Download Benign Mediastinal Lymphadenopathy in Congestive Heart Failure*

had primarily soft-tissue involvement. She did have two small
brain lesions, but did not have evidence of extensive disseminated disease. Second, an aggressive chemotherapy regimen
was combined with a reduction in the immunosuppressive
regimen, which may have added to antifungal efficacy.
Obtaining itraconazole serum or plasma concentrations
has been recommended to: (1) avoid potential drug interactions, (2) determine adequate clinical response, (3) assess
compliance, and (4) determine GI absorption.8 Recommended concentrations of itraconazole based on high-performance liquid chromatography should be in a detectable
concentration (reference ranges of 0.1 to 2.2 g/mL; Specialty
Laboratories; Santa Monica, CA).
In summary, this case describes the successful treatment of D gallopava in a lung transplant patient without
complete surgical excision of the fungal lesions. It is
possible that the surgical incision and drainage of the
right shoulder lesion were required for cure of this
patient, but clearly multiple other lesions, including a
lung abscess, were successfully treated with chemotherapy. We believe that successful treatment was related,
in part, to combination chemotherapy, drug susceptibility testing, and reduction of immunosuppression. Itraconazole has been shown to penetrate the CNS poorly11; therefore, obtaining itraconazole levels may be
helpful in adjusting doses.12 The itraconazole solution in
cyclodextrin (used in this case) has better absorption
and relative bioavailability in either a postprandial or
fasting state as compared with the similar dose of oral
capsules that may improve efficacy.11 The advent of
liposomal amphotericin B preparations has resulted in a class
of agents that achieve higher serum and tissue concentrations, with presumably fewer side effects.13 The use of drug
susceptibility testing definitely aided the clinician’s choice of
antifungal agents in this case.
References
1 Rossmann SN, Cernoch PL, Davis JR. Dematiaceous fungi
are an increasing cause of human disease. Clin Infect Dis
1996; 22:73– 80
2 Singh N, Chang FY, Gayowski T, et al. Infections due to
dematiaceous fungi in organ transplant recipients: case report
and review. Clin Infect Dis 1997; 24:369 –374
3 Sharkey PK, Graybill JR, Rinaldi MG, et al. Itraconazole
treatment of phaeohyphomycosis. J Am Acad Dermatol 1990;
23:577–586
4 Vukmir RB, Kusne S, Linden P, et al. Successful therapy for
cerebral phaeohyphomycosis due to Dactylaria gallopava in a
liver transplant recipient. Clin Infect Dis 1994; 19:714 –719
5 Kralovic SM, Rhodes JC. Phaeohyphomycosis caused by
Dactylaria (human Dactylariosis): report of a case with review
of the literature. J Infect 1995; 31:107–113
6 Mancini MC, McGinnis MR. Dactylaria infection of a human
being: pulmonary disease in a heart transplant patient.
J Heart Lung Transplant 1992; 11:827– 830
7 Barenfanger J, Ramirez F, Tewari RP, et al. Pulmonary
phaeohyphomycosis in a patient with hemoptysis. Chest 1989;
95:1158 –1160
8 Graybill JR. Itraconazole: managing mycotic complications in
immunocompromised patients. Semin Oncol 1998; 25(suppl
7):58 – 63
9 Patel R. Antifungal agents: Part I. Amphotericin B prepara-
tions and flucytosine. Mayo Clin Proc 1998; 73:1205–1225
10 Bajjoka IE, Bailey EM, Vazquez JA, et al. Combination
antifungal therapy for invasive Aspergillosis infection in liver
transplant recipients: report of two patients. Pharmacotherapy 1999; 19:118 –123
11 Grant SM, Clissold SP. Itraconazole: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in
superficial and systemic mycoses. Drugs 1989; 37:310 –344
12 Summers KK, Hardin TC, Gore SJ, et al. Therapeutic drug
monitoring of systemic antifungal therapy. J Antimicrob
Chemother 1997; 40:753–764
13 Paya CV. Fungal infections in solid-organ transplantation.
Clin Infect Dis 1993; 16:677– 688
Benign Mediastinal
Lymphadenopathy in
Congestive Heart Failure*
Abdoukarim Ngom, MD; Pascal Dumont, MD;
Patrice Diot, MD, PhD; and E. Lemarié, MD
We report three cases of benign mediastinal lymphadenopathy revealed by chest radiography in patients ranging in age from 61 to 75 years. All three
patients had severe coronary heart disease and a
history of several episodes of acute cardiac decompensation. Chest CT scanning contributed to the
diagnosis by revealing the existence of multiple enlarged lymph nodes, mostly 10 to 17 mm in short-axis
diameter. CT scanning also confirmed the disappearance of the mediastinal lymph nodes in one
patient on follow-up after treatment with diuretics
and digitalis. Histopathology investigations of biopsy
samples obtained by mediastinoscopy consistently
revealed noninflammatory, benign lesions that did
not affect the node structure. Our report draws
attention to the particular nosology of left heart
disease represented by benign enlarged lymph
nodes of the mediastinum and pulmonary edema.
The diagnostic approach to such lymphadenopathy
should be guided by the radiologic regression seen
on follow-up CT scanning while the patient was
undergoing appropriate therapy for congestive
heart failure, which constitutes a decisive argument
for the congestive heart failure origin.
(CHEST 2001; 119:653– 656)
Key words: left heart failure; mediastinal lymph node
Abbreviation: Sao2 ⫽ arterial oxygen saturation
*From the Department of Pneumology (Drs. Ngom, Diot, and
Lemarié), INSERM EMI-U 00 –10, CHU Betonneau, Tours,
France; and the Department of Thoracic Surgery (Dr. Dumont),
CHU Trousseau, Tours, France.
Manuscript received December 16, 1999; revision accepted July
11, 2000.
Correspondence to: Etienne Lemarié, Department of Pneumology, CHU Bretonneau, 2 bis, Boulevard Tonnellé, 37044 Tours
Cedex, France; e-mail: [email protected]
CHEST / 119 / 2 / FEBRUARY, 2001
Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21958/ on 05/02/2017
653
eft-sided or complete congestive heart failure is a very
L common
clinical situation. Although pulmonary or
pleural edema is the most common radiologic and clinical
finding, mediastinal edema and lymph node enlargement
remain unrecognized in daily practice and have been little
studied. However, according to Slanetz et al,1 at least 50%
of patients with congestive heart failure are likely to
develop enlarged mediastinal lymph nodes without evidence of an infectious, tumor-related, or specific inflammatory cause.
Three patients with advanced cardiac insufficiency and
benign mediastinal lymphadenopathy fell into this etiologic category after routine examinations. Their clinical
features are described.
Case Reports
Case 1
A 73-year-old female nonsmoker was admitted in April 1994
for investigation of enlarged right mediastinal lymph nodes
revealed by chest radiograph following a recent increase in
exertional dyspnea. Her history included ischemic heart disease
for which she had been treated for 5 years, with clear worsening
of her condition in the previous 12 months.
On admission, the patient revealed she had had dyspnea with
dry cough for 3 weeks. On physical examination, she was apyretic
and orthopneic. Pulmonary auscultation revealed crackles, mainly
at the bases of both lungs. Her arterial BP was 140/95 mm Hg. A
mitral systolic murmur was noted along with irregular tachycardia. Hepatomegaly with hepatojugular reflux and malleolar
edema were noted on palpation.
ECG showed sinus rhythm and left-axis deviation with auricular and ventricular extrasystoles. Measurements of arterial blood
gas levels while the patient was breathing room air revealed the
following: Pao2, 54 mm Hg; Paco2, 35 mm Hg; pH, 7.35; and
arterial oxygen saturation (Sao2), 91%.
A chest radiograph showed cardiomegaly, bilateral alveolointerstitial infiltrates predominating in lung bases and a right-sided
homogenous suprahilar fullness with convex border, suggesting
mediastinal lymphadenopathy (Fig 1). A CT scan of the chest
subsequently revealed several lymph nodes of varying size,
between 10 and 17 mm in short-axis diameter in the transverse
plane (normal size, ⬍ 10 mm), located in two mediastinal
compartments, the left anterior mediastinal and the right lower
paratracheal compartments. An abdominal CT scan demonstrated no lymphadenopathy. The WBC count was normal, and
the C-reactive protein level was 3 mg/L. The results of tracheobronchial endoscopy were normal.
Mediastinoscopy was performed for biopsy sampling of the
lymph nodes. Macroscopically, the lymph nodes appeared to be
benign. The pathology examination reported sinus histiocytosis
without inflammatory or tumoral features. RBCs and a few
anthracotic pigments were visible on the sections. The results of
microbiological studies (ie, for tuberculous bacilli, bacteria, parasites, and mycotic agents) were all negative on direct examination and on cultures of lymph node tissue.
The immediate outcome was favorable within 24 h after
treatment with digitalis and diuretics, leading to improvement in
the clinical picture and in blood gas levels while breathing room
air (Pao2, 72 mm Hg; Paco2, 41 mm Hg). A follow-up chest
radiograph demonstrated the clearance of parenchymal and hilar
infiltrates (Fig 2). The morphologic characteristics of the mediastinal lymph nodes remained unchanged on follow-up CT scans
during 10 months of observation.
Figure 1. Chest radiograph taken at presentation (case 1),
showing bibasilar alveolointerstitial infiltrates with right-sided
suprahilar fullness, suggesting mediastinal lymphadenopathy and
cardiomegaly.
Case 2
This 75-year-old man was a smoker (18 pack-years) who had a
history of chronic obstructive bronchitis, chronic arteritis obliterans
of the lower limbs, and ischemic heart disease, which had necessitated a previous hospital admission for acute pulmonary edema.
In May 1997, the patient was admitted with dyspnea, exertionrelated angina, and productive cough with hemoptysis. A clinical
examination revealed a temperature of 38.4°C, an arterial BP of
100/60 mm Hg, a pulse of 80 beats/min, orthopnea, and diffuse
bilateral crackles on pulmonary auscultation. A murmur due to
mitral insufficiency and a grade 3 systolic murmur were noted.
Sensitive hepatomegaly was palpable with hepatojugular reflux
and edema of the lower limbs.
An ECG revealed sinus rhythm and ventricular extrasystoles.
Arterial blood gas values, measured while the patient was breathing room air, were as follows: Pao2, 75 mm Hg; Paco2, 38 mm
Figure 2. Chest radiograph taken after treatment (case 1).
Improvement is marked by moderate clearance of parenchymal
and perihilar infiltrates.
654
Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21958/ on 05/02/2017
Selected Reports
Hg; pH, 7.38; and Sao2, 95%. A chest radiograph revealed
right-sided pleural effusion with heterogeneous parenchymal
infiltrates of the right hemithorax, hypertrophic hila, and cardiomegaly. Chest CT scan showed lymphadenopathy (lymph node
size, 10 to 16 mm on short-axis diameter) in the right paratracheal
compartment and hila. The WBC count was 15,000/␮L with 76%
neutrophils, and the C-reactive protein level was 123 mg/L. The
pleural effusion was a transudate. The results of pleural cytology
and biopsy specimen testing were both negative. Bronchial
endoscopy demonstrated inflammatory features.
Mediastinoscopy was performed. The lymph nodes were macroscopically enlarged. Pathology investigations concluded that
there were lesions of sinus histiocytosis, without changes in
lymph node structure or surrounding tissues. The results of
microbiological examinations were negative.
Treatment with antibiotics, digitalis, and diuretics was followed by resolution of the patient’s temperature 48 h later and
by rapid improvement in blood gas values. Initial improvement
in the pleural and parenchymal features was noted on follow-up radiograph, but the mediastinal features persisted after
8 months.
Case 3
This 61-year-old male smoker (20 pack-years) was admitted
in August 1998 for cough with hemoptysis and dyspnea. He
had a history of coronary artery disease that had necessitated
hospital admission on three occasions for acute congestive
heart failure.
On examination, auscultation indicated bilateral fine crepitant
rales. Palpation revealed hepatomegaly, and there was edema of
the lower limbs. Arterial blood gas values, measured while the
patient was breathing room air, were as follows: Pao2, 82 mm Hg;
Paco2, 35 mm Hg; pH, 7.42; and Sao2, 91%. An ECG showed
signs of ventricular and auricular hypertrophy. Dilatation of the
left ventricle with hypokinesis of the posterior wall and a systolic
ejection fraction of 52% were noted on echocardiographic examination.
A chest radiograph revealed slight bilateral interstitial syndrome, predominating in the left base. A CT scan showed
lymphadenopathy (lymph node size, 10 to 15 mm on short-axis
diameter) located in paratracheal, pretracheal, and subcarinal
compartments. A slight pleural effusion was visualized in the
right hemithorax (Fig 3). Biochemistry study of the pleural
effusion indicated a transudate. Cytologic studies failed to reveal
malignant pleural cells. Bronchial endoscopy demonstrated no
abnormality.
Mediastinoscopy showed enlarged lymph nodes that were
macroscopically normal. Microscopic examination revealed sinus
histiocytosis associated with follicular hyperplasia of the cortex,
and no inflammatory lesions or capsular changes were seen (Fig
4). The results of microbiology studies were negative.
Treatment was started with digitalis and diuretics, resulting in
immediate clinical and radiologic improvement. On follow-up 5
months after the acute phase, a radiograph and CT scan showed
that most of the enlarged mediastinal lymph nodes and the
right-sided pleural effusion had completely disappeared. The few
remaining nodes measured ⬍ 6 mm in diameter (Fig 5).
Figure 3. Chest CT scan demonstrating right-sided lower
paratracheal lymph nodes and pleural effusion (case 3).
underestimated for various reasons, which can be explained mainly by the clinical presentation and the diagnostic circumstances.
Slanetz et al1 reported a study of 46 chest CT scan
examinations in patients with heart failure, which were
performed during periods of acute cardiac decompensation. Their retrospective analysis identified 55% of patients with enlarged lymph nodes that initially were undiagnosed. The enlarged lymph node localizations involved
various mediastinal lymphatic chains but appeared to
indicate higher frequency in the subcarinal, paratracheal,
and hilar nodes. Follow-up of 17 patients with elevated
levels of pulmonary capillary wedge pressure detected 14
patients with enlarged mediastinal lymph nodes (size, 10
to 20 mm on short-axis diameter).
The mechanisms underlying the pathogenesis of lymphadenopathy in cardiogenic pulmonary edema are unclear.
Lymphadenopathy in such cases is the expression of
Discussion
In contrast to alveolointerstitial edema, hypertrophy of
mediastinal lymph nodes is not a usual sign of congestive
heart failure. It is very probable that the frequency of
lymphadenopathy in congestive heart failure is largely
Figure 4. Photomicrograph of a histology slide from a mediastinal lymph node (case 3) demonstrating sinus histiocytosis with
slight follicular hyperplasia of the cortex (hematoxylin-eosinsaffron, original⫻100).
CHEST / 119 / 2 / FEBRUARY, 2001
Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21958/ on 05/02/2017
655
Figure 5. Follow-up chest CT scan (case 3) showing the
disappearance of enlarged lymph nodes 5 months after presentation, after the patient had undergone treatment with digitalis
and diuretics.
diffuse intrathoracic edema affecting the pulmonary parenchyma and neighboring structures, including the mediastinum and associated lymph nodes.
The lymphatic circulation has a primary role in the
regulation of pulmonary fluids. It ensures continuous
low-pressure drainage of excess fluids from the interstitial
space to the collecting ducts via the lymph nodes. These
nodes are distributed along the lymph vessels and filter the
lymph during its circulation. The lymph flow rejoins the
venous blood circulation, thus enhancing interactions between the two circulatory systems.2 Lymphadenopathy,
therefore, might result from mediastinal edema, which
itself is due to massive or repeated pulmonary edema that
is able to extend above the limits of the lungs and the
pleura at a very developed stage of congestive cardiac
failure. Hypertrophy of the lymph nodes, thus, might be
linked to edematous infiltration following lymphatic circulation overloading.
Drake et al3 used an experimental approach in sheep to
demonstrate that sudden induced cardiac insufficiency
was associated with an increase in lymphatic flow measured in the efferent vessel of a previously cannulated
mediastinal lymph node, when venous pressure was ⬍ 15
cm H2O. This process was followed by a significant
slowing of lymphatic flow for a venous pressure level ⬎ 15
cm H2O. Leeds et al4 showed that experimental congestive
heart failure in dogs caused the dilatation of lymphatic
vessels, which was provoked by excessive interstitial fluid.
Slanetz et al1 reported a particular hazy and heterogeneous appearance of mediastinal fat, which was consistently observed around enlarged lymph nodes that were
visualized on CT scans. It was attributed to local effects of
edema. These studies support the hypothesis of hemodynamic mechanisms in lymph node enlargement that are
related to severe cardiac decompensation.
Our report draws attention to the particular nosology of
late heart disease represented by benign enlarged lymph
nodes of the mediastinum and pulmonary edema. The
circumstances revealing the enlarged mediastinal nodes in
the three patients reported were almost identical. All had
known coronary heart disease and had experienced several
episodes of acute congestive heart failure with recently
worsened symptoms. A suspicion of lymphadenopathy was
based on radiographs that were taken to investigate dyspnea and heart failure. The identification of suspicious
features is theoretically easier on follow-up radiographic
examinations, which provide better visibility of hilar and
mediastinal areas, after treatment to reduce pulmonary
edema. Although CT scanning is much more effective for
the identification and follow-up of enlarged mediastinal
lymph nodes,5 such examinations usually are not necessary
in the clinical context of congestive heart failure. However, certain intrathoracic localizations of Hodgkin’s and
non-Hodgkin’s lymphomas, involving the heart and attributable to metastatic infiltration, may cause congestive
heart failure and, therefore, may present similar clinical
pictures.6 The results of lymph node biopsies in all three
patients showed similar histologic abnormalities (ie, sinus
histiocytosis with slight follicular hyperplasia of the cortex
in one patient).
The spectacular regression or disappearance of the
nodes in one of the three patients, who underwent therapy
exclusively for heart disease, is evidence of the likelihood
of cardiac origin. A similar outcome has been reported in
the literature after an acute episode of congestive heart
failure lasting for a month.1 The diagnostic approach to
such lymphadenopathy should be guided by the radiologic
regression seen on follow-up chest radiographs or CT
scans performed while the patient is undergoing appropriate therapy for congestive heart failure, which constitutes a decisive argument for the congestive heart failure
origin.
References
1 Slanetz PJ, Truong M, Shepard JA, et al. Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of
congestive heart failure. AJR Am J Roentgenol 1998; 171:
1307–1309
2 Wiener-Kronish JP, Matthay MA, Callen PW, et al. Relationship of pleural effusion to pulmonary hemodynamics in
patients with congestive heart failure. Am Rev Respir Dis
1985; 132:1253–1256
3 Drake RE, Dhother S, Teague RA, et al. Lymph flow in sheep
with rapid cardiac ventricular pacing. Am J Physiol 1997;
272:1595–1598
4 Leeds SE, Uhley HN, Telesky LB. Direct cannulation and
injection lymphangiography of the canine cardiac and pulmonary efferent mediastinal lymphatics in congestive heart
failure. Invest Radiol 1981; 16:193–200
5 Glazer G, Gross BG, Quint LE, et al. Normal mediastinal
lymph nodes: number and size according to American Thoracic Society mapping. AJR Am J Roentgenol 1985; 144:261–
265
6 Lynch M, Cobbs W Jr, Miller RL, et al. Massive cardiac
involvement by malignant lymphoma. Cardiology 1996; 87:
566 –568
656
Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21958/ on 05/02/2017
Selected Reports