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Surgical interventions in children with meningococcal purpura fulminans—a review of 117 procedures in 21 children
Surgical Interventions in Children With Meningococcal Purpura Fulminans—A Review of 117 Procedures in 21 Children By Jonathan Simon Wheeler, Brian Joseph Anderson, and Tristain M.B. De Chalain Auckland, New Zealand
Background/Purpose: There are few reports describing the surgical management and outcome of children suffering purpura fulminans secondary to meningococcal sepsis. New Zealand is in the grips of a meningococcal epidemic, and, with the attendant sequalae of the disease process, the authors sought to formally review the children who have required surgical involvement. Methods: A retrospective case review of children with the sequalae of meningococcal disease presenting to the Orthopedic and Plastic Surgical Units in a university teaching hospital was undertaken. Results: There were 117 procedures in 21 children performed over a 12-year period. Surgical management was separated into 2 phases— early and late. The mean delay from admission with acute sepsis to the first surgical procedure (ie, early intervention) was 15.9 days. Debridement and autologous skin grafting was the mainstay of managing the necrotic defects; however, allograft skin proved a useful adjunct as a
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EW ZEALAND is in the middle of a meningococcal disease epidemic with a national rate of 15.5 per 100,000.1 Rates are higher in lower socioeconomic areas such as South Auckland (34.5 per 100,000 in 1996).2 Maori and Pacific Island children for the under one-year age group have the highest incidence (283 and 980 per 100,000, respectively). Neisseria meningitidis Serogroup B is the most common, accounting for 57% of isolated organism.3 Fulminant meningococcemia accounts for between 6% and 24% of all cases of meningococcal disease.4-7 The mortality rate of meningococcal disease is reported between 3% and 12%,4-7 and a mortality rate of 6.6% was reported for the period July 1992 to June 1994 in Auckland.3 However the presence of purpura fulminans (PF) increases the mortality rate to between 28% and 60%.4-9 Fulminant meningococcemia is characterized by purpura fulminans (PF) and patchy or confluent skin necrosis, most commonly of the extremities, that may progress to gangrene. In severe disease, the accompanying hypotension, disseminated intravascular coagulopathy (DIC), and multisystem organ failure (MSOF) contribute significantly to mortality. Initial management of suspected meningococcal disease involves the support of the cardiovascular system, antibiotics, and diagnostic procedures including blood cultures for microbiology. Cerebrospinal fluid sampling is a late procedure done once Journal of Pediatric Surgery, Vol 38, No 4 (April), 2003: pp 597-603
physiologic dressing. Local flaps were used with deep defects down to bone, but in the extremities amputation to viable tissue was required once gangrene was demarcated. Amputations were carried out in 9 of 21 children. Late interventions were related to relief of contractures or fibula overgrowth causing stump ulceration. Clinical follow-up showed that all children interviewed over 5 years of age (9 children) attend ordinary regular school classes and were physically active within the context of their physical disabilities. Conclusions: The data would suggest that children requiring surgery for purpura fulminans achieve age-appropriate milestones and are primarily limited by their physical disability related to amputations, scarring, and abnormal bone growth. J Pediatr Surg 38:597-603. Copyright 2003, Elsevier Science (USA). All rights reserved. INDEX WORDS: meningococcemia, purpura fulminans, complications, surgical management.
the coagulopathy has resolved and central nervous system (CNS) function improved. Children with severe meningococcal septicemia may require artificial ventilatory support, volume resuscitation, inotropes, and extracorporeal support such as dialysis or ultrafiltration. The cutaneous manifestations of the disease are managed secondarily. In this report we review the surgical management of these cutaneous manifestations in children admitted to a tertiary pediatric referral unit over a 12year period. MATERIALS AND METHODS From August 1994 to July 2000, case records of the Plastic Surgical and Orthopaedic Services at Middlemore Hospital, a University teaching hospital in South Auckland, were searched. A total of 20 cases in this period and a further case dating back to 1987 gave a total of 21 cases who were identified as having required surgical intervention as a result of the complications of meningococcal purpura fulminans.
From the Centre for Reconstructive and Plastic Surgery at Middlemore Hospital and the Department of Anaesthesia at Auckland Children’s Hospital, Auckland, NZ. Address reprint requests to Dr Jonathan Wheeler, C/-Centre for Reconstructive and Plastic Surgery, Middlemore Hospital, Otahuhu, Auckland, New Zealand. Copyright 2003, Elsevier Science (USA). All rights reserved. 0022-3468/03/3804-0016$30.00/0 doi:10.1053/jpsu.2003.50130 597
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A chart review of each case was undertaken. Where possible, a personal interview by the investigators was conducted with the parents and child concerned. Parents were asked whether age-appropriate milestones had been reached, as defined by the Denver II developmental screen for the under 5-year-old age group, and those older than 5 years were assessed on schooling, academic, and sporting achievements. Physical disabilities and psychosocial difficulties were inquired about. When a personal interview was not possible, a telephone interview was conducted with a parent or caregiver, and the same questions were asked. If personal follow-up was not possible, data were used from the most recent clinic visit notes. Surgical procedures were divided into early and late procedures. Early procedures were those performed during the initial admission to the hospital with acute meningococcemia. Late procedures were defined as those surgical procedures performed after formal discharge from the original admission with meningococcal sepsis. Occasionally, children were sent home with a view to returning to hospital within 2 weeks for a planned, semielective surgical procedure such as debridement, in which case this procedure would be considered part of the original admission.
RESULTS
Twenty-one cases of clinical paediatric meningococcal purpura fulminans were reviewed. Serological evidence of Neisseria meningitidis infection was confirmed in 16 patients, 11 serotype B, one serotype A, and 4 untyped. The remaining 5 children in this series had a clinical diagnosis of meningococcal PF made on the findings at presentation and in the absence of another identifiable causative micro-organism in the context of the current epidemic.2,3 Fifteen of the 21 cases were of Maori (7 children) or Pacific Island descent with over half of the children living in South Auckland. There were 13 boys and 8 girls with an average age of 3.8 years. It is believed that a lipopolysaccharide endotoxin released from the cell wall of N meningitidis is responsible for the clinical manifestations of meningococcal purpura fulminans (PF).7,10-12 Microthrombi occlude dermal venules and capillaries with increased vascular permeability resulting in the rupture of capillaries, and associated vasculitis results in palpable purpura characteristic of meningococcal PF.13 The predominant organism yielded was N meningitidis Type B, which is consistent with the current epidemic3 and experience in other developed countries.14 All required admission to the Pediatric Intensive Care Unit (PICU) at a pediatric tertiary referral hospital. Three of 21 (14%) had seizures, 10 required treatment for pulmonary edema, 6 had acute cardiac impairment, and 4 had documented renal impairment. Patient 8 suffered a ventricular thrombus that resolved successfully with intravenous heparin and subsequent oral coumarin. The mean initial fluid resuscitation volume was 70 mL/kg. Table 1 outlines the initial surgical procedures. All children required debridement and skin grafting. The lower limbs were more commonly grafted (20 of 21) than the upper limbs (10 of 21). Three children required
allograft cadaver skin to cover open lesions that could not be successfully grafted early. These were patients 11, 15, and 17, and the commentary from the clinical notes on all 3 cases suggest that the allograft was successful at maintaining a clean graft bed and do not reflect any adverse effects from use of the graft. Amputations were carried out on 9 of 21 (43%). Most commonly, lower limb amputations were required (8 of 9), and these frequently were bilateral (patients 7, 8, 11, 16, 17, 18, 20) (Fig 1A). Patients 8 and 16 initially underwent amputations of their distal lower limbs to the metatarsophalangeal joint (MTPJ) level but required more proximal amputations when it became evident that the tissue was necrotic at that level. Local flaps were required in 7 children with a total of 11 flaps to cover exposed defects as listed in Table 1. Patient 7 required a delayed flap to the right heel because the flap appeared pale when initially raised. It was returned to its bed and 14 days later was successfully rotated to cover a defect over bone. Nine patients required subsequent operations defined as late procedures (Table 2). Six of these 9 had problems with contractures that required surgical intervention involving release of the contracture, often with a Z-plasty as in patients 10, 11, 16, and 17 and subsequent coverage either with a STSG (patients 10, 11, 19) or a fullthickness skin graft (patients 10, 16, 17) (Fig 1B). Clinical follow-up was attempted on all surgical patients. The same interviewer conducted interviews with 11 of the 21 patients. Two children had recent outpatient pediatric reviews (case 17 and 18). All children over 5 years of age who were interviewed (cases 2, 6, 8, 10, 11, 13, 17, 19, 21) attend ordinary regular school classes and were physically active within the context of their physical disabilities. Apart from cases 3 and 7 with no documented audiology testing, all children had hearing within normal limits. DISCUSSION
This review documents surgical procedures in children suffering meningococcal purpura fulminans (PF) and was separated into 2 phases— early and late. The mean delay from admission with acute sepsis to the first early surgical procedure was 15.9 days. This delay allows necrotic tissue to clearly demarcate before debridement and compares with typical delays of 2 to 3 weeks in other centers.15,16 Debridement and split thickness skin grafting (STSG) are the mainstays of managing the cutaneous necrotic lesions resulting from purpura fulminans. Of those children who did not require amputations, the lower limbs were the most commonly grafted site. Interestingly, the anterior abdominal wall and anterior chest wall were uncommonly involved, and no operation note reviewed
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Table 1. Initial Surgery, Early Procedures No.
Age
Ethnic Group
1
16 mo
2
11 yr
NZ Euro
3 4 5
8 yr 13 mo 6 mo
NZ Euro Maori Maori
6
6 yr
Asian
7
2 yr
PI
Areas of both lower limbs
Bilateral toes to MTPJ level; left fingers to DIPJd
8 9 10
20 mo 3 yr 4 yr
Maori PI NZ Euro
Base of amputations Right thigh ⫹ lower leg Areas left leg
Bilateral Syme forefoot.
11
5 yr
Maori
Both lower legs ⫹ right hand; Allograft used extensively initially
Left hand: all fingers to DIPJ
PI†
Debridement and STSG
Amputations
Lower limbs ⫹ buttocks (1 procedure) Left leg ⫹ several forearm lesions bilaterally Buttocks Patches arms and legs Right leg (needed repeating) Patches lower limbs and elbows
Flaps
Fasciocutaneous flap over right patella for exposed extensor mechanism Right patella rotational advancement flap Left heel adv. flap over os calcus Right heel delayed adv. flap
Local flap over dorsum left foot
Right hand: all fingers to MCPJe Bilateral foot to MTPJ
12
5 yr
Maori
Patches both lower limbs and left upper arm Areas both lower legs
13
3 yr
NZ Euro
14
7 mo
Maori
Buttocks, calves ⫹ thighs; Needed 2 repeat procedures to buttocks because contamination of feces
15
8 mo
Maori
16
2 yr
Allograft and autograft used to regions both arms and legs Split skin graft to right patella, failed; repeated patches both lower legs
Right third and fourth fingers to MCPJ; Left fifth toe to MTPJ Bilateral below knee amputation
Local flap over left heel
Right third, fourth, fifth finger tips
17
2 yr
PI
PI
Allograft used to areas bilateral lower limbs; autografts to both legs ⫹ right arm
Bilateral Syme fore foot; right patella ⫹ partial extensor mechanism (See Fig 1.)
Left dorsally based flap over left mid-foot amputation, initially viable but failed
Right patella ⫹ partial extensor mechanism Decortification right malleoli
Left patella decortification Right patella excision 18 19
6 yr 4 yr
20
6 mo
Maori PI
Lower limbs ⫹ buttocks Both legs
PI
Patches on all 4 limbs
Left first, second, third fingers to MCPJ and fourth finger to proximal interphalangeal joint Left hand third, fourth, fifth to MCPJ
Gastrocnemius flaps bilaterally; right knee flap partially necrosed requiring superiorly based flap
Right hand: first, second, third, fourth to MCPJ Right foot: second, fourth, fifth toes Bilateral patella decortification 21
14 yr
NZ Euro
Buttocks, knees ⫹ left forearm, arm and posterior left elbow
Superiorly based rotational flap over left buttock
Abbreviations: PI, Pacific Island; MTPJ, metatarsophalangeal joint; DIPJ, distal interphalangeal joint; MCPJ, metacarpophalangeal joint.
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Table 2. Late Procedures—After Discharge From Initial Admission No.
1 8
10 11
Indication for Late Procedure
Scar contracture right great toe deviated 60 medially Fibula overgrowth left leg causing ulceration ⫹ ill-fitting prosthesis Recurrence of fibula overgrowth Scar contracture left great toe Contracture again left great toe Breakdown wound right lateral foot Multiple limb contractures
Relapse contractures both wrists 14
16
Bilateral knee flexion contractures ⫹ bilateral fibula overgrowth Ongoing problems with fibula overgrowth, unable to use prostheses ⫹ wound breakdown over stumps
17
Scar contracture left popliteal fossa Raw area right popliteal fossa Multiple contractures
19
Nonhealing multiple lesions
20
Left lower lid defect Bilateral genu valgum from growth arrest proximal tibia right leg Continued problems with marked genu valgum
Procedure
Release scar contracture planned Fibula trimmed 18 mm Awaiting operation Z-plasty ⫹ STSG left first toe Release contracture with full-thickness skin graft STSG Right wrist: Z-plasty ⫹ STSG Right lower leg tibialis anterior tendon divided ⫹ transposition graft ⫹ left lower leg tibialis anterior divided ⫹ extensor mechanism released Left wrist release contracture ⫹ release contracture left elbow Left wrist parascapular free flap ⫹ right wrist release extensor contracture Bilateral release contractures knees with STSG ⫹ trimming bilateral fibulae MRI angiogram-normal vessels to stumps (considered latissimus dorsi flaps) proceeded to bilateral fibula osteotomies directed into the lower part of the remaining tibiae ⫹ release popliteal contractures ⫹ STSG Z-plasty release Full-thickness skin graft right popliteal fossa Full-thickness skin graft to both popliteal fossae, dorsum right foot ⫹ posterior aspect left leg ⫹ Z-plasty right anterior elbow ⫹ dorsum right wrist STSG to patches both legs Policization left index finger to left thumb V-Y advancement left lower lid Osteotomy right proximal tibia and application Ilizarov frame Shifted overseas before further corrective surgery
Abbreviations: STSG, split-thickness skin graft; MRI, magnetic resonance imaging.
from the 117 operation notes detailed STSG to these areas. Furthermore, only cases 16 and 20 had documented facial lesions, and only case 20 required early intervention, a secondary closure of a lower eye lid lesion. A particular problem was of fecal contamination of grafted sites around the buttocks in case 14, with 3 separate procedures involving debridement and split skin grafting as well as meticulous nursing and dressing changes to finally obtain a good “take”, avoiding the need for a diverting colostomy. Three children required allograft skin to maintain a healthy, graft-able bed until definitive autologous graft could be harvested. Other reports have also satisfactorily used allograft,17,18 artificial skin,16 and porcine xenograft.6 A total of 8 fasciocutaneous flaps were used in 6 patients and 3 musculocutaneous flaps in 2 patients. In case 16, the flap necrosed on the dorsum of a foot, and, ultimately, a Syme amputation was performed. Patient 20 had a partially necrosed gastocnemius flap that necessitated a superiorly based fasciocutaneous flap as coverage for the defect. The literature is cautious about the use of local flaps in meningococcal purpura fulminans (PF),19,20 suggesting that it is difficult to clinically assess the extent of microvascular damage adjacent to necrotic lesions, hence, compromising the viability of a
local flap. Our experience has been encouraging and would suggest that local fasciocutaneous and myocutaneous flaps are useful in providing coverage for skin defects as a result of meningococcal PF, and that a distinction between clinically viable and nonviable tissue can be confidently made at the time of surgery. None of the patients in the current series had compartment pressures measured nor had fasciotomies performed. Early monitoring of compartmental pressures and subsequent fasciotomy in children with PF have been proposed to reduce the number of amputations required.12,15,19,21 In a large series of 12 children who required amputations for PF, 3 of these children had fasciotomies but still required amputation.15 An approach adopted by many centers is to monitor compartment pressures and perform fasciotomies as indicated.4,15,22 In the absence of compartment syndrome or wound infection, the gangrenous limb should be allowed to demarcate before debridement15,16,21,23,24 to prevent the possibility of an unnecessarily high amputation. The mean delay to initial amputation in our series was 21 days. The symmetrical nature of amputations required for PF of the lower limbs is reflected in other series24,25 as well as the need for early revision amputations if viable tissue had not been reached.15,24,25 Two of 9
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children in this series required revised amputations with up to half of initial amputations being revised to a higher level in other centers.16,26 Upper limb amputations in our series tended to be at a more distal level comparatively than the lower limb and did not exhibit a similar symmetry. None required amputations any further proximally than the metacarpophalangeal (MCPJ) level in our series, and the reason for this is uncertain. Systemic therapies for purpura fulminans have included the use of Protein C concentrate,27 hemodiafiltration, and plasmapheresis, although these have not yet been shown to clearly improve mortality rate.9 There are case reports of sympathetic blockade28 and even leeches29 improving the outcome of threatened limbs from ischemia. Hyperbaric oxygen therapy has been suggested to improve the tissue oxygenation and improve ischemic lesions if used early,30 but there is only scant evidence for its efficacy, and it is not used widely.31 Heparin was not administered to any patients reviewed here, apart from patient 8 after diagnosis of a ventricular thrombus. Despite much experience with heparin in meningococcal sepsis20,32 there are only limited data to suggest that it may limit skin and bony lesions.33 Heparin is not used routinely in patients with meningococcal sepsis in our Paediatric Intensive Care unit because the theoretical advantages are felt to be outweighed by the potential complications of bleeding, which is consistent with other centers.22 A frequent late problem was that of scar contractures. Physiotherapy and pressure suits are the first line for management of contractures; however, 6 of the original 21 children required scar revisions. Notably, a parascapular free flap was successfully grafted to the left wrist of a child with a problematic contracture 5 years after the initial insult. In the acute setting of PF there is a growing confidence using free tissue transfer as a limb-salvaging technique.4,23,34,35 In 2 children needing bilateral below-knee amputations (patients 8 and 14), the subsequent course was 4™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™ Fig 1. This 2-year-old boy presented with meningococcal septicemia and rapidly developed the purpuric rash as seen in (A). On day 6 of his admission he underwent an initial debridement of his toes and returned on day 10 for bilateral midfoot amputations and had a dorsal fasciocutaneous flap positioned over the left foot. The flap looked well vascularized at the time of surgery; however, the underlying bone was necrotic, and on day 17 he required bilateral Syme through-ankle amputations. He further required excision of his right patella and extensor mechanism with the defect covered with a split-thickness skin graft. (B) shows his legs at 9 months. He required release of a scar contracture behind his right knee at 4 months and required a full-thickness skin graft to cover a raw area behind his right knee at 5 months. He is now almost 4 years and has had problems with raw areas around the stumps of his legs managed with careful bandaging and appropriately designed prosthetic limbs. He is mobilizing well and is otherwise developmentally normal for his age.
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complicated by problems with stump ulceration and fibula overgrowth requiring corrective osteotomies. Grogan et al24 noted in their series of 9 children with amputations secondary to PF, that several children with below-knee amputations (BKAs) had such marked problems with bony overgrowth and fragile skin, notwithstanding the wear of the prosthesis, 3 knee disarticulations were necessary, and further disarticulations are planned for other children. Other investigators have noted the high reoperation rate of children with BKAs for stump breakdown and the later requirement for through-knee disarticulation.15 Patient 20 from our series had continuing difficulty with bilateral genu valgum and poor leg growth. The pathogenesis of this problem is thought to relate to vascular injury to the physis during the acute septic event and subsequent development of an osseous physeal bridge.24 This results in partial physeal arrest causing angular growth deformity.25 These bridges can be excised and normal growth continued from the remaining plate.24 Growth and development after meningococcal PF is initially slow as shown by cases 14 and 20. This delay lasts between 6 and 12 months whereupon developmental pediatric notes reflect that these children have “caught up” and are within their normal peers’ developmental bracket. There are few data describing outcome in children after the insult of meningococcal PF requiring surgical interventions.15 Follow-up in our study suggested that
children who survive the initial septicemic insult go on to live “normal” lives within the context of their physical disability. This is consistent with PICU survivors in general. Butt et al36 reported that 80% of the PICU children 30 months or more and 91% of the survivors will probably lead an independent life. Patient 21 was 14 years old when she had meningococcal sepsis with extensive cutaneous necrosis over her arms, legs, and buttocks as well as concomittant myocardial impairment and pulmonary edema. Five years later she is attending university and is physically active; her main concerns are cosmesis of the grafts and the fact that she sunburns easily over the grafted areas. Other children have concerns about cosmesis (patient 2) and teasing at school because of the scars (patient 18). Also of note is patient 10 who plays golf 5 times a week on the school holidays and patient 19 who plays rugby despite having suffered multiple left finger amputations. Debridement and autologous skin grafting are the mainstay of managing necrotic cutaneous defects; however, allograft skin has proven a useful adjunct as a “physiological” dressing in our series. With deep defects that expose structures such as bone, joint, and tendon, local flaps may be used. In the extremities, amputation to viable tissue is required once gangrene has demarcated. Our data would suggest that these children achieve normal age-appropriate milestones and are primarily limited by their physical disability related to contractures, amputations, abnormal bone growth, and cosmesis.
REFERENCES 1. John SM, Koelmeyer TD: Meningococcal disease and meningitis: A review of deaths proceeding to coroner directed autopsy in Auckland [see comments]. N Z Med J 112:134-136, 1999 2. Bremner C, Lennon D, Martin D, et al. Epidemic meningococcal disease in New Zealand: Epidemiology and potential for prevention by vaccine. N Z Med J 112:257-259, 1999 3. Jefferies C, Lennon D, Stewart J, et al: Meningococcal disease in Auckland, July 1992-June 1994 [see comments]. N Z Med J 112:115117, 1999 4. Herrera R, Hobar PC, Ginsburg CM: Surgical intervention for the complications of meningococcal-induced purpura fulminans [see comments]. Pediatr Infect Dis J 13:734-737, 1994 5. Wong VK, Hitchcock W, Mason WH: Meningococcal infections in children: A review of 100 cases. Pediatr Infect Dis J 8:224-227, 1989 6. Schaller RT Jr, Schaller JF: Surgical management of life-threatening and disfiguring sequelae of fulminant meningococcemia. Am J Surg 151:553-556, 1986 7. Powars D, Larsen R, Johnson J, et al: Epidemic meningococcemia and purpura fulminans with induced protein C deficiency. Clin Infect Dis 17:254-261, 1993 8. Chu DZ, Blaisdell FW: Purpura fulminans. Am J Surg 143:356362, 1982 9. Mok Q, Butt W: The outcome of children admitted to intensive care with meningococcal septicaemia. Intensive Care Med 22:259-263, 1996 10. Brandtzaeg P, Ovsteboo R, Kierulf P: Compartmentalization of
lipopolysaccharide production correlates with clinical presentation in meningococcal disease. J Infect Dis 166:650-652, 1992 11. Francis RB Jr. Acquired purpura fulminans. Semin Thromb Hemost 16:310-325, 1990 12. Brown DL, Greenhalgh DG, Warden GD: Purpura fulminans: A disease best managed in a burn center. J Burn Care Rehabil 19:119123, 1998 13. Adcock DM, Brozna J, Marlar RA: Proposed classification and pathologic mechanisms of purpura fulminans and skin necrosis. Semin Thromb Hemost 16:333-340, 1990 14. Kennedy NJ, Duncan AW: Acute meningococcemia: Recent advances in management (with particular reference to children). Anaesth Intensive Care 24:197-216, 1996 15. Silbart S, Oppenheim W: Purpura fulminans. Medical, surgical, and rehabilitative considerations. Clin Orthop 193:206-213, 1985 16. Besner GE, Klamar JE: Integra Artificial Skin as a useful adjunct in the treatment of purpura fulminans. J Burn Care Rehabil 19:324-329, 1998 17. Harris NJ, Gosh M: Skin and extremity loss in meningococcal septicaemia treated in a burn unit. Burns 20:471-472, 1994 18. Huang S, Clarke JA: Severe skin loss after meningococcal septicaemia: Complications in treatment. Acta Paediatr 86:1263-1266, 1997 19. Potokar TS, Oliver DW, Ross Russell R, et al: Meningococcal septicaemia and plastic surgery—A strategy for management. Br J Plast Surg 53:142-148, 2000
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20. Hjort P, Rapaport S, Jorgenen L: Purpura fulminans: Report of a case successfully treated with heparin and hydrocortisone: Review of fifty cases from the literature. Scand J Haematol 1:169-192, 1964 21. Fritton A, Dickson W, Shortland G, et al: Peripheral gangrene associated with fulminating meningococcal septicaemia. J Hand Surg (Br) 22B:408-410, 1997 22. Huang DB, Price M, Pokorny J, et al: Reconstructive surgery in children after meningococcal purpura fulminans. J Pediatr Surg 34:595601, 1999 23. Huang DB, Price M, Pokorny J, et al: Reconstructive surgery in children after meningococcal purpura fulminans. J Pediatr Surg 34:595601, 1999 24. Grogan DP, Love SM, Ogden JA, et al: Chondro-osseous growth abnormalities after meningococcemia. A clinical and histopathological study. J Bone Joint Surg [Am] 71:920-928, 1989 25. Genoff MC, Hoffer MM, Achauer B, et al: Extremity amputations in meningococcemia-induced purpura fulminans. Plast Reconstr Surg 89:878-881, 1992 26. Chenaille PJ, Horowitz ME: Purpura fulminans. A case for heparin therapy. Clin Pediatr (Phila) 28:95-98, 1989 27. Fijnvandraat K, Derkx B, Peters M, et al: Coagulation activation and tissue necrosis in meningococcal septic shock: Severely reduced protein C levels predict a high mortality. Thromb Haemost 73:15-20, 1995 28. Johansen K, Murphy T, Pavlin E, et al: Digital ischemia com-
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plicating pneumococcal sepsis: Reversal with sympathetic blockade. Crit Care Med 19:114-116, 1991 29. de Chalain T, Cohen SR, Burstein FD: Successful use of leeches in the treatment of purpura fulminans. Ann Plast Surg 35:300-304; discussion 304-306, 1995 30. Waisman D, Shupak A, Weisz G, et al: Hyperbaric oxygen therapy in the pediatric patient: The experience of the Israel Naval Medical Institute. Pediatrics 102:E53, 1998 31. Leclerc F, Leteurtre S, Cremer R, et al: Do new strategies in meningococcemia produce better outcomes? Crit Care Med 28:S60-63, 2000 32. Rodriguez-Erdman F: Bleeding due to increased intravascular blood coagulation. N Eng¿Med J 273:1370-1378, 1965 33. Kupperman N, SH I, Saladino R: The role of heparin in prevention of extremity and digit necrosis in meningococcal purpura fulminans. Pediatr Infect Dis J 13:867-873, 1994 34. Yuen JC: Free-muscle-flap coverage of exposed knee joints following fulminant meningococcemia [see comments]. Plast Reconstr Surg 99:880-884, 1997 35. Redett RJ, Bury TF, McClinton MA: The use of simultaneous free latissimus dorsi tissue transfers for reconstruction of bilateral upper extremities in a case of purpura fulminans. J Hand Surg [Am] 25:559-564, 2000 36. Butt W, Shann F, Tibballs J, et al: Long-term outcome of children after intensive care. Crit Care Med 18:961-965, 1990
Background/Purpose: There are few reports describing the surgical management and outcome of children suffering purpura fulminans secondary to meningococcal sepsis. New Zealand is in the grips of a meningococcal epidemic, and, with the attendant sequalae of the disease process, the authors sought to formally review the children who have required surgical involvement. Methods: A retrospective case review of children with the sequalae of meningococcal disease presenting to the Orthopedic and Plastic Surgical Units in a university teaching hospital was undertaken. Results: There were 117 procedures in 21 children performed over a 12-year period. Surgical management was separated into 2 phases— early and late. The mean delay from admission with acute sepsis to the first surgical procedure (ie, early intervention) was 15.9 days. Debridement and autologous skin grafting was the mainstay of managing the necrotic defects; however, allograft skin proved a useful adjunct as a
N
EW ZEALAND is in the middle of a meningococcal disease epidemic with a national rate of 15.5 per 100,000.1 Rates are higher in lower socioeconomic areas such as South Auckland (34.5 per 100,000 in 1996).2 Maori and Pacific Island children for the under one-year age group have the highest incidence (283 and 980 per 100,000, respectively). Neisseria meningitidis Serogroup B is the most common, accounting for 57% of isolated organism.3 Fulminant meningococcemia accounts for between 6% and 24% of all cases of meningococcal disease.4-7 The mortality rate of meningococcal disease is reported between 3% and 12%,4-7 and a mortality rate of 6.6% was reported for the period July 1992 to June 1994 in Auckland.3 However the presence of purpura fulminans (PF) increases the mortality rate to between 28% and 60%.4-9 Fulminant meningococcemia is characterized by purpura fulminans (PF) and patchy or confluent skin necrosis, most commonly of the extremities, that may progress to gangrene. In severe disease, the accompanying hypotension, disseminated intravascular coagulopathy (DIC), and multisystem organ failure (MSOF) contribute significantly to mortality. Initial management of suspected meningococcal disease involves the support of the cardiovascular system, antibiotics, and diagnostic procedures including blood cultures for microbiology. Cerebrospinal fluid sampling is a late procedure done once Journal of Pediatric Surgery, Vol 38, No 4 (April), 2003: pp 597-603
physiologic dressing. Local flaps were used with deep defects down to bone, but in the extremities amputation to viable tissue was required once gangrene was demarcated. Amputations were carried out in 9 of 21 children. Late interventions were related to relief of contractures or fibula overgrowth causing stump ulceration. Clinical follow-up showed that all children interviewed over 5 years of age (9 children) attend ordinary regular school classes and were physically active within the context of their physical disabilities. Conclusions: The data would suggest that children requiring surgery for purpura fulminans achieve age-appropriate milestones and are primarily limited by their physical disability related to amputations, scarring, and abnormal bone growth. J Pediatr Surg 38:597-603. Copyright 2003, Elsevier Science (USA). All rights reserved. INDEX WORDS: meningococcemia, purpura fulminans, complications, surgical management.
the coagulopathy has resolved and central nervous system (CNS) function improved. Children with severe meningococcal septicemia may require artificial ventilatory support, volume resuscitation, inotropes, and extracorporeal support such as dialysis or ultrafiltration. The cutaneous manifestations of the disease are managed secondarily. In this report we review the surgical management of these cutaneous manifestations in children admitted to a tertiary pediatric referral unit over a 12year period. MATERIALS AND METHODS From August 1994 to July 2000, case records of the Plastic Surgical and Orthopaedic Services at Middlemore Hospital, a University teaching hospital in South Auckland, were searched. A total of 20 cases in this period and a further case dating back to 1987 gave a total of 21 cases who were identified as having required surgical intervention as a result of the complications of meningococcal purpura fulminans.
From the Centre for Reconstructive and Plastic Surgery at Middlemore Hospital and the Department of Anaesthesia at Auckland Children’s Hospital, Auckland, NZ. Address reprint requests to Dr Jonathan Wheeler, C/-Centre for Reconstructive and Plastic Surgery, Middlemore Hospital, Otahuhu, Auckland, New Zealand. Copyright 2003, Elsevier Science (USA). All rights reserved. 0022-3468/03/3804-0016$30.00/0 doi:10.1053/jpsu.2003.50130 597
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A chart review of each case was undertaken. Where possible, a personal interview by the investigators was conducted with the parents and child concerned. Parents were asked whether age-appropriate milestones had been reached, as defined by the Denver II developmental screen for the under 5-year-old age group, and those older than 5 years were assessed on schooling, academic, and sporting achievements. Physical disabilities and psychosocial difficulties were inquired about. When a personal interview was not possible, a telephone interview was conducted with a parent or caregiver, and the same questions were asked. If personal follow-up was not possible, data were used from the most recent clinic visit notes. Surgical procedures were divided into early and late procedures. Early procedures were those performed during the initial admission to the hospital with acute meningococcemia. Late procedures were defined as those surgical procedures performed after formal discharge from the original admission with meningococcal sepsis. Occasionally, children were sent home with a view to returning to hospital within 2 weeks for a planned, semielective surgical procedure such as debridement, in which case this procedure would be considered part of the original admission.
RESULTS
Twenty-one cases of clinical paediatric meningococcal purpura fulminans were reviewed. Serological evidence of Neisseria meningitidis infection was confirmed in 16 patients, 11 serotype B, one serotype A, and 4 untyped. The remaining 5 children in this series had a clinical diagnosis of meningococcal PF made on the findings at presentation and in the absence of another identifiable causative micro-organism in the context of the current epidemic.2,3 Fifteen of the 21 cases were of Maori (7 children) or Pacific Island descent with over half of the children living in South Auckland. There were 13 boys and 8 girls with an average age of 3.8 years. It is believed that a lipopolysaccharide endotoxin released from the cell wall of N meningitidis is responsible for the clinical manifestations of meningococcal purpura fulminans (PF).7,10-12 Microthrombi occlude dermal venules and capillaries with increased vascular permeability resulting in the rupture of capillaries, and associated vasculitis results in palpable purpura characteristic of meningococcal PF.13 The predominant organism yielded was N meningitidis Type B, which is consistent with the current epidemic3 and experience in other developed countries.14 All required admission to the Pediatric Intensive Care Unit (PICU) at a pediatric tertiary referral hospital. Three of 21 (14%) had seizures, 10 required treatment for pulmonary edema, 6 had acute cardiac impairment, and 4 had documented renal impairment. Patient 8 suffered a ventricular thrombus that resolved successfully with intravenous heparin and subsequent oral coumarin. The mean initial fluid resuscitation volume was 70 mL/kg. Table 1 outlines the initial surgical procedures. All children required debridement and skin grafting. The lower limbs were more commonly grafted (20 of 21) than the upper limbs (10 of 21). Three children required
allograft cadaver skin to cover open lesions that could not be successfully grafted early. These were patients 11, 15, and 17, and the commentary from the clinical notes on all 3 cases suggest that the allograft was successful at maintaining a clean graft bed and do not reflect any adverse effects from use of the graft. Amputations were carried out on 9 of 21 (43%). Most commonly, lower limb amputations were required (8 of 9), and these frequently were bilateral (patients 7, 8, 11, 16, 17, 18, 20) (Fig 1A). Patients 8 and 16 initially underwent amputations of their distal lower limbs to the metatarsophalangeal joint (MTPJ) level but required more proximal amputations when it became evident that the tissue was necrotic at that level. Local flaps were required in 7 children with a total of 11 flaps to cover exposed defects as listed in Table 1. Patient 7 required a delayed flap to the right heel because the flap appeared pale when initially raised. It was returned to its bed and 14 days later was successfully rotated to cover a defect over bone. Nine patients required subsequent operations defined as late procedures (Table 2). Six of these 9 had problems with contractures that required surgical intervention involving release of the contracture, often with a Z-plasty as in patients 10, 11, 16, and 17 and subsequent coverage either with a STSG (patients 10, 11, 19) or a fullthickness skin graft (patients 10, 16, 17) (Fig 1B). Clinical follow-up was attempted on all surgical patients. The same interviewer conducted interviews with 11 of the 21 patients. Two children had recent outpatient pediatric reviews (case 17 and 18). All children over 5 years of age who were interviewed (cases 2, 6, 8, 10, 11, 13, 17, 19, 21) attend ordinary regular school classes and were physically active within the context of their physical disabilities. Apart from cases 3 and 7 with no documented audiology testing, all children had hearing within normal limits. DISCUSSION
This review documents surgical procedures in children suffering meningococcal purpura fulminans (PF) and was separated into 2 phases— early and late. The mean delay from admission with acute sepsis to the first early surgical procedure was 15.9 days. This delay allows necrotic tissue to clearly demarcate before debridement and compares with typical delays of 2 to 3 weeks in other centers.15,16 Debridement and split thickness skin grafting (STSG) are the mainstays of managing the cutaneous necrotic lesions resulting from purpura fulminans. Of those children who did not require amputations, the lower limbs were the most commonly grafted site. Interestingly, the anterior abdominal wall and anterior chest wall were uncommonly involved, and no operation note reviewed
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Table 1. Initial Surgery, Early Procedures No.
Age
Ethnic Group
1
16 mo
2
11 yr
NZ Euro
3 4 5
8 yr 13 mo 6 mo
NZ Euro Maori Maori
6
6 yr
Asian
7
2 yr
PI
Areas of both lower limbs
Bilateral toes to MTPJ level; left fingers to DIPJd
8 9 10
20 mo 3 yr 4 yr
Maori PI NZ Euro
Base of amputations Right thigh ⫹ lower leg Areas left leg
Bilateral Syme forefoot.
11
5 yr
Maori
Both lower legs ⫹ right hand; Allograft used extensively initially
Left hand: all fingers to DIPJ
PI†
Debridement and STSG
Amputations
Lower limbs ⫹ buttocks (1 procedure) Left leg ⫹ several forearm lesions bilaterally Buttocks Patches arms and legs Right leg (needed repeating) Patches lower limbs and elbows
Flaps
Fasciocutaneous flap over right patella for exposed extensor mechanism Right patella rotational advancement flap Left heel adv. flap over os calcus Right heel delayed adv. flap
Local flap over dorsum left foot
Right hand: all fingers to MCPJe Bilateral foot to MTPJ
12
5 yr
Maori
Patches both lower limbs and left upper arm Areas both lower legs
13
3 yr
NZ Euro
14
7 mo
Maori
Buttocks, calves ⫹ thighs; Needed 2 repeat procedures to buttocks because contamination of feces
15
8 mo
Maori
16
2 yr
Allograft and autograft used to regions both arms and legs Split skin graft to right patella, failed; repeated patches both lower legs
Right third and fourth fingers to MCPJ; Left fifth toe to MTPJ Bilateral below knee amputation
Local flap over left heel
Right third, fourth, fifth finger tips
17
2 yr
PI
PI
Allograft used to areas bilateral lower limbs; autografts to both legs ⫹ right arm
Bilateral Syme fore foot; right patella ⫹ partial extensor mechanism (See Fig 1.)
Left dorsally based flap over left mid-foot amputation, initially viable but failed
Right patella ⫹ partial extensor mechanism Decortification right malleoli
Left patella decortification Right patella excision 18 19
6 yr 4 yr
20
6 mo
Maori PI
Lower limbs ⫹ buttocks Both legs
PI
Patches on all 4 limbs
Left first, second, third fingers to MCPJ and fourth finger to proximal interphalangeal joint Left hand third, fourth, fifth to MCPJ
Gastrocnemius flaps bilaterally; right knee flap partially necrosed requiring superiorly based flap
Right hand: first, second, third, fourth to MCPJ Right foot: second, fourth, fifth toes Bilateral patella decortification 21
14 yr
NZ Euro
Buttocks, knees ⫹ left forearm, arm and posterior left elbow
Superiorly based rotational flap over left buttock
Abbreviations: PI, Pacific Island; MTPJ, metatarsophalangeal joint; DIPJ, distal interphalangeal joint; MCPJ, metacarpophalangeal joint.
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Table 2. Late Procedures—After Discharge From Initial Admission No.
1 8
10 11
Indication for Late Procedure
Scar contracture right great toe deviated 60 medially Fibula overgrowth left leg causing ulceration ⫹ ill-fitting prosthesis Recurrence of fibula overgrowth Scar contracture left great toe Contracture again left great toe Breakdown wound right lateral foot Multiple limb contractures
Relapse contractures both wrists 14
16
Bilateral knee flexion contractures ⫹ bilateral fibula overgrowth Ongoing problems with fibula overgrowth, unable to use prostheses ⫹ wound breakdown over stumps
17
Scar contracture left popliteal fossa Raw area right popliteal fossa Multiple contractures
19
Nonhealing multiple lesions
20
Left lower lid defect Bilateral genu valgum from growth arrest proximal tibia right leg Continued problems with marked genu valgum
Procedure
Release scar contracture planned Fibula trimmed 18 mm Awaiting operation Z-plasty ⫹ STSG left first toe Release contracture with full-thickness skin graft STSG Right wrist: Z-plasty ⫹ STSG Right lower leg tibialis anterior tendon divided ⫹ transposition graft ⫹ left lower leg tibialis anterior divided ⫹ extensor mechanism released Left wrist release contracture ⫹ release contracture left elbow Left wrist parascapular free flap ⫹ right wrist release extensor contracture Bilateral release contractures knees with STSG ⫹ trimming bilateral fibulae MRI angiogram-normal vessels to stumps (considered latissimus dorsi flaps) proceeded to bilateral fibula osteotomies directed into the lower part of the remaining tibiae ⫹ release popliteal contractures ⫹ STSG Z-plasty release Full-thickness skin graft right popliteal fossa Full-thickness skin graft to both popliteal fossae, dorsum right foot ⫹ posterior aspect left leg ⫹ Z-plasty right anterior elbow ⫹ dorsum right wrist STSG to patches both legs Policization left index finger to left thumb V-Y advancement left lower lid Osteotomy right proximal tibia and application Ilizarov frame Shifted overseas before further corrective surgery
Abbreviations: STSG, split-thickness skin graft; MRI, magnetic resonance imaging.
from the 117 operation notes detailed STSG to these areas. Furthermore, only cases 16 and 20 had documented facial lesions, and only case 20 required early intervention, a secondary closure of a lower eye lid lesion. A particular problem was of fecal contamination of grafted sites around the buttocks in case 14, with 3 separate procedures involving debridement and split skin grafting as well as meticulous nursing and dressing changes to finally obtain a good “take”, avoiding the need for a diverting colostomy. Three children required allograft skin to maintain a healthy, graft-able bed until definitive autologous graft could be harvested. Other reports have also satisfactorily used allograft,17,18 artificial skin,16 and porcine xenograft.6 A total of 8 fasciocutaneous flaps were used in 6 patients and 3 musculocutaneous flaps in 2 patients. In case 16, the flap necrosed on the dorsum of a foot, and, ultimately, a Syme amputation was performed. Patient 20 had a partially necrosed gastocnemius flap that necessitated a superiorly based fasciocutaneous flap as coverage for the defect. The literature is cautious about the use of local flaps in meningococcal purpura fulminans (PF),19,20 suggesting that it is difficult to clinically assess the extent of microvascular damage adjacent to necrotic lesions, hence, compromising the viability of a
local flap. Our experience has been encouraging and would suggest that local fasciocutaneous and myocutaneous flaps are useful in providing coverage for skin defects as a result of meningococcal PF, and that a distinction between clinically viable and nonviable tissue can be confidently made at the time of surgery. None of the patients in the current series had compartment pressures measured nor had fasciotomies performed. Early monitoring of compartmental pressures and subsequent fasciotomy in children with PF have been proposed to reduce the number of amputations required.12,15,19,21 In a large series of 12 children who required amputations for PF, 3 of these children had fasciotomies but still required amputation.15 An approach adopted by many centers is to monitor compartment pressures and perform fasciotomies as indicated.4,15,22 In the absence of compartment syndrome or wound infection, the gangrenous limb should be allowed to demarcate before debridement15,16,21,23,24 to prevent the possibility of an unnecessarily high amputation. The mean delay to initial amputation in our series was 21 days. The symmetrical nature of amputations required for PF of the lower limbs is reflected in other series24,25 as well as the need for early revision amputations if viable tissue had not been reached.15,24,25 Two of 9
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children in this series required revised amputations with up to half of initial amputations being revised to a higher level in other centers.16,26 Upper limb amputations in our series tended to be at a more distal level comparatively than the lower limb and did not exhibit a similar symmetry. None required amputations any further proximally than the metacarpophalangeal (MCPJ) level in our series, and the reason for this is uncertain. Systemic therapies for purpura fulminans have included the use of Protein C concentrate,27 hemodiafiltration, and plasmapheresis, although these have not yet been shown to clearly improve mortality rate.9 There are case reports of sympathetic blockade28 and even leeches29 improving the outcome of threatened limbs from ischemia. Hyperbaric oxygen therapy has been suggested to improve the tissue oxygenation and improve ischemic lesions if used early,30 but there is only scant evidence for its efficacy, and it is not used widely.31 Heparin was not administered to any patients reviewed here, apart from patient 8 after diagnosis of a ventricular thrombus. Despite much experience with heparin in meningococcal sepsis20,32 there are only limited data to suggest that it may limit skin and bony lesions.33 Heparin is not used routinely in patients with meningococcal sepsis in our Paediatric Intensive Care unit because the theoretical advantages are felt to be outweighed by the potential complications of bleeding, which is consistent with other centers.22 A frequent late problem was that of scar contractures. Physiotherapy and pressure suits are the first line for management of contractures; however, 6 of the original 21 children required scar revisions. Notably, a parascapular free flap was successfully grafted to the left wrist of a child with a problematic contracture 5 years after the initial insult. In the acute setting of PF there is a growing confidence using free tissue transfer as a limb-salvaging technique.4,23,34,35 In 2 children needing bilateral below-knee amputations (patients 8 and 14), the subsequent course was 4™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™ Fig 1. This 2-year-old boy presented with meningococcal septicemia and rapidly developed the purpuric rash as seen in (A). On day 6 of his admission he underwent an initial debridement of his toes and returned on day 10 for bilateral midfoot amputations and had a dorsal fasciocutaneous flap positioned over the left foot. The flap looked well vascularized at the time of surgery; however, the underlying bone was necrotic, and on day 17 he required bilateral Syme through-ankle amputations. He further required excision of his right patella and extensor mechanism with the defect covered with a split-thickness skin graft. (B) shows his legs at 9 months. He required release of a scar contracture behind his right knee at 4 months and required a full-thickness skin graft to cover a raw area behind his right knee at 5 months. He is now almost 4 years and has had problems with raw areas around the stumps of his legs managed with careful bandaging and appropriately designed prosthetic limbs. He is mobilizing well and is otherwise developmentally normal for his age.
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complicated by problems with stump ulceration and fibula overgrowth requiring corrective osteotomies. Grogan et al24 noted in their series of 9 children with amputations secondary to PF, that several children with below-knee amputations (BKAs) had such marked problems with bony overgrowth and fragile skin, notwithstanding the wear of the prosthesis, 3 knee disarticulations were necessary, and further disarticulations are planned for other children. Other investigators have noted the high reoperation rate of children with BKAs for stump breakdown and the later requirement for through-knee disarticulation.15 Patient 20 from our series had continuing difficulty with bilateral genu valgum and poor leg growth. The pathogenesis of this problem is thought to relate to vascular injury to the physis during the acute septic event and subsequent development of an osseous physeal bridge.24 This results in partial physeal arrest causing angular growth deformity.25 These bridges can be excised and normal growth continued from the remaining plate.24 Growth and development after meningococcal PF is initially slow as shown by cases 14 and 20. This delay lasts between 6 and 12 months whereupon developmental pediatric notes reflect that these children have “caught up” and are within their normal peers’ developmental bracket. There are few data describing outcome in children after the insult of meningococcal PF requiring surgical interventions.15 Follow-up in our study suggested that
children who survive the initial septicemic insult go on to live “normal” lives within the context of their physical disability. This is consistent with PICU survivors in general. Butt et al36 reported that 80% of the PICU children 30 months or more and 91% of the survivors will probably lead an independent life. Patient 21 was 14 years old when she had meningococcal sepsis with extensive cutaneous necrosis over her arms, legs, and buttocks as well as concomittant myocardial impairment and pulmonary edema. Five years later she is attending university and is physically active; her main concerns are cosmesis of the grafts and the fact that she sunburns easily over the grafted areas. Other children have concerns about cosmesis (patient 2) and teasing at school because of the scars (patient 18). Also of note is patient 10 who plays golf 5 times a week on the school holidays and patient 19 who plays rugby despite having suffered multiple left finger amputations. Debridement and autologous skin grafting are the mainstay of managing necrotic cutaneous defects; however, allograft skin has proven a useful adjunct as a “physiological” dressing in our series. With deep defects that expose structures such as bone, joint, and tendon, local flaps may be used. In the extremities, amputation to viable tissue is required once gangrene has demarcated. Our data would suggest that these children achieve normal age-appropriate milestones and are primarily limited by their physical disability related to contractures, amputations, abnormal bone growth, and cosmesis.
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lipopolysaccharide production correlates with clinical presentation in meningococcal disease. J Infect Dis 166:650-652, 1992 11. Francis RB Jr. Acquired purpura fulminans. Semin Thromb Hemost 16:310-325, 1990 12. Brown DL, Greenhalgh DG, Warden GD: Purpura fulminans: A disease best managed in a burn center. J Burn Care Rehabil 19:119123, 1998 13. Adcock DM, Brozna J, Marlar RA: Proposed classification and pathologic mechanisms of purpura fulminans and skin necrosis. Semin Thromb Hemost 16:333-340, 1990 14. Kennedy NJ, Duncan AW: Acute meningococcemia: Recent advances in management (with particular reference to children). Anaesth Intensive Care 24:197-216, 1996 15. Silbart S, Oppenheim W: Purpura fulminans. Medical, surgical, and rehabilitative considerations. Clin Orthop 193:206-213, 1985 16. Besner GE, Klamar JE: Integra Artificial Skin as a useful adjunct in the treatment of purpura fulminans. J Burn Care Rehabil 19:324-329, 1998 17. Harris NJ, Gosh M: Skin and extremity loss in meningococcal septicaemia treated in a burn unit. Burns 20:471-472, 1994 18. Huang S, Clarke JA: Severe skin loss after meningococcal septicaemia: Complications in treatment. Acta Paediatr 86:1263-1266, 1997 19. Potokar TS, Oliver DW, Ross Russell R, et al: Meningococcal septicaemia and plastic surgery—A strategy for management. Br J Plast Surg 53:142-148, 2000
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20. Hjort P, Rapaport S, Jorgenen L: Purpura fulminans: Report of a case successfully treated with heparin and hydrocortisone: Review of fifty cases from the literature. Scand J Haematol 1:169-192, 1964 21. Fritton A, Dickson W, Shortland G, et al: Peripheral gangrene associated with fulminating meningococcal septicaemia. J Hand Surg (Br) 22B:408-410, 1997 22. Huang DB, Price M, Pokorny J, et al: Reconstructive surgery in children after meningococcal purpura fulminans. J Pediatr Surg 34:595601, 1999 23. Huang DB, Price M, Pokorny J, et al: Reconstructive surgery in children after meningococcal purpura fulminans. J Pediatr Surg 34:595601, 1999 24. Grogan DP, Love SM, Ogden JA, et al: Chondro-osseous growth abnormalities after meningococcemia. A clinical and histopathological study. J Bone Joint Surg [Am] 71:920-928, 1989 25. Genoff MC, Hoffer MM, Achauer B, et al: Extremity amputations in meningococcemia-induced purpura fulminans. Plast Reconstr Surg 89:878-881, 1992 26. Chenaille PJ, Horowitz ME: Purpura fulminans. A case for heparin therapy. Clin Pediatr (Phila) 28:95-98, 1989 27. Fijnvandraat K, Derkx B, Peters M, et al: Coagulation activation and tissue necrosis in meningococcal septic shock: Severely reduced protein C levels predict a high mortality. Thromb Haemost 73:15-20, 1995 28. Johansen K, Murphy T, Pavlin E, et al: Digital ischemia com-
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plicating pneumococcal sepsis: Reversal with sympathetic blockade. Crit Care Med 19:114-116, 1991 29. de Chalain T, Cohen SR, Burstein FD: Successful use of leeches in the treatment of purpura fulminans. Ann Plast Surg 35:300-304; discussion 304-306, 1995 30. Waisman D, Shupak A, Weisz G, et al: Hyperbaric oxygen therapy in the pediatric patient: The experience of the Israel Naval Medical Institute. Pediatrics 102:E53, 1998 31. Leclerc F, Leteurtre S, Cremer R, et al: Do new strategies in meningococcemia produce better outcomes? Crit Care Med 28:S60-63, 2000 32. Rodriguez-Erdman F: Bleeding due to increased intravascular blood coagulation. N Eng¿Med J 273:1370-1378, 1965 33. Kupperman N, SH I, Saladino R: The role of heparin in prevention of extremity and digit necrosis in meningococcal purpura fulminans. Pediatr Infect Dis J 13:867-873, 1994 34. Yuen JC: Free-muscle-flap coverage of exposed knee joints following fulminant meningococcemia [see comments]. Plast Reconstr Surg 99:880-884, 1997 35. Redett RJ, Bury TF, McClinton MA: The use of simultaneous free latissimus dorsi tissue transfers for reconstruction of bilateral upper extremities in a case of purpura fulminans. J Hand Surg [Am] 25:559-564, 2000 36. Butt W, Shann F, Tibballs J, et al: Long-term outcome of children after intensive care. Crit Care Med 18:961-965, 1990