The contribution of ultrasonography and computed tomography in the evaluation of abdominal involvement in paracoccidioidomycosis

Introduction: paracoccidioidomycosis (PCM) is a polymorphic systemic granulomatous inflammatory disease determined by Paracoccidioides brasiliensis, one of the 10 leading causes of morbidity and mortality among the parasitic diseases endemic in Brazil. Objective: To identify the following aspects of PCM by ultrasound (US) and computed tomography (CT): abdominal changes, intensity and characteristics of the observed images, frequency of changes depending on clinical presentation, differences from other nosological entities. Patients and methods: This was a retrospective, observational, cross-sectional study carried out with 35 patients with PCM treated at the Hospital das Clinicas (HC) at the Universidade Federal de Minas Gerais (UFMG). Patients with tuberculosis, bronchial asthma, generalized chronic obstructive pulmonary disease, or in contact with silica or mines, as well as those with granulomatous diseases at any point in their current or past clinical history and detected through serology, anatomopathology or microbiological exams were excluded. Collected The contribution of ultrasonography and computed tomography in the evaluation of abdominal involvement in paracoccidioidomycosis Ivie Braga de Paula1, Ênio Roberto Pietra Pedroso2, Cid Sérgio Ferreira3 1 Médico. Mestre em Ciências da Saúde: infectologia e Medicina Tropical. Médico Infectologista do Setor de Radiologia do Hospital das Clínicas da Universidade Federal de Minas Gerais – UFMG. Belo Horizonte, MG – Brasil. 2 Médico. Doutor Medicina Tropical. Professor Titular do Departamento de Clínica Médica da Faculdade de Medicina da UFMG. Belo Horizonte, MG – Brasil. 3 Médico Radiologista. Professor Titular Aposentado do Departamento de Propedêutica Complementar da Faculdade de Medicina da UFMG. Belo Horizonte, MG – Brasil. Contribuição da ultrassonografia e da tomografia computadorizada na avaliação do acometimento abdominal na paracoccidioidomicose DOI: 10.5935/2238-3182.20140010


pacientes com PCM atendidos no Hospital das Clínicas (HC) da Universidade Federal de Minas Gerais (UFMG). Foram excluídos pacientes com tuberculose, asma brônquica, doença pulmonar obstrutiva crônica generalizada, contato com sílica ou minas, doenças granulomatosas em algum momento de sua história clínica atual ou pregressa e por intermédio da avaliação sorológica, anatomopatológica
The contribution of ultrasonography and computed tomography in the evaluation of abdominal involvement in paracoccidioidomycosis DOI: 10.5935/2238-3182.20140010The contribution of ultrasonography and computed tomography in the evaluation of abdominal involvement in ... or extra-pulmonary, due to primary hematogenous spread, with variable clinical spectrum that depends on the patient's age 5 and immunocompetence.][12] PCM is characterized, especially in children, by febrile systemic clinical manifestations and hepatosplenic lymphadenomegalies, and in adults by oropharyngeal, pulmonary, and lymph-nodal lesions.The respiratory symptoms are usually unspecific and well-tolerated, generally in an insidious form, characterized by unproductive, discreet, and irritating cough [11][12][13][14] or rarely with mucous expectoration.Dyspnea, chest pain, loss of appetite, 2,-15-17 adynamia, odynophagia, and weight loss might be present (15 kg on average).Its evolution can progress in general for months to years and is unpredictable. 2,39][20][21] Imaging methods help to define alterations in organs and systems, however, there are no typical patterns of PCM.
In studies of the abdomen, various methods are used to determine changes that might be associated with PCM such as simple x-rays, which reveals calcifications; barium examination, which helps defining the mucosal surface and indirect signals; and several other tests that help defining abnormalities without determining specificity, such as cholangiography, lymphography, ultrasonography, (US), computed tomography (CT), scintigraphy, MRI, and CT by positron emissions.Another method used for the study of the abdomen is laparotomy on the suspicion of acute abdomen or fungal aneurysm.The necroscopic study helps defining the diagnosis before serious and fatal manifestations. 8,10,15,16,22,23he aim of this study was to describe the contribution from US and CT in the evaluation of abdominal involvement in PCM; identify the structures involved; determine the intensity of the involved organs; determine the frequency of involvement of abdominal structures; describe the imaginological characteristics of alterations; and assess the possible alterations that differentiate this disease from other nosological entities and the prevalence of abdominal alterations depending on the clinical form.

INTRODUCTION
.2][5] It is classified as an infection or illness with acute or subacute forms (juvenile type), moderate or severe or chronic (adult type), uni or multifocal, and light to moderate or severe. 6,77he disease is usually acquired in the childhood or youth, expressing itself in immunocompetent people as an infection through the inhalation of spores of P. brasiliensis, which reach the pulmonary alveoli forming an inflammatory focus and hence reaching the peribronchial lymph nodes and establishing the primary pulmonary complex. 2,5,8,9 Th primary complex does not calcify or is rare in people from endemic zones infected with P. brasiliensis, however, without PCM. 10,11The initial infection may be followed by a hematogenous spread of the fungus to other organs. 12After the development of cellular immunity and hypersensitivity, primary foci suffer necrosis, in general without calcification, and can contain viable and quiescent fungi.Primary lesions may evolve and establish serious lesions, acute bronchopneumonia The contribution of ultrasonography and computed tomography in the evaluation of abdominal involvement in ... three, two, two, and one patients, due to previous or current history of tuberculosis (14.6%), bronchial asthma (5.7%), chronic obstructive pulmonary disease (3.8%), or work in mines (3.8%) or with silica (1.9 %), respectively.The exclusion was determined after serological, anatomopathological, and microbiological evaluation.
The exclusion of other granulomatous diseases such as sarcoidosis, lymphoma, infectious mononucleosis, and toxoplasmosis was determined after anatomopathological, serological, and immunopathological exams.
Patients who performed abdomen US in other services and those who had only conventional radiological exams for abdominal evaluation, such as intestinal transit and barium enema, were also excluded.

Review of the literature
A review of the literature was based on the Medline and LILACS databases using the terms: paracoccidioidomycosis, South American blastomycosis, abdomen, US, and CT.

Analysis of radiological exams
A total of 58 imaging exams were performed, distributed as US; US and CT; and CT in 27, 7 and 1 patients, respectively.
The US was performed through the SonolineSL-2 Siemens, Sonoline Prima Siemens and ATL 3500 Philips apparatuses.The CT was performed in the Somaton DR.G Siemens, Somaton Siemens AR.T, or Auklet Toshiba equipments from the Radiology Service in the HC at the UFMG.
Normal aspects in each organ and the characteristics of alterations found were described in the CT exams such as size, contours, density, shape, relationship with adjacent structures and enhancement after the administration of iodine contrast medium.The US exams described the normal aspects of organs such as size, contours, texture, shape, echogenicity, relationships with adjacent structures, and characteristics of alterations.In both methods, the liver was considered of normal dimensions when presenting up to 11 mm longitudinal diameter in the left lobe, and 15 cm in the right lobe.The spleen was considered of normal dimensions when presenting

PATIENTS AND METHODS
This is a retrospective, observational, cross-sectional study, characterized by an analysis of data from PCM patients' charts and exams, including children and adults, attended at the Clinical Hospital (HC) at the Federal University of Minas Gerais (UFMG).
An initial clinical evaluation was carried out in 52 PCM patients between 1988 and 2003, through a protocol designed for this purpose and transcribed for a specific computer software (SPSS for Windows ® ).
Patients were divided into two groups according to the acute and chronic clinical forms of the disease.The acute form was defined by the clinical history of recent onset, between one and two months, and symptoms compatible with reticuloendothelial involvement such as generalized lymphomegaly and hepatosplenomegaly.The chronic form was characterized by evolution for more than six months, with pulmonary and cutaneous-mucosal involvement. 6moking was present in 56.4% of the studied patients who were not excluded from the analysis.

Ethical aspect
All patients included in the study received information about the type of service provided based on an informed consent provided in their first consultation.The identity of patients or any information that would identify them was preserved; their initials or record numbers were used when necessary, in presentations of results or reports.The study was approved by the Ethics Committee of the UFMG (ETIC 082/00).

Inclusion criteria
Clinical and imaginological aspects were evaluated in 35 patients, characterized by time of symptoms' onset, main complaint, and most frequent signs and symptoms.The PCM diagnosis was confirmed by the identification of the fungus in the sputum examination or in biopsies of cutaneous-mucosal lesions.

Exclusion criteria
A total of 17 out of the 52 initially evaluated patients were excluded from the analysis being: nine, The contribution of ultrasonography and computed tomography in the evaluation of abdominal involvement in ... The imaging exams showed that the most affected organs in both phases of the disease (Figure 1 and Table 3) were the liver (37 percent), abdominal lymph nodes (40 percent), spleen (37%), and adrenals (17 percent).up to 12 cm longitudinal diameter.Both organs exhibited homogeneous texture without lumps when normal.Lymph nodes with more than 1 cm in their smallest diameter were considered involved. 24he exams were analyzed independently and single blinded by two radiologists; divergent opinions were resolved by a third radiologist.

STATISTICAL ANALYSIS OF THE DATA
Data analysis was performed using the Epi-Info 6.04 and SPSS for Windows V10.A p value > 0.05 was considered significant.
The data were subjected to statistical analysis with the development of frequency tables and Chi--square test analyzed using the Epi-info 6.04 and SPSS for Windows programs.

RESULTS
The patients were distributed according to genders in 21 men (60%) and 14 women (40%), with an average age of 32.9 ± 15.5 years (four were 62 years old).
The acute and chronic form or sequel were diagnosed in 13 (8 women) and 22 (6 women) patients, respectively.The acute and chronic phase patients had an average age of 19.8 ± 9.4 and 40.5 ± 12.9 years, respectively.
A total of 58 exams were conducted, 24% (14) were normal or had findings unrelated to PCM, such as renal cortical cysts or aerobilia due to prior digestive surgery.The 44 remaining exams (76%) revealed some alteration related to PCM (Tables 1 and 2).In the acute form, alterations were observed in 92% of patients (12), with 95% of exams detecting some alteration.In the chronic form, alterations were observed in 50% (11) of patients.The exam was normal in only one patient (Tables 1 and 2).The contribution of ultrasonography and computed tomography in the evaluation of abdominal involvement in ... The adrenals were involved, bilaterally, in six patients (17%); the US revealed a hypoechoic lump, and the CT revealed central necrosis.Calcification was found in one patient (Figure 4).
Hepatomegaly was discrete (16 cm), mainly in the right lobe, without concomitance of hepatic nodules, with periportal thickening in two, and bile duct dilation in four patients, respectively.This dilation was associated, in two patients, with a periportal or mesenteric lymph node mass; in one of them, located in the left lobe without lymphomegaly and in the other two concurrent with parietal alteration of the gallbladder, one of them in acute form, with ascites and diffuse parietal thickening and the other with the chronic form presenting nodular parietal thickening (Figure 2).Portal thrombosis was identified in one patient with the chronic form concomitant with previous thrombosis of the portal vein with collateral periportal veins and splenomegaly (Figure 3).
The pancreas was normal in all patients.The contribution of ultrasonography and computed tomography in the evaluation of abdominal involvement in ... The splenomegaly was observed in 13 (37%) patients, even moderate (16 cm), with a homogeneous texture and focal lesions in three patients (Figure 6).
Ascites and bilateral pleural effusion were identified in six (Figure 8) and four (11%) patients (Figure 9), respectively.Two muscular abscesses were identified in two patients (Figure 10) and mesenteric cystic formations in two other patients, who were no longer present in subsequent examinations (Figure 11).The contribution of ultrasonography and computed tomography in the evaluation of abdominal involvement in ... ic forms are prevalent in the second and third, and fourth and fifth decades of life, respectively.The involvement of men and women was in the ratio of 1.5:1 and 1:2.33 in the acute and chronic forms, respectively.The acute form is seen in children and adolescents with equal distribution between boys and girls, whereas the chronic form predominates in young adults, with higher prevalence in men than women.5][16][17][18] The hepatomegaly and lymph node involvement were more frequent in patients with the acute than the chronic form; ascites was only found in the acute form of PCM.An association between lymph node involvement and hepatomegaly or splenomegaly was observed (Tables 4 and 5).

DISCUSSION
][31][32][33] The most commonly observed histological alterations were of normal parenchyma with chronic inflammatory infiltrate in the region of port spaces, focal areas of parenchymal necrosis, granulomas and periportal chronic inflammatory infiltrate, periportal fibrosis, and alterations due to cholestasis.Periportal fibrosis with port hypertension has been reported in previous studies, however, without the exclusion of schistosomiasis mansoni.Patients in this study presented portal hypertension without associated periportal fibrosis but previous portal vein thrombosis. 34,35he gallbladder is rarely involved; however, acute cholecystitis with granulomatous inflammatory infiltrate and fungi on the vesicular wall and thickening and diffuse parietal associated with ascites, hepatitis, hypoalbuminemia, and cholecystitis have already been described. 34,35he adrenals were involved, bilaterally, with hypoechoic nodule and central necrosis with variable characteristics observed through the imaging methods and indistinct from other granulomatous disorders.7][38][39][40][41] The adrenal hypo function is not always possible to be diagnosed.][38][39][40][41][42] The kidneys were increased in echogenicity suggesting glomerular or tubular damage, which is associated to the use of amphotericin B. 5,9,11,16,17 The splenomegaly was observed in approximately one third of patients, even moderate (16 cm), with homogeneous texture, which may contain focal lesions.The frequency of splenomegaly was similar to that of other series, in which it ranged from 23 to 42%.Focal lesions presented aspect similar to that determined by the lymphoma..43The lymphomegaly was recorded in peripancreatic, mesenteric, and retroperitoneal chains in addition to forming lynphonodal conglomerates with rounded and hypoechoic aspect, in both forms of PCM, which are characteristics similar to those described in the literature.The lymphomegaly is the most common finding on abdominal PCM, identified in 48% of patients undergoing CT. [44][45][46][47][48][49][50] The involved lymph nodes The alterations observed in abdominal images occurred in 92 and in 50% of patients with an acute and chronic form, respectively.Because of its systematization, the acute form affects several organs and systems including abdominal structures; whereas the chronic form is more localized, affecting mucous membranes and skin, and lymph nodes in soft tissues, which naturally determines more intensity and PCM generalization in childhood and adolescence.][25][26][27][28][29] The discreet hepatomegaly was characterized by periportal thickening and bile ducts dilation associated with periportal or mesenteric lymph node mass and the concomitant with gallbladder parietal thickening, diffuse or nodular.Portal thrombosis was also identified, concomitant to previous thrombosis in the portal vein with collateral periportal veins and splenomegaly.Hepatic alterations are present in 36 to 59% of multiple  The contribution of ultrasonography and computed tomography in the evaluation of abdominal involvement in ...

CONCLUSIONS
The CT and US exams allowed demonstrating the involvement of abdominal organs in all forms of PCM.The most involved organs were lymph nodes, liver, spleen, and adrenals.
Gallbladder, retroperitoneal musculature, ascites, and pleural effusion showed alterations.Lymph node calcification, adrenal involvement, and ascites constitute evidences of high probability of PCM; however, they do not allow differentiation from tuberculosis.
In the chronic forms and with sequels, abdominal involvement is more frequent than what clinical forms indicate such as in patients without abdominal symptoms with hepatomegaly, lymphomegaly, and adrenal involvement.
tend to be rounded and with a necrotic center, similar to tuberculosis.Lymph node involvement can be identified at up to 10 years after the initial contact with the fungus.][46][47][48][49][50] Ascites and pleural effusion are associated to severe clinical manifestations and can have chylous content.Pleuritis and fibrinous peritonitis have been reported with a large amount of parasites.Mesenteric cystic formations that disappeared after treatment have a high probability of lymphatic origin.Muscular abscesses were observed, similar to those in other descriptions, 25 with regression after specific treatment.
The pancreas showed no alterations, which is also reported in other studies. 8,16,17,28epatomegaly and lymph node involvement were more frequent in the acute than in the chronic form; ascites was only found in the acute form of PCM, noting the association between lymph node involvement and hepatomegaly or splenomegaly.34]43 Greater abdominal involvement has been reported in the acute form of PCM than suspected in clinical examination.][53][54][55] The differential diagnosis of PCM mainly consists of tuberculosis and lymphoma and other deep mycoses.Lymphomegaly in tuberculosis and PCM may have central necrosis and calcification.In the lymphoma, lymph nodes are more homogeneous and may calcify after treatment.PCM has the tendency to affect the adrenals more than tuberculosis, which it does in about 5% of cases.Adrenal calcifications are more frequent in TB than in PCM.][58][59][60] The limitations of this study are represented by the fact that some of the intra-abdominal lesions were not biopsied for the confirmation of a PCM diagnosis.However, the exclusion of other diseases was determined by the anatomical, pathological study of materials from another location or serology, by the evolutionary evaluation for up to five years followup, and therapeutic response to antifungal treatment.

Figure 3 -
Figure 3 -Patient in the chronic phase of the disease showing old thrombosis in the porta vein with periportal collateral veins and splenomegaly.

Figure 5 -
Figure 5 -Kidneys with increased echogenicity in the parenchyma.

Figure 11 -
Figure 11 -Mesenteric cystic formations followed up during five years in the HC/UFMG.

Table 1 -
Ratios between normal and altered exams and clinical forms of paracoccidioidomycosis in patients treated at the Clinical Hospital at UFMG between 1988 and 2003 2test with Yates correction: 6.46; Value of p: 0,01.

Table 2 -
Ratios between the number of patients with normal and altered exams and clinical forms of paracoccidioidomycosis in patients treated at the Clinical Hospital at UFMG between 1988 and 2003

Table 3 -
Main detected alterations according to abdominal MRI and ultrasonography in 35 patients with PCM, in absolute and percentage values, and according to the clinical forms; patients followed up for 5 years at the HC at UFMG X 2 test with Yates correction; **Fisher's exact test.

Table 4 -
Description of the main hepatic alterations observed in 22 out of the 35 patients with paracoccidioidomycosis according to abdominal MRI and ultrasonography, in absolute and percentage values, and according to the clinical forms; patients followed up for 5 years at the HC at UFMG

Table 5 -
Relative frequencies of involvement of intra-abdominal organs, observed in paracoccidioidomycosis, according to MRI and ultrasonography in patients with paracoccidioidomycosis followed up for 5 years at the HC at UFMG *Chi-square Yates test; **Fisher's exact test.