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Cellulitis: evaluation of possible predisposing factors in hospitalized patients
Cellulitis: Evaluation of Possible Predisposing Factors in Hospitalized Patients Polyxeni Koutkia, Eleftherios Mylonakis, and John Boyce
We conducted a prospective study among 62 hospitalized adults, to evaluate the factors that contribute to the development of cellulitis. The majority of patients had multiple possible predisposing factors, and the most common were: diabetes mellitus (31/62), history of cellulitis (30/62), edema (28/62), peripheral vascular disease (25/62), and skin changes sugges-
tive of tinea pedis (20/62). A significant number of patients reported and were clinically noted to have dry skin (42/62). Large controlled studies are needed to evaluate whether aggressive control of possible risk factors can reduce the incidence of cellulitis. © 1999 Elsevier Science Inc.
INTRODUCTION
by the Institutional Review Board of our hospital. Patients were examined and a history was obtained using a standardized questionnaire. We included patients with erythema, swelling, local warmth, pain, and the clinical appearance consistent with cellulitis, with or without local fluid collection. Our exclusion criteria were minimal erythema, swelling without erythema, wound infection, lymphangitis, or thrombophlebitis. Patients were carefully examined for the presence of peripheral pulses, and for evidence of dryness, roughness, or cracking of the skin. In patients with cellulitis of the lower extremities, the skin of the patients’ feet was examined for clinical signs suggestive of tinea pedis, including erythema, scaling, cracking, or maceration of the interdigital spaces. Patients with cracks, scaling, or maceration of the skin in the interdigital toe-web spaces and nail hyperkeratosis were considered to have probable tinea pedis, but no fungal cultures were obtained.
Cellulitis is an infectious disease common in both outpatient and hospital practice (Hook et al. 1986; Tanner and Hale 1983). It is defined as an acute inflammatory condition characterized by cutaneous erythema, warmth, edema, and/or pain (Kielhofner et al. 1988; Leyden 1989; Sachs 1991). Since the beginning of the century clinicians have reported strategies for the prevention of cellulitis (Ginsberg 1981). However, few systematic studies have been done to evaluate the possible predisposing factors leading to this infection. The aim of our study was to evaluate the relative frequency of risk factors that may lead to cellulitis and to define patient populations that may have increased risk for developing this infection.
PATIENTS This prospective study included patients with the admitting diagnosis of cellulitis and it was approved From the Miriam Hospital, Brown University, Providence, Rhode Island. Address reprint requests to Eleftherios Mylonakis, M.D., The Miriam Hospital, 164 Summit Avenue, Providence, RI 02906 USA. Received 20 November 1998; revised and accepted 24 January 1999.
DIAGN MICROBIOL INFECT DIS 1999;34:325–327 © 1999 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
RESULTS The study population consisted of 62 patients (40 male and 22 female), with an age range from 18 to 88 years (median 66 years). The duration of symptoms prior to admission was 2 to 20 days (median 7 days).
0732-8893/99/$–see front matter PII S0732-8893(99)00028-0
Koutkia et al.
326 On admission 14 of 62 (22.5%) patients had oral temperature of 37.7°C or more (median 37.3°C) and none had vital sign compromise (systolic blood pressure: range 95–180 mmHg, median 125 mmHg; diastolic blood pressure: range 55–105 mmHg, median 70 mmHg). White blood cell count on admission was performed in 61 of 62 patients (one patient refused) and ranged from 3,600 to 22,200 cells/mL (median 11,600 cells/mL). Blood cultures, prior to the onset of antibiotic therapy, were performed in 36 of 62 (58%) of the patients. Usually two blood cultures for aerobic and two for anaerobic pathogens were obtained (except of one patient who had one and two patients who had three sets of blood cultures) and in all patients (36/36) blood cultures were negative. Most patients (48/62, 77%) had cellulitis involving the lower extremities. Other affected areas were upper extremities (8/62, 13%), face (2/62, 3%), lower abdomen (2/62, 3%), head (1/62, 2%) and back (1/62, 2%). A possible portal of entry was found in 20/62 (32%) of the patients. Three of our younger patients were intravenous drug users and all had injection sites in the upper extremities where they developed the infection. In Table 1 we summarize the most common predisposing factors and comorbid conditions in our study. Only five patients had one possible predisposing factor (dry skin in three and diabetes mellitus in two patients). The remaining patients (57/62, 92%) had more than one possible predisposing factor (Table 2), making it difficult to evaluate the relative impact of each of those conditions. Ten patients with diabetes (10/31, 32%) were found to have skin changes suggestive of tinea pedis. Four of the patients with dry skin had hypothyroidism that may have contributed to dry skin and local edema. Of note is that almost all (25/27, 92%) of the patients with saphenous venectomy in our cohort were not informed about the possible risk of developing infec-
TABLE 1 Possible Predisposing Factors and Comorbid Conditions among 62 Hospitalized Adults with Cellulitis Predisposing Factors and Comorbid Conditions
No. of Patients (%)
Dry skin Diabetes mellitus History of cellulitis (⬎1 episode) Edema of the affected lower extremity Peripheral vascular disease Trauma involving the affected area Skin changes suggestive of tinea pedis Saphenous venectomy Neoplastic disease Radiation therapy involving the affected area
42 (68) 31 (50) 30 (48) 28 (45) 25 (40) 20 (32) 20 (32) 17 (27) 8 (13) 2 (3)
TABLE 2 Number of Possible Predisposing Factors and Comorbid Conditions among 62 Hospitalized Adults with Cellulitis Number of Predisposing Conditions 1 2 3 4 5 or more
No. of Patients (%) 5 (8%) 11 (18%) 11 (18%) 12 (19%) 23 (37%)
tion after the operation, underlying the importance of foot hygiene in this population. Among the 30 patients with multiple episodes of cellulitis, the most common possible predisposing factors and comorbid conditions were dry skin (22/30, 73%), diabetes mellitus (17/30, 57%), edema (13/30, 43%), and skin changes suggestive of tinea pedis (8/30, 27%). Of the patients in our study, 61 of 62 received intravenous antibiotic therapy (one patient refused). Five individuals required prolonged hospitalization and antibiotic therapy due to problems not related to cellulitis, and one of them died. Also, two patients left against medical advice and eight were discharged for further intravenous antibiotic therapy as outpatients. The remaining 46 patients received intravenous antibiotic therapy for 2 to 14 days (median 5 days) and were hospitalized for 3 to 19 days (median 6 days). Four patients required drainage of softtissue abscesses (Gram stain revealed polymorphonuclear cells in four of four cases, but cultures were positive in two of four cases and both yielded Staphylococcus aureus), and one patient with diabetes mellitus underwent transmetatarsal amputation and another diabetic patient underwent vascular surgery to improve blood supply to the affected limb.
DISCUSSION Diabetes mellitus, history of previous episodes of cellulitis, edema of the lower extremities, and peripheral vascular disease were the most common established underlying conditions in our study. Diabetic patients have decreased immunocompetence, abnormal proprioception, and neuropathy that predisposes them to cellulitis (Olefsky 1996; Suss and Middleton 1987). Chronic venous stasis and edema results in tissue hypoxia and in altered white blood cell and antibody penetration into the edematous tissue (Baddour and Bisno 1985; Suss and Middleton 1987). Also, once an episode of cellulitis has occurred, the resultant inflammation may lead to local
Cellulitis destruction of lymphatic channels, thus further impairing lymphatic flow and creating a vicious cycle (Baddour and Bisno 1985; Leyden 1989; Sachs 1991; Simon and Cody 1992; Staren et al. 1996). Better patient education and measures that would facilitate venous and lymphatic drainage (support stockings, elevation of the extremities when sitting) and medical management of lower-extremity edema may be of benefit (Greenberg et al. 1982). Diabetic patients should not walk barefoot, need to inspect their feet daily, keep them dry, clean between the toes, wear properly fitting soft shoes, cut toenails straight across, and visit their foot care specialist regularly (Olefsky 1996). The most common, but less well studied, possible predisposing condition in our study was dry skin. Almost all the patients with dry skin reviewed herein complained of cracks in their skin. Breaks in the skin may allow the penetration of the pathogens, resulting in acute infection. The association between dry skin and cellulitis needs more investigation in order to evaluate this new possible risk factor. Patients with dry skin should lubricate it using a nongreasy
327 lotion or cream to avoid cracking. Physicians should look for evidence of dry skin and treat underlying dermatological problems. Especially, clinicians should regularly examine the feet of high-risk patients for the presence of athlete’s foot and in highrisk patients any break in the skin of the affected leg should be carefully treated (Baddour and Bisno 1982, 1984; Greenberg et al. 1982; Leicht 1996; Leyden and Kligman 1975, 1978; Semel and Goldin 1996). In conclusion, certain patient populations are at increased risk for developing cellulitis. Identification of these patients may lead to better prevention (Baddour and Bisno 1984; Greenberg et al. 1982; Hook 1987; Semel and Goldin 1996). Dry skin and tinea pedis need to be treated to minimize recurrences of cellulitis because these possible predisposing factors are amenable to prevention. Further studies are needed to determine if tight blood glucose control and amelioration of peripheral vascular disease can decrease the incidence of cellulitis. A large casecontrol study may provide better insight on the relative impact of each of the predisposing factors in the development of cellulitis.
REFERENCES Baddour LM, Bisno AL (1982) Recurrent cellulitis after saphenous venectomy for coronary bypass surgery. Ann Intern Med 97:493–496. Baddour LM, Bisno AL (1984) Recurrent cellulitis after coronary bypass surgery. Association with superficial fungal infection in saphenous venectomy limbs. JAMA 251:1049–1052. Baddour LM, Bisno AL (1985) Non-group A betahemolytic streptococcal cellulitis. Association with venous and lymphatic compromise. Am J Med 79:155–159. Ginsberg MB (1981) Cellulitis: Analysis of 101 cases and review of the literature. South Med J 74:530–533. Greenberg J, DeSanctis RW, Mills RM Jr (1982) Vein-donorleg cellulitis after coronary artery bypass surgery. Ann Intern Med 97:565–566. Hook 3d EW, Hooton TM, Coyle MB, Ramsey PG, Turck M (1986) Microbiologic evaluation of cutaneous cellulitis in adults. Arch Intern Med 146:295–297. Hook 3d EW (1987) Acute cellulitis. Arch Dermatol 123:460– 461. Kielhofner MA, Brown B, Dall L (1988) Influence of underlying disease process on the utility of cellulitis needle aspirates. Arch Intern Med 148:2451–2452. Leicht S (1996) Multiple recurrent cellulitis [letter]. Arch Dermatol 132:1131–1132. Leyden J (1989) Cellulitis. Arch Dermatol 125:823–824.
Leyden J, Kligman AM (1975) Aluminum chloride in the treatment of symptomatic athlete’s foot. Arch Dermatol 111:1004–1010. Leyden J, Kligman AM (1978) Interdigital athlete’s foot. The interaction of dermatophytes and resident bacteria. Arch Dermatol 114:1466–1472. Olefsky JM (1996) Diabetic foot diabetes mellitus. In: Cecil’s textbook of medicine. 20th ed. Eds, Bennett JC, Plum F. Philadelphia: WB Saunders Company, pp. 1275–1277. Sachs MK (1991) Cutaneous cellulitis. Arch Dermatol 127: 493–496. Semel JD, Goldin H (1996) Association of athlete’s foot with cellulitis of the lower extremities: Diagnostic value of bacterial cultures of ipsilateral interdigital space samples. Clin Infect Dis 23:1162–1164. Simon MS, Cody RL (1992) Cellulitis after axillary lymph node dissection for carcinoma of the breast. Am J Med 93:543–548. Staren ED, Klepac S, Smith AP, Hartsell WF, Segretti S, Witt TR, Griem K, Bines SD (1996) The dilemma of delayed cellulitis after breast conservation therapy. Arch Surg 131:651–654. Suss SJ, Middleton DB (1987) Cellulitis and related skin infections. Am Fam Physician 36:126–136. Tanner MH, Hale DC (1983) The nature of an infectious disease practice in a community hospital. Rev Infect Dis 5:1049–1060.
We conducted a prospective study among 62 hospitalized adults, to evaluate the factors that contribute to the development of cellulitis. The majority of patients had multiple possible predisposing factors, and the most common were: diabetes mellitus (31/62), history of cellulitis (30/62), edema (28/62), peripheral vascular disease (25/62), and skin changes sugges-
tive of tinea pedis (20/62). A significant number of patients reported and were clinically noted to have dry skin (42/62). Large controlled studies are needed to evaluate whether aggressive control of possible risk factors can reduce the incidence of cellulitis. © 1999 Elsevier Science Inc.
INTRODUCTION
by the Institutional Review Board of our hospital. Patients were examined and a history was obtained using a standardized questionnaire. We included patients with erythema, swelling, local warmth, pain, and the clinical appearance consistent with cellulitis, with or without local fluid collection. Our exclusion criteria were minimal erythema, swelling without erythema, wound infection, lymphangitis, or thrombophlebitis. Patients were carefully examined for the presence of peripheral pulses, and for evidence of dryness, roughness, or cracking of the skin. In patients with cellulitis of the lower extremities, the skin of the patients’ feet was examined for clinical signs suggestive of tinea pedis, including erythema, scaling, cracking, or maceration of the interdigital spaces. Patients with cracks, scaling, or maceration of the skin in the interdigital toe-web spaces and nail hyperkeratosis were considered to have probable tinea pedis, but no fungal cultures were obtained.
Cellulitis is an infectious disease common in both outpatient and hospital practice (Hook et al. 1986; Tanner and Hale 1983). It is defined as an acute inflammatory condition characterized by cutaneous erythema, warmth, edema, and/or pain (Kielhofner et al. 1988; Leyden 1989; Sachs 1991). Since the beginning of the century clinicians have reported strategies for the prevention of cellulitis (Ginsberg 1981). However, few systematic studies have been done to evaluate the possible predisposing factors leading to this infection. The aim of our study was to evaluate the relative frequency of risk factors that may lead to cellulitis and to define patient populations that may have increased risk for developing this infection.
PATIENTS This prospective study included patients with the admitting diagnosis of cellulitis and it was approved From the Miriam Hospital, Brown University, Providence, Rhode Island. Address reprint requests to Eleftherios Mylonakis, M.D., The Miriam Hospital, 164 Summit Avenue, Providence, RI 02906 USA. Received 20 November 1998; revised and accepted 24 January 1999.
DIAGN MICROBIOL INFECT DIS 1999;34:325–327 © 1999 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
RESULTS The study population consisted of 62 patients (40 male and 22 female), with an age range from 18 to 88 years (median 66 years). The duration of symptoms prior to admission was 2 to 20 days (median 7 days).
0732-8893/99/$–see front matter PII S0732-8893(99)00028-0
Koutkia et al.
326 On admission 14 of 62 (22.5%) patients had oral temperature of 37.7°C or more (median 37.3°C) and none had vital sign compromise (systolic blood pressure: range 95–180 mmHg, median 125 mmHg; diastolic blood pressure: range 55–105 mmHg, median 70 mmHg). White blood cell count on admission was performed in 61 of 62 patients (one patient refused) and ranged from 3,600 to 22,200 cells/mL (median 11,600 cells/mL). Blood cultures, prior to the onset of antibiotic therapy, were performed in 36 of 62 (58%) of the patients. Usually two blood cultures for aerobic and two for anaerobic pathogens were obtained (except of one patient who had one and two patients who had three sets of blood cultures) and in all patients (36/36) blood cultures were negative. Most patients (48/62, 77%) had cellulitis involving the lower extremities. Other affected areas were upper extremities (8/62, 13%), face (2/62, 3%), lower abdomen (2/62, 3%), head (1/62, 2%) and back (1/62, 2%). A possible portal of entry was found in 20/62 (32%) of the patients. Three of our younger patients were intravenous drug users and all had injection sites in the upper extremities where they developed the infection. In Table 1 we summarize the most common predisposing factors and comorbid conditions in our study. Only five patients had one possible predisposing factor (dry skin in three and diabetes mellitus in two patients). The remaining patients (57/62, 92%) had more than one possible predisposing factor (Table 2), making it difficult to evaluate the relative impact of each of those conditions. Ten patients with diabetes (10/31, 32%) were found to have skin changes suggestive of tinea pedis. Four of the patients with dry skin had hypothyroidism that may have contributed to dry skin and local edema. Of note is that almost all (25/27, 92%) of the patients with saphenous venectomy in our cohort were not informed about the possible risk of developing infec-
TABLE 1 Possible Predisposing Factors and Comorbid Conditions among 62 Hospitalized Adults with Cellulitis Predisposing Factors and Comorbid Conditions
No. of Patients (%)
Dry skin Diabetes mellitus History of cellulitis (⬎1 episode) Edema of the affected lower extremity Peripheral vascular disease Trauma involving the affected area Skin changes suggestive of tinea pedis Saphenous venectomy Neoplastic disease Radiation therapy involving the affected area
42 (68) 31 (50) 30 (48) 28 (45) 25 (40) 20 (32) 20 (32) 17 (27) 8 (13) 2 (3)
TABLE 2 Number of Possible Predisposing Factors and Comorbid Conditions among 62 Hospitalized Adults with Cellulitis Number of Predisposing Conditions 1 2 3 4 5 or more
No. of Patients (%) 5 (8%) 11 (18%) 11 (18%) 12 (19%) 23 (37%)
tion after the operation, underlying the importance of foot hygiene in this population. Among the 30 patients with multiple episodes of cellulitis, the most common possible predisposing factors and comorbid conditions were dry skin (22/30, 73%), diabetes mellitus (17/30, 57%), edema (13/30, 43%), and skin changes suggestive of tinea pedis (8/30, 27%). Of the patients in our study, 61 of 62 received intravenous antibiotic therapy (one patient refused). Five individuals required prolonged hospitalization and antibiotic therapy due to problems not related to cellulitis, and one of them died. Also, two patients left against medical advice and eight were discharged for further intravenous antibiotic therapy as outpatients. The remaining 46 patients received intravenous antibiotic therapy for 2 to 14 days (median 5 days) and were hospitalized for 3 to 19 days (median 6 days). Four patients required drainage of softtissue abscesses (Gram stain revealed polymorphonuclear cells in four of four cases, but cultures were positive in two of four cases and both yielded Staphylococcus aureus), and one patient with diabetes mellitus underwent transmetatarsal amputation and another diabetic patient underwent vascular surgery to improve blood supply to the affected limb.
DISCUSSION Diabetes mellitus, history of previous episodes of cellulitis, edema of the lower extremities, and peripheral vascular disease were the most common established underlying conditions in our study. Diabetic patients have decreased immunocompetence, abnormal proprioception, and neuropathy that predisposes them to cellulitis (Olefsky 1996; Suss and Middleton 1987). Chronic venous stasis and edema results in tissue hypoxia and in altered white blood cell and antibody penetration into the edematous tissue (Baddour and Bisno 1985; Suss and Middleton 1987). Also, once an episode of cellulitis has occurred, the resultant inflammation may lead to local
Cellulitis destruction of lymphatic channels, thus further impairing lymphatic flow and creating a vicious cycle (Baddour and Bisno 1985; Leyden 1989; Sachs 1991; Simon and Cody 1992; Staren et al. 1996). Better patient education and measures that would facilitate venous and lymphatic drainage (support stockings, elevation of the extremities when sitting) and medical management of lower-extremity edema may be of benefit (Greenberg et al. 1982). Diabetic patients should not walk barefoot, need to inspect their feet daily, keep them dry, clean between the toes, wear properly fitting soft shoes, cut toenails straight across, and visit their foot care specialist regularly (Olefsky 1996). The most common, but less well studied, possible predisposing condition in our study was dry skin. Almost all the patients with dry skin reviewed herein complained of cracks in their skin. Breaks in the skin may allow the penetration of the pathogens, resulting in acute infection. The association between dry skin and cellulitis needs more investigation in order to evaluate this new possible risk factor. Patients with dry skin should lubricate it using a nongreasy
327 lotion or cream to avoid cracking. Physicians should look for evidence of dry skin and treat underlying dermatological problems. Especially, clinicians should regularly examine the feet of high-risk patients for the presence of athlete’s foot and in highrisk patients any break in the skin of the affected leg should be carefully treated (Baddour and Bisno 1982, 1984; Greenberg et al. 1982; Leicht 1996; Leyden and Kligman 1975, 1978; Semel and Goldin 1996). In conclusion, certain patient populations are at increased risk for developing cellulitis. Identification of these patients may lead to better prevention (Baddour and Bisno 1984; Greenberg et al. 1982; Hook 1987; Semel and Goldin 1996). Dry skin and tinea pedis need to be treated to minimize recurrences of cellulitis because these possible predisposing factors are amenable to prevention. Further studies are needed to determine if tight blood glucose control and amelioration of peripheral vascular disease can decrease the incidence of cellulitis. A large casecontrol study may provide better insight on the relative impact of each of the predisposing factors in the development of cellulitis.
REFERENCES Baddour LM, Bisno AL (1982) Recurrent cellulitis after saphenous venectomy for coronary bypass surgery. Ann Intern Med 97:493–496. Baddour LM, Bisno AL (1984) Recurrent cellulitis after coronary bypass surgery. Association with superficial fungal infection in saphenous venectomy limbs. JAMA 251:1049–1052. Baddour LM, Bisno AL (1985) Non-group A betahemolytic streptococcal cellulitis. Association with venous and lymphatic compromise. Am J Med 79:155–159. Ginsberg MB (1981) Cellulitis: Analysis of 101 cases and review of the literature. South Med J 74:530–533. Greenberg J, DeSanctis RW, Mills RM Jr (1982) Vein-donorleg cellulitis after coronary artery bypass surgery. Ann Intern Med 97:565–566. Hook 3d EW, Hooton TM, Coyle MB, Ramsey PG, Turck M (1986) Microbiologic evaluation of cutaneous cellulitis in adults. Arch Intern Med 146:295–297. Hook 3d EW (1987) Acute cellulitis. Arch Dermatol 123:460– 461. Kielhofner MA, Brown B, Dall L (1988) Influence of underlying disease process on the utility of cellulitis needle aspirates. Arch Intern Med 148:2451–2452. Leicht S (1996) Multiple recurrent cellulitis [letter]. Arch Dermatol 132:1131–1132. Leyden J (1989) Cellulitis. Arch Dermatol 125:823–824.
Leyden J, Kligman AM (1975) Aluminum chloride in the treatment of symptomatic athlete’s foot. Arch Dermatol 111:1004–1010. Leyden J, Kligman AM (1978) Interdigital athlete’s foot. The interaction of dermatophytes and resident bacteria. Arch Dermatol 114:1466–1472. Olefsky JM (1996) Diabetic foot diabetes mellitus. In: Cecil’s textbook of medicine. 20th ed. Eds, Bennett JC, Plum F. Philadelphia: WB Saunders Company, pp. 1275–1277. Sachs MK (1991) Cutaneous cellulitis. Arch Dermatol 127: 493–496. Semel JD, Goldin H (1996) Association of athlete’s foot with cellulitis of the lower extremities: Diagnostic value of bacterial cultures of ipsilateral interdigital space samples. Clin Infect Dis 23:1162–1164. Simon MS, Cody RL (1992) Cellulitis after axillary lymph node dissection for carcinoma of the breast. Am J Med 93:543–548. Staren ED, Klepac S, Smith AP, Hartsell WF, Segretti S, Witt TR, Griem K, Bines SD (1996) The dilemma of delayed cellulitis after breast conservation therapy. Arch Surg 131:651–654. Suss SJ, Middleton DB (1987) Cellulitis and related skin infections. Am Fam Physician 36:126–136. Tanner MH, Hale DC (1983) The nature of an infectious disease practice in a community hospital. Rev Infect Dis 5:1049–1060.