A Case of Widespread Tender, Erythematous Nodules in a Toddler During Chemotherapy
A 22-month-old girl developed skin lesions while on a chemotherapy regimen for acute lymphocytic leukemia. A dermatologist was consulted to evaluate the tender nodules on the child’s arms, legs, and trunk (Figures 1 and 2). The patient had an indwelling central venous line.
What is the best next step?
A. A trial of topical corticosteroid therapy
B. A trial of topical antibiotic therapy
C. Cool compresses
D. Skin biopsy
E. Computed tomography scan of the chest and abdomen
(Answer and discussion on next page)
Answer: D, skin biopsy
A skin biopsy was obtained, and routine histologic evaluation revealed fungal organisms. A periodic acid–Schiff stain (PAS) highlighted the blastospores and pseudohyphae of the organisms at the junction of the reticular dermis and panniculus (Figure 3).
The location of the organisms supported the clinical suspicion of a disseminated infection. Blood, urine, and catheter tip cultures revealed Candida tropicalis. The child was placed on an empirical regimen of liposomal amphotericin B and caspofungin therapy. Sensitivity studies revealed that the candida was sensitive to fluconazole. She was placed on fluconazole therapy, after which the nodules gradually resolved.
Discussion
The development of nodules in the setting of chemotherapy is an ominous sign. Infection is the most likely cause, and biopsy for routine histologic evaluation and culture is an efficient way of clarifying the diagnosis. Erythematous nodules in infants and young children raise a broad differential diagnosis that includes inflammatory conditions such as sarcoidosis, medication reactions, arthropod bite reactions, folliculitis, and even entities such as cold panniculitis.
A trial of topical treatment with close follow-up can be a very reasonable course of action to help clarify a diagnosis in a variety of situations. The chemotherapy setting, however, is fraught with difficulty, and accurate and timely diagnosis is critical to avoid rapid deterioration. Patients with neutropenia are particularly susceptible to infection, and patients who seem well can experience a rapid deterioration of clinical status.1 Skin biopsy is mandatory in this situation.
In our patient’s case, culture results confirmed a diagnosis of candidemia, but the skin biopsy allowed for rapid and definitive evaluation of the nodules that were noted on clinical inspection.
Candidemia is a well recognized complication in patients with neutropenia. The 3 main routes by which candida can enter the bloodstream are through intravascular catheters, the gastrointestinal system, or from a localized infectious source such as pyelonephritis.2
The clinical signs of candidemia in the pediatric population can range from an absence of observable signs to multiorgan failure. When skin lesions present, they can range from tiny pustules that are often difficult to identify to nodules with necrotic centers that are often a few centimeters in diameter. The mortality can be as high as 50%.3
Although fluconazole has been very effective, resistant organisms are becoming more common. Organisms other than Candida albicans also are increasingly prevalent.4 Standardized polymerase chain reaction assays and assays for the cell wall component β-D-glucan hold promise for increasing diagnostic capabilities. Other nonculture assays that show promise for the prompt diagnosis of candidemia include mannan antigen and antimannan-antibody assays.1
The number of effective drugs available to treat candidemia is increasing. In most neutropenic patients, an echinocandin such as caspofungin, micafungin, or anidulafungin is recommended. In less-ill neutropenic patients who have had no recent exposure to azoles, fluconazole can be used. Generally, voriconazole is used if additional fungal coverage is needed.3 If echinocandin resistance is a possibility, amphotericin B should be initiated until the results of sensitivity studies become available.3,5-7 Treatment should be continued for 2 weeks after cultures have failed to reveal growth.
In addition, all patients with candidemia should undergo an ophthalmologic examination to rule out abnormalities such as chorioretinitis and endophthalmitis, which can occur simultaneously with the onset of candidemia.
Leesha Alex, BS, is a medical student at the State University of New York (SUNY) Upstate Medical University in Syracuse, New York.
Ted C. Ondracek, MD, is a clinical assistant professor at the SUNY University at Buffalo School of Medicine and Biomedical Sciences in Buffalo, New York
Ilene L. Rothman, MD, is an assistant professor of pediatrics chief of the Department of Pediatric Dermatology at Women & Children’s Hospital of Buffalo in Buffalo, New York.
Thomas N. Helm, MD, is a clinical professor of dermatology and pathology at the SUNY University at Buffalo School of Medicine and Biomedical Sciences in Buffalo, New York.
References
1. Mikulska M, Calandra T, Sanguinetti M, Poulain D, Viscoli C; Third European Conference on Infections in Leukemia Group. The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia. Crit Care. 2010;14(6):R222.
2. Fridkin SK. The changing face of fungal infections in health care settings. Clin Infect Dis. 2005;41(10):1455-1460.
3. Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Disease Society of America. Clin Infect Dis. 2009;48(5):503-535.
4. Oxman DA, Chow JK, Frendl G, et al. Candidaemia associated with decreased in vitro fluconazole susceptibility: is Candida speciation predictive of the susceptibility pattern? J Antimicrob Chemother. 2010;65(7):1460-1465.
5. Stamos JK, Rowley AH. Candidemia in a pediatric population. Clin Infect Dis. 1995;20(3):571-575.
6. Kofteridis DP, Lewis RE, Kontoyiannis DP. Caspofungin–non-susceptible Candida isolates in cancer patients. J Antimicrob Chemother. 2010;65(2):293-295.
7. Blyth CC, Chen SCA, Slavin MA, et al; Australian Candidemia Study. Not just little adults: candidemia epidemiology, molecular characterization, and antifungal susceptibility in neonatal and pediatric patients. Pediatrics. 2009;123(5):1360-1368.