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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 52  |  Issue : 3  |  Page : 321-324
Histopathological study of pruritic papular eruptions in HIV-infected patients in relationship with CD4, CD8 counts


1 Department of Pathology, Sree Siddhartha Medical College, Hospital & Research Centre, Tumkur, India
2 Department of Pathology, BLDEA's Shri B. M. Patil Medical College, Bijapur, Karnataka, India
3 Department of Dermatology, Venereology & Leprosy, BLDEA's Shri B. M. Patil Medical College, Bijapur, Karnataka, India

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Date of Web Publication12-Aug-2009
 

   Abstract 

Background: Pruritic papular eruptions (PPE) are common cutaneous manifestations in HIV-infected patients. Their frequencies, patterns and associated factors vary from region to region. There is no clear consensus on the etiology of PPE, the exact spectrum of the condition, the pathologic findings, or treatment. The present study is aimed at documenting the histopathological patterns of PPE, and their relation with CD4, CD8 counts in HIV-infected patients. Materials and Methods: The present study lasted for 12 months (September 2005 to August 2006). After informed consent, data on skin disorders, HIV status, CD4 and CD8 counts were obtained by physical examination and laboratory methods. Results: Of the 36 HIV-infected patients with clinical diagnosis of PPE, the most common histopathological patterns were prurigo simplex and eosinophilic folliculitis. The mean CD4 count of PPE was 186.49 cells/mm 3 with mean CD8 count of 619.60 cells/ mm 3 , and the CD4:CD8 ratio was 0.32. Patients with prurigo simplex had significantly lower mean CD4 counts (50.36 ± 30.67 cells/cmm 3 , P < 0.001) while in eosinophilic folliculitis, the mean CD8 counts were higher (1239.77 ± 402.30 cells/cmm 3 ). Conclusion: We conclude that histopathology helps in specifying the pattern of PPE and also indicates underlying immunosuppression and can be a marker of advanced HIV infection. Thus, correlation between the histopathology and immunology findings helps to know the disease process.

Keywords: CD4, CD8 counts, HIV, histopathology, pruritic papular eruptions.

How to cite this article:
Annam V, Yelikar B R, Inamadar AC, Palit A. Histopathological study of pruritic papular eruptions in HIV-infected patients in relationship with CD4, CD8 counts. Indian J Pathol Microbiol 2009;52:321-4

How to cite this URL:
Annam V, Yelikar B R, Inamadar AC, Palit A. Histopathological study of pruritic papular eruptions in HIV-infected patients in relationship with CD4, CD8 counts. Indian J Pathol Microbiol [serial online] 2009 [cited 2019 Oct 15];52:321-4. Available from: http://www.ijpmonline.org/text.asp?2009/52/3/321/54984



   Introduction Top


Pruritic papular eruptions (PPE) are characterized by chronic pruritus and symmetric papular eruptions on the trunk and extremities with the absence of other definable causes of itching in an HIV-infected patient. [1] Nevertheless, it remains the most common cutaneous manifestation in HIV- infected patients, with a prevalence that varies between 11 and 46% according to the geographic area. [2],[3],[4],[5],[6] Retrospective analysis has shown that it was impossible to differentiate clinically between prurigo and eosinophilic folliculitis, and recommended biopsy confirmation of these lesions. [7] However, comprehensive histopathological studies in HIV-infected patients with PPE and their relation with CD4, CD8 counts have not been reported. Hence, the present study was undertaken.


   Materials and Methods Top


The present prospective cross-sectional study was carried out for a period of 12 months (September 2005 to August 2006) in the Department of Pathology at a tertiary referral center. The skin biopsies from HIV- positive patients with clinical diagnosis of PPE were received from the Department of Dermatology.

After informed consent, information was obtained through structured questionnaire from patients on their socio-demographic status and antiretroviral therapy. Patients on antiretroviral therapy were excluded from the study. Antibodies to HIV were demonstrated by three different methods (Tridot, Capillus and Combaids tests). Physical examination was done to identify the PPE. Skin biopsies were performed in these patients for identification of specific histological pattern of PPE. Paraffin-embedded 3 to 5-µm thick tissue sections were assessed using hematoxylin and eosin stain. Multiple serial histological sections were examined in all these cases to rule out any folliculocentric pathological process. The measurement of peripheral blood CD4, CD8 counts was performed by Tricolor Flow Cytometry.

The Student's t -value was used to determine the strength of association between PPE with CD4 count and CD8 count. P value was considered significant when it was less than or equal to 0.05.


   Results Top


A total of 36 HIV-infected patients with clinically PPE accepted to take part in the study. The risk factors in men and women included heterosexual contact with multiple sexual partners, while in the pediatric group was vertical transmission. The age ranged from six to 60 years with male:female ratio being 2.6:1. Specific histopathological findings in these PPE were seen in 97.22% (35/36) cases while one case showed nonspecific changes which did not contribute to one or another disease. The most common type of PPE on histopathology were prurigo simplex, followed by eosinophilic folliculitis, prurigo nodularis and lymphocytic vasculitis.

The mean CD4 count of PPE was 186.49 cells/mm 3 with mean CD8 count of 619.60 cells/ mm 3 and the CD4:CD8 ratio being 0.32; 67.74% had CD4 counts of less than 200 cells/mm 3 . The strength of association of PPE with CD4 count and CD8 count was done by Student's t -value (6.91) and the P value <0.001. The relationship of mean CD4, CD8 counts and CD4:CD8 ratio with various histopathological patterns of PPE is enlisted [Table 1].


   Discussion Top


Of the spectrum of cutaneous lesions in HIV-infected patients, PPE are a unique dermatosis associated with advanced HIV infection. Previous studies have shown that PPE were one of the most frequent clinical diagnoses. [8],[9] These eruptions can occur as non-follicular or follicular lesions. [10] In our study, the non-follicular lesions included prurigo simplex and lymphocytic vasculitis while the follicular lesion constituted only eosinophilic folliculitis (EF). A few studies [9],[11] have observed that the mean CD4 count was <200 cells/mm 3 in these pruritic lesions which was consistent with the present study (mean CD4 count 186.49 cells/mm 3 , Student's t -value (6.91) and P value <0.001).

Prurigo simplex was diagnosed after we had ruled out systemic causes for the symptoms and other infectious and/or inflammatory processes. Prurigo simplex can lead to prurigo nodularis. [12] The distribution of cutaneous papular lesions was all over the body except genitalia. Clinically, in early prurigo simplex, the cutaneous lesions are erythematous papules [Figure 1] while the late lesions have papules with central crust [Figure 2]. In patients with prurigo simplex, the histological feature of early papule was mild acanthosis and mild spongiosis of the epidermis while lymphocytic infiltrate in a largely perivascular arrangement was observed in the superficial dermis [Figure 1]a. There was partial absence of the epidermis in the late lesions as they are covered with a crust containing degenerated nuclei of inflammatory cells [Figure 2]a. Intense, intractable pruritus among HIV-infected patients is thought to be due to immune dysregulation; previous studies have found higher levels of IgE and increased concentrations of certain helper T-cell type cytokines (interleukins 4 and 5) in HIV patients with idiopathic pruritis, as compared with HIV patients without pruritis. [13] The levels of IgE are known to increase with advancing disease (decreasing CD4 cell count). Therefore, it was not surprising that we found CD4 counts less than 100cells/mm 3 ( P <0.001) in prurigo simplex. All these HIV-infected patients with prurigo simplex were treated with highly active antiretroviral therapy. It was observed that the reduction in lesions of prurigo simplex following the use of highly active antiretroviral therapy could be secondary to immune reconstitution and "re-regulation" of immune system.

The distribution and morphological features of cutaneous lesions in HIV-EF were itchy erythematous papules distributed over the face, upper limbs [Figure 3] and trunk. In 11/36 (30.55%) patients with EF, we found the histology to be characterized by perifollicular and intrafollicular infiltrate of lymphocytes and eosinophils [Figure 3]a, focused at the level of the follicular isthmus [Figure 3]b. In the early lesions of EF, lymphocytes predominate over the eosinophils and were distributed perifollicularly, and also interstitially while in the late developed lesions of EF, the eosinophils predominate over the lymphocytes and were confined to the perifollicular and follicular region. Previous studies on immunophenotypic analysis showed the lymphocytes to be T cells with a marked CD8 predominance (CD8/CD4 ratio of 10:1), [7],[14] which was observed in the present study (CD8/CD4 ratio of 4.1:1). The CD4 count in HIV-EF was <250 cells/mm 3 in other studies, [10] but in our study the mean CD4 count was 302.36cells/mm 3 . The exact etiology of HIV-EF remains unknown. Any explanation must take into account the prominence of eosinophils in the cellular infiltrate, the folliculo-centric nature of the disease and the typical distribution of the eruption in the context of profound immunodysregulation. [15] Several theories postulated center around the possibility that opportunistic organisms are involved. [7] In 2/11 patients with HIV-associated EF, we found mite fragments suggestive of Demodex folliculorum within the infundibulum of the involved follicle.

There was also one case each of lymphocytic vasculitis and nonspecific dermatitis.


   Conclusions Top


PPE has a major impact on the quality of life of the affected patient, both from a medical and a cosmetic point of view, subjecting patients to HIV-related stigma in their communities. The correlation between the histopathological findings and immunological features helps to know the underlying disease process. PPE in HIV-infected patients indicates underlying immunosuppression and can be a marker of advanced HIV infection. Thus recognizing PPE helps in allowing better treatment of this recalcitrant and distressing condition.

 
   References Top

1.Fischer BK, Warner LC. Cutaneous manifestations of the acquired immunodeficiency syndrome. Int J Dermatol 1987;26:615-30.  Back to cited text no. 1    
2.Bason MM, Berger TG, Nesbitt LT Jr. Pruritic papular eruption of HIV-disease. Int J Dermatol 1993;32:784-9.  Back to cited text no. 2  [PUBMED]  
3.Liautaud B, Pape JW, DeHovitz JA, Thomas F, LaRoche AC, Verdier RI, et al . Pruritic skin lesions: A common initial presentation of acquired immunodeficiency syndrome. Arch Dermatol 1989;125:629-32.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Rosatelli JB, Machado AA, Roselino AM. Dermatoses among Brazilian HIV-positive patients: Correlation with the evolutionary phases of AIDS. Int J Dermatol 1997;36:729-34.  Back to cited text no. 4  [PUBMED]  
5.Hira SK, Wadhawan D, Kamanga J, Kavindele D, Macuacua R, Patil PS, et al . Cutaneous manifestations of human immunodeficiency virus in Lusaka, Zambia. J Am Acad Dermatol 1988;19:451-7.  Back to cited text no. 5  [PUBMED]  
6.Colebunders R, Mann JM, Francis H, Bila K, Izaley L, Kakonde N, et al . Generalized pruritic papular eruptions in African patients with HIV infection. AIDS 1987;1:117-21.  Back to cited text no. 6  [PUBMED]  
7.Fearfield LA, Rowe A, Francis N, Bunker CB, Staughton RC. Itchy folliculitis and human immunodeficiency virus infection: Clinicopathological and immunological features, pathogenesis and treatment. Br J Dermatol 1999;141:3-11.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Goldstein B, Berman B, Elizabeth S, Frankel SJ. Correlation of skin disorders with CD4 lymphocyte counts in patients with HIV/AIDS. J Am Acad Dermatol 1997;36:262-4.  Back to cited text no. 8    
9.Josephine M, Issac E, George A, Ngole M, Albert SE. Patterns of skin manifestations and their relationships with CD4 counts among HIV/AIDS patients in Cameroon. Int J Dermatol 2006;45:280-4.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Saple DG, Maniar JK. Dermatologic manifestations in HIV/AIDS. AIDS research and review 1999;2:69-77.  Back to cited text no. 10    
11.Kumarasamy N, Solomon S, Madhivanan P, Ravikumar B, Thyagarajan SP, Yesudian P. Dermatologic manifestations among human immunodeficiency virus patients in South India. Int J Dermatol 2000;39:192-5.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Zancanaro PC, McGirt LY, Mamelak AJ, Nguyen RH, Martins CR. Cutaneous manifestations of HIV in the era of highly active antiretroviral therapy: An institutional urban clinic experience. J Am Acad Dermatol 2006;54:581-8.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Milazzo F, Piconi S, Trabattoni D, Magni C, Coen M, Capetti A, et al . Intractable pruritis in HIV infection: Immunologic characterization. Allergy 1999;54:266-72.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Fields LL, Toro J, Maurer T. Detection of perifollicular IL-4 and IL-5 in HIV associated eosinophilic folliculitis. J Invest Dermatol 1989;92:408.  Back to cited text no. 14    
15.Budavari JM, Grayson W. Papular follicular eruptions in human immunodeficiency virus-positive patients in South Africa. Int J Dermatol 2007;46:706-10.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]

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Correspondence Address:
Vamseedhar Annam
Department of Pathology, Sree Siddhartha Medical College and Research Centre, Tumkur, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.54984

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