Mucocutaneous

1. MUCOCUTANEOUS DISORDERS

2. MUCOCUTANEOUS DISORDERS OF ORAL CAVITY INFECTIVE NON-INFECTIVE GENODERMATOSES

3. GENODERMATOSES White sponge nevus Darrier’s disease Peutz-Jeghers syndrome Dyskeratosis congenita Hereditary benign interepithelial dyskeratosis Panchyonychia congenita Hyalinosis cutis et mucosa oris Pseudoxanthoma elasticum

4. INFECTIVE Primary herpetic ginigivostomatitis Secondary herpetic ginigivostomatitis Varicella ( chickenpox) Shingles ( Herpes zoster) Measles Hand- foot-mouth disease Small pox and cat scratch disease Infectious mononucleosis Herpangia Acute lymphonodular phayngitis AIDS

5. NON-INFECTIVE VESICULAR NON-VESICULAR COLLAGEN DISORDER DEGENERATIVE AND RELATIVE DISORDER PIGMENTATION

6. A. VESICULAR Erythema multiforme Pemphigus Benign mucous membrane pemphigoid Bullous pemphigoid Epidermolysis bullosa Bullous lichen planus

7. B. NON VESICULAR Lichen planus Benign migratory glossitis

8. Lupus erythematous Scleroderma Polyarteritis nodosa Vasculitis Ischemic lingual necrosis Wegner granulomatosis Midline lethal granuloma C. COLLAGEN DISORDER

9. D.DEGENERATIVE AND RELATIVE DISORDER Amyloidosis Oral submucous fibrosis Senile solar elastosis

10. E . PIGMENTATION Racial pigmentation Endocrinopathy Addison disease Albert syndrome Bronze diabetes Anemia

11. ERYTHEMA MULTIFORME

12. ERYTHEMA MULTIFORME(EM) Erythema multiforme is an acute limiting dermatitis characterized by distinctive eruption manifested as the iris or target lesion. TYPES : EM Minor – Localized eruption with no or mild mucosal involvement EM Major – Mucosal erosions of raised atypical target lesions STEVEN JOHNSON SYNDROME(SJS) – Mucosal erosions ; widespread distribution of flat atypical targets or purpuric macules

13. Infectious agents : a.HSV { accounts for 55% of EM major} b. Mycoplasma infection c. Subclinical infection of HSV {EM minor} Drugs: Sulfa drugs are most common trigger factors (i)ETIOLOGY

14. Young adults – fourth or fifth decades of life Common in males Disease is characterized by occurrence of asymptomatic, vividly erythematous discrete macules, papules or occasionally vesicles and bullae distributed in a rather symmetrical pattern most commonly over the hands and arms, feet and legs , face and neck. (ii)CLINICAL FEATURES

15. TARGET LESIONS A concentric ring like appearance of the lesions , resulting from the varying shades of Erythema , occurs in the some cases and has give rise to TARGET or IRIS or BULL’S EYE describing them. Appears rapidly within a day or two and persist from several days to a few weeks , gradually fading and eventually clearing

16. Pain and discomfort Hyperemic macules , papules or vesicles may become eroded or ulcerated and bleed freely Common: Tongue , palate , buccal mucosa and gingiva ORAL MANIFESTATIONS OF EM

17. A severe Bullous form of Erythema multiforme It commences with the abrupt occurrence of fever, malaise, photophobia and eruptions of the oral mucosa, genital and skin Patients usually recover unless they succumb to a secondary infection STEVEN-JOHNSON SYNDROME

18. Oral manifestations SJS Severe and painful making mastication impossible Mucosal vesicles or bullae occur which ruptures leaving it covered with a thick white or yellow exudate Lips exhibit ulceration with bloody crusting and are painful Erosions of pharynx also common Mistaken for ANUG

19. EYE LESIONS: Photophobia Conjunctivitis Panophthalmitis Keratoconjunctivitis sicca GENITAL LESIONS: Non specific urethritis Balnitis Vaginal ulcers Others: Tracheo bronchial ulceration and pneumonia

20. HISTOPATHOLOGY In general the lesion show intercellular & intracellular edema of the epithelium with focal micro vesicle formation. Sometimes the edema results in a pooling of an eosinophilic coagulum within the epithelium. A generalized diffuse infiltration of both acute & chronic inflammatory cells are seen in the underlying C.T. with vasodilatation of blood vessels C.T. edema & sub-epithelial cleft.

21. TREATMENT If drug reaction is suspected ,it should be withdrawn Infections should be treated appropriately after culture / serologic tests have been performed Symptomatic treatment : Oral antihistamines Local skin care Topical steroids Soothing mouth washes Liquid antiseptics { 0.05% chlorhexidine } Systemic corticosteroids are controversial

22. PEMPHIGUS

23. Chronic skin disease characterized by the appearance of vesicles and bullae , small or large fluid filled blisters that develop in cycle Characterized by intraepithelial bulla formation TYPES: Pemphigus vulgaris Pemphigus foliaceous Paraneoplastic Pemphigus Pemphigus vulgaris is the most common type of oral lesion

24. Epithelial cell separation : Binding of IgG antibody to Pemphigus antigen leads to the epithelial cell separation by triggering complement activity . Separation of cell takes place in lower layer of stratum spinosum Associated factors : Autoimmune disorders like thymoma, myasthenia gravis and multiple autoimmune disorders, it may also be triggered by drug therapy like penicillamine, penicillin etc (i)MECHANISM

25. 5 th to 6 th decades of life Size : thin walled bullae or vesicles varying in diameter from few mm to several cm on normal skin Signs : lesion contain thin , watery fluid shortly after development , but may become purulent later . They rapidly break and continue to extend peripherally , leaving behind large denuded skin Nikolsky sign : Application of pressure in normal skin >>> New lesion appears ; reason: upper layer of skin pulling away from basal layer and prevesicular edema which disrupts the dermal-epidermal junction. (ii)CLINICAL FEATURES

26. Sites: Buccal mucosa { reason : it has less intercellular substance and fewer intercellular junctions leading to easier acantholysis} ; palate and gingiva Onset: classic bullae on non inflamed base > ruptures > shallow ulcers Symptoms : bleed easily ; severe pain ; unable to eat Signs: thin layer of epithelium peels easily in a irregular pattern leaving behind denuded base (iii)ORAL MANIFESTATIONS

27. Intraepithelial vesicle or bullae just above basal layer producing distinctive suprabasilar split Prevesicular edema appears which weakens the intercellular bridges and junctions Loss of cohesiveness { ACANTHOLYSIS} because of which clumps of epithelium are often found lying free in the vesicular space { TZANCK CELLS } Fluid in the vesicles : variable numbers of PMN leukocytes and lymphocytes SCARCITY of inflammatory cell infiltrate in CT and vesicular fluid differentiate Pemphigus from other Bullous (iv)HISTOLOGY

28. Tzanck test, also Tzanck smear, is scraping of an ulcer base to look for Tzanck cells. Tzanck test is very useful for the diagnosis of PV, particularly in the early stages of oral Pemphigus where a biopsy is uncomfortable to the patient It reveals multiple acantholytic cells (Tzanck cells). A typical Tzanck cell is a large round keratinocyte with a hypertrophic nucleus, hazy or absent nucleoli, and abundant basophilic cytoplasm. The basophilic staining is deeper peripherally on the cell membrane ("mourning edged" cells) due to the cytoplasm′s tendency to get condensed at the periphery, leading to a perinuclear halo. TZANCK TEST

29. Intercellular staining of epidermal skin cells with fluorescent markers in a patient with pemphigus vulgaris using direct immunofluorescence .

30. Pemphigus foliaceous Mild form, common in older adults Bullous ruptures and DRY to leave masses of flakes or scales suggestive of an exfoliative dermatitis or eczema Pemphigus erythematosus Senear-usher syndrome Bullae or vesicles concomitant with crusted patches , ultimate terminate to vulgaris of foliaceous Associated fever or malaise Paraneoplastic Pemphigus Neoplasm like lymphoma or chronic leukemia Palmar or plantar bullae appear , which does not occur in other types

31. Corticosteroids : Topical and systemic prednisolone Combination therapy : High dose of corticosteroids + immunosuppressive drugs such as cyclosporine or azathropine Plasmapheresis (v)MANAGEMENT

32. BENIGN MUCOUS MEMBRANE PEMPHIGOID { CICATRICIAL PEMPHIGOID}

33. Cicatricial pemphigoid  (also known as "Benign mucosal pemphigoid," "Benign mucous membrane pemphigoid" ,"Ocular pemphigus "and "Scarring pemphigoid") is a rare chronic autoimmune sub epithelial blistering disease characterized by erosive skin lesions of the mucous membranes and skin that results in scarring of at least some sites of involvement. Etiology : Auto antibodies of IgG subclass , particularly IgG4 are associated Common : Females ; 4 th to 5 th decades of life ; Sites: oral and eye lesion ; also affects skin and genitals Feature : Heals by scar

34. Ocular involvement are the most serious complication Adhesions develop between palpebral and bulbar conjunctivae Opacity of cornea leads to blindness

35. Sub epidermal vesicle or bullae No acantholysis Non specific Chronic inflammatory infiltrate in connective tissue chiefly lymphocytes and plasma cells HISTOPATHOLOGY

36. BULLOUS PEMPHIGOID {Parapemphigus}

37. An chronic, autoimmune , subepidermal blistering skin disease that involve mucous membranes. The antigens are bullous pemphigoid-antigen 1 (BPAG1; 230kD) which belongs to a family of genes that includes desmoplakin and bullous pemphigoid antigen 2 (BPAG2; 180kD; Type VII collagen). The primary lesion of B.P. is a tense blister which arises on either normal appearing or erythematous skin At times the lesions may arise on urticarial plaques Most commonly the lesions are found in the flexural areas Oral lesions are far less frequent

38. Oral blisters if present, are mild and transient in contrast to pemphigus Rarely involves oral mucosa Gingival lesions resembles Cicatricial pemphigoid Appears extremely erythematous and may desquamate Also occurs on buccal mucosa, palate, floor and tongue Positive Nikolsky sign ORAL MANIFESTATIONS

39. HISTOPATHOLOGY: The dermal papillae are well preserved but edematous Unlike cicatricial , basement membrane remains attached to connective tissue No acantholysis Vesicles contain a fibrinous exudate admixed with occasional inflamatory cells Direct immunofluorescent examination remains the standard way to confirm the diagnosis

40. EPIDERMOLYSIS BULLOSA

41. Epidermolysis bullosa ( EB) is a group of inherited bullous disorders characterized by blister formation in response to mechanical trauma Etiology: Mutation of genes It classified into three types: 1.Epidermolysis bullosa simplex- keratinin genes 2.Junctional Epidermolysis bullosa- laminin genes 3.Dystrophic Epidermolysis bullosa-type VII collagen

42. Blistering of the skin Tooth decay Deformed or lack of finger/toe nails Internal blistering in the throat, stomach, and intestines Scalp blistering and loss of hair Excessive sweating Hardening of the skin on the feet or hands Thin skin appearance and white bumps Difficulty swallowing The symptoms vary from the different types. (ii) Signs and symptoms

43. (iii) ORAL MANIFESTATIONS SOFT TISSUE MANIFESTATIONS: Increased fragility Perioral lesions Microstomia Ulcerations Ankyloglossia Obliteration of oral vestibule DENTAL MANIFESTATIONS: Junctional EB have severe enamel hypoplasia Risk for dental caries Severe dental crowding and deep bite

44. Histologic sections of skin show separation of the epidermis from the dermis in a subepidermal plane. There is absence of a significant inflammatory response. The adjacent epidermis is normal.

45. ORAL LICHEN PLANUS

46. Most common mucocutaneous lesion Chronic inflammatory disease of the  oral  mucosa and skin Etiology: Although the cause is not well known, T cell-mediated autoimmune phenomena are involved in the pathogenesis of lichen planus. Possible etiology for unmasking the antigen are contact allergens in restorations or tooth paste. Lichenoid drug reaction may be due to drugs Characteristic feature: Bilateral white striations, papules, plaques on the buccal mucosa, tongue and gingiva

47. Lichen planus affects primarily middle-aged a dults, and the prevalence is greater among women. The classic skin lesions of the cutaneous form of lichen planus can be described as six "Ps":  pruritic, polygonal, planar, purple ,papules and plaques (i) CLINICAL FEATURES

48. (ii) Signs and symptoms The lesions may appear as: Lacy, white, raised patches of tissues Red, swollen, tender patches of tissues Open sores Location Inside of the cheeks, the most common location Gums Tongue Inner tissues of the lips Throat Esophagus Pain or discomfort The red, inflamed lesions and open sores of oral lichen planus can cause a burning sensation or pain. The white, lacy patches alone usually don't cause discomfort, except when they appear on the tongue.

49. Other signs or symptoms A metallic taste or a blunted taste sensation if the tongue is affected Dry mouth Difficulty swallowing if the throat or esophagus is affected Sensitivity to hot or spicy foods Bleeding and irritation with tooth brushing Skin.  Lesions usually appear as purplish, flat-topped bumps that are often itchy. Genitals.  Lesions on external genitalia resemble those affecting the skin. Lesions affecting the mucous membrane of the vagina resemble those affecting the mouth. Scalp.  When skin lesions appear on the scalp — a rare condition — they may cause temporary or permanent hair loss. Nails.  Lichen planus of the toenails or fingernails, also rare, may result in ridges on the nails, thinning or splitting of nails, and temporary or permanent nail loss.

50. WICKHAM’S STRIAE Wickham striae  are Characteristic, fine, white or grey lines or dots seen on the top of the pruritic papular rash of lichen planus The macroscopic appearance of the histologic phenomenon and hypergranulosis, and named for Louis Frédéric Wickham.

51. 1.The Reticular Pattern: The reticular pattern is considered the classic form of lichen planus. This form occurs most frequently, and its white lacy lines called Wickham's striae characterize the lesions   Commonly, the tissue is somewhat raised and the patient may report that the areas in contact with the tongue feel rough in texture

52. 2.The Plaque Form  is represented by thick, plaques of varying sizes, that may be smooth and appearing somewhat lighter in color than surrounding tissue (non-descriptive leukoplakia)  The tongue is a particular area where these plaques may be noticed.  They often appear as a "bald" area of concern with denuded papillae.  Higher association with malignant transformation

53. 3.The Papular Pattern  : The papular pattern is noted by the small, pin point papules appearing as small white dots measuring approximately 0.5 mm in size.  The papular pattern may be in conjunction with other forms of lichen planus and may be over looked in an oral examination depending upon the number of papules and the distinct appearance of the lesions

54. 4.The Bullous Form:   The bullous form consists of vesicles ranging from a few millimeters in diameter to much larger vesicles. Eating and speaking will usually cause the vesicles to rupture soon after forming. This form is seen most often on the buccal mucosa followed by the tongue

55. 5.The Atrophic Form - also called erythematous form. The atrophic form presents as diffuse reddened patches that may be in combination with other forms of lichen planus such as the white striations of the reticular form. Often found on the attached gingiva , the patient may complain of irritation or burning sensations. Lesions are poorly defined and may have striae at the peripheral areas. When this form involves the gingiva, it is sometimes referred to as " desquamative gingivitis" which is a clinical term used by some clinicians denoting a reddened appearance of the tissue. Other skin diseases may appear similar and this term is not diagnostic . In addition, the atrophic form may be confused with BMMP and may appear similar to the gingival depicted 

56. Atrophic Form consists of red, erythematous areas and may include a reticular/plaque like surface. Atrophic form sometimes described as desquamative gingivitis. This form when affecting the gingiva is definitively diagnosed through biopsy and immunofluorescence. Red marginal area affected by the lichen planus and the noted plaque-like areas superior to the marginal areas.

57. 6.The Ulcerative Form.   As the term indicates, the ulcerative form features one or several ulcers that are often seen in association with any of the other disease forms. This form is quite painful for the patient and the soreness of the tissue will affect eating and brushing of the teeth. The ulcerations may affect any tissue surface and may even extend into the soft tissues of the tonsillar pillars and esophageals areas. This form is reported as having a higher number of malignant tissue changes. The ulcerative nature of this form probably allows more detrimental tissue changes with chronic irritation and possibly a port of entry for pathogens.

58. Highly erosive area of lichen planus in the soft plate region A mixture of erosive and reticular lichen planus with some candida albicans present on tongue and buccal mucosa. Erosive type of lichen planus with loss of surface epithelium in the buccal mucosa.

59. Lichenoid Reactions: The most common material used in dentistry that may cause a lichenoid reaction is amalgam, although other known dental materials have been implicated as well.  The mercury in the metal alloy usually causes the hypersensitivity reactions  Hypersensitivity reactions may also be due to flavoring agents or food products or drugs  The lesions are usually isolated and they do not subside as long as the tissue is in contact with the restoration

60. The epidermis is  hyperkeratotic  with  irregular acanthosis  and focal thickening in the granular layer .(wedge-shaped hypergranulosis) The upper dermis has a  band like infiltrate of lymphocytic (primarily helper T) and histiocytic cells with many Langerhans cells at the dermal-epidermal junction . The lymphocytes are intimately associated with basal keratinocytes , which shows degeneration ,necrosis & resemblance in size & contour to more mature cells of Stratum spinosum. This is SQUAMATIZATION. As a consequence to this destructive infiltration ,results in redifining of normal smoothly undulating configuration of dermoepidermal junction to more angulated zigzag contour ("saw-tooth" appearance of the rete pegs). Pigment incontinence  due to damage of basal keratinocytes and melanocytes.(this leads to hyperpigmentation of lesion ) (iii) HISTOPATHOLOGY

61. Saw tooth rete pegs

62. CIVATTE BODIES: Anucleate ,necrotic basal cells  become incorporated into inflamed papillary dermis -these are civatte bodies or colloid bodies. These are  characteristic of lichen planus  (but can be found in any chronic dermatitis where basal keratinocytes are injured) In addition to  apoptotic keratinocytes, colloid bodies are composed of globular deposits of IgM (occasionally immunoglobulin G [IgG] or immunoglobulin A [IgA]) and   complement. Max Joseph clefts : Basal keratinocytes weakens the epithelial interface causing histologic clefts

63. 1.Corticosteroids Corticosteroids may reduce inflammation associated with oral lichen planus. The side effects vary depending on types of usage Topical.  mouthwash or ointment Oral.   taken as a pill Injections.  Injections may be administered directly into lesions. Repeated use of corticosteroid injections can cause some of the same side effects as oral corticosteroids. 2.Retinoids Retinoid are synthetic versions of vitamin that can be applied as a topical ointment or taken orally. 3.Nonsteroidal ointments Calcineurin inhibitors, which are closely related to or identical to oral medications used to prevent rejection of transplanted organs. These treatments appear to be effective for the treatment of oral lichen planus. Examples :Tacrolimus (Protopic ointment) and pimecrolimus (Elidel cream). 4.Addressing triggers Drugs.  stop the drug or try an alternative drug Allergen. advised to avoid the allergen Stress.   stress may be a factor that complicates symptoms or triggers the recurrence (iv) MANAGEMENT

64. WHITE SPONGE NEVUS {CANNON’S DISEASE , HEREDITARY LEUKOKERATOSIS OF MUCOSA}

65. White sponge nevus (WSN) is a rare autosomal dominant disorder, w ith a high degree of penetrance and variable expressivity. The cause is a mutation in the mucosal keratin 4 or keratin 13 genes. Since it is inherited, it can be present at birth or at puberty. It is a benign, uncommon, and predominantly affects non-keratinized stratified-squamous epithelia

66. ( i) ORAL MANIFESTATIONS A thick, corrugated bilateral white plaque with a spongy texture, usually on the buccal mucosa, but sometimes on the labial mucosa, alveolar ridge or floor of the mouth. Asymptomatic The gingival margin and dorsum of the tongue are almost never affected . Although this condition is perfectly benign, it is often mistaken for leukoplakia Ragged white areas which can be removed by gentle rubbing

67. ( ii) HISTOPATHOLOGY Hyperparakeratosis epithelium , acanthosis present Basal layer intact Cells of spinous layer show Intracellular edema Submucous have inflammatory cell infiltrate Vacuolated and dyskeratotic epithelial keratinocytes are present that demonstrate perinuclear eosinophilic condensations.

68. Hyperparakeratosis , acanthosis, and spongiosis in stratified squamous epithelium. The associated connective tissue is usually free of inflammation  cells of spinous layer show a shrunken nucleus  (fried egg appearance)