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Table of Contents   
ORIGINAL RESEARCH  
Year : 2017  |  Volume : 28  |  Issue : 5  |  Page : 549-554
Correlation of mucocutaneous manifestations of HIV-infected patients in an ART center with CD4 counts


Department of Oral and Maxillofacial Pathology, Vokkaligara Sangha Dental College, Bengaluru, Karnataka, India

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Date of Web Publication25-Oct-2017
 

   Abstract 

Background: As the search for reliable clinical indicators for management of human immunodeficiency virus/AIDS continues, mucocutaneous manifestations of HIV are considered among key clinical indicators for prediction of underlying degree of immunosuppression, systemic opportunistic infections, and disease progression. Objectives: (1) To study the prevalence of mucocutaneous manifestations in HIV-seropositive patients attending the ART center of our hospital (2) To correlate mucocutaneous manifestations with CD4 cell counts. Materials and Methods: A total of 200 HIV-seropositive patients of adult age group visiting our hospital were included in the study. Information on demographics such as age, sex, transmission route, socioeconomic status, educational status, CD4 counts, and mucocutaneous findings was collected through interview administered survey and case records followed by oral and cutaneous examination. Results: Mean CD4 cell count of asymptomatic HIV/AIDS patients was 580.96 cells/mm3. In comparison with the CD4 cell count of asymptomatic HIV-positive patients, (mean 580.96 cells/mm3) CD4 cell count of HIV-positive patients with various mucocutaneous manifestations (mean 409.65 cells/mm3) was correlated using student t-test and was statistically significant (P = 0.017). Conclusion: This study revealed maximum mucocutaneous lesions in the CD4 count range of 200–500. Nail changes accounted for the most common cutaneous manifestation with 53%, and pigmentation accounted for the most common oral manifestation with 39%. Mucocutaneous manifestations can arouse one to suspect the diagnosis of HIV infection in an otherwise healthy unwary patient. They can serve as a dependable marker of HIV disease.

Keywords: CD4 count, HIV, Mucocutaneous manifestations

How to cite this article:
Lahoti S, Rao K, Umadevi H S, Mishra L. Correlation of mucocutaneous manifestations of HIV-infected patients in an ART center with CD4 counts. Indian J Dent Res 2017;28:549-54

How to cite this URL:
Lahoti S, Rao K, Umadevi H S, Mishra L. Correlation of mucocutaneous manifestations of HIV-infected patients in an ART center with CD4 counts. Indian J Dent Res [serial online] 2017 [cited 2020 Feb 26];28:549-54. Available from: http://www.ijdr.in/text.asp?2017/28/5/549/217188

   Introduction Top


Mucocutaneous lesions are usually the first manifestation of HIV which ensure early diagnosis and prompt treatment.[1] They act as diagnostic factors in the monitoring of immune status of the patients.[2] More than 90% of patients develop skin lesions and 30%–80% of patients develop oral manifestations during the disease. Mucocutaneous lesions in HIV patients have been correlated with CD4 counts in many studies as serial CD4 counts have a prognostic significance which are used as markers for assessing progression from HIV infection to AIDS.[3] Hence, this study is an attempt to correlate mucocutaneous manifestations of HIV infection with CD4 cell counts.


   Materials and Methods Top


A total of 200 HIV-seropositive patients of adult age group, i.e., above 18 years attending ART center of our hospital were included in the study. Out of 200, 191 patients were on ART, and 9 patients were without ART. Informed consent was taken from the patients. Demographic details were recorded on a structured pro forma. A thorough clinical examination of the skin and oral cavity was done. The most recent CD4 counts (cells/mm3) of the patients were obtained from the medical records. Ethical approval for the study was obtained from the Ethical Committee of Our Institution. Diagnoses were mainly clinical and scrapings were taken from few cases and stained with periodic acid–Schiff (PAS) special stain for confirmation. The results were statistically evaluated using Student's t-test and Chi-square test.


   Results Top


Demographic data showed that a total of 94 males and 106 females were included in the study. The mean age group was 37.5 years. The main risk factor for HIV transmission was heterosexual contact. Majority of the patients belonged to average socioeconomic strata and were illiterate. Out of 200 cases, 169 cases showed signs and symptoms of mucocutaneous disease whereas 31 cases were asymptomatic.

The major mucocutaneous findings reported by HIV-seropositive patients attending the clinic were nail changes, cutaneous and oral pigmentation, xerosis, fungal infections, gingivitis, periodontitis, angular cheilitis, and depapillation of the tongue. Other conditions such as viral infections, pruritic papular eruptions (PPEs), ichthyosis, hair loss, stomatitis, and oral hairy leukoplakia (OHL) were also occasionally present.

Patients with various clinical presentations were stratified into four groups of CD4 cell counts (Group I CD4 <200, Group II CD4 200–500, Group III CD4 500–1000, and Group IV CD4 >1000). Mucocutaneous manifestations and their correlation with CD4 counts, mean CD4 cells, and standard deviation are represented below in a tabular form.

Various mucocutaneous manifestations in correlation with CD4 counts are summarized in [Table 1].
Table 1: Correlation of mucocutaneous manifestations with CD4 counts

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Maximum lesions were seen in patients with CD4 count 200–500 as shown in [Table 2].
Table 2: Number of disorders in each group of CD4 cell count

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Correlation of each mucocutaneous disorders with Mean CD4 Cells and Standard Deviation are summarized in [Table 3].
Table 3: Correlation of each mucocutaneous disorders with mean CD4 cells and standard deviation

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Mean CD4 count of asymptomatic and symptomatic HIV patients was computed and Student's t-test was applied as shown in [Table 4].
Table 4: P value for student's t test

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Mean CD4 Count of asymptomatic and symptomatic HIV patients in various groups was computed and Chi-square test was applied as shown in [Table 5].
Table 5: P value for chisquare test

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To determine the percentage occurrence, a total 57 cases of xerosis, hair loss, ichthyosis, PPEs, and other cutaneous findings were included in the cutaneous miscellaneous group. Oral miscellaneous group included 72 cases of gingivitis, periodontitis [Figure 1], angular cheilitis, depapillation of the tongue, white lesions, and stomatitis.
Figure 1: Depapillation of tongue

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The same is represented in [Graph 1]



Various mucocutaneous disorders in correlation with the percentage occurrence are as follows: nail changes 53%, cutaneous pigmentation 41.5%, oral pigmentation 39%, fungal infections 9.5%, viral infections 2.5%, cutaneous miscellaneous 29%, and oral miscellaneous 36%.

Various mucocutaneous disorders in correlation with the mean CD4 count are as follows: nail changes 391.924, cutaneous pigmentation 386.132, oral pigmentation 386.025, fungal infections 432.315, viral infections 422.6, cutaneous miscellaneous 359.518, and oral miscellaneous 287.643.

The same is represented in [Graph 2]




   Discussion Top


The main target of the HIV appears to be the CD4 cell population. A progressive reduction in the number and function of the CD4 cell population is one of the most striking and consistent immunological features of HIV-related disorders.[8] In general, the CD4 count progressively decreases as HIV disease advances.[11] It is thought that the incidence and severity of skin disorders increase as immune function deteriorates.[12] In the current study, 169 out of 200 patients had multiple mucocutaneous manifestations with an average of 2.045 conditions per patient. Vijaya Kumari et al. reported an average of 1.9 conditions per patient,[2] Tzung et al. reported an average of 2.2 conditions per patient,[4] Singh et al. reported an average of 2.35 conditions per patient.[6]

Cutaneous lesions can be classified into five groups: infectious, autoimmune, drug-induced, HIV-related, and cutaneous malignancies. Often, these conditions present atypically, are much more severe, and need prolonged treatment in HIV-infected patients than in the general population.[5] The various oral manifestations can be categorized into (1) Infections: Bacterial, fungal, viral, (2) Neoplasms: Kaposi's sarcoma, non-Hodgkin's lymphoma, (3) Immune mediated: Major aphthous, necrotizing stomatitis, (4) Others: Parotid disease, nutritional, xerostomia (5) Oral manifestations as adverse effects of antiretroviral therapy.[10]

Very often, the infections in HIV are not the new infections but the reactivation of old infection. In this study, we did not encounter any case of bacterial and parasitic infection. Clinically, there were 5 cases of viral infection, out of which three were HSV one infection of oral mucosa involving anterior labial maxillary gingiva and two were HPV infection of skin resembling verruca vulgaris [Figure 2]. Maximum cases of viral infections were seen in CD4 count of 200–500 with the mean CD4 cells/mm3 value of 422.6. Munoz-Perez et al. in their study mentioned that HIV infection itself predisposes to an increased risk of HPV infection that is not directly related to the degree of immunosuppression.[9]
Figure 2: Viral infection: HPV

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Oral or pharyngeal candidiasis is the most common fungal infections observed as the initial manifestation of symptomatic HIV infection.[10] The pseudomembranous “white patches” variant of candidiasis is associated with more severe immunosuppression than the erythematous, hyperplastic, or angular cheilitis types.[5] Oral candidiasis is usually observed at CD4 counts of <300/ul.[10] In the present study, out of 19 cases with fungal infections, 17 cases clinically showed oral candidiasis of tongue [Figure 3], and two cases had other dermatophytoses, one involving corners of the mouth resembling cryptococcosis and the other in the web space between the fingers resembling intertrigo. Maximum cases of fungal infections were seen in CD4 count of 200–500, with the mean CD4 cells/mm3 of 432.3. Scrapings were taken from oral candidiasis cases which were followed by PAS staining to arrive at a confirmatory diagnosis.
Figure 3: Fungal infection: Pseudomembranous candidiasis

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The most common noninfectious skin manifestation found in our study were nail changes. All 20 nails were examined, positive cases showed findings such as longitudinal melanonychia, paronychia, transverse and longitudinal ridging, and onychomycosis. There were a total of 106 cases with maximum cases in the CD4 count of 200–500 with a mean CD4 cells/mm3 of 391.9. Longitudinal melanonychia was the most frequent finding among others [Figure 4]. The occurrence of longitudinal melanonychia in HIV-positive patients is now well established. It has been attributed to the use of Zidovudine, but it has also been described in patients who were not receiving antiretroviral treatments. This symptom could be due to increased levels of α melanocyte–stimulating hormone.[7]
Figure 4: Nail changes

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Nail changes were followed by cutaneous pigmentation which was mostly seen on the face, neck, and legs [Figure 5]. There were a total of 83 cases of skin pigmentation with maximum cases in the CD4 count of 200–500 with a mean CD4 cells/mm3 of 386.1. Xerosis is generally associated with a late stage disease. Nutritional factors may contribute to xerosis because these patients usually suffer considerable weight loss and cachexia.[9] Thirty-seven cases showed xerosis with maximum cases in the CD4 count of 200–500 with a mean of CD4 cells/mm3 of 353.4.
Figure 5: Cutaneous pigmentation

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PPE is a unique dermatosis associated with advanced HIV infection, characterized by sterile papules, nodules, or pustules with a hyperpigmented, urticarial appearance, and pruritus. When patients present with intractable, unexplained itching, physicians must consider a diagnosis of PPE and investigate for HIV infection.[5] Our study showed six cases of PPE with maximum cases having CD4 count of 500–1000 with a mean CD4 cells/mm3 of 588.5. Acquired ichthyosis is a very common finding on the lower legs in HIV-infected patients. The dermatosis is characterized by variably sized plate such as scales, xerosis, and an absence of inflammation.[13] This study showed six cases of ichthyosis mostly involving lower legs [Figure 6] with maximum cases having CD4 count of 200–500 with a mean CD4 cells/mm3 of 236.1. There were four cases of hair loss with two cases having CD4 count of <200 and two cases with CD4 count of 200–500. Mean CD4 cells/mm3 was 259.2.
Figure 6: Ichthyosis

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Other cutaneous findings included two cases of dermatitis, one case of psoriasis, one case of pyogenic granuloma, and one case of polymorphous light eruption.

There is no particular oral lesion which is associated only with HIV-AIDS, but there are certain manifestations such as oral candidiasis, OHL which are associated very frequently and are considered AIDS-defining diseases and have also been included in the clinical classification of HIV by CDC in category B.[10] OHL is the lesions usually seen on the lateral surface of tongue and appear as vertical white striations, corrugations, or as flat plaques or raised shaggy plaques with hair-like keratin projections and associated with a localized Epstein-Barr viral infection.[10] Worldwide, the prevalence of OHL among HIV-infected individual ranges from 0% to 26%.[5] There was only one case of OHL in our study [Figure 7]. OHL usually occurs in CD4 counts of <200/ul.[10] Our case had CD4 count of 107/ul.
Figure 7: White lesion: Oral hairy leukoplakia

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Oral pigmentation, patchy brown to brownish-black asymmetrical lesions usually >1 cm, which are distinctive from racial oral pigmentation, have been reported in up to 23% of HIV-positive individuals.[5] Our study showed 83 cases (39%) with oral pigmentation [Figure 8] with the maximum cases having CD4 count of 200–500 with a mean CD4 cells/mm3 of 386.
Figure 8: Oral pigmentation

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HIV infection is associated with three characteristic presentations of periodontal disease: necrotizing periodontal disease, linear gingival erythema, and exacerbated attachment loss.[5] Thirty-three out of 200 patients showed periodontal infections with maximum cases in CD4 cell count of 200–500. In the case of periodontal infections, the bacterial flora is same as that in a healthy individual with periodontal disease. Thus, the clinical lesion is a manifestation of the altered immune response to the pathogens.[10]

We did not find any case of neoplastic lesion, i.e., Kaposi's sarcoma, lymphoma, or any other cutaneous malignancies. Chawhan et al.,[3] Wiwanitkit,[14] Lanjewar 2011[15] also found striking low prevalence of cutaneous and other malignancies in their studies.


   Conclusion Top


There is a strong negative association between CD4 counts and the incidence and severity of mucocutaneous lesions in HIV/AIDS patients. Fluctuations in CD4 levels observed in mucocutaneous disease require further studies to establish the underlying pathophysiology.[16] HIV infection should be suspected when a cutaneous lesion tends to be chronic, severe, bizarre and involves more than one dermatome.[17] This small cross-sectional study highlights that there are myriads of mucocutaneous lesions associated with HIV/AIDS and low CD4 counts. It is necessary to plan and execute studies using larger sample size in different areas which would help in the better interpretation and also the use of CD4 counts may provide guidelines for possible intervention.[8]

Acknowledgment

I would like to thank the staff of ART center of our hospital and staff of Department of Community Dentistry, Vokkaligara Sangha Dental College and Hospital for their valuable support. I would like to especially thank all the staff and my fellow postgraduate colleagues of Department of Oral and Maxillofacial Pathology for all the help, support and encouragement.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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Wiwanitkit V. Prevalence of dermatological disorders in Thai HIV-infected patients correlated with different CD4 lymphocyte count statuses: A note on 120 cases. Int J Dermatol 2004;43:265-8.  Back to cited text no. 14
    
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Correspondence Address:
Sonal Lahoti
Department of Oral and Maxillofacial Pathology, Room No. 9, Vokkaligara Sangha Dental College, VV Puram, KR Road, Bengaluru - 560 004, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdr.IJDR_352_16

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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