Necrotizing fasciitis

Necrotizing fasciitis

Kavitha S. Kotrappa

Necrotizing fasciitis is a serious invasive soft-tissue infection that is rather uncommon but often life-threatening. It is characterized by widespread, rapidly developing necrosis of the subcutaneous tissue and fascia. Media attention regarding this clinical disorder has been intense in recent months, although no major variation in the number of cases or frequency of occurrence has been noted. This is not a new or mysterious disease. Its earliest reference dates back to the 15th century B.C., when Hippocrates described it as a complication of “erysipelas.”[1] Joseph Jones, a Civil War Army surgeon, reported necrotizing fasciitis in 2,642 soldiers, with a mortality rate of 46 percent.[2] In 1903, Fournier reported the occurrence of necrotizing fasciitis in the genital area, and in 1924, Meleney and Breuer noted it to be a lethal streptococcal infection.[3]

Necrotizing fasciitis must be promptly recognized and aggressively treated since it has very high rates of morbidity and mortality if treatment is delayed. We report two cases of rapidly progressive necrotizing fasciitis.

Illustrative Case 1

A 33-year-old man presented to the emergency department of a local hospital with complaints of a painful, swollen scrotum, difficulty in breathing and a purplish, diffuse, blotchy rash over the right flank area. The patient stated that he had been ill for about nine days. Pneumonia was diagnosed and doxycycline (Vibramycin) was prescribed; therapy was subsequently changed to azithromycin (Zithromax).

The patient’s symptoms did not improve, and an erythematous rash developed on the right lateral aspect of the abdomen and progressively worsened. Allergic drug reaction was considered, and diphenhydramine (Benadryl) and oral penicillin were started. The rash spread to the right side of the abdomen, and the scrotum continued to swell, with considerable pain that progressively worsened. The patient denied a history of trauma, fever, headache, nausea, vomiting or arthralgia. The only other significant factor in the medical history was intravenous drug use, although the patient denied any drug use during the past two years.

Physical examination revealed a well-built and well-nourished man who was in considerable pain and was extremely restless. He had a regular pulse rate of 130 per minute, a temperature of 97.6[degrees] F (36.4 [degrees] C), a respiratory rate of 24 per minute and blood pressure of 105/77 mm Hg. A bluish purple, blotchy rash with bullous formation extended from the right lateral abdomen, up to the neck and down to the superior iliac crest anteriorly, and was warm and tender (Figure 1). The scrotum was grossly enlarged, very tender and warm to touch (Figure 2). The rest of the examination, including the lungs, was otherwise normal. The rash continued to spread while the patient was in the emergency department.

Laboratory evaluation revealed a hemoglobin measurement of 15 g per dL (150 g per L); hematocrit, 43 percent (0.43); white blood cell count, 29,900 cells per [mm.sup.3] (29.9 X [10.sup.9] per L), with 68 percent (0.68) polymorphonuclear cells and 24 percent (0.24) bands. The patient’s platelet count was 226,000 per [mm.sup.3] (226 x [10.sup.9] per L). Urinalysis was normal. Blood urea nitrogen measurement was 118 mg per dL (42.0 [mu]mol per L); creatinine was 5.4 mg per dL (480 [nu]mol per L); uric acid was 13.8 mg per dL (820 [mu]mol per L). Creatine kinase measurement was 442 U per L. Total bilirubin was 1.8 mg per dL (30 [mu]mol per L); conjugated bilirubin was 1.5 mg per dL (26 [mu]mol per L); aspartate aminotransferase was 99 U per L; lactate dehydrogenase was 714 U per L; serum albumin was 2.3 g per dL (23 g per L); serum amylase was 22 U per L, and lipase was 25 U per L.

Chest radiographs were normal. Gram’s stain of material aspirated from the advancing edge of the rash showed gram-positive cocci in chains, resembling Streptococci. Culture of the material eventually revealed group A beta Streptococcus.

The patient was aggressively treated with fluids, meperidine (Demerol), 5 million units of intravenous penicillin every six hours and ceftriaxone (Rocephin), 1 g every 12 hours. Surgery service was consulted, and the patient underwent immediate surgery with extensive debridement.

HOSPITAL COURSE

During the next five days, debridement was performed twice (Figure 3) and the patient required 16 units of blood, 12 units of fresh frozen plasma and 11 units of platelets. The patent continued to receive large doses of penicillin, with the addition of aztreonam (Azactam), 1 g every 12 hours, metronidazole (Flagyl), 500 mg every eight hours, and supplemental parenteral nutrition.

Gross macroscopic and microscopic examination of the debrided tissue confirmed acute subcutaneous necrosis with the presence of numerous gram-positive cocci. Culture revealed many group A Streptococci.

In view of the patient’s extensive surgical wounds, he was transferred to a major medical center after a week. Other complications occurred during this period, including bilateral pleural effusion, nosocomial pneumonia with Staphylococcus aureus and Enterobacteriaceae, and Pseudomonas urinary tract infection. The patient underwent two more debridements, a segmental latissimus dorsi muscle flap, and subsequently a full-thickness skin graft of 700 [cm.sup.2] area. During his stay at the medical center, he received broad-spectrum antibiotics, including nafcillin (Unipen), piperacillin (Pipracil) and gentamicin (Garamycin), with continued nutritional support.

Although the patient’s recovery has been slow, recent evaluation showed that the graft was healing well (Figure 4) and the patient was asymptomatic.

Illustrative Case 2

A 63-year-old man was initially evaluated by his private physician for pain and tenderness over the left shoulder. The pain was considered to be musculoskeletal in origin as a result of excessive exercise. He was given ibuprofen, with partial relief. However, over the next 24 hours the severity of the pain progressively increased, and a purplish skin lesion appeared over the shoulder area, almost mimicking a bruise. The skin rash progressed at a rapid rate (within hours in the physician’s office), and the patient’s systolic blood pressure dropped to 70 to 80 mm Hg. He was immediately transferred to the local emergency department, where he received intravenous fluids. By this time, the skin lesion had involved the pectoral area and left lateral chest with excruciating pain, tenderness and blistering.

The patient had a medical history of non-insulin-dependent diabetes mellitus for which he received treatment with an oral agent. He had a history of multiple surgeries for a left forearm injury that had resulted in fracture of both the radius and the ulna.

Clinical examination in the emergency room revealed a diaphoretic, very illappearing man with moderate tachycardia and hypotension. The skin over the left shoulder and left lateral chest had bluish discoloration with bullae. Aspiration of the bullae revealed gram-positive cocci in chains.

Laboratory evaluation revealed a white blood cell count of 2,900 cells per mm3 (2.9 X [10.sup.9] per L), 28 percent (0.28) polymorphonuclear cells, 45 percent (0.45) bands. The patient’s hemoglobin level was 8.6 g per dL (86 g per L), with a platelet count of 26,000 per [mm.sup.3] (26 X [10.sup.9] per L). Arterial blood gas measurements were as follows: pH, 7.06; partial pressure of carbon dioxide ([PCO.sub.2]), 32; partial pressure of oxygen ([PO.sub.2]), 98; and oxygen saturation, 94 percent. The blister fluid culture eventually grew pure colonies of group A Streptococcus. Histopathology of the debrided material showed extensive necrotizing dermatitis and panniculitis.

HOSPITAL COURSE

After surgical consultation, the patient was taken promptly to surgery, where extensive debridement of the area was performed with removal of necrotic skin, subcutaneous tissue and muscle extending from the left side of the neck, left shoulder, left upper and lower arm, and left side of the chest extending up to the upper abdomen. Blood loss during the surgery was extensive. Postoperatively, he was monitored the intensive care unit but continued to be hypotensive, leading to total anuria and a comatose state.

He was given intravenous fluids and blood and was started on therapy with 20 million units of penicillin intravenously, 900 mg of clindamycin (Cleocin) every six hours and 1 g of aztreonam every eight hours. Despite aggressive treatment efforts, the patient died within 18 hours of hospitalization.

Pathophysiology

Necrotizing fasciitis is known by various other designations, including hospital gangrene, necrotizing erysipelas, hemolytic streptococcal gangrene, suppurative fasciitis or acute dermal gangrene.[4] At present, necrotizing fasciitis is the preferred term since the syndrome is characterized by a pathognomonic, rapidly progressive necrosis and edema affecting the subcutaneous tissue and adjacent fascia that spares the muscles.[4] This spreading tissue inflammation may initially look like erysipelas or cellulitis, but proceeds rapidly to localized blistering, ulceration and necrosis. In the past, the pathologic changes of necrotizing fasciitis were attributed to widespread thrombi of nutrient blood vessels passing between the skin and the deep tissue.[5] However, it has recently been postulated[6] that certain super antigens (SPE-A, SPE-B and SPE-C) secreted by certain strains of beta-hemolytic Streptococci can cause clones of [T.sub.4] lymphocytes to activate several cytokinins, predominantly alpha and beta tumor necrosis factor, complement and the clotting cascade with the production of oxygen-free radicals and nitrous oxide, resulting in shock and multiple organ failure.[7]

Predisposing Factors

Necrotizing fasciitis usually occurs in immunocompromised patients, such as those with uncontrolled diabetes, alcoholism, malignancy, severe malnutrition or severe peripheral vascular disease. The portal of entry of the infection is usually through minor episodes of trauma, burrows, intravenous drug injections, surgical incisions, perirectal abscesses, diverticulitis, cutaneous infection, ulcers or animal or insect bites. Rarely, necrotizing fasciitis has been reported to occur spontaneously.(8,9)

Bacterial Etiology

Bacteriologically, necrotizing fasciitis is grouped into two entities.[10-12] In the type I form, at least one anaerobic species is present, most commonly Bacteroides, Peptococcus, Fusobacterium, Clostridium or Corynebacterium. These may be isolated in combination with one or more facultative aerobes such as streptococci (other than group A), Streptococcus viridans, Escherichia coli, or Enterobacter, Klebsiella or Proteus species.[2] The Type II form, hemolytic streptococcal gangrene, is caused by group A Streptococci, either alone or in combination with other species such as Staphylococcus aureus.

Clinical Course

Necrotizing fasciitis usually has an acute, rapidly progressive course but may be subacute in some cases. The disease may affect any part of the body, but it most commonly involves the extremities. There is a low incidence of fasciitis of the abdominal wall, of the perianal or groin area and of postoperative wounds.[13] When fasciitis is in its developed state, the affected area is initially erythematous, swollen, firm, hot, shiny with nondefinable margins, and extremely painful and tender.[9] Within several hours days, the skin color changes from reddish purple to patches of blue-gray, associate with formation of bullae that contain thick pink or purple fluid; subsequently, frank cutaneous gangrene occurs. However, in some patients (as in the second illustrative case) pain and tenderness may be the only sign and symptom early in the course. The pain invariably disappears after the skin becomes necrotic, and there may be watery, grayish, foul-smelling, fluid extravasation.

Subcutaneous crepitus can often be elicited in patients with the polymicrobial form of fasciitis, Predominantly those with diabetes mellitus. The patient usually is toxic with high fever. The temperature may range from 102 [degrees] to 105 [degrees] F (38.80 [degrees] to 40.5 [degrees] C), and fever may be associated with chills and constitutional symptoms. To differentiate necrotizing fasciitis from severe cellulitis, a hemostat may be introduced through a limited incision. An easy passage of the instrument along a plane just superficial to the fascia is indicative of necrotizing fasciitis.[11] However, surgical exploration is the definitive diagnostic procedure.

In severe cases, shock, hypotension, disseminated intravascular coagulation and multiple organ failure may develop, culminating in death.

Diagnosis

The diagnosis of necrotizing fasciitis is clinical.[14] A high index of suspicion is necessary to make an early diagnosis. Necrotizing fasciitis should be included in the differential diagnosis whenever a patient looks acutely ill, toxic and complains of disproportionate pain with minor skin changes, particularly in the early phase. Microscopy of the aspirate from the subcutaneous tissue may show the organisms, and imaging techniques may reveal spreading infection along the fascial plane. When in doubt, surgical exploration may be the best diagnostic tool. The classic finding of gray, edematous fat that strips off easily from the underlying fascia is indicative of necrotizing fasciitis. A pus sampling for urgent Gram’s stain and culture is helpful.

Laboratory evaluation usually reveals leukocytosis with a left shift. One-half to two-thirds of patients have evidence of normocytic, normochromic anemia with an elevated erythrocyte sedimentation rate. Hypocalcemia and acidosis tend to occur when necrosis is extensive, although acidosis may occur in the absence of extensive necrosis.[9] A Gram’s stain of the exudate usually reveals either a mixture of organisms or gram-positive cocci in chains. Culture of the exudate or blood is frequently positive. Radiographs of the soft tissue may reveal the presence of gas in the subcutaneous area.

Management

The cornerstone of management of necrotizing fasciitis is early diagnosis and aggressive treatment to reduce morbidity and mortality.[5] Specific measures include surgical debridement, antibiotic therapy and prompt resuscitation with intravenous fluids, with careful hemodynamic monitoring in an intensive care setting.

Radical debridement of an devitalized tissue should be immediately performed. Involved skin and fat should also be excised. Amputation is rarely needed unless the fascial barrier has been breached. The aim should be to perform definitive debridement, no matter how radical, at the first operation. Wound inspection under anesthesia is usually performed within 24 hour,s to ensure adequacy of debridement. Most debridement procedures will leave open wounds, which will require plastic reconstructive repair at a later date.15

Antibiotics alone will not cure necrotizing fasciitis.[16] The surgeons and the attending physicians should not be tempted to defer surgery or perform a less mutilating and less effective procedure. Broad-spectrum parenteral antibiotics should be given to target streptococcal species and anaerobic organisms. One option is triple antibiotic therapy that includes a penicillin, an aminoglycoside or third-generation cephalosporin, and either clindamycin or metronidazole. Accurate intraoperative culture should guide postoperative antibiotic coverage.

Other treatment modalities that have been considered include hyperbaric oxygen and intravenous immunoglobulin G. Hyperbaric oxygen is not readily available in most hospitals, and no hard data support its beneficial effect.[16,17] Intravenous immunoglobulin has been given in an attempt to reduce hyperproliferation of T cells and thereby inhibit production of tumor necrosis factor. However, no documented controlled studies have evaluated the efficacy of this mode of therapy

Nutritional support of these patients is equally important. Either oral or intravenous hyperalimentation may be needed initially. Caloric intake of twice the basic need is associated with a lower complication rate.[13]

Prognosis

Over the past decade, with aggressive therapy, the case fatality rate in patients with necrotizing fasciitis has fallen to a range of 29 to 33 percent, compared with previous studies conducted between 1924 and 1986 showing mortality rates as high as 73 percent.2,9,18 Arteriosclerosis (peripheral vascular disease) and the presence of diabetes may be associated with a mortality rate in excess of 80 percent. Obesity, older age (over 50 years), immunosuppression, intravenous drug use, chronic renal failure and malnutrition also contribute to a poor prognosis. The site of infection is a major contributing factor to mortality. Upper limb involvement with mild infections has a better outcome than involvement of the abdomen, groin or perineum.

The most important factor to consider in the prognosis is the interval from the onset of the disease to treatment and the aggressiveness of operative debridement. Patients in whom diagnosis and treatment were delayed had a mortality rate over 92 percent.[18] Similarly, when debridement was ineffectively performed and when more than one debridement was required, the mortality rate was 83 percent.[9,15,18] With aggressive surgical debridement, appropriate antibiotic therapy and intensive support care, the outcome of patients with necrotizing fasciitis can be favorable.

The Authors

KAVITHA S. KOTRAPPA, M.D. is serving a residency in family practice at Kern Medical Center, Bakersfield, affiliated with the University of California School of Medicine, Irvine. Dr. Kotrappa’s medical degree is from Kempegowda Institute of Medical Sciences, Bangalore, India.

RADHEY S. BANSAL, M.D. is an internist in private practice in Delano, Calif. Dr. Bansal served a residency in internal medicine at Albert Einstein College of Medicine-Lincoln Hospital, Bronx, N.Y., and received a medical degree from Government Medical College, Rohtak, India.

NAVIN M. AMIN, M.D. is chairman of the family practice residency program at Kern Medical Center, Bakersfield, Calif., and associate professor of internal medicine at the UCLA School of Medicine. He is a professor of family medicine at the University of California School of Medicine, Irvine. Dr. Amin received his medical degree from Grant Medical College, Bombay, India.

REFERENCES

[1.] Descamps V, Aitken J, Lee MG. Hippocrates on necrotising fasciitis [Letter]. Lancet 1994;344:556. [2.] Pessa ME, Howard RJ. Necrotizing fasciitis. Surg Gynecol Obstet 1985;161:357-61. [3.] Meleney FL. Hemolytic streptococcal gangrene. Arch Surg 1924;9:317-64. [4.] Janevicius RV, Hann SE, Batt MD. Necrotizing fasciitis. Surg Gynecol Obstet 1982;154:97-102. [5.] Barker FG, Leppard BJ, Seal DV Streptococcal necrotising fasciitis: comparison between histological and clinical features. J Clin Pathol 1987,40:335-41. [6.] Zumla A. Superantigens, T cells, and microbes. Clin Infect Dis 1992;15:313-20. [7.] Yong JM. Necrotising fasciitis [Letter]. Lancet 1994;343:1427. [8.] Stevens DL. Invasive group A streptococcus infections. Clin Infect Dis 1992;14:2-11. [9.] Sudarsky LA, Laschinger JC, Coppa GF, Spencer FC. Improved results from a standardized approach in treating patients with necrotizing fasciitis. Ann Surg 1987;206:661-5. [10.] Galbut DL, Gerber DL, Belgraier AH. Spontaneous necrotizing fasciitis. Occurrence secondary to occult diverticulitis. JAMA 1977;238:2302. [11.] Swartz MN. Necrotizing fasciitis in principle and practice of infectious disease. in: Mandell GL, Douglas RG Jr, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 3d ed. New York: Churchill Livingstone, 1990:810-2. [12.] Giuliano A, Lewis F Jr, Hadley K, Blaisdell FW. Bacteriology of necrotizing fasciitis. Am J Surg 1977;134:52-7. [13.] Majeski JA, Alexander JW Early diagnosis, nutritional support, and immediate extensive debridement improve survival in necrotizing fasciitis. Am J Surg 1983;145:784-7. [14.] Burge TS, Watson JD. Necrotising fasciitis [Editorial]. BMJ 1994;308:1453-4. [15.] Ward RG, Walsh MS. Necrotizing fasciitis: ten years’ experience in a district general hospital. Br J Surg 1991;78:488-9. [16.] Burge TS. Hyperbaric oxygen. Still unproved in necrotising fasciitis. BMJ 1993;307:936. [17.] Tehrani MA, Ledingham IM. Necrotizing fasciitis. Postgrad Med J 1977;53(619):237-42. [18.] Rouse TM, Malangoni MA, Schulte WJ. Necrotizing fasciitis: a preventable disaster. Surgery 1982,92:765-70.

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