Autopsy Findings in AIDS Patients from a Reference Hospital in Brazil: Analysis of 92 Cases

PATHOLOGY

Original Paper

RESEARCH AND PRACTICE © Urban & Fischer Verlag http://www.urbanfischer.de/journals/prp

Autopsy Findings in AIDS Patients from a Reference Hospital in Brazil: Analysis of 92 Cases Patricia M. Cury, Carla F. Pulido*, Verônica M. G. Furtado, Fabio M. C. da Palma Department of Pathology, Faculdade de Medicina de São José do Rio Preto-SP, Brazil *Universidad Autónoma de Barcelona, Spain

Summary The aim of this work was to evaluate the opportunistic diseases and the cause of death of AIDS patients who were submitted to autopsy. We included all AIDS patients submitted to autopsy at a reference hospital of a medical school in São Paulo, Brazil, during the period of 1993 to 2000. Out of 1,478 autopsy cases in this period, 92 patients (6.22%) had the previously confirmed diagnosis of AIDS. Sixty-nine patients (75%) were men ranging in age from 19 to 68 years (mean 34.8). Eighty-five patients (92.4%) died due to infectious diseases, while only two died of neoplasia. Forty-four (48%) patients died from pulmonary infection, 14 (15%) from sepsis, 14 (15%) from disseminated mycobacteriosis, and six (7%) from Central Nervous System (CNS) infection. The opportunistic diseases found were mycobacteriosis (n = 25), Pneumocystis carinii infection (n = 16), Cytomegalovirus infection (n = 17), toxoplasmosis (8 CNS cases), candida sp infection (n = 12), histoplasmosis (n = 5), cryptococcus (n = 4), and one case of blastomycosis in the lung. Most of our AIDS patients are dying of infectious and opportunistic diseases that are not always diagnosed during their lifetime. Key words: Autopsy – AIDS – Death cause – Pathology

Introduction The incidence of HIV infection is increasing worldwide, despite preventive care and massive epidemiology camPathol. Res. Pract. 199: 811–814 (2003)

paigns. In Brazil, the incidence is 9.55/100,000 inhabitants [3]. Thankfully, the survival rate of patients with this syndrome is also increasing, mainly due to the development of new drugs in this field [7, 10]. Nonetheless, patients are still dying, usually due to opportunistic infections or neoplasms, some of which are not diagnosed in life [1, 11]. The cause of death varies according to geographical location and economic conditions. Whereas in developed countries, there is a prevalence of neoplasms over infections, the opposite occurs in nondeveloped countries, most likely due to lack of drug therapies or non-adherence to medications [7, 10]. In Brazil, although HAART is used, we observed a low incidence of adherence (data not published). Autopsies provide more information about the diseases associated with AIDS. For this reason, we decided to study the autopsy-morphological findings of patients submitted to this procedure in our hospital in order to verify the cause of death in AIDS patients and its associated diseases.

Materials and Methods All data from patients submitted to autopsy in our hospital (Hospital de Base) during the period of 1993 to 2000 and sent to the Pathology Department were analyzed. However, we did not have access to more complete patient information, such as therapy performed in hospital

Address for correspondence: Patricia M. Cury, Faculdade de Medicina de de São José do Rio Preto, Departamento de Patologia, Av. Brigadeiro Faria Lima, 5416 CEP 15.090-000, São José do Rio Preto-SP, Brazil. E-mail: [email protected] 0344-0338/03/199/12-811 $15.00/0

812 · P. M. Cury et al.

or CD4/CD8 counting. Most patients had low adherence to HAART. The criterion for autopsy performance was the consent of family members, legally requested for this procedure. Only cases with clinically and laboratory proven diagnoses of HIV infection were selected, and the report and all slides of each case were reviewed by the authors. The slides contained parenchymal organs (liver, heart, lungs, adrenal glands, Central Nervous System, pancreas, and spleen), as well as gastrointestinal tract and urinary bladder. When a differentiation in an organ was detected macroscopically during autopsy, it was also studied microscopically. This was done by an experienced pathologist (P.M.C.) who reviewed all cases with pathology residents (V.M.G. and F.MC.P.).

Results Out of 1,478 patients autopsied, 92 (6.22%) had the previously confirmed diagnosis of HIV. Sixty-nine patients (75%) were men ranging in age from 19 to 68 years (mean 34.8). In Table 1, the number of cases per year are shown. When analyzing the cause of death, we found that 43 patients (47%) died of pulmonary infection,

Table 1. Number of patients per year Year

Number of patients

Men

Women

Mean age Age range

1993 1994 1995 1996 1997 1998 1999 2000

4 21 14 9 16 3 10 15

4 17 10 8 11 2 8 9

0 4 4 1 5 1 2 6

25.2 33.8 38.9 38.4 30.8 38.0 36.6 36.7

20–29 20–58 19–68 29–54 19–52 24–64 28–49 25–60

14 (15%) of disseminated mycobacteriosis, 13 (14%) of sepsis, eight (9%) of Central Nervous System (CNS) infection, two of disseminated histoplasmosis, two of disseminated cryptococcosis, three of acute pulmonary edema, two of lymphoma, and two of heart failure. Three patients died from other diseases: one case of intestinal bleeding, one acute peritonitis, and one acute pancreatitis. The diagnosis was based on laboratory or histological examination. The etiology of the all patients with pulmonary infection, as well as those who died from it, is described in Table 2.The most frequent agents were Mycobacterium (n = 25), Pneumocystis carinii (n = 14) and Cytomegalovirus (n = 8). The etiology of the Central Nervous System infection was toxoplasmosis (n = 9), cryptococcus (n = 3), P. carinnii (n = 1), histoplasmosis (n = 1), and Mycobacterium (n = 1). In five cases with purulent meningitis, the agent was not found and none contained malignant cells (Table 3). The patients who died from CNS infection are shown in Table 3. All diagnoses were based on histological examination with special stains. Subsequently, some of the diseases had no specie identification. The opportunistic diseases most frequently found in our cases were mycobacteriosis (8 pulmonary and 17 disseminated) and Pneumocystis carinnii infection (12 pulmonary, 2 disseminated, one in adrenal and one in CNS). In one of these cases, P. carinii was found in lung and in duodenum. Other common infections were Cytomegalovirus infection (7 pulmonary, 8 in adrenal, one disseminated, and one in intestines), toxoplasmosis (8 CNS cases) and candidiasis (10 in the digestive tract, one pulmonary, and one in CNS). There were five cases of histoplasmosis (2 pulmonary, 2 disseminated, and one in CNS), four cases of cryptococcus (one in the lung, one in CNS, and two disseminated), and one case of pulmonary paracoccidioidomicosis (Table 4). We found only three cases associated with malignancy: two non-Hodgkin and one Hodgkin lymphoma; no cases of Kaposi’s Sarcoma were found. Three patients presented

Table 2. Etiology of pulmonary infection (1993–2000) Etiology

1993

1994

1995

1996

1997

1998

1999

2000

Number % of patients

Mycobacteriosis Pneumocystis carinii Cytomegalovirus Histoplasmosis Blastomicosis Candida albicans Cryptococus Unknown agent Total:

– 1 – 1* – 1* 1* –

9 (3*) 5 (4*) 2* 1* – – – 2*

4 (3*) 2* 3 (1*) 1 – – 1 4 (2*)

4 – – – – – – 3 (1*)

5 (1*) 1* 3 (1*) 1 1* – – 5 (2*)

1* – – – – – – 2*

2 1* – – – – 1 2*

– 4 (3*) – – – – – 6 (4*)

25 14 8 4 1 1 3 24 80

* immediate cause of death

31.3 17.5 10.0 5.0 1.3 1.3 0.4 30.0

Autopsy in AIDS Patients from Brazil · 813 Table 3. Etiology of CSN infection (1993–2000) Etiology

1993

1994

1995

1996

1997

1998

1999

2000

Number of patients

%

Toxoplasma gondii Pneumocystis carinii Cryptococusis Histoplasmosis Mycobacterium Purulent meningitis with unknown agent Unknown agent Total:

1* – – – – –

3 (1*) – – – – 2 (1*)

– – – – – 1*

1 1 1* 1 1

1 – 1 – – –

– – – – – –

– – 1* – – 1

3 – – – – –

9 1 3 1 1 5

40.9 4.5 13.6 4.5 4.5 22.7

–

1

–

–

1

–

1

1*

2 22

9.1

* immediate cause of death Table 4. Opportunistic infection: general findings (1993–2000) Etiology

Total number of patients

Committed organ (number of cases)

Mycobacteriosis Cytomegalovirus Pneumocystis carinii Toxoplasma gondii Candida sp. Histoplasmosis Cryptococosis Blastomicosis

25 16 15 8 6 5 4 1

Disseminated (17), lung (8) Adrenal (8), lung (7), disseminated (1), intestine (1) Lung (12), adrenal (1), CNS (1), disseminated (2) CNS (8) Esophagus (5), lung (1), trachea (1), oral cavity (4), CNS (1) Lung (2), disseminated (2), CNS (1) CNS (1), disseminated (2), lung (1) lung (1)

syphilis (laboratory diagnosed), six had Chagas disease (cardiac presentation) associated, six had viral chronic hepatitis, five presented parenchymal abscess (three hepatic and two renal), and in two cases, acute colitis was observed. None of the diseases mentioned above contributed to death. One patient had viral encephalitis with unknown agent, and one had infective endocarditis, both contributing to death. In these latter infections, the diagnosis was based only on morphological aspects, such as polymorphonuclear infiltrate. Routinely, in all AIDS cases, we searched for mycobacteriosis and fungi using Ziehl-Nielsen and Groccott stains.

Discussion The incidence of autopsy procedure is decreasing worldwide, but its importance is still relevant in many studies [1, 2, 4, 18]. Our results show the variability of diseases found in AIDS patients, some of which were not diagnosed in life as other studies show [5, 19]. Unfortunately, we did not have all the patient data and clinical diagnoses for comparison, except in a few cases (68 patients). To our knowledge, there is no official data

in Brazil showing the etiologic agent in patients with HIV infection. Two recent publications, i.e., retrospective studies of autopsy findings collected over the last 15 years [7, 10], one in the USA and the other in Austria, had both similar and differing conclusions. While we found that the great majority of the patients were dying from an opportunistic infection, these papers state a greater incidence of non-Hodgkin lymphomas and Kaposi sarcomas, as well as an increase in bacterial infections over the recent years. We did not discover any cases with Kaposi’s sarcoma (KS), but we found two cases with malignant non-Hodgkin’s lymphoma (NHL) and one case of Hodgkin’s lymphoma. The incidence of NHL associated with AIDS has been stable during the last two decades in well-developed countries, although KS seems to be decreasing [12]. In the brain, some studies found a high incidence of HIV- related neuropathy [7, 8, 10]. In our study, one case was classified as viral encephalitis that could be associated with HIV virus, but there was no clinical or laboratory confirmation. Like Smith et al. [17], we had a great number of disseminated mycobacteriosis, which were not always clinically diagnosed. The same high incidence of mycobacteriosis, pulmonary and disseminated, was found in two African

814 · P. M. Cury et al.

studies [9, 13]. According to Sehonanda et al. [14], the incidence of mycobacteriosis associated with multiple infections is increasing, whereas pulmonary P. carinii infection is decreasing, an occurrence also found in other studies [6, 15]. A study conducted by Shahinian et al. [16] found a great incidence of HIV infection in the kidney. We did not detect HIV-typical, morphological infection in the brain or in lymph nodes of our patients. Bacterial infection was not frequent. We think that these differences are the result of economic conditions and geographical location. In Brazil, the population affected by AIDS has a low income and lives under inadequate social conditions. Although the retroviral drugs and prophylactic anti-opportunistic infection treatment are accessible for most patients, the adherence of HAART in our population is low; therefore, the incidence of opportunistic infection remains high. Methods that improve adherence should be studied. As this study demonstrates, each of these important factors, including the characteristics of the local population, seems to affect the correct clinical treatment.

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Received: September 9, 2002 Accepted in revised version: November 17, 2003