The Pediatric Infectious Disease Journal Issue: Volume 15(5), May 1996, pp 464-465 Copyright: (C) Williams & Wilkins 1996. All Rights Reserved. Publication Type: [Brief Report] ISSN: 0891-3668 Accession: 00006454-199605000-00018 Keywords: Cutaneous aspergillosis, neonate [Brief Report] CUTANEOUS ASPERGILLOSIS IN A NEONATE Gupta, Meera M.D.; Weinberger, Barry M.D.; Whitley-Williams, Patricia N. M.D. Author Information Accepted for publication Jan. 31, 1996. Reprints not available. ---------------------------------------------- Outline REFERENCES Neonatal aspergillosis is rare. The first case was reported in 1955 and since then 22 additional cases have been described in the literature with only 6 survivors.1 The majority of the cases have been reported in the past decade as technology and skills in the management of critically ill premature infants have advanced with resultant improvement in their survival. Preterm infants are at high risk for fungal infections because of their impaired phagocytic and neutrophil chemotactic functions 2 and the fact that they frequently receive antibiotics and hyperalimentation and have several vascular catheters and invasive procedures performed on them. Most of the cases of neonatal aspergillosis described were disseminated and were diagnosed postmortem. Few cases of Aspergillus infection limited to the skin, in neonates, have been described.3-6 We report a case of primary cutaneous aspergillosis in a neonate, presenting as a subcutaneous abscess. Case report. Patient P was a 1470-g female infant born at 32 weeks of gestation by emergency cesarean section for fetal bradycardia. The mother of this infant was a 27-year-old white A/Rh+ female who had one previous uncomplicated pregnancy. The present pregnancy was unremarkable until late gestation when her anti-C antibody titers rose from 1:4 to 1:28. An ultrasound examination revealed hydropic changes in the fetus and amniocentesis revealed Zone 3 hyperbilirubinemia. Fetal transfusions were performed by cordocentesis at 28 and 30 weeks with resolution of hydrops and good fetal growth. Fetal distress preempted a third scheduled transfusion at 32 weeks leading to an emergent delivery of a severely depressed, limp, jaundiced infant with Apgar scores of 1, 1 and 4 at 1, 5 and 10 min, respectively. The baby required intensive resuscitative measures (intubation, assisted ventilation, blood transfusion, sodium bicarbonate and epinephrine). The baby was anemic at birth with a hemoglobin of 6 g/dl. An exchange blood transfusion was performed via the umbilical vein raising the hemoglobin to 13 g/dl. Ampicillin and gentamicin were administered for 7 days for suspected sepsis (blood culture was sterile). Ultrasound examination of the head on Day 2 of life revealed a small parenchymal lesion consistent with a hemorrhage in the periphery of the right temporal lobe which was confirmed on computerized tomography scan. An echocardiogram showed poor ventricular function with mild biventricular hypertrophy. Initial laboratory data revealed a white blood cell count of 4900/mm3 with 34% polymorphonuclear cells, 6% band forms and 60% lymphocytes; platelet count was 29 000/mm3; liver function tests were elevated: aspartate aminotransferase 852 U/l; alanine aminotransferase 588 U/l; gamma-glutamyl-transpeptidase 123 U/l, total bilirubin 4.9 mg/dl; direct bilirubin 2.7 mg/dl. Blood urea nitrogen was 37 mg/dl and creatinine was 2.7 mg/dl; the values peaked at 53 and 4.2 mg/dl, respectively, on the 8th day. Renal ultrasound examination showed echogenic kidneys with normal renal blood flow. The infant received several blood and platelet infusions, was stabilized and extubated on Day 6 and had a normal neurologic examination on Day 7 of life. Thrombocytopenia resolved on the 5th day of life. At 13 days of life a firm, indurated and nonfluctuant, 1.5-by 1.5-cm mass was palpated in the right axilla. The overlying skin was erythematous with no puncture wound seen and there was no localized axillary or generalized lymphadenopathy. The anterior fontanelle was flat; auscultation of the heart and lungs were normal; the liver edge was palpable 4cm below the costal margin and the spleen tip was palpable; there were no other skin lesions. Ultrasound examination of the axillary mass suggestive of an abscess. Multiple hypoxic episodes and poor feeding prompted cultures of blood and cerebrospinal fluid and initiation of vancomycin and cefotaxime therapy on Day 13 of life. Coagulase-negative Staphylococcus species were isolated in this blood culture. Cerebrospinal fluid demonstrated a glucose of 51 mg/dl, protein 93 mg/dl, red blood cells 20/ml, white blood cells 4/ml with an unremarkable Gram-stained smear. Cerebrospinal fluid and follow-up blood cultures were negative for bacteria and fungus (cultures were held for fungal isolation). The following day purulent drainage was noted from the mass. Surgical incision and drainage of the mass yielded 3 ml of purulent material. The Gram-stained smear showed a few white blood cells with no organisms. Two culture specimens of the drainage grew Aspergillus which was not further speciated. Amphotericin B and flucytosine therapy was started. Repeated blood and urine cultures yielded no growth of Aspergillus. Evaluation by ophthalmoscopy, chest roentgenogram, bone scan, echocardiogram and ultrasound examination of the liver, spleen and kidney revealed no evidence of dissemination and an ultrasound examination of the head on Day 17 of life revealed no change. Follow-up culture of the lesion 5 days later was negative for Aspergillus. The baby continued to be stable. Wound granulation was apparent on Day 10 of treatment and complete healing of the skin occurred by 4 weeks. Ultrasound examination of the head on Day 30 of life showed decrease in the size of the hemorrhage. The baby received 32 mg of amphotericin B during 46 days with an initial 2-week course of flucytosine. At a follow-up visit at 3 months of age, the baby was gaining weight and had no evidence of recurrent abscess or other infections. Discussion. Cutaneous aspergillosis is uncommon and is usually part of a systemic infection or an initial manifestation of disseminated disease. It is usually observed in immunosuppressed hosts. Primary cutaneous aspergillosis in a neonate is a rarity. The cutaneous manifestations can be as subcutaneous abscesses, pustules, cellulitis and ulcerations, purpura and toxic epidermal necrolysis.7 In primary cutaneous aspergillosis the lesion can occur as nodules or indurated, erythematous plaques that progress to ulceration with formation of black eschar.7, 8 Conditions that must coexist to allow for infection are: a breach in the integrity of the skin that provides a portal of entry; a state of increased susceptibility as occurs in immunocompromised state and prematurity; an ecologic disturbance created by use of a combination of chemotherapeutics, antibiotics, steroids and deep vascular catheters; and exposure to Aspergillus spores or conidia.9 The portal of entry is not identified in most neonates. In adults inhalation of air-borne conidia with pulmonary involvement is usually the case. However, in neonates several routes have been incriminated: the intestines during necrotizing enterocolitis 5; umbilical vessel catheter insertion under nonsterile conditions for exchange transfusion 9, 10; cellulitis/infiltration at catheter sites 5; and moist macerated skin of preterm neonates that are inadequate barriers to pathogens. In our patient it is possible that the infection could have been introduced during exchange transfusion after birth. It is also possible that a needle injury during intrauterine fetal transfusion causing integumentary disruption allowed inoculation of the skin postnatally. The source of conidia could be an ascending vaginal infection, although not clearly proved 5 (no case of congenital aspergillosis has been documented), or prolonged contact with adhesive tapes and gauze used to secure intravenous armboards 3, 7, 8 and bedding 5 that may harbor conidia. In our patient no invasive procedures or occlusive dressings were previously applied at the axillary site. Previous reports have noted the presence of environmental Aspergillus and the potential for nosocomial infection. This was not thought to be a source because no construction was ongoing during this period in the intensive care nursery or the obstetric suite. Histologic evidence is required for definitive diagnosis. The presence of slender, septate hyphae with dichotomous branching at 45-degree angles is suggestive of Aspergillus,10 and culture identifies the species. Histology was not available in our patient because of the parents' refusal to consent. Diagnosis in our case was made no the basis of isolation of Aspergillus from two specimens (including the intraoperative specimen) from the abscess as well as response to therapy. It is doubtful that the coagulase-negative staphylococci played a role in the abscess formation because this is not the usual mode in which this organism manifests itself. Because Aspergillus tends to invade blood vessels, the potential for dissemination exists and search for other areas of involvement is indicated. Despite extensive search in our patient there was no evidence of dissemination. Amphotericin B is the drug of choice and has a good success rate in cutaneous disease, especially when combined with extensive debridement of lesions.5 Surgical resection alone 3 and medical therapy 5, 6 have been effectively used to cure cutaneous Aspergillus infection. However, if lesions progress despite systemic antifungal therapy, surgical excision should be considered. Our patient responded to medical therapy with surgical drainage. Meera Gupta, M.D.; Barry Weinberger, M.D.; Patricia N. Whitley-Williams, M.D. Departments of Pediatrics, Divisions of Immunology, Allergy and Infectious Diseases (MG, PNWW) and Neonatology (BW) UMDNJ-Robert Wood Johnson Medical School New Brunswick, NJ REFERENCES 1. Remington JS, Klein JO. Infectious diseases of the fetus and newborn infant. Philadelphia: Saunders, 1995:717-20. 2. Gotoff SP. Neonatal immunity. J Pediatr 1974;85:149-54. Full text via Find It Bibliographic Links 3. Granstein RD, First LR, Sober AJ. Primary cutaneous aspergillosis in a premature neonate. Br J Dermatol 1980;103:681-4. Full text via Find It Bibliographic Links 4. Roth JG, Troy JL, Esterly NB. Multiple cutaneous ulcers in a premature neonate. Pediatr Dermatol 1991;8:253-5. Full text via Find It Bibliographic Links 5. Rowen JL, Correa AG, Sokol DM, et al. Invasive aspergillosis in neonates: report of five cases and literature review. Pediatr Infect Dis J 1992;11:576-82. Ovid Full Text Full text via Find It Bibliographic Links 6. Perzigian RW, Faix RG. Primary cutaneous aspergillosis in a preterm infant. Am J Perinatol 1993;10:269-71. Full text via Find It Bibliographic Links 7. Carlile JR, Millet RE, Cho CT, et al. Primary cutaneous aspergillosis in a leukemic child. Arch Dermatol 1978;114:78-80. Full text via Find It Bibliographic Links 8. McCarty JM, Flam MS, Pullen G, Jones R, Kassel SH. Outbreak of primary cutaneous aspergillosis related to intravenous arm boards. J Pediatr 1986;108:721-4. Full text via Find It Bibliographic Links 9. Luke JL, Bolande RP, Gross S. Generalized aspergillosis and Aspergillus endocarditis in infancy: report of a case. Pediatrics 1963;31:115-22. Full text via Find It Bibliographic Links 10. Gonzalez-Crussi F, Mirken LD, Wyllie RM, Escobedo M. Acute disseminated aspergillosis during the neonatal period, report of an instance in a 14-day old infant. Clin Pediatr 1979;18:137-43. Full text via Find It Bibliographic Links Key words: Cutaneous aspergillosis; neonate