1. WHITE LESIONS OF ORAL MUCOSA

2. “White patch” is a term used clinically to describe the appearance of lesions presenting as white area on the oral mucosa”

3. white patch may be: Non- keratotic (transient): easily wiped off
e.g. chemical burn & thrush
Keratotic (persistent): firmly adherent & resist rubbing
e.g. most keratotic lesions
Easily rubs away with gauze:
Pseudomembranous candidosis
Traumatic lesions
Not easily rubs away with gauze:
Leukoplakia
LP and lichenoid reactions
SLE
Chronic hyperplastic candidosis
Oral warts

4. White lesions Classification based on etiology
Developmental, hereditary or genokeratosis
Traumatic
Inflammatory:
Infective:
Viral
Bacterial
Fungal
Non infective dermatological conditions: LP, LE
Neoplastic or preneoplastic
Metabolic
Miscellaneous: skin grafts, scars, materia alba

5. Developmental white lesions (Genokeratosis)
Many types
All are rare
There may be a family history
All of those with family history inherited as autosomal dominant except dyskeratosis conginita
All manifest clinically in the mouth as white patch and associated with skin lesions and other features

6. TYPES OF DEVELOPMENTAL WHITE LESIONS
White sponge nevus
Hereditary benign intraepithelial keratosis
Keratosis follicularis (Darier’s disease)
Pachyonychia congenita
Dyskeratosis congenita

7. pachyonychia congenita
white thickening lateral side and dorsum of the tongue
characteristics thickening of the nails

8. White lesion in a patient with Darier's disease

9. Dyskeratosis conginita

10. White sponge nevus Autosomal dominant but family history may be absent
Appears early in life but may manifest at later stage on oral mucosal surfaces
Asymptomatic, diffuse white lesions with shaggy wrinkled surface
May involve other areas like pharynx, esophagus, nose and genital areas
Diagnosis is made on clinical basis
Incisional biopsy is confirmatory of its diagnosis

11. White sponge nevus

12. Thermal e.g. tobacco smoking
Nicotinic stomatitis

13. Traumatic white lesions
Mechanical:
Frictional keratosis:
Caused by sharp standing tooth, ill fitting denture or cheeck biting
Has no malignant potential
Resolve if the cause is eliminated
Habitual cheeks biting

14. Frictional keratosis

15. Traumatic white lesions
Chemical e.g. aspirin burn
close to badly carious tooth
patient most often admits using the chemical
may be caused by any other strong caustic substance applied to oral mucosa
Scrabable
Physical e.g. radiation mucositis

18. Traumatic white lesions
A combination of one or more of the above (thermal, mechanical and chemical):
smoker’s keratosis:
pipe smoking: nicotinic stomatitis (smoker’s palate)
tobacco chewing, snuff dipping and other smokeless tobacco habits may produce white verrucous keratosis
Nicotinic stomatitis is reversible with no malignant potential

19. Infective white lesions
Bacterial:
Syphilitic leukoplakia
Viral:
Hairy leukoplakia
Focal epithelial hyperplasia (Heck’s disease)
Oral warts
for more details go to the appropriate topics in the course
Fungal:
Acute pseudomembranous candidosis
Chronic hyperplastic candidosis

20. Infective white lesions
Syphilitic leukoplakia:
Rare nowadays
Dorsum of tongue
Patient may show other features of tertiary syphilis
Syphilitic leukoplakia is premalignant condition
Active syphilis should be treated but the leukoplakic lesion will not resolve
Periodic check-up is essential to detect early any neoplastic changes

21. Infective white lesions
Hairy leukoplakia
Observed in 1980 among young homosexuals men who were HIV positive
It is usually an oral manifestation of HIV infection
Also reported in patients under immunosupression
EBV is the probable cause
Secondary Candida infection may be present

22. Infective white lesions
Hairy leukoplakia
Typically it is corrugated white areas on lateral border of the tongue but it may affect buccal mucosa
Usually asymptomatic and self limiting or may cause some discomfort
Poor prognostic sign HIV in patients as the majority of patients with HL develop AIDS within 4 year

23. Infective white lesions
Hairy leukoplakia
Because biopsy in HIV+ is not popular, cells harvested from swabs or scrapings from the lesion can be analyzed by in-situ hypridization or examined under EM to detect EBV
Test for HIV antibodies
In situ hybridization (ISH) is a type of hybridization that uses a labeled complementary DNA, RNA or modified nucleic acids strand (i.e., probe) to localize a specific DNA or RNA sequence in a portion or section of tissue (in situ), or, if the tissue is small enough (e.g., plant seeds, Drosophila embryos), in the entire tissue (whole mount ISH), in cells, and in circulating tumor cells (CTCs). This is distinct from immunohistochemistry, which usually localizes proteins in tissue sections.

25. Hairy leukoplakia Management
If asymptomatic, no treatment is necessary
Treat Candida infection if present
Acyclovir 200 mg tab bd/ 3 weeks and may recur after cessation of treatment

26. Acute pseudomembranous candidosis (thrush)
White/creamy lightly adhered plaques affect tongue, lip and palate
Easily rubbed off
Seen in infants and adults with serious illness or on certain drugs
Always look for predisposing factor

27. Chronic mucocutaneous candidosis
They represent one of the very few causes of leukoplakia-like lesions in children
Dense white firmly adherent plaque/s
Buccal mucosa, tongue, comissures are common sites
Usually there is immune system impairment
They may have premalignant potential

28. Chronic hyperplastic candidosis (candidal leukoplakia

29. Inflammatory non infective lesions (Dermatological white lesions)
Lichen planus
Lupus erythematosus

30. Lichen planus
Ch. Mucocutaneous disease that may affect skin alone, mouth alone or in combination
Unknown etiology but it is believed to be immunologically cell mediated disease. Stress may be predisposing factor
Some studies associate LP with HCV and ch. Liver diseases
Believed to be a hypersensitivity reaction to unknown antigen, characterized by T lymphocyte mediated destruction of basal cell kerationocytes
More common among middle-aged females (65%)
Age: years

31. Lichen planus Affects 1-2% of the population
Oral lesions are usually bilateral and may take one or more of the following six forms:
Papular
Reticular
plaque like
atrophic
erosive
bullous type
(Anderson, 1968)

32. Lichen planus
Silverman (1989) classify LP as: reticular, atrophic and erosive
More than one subtype may be present in the same mouth
Clinical form may changeover time from one type to another
Tongue, gingiva, palate, buccal mucosa may be involved but rare on the palate
Desqumative gingivitis is common finding
Long standing oral LP may appear as hyperpigmented areas

33. Lichen planus
Oral lesions may be asymptomatic, cause some discomfort or even soreness
LP is considered as premalignant condition although the risk is between 0.5-2% and it is mainly associated with atrophic and erosive types
10-45% of patients with oral LP show skin involvement (1/3 of the cases)

34. Lichen planus Other area may be affected:
Skin: pruretic maculo-papular rash with glistening surface on flexor surfaces of arm, shins and genital areas showing Wickame’s striae
Scalp: alopecia
Nails: vertical ridges and pitting
Scrotum:
Positive Khoebner phenomenon

35. Desqumative gingivitis

36. Typical skin lesions in LP
Polygonal, pruritic with Wickham straiae with + Koebner phenomenon

39. Nail features of LP

40. Alopecia in LP

41. Alopecia in LP

42. LP; reticular form In buccal mucosa

43. LP

44. LP; plaque like associated with some areas of erosion or ulceration

45. Erosive LP of tongue

46. LP

47. Histology of LP

48. Histology of LP

49. lichenoid reactions
Oral lesions are very similar clinically and histologically to those of LP
Associated with:
Oral antidiabetics
Antihypertensive
Gold salts
Amalgam restorations
Antimalarial
GVHD in allergenic BM grafts
Recently it has been associated with composite restorative materials also

50. lichenoid reactions More common on the hard palate
Not symmetrically distributed as in LP (unilateral)
Resolve on the discontinuation of the offending drug
Patch test may be positive if amalgam is incriminated as a cause

51. LP Diagnosis of LP: histological features:
history & clinical presentation may be enough to make a diagnosis but biopsy may be needed
histological features:
Hyperparakeratosis, hyperorthokeratosis
Epithelial atrophy
Acanthosis
Civatte bodies
Liquefaction degeneration of the basal cell layer
Irregular rete pegs -"saw tooth" pattern
Subepithelial band like infiltrate of lymphocytes and histiocytes

52. LP Diagnosis of LP: Histological features:
When the lesion is ulcerated:
Plasma cells may be present
There is a deeper perivascular infiltrate of inflammatory cells
The surface is covered by a fibrinous slough
DIF: non-specific & show anti IgM & fibrinogen along BMZ

53. epithelium is atrophic and shows hyperkeratosis & epithelium is atrophic and shows hyperkeratosis

54. LP civette bodies & liquefactive degeneration

55. DIF: non-specific & show anti IgM & fibrinogen along BMZ

56. LP epithelial atrophy and ulcer

57. LP D.D: Lupus erythematosus Chronic oral ulcerative stomatitis
Keratosis
Carcinoma
Leukoplakia
candidosis

58. Management of LP
Patient education: about the over all benign nature & course of the disease & treatments available …. etc.
No symptoms: no treatment but follow up may be essential as the disease course is unpredictable
if it is symptomatic:
Topical steroids for mild cases:
hydrocortisone hemisuccinate pellets 2.5 mg tds
betametasone sodium phosphate .5 mg tds (to be dissolved in the area)
triamcinolone acetanoid in orabase 0.1%
intralesional injections of steroids (triamcinolone)

59. Management of LP
Systemic steroids for more severe cases or cases that fail to respond to local therapy:
in severe cases with no response to topical treatment
Under OM specialist care
prednisolone tab mg in divided doses or single 40 mg dose in the morning for a week or 10 day tapered over 2 weeks followed by topical steroids
Cyclosporine: to control lymphocyte cell mediated inflammatory process

60. Management of LP Dapsone Retenoids
Antiseptic mouthwash ( benzydamine hydrochloride)
Anxyolytic therapy: 5-10 mg diazepam or tricyclic antidepressants in severely anxious patient
Avoid spicy food

61. ALL THESE TREATMENT MODALITIES ARE NOT CURATIVE
LIFE LONG FOLLOW UP IS A MANDATORY FOR ALL CASES OF LP with minimizing of tobacco and alcohol intake

62. Lupus erythematosus Three forms: Discoid lupus erythematosus (DLE)
Subacute cutaneous LE:
is more extensive and involve skin areas that are not
exposed to sun like neck, trunk and extensor surfaces
of the arm
show mild systemic manifestations as fatigue
malaise & joint pain
Systemic lupus erythematosus (SLE); multisystem

63. Discoid lupus erythematosus (DLE)
Affect years patients
Confined to sun exposed skin of the face, scalp & ears but may also involve oral mucosa
No systemic involvement
More common than SLE
Skin lesions are similar to SLE but almost always present (butterfly signs as macule covered by gray scaly layer, it is not pathognomic as it seen also in seborrheic dermatitis

64. Lupus erythematosus
Oral lesions are similar to SLE but usually they are not symmetrical (25-50% of cases)
May progress to SLE over a period of time
No serological markers
It has 3-4% malignant potential (premalignant lesion)

65. Systemic lupus erythematosus (SLE)
Etiology:
there genetic predisposition
it is an autoimmune disease characterized by formation of autoantibodies against DNA , nuclear and RNA antigens with immuncomplexes deposited along the BMZ
it may be induced by viral infection
similar lesions has been associated wit some drugs like: hydralazine, phenytoin & quinidine

66. Systemic lupus erythematosus (SLE)
Clinical features:
it is multisystem disease
M:F = 1:10
General symptoms: weight loss, malaise, fever
joints:
Arthralgia
Arthritis

67. Systemic lupus erythematosus (SLE)
cutaneous: variable
raised, erythematous scaly patches and plaques on the skin and scalp & erythematous patches similar to LP
‘facial butterfly’
vasculitic dermatitis
photosensitivity

68. Systemic lupus erythematosus (SLE)
heart:
Pericaraditis
Myocaraditis
Non-infective endocaraditis
lung:
Fibrosis & pneumonitis
kidney:
Glomerulonephritis: common cause of death in such patients
Hematuria & proteinurea
CNS:
Neurosis
Psychosis
Strokes & seizures

69. Systemic lupus erythematosus (SLE)
blood:
Anemia
Purpura
Leukopenia
oral mucosa:
erythematous, erosion ulceration, pain and soreness may be present
central erythema, white spots or papulous plus radiating white straiae from the margin (similar to LP)
may be associated with Sjogren’s syndrome in 30% of cases

70. Oral mucosal lesions in SLE

71. Systemic lupus erythematosus (SLE)
D.D:
As in LP

72. Systemic lupus erythematosus (SLE)
Investigations:
biopsy:
similar to LP but with perivascular lymphocytic infiltration + keratotic plugging in chronic cases
CBC:

73. SLE keratin plugging

74. Systemic lupus erythematosus (SLE)
immunology:
Hypergammaglubinaemia
Antinuclear antibodies: anti DNA & anti RNA
False positive serology for syphilis
DIF: 100% in SLE (IgM, IgA & IgG)
Lupus band test: immunoflurescence in non-lesional area
not specific
characterized by granular immune deposits along the BMZ

75. lesions of LP may be very difficult to differentiate clinically or histologically or immunologically from LE
few patients may have LP-LE overlap syndrome
DLE is premalignant lesion and 3-4% of cutaneous lesions may develop cancer

76. Treatment:
Steroids as in LP; topical or systemic depending on the severity of the case
immunosuppressive and cytotoxic
Azathioprine
Cyclophosphamide
antimalarial drugs: gold, chloroquine or dapsone

77. Neoplastic white lesion
Carcinoma in situ
Squamous cell carcinoma
Squamous cell papiloma

78. Metabolic white lesions
As in chronic renal failure

79. Miscellaneous white lesions skin graft

80. Idiopathic white lesions (leukoplakia)
It is the only condition where the WHO definition of leukoplakia can be applied without any reservation
Form the majority of persistent white lesions of the mouth
Both clinical presentation and histological finding may be variable (from simple keratosis to severe dysplasia or even squamous cell carcinoma)
Has a higher risk of developing cancer than other types of white lesions
Biopsy is always essential

82. Diagnosis of white lesions
If lesion rubs away with gauze:
Thrush
Thermal or chemical lesions
If lesion does not rubs away with gauze:
Leukoplakia LP
SLE
Oral warts
Hereditary
If lesion is present since childhood and bilateral with symmetrical distribution:
white spongy nevus

83. If patient uses tobacco products:
Smoker’s keratosis
Nicotinic stomatitis
Smokeless tobacco keratosis
If lesion is bilaterally on lateral side of tongue in HIV RISK patient:
Hairy leukoplakia
If lesion show bilateral symmetrical and classical reticular striae:
LP and lichenoid reactions
If there is no apparent cause
Leukoplakia