SHORT REPORT

Skin and soft tissue infections in cirrhotics: A prospectiveanalysis of clinical presentation and factors affecting outcome

Ajit Sood & Vandana Midha & Omesh Goyal & Prerna Goyal &Pramod Sood & Suresh Kumar Sharma & Neena Sood

Received: 28 June 2013 /Accepted: 25 August 2013 /Published online: 5 April 2014# Indian Society of Gastroenterology 2014

Abstract Skin and soft tissue infections (SSTI) are an impor-tant cause of morbidity and mortality in patients with cirrho-sis. This prospective study aimed to analyze the clinical pro-file and factors affecting outcome of SSTIs in cirrhotics. Allcirrhotics hospitalized between September 2007 and August2010 were included. Frequency, site, extent, and type of SSTIwere noted. Of 1,395 cirrhotics, 19.4% (n = 271) had bacterialinfections, out of which 32.8 % (89/271) had SSTI. Alcoholwas the predominant etiological factor for cirrhosis; 95.2 %belonged to Child class B/C, and 67% gave history of barefootwalking. The most common site of SSTI was the lower limbs(87.1 %), cellulitis was the most common type (61.2 %), andgram-negative bacilli (GNB) is the most common organism(86.7 %). Mortality rate was 23.5 %. Serum creatinine andmodel for end-stage liver disease (MELD) score were in-dependent predictors of mortality. SSTIs in cirrhotics werecommon and mostly involved the lower limbs. Cellulitis wasthe most common type, and GNB was the most commonorganism. Serum creatinine and MELD score were indepen-dent predictors of mortality.

Keywords Cellulitis . Gram-negative bacilli . Liverdisease . Mortality

Introduction

Cirrhosis is associated with high morbidity and mortalitydue to either direct complications of the loss of liverfunction and/or portal hypertension or indirect complica-tions like hepatorenal syndrome and hepatocellular carci-noma. In addition, infections are an important cause ofmorbidity and mortality in cirrhotics [1]. Predisposition ofcirrhotics to various infections may be related to multipleimmune system defects like complement deficiency,reduced chemo-attractant activity, decreased polymorpho-nuclear leukocyte activity, and reduced number of Kupffercells [1].

Most of the existing data on bacterial infections incirrhosis refer to spontaneous bacterial peritonitis (SBP)which accounts for only 25 % to 31 % of the bacterialinfections [1, 2]. Other infections like urinary tract infec-tion, respiratory tract infection, meningitis, endocardititis,etc. have also been reported, though less frequently [2].Skin and soft tissue infections (SSTI) are also known tooccur in cirrhotics but have not been very well reported[3–10]. Also, physicians might not be able to appreciatethat SSTIs in cirrhotics may behave differently fromthat in noncirrhotics, and if not timely diagnosed andadequately treated, can result in significant morbidityand mortality. The aim of the present study was to eval-uate the clinical and microbiological profile of SSTIs incirrhotics and to identify factors influencing the outcomeof the disease.

A. Sood (*) :O. GoyalDepartment of Gastroenterology, Dayanand MedicalCollege and Hospital, Ludhiana 141 001, Indiae-mail: ajitsood10@in.com

V. Midha : P. Goyal : P. SoodDepartment of Medicine, Dayanand Medical College and Hospital,Ludhiana 141 001, India

N. SoodDepartment of Pathology, Dayanand Medical College and Hospital,Ludhiana 141 001, India

S. K. SharmaCollege of Nursing, Dayanand Medical College and Hospital,Ludhiana 141 001, India

Indian J Gastroenterol (May–June 2014) 33(3):281–284DOI 10.1007/s12664-014-0454-2

Material and methods

This prospective study included all cirrhotics admitted toa tertiary care hospital in northern India from September2007 to August 2010. The diagnosis and etiological workup of cirrhosis was performed according to standardcriteria. Detailed history, clinical examination, and routinelaboratory work up was carried out. Child–Turcotte–Pugh(CTP) score and model for end-stage liver disease(MELD) score were calculated. Cultures from the localSSTI site were sent, wherever possible. Venous Dopplerof the lower limb was done, where indicated. Exclusioncriteria included uncontrolled diabetes, advanced cardio-pulmonary disease, chronic renal failure, lymphedema,significant trauma preceding development of SSTI, orintake of immunosuppressives or corticosteroids.

SSTI was defined as an infection involving skin, subcuta-neous tissue, fascia, or muscle. Detailed information regardingthe site extent, presence of edema, and nature/severity (mildincluding cellulitis, pustules, hemorrhagic bullae, ulcers, anddischarging sinuses and severe including necrotising fascitisor myonecrosis) of SSTI were noted.

Data is presented as mean±standard deviation (SD)for quantitative variables and proportions for qualitativevariables. Multiple logistic regression analysis was performedto find factors affecting mortality in cirrhotics with SSTIs. Ap -value of <0.05 was considered significant.

Results

Of the 1,395 patients with cirrhosis, 19.4 % (271/1,395) werediagnosed to have bacterial infections [SBP, 45 % (122/271);SSTI, 32.8 % (89/271); UTI, 24.5 % (66/271); bacteremia,12.9 % (35/271); RTI, 8.9 % (24/271); and meningitis, 0.74%(2/271)]. Sixty-three (22.9 %) patients had multiple infections.Of the SSTI patients, two (2.4 %) had concomitant UTI andone (1.2 %) had concomitant SBP. Comparison of variousclinical and lab parameters between cirrhotics who developedSSTI and those who did not is shown in Table 1. On multi-variate analysis, CTP and MELD scores were independentpredictors of development of SSTI (p=0.001).

Of the 89 patients with SSTI, four were excluded (uncon-trolled diabetes, two; chronic renal failure, one; and conges-tive cardiac failure, one), and the remaining 85 were includedfor further analysis. Mean age was 49.8±10.2 years, and96.5%were males. A history of SSTI was the chief presentingcomplaint in 16 (18.8 %) patients, one of the presentingcomplaints in 52 (61.2 %), while 17 (20 %) patients did notcomplain of SSTI. The mean duration of presence of SSTIwas 15.3±20.5 days. Four (4.7 %) patients had a history ofrecurrent/persistent (>4 weeks) SSTI of the lower limb(Fig. 1). Other presenting complaints in patients with SSTI

Table 1 Clinical and laboratory parameters in cirrhotics with andwithoutbacterial infection

Characteristic Cirrhotics withoutSSTI (n=1,306)

Cirrhotics withSSTI (n =85)

p-value

Age (years) 51.1±11.2 49.8±10.2 0.297

Male sex 83.7 (1,094) 97.6 (83) 0.0001

Alcoholic cirrhosis 57.7 (754) 67.1 (57) 0.111

Bilirubin (mg/dL) 4.72±6.7 5.94±6.2 0.102

Albumin (g/dL) 2.59±1.4 2.72±2.3 0.429

Creatinine (mg/dL) 1.1±0.4 1.46±0.89 0.0001

INR 2.02±0.82 2.19±0.85 0.065

CTP score 9.6±2.2 10.1±2.1 0.042

MELD score 18.3±6.0 22.4±8.0 0.0001

Data are expressed as mean±SD or percentages (number)

CTP Child–Turcotte–Pugh, INR international normalized ratio, MELDmodel for end-stage liver disease, SSTI skin and soft tissue infection

Fig. 1 a Multiple ulcers and cellulitis involving both the lower limbs in apatient with persistent SSTI. b Hemorrhagic bulla and cellulitis on thedorsal aspect of foot in a patient with acute skin and soft tissue infection

282 Indian J Gastroenterol (May–June 2014) 33(3):281–284

were fever (31), abdominal distension (33), gastrointestinalbleed (18), jaundice (21), altered sensorium (14), anddecreased urine output (n=7). Sixty-two (73 %) of thesepatients were engaged in agriculture, and 57 (67 %) gave ahistory of barefoot walking.

Etiology of cirrhosis in patients with SSTI was alcoholalone (38); HCV alone (11); alcohol and HCV (17); HBValone (3); alcohol plus HBV (2); and HBV plus HCV (1),NAFLD (3), and cryptogenic (10). History of beta-blockerintake as a secondary prophylaxis for variceal bleed waspresent in 76.7 % (46/60) of the known cirrhotics. Hepa-tomegaly was present in 32.9 % (n=28) patients, spleno-megaly in 12.9 % (n=11), and ascites in 62.4 % (n=53)patients. Baseline clinical and lab parameters of cirrhoticswith SSTI are shown in Table 1. Other baseline labparameters were total leukocyte count (11.39±9.4 cells/mm3), polymorphs (70.5±15.9 %), platelets (114.4±71×1,000/mm3), and urea (66.3±53.1 mg/dL). Of the SSTIpatients, 56.4 and 38.8 belonged to Child classes B and C,respectively.

The most common site of SSTI was lower limbs(n=74, 87.1 %; Fig. 1), followed by abdominal wall(n=5, 5.9 %), upper limbs (n=2, 2.4 %), and glutealregion (n=1, 1.2 %). Among the patients with lowerlimb involvement, left limb was involved in 33(44.6 %), right in 31 (41.9 %), and both in 10(13.5 %) cases. Forty-eight (64.8 %) patients with SSTIof the lower limb had history of preceding edema oflower limbs. Venous Doppler was performed in patientswith unilateral lower limb edema (n=8), but it did notshow any evidence of deep vein thrombosis. The typesof SSTI were cellulitis (n=52, 61.2 %), hemorrhagicbullae (n=12, 14.1 %), pustules (n=9, 10.6 %), ulcers(n=8, 9.4 %), discharging sinuses (n=2, 2.4 %), andnecrotizing fasciitis (n=2, 2.4 %).

Cultures from local SSTI site were positive in 15/28(53.6 %) patients. Predominant type of organisms wereGram-negative bacilli (GNB; 13/15, 86.7 %) and therest were Gram-positive cocci (GPC; 2/15, 13.3 %)[Pseudomonas (n=5), Klebsiella (n=4), Escherichiacoli (n=4), Acinetobacter (n=3), Staphylococcus(n=32), and Proteus (n=31)].

All patients received parenteral antibiotics. Fasciotomywas done in four patients, and two patients underwentsurgical debridement. Overall mortality rate was 23.5 %(20/85), being more in patients with necrotizing fasciitis(100 %, n=32/2) compared to those with cellulitis(3.8 %, n=32/52; p=0.0042). Univariate analysis ofvarious factors predicting mortality in cirrhotics withSSTI is shown in Table 2. On multivariate analysis,serum creatinine (p=0.018), and MELD score (p=0.034) were found to be independent predictors ofmortality.

Discussion

Skin and soft tissue infections are an important cause ofmorbidity and mortality in cirrhotics. However, the descrip-tion of SSTIs in literature is mostly limited to small casereports/case series [3–9]. The present study is one of thelargest prospective studies describing the presentation, bacte-riological profile, and factors affecting outcome of SSTI inpatients with cirrhosis.

The primary mechanism leading to the development ofSSTI in cirrhotics appears to be same as that for SBP.Increased bacterial translocation from gut due to alteredintestinal immunity and bacterial overgrowth in cirrhoticsproduces Gram-negative bacteremia giving an opportunityfor distant invasion by these microorganisms [1]. Thegrowth of Gram-negative enteric organisms from the localSSTI site [8, 9] (as also in the present study) supports thishypothesis.

In the present study, SSTIs were the second most com-mon type of bacterial infection, next only to SBP. Another

Table 2 Univariate analysis of clinical and laboratory parameters insurvivor and nonsurvivor cirrhotics with skin and soft tissue infection

Parameter Survivors(n =65)

Nonsurvivors(n =20)

p-value

Age (years) 49.2±10.3 51.7±9.7 0.355

Male sex 96.9 95 0.684

Alcoholic cirrhosis 63.1 80 0.159

Duration of cirrhosis(months)

16.8±13.8 21.2±29.0 0.106

Ascites 60 70 0.420

Encephalopathy 18.5 50 0.005

TLC (×106/cumm) 9.43±5.2 17.5±11.7 0.000

Urea (mg/dL) 57.9±39.2 106.9±73.2 0.000

Creatinine (mg/dL) 1.19±0.6 2.36±1.2 0.000

Bilirubin (mg/dL) 4.73±5.5 9.89±9.41 0.003

Albumin (g/dL) 2.84±2.6 2.33±0.4 0.382

INR 2.08±0.8 2.53±0.8 0.035

CTP 9.37±2 11.1±1.6 0.001

MELD 20.3±7 29.4±7 0.0001

Type of lesion

Cellulitis 76.9 (50) 10 (2) 0.0001

Hemorrhagic bullae 1.5 (1) 55 (11) 0.0001

Pustules 9.2 (6) 33.3 (3) 0.4336

Ulcers 10.8 (7) 12.5 (1) 0.6739

Discharging sinuses 1.5 (1) 50 (1) 0.4174

Necrotizing fasciitis 0 (0) 10 (2) 0.0532

Data are expressed as mean±SD or percentages (number)

CTP Child–Turcotte–Pugh, INR international normalized ratio, MELDmodel for end-stage liver disease, TLC total leukocyte count

Indian J Gastroenterol (May–June 2014) 33(3):281–284 283

important aspect of the SSTIs noticed in our study is thatmost of the SSTI cases (87.1 %) involved lower limbs.Both of these findings could be explained by the presenceof possible risk factors like lower limb edema (65 %) andbarefoot walking (67 %) in a significant proportion of ourpatients. In cirrhotics, chronic edema and venous insuffi-ciency of the lower limbs related to functional obstructionof inferior vena cava, due to tense ascites, may favorseeding of the bacteria in the lower limbs [11]. Secondly,minor trauma while walking barefoot, may act as a trigger-ing factor for SSTI of the lower limb. Mohan et al. hasreported barefoot walking as a significant risk factor fordeveloping SSTI in cirrhotics [9].

The bacteria responsible for causing various infections incirrhotics may be different from those in noncirrhotics. Incirrhotics, GNB, mainly E. coli , predominate in SBP andurinary tract infections, while GPC predominate in patientswith pneumonia and bacteremia associated with invasive pro-cedures [12]. Data regarding the type of bacteria causing SSTIis scarce [8, 9]. Horowitz et al. reported four cases of fulmi-nant bullous cellulitis in cirrhotics caused by GNB [8]. Similarresults were noted in the present study. This is in contrast toSSTI in noncirrhotics, where GPC usually predominate.Awareness about this difference in the spectrum of micro-organisms is important as early administration of specificantibacterial therapy may help to achieve better outcome.

The mortality rate in cirrhotics with SSTI varies from 19%to 100 %, depending on disease severity [8, 9]. The overallmortality rate associated with SSTIs in our study was 23.5 %and that for necrotizing infections was 100 %. Hemorrhagicbullae and Child–Pugh grade C have been reported as possiblepredictors of mortality in cirrhotics with SSTI [4, 5]. In thepresent study, on multivariate analysis, serum creatinine andMELD score were found to be independent predictors ofmortality.

Potential limitations of our study are the absence of acontrol group of noncirrhotics with SSTI and the lack offollow up. It would be important to follow up SSTI patientsfor development of recurrent SSTI or other bacterial infec-tions, as underlying predisposing factors are expected to per-sist in a particular patient. Also, long-term antibiotic use assecondary prophylaxis for SSTI, similar to that for SBP, needsconsideration in view of high morbidity and mortality associ-ated with SSTIs.

To conclude, SSTIs in cirrhotics were common andmainly involved lower limbs. Cellulitis was the most

common type, and GNB was the most common organism.Serum creatinine and MELD score were independent pre-dictors of mortality. Early institution of antibiotics cover-ing GNB and surgical intervention, where indicated, maylead to better outcome.

Conflict of interest Ajit Sood, Vandana Midha, Omesh Goyal, PrernaGoyal, Pramod Sood, Suresh Kumar Sharma and Neena Sood declarethat they have no conflict of interest.

Ethics statement The authors declare that the study was performed in amanner to conform with the Helsinki Declaration of 1975, as revised in2000 and 2008 concerning Human and Animal Rights, and the authorsfollowed the policy concerning Informed Consent as shown on www.Springer.com.

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