Pulmonary-actinomycosis-Case-report-and-retrospective-analysis-of-the-literature-in-China.doc

Pulmonary actinomycosis: Case report and retrospective analysis of the literature in China

Baiquan Yu1*,Yaxin Liu1*, Fuzhen Lv1#
1Department of Respiratory, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
*These two authors contribute equally to this work.
# Corresponding Author: Fuzhen lv, M.D., Ph.D.
Email addresses:
Baiquan Yu: yubaiquan76@
Yaxin Liu: aliu0707@
Fuzhen Lv: lvfuzhen01@

Abstract: Pulmonary actinomycosis is a rare but frequently misdiagnosed disease that is commonly confused with other chronic inflammatory diseases and malignancies. In this report, we aimed to evaluate the clinical manifestations and imaging features of pulmonary actinomycosis for early recognition which could prevent the considerable physical damage caused by delayed diagnosis. We reported a 52-year-old Chinese man, suffered by a 15-day history of cough, copious purulent sputum and intermittent fever, was final diagnosed as pulmonary actinomycosis by B-mode ultrasonic-guided transthoracic needle biopsy. Then 24 confirmed cases, including our patient from year 2005 to 2010, were reviewed and their clinical manifestations, diagnosis and treatment were analyzed. In our series the median age of the patients was 46.5 years, and the male-to-female ratio was 3:1. The most common symptoms include cough, sputum, haemoptysis, fever and chest pain . The main radiological features were peripheral mass or nodule complicated cavity, burr, pleural effusion. Malignancy possessed the highest rate for misdiagnosis (33.3%), followed by pneumonia (25%) and tuberculosis (16.7%) among these cases. Patients were confirmed by fiberoptic bronchoscopy (20.8%), transthoracic needle biopsy (33.3%), or surgery (33.3%). With regard to the treatment, 12 cases (50%) were treated by antibiotics only and 5 cases (20.8%) by surgery only, and 4 cases (16.7%) by surgery combined with antibiotics. When a middle-aged male patient presents with cough, sputum and haemoptysis, together with radiologic findings of a peripheral mass or mediastinal lymphadenopathy, respiratory physicians should suspect pulmonary actinomycosis and give the proper treatment to prevent unwarranted surgery or unnecessary death.

Key words: Actinomyces, pulmomary actinomycosis, bronchoscopy, antibiotics

Introduction
Pulmonary actinomycosis is a rare respiratory diseases with chronic, progressive, and suppurative characteristics. Recently the incidence of pulmonary actinomycosis has increased along with the wide application of antibiotics, hormones, cytotoxic drugs and immunosuppressants (1). Because of few typical clinical features and limited specific laboratory tests available for diagnosis of human actinomycosis, the probability of misdiagnosis and missed diagnosis of the disease increased. In the present study, we reviewed 24 cases of pulmonary actinomycosis in China, including 1 case from our hospital and 23 cases reported from domestic literatures from 2005 to 2010 (2-13), and analyzed clinical manifestations, diagnosis and treatment of the disease with intent to help early diagnosis and treatment.
Case report
A 52-year-old man was admitted to the Second affiliated Hospital of Harbin Medical University with a 15-day history of cough, copious purulent sputum and intermittent irregular fever with chills. His temperature peaked at 39.0°C. He had no other diseases before and had no any associated complains such as dyspnea, exercise limitation, chest pain, haemoptysis, night sweats, skin rash, or joint pains besides anorexia, weight loss and fatigue. He had been diagnosed pneumonia according to his clinical manifestations and had received antibiotics treatments but failed in other hospital before he came to our department.
Physical examination revealed that he got a high temperature at 38.7°C, pulse rate was 82 beats/min, respirations was at 18/min and blood pressure was 110/70 mmHg. With normal development, he was poorly nourished. Respiratory system examination revealed that breath sounds were decreased and moist rales could be heard in two upper lobes. The rest of the physical examination was unremarkable. Laboratory examination showed his white blood cell count (WBC) was increased to 19.3×109/L (normal, 4.0-10.0×109/L), differential count of polymorphs and lymphyocytes were 85.2% and 10.9% respectively. Platelet count was 441×109/L (normal, 100-300×109/L). Aspartate aminotransferase (AST) was 44 U/L (normal, <40 U/L), Alanine aminotransferase (ALT) was 89 U/L (normal, <40 U/L), Albumin was 30.8 g/L (normal, 35-55 g/L). Fecal occult blood was positive. The results from other laboratory examinations, including hemoglobin, serum electrolytes, renal function, coagulation profile, urine analysis, room air arterial blood gases and sputum detection of acid-fast bacilli, were within normal range. Results of sputum bacterial and fungal cultivation were also normal or negative. Cytology of bronchial washing and brushing specimens was negative for malignancy. Postero-anterior chest X-ray view revealed a mass with a cavity next to heart in left lower lobe of the lung (Fig. 1). A round uniform mass with clear borders, measuring 7.5×5.0 cm, located in the lower lobe of left lung and enlarged mediastinal lymph nodes was confirmed with CT scan of the chest (Fig. 2A.B).
Histopathologic examination was carried out with the tissue taken from left lower lobe lesion by B-mode ultrasonic-guided transthoracic needle biopsy. The tissue was translucent and jelly-like with sulfur granules. Actinomycetes groups were revealed under a microscope (Fig. 3A.B), thus the diagnosis was confirmed as actinomycosis.
The patient was treated with continuous IV amoxicillin/sulbactam 6.0 gram/pre day divided into 2 doses for 20 days, then cough and fever relieved significantly, a repeat CT scan of his chest showed the lesion in the left lung reduced obviously. He was followed by tablets of Penicillin-V, 2 gram/per day, divided into 4 doses P.O., for a total of half past three months. After 3.5 months of treatment, cough and fever were extincted, and the repeat CT scan showed the lesion almost disappeared. (Fig. 4A,B)
Retrospective analysis of the Pulmonary actinomycosis cases in China
Patients and Methods
We retrospectively reviewed 24 cases of pulmonary actinomycosis confirmed by histopathology reported from 2005 to 2010 on Chinese National Knowledge Infrastructure (CNKI). Clinical data of 24 patients including age, sex, occupation, underlying diseases, symptoms, physical signs, imaging findings, laboratory findings, initiatory diagnosis, methods of confirmed diagnosis and treatment were obtained and integratively analyzed.
Results
A total of 24 pulmonary actinomycosis cases including 18 men and 6 women (a male-to-female ratio of 3:1) were identified and evaluated. Age range was 20-65, and the median age was 46.5. Courses of disease lasted 5 days-1.5 years, and the majority of which lasted 3-5 months. Cough, sputum, haemoptysis and chest pain were the commonest presenting symptoms of the disease. Systemic symptoms such as fever and fatigue were also noted (Table 1). A few positive results were show on laboratory examination, eight cases (33.3%) had high WBC count or high polymorphs. The imaging manifestations of actinomycosis were various, main features were mass-like lesion or infiltration, lymph nodes enlargement and multifocal nodular (Table 2). Right lungs were more frequent than left lungs, and single lesions were more frequent than multiple (Table 3). According to the initial diagnosis in 24 cases, the rate of misdiagnosis in the sequence of diminishing were malignancy (n=8, 33.3%), pneumonia (n=6, 25%), tuberculosis (n=4, 16.7%) and lung abscess (n=1, 4.1%), atelectasis (n=1, 4.1%), inflammatory pseudotumor (n=1, 4.1%) and so on. In this study, patients were confirmed the diagnosis through obtaining histopathology by transthoracic needle biopsy (n=8, 33.3%) and bronchofiberscopy (n=5, 20.8%), those who were misdiagnosed malignancy were confirmed through surgery (n=8, 33.3%). Twelve cases (50%) were treated only with antibiotics, five cases (20.8%) were treated with surgery alone, and 4 cases (16.7%) were treated with surgery combined with antibiotics, there were no follow-up data in three cases (8.3%).
Discussion
Actinomycosis is a chronic, progressive, suppurative disease usually caused by infection of Actinomyces israeli, which is a Gram-positive, anaerobic-to-microaerophilic bacterium. Actinomycetes are endogenous oral saprophytes that dwell in carious teeth, dental plaque, gingival and tonsillar crypts(1,14). Pulmonary actinomycosis is mainly acquired through aspiration of organisms from the oropharynx. Features of a developing actinomycosis include disruption of the mucosal barrier, spreading from the bronchi into the surrounding lung, forming infiltration and granuloma, followed by invasion of pleural or chest wall (14).
The morbidity of pulmonary actinomycosis has increased recently due to the wide application of antibiotics, hormones, cytotoxic drugs and immunosuppressants (1) As a bacterial parasite, actinomycetes causes disease possibly in connection with poor oral hygiene, inspiring secretions with actinomycetes granules (15). Other established risk factors for pulmonary actinomycosis may include individual susceptibility, tumor, diabetes and application of steroid-hormones or other immune suppressants (16). In our study, one case (4.1%) had diabetes and one (4.1%) had fixed dentures who had the hidden dangers of oral health problems. Though other cases' histories were unknown, 15 of the 24 patients (62.5%) were farmer who may have problems with oral hygiene or excessive alcohol drinking.
Within the 24 cases of pulmonary actinomycosis plus the one reported here, the demographic findings were similar to those of previous reports (17, 18) In our case series, and the major symptoms were cough (87.5%), sputum (87.5%), haemoptysis (54.2%), fever (41.7%) and chest pain (33.3%). Fourteen (58.3%) cases had phlegm sputum, only one patient (4.1%) discharged sulphur granules. Seven (29.2%) cases developed a lower-grade fever, while three (12.5%) cases' temperatures were over 38.5°C. Some other non-typical symptoms including joint pain, shortness of breath, and systemic symptoms such as fatigue, anorexia and weight loss were also found in the patients. In conclusion, cough, phlegm sputum, sputum with blood and low-grade fever are the commonest presenting symptoms of the disease in China. When a patient has these symptoms at the same time, respiratory physicians should suspect pulmonary actinomycosis.
There is little helpful information for diagnosis on both chest radiograph and computed tomography (CT) findings in pulmonary actinomycosis. So it's difficult to distinguish actinomycosis from other pulmonary diseases such as pneumonia, lung abscess, tuberculosis, lung cancer, bronchiectasis by means of imaging methods (19, 20). Most of the published series are small retrospective studies (21, 22). A range of findings have been described on CT in pulmonary actinomycosis, including patchy air-space consolidation, multifocal nodular appearances, cavitation, pleural thickening, pleural effusions and hilar, and mediastinal lymphadenopathy (21, 23, 24). These information may be missed by chest radiography. Though the imaging manifestations of actinomycosis vary, in our study key performances were mass-like lesions or infiltration. Usually in irregular shape and with heterogeneous density, the mass like lesion were more frequently found in peripheral lung lobes. In addition to the main lesion, other lesions could be seen in surrounding lung such as patchs, spots and strips (21, 25-27). Mediastinal lymphadenopathy may be found more commonly than previously thought. There were 5 cases (20.8%) with mediastinal lymph nodes enlarged and 3 cases (12.5%) with hilar lymph nodes enlarged in our study. In our series, the lesion distributions in lungs were more common in right lungs (54.2%) and in lower lobes (45.8%). However, the destruction of pulmonary actinomycosis is extensive due to actinomyces often extending into surrounding lung tissues directly. Pulmonary actinomycosis is not limited to pulmonary segments, lobes and anatomical spaces (25, 28). Many cases reviewed in our study involved in multiple lung lobes or segments which were consistent with the spread characteristic of actinomycosis. There were 7 cases (29.2%) crossing lobes, 2 cases (8.3%) crossing segments, 1 case (4.1%) crossing mediastinal and 7 cases (29.2%) invading pleura confirmed by surgery and pathology. Other benign or malignant lung lesions rarely have the features that will be useful for differential diagnosis.
Actinomyces are anaerobic bacteria and sensitive to most of the antibiotics, even a single dose of an antibiotic before culture may inhibit its growth (29). Sometimes positive sputum culture may represent bacteria colonization only. Sulphur granules are the pathological hallmark of the disease. They are round or oval basophilic masses with a radiating arrangement of eosinophilic clubs on the surface (30). Although they are usually highly suggestive of actinomycosis, their positive rate is very low (17). With our patient, we failed to culture actinomyces although sulphur granules were found in his sputum smear. Positive rate can be increased through obtaining deep lung secretions or lung tissue. Therefore the majority patients in this study were confirmed diagnosis through obtaining histopathology by transthoracic needle biopsy (33.3%), surgery (33.3%) and bronchofiberscopy (20.8%). Bronchofiberscopy and transthoracic needle biopsy guided by ultrasound or CT should be carried out to avoid unnecessary surgery when the clinically highly suspected (31).
Pulmonary actinomycosis has an excellent prognosis with a very low mortality, because actinomyces are sensitive to most of the antibiotics including penicillin, acheomycin, streptomycin and lincomycin used in practice (29, 32, 33). Treatment require individualized, large dose, long course, and viable from veins to oral sequential therapy. Surgery is necessary when patients accompany serious lung destruction or underlying lung disease (34). Antibiotic therapy after surgery could improve the cure rate (35).
In conclusion, pulmonary actinomycosis is a frequently misdiagnosed disease that has no specificity of clinical features. Clinicians should be alert to the possibility of pulmonary actinomycosis if patients who have risk factors or underlying lung diseases present with chronic cough, purulent sputum, hemoptysis and fever. Histopathology by bronchofiberscopy and transthoracic needle biopsy is one of the most important methods for diagnosis because the diagnostic power of traditional bacterial culture is very low. When the infection is recognized early and proper treatment is applied, pulmonary actinomycosis