Primary cutaneous aspergillosis and idiopathic bone marrow aplasia* * Work performed at the Hospital do Servidor Público Estadual (HSPE) - São Paulo (SP), Brazil.

Karina Colossi Furlan Mario Cezar Pires Priscila Kakizaki Juliana Cabral Nunes Chartuni Neusa Yuriko Sakai Valente About the authors

Abstract:

We describe the case of a 9-year-old boy with idiopathic bone marrow aplasia and severe neutropenia, who developed skin ulcers under cardiac monitoring electrodes. The diagnosis of primary cutaneous aspergillosis was made after the second biopsy and culture. Imaging investigation did not reveal internal fungal infection. The child was treated, but did not improve and died 3 months after admission. The report highlights and discusses the preventable risk of aspergillus skin infection in immunocompromised patients.

Keywords:
Aspergillosis; Bone marrow; Immunosuppression; Spores, fungal

INTRODUCTION

Aspergillus spps. is the second most common cause of opportunistic fungal infection in humans after Candida albicans.11 Tahir C, Garbati M, Nggada HA, Yawe EH, Abubakar AM. Primary cutaneous aspergillosis in an immunocompetent patient. J Surg Tech Case Rep. 2011;3:94-6. It causes severe infections in immunocompromised patients, resulting in high mortality, specially in neonates.22 Andresen J, Nygaard EA, Størdal K. Primary cutaneous aspergillosis (PCA)-a case report. Acta Paediatr. 2005;94:761-2. The usual infection organs are the lungs, central nervous system (CNS) and paranasal sinuses.

Primary cutaneous aspergillosis (PCA) is a rare condition, usually associated with immunodeficiency, secondary to hematologic disorders.11 Tahir C, Garbati M, Nggada HA, Yawe EH, Abubakar AM. Primary cutaneous aspergillosis in an immunocompetent patient. J Surg Tech Case Rep. 2011;3:94-6. There are two different inoculation routes into the skin: non-sterile devices or airborne Aspergillus conidia colonization of the traumatized skin.33 Anderson A, Foster RS, Brand R, Blyth CC, Kotecha RS.Acute Onset of Pustules at the Site of Tape Placement in an Immunocompromised Infant with Acute Myeloid Leukemia. Pediatr Dermatol. 2014;31:609-10. Herein, we evidence the first case of PCA under the cardiac monitoring electrodes, in a child with idiopathic bone marrow aplasia.

CASE REPORT

A 9-year-old boy diagnosed with idiopathic bone marrow aplasia was admitted to the pediatric intensive care unit (ICU) with septic shock and respiratory insufficiency, requiring mechanical ventilation and cardiac monitoring. He suffered from severe neutropenia and after a few weeks, developed a fever of unknown origin (FUO). The patient received broad-spectrum antibiotic and antifungal therapy, without clinical improvement.

After 45 days on the pediatric ICU, the patient developed circular erythematous lesions with a necrotic center under the cardiac monitoring electrodes (Figure 1). The lesions underwent extensive necrosis in 10 days (Figure 2). The second biopsy performed showed septate hyaline hyphae upon hematoxylin-eosin staining (Figure 3). Grocott staining showed many septate hyphae with branches at acute angles (Figure 4). Culture of the material in Sabouraud dextrose agar plate revealed darker reverse coloration, while microcultive in lamina technique confirmed the presence of the Aspergillus niger species (Figure 5). A whole body computed tomography scan did not reveal disseminated fungal infection.

Figure 1 :
Erythematous circular lesion with a necrotic center under the cardiac monitoring electrode

Figure 2 :
Necrotic circular lesion under the cardiac monitoring electrode

Figure 3 :
Septate hyaline hyphae on tissue sample (Hematoxylin- Eosin staining)

Figure 4 :
Grocott staining on tissue sample shows many septate hyphae with branches at acute angles

Figure 5 :
Microcultive in lamina confirmed the species Aspergillus niger

The patient was already receiving amphotericin B and fluconazole. After the diagnosis, voriconazole was added to antifungal therapy, though there was no improvement and the patient died 3 months after admission.

DISCUSSION

Cutaneous aspergillosis can be either primary or secondary. Primary cutaneous lesions usually result from direct inoculation of the Aspergillus species due to trauma, especially in patients on catheter care, trauma from arm boards, burns and infected dressings. There are also reported cases of fungi in aerosol at neonatal ICUs during building renovation.11 Tahir C, Garbati M, Nggada HA, Yawe EH, Abubakar AM. Primary cutaneous aspergillosis in an immunocompetent patient. J Surg Tech Case Rep. 2011;3:94-6. Secondary cutaneous aspergillosis stems from disseminated infection.11 Tahir C, Garbati M, Nggada HA, Yawe EH, Abubakar AM. Primary cutaneous aspergillosis in an immunocompetent patient. J Surg Tech Case Rep. 2011;3:94-6.

PCA is usually caused by Aspergillus flavus, A. terreus, A. niger and A. ustus. The lesion may present as erythematous, indurated macules, papules, plaques or hemorrhagic bullae, which can progress to necrotic ulcers that are covered by black eschar. Although rare, nodules and pustular lesions can also be present.44 Ajith C, Dogra S, Radotra BD, Chakrabarti A, Kumar B. Primary cutaneous aspergillosis in an immunocompetent individual. J Eur Acad Dermatol Venereol. 2006;20:738-9.,55 Ozer B, Kalaci A, Duran N, Dogramaci Y, Yanat AN. Cutaneous infection caused by Aspergillus terreus. J Med Microbiol. 2009;58:968-70.

Tahir et al.11 Tahir C, Garbati M, Nggada HA, Yawe EH, Abubakar AM. Primary cutaneous aspergillosis in an immunocompetent patient. J Surg Tech Case Rep. 2011;3:94-6. described an immunocompetent female with multiple ulcers in the axillae and perineum. She most probably contracted the infection from contaminated palm oil on which she was conducting a research and got inoculated after shaving her axillae and perineum with razor blades. The patient fully recovered after wound surgery.11 Tahir C, Garbati M, Nggada HA, Yawe EH, Abubakar AM. Primary cutaneous aspergillosis in an immunocompetent patient. J Surg Tech Case Rep. 2011;3:94-6. Anderson et al.33 Anderson A, Foster RS, Brand R, Blyth CC, Kotecha RS.Acute Onset of Pustules at the Site of Tape Placement in an Immunocompromised Infant with Acute Myeloid Leukemia. Pediatr Dermatol. 2014;31:609-10. described a child diagnosed with acute myeloid leukemia, who developed two asymptomatic, geometric, erythematous dermal plaques on his right forearm. The skin lesions occurred at the site of tapes applied to secure an arm board for intravenous access and the culture isolated Aspergillus niger. The eruption rapidly resolved with systemic anti-fungal therapy.33 Anderson A, Foster RS, Brand R, Blyth CC, Kotecha RS.Acute Onset of Pustules at the Site of Tape Placement in an Immunocompromised Infant with Acute Myeloid Leukemia. Pediatr Dermatol. 2014;31:609-10. Stock et al. reported necrotic skin lesions in the back, perineum, and axillae in a premature neonate.66 Stock C, Veyrier M, Raberin H, Fascia P, Rayet I, Lavocat MP, et al. Severe cutaneous aspergillosis in a premature neonate linked to nonsterile disposable glove contamination? Am J Infect Control. 2012;40:465-7Aspergillus fumigatus was isolated and a disposable, non-sterile glove was found to be contaminated with Aspergillus fumigatus. This glove could have infected the neonate's skin.66 Stock C, Veyrier M, Raberin H, Fascia P, Rayet I, Lavocat MP, et al. Severe cutaneous aspergillosis in a premature neonate linked to nonsterile disposable glove contamination? Am J Infect Control. 2012;40:465-7 The routes of inoculation in our patient include the use of non-sterile cardiac monitoring electrodes, harboring aspergillus on the skin.

The diagnosis of PCA is carried out with a biopsy and culture. In some cases, hyphae can be observed upon mycological examination under direct microscopic examination.77 Saghrouni F, Ben Youssef Y, Gheith S, Bouabid Z, Ben Abdeljelil J, Khammari I, et al. Twenty-nine cases of invasive aspergillosis in neutropenic patients. Med Mal Infect. 2011;41:657-62.

The treatment of aspergillosis is made with systemic antifungal drugs like amphotericin B and itraconazole. Treatment of primary cutaneous fungal infection is controversial; both medical and surgical modalities have been used.88 Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327-60. Voriconazole and deoxycholate amphotericin B are the only licensed drugs in the United States for primary treatment of invasive aspergillosis. Itraconazole and caspofungin have been approved for salvage therapy of invasive aspergillosis.88 Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327-60.

In immunocompromised patients with unusual skin lesions, we should always suspect infectious disease. Biopsy and cultures are essential for pathogen identification and more than one sample may be required for correct diagnosis. We strongly recommend the use of sterile disposable devices in immunocompromised patients. Our case highlights the preventable risk of PCA and the importance of closely monitoring the evolution of skin changes associated with the use of medical devices.

  • Financial Support: None.
  • *
    Work performed at the Hospital do Servidor Público Estadual (HSPE) - São Paulo (SP), Brazil.

REFERENCES

  • 1
    Tahir C, Garbati M, Nggada HA, Yawe EH, Abubakar AM. Primary cutaneous aspergillosis in an immunocompetent patient. J Surg Tech Case Rep. 2011;3:94-6.
  • 2
    Andresen J, Nygaard EA, Størdal K. Primary cutaneous aspergillosis (PCA)-a case report. Acta Paediatr. 2005;94:761-2.
  • 3
    Anderson A, Foster RS, Brand R, Blyth CC, Kotecha RS.Acute Onset of Pustules at the Site of Tape Placement in an Immunocompromised Infant with Acute Myeloid Leukemia. Pediatr Dermatol. 2014;31:609-10.
  • 4
    Ajith C, Dogra S, Radotra BD, Chakrabarti A, Kumar B. Primary cutaneous aspergillosis in an immunocompetent individual. J Eur Acad Dermatol Venereol. 2006;20:738-9.
  • 5
    Ozer B, Kalaci A, Duran N, Dogramaci Y, Yanat AN. Cutaneous infection caused by Aspergillus terreus. J Med Microbiol. 2009;58:968-70.
  • 6
    Stock C, Veyrier M, Raberin H, Fascia P, Rayet I, Lavocat MP, et al. Severe cutaneous aspergillosis in a premature neonate linked to nonsterile disposable glove contamination? Am J Infect Control. 2012;40:465-7
  • 7
    Saghrouni F, Ben Youssef Y, Gheith S, Bouabid Z, Ben Abdeljelil J, Khammari I, et al. Twenty-nine cases of invasive aspergillosis in neutropenic patients. Med Mal Infect. 2011;41:657-62.
  • 8
    Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327-60.

Publication Dates

  • Publication in this collection
    May-Jun 2016

History

  • Received
    29 June 2015
  • Accepted
    05 Sept 2015
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