Pages

Anaerobic Soft Tissue & Muscular Infections


Skin, soft-tissue and muscular infections are common, potentially life-threatening, and may progress rapidly. Early recognition and proper medical and surgical management is the cornerstone of therapy. Secondary bacterial infection in skin lesions such as scabies, psoriasis, poison ivy, atopic dermatitis, eczema herpeticum and kerionis a common problem.

Some of the clues to the anaerobic origin of these infections are putrid discharge, gas production, and extensive tissue necrosis with a tendency to burrow through subcutaneous and fascial planes.

Classification & Diagnosis

Impetigo
Impetigo is a superficial small vesicles that pustulate ruptures and dries forming a golden-yellow crust .1

Impetigo


Cellulitis
Cellulitis generally appears as local tenderness, pain and erythema. The area involved is red, sharply demarcated, hot, swollen, with non-elevated borders. Regional lymphadenitis and bacteremia are common and can cause thrombophlebitis.


Cellulitis



Infectious Gangrene (Gangrenous cellulitis).1-2,2a. 

This is a rapidly progressive infection that involves extensive subcutaneous tissues and overlying skin necrosis. It includes several entities:

1)   Necrotizing fasciitis
2)   Gas gangrene (clostridium and non-clostridial anaerobic cellulitis)
3)   Progressive bacterial synergistic gangrene
4)   Synergistic necrotizing cellulitis and fasciitis,
5)   Localized skin necrosis complicating cellulitis
6)   Gangrenous cellulitis in the immunocompromised patient

Necrotizing fasciitis (NF): NF has two bacteriological entities: streptococci., and polymicrobial (evolving at least one anaerobe). Streptococcal gangrene starts as painful erythema and edema, followed in 24-72 hours by dusky skin, and yellowish to red-black fluid filled bullae. The area is demarcated and covered by necrotic eschar, surrounded by erythema. A rapid progression occurs with frank cutaneous gangrene, accompanied sometimes by myonecrosis. Penetration along facial planes can occur, followed by thrombophlebitis in the lower extremities, bacteremia with metastatic abscesses and rapid death. Differentiation between cellulitis and NF is important. Cellulitis can be treated with antimicrobials alone while NF requires also surgical debridment.


Necrotizing fasciitis



Group A beta-hemolytic streptococcal (GABHS) infection can be associated with streptococcal toxic shock like syndrome (TSLS), manifested by fever, tachycardia, hypotension, multi-organ failure, and in 80% evidence of soft tissue involvement.

NF due to mixed anaerobic-aerobic flora is usually associated with an endogenous organism(s), and presents in slightly different fashion. The involved area is first erythematous, swollen, hot, tender, painful and has no sharp margin. Progression occurs within 3–5 days, with skin breakdown with bullae, and cutaneous gangrene. The involved area becomes anesthetic because of thrombosis of the small vessels that supply the superficial nerves. This can antedate the appearance of skin necrosis, and signifies the presence of NF and not simple cellulitis. Easy probing with a hemostat through an incision in the lesion along a plane, is diagnostic. Subcutaneous gas and foul smell are often present, especially in diabetics. Systemic toxicity and elevated temperature are common. NF of the face, eyelids, neck and lips2 are rare but can be life-threatening. Crepitus, severe pain and necrosis of the epidermis and superficial fascia are evident. The infection can spread rapidly to other areas in the neck. NF was recently described after laryngectomy.2b

Gas gangrene, anaerobic cellulitis: In clostridial and non-clostridial anaerobic cellulitis, the onset is gradual no local pain and swelling and no systemic toxicity. A thin, dark, sometimes foul smelling discharge and extensive tissue gas formation manifesting crepitus is seen.

Gas gangrene 


Progressive bacterial synergistic gangrene: Starts with local tenderness, swelling and erythema that subsequently ulcerates. The painful ulcer enlarges and is surrounded by violaceous zone that fades into pink edematous border. Left untreated, the ulcer enlarges and may burrow through tissue emerging in distant sites (Meleney's ulcer).

Synergistic necrotizing cellulites and fasciitis: This infection starts as cellulitis, adjacent to the entry point, and involves the deep fascia. Pain, fever and systemic toxicity occur. When it occurs in the male genitals it is called “Fournier's gangrene”. Swelling and crepitus of the scrotum increases, and gangrene develops. Abdominal wall involvement can be especially rapid in diabetics.


Fournier gangrene




Gangrenous cellulitis in the immunocompromised host: Cellulitis can be caused by expected as well as opportunistic pathogens and is often seen after trauma. Pseudominas aeroginosa is the most common pathogen and cause a sharply demarcated necrotic area with black eschar and surrounding erythema.



Diabetic, decubitus and other secondary bacterial infections complicating skin lesions. Infections in the diabetics are divided into non-limb-threatening and limb-threatening. Non-limb-threatening infections are superficial, lack systemic toxicity, have minimal cellulitis that extends <2 cm from port of entry, if ulceration is present it does not extend through the skin, and does not show signs of ischemia. Limb-threatening infections are associated with ischemia, have extensive cellulitis, lymphangitis, and the ulcers penetrate through the skin into the subcutaneous tissue. Epidermal cysts in the chest, trunk, extremities and vulvovaginal and scrotal areas can also become severely infected.3 Other skin lesions that can be secondarily infected with aerobic and anaerobic bacteria are: scabies, eczema herpeticum, psoniasis, poision ivy, draper dermatitis, Kerion and atopic dermatitis.

Diabetic ulcer




                                                                  Diabetic ulcer





Decubitus ulcer



Myositis

Muscular infections frequently occur in areas of the body that have been compromised or injured by foreign body, trauma, ischemia, injection of illicit drug, malignancy or surgery. These infections can develop very rapidly to life-threatening systemic illness. Pyogenic myositis can be classified into either GABHS necrotizing myositis, clostridial myonecrosis (gas gangrene), and nonclostridial (crepitant) myositis.

Clostridial myonecrosis


Microbiology (Table 2 ) 

Impetigo:

The bullous form of impetigo is due to Staphylococcus aureus (phage group II, usually type 71). The most severe form of S. aureus infection is Staphylococcal scalded skin syndrome (SSSS), which is caused by a strain that produces an exfoliative exotoxin, producing widespread bullae and exfoliation, with a positive Nikolsky sign. 1

Iimpetigo and cellulitis are generally attributed to S. aureus and GABHS alone or in combination (18). Anaerobes are recovered in about third of the patients, 2/3 of the time mixed with aerobic organisms. 5  The predominant anaerobes are Peptostreptococcus, pigmented Prevotella, and Fusobacterium spp. Peptostreptococcus spp. are isolated from all body sites. Peptostreptococcus, Prevotella  or Fusobacterium spp. is mostly found in infections of the head and neck, while E. coli mixed with Bacteroides fragilis and Peptostreptococcus spp. are isolated from infection of the buttocks area.

Cellulitis:

GABHS is the major and S. aureus is a minor cause of the classic erysipelas. Enterobacteriaceae P. aeruginosa and fungiare recovered from cellulitis in the immunocompromised. Anaerobes are recovered in about half of the patients, half of the time mixed with aerobic organisms. 6 The highest recovery rate of anaerobes is from the neck, trunk, groin, external genitalia and leg areas. The predominant anaerobes are Peptostreptococcus spp., B. fragilis group, PrevotellaPorphyromonas  and Clostridium spp.

Certain clinical findings correlate with the following organisms: swelling and tenderness with Clostridium spp., Prevotella spp., S. aureus and GABHS; regional adenopathy with B. fragilis group; bulbous lesions with Enterobacteriaceae; gangrene and necrosis with Peptostreptococcus spp., B. fragilis group, Clostridium spp. and Enterobacteriaceae; foul odor with Bacteroides spp.; and gas in tissues with Peptostreptococcus spp., B. fragilis group and Clostridium spp. 6

Certain predisposing conditions correlated with the following organisms: trauma with Clostridium spp.; diabetes with Bacteroides spp., Enterobacteriaceae and S. aureus; and burn with P. aeruginosa.


Necrotizing Fasciitis

There are two main bacterial causes of NF: GABHS and synergistic infection due to facultative and anaerobic bacteria. Streptococcal gangrene is due to either groups A, C or G streptococci. However, GABHS can be recovered with other organisms. The predominant organisms present in synergistic infection, including those of the male genital area, Enterobacteriaceae, S. aureusPeptostreptococcus Clostridium , and Fusobacterium spp., and Bacteroides fragilis group. 2

Anaerobes outnumber aerobes at all body sites, but their highest recovery rate is in the buttocks, trunk, neck, external genitalia, and inguinal areas.

Some clinical findings correlated with certain bacteria: edema with B. fragilis group, Clostridium spp., S. aureusPrevotella spp. and GABHS; gas and crepitation in tissues with Enterobacteriaceae and Clostridium spp.; and foul odor with Bacteroides spp. 2
Certain predisposing conditions correlated with some organisms: trauma with Clostridium spp.; diabetes with Bacteroides spp., Enterobacteriaceae and S. aureus; and immunosuppression and malignancy with Pseudomonas spp. and Enterobacteriaceae.


Gas gangrene, and crepitant cellulitis:

Clostridium perfringens is the most common Clostridium species causing the infection, but other species (Clostridium septicum Clostridium novyiClostridium bifermentansClostridium histolyticum and Clostridium fallax) have also been recovered. Occasionally the clostridium is recovered mixed with other aerobic and anaerobic bacteria. Non clostridial infection is due to various nonspore-forming anaerobes ( including  Bacteroides spp. and anaerobic streptococci) and Enterobacteriaceae.

Progressive bacterial synergistic gangrene:

Anaerobic or microaerophilic streptococci are recovered from the advanced margin of the lesion, while S. aureus and sometimes Gram-negative aerobic bacilli (especially Proteus spp.) can be isolated from the ulcerated area.

Diabetic, decubius and other chronic superficial skin ulcers and subcutaneous abscesses

Decubitus ulcers can be colonized and infected by a variety of aerobic and anaerobic bacteria. The distribution of organisms depends on the location of the ulcer. While GABHS and S. aureus can be isolated in all body sites, organisms of oral flora origin (pigmented Prevotella and Porphyromonas, Fusobacterium, and Peptostreptococcus spp.) are isolated in ulcers and wounds proximal to that site, while organisms of colonic or vaginal flora origin (B. fragilis group, Clostridium spp., Peptostreptococcus spp., and Enterobacteriaceae) can be recovered from lesions proximal to the perianal area (Figure 1).  This principle applies to recovery of organisms in other skin and soft tissue wounds and abscesses, secondarily infected wounds and skin lesions caused by scabies, superficial thrombophlebitis, decubitus ulcers, diaper dermatitis, atopic dermatitis, secondarily infected eczema herpeticum,  psoriasis, Kerion lesions, and poison ivy lesions. 4 Foot infections in diabetic patients are infected with S. aureus, group B StreptococciEnterococcus spp., Enterobacteriaceae and other Gram-negative aerobic bacteria, as well as Peptostreptococcus spp. and B. fragilis group. 8


Myositis

S. aureus is the predominant cause of tropical and non-tropical infection . GABHS as well as other groups (B, C and G), as well as Spneumoniae and Streptococcus anginosus can be recovered. Gram-negative aerobic and facultatives have also been rarely recovered. These include EnterobacteriaceaeYersinia enterocoliticaPseudomonas spp., Haemophilus influenzaeNeisseria gonorrhoeae, and Aeromonas spp.
Anaerobic bacteria such as BacteroidesFusobacterium, Clostridium and Peptostreptococcus spp. have also been recovered in studies where proper methods for their isolation were employed. 9,10

Pyogenic myositis can be classified according to the organisms recovered: GABHS necrotizing myositis, clostridial myonecrosis (gas gangrene), and nonclostridial (crepitant) myositis. C. perfringens accounts for 80–95% of cases, C. novyi for 10–40%, and C. septicum for 5–15%. Rarely other clostridial species can be isolated: C. bifementansC. fallax and C. histolyticum. Other organisms such as E. coliEnterococci and Enterobacter spp. can also be recovered mixed with Clostridium spp. Non-clostridial myositis can be divided into subgroups: Anaerobic streptococcal myonecrosis - which is a mixed infection of GABHS or S. aureus with Peptostreptococcus spp.; synergistic non-clostridial anaerobic myonecrosis - due to polymicrobial flora; infected vascular gangrene - due to Bacteroides and other anaerobes plus Proteus sp., and Aeromonas hydrophila - myonecrosis. Psoas abscess - is generally due to S. aureus or polymicrobial aerobic-anaerobic flora. 


Pathogenesis

Soft tissue and muscular infections frequently occur in areas compromised or injured by foreign body, trauma, ischemia, malignancy or surgery. Because the indigenous local microflora usually is often responsible for these infections, anatomic sites that are subject to fecal or oral contamination are particularly at risk. These include wounds associated with surgery of the intestine or pelvis, human bites, decubitus ulcers in the perineal area, pilonidal cysts, omphalitis, and cellulitis around the fetal monitoring site.

Skin and subcutaneous infection.

Predisposing conditions to progressive bacterial synergistic gangrene are listed in table 3.
Decubiti and nonhealing wounds usually are produced by pressure or by circulatory dysfunction.11  In an area without sensation, the ulcer develops when pressure is placed on one site for a critical period of time, causing ischemia and necrosis. Ulcers caused by circulatory dysfunction may result from large- or small-vessel disease or from venous stasis. Bedridden patients are prone to decubitus ulcers. Poor nutrition, low serum albumin, anemia, and circulatory impairment add seriously to the hazard of this development.1 Osteomyelitis and anaerobic bacteremia can occur in extensive or invasive ulcers.

Infection in diabetic patients generally follows minor trauma in individuals with neuropathy and arterial vascular insufficiency. 8 The infection may progress to cellulitis, soft tissue necrosis, osteomyelitis with a draining sinus. Proximity to mucous membrane orifices (anal, vaginal, or oral) enables the adjacent endogenous flora to invade the ulcers.

Clostridial anaerobic cellulitis follows introduction of organisms into subcutaneous tissues through a contaminated or inadequately debrided wound. The source can also be a pre-existing infection of the perineum, abdominal wall, buttocks and lower extremities that are contaminated with fecal flora. The necrotic tissue or foreign material in the wound enhances the infection with Clostridium spp.

Gangrenous cellulitis generally follows introduction of pathogens to the infected site. It can also develop from extension of the infection from deeper sites to the subcutaneous and skin tissues.

Spontaneous, nontraumatic gas gangrene is often due to C. septicum, that spreads by bacteremic route. Intestinal abnormalities that include necrotizing enterocolitis, volvulus, colon cancer, diverticulitis and bowel infarction.  leukemia, neutropenia and diabetes mellitus are the major predisposing conditions.

Predisposition to Fournier's gangrene include local trauma, diabetes, paraphimosis, periurethral extravasation of urine, and perirectal or perianal infection and surgery in the area (i.e., herniorrhaphy, circumcision). The infection can extend to the abdominal wall, especially in patients with diabetics, obesity, advanced age and cardiorenal disease.
Trauma often predisposes to NF of the periorbital or facial areas. The portal of entry of abdominal wall infection include trauma, laparotomy, perirectal abscess, and decubitus ulcers. Predisposing conditions include diabetes mellitus, alcoholism and parenteral drug abuse.


Myositis

Myositis can originate from contiguous sites including skin and subcutaneous abscesses, ulcers, compound fracture, penetrating wounds, surgical wounds ( especially following bowel or biliary tract surgery ), osteomyelitis, arterial insufficiency, from a parenteral injection, and through hematogenous spread. Predisposing condition to tropical myositis include diabetes, alcoholism, corticosteroid and immunosuppressive therapy, hematological illnesses, and human immune deficiency (HIV) infection.

Psoas abscess generally results from an adjacent infected structure. These include intra-abdominal infection (appendicitis, diverticulitis, chrons’ disease), osteomyelitis of the vertebra or illium, septic arthritis of the sacro-iliac joint, perinephric abscess, or infected retroperitoneal hematoma.


Diagnosis

The recovery of fastidious organisms depends on employment of proper methods for collection, and transportation of specimen, and cultivation of organisms.
Radiological studies of soft tissue can reveal the presence of free gas. This can assist in the differentiation between NF due to either streptococcal or mixed polymicrobial aerobic-anaerobic infection. A feathery lineary pattern of gas can be observed in infected muscles in clostridial myonecrosis.

Osteomyelitis can be detected by radiological and radionuclide scanning studies.
Radionuclide (67 Ga) and CT scanning are used to diagnose pyomyositis. MRI can detect alteration in soft tissue and can differentiating cellulitis from pus and abscess. MRI can show enlargement of involved muscles and fluid collection. Sonography or CT can be used to guide diagnostic aspiration.


Management

Intensive surgical and medical therapy that includes the administration of intravenous fluids and management of septic shock are the hallmarks of treatment.
Rapidly progressing SSSS, and streptococcal toxic shock like syndrome (TSLS) require prompt and urgent action. Rapid surgical and medical responses are indicated in: cellulitis that progresses into thrombophlebitis and bacteremia, and any of the Infectious gangrenes (especially NF). Special attention should be given to the immunocompromised host with gangrenous cellulitis.  NF of the face, eyelids, neck and lips can be life-threatening.
Treatment of infectious gangrene and gangrenous cellulitis consists of immediate surgical drainage with longitudinal incisions extending throughout the deep fascia and beyond the gangrenous and undermined areas. Areas of cutaneous necrosis should be excised and nonviable fascias should be debrided. Wide excision of the tissues should extend well into the normal tissue.

Necrotic fascia and fat should be excised, and the wound should be left open. An additional second procedure is often needed within 24 hours, to ensure the adequacy of the initial debridement. 

In decubitus ulcers adequate pressure relief and further protection of vulnerable areas is needed. Surgical management of diabetic foot and decubitus ulcers includes unroofing of encrusted areas and wound probing to determine the extent of tissue destruction and potential bone involvement. The wound can be treated, primarily by skin grafting or flaps or secondarily by wound contraction. Topically applied antibacterial agents include organic synthetic iodide preparations, silver sulfadiazine, and mafenide cream. Surgical debridement and drainage should be performed in those with deep tissue necrosis or suppuration. Infected cysts and subcutaneous abscesses should be promptly drained.
In pyomyositis, an emergency surgical exploration is warranted to define the nature of the process by direct examination of the involved muscles and perform appropriate debridement. Immediate extensive surgery is needed to treat gas gangrene. The muscles involved should be removed, and fasciotomies to decompress and drain the fascial compartment are performed. Complete amputation may be necessary
.
Antimicrobial therapy is an essential in management of skin, soft tissue and muscle infection. Establishing the bacterial etiology and their susceptibility initially by gram stain, and later by culture can allow for selection of proper antimicrobial therapy. Often, the initial therapy is empiric, based on epidemiological, historical and clinical features.

Where streptococcal etiology is suspected, parenteral penicillin is used. If staphylococcal is suspected, or when no initial clue for etiology is available, a penicillinase-resistant penicillin (e.g., oxacillin) is given. Macrolides, vancomycin or linezolid can be used in penicillin allergic individuals, and an aminoglycoside, a quinolone, or a third generation cephalosporin (i.e., ceftazidime, cefipime) can be given to cover Gram-negative aerobe bacilli.

Antimicrobial therapy for mixed aerobic and anaerobic bacterial infections is required when polymicrobial infection is suspected. The combination of penicillin and clindamycin is recommended for Clostridium spp.. Antimicrobials that generally provide coverage for Saureus as well as anaerobes include cefoxitin, clindamycin, a carbapenem ,  and the combinations of a b-lactamase inhibitor and a penicillin and the combination of metronidazole plus a b-lactamase-resistant penicillin. Cefoxitin, the carbapenems, and a penicillin plus a b-lactamase inhibitor also cover the Enterobacteriaceae. However, agents effective against these organisms (i.e., aminoglycosides, fourth generation cephlosporins, and quinolones) should be added to the other agents when treating infections that include these bacteria.
Hyperbaric oxygen therapy for clostridial myonecrosis is controversial. However, it should be considered when the involved tissue cannot be completely excised surgically.


REFERENCES

1.   Elias, P.M., Fritsch, P., Epstein, E.H. Jr.: Staphylococcal scalded skin syndrome: Clinical features, pathogenesis, and recent microbiological and biochemical developments. Arch Dermatol 113:207–219, 1977.
2.  Brook I; The role of anaerobic bacteria in skin and soft tissue abscesses and infected cysts. anaerobes 3:171-7, 2007.
2a.   Brook, I., Frazier, E.H.: Clinical and microbiological features of necrotizing fasciitis. J Clin Microbiol 33:2382–2387, 1995.
2b.Danic Hadzibegovic A, Sauerborn D, Grabovac S, Matic I, Danic D.Necrotizing fasciitis of the neck after total laryngectomy. Eur Arch Otorhinolaryngol. 2012 Mar 21.
3.   Brook, I.: Microbiology of infected epidermal cysts. Arch Dermatol 125:1658–1661, 1989a.
4.   Brook I, Secondary bacterial infections complicating skin lesions.
J Med Microbiol.;51:808-12. 2002.
5.   Brook, I., Frazier, E.H., Yeager, J.K.: Microbiology of nonbulbous impetigo. Pediatr Dermatol 14:192–195, 1997.
6.   Brook, I., Frazier, E.H.: Clinical features and aerobic and anaerobic characteristics of cellulitis. Arch Surg 130:786–792, 1995b.
7.   Brook, I., Finegold, S.M.: Aerobic and anaerobic bacteriology of cutaneous abscess in children. Pediatrics 67:891–895, 1981.
8.   Sapico, F.L., Witte, J.L., Canawati, H.N., et al.: The infected foot of the diabetic patient: Quantitative microbiology and analysis of clinical features. Rev Infect Dis 6(Suppl 1):S171–S176, 1984.
9.   Brook, I., Frazier, E.H.: Aerobic and anaerobic microbiology of infection after trauma. Am J Emerg Med 16:585–91, 1998.
10Brook, I.,: Pyomyositis in children, caused by anaerobic bacteria. J Pediatr Surg 31:394–6, 1996.
11. Brem H, Nierman DM, Nelson JE. Pressure ulcers in the chronically critically ill patient.
Crit Care Clin.;:683-94. 2002.
12. Iorianni, P., Oliver, G.C.: Synergistic soft tissue infections of the perineum. Dis Colon Rectum 35:640–644, 1992.


Table 1. Clinical presentations of soft tissue infections.

Necrotizing fasciitis
Gas gangrene
Progressive bacterial
Synergistic necrotizing
Pseudomonas

(streptococcal gangrene)
(clostridial myonecrosis)
synergistic gangrene
Cellulitis
gangrenous cellulitis
Fever
High
Moderate to high
Minimal or absent
Moderate
High
Systemic toxicity
Significant
Very significant
Minimal
Significant
Significant
Pain
Minimal
Significant
Significant
Significant
Mild
Crepitus
Absent
Present
Absent
Often present
Absent
Anaesthesia of lesions
Sometimes present
Absent
Absent
Absent
Sometimes present
Appearance of infection
Subcutaneous tissue and fascial necrosis. Overlying skin necrotic and dark
Significant oedema. Yellow-brown discolouration of skin. Brown bullae. Necrotic area composed of green-black patches. Serosanguinous discharge
Necrotic central ulcer, dusky margin and erythematous periphery
Crepitus cellulitis with foul-smelling, thick discharge from necrotic skin
Black discharge with surrounding erythema





Table 2. Bacterial aetiology.

Impetigo and cellulitis, diabetic and chronic skin ulcers
Streptococcus group A
Staphylococcus aureus

Anaerobic oral flora (Prevotella, Fusobacterium and Peptostreptococcus spp.) around oral area and head and neck
Colonic flora: Enterobacteriaceae and anaerobes (i.e. Escherichia coli   and Bacteroides fragilis group) around rectum and lower extremity

Necrotizing fasciitis
Streptococcus group A (rarely also groups C or E)
Staphylococcus aureus
Enterobacteriaceae
Enteric or oral anaerobes

Gas gangrene and crepitus cellulitis
Clostridium perfringens and other Clostridium species

Progressive bacterial gangrene
Peptostreptococcus spp.
Microaerophilic streptococci
Proteus spp.

Myositis
Staphylococcus aureus
Streptococcus groups A, B, C and G
Enterobacteriaceae
Yersinia entercolitica
Pseudomonas spp.
Aeromonas spp.
Clostridium spp. (especially perfringens)
Peptostreptococcus spp.
Bacteroides spp.


Table 3. Risk factors for soft tissue and muscular infections.

Skin and subcutaneous infection
Progressive bacterial synergistic gangrene
―Surgery, draining sinus trauma

Synergistic necrotizing cellulitis
―Diabetes, trauma

Streptococcal gangrene
―Trauma, diabetes, myxoedema, abdominal surgery, steroid
and non-steroidal anti-inflammatory, varicella

Clostridial myonecrosis (gas gangrene)
―Diabetes, corticosteroid therapy, trauma

Necrotizing cutaneous mucormycosis
―Diabetes, corticosteroid therapy

Bacterial pseudomonal gangrenous cellulitis
―Burns, immunosuppression

Pyoderma gangrenosum
―Ulcerative colitis, rheumatic fever