Hemorrhagic bullae are not only skin deep
Abstract
Background: Dermatologic complaints are common presentations in the ED. Hemorrhagic bullae are an example of dermatologic manifestation caused by variable etiologies. The life-threatening skin lesion usually is an external sign of a systemic or immune response stimulated by an infection, toxin, medication, or disease process. Although most patient with life-threatening skin lesion, such as hemorrhagic bullae, may appear ill, patients who present in the early course of illness may appear well but deteriorate rapidly. For greater comprehension of hemorrhagic bullae, we prospectively followed 42 patients who presented with hemorrhagic bullae at the ED and analyzed their clinical characteristics and their confirmative diagnoses.
Methods: This is a prospective, observational cohort study conducted at a university-affiliated community hospital. Data were collected from January 2002 to January 2007. Patients presenting to the ED with hemorrhagic bullae were enrolled prospectively.
Results: All of our patients with hemorrhagic bullae had evidence of a serious disease: necrotizing fasciitis (42 case, 100%). The most common comorbidity was diabetes mellitus (18 cases; 42.9%). Vibrio species was the most common organism from blood culture (8/16 cases) and wound culture (17/ 27 cases). Streptococcal species was found in only 1 patient via blood culture and 4 patients via wound culture. The yield of positive wound culture with Vibrio species was significantly greater than with streptococcal species (P b .05). Fourteen (33.3%) patients came to the ED for help 48 hours later after the onset of hemorrhagic bullae. None of these 14 patients died. In our total of 42 patients, 8 (19%) died.
Conclusion: In our study, the most common causative disease of hemorrhagic bullae was necrotizing fasciitis. Hemorrhagic bullae are a more common clinical feature in Vibrio infection than in streptococcal infection. Hemorrhagic bullae may occur in the early stage of necrotizing fasciitis. Necrotizing fasciitis may be the first sign that emergency physicians come across in patients with hemorrhagic bullae that are not in the oral, genital, anal, ocular area, and high index of suspicion of Vibrio infection should be considered. More aggressive treatment may be needed as hemorrhagic bullae may occur in the early stage of a serious disease. Further multi-institution study may be required to support these findings.
(C) 2008
* Corresponding author. Department of Emergency Medicine, Chang Gung Memorial Hospital, Puzih City, Chiayi County 613, Taiwan.
E-mail address: [email protected] (I.-C. Chen).
0735-6757/$ - see front matter (C) 2008 doi:10.1016/j.ajem.2007.07.014
Hemorrhagic bullae are not only skin deep
Introduction
Dermatologic complaints are common presentations in the ED. Hemorrhagic bullae are also a dermatologic manifestation caused by variable etiologies, including infection, drugs, hypersensitivity, autoimmune, and vascular problems [1-5]. Of these, there are a number of causes of hemorrhagic bullae with high rate of morbidity and mortality. Early recognition of serious underlying diseases accounting for hemorrhagic bullae is important. The life- threatening skin lesion usually is an external sign of a systemic or immune response stimulated by an infection, toxin, medication, or disease process. Although most patients with life-threatening skin lesion, such as hemor- rhagic bullae, may appear ill, patients who present in the early course of illness may appear well but deteriorate rapidly. For more comprehension of hemorrhagic bullae, we prospectively followed 42 patients who presented with hemorrhagic bullae at the ED and analyzed their clinical characteristics and their confirmative diagnoses.
Methods
This is a prospective, observational cohort study con- ducted at a university-affiliated community hospital. From January 2002 to January 2007, patients presenting to the ED with hemorrhagic bullae were enrolled prospectively. Hemorrhagic bullae were defined as cutaneous blisters of diameter greater than 0.5 cm with hemorrhagic base. Patients younger than 18 years (including 18-year-olds) and patients
Table 1 Demographic data and comorbidities of patients with
hemorrhagic bullae
Demographic data
Comorbidities Diabetes mellitus Adrenal insufficiency Liver cirrhosis Cancer
End-stage renal disease Drug abuser Alcoholism
Coronary artery disease Chronic renal insufficiency Chronic hepatitis
Gouty arthritis Rheumatic arthritis Rheumatic heart disease Asthma
No comorbidities
No. of patients (N = 42)
26 (61.9%)
16 (38.1%)
18 (42.9%)
10 (23.8%)
6 (14.3%)
4 (9.5%)
1 (2.4%)
1 (2.4%)
3 (7.1%)
1 (2.4%)
1 (2.4%)
4 (9.5%)
5 (11.9%)
1 (2.4%)
1 (2.4%)
1 (2.4%)
7 (16.7%)
317
|
Symptoms or signs
|
||
|
Swelling |
36 |
(85.7%) |
|
Erythema |
23 |
(54.8%) |
|
Local wound |
22 |
(52.4%) |
|
Pain |
20 |
(47.6%) |
|
Fever |
18 |
(42.9%) |
|
Hypotension |
17 |
(40.5%) |
|
History of seawater contact |
13 |
(31%) |
|
History of fish prick |
4 |
(9.5%) |
with hemorrhagic bullae in the oral, genital, anal, and ocular area were excluded. To preserve the assumption of independence of observations, only the first episode of a hemorrhagic bullae was recorded for an individual patient to be used in the analysis. Of each enrolled patients, the age, sex, comorbidities, clinical symptoms/signs, site of hemor- rhagic bullae, admitting and discharge diagnosis, laboratory findings at ED, microbiology of wound culture and blood culture, pathologic results of tissue biopsies obtained during operation were routinely documented. The duration of hospitalization, the antibiotics, and the mortality rate were also recorded.
Table 2 Clinical presentations of patients with hemorrhagic bullae
Statistical analysis
Numeric variables are presented as means with SDs. We compared the proportions of patients identified as positive wound culture using ?2 tests. Statistical software (SPSS statistical software version 12, SPSS, Inc, Chicago, Ill) was used for data analysis and management. A 2-sided P value less than .05 was considered to be statistically significant.
Results
A total of 42 cases of hemorrhagic bullae at ED were enrolled and analyzed; 26 were male and 16 were female, with a mean age of 64.2 years (SD, 13.6). Table 1 summarizes their demographic characteristics and comorbidities. The most common comorbidity was diabetes mellitus (18 cases; 42.9%). Other comorbidities included adrenal insufficiency (10 cases, 23.8%), liver cirrhosis (6 cases, 14.3%), cancer
(4 cases, 9.5%), end-stage renal disease (1 case, 2.4%), drug
abuser (1 case, 2.4%), gouty arthritis (5 cases, 11.9%), chronic renal insufficiency (1 case, 2.4%), chronic hepatitis (4 cases, 9.5%), rheumatic arthritis (1 case, 2.4%), coronary artery disease (1 case, 2.4%), rheumatic heart disease (1 case, 2.4%), asthma (1 case, 2.4%), and alcoholism (3 cases, 7.1%). Seven patients (16.7%) had no comorbidities.
Table 2 lists the clinical presentations of patients with hemorrhagic bullae at ED. Swelling was the most common
clinical presentation (36 cases; 85.7%). Erythema (23 cases;
54.8%), local wound (22 cases; 52.4%), pain (20 cases; 47.6 %), fever (18 cases; 42.9%), and hypotension (17 cases; 40.5%) were other common clinical signs or symptoms.
Thirteen (31.0%) patients had history of seawater contact and 4 (9.5%) patients had a wound caused by a fish bone.
The initial admitting diagnosis made by emergency phy- sicians for each patient was necrotizing fasciitis (42 cases; 100%). The final discharge diagnosis of our 42 patients was necrotizing fasciitis (42 cases; 100%) (Table 3). Fifteen patients (35.7%) came to the ED for help within 24 hours after onset of hemorrhagic bullae. The white blood cell count was greater than 20 000 cells per cubic millimeter in 7 patients (16.7%). Eight patients (19.0%) had band form of 10% or greater. Twenty (47.6%) patients had serum creatinine of less than 1.5 mg/dL.
wound cultures and blood cultures of each patient were analyzed (Table 4). Blood cultures were positive in 16 patients (38.1%). A single organism was identified in 16 patients, multiple organisms were identified in 0 patients, and no organism was identified in 26 patients. Vibrio species was the most common pathogen in blood cultures. Wound cultures were positive in 27 patients (64.3%). A single organism was identified in 27 patients (64.3%), multiple organisms were identified in 0 patients (0%), and no organism was identified in 15 (35.7%) patients. Vibrio species (17 cases) and streptococcal species (4 cases) were common pathogens in wound cultures. The yield of positive wound culture with Vibrio species was significantly greater than with Streptococcal species (P b .05).
surgical interventions (debridement and/or amputation) were performed in 40 patients. Two patients did not receive operation because one of them was too critical to receive operation and another patient refused operation. These
2 patients’ clinical features, blood cultures, and wound
Table 3 Diagnosis and laboratory data
No. of patients (N = 42)
Initial admission diagnosis Necrotizing fasciitis
Final discharge diagnosis Necrotising fasciitis
Time from onset of hemorrhagic bullae to ED
b24 h b24 h N48 h
White blood cell count (cells/mm3)
N20 000
?20 000
Band form ?10% Band form b10%
Serum creatinine (mg/dL)
b1.5
?1.5
42 (100%)
42 (100%)
15 (35.7%)
27 (64.3%)
14 (33.3%)
7 (16.7%)
35 (83.3%)
8 (19.0%)
34 (81.0%)
20 (47.6%)
42 (52.4%)
Table 4 Microbiology
Positive blood culture Streptococcus group A Serratia marcescens Vibrio species Aeromonas species Positive wound culture Streptococcus group A
Streptococcus non-group A or group B or group D
Staphylococcus aureus Vibrio species Aeromonas species Serratia marcescens
No. of patients (N = 42)
16
1
1
11
3
27
3
1
1
17
4
1
cultures were consistent with the diagnosis of necrotizing fasciitis. Eleven patients (26.2%) required amputation. The mean time from admission to operation was 21.2 hours (SD, 37.1). The mean number of surgical interventions was
2.4 (SD, 1.19). Thirty-two patients received surgery within
24 hours from admission to operation. In our total of 42 patients, 8 (19%) died.
Discussion
Our study evaluated the presence of hemorrhagic bullae and their underlying disease. We found that all of our patients with hemorrhagic bullae have a serious disease: necrotizing fasciitis (42 case, 100%). This could mean that the presence of hemorrhagic bullae may be a specific sign of necrotizing fasciitis. More comprehension of the etiologies of hemor- rhagic bullae is important as different etiologies direct different therapies. Although there are other causes of hemorrhagic bullae, the results of our study show that severe soft tissue infection, such as necrotizing fasciitis, may be the most common cause of hemorrhagic bullae. Previous studies had shown that Polymicrobial infection was the most common type of infection [6-8]. Vibrio species was considered as a rare pathogen of necrotizing fasciitis [9]. In our study, Vibrio species was the most common organism from blood culture (11/16 cases) and wound culture (17/27 cases). In contrast, Streptococcal species was found in only 1 patient via blood culture and 4 patients via wound culture. The yield of positive wound culture with Vibrio species was significantly greater than with Streptococcal species (P b
.05). We propose that hemorrhagic bullae may be a more common presentation in Vibrio infection than in Strepto- coccal infection. In previous studies, hemorrhagic bullae is a late sign of necrotizing fasciitis [10], but our study is not totally consistent with this. Fourteen (33.3%) patients came to the ED 48 hours after the onset of hemorrhagic bullae. None of the 14 patients died. Necrotizing fasciitis is a
Hemorrhagic bullae are not only skin deep 319
fulminate disease with high mortality [6,11,12]. The possible reason for this is that the presence of hemorrhagic bullae may not be a late sign in the course of the disease. If hemorrhagic bullae is a late sign of necrotizing fasciitis, these 14 patients may have been in the late course of the disease with high probability of mortality. Further studies for this theory may be needed.
Our study is the first study on the clinical characteristics and confirmative diagnosis of hemorrhagic bullae, but there are still some limitations to our study. The first limitation is that the number and size of the hemorrhagic bullae have not been defined and described clearly in our study; therefore we cannot analyze the correlation of Severity of disease and the number or size of hemorrhagic bullae. The second limitation is that the number of enrolled patients is still too small (totally, 42 patients were enrolled). Further study or multi- institution study may be needed.
Conclusion
In our study, the most common causative disease of hemorrhagic bullae was necrotizing fasciitis. Hemorrhagic bullae are a more common clinical feature in Vibrio infection than in Streptococcal infection. Hemorrhagic bullae may occur in the early stage of necrotizing fasciitis. We suggest that necrotizing fasciitis should be suspected once emer- gency physicians come across patients with hemorrhagic bullae that are not in the oral, genital, anal, and ocular area, and high index of suspicion of Vibrio infection should be
considered. More aggressive treatment may be needed as hemorrhagic bullae may occur in the early stage of a serious disease. Further multi-institution study may be required.
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