Journal of Infection (I992) 25, 299-302
CASE R E P O R T S Streptococcal
necrotising
fasciitis
M. J. W e i n b r e n a n d R. M. P e r i n p a n a y a g a m
Department of Microbiology, Queen Mary's University Hospital, Roehampton Lane, London SWI 5 5PN, U.K. Accepted for publication I7 February I992 Summary Three cases of streptococcal necrotising fasciitis are described. Its relative rarity and the lack of superficial inflammation leading to diagnostic difficulty is emphasised. The diagnosis is readily confirmed microbiologically but the clinician should bear in mind that antibiotics may not be curative and that surgery is often required.
Introduction
Streptococcus pyogenes causes several distinct infective syndromes of the skin and subcutaneous tissues. From the skin internally these are impetigo, erysipelas, cellulitis and necrotising fasciitis. In most of these conditions a clinical diagnosis is readily made, often in the absence of positive bacteriology, and the patient responds to antibiotics. Necrotising fasciitis, however, is different; the clinical diagnosis is often missed despite positive bacteriology and there is an incomplete response to antibiotics. T h e importance of recognising this condition is that unlike the other streptococcal infections surgical intervention is required as antibiotic therapy alone is inadequate and may not prevent a fatal outcome. Although attention was focused on this condition in I98O and ~98I, 1-8 and several other excellent papers 4'5 have subsequently been published, the diagnosis is still missed. We describe three cases and discuss how clinical management may be improved.
Case reports Case I A previously fit 56-year-old man was admitted to hospital following the acute onset of pain in his right calf. He had been unwell for 4 days with a sore throat, fever and generalised aches. On examination he was pyrexial and the calf notably tender but not erythematous. A clinical diagnosis of deep vein thrombosis was made and the patient anticoagulated. By the next day, he was in a shocked state. T h e differential diagnosis was of massive pulmonary embolus or chest infection. Accordingly streptokinase and antibiotics were started which resulted in some clinical improvement. Blood cultures taken on admission were now positive and streptococci, later identified as S. pyogenes, were seen on Gram-staining. High-dose benzyl penicillin was o163-4453/92/o6o299+o4 $08.00/0
© I992 The British Society for the Study of Infection
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started. By this time a large number of haemorrhagic bullae had appeared on the calf but fluid from them showed no red or white cells on microscopy and yielded no growth on culture. Despite appropriate antibiotic therapy the patient's condition deteriorated and his death 2 weeks later was attributed to continuing sepsis. Case z
A 77-year-old woman was admitted after having been found collapsed at home. History from a relative revealed that 5 days previously she had had a sore throat. On examination she was pyrexial, appeared 'toxic', and was thought to have a bruise on her leg. Treatment with broad spectrum antibiotics was started after cultures had been taken. T h e following day streptococci were seen in blood cultures, later identified as S. pyogenes. T h e patient was reviewed by the microbiologists who noted that the bruise was in reality a partly ruptured bulla, still containing haemorrhagic fluid. T h e underlying skin had a dusky purple appearance. Laboratory analysis of aspirated fluid showed no RBC and WBC, but a high titre ( > I:5o) of Lancefield group A antigen.* A diagnosis of necrotising fasciitis was made and therapy changed to high-dose penicillin with clindamycin, and surgery advised. However, the latter had to be deferred because of acute hypotension, D I C and renal failure. Although her general condition markedly improved during the next 5 days, the area of fasciitis continued to spread. Surgical d6bridement together with skin grafting was then performed. T h e day following surgery saw a further significant improvement in her condition such that she remarked that she felt well for the first time since her illness had started. Case 3
A 45-year-old man sustained a fracture of the tibia and fibula which was corrected by insertion o f ' K ' wires and covered with a plaster cast. Four days later, because of the onset of fever and pain in the leg, the cast was removed. On examination a cellulitis extended from toe to knee and there were what appeared to be 'fracture blisters'. Fluid was aspirated from the blisters and erythromycin, later changed to cefotaxime, was started. Examination of the fluid deposit showed numerous Gram-positive cocci in chains, but no white blood cells. A test for Lancefield group A antigen was positive, and a heavy pure growth of S. pyogenes obtained on culture. T h e clinical team felt this was a cellulitis with secondary infection of 'fracture blisters'. Following poor response to antibiotics a microbiological opinion was sought. T h e appearance was felt to be typical of necrotising fasciitis and urgent surgery advised. Specimens taken at operation grew S. pyogenes despite 4 days antibiotic treatment. T h e patient made an uneventful recovery. * G r o u p A antigen was detected using Oxoid streptococcal antigen kit. Bulla fluid was mixed in equal volumes with latex antisera and observed for agglutination as described in the kit. I n case 2, antigen was detected without the need for extraction. I n case 3, antigen was only detected after enzyme extraction of spun deposit.
Streptococcal necrotising f asciitis
3oi
Discussion
Although originally described by Meleney° more than 60 years ago, and despite subsequent reports highlighting streptococcal necrotising fasciitis, the diagnosis is still missed, 5 as in our first case. Necrotising fasciitis occurs in two forms, 7 although this classification has recently been questioned. 8 T y p e I is due to a mixture of anaerobes and facultative anaerobes and occurs most frequently on the trunk in association with abdominal pathology/surgery. T y p e 2, also termed streptococcal gangrene, occurs predominantly on the extremities following trauma or minor injury, and is usually due to S. pyogenes. T h e streptococcal variety typically follows a fulminating course although a more chronic variant has been described. 4 T h e patient is often toxic on admission, but the appearance of the local lesion varies according to the stage of the illness. It begins as an area of erythema and oedema which spreads rapidly. During the next I-3 days dusky purple areas appear in the skin usually accompanied by bullae containing red/black fluid. By days 5-7 the lesion has developed into a sharply demarcated area of necrotic eschar surrounded by a border of erythema. Diagnosis is essentially clinical, the hallmark being the dusky purple areas of necrosis 9 which herald impending gangrene. T h e pathological basis for this is that as infection spreads along fascial planes it causes thrombosis of perforating vessels from which the skin normally derives an endarterial blood supply. T h e microbial aetiology is readily ascertained provided that appropriate specimens (blood, bulla fluid, tissue biopsy) are taken prior to therapy. Once antibiotics have been started cultures are often negative, but if bulla fluid is available it may be positive for Lancefield group A antigen a constituent of the cell wall of S. pyogenes (see cases 2 and 3). Growth from swabs taken from the surface of the lesion tends to be misleading, revealing only a variety of contaminating organisms. In all three specimens of bulla fluid we examined, there was a conspicuous absence of white blood cells. Organisms are thought to reach the fascia by direct implantation through local trauma, signs of which may or may not be apparent. However, in cases I and 2 the preceding history of sore throat with systemic symptoms suggests the possibility of bacteraemic seeding. Closed trauma to which the limbs are subject could provide a nidus for circulating organisms to settle and initiate infection. Failure to diagnose the condition is common and occurs in two ways. I f local symptoms predominate, non-infective conditions, including haematoma, 5 burn, I° thrombophlebitis (case I), may be diagnosed and antibiotics not prescribed. Alternatively when systemic toxicity is obvious, the infective nature is apparent, but the local lesion is either not recognised (case 2), or diagnosed as another infection (case 3)- Incorrect diagnosis is attributable to the rarity of this infection and concomitant lack of experience. In addition local signs of inflammation are less marked than in cellulitis, which accounts for some mistaken diagnoses of non-infective conditions, and is presumably due to infection being initiated at a deeper level together with vessel
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thrombosis preventing migration of inflammatory cells to the surface. T h e absence of W B C s in all specimens of bulla fluid examined is in keeping with a lack of superficial inflammatory response, b u t could also reflect destruction b y streptococcal toxins. Effective therapy requires a combination o f high-dose antibiotic with early surgical d 6 b r i d e m e n t of infected necrotic tissue. Antibiotics alone are not curative and this is explained b y the histological picture of vessel thrombosis which prevents delivery of drugs to the site of infection. T h e y m a y p r o d u c e an initial response b u t this should not preclude surgical intervention. In case i the patient died o f continuing sepsis possibly due to lack o f surgical removal of the septic focus. Similarly in case 2 antibiotics p r o d u c e d a dramatic initial response b u t the fasciitis continued to spread. In s u m m a r y , diagnosis of this condition is clinical and can be considered in two stages. At the bedside the presence of dusky purple areas should alert one to suspect fasciitis rather than other skin infections. It should also be considered as a differential diagnosis of non-infective conditions such as t h r o m b o p h l e b i t i s and appropriate cultures taken, especially w h e n there is a history of preceding sore throat. In the laboratory the microbiologist m u s t also be aware of this condition and alert the clinician to the possibility and the need for surgical intervention whenever S. pyogenes is g r o w n from b l o o d culture or bulla fluid. H e / s h e is often in the best position to make the diagnosis having access to cultures from a variety of clinical specialities. (We thank Dr D. Seal for his helpful criticism of the text.)
References I. Redding PJ. Streptococcus pyogenes infection (Letter). Br Med ff I98O; 281: 1639-I64O. 2. Hawkey PM, Pedler SJ, Southall PJ. Streptococcus pyogenes: a forgotten occupational hazard in the mortuary. Br M e d J I98O; 28I: IO58. 3. Cruickshank JG, Hart RJC, George M, Feest TG. Fatal streptococcal septicaemia. Br Med J I98I; 282:I944-I945. 4. Leppard BJ, Seal DV. The value of bacteriology and serology in the diagnosis of necrotising fasciitis. Br J Dermatol I983; IO9: 37-44. 5. Aitken DR, Mackett MCT, Smith LL. The changing pattern of haemolytic streptococcal gangrene. Arch Surg r982; II7: 561-567. 6. Meleney FL. Haemolytic streptococcus gangrene. Arch Surg I924; 9: 317-364. 7. Swartz MN. Skin and soft tissue infections. In: Mandell GL, Douglas RG, Bennett JE, Eds. Principles and practice of infectious diseases, 2nd ed. New York: John Wiley & Sons, r985 : 598-624. 8. Kingston D, Seal DV. Current hypotheses on synergistic microbial gangrene. Br J Surg 199o; 77: 26o-264. 9. Seal DV, Leppard B. Necrotising fasciitis--a disease of temperate and warm climates. Trans R Soc Trop Med Hyg I982; 76: 392-395. Io. Paine TF, Novick R, Hall WH. Fatal gangrene caused by Streptococcus pyogenes. Arch Intern Med 1963; 112: 936-939.
CASE R E P O R T S Streptococcal
necrotising
fasciitis
M. J. W e i n b r e n a n d R. M. P e r i n p a n a y a g a m
Department of Microbiology, Queen Mary's University Hospital, Roehampton Lane, London SWI 5 5PN, U.K. Accepted for publication I7 February I992 Summary Three cases of streptococcal necrotising fasciitis are described. Its relative rarity and the lack of superficial inflammation leading to diagnostic difficulty is emphasised. The diagnosis is readily confirmed microbiologically but the clinician should bear in mind that antibiotics may not be curative and that surgery is often required.
Introduction
Streptococcus pyogenes causes several distinct infective syndromes of the skin and subcutaneous tissues. From the skin internally these are impetigo, erysipelas, cellulitis and necrotising fasciitis. In most of these conditions a clinical diagnosis is readily made, often in the absence of positive bacteriology, and the patient responds to antibiotics. Necrotising fasciitis, however, is different; the clinical diagnosis is often missed despite positive bacteriology and there is an incomplete response to antibiotics. T h e importance of recognising this condition is that unlike the other streptococcal infections surgical intervention is required as antibiotic therapy alone is inadequate and may not prevent a fatal outcome. Although attention was focused on this condition in I98O and ~98I, 1-8 and several other excellent papers 4'5 have subsequently been published, the diagnosis is still missed. We describe three cases and discuss how clinical management may be improved.
Case reports Case I A previously fit 56-year-old man was admitted to hospital following the acute onset of pain in his right calf. He had been unwell for 4 days with a sore throat, fever and generalised aches. On examination he was pyrexial and the calf notably tender but not erythematous. A clinical diagnosis of deep vein thrombosis was made and the patient anticoagulated. By the next day, he was in a shocked state. T h e differential diagnosis was of massive pulmonary embolus or chest infection. Accordingly streptokinase and antibiotics were started which resulted in some clinical improvement. Blood cultures taken on admission were now positive and streptococci, later identified as S. pyogenes, were seen on Gram-staining. High-dose benzyl penicillin was o163-4453/92/o6o299+o4 $08.00/0
© I992 The British Society for the Study of Infection
300
M . J. W E I N B R E N AND R. M . P E R I N P A N A Y A G A M
started. By this time a large number of haemorrhagic bullae had appeared on the calf but fluid from them showed no red or white cells on microscopy and yielded no growth on culture. Despite appropriate antibiotic therapy the patient's condition deteriorated and his death 2 weeks later was attributed to continuing sepsis. Case z
A 77-year-old woman was admitted after having been found collapsed at home. History from a relative revealed that 5 days previously she had had a sore throat. On examination she was pyrexial, appeared 'toxic', and was thought to have a bruise on her leg. Treatment with broad spectrum antibiotics was started after cultures had been taken. T h e following day streptococci were seen in blood cultures, later identified as S. pyogenes. T h e patient was reviewed by the microbiologists who noted that the bruise was in reality a partly ruptured bulla, still containing haemorrhagic fluid. T h e underlying skin had a dusky purple appearance. Laboratory analysis of aspirated fluid showed no RBC and WBC, but a high titre ( > I:5o) of Lancefield group A antigen.* A diagnosis of necrotising fasciitis was made and therapy changed to high-dose penicillin with clindamycin, and surgery advised. However, the latter had to be deferred because of acute hypotension, D I C and renal failure. Although her general condition markedly improved during the next 5 days, the area of fasciitis continued to spread. Surgical d6bridement together with skin grafting was then performed. T h e day following surgery saw a further significant improvement in her condition such that she remarked that she felt well for the first time since her illness had started. Case 3
A 45-year-old man sustained a fracture of the tibia and fibula which was corrected by insertion o f ' K ' wires and covered with a plaster cast. Four days later, because of the onset of fever and pain in the leg, the cast was removed. On examination a cellulitis extended from toe to knee and there were what appeared to be 'fracture blisters'. Fluid was aspirated from the blisters and erythromycin, later changed to cefotaxime, was started. Examination of the fluid deposit showed numerous Gram-positive cocci in chains, but no white blood cells. A test for Lancefield group A antigen was positive, and a heavy pure growth of S. pyogenes obtained on culture. T h e clinical team felt this was a cellulitis with secondary infection of 'fracture blisters'. Following poor response to antibiotics a microbiological opinion was sought. T h e appearance was felt to be typical of necrotising fasciitis and urgent surgery advised. Specimens taken at operation grew S. pyogenes despite 4 days antibiotic treatment. T h e patient made an uneventful recovery. * G r o u p A antigen was detected using Oxoid streptococcal antigen kit. Bulla fluid was mixed in equal volumes with latex antisera and observed for agglutination as described in the kit. I n case 2, antigen was detected without the need for extraction. I n case 3, antigen was only detected after enzyme extraction of spun deposit.
Streptococcal necrotising f asciitis
3oi
Discussion
Although originally described by Meleney° more than 60 years ago, and despite subsequent reports highlighting streptococcal necrotising fasciitis, the diagnosis is still missed, 5 as in our first case. Necrotising fasciitis occurs in two forms, 7 although this classification has recently been questioned. 8 T y p e I is due to a mixture of anaerobes and facultative anaerobes and occurs most frequently on the trunk in association with abdominal pathology/surgery. T y p e 2, also termed streptococcal gangrene, occurs predominantly on the extremities following trauma or minor injury, and is usually due to S. pyogenes. T h e streptococcal variety typically follows a fulminating course although a more chronic variant has been described. 4 T h e patient is often toxic on admission, but the appearance of the local lesion varies according to the stage of the illness. It begins as an area of erythema and oedema which spreads rapidly. During the next I-3 days dusky purple areas appear in the skin usually accompanied by bullae containing red/black fluid. By days 5-7 the lesion has developed into a sharply demarcated area of necrotic eschar surrounded by a border of erythema. Diagnosis is essentially clinical, the hallmark being the dusky purple areas of necrosis 9 which herald impending gangrene. T h e pathological basis for this is that as infection spreads along fascial planes it causes thrombosis of perforating vessels from which the skin normally derives an endarterial blood supply. T h e microbial aetiology is readily ascertained provided that appropriate specimens (blood, bulla fluid, tissue biopsy) are taken prior to therapy. Once antibiotics have been started cultures are often negative, but if bulla fluid is available it may be positive for Lancefield group A antigen a constituent of the cell wall of S. pyogenes (see cases 2 and 3). Growth from swabs taken from the surface of the lesion tends to be misleading, revealing only a variety of contaminating organisms. In all three specimens of bulla fluid we examined, there was a conspicuous absence of white blood cells. Organisms are thought to reach the fascia by direct implantation through local trauma, signs of which may or may not be apparent. However, in cases I and 2 the preceding history of sore throat with systemic symptoms suggests the possibility of bacteraemic seeding. Closed trauma to which the limbs are subject could provide a nidus for circulating organisms to settle and initiate infection. Failure to diagnose the condition is common and occurs in two ways. I f local symptoms predominate, non-infective conditions, including haematoma, 5 burn, I° thrombophlebitis (case I), may be diagnosed and antibiotics not prescribed. Alternatively when systemic toxicity is obvious, the infective nature is apparent, but the local lesion is either not recognised (case 2), or diagnosed as another infection (case 3)- Incorrect diagnosis is attributable to the rarity of this infection and concomitant lack of experience. In addition local signs of inflammation are less marked than in cellulitis, which accounts for some mistaken diagnoses of non-infective conditions, and is presumably due to infection being initiated at a deeper level together with vessel
302
M. J. WEINBREN AND R. M. PERINPANAYAGAM
thrombosis preventing migration of inflammatory cells to the surface. T h e absence of W B C s in all specimens of bulla fluid examined is in keeping with a lack of superficial inflammatory response, b u t could also reflect destruction b y streptococcal toxins. Effective therapy requires a combination o f high-dose antibiotic with early surgical d 6 b r i d e m e n t of infected necrotic tissue. Antibiotics alone are not curative and this is explained b y the histological picture of vessel thrombosis which prevents delivery of drugs to the site of infection. T h e y m a y p r o d u c e an initial response b u t this should not preclude surgical intervention. In case i the patient died o f continuing sepsis possibly due to lack o f surgical removal of the septic focus. Similarly in case 2 antibiotics p r o d u c e d a dramatic initial response b u t the fasciitis continued to spread. In s u m m a r y , diagnosis of this condition is clinical and can be considered in two stages. At the bedside the presence of dusky purple areas should alert one to suspect fasciitis rather than other skin infections. It should also be considered as a differential diagnosis of non-infective conditions such as t h r o m b o p h l e b i t i s and appropriate cultures taken, especially w h e n there is a history of preceding sore throat. In the laboratory the microbiologist m u s t also be aware of this condition and alert the clinician to the possibility and the need for surgical intervention whenever S. pyogenes is g r o w n from b l o o d culture or bulla fluid. H e / s h e is often in the best position to make the diagnosis having access to cultures from a variety of clinical specialities. (We thank Dr D. Seal for his helpful criticism of the text.)
References I. Redding PJ. Streptococcus pyogenes infection (Letter). Br Med ff I98O; 281: 1639-I64O. 2. Hawkey PM, Pedler SJ, Southall PJ. Streptococcus pyogenes: a forgotten occupational hazard in the mortuary. Br M e d J I98O; 28I: IO58. 3. Cruickshank JG, Hart RJC, George M, Feest TG. Fatal streptococcal septicaemia. Br Med J I98I; 282:I944-I945. 4. Leppard BJ, Seal DV. The value of bacteriology and serology in the diagnosis of necrotising fasciitis. Br J Dermatol I983; IO9: 37-44. 5. Aitken DR, Mackett MCT, Smith LL. The changing pattern of haemolytic streptococcal gangrene. Arch Surg r982; II7: 561-567. 6. Meleney FL. Haemolytic streptococcus gangrene. Arch Surg I924; 9: 317-364. 7. Swartz MN. Skin and soft tissue infections. In: Mandell GL, Douglas RG, Bennett JE, Eds. Principles and practice of infectious diseases, 2nd ed. New York: John Wiley & Sons, r985 : 598-624. 8. Kingston D, Seal DV. Current hypotheses on synergistic microbial gangrene. Br J Surg 199o; 77: 26o-264. 9. Seal DV, Leppard B. Necrotising fasciitis--a disease of temperate and warm climates. Trans R Soc Trop Med Hyg I982; 76: 392-395. Io. Paine TF, Novick R, Hall WH. Fatal gangrene caused by Streptococcus pyogenes. Arch Intern Med 1963; 112: 936-939.
