Thank you for the comments on our practice pointer article about necrotising fasciitis. The majority of responses to our article were around microbiological diagnosis and management. We were unaware of the work around the potential usefulness of immunoglobulin in managing this condition, this is unlikely ever to achieve more than level five evidence given the difficulties in conducting controlled trials in this area, but seems to have little harm and is biologically plausible. The focus of our article was on improving diagnosis promptly as this is where the greatest gains are. Discussing microbiological causation or operative management of the condition was not the main aim of the article. Trying to distinguish microbiological subtypes clinically is interesting, but the main pitfall in this condition is failure to consider the diagnosis at all. There are doubtful cases, especially early on in the disease process, where scoring systems and imaging may have a role, but fully agree that surgery should not be delayed once the diagnosis is made.

Competing interests: None declared

Dear Sir,

We read with great interest your article on necrotising fasciitis, which provided an excellent overview of this rare but potentially devastating condition. In addition to the points covered, we would like to raise a few other key aspects in aiding diagnosis and management. Cases of necrotising fasciitis in children often appear in otherwise healthy individuals with no predisposing factors for infection or any chronic conditions. By contrast, around 75% of adults with NF have an underlying condition such as diabetes, chronic renal failure, metastatic carcinoma and peripheral vascular insufficiency. [1]

The diagnosis of necrotising fasciitis in children may be difficult to establish, particularly in the early stages. Firstly, dependent on age it may be difficult to obtain a history from the child and a distressed parent. Secondly, clinical markers such as blood pressure readings may not be as reliable in younger children. In addition, the assessment of a child who is in extreme pain might be more challenging and add to delays in performing clinical investigations such as blood tests. As NF is a rare condition in children, some may be labelled as having cellulites and treated as such until frank necrosis becomes apparent. The use of ultrasound scans has been mentioned in the literature as a diagnostic aid, however it is imperative that any form of imaging must not delay the emergency surgical debridement that is required in these cases. [1,2]

In the paediatric population it is interesting to note that the use of non steroidal anti inflammatory medication has long been implicated as a contributory factor in the development of necrotising fasciitis particularly in those with chicken pox. It is widely understood that NSAIDs act by reducing the ability of granulocytes to perform chemotaxis, phagocytosis and bacterial killing .However, it is still unclear whether they simply mask symptoms and delay diagnosis, or are actually involved in the development of the disease thus resulting in worse outcome.[3].

Case control studies have highlighted the association of ibuprofen use with the development of necrotising fasciitis in the setting of primary varicella zoster infections. It was noted that children who developed necrotising fasciitis were more likely than controls to have used ibuprofen prior to hospitalization. In most children ibuprofen was commenced after diagnosis of the primary infection. Furthermore, those who developed renal insufficiency were more likely to have been treated with ibuprofen [2].

Although there are no published guidelines for the management of necrotising fasciitis, the guidelines for management of severe sepsis indicate that early multidisciplinary care is paramount, particularly input from the critical care team even within the emergency department [4].

Considering treatment modalities in necrotising fasciitis, whilst early surgical debridement is well recognised as the mainstay of management other adjuncts have been well described in the literature. The potential benefit of intravenous immunoglobulin (IVIG) has been investigated due to its use in other inflammatory and autoimmune diseases, with relatively little adverse events. Rationale behind its use in necrotising fasciitis has been based on the potential for modulation of immune response to the so-called streptococcal superantigens. These are thought to be streptococcal exotoxins which can bypass traditional routes of antigen processing to directly stimulate T-cell and macrophages, resulting in massive release of pro-inflammatory cytokines and the devastating clinical manifestations of necrotising fasciitis and toxic shock syndrome [5,6]. Following of from early in vitro work demonstrating the role of IVIG in inhibiting superantigen elicited T-cell activation [7], there have been in vivo studies reporting improved survival within the IVIG-treated necrotising fasciitis population [8,9]. Unfortunately, all studies have been limited by small patient numbers in a mix of controlled or uncontrolled case series. Further difficulty lies in attributing patient survival to the use of IVIG alone, particularly where multiple adjuncts to surgical debridement have been utilised. Currently, there is insufficient evidence to vehemently support or indeed refute the role of immunogloblubin in the superantigen-mediated processes occurring in necrotising fasciitis, but it remains an important avenue of exploration.

1. Shirley RA, Mackey SB, Meagher P. Necrotising fasciitis: A sequelae of varicella zoster infection. JPRAS 2011; 64: 123-127
2. Zerr DM, Alexander ER, Duchin JS et al. A case-control study of necrotizing fasciitis during primary varicella. Pediatrics. 1999 Apr;103(4 Pt 1):783-90.
3. Peterson C, Vugia D, Meyers H, et al. Risk factors for invasive group A streptococcal infections in children with varicella a case control study. Pediatr Infect Dis J 1996 February;15:151e6.
4. Steer JA, Lamagni T, Healy B,etal. Guidelines for prevention and control of group A streptococcal infection in acute healthcare and maternity settings in the UK, JInfect 2012 Jan;64(1):1-18.
5. Darabi K, Abdel-Wahab O, Dzik WH. Current usage of intravenous immune globulin and the rationale behind it: the Massachusetts General Hospital data and a review of the literature. Transfusion. 2006 May;46(5):741-53.
6. Carter PS, Banwell PE. Necrotising fasciitis: a new management algorithm based on clinical classification. Int Wound J. 2004 Sep;1(3):189-98.
7. Takei S, Arora YK, Walker SM. Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens J Clin Invest 1993;91:602-7.
8. Kaul R, McGeer A, Canadian Infectious Diseases Society (CIDS) Ontario Group A Streptococcal Study, Norrby-Teglund A, Kotb M, Low DE. Intravenous immunoglobulin (IVIG) therapy in streptococcal toxic shock syndrome (STSS): results of a matched case-control study [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy 1995.
9. Norrby-Teglund A, Kaul R, Low DE, McGeer A et al. Plasma from patients with severe group A streptococcal infections treated with normal polyspecific IgG (IVIG) inhibits streptococcal superantigen-induced T cell proliferation and cytokine production. J Immunol 1996;156:3057—64.

Competing interests: None declared

In the section of this article entitled "How is necrotising fasciitis managed?" the authors recommend "Broad spectrum antibiotics such as benzylpenicillin and flucloxacillin", and, additionally, clindamycin, for its antistreptococcal mechanism.

The microbial aetiology of necrotising fasciitis is not discussed in this article. Although terminology varies to some extent, it is generally recognised that there are two major types of necrotising fasciitis, Type 1 and Type 2. Type 1 necrotising fasciitis is polymicrobial, caused by a mixture of organisms, usually including enteric Gram-negative bacilli and anaerobes. Type 2 necrotising fasciitis is caused by Streptococcus pyogenes, and is usually monomicrobial.

The antimicrobial spectrum of benzylpenicillin and flucloxacillin does not include enteric Gram-negative bacilli. Whilst it would be appropriate to treat streptococcal necrotising fasciitis with high dose penicillin and clindamycin, it would be inappropriate to use these antibiotics (with or without flucloxacillin) in a patient who might have polymicrobial infection, i.e. who does not yet have a microbiological diagnosis. In this situation the antibiotic choice would need to include agents with a broader spectrum, such as beta-lactam/beta-lactamase combinations, carbapenems etc., to cover Gram-positives, Gram-negatives and anaerobes.

In the same issue of the BMJ an "Authors' reply" was published to letters received concerning a recent review article on cellulitis (Phoenix G, Das S, Joshi M. Diagnosis and management of cellulitis. BMJ 2012;345:e4955), which had contained numerous antibiotic errors.

The two articles, on subjects that would not usually be considered complex, serve to demonstrate that the choice of appropriate antimicrobial therapy may be more complex than appreciated, and reinforce the need to have appropriate antibiotic guidelines and/or specialist advice available at all times.

Competing interests: None declared