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Case Report/Case Series
June 2015

Trichosporon inkin as an Emergent Pathogen in Patients With Severe Pemphigus

Author Affiliations
  • 1Central Laboratory Division, LIM 03, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
  • 2Laboratory of Medical Mycology (LIM 53), Division of Dermatology Clinic, Hospital das Clínicas da Faculdade de Medicina da Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, São Paulo, Brazil
  • 3Pathology Division, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
  • 4Department of Dermatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
JAMA Dermatol. 2015;151(6):642-645. doi:10.1001/jamadermatol.2014.5462
Abstract

Importance  To our knowledge, these are the first reports of bloodstream infections by Trichosporon inkin in patients with pemphigus.

Observations  Trichosporon inkin, a novel organism causing bloodstream infection, was detected in 2 patients with pemphigus. An elderly man with pemphigus foliaceus died despite treatment with liposomal amphotericin B, 3 mg/kg/d, and a young girl with pemphigus vulgaris responded to treatment with voriconazole, 8 mg/kg/d, for 24 days. One of the T inkin isolates had a minimal inhibitory concentration of 2 mg/L against amphotericin B, suggesting resistance to the drug.

Conclusions and Relevance  Delayed suspicion of invasive infection by T inkin may result in a poor outcome in patients with severe forms of pemphigus. This opportunistic infection is highly refractory to conventional potent antifungal treatment.

Introduction

Treatment for pemphigus relies on systemic corticosteroids, usually administered with other immunosuppressant agents. Treatment controls disease activity but may lead to severe infections.1 Mortality rates can reach 80% to 100% in patients with pemphigus who develop septicemia.2,3

Trichosporon inkin is the etiologic agent of white piedra, a benign disease of hair shafts.4 Invasive fungal infection caused by this species was described4 in patients with predisposing factors, such as oncohematologic diseases and neutropenia. Recently, invasive fungal infection caused by T inkin was reported in patients in our hospital who underwent solid organ transplantation.5 Our aim is to report what we believe to be the first cases of deep-seated infections related to T inkin in patients with pemphigus.

Positive blood cultures (obtained using Bactec Plus Aerobic/F; Becton Dickinson and Company) were platted (CHROMagar Candida; Becton Dickinson and Company), and phenotypic identification was carried out by urease test, slide culture, and the carbon assimilation panel (API 20AUX; bioMérieux). To confirm species identification, double-strand sequencing of the ribosomal DNA intergenic spacer 1 region was performed6; sequences were then compared with those in the GenBank database (http://www.ncbi.nlm.nih.gov). Antifungal susceptibility testing for amphotericin B, fluconazole, itraconazole, and voriconazole was carried out using the recently revised European Committee on Antimicrobial Susceptibility Testing microdilution method for yeasts.7

Report of Cases
Case 1

A 71-year-old man who had developed pemphigus foliaceus 6 months before the hospital consultation had disseminated erythematous, desquamative skin lesions and pustules restricted to his buttocks and lower extremities. He was receiving systemic treatment with prednisone, 1 mg/kg/d. Laboratory evaluation results showed (1) pemphigus foliaceus with secondary impetiginization (Figure 1A), (2) intraepidermal intercellular IgG and C3 deposits (Figure 1B), and (3) intercellular intraepidermal staining (titer, 1:5120) (Figure 1C).

Figure 1.
Clinical and Histopathologic Findings From Case 1
Clinical and Histopathologic Findings From Case 1

A, Pemphigus foliaceus extending from the patient’s back to his lower extremities. B, Histopathologic findings demonstrate subcorneal cleavage in pemphigus foliaceus (hematoxylin-eosin, original magnification ×100). C, Direct immunofluorescence shows intraepidermal intercellular IgG deposits (hematoxylin-eosin, original magnification ×200).

The prednisone dose was increased to 1.5 mg/kg/d, and cephalexin, 2 g/d for 14 days, was prescribed for treatment of a secondary bacterial skin infection. The patient had persistent hyperglycemia, which was treated with insulin. Although his skin lesions improved, the patient developed fever and respiratory symptoms due to right-sided pneumonia 30 days after the prednisone dose was increased. Despite antimicrobial therapy with piperacillin sodium–tazobactam sodium, 16 g/d, and vancomycin hydrochloride, 2 g/d, the infection progressed, and the patient developed septic shock, respiratory failure, and renal failure. He was transferred to the intensive care unit and underwent mechanical ventilation and hemodialysis. On day 34, 2 sets of blood cultures that were collected on the patient’s admission to the intensive care unit revealed budding yeast cells that were identified as Candida albicans (day 38). Therapy with liposomal amphotericin B, 3 mg/kg/d, was started. On day 39, the patient developed a new episode of septic shock. A primary culture of tracheal aspirates yielded yeast cells interpreted as “colonizing agents.” Skin scrapings collected from the patient’s face and anterior abdomen on the same day also showed abundant yeast cells and arthroconidia (Figure 2). The patient died 2 days later.

Figure 2.
Skin Scraping From the Patient With Pemphigus Foliaceus
Skin Scraping From the Patient With Pemphigus Foliaceus

Yeastlike cells and arthroconidia (arrowheads) are suggestive of Trichosporon (hematoxylin-eosin, original magnification ×1000).

Three consecutive sets of blood cultures collected during amphotericin B treatment on days 39, 40 (through the central venous catheter), and 41 were positive, with budding and arthrosporic fungal elements on Gram stain. Trichosporon inkin was identified in the 3 samples.

Case 2

A 9-year-old girl with pemphigus vulgaris was hospitalized with fever and worsening skin lesions. She was receiving oral prednisone, 1 mg/kg/d. Physical examination revealed extensive oral mucosal erosions and ulcerations with superficial bullae on her trunk as well as her upper and lower limbs. Laboratory evaluation results showed (1) suprabasal epidermal acantholysis, clefting, and blister formation; (2) intercellular IgG and C3 deposits at the lower layers of the epidermis; and (3) intercellular intraepidermal staining, titer 1:2560.

Bacterial infection of the skin was treated with vancomycin, 1 g d, and piperacillin-tazobactam, 6.75 g/d. Blood cultures collected on admission were negative for organisms; the prednisone dose was increased to 1.5 mg/kg/d and then was replaced by betamethasone sodium phosphate, 6 mg/d. On day 5, the patient experienced a new episode of fever. Subsequent blood cultures showed budding yeast cells on direct examination, and T inkin was identified 2 days later. Fluconazole, 300 mg/d, was prescribed. Despite antimicrobial and antifungal therapy, the fever persisted. On day 15, treatment was switched to voriconazole, 8 mg/kg/d, which was maintained for 24 days. The patient was discharged after 112 days of hospitalization.

Discussion

The 2 urease-positive isolates were initially identified as T inkin. Ribosomal DNA intergenic spacer 1 region sequencing confirmed the species identification. Antifungal susceptibility testing revealed that the isolate of T inkin from the patient in case 1 had a minimal inhibitory concentration (MIC) of 2.0 mg/L for amphotericin B, suggesting resistance to this drug. The T inkin isolates in both patients had 100% similarity to a sequence available in GenBank (FJ153608.1). The MICs for cases 1 and 2, respectively, were amphotericin B, 2.0 and 0.5 mg/L; fluconazole, 2.0 and 1.0 mg/L; voriconazole, 0.03 and 0.03 mg/L; and itraconazole, 0.06 and 0.25 mg/L.

Opportunistic infections in pemphigus, although not rare, are seldom reported. In one study,8Nocardia, cytomegalovirus, Legionella, and Listeria were the most frequent organisms linked to opportunist infections, affecting elderly patients as well as those receiving prophylaxis for Pneumocystis jirovecii. Although neutropenia is the major predisposing risk factor for invasive trichosporonosis, both of our patients had white blood cell counts within the reference range.9 The severity of cutaneous/mucosal involvement and development of diabetes mellitus, which were present in our patients, are also risk factors for infections in patients with pemphigus vulgaris.2

Features shared by our patients were previous antibiotic therapy, indwelling catheters, and breakthrough infection during amphotericin B or fluconazole therapy. Cultures obtained from wounds, respiratory tract samples, and intravenous catheters are often positive for Trichosporon before or during the episode of invasive infection.10 In the present report, the patient in case 1 demonstrated yeast in the tracheal aspirate skin sample collected on the same day as the first blood culture that identified T inkin. Despite belonging to the normal microbiota of the human gastrointestinal tract, respiratory tract, and skin, T inkin is potentially acquired through the hospital environment.11 Neither of our patients had hair lesions compatible with white piedra. Our cases therefore were nosocomial infections of unknown sources caused by T inkin.

Clinical breakpoints have not been defined for Trichosporon species, and the MICs cannot be reliably interpreted as indicating resistance or susceptibility.7,12Trichosporon asahii is the most commonly isolated species in invasive trichosporonosis, and a high percentage of these isolates have MICs above 1.0 mg/L, suggestive of resistance to amphotericin B.13 Among the few clinical isolates of T inkin tested, some MICs above 1.0 mg/L for amphotericin B have been described. One of our isolates had an MIC of 2.0 mg/L for amphotericin B. Among the azole derivatives, voriconazole seems to have the strongest in vitro activity against Trichosporon isolates.13

Conclusions

The identification of yeasts from nonsterile sites, such as the respiratory tract and skin, may cause suspicion of T inkin infection in patients with pemphigus. In such instances, voriconazole therapy should be promptly initiated.

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Article Information

Accepted for Publication: December 11, 2014.

Corresponding Author: João Nobrega de Almeida Júnior, MD, PhD, Central Laboratory Division, LIM 03, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil (jnaj99@gmail.com).

Published Online: March 18, 2015. doi:10.1001/jamadermatol.2014.5462.

Author Contributions: Drs Nobrega de Almeida Júnior and Benard had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Nobrega de Almeida Júnior, Buccheri de Oliveira, Lopes Motta, Sachiko Yamamoto de Figueiredo, Aoki, Wakisaka Maruta, Giuli Santi, Benard.

Acquisition, analysis, or interpretation of data: Buccheri de Oliveira, Duarte, Lopes Motta, Rossi, Sachiko Yamamoto de Figueiredo, Barbaro Del Negro, Aoki, Wakisaka Maruta, Giuli Santi.

Drafting of the manuscript: Nobrega de Almeida Júnior, Buccheri de Oliveira, Duarte, Lopes Motta, Sachiko Yamamoto de Figueiredo, Barbaro Del Negro, Aoki, Giuli Santi.

Critical revision of the manuscript for important intellectual content: Lopes Motta, Rossi, Sachiko Yamamoto de Figueiredo, Aoki, Wakisaka Maruta, Giuli Santi, Benard.

Administrative, technical, or material support: Buccheri de Oliveira, Duarte, Lopes Motta, Rossi, Barbaro Del Negro, Aoki, Wakisaka Maruta, Giuli Santi.

Study supervision: Nobrega de Almeida Júnior, Lopes Motta, Aoki, Wakisaka Maruta, Giuli Santi, Benard.

Conflict of Interest Disclosures: None reported.

Additional Contributions: Anna Sara Shaferman-Levin, MD, PhD, Infectious Diseases Department, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, edited the manuscript. There was no financial compensation

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