A Case of Legionnaires’ Disease with Extensive Concurrent Deep Vein Thrombosis
YASEEN S. SAMMAN, MOHAMED A. ABDELAAL, SIRAJ O. WALI, ABDULLAH H. ALMALKI and MUNTASIR M. ABDELAZIZ
From the Department of Medicine, King Khalid National Guard Hospital, Jeddah, Saudi Arabia
A previously healthy 37-y-old male presented with community-acquired pneumonia and extensive upper limb deep vein thrombosis. The diagnosis of Legionella pneumonia was made based on a positive direct immunofluorescence of the bronchial wash. An extensive investigation for hypercoagulable states was negative. The possible association between Legionella infection and deep vein thrombosis is highlighted.
Y. S. Samman, Respiratory Section, Department of Medicine, King Khalid National Guard Hospital, PO Box 9515, Jeddah 21423, Saudi Arabia (Tel. /966 2 624 0000 extn 1372/3, fax. /966 3 624 7234 or 624 0000 extn 1573, e-mail.
INTRODUCTION
Legionella was first identified as the aetiological agent of the 1976 epidemic of acute respiratory disease that occurred in Philadelphia at the National Convention of American Legion (1). Legionella is a genus of fastidious flagellated aerobic Gram-negative coccobacilli which includes at least 43 distinct species and 63 serogroups. Human infection with serogroups 1, 4 and 6 accounts for 80
/90% of cases of pneumonia due to Legionella pneumophila (2). Among patients with nosocomial pneumonia, the reported incidence of Legionella infection has varied from 1% to 40% (3).
Worldwide, legionellosis accounts for 2
/15% of all cases of community-acquired pneumonia (CAP) severe enough to require hospitalization (4). Legionnaires’ disease is a severe form of legionellosis with a wide spectrum of extrapulmon- ary manifestations such as involvement of the gastrointest- inal tract, kidneys, central nervous system, liver, spleen, myocardium, bone marrow and lymph nodes (5, 6). Legion- naires’ disease is associated with a significant mortality rate of about 20% (6). Delay in administration of appropriate therapy has been associated with increased mortality (7).
Although a case of Legionnaires’ disease associated with deep venous thrombosis (DVT) was reported in 1980 (8), extensive MEDLINE search showed no further report of such an association. We describe here a case of Legionnaires’
disease presenting with concurrent extensive right upper limb DVT with no identifiable hypercoagulable state, raising the possibility of association between legionellosis and venous thrombosis.
CASE REPORT
A 37-y-old male presented to our hospital with cough, productive yellow sputum, progressive swelling of the right upper limb for 10 d, with worsening dyspnoea, decreased level of consciousness and disturbed speech. Systemic enquiry and past medical history were unremarkable. He was a non-smoker and married and had no family history of thrombosis. On examination he was very ill, cyanosed, sleepy but arousable, sweaty with warm extremities, flapping tremor and erythematous palms. His temperature was 37.28C, respiratory
rate 28/min and BP105/60 mm Hg. The right upper limb was grossly swollen from mid forearm to the shoulder, warm, non-tender, and non-pitting with venous collaterals on the right chest wall. Chest examination showed reduced chest expansion and intensity of breath sounds with coarse crackles on the right base. The rest of the physical examination was unremarkable. A provisional diagnosis of severe CAP with respiratory failure and right subclavian vein thrombosis was made.
Laboratory investigations showed neutrophil leukocytosis of 16/
109/l, Hb of 160 g/l and a platelet count of 312/109/l. Arterial blood gases revealed respiratory acidosis with pH 7.0, Po27.0 Kpa, Pco215 Kpa, HCO332 mmol/l and oxygen saturation of 75% at room air.
Urea was 13.7 mmol/l and creatinine 231 mmol/l, Na 128 mmol/l, K 5.3 mmol/l, albumin 48 g/l, total protein 78 g/l, bilirubin 158 mol/l, AST 439 IU/l, ALT 340 IU/l, LDH 1384 IU/l, and creatinine phosphokinase 339 IU/l. The coagulation profile revealed PT 19 s (control 12) and APTT 50 s (control 34), thrombin time 21 s (control 17) and fibrinogen 3.5 g/l (reference range 2.0/4.0). Hepatitis serology was negative. ECG was normal. Chest X-ray revealed diffuse opacities in both lung fields obscuring the cardiac borders, in addition to small right pleural effusion.
The patient was admitted to the intensive care unit, intubated and mechanically ventilated. Blood culture and samples for atypical microorganisms including Legionella, Mycoplasma and Chlamydia were taken and the patient was started on intravenous ceftazidime and erythromycin in addition to intravenous heparin. Contrast enhanced CT scan of the chest showed a large luminal defect in the distal right subclavian vein extending to the right innominate vein up to the junction with the left innominate vein and at the origin of the superior vena cava with no masses or adenopathy compressing the venous structures. Right upper limb venogram demonstrated no opacification of the right subclavian and brachiocephalic veins with engorged and dilated collaterals, a finding consistent with extensive DVT. Blood culture, sputum culture for Mycoplasma and serology for Chlamydia pneumoniae were all negative. The bronchial washing direct immunofluorescent antibody staining for Legionella pneumo- phila was strongly positive. Pleural fluid analysis showed protein 31 g/l, LDH 195 IU/l, and reactive mesothelial cells.
The patient showed rapid clinical improvement to antibiotics and anticoagulant therapy, with complete normalization of disturbed baseline haematological and biochemical profiles, and was extubated on d 16 of intensive care unit admission, and erythromycin was continued for a total of 21 d. He was discharged home on warfarin therapy, and on follow-up he remained asymptomatic and com- pleted 3 months of oral anticoagulation therapy with resolution of signs of the DVT.
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Two weeks after discontinuation of warfarin therapy, PT, APTT, TT and fibrinogen level and antithrombin III and protein C activity were all within reference range. Total protein S, measured by polyclonal ELISA (9) and free protein S, measured directly in plasma by ELISA using 2 monoclonal antibodies specific for free protein S (10), were both normal. Levels of anticardiolipin antibodies (IgG and IgM), as measured by ELISA technique, were within reference range. Plasminogen activity using amidolysis of chromogenic substrate and plasminogen inhibitor activity, by 2-stage indirect enzymatic assay, were normal. Reverse hybridization assay for combined molecular genetic analysis of point mutations 1691 A in factor V and 20 210 in factor II using thrombotype test (F Hoffman-La Roche AG, CH-4002 Basel, Switzerland) according to the manufacturer’s instructions was negative. Total homocysteine concentration was 15mmol/l (reference range 7/17), when measured in citrated plasma by automated high pressure liquid chromatogra- phy on fasting blood specimen collected into EDTA tube and promptly separated and stored frozen at/808C (11).
DISCUSSION
Although some symptoms and signs are typical of legionel- losis, none reliably distinguishes it from other forms of CAP (3, 4). The diagnosis of Legionella pneumonia in this patient was based on the result of direct immunofluorescent staining of the bronchial wash.
Identification of Gram-negative coccobacilli in respiratory secretions is an important clue to the diagnosis (12, 13).
Several staining techniques have been described for identi- fication of the organism in lung specimens, e.g. Gimenez or Dieterie Silver impregnation techniques and Wolbach mod- ification of the Giemsa Stain (14, 15). The most reliable method of identifying Legionella is by direct immunofluor- escent or immunohistochemical staining of respiratory tract secretions or tissue (16, 17). Serological methods using ELISA and microagglutination depend on a 4-fold increase in antibody titre over 4 to 8 weeks for diagnosis.
Legionnaires’ disease shows a propensity for older men with a male to female ratio of 2
/3:1 and most cases occur in patients with preexisting diseases, e.g. malignancy, renal failure and immunodeficiency states (18). Our patient was only 37 y old and was previously healthy. The source of infection in our patient remains speculative but probably related to contaminated water or cooling towers.
The spectrum of legionellosis varies from Pontiac fever, which is usually a mild influenza-like illness, to severe fulminating cases of Legionnaires’ disease with frequent occurrence of a variety of extra-pulmonary manifestations (3, 15, 19, 20). Our patient presented with severe CAP, due to Legionella, and developed hypoxaemia, disturbed liver function tests and renal impairment. In addition, he had an extensive DVT in the upper limb. In 1980, Segnestam et al. (8) reported a case of legionellosis that was complicated with DVT. Unlike our patient, DVT occurred in the lower limb 4 weeks after the diagnosis of Legionnaires’ disease and no test was cited in the report to exclude a coexisting thrombophilia (8). In contrast, our patient presented con- currently with Legionella CAP and DVT at an unusual site
in the absence of any demonstrable hypercoagulable state, raising the possibility of an association between Legion- naires’ disease and DVT.
Septicaemia frequently results in disturbance of haemo- static mechanisms (21, 22). Endotoxin, a lipopolysaccharide present in the outer membrane of Gram-negative bacteria, plays an important role in the development of the clinical and laboratory manifestations of septicaemia (22). Tissue factor, an integral membrane glycoprotein of the suben- dothelial component of the vessel wall comes into contact with blood and hence activates the coagulation cascade via intrinsic pathway, after there has been damage to the vessel wall by the bacteria. Moreover, vascular endothelial cells and monocytes can both be induced to express tissue factor by interleukin-I and bacterial endotoxin (22). Vasculitis and thrombosis of small vessels of the lungs have been described in several reports of Legionella pneumonia (23, 24).
Acquired antithrombin deficiency is commonly found in sepsis (25) and may occur in venous thrombosis associated with sepsis, although not investigated in the acute phase of the present case.
In conclusion, DVT may be an extrapulmonary manifes- tation associated with Legionnaires’ disease.
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Submitted June 3, 2004; accepted July 12, 2004
DOI: 10.1080/00365540410020947
Successful Treatment of Pulmonary Mucormycosis in an Allogenic Bone-marrow Transplant Recipient with Combined Medical and Surgical Therapy
JULIETTE PAVIE
1, MATTHIEU LAFAURIE
1, CLAIRE LACROIX
2, ANNE MARIE ZAGDANSKI
3, DENIS DEBROSSE
5, GE ´ RARD SOCIE´
4, FRANCIS DEROUIN
2, ELIANE GLUCKMAN
4and JEAN MICHEL MOLINA
1From the1Service des Maladies Infectieuses et Tropicales,2Laboratoire de Mycologie et Parasitologie,3Service de Radiologie,
4Service de Greffe de Moe¨ lle, Hoˆpital Saint Louis, Assistance Publique-Hoˆpitaux de Paris, and5Service de Chirurgie Thoracique, Institut Mutualiste Montsouris, Paris, France
Mucormycosis is a rare, but severe, complication in allogenic bone-marrow recipients with a mortality rate of about 80%.
Moreover, its incidence appears to have increased within the last decade. We report a case of pulmonary and nasal mucormycosis in a 55-y-old patient, which occurred 1 y after BMT. Treatment combining 4 months of amphotericin B, early surgical resection of infected tissue and discontinuation of immunosuppressive treatment allowed the cure of this mould infection.
J. Molina, Service de Maladies Infectieuses, Hoˆpital Saint Louis, 1 Avenue Claude Vellefaux, FR-75010 Paris, France (Tel.
/01 42 49 90 66, fax./01 42 49 9067, e-mail. [email protected])
INTRODUCTION
Mucormycosis is an opportunistic infection due to moulds from the order Mucorales, in the Zygomycetes class. It is a rare but severe infection in allogenic bone-marrow recipients.
The mortality rate is about 80% (1). Its incidence, in this population, appears to have increased during the past decade with 7 cases reported between 1985 and 1989, 8 between 1990 and 1995, and 14 between 1995 and 1999 in the same institution (2).
Main risk factors associated with the development of mucormycosis after bone-marrow transplantation (BMT) include underlying myelodysplastic syndrome, recipient of an allogenic BMT from an HLA-mismatched or unrelated donor, severe acute graft-vs-host disease, and immunosup- pressive treatment including steroids (2, 3). Neutropenia is
observed in only half of the cases (2). Infection with Zygomycetes occurs more frequently late (i.e.
/90 d) after transplantation.
We report a case of pulmonary mucormycosis in a patient who underwent allogenic BMT 1 y earlier. Outcome was favourable after medico-surgical treatment and discontinua- tion of immunosuppressive therapy.
CASE REPORT
A 55-y-old male was diagnosed with a low grade non-Hodgkin’s lymphoma in March 1994. After 3 relapses treated by chemotherapy and radiotherapy, allogenic stem cell transplantation was performed with an HLA-identical donor after a non-myeloablative condition- ing regimen (cyclophosphamide, fludarabine and ATG sera) in November 2000. Seven months later, because of relapse, he received chemotherapy (including cyclophosphamide and etoposide), anti-
Scand J Infect Dis 36 Case Reports
