Bullous erysipelas: A retrospective study of 26 patients

Bullous erysipelas: A retrospective study of 26 patients Dror Guberman, MD,a* Leon T. Gilead, MD, PhD,b* Abraham Zlotogorski, MD,b and Julian Schamroth, MDb Jerusalem, Israel Background: Erysipelas is a superficial form of cellulitis caused by a variety of microbes, and it responds to antibiotic treatment. During the past few years we treated several patients with a bullous form of erysipelas involving the lower legs. We believe their disease had a more protracted course than patients with nonbullous erysipelas. Objective: We studied bullous erysipelas by conducting a retrospective analysis of 26 patients with bullous erysipelas of the legs treated by the authors during a 5-year period. Methods: We conducted a retrospective review of the records of all patients with a diagnosis of bullous erysipelas who were treated at the Department of Dermatology, Hadassah Medical Center, Jerusalem, between the years 1992 and 1996. Data regarding patients with nonbullous erysipelas were obtained from the medical center’s computerized data pool. Results: A total of 26 cases of bullous erysipelas were found, comprising 22 women and 4 men whose ages ranged from 28 to 87 (mean, 58.8) years. The average hospital stay was 20.57 days (range, 12 to 46 days). The average hospital stay for patients with nonbullous erysipelas and cellulitis treated in the same department by the authors during the study period was 10.6 days (range, 2 to 54 days). Conclusion: Bulla formation is a complication of erysipelas, seen in our series in 5.2% of the patients (26 of 498 admissions for erysipelas and cellulitis). The course of the disease is protracted, requiring longer medical attention. (J Am Acad Dermatol 1999;41:733-7.)

E

rysipelas is a superficial form of cellulitis caused by a variety of microbes; it responds to antibiotic treatment. The typical clinical presentation includes leg tenderness, sharply demarcated erythema, and edema. Lymphangitis and inguinal lymphadenopathy may be present, and the onset is usually accompanied by fever and sometimes shivering.1 During the past few years we have treated several patients with a bullous form of erysipelas involving the lower legs. We believe they had a more protracted course of the disease than did patients with nonbullous erysipelas. This is a retrospective study of 26 patients with bullous erysipelas of the legs treated by the authors over a 5-year period.

From private practicea and the Department of Dermatology, Hadassah Medical Center.b *The first two authors are equal contributors. Accepted for publication April 27, 1999. Reprint requests: Dror Guberman, MD, 11 Gordon St, Jerusalem, Israel 96545. Copyright © 1999 by the American Academy of Dermatology, Inc. 0190-9622/99/$8.00 + 0 16/1/99552

METHODS We conducted a retrospective review of all records of patients with a diagnosis of bullous erysipelas who were treated at the Department of Dermatology, Hadassah Medical Center, Jerusalem, between the years 1992 and 1996. Data regarding patients with nonbullous erysipelas were obtained from the medical center’s computerized data pool.

RESULTS The parameters evaluated were summarized in Tables I and II for prehospitalization course and inhospital course, respectively. The 26 patients were 22 women and 4 men ranging in age from 28 to 87 years (mean, 58.8 years). All patients had erysipelas manifested by fever, leg pain, erythema, edema, increased local warmth and tenderness, and tender inguinal lymphadenopathy, with the exception of 6 patients (1 who was admitted for treatment of post-bullous erysipelas erosions and 5 who were afebrile on admission). Predisposing leg conditions, such as previous erysipelas, thrombophlebitis or bone fracture, onychomycosis or tinea pedis, venous insufficiency 733

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Table I. Prehospitalization course Patient No.

Age (y)/ Sex

1 2

53/F 51/F

3

61/F

4

42/M

5

82/F

6 7

44/F 70/F

8 9

87/F 49/F

10

85/M

Laryngectomy for laryngeal carcinoma

11 12 13

42/F 78/F 83/F

Obesity Duodenal ulcer Carcinoma of vulva, diabetes mellitus type 2

Trauma Drainage of inguinal abscess

14 15

34/F 43/F

Dry eyes

Poliomyelitis, tinea pedis

16

75/F

Venous insufficiency

17 18

47/F 64/F

19 20

77/F 66/F

21

75/M

Ischemic heart disease, hypertension Anemia Diabetes mellitus type 2, hypertension, obesity Arthralgia Thalassemia minor, hypertension Diabetes mellitus type 2, obstructive lung disease

22

63/F

23

28/F

24 25 26

39/M 38/F 54/F

Medical history

Diabetes mellitus type 2, hypertension, atrial fibrillation Gout

Diabetes mellitus type 2, hypothyroidism Iron deficiency Bronchial asthma, osteoarthritis Hypothyroidism

Predisposing leg factors

Fracture left femur, sciatic nerve injury, previous erysipelas Previous erysipelas

3 3

During hosp During hosp

Doxycycline

1

During hosp

3

During hosp

3

Pre hosp

4 1

During hosp During hosp

1 8

During hosp Pre hosp

1

During hosp

3 7 7

During hosp During hosp During hosp

5 2

Pre hosp Pre hosp

2

Pre hosp

Amoxicillin, dicloxacillin Erythromycin Onychomycosis of toe nails Stasis dermatitis Healed fracture of left ankle, deep vein thrombosis, tinea pedis Tinea pedis

Bullae onset

Cephalexin Erythromycin

Deep vein thrombosis of right leg, surgery for foot malalignment

Amoxicillin, cephalexin Cephalexin, amoxicillin/ clavulanic acid Penicillin

Dicloxacillin Amoxicillin, dicloxacillin

Recurrent erysipelas

Erythromycin Cefuroxime

4 3

During hosp Pre hosp

Tinea pedis Recurrent erysipelas, tinea pedis Tinea pedis

Doxycycline Cefuroxime

7 3

Pre hosp During hosp

Penicillin, cephalexin Amoxicillin/ clavulanic acid Amoxicillin/ clavulanic acid, dicloxacillin Cefazolin Cefazolin Dicloxacillin

4

Pre hosp

14

Pre hosp

1

During hosp

1 6 30

During hosp During hosp

Stasis dermatitis, varicose veins, trauma Anemia (iron deficiency)

Diabetes mellitus type 2 Asthma, carcinoma of the uterus

Treatment

Illness before admission (days)

Trauma Chronic edema

or varicosed veins, or stasis dermatitis, were found in 18 patients, and non-insulin–dependent diabetes mellitus in 6 patients. In only 3 patients were no systemic or local predisposing factors identified.

Twenty of the patients were partially treated with oral antibiotics before admission. Bullae occurred during hospitalization in 16 patients and the rest were hospitalized with the bullous lesions already

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Table II. In-hospital course Patient No.

Blood culture

Bulla culture

1 2 3 4 5

Sterile Not done Sterile Not done Not done

Sterile Mixed enteric flora Not done Not done Sterile

6 7 8 9 10 11 12 13

Sterile Sterile β-Hemolytic strep† Not done Sterile§ Not done Sterile Sterile

Not done Sterile Coagulase (-) staph‡ Not done Sterile Not done Not done Sterile

14 15 16 17 18

Sterile Not done Not done Sterile Sterile

Sterile Sterile Sterile Not done Sterile

19 20

Sterile Sterile

21 22 23 24 25 26

Not done Not done Sterile Sterile Not done Not done

Sterile Sterile→coag (+) staph Not done Sterile Not done Not done Not done Not done

Treatment*

Complications

Duration (days)

Cefazolin Dicloxacillin Cefuroxime, metronidazole Cefazolin Cefuroxime and metronidazole (diarrhea), cefazolin Clindamycin (allergy), cefazolin Cefazolin Cefazolin

19 30 16 14 17

Amoxicillin/clavulanic acid Cefazolin, amoxicillin/clavulanic acid Cefazolin Dicloxacillin Ceftazidime, vancomycin, cefamezine, metronidazole Cefazolin Cefazolin Cefazolin, penicillin, dicloxacillin Clindamycin (rash) Cefuroxime, metronidazole, clindamycin, ciprofloxacin Cefazolin Cefazolin, metronidazole, clindamycin

13

Cefuroxime, metronidazole, dicloxacillin Cefazolin Cefazolin Cefazolin Cefazolin Dicloxacillin

17 46 17

Leg ulcer

16 45 20 14 14 14 14 34

GIT bleeding (NSAID) Hemolysis, leg ulcer

25 44 14 13 16 18 16 12

GIT, Gastrointestinal tract. *Topical therapy included aluminum acetate or saline compresses, 1% silver sulfadiazine cream or 1% bacitracin ointment dressing, and mechanical whirlpool debridement. †Streptococcus. ‡Staphylococcus. §Anti-streptolysin titer 1:320.

present. The bullae were all flaccid bullae several centimeters in diameter, and a few of them contained blood (Fig 1). Despite several attempts to isolate a pathogen, the causative bacteria was found in the blood of only 1 patient (case 8) out of 15 patients. This patient, who presented with confusion and severe systemic signs, was found to be infected with a beta-hemolytic streptococcus. Of 14 attempts to isolate a pathogen from the eroded bullae, all early (pre-erosion) cultures were sterile. In subsequent cultures, only in 1 case was there a finding considered to be significant: a coagulase-positive Staphylococcus aureus. The coagulase-negative staphylococci and mixed enteric flora isolated from the eroded bullae

of 2 other patients were probably the result of contamination. The initial parenteral in-hospital antibiotic regimen included cefazolin in 15 patients, a combination of cefuroxime and metronidazole in 4 patients, clindamycin in 4 patients, and dicloxacillin in 3 patients. In addition amoxicillin/clavulanic acid were administered in 2 patients, and vancomycin, ciprofloxacin, and ceftazidime were each given to 1 patient. A change in antibiotic therapy was necessary because of an allergic reaction (2 cases), drug intolerance (1 case), and an unsatisfactory therapeutic response (6 cases). The average time for defervescence was 5.15 days (range, 2 to 12 days). The average hospital stay was 20.57 days (range, 12 to 46 days). In all 26 cases,

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Fig 1. Leg of patient with bullous erysipelas. Large denuded area on lateral aspect of calf with remnants of flaccid bullae present at edges.

the course of the disease was protracted without any other causes influencing its length except for the bullous erysipelas and the concomitant erosions; many cases required 3 or more weeks of hospitalization. All patients were reported to have suffered significant discomfort and pain because of the bullous complication. Recovery was complete in all patients, although 2 patients were subsequently rehospitalized for recurrent (nonbullous) erysipelas, and 2 patients suffered from postbullous ulcerations. None of the 26 patients had necrotizing fasciitis or organ failure. A retrospective analysis of data regarding all patients admitted for erysipelas and cellulitis to the department of dermatology during the designated 5year period was performed. A total of 472 patients were admitted to the department of dermatology during that time. The average age of the patients was 53.4 years (range, 15 to 93 years), and the female to male ratio was 43.4% (216/498). The average hospital stay was 10.6 days (range, 2 to 54 days). No significant difference was found in the rate of the various predisposing factors compared with those found in the bullous erysipelas group. No significant differences were noted in the extent of skin involvement in bullous erysipelas as compared with that seen in cases where bullae did not occur.

DISCUSSION The bullous form of erysipelas is mentioned only briefly in the textbooks: “Bullae and vesicles may develop.”2,3 Surprisingly, the medical literature regarding bullous erysipelas or bullous cellulitis is scant. Of 100 patients in one retrospective study, 30 experienced bul-

lae.4 Agnholt, Andersen, and Sondergaard5 reported a fatal case of bullous erysipelas in which culture of blood and cutaneous swabs revealed the presence of beta-hemolytic streptococcus. They regarded it as a new cutaneous manifestation of streptococcal infection. Other reports of invasive streptococcal infections have been described, including 1 case of bullous cellulitis in the leg of a surgeon who was exposed to peritoneal fluid of a streptococcus-infected patient.6 Streptococci and staphylococci are the most common causes of erysipelas in immunocompetent patients. However, other bacteria may cause bullous cellulitis. In a study of 7 patients with cirrhosis and cellulitis, Corredoira et al7 described 5 events of bullous erysipelas. Various gram-negative enteric organisms were cultured from needle aspiration of cutaneous lesions. Bacteremia was found in 6 patients and the disease was fatal in 4. Bacteremic bullous cellulitis may also be caused by the marine bacteria Vibrio vulnificus,8 and has been caused by streptococcus pneumonia.9 Hemorrhagic cellulitis was referred to as a separate entity with significant mortality, and glucocorticosteroids were believed to be needed.10 Only mild complications of bullous erysipelas such as milia11 were described to date. The mechanism of bulla induction remains unclear. Although a biopsy of a bulla could probably contribute to the understanding of the mechanism and etiology, skin biopsies were contraindicated because of the significant probability of a secondary ulceration in an already severely ill limb. However, all bullae were flaccid and therefore were clinically considered intraepidermal, and almost all of them cleared

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without scarring. We can therefore only speculate on the basis of the present data that the bulla is produced by severe intraepidermal spongiosis caused by the superficial dermal and epidermal infectious and inflammatory process. It is possible that the extent of skin involvement in the basic infection is significant in the occurrence of the bullae; however, our clinical impression is that this was not a significant factor. The lymphangitis typically seen in erysipelas may also be a factor, because lymphatic drainage is impaired. Bullae may also be formed as a result of direct bacterial invasion. However, this possibility is probably ruled out because blister fluid cultures are usually sterile or grow irrelevant local contaminating bacteria. Toxinmediated blister formation for bullous infections, including bullous impetigo and scalded skin syndrome, is another possible mechanism. In these diseases an exotoxin activity results in a subcorneal separation within the epidermis. Bacterial elements may also function as superantigens, and thus activate inflammatory cascades.12 Mechanical pressure may be a contributory factor in bullae production, such as that occurring in friction blisters. Our failure to culture pathogens from intact bullae is not surprising. It is known that the yield of cultures in erysipelas is very low. Although blood cultures were reported to identify the responsible pathogen in only 5%,13 needle aspiration cultures give about 5% to 12.5% positive and relevant results.13 Lesional skin biopsy cultures yield 10% to 20% bacterial isolations.12 Although the yield is low, cultures of both blood and bullae fluid should probably be performed in all such patients. The retrospective nature of our study and the lack of consistency in initial antibiotic therapy throughout the reviewed years prevents us from assessing the efficacy and significance of the various antibiotics and topical medications that were used. However, because the treatments in the control population were the same, no relationship between the type of systemic treatment and final outcome was identified. Topical treatment seems important in bullous erysipelas. Our therapeutic approach included mainly leg elevation. Whirlpool jets were used to debride some of the lesions, and dressings with either 1% bacitracin or 1% silver sulfadiazine were applied topically. Subcutaneous enoxaparin was administered for deep vein thrombosis prophylaxis for patients with previous thrombosis or morbid obesity. We have treated macerated interdigital tinea pedis, prescribed elastic support stockings where not contraindicated, and used antibiotic prophylaxis in patients suffering from multiple recurrent erysipelas. The control population, although not matched, serves as a statistically significant control group

Guberman et al 737

because of its size and intrinsic properties. The difference in the length of hospitalization (20.57 days in bullous erysipelas patients as compared with 10.6 in the control population is of high statistical significance (P < .001). The mean age difference between the 2 groups is not statistically significant, and no other relevant significant differences were found between groups. We believe the striking 84.6% female predominance (22/26 patients with bullous erysipelas) in the bullous erysipelas group as compared with the 43.4% seen in the control population is coincidental. Despite the retrospective nature of this study, which prevents the drawing of significant conclusions for many of the questions it may raise, we believe that bullous erysipelas is a significant complication of severe erysipelas induced by a yet unknown mechanism that, as this series of cases indicates, results in a protracted hospitalization and significant discomfort to the patients. The lack of publications dealing with this complication is surprising especially in view of its relative frequency (5.2% of the patients [26/498 admissions for erysipelas and cellulitis] in our series). REFERENCES 1. Braverman IM. Skin signs of systemic disease. Philadelphia: Saunders; 1998. p. 577-81. 2. Swartz MN, Weinberg AN. Infections due to gram-positive bacteria. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, editors. Dermatology in general medicine. New York: McGraw-Hill Inc; 1993. p. 2313-5. 3. Stevens DL. Infections of the skin, muscle, and soft tissues. In: Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL, editors. Harrison’s principles of internal medicine. New York: McGraw-Hill Inc; 1994. p. 562. 4. Crickx B, Chevron F, Sigal-Nahum M, Bilet S, Faucher F, Picard C, et al. Erysipelas: epidemiological, clinical, and therapeutic data (111 cases). Ann Dermatol Venereol 1991;118:11-6. 5. Agnholt J, Andersen I, Sondergaard G. Necrotic bullous erysipelas. Acta Med Scand 1988;223:191-2. 6. Schwartz B, Elliott JA, Butler JC, Simon PA, Jameson BL, Welch GE, et al. Clusters of invasive group A streptococcal infections in family, hospital, and nursing home settings. Clin Infect Dis 1992;15:277-84. 7. Corredoira JM, Ariza J, Pallares R, Carratala J, Viladrich PF, Ruff J, et al. Gram-negative bacillary cellulitis in patients with hepatic cirrhosis. Eur J Clin Microbiol Infect Dis 1994;13:19-24. 8. Penman AD, Lanier DC, Avara WT, Canant KE, DeGroote JW, Brackin BT, et al. Vibrio vulnificus wound infection from the Mississippi gulf coastal waters: June to August 1993. South Med J 1995;88:531-3. 9. House NS, Helm KF, Marks JG Jr. Acute onset of bilateral hemorrhagic leg lesions. Arch Dermatol 1996;132:81-6. 10. Heng MC, Khoo M, Cooperman A, Fallon-Friedlander S. Haemorrhagic cellulitis: a syndrome associated with tumor necrosis factor-alpha. Br J Dermatol 1994;130:65-74. 11. Lapidoth M, Hodak E, Segal R, Sandbank M. Secondary milia following bullous erysipelas. Cutis 1994;54:403-4. 12. Sachs MK. Cutaneous cellulitis. Arch Dermatol 1991;127:493-6. 13. Goldgeier MH. The microbial evaluation of acute cellulitis. Cutis 1983;31:649-56.