Saranaz Present Cus

8/2/2019 Saranaz Present Cus

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In the name of godIn the name of god


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CASE 1

A 75-year-old white woman was referred by her rheumatologist tothe Oral Medicine Clinic for evaluation of oral dryness and pain. Herchiefcomplaint was painfulchiefcomplaint was painfultongue,soretongue,sore gumgum anddifficultyinanddifficultyineating,eating, She had been diagnosed with Sjgrens syndrome about 1year before. Oral examination revealed ulcerations of the maxillary

facial gingiva, especially prominent around the cervical areas of theanterior maxilla. The anterior dorsal tongue was atrophic anddepapillated, and multiple ulcerations were noted on lateral/ventraltongue border as well as the left ventral tongue. These ulcers onthe tongue were mostly surrounded by faint to prominent whitestriations. The ulcer on the right ventral/lateral surface was linear

and especially painful Also areas of erythema on the gingiva, thebuccal mucosa, and the tongue were seen


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A biopsy of the lateral/ventral tongue lesionwas performed and tissues submitted forroutine HE staining as well as DIF studies.

Upon confirmation of CUS, the patient wasplaced on 200 mg/day hydroxychloroquine(Plaquenil) and 25mg/day prednisone. The

patient reported dramatic improvement andhealing of the ulcers after 3 months oftherapy.


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CASE 2

A 71-year-old white woman was referred for evaluation andtreatment ofvery painful and persistent sores presenting as ulcerson her tongue and irritated erythematous areas on her buccalmucosa. These lesions had been present for about 1 year. Hermedical history included dry eyes and dry mouth.

She had also been treated intermittently with steroids for bronchitisand asthma. Examination of the oral mucosa revealed faint whiteareas on the anterior third of the tongue and a 2.5 0.6 cm linearcrateriform ulcer on the left ventral/lateral tongue. The ulceratedarea was very tender, and the patient had difficulty moving hertongue.

The left buccal mucosa exhibited an erythematous and erodedrectangular lesion measuring approximately 1.5 1.0 cm which

was surrounded by white striation


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Differential diagnosis included lichenoid ulceration/mucositis, erosivelichen planus,and squamous cell carcinoma (for the tongue lesion).

incisional biopsy was performed and tissue obtained for both hematoxylin-eosin (HE) histologic examination and DIF testing. The DIF findingsrevealed positive IgG in the basal and parabasal cell layers. This was

considered consistent with CUS. With a diagnosis of CUS, the patient was initially treatedwith 0.05%

clobetasol propionate ointment applied twice daily for 2 weeks and twicedaily rinses of 0.5 mg/5 mL.dexamethasone elixir. This resulted in minimalimprovement.

The ulcerations worsened after discontinuation of the medications.

She was treated with hydroxychloroquine 800 mg/day in four divideddoses. At follow-up 6 months later, the patient was relatively symptomfree, and almost total resolution of the tongue ulceration was noted . Shecontinues to be on hydroxychloroquine


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CASE 3

A 40-year-old white woman was examined for

oral dryness and pain. She presented with a

chief complaint of sore gums, painful tongue,

and difficulty in eating. The soreness had lasted

for more than 1.5 years. Clinical examination

revealed extensive erythematous ulceration of

the gingiva


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a diagnosis of CUS was made and the patient

was placed on 200 mg hydroxychloroquinetwice daily and is currently scheduled for

follow-up examination.


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Chronic

Ulcerati

ve

Stomatitis


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Definition

Chronic ulcerative stomatitis is a rare oral disease withcharacteristic immunofluorescent pattern

A unique entity first described in 1990 Painful exacerbating and remitting oral lesions

Etiology

Autoimmune disease with specific antinuclear antibodies

directed against the stratified epithelium. Circulating and tissue bound autoantibodies to delta

Np63 alpha protein which is a normal component ofstratified epitheliae


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Diagnostic criteria 1998

Major criteria

Erosive or exfoliative lesions in mouth

Characteristic indirect and directimmunofluorescence

Minor criteria

Chronic course with relapses

Female in older age groupResponse to hydroxychloorquine alone or combinedwith small doses of cortisone


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DeltaNp63alpha is a member of a family ofnuclear transcription factors, includingp63, p73,and thep53 tumor suppressor gene, which shareconsiderable sequence homology

Np63 is involved in multiple functions duringskin development and inadult stem/progenitorcell regulation

It is essential for maintenance of proliferativepotential and epithelial integrity

Autoantibodies to deltaNp63alpha have beenshown in cases of lung and head and neck SCC


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Mutations in the TP63 gene are associated

with ectrodactyly-ectodermal dysplasia-cleft

syndrome, HayWells syndrome, cleft

lip/palate syndrome 3 (EEC3); split-hand/foot

malformation 4 (SHFM4); ankyloblepharon-

ectodermal defects-cleft lip/palate; ADULT

syndrome (acro-dermato-ungual-lacrimal-tooth); limb-mammary syndrome; Rap-

Hodgkin syndrome (RHS); and orofacial cleft 8


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Chronic ulcerative stomatitis, gingival lesions i

the form of desquamative

gingivitis.

Chronic ulcerative stomatitis, erosions on the

buccal mucosa identical tolichen planus.


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Clinicalfeatures

The disease involves, almost exclusively, the oral mucosa and has a chroniccourse with recurrences,mostly seen in white women,average age of 59

Sore gingiva,painful tongue,difficulty eating,unintentional weight losswith exacerbating and remission of symptoms

the lesions of gingiva appear in the form ofdesquamative gingivitisor aslocalized painful erythema and ulcerations

Tongue is the most common location followed by buccal mucosa

Painful superficial ulcerations, usually associated with reticular whitelesions identical to those seen in oral lichen planus, and discoid lupus

erythematosus may also occur on the buccal mucosa and the tongue

The clinical diagnosis should be confirmed by laboratory examination.


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Laboratorytests

Histopathological examination,

direct and indirect immunofluorescent tests.


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Current gold standard diagnostic test is directIF

Reveals the presence of IgG antibodies bound

to nuclei of keratinocytes of the basal andlower one third cell layer

Unique stratified epithelial specific anti

nuclear antibody(SES-ANA) ANA pattern in other diseases(i.e SLE) is in the

stratum spinosum and not in basal layer


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cont

Positive deposits of fibrinogen have been

reported with irregular extensions into the

superficial lamina propria,giving a shaggy

appearance but it is not thought to be a part

of diagnostic criteria

Some cases showed tissue bound IgA which

these patients had more severe disease


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DIF mechanism


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Chroniculcerativestomatitis

OralDiseases

Volume 14, Issue 5, pages 383-389, 28 JUN 2008 DOI: 10.1111/j.1601-0825.2008.01446.xhttp://onlinelibrary.wiley.com/doi/10.1111/j.1601-0825.2008.01446.x/full#f2


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Direct immunofluorescence of an oral mucosal

specimen shows lgG autoantibodies bound to

the nuclei of basal epithelial

cells,demonstrating the SES-ANA pattern


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DIF SLE


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OralDiseases



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specimen for fibrinogen shows a linear

fluorescence outlining the basement

membrane zone.

Irregular extensions into the superficial

lamina propria give a shaggy appearance.


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DIF lichen planus


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OralDiseases



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specimen with IgA autoantibodies bound to

the nuclei of basal epithelial cells and

demonstrating the SES-ANA pattern


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Challenges of obtaining a dignosis

Biopsy samples should be from perilesional

mucosa

DIF requires Michel transport media Cryostat is required for sectioning

If the epithelium is atrophic or cut tangentially

a IIF may be necessary


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IIF

CUS patients have circulating antibodies with

SES-ANA pattern on esophagus substrate

Guinea pig esophagus is the most sensitive


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IIF mechanism


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OralDiseases

Volume 14, Issue 5, pages 383-389, 28 JUN 2008 DOI: 10.1111/j.1601-0825.2008.01446.x

http://onlinelibrary.wiley.com/doi/10.1111/j.1601-0825.2008.01446.x/full#f5


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Indirect immunofluorescence of CUS sera on

monkey esophagus substrate shows lgG

antibodies bound to the substrate in the SES-

ANA pattern


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MANAGEMENT

HYDROXYCHLOROQUINE(plaquenil)is the mosteffective drug for CUS with off label use

800 mg daily in four divided doses

It was initially developed as antimalari drug

Autoantibody titer is reduced with this drug

Mechanism of action is interference with antigen

processing mechanism of macrophages and otherantigen presenting cells resulting indownregulation of immune response


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cont

Side effects include retinopathy,toxic

psychosis,neuromyopathy,agranulocytosis,apl

astic anemia

Neuromascular and hematologic

complications are usually

reversible,retinopathy is not

Close follow up is warranted


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Relationship of CUS and OLP

Oral lichen planus lesions rarely undergo spontanousremission

OLP shows a fibrillar pattern of fibrin deposition at

basement membrane but it is not specific to OLP and itis suggestive of orconsistent with OLP

Studies of inflammatory infiltrate of LP show CD4 Tcellsin early lesions and predominantly CD8 Tcells in chroniclesions

Pathogenesis of LP is a lymphocytic immunologicreaction to epithelial basal cells,but no antigen hasbeen identified yet


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cont

During inflammatory process it is likely thatnormally sequestered proteins such asdeltaNp63alpha(nuclear transcription factor)areexposed to the immune system and stimulate an

autoimmune reaction in susceptible individuals Autoimmune diseases are associated with

particular HLA types

An increase in frequency of certain HLA has not

been shown in LP cases HLA typing on CUS patients has not been

reported


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cont

If CUS is a subset of OLP,perhaps the MHC molecules of theCUS patients are particularly adept at presenting theDeltaNp63alpha autoantigen and stimulating a humoralimmune response. Other LP patients may present this self-antigen in a form that is not immunogenic.

LP patients without autoantibodies may have a primarily T-cell-mediated response, whereas CUS patients may have aprimarily B-cell-mediated humoral response

Another theory is that perhaps there is a subset of LPpatients who produce IgG in a titer high enough to bediscerned as SES-ANAs on direct IF, where a diagnosis ofCUS is made.


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cont

Immunoblotting led to the detection ofantibodies against various p63 and p73isoforms in serum of OLP patients

Asymptomatic cases are usually not biopsied,and thus antibodies to DeltaNp63alpha havenot been discovered by direct IF of non-erosive lichenoid disease

ELISA is another sensitive test but goldstandard is DIF


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case4

An 81-year-old white female was referred with a chiefcomplaintofseverepainandassociatedsorenessofthegingivaandlateralandventralsurfacesofthetongue. Previous biopsy (report not available) was

diagnosed as chronic lichenoid mucositis withulceration.

Her medical history included hypertension andhypothyroidism which were currently being treated byher physician.

Oral examination revealed severely erythematous anddesquamative lesions of the gingiva which wasgeneralized throughout the oral cavity.


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. A clinical differential diagnosis of erosive lichen

planus, benign mucous membrane

pemphigoid,and pemphigus vulgaris was

considerd


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Routine histology of the incisional biopsy revealedpartially ulcerated surface epithelium that was atrophicin areas with saw-toothed rete ridge formation. Partial

destruction of the basal cell layer was noted . A denseband-like inflammatory infiltrate composed mainly oflymphocytes and plasma cells was noted

Tissue submitted for DIF staining revealed positivestaining in the basal and parabasal cells for IgG in a

perinuclear distribution, Also, a linear fibrinogenpositive band was seen along the basement membranezone

HistopathologyandDIF


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case5

A 54-year-old Caucasian woman was referred to a periodontist with achiefcomplaintofgumsoreness.

Her past medical history was significant for 2 previous episodes of bullousskin lesions at ages 38 and 51 that were diagnosed clinically as LP by herprimary physician and a dermatologist. The skin lesions were treated withsystemic and topical corticosteroids. She correlated the onset of her oralsymptoms with an increase in psychological stress that occurred in theprevious 2 months. The only medication she was taking at that time was aconjugatedestrogen, for hormone replacement.

On oral examination, a prominent finding was the bilateral presence ofdeeply erosive lesions on the buccal mucosa adjacent to the molar areas .

A clinical diagnosis of erosive oral LP was made, and lesional tissuebiopsies were submitted for hematoxylin and eosin (HE) and DIF.

Histopathologic examinationshowed a specimen that was devoid ofepithelium and covered by a fibrinopurulent exudate with a mixedinflammatory infiltrate in the underlying connective tissue.


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The diagnosis was nonspecific ulceration of the buccal mucosa.

DIF revealed an SES-ANA reaction in the lower levels of thestratified squamous epithelium.characteristic of CUS. Serum studieswere requested

for IIF, and positive findings confirmed the diagnosis of CUS

The initial treatment consisted of scaling and prophylaxis of theteeth and prescriptions for chlorhexidine and 0.05% fluocinonideointment. When the patient returned for a 3-month follow-up, shehad not filled the prescriptions but reported that she currently wascomfortable despite refractory areas of mucosal erosion. At thisvisit, the patient reported feeling less stress, which seemed to

correlate with the symptomatic improvement of her condition.


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Clinical photo shows the left buccal mucosa, which is

diffusely erythematous with subtle, irregular diffusewhite borders.

A shallow, linear erosion is present on the mucosaopposite the maxillary molars. Clinical photo of adifferent CUS patient shows the presentation of CUS asa desquamative gingivitis affecting the buccal gingivalof the mandibular left premolar and molar area. A

small shallow ulcer is present on the free gingivalmargin of the first molar


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Thanks foryour attention

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Saranaz Present Cus