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Clinical REVIEW
Cel ulitis is a relatively common infection of the skin and subcutaneous tissue associated with high morbidity and a burden on healthcare resources. Lymphoedema — the accumulation of fluid in interstitial spaces — can occur as a consequence of cel ulitis. Similarly, the presence of chronic lymphoedema can predispose to recurrent episodes of cellulitis. This article explores the relationship between lymphoedema and cellulitis, with emphasis on diagnosis, management and methods of prevention. tests have a relatively low diagnostic yield. mild to a more severe form with systemic are not helpful, but the yield of positive entry is present or if there is secondary and Swartz, 2004). A typical presentation is painful swel ing with erythema that is exudate and ulcerations, if present, may by ‘flu-like’ symptoms. Potential long- pyogenes or Staphylococcus aureus leg is the most affected site, accounting cellulitis is that the infection is of the dermis, not of the skin surface, so it is cellulitis. Streptococcal cellulitis associated cellulitis is hard to estimate but a review of all hospital admissions in a UK district 3% of all admissions were for cellulitis Identifying cellulitis
Cel ulitis is often clinical y apparent due cellulitis showed that only 26% had fever at the time of active cellulitis (Hook et for cellulitis in 2003–2004, costing the with cellulitis admitted to hospital were apyrexial and systemically well (Cox et al, present. Blistering and ulceration occur in 1998). Hospital clinicians are aware that severe forms of cellulitis, often associated are ‘not getting better’ despite antibiotic Firas Al-Niaimi is Specialist Registrar in Dermatology, Salford
Royal Hospital, Manchester, UK and Neil Cox is Consultant
been used for diagnosis of cel ulitis by redness or swelling which can persist for Dermatologist, Cumberland Infirmary, Carlisle, UK
microbiological culture, but overall these some time after antibiotic treatment.
Journal of Lymphoedema, 2009, Vol 4, No 2 Clinical REVIEW
contribute to the reduction in morbidity in London involving 823 patients, 28% of to give a low yield for diagnosis in the as well as future recurrence (Collins et al, episode of cellulitis within the previous 12 acquired cel ulitis showed that only 2% of Risk factors for cellulitis
patients had a significant patient-specific microbial strain isolated (Perl et al, 1999). strongly associated with a predisposition A slightly higher rate of positive blood for cel ulitis. General factors that might be cultures in patients with leg lymphoedema regarded as risk factors include obesity, involving 167 patients with 294 controls. mellitus. The association with diabetes, had two or more episodes of leg cellulitis were investigated with lymphoscintigraphy in retrospective studies (Dupuy et al, 1999), with an increased risk (Scheinfeld, 2004). not appear to be cost-ef ective. This does not however apply for necrotising fasciitis, Local factors causing defects in the skin which is a more serious infection affecting barrier may increase the risk of developing cel ulitis by acting as a portal of entry for cel ulitis, suggesting that pre-existing with high mortality and systemic sepsis. 2004; Cox, 2002; Dupuy et al, 1999). Skin occurrence of clinical cellulitis. Stoberl necrotising fasci tis is often confused with trauma, lacerations, puncture wounds, leg cel ulitis, particularly at its early phase of presentation where blood cultures have a and tinea pedis fal into this group. In a higher diagnostic yield (Cox, 2002).
study involving 647 patients, 77% had local portals of entry, 50% of which were fungal in the affected limb also had evidence of infections (mostly of the toe web) (Morris, impaired drainage in the unaffected limb.
in retrospect, as this blood test result 2004). Among the aforementioned factors, leg ulcers form the strongest risk (Dupuy be present among patients with cellulitis. Early detection of lymphatic abnormalities patients who are less likely to have a non- streptococcal aetiology (e.g. patients with excoriated eczema, carbuncles, abscesses et al, 2000). This risk increases particularly or leg ulcers), as a negative test helps to if other factors are present (Bjoornsdottir exclude a streptococcal cause. Conversely, et al, 2005).
confirming streptococcal infections can be episodes of cellulitis. However, there are obvious practical limitations to this, as the with cel ulitis who were fol owed for up history of recurrent episodes (Cox, 2006). been shown to be of limited value in the Management of cellulitis
diagnosis of cellulitis, but may have a role in excluding some differential diagnoses first three years after their initial cel ulitis resolution of the symptoms, reducing the such as vasculitis or eosinophilic cel ulitis in those with atypical presentations (Tsao and ulceration. General measures such as bed rest, elevation of the affected leg, skin risk factor for cellulitis (Dupuy et al, 1999; Duvanel et al, 1989), particularly first-line treatments for cellulitis (Morton or intravenous) will be discussed later, in recurrent cellulitis. This is specifically and Swartz, 2004; Cox, 2002). Antibiotics onychomycosis, tinea pedis or leg ulcers insufficiency. In an epidemiological study antibiotic therapy for cellulitis varies. Journal of Lymphoedema, 2009, Vol 4, No 2 Clinical REVIEW
Generally, oral antibiotics are used for the the bacteria). However, penicil in alone is milder forms of cel ulitis where systemic prophylaxis in cel ulitis is suggested by the in the UK, due to its limited effect against BLS if two or more episodes of cel ulitis Mortimer et al, 2006). This is potential y for phenoxmethylpenicil in is partly due especial y in early localised cel ulitis or in the risk of hepatic toxicity if used long cel ulitis with a wound as the portal of entry. Flucloxacillin as first-line treatment, also because recurrent cellulitis, with or most likely to be streptococcal infection.
flucloxacil in as the first-line antibiotic in addition has anti-staphylococcal action. (intravenously in severe cases), with the Lymphoedema
macrolide clarithromycin for patients who are allergic to penicillin. In severe cases, for streptococci, flucoxacillin’s MIC is sufficiently low that the addition of benzyl a substitute for clarithromycin in cases of penicil in to flucloxacil in in patients who do not respond to the latter is unlikely to produce added beneficial value. This has drainage. Increases in interstitial fluid flucloxacil in as first-line and erythromycin or clarithromycin in the case of penicil in This is the main process responsible for flucloxacil in versus a group treated with interstitial fluid drainage. Impairment of flucloxacillin and benzyl penicillin (Leman forms. There is limited evidence available for the estimated duration of treatment. Treatment of recurrent cellulitis
is rarely used for cel ulitis in the UK) recurrent cellulitis, prophylactic therapy occurs after five days, further treatment leg is mainly an active process achieved with lymphoedema dif ers slightly as the the col ecting ducts is under the influence of the sympathetic system as well as the influx streptococcal. Based on this, the British in no recurrences in cel ulitis compared amoxicillin as first-line therapy for cellulitis therefore, likely to be partly through their large multi-centre national study, being allergic to penicillin (Mortimer et al, 2006).
is general y believed to contribute to an the largest of the above studies (170 to range of pathologies, all of which present clinically as chronic swelling of one or Antibiotics for the Treatment of Cel ulitis uncomplicated cel ulitis (Societe Francaise de Dermatologie, 2001). Benzyl penicil in episodes of cellulitis in patients who had is caused by increased capillary filtration cellulitis (UK Dermatology Clinical Trials Network’s PATCH Study Group, 2007).
Journal of Lymphoedema, 2009, Vol 4, No 2 Clinical REVIEW
an abnormality of lymphatic development, that the relationship between cel ulitis malformations in the collecting ducts (such where each episode of cel ulitis further syndrome), or due to acquired abnormalities contribute by reducing the venous pressure and subsequently the filtration. It is often used in conjunction with other risk for cel ulitis (Col ins et al, 1989; Woo measures, as leg elevation on its own has et al, 2000). In unpublished original data Executive Committee, 2003). This represents little effect on the lymphatic drainage.
will have at least one episode of cellulitis or related skin infection in the affected root of the limb to the draining lymphatic the primary aetiology of the lymphoedema and is thought to be multifactorial. The protein-rich lymphatic fluid serves as an excel ent medium for bacteria to grow, and stagnation of the lymphatic fluid due to reduction in lymphatic clearance creates a systemic cause is likely to be found (e.g. method is designed to inflate and deflate state of local immune deficiency, which, in around a swol en limb, exerting a pressure turn, can increase the risk of local cel ulitis of 30–40mmHg. Although it increases the reabsorption of interstitial fluid, it has no ef ect on the reabsorption of proteins. This leads to an increase in the concentration swelling, pitting and thickening of the skin, and/or antibiotics and are cleared efficiently by lymphatic drainage (Jeffs, 1998).
on lymph flow, and the high pressures can damage the superficial lymphatics. Treatment of lymphoedema
that bacterial toxins which were ‘pooled’ in insufficiently drained lymphatic tissue complicating lymphoedema. This is largely retention (Mortimer and Levick, 2004).
attributable to the release of cytokines as a host response to the presence of Exercise induces changes in interstitial excessive lymph. It is unclear why there fluid pressure which leads to an increase seems to be a great individual variance in in both the lymphatic filling and pressure, contractility of the lymphatic ducts. An increase in the flow of the non-contractile treatment(s) based on the degree of lymph ducts is likely to be influenced severity and any associated complications. difficult and there is a risk of reactivation of cel ulitis if the local immune system is swel ing which is subsequently maintained interstitial pressure by opposing capil ary filtration, leading to an increased venous Relationship between lymphoedema
and cellulitis
clindamycin and macrolides, as these have Journal of Lymphoedema, 2009, Vol 4, No 2 Clinical REVIEW
anti-streptococcal activity, and therefore Prodigy Guidance. Cellulitis. http://www.cks.
(1991) Long-term antimicrobial therapy in the prevention of recurrent soft-tissue infections. J
Infect 22(1): 37–40
complicates lymphoedema (Ritts, 1990).
Clinical Resource Efficiency Support Team (2005) Guidelines on the Management of Leman P, Mukherjee D (2005) Flucloxacillin Conclusion
Cellulitis in Adults. Crest, Belfast. Available online at: www.crestni.org.uk/publications/ to treat lower limb cellulitis: a randomised controlled trial. Emerg Med J 22(5): 342–6
Collins PS, Villavicencio JL, Abreu SH, et al Levick JR (2004) Revision of the starling (1989) Abnormalities of lymphatic drainage principle: new views of tissue fluid balance. J in lower extremities: a lymphoscintigraphic Physiol 557(3): 704
factors have been found to predispose to study. J Vasc Surg 9(1): 145–52
cel ulitis, with lymphoedema showing the strongest link. The relationship between Society of Lymphology Executive Committee problem. Q J Med 96: 731–8
cel ulitis and lymphoedema appears to be Morris A (2004) Cellulitis and erysipelas. a vicious cycle; a pre-existing lymphatic peripheral lymphoedema. Lymphology 36:
Clin Evid 12: 2271–7. Available online at:
defect predisposes to cellulitis, episodes www.clinicalevidence.com/ceweb/conditions/skd/1708/1708.jsp of cellulitis damage the lymphatic system, Cox NH (2002) Management of lower leg
cellulitis. Clin Med JRCPL 2: 23–7
and either the primary or post-cel ulitic Mortimer PS, Cefai C, Keeley V, et al (2006) Consensus Document on the Management of Cox NH (2006) Oedema as a risk factor for multiple episodes of cellulitis/erysipelas of the Cellulitis in Lymphoedema. British Lymphology lower leg: a series with community follow-up. Society, Cheltenham. Available online at: Br J Dermatol 155(5): 947–50
Management and morbidity of cellulitis of the peripheral oedema: the critical role of the leg. J R Soc Med 91(12): 634–7
lymphatic system. Clin Med 4: 448–53
Morton N, Swartz MN (2004) Cellulitis. N Engl J Med 350: 904–12
be beneficial in reducing the recurrence prospective quantitative scintigraphic study Recurrent erysipelas: risk factors. J Dtsch of 40 patients with unilateral erysipelas of the Dermatol Ges 2: 89–95
leg. Br J Dermatol 158: 1210–5
evidence base, particularly when cel ulitis Perl B, Gottehrer NP, Raveh D, et al (1999) Cost-effectiveness of blood cultures for adult et al (2000) Lymphoscintigraphic evaluation large, ongoing multi-centre trial described patients with cellulitis. Clin Infect Dis 29(6):
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earlier, investigating the use of prophylactic antibiotics in cellulitis (PATCH study), may Ritts RE (1990) Antibiotics as biological response modifiers. J Antimicrob Chem in time provide this evidence. JL
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Scheinfeld NS (2004) Obesity and
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Journal of Lymphoedema, 2009, Vol 4, No 2

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