Lichen planus and lichenoid disorders

post graduate at narayana medical college

1. LICHEN PLANUS AND LICHENOID DISORDERS - Dr M.HIMA VINUTHNA M.D (DVL) PG

2. LICHEN PLANUS Idiopathic,Chronic,Inflammatory disease that affects the Skin,Mucous membranes and Appendages.

3. MORPHOLOGICAL Extremely pruritic Flat topped Polygonal Violaceous papules and plaques

4. Compact hyperkeratosis Wedge shaped hypergranulosis Irregular acanthosis ' Saw-toothing ' of rete ridges Vacuolar degeneration of basal epidermal keratinocytes Band like infiltrate that often obscures the DEJ HISTOLOGICAL Degenerative keratinocytes (colloid bodies) in the lower epidermis Ocassionally,space between epidermis and dermis (Max-Joseph space) seen due to interface inflammation

5. EPIDEMIOLOGY FREQUENCY - 0.1-4% DISTRIBUTION – World wide - High prevalence rate in Indian subcontinent . RACE – Not significant. SEX – Not significant - But females are affected earlier than males. AGE – Can occur at any age but more in people aged between 30-60 years. FAMILY HISTORY – Positive family history in childhood LP cases than adult LP cases. INVOLVEMENT – Mucous membrane -30-70% - Nail -10%

6. ETIOLOGY Auto immune Drugs T-cell theory Infections & vaccines

7. Auto immune theory : increased association between LP & other auto immune diseases such as -Ulcerative colitis -Myasthenia gravis -Lupus erythematosus -Alopecia areata -Diabetic mellitus Infections & vaccines : Hepatitis C & B Killed Influenza MMR DPT

8. Drugs :

9. T-Cell Theory(CD4+,CD8+,Th17) : Induces production of chemokines and other cytokines which upregulate local inflammatory infiltrate .

10. PATHOGENESIS Autoimmune Familial Viruses Dental Amalgam Miscellaneous

11. Autoimmune T-cells CD4+ CD8+ Th17 Cytokines IFNγ TNFa NF-kB IL-1a,IL-6,IL-8 Fas/2 Apo-1 & Bcl-2

12. Familial : HLA-B7(1) HLA-28 Viruses : Hepatitis C virus Dental Amalgam : Dental restorative materials containing silver-Mercury compounds have known to induce oral lichenoid lesions. Allergens that elicit a positive reaction are- METALS – Silver,Mercury,gold,nickel,palladium CEMENT – Eugenol,potassium dichromate,cobalt chloride PERFUME – Balsam of peru Miscellaneous : Anxiety,Depression,Stress Radiotherapy

13. CLINICAL FEATURES CLASSIC FORM : Extremely pruritic,flat topped, polygonal,violaceous papules and plaques of size 3-15mm in diameter Delicate radiating white scales ( wickham’s striae ) Positive koebner’s phenomenon SITES INVOLVED : Flexor surface of wrist and forearms Dorsal surface of hands Anterior aspect of lower legs Neck and lower back

14. VARIANTS OF LICHEN PLANUS MORPHOLOGY HYPERTROPHIC ATROPHIC EROSIVE / ULCERATIVE ERUPTIVE / GUTTATE FOLLICULAR / LICHEN PLANOPILARIS VESICULOBULLOUS ACTINIC LP PIGMENTOSUS CONFIGURATION ANNULAR LINEAR DISTRIBUTION ORAL OESOPHAGEAL MUCOSAL GENITAL INVERSE PALMOPLANTAR NAIL SPECIAL LP- LE OVERLAP SYNDROME LP PEMPHIGOIDES CONJUNCTIVAL

15. MORPHOLOGY 1. Hypertrophic lp Shin and Ankles Extremely pruritic Thicked and Elevated,Pruritic or reddish brown Hyperkeratotic Ocassionally,with time they form thick verrucous plaques & central depigmentation SCC in long standing cases. Psedoepitheliomatous hyperplasia Compact hyperkeratosis Irregular acanthosis Interface infiltrate less band-like Cystic dilatation of hair follicles DD : Nodular prurigo , LSC, Lichen Amyloidosis, Warts

16. 2. ATROPHIC LP Lower limbs Occurs after resolution of typical LP They start as violaceous papules & coalesce to form large plaque with depressed atrophied centre Thinning of epidermis upto granular layer Fibrosis of papillary dermis Effacement of rete ridges Fewer colloid bodies DD : Lichen sclerosus et atrophicus , Morphea

17. 3.EROSIVE/ULCERATIVE LP Mucosal surfaces of oral cavity and genatalis . Rarely- Palms and Soles Aggressive form of LP & may end to SCC Presence of erosions on surface of papular lesions Epidermal ulceration with typical changes of LP at margin of the ulcer

18. 4.ERUPTIVE/GUTTATE LP Trunk, inner aspect of wrist , dorsum of feet. Acute or Exanthemous LP Widely distributed & Disseminated lesions DD: Guttate psoriasis Pityriasis lichenoides chronica papulosquamous secondary syphilis

19. 5.FOLLICULAR LP/LPP Frontocentral scalp and Crown Women Lesions are multifocal and eventually may coalesce to produce large area of hairloss ; underlying skin is hypopigmented and devoid of follicular ostia Perifollicular erythema and perifollicular scales are typically present at the periphery of active lesions. Disease activity is greater at periphery of alopecia patch. LPP usually presents as irregular patchy haiross , with loss of follicular ostia , a hallmark of cicatricial alopecia Moderate to severe scalp pruiritis and dysesthesia are common. RARE VARIANTS OF LPP: Graham-Little- Piccardi - Lassueur Syndrome Frontal Fibrosing Alopecia

20. Compact orthokeratosis. Dilated follicular infundibula filled with hyperkeratosis. Slight hypergranulosis . Atrophic follicular epithelia with perifollicular fibrosis and new collagen formation. Dense lichenoid infiltrate of lymphocytes and histiocytes at DEJ of the upper portion hair follicles. Prominent vacuolar degeneration & keratinocytic necriosis of basal layer DD : SKIN - lichen nitidus,lichen spinulosus SCALP - DLE, cicatricial pemphigoid,PIF,alopecia areata

21. 6.VESICULOBULLOUS LP Shin,upper limbs and thighs Development of bristles within the papules of LP due to severe liquefactive degeneration of basal layer of epidermis Typical histopathological changes of LP with subepidermal bulla. There is a heavy dermal infiltrate with numerous colloid bodies.

22. 7.ACTINIC LP Forehead and Face followed by dorsal surface of Hands and Neck. Young adults and children Summer Lesions are blue,brown plaques that show annular configuration with atrophied centre and hypopigmented raised border Epidermis is atrophic at centre of lesion Focal parakeratosis. Melanophages are more abundant Pigment incontinence more intense DD: PMLE HISTOLOGY

23. 8.LP PIGMENTOSUS Sun exposed areas and flexural folds Seen in skin types 3 & 4 Slate grey to brownish-black macules Diffuse pattern of pigmentation is more common Prominent pigment incontinence extending to the reticular dermis Inflammatory infiltrate less prominent DD : Erythema dyschromicum perstans

24. CONFIGURATION Glans penis or trunk Typical violaceous papules arranged in ring like fashion or a single large plaque showing central clearing. Most unusual variant- ANNULAR ATROPHIC LP 1.ANNULAR LP (Ring-like lesion) DD : Granuloma annulare

25. 2.LINEAR LP Limbs, Trunk Lesions are in linear pattern along the Lines of Blaschko . Not to be confused with koebner phenomenon DD: Lichen spinulosus linear verrucous epidermal naevus

26. DISTRIBUTION Buccal mucosa,lateral margins of tongue,Gingiva,Lips & Hard Palate MORPHOLOGICAL TYPES: A) ORAL LP: 1.MUCOSAL LP Reticular Plaque- like Bullous Atrophic Erosive Papular Reticular oral LP - Assymtomatic,irregular,atrophic plaques with white streaks in a lacy pattern involving posterior buccal mucosa bilaterally Dental amalgam materials cause oral LP Stress,spicy and acid foods flare-up the disease. DD: leuloplakia , oral pemphigus

27. B) GENITAL LP: Males- Glans penis,shaft,prepuce,srotum Females - Vulva,vagina Annular lesions more common in men Vulval introital erosions surrounded by white,lacy,reticulate borders extending onto vagina. DD: Males - psoriasis,lichen sclerosus et atrophicus Females - leukoplakia,lichen sclerosus et atrophicus

28. Rarely involves esophagus Middle aged women Dysphagia, Odynophagia or both Esophageal stricture & SCC Endoscopy to be done C) OESOPHAGEAL LP: D) CONJUNCTIVAL LP : May manifest as cicatricial conjuctivitis

29. 2.NAIL LP Most common in adults(50-60years) Usually affect several or most nails with a chronic course Finger nails nails more commonly affected than toe nails . PUP- TENT Sign

30. Unusual changes of LP Granular layer is present Colloid bodies are rare DD: Onychomycosis,nail psoriasis HISTOLOGY

31. 3.PALMOPLANTAR LP Internal plantar arch and palms with sparing of finger tips Young Men aged between 20-40yrs. Highly Pruirigenous , Erythematous,Scaly Plaques with or without Palmoplantar Keratoderma. DD: Callosities,Warts,Secondary Syphillis

32. 4.INVERSE LP Axillae,groin,cubital and popliteal fossa. Reddish brown,discrete papules and nodules

33. SPECIAL FORMS 1. LP PEMPHIGOIDES Distal limbs Tense blisters occurs both on LP lesions and unaffected skin DIF shows linear deposition of IgG & C3 along the BMZ On uninvolved skin : Sub epidermal bullae Dermal infiltrate not band like Plenty of eosinophils On LP : Features same as LP Few neutrophils and eosinophils. DD: Bullous LP

34. 2.LP-LE OVERLAP SYNDROME Patients have overlapping clinical, histological & immunological features of LP-LE.

35. DIAGNOSIS Based on the characteristic clinical and histological features. DIF reveals ragged or shaggy fibrin BMZ band. Globular deposition of colloid bodies staining with IgM mainly & lesser extent with IgA, IgG, C3 is seen in upper dermis.

36. TREATMENT 1 ST LINE THERAPY – TOPICAL CORTICOSTEROIDS - 1 ST GENERATION ANTI-HISTAMINES ( Hydroxyzine&Chlorphenaramine ) - INTRALESIONAL STEROIDS ( Hypertrophic,NLP,Erosive LP) - IMMUNOMODULATOR ( Tacrolimus&Pimicrolimus ) - TOPICAL MINOXIDIL (LPP) 2 ND LINE THERAPY – SYSTEMIC CORTICOSTEROIDS ORAL - Oral prednisolone (0.5-1mg/kg/day) for 4-6weeks or - Oral minipulse therapy with Betamethasone IM - Triamcinolone (40-80mg) every 6-8 weeks - ORAL RETINOIDS – Acitretin 30mg daily for 8 weeks - PHOTOTHERAPY – NVUVB/PUVA CUTANEOUS LP

37. 3 rd LINE THERAPY – IMMUNOSUPPRESSIVE AGENTS Methotrexate - 10-15mg/week (Severe Erosive & Generalized LP) Cyclosporine - 5mg OD for 4-6 wks (LPP) Others- Azathioprine, Cyclophosphamide, Myophenolate mofetil MUCOSAL LP: 1st LINE THERAPY – TOPICAL STEROIDS - Clobetasol propionate (Oral LP) ILS ( Localised chronic ulcerative LP) TOPICAL TACROLIMUS&PIMICROLIMUS (ulcerative cases) 2 nd LINE THERAPY – Hydroxychloroquine (Oral LP) - Local phototherapy - NVUVB,PUVA (Oral LP)

38. COURSE Skin lesions subside in about 24months in majority of patients, but in 20% of patients they relapse Eruptive LP for short course with remission in 3-9 months Oral,Hypertrophic , LPP- protracted course

39. LICHENOID DISORDERS Conditions which simulate lesions of LP clinically are called Lichenoid Disorders. They include Lichenoid Drug Eruptions Lichenoid Contact Dermatitis Lichen Striatus Lichen Nitidus Lichen Spinulosus Benign Lichenoid Keratosis Nekam’s Disease Frictional Lichenoid Eruption Graft Vs Host Disease

40. LICHENOID DRUG ERUPTIONS Many drugs may induce lichenoid dermatitis and lesions develop over weeks to months after starting the therapy. Resembles LP on clinical & Histological basis

41. LICHENOID CONTACT DERMATITIS & MUCOSITIS Chemicals which induce LCD are- Methacrylic Acid,nickel,silver,gold,musk Ambrette,dental Restorative Materials,developers used in processing color films . Lesions start at site of contact and may spread subsequently Intra oral metal contact allergy occur due to contact with Dental Amalgam materials result in Mucositis Resolution after removal of Dental Amalgum SITES - Buccal Mucosa and Tongue adjacent to amalgum Histopathology That Distinguish Amalgum Associated Oral Lichenoid Reaction From Oral LP Are : Inflammatory infiltrate locater deeper in interface infiltrate on some or all areas. A focal perivascular infiltrate Plasma cells & neutrophils in connective tissue

42. LICHEN STRIATUS Uncommon,benign,self limiting,linear,inflammatory dermatoses of unknown etiology They are shiny,flat topped,erythematous papules-cluster in a continuous or interrupted linear pattern of width 1-3cm Along the lines of Blaschko’s . Unilateral & solitary Common site-Legs. Sudden in onset and progress to clinical picture in days to weeks. Symptoms – Intense pruiritis Nail involvement- Onychodystrophy and sub ungual hyperkerstosis . Restricted to single lane and limited to medial or lateral portion. Hair involvement- transient focal hairloss

43. ETIOPATHOGENESIS Combination of genetic and environmental factors Viral infection or immunization may trigger onset of LS. Strong association of atopy Happle proposed a theory of epigenetic mosaicism Epidermal hyperkeratosis Focal parakeratosis Band like lymphohistiocytic infiltration of dermis- this surrounds eccrine sweat glands and duct DIF : Civatte body staining with IgM,IgG C3-negative in LS

44. TREATMENT Spontaneous resolution Topical corticosteroids to hasten resolution Topical Tacrolimus for no risk of skin atrophy that is seen with steroids .

45. LICHEN NITIDUS Benign inflammatory skin disorder of unknown etiology Children Numerous,pin point to pin head cells sized,flesh to pink colored papules with flat and shiny surface and localized Exhibit Koebner phenomenon. Abdomen,chest,penis&flexural surface of extremities

46. Mucosal involvement - rare. but if present- discrete,grouped,yellowish papules of 1mm on hard palate and gum. Nail involvement - longitudinal beaded ridges,terminal splitting & irregular pittings Clinical variants : Confluent Vesicular Haemorrhagic Palmoplantar Spinous Follicular Perforating Actinic- summertime actinic lichenoid eruption linear ‘Claw clutching a ball’ Ball represents-well circumscribed area of lymphohistiocytic infiltrate in papillary dermis close to DEJ. Claw represents- elongated rete ridges near the margins. Epidermis often thinned out.

47. DD : Keratosis pilaris,lichen spinulosus,verruca plana TREATMENT Spontaneous resolution in 1year without scarring or pigmentary changes Therapeutic mordalities-PUVA,NBUVB,Systemic steroids,itraconazole,isoniazid .

48. LICHEN SPINOSUS Idiopathic disorder Children and adolescents Males Skin colored and asymptomatic,scattered 2-6cm patches of keratotic follicular papules.individual papules have hair like horny spine that gives NUT MEG GRATER feel on palpation. Etiology -Atopy and genetic factors. Treatment - emollients,midpotency topical corticosteroids,salicylic acid,12%lactic acid,tretinoin gel(0.04%

49. BENIGN LICHENOID KERATOSIS LP-Like keratosis 5 th and 6 th Decade Women Upper Trunk and Extremities Single,slightly raised , grayish brown or red-brown papule or plaque with 3-19mm diameter Histopathology : similar to LP ocassionally reminiscent of seborrheic keratosis or solar lentigen seen at periphery of lesion.

50. KERATOSIS LICHENOID CHRONICA (NEKAM’S DISEASE) Adults btw age 20-40 yrs.children occasionally Violaceous ,p a pular & nodular lesions arranged in linear and reticulate pattern Extremities,buttocks,face Extensive disease -antecubital fossae,externsor aspect of forearms forearms,lumbosacral area,buttocks,posterior aspect of thigh,popliteal fossae Oral manifestations -recurrent aphthous ulcers,large chronic ulcers,erythrokeratotic papules Nail manifestations - thickened,longitudinal ridging,prone to paronychia

51. HISTIOPATHOLOGY - Diffuse from LP by presence of TREATMENT Focal parakeratosis Alternating areas of acanthosis and epidermal thinning Heavier upper dermal infiltrate Presence of plasma cells PUVA alone or in combination with retinoides Topical calcipotriol,oral isotretin and combination of tacalcitol & acitretin are benefited

52. FRICTIONAL LICHENOID ERUPTION Children between 2 & 12 yrs of age Male:female-3:1 Flat,lichenoid,reddish to skin colored papules,1-2mm in diameter that often coalesce Elbows,knees,dorsum of hands and fingers rarely-cheeks and buttocks. H/O Atopy Pathogenesis - Contact with an abrasive material Histology- Slight hyperkeratosis,Acanthosis & a perivascular,peri adnexal,lymphocytic infiltrate in upper epidermis that does not reach DEJ.

53. GRAFT VERSUS HOST DISEASE Frequent complication of allogenic bone marrow transplantation,heart or liver transplantation and after blood transfusion DIFFERENT FORMS : 1.Acute GVHD 2.Chronic GVHD

54. 1.ACUTE GVHD Occurs during the first 3 months following bone marrow transplantation Target organs - skin,GIT,liver Cutaneous eruptions - mild,morbilli form rash with acral accentuation or rarely a severe toxic epidermal necrosis They develop spontaneously or triggered by UV radiation,physical trauma or infections

55. 2.CHRONIC GVHD Develop after 3rd month following transplantation TH2 cytokine play a predominant role in pathogenesis Cutaneous eruptions may appear in continuity of previous acute GVHD Skin and mouth are involved Cutaneous manifestations- 1.Lichenoid 2.sclerodermoid

56. 1.LICHENOID GVHD Violaceous papules and plaques that resemble idiopathic LP Sites-Periorbital region,ears,palms and soles. Nails and oral lesions similar to that of idiopathic LP. Genital mucosa may be affected with development of phimosis and vaginal strictures. Treatment -combination of corticosteroids and immuno-suppressants like azathioprine,cyclosporine,methotrexate . High dose Thalidomide( 200-800mg/day) PUVA THERAPY,NVUVB are tried in management of chronic GVHD

57. REFERENCES IADVL Rook’s text book of dermatology Fitzpatrick Dermatology in GM Articles- ijdvl,aad