]'', most commonly [[Clostridium perfringens alpha toxin|alpha toxin]]-producing ''C. perfringens'', or various nonclostridial species.<ref name="Yang_2015" /><ref name="Sakurai_2004">{{cite journal | vauthors = Sakurai J, Nagahama M, Oda M | title = Clostridium perfringens alpha-toxin: characterization and mode of action | journal = Journal of Biochemistry | volume = 136 | issue = 5 | pages = 569–574 | date = November 2004 | pmid = 15632295 | doi = 10.1093/jb/mvh161 | s2cid = 12940936 | doi-access = free }}</ref> Infection spreads rapidly as the gases produced by the bacteria expand and infiltrate healthy tissue in the vicinity. Because of its ability to quickly spread to surrounding tissues, gas gangrene should be treated as a [[medical emergency]].

Gas gangrene is caused by bacterial [[exotoxin]]-producing clostridial species, which are mostly found in soil, and other anaerobes such as ''[[Bacteroides]]'' and anaerobic [[Streptococcus|streptococci]]. These environmental bacteria may enter the muscle through a wound and subsequently proliferate in necrotic tissue and secrete powerful toxins that destroy nearby tissue, generating gas at the same time. A gas composition of 5.9% hydrogen, 3.4% carbon dioxide, 74.5% nitrogen, and 16.1% oxygen was reported in one clinical case.<ref>{{cite journal | vauthors = Chi CH, Chen KW, Huang JJ, Chuang YC, Wu MH | title = Gas composition in Clostridium septicum gas gangrene | journal = Journal of the Formosan Medical Association = Taiwan Yi Zhi | volume = 94 | issue = 12 | pages = 757–759 | date = December 1995 | pmid = 8541740 | author-link4 = Chuang Yin-ching }}</ref>

Gas gangrene can cause necrosis, gas production, and sepsis. Progression to [[bacteremia|toxemia]] and [[septic shock|shock]] is often very rapid.<ref>{{cite web | title = Gas Gangrene | url = https://www.lecturio.com/concepts/gas-gangrene/ | website = The Lecturio Medical Concept Library | access-date = 22 July 2021 }}</ref>

===Other types===
* [[Necrotizing fasciitis]] is a rare infection that spreads deep into the body along tissue planes. It is categorized into four subtypes, with the first two being the most common. Type 1 requires an infection with an anaerobe and a species in the Enterobacteriaceae family, while type 2 is characterized by infection with ''[[Streptococcus pyogenes]]'', a Gram-positive cocci bacteria, and thus is also known as hemolytic streptococcal gangrene.<ref>{{Cite web | title = For Clinicians: Type II Necrotizing Fasciitis | date = 2019-02-21 | url = https://www.cdc.gov/groupastrep/diseases-hcp/necrotizing-fasciitis.html | website = www.cdc.gov | language = en-us | access-date = 2019-08-05 }}</ref><ref>{{cite journal | vauthors = Puvanendran R, Huey JC, Pasupathy S | title = Necrotizing fasciitis | journal = Canadian Family Physician | volume = 55 | issue = 10 | pages = 981–987 | date = October 2009 | pmid = 19826154 | pmc = 2762295 | publisher = cfpmfc }}</ref>
* [[Noma (disease)|Noma]] is a gangrene of the face most often found in Africa, Southeast Asia and South America.<ref>{{cite book | vauthors = Sivapathasundharam B, Rajendran A | title = Shafer's Textbook of Oral Pathology | page = 333 | date = 30 June 2012 | publisher = Elsevier Health Sciences | isbn = 978-81-312-3800-4 | url = https://books.google.com/books?id=WnhtAwAAQBAJ&pg=PA333 | language = en }}</ref>
* [[Fournier gangrene]] is a type of necrotizing fasciitis that usually affects the genitals and groin.<ref>{{cite journal | vauthors = Eke N | title = Fournier's gangrene: a review of 1726 cases | journal = The British Journal of Surgery | volume = 87 | issue = 6 | pages = 718–728 | date = June 2000 | pmid = 10848848 | doi = 10.1046/j.1365-2168.2000.01497.x }}</ref><ref>{{cite journal | vauthors = Levenson RB, Singh AK, Novelline RA | title = Fournier gangrene: role of imaging | journal = Radiographics | volume = 28 | issue = 2 | pages = 519–528 | date = March–April 2008 | pmid = 18349455 | doi = 10.1148/rg.282075048 | s2cid = 2930176 }}</ref>
* Venous limb gangrene may be caused by [[Heparin-induced thrombocytopenia]] and [[thrombosis]].<ref>{{cite journal | vauthors = Warkentin TE | title = Agents for the treatment of heparin-induced thrombocytopenia | journal = Hematology/Oncology Clinics of North America | volume = 24 | issue = 4 | pages = 755–75, ix | date = August 2010 | pmid = 20659659 | doi = 10.1016/j.hoc.2010.05.009 }}</ref>
* Severe [[mesenteric ischemia]] may result in gangrene of the [[small intestine]].{{citation needed|date=February 2021}}
* Severe [[ischemic colitis]] may result in gangrene of the [[large intestine]].{{citation needed|date=February 2021}}

==Treatment==
Treatment varies based on the severity and type of gangrene.<ref name="Al_Wahbi_2018" />

===Lifestyle===
Exercises such as walking and massage therapy may be tried.<ref name="Al_Wahbi_2018" />

===Medication===

Medications may include pain management, medications that promote circulation in the [[circulatory system]] and antibiotics. Since gangrene is associated with periodic pain caused by too little blood flow, pain management is important so patients can continue doing exercises that promote circulation. Pain management medications can include opioids and opioid-like analgesics. Since gangrene is a result of [[ischemia]], circulatory system management is important. These medications can include [[antiplatelet drug]], [[anticoagulant]], and [[fibrinolytics]]. As infection is often associated with gangrene, [[antibiotics]] are often a critical component of its treatment. The life-threatening nature of gangrene requires treatment with intravenous antibiotics in an inpatient setting.<ref name="Al_Wahbi_2018" /> Antibiotics alone are not effective because they may not penetrate infected tissues sufficiently.<ref>{{cite journal | vauthors = Lipsky BA | title = Evidence-based antibiotic therapy of diabetic foot infections | journal = FEMS Immunology and Medical Microbiology | volume = 26 | issue = 3–4 | pages = 267–276 | date = December 1999 | pmid = 10575138 | doi = 10.1016/s0928-8244(99)00143-1 | doi-access = free }}</ref>

===Surgery===

Surgical removal of all dead tissue, however, is the mainstay of treatment for gangrene. Often, gangrene is associated with underlying infection, thus the gangrenous tissue must be [[debridement|debrided]] to hinder the spread of the associated infection. The extent of surgical debridement needed depends on the extent of the gangrene and may be limited to the removal of a finger, toe, or ear, but in severe cases may involve a [[amputation|limb amputation]].<ref name="Al_Wahbi_2018" />

Dead tissue alone does not require debridement, and in some cases, such as dry gangrene, the affected part falls off (autoamputates), making surgical removal unnecessary. Waiting for autoamputation, however, may cause health complications as well as decreased quality of life.<ref name="Al_Wahbi_2018" />

After the gangrene is treated with debridement and antibiotics, the underlying cause can be treated. In the case of gangrene due to [[critical limb ischemia]], revascularization can be performed to treat the underlying peripheral underlateral artery disease.{{citation needed|date=February 2021}}

Ischemic disease of the legs is the most common reason for amputations. In about a quarter of these cases, the other side requires amputation in the next three years.<ref>{{EMedicine|article|1232102|Amputations of the Lower Extremity}}</ref>

Angioplasty should be considered if severe blockage in lower leg vessels ([[Posterior tibial artery|tibial]] and [[peroneal artery]]) leads to gangrene.<ref>{{cite web | title = Angioplasty and stent placement – peripheral arteries | url = https://www.medlineplus.gov/ency/article/007393.htm | access-date = July 24, 2013 }}</ref>

===Other===
[[Hyperbaric medicine|Hyperbaric oxygen therapy]] treatment is used to treat gas gangrene. It increases pressure and oxygen content to allow blood to carry more oxygen to inhibit anaerobic organism growth and reproduction.<ref>{{cite journal | vauthors = Liu R, Li L, Yang M, Boden G, Yang G | title = Systematic review of the effectiveness of hyperbaric oxygenation therapy in the management of chronic diabetic foot ulcers | journal = Mayo Clinic Proceedings | volume = 88 | issue = 2 | pages = 166–175 | date = February 2013 | pmid = 23374620 | doi = 10.1016/j.mayocp.2012.10.021 }}</ref>

[[Peter DeMarco|Regenerative medical]] treatments and [[stem-cell therapies]] have successfully altered gangrene and ulcer prognosis.{{citation needed|date=October 2021}}

==History==
[[File:Milton Wallen, CWMI098C, National Museum of Health and Medicine (373561781).jpg|thumb|upright=1.3|[[Union Army]] Private Milton E. Wallen lies in bed with a gangrenous amputated arm]]
As early as 1028, [[fly|flies]] and [[maggot]]s were commonly used to treat chronic wounds or [[Ulcer (dermatology)|ulcers]] to prevent or arrest necrotic spread,<ref name="Shi_2014">{{cite journal | vauthors = Shi E, Shofler D | title = Maggot debridement therapy: a systematic review | journal = British Journal of Community Nursing | volume = ((Suppl Wound Care)) | pages = S6–13 | date = December 2014 | pmid = 25478859 | doi = 10.12968/bjcn.2014.19.Sup12.S6 }}</ref> as some species of maggots consume only dead flesh, leaving nearby living tissue unaffected. This practice largely died out after the introduction of antibiotics to the range of treatments for wounds. In recent times, however, [[maggot therapy]] has regained some credibility and is sometimes employed with great [[efficacy]] in cases of chronic tissue necrosis.<ref>{{cite web | title = Product Classification: Maggots, Medical | url = https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm?id=6212 | website = fda.gov | publisher = [[Food and Drug Administration]] | place = US }}</ref><ref>{{Cite web | title = FDA CDRH 510(k) summary | url = http://www.accessdata.fda.gov/cdrh_docs/pdf7/K072438.pdf }}</ref><ref>{{cite journal | vauthors = Sun X, Jiang K, Chen J, Wu L, Lu H, Wang A, Wang J | title = A systematic review of maggot debridement therapy for chronically infected wounds and ulcers | journal = International Journal of Infectious Diseases | volume = 25 | pages = 32–37 | date = August 2014 | pmid = 24841930 | doi = 10.1016/j.ijid.2014.03.1397 | doi-access = free }}</ref>

The French [[Baroque music|Baroque composer]] [[Jean-Baptiste Lully]] contracted gangrene in January 1687 when, while conducting a performance of his ''[[Te Deum]]'', he stabbed his own toe with his pointed staff (which was used as a [[baton (conducting)|baton]]). The disease spread to his leg, but the composer refused to have his toe [[amputation|amputated]], which eventually led to his death in March of that year.<ref>{{cite web | title = Music Trivia – The Death of Lully | date = August 2010 | url = http://www.utahsymphony.org/blog/2010/08/music-trivia-the-death-of-lully/ | website = The Musician's Lounge | publisher = Utah Symphony Orchestra | access-date = March 7, 2017 }}</ref>

French King [[Louis XIV of France|Louis XIV]] died of gangrene in his leg on 1 September 1715, four days prior to his 77th birthday.<ref>{{cite web | vauthors = Laurenson J | title = The strange death of Louis XIV | date = 21 November 2015 | url = http://www.spectator.co.uk/2015/11/the-strange-death-of-louis-xiv/ | website = The Spectator | access-date = 12 March 2017 }}</ref>

[[Sebald Justinus Brugmans]], Professor at [[Leyden University]], from 1795 on Director of the Medical Bureau of the Batavian Republic, and inspector-general of the French Imperial Military Health-Service in 1811, became a leading expert in the fight against hospital-gangrene and its prevention. He wrote a treatise on gangrene in 1814 in which he meticulously analyzed and explained the causes of this dreadful disease, which he was convinced was contagious. He completed his entry with a thorough evaluation of all possible and well experienced sanitary regulations. His work was very well received and was instrumental in convincing most later authors that gangrene was a contagious disease.<ref>{{cite book | vauthors = van Heiningen F | title = Sebald Justinus Brugmans' strijd tegen de hospitaalversterving | trans-title = Sebald Justinus Brugmans' fight against hospital mortification | language = Dutch | publisher = Leiden University | id = URN:NBN:NL:UI:10-1-112565 }}</ref><ref>{{Cite web | vauthors = Brugmans SJ | title = Verhandeling ter beantwoording der vrage: Kan de gesteldheid en zamenstelling van den dampkring, welke onmiddelijk tot de Hospitaal-versterving (Gangraena NosocomialisZ) aanleiding geeft, door Natuur- of Scheikundige middelen worden ontdekt? | date = May 24, 1814 | url = https://books.google.com/books?id=bliOuPEr9QIC&pg=PA1 | publisher = J. van der Heij | via = Google Books }}</ref>

John M. Trombold wrote: "Middleton Goldsmith, a surgeon in the [[Union Army]] during the American Civil War, meticulously studied hospital gangrene and developed a revolutionary treatment regimen. The cumulative Civil War hospital gangrene [[Case fatality rate|mortality]] was 45%. Goldsmith's method, which he applied to over 330 cases, yielded a mortality under 3%."<ref>{{cite journal | vauthors = Trombold JM | title = Gangrene therapy and antisepsis before lister: the civil war contributions of Middleton Goldsmith of Louisville | journal = The American Surgeon | volume = 77 | issue = 9 | pages = 1138–1143 | date = September 2011 | pmid = 21944621 | doi = 10.1177/000313481107700924 | s2cid = 26732207 | doi-access = free }}</ref> Goldsmith advocated the use of debridement and topical and injected [[bromide]] solutions on infected wounds to reduce the incidence and virulence of "poisoned miasma".  Copies of his book<ref>{{cite report | vauthors = Goldsmith M | url = https://archive.org/details/areportonhospit00goldgoog | title = A report on hospital gangrene, erysipelas and pyaemia | date = 1863 | publisher = Bradley & Gilbert }}</ref> were issued to Union surgeons to  encourage the use of his methods.<ref>{{cite web | vauthors = Watson S | title = Hospital Gangrene During The Civil War – Civil War Medicine | url = http://www.civilwarmedicalbooks.com/hospital_gangrene_civil_war.html | access-date = 2014-04-15 }}</ref>

== References ==
{{Reflist}}

== External links ==
{{Wiktionary|gangrene|festering}}
* {{Commons category-inline|Gangrene}}

{{Medical condition classification and resources
| DiseasesDB      = 19273
| ICD10           = {{ICD10|R|02||r|00}},  {{ICD10|I|70|2|i|70}},  {{ICD10|E|10|2|e|10}},  {{ICD10|I|73|9|i|70}}
| ICD9            = {{ICD9|040.0}}, {{ICD9|785.4}}
| ICDO            =
| OMIM            =
| MedlinePlus     = 007218
| eMedicineSubj   = article
| eMedicineTopic  = 217943
| eMedicine_mult  = {{eMedicine2|article|782709}} {{eMedicine2|article|214992}} {{eMedicine2|article|438994}} {{eMedicine2|article|2028899}} {{eMedicine2|article|2051157}}
| MeshID          = D005734
| SNOMED CT       = 372070002
|ICD11={{ICD11|MC85}}
}}
{{Ischaemia and infarction}}
{{pathology}}
{{Bacterial cutaneous infections}}
{{Authority control}}

[[Category:Gangrene| ]]
[[Category:Health effects of tobacco]]
[[Category:Symptoms and signs: Vascular]]
[[Category:Necrosis]]
[[Category:Causes of amputation]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Causes of death]]