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Radiological Reasoning: Miliary Disease, Vertebral Osteomyelitis, and Soft-Tissue Abscesses

¹ Department of Radiology, Christiana Care Health System, 4755 Ogletown-Stanton Rd., Newark, DE 19718.

Received May 26, 2007; accepted after revision June 11, 2007.

 
Address correspondence to G. E. Wilde (gwilde{at}christianacare.org).

Abstract

Top Abstract Case History Initial Imaging Expert Discussion (Dr. Wilde) Clinical Management Further Imaging Expert Discussion (Dr. Wilde) Further Clinical Management Commentary References

 
Objective

We present a case of disseminated coccidioidomycosis with miliary disease and extrathoracic spread to the breast, the retroperitoneum, the soft tissues of the neck, and multiple vertebrae with spinal cord compression. We discuss the differential diagnosis of the imaging presentation, as well as the specific clinical and imaging features of coccidioidomycosis.

Conclusion

Disseminated coccidioidomycosis in a nonendemic area can be difficult to diagnose, even with an excellent clinical history, as almost every organ system can be involved. Widespread disease can be seen and spinal involvement can easily be mistaken for malignancy, Pott's disease, or other granulomatous disease. Miliary disease with concomitant breast involvement is a rare presentation of disseminated disease. Detection of specific radiographic patterns of involvement and recognition of travel to or from an endemic area can lead to an accurate diagnosis and earlier treatment.

Keywords: CNS • disseminated coccidioidomycosis • Coccidioides immitis • miliary pattern • soft-tissue abscesses • vertebral osteomyelitis

Case History

Top Abstract Case History Initial Imaging Expert Discussion (Dr. Wilde) Clinical Management Further Imaging Expert Discussion (Dr. Wilde) Further Clinical Management Commentary References

 
A 42-year-old African-American woman with chronic paranoid schizophrenia who lived in California since 1995 was brought to Delaware by her sister because of impressive weight loss, fever, and malaise. The patient had previously been evaluated at a California hospital for multiple vertebral lesions and a right breast mass that was eroding through the right anterior chest wall.

Initial Imaging

Top Abstract Case History Initial Imaging Expert Discussion (Dr. Wilde) Clinical Management Further Imaging Expert Discussion (Dr. Wilde) Further Clinical Management Commentary References

 
A CT scan of the chest, abdomen, and pelvis with IV contrast material shows random, diffuse micronodular densities less than 3 mm in diameter throughout both lungs compatible with a miliary pattern (Fig. 1A). A moderate-sized area of consolidation containing air bronchograms and dilated bronchi is noted within the right lower lobe (Fig. 1A). A large fluid collection is also noted in the right breast impressing on the anterior chest wall in the first and second intercostal spaces and measuring 4.5 x 8.1 x 11 cm (Fig. 1B). A fluid collection measuring approximately 5.5 x 3.2 cm lies adjacent to the left lobe of the thyroid gland and displaces the trachea to the right (Fig. 1C). A second septated fluid collection measuring 3.3 x 2.3 x 12 cm extends from the lower neck into the posterior mediastinum associated with osseous destruction of T1, T2, and T3 (Fig. 1C). There is gross vertebral body destruction of T8 with multiple foci of air, disruption of the posterior cortex, and epidural extension causing moderate to severe central spinal canal stenosis (Fig. 1D). A large fluid collection is identified in the right iliopsoas muscle measuring 5.6 x 7.6 x 30 cm (Fig. 1E). Lytic destruction of T12, L2, and the sacrum is associated with a paravertebral soft-tissue mass (Fig. 1E).

View larger version (138K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —42-year-old African-American woman with chronic paranoid schizophrenia who presented with impressive weight loss, fever, and malaise. Patient had previously been evaluated at another hospital for multiple vertebral lesions and right breast mass that was eroding through right anterior chest wall. Axial CT image shows miliary pattern in both lungs, consolidation in right lower lobe with several dilated bronchi (arrow), and superior portion of patient's breast abscess (arrowheads), better visualized with soft-tissue window as shown in B.

View larger version (71K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —42-year-old African-American woman with chronic paranoid schizophrenia who presented with impressive weight loss, fever, and malaise. Patient had previously been evaluated at another hospital for multiple vertebral lesions and right breast mass that was eroding through right anterior chest wall. Axial CT image shows large right breast abscess impressing on anterior chest wall (arrowheads). Second region of consolidation with bronchial dilatation (arrow) is noted in left lung.

View larger version (81K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1C —42-year-old African-American woman with chronic paranoid schizophrenia who presented with impressive weight loss, fever, and malaise. Patient had previously been evaluated at another hospital for multiple vertebral lesions and right breast mass that was eroding through right anterior chest wall. Axial CT image shows abscess (arrowheads) within left neck causing displacement of trachea and thyroid gland anteriorly and to right. There is osseous destruction of T2 (long black arrow).

View larger version (108K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1D —42-year-old African-American woman with chronic paranoid schizophrenia who presented with impressive weight loss, fever, and malaise. Patient had previously been evaluated at another hospital for multiple vertebral lesions and right breast mass that was eroding through right anterior chest wall. Magnified axial CT image shows osseous destruction of T8 with multiple foci of gas. There is anterior and left lateral epidural soft-tissue mass (short arrow) causing severe central canal stenosis. There is extension into paraspinal space bilaterally (arrows).

View larger version (140K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1E —42-year-old African-American woman with chronic paranoid schizophrenia who presented with impressive weight loss, fever, and malaise. Patient had previously been evaluated at another hospital for multiple vertebral lesions and right breast mass that was eroding through right anterior chest wall. Magnified axial CT image shows large right psoas abscess (arrowheads) and destructive lesion (arrow) within right sacrum involving neural foramina on right.

Top Abstract Case History Initial Imaging Expert Discussion (Dr. Wilde) Clinical Management Further Imaging Expert Discussion (Dr. Wilde) Further Clinical Management Commentary References

The most likely causes for the miliary pattern in this patient include tuberculosis, coccidioidomycosis, blastomycosis, histoplasmosis, and cryptococcosis. Sarcoidosis and varicella-zoster, although less likely to account for the constellation of findings in this patient, will also be discussed.

In recent years, there has been an increase in the incidence of pulmonary tuberculosis and, consequently, of extrapulmonary tuberculosis. This increase has been attributed to a larger number of immunocompromised patients, an aging population, and the development of multi-drug-resistant strains of the organism [2].

Tuberculous spondylitis occurs in 25–60% of cases of skeletal tuberculosis. Involvement of the sacrum and cervical spine, as seen in our patient, is least common, with the first lumbar vertebra most commonly affected [3]. The organism has a striking predilection for the anterior vertebral body adjacent to the subchondral endplate. Subsequently, there is spread to the intervertebral disk beneath the anterior or posterior longitudinal ligament. Typically there is delay in disk destruction, and only rarely is there extension of infection to the posterior elements [3]. Frequently there is paraspinal extension to the surrounding ligaments and soft tissues, usually anterolaterally [3]. Psoas abscesses complicate 5% of cases of tuberculous spondylitis and can contain calcification, whereas nontuberculous psoas abscesses rarely calcify [2]. Notably in our patient there was no calcification within the psoas collection.

Fungal infections can be difficult to differentiate from tuberculosis. Both coccidioidomycosis and blastomycosis can cause a miliary pattern and nonpyogenic vertebral osteomyelitis. Both are associated with specific endemic areas, but with widespread travel, geographic borders have become less meaningful. Blastomycosis is endemic to the central and southeastern United States. Within the spine, it usually causes disk destruction as well as adjacent rib destruction [3]. Bone lesions develop in as many as 50% of patients with disseminated disease. Granulomatous skin lesions, subcutaneous nodules, draining sinuses, and ulcers are common [4, 5]. Coccidioidomycosis, on the other hand, like tuberculosis, tends to be disk-sparing and typically is seen in the southwestern United States and the desert areas of California.

Histoplasmosis is endemic to the Ohio and Mississippi River valleys; when disseminated, histoplasmosis typically causes extrapulmonary lymphadenopathy, hepatosplenomegaly, intestinal ulcers, meningitis, endocarditis, and cutaneous and ocular lesions [6]. Histoplasmosis can result in a miliary pattern in disseminated disease, but does not commonly cause vertebral osteomyelitis [6].

Three general types of pulmonary cryptococcosis have been described [7]: The first is a well-circumscribed mass or nodule in the lower half of either lung; the second is an irregular opacity, more frequent in the upper than the lower lobe; and the third is widespread miliary pattern, typically in immunocompromised individuals.

When cryptococcosis presents with a miliary pattern, there is almost always concurrent CNS disease in the form of meningitis [7]. The absence of meningitis in our patient virtually excluded the possibility of cryptococcosis. Osseous involvement appears in 5–10% of cases of disseminated disease, with the spine most commonly affected. Osteolytic lesions predominate, typically with discrete sclerotic margins [2].

Sarcoidosis typically is associated with adenopathy in both the hila and the mediastinum. In pulmonary sarcoidosis, noncaseating granulomas occur predominantly in the interstitium of the peribronchial, perivascular, and subpleural spaces and along the interlobular septa [8–10]. Nodules visible on CT represent aggregates of granulomas and are usually 2 mm to 1 cm in diameter, predominantly in a perilymphatic distribution [9]. However, nodules may be quite small, in the 1- to 3-mm range, and may be randomly distributed throughout the lung fields in a miliary pattern [8]. Vertebral granulomatous change can also rarely be seen, usually manifesting as a lytic focus with marginal sclerosis [2]. Soft-tissue involvement or abscess formation is unusual and suggests accompanying infection. Neurosarcoidosis typically presents as diffuse leptomeningitis or focal granulomas with characteristic involvement of the hypothalamus or pituitary infundibulum. Cutaneous lesions, ocular involvement, and myocarditis are other possible manifestations.

The nodules seen in varicella-zoster pneumonia range from 1 to 10 mm and are randomly distributed in secondary pulmonary lobules [11]. In a few patients the lesions calcify and remain indefinitely as random 2- to 3-mm dense calcifications [11, 12] The nodules in our patient were uniform in size and less than 3 mm. The rash associated with varicella-zoster pneumonia was not seen in our patient. Also, intraabdominal and neck abscesses as well as spinal involvement would be unexpected for varicella-zoster pneumonia.

Based on the initial CT scan, and the fact that the patient had lived for the past 10 years in California, the most likely causes were thought to be coccidioidomycosis or tuberculosis. Blastomycosis could also produce the findings of the initial CT scan, but the lack of a pertinent geographic history decreased the likelihood of that diagnosis.

Clinical Management

Top Abstract Case History Initial Imaging Expert Discussion (Dr. Wilde) Clinical Management Further Imaging Expert Discussion (Dr. Wilde) Further Clinical Management Commentary References

 
Workup of the patient was slowed by the patient's psychiatric illness and her refusal of diagnostic procedures and treatment. Ultimately, while hospitalized, the patient consented to a biopsy of the right psoas mass. The histology results showed extensive necrotic material and spores by a Grocott's Methanamine Silver (GMS) stain consistent with Coccidioides immitis. A fungal sputum culture also revealed Coccidioides immitis. Test results for HIV were negative. The patient was placed on IV fluconazole (Diflucan, Pfizer), was eventually switched to oral therapy, and was discharged from the hospital. One month after discharge, however, the patient returned to the hospital with recurrent fevers and severe neck pain, partially due to medication noncompliance.

Further Imaging

Top Abstract Case History Initial Imaging Expert Discussion (Dr. Wilde) Clinical Management Further Imaging Expert Discussion (Dr. Wilde) Further Clinical Management Commentary References

 
A CT scan of the neck with contrast material shows multiple peripherally enhancing and centrally low-attenuation collections in the neck, predominantly to the left of midline, beginning at the level of C2 and extending inferiorly into the mediastinum. These collections cause a marked deviation of the larynx to the right and vascular structures to the left with a component invaginating through the thyrohyoid membrane involving the left paralaryngeal space (Fig. 2A). There is extensive bone destruction involving the vertebral column at every level from C5 to T3.

View larger version (72K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —42-year-old African-American woman with chronic paranoid schizophrenia who presented with impressive weight loss, fever, and malaise. Patient had previously been evaluated at another hospital for multiple vertebral lesions and right breast mass that was eroding through right anterior chest wall. Axial CT image shows large peripherally enhancing fluid collections (arrowheads) in left neck, which cause rightward displacement of larynx and hyoid bone. There is extension of fluid collection (arrow) through thyrohyoid membrane with paralaryngeal involvement.

View larger version (142K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —42-year-old African-American woman with chronic paranoid schizophrenia who presented with impressive weight loss, fever, and malaise. Patient had previously been evaluated at another hospital for multiple vertebral lesions and right breast mass that was eroding through right anterior chest wall. Sagittal T2-weighted MR image of cervical spine shows large paraspinal fluid collection (arrowheads) with contiguous vertebral body involvement from C5 to T3 with relative sparing of intervertebral disks.

View larger version (140K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C —42-year-old African-American woman with chronic paranoid schizophrenia who presented with impressive weight loss, fever, and malaise. Patient had previously been evaluated at another hospital for multiple vertebral lesions and right breast mass that was eroding through right anterior chest wall. Sagittal T2-weighted MR image of thoracic spine shows T7–T8 discitis and osteomyelitis with anterior epidural extension (arrow) and resultant spinal cord compression and edema (arrowhead).

Top Abstract Case History Initial Imaging Expert Discussion (Dr. Wilde) Clinical Management Further Imaging Expert Discussion (Dr. Wilde) Further Clinical Management Commentary References

MRI is useful in establishing the extent of disease and plan surgical débridement. The most definitive description of MR findings associated with coccidioidal spondylitis appeared in the literature in 1998 [13]. Despite the preservation of disk height on radiographs, disk space involvement is almost always present on MRI. The MR marrow space abnormality is always larger than the radiographic, CT, or bone scan abnormality. Heterogeneous changes in the marrow are the rule. Epidural disease, spread of infection along the longitudinal ligaments, and paraspinal disease are common [13]. Cord compression and nerve root impingement also commonly occur, particularly with advanced disease. The extensive liquefied paraspinal abscess from which necrotic material was aspirated in our patient was not typical in the MRI series reported by Olson et al. [13]. They found that the soft-tissue abnormality is usually phlegmonous, enhancing, and nonliquefied tissue rather than frank abscess [13].

View larger version (93K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2D —42-year-old African-American woman with chronic paranoid schizophrenia who presented with impressive weight loss, fever, and malaise. Patient had previously been evaluated at another hospital for multiple vertebral lesions and right breast mass that was eroding through right anterior chest wall. High-power photomicrograph of sample aspirated from patient's psoas abscess shows characteristic endospores within spherules of Coccidioides immitis. Endospores within spherules are released and can each initiate development of new spherules, resulting in exponential reproduction.

Top Abstract Case History Initial Imaging Expert Discussion (Dr. Wilde) Clinical Management Further Imaging Expert Discussion (Dr. Wilde) Further Clinical Management Commentary References

Commentary

Top Abstract Case History Initial Imaging Expert Discussion (Dr. Wilde) Clinical Management Further Imaging Expert Discussion (Dr. Wilde) Further Clinical Management Commentary References

 
Posada [18] first described coccidioidomycosis in an Argentinian soldier in 1892 as a distinct disease that was thought to be parasitic in nature. In 1900, a dimorphic fungus was recognized as the causative agent [19]. Its scientific name refers to the round spherules that resemble a coccidian parasite (Coccidioides organisms) and the fact that the disease was initially thought to be fatal in all cases (immitis) [19]. It is endemic to the arid areas of the Americas, including the southwestern United States, northwestern Mexico, Central America, and South America (Argentina, Columbia, Paraguay, and Venezuela) [20]. Coccidioidomycosis has become a mandatory reportable disease in California and Arizona. A dramatic increase in the incidence of this disease has been seen in Arizona, with 3,346 new cases reported in 2002 compared with 1,551 new cases in 1998, a 54% increase in incidence over a 4-year period [21]. The estimated number of infections per year has risen to approximately 150,000 as a result of population increases in southern Arizona and central California [22].

Outside endemic areas, diagnosis often is delayed because the infection is not considered initially. Such cases may occur because of a recent visit to an area of endemic disease; reactivation of an infection acquired earlier in such an area; or infection by fomites from an area of the endemic disease, such as spores on an automobile or on fruit [23]. Soil disturbances during construction can also lead to upsurges in cases, as were seen after the Los Angeles earthquake in 1993 [23].

Sixty percent of people who are infected have no symptoms or have an illness indistinguishable from an upper respiratory infection. Twenty-five percent of infections result in "valley fever" (named for the San Joaquin Valley, the center of the endemic area), which is a constellation of arthralgias, fever, and skin lesions that range from a nonspecific maculopapular eruption to erythema nodosum [19].

One of 200 people infected with Coccidioides immitis develops symptomatic extrapulmonary disease. Although every organ, except perhaps the gastrointestinal tract, may be affected, the common sites are the meninges, bones and joints, skin, and soft tissues [19]. Disease outside the lungs usually develops within 1 year after the initial pulmonary infection, but may appear much later if immunity is impaired. Disseminated infections are most common in men, pregnant women, immunocompromised individuals, and nonwhite people [23].

A miliary pattern on chest radiography or CT, as seen in our patient, is indicative of hematogenous spread of the fungus and is characterized by the development of multiple coccidioidal granulomas throughout the lungs and other organs [24]. Most patients with miliary dissemination succumb to progressive respiratory failure [25]. The frequency of a miliary pattern is unknown in coccidioidomycosis patients, with few cases reported in the literature [25]. In the largest cohort of coccidioidomycosis patients since the 1950s, Crum et al. [19] describe a single case with a miliary pattern among those that presented to the Naval Medical Center in San Diego from 1994 to 2002.

Bone or joint disease occurs in 20% of those with disseminated disease. Most frequently the axial skeleton, particularly the thoracic vertebrae, is involved. Three major patterns of bone and joint involvement have been described in a large population with disseminated disease [26]: The first pattern is well-marginated, punched-out osteolytic lesions, typically involving long and flat bones; the second pattern is permeative bone destruction, which is rarely accompanied by periosteal reaction; and the third is septic arthritis, usually monoarticular and usually associated with adjacent osseous involvement.

Vertebral involvement was discussed earlier. In disseminated osteomyelitis there is a tendency for distal involvement and a preference for bone prominences such as the tibial tuberosity, malleoli of the ankles, radial styloids of the wrist, and acromial process of the scapula [27]. Bone scanning is the screening test of choice to rule out multifocal osteomyelitis.

Coccidioidomycosis rarely involves the thyroid, breast, peritoneum, uterus, scrotum, prostate, orbit, pericardium, liver, or larynx [19]. Laryngeal involvement is rare and may be caused by direct inoculation from inhalation, infection from organisms within the sputum, hematogenous spread, or communication with adjacent abscesses within the neck, as in our patient [20]. Symptoms may include dysphonia, stridor, or a lump in the throat. Involvement of the subglottic tissue, true vocal cords, false cords, and epiglottis has been reported [20].

Cases involving the breasts, as was seen in our patient, have rarely been reported in the literature [28]. Almost all cases were seen in patients who were immunosuppressed at the time of diagnosis and were initially presumed to have a breast neoplasm.

In conclusion, as shown in our patient, disseminated coccidioidomycosis typically is multifocal and can involve almost every organ system. Detection of specific radiographic patterns of involvement and recognition of travel to or from an endemic area can lead to earlier treatment and differentiation from other more common disease entities.

References

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This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wilde, G. E. Articles by Lally, J. F. Search for Related Content PubMed PubMed Citation Articles by Wilde, G. E. Articles by Lally, J. F. Social Bookmarking                      What's this? Hotlight (NEW!) What's Hotlight?