Coccidioides immitis Osteomyelitis of the Radius Presenting as Ewing’s Sarcoma

[Guest guest]

Boy does this sound familiar.

Coccidioides immitis Osteomyelitis of the Radius Presenting as

Ewing's Sarcoma

Ortho SuperSite - Thorofare,NJ*

By ph E. Sheppard, MD; N. Switlick, MD

ORTHOPEDICS 2008; 31:607

June 2008

http://www.orthosupersite.com/view.asp?rID=28258

Coccidioides immitis osteomyelitis is a relatively rare

manifestation of a disease that most commonly presents with

pulmonary infection. Disseminated disease occurs in approximately 1%

of infected individuals, with bony involvement in 10% to 50% of

those patients with extra pulmonary infection.1,2 Diagnosis and

treatment of patients with primarily osteoarticular complaints is

frequently delayed, which may result in progression of disease and

suboptimal results. This article report discusses the successful

treatment of a patient whose initial presentation was suggestive of

Ewing's sarcoma,3-6 but was found on biopsy to have

coccidioidomycosis osteomyelitis. She was treated with debridement

and systemic as well as intralesional antifungal therapy.

Case Report

A 7-year-old girl presented with left proximal forearm pain and

swelling. Two weeks previously, she had fallen on her elbow, with

onset of swelling the following day. She was previously in good

health with no complaints or other trauma. She had no fever, chills,

malaise, cough, or shortness of breath. Her parents noted that she

had a respiratory illness lasting 3 to 4 days 2 months prior to her

fall, but did not have any fever or skin lesions at that time or

subsequently. She had no other bone or joint complaints, nor

headaches or lymphadenopathy. She lived in a low desert region of

southern Arizona. Her immunizations were up to date.

Physical examination was significant for a well-nourished Hispanic

girl in no distress. She had mild swelling of the proximal lateral

forearm with a firm, tender mass at the level of the proximal

radius. Elbow range of motion was without significant tenderness,

with 30°to 110° of flexion, 10° of supination, and 20° of pronation.

A 1×1.5-cm mobile, nontender lymph node palpable was noted in the

left axilla. Motor, sensory, and vascular examinations were normal,

as were the remaining extremities.

She had no rashes or overlying skin changes. Lungs were clear and

there were no abnormal abdominal masses. White blood cell count was

8700, with 70% polymorphonuclear cells, 23% lymphocytes, 7%

mononuclear cells, and no eosinophils or basophils. The radiograph

is shown in Figure 1.

Bone scan showed markedly increased radiotracer uptake involving the

proximal radial metaphysis and a portion of the diaphysis, with no

other abnormal uptake. Magnetic resonance imaging with and without

gadolinium enhancement showed a lesion of abnormal signal intensity

involving the proximal half of the radius with associated pathologic

fracture and inhomogeneous enhancement, and significant soft tissue

extension (Figure 2). Chest computed tomography demonstrated no

nodules, lesions, or effusion. There was a left axillary node of <1

cm, but no hilar or mediastinal lymphadenopathy.

A biopsy was planned to determine the etiology of the lesion and

further treatment. Imaging studies and patient presentation were

consistent primarily with malignancy. The differential diagnosis of

the lesion included Ewing's sarcoma, low grade osteosarcoma,

eosinophilic granuloma or possible osteomyelitis, although the

patient did not have systemic symptoms or white blood cell count to

suggest an infectious etiology.

This patient presented with the clinical and radiographic findings

most consistent with the diagnosis of Ewing's sarcoma. Her primary

complaint was pain, which is the most common presenting symptom in

Ewing's sarcoma, observed in approximately 96% of patients.7 She

also presented with swelling, which occurs in approximately 61% of

patients.7 She had no previous febrile episodes that may be present

in approximately 21% of patients with Ewing's sarcoma.7

Although the radius is a relatively uncommon location, distal

locations such as the tibia, fibular, radius, ulna, hands and foot

were involved in 20% of cases reported by the Mayo Clinic in 1986.7

The preoperative discussion with family centered on the contemporary

management of this problem, which most recently includes a

resurgence of selective surgery and limb salvage for Ewing's

sarcoma.8-11

On biopsy, a submuscular rim of reactive tissue encapsulated a white

casseous material. Frozen section demonstrated evidence of acute and

chronic osteomyelitis with doubly refractile cocci fungal spores

(Figure 3), and no evidence of neoplasm. The lesion was curetted and

irrigated with 50% peroxide and saline, followed by saline alone and

the wound was closed. Gram stain of intraoperative swabs showed 3+

white blood counts but no organisms. Fungal cultures grew

Coccidioides immitis, but no aerobic or anaerobic organisms. Cocci

serologies were positive for cocci IgG, negative for cocci IgM, and

serum quantitative titers were 32:1. Infectious disease consultation

was obtained and the patient was placed on amphotericin B.

The patient required repeat irrigation and debridement 1 month after

her index procedure due to persistent seropurulent drainage from the

operative wound and a residual lytic lesion on radiograph, despite

evidence of bone healing of the remainder of the original lesion. At

that time, following curettage, Amphotericin B was injected into the

lesion, and amphotericin B impregnated gelfoam packed into the

cavity. She received a 10-day course of intravenous amphotericin B

followed by oral fluconazole 300 mg daily indefinitely. Two years

after the index procedure, she is pain free and with no other

symptoms of disease. Her range of motion is full and she has

radiographic evidence of consolidation of the lesion (Figure 4).

Discussion

Coccidioidomycosis is a fungal infection endemic to the lower

Sonoran regions of central and southern California, Arizona, New

Mexico and parts of Texas and northern Mexico.11 While rarely seen

outside of these regions, tourists and military personnel who have

spent even a short period of time in an endemic area may later

present with the disease due to a latent period of up to a year or

more. Lack of familiarity with the disease often results in a

significant delay in diagnosis, with an average delay of 4 years in

Bayer's series of 19 patients with coccidioidomycosis arthritis.1

Delayed diagnosis has been associated with more advanced destruction

and a worse outcome.1,2

Coccidioides immitis is a saprophytic soil fungus that becomes

airborne in spore form and results in respiratory infection. The

majority of people infected with C immitis remain asymptomatic, but

approximately 40% develop various nonspecific complaints including

cough (typically nonproductive), chest pain, fever, chills, night

sweats, headache, myalgias and arthralgias.2 Patients may also

develop erythematous bumps on the skin. Infection rarely results in

disseminated disease, which may present with a variety of

manifestations, including severe pulmonary involvement, extensive

rash, lymphadenopathy, chronic arthritis or osteomyelitis. Although

whites are commonly infected, disseminated disease is more common in

nonwhites, particularly blacks and Filipinos.2,12 Disseminated

disease may also occur in immunocompromised hosts.

Cocci osteomyelitis typically occurs at the ends of bones or bony

prominences, and may be symmetric.12-14 Common sites include the

vertebral bodies, skull, tibial tubercle, ankle malleoli, acromion,

medial clavicle, and ribs.13 Soft tissue extension is common with

abscess and sinus tract formation. Extension from ribs to the

pleural space and from vertebrae to the spinal cord and meninges may

occur. Arthritis may occur from direct extension from adjacent bony

involvement or from hematogenous seeding to the synovium.

Diagnosis is made based on symptoms, history of exposure to endemic

region, and laboratory tests. Skin test reactivity to coccidioidin

indicates prior infection, but may be negative in patients with

dissemination, therefore serologic tests should be performed. While

complement fixation titers increase with disseminated disease, they

may not be predictive of failure or success of treatment.12,15

Ultimately, fungal cultures of debrided tissue should be obtained to

identify cocci osteomyelitis, and visualization of cocci spherules

on microscope evaluation of pathology specimens is also diagnostic.

Treatment of disseminated disease has improved dramatically over the

past 30 years, prior to which mortality approached 50%.2 Multiple

treatment modalities for cocci osteomyelitis have been advocated;

however, medical treatment alone typically is not curative.12,15-18

Recent evidence supports a combined surgical and medical approach

with thorough debridement of lesions and long term antifungal

therapy, typically with imidazoles or amphotericin B.12,15-18 Due to

the significant toxicity of amphotericin B, efforts have been made

to limit systemic effects by local instillation via intralesional

injection or placement of amphotericin impregnated cement or calcium

sulfate into curetted lesions.19,20 While anecdotal evidence

supports the efficacy of these methods, studies evaluating the

efficacy and safety of this mode of delivery have not been

performed, and amphotericin is not approved by the Food and Drug

Administration for intralesional use.1,12,18

References

Drutz DJ, Catanzaro A. Coccidioidomycosis, I. Am Rev Respir Dis.

1978; 117(3):559-585.

Deresinski SC, s DA. Bone and joint coccidioidomycosis treated

with miconazole. Am Rev Respir Dis. 1979; 120(5):1101-1107.

Dahlin DC, Unni KK. Bone Tumors: General Aspects and Data on 8,542

Cases. 4th ed. Springfield, Il: C. ; 1986.

Codman EA. Bone Sarcoma: An Interpretation of the Nomenclature Used

by the Committee on the Registry of Bone Sarcoma of the American

College of Surgeons. New York, NY: P.B. Hoeber Inc; 1925.

Peltier LF. Orthopedics: A History and Iconography. San Francisco,

CA: Norman Publishing; 1993.

Codman EA. The use of the x-ray and radium in surgery. In: Keen WW,

ed. Surgery, Its Principles and Practice by Various Authors. Vol 5.

Philadelphia, PA: W.B. Saunders; 1909:1170-1171.

Wilkins RM, Pritchard DJ, Burgert EO Jr, Unni KK. Ewing's sarcoma of

bone. Experience with 140 patients. Cancer. 1986; 58(11):2551-2555.

Marcove RC, Rosen G. Radical en bloc excision of Ewing's sarcoma.

Clin Orthop Relat Res. 1980; (153):86-91.

O'Connor MI, Pritchard DJ. Ewing's sarcoma. Prognostic factors,

disease control, and the reemerging role of surgical treatment. Clin

Orthop Relat Res. 1991; (262):78-87.

Pritchard DJ. Indications for surgical treatment of localized

Ewing's sarcoma of bone. Clin Orthop Relat Res. 1980; 153:39-43.

Toni A, Neff JR, Sudanese A, et al. The role of surgical therapy in

patients with nonmetastatic Ewing's sarcoma of the limbs. Clin

Orthop Relat Res. 1993;286:225-240.

Horsburgh CR Jr, Cannady PB Jr, Kirkpatrick CH. Treatment of fungal

infections in the bones and joints with ketoconazole. J Infect Dis.

1983; (147):1064-1069.

Drutz DJ, Catanzaro A. Coccidioidomycosis, II. Am Rev Respir Dis.

1978; 117(6):727-771.

Bayer AS, Yoshikawa TT, Galpin JE, Guze LB. Unusual syndromes of

coccidioidomycosis: diagnostic and therapeutic considerations: a

report of 10 cases and review of the English literature. Medicine.

1976; 55(2):131-152.

Schwarz J. What's new in mycotic bone and joint diseases? Pathol Res

Pract. 1984; 178(6):617-634.

Dalinka MK, Dinnenberg S, Greendyke WH, Hopkins R. Roentgenographic

features of osseous coccidioidomycosis and differential diagnosis. J

Bone Joint Surg Am. 1971; 53(6):1157-1164.

Holley K, Muldoon M, Tasker S. Coccidioides immitis osteomyelitis: a

case series review. Orthopedics. 2002; 25(8):827-832.

Curtiss PH Jr. Some uncommon forms of osteomyelitis. Clin Orthop

Relate Res. 1973; 96:84-87.

Bried JM, JB, Galgiani JN. Coccidioides immitis: an unusual

presentation. Orthopedics. 1990; 13(3):345-347.

Bried JM, Speer DP, Shehab ZM. Coccidioides immitis osteomyelitis in

a 12-month-old child. J Pediatr Orthop. 1987; 7(3):328-330.

Authors

Drs Sheppard and Switlick are from the Department of Orthopedic

Surgery, University of Arizona Health Sciences Center, College of

Medicine, Tucson, Arizona.

Drs Sheppard and Switlick have no relevant financial relationships

to disclose.

Correspondence should be addressed to: ph E. Sheppard, MD,

Department of Orthopedic Surgery, University of Arizona Health

Sciences Center, College of Medicine, PO Box 245064, Tucson, Arizona

85724-5064.