Oral Hairy Leukoplakia: A Predictor and Prognostic Factor of HIV

Infection

Yusuf Wibisono, Septiana Widyantari, Cita Rosita Sigit Prakoeswa

Department of Dermato-Venereology, Faculty of Medicine,Universitas Airlangga/Dr. Soetomo General Hospital Surabaya,

Indonesia

Keywords: Oral Hairy Leukoplakia, HIV, Acyclovir, ARV

Abstract: Introduction: Oral hairy leukoplakia (OHL), also known as benign hyperplasia of oral mucosa, is an

asymptomatic white corrugated plaque that is most commonly found on the lateral borders of the tongue.

This condition is caused by Epstein-Barr Virus (EBV). OHL is commonly found in immunocompromised

patient, with the prevalence around 20-25% among HIV patients and indicates decline of CD4 counts. Case:

A 29 year-old-male came to the Dermato-Venereology Outpatient Clinic of Dr. Soetomo General Hospital

Surabaya with complaint of persistent asymptomatic whitish color on lateral side of his tongue. From

history taking, the lesion was first appeared all over the tongue, and after consumption of antifungal

treatment, the lesion subsided and persisted only on lateral border of the tongue. There were history of

diarrhea, fever and cough for almost 1 month. He also has multiple sexual partners. From physical

examination, we found painless white demarcated plaque with corrugated appearance on the left lateral

border of the tongue. Further examination on HIV panels using three methods showed reactive result. Based

on history taking, clinical and laboratory findings, the patient was diagnosed with OHL and HIV. The

patient was treated with Acyclovir 800 mg, 5 times daily, and HAART (Duviral 2x1 tab + Neviral 1x1 tab).

After 2 weeks of treatment, the lesion disappeared. Conclusion: The appearance of OHL is commonly

associated with immunocompromised condition. The establishment of OHL has a diagnostic value for HIV

infection. Systemic antiviral therapy and prevention of recurrence using antiretroviral medication showed

satisfying result.

1 INTRODUCTION

Oral Hairy Leukoplakia (OHL) which also known as

benign epithelial hyperplasia of oral mucosa, is an

oral mucosal lesion associated with infection and

replication of the Epstein-Barr virus (EBV)

(Murtiastutik et al., 2008). The clinical presentation

of OHL is a painless, white proliferative oral

epithelial lesion that usually occured on the lateral

margins of the tongue.

This white patch is non-

removable, with wide variation in size, severity, and

surface characteristics.

OHL has been listed in the classification of oral

lesions as a Group I lesion strongly associated with

HIV infection (Classification and diagnostic criteria

for oral lesions in HIV infection, 1993; Uihlein et

al., 2011). It is also considered as a marker of poor

prognosis that frequently precedes the onset of

acquired immunodeficiency syndrome (Kreuter &

Wieland, 2011).

The lesion usually presents itself

when the CD4 cell counts fall below 0.3x10

(Bravo et al., 2006).

However, OHL is also found in

other immunosuppressive non-HIV condition, such

as transplant recipients, in patients with

hematological malignancies, and in patients required

under systemic steroid treatment (Piperi et al.,

2010).

HIV is a lymphotropic human retrovirus, which

is predominantly transmitted through sexual contact.

HIV is also transmitted through exposure to infected

blood (i.e needles shared by injecting drug users)

and transmission from infected mother to her infant

during pregnancy, delivery or breastfeeding (Uihlein

et a., 2011). OHL has been associated with more

rapid progression to AIDS with HIV viral loads

exceeding 20.000 copies/ml, and with CD4+ counts

below 200/mm

or 0.3x10

/L (Bravo et al., 2006).

A case of OHL in 29-year-old patient who was later

diagnosed with HIV positive is reported. The

diagnosis was established by history taking, physical

Wibisono, Y., Widyantari, S. and Prakoeswa, C.

Oral Hairy Leukoplakia: A Predictor and Prognostic Factor of HIV Infection.

DOI: 10.5220/0008160805050509

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 505-509

ISBN: 978-989-758-494-7

505

examination, and later the establishment of HIV

diagnose. This report discusses the clinical

manifestation, diagnosis and treatment of this

condition.

2 CASE

A twenty-nine-year-old Javanese male came to the

Outpatient Clinic of Dermato-Venereology

Department at Dr. Soetomo General Hospital

Surabaya with the chief complaint whitish color all

over the tongue since 2 months before visitation. He

went to see doctor and was diagnosed with fungal

infection and then prescribed ketoconazole 1 x 200

mg daily for 4 weeks. The whitish color on the

middle part has gone, but parts on the borders still

persist. The patient tried to remove the whitish color

with tooth brush but there was no result.

The patient also complained of cough and fever

for more than 2 weeks. There was also complaint of

watery stool for 1 month and report of weight loss

and loss of appetite. There was history of sexual

relationship with multiple partners. History of sexual

transmitted disease was denied. Patient has

homosexuality preference.

The dermatological examination on his tongue

showed bilateral painless white well demarcated

plaque with corrugated appearance on the lateral

borders of the tongue. The lesion can not be scrub

off. Other physical examinations revealed normal

findings.

The patient was consulted to the UPIPI

outpatient clinic to have Voluntary Counseling and

Testing (VCT) for HIV, and was told to do Rapid

test and blood and urine examination. The HIV test

result for all three methods (Imunochromatography,

Imunodot, ELISA) were reactive.

The patient was then consulted to the internal

department, and was diagnosed with s HIV stage 3.

Complete blood count examination was conducted

and the result was within normal limit. The absolute

CD4 count was performed, and it was obtained that

the absolute CD4 count was 1 cells/uL and CD4

percentage was 0.05%, considered as a very low

CD4 count. The patient was also consulted to

pulmonology department, and based on chest x ray

and acid fast stain there was no abnormalities found,

so the assessment of tuberculosis can be excluded.

A cytopathology examination was performed by

scrapping of the lateral border of the tongue. From

the examination, there was squamous epithelial and

mononuclear inflammatory cells present. There was

no dysplasia cell founded. Based on those result, it

concluded that this condition caused by

microorganism infection, and not a malignancy

process.

Based on history taking, clinical findings and the

laboratory examination, the patient was then

diagnosed with Oral Hairy Leukoplakia and AIDS.

The diagnosis of AIDS in this patient was obtained

from the presence of OHL, reactive results of HIV

panel test, and the CD4 cell count below 200/μL.

The patient was then treated with acyclovir 800

mg, administered 5 times a day, along with the

administration of cotrimoxazole 1 times 960 mg as a

Cotrimoxazole Prevention Treatment 2 weeks before

starting the HAART. After 1 week of treatment, the

lesion on the lateral border had subsided, the therapy

was then continued for another week to make sure

the lesion has totally disappeared. Clinical

progression of the lesion

After outpatient clinic visit until the end of

February 2017, patient no longer came to Dermato-

venerology outpatient clinic. When we tried to

contact the patient, he said he already moved to

Papua for business affairs, and never come back to

Surabaya ever since.

3 DISCUSSION

Oral hairy leukoplakia is a specific lesion in HIV

infection caused by Epstein Barr virus, and has been

reported in over more than 28% patients and is a

sign of disease progression (Murtiastutik et al.,

2008)

OHL appear clinically as an asymptomatic,

white or grayish white, well demarcated plaque with

corrugated texture. The “hairy” surface vary in size

and typically occurs on the lateral tongue. The lesion

is painless and irremovable by blunt manipulation

(Triantos et al., 1997).

In our case, the patient complaint loss of appetite

regarding the lesion on his tongue. He was first

treated with ketoconazole 1 x 200 mg. After given

treatment for 4 weeks, the lesion subsided, but the

lesion on both lateral borders persist. No pain,

wound or swelling was reported.

EBV primarily transmitted through saliva as

infected cells are shed into the surface of the oral

mucosa. Primary infection activates the innate and

adaptive immune systems, and the virus remains

latent lifelong by living in circulatory B

lymphocytes, which serve as the cellular reservoir

(Walling et al., 2003).

Severe immunosuppressive

condition can lead into reactivation of EBV

replication in the oropharynx of EBV-seropositive

patients (Cruchley et al., 1989).

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506

Figure 1: Patient’s clinical condition before (left) and after 2-weeks-treatment (right).

Figure 2: Opportunistic Infections Correlating with CD4+ Cell Count

11.

The lateral border of the tongue is the most

common location of OHL. The development of on

the tongue may be due to the accumulation of saliva

in the floor of the mouth (Piperi et al., 2010).

The

lateral border of the tongue is also an area which

prone to trauma, thus becomes a predilection area.

Another explanation is the decreased number of

Langerhans cells in OHL lesions compared with non

lesional oral mucosa. A comparative study of normal

mucosa revealed that the lowest density of

Langerhans cells was found on the lateral border of

the tongue and the sublingual region. Thus normal

epithelium of the lateral and ventral sides of the

tongue is more susceptible to EBV infection

(Cruchley et al., 1989).

In our patient, from physical examination we

found bilateral painless white well demarcated

plaque with corrugated appearance on the lateral

borders of the tongue, in accordance with the usual

location of OHL, which is on the lateral borders of

the tongue.

The importance of OHL as an indicator of

immunosuppressive condition was recognized soon

after it was first described in 1984 (Greenspan et al.,

1984). OHL has been listed in the classification of

oral lesions as a Group I lesion strongly associated

with HIV infection (Classification and diagnostic

criteria for oral lesions in HIV infection, 1993).

In this patient, after the initial diagnosis of OHL,

the patient was then referred to do VCT. The HIV

panel test result was reactive, which explain the

immunocompromised condition as predisposing

factor of OHL. OHL findings in patients with HIV

can also provide some predictive immunity

condition of how progressive the infection is, as it is

believed to have correlation with CD4 T cell counts.

The absolute CD4 count of the patient was 1

cells/uL (N = 410-1590 cells/uL) and CD4

percentage was 0.05% (N = 31-60%), which

Oral Hairy Leukoplakia: A Predictor and Prognostic Factor of HIV Infection

507

considered as a very low CD4 count.This is in

accordance with data provided in figure 2, where

OHL is correlated with CD4 T cell counts <200/μL.

According to WHO clinical staging of

HIV/AIDS for Adults and Adolescents, patient with

OHL is classified as HIV stage 3, (WHO, 2007)

but

CDC stated that when the number of CD4 cells falls

below 200 cells/mm, the patient is considered as

AIDS. (Greenspan et al., 1984). Diagnosis of AIDS

can also be established when one or more

opportunistic infection occured, regardless of the

CD4 count.

Therefore the patient was diagnosed

with OHL and AIDS.

In order to diagnosed patient with EBV infection,

further examination to obtain EBV in the lesion

needed. This can be done by performing

histopathology, exfoliative cytology, in situ

hybridization (ISH), or PCR examination. The most

common histopathological features of OHL include

hyperparakeratosis, epithelial hyperplasia, koilocyte-

like cells within the prickle cell layer and minimal or

complete absence of inflammatory cells in the

lamina propria. A band-like layer of cells with clear

cytoplasm (ground glass appearance) with basophilic

nuclear inclusions, ballooning of cytoplasm and

intracellular edema can also be seen in the upper

spinous layer (Davis et al., 2017).

In our patient, the result of cytopathology

examination does not specific for OHL. A study

revealed that only 50% of HIV patients with clinical

OHL had nuclear change (Reginald et al., 2017).

Suggestive clinical findings, the typical involvement

of lateral borders, the lack of response to

ketoconazole treatment and the patient’s HIV status

is sufficient to make the diagnosis.

The differential diagnosis of OHL include oral

candidiasis, lichen planus, tobacco-associated

leukoplakia, frictional keratosis, human papilloma

virus–induced oral intraepithelial neoplasia, and oral

squamous cell carcinoma (Radwan Ozcko &

Mendak, 2011). In most instances, OHL can be

diagnosed clinically and does not require a

confirmatory biopsy (Triantos et al., 1997).

OHL is a disease of minimal morbidity that does

not always require intervention. Therapy is indicated

when symptoms become troubling or when it is

associated with HIV infection. Treatments for OHL

when required consist of varying options. Usually

the institution of highly active antiretroviral therapy

(HAART) will reduced viral load and increased CD4

count which help decreasing prevalence of OHL

significantly. Other therapeutic options including

systemic antiviral agents such as acyclovir and

valacyclovir, topical podophyllin, topical retinoids,

cryotherapy and surgical excision (Triantos et al.,

1997; Uihlein et al., 2011).

In our case, the patient was administered

acyclovir 800 mg oral 5 times daily, which is

corresponding with guidelines in the literature, for 2

weeks.After the 1

week, the lesion on the lateral

borders had subsided, the therapy was then

continued for another week to make sure the lesion

has totally disappeared. The institution of HAART

could also prevent the recurrence of OHL in this

patient.

4 CONCLUSION

Oral hairy leukoplakia is a predictor and prognostic

factor of HIV infection. It cannot be occured in

immunocompetent patient so immunocompromised

condition which can be caused by HIV must be ruled

out before considering other immunocompromised

etiologies. Oral manifestations are the earliest and

most important indicators of HIV infection. OHL is

often misdiagnosed and thus proper treatment is

delayed.

In early diagnosis of OHL, health care provider

must be cautious for and perform further

examination to establish the diagnosis of HIV

infection. Institution of HAART on HIV-related

OHL patient significantly decline the prevalence of

OHL. Other treatments such as systemic antiviral

accelerate the resolution process. The ability to

recognize early OHL manifestation in patient with

HIV is key to providing optimal and appropriate

care, administer early medical intervention and thus

prolonging patient’s life and improve their quality of

life.

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