American Journal of Clinical Dermatology 2010;

This material is the copyright of the original publisher. Unauthorised copying and distribution is prohibited.

Terms and Conditions for Use of PDF The provision of PDFs for authors' personal use is subject to the following Terms & Conditions:

The PDF provided is protected by copyright. All rights not specifically granted in these Terms & Conditions are expressly reserved. Printing and storage is for scholarly research and educational and personal use. Any copyright or other notices or disclaimers must not be removed, obscured or modified. The PDF may not be posted on an open-access website (including personal and university sites).

The PDF may be used as follows: • to make copies of the article for your own personal use, including for your own classroom teaching use (this includes posting on a closed website for exclusive use by course students); • to make copies and distribute copies (including through e-mail) of the article to research colleagues, for the personal use by such colleagues (but not commercially or systematically, e.g. via an e-mail list or list serve); • to present the article at a meeting or conference and to distribute copies of such paper or article to the delegates attending the meeting; • to include the article in full or in part in a thesis or dissertation (provided that this is not to be published commercially). Am J Clin Dermatol 2010; 11 (5): 363-366 CASE REPORTS 1175-0561/10/0005-0363/$49.95/0

Cutaneous Infectious Granuloma Caused by Phenylobacterium in an Adult with Myelodysplastic Syndrome A First Case Report

Xiao-hua Zhu, Feng Li, Jin-hua Xu, Lei-hong Xiang and Ke-fei Kang Department of Dermatology,This Huashan Hospital, Fudan material University, Shanghai, China is

Abstract Painful granulomatous lesions appeared on the face of a 36-year-old man with myelodysplastic syn- thedrome. Skincopyright biopsy revealed chronic inflammatory granuloma. of Bacterial the cultures of the lesions and blood indicated the same unknown Gram-negative rod bacterium. The 16S ribosomal RNA sequence of the unknown bacterium yielded Phenylobacterium. Thus, we diagnosed cutaneous infectious granuloma caused by Phenylobacterium and myelodysplastic syndrome/refractory cytopenia with multi-lineage dysplasia. originalAfter treatment with combined antibacterials publisher. that were selected based on the tests for drug sensitivity, the lesions disappeared with only scars remaining and without any signs of relapse after 1 year. This is the first case report of cutaneous infectious granuloma caused by Phenylobacterium.

InfectiousUnauthorised granulomatous lesions may present as skin hemoglobin copying 8.3 g/dL (reference value 12–16 g/dL), and granulomas infected by Mycobacterium, Trypanosoma cruzi, platelets 32.9 · 109/L (reference value 100–300 · 109/L). Bone and Leishmania species. We report a case of a patient with marrow aspirate indicated myelodysplastic syndrome/refractory myelodysplastic syndrome complicated with Phenylobacterium- cytopenia with multi-lineage dysplasia. Cytogenetic analysis infected granulomatous lesionsand on his face. distributionwas abnormal: 46, XY, trp (1) (q21q32) [20]. Erythrocyte sedimentation rate was 28 mm/h (reference value 0–10 mm/h). Liver and renal function, electrolytes, blood sugar, and tumor markers such as prostate-specific antigen, carcino-embryonic 1. Case Report is prohibited.antigen, a-fetoprotein, and carbohydrate antigen 50 were nor- A 36-year-old Chinese man visited our department in mal. Hepatitis B surface antigen (HBsAg), hepatitis B envelope January 2007, presenting with painful pyogenic granulomatous antigen (HBeAg), antibodies to HBeAg, hepatitis B core anti- lesions on his face. The lesions were tender and had been pre- gen, hepatitis A virus IgM, hepatitis C virus, HIV, the rapid sent for 15 months. He had been treated with systemic peni- plasma reagin test, and rheumatoid factor were all negative. cillins and mupirocin ointment at primary-care centers, with no Lesion biopsy showed epithelial proliferation, and dermal improvement, and his lesions had subsequently worsened. He inflammation characterized by diffuse infiltration of primary had a history of trauma to the face. A diagnosis of myelodys- lymphocytes, histiocytes, plasmocytes, with occasional neutro- plastic syndrome was confirmed by an internal medicine spe- phils, and multinucleated giant cells (figure 2a) indicating chronic cialist 2 months prior to the lesions occurring. inflammatory granuloma. Physical examination showed many nodules ranging from Bacterial cultures of the lesional surface indicated the size of a pinhead to 2–3 cm in diameter distributed around Staphylococcus epidermidis. Fungal and Mycobacterium cul- the cheek, nasal, and submaxilla regions. Most of the lesions tures of the lesional surface and blood were negative. However, were ulcerated and covered with crusts (figure 1a). bacterial cultures of the lesions and blood both indicated the Laboratory tests showed peripheral blood pancytopenia: same unknown Gram-negative bacterium, with a rod shape and white blood cell count 2.3 · 109/L (reference value 4.5–11 · 109/L), varying in size from 0.3–0.5 mm in diameter and 0.5–2 mmin 364 Zhu et al.

a b

This material is the copyright of the cd original publisher. Unauthorised copying and distribution is prohibited. Fig 1. (a) Lesions before treatment; (b) lesions after 1 month of treatment; (c) lesions after 3 months of treatment; and (d) lesions 1 year later. length (figure 2b).The cultures were plated onto blood agar (5% gene (primers: 23F, AGAGTTTGATC(C/A)TGGCTCAG; sheep erythrocytes) and incubated in a humidified incubator at 1492R, TACGG(C/T)TAC CTTGTTACGACTT). The PCR 37C for 4 days. The colonies were grayish, circular, and convex product was 1504 bp (figure 2d), and was followed by sequen- with smooth edges and a smooth surface (figure 2c). The un- cing using the ABI Prism 377 DNA Sequencer (Shanghai known bacterium was further studied with the API 20NE test Invitrogen Biotech Co. Ltd, Shanghai, China). The 16S rRNA kit (for identification of Pseudomonas alcaligenes or Coma- sequence of the unknown bacterium was compared with the monas testosteroni) [bioMe´rieux, Marcy l’Etoile, France] with known sequences in the GenBank/EMBL/DDBJ databases. negative results. Drug sensitivity tests showed that the bacter- The unknown bacterium shares 99% identity of the 16S rRNA ium was sensitive to erythromycin, gentamicin, ciprofloxacin, sequences with Phenylobacterium (gene bank accession number cefoperazone, ceftazidime, aztreonam, and meropenem, and AY628697). Even though Phenylobacterium, P. alcaligenes, resistant to piperacillin and piperacillin/tazobactam. and C. testosteroni all belong to the Proteobacteria group, since Purified DNA 0.5 mg was subjected to polymerase chain re- Phenylobacterium is not identified by the API 20NE test kit, action (PCR) amplification for the 16S ribosomal RNA (rRNA) the unknown bacterium was then convincingly categorized into

the genus Phenylobacterium. Thus, the patient was diagnosed bacteriology, and molecular biology to confirm the diagnosis of with cutaneous infectious granuloma caused by Phenylo- cutaneous infectious granuloma caused by Phenylobacterium. bacterium and myelodysplastic syndrome/refractory cytopenia To our knowledge, this is the first case in a human that has with multi-lineage dysplasia. been reported in the literature. The genus Phenylobacterium at We commenced treatment with oral erythromycin (1 g/day), present comprises four species,[1-4] which have been isolated levofloxacin (500 mg/day), testosterone undecanoate (andriol; from a subsurface aquifer, alkaline groundwater, soil, and 80 mg/day), leucogen (60 mg/day), folic acid (30 mg/day), and activated sludge from a wastewater treatment plant, respect- vitamin B12 (cyanocobalamin; 75 mg/day) simultaneously. One ively. In our case, it appears that the skin wound on the month later, the lesions had shrunk in size and reduced in patient’s face caused this opportunistic infection. It has been number and no new lesions had occurred (figure 1b). The peri- recently documented that a new strain of Phenylobacterium pheral blood cell count had increased. Three months later, all was isolated from a human erythroleukemia cell line,[5] so the lesions had disappeared,This with only the scars material remaining clinicians need to be awareis of the pathogenic relevance to (figure 1c). The antibacterial treatment was then withdrawn. human disease. The patient remained in remission at the 1-year follow-up Myelodysplastic syndrome is characterized by one or more without any signs of clinical relapse (figure 1d). cytopenias despite a relatively hypercellular bone marrow, and the copyrighthas a tendency of to transform the into acute myeloid leukemia. Op- portunistic infections have been reportedly associated with 2. Discussion myelodysplastic syndrome; Mycobacterium avium,[6] Myco- We present an unusual case with multiple tumor-like granu- bacterium kansasii,[7] and Bordetella hinzii[8] have been isolated lomas on the face. Theoriginal lesions were studied by histopathology, publisher.from patients with myelodysplastic syndrome. Unauthoriseda b copying and distribution is prohibited. cd bp

2000 1504

1000

Fig 2. (a) Histopathology showing chronic inflammatory granuloma (hematoxylin and eosin stain; original magnification ·100). (b) Bacterial culture indicated the unknown Gram-negative rod bacterium with varying sizes of 0.3–0.5 mm in diameter and 0.5–2 mm in length. (c) Colonies were convex and grayish with smooth edges and a smooth surface on the blood agar (5% sheep erythrocytes). (d) The black arrow indicates the band of the polymerase chain reaction product with 1504 bp.

3. Conclusion 3. Lingens F, Blecher R, Blecher H, et al. Phenylobacterium immobile gen. Nov., sp. Nov., a gram-negative bacterium that degrades the herbicide chloridazon. Our findings suggest that Phenylobacterium might be a Int J Syst Bacteriol 1985; 35 (1): 26-39 potential opportunistic organism in immunocompromised 4. Tiago I, Mendes V, Pires C, et al. Phenylobacterium falsum sp. nov., an alphapro- teobacterium isolated from a nonsaline alkaline groundwater, and emended patients with myelodysplastic syndrome. description of the genus Phenylobacterium. Syst Appl Microbiol 2005; 28 (4): 295-302 5. Zhang K, Han W, Zhang R, et al. Phenylobacterium zucineum sp. nov., a Acknowledgments facultative intracellular bacterium isolated from a human erythroleukemia cell line K562. Syst Appl Microbiol 2007; 30 (3): 207-12 The authors thank Prof. Ju Li-wen, Department of Epidemiology of 6. Tsukada H, Chou T, Ishizuka Y, et al. Disseminated Mycobacterium avium- School of Public Health Safety, Ministry of Education, Fudan University, intracellulare infection in a patient with myelodysplastic syndrome (refractory Shanghai, China, for her assistance with the necessary research of bacterial anemia). Am J Hematol 1994 Apr; 45 (4): 325-9 cultures and organization of materials required to prepare this report. No 7. Komeno T, Itoh T, Ohtani K, et al. Disseminated nontuberculous myco- sources of funding were used to assist in the preparation of this case report. bacteriosis caused by mycobacterium in a patient with myelodysplastic syn- The authors have no conflicts ofThis interest that are directly material relevant to the drome. Intern Med 1996; is 35 (4): 323-6 content of this case report. 8. Fry NK, Duncan J, Edwards MT, et al. A UK clinical isolate of Bordetella hinzii from a patient with myelodysplastic syndrome. J Med Microbiol 2007; 56 (Pt 12): 1700-3 References 1. Aslam Z, Im WT,the Ten LN, et al. Phenylobacterium copyright koreense sp. nov., isolated of the from South Korea. Int J Syst Evol Microbiol 2005; 55 (5): 2001-5 Correspondence: Dr Jin-hua Xu, Department of Dermatology, Huashan 2. Kanso S, Patel BK. Phenylobacterium lituiforme sp. nov., a moderately ther- Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, mophilic bacterium from a subsurface aquifer, and emended description of the China. genus Phenylobacteriumoriginal. Int J Syst Evol Microbiol 2004; 54 (6): 2141-6 publisher.E-mail: [email protected] Unauthorised copying and distribution is prohibited.