Title : Study of epidemiology, clinical, histopathological characterstics and  immunohistochemical  findings in patients with Lichen planus pigmentosus.

Key Words : Lichen planus pigmentosus, epidemiology, immunohistochemistry

1.Present update on topic

Lichen planus pigmentosus (LPP), first described by Bhutani et al.¹  is a fairly frequently encountered disorder of hyperpigmentation in Indians.

 It is characterized by the insidious  onset of dark brown macules in sun-exposed areas  and flexural folds with or without slight pruritus.

 There are very few reports about clinicopathological features

of  LPP available in the literature .

The aim of this study is to assess the clinical, epidemiological, histopathological characteristics as well as immunohistochemical findings of patients with LPP.

It generally starts in the third or fourth decade of life. While Vega et al.² reported female preponderance, Bhutani et al. observed no difference in sex distribution in their patients. A significant proportion of patients with LPP may have lesions of LP. According to mutairi et al³ HCV may be one of the factors associated with LPP.

A significant number of patients give history of using mustard oil and amla oil for body massage and ⁄or hair dressing for variable periods of time. Mustard oil contains allyl thiocynate, a potential photosensitizer, which could play a role in the pathogenesis of

LPP.

Clinically, Lesions initially appear as small, ill-defined oval to round macules , which later become confluent to form large areas of pigmentation. Pigmentation in different patients varies from slate grey

to brownish-black. It is mostly diffuse or reticular in

pattern. Although distribution is variable, the face and neck are the most frequent initial sites of involvement. With time the upper extremities and upper part of the back and trunk may also be involved. Infrequently, the flexures, i.e. the axillae , groin and

inframammary areas, and bald scalp are also involved. Lesions are generally bilaterally symmetrical predominantly in the exposed areas¹.

The main histopathological features of LPP include atrophy of the epidermis, vacuolar degeneration of the basal cell layer and scarce dermal perivascular or lichenoid infiltrate. Presence of dermal melanophages and pigment incontinence are the two

constant features seen in histopathology³. The characteristic band-like infiltrate in the basement membrane zone is dominated by CD4+ and CD45RO+ T cells. Cytotoxic T cells (CD8+), mainly of the CD45RO subset, are largely found high in the dermis⁴.

Regarding etiology, cause of  LPP is unknown but an autoimmune attack is generally accepted and it was demonstrated that  the inflammatory infiltrate is composed mainly of T-lymphocytes, with varying populations of  CD4+ and CD8+ cells.

T- lymphocytes are pivotal , as they regulate epidermal cell recognition, the lichenoid response and epithelial destruction.The exact role of T- helper CD4+ T  cells is not fully determined but they are known to propagate CD 8+ T cells.

Some studies have shown a predominance of cytotoxic T-lymphocytes (CD8+), especially in late lesions.

Apoptosis of keratinocytes is accepted to be mediated by CD8+ T- and natural killer (NK) cells in two distinct ways: by the release of cytotoxic molecules, such as perforin and granzyme B; or by the Fas/FasL system⁵. The expression of granzyme  B was measured to determine the cytotoxic capacity of the immune reaction⁶.

2. Objective and scope of the project :

a.      To study epidemiology ( age, sex, family history, aggravating factors and associated diseases) and clinical patterns of  LPP.

b.       To assess the histopathological findings .

c.       To assess the immunohistochemical findings in LPP by subjecting immune infiltrate to HAM 56 & MAC 387 (macrophage) , UCHL-1 (anti- CD 45 RO) ,CD8 , CD 4 Granzyme B, Perforin  and ICAM-1 antibodies.

3. Rationale of  the research :

The role of immune mediation has been shown in LPP. This study will provide us with information regarding the epidemiology ( age, sex,family history, aggravating factors and associated diseases), clinical patterns, histopathological findings and various subtypes of

 T – lymphocytes in the infilterate.

Few studies are available regarding the relation between Hepatitis B and C virus and LPP. This study can be used to  detect the association between two.

4. Summary of  the methodology :

 Approval of the ethical committee of the institution will be taken.

A duration of 12 months for the study will be considered. Thirty untreated patients with clinical diagnosis of LPP will be recruited in the study after taking informed consent.

       A skin biopsy  for confirmation of  LPP along with immunohistochemistry will be done at the time of presentation. Routine blood investigations including haemoglobin , total count ,

Differential count , random blood sugar , liver function test and serology for Hepatitis C & B will be performed.

INCLUSION CRITERIA

1.      Patients willing to voluntarily participate in the study with a written informed consent.

2.      Age group of above 18 years.

3.      Untreated cases of  LPP willing for necessary investigations.

EXCLUSION CRITERIA

1.      Patient not willing to give consent.

2.      Immunocompromised patients and pregnant women.

3.      Patients who have taken treatment for LPP in the last 3 months.

5. Present research base and relationship to the project :

There are very few reports about clinicopathological features

of  LPP available in the literature .The present knowledge  base about infilterate in LPP is contradictory. The predominance of CD4+ or CD8+ T- cells has not been mentioned with uniformity. 

6. Situation of  the available research equipments correlated to the

    project :

The research centre is a tertiary care hospital with the available facilities of a full fledged laboratory for routine blood investigations and for histopathological examination of skin biopsies.

 However . for the purpose of immnohistochemistry , the same will be sent to an outside pathology  laboratory through the pathologist for processing and reporting the same.

7.     Expected results and conclusion :

At the end of this project , we expect to see the following results :

1. Presence of dermal melanophages and pigment incontinence will be seen on histopathology.

2.      Cytotoxic T cells (CD8+), mainly of the CD45RO subset, will be  found high in the dermis.

8.     Project schedule :

       The project if selected will be initiated in January 2013. A 12 months period of  patient selection will be required. The project will be completed in January 2014.