Beyond the Red Leg: Cellulitis and its Mimickers - Daniela Kroshinsky, M.D. M.P.H. Associate Professor of Dermatology Director of Inpatient ...
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Beyond the Red Leg: Cellulitis and its
Mimickers
Daniela Kroshinsky, M.D. M.P.H.
Associate Professor of Dermatology
Director of Inpatient Dermatology
Director of Pediatric Dermatology
www.mghcme.org
Disclosures
Neither I nor my spouse/partner has a relevant
financial relationship with a commercial interest
to disclose
www.mghcme.org
Overview
• Cellulitis & Pseudocellulitis: Background
• Diagnosis: Typical vs. Variant vs. Pseudocellulitis
• Pseudocellulitis
www.mghcme.org
Raff AB, Kroshinsky D. Cellulitis: A Review. JAMA. 2016 Jul 19;316(3):325-37. www.mghcme.org
Raff AB, Kroshinsky D. Cellulitis: A Review. JAMA. 2016 Jul 19;316(3):325-37. www.mghcme.org
Cellulitis
• Deep skin and subcutaneous fat infection
• Poorly-demarcated erythema, warmth, tenderness,
edema
• Rubor, calor, dolor, tumor: inflammation
• 2.2% of all general practitioner office visits
• US Outpatient + ED 2006: 14.5 million cases, $3.7 billion
• 4.6 million cases in 1997
The DRG Handbook: Comparative Clinical and Financial Benchmarks. Evanston, IL: Solucient; 2006.
Cox NH, Colver GB, Paterson WD. Management and morbidity of cellulitis of the leg. J R Soc Med. 1998;91(12):634-637.
Arakaki RY, Strazzula L, Woo E, Kroshinsky D. The impact of dermatology consultation on diagnostic accuracy and antibiotic use among patients with suspected cellulitis seen at outpatient
internal medicine offices: A randomized clinical trial. JAMA Dermatol. 2014. David CV, Chira S, Eells SJ, et al. Diagnostic accuracy in patients admitted to hospitals with cellulitis. Dermatol Online
J. 2011;17(3). www.mghcme.org
Cellulitis
• 10% of infectious disease-related US hospitalizations ‘98-’06
• Average length of stay 7-10 days, 15 days if recurrent
cellulitis
• 400,000 days/ year in the English National Health Service
• 73% increased rate of hospitalization in US from 1997-2011
– Five-fold increased hospitalization from 54yo to >=85yo
– Over 650,000 admissions
Healthcare Cost and Utilization Project (HCUP). Nationwide Inpatient Sample (NIS) Most Frequent Conditions in U.S. Hospitals, 2011.
Christensen KLY, et al. Infectious disease hospitalizations in the United States. Clin Infect Dis Off Publ Infect Dis Soc Am. 2009;49(7):1025-1035.
Hersh AL, Chambers HF, Maselli JH, Gonzales R. National trends in ambulatory visits and antibiotic prescribing for skin and soft-tissue infections. Arch Intern Med. 2008;168(14):1585-1591.
Goettsch WG, Bouwes Bavinck JN, Herings RMC. Burden of illness of bacterial cellulitis and erysipelas of the leg in the Netherlands. J Eur Acad Dermatol Venereol JEADV. 2006;20(7):834-839.
McNamara DR, Tleyjeh IM, Berbari EF, et al. Incidence of lower-extremity cellulitis: a population-based study in Olmsted county, Minnesota. Mayo Clin Proc. 2007;82(7):817-821.
www.mghcme.org
Cellulitis at MGH: #15 Admission, #1 Readmission
Chart1
HMG FY11 Readmissions FY11 Qty
Cum %
45 100.00%
40 90.00%
80.00%
35
70.00%
30
% Total Readmissions
# Readmissions
60.00%
25
50.00%
20
40.00%
15
30.00%
10
20.00%
5 10.00%
0 0.00%
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Pseudocellulitis: The Problems
• Preliminary data: 7% of 500 inpatient consults over nine
months for unresponsive cellulitis
– 85% = pseudocellulitis
• Very little agreement on the ‘gold standard’
– No laboratory criteria exist to confirm dx
• Dermatologist expertise facilitates the identification and
proper treatment of actual mimicking diagnoses, reduced
antibiotic use
Arakaki RY, Strazzula L, Woo E, Kroshinsky D. The impact of dermatology consultation on diagnostic accuracy and antibiotic use among patients with
suspected cellulitis seen at outpatient internal medicine offices: A randomized clinical trial. JAMA Dermatol. 2014.
David CV, Chira S, Eells SJ, et al. Diagnostic accuracy in patients admitted to hospitals with cellulitis. Dermatol Online J. 2011;17(3).
www.mghcme.org
Cellulitis vs Pseudocellulitis
• Up to 33% represent ‘pseudocellulitis’, or other mimicking inflammatory
skin conditions
• Diagnostic criteria are unclearly defined, variably applied
• Poorly-demarcated erythema, warmth, tenderness, edema
• Rubor, calor, dolor, tumor: inflammation (Celsus, 1st century AD)
• Per year, cellulitis misdiagnosis, hospitalization, and antibiosis leads to an
estimated:
• 50,000 unnecessary hospitalizations
• $195 million in avoidable health care spending
• 9,000 nosocomial infections, 1,000 C. difficile infections
• Dermatology or Infectious Diseases consultation proposed as clinical gold
standard
David11
CV et al. Diagnostic accuracy in patients admitted to hospitals with cellulitis. Dermatol Online J. 2011 Mar 15;17(3):1.
Weng QY, Raff AB, Cohen JM, Gunasekera N, Okhovat JP, Vedak P, Joyce C, Kroshinsky D, Mostaghimi A. Costs and Consequences Associated With
Misdiagnosed Lower Extremity Cellulitis. JAMA Dermatol. 2016 Nov 2. www.mghcme.orgAssociated Risk Factors
80
70
P>.05
% Affected Patients
60
50
Cellulitis
40 Pseudocellulitis
30
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Strazzula L et al. Inpatient dermatology consultation aids diagnosis of cellulitis among Factors
hospitalized patients: A multi-institutional analysis. J AmAcadDermatol. 2015 Jul;73(1):70-5
www.mghcme.orgLocal risk factors are more significant in the development of
leg cellulitis than systemic risk factors
• A systematic review and meta-analysis over 70y
• Local significant risk factors: prior cellulitis, prior leg
surgery, a ‘site of bacterial entry’ from wound,
ulceration, excoriating skin disease or toe-web
disease, chronic leg edema
• Obesity was the only potentially significant global
health factor
• Evaluation and management of predisposing factors
via regular follow-up visits may minimize risk
Quirke M et al. Risk factors for nonpurulent leg cellulitis: a systematic review and meta-analysis. Bjd.
Literature review 19;45-7/15. www.mghcme.orgMultidisciplinary Approach to Cellulitis at MGH • Dermatology consultation for patients presenting for presumed cellulitis within 24 hours of IV antibiotic initiation • 31% misdiagnosis rate • Decrease in IV antibiotic use (
Levell et al. Severe lower limb cellulitis is best diagnosed by dermatologists
and managed with shared care between primary and secondary care. Br J
Dermatol. 2011 Jun;164(6):1326-8.
• 210/ 635 referrals for lower limb cellulitis (33%) had other
diagnoses which did not require admission
• 96% true cellulitis pts managed entirely as outpatients, many at
home
• 28% patients with cellulitis had an underlying skin disease
identified and treated → reduced the risk of recurrent cellulitis,
leg ulceration, and lymphedema
• 18 /635 patients referred with lower limb cellulitis required
hospital admission for conventional treatment (3%)
www.mghcme.orgMicrobiology: Common Pathogens
• Adults:
- Streptococcus pyogenes, Staphylococcus aureus
- MSSA>>>MRSA, unless traumatic
• Children:
• Staphylococcus aureus
– Previously Haemophilus influenza
www.mghcme.orgMicrobiology: Immunosuppression
• Mild/Moderate: DM, ESRD, Cirrhosis, PDN20mg, other
immunosuppressives, AIDS
– Staphylococci, streptococci, GNR
– Atypical mycobacteria, deep fungal, nosocomials
Adapted from Bolognia Dermatology Fig 73.7
www.mghcme.orgMultidisciplinary Approach to Cellulitis at MGH:
Antibiotic Stewardship
• Mean number of antibiotics used: 2.8 (SD 1.3)
• 57.7% of all patients given longer than IDSA recommended
maximum antibiotic courses
• 68% of control patients given >=10days of antibiotics vs.
49% of intervention patients (pVancomycin in the Emergency Department
J Emerg Med. 2015 Jul; 49(1): 50–57.
19
www.mghcme.orgAntibiotic Stewardship: Treatment Algorithm
for Nonpurulent Cellulitis
(Add clindamycin if concern for necrotizing
fasciitis)
Adapted from: Raff AB, Kroshinsky D. Cellulitis: A Review. JAMA. 2016 Jul 19;316(3):325-37.
www.mghcme.orgAntibiotic Stewardship: Treatment Algorithm for Purulent Cellulitis
www.mghcme.org
21Raff AB, Kroshinsky D. Cellulitis: A Review. JAMA. 2016 Jul
19;316(3):325-37.
TMP/SMX: 2 DS tabs BID for patients
>100kg, immunosuppression, trauma-
induced SSTI
22
www.mghcme.orgOutpatient Prescriptions
• Multicenter, double-blind, randomized superiority trial in 5 US EDs
• 500 cellulitis outpatients > 12 yo with no wound, purulent
drainage, or abscess (confirmed by bedside ultrasound)
• Randomized to two treatment arms:
– Cephalexin, 500 mg 4 times daily, plus SMX-TMP, 320 mg/1600 mg
twice daily, for 7 days or
– Cephalexin plus placebo for 7 days
• Clinical cure in 83.5% of cephalexin plus SMX-TMP group vs
85.5% in the cephalexin group (95% CI, −9.7% to 5.7%; P = 0.50)
Moran GJ, et al. Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole vs Cephalexin Alone on Clinical Cure of Uncomplicated
Cellulitis: A Randomized Clinical Trial. JAMA 2017;317(20):2088-96.
23
www.mghcme.orgPredisposing factors to cellulitis
• Trauma:
– Piercings
– IVDA/‘popping’
– Bites
– Self-induced
• Tinea pedis/ onychomycosis
• Uncontrolled edema
Bjornsdottir S et al. Risk factors for acute cellulitis of the lower limb; a prospective case-control study. Clin Infect Dis 2005; 41: 1416-1422.
Roujeau JC et al. Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: a case-control study. Dermatology
2004; 209; 301-307.
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Chronic Ulcers & Infection
• Diabetic, stasis, decubitus
• Culture usually
– Polymicrobial
– Not involved in cellulitis
– Unnecessarily broad
coverage
-Lee PC, Turnidge J, McDonald PJ. Fine-needle aspiration biopsy in diagnosis
of soft tissue infections. J Clin Microbiol. 1985;22(1):80-83.
-Drinka P, Bonham P, Crnich CJ. Swab culture of purulent skin infection to
detect infection or colonization with antibiotic-resistant bacteria. J Am Med
Dir Assoc. 2012;13(1):75-79.
www.mghcme.orgChronic Ulcers & Infection
• Signs of infection:
– New onset pain
– Increased erythema
• Usually multiorganism
– Anaerobes, Gram-negative aerobes
www.mghcme.orgPredisposing Factors for Recurrence
• Peripheral vascular disease
• LN dissection
• XRT
• Liposuction
• Leg vein harvesting for CABG
• IVDA, skin popping
• Tinea pedis, onychomycosis
• Underlying vascular and lymphatic disease due to prior episodes
www.mghcme.orgPossible Complications of Typical Cellulitis
• Bacteremia
• Lymphadenitis
• Subacute bacterial endocarditis
• Glomerulonephritis
• Elephantiasis nostra verrucosa
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3
4
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Evaluation
• History
– Onset and duration: first or recurrent episode
– Local symptoms: pain/ pruritus/ burning/ dysesthesia
– Associated symptoms: SOB, arthritis, diarrhea, headache,
cough, chills, fever
– Course/ progression
• Past medical, family, social history
• Medications
www.mghcme.orgEvaluation: Objective
• General appearance
• Vital Signs:
– Fever: infection or systemic inflammation
• Pattern of fever (ie diurnal- Still’s disease)
– Tachycardia, hypotension
• LAD: infectious, inflammatory, neoplastic
www.mghcme.orgAtypical Features or Unresponsive to Treatment:
• Resistant pathogens
• Cellulitis variant (ie- necrotizing, fungal)
• Pseudocellulitis
www.mghcme.orgDiagnostic Testing for Cellulitis
• Labs
• Cultures
• Biopsy
• Imaging
• Special tests directed at pseudocellulitis
www.mghcme.orgDiagnostic Testing for Cellulitis
• Labs: CBC w/ differential, CMP
• Cultures:
– Blood: 91% negative and usually not helpful
• 19% S.pyogenes, 38% other β-hemolytic streptococci, 14% S.aureus,
28% Gram-negative
• ~50% of positive blood cultures represent contaminants
– Skin swabs, biopsy, aspiration usually low yield
• Highly variable results
– Not recommended for uncomplicated/routine cellulitis
Lazzarini L, Conti E, Tositti G, Lalla F de. Erysipelas and cellulitis: clinical and microbiological spectrum in an Italian tertiary care hospital. J Infect. 2005;51(5):383-389. Hook EW 3rd, Hooton TM, Horton CA, Coyle MB,
Ramsey PG, Turck M. Microbiologic evaluation of cutaneous cellulitis in adults. Arch Intern Med. 1986;146(2):295-297.
Krasagakis K, Valachis A, Maniatakis P, Krüger-Krasagakis S, Samonis G, Tosca AD. Report: Analysis of epidemiology, clinical features and management of erysipelas. Int J Dermatol. 2010;49(9):1012-1017
Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of america. Clin Infect Dis Off Publ
Infect Dis Soc Am. 2014;59(2):e10-e52.
Bates DW, Goldman L, Lee TH. Contaminant blood cultures and resource utilization. The true consequences of false-positive results. JAMA. 1991;265(3):365-369.
Duvanel T, Auckenthaler R, Rohner P, Harms M, Saurat JH. Quantitative cultures of biopsy specimens from cutaneous cellulitis. Arch Intern Med. 1989;149(2):293-296
Chira S, Miller LG. Staphylococcus aureus is the most common identified cause of cellulitis: a systematic review. Epidemiol Infect. 2010;138(3):313-317.
Gunderson CG, Martinello RA. A systematic review of bacteremias in cellulitis and erysipelas. J Infect. 2012;64(2):148-155.
www.mghcme.orgInability of PCR, Pyrosequencing, and Culture to Identify
the Cause of Cellulitis
• US ED evaluation of 49 subjects
– Samples taken from infected and unaffected skin
– No statistically significant differences between sides
– S. pyogenes > MSSA, no MRSA
• Conclusions: bacterial cause cannot be determined by
comparison of prevalence and quantity of pathogens
Crisp JG et al. Inability of Polymerase Chain Reaction, Pyrosequencing, and Culture of Infected and Uninfected Site Skin Biopsy Specimens to Identify
the Cause of Cellulitis. Clin Infect Dis. 2015 Aug 3.
www.mghcme.orgBlood Cultures in Cellulitis
• 183 patients presenting to the MGH ED 10/2014 – 2/2016
with a presumed diagnosis of cellulitis
• 32.8 % (60) patients received blood cultures
– 90% (54/60) did not meet IDSA guidelines
– 96.7% (58/60) no growth (1 growth, 1 contaminant)
• Extrapolated annual national cost of diagnostic imaging and
blood cultures for presumed cellulitis: $226.9 million dollars
Ko L, Kroshinsky D. JAMA Internal Medicine. www.mghcme.orgWhen to Biopsy
• Atypical case in immunosuppressed patient
• Concern about non-bacterial etiology
– Special stains, cultures
• Concern for pseudocellulitis
www.mghcme.orgDifferential diagnosis
for cellulitis
Raff AB, Kroshinsky D. Cellulitis: A Review. JAMA.
2016 Jul 19;316(3):325-37. www.mghcme.orgImaging: only to rule out other conditions • X-ray – Osteomyelitis (chronic), foreign body • Ultrasound – Abscess, pyomyositis • CT – Osteomyelitis, pyomyositis*, necrotizing fasciitis* • MRI – Osteomyelitis*, pyomyositis, necrotizing fasciitis Gold, RH, Hawkins, RA, Katz, RD. Bacterial osteomyelitis: Findings on plain radiography, CT, MR, and scintigraphy. AJR Am J Roentgenol 1991; 157:365. www.mghcme.org
Imaging in Cellulitis
• 183 patients presenting to the MGH ED 10/2014 – 2/2016 with a
presumed diagnosis of cellulitis
• 67.8% received imaging
• 22.3% received more than one test, up to four
Test Total Tests Tests Changing
Obtained Diagnosis
Ultrasound - N(%) 85 (46.4) 1 (1.1)
Plain Radiograph - N(%) 53 (29.0) 1(1.9)
Computed Tomography - N(%) 29 (15.8) 2 (6.9)
Magnetic Resonance - N(%) 11 (6.0) 4(36.4)
Ko L, Kroshinsky D. JAMA Internal Medicine.
www.mghcme.orgConclusions
• Cellulitis is a common, costly, frequently
overdiagnosed condition
• Consider alternate diagnoses in atypical cases or
cases unresponsive to standard treatment
• Limit use of biopsies, imaging, ulcer and blood
cultures
• Review antibiotic stewardship guidelines
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