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Penicillium marneffei osteomyelitis

Introduction

Osteomyelitis can be caused by bacteria as well as fungi.The disease is treatable with appropriate antibiotics orantifungal agents. During investigations, it is importantto remember to look out for fungal infection. Doing sowill allow a proper and accurate diagnosis to be made.In this way, appropriate treatment can be commencedand potentially serious complications can be avoided.

Case report

A 30-year-old Filipino woman presented to the QueenMary Hospital (QMH) in April 1993 with pyrexia ofunknown origin and cervical lymphadenopathy. Thepatient had a history of mixed connective disease andhad attended regular follow-up at the Department ofMedicine of the QMH. Fever had developed 2 weeksbefore the hospital admission. On arrival at the QMH,she was emaciated, in a toxic condition, and had inter-mittent fever without any bone pain. A soft-tissue masswas felt over the forehead. Multiple firm and enlargedcervical lymph nodes were also palpable.

Laboratory investigations showed a white blood cellcount of 30.3 x 109 /L (normal range, 3.2-9.8 x 109 /L)with 93.6% neutrophils, haemoglobin level of 86 g/L(normal range, 120-150 g/L), erythrocyte sedimentationrate of 133 mm/h (normal range, 0-30 mm/h), and C-

Department of Orthopaedics and Traumatology, The University ofHong Kong, Queen Mary Hospital, Pokfulam, Hong KongTS Pun, MB, BS, FRCS (Edin)306 Tak Shing House, 20 Des Voeux Road, Central, Hong KongD Fang, FRCS (Edin), FHKAM (Orthopaedic Surgery)

Correspondence to: Dr TS Pun

A case of Penicillium marneffei osteomyelitis involvingthe axial skeletonTS Pun, D Fang

Fungal infection of bone by Penicillium marneffei is rare. We report on a case of Penicillium marneffeiinfection in a Filipino woman, which involved multiple soft-tissue abscesses and infection of the axialskeleton. Early diagnosis and treatment of this potentially reversible disease is emphasised. Such anapproach is essential to prevent bony destruction from becoming too advanced and, more importantly,to prevent any damage to the spinal cord from occurring.

HKMJ 2000;6:231-3

Key words: Antifungal agents; Bone diseases/etiology; Bone diseases/radiology; Osteomyelitis; Penicillium

reactive protein level of 180 mg/L (normal range, 100-270 mg/L). Blood culture was negative for bacteriaand fungi. All tests to detect viruses, including humanimmunodeficiency virus types 1 and 2, gave negativeresults. Antinuclear factor was present, at a titre of 1:1080;rheumatoid factor and antibodies to double-strandedDNA were absent. Biopsy examination of the bonemarrow did not show any haematological diseases.

The X-ray of the cervical spine showed lyticlesions at the C2 vertebral body (Fig 1) and the head ofleft humerus. Multiple lytic lesions were also visibleover the proximal shaft of the right femur. Galliumbone scanning detected multiple sites of abnormaluptake in the upper cervical spine, left shoulder, rightside of manubrium, and right femur, which corres-ponded to multiple sites of infection. The chest X-rayshowed no evidence of pulmonary infection.

An excisional biopsy examination of a cervicallymph node showed granulomatous lymphadenitis,but this finding was inconclusive. The biopsy sitefailed to heal and persisted as a skin ulcer. Staining foracid-fast bacilli and fungi were negative. The patientwas given antituberculous drug treatment empirically.Fine-needle aspiration of the soft-tissue mass on theleft side of the forehead revealed yeast cells. Histo-logical examination of decalcified sections of a corebiopsy sample from the left humerus showed diffusefibrosis of the intertrabecular space and infiltration ofhistocytes. Well-formed granulomas or giant cellswere absent. However, yeast-form fungi of 5 to 6 µmin diameter were detected after special staining testshad been performed. These findings were consistentwith tissue infection with Penicillium species.

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The bony trabeculae were unremarkable and therewas no evidence of lymphomatous infiltration. Micro-biological examination revealed dimorphic fungus, andfungal culture was positive for Penicillium marneffei.The culture of the fine-needle aspirate from the fore-head mass was also positive for P marneffei. The pa-tient developed a left-arm abscess in the subcutaneousplane, which extended up to the axilla about 1 weekafter core biopsy of the left humerus. Fifty millilitresof pus was drained; its culture confirmed infection withP marneffei.

Further abscesses developed despite the commence-ment of antifungal treatment. The patient was givenintravenous amphotericin B and fluconazole. A retro-pharyngeal abscess presented itself with acute stridorand dyspnoea several days later. Another abscessdeveloped at the lateral aspect of the right thigh,with underlying osteomyelitis of the femur (Fig 2).Both conditions were treated by performing surgicaldebridement. The involvement of the C2 vertebral bodywas treated with antifungal medication. There was noneurological deficit or progression of the bony erosions.

The fever then subsided, and the results of blood in-vestigations such as white blood cell count and measure-ment of the erythrocyte sedimentation rate and C-reactiveprotein level gradually returned to normal over 3 to 4

weeks. The patient’s general condition improved, andshe was able to walk with support. She later returnedto the Philippines while continuing antifungal therapy.

Discussion

Human infection with P marneffei was first documentedin 1956 by Capponi.1 That case involved the accidentalinoculation of the fungus into a laboratory investigator,and the infection subsided with antifungal drug treat-ment. The organism has been isolated from the liver ofbamboo rats from Vietnam.2 Other case reports showedthat the patients with P marneffei infection either livedin South-East Asia or had a history of travelling to thisregion.3 Clinical infection with the organism has beenreported in immunocompromised patients as well as inhealthy individuals.4

The combination of fever, lymphadenopathy, and thedevelopment of abscesses are common manifestationsof infection with P marneffei. The lymphadenopathymay ulcerate and cause mediastinal compression—asituation that may often mimic tuberculosis. Lymphnode biopsy is usually not helpful in distinguishingbetween the two diagnoses.5 Without appropriate treat-ment, the infection may become disseminated to thelung and liver. Eventually, the infection may be fatal.2,6

The clinician should bear this differential diagnosis in

Fig 1. X-ray showing bone destruction in the anteriorpart of the C2 vertebral body

Fig 2. X-ray showing involvement of the right proximalfemur

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mind when such clinical features are encountered.Most of the previously reported cases showed involve-ment mainly in soft tissues and abdominal organs.2,6

Chan and Woo3 reported on a patient with mainlyperipheral skeletal involvement, which was mani-fested by multiple joint pain, swelling, and multipleradiolucent areas at the ends of various long bonesand phalanges. Jayanetra et al6 described involvementof the long bones, skull, and ribs in two patients oftheir series. Louthrenoo et al7 reported that one ofeight patients showed major involvement of the axialskeleton.

In the patient in this report, the P marneffei infec-tion progressed rapidly with bony destruction, soonafter the onset of disease. When the spine is involved,this rapid progression can be potentially serious,result in severe neurological deficit, and eventuallybe fatal. Early treatment is very important to preventany irreversible damage to the spinal cord. Despitegiving full-dose antifungal treatment to this patient,more soft-tissue abscesses developed. These symptomsprobably reflect a slow onset of the effect of anti-fungal agents. This delay further emphasises the needfor early treatment.

Conclusion

Penicillium marneffei infection in bone is rare. Whenit occurs, systemic upset can be severe. There are multi-

focal bony lytic lesions, which can be rapidly progres-sive. Both the axial and peripheral skeleton can be in-volved, and the soft tissues are usually also affected.Recent contact in South-East Asia should raise sus-picion of infection with P marneffei. Early treatment isessential so that the bony destruction does not becometoo advanced and, more importantly, to prevent anydamage to the spinal cord from occurring.

References

1. DiSalvo AF, Fickling AM, Ajello L. Infection caused byPenicillium marneffei: description of first natural infection inman. Am J Clin Pathol 1973;60:259-63.

2. Deng Z, Connor DH. Progressive disseminated penicillosiscaused by Penicillium marneffei: report of eight cases anddifferentiation of the causative organism from Histoplasmcapsulatum. Am J Clin Pathol 1985;84:323-7.

3. Chan YF, Woo KC. Penicillium marneffei osteomyelitis. J BoneJoint Surg 1990;72:500-3.

4. Tsui WM, Ma KF, Tsang DN. Disseminated Penicilliummarneffei infection in HIV-infected subject. Histopathology1992;20:287-93.

5. Yuen WC, Chan YF, Loke SL, WH Seto, GP Poon, KK Wong.Chronic lymphadenopathy caused by Penicillium marneffei: acondition mimicking tuberculous lymphadenopathy. Br J Surg1986;73:1007-8.

6. Jayanetra P, Nitujanant P, Ajello L, et al. Penicillosis marneffeiin Thailand: report of five human cases. Am J Trop Med Hyg1984;33:637-44.

7. Louthrenoo W, Thamprasert K, Sirisanthana T. Osteoarticularpenicilliosis marneffei. A report of eight cases and review ofthe literature. Br J Rheumatol 1994;33:1145-50.