What's Your Diagnosis?

16-month-old female is admitted to PICU with concerns for sepsis

A 16-month-old female is admitted to the PICU with fever and concerns for sepsis. A few weeks earlier, she had the onset of a generalized maculopapular rash. The rash seemed to wax and wane, and then 4 days prior to admission, she was seen and treated with oral amoxicillin for fever and acute otitis media. The rash had since transitioned into several dark skin lesions with some surrounding erythema. Several lesions had become significantly larger, especially a presacral lesion (Figure 1), as well as lesions on both upper and lower lips (Figure 2) and her right ankle. A swab of the surface of the presacral lesion was sent for routine bacterial culture, growing three organisms: methicillin-sensitive Staphylococcus aureus (MSSA), Enterobacter and Klebsiella.

James H. Brien

Further history revealed that the patient was a previously healthy 16-month-old female twin, with no travel and no animal contact. There was no history of injuries, insect bites or prior skin problems. She had no sick contacts, including her twin sibling.

Figure 1. Lesion over the sacrum on admission.

Source: James H. Brien, DO

Figure 2. Lip lesion on admission.

In the PICU, antimicrobial therapy was initiated with meropenem plus vancomycin. The next day, she was transferred to the general pediatric ward, where the antimicrobials were changed to piperacillin/tazobactam plus clindamycin. Her exam was otherwise unremarkable except for the rash noted above. Pertinent lab results included a CRP of 131, thrombocytopenia with neutropenia (absolute neutrophil count of 140). Her blood cultures remained negative, and she had gradual improvement in her activity and appetite, and a rapid resolution of the fever. A biopsy was obtained on the day of admission, with a negative Gram stain, fungal stain and acid-fast bacilli stain. The histology revealed “deep perivascular mixed inflammatory infiltrate with neutrophils with karyorrhectic debris (destructive fragmentation of the nucleus of dying cells) and extravasated red blood cells and overlying epidermis with necrotic keratinocytes.” Biopsy tissue culture grew MSSA.

During the 2 weeks in the hospital, the black lesions underwent progressive demarcation with normalization of the surrounding skin.

What’s your diagnosis?

A. Cutaneous anthrax

B. Ecthyma gangrenosum

C. S. aureus ecthyma

D. Toxic epidermal necrolysis

The best answer is C, S. aureus ecthyma. S. aureus growing from the tissue biopsy material strongly supports the diagnosis. Some experts may call this ecthyma gangrenosum; however, most consider that diagnosis virtually synonymous with Pseudomonas sepsis in the immunocompromised host. There are several case reports of S. aureus ecthyma in patients with transient neutropenia, as noted in this patient. Her immune system was thoroughly evaluated with no other abnormalities, and the neutropenia, leukopenia and thrombocytopenia all resolved. The patient was discharged home on oral clindamycin for 2 additional weeks, and at 10-month follow-up, there was only some residual scarring of all lesions (Figure 3). It should be noted that since the organism was methicillin-sensitive, an anti-staph penicillin or cephalosporin could have been used instead of clindamycin, which many children would resist taking due to taste of the suspension.

Figure 3. Presacral scarring at 10-month follow-up.
Figure 4. Ecthyma gangrenosum lesions on a neutropenic cancer patient.

Hypothetically, the neutropenia at the time of admission may have been the result of a previous viral infection that occurred at a time of coincident MSSA bacteremia, causing this cascade of events. We may never know.

Cutaneous anthrax is a well-recognized, mostly zoonotic infection that results in a chronic skin lesion with an eschar. This patient had no exposure to animals, and with the pre-existing generalized rash and negative tissue Gram stain, this would seem to be ruled out, subsequently confirmed with a positive MSSA culture. In addition, one would not expect to see cutaneous anthrax at multiple sites.

Ecthyma gangrenosum is almost always seen in the face of severe underlying immune deficiency, such as patients on chemotherapy for cancer, and it is by far most commonly a result of P. aeruginosa sepsis, with septic emboli. These lesions typically began as small, erythematous papules or even vesicles with surrounding erythema but rapidly progress in size and into dark lesions consistent with necrosis (Figure 4). This is usually a sign of a life-threatening infection and should be treated very aggressively.

Toxic epidermal necrolysis is accompanied by widespread erythroderma with necrolysis due to injury to the deeper, subepidermal layers of the skin, usually as a result of a reaction to a drug — typically a sulfa or anticonvulsant — with the development of diffuse, various-sized blisters that remain intact due to the thickness of the overlying skin. Such was not the case with this patient.

Disclosure: Brien reports no relevant financial disclosures.

A 16-month-old female is admitted to the PICU with fever and concerns for sepsis. A few weeks earlier, she had the onset of a generalized maculopapular rash. The rash seemed to wax and wane, and then 4 days prior to admission, she was seen and treated with oral amoxicillin for fever and acute otitis media. The rash had since transitioned into several dark skin lesions with some surrounding erythema. Several lesions had become significantly larger, especially a presacral lesion (Figure 1), as well as lesions on both upper and lower lips (Figure 2) and her right ankle. A swab of the surface of the presacral lesion was sent for routine bacterial culture, growing three organisms: methicillin-sensitive Staphylococcus aureus (MSSA), Enterobacter and Klebsiella.

James H. Brien

Further history revealed that the patient was a previously healthy 16-month-old female twin, with no travel and no animal contact. There was no history of injuries, insect bites or prior skin problems. She had no sick contacts, including her twin sibling.

Figure 1. Lesion over the sacrum on admission.

Source: James H. Brien, DO

Figure 2. Lip lesion on admission.

In the PICU, antimicrobial therapy was initiated with meropenem plus vancomycin. The next day, she was transferred to the general pediatric ward, where the antimicrobials were changed to piperacillin/tazobactam plus clindamycin. Her exam was otherwise unremarkable except for the rash noted above. Pertinent lab results included a CRP of 131, thrombocytopenia with neutropenia (absolute neutrophil count of 140). Her blood cultures remained negative, and she had gradual improvement in her activity and appetite, and a rapid resolution of the fever. A biopsy was obtained on the day of admission, with a negative Gram stain, fungal stain and acid-fast bacilli stain. The histology revealed “deep perivascular mixed inflammatory infiltrate with neutrophils with karyorrhectic debris (destructive fragmentation of the nucleus of dying cells) and extravasated red blood cells and overlying epidermis with necrotic keratinocytes.” Biopsy tissue culture grew MSSA.

During the 2 weeks in the hospital, the black lesions underwent progressive demarcation with normalization of the surrounding skin.

What’s your diagnosis?

A. Cutaneous anthrax

B. Ecthyma gangrenosum

C. S. aureus ecthyma

D. Toxic epidermal necrolysis

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The best answer is C, S. aureus ecthyma. S. aureus growing from the tissue biopsy material strongly supports the diagnosis. Some experts may call this ecthyma gangrenosum; however, most consider that diagnosis virtually synonymous with Pseudomonas sepsis in the immunocompromised host. There are several case reports of S. aureus ecthyma in patients with transient neutropenia, as noted in this patient. Her immune system was thoroughly evaluated with no other abnormalities, and the neutropenia, leukopenia and thrombocytopenia all resolved. The patient was discharged home on oral clindamycin for 2 additional weeks, and at 10-month follow-up, there was only some residual scarring of all lesions (Figure 3). It should be noted that since the organism was methicillin-sensitive, an anti-staph penicillin or cephalosporin could have been used instead of clindamycin, which many children would resist taking due to taste of the suspension.

Figure 3. Presacral scarring at 10-month follow-up.
Figure 4. Ecthyma gangrenosum lesions on a neutropenic cancer patient.

Hypothetically, the neutropenia at the time of admission may have been the result of a previous viral infection that occurred at a time of coincident MSSA bacteremia, causing this cascade of events. We may never know.

Cutaneous anthrax is a well-recognized, mostly zoonotic infection that results in a chronic skin lesion with an eschar. This patient had no exposure to animals, and with the pre-existing generalized rash and negative tissue Gram stain, this would seem to be ruled out, subsequently confirmed with a positive MSSA culture. In addition, one would not expect to see cutaneous anthrax at multiple sites.

Ecthyma gangrenosum is almost always seen in the face of severe underlying immune deficiency, such as patients on chemotherapy for cancer, and it is by far most commonly a result of P. aeruginosa sepsis, with septic emboli. These lesions typically began as small, erythematous papules or even vesicles with surrounding erythema but rapidly progress in size and into dark lesions consistent with necrosis (Figure 4). This is usually a sign of a life-threatening infection and should be treated very aggressively.

Toxic epidermal necrolysis is accompanied by widespread erythroderma with necrolysis due to injury to the deeper, subepidermal layers of the skin, usually as a result of a reaction to a drug — typically a sulfa or anticonvulsant — with the development of diffuse, various-sized blisters that remain intact due to the thickness of the overlying skin. Such was not the case with this patient.

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Disclosure: Brien reports no relevant financial disclosures.