(Chest. 2001;120:1014-1017.)
© 2001
American College of Chest Physicians
A Patient With Myelodyplastic Syndrome, Pulmonary Nodules, and Worsening Infiltrates*
Juliette L. Wohlrab, MD;
Eric D. Anderson, MD, FCCP and
Charles A. Read, MD, FCCP
*
From the Division of Pulmonary and Critical Care Medicine, Georgetown University Medical Center, Washington, DC.
Correspondence to: Juliette L. Wohlrab, MD, Division of Pulmonary and Critical Care Medicine, Georgetown University Medical Center, B100 Kober-Cogan, 3800 Reservoir Rd, NW, Washington, DC 20007; e-mail: wohlrabj{at}aol.com
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Introduction
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A 63
-year-old white man with stage IIA Hodgkin disease and myelodysplastic
syndrome was admitted to the hospital with fevers and chills. The
Hodgkin disease was diagnosed 3 years previously, and he received
treatment with MOPP/ABV (nitrogen mustard, vincristine, procarbazine,
prednisone, doxorubicin, vinblastine, bleomycin). The myelodysplastic
syndrome developed 1 year prior to hospital admission and was thought
to be secondary to his chemotherapy. His medical history was also
significant for bronchiolitis obliterans organizing pneumonia (BOOP)
diagnosed 2 years earlier using transbronchial biopsy. The BOOP
responded to steroids, but diffuse infiltrates subsequently developed
during treatment. Open-lung biopsy results showed Pneumocystis
carinii pneumonia, which resolved after treatment with
trimethoprim/sulfamethoxazole. Prior to hospital admission, the patient
was noted to have new bilateral pulmonary nodules on surveillance CT,
for which he was scheduled to undergo CT-guided biopsy. He was
asymptomatic from a pulmonary standpoint and had no localizing
infectious symptoms to account for his fever. Medications prior to
hospital admission included dexamethasone, 4 mg/d; folic acid;
filgrastim; aminocaproic acid; and omeprazole. He also received
periodic platelet and RBC transfusions.
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Physical Examination
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The patient’s temperature was 39.3°C, BP was 110/58 mm Hg,
pulse rate was 86 beats/min, respiration rate was 22 breaths/min, and
pulse oximetry was 97% on 2 L of oxygen via nasal cannula. Bibasilar
crackles and left posterior egophony were evident on chest examination.
Cardiovascular examination findings were normal without murmurs. The
abdomen was normal, and the extremities had 1+ edema and petechiae
around the ankles. A Groshong catheter (Bard Access Systems; Murray
Hill, NJ) was present in the right anterior chest wall, and the
site was without erythema or tenderness.
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Laboratory Findings
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The WBC count was 10,400/µL, with 48% neutrophils and
37% bands. Hematocrit was 23%; platelet count, 2,000/µL;
creatinine, 1.7 mg/dL (baseline, 0.9 mg/dL); bicarbonate, 24 mmol/L;
glucose, 135 mg/dL; and lactate dehydrogenase, 287 IU/L. Blood culture
results were positive for Gram-negative rods. Chest radiographic
findings were significant for the known nodules, which were unchanged,
and a new lingular infiltrate. Urinalysis and culture findings were
negative for infection.
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Hospital Course
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The patient received treatment with vancomycin and
ceftazidime empirically until culture findings revealed
Escherichia coli. Treatment with antibiotics was then
tailored to piperacillin/tazobactam. Stress-dose steroids with
hydrocortisone were administered, 100 mg q8h. It was thought that this
was likely a line-related infection, as this was his second episode of
bacteremia with the same organism in the past month and no other source
could be identified. The Groshong catheter was removed. Flexible
bronchoscopy was performed to rule out a pulmonary infection given the
new lingular infiltrate. BAL demonstrated only alveolar macrophages and
lymphonuclear cells. All culture and stain results were negative. No
transbronchial biopsy was performed secondary to his underlying
thrombocytopenia. The patient’s oxygenation progressively deteriorated
over the following week. Subsequent radiographs showed worsening of the
lingular infiltrate with cavitation and interstitial changes
bilaterally (Fig 1
), which were confirmed by CT (Fig 2
). IV liposomal amphotericin B, trimethoprim/sulfamethoxazole, and
azithromycin were added to cover possible fungus, P carinii
pneumonia, and atypical organisms, respectively.
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What diagnosis should be considered in evaluating this
patient?
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Diagnosis: Pulmonary mucormycosis, BOOP
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Mucor is a zygomycete of the order Mucorales. Mucorales infections
are generally rapidly progressive and often fatal. The organisms are
ubiquitous saprophytes and can be found on fruits and moist bread, in
soil, and on decaying organic matter. In contrast to Aspergillus, Mucor
is generally not found in hospital environments. It has worldwide
distribution and affects patients with underlying conditions such as
diabetes mellitus, lymphoid and hematologic malignancies, burns,
trauma, cirrhosis, renal failure, and transplantation and other
immunodeficiency states. It is also seen in patients receiving
deferoxamine and long-term steroid therapy. Hyperglycemia and metabolic
acidosis provide an environment conducive to fungal growth. Normal
macrophage and lymphocyte function usually provide immune protection
against clinical infection. A reduction in phagocytosis by
bronchoalveolar macrophages has been demonstrated in animals with
diabetes or receiving steroid therapy. These macrophages normally
inhibit spore germination and tissue invasion.
Infection is likely initiated by inhalation of asexual spores that
settle in the nasal passages and sinuses. It can then extend to the
retro-orbital tissues, cerebrum, and lower respiratory tract. These
fungi have a predilection for blood vessel invasion and can lead to
arterial and venous thrombosis and subsequent tissue infarction.
Rhinocerebral disease is the most common manifestation and occurs
almost exclusively in the setting of diabetic ketoacidosis. Isolated
pulmonary mucormycosis occurs and can lead to pneumonia, abscess,
hemorrhage, and infarction. Pulmonary infection can be complicated by
massive hemoptysis and superinfection with bacterial organisms.
Lymphatics can also be involved and lead to a more indolent process.
Other clinical manifestations include GI, cutaneous, cardiac, and bone
involvement. Disseminated disease occurs when two or more organ systems
are involved. The disease course is usually acute and fulminant but can
be subacute. The overall mortality is 80% for isolated pulmonary
involvement and 95% for disseminated disease.
The radiographic appearance is usually a patchy infiltrate that
consolidates and leads to cavity formation despite antibiotic therapy.
Other radiographic features include lobar or multilobar consolidation,
solitary or multiple nodules, and adenopathy. The presence of an
air-crescent sign appears to be associated with an increased risk of
hemoptysis. Mucor has a predilection for the upper lobes. Diagnosis is
rarely made using sputum culture or Gram’s stain. Bronchoscopy with
BAL and transbronchial biopsy is often required. A recent report on the
role of BAL for diagnosis of pulmonary mucormycosis suggests that given
the appropriate clinical setting, demonstration of Mucor in BAL fluid
can be diagnostic of invasive disease when transbronchial biopsy or
open biopsy is contraindicated. Open-lung biopsy may be needed if
bronchoscopy is nondiagnostic. Histologic examination reveals large,
broad, nonseptated hyphae with wide-angle branching. Direct plating on
blood or Sabouraud agar at 37°C increases culture yield, but it is
generally poor.
The differential diagnosis includes other infectious agents that are
more likely to affect an immunocompromised host, such as Aspergillus
and Nocardia, and would produce similar clinical syndromes.
Pneumocystis and cytomegalovirus can lead to pulmonary symptoms in the
immunocompromised patient, but cavitation would be rare. Legionella can
also lead to cavitation, but this would be uncommon.
Prompt initiation of therapy with IV amphotericin B should begin as
soon as Mucor is suspected. Generally between 1 g and 2 g is
administered, but the total dose needed for cure is not known. Surgical
resection is usually necessary for cure and has been shown to reduce
mortality to 45% vs 70 to 80% with medical management alone for
isolated pulmonary disease.
BOOP is defined as granulation tissue within the lumen of small
airways, with fibrinous exudates and accumulation of foamy macrophages.
It can be a primary or secondary disease. Secondary BOOP is seen in
association with connective tissue disorders, myelodysplastic syndrome,
AIDS, solid organ and bone marrow transplantation, radiation,
drugs, or viruses. Secondary BOOP requires treatment of the
underlying disorder. Idiopathic BOOP generally responds favorably to
treatment with corticosteroids. Radiographic appearance includes
diffuse, bilateral, alveolar infiltrates with peripheral predominance.
Linear or nodular opacities occur less commonly. Pleural effusions,
pleural thickening, and cavitation are rare.
This patient had a history of BOOP that responded to steroid therapy
with radiographic resolution. He had a known underlying associated
disease, myelodysplastic syndrome. This syndrome appeared to be well
controlled, and the recrudescence of BOOP could be related to the Mucor
infection. Given the fact that the patient’s clinical and radiographic
course deteriorated during treatment with high-dose steroids, the BOOP
was likely secondary in nature.
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Hospital Course
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The patient was referred for open-lung biopsy. His lingula and
left upper lobe were resected, and pathology findings are demonstrated
in Figures 3
, 4
. After surgical resection, he improved considerably with antifungal
therapy. Treatment with trimethoprim/sulfamethoxazole was changed to
prophylactic doses, and the steroids were rapidly tapered. A CT scan of
the sinuses showed no rhinocerebral involvement. Despite his initial
improvement, his hospital course was complicated by recurrent sepsis
and renal deterioration. He wished no further aggressive care and
eventually died.
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Clinical Pearls
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- Fungal infection should be considered in the
differential diagnosis of any immunocompromised patient with worsening
radiographic changes or fevers despite treatment with broad-spectrum
antibiotics.
- Prompt referral for open-lung biopsy should be made if
bronchoscopy is nondiagnostic in the setting of a deteriorating
clinical picture.
- Overall mortality in isolated pulmonary mucormycosis can
be reduced with surgical resection in combination with amphotericin
B.
- Mucormycosis can be isolated to the pulmonary parenchyma
or disseminated, and the extent of disease affects overall
mortality.
- BOOP can be a primary or secondary disease process.
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Suggested Readings
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Epler GA. Bronchiolitis obliterans organizing pneumonia:
definition and clinical features. Chest 1992; 102:2S–6S
Glazer M, Nusair S, Brewer R, et al. The role of BAL in the diagnosis
of pulmonary mucormycosis. Chest 2000; 117:279–282
Harada M, Manabe T, Yamashita K, et al. Pulmonary mucormycosis with
fatal hemoptysis. Acta Pathol Jpn 1992; 42:49–55
Lee FY, Mossad SB, Adal KA. Pulmonary mucormycosis: the last 30 years.
Arch Intern Med 1999; 159:1301–1309
McAdams H, Rosado de Christenson M, Strollo D, et al. Pulmonary
mucormycosis: radiologic findings in 32 cases. AJR Am J Roentgenol
1997; 168:1541–1548
Meyers BR, Gurtman AC. Phycomycetes. In: Gorbach SL, Bartlett JG,
Blacklow NR, eds. Infectious diseases. Philadelphia, PA: W.B. Saunders,
1994; 1941–1945
Murphy RA, Miller WT. Pulmonary mucormycosis. Semin Roentgenol 1996;
31:83–87
Tedder M, Spratt J, Anstadt M, et al. Pulmonary mucormycosis: results
of medical and surgical therapy. Ann Thorac Surg 1994; 57:1044–1050
Waldorf AR, Levitz SM, Diamond RD. In vivo bronchoalveolar
macrophage defense against Rhizopus oryzae and
Aspergillus fumigatus. J Infect Dis 1984; 150:752–760
Received for publication February 28, 2001.
Accepted for publication April 17, 2001.
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Introduction
Physical Examination
