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 Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 3  |  Issue : 1  |  Page : 29-34

Epidemiological and clinical features of AIDS-Associated Kaposi's sarcoma in Northern Nigeria


1 Department of Surgery, Ahmadu Bello University, Teaching Hospital Zaria, Nigeria
2 Department of Hematology and Blood Transfusion, HIV Control Programme, Ahmadu Bello University, Teaching Hospital Zaria, Nigeria
3 Department of Paediatrics, Ahmadu Bello University, Teaching Hospital Zaria, Nigeria

Date of Web Publication28-Aug-2013

Correspondence Address:
Adamu Ahmed
Department of Surgery, Ahmadu Bello University Teaching Hospital Zaria
Nigeria
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DOI: 10.4103/2278-9596.117132

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  Abstract 

Introduction : The incidence of AIDS-associated Kaposi's sarcoma (AAKS) is increasing in the West African sub-region. The objective of this study was to describe the epidemiologic and clinical features of AAKS.
Materials and Methods : This study was carried out in a tertiary health center with a federal government supported AIDS treatment program in Zaria, Nigeria. The subjects comprised 137 consecutive patients evaluated for AAKS from 2006 to 2011. Following evaluation appropriate specimens were taken for histologic, virologic, and immunologic assessment.
Result : There were 137 patients representing 1.4% of HIV infected patients seen during the study period. The male to female ratio was 1.3:1. Their ages ranged from 2 to 58 years, mean of 32 ± 6 and females were younger than males. Mean duration of symptoms was 4.2 ± 1.5 months. Kaposi's sarcoma was the AIDS-defining disease in 95 (69.3%) patients while in 42 (30.7%) it was diagnosed between 1 and 15 months after the diagnosis of HIV infection. The lower limbs were the most frequent sites of lesions. Females had more disseminated lesions involving an increased number of lesions at multiple anatomical sites compared with more localized lesions in the males (OR 2.7, 95% CI 1.5-7.0). The CD4 count ranged from 19 to 798 cells/mm 3 , median 132; interquatile range 102-317 cells/mm 3 while the median HIV RNA copies/ml of plasma was 51,723 (ranged 250-917, 254).
Conclusion : The prevalence of AAKS is increasing in our institution. Female patients were younger and had more disseminated disease that progressed faster than in males. Timely identification of HIV-infected patients is essential to avoid the consequences of immunological deterioration associated with delayed anti-retroviral therapy.

Keywords: AIDS, clinicopathology, immunology, Kaposi′s sarcoma


How to cite this article:
Ahmed A, Muktar HM, Bugaje MA. Epidemiological and clinical features of AIDS-Associated Kaposi's sarcoma in Northern Nigeria. Arch Int Surg 2013;3:29-34

How to cite this URL:
Ahmed A, Muktar HM, Bugaje MA. Epidemiological and clinical features of AIDS-Associated Kaposi's sarcoma in Northern Nigeria. Arch Int Surg [serial online] 2013 [cited 2014 Nov 27];3:29-34. Available from: http://www.archintsurg.org/text.asp?2013/3/1/29/117132


  Introduction Top


Before the HIV epidemic, Kaposi's sarcoma (KS) was very infrequent in Western countries with an incidence rate of 0.3 per 100,000 from 1978 to 1993 in the United States of America. [1] However, KS has become the most common neoplasm in AIDS patients since it was first reported among homosexual men in the United States at the beginning of the AIDS epidemic. [2] In the past, the incidence of KS was over 20,000 times higher in patients with AIDS than in the general population. [3] However, the discovery and widespread use of highly active antiretroviral therapy (HAART) in developed countries has led to a substantial decrease in the incidence of AIDS-associated Kaposi's sarcoma (AAKS). [4] The cohort study 'EuroSIDA' reported a decrease in the incidence rate from 24.7 cases (95% CI 17.2-32.2) per 1000 per year in 1994 to 4.7 (95% CI 2.7-6.7) per 1000 in 1997 and 1.7 (95% CI 0.7-3.4) per 1000 in recent years among HIV-infected individuals. [4] In addition, patients on HAART present with less aggressive disease which is associated with less morbidity and mortality. [4] The burden of HIV infection and AIDS is greatest in the developing world and neoplastic complications are increasingly encountered. [5] Although KS was endemic in central and east Africa before the AIDS epidemic, AAKS has become the most frequently diagnosed tumor (T) in several African countries. [6],[7] The incidence has been steadily increasing partly because of limited access to antiretroviral drugs and other preventive or curative therapies for AIDS-associated cancers. In countries with long-standing AIDS epidemic such as Uganda and Zimbabwe, the incidence of KS has increased 20-fold to become the most common cancer in men and the 2 nd most common in women. [6],[7] Before the advent of the AIDS epidemic in South Africa, approximately 100 new cases of histologically diagnosed KS cases were reported to the National Cancer Registry each year accounting for 0.3% of female and 0.7% of male cancer patients. [8] Since 1993, the incidence of KS in South Africa has doubled in men and increased 7-fold in women. [8] A study conducted in Rwanda found a clear association between HIV infection and KS with odd ratios ranging from 21.9 (95% CI 12.5-38.6) to 47.1 (95% CI 31.9-69.8). [9]

The incidence of HIV/AIDS in Nigeria is estimated to be 4.1 million and is on the downward trend. [10] In the past, KS was reported particularly from the southeastern parts of Nigeria where the absence of AAKS was emphasized. [11] However, since the advent of the AIDS pandemic KS is now reported from regions not previously considered endemic for the disease. [12],[13] Our patients present with advanced HIV infection and poor-risk KS. This together with limited therapeutic facilities resulted in poor outcome of treatment. [13] Our institution is one of the Federal Government HIV/AIDS designated treatment center and we see patients from various parts of Nigeria. This study describes the epidemiologic, clinical, immunologic and virologic features of AAKS at a major teaching hospital in Zaria, Nigeria, over the 6-year-period (2006-2011).


  Materials and Methods Top


This study was a cross-sectional analysis of consecutive patients with AAKS. The Institutional Review Boards of the hospital approved this study. Informed consent was obtained from every patient after adequate counseling. All patients diagnosed of AAKS from January 2006 to December 2011 were included. Only patients with concurrent HIV infection and histologically confirmed KS were included.

Patients were assessed at the time of diagnosis of AAKS. The weight, vital signs and KS symptoms including pain, limb swelling, ulceration and disfigurement were recorded, and a physical examination was performed. The dimension, appearance and location of KS lesions were recorded. Accessible lesions were photographed. T size was defined as the sum of the greatest diameters of each measurable T. The Karnoffsky score status of the patients was also recorded. KS was staged into good or poor prognosis categories according to AIDS Clinical Trials Group (ACTG) classification using the T, immune system (I) and systemic illness (S). [14] HIV antibody testing was performed by parallel testing using Enzyme-linked immunoabsorvent assay with Immunocomb II, HIV-1 and HIV-2 combifirm (M/S Organics, Ltd. Israel) and Stat Pak (Trinity Biotech, Wicklow, Ireland). The CD4 cell counts were performed using the Dynabeads method (Dynal Biotech LLC, Milwaukee, WI, USA). In every patient, biopsied tissue from representative KS lesion was fixed in 10% formalin and embedded in paraffin wax. Routine histological sections were prepared using standard staining methods with H and E. Special stains were employed in selected cases. HIV viral load was measured using the Roche-Ampiclor HIV-1 monitor test, (version 1.5, Roche-Ampiclor-Roche Diagnostics, Branchburg, USA). The HIV RNA levels <400 copies/mL was considered undetectable. Other investigations performed include serum urea and electrolytes, liver function test and complete blood count with differential and platelet count. Chest radiographs, abdominal ultrasound, fecal occult blood and gastrointestinal endoscopic examination were performed when indicated.

Statistical analysis

The data were analyzed with SPSS statistical software (version 17.0, SPSS, Chicago IL). Data were reported as proportions, mean ± standard deviation (SD) or median (range). Categorical variables and proportions were compared by Fisher's exact test while continuous variables were compared by Wilcoxon two-sample test. We considered p < 0.05 to be statistically significant.


  Results Top


During the study period 137 patients with AAKS were seen. This constituted 1.4% of HIV infected patients seen during the study period. Seventy (51.1%) patients were seen between January 2010 and December 2011. There were 78 males and 59 females, male-to-female ratio of 1.3:1. The male to female ratio decreased from 1.5:1 in 2006 to 1:1 in 2011. Their ages ranged from 2 to 58 years, mean of 32 ± 6 years. The highest incidence was in the age group 31-40 years. Females were significantly younger (mean age 31 ± 5 SD years) than males (mean age 37 ± 7 SD years) (p < 0.03). Duration of symptoms ranged from 2 weeks to 13 months, mean of 4.2 ± 1.5 months. KS was the AIDS-presenting disease in 95 (69.3%) patients while in the remaining 42 (30.7%) it was diagnosed between 1 and 15 months after the diagnosis of HIV infection. The most common symptoms were swelling of extremities [Figure 1] 75 (54.7%), pain in 62 (45.3%) and cosmetic disabilities in 26 (19.0%) patients. In 12 (8.8%) patients there were no symptoms, as KS was discovered during routine clinical evaluation in the anti-retroviral (ARV) clinic. Most patients (67.2%) had Karnofsky performance score ≥70 at the time of diagnosis [Table 1]. The anatomical distribution of KS lesions is shown in [Table 2]. Three and two patients had KS lesions in the rectum and stomach, respectively. At the time of diagnosis, the stage of KS was T1 I1 S1 in 62 (45.2%) patients, T1 I1 S0 in 26 (19.0%), T0 I0 S1 in 15 (11.0%), and T0 I0 S0 in 34 (24.8%) patients, respectively. Overall 103 (75.2%) patients had poor prognosis disease comprising 54 (91.5%) females and 49 (62.8%) males. However, there were no gender related differences in CD4 counts or plasma HIV viral load. Females had more disseminated cutaneous lesions [Figure 2] involving an increased number of lesions at multiple anatomical sites compared with more localized lesions in the males (OR 2.7, 95% CI 1.5-7.0). Twenty three patients (16.8%) were on antiretroviral therapy at the time of diagnosis and their CD4 count ranged from 136 to 798 cells/mm 3 . Overall, CD4 count ranged from 19 to 798 cells/mm 3 , median of 132, interquartile range 102-317 cells/mm 3 . The median HIV RNA copies/ml of plasma was 51,723 with a range of 250-917,254. One patient had both tuberculous and KS lymphadenopathy [Table 3].
Figure 1: Nodular Kaposi's sarcoma with edema of the lower limb

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Figure 2: Kaposi's sarcoma lesions involving the thigh and perineum

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Table 1: Characteristics of patients with AIDS-associated Kaposi's sarcoma

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Table 2: Tumor characteristics in patients with AIDS-associated Kaposi's sarcoma

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Table 3: Associated diseases in patients with AIDS-associated Kaposi's sarcoma

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  Discussion Top


This study revealed an increasing prevalence of AAKS which was found in 1.4% of HIV-infected patients. The male to female ratio was 1.3:1 and females were significantly younger than males. The most common symptoms include pain, swelling of extremities, and cosmetic disabilities. Fifty four (91.5%) females had poor prognosis disease consisting of disseminated cutaneous and visceral lesions involving an increased number of lesions at multiple anatomical sites compared with a more localized disease in males although there were no significant gender-related differences in CD4 counts or plasma HIV viral load. In 108 (78.8%) patients the CD4 count was ≤200 cells/mm 3 while 114 (83.2%) had viral load >10,000 copies/ml. Many patients had additional AIDS-associated diseases the most common being candidiasis and pulmonary tuberculosis.

In Western countries, the incidence of AAKS has dropped from about 15% at the beginning of the AIDS outbreak to 0.3%. [1] In Thailand, the incidence is 0.026 per 100,000 despite high incidence of HIV infection because HHV-8 infection is low at 4.0%. [15] The prevalence of AAKS is increasing in Nigeria. A report from Lagos, reported AAKS in 0.52% of HIV infected patients seen between 1992 and 1996. [16] A decade later, studies from Benin and Abuja reported incidence of 0.8%. [17],[18] In the present study, AAKS was seen in 1.4% of patients similar to the 1.6% reported from Jos, Nigeria. [19] However, it is less than 17-32% reported from Central and Southern African countries. [6],[7],[8] Whilst HAART is not readily available in sub-Saharan Africa, HIV-infected patients live longer such that they are exposed to severe and sustained immunodeficiency which predisposes them to KS. In addition, infection by HHV-8 is common in sub-Saharan Africa with rates of >60% reported in some studies. [7],[20]

In the absence of immunosuppression KS is 10 times more common in males. [10],[13],[21] Previously we reported a male to female ratio of 4:1 among 40 patients with KS seen between 1991 and 1995. [13] In the present study, the male to female ratio was 1.3:1. However, the ratio decreased gradually from 1.5:1 at the beginning of the study to 1:1 5 years later. This is similar to the ratio of 1:1 reported from South Africa but higher than the report from Jos in which there is a reversal of the gender ratio to 1:1.4. [8],[19] The high proportion of females is probably because women constitute over 60% of individuals infected with HIV in sub-Saharan Africa. In addition, women are more frequently subjected to HIV testing as routine counseling and testing has been applied to perinatal settings, and this may have allowed for a greater number of AAKS cases to be identified among women. [5]

The median age of our patients was 32 years which is about two decades younger than patients with endemic KS. This is because the highest incidence of HIV infection in sub-Saharan Africa is in 20-40-year-old individuals due to high-risk behavior. [22] In addition, childhood KS which was uncommon in the past was seen in 10 children among our patients and such trend has been reported in other studies. [12],[13],[18] The finding that females presented at significantly younger age than males is similar to the findings in other studies. [8],[19],[23] This could indicate that females were infected with HIV at an earlier age or that immunosuppression from HIV infection and KS pathogenesis progresses more rapidly in females.

AIDS-associated KS varies in its presentation from an indolent process with minimal clinical consequences to an extensively disseminated cutaneous and visceral disease. Severe symptoms including pain, cosmetic disability, and destruction of self-image were frequently encountered in our patients. [24] In the present study women with AAKS were more symptomatic probably because of greater burden of disease. In addition, men are less concern about cosmetic disability compared with women. [24] The earliest skin lesions are faint, flat, and macular lesions which can be overlooked by the patient and would be discovered only during clinical evaluation. This was the case in 12 (8.8%) of our patients. Other patients had multifocal, widespread nodules which coalesce to form large ulcerated tumorous lesion. Lower limb lesions were more common and more debilitating in males and were associated with lymphedema. Severe edema of the legs may be complicated by reduced mobility, diffuse serous drainage with protein loss, skin ulceration, and cellulitis. Oral lesions were more common in females and presented on the palate as diffused nodular lesions which rapidly become exophytic and ulcerated. These lesions often interfere with eating and speaking and rarely compromise the airways. Involvement of the oral cavity has been associated with KS in other areas of the gastrointestinal tract. [25] As with other HIV-infected individuals, our patients often have moderately enlarged lymph nodes. Routine biopsy of such lymph node often reveals focal KS involvement, a finding that appears to have little clinical consequence. [26] However, 13 of our patients had massive lymphadenopathy in the absence of KS elsewhere, which can be confused with lymphoma, tuberculosis, and other HIV-related lymphadenopathy. Histology provides the most efficient and cost-effective definitive diagnosis, since under the microscope, the different diagnoses are easily identifiable due to nuclear staining features in T-cells. [27] However, in a few patients co-existing lesions can be misdiagnosed even in biopsy material if special stains for demonstration of micro-organisms are not performed. [27]

In the present study females presented with more advanced AAKS, a finding that had been reported previously. [8],[24],[28] In addition, they have more aggressive disease which progressed rapidly. The reason why AAKS is more severe and progressed faster in females is not clear but does not seem to be related to immunologic or virology differences since there was no significant difference between the viral load and CD4 cells counts in males and females. In addition, there was no correlation between gender-related disease severity and CD4 count, similar to the findings in the South African and Zimbabwean studies but in variance to the Ugandan study. [8],[23],[28] However, when males and females were analyzed separately we found that within each gender group, there was a significant relationship between lower CD4 counts and more advanced AAKS. Earlier reports suggested that AAKS is usually seen in patients with advanced immune deficiency and CD4 count of <200 cells/mm 3 . However, 23 (18.4%) of our patients had CD4 >350 cells/mm 3 indicating that in African patients severe immunosuppression is not necessary for the development of AAKS. Similar observation has been made from other countries. [19],[23] Similarly, the occurrence of AAKS in patients with high CD4 cells count and undetectable viral loads has been reported from United States. [29] It has been suggested that with the ageing of HIV-infected patients especially those who are co-infected with HHV-8 may develop KS despite good control of HIV infection. [28]

In the present study, many patients with gastrointestinal or respiratory symptoms were not evaluated endoscopically due to financial constraints. However, such patients were adequately evaluated with abdominal ultrasound and conventional radiological examinations to detect such lesions. This means that some of the patients with gastrointestinal or respiratory tract KS were not histologically proven. These constitute the limitations of this study.

In conclusion our study showed an increased prevalence of AAKS. Female patients were younger and had more severe disease which progressed faster than in males although there was no significant difference in the CD4 cells count and viral load between males and females. These lesions have serious social and emotional consequences that impact negatively on their quality of life. AAKS is a disease that affects individuals with AIDS who are severely immunosuppressed. Therefore, timely identification of HIV-infected patients is essential to avoid the consequences of immunological deterioration associated with delayed HAART use.

 
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