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Hilton CMH1*
and Vedtofte T2
1
Department of Plastic Surgery and Breast Surgery, Roskilde Hospital, Denmark
2
Department of Otorhinolaryngology, Head and Neck Surgery, North Zealand Hospital Hilleroed, Denmark
*
Corresponding author:
Carolina Maria Helena Hilton,
Department of Plastic Surgery and Breast
Surgery, Roskilde Hospital, Hælderne 5, 2850
Nærum, Denmark, Tel: 004581197044;
E-mail: carro_hilton@hotmail.com
ORCID: 0000-0001-7173-4528
Received: 01 Jan 2023
Accepted: 13 Feb 2023
Published: 20 Feb 2023
J Short Name: COS
Copyright:
©2023 Hilton CMH, This is an open access article dis-
tributed under the terms of the Creative Commons Attri-
bution License, which permits unrestricted use, distribu-
tion, and build upon your work non-commercially.
Citation:
Hilton CMH. Necrotizing Fasciitis - A Single Center
Case Series. Clin Surg. 2023; 9(1): 1-6
Necrotizing Fasciitis - A Single Center Case Series
Clinics of Surgery
Case Series ISSN: 2638-1451 Volume 8
clinicsofsurgery.com 1
1. Abstract
1.1. Aims: Necrotizing fasciitis is a potentially life-threatening
infection with rapidly spreading necrosis of the superficial fascia
and involvement of subcutaneous tissue. The aim of this study is
to address the mortality, comorbidities, pre-disposing factors, dif-
ference in virulence, treatment and outcome among patients diag-
nosed with necrotizing fasciitis in Denmark.
1.2. Methods: This study is a retrospective cohort study enroll-
ing patients admitted to the University Hospital, Rigshospitalet,
Denmark in 2010-2012. Inclusion criteria were the ICD3 code
DM725A and the diagnosis was validated by an operational de-
scription of either necrosis of the fascia, dishwater pus, lack of
bleeding or a positive finger test (lack of resistance to finger dis-
section in normally adherent tissues).
1.3. Results: 115 patients were identified. The 30-day mortali-
ty was 7,8% and the 90-day mortality 19,1%. In 2005-2008 the
numbers were 8,2% and 11, 8%. Men, 69%, were overrepresented.
13,9% had a skin disease at the place of NF, 21,7% had had sur-
gery within 4 weeks prior to the diagnosis and 13,9% had a cancer
diagnosis at the time of diagnosis.
1.4. Conclusion: The present study compared with earlier findings
show unchanged 30-day mortality and a slight increase in 90-day
mortality. Of interest regarding predisposing factors 13,9% had a
skin disease at the place of debut of necrotizing fasciitis. It is im-
portant to validate the diagnosis, as 8,7% hereafter were excluded
in this study.
2. Introduction
Necrotizing Fasciitis (NF) is a rare infection, potentially life-threat-
ening, with rapidly spreading necrosis of the superficial fascia and
involvement of the subcutaneous tissue. NF is classified into the
following categories; Type 1 (polymicrobial/synergistic, mixed
aerobes and anaerobes), Type 2 (often monomicrobial, usually
group A B hemolytic streptococcus), Type 3 (gram negative, of-
ten marine-related, most commonly Vibrio species) and Type 4
(Fungal) [1]. Early symptoms are erythema, edema, fever and pain
(typically out of proportion to objective findings). Later symp-
toms are bullae, dysesthesia/anesthesia, hard skin upon palpation,
crepitation, discoloration and systemic manifestations. Mortality
is reported from 6-76% in the literature, most commonly around
15-35% [2-13]. Concerning mortality, time to diagnosis and surgi-
cal resection is of great importance [14]. It is not known why the
same pathogens cause this severe infection in some patients and
not in others, and why it is also diagnosed among patients without
comorbidity [15].
Treatment of necrotizing fasciitis with a possible need for HBO
was in 2010 – 2012 centralized to two centers in Denmark. Treat-
ment consists of intensive care therapy, extensive surgery until
vital bleeding tissue, early broad spectrum antibiotics, HBO (dai-
ly for the first three days, hereafter optional), although, if the pa-
tient’s condition is esteemed as too unstable, hyperbaric treatment
awaits, and finally, optionally IVIG. In Danish guidelines IVIG is
recommended (25 g x 1) during the first three days to patients with
Keywords:
Necrotizing fasciitis; Hyperbaric oxygen;
Intravenous immunoglobulin; Validated diagnosis
clinicsofsurgery.com 2
Volume 9 Issue 1 -2023 Case Series
confirmed shock and suspected/verified streptococcal infection,
typically seen in patients with an extremity focus. Initial antibiotic
treatment consists of meropenem (2 g x 3) and clindamycin (600
mg x 3). Surgical resection is performed immediately if allowed by
clinical condition, hereafter debridement is performed at regular
intervals guided by clinical and surgical state of the patient, daily
if needed. Nutritional therapy, fluid and volume resuscitation starts
early and patients with large skin resections are treated in a heated
room by open exposition, imitating the treatment given to burn
victims as they might become poikilothermic (having a body tem-
perature strongly correlated with that of the external environment).
The aim of this article is to address the comorbidities, pre-dispos-
ing factors, microbiology, treatment and outcome among patients
diagnosed with NF in Denmark. Further to compare the results
with a similar earlier study [2].
3. Materials and Methods
The present study is a retrospective single-centre cohort study of
patients diagnosed with NF. Patients were identified through the
database at the Copenhagen University Hospital Rigshospitalet,
Denmark, by the diagnostic code; DM725A; fasciitis necroticans.
The inclusion period was from the 01/01/2010 until the 20/06/2012
and the search resulted in 126 patients. The diagnostic code was
validated by a surgical description of necrosis of the fascia, dish-
water pus (dishwater colored fluid), lack of bleeding or a positive
finger test (lack of resistance to finger dissection in normally ad-
herent tissues), this resulted in exclusion of 11 patients.
Data on co-morbidities, predisposing factors, treatment, localiza-
tion, outcome and microbiology were obtained from hospital files.
Microbiological findings included biopsies taken within 48 hours
of admission to the hospital.
4. Results
During the inclusion period a number of 115 patients were identi-
fied. Men, 69%, were overrepresented, 13,9% had a skin disease
at the place of NF, 24,3% had diabetes mellitus (DM), 21,7% had
had an operation within 4 weeks prior to NF diagnosis and 13,9%
had cancer at the time of diagnosis (Table 1).
We found a 30-day mortality of 7,8% and a 90-day mortality of
19,1% (Table 3). Number of revisions had a mean of 5.4. 82,6%
received HBO, most often 2 or more HBO-treatments (64,3%).
Most cases had a known point of entry, 55,7 %. In patients with
monomicrobial growth in a sample taken within 48 hours from
admission, hemolytic streptococcus was overrepresented (56,1%),
and this organism was also found in 25% of polymicrobial cases.
64,3% of the patients developed septic shock. 27,8 % Multiple
Organ Dysfunction Syndrome (MODS), 11,3 % Disseminated In-
travascular Coagulation (DIC) and 17,4 % Acute Tubulointerstitial
Nephritis (ATIN) (Table 2).
Data regarding demographics, comorbidity, treatment, etiology
and outcome among the patients who died within 30 days of the
diagnosis is shown in table 3.
Table 1: Demographic data & comorbidity
Sex, n (%)
Female 36 (31)
Male 79 (69)
Age, median, (range)
60 (5 –
86)
Weight, n (%)
BMI < 18,5 0 (0)
BMI 18,5 - 25 65 (56.5)
BMI > 25 50 (43.5)
Smoking, n (%)
Yes 54 (47)
No 32 (27.8)
Earlier 17 (14.8)
Alcohol abuse*, n (%)
Yes 33 (28.7)
No 75 (65.2)
Earlier 7 (6.1)
Hypertension, n (%) 44 (38.3)
Hypercholesterolemia, n (%) 9 (7.8)
Diabetes Mellitus (DM), n (%) 28 (24.3)
Skin disease at the place of NF**, n (%) 16 (13.9)
Cancer, n (%)
At the time of NF diagnosis 16 (13.9)
Earlier 5 (4.3)
HIV, n (%) 2 (1.7)
I.v. drug abuse, n (%) 3 (2.6)
Liver cirrhosis, n (%) 6 (5.2)
Hepatitis, n (%)
Alcoholic hepatitis 2 (1.7)
Hepatitis C 4 (3.5)
Chronic Obstructive Pulmonary Disease (COPD), n (%) 18 (15.7)
Operation within 4 weeks, n (%)*** 25 (21.7)
Crepitation/air development, n (%) 45 (39.1)
*In Denmark defined as 84 g of alcohol/week for women and 168 g/week
for men
**Represented diagnoses where; chronical itching skin disease, chroni-
cal/bad healing wounds, tendency to fistulas/abscesses/erysipelas/cysts or
polyps, seborrheic dermatitis)
***The patient had had surgery, including dental surgery/extraction with-
in 4 weeks prior to NF diagnosis
clinicsofsurgery.com 3
Volume 9 Issue 1 -2023 Case Series
Table 2: Treatment, Etiology and Outcome
Number of revisions
Mean 5.4
Median (Range) 4 (0-28)
Number of Hyperbaric Oxygen Treatment (HBO) treatments, n (%)
0 20 (17,4)
1 21 (18,3)
2 36 (31,3)
3 16 (13,9)
4 12 (10,4)
5 6 (5,2)
6 3 (2,6)
7 1 (0,9)
Known point of entry, n (%) 64 (55,7)
Abscess, n (%) 25 (21,7)
Microbiology (sample taken within 48 hours from admission)
Polymicrobial, n (%) 48 (41,7)
-Haemolytic streptococcus 12 (25)
Monomicrobial, n (%) 41 (35,7)
-haemolytic streptococcus 23 (56,1)
- Clostridium septicum 1 (2,4)
- E.coli 4 (9,8)
- Staphylococcus aureus 3 (7,3)
- Staphylococcus epidermidis 1 (2,4)
- Streptococcus anginosus 2 (4,9)
- Streptococcus constellatus 2 (4,9)
- Streptococcus 4 (9,8)
- Gram positive coccus 1 (2,4)
Unknown etiology, n (%) 26 (22,6)
Stage of sepsis, n (%)
No sepsis 19 (16,5)
Sepsis 14 (12,2)
Severe sepsis 8 (7)
Septic shock 74 (64,3)
Amputated, n (%) 26 (22,6)
Multiple Organ Dysfunction Syndrome (MODS), n (%) 32 (27,8)
Disseminated Intravascular Coagulation (DIC), n (%) 13 (11,3)
Acute Tubulo Interstitial Nephritis (ATIN), n (%) 20 (17,4)
Toxic Shock Syndrome (TSS), n (%) 1 (0,9)
clinicsofsurgery.com 4
Volume 9 Issue 1 -2023 Case Series
Table 3: Demographics, comorbidity, etiology, treatment and outcome among patients who died within 30 days
Patients who died
within 30 days
1 2 3 4 5 6 7* 8 9
Sex M M M M M M M F F
Age 53 53 83 50 84 73 5 63 61
Cancer x x x
Skin disease at the
place of NF
x x
Operated within 4
weeks prior to
diagnosis
x x
Localization Multiple Multiple Fourniers Fourniers
Lower
extremity
Lower
extremity
Urogenital Urogenital Urogenital
Number of
revisions
3 5 1 1 1 5 0 11 3
Number of HBO
treatments
0 0 1 2 1 1 0 6 0
Known point of
entry
x x x x x
Septic shock x x x x x x x x
Amputation x x x x
MODS x x x
DIC x x x
ATIN
TSS
Microbiology S. aureus Poly Poly Unknown Unknown G+ coccus
S.
epidermidis
Poly Poly
*Patient suffered from leukemia and died before surgery was possible
The 30 day mortality from NF was 9/115 = 7,8 %.
The 90 day mortality was 9+13/115 = 19,1%.
5. Discussion
The 30-day mortality in 2005-2006 was 8,2% [2]. This article
shows a 30-day mortality approximately the same, 7,8%. Although
the 30-day mortality has not changed a lot, the 90-day mortality
has. In 2005-2006 it was 11,8%, and this article shows a mortality
of 19,1%. The difference could among other causes reflect a differ-
ence in localization of the infection or different microbiology, with
a shift towards more resistant bacteria [16, 17] or a difference in
patient care after discharge.
We found an overrepresentation of the male sex in the material
(69%) just as in the article by Skovsen et al. (67%) [2]. The local-
izations were the extremities (42,2%), urogenital (31,8%), abdom-
inal (14,1%), and head/neck/thoracic region (11,8%) in the article
by Skovsen et al [2]. We found a difference in locations with more
patients (20,9%) with the localization head/neck/thoracic region,
and fewer with the other localizations; extremities (30,4%), uro-
genital (22.7%) and abdominal (6.1%). Although we also had a
group called “many regions” (20%), including at least one other
localization than the extremities, this might have contributed to
the difference in mortality. It might be more difficult to perform
surgery in the head/neck/thorax area than at the extremities and the
surgery might be more hazardous for the patient. It might also be
more difficult to remove enough tissue, to be extensive enough and
the surgeon might be more careful, wanting to spare as much tissue
as possible with regards to cosmetic and social disabilities. This
could result in less extensive surgery with incomplete radicality.
Furthermore, amputation is not an option in the head/neck/thoracic
region, which is a possibility with extremities and the male genital
area, to stop infections that are out of control.
In the article by Skovsen et al. 65,9 % of patients had septic shock,
24,7% ATIN and 12,9% DIC [2]. We found septic shock in 64,3%,
17,4% suffered from ATIN and 11,3% from DIC. Possibly we have
become better at treating septic shock, but with more resistant bac-
teria, this effect might not be seen. Similarly to Skovsen et al. we
found that 21,7 % had had an operation in short time before they
got their NF diagnosis, compared to 18,9%, indicating this as a
predisposing condition and there might be more to this than just
being an entry point for bacteria.
HBO and Intravenous Immunoglobulin (IVIG) are among the
most discussed treatment options. HBO is a medical treatment
where the patient, enclosed in a chamber, breathes 100% oxygen
at a pressure > 1 atmosphere absolute. The proposed benefits are;
enhanced ability for white blood cells to kill aerobic bacteria, stim-
ulation of collagen formation, increased levels of superoxide dis-
clinicsofsurgery.com 5
Volume 9 Issue 1 -2023 Case Series
mutase, vasoconstriction and thereby decreased edema formation
and increased tissue oxygen tension with increased effect of anti-
biotics. A “super oxygenated zone” builds, forming a barrier which
slows spreading of the infection, cause damping of the systemic
inflammatory response, impair the virulence of bacterial patho-
gens, promote angiogenesis and healing of wounds, promote the
pliability of red blood cells and terminate lipid peroxidation [6, 8].
A systematic review from 2015 (searching the Cochrane Central
Register of Controlled Trials, MEDLINE, the Cumulative Index to
Nursing and Allied Health Literature, EMBASE and the Database
of Randomized Controlled Trials in Hyperbaric Medicine) failed to
locate relevant clinical evidence to support or refute the effective-
ness of Hyperbaric Oxygen Treatment (HBOT) in the management
of necrotizing fasciitis. Good quality clinical trials are needed to
define the role, if any, of HBOT in the treatment of individuals
with necrotizing fasciitis [18]. There are few small retrospective
studies that show positive results from HBO [5]. In a Danish co-
hort study including patients with Necrotizing Soft Tissue Infec-
tions (NSTI) an improved 30-day and 90-day survival in hospitals
offering HBOT as an adjunct to the multidisciplinary treatment
was reported. However, authors state that these results should be
interpreted cautiously due to missing confounders, such as clinical
variables and potentially different treatment modalities across hos-
pitals. Mortality among HBOT-treated individuals was noticeably
reduced compared with those who did not receive HBOT. Again
authors state that the difference should be interpreted carefully
due to potential selection bias based on which patients are offered
HBOT as an adjunct. Presumably, some may have been in such
critical hemodynamic condition were in-hospital transportation
to HBOT were deemed unachievable, thereby indicating that the
HBOT-treated patients represent a selected cohort [15]. IVIG was
primarily used in the treatment of Toxic Shock Syndrome (TSS).
The proposed mechanisms of action are that IVIG may opsonize
Group A Streptococcal bacteria, promote clearance, antagonize
or neutralize streptococcal super antigens and modulate immune
cytokine responses [3, 8]. A randomized, blinded, placebo-con-
trolled trial with 87 patients included concluded that in patients
with NSTI treated in an intensive care unit, there were no apparent
effects of adjuvant IVIG on self-reported physical functioning at
6 months[19]. An observational study reported that one 25g IVIG
dose was sufficient to yield plasma-neutralizing activity against
streptococcal superantigens, why this study recommend the use
of IVIG [20]. Though all proposed mechanisms of action, there
are also side effects from HBO (reversible myopia, barotraumatic
lesions (ear, lung), CNS and pulmonary oxygen toxicity) [21] and
IVIG (anaphylaxis and possibly renal impairment) [22]. We had
a higher proportion of patients 17.4% that did not receive HBO,
whereas Skovsen et al. reported 3.5%, this might have contribut-
ed to the difference in 90 day mortality rates. The reasons for the
difference in number of patients who were not treated with HBO
might have been a different judgment concerning if a patients clin-
ical condition was stable enough, the patients could have been di-
agnosed at a later point in their infection, they might have had a
more aggressive infection or it might have been at a different lo-
calization. There is a need for controlled studies with a large num-
ber of patients, possibly in countries where HBO is not a standard
regimen as it is unethical to remove a treatment we have already
introduced believing in its potential. For example, in the USA only
1% of patients received HBO at specialized centers [23]. In the
study by Skovsen et al. 8% had DM and among them there was a
mortality of 0%. In this study 24,3% had DM, of which 2 of the
9 patients who died within 30 day and 5 of the 22 patients who
died within 90 day had diabetes. A proposed predisposing factor
we looked into in this study was if the patients had a skin disease
at the place of NF. Skin diseases reported were chronically itching
skin disease, chronically/bad healing wounds, tendency to fistu-
las/abscesses/cysts/erysipelas or polyps and seborrheic dermatitis.
13,9% of the patients had a skin disease, which might indicate a
connection.
Our main limitations are the single-centre and retrospective nature
of our study. Although treatment is centralized and transport routes
are not that far in Denmark, patients might have been too critically
ill upon diagnosis for transportation.
6. Conclusions
The present study compared with earlier findings show unchanged
30-day mortality and a slight increase in 90-day mortality. Of in-
terest regarding predisposing factors 13,9% had a skin disease at
the place of debut of NF. It is important to validate the diagnosis,
as 8,7% hereafter were excluded in this study. There is a need for
controlled studies with a large number of patients documenting the
effect and regimen of HBO, possibly in countries where this is not
a standard regimen as it is unethical to remove a treatment we have
already introduced believing in its potential.
References
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3. Young MH, Aronoff DM, Engleberg NC. Necrotizing fasciitis:
pathogenesis and treatment. Expert Rev. Anti. Infect. Ther. 2005;
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4. Sarani B, Strong M, Pascual J, Schwab CW. Necrotizing fasciitis:
current concepts and review of the literature. J. Am. Coll. Surg.
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retrospective chart review. BMC Infect. Dis. 2012; 12(348).
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Necrotizing Fasciitis - A Single Center Case Series

  • 1. Hilton CMH1* and Vedtofte T2 1 Department of Plastic Surgery and Breast Surgery, Roskilde Hospital, Denmark 2 Department of Otorhinolaryngology, Head and Neck Surgery, North Zealand Hospital Hilleroed, Denmark * Corresponding author: Carolina Maria Helena Hilton, Department of Plastic Surgery and Breast Surgery, Roskilde Hospital, Hælderne 5, 2850 Nærum, Denmark, Tel: 004581197044; E-mail: carro_hilton@hotmail.com ORCID: 0000-0001-7173-4528 Received: 01 Jan 2023 Accepted: 13 Feb 2023 Published: 20 Feb 2023 J Short Name: COS Copyright: ©2023 Hilton CMH, This is an open access article dis- tributed under the terms of the Creative Commons Attri- bution License, which permits unrestricted use, distribu- tion, and build upon your work non-commercially. Citation: Hilton CMH. Necrotizing Fasciitis - A Single Center Case Series. Clin Surg. 2023; 9(1): 1-6 Necrotizing Fasciitis - A Single Center Case Series Clinics of Surgery Case Series ISSN: 2638-1451 Volume 8 clinicsofsurgery.com 1 1. Abstract 1.1. Aims: Necrotizing fasciitis is a potentially life-threatening infection with rapidly spreading necrosis of the superficial fascia and involvement of subcutaneous tissue. The aim of this study is to address the mortality, comorbidities, pre-disposing factors, dif- ference in virulence, treatment and outcome among patients diag- nosed with necrotizing fasciitis in Denmark. 1.2. Methods: This study is a retrospective cohort study enroll- ing patients admitted to the University Hospital, Rigshospitalet, Denmark in 2010-2012. Inclusion criteria were the ICD3 code DM725A and the diagnosis was validated by an operational de- scription of either necrosis of the fascia, dishwater pus, lack of bleeding or a positive finger test (lack of resistance to finger dis- section in normally adherent tissues). 1.3. Results: 115 patients were identified. The 30-day mortali- ty was 7,8% and the 90-day mortality 19,1%. In 2005-2008 the numbers were 8,2% and 11, 8%. Men, 69%, were overrepresented. 13,9% had a skin disease at the place of NF, 21,7% had had sur- gery within 4 weeks prior to the diagnosis and 13,9% had a cancer diagnosis at the time of diagnosis. 1.4. Conclusion: The present study compared with earlier findings show unchanged 30-day mortality and a slight increase in 90-day mortality. Of interest regarding predisposing factors 13,9% had a skin disease at the place of debut of necrotizing fasciitis. It is im- portant to validate the diagnosis, as 8,7% hereafter were excluded in this study. 2. Introduction Necrotizing Fasciitis (NF) is a rare infection, potentially life-threat- ening, with rapidly spreading necrosis of the superficial fascia and involvement of the subcutaneous tissue. NF is classified into the following categories; Type 1 (polymicrobial/synergistic, mixed aerobes and anaerobes), Type 2 (often monomicrobial, usually group A B hemolytic streptococcus), Type 3 (gram negative, of- ten marine-related, most commonly Vibrio species) and Type 4 (Fungal) [1]. Early symptoms are erythema, edema, fever and pain (typically out of proportion to objective findings). Later symp- toms are bullae, dysesthesia/anesthesia, hard skin upon palpation, crepitation, discoloration and systemic manifestations. Mortality is reported from 6-76% in the literature, most commonly around 15-35% [2-13]. Concerning mortality, time to diagnosis and surgi- cal resection is of great importance [14]. It is not known why the same pathogens cause this severe infection in some patients and not in others, and why it is also diagnosed among patients without comorbidity [15]. Treatment of necrotizing fasciitis with a possible need for HBO was in 2010 – 2012 centralized to two centers in Denmark. Treat- ment consists of intensive care therapy, extensive surgery until vital bleeding tissue, early broad spectrum antibiotics, HBO (dai- ly for the first three days, hereafter optional), although, if the pa- tient’s condition is esteemed as too unstable, hyperbaric treatment awaits, and finally, optionally IVIG. In Danish guidelines IVIG is recommended (25 g x 1) during the first three days to patients with Keywords: Necrotizing fasciitis; Hyperbaric oxygen; Intravenous immunoglobulin; Validated diagnosis
  • 2. clinicsofsurgery.com 2 Volume 9 Issue 1 -2023 Case Series confirmed shock and suspected/verified streptococcal infection, typically seen in patients with an extremity focus. Initial antibiotic treatment consists of meropenem (2 g x 3) and clindamycin (600 mg x 3). Surgical resection is performed immediately if allowed by clinical condition, hereafter debridement is performed at regular intervals guided by clinical and surgical state of the patient, daily if needed. Nutritional therapy, fluid and volume resuscitation starts early and patients with large skin resections are treated in a heated room by open exposition, imitating the treatment given to burn victims as they might become poikilothermic (having a body tem- perature strongly correlated with that of the external environment). The aim of this article is to address the comorbidities, pre-dispos- ing factors, microbiology, treatment and outcome among patients diagnosed with NF in Denmark. Further to compare the results with a similar earlier study [2]. 3. Materials and Methods The present study is a retrospective single-centre cohort study of patients diagnosed with NF. Patients were identified through the database at the Copenhagen University Hospital Rigshospitalet, Denmark, by the diagnostic code; DM725A; fasciitis necroticans. The inclusion period was from the 01/01/2010 until the 20/06/2012 and the search resulted in 126 patients. The diagnostic code was validated by a surgical description of necrosis of the fascia, dish- water pus (dishwater colored fluid), lack of bleeding or a positive finger test (lack of resistance to finger dissection in normally ad- herent tissues), this resulted in exclusion of 11 patients. Data on co-morbidities, predisposing factors, treatment, localiza- tion, outcome and microbiology were obtained from hospital files. Microbiological findings included biopsies taken within 48 hours of admission to the hospital. 4. Results During the inclusion period a number of 115 patients were identi- fied. Men, 69%, were overrepresented, 13,9% had a skin disease at the place of NF, 24,3% had diabetes mellitus (DM), 21,7% had had an operation within 4 weeks prior to NF diagnosis and 13,9% had cancer at the time of diagnosis (Table 1). We found a 30-day mortality of 7,8% and a 90-day mortality of 19,1% (Table 3). Number of revisions had a mean of 5.4. 82,6% received HBO, most often 2 or more HBO-treatments (64,3%). Most cases had a known point of entry, 55,7 %. In patients with monomicrobial growth in a sample taken within 48 hours from admission, hemolytic streptococcus was overrepresented (56,1%), and this organism was also found in 25% of polymicrobial cases. 64,3% of the patients developed septic shock. 27,8 % Multiple Organ Dysfunction Syndrome (MODS), 11,3 % Disseminated In- travascular Coagulation (DIC) and 17,4 % Acute Tubulointerstitial Nephritis (ATIN) (Table 2). Data regarding demographics, comorbidity, treatment, etiology and outcome among the patients who died within 30 days of the diagnosis is shown in table 3. Table 1: Demographic data & comorbidity Sex, n (%) Female 36 (31) Male 79 (69) Age, median, (range) 60 (5 – 86) Weight, n (%) BMI < 18,5 0 (0) BMI 18,5 - 25 65 (56.5) BMI > 25 50 (43.5) Smoking, n (%) Yes 54 (47) No 32 (27.8) Earlier 17 (14.8) Alcohol abuse*, n (%) Yes 33 (28.7) No 75 (65.2) Earlier 7 (6.1) Hypertension, n (%) 44 (38.3) Hypercholesterolemia, n (%) 9 (7.8) Diabetes Mellitus (DM), n (%) 28 (24.3) Skin disease at the place of NF**, n (%) 16 (13.9) Cancer, n (%) At the time of NF diagnosis 16 (13.9) Earlier 5 (4.3) HIV, n (%) 2 (1.7) I.v. drug abuse, n (%) 3 (2.6) Liver cirrhosis, n (%) 6 (5.2) Hepatitis, n (%) Alcoholic hepatitis 2 (1.7) Hepatitis C 4 (3.5) Chronic Obstructive Pulmonary Disease (COPD), n (%) 18 (15.7) Operation within 4 weeks, n (%)*** 25 (21.7) Crepitation/air development, n (%) 45 (39.1) *In Denmark defined as 84 g of alcohol/week for women and 168 g/week for men **Represented diagnoses where; chronical itching skin disease, chroni- cal/bad healing wounds, tendency to fistulas/abscesses/erysipelas/cysts or polyps, seborrheic dermatitis) ***The patient had had surgery, including dental surgery/extraction with- in 4 weeks prior to NF diagnosis
  • 3. clinicsofsurgery.com 3 Volume 9 Issue 1 -2023 Case Series Table 2: Treatment, Etiology and Outcome Number of revisions Mean 5.4 Median (Range) 4 (0-28) Number of Hyperbaric Oxygen Treatment (HBO) treatments, n (%) 0 20 (17,4) 1 21 (18,3) 2 36 (31,3) 3 16 (13,9) 4 12 (10,4) 5 6 (5,2) 6 3 (2,6) 7 1 (0,9) Known point of entry, n (%) 64 (55,7) Abscess, n (%) 25 (21,7) Microbiology (sample taken within 48 hours from admission) Polymicrobial, n (%) 48 (41,7) -Haemolytic streptococcus 12 (25) Monomicrobial, n (%) 41 (35,7) -haemolytic streptococcus 23 (56,1) - Clostridium septicum 1 (2,4) - E.coli 4 (9,8) - Staphylococcus aureus 3 (7,3) - Staphylococcus epidermidis 1 (2,4) - Streptococcus anginosus 2 (4,9) - Streptococcus constellatus 2 (4,9) - Streptococcus 4 (9,8) - Gram positive coccus 1 (2,4) Unknown etiology, n (%) 26 (22,6) Stage of sepsis, n (%) No sepsis 19 (16,5) Sepsis 14 (12,2) Severe sepsis 8 (7) Septic shock 74 (64,3) Amputated, n (%) 26 (22,6) Multiple Organ Dysfunction Syndrome (MODS), n (%) 32 (27,8) Disseminated Intravascular Coagulation (DIC), n (%) 13 (11,3) Acute Tubulo Interstitial Nephritis (ATIN), n (%) 20 (17,4) Toxic Shock Syndrome (TSS), n (%) 1 (0,9)
  • 4. clinicsofsurgery.com 4 Volume 9 Issue 1 -2023 Case Series Table 3: Demographics, comorbidity, etiology, treatment and outcome among patients who died within 30 days Patients who died within 30 days 1 2 3 4 5 6 7* 8 9 Sex M M M M M M M F F Age 53 53 83 50 84 73 5 63 61 Cancer x x x Skin disease at the place of NF x x Operated within 4 weeks prior to diagnosis x x Localization Multiple Multiple Fourniers Fourniers Lower extremity Lower extremity Urogenital Urogenital Urogenital Number of revisions 3 5 1 1 1 5 0 11 3 Number of HBO treatments 0 0 1 2 1 1 0 6 0 Known point of entry x x x x x Septic shock x x x x x x x x Amputation x x x x MODS x x x DIC x x x ATIN TSS Microbiology S. aureus Poly Poly Unknown Unknown G+ coccus S. epidermidis Poly Poly *Patient suffered from leukemia and died before surgery was possible The 30 day mortality from NF was 9/115 = 7,8 %. The 90 day mortality was 9+13/115 = 19,1%. 5. Discussion The 30-day mortality in 2005-2006 was 8,2% [2]. This article shows a 30-day mortality approximately the same, 7,8%. Although the 30-day mortality has not changed a lot, the 90-day mortality has. In 2005-2006 it was 11,8%, and this article shows a mortality of 19,1%. The difference could among other causes reflect a differ- ence in localization of the infection or different microbiology, with a shift towards more resistant bacteria [16, 17] or a difference in patient care after discharge. We found an overrepresentation of the male sex in the material (69%) just as in the article by Skovsen et al. (67%) [2]. The local- izations were the extremities (42,2%), urogenital (31,8%), abdom- inal (14,1%), and head/neck/thoracic region (11,8%) in the article by Skovsen et al [2]. We found a difference in locations with more patients (20,9%) with the localization head/neck/thoracic region, and fewer with the other localizations; extremities (30,4%), uro- genital (22.7%) and abdominal (6.1%). Although we also had a group called “many regions” (20%), including at least one other localization than the extremities, this might have contributed to the difference in mortality. It might be more difficult to perform surgery in the head/neck/thorax area than at the extremities and the surgery might be more hazardous for the patient. It might also be more difficult to remove enough tissue, to be extensive enough and the surgeon might be more careful, wanting to spare as much tissue as possible with regards to cosmetic and social disabilities. This could result in less extensive surgery with incomplete radicality. Furthermore, amputation is not an option in the head/neck/thoracic region, which is a possibility with extremities and the male genital area, to stop infections that are out of control. In the article by Skovsen et al. 65,9 % of patients had septic shock, 24,7% ATIN and 12,9% DIC [2]. We found septic shock in 64,3%, 17,4% suffered from ATIN and 11,3% from DIC. Possibly we have become better at treating septic shock, but with more resistant bac- teria, this effect might not be seen. Similarly to Skovsen et al. we found that 21,7 % had had an operation in short time before they got their NF diagnosis, compared to 18,9%, indicating this as a predisposing condition and there might be more to this than just being an entry point for bacteria. HBO and Intravenous Immunoglobulin (IVIG) are among the most discussed treatment options. HBO is a medical treatment where the patient, enclosed in a chamber, breathes 100% oxygen at a pressure > 1 atmosphere absolute. The proposed benefits are; enhanced ability for white blood cells to kill aerobic bacteria, stim- ulation of collagen formation, increased levels of superoxide dis-
  • 5. clinicsofsurgery.com 5 Volume 9 Issue 1 -2023 Case Series mutase, vasoconstriction and thereby decreased edema formation and increased tissue oxygen tension with increased effect of anti- biotics. A “super oxygenated zone” builds, forming a barrier which slows spreading of the infection, cause damping of the systemic inflammatory response, impair the virulence of bacterial patho- gens, promote angiogenesis and healing of wounds, promote the pliability of red blood cells and terminate lipid peroxidation [6, 8]. A systematic review from 2015 (searching the Cochrane Central Register of Controlled Trials, MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, EMBASE and the Database of Randomized Controlled Trials in Hyperbaric Medicine) failed to locate relevant clinical evidence to support or refute the effective- ness of Hyperbaric Oxygen Treatment (HBOT) in the management of necrotizing fasciitis. Good quality clinical trials are needed to define the role, if any, of HBOT in the treatment of individuals with necrotizing fasciitis [18]. There are few small retrospective studies that show positive results from HBO [5]. In a Danish co- hort study including patients with Necrotizing Soft Tissue Infec- tions (NSTI) an improved 30-day and 90-day survival in hospitals offering HBOT as an adjunct to the multidisciplinary treatment was reported. However, authors state that these results should be interpreted cautiously due to missing confounders, such as clinical variables and potentially different treatment modalities across hos- pitals. Mortality among HBOT-treated individuals was noticeably reduced compared with those who did not receive HBOT. Again authors state that the difference should be interpreted carefully due to potential selection bias based on which patients are offered HBOT as an adjunct. Presumably, some may have been in such critical hemodynamic condition were in-hospital transportation to HBOT were deemed unachievable, thereby indicating that the HBOT-treated patients represent a selected cohort [15]. IVIG was primarily used in the treatment of Toxic Shock Syndrome (TSS). The proposed mechanisms of action are that IVIG may opsonize Group A Streptococcal bacteria, promote clearance, antagonize or neutralize streptococcal super antigens and modulate immune cytokine responses [3, 8]. A randomized, blinded, placebo-con- trolled trial with 87 patients included concluded that in patients with NSTI treated in an intensive care unit, there were no apparent effects of adjuvant IVIG on self-reported physical functioning at 6 months[19]. An observational study reported that one 25g IVIG dose was sufficient to yield plasma-neutralizing activity against streptococcal superantigens, why this study recommend the use of IVIG [20]. Though all proposed mechanisms of action, there are also side effects from HBO (reversible myopia, barotraumatic lesions (ear, lung), CNS and pulmonary oxygen toxicity) [21] and IVIG (anaphylaxis and possibly renal impairment) [22]. We had a higher proportion of patients 17.4% that did not receive HBO, whereas Skovsen et al. reported 3.5%, this might have contribut- ed to the difference in 90 day mortality rates. The reasons for the difference in number of patients who were not treated with HBO might have been a different judgment concerning if a patients clin- ical condition was stable enough, the patients could have been di- agnosed at a later point in their infection, they might have had a more aggressive infection or it might have been at a different lo- calization. There is a need for controlled studies with a large num- ber of patients, possibly in countries where HBO is not a standard regimen as it is unethical to remove a treatment we have already introduced believing in its potential. For example, in the USA only 1% of patients received HBO at specialized centers [23]. In the study by Skovsen et al. 8% had DM and among them there was a mortality of 0%. In this study 24,3% had DM, of which 2 of the 9 patients who died within 30 day and 5 of the 22 patients who died within 90 day had diabetes. A proposed predisposing factor we looked into in this study was if the patients had a skin disease at the place of NF. Skin diseases reported were chronically itching skin disease, chronically/bad healing wounds, tendency to fistu- las/abscesses/cysts/erysipelas or polyps and seborrheic dermatitis. 13,9% of the patients had a skin disease, which might indicate a connection. Our main limitations are the single-centre and retrospective nature of our study. Although treatment is centralized and transport routes are not that far in Denmark, patients might have been too critically ill upon diagnosis for transportation. 6. Conclusions The present study compared with earlier findings show unchanged 30-day mortality and a slight increase in 90-day mortality. Of in- terest regarding predisposing factors 13,9% had a skin disease at the place of debut of NF. It is important to validate the diagnosis, as 8,7% hereafter were excluded in this study. There is a need for controlled studies with a large number of patients documenting the effect and regimen of HBO, possibly in countries where this is not a standard regimen as it is unethical to remove a treatment we have already introduced believing in its potential. References 1. Morgan MS. Diagnosis and management of necrotising fasciitis: A multiparametric approach. J Hosp Infect. 2010; 75(4): 249-57. 2. Skovsen AP, Bonde J, Andersen JS, Jansen EC, Tvede M. Necrotiz- ing fasciitis. Ugeskr. Laeger. 2010; 172(6): 440-4. 3. Young MH, Aronoff DM, Engleberg NC. Necrotizing fasciitis: pathogenesis and treatment. Expert Rev. Anti. Infect. Ther. 2005; 3(2): 279-94. 4. Sarani B, Strong M, Pascual J, Schwab CW. Necrotizing fasciitis: current concepts and review of the literature. J. Am. Coll. Surg. 2009; 208(2): 279-88. 5. Hunter J, Quarterman C, Waseem M, Wills A. Diagnosis and man- agement of necrotizing fasciitis. Br. J. Hosp. Med. (Lond). 2011; 72(7): 391-5. 6. Jallali N, Withey S, Butler PE. Hyperbaric oxygen as adjuvant ther- apy in the management of necrotizing fasciitis. Am. J. Surg. 2005; 189(4): 462-6.
  • 6. clinicsofsurgery.com 6 Volume 9 Issue 1 -2023 Case Series 7. Wang JM, Lim HK. Necrotizing fasciitis: eight-year experience and literature review. Braz. J. Infect. Dis. 2014; 18(2): 137-43. 8. Shimizu T, Tokuda Y. Necrotizing fasciitis. Intern. Med. 2010; 49(12): 1051-7. 9. Puvanendran R, Huey JCM, Pasupathy S. Necrotizing fasciitis. Can. Fam. Physician. 2009; 55(10): 981-7. 10. Lee CY, Kuo LT, Peng KT, Hsu WH, Huang TW, Chou YC. Prog- nostic factors and monomicrobial necrotizing fasciitis: gram-posi- tive versus gram-negative pathogens. BMC Infect. Dis. 2011; 11(5). 11. Das DK, Baker MG, Venugopal K. Risk factors, microbiological findings and outcomes of necrotizing fasciitis in New Zealand: a retrospective chart review. BMC Infect. Dis. 2012; 12(348). 12. Krieg A, Röhrborn A, Esch JSA, Schubert D, Poll LW, et al. Nec- rotizing fasciitis: microbiological characteristics and predictors of postoperative outcome. Eur. J. Med. Res. 2009; 14(1): 30-6. 13. Goh T, Goh LG, Ang CH, Wong CH. Early diagnosis of necrotizing fasciitis. Br. J. Surg. 2014; 101(1): e119-25. 14. Voros D, Pissiotis C, Georgantas D, Katsaragakis S, Antoniou S, Papadimitriou J. Role of early and extensive surgery in the treat- ment of severe necrotizing soft tissue infection. Br. J. Surg. 1993; 80(9): 1190-1. 15. Hedetoft M, Madsen MB, Madsen LB, Hyldegaard O. Incidence, comorbidity and mortality in patients with necrotising soft-tissue infections, 2005-2018: A Danish nationwide register-based cohort study. BMJ Open. 2020; 10: 10. 16. Rossolini GM, Mantengoli E. Antimicrobial resistance in Europe and its potential impact on empirical therapy. Clin. Microbiol. In- fect. 2008; 14 Suppl 6: 2-8. 17. de Kraker MEA, Jarlier V, Monen JCM, Heuer OE, van de Sande N, Grundmann H. The changing epidemiology of bacteraemias in Europe: trends from the European Antimicrobial Resistance Surveil- lance System. Clin. Microbiol. Infect. 2013; 19(9): 860-8. 18. Levett D, Bennett MH, Millar I. Adjunctive hyperbaric oxygen for necrotizing fasciitis. Cochrane Database of Systematic Reviews. 2015; 1(1): CD007937. 19. Madsen MB, Hjortrup PB, Hansen MB, Lange T, Norrby-Teglund A, Hyldegaard O, et al. Immunoglobulin G for patients with necro- tising soft tissue infection (INSTINCT): a randomised, blinded, pla- cebo-controlled trial. Intensive Care Med. 2017; 43(11): 1585-93. 20. Bergsten H, Madsen MB, Bergey F, Hyldegaard O, Skrede S, Ar- nell P, et al. Correlation between immunoglobulin dose administered and plasma neutralization of streptococcal superantigens in patients with necrotizing soft tissue infections. Clin. Infect. Dis. 2020; 71(7): 1772-5. 21. Plafki C, Peters P, Almeling M, Welslau W, Busch R. Complications and side effects of hyperbaric oxygen therapy. Aviat Space Environ Med. 2000; 71(2): 119-24. 22. Levy JB, Pusey CD. Nephrotoxicity of intravenous immunoglobu- lin. QJM An Int. J. Med. 2000; 93(11): 751-5. 23. Soh CR, Pietrobon R, Freiberger JJ, Chew ST, Rajgor D, Gandhi M, et al. Hyperbaric oxygen therapy in necrotising soft tissue infections: A study of patients in the United States Nationwide Inpatient Sam- ple. Intensive Care Med. 2012; 38(7): 1143-51.