7 THE ANTISEPTIC July 2016

A Study of Etiological Spectrum and Prevalence of Lymphadenopathy in HIV Positive Patients and its Relation to CD4 CountPAVAN KUMAR V., BARJATYA H.C., ANIL SAMARIA, DEEPAK SHARMA, SAILENDER SINGH,

MANWEEN

Introduction

The HIV infection leading to AIDS is one of the major public health problems. South-east Asia has become the epicentre of HIV/AIDS pandemic.1 Dr. Pavan Kumar V. Resident Doctor,Dr. H. C. Barjatya, Senior Professor & HOD,Dr. Anil Samaria, Professor,Dr. Deepak Sharma, Resident Doctor,Dr. Sailender Singh, Resident Doctor,Dr. Manween, Resident Doctor,Department of Medicine, J.L.N, Medical College, Ajmer (Rajasthan).

Specially Contributed to "The Antiseptic" Vol. 113 No. 7 & P : 7 - 10

Back ground: Lymphadenopathy in HIV infection is very common. Apart from other causes of lymphadenopathy, HIV infection itself may produce persistent generalized lymphadenopathy. Various opportunistic infections and malignancies may be responsible for lymphadenopathy in HIV / AIDS.Objectives:The present study was undertaken to find out the prevalence and describe various etiologies causing lymphadenopathy in HIV / AIDS patients, make a differential diagnosis using a case study approach, to find out pathological changes in lymph nodes by FNAC, and to establish correlation between FNAC finding and CD4 Count.Methods:200 HIV positive patients with age >15years attending the outpatient department and inpatient department of J.L.N medical college & hospital Ajmer were studied. Patients with Rheumatoid Arthritis, SLE, MCTD and those on drugs like Phenytoin, Hydralazine, Allopurinol & Gold were excluded. FNAC of largest non - inguinal lymph

node was done and CD4 count determined by Flowcytometry. Results:There were 124 males and 76 females in the study. The mean age was 35.52 years. 68 patients had lymphadenopathy. Tuberculous lymphadenitis was seen in 43(63.23%) cases with mean CD4 count of 117.44, Reactive lymphadenitis was seen in 16(23.53%) cases with mean CD4 Count of 276 and Suppurative lymphadenitis was seen in 9(13.24%) cases with mean CD4 Count of 27.77. Interpretation and conclusion:Opportunistic infections were the cause of lymphadenopathy in cases with CD4 Count of <200. Tuberculosis was the most common opportunistic infection. Suppurative lymphadenitis were seen in patients with CD4 Count <50. FNAC is a simple inexpensive rapid investigative procedure which can reduce surgical excision. Most bacterial and fungal opportunistic infections can be correctly identified and appropriate treatment can be started earliest.

ABSTRACT

CD4+ T cell is the major target of HIV infection. In the course of HIV infection, CD4+ T cell gets depleted resulting in reduced cell mediated immunity. As the HIV virus primarily infects the lymphocytes, lymph nodes are commonly involved during all stages of infection and are one of the earliest signs in HIV infected patients.2

According to the US Centers for Disease Control and Prevention

classification of the clinical course of HIV and AIDS, there are 4 stages of progression of HIV infection. Stage I is the seroconversion stage, which persists for about 1 to 3 months, and during this period, 50% of HIV-infected individuals suffer from fever, myalgia, arthralgia, headache, lymphadenopathy, skin rash, and so on. Stage II is the long asymptomatic stage of about 8 to 10 years during which

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the virus remains latent. Stage III is the persistent generalized lymphadenopathy (PGL) stage, which involves 2 or more extra-inguinal lymph nodes, with nodes being more than 1 centimeter, not matted, and persisting for more than 3 months duration. Stage IV is the stage of symptomatic HIV infection during which the patient suffers from various opportunistic infections involving the lymph nodes too.2

Hence, lymphadenopathy remains the most consistent sign throughout the clinical course of HIV infection.3

FNAC, a relatively non-invasive, pain free, cheap, outpatient procedure with no morbidity, can effectively diagnose the cause of lymphadenopathy in HIV-positive patients and will help to institute effective therapy at the earliest. Material and Methods

In this study, 200 HIV positive patients attending the outpatient department and inpatient department of J.L.N medical college & hospital Ajmer from 10/10/2014 to 31/12/2015 were included.

After taking written consent of the patients and the relevant history, these patients were subjected to complete clinical examination.Inclusion Criteria

Patient’s positive for HIV by TRI DOT TEST and registered at ART centre J.L.N medical college and hospital Ajmer.Exclusion Criteria

i. Age less than 15 years.ii. Patients with Rheumatoid

arthritis, mixed connective t issue disease, SLE, Dermatomyositis, Sjogrens syndrome, Gauchers disease, Niemann - pick disease, Hodgkin's disease, Non-Hodgkins disease, Leukemia.

iii. Patient’s on drugs like d i p h e n y l h y d a n t o i n , hydralazine, Allopurinol, gold, primidone.Detailed history, clinical

examination and relevant laboratory investigations were done as per the Performa

Lymph node detected were described under site, size, consistency, number, tenderness, mobility, matted / nonmatted.Following investigations were done.

1. Complete blood with differential count

2. Chest X-Ray to detect mediastinal lymphadenopathy

3. FNAC of the superficial Lymph node

4. CD4 count Statistical analysis

Statistical analysis were done using computer software (SPSS 20 Trial version primer). Results on continuous measurements are presented on Mean ± SD (Min-Max) and results on categorical measurements are presented in number (%). Significance is assessed at 5 % level of significance. The difference in proportion was analysed by using Chi-square test. Analysis of variance has been used to find the significance of CD4 according to FNAC lesions.

Result

Table No 1: Age distribution with gender

Age in years Male Female Total No % No % No %16-20 1 0.81 2 2.63 3 1.5021-29 30 24.19 28 36.84 58 29.0030-39 47 37.91 21 27.63 68 34.0040-49 32 25.81 17 22.37 49 24.5050-59 10 8.06 7 9.21 17 8.5060-69 4 3.22 1 1.32 5 2.50Total 124 100 76 100 200 100Mean ± SD 36.27 ± 9.6 33.44 ± 10.0 35.2 ± 9.8

Among the cases, the youngest patient was 17 years and the oldest was 68 years. Out of 200 patients 124 (62%) were male, and 76 (38%) were female .

Highest number of male patients are in age group 30-39 ie 47 and in female group highest number of patients are in 21-29 ie 28,overall highest number of patients are in age group 30-39 ie 68.Table No 2: Region wise distribution of lymphadenopathy

Lymph nodes Number of patients %Cervical (anterior) 16 23.53Posterior cervical 26 38.23Supraclavicular 6 8.82Axillary 11 16.18Generalized 9 13.24Total 68 100

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Of the 68 patients who had lymphadenopathy, 9 (13.24%) patients had generalized lymphadenopathy and 59 (86.76%) patients had localized lymphadenopathy. 26 (38.23%) patients had involvement of posterior cervical group of lymph node which is commonest involved and 6 (8.82%) patients had involvement of supraclavicular group of lymph node which is least involved. Table No. 3: Relation between FNAC and CD4 Count

FNAC findings No of patients Mean cd4 ± SD count Suppurative Lesion 9 27.77 15.53Reactive Lymphadenitis 16 276.00 87.99Granulomatous Lymphadenitis 26 138.80 39.64Caseous Granulomatous Lymphadenitis 6 68.16 29.35Caseous TB Lymphadenitis 11 93.81 29.04Total 68 142.88 ±97.21Significance F=42.8894

Granulomatous lymphadenitis was the most common FNAC finding. It was seen in 26(38.24%) patients. The next common FNAC finding was Reactive lymphadenitis, found in 16(23.52%) patients.

The f-ratio value is 42.8894. The p-value is < .00001. The result is significant at p < .01.

Patients with reactive lymphadenitis had highest CD4 count, mean CD4 count in these patients was 276.00 ± 87.99.

Lowest CD4 count was found in patients with suppurative lymphadenopathy, mean CD4 count in these patients was 27.77 ± 15.53.

Opportunistic infections of lymph nodes were seen mainly in patients with CD4 < 200. Most common opportunistic infection was Tuberculosis. Suppurative lymphadenitis is the other opportunistic infections seen with lesser CD4 count.Table 4: Opportunistic Infections and its relation to CD4 Count

CD4 count Opportunistic infection Total Present Absent <200 54 30 84 64.29% 35.71% 100.0%>200 14 102 116 12.07% 87.93% 100.0%Total 68 132 200 34% 66% 100.0%The chi-square statistic is 59.1976.P<0.01, Significantly more Opportunistic infections in cases if CD4

count <200. Most common opportunistic infection was Tuberculosis. Suppurative lymphadenitis is the other opportunistic infections seen with lesser CD4 count.

Discussion

Lymphoid tissues are one of the prime targets in HIV/AIDS. Regardless of the portal of entry of HIV, these are the major anatomic sites for establishment and propagation of HIV infection. The commonest opportunistic infection among HIV seropositive cases is tuberculosis. Extrapulmonary involvement occurs frequently and earlier than the other opportunistic infections, especially in individuals dually infected with HIV and tuberculous bacilli. Occurrence of extrapulmonary tuberculosis has increased by 20 per cent as compared to 3 per cent increase in cases of pulmonary tuberculosis and is believed to be due to more severe immunodeficiency in the HIV-infected patient.

This study was conducted at J.L.N Medical College, Ajmer between 10/10/214 to 31/12/15.

200 HIV positive patients were studied.124(62%) were males and 76 (38%) were females. The mean age of patients in our study was 35.2 years. The study done by Shobhana. A et al27, who had studied 54 HIV positive patients with lymphadenopathy consisting of 40 (74%) males, and 14 (26%) females and the mean age was 29.5 years. Thus, both the studies show that HIV affects mainly young males who are in their productive age group.

The CD4 Count of patients in our study ranged from 8 to 1017 cell / micro liter with the mean of 279.16. In study done by Shobhana. A et al4, the CD4 count ranged from 79 to 945 cell / micro liter.

In the present study, the prevalence of lymphadenopathy was 34%, in another study done by Shobana. A et al4, the prevalence was 29.2% and in a study done by Hung CC et al5, of Taiwan lymphadenopathy was seen in 32%.Hence the prevalence of

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lymphadenopathy in our study is comparable to the Shobana A et al4, and Hung CC et al5.

Cervical group of lymph nodes are most commonly involved in our study. It was involved in 42 cases (61.76%). Cervical lymph nodes were also commonest involved group of lymph nodes in a study done by H R Vanisiri et al6 & Rajesh Singh Laishram et al7.

The causes of lymphadenopathy in our study were Tuberculosis in 43(63.23%) cases, Reactive lymphadenitis in 16(23.52%) cases, Suppurative lesion in 9(13.2323%) cases.

Tuberculosis was the most common cause of lymphadenitis in our study seen in 63.23% cases. H R Vanasiri et al6, Nayak et al8 and Priya gupta et al9 also reported tuberculosis as the commonest cause seen in 58.3%, 46.8% & 51.35% respectively. However, reactive lymphadenitis (53.5%) was the commonest cause in study done by Shobhana A et al4.

This difference could be because of the differences in patient selection, socio-economic strata of patients & CD4 counts. Relation between etiology of lymphadenopathy and CD4 count:

Shobhana A et al4 found that there was correlation between absolute CD4 counts and the FNAC findings. The median value of CD4 Count was 672 and 212 cells / µl in case of reactive hyperplasia and tuberculous lymphadenitis respectively. Thus the above study revealed that opportunistic infections of lymph nodes occur in patients with lower CD4 counts.

Tuberculosis was the most common cause of lymphadenopathy in our study in patients with mean CD4 Count of 117.44. Reactive lymphadenitis was seen in patients with mean

CD4 Count of 276. Suppurative lymphadenitis was diagnosed in patients with mean CD4 Count of 27.77.Thus, our study also found that patients with CD4 count of <200 were more prone for opportunistic infections. Conclusion

Lymphadenopathy in HIV infection is very common. The present study revealed 3 causes of lymphadenopathy in HIV patients. Reactive lymphadenitis was seen in patients with CD4 of >200. At CD4 <200 opportunistic infections were seen. The most common opportunistic infection was tuberculosis seen at CD4 Count between 100 - 200 cells / µl followed by Suppurative lymphadenitis, seen at mean CD4 Count of <50cells / µl. Thus, the study revealed a definite correlation exists between FNAC finding of lymphadenopathy & CD4 count.

Thus FNAC can be used as effective tool for making early and specific diagnosis of lymphadenopathy in HIV patients.Bibliography

1. Merrtens T.E, Low Beer D. "HIV and AIDS - where is the epidemic going?" Bulletin of World Health Organization 1996; 74: 12-19 .

2. 1993 Revised classification system for HIV infection expanded

surveillance case definition for AIDS among adolescents and adults. MMWR Morb Mortal Wkly Rep. 1992; 41:1-19.

3. Susan Coffey, Lymphadenopathy, Clinical manual for management of HIV infected adult. 2006, The AIDS Education & Training Centers National Resource Center .

4. Shobhana A, Guha SK, Mitra K, Dasgupta A, Neogi DK, Hazra SC. People living with HIV infection / AIDS - A study on lymph node FNAC and CD4 count. Indian J Med Microbiol 2002; 20: 99-101.

5. Hung CC, Chen MY, Chen CL, Chen YC, Chuang CY. Etiology of lymphadenopathy in patients with AIDS in Taiwan. J Formos Med Assoc. 1996;95(2):119–125.

6. Vansiri HR, Nandini NM, Sunila R. Fine-needle aspiration cytology findings in human immunodeficiency virus lymphadenopathy. Indian J Pathol Microbiol. 2008;51(4):481–484.

7. Rajesh Singh Laishram, RK Tamphasana Devi, Sushma Khuraijam, Khuraijam Ranjana Devi, Sucheta Khuraijam, L Durlav Chandra Sharma. Fine needle aspiration cytology of HIV-related lymphadenopathy in Manipur. Indian Academy of Clinical Medicine 2014 ;15(2): 111-5.

8. Nayak S , Mani R , Kavatkar AN, Puranik SC , Holla VV . Fine- needle aspiration cytology in lymphadenopathy of HIV-positive patients. Diagn Cytopathol. 2003 Sep: 29(3): 146-8.

9. Gupta Priya, Singh Kuldeep. Fine Needle Aspiration Cytology of Lymphadenopathy in HIV-Infected Patients. JK Science Journal of Medical Education and Research. 2014 Jan-Mar; 16(1): 24-28.

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