19-year-old male with painful skin lesions

This month’s guest columnist is Elizabeth Dufort, MD.

A 19-year-old man with pre B-cell ALL on chemotherapy was admitted to the hospital with fever, neutropenia and some painful skin lesions. The onset of fever was the day prior to admission; however, he had fever intermittently over the last six weeks, with an admission to the PICU about a month ago. He was given empiric broad- spectrum antibiotics at that time and slowly improved without an organism being recovered and was discharged to continue his chemotherapy.

His past medical history is positive for having been diagnosed with Sjögren syndrome. He also has seasonal allergies. Otherwise, he was a healthy adolescent male prior to being diagnosed with ALL.

His immunizations are up to date and he has had no sick contacts.

Examination on admission revealed a temperature of 98.2° F, however, he had a documented fever of 101.8° F prior to arrival. His pulse and respirations were a bit rapid at 163 and 38 respectively, and his BP was 141/87. His oxygen saturation was 95% on room air. He was alert and oriented but somewhat toxic-appearing with significant pain in the areas of the rash. He also had some mucousitis associated with the chemotherapy and a port. The skin exam revealed several painful lesions on the arms and chest that were somewhat raised and erythematous as shown in figures 1 – 3.

Lab tests done included a CBC that revealed profound neutropenia and thrombocytopenia. Emergent punch biopsy of one of the lesions revealed Gram-negative rods. The cultures of blood, urine and biopsy material are pending.

What’s Your Diagnosis?

1. Disseminated candidiasis with sepsis
2. Ecthyma gangrenosum
3. Aspergillosis
4. Stenotrophomonas maltophilia sepsis

Case Discussion

This is a very unfortunate example of sepsis with Stenotrophomonas maltophilia in a severely immune suppressed cancer patient as this is what grew from the tissue culture as well as the central line.

Treatment was begun with trimethoprim sulfamethoxazole and ticarcillin-clavulanate. The patient then quickly decompensated, becoming hypotensive with septic shock and respiratory failure, requiring transfer to the pediatric ICU. He was intubated and treated with vasopressors. His port was removed two days later. He then developed ARDS, DIC, pulmonary hemorrhage, and was started on high frequency oscillation ventilation. The patient expired five days after the initial gram negative rods were noted on skin biopsy tissue gram stain.

An important teaching point from this case is that skin lesions may provide a window into an ongoing systemic infection. Oftentimes, skin lesions in the immunocompromised host may be the presenting sign of a disseminated infection. Early evaluation of skin findings may lead to earlier diagnosis and appropriate therapy, and therefore, decreased morbidity and mortality.

The differential diagnosis in this case includes multi-drug resistant organisms and fungal pathogens that often affect the high risk, hospitalized, immunocompromised patient on broad-spectrum antibiotics. All of the pathogens listed in the choices above (and more) are known to cause fever and skin lesions in the immunocompromised host. Furthermore, the consideration of each of these pathogens is important for empiric therapy given the possibility of early appropriate therapy, which may reduce morbidity and mortality.

Stenotrophomonas maltophilia was formerly known as Pseudomonas, and then Xanthomonas maltophilia. S. maltophilia commonly causes pneumonia and central venous catheter (CVC) associated bacteremia in the immunocompromised host. The portal of entry is often the respiratory tract or the central venous catheter.

Predictors of poor outcome include hematologic malignancy, transplant, severe neutropenia, severe shock at onset and delay in appropriate treatment. S. maltophilia infection may present with skin lesions. The mucocutaneous manifestations include oral ulcers, localized wound infections, primary cellulitis (which can lead to bacteremia), metastatic cellulitis (which is a result of bacteremic spread), and less commonly ecthyma gangrenosum. The metastatic lesions are tender, firm, erythematous, ecchymotic nodules, with surrounding cellulitis. These lesions may mimic fungal infections or pseudomonas lesions.

S. maltophilia is a highly resistant organism. Trimethoprim-sulfamethoxazole (TMP/SMX) is the most active agent. However, global emergence of TMP/SMX resistance is being reported; linked to the acquisition of the sul genes (EID. 2007; vol 13:559-565). Some activity is seen in vitro with tetracyclines and ticarcillin-clavulanate. It is also important to remember that the central venous catheter is an important portal of entry and early removal of the CVC in cases of S. maltophilia CVC-associated bacteremia may improve outcomes.

Disseminated candidiasis can certainly cause sepsis in immunocompromised patients; however, one might expect to see more mucocutaneous evidence of candida. Sometimes, the only evidence of candida sepsis may be by finding lesions in the liver on abdominal ultrasound or in the retina on dilated eye exam. Fortunately, candida usually grows readily on standard blood culture media.

Aspergillus sepsis may have cutaneous lesions that look exactly like those of the patient presented.

Another relative newcomer fungus plaguing cancer patients that can also do this is Fusarium, which has a tendency to invade through vessels as shown in figure 4. Figures 5 & 6 show the cutaneous manifestations and malignant spread of fusarium sepsis over several days; note the necrotic centers. The recommended treatment for both these fungi is high-dose amphotericin B or Voriconazole.

Lastly, ecthyma gangrenosum is a term that is almost pathognomonic with Pseudomonas sepsis in the immunocompromised. The cutaneous manifestations begin as hemorrhagic pustules as shown in figure 7. If the patient lives long enough, they will evolve into the necrotic lesions shown in figure 8 (from the Jim Bass collection). A tissue Gram stain from the patient in figure 7 is shown in figure 9, revealing a large number of Gram-negative rods. The patient presented probably had a Gram stain that looked very similar. While Pseudomonas is by far the most common cause, a wide rang of other bacteria and fungi have been recovered as well.

Columnist comments

The recent tragedy in Haiti should make us all realize how good we have it. It also brings into focus the importance of volunteer medical aid, whether driven by religion or an unselfish desire to help, or both. In the wake of the Haiti disaster, I received the following, very touching note from Christine Symes, RN, from Kansas City about such a person:

“A pediatrician in my community has long been an advocate for underserved children. His name is Dr. Frank Vaughters. He works in private practice and also started a clinic in1989 in Kansas City called The Turner House Children’s Clinic, which is the only stand-alone safety net clinic for children in our area. They now have 10,000 patient visits per year. Dr. Vaughters frequently did medical mission trips to Haiti over the years, then in 2002 decided to do more. He started a foundation and opened the Project for Family Planning and Aid for Children Clinic in Port-Au Prince. He would return to Haiti several times per year to work and make sure things were running smoothly. He wanted to impact the statistic that 50% of children die by the age of 5 in that region of Haiti. He was in Haiti on Jan. 12 and was at a meeting at the time of the earthquake in a building that was completely destroyed. He has not been heard from since. The community, his family, and his patients are devastated. Dr. Vaughters has four children of his own. This is a man that gave tirelessly to children of the world. I worked with him when he would come to make rounds on new babies or ill babies in the nursery and he was always kind and meticulous with his patients. He was a hero that will be missed.”

Dr. Vaughters on one of his trips to Haiti.

My thanks go to Christine Symes for bringing this story to my attention. I hope Dr. Vaughters’ family and friends find comfort in the work that he did for children.

More to come on Haiti next month.

I would like to thank Dr. Elizabeth Dufort for contributing this great case of S. sepsis for this month.

Elizabeth Dufort, MD, is an Assistant Professor in the Department of Pediatrics, Division of Pediatric Infectious Diseases at Hasbro Children’s Hospital/Brown University, Providence, Rhode Island.

James H. Brien, DO, is Head of the Pediatric Infectious Diseases Section at The Children’s Hospital at Scott and White and is the Associate Professor of Pediatrics at Texas A&M University, College of Medicine, Temple, Texas. E-mail: jhbrien@aol.com.