Establishing the Diagnosis Histopathology Findings of Papular

Pruritic Eruption in HIV-infected Patients: Preliminary Study

Hajar Imtihani

*, Mochammad Rifky Luthfiandi

, Qamariah

, Hanggoro Tri Rinonce

Nurwestu Rusetiyanti

, Devi Artami Susetiati

, Satiti Retno Pudjiati

and Sunardi Radiono

Departement of Dermatology and Venereology, Universitas Gadjah Mada/Sardjito General Hospital, Yogyakarta-

Indonesia

Department of Anatomical Pathology, Universitas Gadjah Mada/Sardjito General Hospital, Yogyakarta-Indonesia

Keywords: Papular pruritic eruption, PPE, HIV, histopathology

Abstract: Papular Pruritic Eruption (PPE) is a common clinical manifestation in patients infected with Human

Immunodeficiency Virus (HIV). The hallmark of PPE is a chronic pruritus with a symmetrically scattered

papular eruption on the body and extremities. The pathophysiology of PPE is still unknown. Clinically, PPE

is difficult to distinguish between prurigo nodularis, insect bite, or other dermatitis, thus requiring

histopathologic examination to exclude other diagnosis. Nevertheless, the consensus on the histopathology

picture of PPE is still limited. So the of this study was to found the histopathology spectrum of PPE in HIV-

infected patients. This is a descriptive analitycal study to characterize the histopathology pattern in some PPE

cases.

1 INTRODUCTION

The distinctive mark of Human Immunodeficiency

Virus (HIV) infection is progressive

immunosuppression leading to a diverse spectrum of

clinical manifestations such as opportunistic

infections and tumors, wasting syndrome, and failure

of various central nervous systems (Sued et al., 2016)

Skin disorders that are often associated with HIV

infection include seborrhoeic dermatitis, molluscum

contagiosum, tinea corporis, and Kaposi sarcoma, as

well as pruritus and dermatitis with unclear causes,

such as papular pruritic eruptions (PPE) (Chua et al.,

2014). The prevalence of PPE varies in different parts

of the world, ranging from 11% to 46%.(Chua et al.,

2014; Kaushik et al., 2014) A study in Surabaya

showed a 15.4% prevalence of PPE from all patients

with HIV (Arista et al., 2015).

Clinical features of PPE are very similar to

eosinophilic folliculitis in HIV patients, usually

occurs in HIV patients with low CD4 counts, and may

also be part of the Immune Reconstitution

Inflammatory Syndrome (IRIS) (Mostwaledi et al.,

2014). Also, the possibility of drug reaction should be

considered in any case of inflammatory dermatosis in

HIV infection. Therefore, skin biopsy has an

important diagnostic role when some form of this

distinct skin disorder arises as a similar clinical

manifestation, but the normative histopathology

criteria of PPE does not exist yet. This objective of

this study was to characterize the PPE

histopathological findings.

2 METHODS

This research is a descriptive analytical study that

conducted in the sexually transmitted disease clinic,

Department of Dermatology and Venereology in

Sardjito General Hospital, Yogyakarta, during

October to December 2017. The study subjects were

HIV-infected adult patients, who had pruritic,

symmetrically scattered multiple papule lesions with

a duration of at least 1 month. Skin biopsy was

performed on the latest skin lesion with a punch

technique, 5mm in size. The tissue is then delivered

and processed in Anatomical Pathology laboratory of

Sardjito General Hospital. The tissue preparation is

cut and stained with standard hematoxylin and eosin.

Interpretation is focused on the pattern of skin

reaction, exocytosis in the epidermis, and dermis

infiltrate, such as type, density, and location of the

Imtihani, H., Luthﬁandi, M., Qmariah, ., Rinonce, H., Rusetiyanti, N., Susetiati, D., Pudjiati, S. and Radiono, S.

Establishing the Diagnosis Histopathology Findings of Papular Pruritic Eruption in HIV-infected Patients: Preliminary Study.

DOI: 10.5220/0008153501810185

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 181-185

ISBN: 978-989-758-494-7

181

infiltrate. Inflammatory cell counts were performed

using a direct observation under microscopy in high

power field in 5 field of view, with a single observer

of anatomical pathologist.

3 RESULT

There were 8 patients included, consisting of 2 female

and 6 male (Table 1). The mean age of patient is 38.87

years old. Four patients received a combination of

drugs in the form of Tenovofir, Hiviral, and Efavirenz

(THE), while the rest received Duviral and Neviral.

Duration of the patient's complaint varies from 3

months to 2 years. Two patients complained of

itching after dropping out of the first drug regimen,

while the rest complained of itching before starting

ARV. The mean CD4 count in peripheral blood are

138,25 cells/mm

(Arista et al., 2015).

As shown in table 2, orthokeratosis basket weave type

is the most common feature of epidermis, with normal

stratum granulosum and stratum spinosum, however

one specimen showed mild spongiosis and one

specimen showed severe spongiosis with

intraepidermal cleft.

Table 1. Overview of the patients

Case

no.

Sex Age Blood CD4

count

1 Male 30 y.o 79 cells/mm

2 Female 48 y.o 300 cells/mm

3 Male 21 y.o 144 cells/mm

4 Male 30 y.o 245 cells/mm

5 Male 48 y.o 23 cells/mm

6 Male 50 y.o 247 cells/mm

7 Female 44 y.o 17 cells/mm

8 Male 32 y.o 51 cells/mm

Table 2. Histopathological findings in 8 cases of PPE

Epidermis

Orthokeratosis basket weave type 87,5%

Normal epidermis 12,5%

Acanthosis 12,5%

Eugranulosis 100%

Mild spongiosis 12,5%

Severe spongiosis with intraepidermal cleft 12,5%

Vacuolar degeneration of basal cell 62,5%

Hyperpigmentation 25%

Exocytosis 12,5%

Dermal-epidermal

interface

Clear 100%

Dermis

Type of infiltrate Lymphocyte 100%

Eosinophil 75%

Density Sparse 37,5%

Moderate 62,5%

Distribution Perivascular 100%

Periadnexal 50%

Wedge-shape 0%

Eosinophils count/ 0 12,5%

5 HPF 1-20 50%

21-50 25%

>50 12,5%

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Figure 1. A. Epidermis showing orthokeratosis basket weave and normal layer of granulosum and spinosum. There is

perivascular and periadnexal distribution of inflammatory infiltrate in the dermis. B. Lymphocytes predominance of infiltrate

in periadnexal. C. Eosinophils are moderately scattered.

There is lymphocytic and eosinophilic infiltrate

inside this cleft, showing a feature of spongiotic

pustule. This specimen also have an exocytosis of

eosinophil. There was only one specimen showing

acanthosis of epidermis. All specimens showed clear

dermal-epidermal interface.

In the dermis, all specimens show lymphocyte

infiltrate predominance. They are scattered in the

dermis, and four of them showed sparse infiltrate in

perivascular distribution only, while the rest of them

have both periadnexal and perivascular infiltration

with moderate density. Other infiltrate found is

eosinophils in six cases (75%). In contrast to previous

studies, no single specimen with wedge shaped

infiltrate was found in this study.(7)

Eosinophils are inflammatory cells thought to

play an important role in the mechanism of PPE

before, so we calculated the amount of eosinophils in

high power field magnification (HPF) (400x) in 5

fields of view. Based on the number of eosinophils,

the samples are classified into three categories: 0 or

no eosinophil, 1-20, 21-50, and >50, to illustrate the

number of eosinophil scattered. Most of the spesimen

have eosinophil count 1-20 cells in 5 HPF or

moderately dense. The largest number of eosinophils

count is 133 cells/5 HPF.

4 DISCUSSION

Skin is the most frequent organ affected in HIV

infection and the lesion of skin disorders have a

higher clinical severity than the general population.

Some noninfectious dermatoses are important to note

because of their high prevalence, uncommon

manifestation, extensive or resistant clinical lesions.

In addition, atypical histopathologic features often

make it misdiagnose. This study was conducted to

observe the histopathologic characteristics of one of

the most common non-infectious dermatoses, papular

pruritic eruption (PPE) that is defined as a very itchy,

chronic, and symmetrically scattered papule,

especially on the extremities (Chua et al., 2014).

Because of its very itchy complaints, the papules will

become excoriated and susceptible to secondary

infections, or are characterized by prurigo-like

features (Mostwaledi et al., 2014)

The most commonly observed of histopathologic

finding from previous studies were insect bite feature.

A various cutaneus lesions (maculae, urticae, papules,

vesicle, and nodules) are associated with cutaneous

lesion of insect bite, will showed variation in

histological finding. Spongiosis was the predominant

feature charaterizing the epidermal change.

Sometimes there are erosion or ulceration, or scale

crust with neutrophils or eosinophils above the

keratin layer. The keratin layer will show a

orthokeratosis with some case showed mild

acanthosis. Dermis showed an edema in the papillary

dermis and wedge-shaped infiltrate with moderately

dense distribution in perivascular and periadnexal,

consisted mostly by lymphocytes, eosinophil, and

neutrophils, sometimes macrophages, with no plasma

cells. Most infiltration could involve the adnexal

structures such as sweat glands, hair follicle, and

sebaceous glands (Miteva et al., 2009).

Establishing the Diagnosis Histopathology Findings of Papular Pruritic Eruption in HIV-infected Patients: Preliminary Study

183

Prurigo simplex and eosinophilic folliculitis

sometimes shows similar lesion clinically.

Histopathological findings of prurigo simplex include

compact orthokeratosis, irregular acanthosis,

hypergranulosis, and sometimes focal parakeratosis

in the epidermis. Dermis will showed fibrosis in

papillary to reticular dermis, with main infiltrate are

lymphocytes and macrophages, sometimes

eosinophils (Miteva et al., 2009). Histological feature

of eosinophilic folliculitis include eusinophilic

spongiotic pustulosis involving infundibular region

of the hair follicle, and the infiltrate extends to

attached sebaceous glands. Sometimes there is

disruption or destruction of the follicular wall by

inflammatory infiltrate, including follicular necrosis

and folliculocentric necrotizing eosinophilic

vasculitis. Inflammatory infiltrate are moderately

dense, with perivascular and perifollicular

distribution composed of lymphocytes, mast cell,

neutrophils, and prominent eusinophils (Fujiyama et

al., 2013).

In this study, the pattern of epidermal reactions

and the characteristics of the infiltrate found in the

dermis were not too match to the findings of the insect

bite. Although there was 87,5% specimens showed

orthokeratosis of epidermis, only two specimens

showing spongiosis. Specimens with severe

spongiosis with moderate density of lymphocyte and

eosinophils might be resemble of vesicular stage of

insect bites. But we have no perfectly wedge-shaped

infiltrate found in all specimens. None of specimens

in this study also showed an adnexal structure

disruption, although there were infiltration around

adnexal structure. Our results are inconsistent with

previous research that stated the histopathologic

features of PPE are resemble the insect bite, instead it

showed variable feature of perivascular infiltrate of

lymphocyte and eusinophils.(Resneck et al., 2004;

Weedon, 2010) Although clinically the papules of

PPE closely similar, the histopathological feature of

prurigo simplex and eusinophilic folliculitis were not

found in this study.

Etiologic factors that suspected play a role in PPE

pathogenesis are: arthropod bites, hypersensitivity to

insect bites, generalized hypersensitivity to insect

saliva, host immune response to abnormal infection

(e.g scabies, demodecidosis, bacterial infection),

drugs, or direct effect of the virus through skin

immune disregulation. One of the study found that

there was an increase in local antibodies against

mosquito saliva antigens. It is thought that pruritus is

a form of chronic delayed type hypersensitivity

reaction that generalized to antigen based on non-

spesific B cell activation, common reaction that

involving a humoral reaction with Th2 predominant.

This phenomenon is also thought to be related to other

conditions in similar complaints that appear in

malignant diseases (Tokura et al., 2001). The variable

feature seen in this study that not so spesific does

made a estimation that PPE is only a part of HIV

immunosuppresion progression. Therefore, it may

further explain why PPE can improve with ARV

administration only.

As the HIV infection progression, there will be a

reduction of CD4 lymphocytes and increase of CD8

lymphocytes count.( Weedon, 2010; Rosatelli et al.,

2000) It is shown in this study by low mean CD4

count that are below 200 cells/mm

.(Samanta et al.,

2009). An increase in CD8 cells may exert functions

similar to the Th0/Th2 response, these cells could be

responsible for the production of cytokines,

explaining the increase of eosinophils in the

infiltrate.(Rosatelli et al., 2000) This normal response

also include an increase number of macrophage and

mast cells, that thought to be responsible to intense

itching complain of PPE patients. Observation of

mast cells count with toluidin blue staining might be

useful in future study, along with

immunohistochemistry staining such as CD4, CD8,

and CD20 to confirm the B cell role in this disease.

5 CONCLUSION

The histopathological findings of PPE in this study

are variable. The most observe feature are

orthokeratosis basket weave type, normal stratum

granulosum and spinosum, without dermal-epidermal

interface reaction, infiltration of inflammatory cells in

perivascular and periadnexa with lymphocyte

predominance and moderately dense eusinophils.

This findings was not spesifically resemble insect

bites feature like previous study stated. However,

owing to small number of patients in this study, it is

difficult to identify the true variability of PPE

histopathological feature. Therefore, studies with

larger numbers of patients and more

immunohistochemistry staining are required to

determine the complete characterization and compile

a histopathologic criteria of PPE.

ACKNOWLEDGEMENT

The research was funded by the Faculty of Medicine,

Universitas Gadjah Mada, Yogyakarta, Indonesia.

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184

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