Lichenoid Dermatoses

Lichenoid Dermatoses

They represent a heterogeneous inflammatory group of conditions that resemble idiopathic LP in terms of their clinical appearance and histological appearancedemonstrating lichenoid tissue reaction characterized by;

• Liquefaction degeneration of epidermal basal cells

• Band-like infiltrate primarily lymphocytes in the papillary dermis.

Major Lichenoid Dermatoses1. Lichen planus2. Lichen striatus3. Lichen nitidus4. Graft-versus-host disease5. Erythema dyschromicum

perstans6. Lichenoid drug eruption7. Fixed drug eruption 8. Keratosis lichenoides

chronica9. Pityriasis Lichenoides

10. Erythema multiforme11. Lupus erythematosus 12. Dermatomyositis13. Paraneoplastic pemphigus14. Mycosis fungoides 15. Lichenoid pigmented

purpura16. Secondary syphilis 17. Lichen sclerosus (Lichen

sclerosus et atrophicus)

Lichen planus

Lichen planus (LP)

• Introduction

• Epidemiology

• Etiology

• Pathogenesis

• Clinical Features & Clinical variants

• Histopathology

• Immunohistochemistry

• Differential Diagnosis

• Treatment

Introduction

• LP is an idiopathic inflammatory papulosquamous disease of the skin and mucous membranes with varying clinical presentation.

• Where the trigger is known, a lesion is known as a lichenoid lesion.

• Lichen planus lesions are so called because of their "lichen-like" appearance.

Epidemiology

• PREVALENCE:– Cutaneous LP 0.2% to 1% of the adult population.– Oral LP have been observed in up to 1–4% of the population.

• AGE: – Onset of LP occurs most commonly during the fifth or sixth

decade.– LP is rare in both infants and the elderly but it is more common

in children in Arab populations. • SEX: Females>males.

Etiology

• Exact etiology is unknown

Etiology• Autoimmune reaction against epitopes on lesional keratinocytes that may have been modified by

any of the following factors;

1. VIRAL INFECTION: hepatitis C virus infection (oral LP is most commonly viewed as a manifestation of HCV infection), HHV6, HHV7.

2. MEDICATIONS: Cutaneous eruptions similar or even identical to LP (both clinically and histologically) have been linked to a variety of drugs. The terms “lichen planus-like” and “lichenoid” are often used to describe this phenomenon.

3. CONTACT ALLERGEN: metallic dental restorations or constructions (amalgam, copper and gold), positive patch test results, and then regression or complete clearing after removal of the sensitizing metal and replacement with other materials.

4. Others; Stress, diabetes, trauma, vaccinations (HBV vaccines), chronic active hepatitis, and primary biliary cirrhosis. It may be found with other diseases of altered immunity, such as ulcerative colitis, lichen sclerosis, myasthenia gravis, chronic graft-versus-host disease of the skin etc.

DRUGS IMPLICATED IN LICHENOID DRUG ERUPTIONS

CLASS AGENTS

ANTIMICROBIALS • Griseofulvin• Isoniazid

• Ketoconazole• Tetracyclines

• Streptomycin• Sulfamethoxazole

ANTIHYPERTENSIVES • Captopril• Enalapril

• Labetalol• Doxazosin

• Methyldopa• Propranolol

ANTIARRHYTHMICS • Quinidine

ANTIMALARIALS • Chloroquine • Quinacrine • Hydroxychloroquine

Anti-TNF-α • Etanercept • Infliximab

ANTIPSYCHOTICS • Chlorpromazine

ANTICONVULSANTS • Phenytoin

ANTIDEPRESSANTS • Amitriptyline • Imipramine

ANTIDIABETICS • Glyburide • Tolbutamide

METALS • Gold salts• Arsenic

• Bismuth• Mercury

Pathogenesis

LP represents T-cell-mediated autoimmune damage to basal

keratinocytes that express altered self antigens

(epitopes) on their surface

Pathogenesis

PHASES OF LPA. INDUCTION PHASE

B. EVOLUTION PHASE

C. RESOLUTION PHASE

Pathogenesis

A. INDUCTION PHASE

Self-peptides modified by exogenous antigens [viruses, medications and contact allergens]) stimulation of keratinocytes and plasmacytoid dendritic cells (pDCs), release IFN-α activation and migration of DCs Ag presentation to naïve T-cells in lymph node differentiation into CD8+ effector memory T cells attracted by chemokines (released locally by pDCs) migrate into the inflammatorysite.

Pathogenesis

B. EVOLUTION PHASE

Effector T cells (Te) expressing skin-homing receptors (E-selectin ligands) recognition of antigens activated and release proinflammatory cytokines and cytotoxic granulesepidermal injury.

Pathogenesis

TWO DIFFERENT MECHANISMS OF T-CELL CYTOTOXICITY: 1. Perforin which forms pores in the target cell's plasma membrane this

causes ions and water to flow into the target cell, making it expand and eventually lyse then Granzyme B that can enter target cells via the perforin-formed pore and induce apoptosis. IFN-γ and TNF-α, released by both CD4+ T cells and CD8+ T cells, can induce keratinocyte expression of ICAM-1, thereby rendering these T-cells more adhesive to the keratinocytes and thus facilitating exocytosis of granules containing perforin and granzymes.

2. Activation of the death receptor Fas on the target cell by expressing the cognate death ligand Fas L. The activated Fas also triggers apoptosis.

PathogenesisC. RESOLUTION PHASE• “Inflammatory” and “ ‘homeostatic” chemokines produced by keratinocytes

direct the traffic of not only “pathogenic” T cells (Te) but also “immune surveillance” T cells (Ts) or regulatory T cells (Treg) into the sites; the relative balance of chemokines produced may determine the outcome of the T-cell-mediated immune responses .

• Because keratinocytes are not only targets but also produce granzyme B, perforin and Fas L to protect themselves from immune-mediated damage, Fas L-bearing keratinocytes can induce Fas/Fas L-mediated death in neighboring Fas-bearing T cells, contributing to the resolution of the lichenoid tissue reaction. This pathway serves to eliminate potentially harmful auto-aggressive T-cells. Recovery from the inflammation is associated with the migration of regulatory T (Treg) cells into the site which have the capacity to suppress activated T-cells.

Clinical Features

• Cutaneous LP resolves approximately in 12-18 monthswhile Oral LP resolves approximately in 5 years.

• Mucosal involvement, particularly oral lesions, may be observed in up to 75% of patients with cutaneous LP, but the oral LP can be the only manifestation of the disease.

• Only 10–20% of patients whose initial presentation is oral

LP will eventually develop cutaneous LP.

• 15% to 20% of cases follow a relapsing course for years.

Clinical FeaturesTHE TYPICAL OR CLASSICAL LP RASH;

1. Papules may be discrete or gradually coalesce into plaques.

2. Bilaterally symmetrical.

3. Sharply demarcated.

4. Increase in size if subjected to any irritation.

5. Surface: shiny or scaly looking.

6. Initially red purple or violaceoushue a dirty brownish color.

7. Periods of regression and recurrence.

8. Pruritus; rubbing than scratching.

9. Koebner’s phenomenon.

10. Most often on flexural wrist, forearms, knees, flanks. trunk, medial thighs, shins of tibia, genitals especially glans penis, nails, scalp & oral mucosa.

11. Face remains uninvolved.

12. May be covered with thin white streaks (called Wickham's striae).

13. After lesions subside, post lichenhyperpigmentation occurs.

The P's to Describe LP Lesions

1. Papulosquamous disorder (Papules/Plaques)

2. Planar (flat-topped)

3. Purple (violaceous)

4. Polygonal

5. Pruritic

6. Post-inflammatory hyperpigmentation

Clinical variants

1. Mucosal lichen planus (oral & genital/vulvovaginal)

2. Lichen planus of the nails

3. Follicular LP (LPP)

4. Hypertrophic lichen planus

5. Annular lichen planus

6. Atrophic lichen planus

7. Ulcerative lichen planus

8. Bullous lichen planus

9. LP pemphigoides

10.LP pigmentosus

11.Inverse lichen planus

12.Linear lichen planus

13.Zosteriform LP

14.Actinic lichen planus

15.Acute (exanthematous) LP

16.Drug-induced LP (Lichenoid drug eruption)

Mucosal LP

• The most common location of mucosal lichen planus is the oral mucosa.

• Predominantly women are affected.

TYPE DESCRIPTION

1.RETICULAR

• Most common presentation.• Commonly on buccal mucosa and buccal vestibule. Sometimes on tongue, gingiva, lips and floor

of the mouth.• The lesions tend to be bilateral and are asymptomatic:(a) Slightly elevated fine grey-white lines (Wickham’s striae) lacelike pattern or a pattern of fine radiating lines or;(b) Annular lesions- lesions, develop gradually from single small pigmented spots into circular groups of papules with clear, central unaffected mucosa.

2.EROSIVE/

ULCERATIVE

• Commonly on buccal mucosa and vestibule.• Complication of the atrophic process after trauma or ulceration .• May be covered with Pseudomembrane.• Asymptomatic- uncomfortable -mild burning to severe pain provoked by sour, spicy or hot foods• Central area of erosion with yellowish fibrinous exudate surrounded by erythema. Bleeding may

occur. • Wickham's striae may also be seen near these ulcerated areas. This form may undergo malignant

transformation.

3.ATROPHIC

• Inflamed areas of oral mucosa covered by thinned red-appearing epithelium.• Smooth, poorly defined erythematous areas with or without peripheral striae.• Usually associated with desquamative gingivitis.• Pain and burning sensation.

TYPE DESCRIPTION

4.BULLOUS

• Rare form characterized by large vesicles or bullae (4mm to 2cm).• Combined with reticular or erosive pattern.• Lesions usually develop within an erythematous base, rupture

immediately leaving painful ulcers.• Usually have peripheral radiating striae and seen on posterior part of

buccal mucosa.

5.PAPULAR• Form minute white papules which gradually enlarge and coalesce to form

either a reticular, annular, or plaque pattern.

6.PLAQUE-LIKE • Flattened white areas favors dorsal surface of tongue.

7.HYPERTROPHIC • Well circumscribed, elevated white lesion resembling leukoplakia• Biopsy needed for diagnosis

8.PIGMENTED • Rare type shows flanked brown macular foci.• Can be associated with other types particularly erosive.

Vulvovaginal LP

• Most common appears to be erosive disease.

• Vaginal involvement occurs in up to 70% of women with erosive vulvar LP, and if there is oral mucosal involvement “vulvovaginal–gingival syndrome”.

• Scarring may be a sequel.

LP of the nails• Nail lesions can precede the appearance of LP on the rest of the skin or on the mucous membranes or develop in a delayed fashion.• 10% of patients with LP.• These changes are manifestations of matrix damage, which can lead to scarring and dorsal pterygium formation if

left untreated. • Nail changes include;

1. Thinning of the nail plates2. Longitudinal ridging 3. Pterygium unguis 4. Trachyonychia: marked roughness of the nail plate, loss of transparency and often by a gray discoloration

when widespread trachyonychia involving all 20 nails Twenty-nail dystrophy (more common in children).5. Onycholysis6. Onychorrhexis7. Koilonychia8. Subungual hyperkeratoses

Lichen planopilaris (LPP/Follicular LP) • Involvement of the hair follicle is observed, both clinically & histologically.• Multiple, keratotic plugs surrounded by a narrow violaceous rim are

observed primarily on the scalp, although other hair bearing areas can also be affected.

• The inflammatory process may result in scarring and loss of follicular structure, i.e. a permanent alopecia. Over time, the areas of involvement often “burn out” centrally and are indistinguishable from other causes of “end stage” cicatricial alopecia.).

• Women are more frequently affected than men, and this form may occur alone or with typical LP lesions elsewhere.

• Variants of lichen planopilaris:I. Graham–Little–Piccardi–Lassueur syndrome: is characterized by

the triad of (need not be present simultaneously ): 1. Non-cicatricial loss of pubic and axillary hairs and disseminated spinous or

acuminated follicular papules. 2. Typical cutaneous or mucosal LP.3. Scarring alopecia of the scalp with or without atrophy .

II. Frontal fibrosing alopecia: progressive frontotemporal hair loss occurs primarily in elderly women.

Hypertrophic LP (LP Verrucosus)• Extremely pruritic, thick hyperkeratotic reddish-brown plaques are seen

primarily on the shins or dorsal aspect of the foot and may be covered by a fine adherent scale.

• The lesions are usually symmetric and tend to be chronic because of repetitive scratching.

• The average duration of hypertrophic LP in patients whose lesions had cleared was reported to be 6 years.

• Chronic venous stasis frequently contributes to the development of this condition.

• Squamous cell carcinoma may develop within a background of longstanding hypertrophic LP.

Annular LP

• This form is thought to occur when papules spread peripherally and the central area resolves.

• The annular edge is slightly raised and typically purple to white in color, while the central portion is hyperpigmented or skin-colored.

• Annular lesions occur in about 10% of patients with LP and are usually scattered among more typical lesions, but may represent the predominant finding.

• The most common site of involvement is the axilla, followed by the penis, extremities and groin.

• Most patients are asymptomatic, while some have pruritus.

Atrophic LP

• Atrophic LP may represent a resolving phase of LP, given the history of the lesions: papules coalesce to form larger plaques that often, over time, become centrally depressed and atrophic with residualhyperpigmentation.

• The clinical appearance of atrophic LP is likely a result of thinning of the epidermis rather than degeneration of elastic fibers, and the epidermal atrophy may be accentuated by the use of potent topical corticosteroids. The most common site of involvement is the lower extremity.

• Occasionally, morphea of the trunk has been reported in association with oral LP, as has the simultaneous occurrence of LP and/or lichen sclerosus.

Ulcerative LP

• Can occur at the nails or palmoplantar lesions of LP, particularly those on the soles.

• Typical LP lesions may be present in additional sites of the body.

• More common in female patients.

• The ulcers are intensely painful and often recalcitrant to conventional therapy. Chronic ulcerative lesions are at risk of developing SCC.

Bullous LP & LP pemphigoidesBULLOUS LP LP PEMPHIGOIDES

CLINICAL• Occur in longstanding preexisting lesions blisters

arise only on or near the lesions of LP.

• Lesions last for short duration.

• LP acute and generalized and is followed by the

sudden appearance of large bullae mainly on

uninvolved skin.

• May evolve into pemphigoid nodularis.

PATHOGENESIS• Intense lichenoid infiltration of lymphocytes =>

severe liquefaction degeneration of the basal cell

layer => exaggerated Max-Joseph spaces.

• Lichenoid infiltrate => damage to the basal layer=>

expose hidden antigens to the autoreactive T-cell =>

formation of circulating IgG autoantibodies directed

against the 180 kDa BP antigen (BPAG2, type XVII

collagen), => subepidermal bulla.

HISTOLOGICAL• Subepidermal bulla formation with typical changes of

LP.

• Subepidermal bulla with no evidence of associated LP

with an abundance of eosinophils.

IMF• Direct and indirect.

• IMF is negative.

• Direct IMF shows linear basement-membrane-zone

deposition of IgG and C3 in perilesional skin.

IMMUNOELECTRON-

MICROSCOPY• Negative.

• Deposition of IgG and C3 in the base of the bulla and

not in the roof as found in bullous pemphigoid.

LP pigmentosus

• LP pigmentosus typically presents in individuals with skin types IIIand IV as brown to gray–brown macules or patches in sun-exposedareas of the face and neck, usually with no preceding erythemaand often evolving into diffuse or reticulated pigmentation.

• Involvement of intertriginous sites is occasionally observed, and a linear distribution following Blaschko’s lines has also been described.

• Histologically; marked pigment incontinence and epidermal atrophy.

• Coexistence of classic LP lesions in approximately 20% of patients.

Inverse LP

• Pink to violaceous papules and plaques appear in intertriginous zones (axillae >inguinal and inframammaryfolds) and less often in the popliteal and antecubital fossae. Occasionally, LP lesions occur elsewhere on the body.

• Hyperpigmentation is usually present as well and it may be the sole manifestation, leading to overlap with LPpigmentosus.

Linear LP

• Lesions that appear spontaneously within the lines of Blaschko.

• Usually seen in patients in their late 20s or early 30s.

• Presumably this pattern reflects somatic mosaicism, but how the involved and uninvolved skin differ is not known.

Zosteriform LP

• Koebnerization of LP into the site of a previous herpes zosterinfection.

• When LP has a strictly dermatomal pattern, this represents an isotopic phenomenon following “zoster sine herpete”.

Actinic LP (LP actinicus)

• Most patients are young adults or children with a dark skin type.

• The onset of this variant is during the spring and summer, and the lesions primarily involve sun-exposed skin of the forehead and face, followed by the dorsal surfaces of the arms and hands and the neck.

• The lesions usually consist of red–brown plaques with an annularconfiguration, but melasma-like hyperpigmented patches may occur.

Acute (exanthematous/eruptive) LP• Because lesions are usually widely distributed and

disseminate rapidly.

• The commonly affected areas include the trunk, the inneraspects of the wrists and the dorsal aspect of the feet.

• Probably due to lichenoid drug eruptions.

• The clinical course is usually self-limited and, in general, lesions resolve with hyperpigmentation within 3 to 9 months.

Drug-induced LP (Lichenoid drug eruption)• Despite the significant overlap between LP and lichenoid drug

eruption there are both clinical and histologic clues that favor one diagnosis over the other.

• There is usually a latent period of several months from drug introduction to the appearance of the cutaneous eruption.

• The latent period varies depending not only on the offending drug, but also on other factors such as the frequency of drug administration, the dosage, and the intensity of the patient’s individual reaction to the offending drug.

Complications

1. Squamous cell carcinoma may develop in oral ulcers (rare < 0.4-5.3%), cutaneous ulcers or hypertrophic LP that are present for a long time.

2. Cicatricial alopecia in scalp LP.

3. Postinflammatory hyperpigmentation.

4. Atrophy and scarring are seen following hypertrophic lesions.

5. Erythroderma. Rare.

HistopathologyLAYER FINDINGS

HORNY CELL LAYER1. Hyperkeratosis w/o parakeratosis2. Oral LP parakeratosis rather than hyperkeratosis

GRANULAR CELL LAYER • Focal hypergranulosis grey white puncta

PRICKLE CELL LAYER1. Irregular acanthosis with saw-toothed rete ridges (older lesions)2. Intercellular edema

BASAL CELL LAYER1. Vacuolar alteration )Liquefaction degeneration( of the basal cells2. Colloid (Civatte, hyaline or cytoid) bodies 3. Max Joseph spaces (Clefts between the epidermis & dermis)

PAPILLARY DERMIS

1. Lichenoid lymphohistiocytic infiltrate dense, band-like infiltrate (interface dermatitis) 2. Colloid (Civatte, hyaline or cytoid) bodies 3. Melanin incontinence Melanophages4. LPP lymphohistiocytic infiltrate around hair follicle its destruction

Immunohistochemistry• In a nonspecific “sponge-like”

manner, colloid bodies often stain with fibrin, IgM, IgA, IgG or C3, and this is the characteristic finding by DIF.

• In LPP lesions, IgM, IgG and IgAare found in varying combinations along the follicle–dermalinterface.

Differential Diagnosis

DDx of Oral LP1. Lichenoid reactions2. Leukoplakia3. Candidiasis4. Chronic Ulcerative Stomatitis 5. Pemphigus Vulgaris 6. Cicatricial pemphigoid7. Erythema multiforme8. Syphilis9. Recurrent aphthae10. Lupus erythematosus11. Squamous cell carcinoma12. Frictional keratosis

Treatment

• Currently there is no definite cure for lichen planus but there are certain types of medicines used to reduce the effects of the inflammation.

• Lichen planus may go into a dormant state after treatment.• Principal aims: resolution of painful symptoms, resolution of

mucosal lesions, reduction of risk of cancer & maintenance of good oral hygiene.

Treatment

I. GENERAL MEASURES

II. LOCAL THERAPY

III. SYSTEMIC THERAPY

IV. PHOTO(CHEMO)THERAPY

V. SURGICAL TREATMENT

Treatment

I. GENERAL MEASURES “5”

1. Assurance

2. Avoidance of stress

3. Avoidance of sun in case of actinic LP

4. Stop offending drug

5. Rx of viral infection if present

TreatmentII. LOCAL THERAPY “5”

1. Topical steroid: Fluorinated e.g. clobetasol for cutaneous LP or triamcinolone, fluticasone (nasal spray) for oral LP.

2. Topical retinoids3. Topical calcineurin inhibitors: Tacrolimus or

pimecrolimus particularly for mucosal, ulcerative or hypertrophic LP (under occlusion).

4. Mouth washes: for oral LP e.g. lidocaine to numb the area and make eating more comfortable, steroids e.g. Dexamethasone elixir & antiseptics.

5. Intralesional corticosteroids; particularly for hypertrophic LP & LP of nails.

TreatmentIII. SYSTEMIC THERAPY “10”

1. Oral corticosteroids: indicated for short period when fail to respond to topical steroids. Prednisone 40 to 80 mg daily for less than 10 days without tapering & more prolonged course in sever cases.

2. Oral retinoid: acitretin.3. Immunosuppressant

medicationsa) MTX (low dose/week for oral

LP) , b) Cyclosporine (in severe

recalcitrant cases particularly LPP)

c) Sulfasalazined) Mycophenolate mofetil

4. Antimalarials: Hydroxychloroquin 200 mg b.i.d for actinic LP/LPP.

5. Dapsone: in resistant cases of erosive OLP.

6. Antihistamines7. Biologics: TNF alpha inhibitors,

basiliximab8. Thalidomide

9. Metronidazole: 500 mg b.i.d for 20-40d.

10. Grizofulvin for long term 3-6 mo.

Treatment

IV. PHOTO(CHEMO)THERAPY “5”

1. Narrow-band or broadband UV-B.

2. Psoralen with UV-A (PUVA).

3. UVA1

4. Excimer laser for oral LP.

5. Extracorporeal Photopheresis.

V. SURGICAL TREATMENT

• To remove high-risk dysplastic areas in OLP

1. Surgical excision

2. Cryotherapy

3. CO2 laser

4. ND:YAG laser

Treatment

Rx of oral LP

References• Dr shabeel pn Royal dental college

(Presentation).• Aaron Sarwal (BDS 3rd Prof.) (Presentation).• Raghavendra Kini, DV Nagaratna, Ankit Saha• Jp journals, 2011, 2(3): 249- 253 (Presentation

By Dr. Priyadershini A. Rangari).• Bolognia 3rd ed.