Ecthyma gangrenosum in a burned child

578

Burns (1986) 12, (8). 578-585

Printedin Great Britain

Ecthyma gangrenosum

in a burned child

J. P. Eldridge The Jewish Hospital of Cincinnati, USA

E. D. Baldridge The Good Samaritan

Hospital of Cincinnati, USA

and B. G. MacMillan* The Shriners Hospital for Crippled Children, and Burns Institute, Cincinnati Unit, USA

Summary The history of ecthyma gangrenosum has been presented. as well as its pathological diagnosis, prognosis and natural history. The history of forms of treatment has been outlined and the grave prognosis is emphasized. A case presentation introduces the experience at the Cincinnati Shriners Burns Institute. From a review of the literature and the experience at the Shriners Burns Institute, a suggestion for optimal treatment has been proposed. The particulars of this treatment include: early recognition, general nutritional and metabolic support, as well as high-dose aminoglycoside and semi-synthetic penicillin therapy, administered parentally and by sub-eschar clysis. Despite the grave prognosis, attention to these factors should result in optimal survival of patients with ecthyma gangrenosum.

INTRODUCTION ECTHYMA gangrenosum is a cutaneous manifestation of Pseudomonas septicaemia generally characterized by a fulminant clinical course. In 1897, both Barker (Barker, 1897) and Hitchmann (Hitchmann and Kreibich, 1897) described lesions of ecthyma and reported them to be ‘pathognomonic’ of disseminated Pseudomonas infection. In 1906, Fraenkel, reported ecthyma in unburned skin of thermally injured patients (Fraenkel, 1906). Subsequently, over the years other authors have also described lesions of

* Deceased.

Pseudomonas ecthyma gangrenosum (Stanley, 1947; Forkner et al., 1958; Kohlesbrewer et al., 195X; Teplitz, 1965; Hall et al., 1968; Dorff et al., 1971; Mushen, 1980). The condition is usually associated with debilitating illness, such as burns (Markley et al., 1957; Rabin et al., 1961; Loebl et al., 1974; Solem et 1979), leukaemia and other malignancies $: I IV en, 1969; Rabinowitz and Lewis, 1980), cystic fibrosis (Garrard et al., 1951) and immunodeficiency states (Spiers et al., 1963; Lim et al., 1978). Ecthyma has been reported in infants and children with diarrhoea (Mirabel, 1952; Geppert et al., 1952; Anderson, 1979; Koopman and Coulthad, 1982). It has been reported in heroin addicts with Pseudomonas cepacia endocarditis (Mandell et al., 1977). It has also been described in otherwise healthy patients following an upper respiratory tract infection or antibiotic therapy (Anderson, 1979; Heffner and Smith, 1960; Reed et al., 1976; Fast et al., 1979; Schuster, 1981). In 1958, Forkner et al. reported approximately 30 per cent incidence of ecthyma gangrenosum in 23 cases of Pseudomonas sepsis. More recently in a review of 108 cases of Pseudomonas bacteraemia, Flick and Cluff (1976) reported less than 3 per cent incidence of ecthyma. The critical nature of ecthyma gangrenosum is reflected in its mortality rate. Markley et al. (1957) reported the condition was universally fatal once the characteristic lesions developed. In

CASE PRESENTATION A 13-month-old white female (patient S.N.) sustained a scald injury from hot water covering over 40 per cent of total body surface area on 9 January 1984 (Figs. I, 2 and 3). The patient was resuscitated with Ringers lactate, placed on Silvadene dressings, and given a DPT booster and a single dose of penicillin-G. The patient was transferred to the Cincinnati Shriners Burns Institute 3 days after injury. Her clinical course is summarized in Figs. 4, 5 and 6. On admission her vital signs were: temperature 101.4”F (rectal); pulse, 176 per min; respiratory rate, 44 per min; blood pressure 146/ 76 mmHe. She had deen. oartial skin loss burns involving all four extremities. Full skin thickness burns were present on the dorsa of the feet. Five days after burning she developed temperature instability, leukocytosis. and intolerance to enteral feedings. She was started on a 7-day course of nafcillin and tobramycin for what clinically appeared to be sepsis. Tobramycin was increased to 12 mg/kg/day to obtain peak and trough levels of 7.1 &ml and 0.6 Kg/ml, respectively. Eight days after burning the patient underwent debridement and autografting of her left foot and ankle. She was placed in a Furacin occlusive dressing at that time. Post-operatively she was started on peripheral hyperalimentation. On post-operative day 3, the dressings were changed and the debrided areas and graft appeared to I

continued dopamine

to have episodes of bradycardia for which was changed to cpinephrine infusion at a rate

Fig. 3. Admission

scald injury to right upper extremity.

580

Burns (1986)Vol. 12/No. 8

Fig. 4. Patient’s

clinical

Fig. 5. Patient’s

of 0.6 ug/kg/min. The patient also received a single bolus of Solu-Medrol 30 “g/kg. Biopsies of gangrenous areas showed typical ecthyma gangrenosum. Wound cultures and blood cultures taken on day 13 subsequently grew Pseudomonas aeruginosa sensitive to amikacin but resistant to other aminoglycosides. The organism was also intermediately sensitive to piperacillin and cefotaxime. Between days 15 and 17 the patient developed a mild disseminated

prodromal

acute

clinical

course.

course.

intravascular coagulation (DIC). Due to persistant hypernatraemia and hypokalaemia, piperacillin was stopped and cefotaxime 200 mg/kg/day was started. Throughout her critical course, she was maintained on hyperalimentation and received multiple transfusions of whole blood, fresh frozen plasma and platelets. Amikacin was increased to 72 mg/kg!day to obtain peak and trough levels of 36.8 tug/ml and 6.2 ug/ml, respectively.

581

Eldridge et al.: Ecthyma gangrenosum

Fig. 6. Patient’s

clinical recovery.

to review the experience Burns Institute in dealing

of the Cincinnati

Shriners

with ecthyma gangrenosum.

DISCUSSION Including the above patient, five children with ecthyma gangrenosum have been treated at the Cincinnati Shriners Burns Institute between 1968 and 1984. This data is summarized in Table 1. Three

FIR. 7. Ecthyma trcmity.

gangrenosum

lesion of left lower ex-

With further stabilization of her condition. she underwent serial debridements of ecthyma followed later by skin grafting to all open wounds. Following a prolonged recovery period. she was discharged in a satisfactory condition 52 days after burning. The survival of this patient prompted the authors

of these

five children

died,

indicating

the

poor prognosis and serious nature of this disease. Two of these mortalities occurred before 1975, a period in which widespread serum monitoring of aminoglycoside levels was not available. Despite the lack of serum monitoring, the first two patients in our series were treated with gentamicin at doses of 1.5-3 mg/kg/day, these doses are sub-therapeutic in burn patients. Furthermore, good supportive treatment, including hyperalimentation, was not widely available before 1975. Since 1979, two of the three patients with ecthyma gangrenosum have survived. The one patient who died had aminoglycoside levels which were noted to be sub-therapeutic. Interestingly, this one patient (S.P.) is the only patient in the series who was treated by sub-eschar clysis. Baxter advocated the use of sub-eschar clysis in cases of ecthyma gangrenosum and has published a series of patients half of which survived utilizing this technique (Baxter et al., 1973; Loebl et al., 1974). Sub-eschar infusion of semi-synthetic penicillins has been shown to be an effective

4yr

17 mth

2 yr

13mth

1872

1979

1982

1984

J.T.

AR

S.P.

S.N.

F

F

F

F

M

55

57

44

46

40

13

17

43

17

18

gangrenosum;

Scald

Flame

Scald

Flame

Flame

Yes

Yes

No

No

No

+ Pseudo.

S

+ Staph. + Pseudo.

S

-

+ Pseudo.

D

D

+ Pseudo.

D

320 mg/kg/dose.

Pen. G Naf. Tobra.

and amikacin,

15.6mglkgldose.

Furacin Silvadene Silver nitrate

D, Death;

HAL Debrid. Graft Transf.

clysis*

S, survival;

EG, ecthyma

Amik. peak. 16 uglml; trough, 7.3 uglml Amik. peak. 37 pg/ml; trough, 6 pg/ml HAL Debrid. Transf. Silvadene

Amikacin: 32 mglkgld Piperacillin: 160 mglkgld

Amp. Naf. Keflex Gent.

Amk: 72 mglkgld Pip: 300 mglkgld Cef. 200 mglkgld

Gent. peak, 11-12 pglml; trough, 2.3 pglml

HAL Debrid. Gamma Glob. (hyperimmune) Graft. Silvadene Furacin Gent.

Gentamicin: 8 mglkgld Carb.: 675 mglkgld

Pen. G Chloro. Vance.

Tetra.

n.a.

ma.

Debrid. Transf. Gamma Glob. Vit K Debrid.

Treated open without topical antibiotic for 7 d, then Silvadene Sulphamylon Betadine

Gentamicin: 1.5 mglkgld

Gentamicin: 3 mglkgld Carb.: 480 mglkgld

Pen. G

at the Cincinnati Shriners Burns Institute

with sub-eschar clysis using piperacillin. n.a., not available; HAL, hyperalimentation.

* I.v. antibiotics supplemented

9yr

of cases treated with ecthyma gangrenosum

1968

Table 1. Summary

g m

2 .

?I z 8 c”

F

Eldridge

et al.: Ecthyma

583

gangrenosum

in the care of the patient with Pseudomonas burn-wound infection (McManus et al., lYX3). Four of the five patients had the onset of ccthyma gangrenosum within 2 to 3 weeks following their initial burns. Furthermore, all patients had large body surface area burns, ranging from 40 to 55 per cent. In all cases the patients had been treated with broad-spectrum antibiotics before the onset of ecthyma gangrenosum.

adjunct

Diagnosis and treatment Gram-negative enteric bacilli (GNB) that produce sepsis in man are known to produce secondary cutaneous manifestations occasionally. Examples of these skin and subcutaneous lesions are ecthyma gangrenosum (Hall et al.. lY68; Dorff et al., lY71: Mushen, 1980). cellulitis. thrombophlebitis and ecthyma multiforme. Classical ecthyma gangrenosum has been considered by some authors to be pathognomonic of Pseudomonas septicaemia (Hall et al.. 196X; Fast et al.. lY7Y) and by others to be characteristic of Gram-negative bacillary sepsis (Mushen, 1980). Identical lesions to ecthyma gangrenosum may appear in the absence of infection and have been reported in cases of vasculitis as well as malignant infiltration alone (Mushcn, 1980). Ecthyma gangrenosum commonly occurs in P.sc~rrrlon~~na.s arr~4ginostr septicaemia, especially with patients who have extensive burns or other immunological compromise. Far less frequently, these lesions are reported in severe infections of Awornorms, Srrrmtirr. E.

Prolru.s, coli and

Klehsiella,

Enterohucter.

disseminated candidiasis (File et al.. 1979: Mushen, 1980; Fine et al.. IYXI: Rajan, 1YX2). The lesions are particularly seen with the above infections in a patient who is immunocompromised (Rajan. 1982). It appears that Pseudomonas septicaemia is infrequent without some change in host-defence mechanisms. Immunological studies have not generally been reported for adults or children with ecthyma gangrenosum, which makes it impossible to know if specific immune defects are commonly present (Fast et al., 1970); however. immune defects are highly suspected. The lesions of ecthyma gangrenosum are typically isolated, opalescent, often tense vesicles surrounded by a narrow pink to violacious halo of erythema (Hail et al., 196X; Koopman and Coulthad, 19X2).’ They widely progress to become papular with central bullae or vesicles, and necrosis is usually seen within 24 to 4X h of their initial appearance. The lesions may be single or

multiple and are located more commonly on the buttocks and extremities, often sparing the palmar, plantar and mucosal surfaces (Hall et al., lY68). Histologically. the lesions of ecthyma gangrenosum have three hallmarks: (1) artery and vein wall invasion by bacteria, (2) little accompanying inflammation. and (3) no intimal involvement. In an experimental model. Teplitz (1965) showed that the lesions are initiated at the capillary level by massive perivascular bacillary infiltration with associated arteritis. These lesions do not form from septic thrombosis, as had previously been described in past medical literature. In the late fifties and sixties, various investigators began exploring immunological methods of prevention and treatment of Pseudomonas infections. These studieS demonstrated the need for: (I) antibody for opsonization of Pseudomonas organisms (Ogle, 1980) and (2) adequate neutrophil function for phagocytosis of the opsonized Pseudomonas organism (Alexander and Fisher, 1970). They also led to the development of hyperimmune globulin for passive immunization and Pseudomonas vaccine for active immunization in an attempt to treat and prevent Pceudomonas infections. In 1968 Feller and Pierson reported favourable results by a monovalent vaccine alone with routine administration of fresh frozen plasma for the treatment of Pseudomonas infections in burn patients. Likewise, Jones et al. (1970) reported improved survival from established Pseudomonas sepsis with therapeutic administration of Pseudomonas hyperimmune globulin and plasma. In IYhY Alexander et al. (lY6Y) reported the results of a pilot study using commercially available heptavalent vaccine against approximately YO per cent of clinically important Pseudomonas isolates. They showed the vaccine to be effective for preventing invasive Pseudomonas infections in most patients with large burns when given by the appropriate route, dosage and interval. The efficacy of the vaccine was also documented by other clinical investigations (Alexander et al., 1971; Alexander and Fisher, 1974). Other studies, however, did not support the use of hyperimmune globulin and/or vaccines. With the advent of newer and better anti-pseudomonal antibiotics, hyperalimentation and supportive care, the era of immunolgical prophylaxis and treatment waned. Hyperimmune globulin has been used at the Shriners Burns Institute, Cincinnati, in a group of three to five burn patients who were invaded

584

by Pseudomonas aeruginosa. The results have been good. The product which has been used is Gamimune (B. G. MacMillan, unpublished results). The optimal treatment of ecthyma gangrenosum begins with the early recognition of the lesion. Typical cutaneous manifestations will lead the astute clinician to suspect the diagnosis. Once the diagnosis is entertained, appropriate blood and wound cultures should be obtained as well as a biopsy of the wound to examine it for pathological changes consistent with Pseudomonas ecthyma gangrenosum. Before the results of cultures and pathology are received, immediate treatment with appropriate systemic antibiotics is indicated. High-dose aminoglycoside therapy must be initiated early. Gentamicin, tobramycin, and amikatin are commonly used. Carbenicillin and piperacillin have been shown to create synergistic activity when used in combination w.ith these aminoglycosides. It has also been suggested that aminoglycoside antibiotics perietrate into burn eschar and appear to have a substantial effect on eschar microbiology (Polk, 1983). If histological or clinical data support a diagnosis of Pseudomonas burn-wound infection, subeschar clysis of the infected burn wound should be performed using a semi-synthetic penicillin and/or an aminoglycoside. It is imperative that high aminoglycoside doses be used with repeated serum peak and trough measurements as the guide to dosage and frequency. During the treatment of Gram-negative bacillary infections in severely burned children, it has been noted by Clew et al. (1976) and others (Zaske et al., 1976) that the administration of standard dosages of gentamicin commonly produce low serum levels. Clearance studies in some children suggest that the increased requirement for gentamicin can result from either loss of the antibiotic across burn wounds or from increased urinary excretion (Clew et al., 1976). Early excision of infected tissue is to be considered when there is a need to remove full thickness infected tissue because of extension of existing lesions or new foci- of wound infection as well as persistent or worsening systemic sepsis (McManus et al., 1983). Finally, metabolic and nutritional support is essential to the survival of any severely burned patient, and this is especially true in a patient with ecthyma gangrenosum. Nutritional support should be administered to maintain a positive nitrogen balance with thk goal of no patient weight loss.

Burns (1986) Vol. lZ/No. 8

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3 June 10X6.