Palatal ulceration Kabir Sardana MD, Shuchi Bansal MD PII: DOI: Reference:

S0738-081X(14)00057-1 doi: 10.1016/j.clindermatol.2014.02.023 CID 6840

To appear in:

Clinics in Dermatology

Please cite this article as: Sardana Kabir, Bansal Shuchi, Palatal ulceration, Clinics in Dermatology (2014), doi: 10.1016/j.clindermatol.2014.02.023

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ACCEPTED MANUSCRIPT TITLE: Palatal Ulceration Table 2;Figure 8 AUTHORS:

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Kabir Sardana MD, **

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Shuchi Bansal * MD ** Associate Professor of Dermatology and Sexually Transmitted Diseases *Senior Resident Maulana Azad Medical College and Lok Nayak Hospital, New Delhi ,India

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CORRESPONDING AUTHOR: Dr Kabir Sardana

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466, Sector 28 NOIDA, UP, India

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201303 [email protected]

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CONFLICT OF INTEREST: “no conflict of interest”

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Palatal Ulceration

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Abstract

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Palatal ulcers are a common presentation and can be conveniently divided into developmental and acquired causes, the latter of which is subdivided into acute and chronic causes. Most commonly seen dermatological causes have associated skin manifestations. Acute and multiple ulcers are usually infectious or drug induced in origin .Recurrent ulcers are largely dominated by aphthosis, while chronic ulcers are seen in immunocompromised patients and can occasionally be malignant .It is essential to involve the oral and maxillofacial surgeons early in the therapeutic management to tackle the inevitable complications that may ensue in the chronic cases.

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Palatal Ulceration

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Palatal ulceration is a clinical problem which is a diagnostic issue specially in cases without

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cutaneous involvement (Fig1) and in cases with a chronic ulcer . Palatal ulcers are consequent to a loss of tissue (both the epithelium and the underlying connective tissue), and may involve

developmental causes

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both the keratinized or non-keratinized oral mucosa .1,2. The causes are diverse, ranging from to a variety of inflammatory (fig2) , infectious(fig 3,4,5) ,immune3,4

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mediated (fig 6), iatrogenic(fig5), and neoplastic causes.

The ulceration may either be limited

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to the palate or represent a part of a generalized pathological process involving the entire oral mucosa. The latter is commoner and diagnosis relatively easy as compared to when the lesions

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are limited solely to the palate. A battery of investigations is often required to delineate the etiology, and the time period between onset and institution of therapy can range from months to

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years. The present review discusses the etiology, pathogenesis, classification, diagnosis and

Classification

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management of palatal ulcers.

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The causative factors can broadly be divided into developmental and acquired causes . Among the developmental causes, cleft palate is the commonest, while in the acquired, recurrent aphthous stomatitis is probably the most common cause .1,5 A comprehensive list is enumerated in Table 1 with a special emphasis on common and rare causes. There are two approaches to diagnose these disorders . The first is based on the site of involvement (fig1) the second is based on the onset ,number of ulcers and the course of the disease (fig 7,8). A judicious use of this (fig 1,7,8) can help to narrow down the common cause and probable diagnosis .

ACCEPTED MANUSCRIPT Brief description of common entities Aphthous stomatitis

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This is perhaps one of the commonest cause of oral ulceration .1 Although various factors

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including genetic, autoimmune, hormonal changes, hypersensitivity to certain foods, drugs, blood deficiency, zinc deficit, and stress, etc have been implicated in the etiology, none of them

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can be solely held responsible for a particular episode, and hence the therapy is primarily directed at suppressing the inflammation and pain associated with lesions. 6 Three types have

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been identified: minor, major and herpetiform ulcers. 7 Only the major and herpetiform variants

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are seen on the palate.

Major aphthae (also known as periadenitis mucosa necrotica recurrens or Sutton’s disease) are

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generally > 10 mm in size and painful (Figure 2). They can occur as single or multiple ulcers. and persist for more than 6 weeks and heal with scars.8 Herpetiform aphthae are characterized by

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multiple (50–100), small (2–3 mm) and painful ulcers which tend to coalesce and form ulcers of

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larger size. They usually heal within 7–10 days without leaving any sequelae. Apart from palate, the major and herpetiform variants may also involve the lips, cheeks, tongue, floor of the mouth

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and pharynx.6 Since, the non-keratinized mucosa is more commonly involved, the lesions are seen on the soft palate, an important point which differentiates it from herpetic stomatitis that involves chiefly the keratinized part of the mucosa.9 Various systemic disorders have been associated with recurrent aphthous stomatitis including behcet’s syndrome, sweet’s syndrome, agranulocytosis, cyclic neutropenia and periodic fever syndrome.6,10 Behcet’s syndrome is the most well-recognized and should be considered in case the patient has co-existing genital ulcers, visual complaints, joint pains and neurological symptoms.

ACCEPTED MANUSCRIPT Treatment Medication prescribed should relate to the severity of the disease. In mild cases with two or three

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small lesions, use of a topical steroid in Orabase is all that is necessary. 11 Pain relief of minor

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lesions can be obtained with use of a topical anesthetic agent or topical diclofenac (not available in all countries) .The steroid used is fluocinonide, betamethasone or clobetasol which is effective

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in a gel preparation if applied to the lesion after meals and at bedtime two to three times a day.

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For larger lesions, a gauze containing the topical steroid can be held next to the ulcer. Other topical preparations that are useful include amlexanox paste, topical tetracycline, and

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intralesional steroids (major RAS lesions). 12 Hydrogen peroxide gargles in a dilution of 50% is useful to prevent infection and enhance healing. In most cases of major aphthae and severe cases

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of multiple minor aphthae the use of systemic therapy is useful and includes colchicine,

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pentoxifylline, dapsone, short bursts of systemic steroids, and thalidomide.10,11 All clinicians prescribing thalidomide in the United States must be registered in the STEPS (System for

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Thalidomide Education and Prescribing Safety) program, and patients receiving the drug must be

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thoroughly counseled regarding effective birth control methods that must be used whenever thalidomide is prescribed. Bacterial infections

Palatal ulcerations due to syphilis, a well-known entity in the past is uncommonly seen now-days due to rapid and effective treatment of the disease in the early stages. Although ulcers can be seen in all the three stages of syphilis, the syphilitic gummas, seen in the tertiary stage can involve the palate .13 The lesions present as painless ulcerated nodules on the hard palate, which can perforate causing interference with speech and swallowing. A more common presentation is of shallow mucous ulcers and patches that are seen in the secondary stage, though rarely a primary syphilitic chancre can present as a palatal ulcer. 4,14 Diagnosis is primarily based on

ACCEPTED MANUSCRIPT positive specific serological tests (TPHA/FTAbs). Dark ground examination is generally not preferred for oral lesions, owing to high probability of false positivity due to saprophytic

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spirochaetes. In leprosy, the palatal ulcers are generally seen in the advanced multibacillary cases. 15 The sites

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vary from the mid-forward area to the soft palate. The lesions begin as yellow-red nodules or diffuse infiltration, which progress to large chronic ulcers with eventual perforation if not

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treated in time .16 Diagnosis is based on the demonstration of acid fast bacilli and typical

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histopathologic changes from the ulcer along with other clinical features of Hansen’s disease. Mycobacterial infections due to Mycobacterium leprae and Mycobacterium tuberculosis are

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other important causes of palatal ulcers. Tuberculosis cutis orifacialis often presents with a palatal ulcer though the tongue is the commoner site in this condition.17 The ulcer can occur

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Diagnosis is confirmed by the presence of characteristic caseating granulomas

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tuberculosis.

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either as a primary infection of the palate or more commonly secondary to active pulmonary

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on histopathology and demonstration of acid fast bacilli on special stains. Rhinoscleroma primarily involves the nasal cavity, although palatal scleromas and ulcerations have rarely been reported.20 It is a granulomatous disease caused by Klebsiella rhinoscleromatis, and diagnosis is confirmed by the presence of classical Mikulicz cells. Acute necrotizing ulcerative gingivitis (ANUG) is an endogenous oral infection accompanied by an overgrowth of organisms prevalent in normal oral flora. The organisms implicated are the fusiform bacillus and spirochetes. Samples taken from ANUG patients demonstrate an anaerobic flora of Treponema spp, Selenomonas spp, Fusobacterium spp, and Bacteroides intermedius. 21 The tissue destruction is thought to be caused by endotoxins that act directly on the tissues or

ACCEPTED MANUSCRIPT indirectly by triggering immunologic and inflammatory reactions. 11 Classic ANUG in patients without an underlying medical disorder is found most often in those between the ages of 16 and

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30 years, and it is associated with three major factors: 1. Poor oral hygiene with pre-existing marginal gingivitis or faulty dental restorations

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2. Smoking

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3. Emotional stress

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Systemic disorders associated with ANUG include leukemia or aplastic anemia, marked malnutrition, and HIV infection. In HIV infection three oral lesions have been described linear

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gingival erythema (LGE), necrotizing ulcerative gingivitis (NUG), and necrotizing ulcerative

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periodontitis (NUP).11

The onset of acute forms of ANUG is usually sudden, with pain, tenderness, profuse salivation, a

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peculiar metallic taste, and spontaneous bleeding from the gingival tissues11. The teeth are

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slightly extruded, sensitive to pressure and have a “woody sensation.” The signs noted most frequently are gingival bleeding and blunting of the interdental papillae. The typical lesions of are necrotic punched-out ulcerations, developing most commonly on the interdental papillae and the marginal gingivae and involve the cheeks, lips, tongue, palate and the pharyngeal area. In cases the lesions involve sites beyond the gingivae, blood dyscrasias and immunodeficiency should be ruled out by ordering appropriate laboratory tests 11. A multidisciplinary approach is needed with a use of hydrogen peroxide washes and oral antibiotics in patients with extensive gingival involvement, lymphadenopathy, presence of

ACCEPTED MANUSCRIPT systemic signs, and in cases in which mucosa other than the gingivae is involved. Metronidazole and penicillin are the preferred antibiotics .22

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Cancrum oris, rarely seen these days, is triggered by a constellation of micro organisms of which Fusobacterium necrophorum is a key component.23 It is an ulcerative gangrenous stomatitis

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causing massive necrosis of the tissues of lips and cheeks. This gangrenous process spreads

Fungal infections

Chronic

oral

ulcers

are

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common

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rapidly causing necrotic ulcers in the hard and soft palate, and the adjoining soft tissues.

occurrence

in

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variety

of

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fungal

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infections24,25,26,27,28,29,30(Table 1,fig 3,4). Palatal ulceration may be the only oral manifestation in

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some cases, while in others, it may be accompanied by ulcers in other parts of oral mucosa. Immunocompromised patients and co-existing diseases like diabetes are a common predisposing

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factor.31

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In histoplasmosis, oral involvement is usually secondary to pulmonary involvement and occurs in a significant percentage of patients with disseminated histoplasmosis. Oral mucosal lesions

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may appear as a papule, a nodule, an ulcer, or a vegetation. 32 If a single lesion is left untreated, it progresses from a firm papule to a nodule, which ulcerates. There is usually involvement of cervical lymph nodes and the clinical appearance and the accompanying lymphadenopathy, can be mistaken for squamous cell carcinoma, other chronic fungal infections and Hodgkin’s disease. Blastomycosis presents as a nonspecific painless verrucous ulcer with indurated borders, often mistaken for squamous cell carcinoma.11 The histopathologist can confuse the characteristic pseudoepitheliomatous hyperplasia as a malignant changes. Other oral lesions that have been reported include hard nodules and radiolucent jaw lesions.

ACCEPTED MANUSCRIPT Mucormycosis presents as ulceration of the palate which is consequent to necrosis due to invasion of the palatal vessels.24 The lesion is characteristically large and deep, causing

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denudation of underlying bone (Figure 3). Mucormycosis can also involve the gingiva, lip, and

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alveolar ridge (Fig 3) .33 The initial manifestation of the disease may be confused with dental

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caries or bacterial maxillary sinusitis..

Palatal ulcers have also been reported in sporotrichosis, coccidiomycosis ,and trichosporonosis

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(Figure 4).

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A presumptive diagnosis of a fungal etiology can made on the basis of presence of spores or hyphae on KOH examination.hHistopathologic examination from the base of the ulcer along

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with special stains and fungal culture helps confirm the diagnosis. Culture is the gold standard though frequent contamination requires sub culturing or repeated cultures . Prolonged antifungal

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therapy is often required. In case of perforation, reconstructive procedures may be required after

Viral infections

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completion of antifungal therapy

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Although viral infections cause palatal ulcers, they are usually associated with ulcers in other parts of the oral cavity. Herpes simplex is the commonest viral infection causing oral/palatal ulcers. Acute onset with history of vesicles and characteristic polycyclic margins usually helps in making a diagnosis.34 In primary oral herpes there is a history of a generalized prodrome that precedes the local lesions by 1 or 2 days. This information is helpful in differentiating this viral infection from allergic stomatitis or erythema multiforme, in which local lesions and systemic symptoms appear together. Approximately 1 or 2 days after the prodromal symptoms occur, small vesicles are seen on the oral mucosa which rupture, leaving shallow round discrete ulcers and are seen on the keratinized part of the mucosa. As the disease progresses, several lesions

ACCEPTED MANUSCRIPT may coalesce, forming larger irregular lesions. An important diagnostic criterion in this disease is the appearance of generalized acute marginal gingivitis.11 In immunodeficient patients and

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those on steroid therapy, the ulcers can be significantly deep and lack the characteristic

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polycyclic outline. They may be single or multiple and also occur on the non-keratinizing mucosa, a typical feature of herpes simplex in immunocompromised patients.

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The simplest

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bedside test that can be done is a tzanck smear from a fresh vesicle or ulcer which shows

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multinucleated giant cells. Fluorescent antibody technique, can also be used which has high

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sensitivity and specificity.

Palatal ulcers can also be caused by coxsackie virus (herpangina) and Epstein Barr virus

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(infectious mononucleosis). Lesions start as punctate macules, which quickly evolve into papules and vesicles involving the posterior pharynx, tonsils, faucial pillars, and soft palate. 11 Lesions are

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found less frequently on the buccal mucosa, tongue, and hard palate. The self-limiting nature of

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ulcers and the presence of other associated signs usually helps in reaching a diagnosis.

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Herpangina may be clinically distinguished from primary HSV infection by several criteria: 1. Herpangina occurs in epidemics; HSV infections do not. 2. Herpangina tends to be milder than HSV infection. 3. Lesions of herpangina occur on the pharynx and posterior portions of the oral mucosa, whereas HSV primarily affects the anterior portion of the mouth. 4. Herpangina does not cause a generalized acute gingivitis like that associated with primary HSV infection. 5. Lesions of herpangina tend to be smaller than those of HSV.

ACCEPTED MANUSCRIPT In Hand foot and mouth disease the oral lesions are more extensive than are those described for herpangina, and lesions of the hard palate, tongue, and buccal mucosa are common. The skin

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manifestations are also characteristic and involve the palms as linear vesicles. 37 Varicella zoster is usually easy to diagnose as the dermatomal cutaneous involvement is classic

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and each individual oral lesion of HZ resembles lesions seen in herpes simplex infections. 38 The diagnosis is based on a history of pain and the unilateral nature and segmental distribution of the

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lesions.(Fig 5) Oral HZ can be distinguished clinically from other acute multiple lesions of the

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mouth, which are bilateral and are not preceded or accompanied by pain along the course of a cranial nerve.

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HIV infection does not per se cause palatal ulcers, but it does increase the incidence and severity of ulcers due to a variety of bacterial, viral and fungal pathogens. 39,40 Hence, HIV testing should

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Parasitic causes

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be done routinely in all long-standing cases and or recurrent cases of palatal ulcers.

Amongst the parasitic causes, leishmaniasis is an uncommon cause of oral ulceration except in

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endemic areas . 41 Here the ulcers are restricted to the hard and/or soft palate. Mucosal ulceration generally becomes evident after several years of resolution of the original cutaneous lesions. Diagnosis is often difficult as the organism is seldom demonstrated on histopathologic examination of the tissue samples. Serology and molecular techniques like polymerase chain reaction and DNA sequencing can help confirm the diagnosis in difficult situations. Lupus erythematosus (LE)

Oral mucosal lesions occur in 26% cases of LE, usually on the palate (82%).42 Lesions start as small erythematous or purpuric areas, which break down to form shallow and sometimes painful ulcers, with a dirty yellow base and surrounding reddish halo. Histology and immunohistology

ACCEPTED MANUSCRIPT shows changes consistent with LE similar to those in the skin. The lesions are mostly seen in the active stages of the disease.43

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Vasculitic disorders

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Wegener’s granulomatosis (WG) is a rare granulomatous necrotizing vasculitis of small and medium vessels which has predilection for upper airways, lungs and kidney. Infiltration of palate

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is probably a consequence of primary involvement of the upper airway mucosa. Deep irregular

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palatal ulcers are seen with purulent discharge which can progress eventually to perforation.44 Cutaneous manifestations may also occur in the form of palpable purpura on dependent skin

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sites, tender subcutaneous nodules, papules, vesicles and petechiae, as well as non-specific ulcers or pyoderma gangrenosum like lesions.45 Biopsy is usually done to rule out other causes of

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palatal ulcer. The classical findings of

leukocytoclastic vasculitis and/or granulomatous

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inflammation is present in only up to 50% of biopsy specimens. Diagnosis is confirmed by the presence of positive cytoplasmic antinuclear cytoplasmic antibody (with anti-PR3 specificity).46

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Remission can be induced by using a combination of corticosteroids and cytotoxic agents, such

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as cyclophosphamide.

A single case of palatine ulceration due to Churg Strauss syndrome has also been reported.47 The presence of asthma, peripheral eosinophilia, neuropathy and eosinophilic vasculitis on histopathologic examination can usually help differentiate it from the more common wegener’s granulomatosis. Isolated cases of palatal ulceration due to granulomatous disorders like Crohn’s disease and Sarcoidosis as well as due to neutrophilic dermatosis like Sweet’s syndrome have also been reported.48,49,50 Oral lesions are usually accompanied by other classical manifestations of the disease, which provide an useful clue to the diagnosis.

ACCEPTED MANUSCRIPT Immunobullous disorders

Oral ulcerations are seen in both intra-epidermal and sub-epidermal group of immunobullous

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disorders.51 The lesions involve all parts of oral mucosa including the palate. The erosions are ill-

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defined, irregular shaped having an erythematous base and are very slow to heal. Other mucosal sites and skin are usually involved, while in pemphigus vulgaris presents oral lesions are seen in

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50 to 70% of patients.52 A simple bedside test which helps differentiate intraepidermal group of disorders from the subepidermal group is the presence of acantholytic cells on tzanck smear.

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Histology demonstrates suprabasilar acantholysis though the diagnosis is confirmed by

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demonstrating immunoglobulin deposits and complement on direct immunofluorescence from either the perilesional skin or from the oral mucosa.

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Drug related causes

Palatal ulcers due to drugs can either occur exclusively or as a part of the generalized drug

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reaction. The former includes ulcers due to cocaine and methotrexate, while the latter comprises

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of severe drug reactions like erythema multiforme and Stevens Johnson syndrome. Palatal ulcers and mid palatine perforations as a result of cocaine use are well documented in the

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literature.53,54,55,56 The likely cause is the vasoconstrictive and caustic effect of the drug which produces direct irritation and ischemia of the nasal and palatine mucosa, which with continued use causes an oronasal perforation secondary to maxillary bone destruction. Most of the lesions are located on the hard palate (77.7%) with only 5.5% being found in the soft palate.57 The most frequent clinical manifestation is rhinolalia together with the regurgitation of solid food and liquids through the nares. Management consists of a combination of antibiotics, analgesics, prostheses (obturators), and surgical reconstruction of the defect. Methotrexate, a widely used antimetabolite and immune modulating drug is also known to cause oral and palatal ulcers.58 The most likely cause of mucositis and oral ulceration due to

ACCEPTED MANUSCRIPT methotrexate is folate deficiency and use of other antifolate drugs. 59 It is a common feature of the short term, high dose methotrexate regimes especially used in the treatment of malignant disease.

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Ulceration in the low dose regimen is uncommon, but may be related to dosage error or drug

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interactions and these issues should be clarified in patients who present with oral ulceration whilst taking methotrexate.

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Recently, there have been reports of palatal ulceration and necrosis secondary to long-term

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bisphosphonate therapy and this history should always be elicited in patients presenting with chronic palatal ulceration.60,61

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Palatal ulcers can also occur as part of the generalized drug reaction as in erythema multiforme (EM) and Stevens Johnson syndrome. Acute onset, concomitant skin lesions (typical or atypical

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targets) and systemic symptoms provide an useful clue to the diagnosis (Figure 6).62 The

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differentiation from HSV is crucial as steroids which are occasionally administered in EM invariably worsen if the cause is HSV. The rapidity of onset and a history of drug intake are a

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useful indicator of EM. The oral lesions start as bullae on an erythematous base, but intact bullae

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are rarely seen by the clinician because they break rapidly into irregular ulcers.61 Viral lesions are small, round, symmetric, and shallow, but EM lesions are larger, irregular, deeper, and often bleed. Lesions may occur anywhere on the oral mucosa with EM, but involvement of the lips is especially prominent (Figure 6), and gingival involvement is rare. This is an important clinical criterion for distinguishing EM from primary herpes simplex infection, in which generalized gingival involvement is characteristic. 11 Healing occurs within 2 weeks in a majority of cases, but, in some severe cases, extensive disease may continue for several weeks. Management includes withdrawal of suspected drug and conservative therapy without the use of steroids which do not alter the course of the disease and can add to the mortality. 63,64

ACCEPTED MANUSCRIPT Neoplasms

Neoplasms constitute an important cause of long standing palatal ulcers. By far, the commonest

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malignancy affecting the hard palate is squamous cell carcinoma (SCC). SCCs of the palate

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manifest as ulcerative surface lesions. Often, patients are asymptomatic in the early stages, but they may experience pain in advanced stages. A palate mass, bleeding, a foul odor, ill-fitting

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dentures in edentulous patients, or loose teeth may be the presenting symptoms. In persons with advanced soft palate cancers, velopharyngeal insufficiency, altered speech, difficulty

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swallowing, referred otalgia, trismus, or a neck mass may be present.65 History of tobacco

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chewing, betel use, smoking and irradiation should be elicited in all cases. Minor salivary gland tumours can also present as palatal ulcers. These include mucoepidermoid

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carcinoma, adenoid cystic carcinoma and anaplastic carcinoma. 66 A single case of squamous cell carcinoma developing from persistent palatal ulcer in systemic lupus erythematosus has also

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been reported.67 Surgery along with adjuvant radiotherapy and/or chemotherapy is required in all

Iatrogenic causes

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cases.

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Acute palatal ulceration can also follow surgical procedures like maxillectomy, septoplasy and tooth extraction (Figure 5).68 An unusual case of a patient who developed bilateral ulcers of the palate after intense vomiting caused by excessive tightening of her gastric band has also been reported.69 The diagnosis is obvious in most cases. Management involves use of analgesics, obturators and surgical closure if required. Necrotizing sialometaplasia

Necrotizing sialometaplasia (NS) was first described as an inflammatory necrotizing reactive process affecting minor salivary glands of the hard palate. The usual presentation is a deep crateriform ulcer with indurated and well-defined edges or, less often, as a non-ulcerated mass.

ACCEPTED MANUSCRIPT Many risk factors have been described, including: local trauma due to surgery, intubation, poorfitting prostheses, alcohol, tobacco or cocaine use, radiation, respiratory infections or allergies,

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previous adenoidectomy etc.70 The basic cause appears to be ischemia, leading to infarction and

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subsequent necrosis of the tissue Specific histopathologic criteria have been proposed by Adams et al71 for diagnosis of necrotizing sialometaplasia. These include necrosis of acinary cells of

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seromucinous glands; squamous metaplasia of salivary ductal epithelial and acini;

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pseudoepitheliomatous hyperplasia of the epithelium lining the gland; mucous release; inflammatory response associated with granulation tissue in or around the glands; intact lobular

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architecture; and histologically benign nuclear morphology, although normal mitoses can sometimes be observed. The lesions usually heal by secondary intention without treatment within

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4-10 weeks.

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Squamous metaplasia of the ductal epithelium, accompanied by pseudoepitheliomatous

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hyperplasia of the overlying epithelium, might be confused with squamous cell carcinoma, but, preserved general lobular morphology, bland appearance of squamous islands or nests with no

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cytological evidence of malignancy and no findings of residual ductal lumina in any nest helps rule out malignancy in difficult cases.72 Idiopathic Lethal midline granuloma(LMG)

The condition is also known as malignant granuloma or idiopathic lethal granulomatous ulceration of the nose and face. It is essentially an idiopathic lethal tumor of granulation tissue arising in the nose or palate.

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It is a diagnosis that should be considered in a chronic

destructive process of the face . It is now considered by some to be essentially similar to nasal natural killer (NK) T-cell lymphoma (LMG-NTL) ,though this diagnosis requires an extensive investigation to rule out other causes . 75 It must be appreciated though that a diagnosis is not

ACCEPTED MANUSCRIPT always easy in LMG , as a study that found that out of 6 patients only 2 patients had natural killer/T-cell lymphoma, 2 were cases of Wegener's granulomatosis while in 4 no cause could be

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found despite a extensive workup.76 The clinical diagnosis is based on the site of origin, the nose

and the evidently idiopathic nature.

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or palate, the inexorable progression , ulceration and destruction of the central facial structures, The disease usually starts with discomfort or stuffiness in

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the nose with watery or serosanguinous discharge. The nose is gradually filled with adherent

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often gelatinous crusts which on removal reveal areas of ulceration. As the ulcerating granulomatous area spreads perforations of the septum, palate, and later the soft parts of the face

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appear. The diagnosis is arrived after excluding other causes of palatal ulceration . Histopathology mainly shows a chronic inflammatory process, with proliferation of endothelial

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cells, lymphocytes, and plasma cells, and formation of granulation tissue, at first cellular, which

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consequentially shows marked fibrosis.66 In cases where lymphoma is suspected special markers

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for T cells can be employed to arrive at a diagnosis Developmental causes

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The commonest and the most important developmental cause of palatal ulcer is the cleft palate. The palatal defect can either present alone or along with unilateral or bilateral defect of the lip. In cleft palate, the septum is usually midline and is attached to the hard palate as far back as the anterior extent of the hard palate cleft. In complete unilateral cleft lip cleft palate, the vomer is attached to the palate on the noncleft side. In complete bilateral cleft lip cleft palate, the vomer is attached anteriorly to the pre maxilla and remains free of attachments to the palatal shelves.78 Surgical intervention in the early years of life is recommended for best results. Another uncommon developmental cause of palatal ulcer is the torus palatinus. It is essentially a bony protrusion of the palate situated in the midline of the hard palate. Although, autosomal

ACCEPTED MANUSCRIPT dominant inheritance has been frequently suggested for its occurrence, other factors have also been proposed.79 It is possible for ulcers to form on the area of the tori due to repeated trauma.

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Surgical removal of the exostosis is all what is required, and recently Er:Yag laser has been used

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successfully to remove the tori and prevent subsequent ulceration. 80

Approach to diagnosis

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In some cases where the skin is involved (EM) or where the mucosal involvement is involved

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(Aphthosis) the diagnosis is fairly simple (fig 1). Most of the common conditions can be

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diagnosed using a step wise approach as detailed in the flow charts in figures 7 and 8.

History taking: The salient points include –

Duration and recurrence of the ulcer (fig7,8)

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Any history of previous episodes or trauma

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History of prodrome (usually indicates an infective etiology)

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History of recent sexual contact

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History suggestive of tuberculosis or leprosy

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History of surgical procedure / tooth extraction

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History of drug intake

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H/O diabetes, high dose steroids, malignancy or HIV

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

Examination:

On examination, a note should be made of the following points

Nature of the ulcer: number,(fig7) size, shape, margins, surface, discharge

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Examine other parts of oral mucosa and other mucosal surfaces(fig1)

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Look for any skin lesions(fig1)

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Examine nasal cavity for discharge / ulceration

ACCEPTED MANUSCRIPT Investigations:

.

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Bedside testsGram’s stain: for diphtheria, actinomycetes

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Giemsa stain: herpes (multinucleate giant cells), leishmaniasis (leishmania Donovan bodies),

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Acid fast stain: for leprosy, tuberculosis

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pemphigus (acantholytic cells).

KOH mount: fungal pathogens

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DG: Dark ground microscopy for Syphilis

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Biopsy-

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A biopsy from the edge of the ulcer is usually required in case of chronic ulcers. The specimen must include part of the ulcer and the perilesional tissue, including the unaffected surrounding

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epithelium. The centre of the ulcer alone usually does not show diagnostic features. In case of small ulcers (< 5 mm in diameter), an excisional biopsy is recommended (including 2 mm of perilesional tissue), whereas in larger ulcers (> 5 mm in diameter) an incisional biopsy is preferred.2 Both routine hematoxylin and eosin stains as well as special stains and markers for carcinoma are done based on the clinical suspicion and results of bedside tests. The biopsy specimen should be sent for culture specially in chronic cases to rule out an infectious pathology (bacterial, mycobacterial or fungal).

ACCEPTED MANUSCRIPT Laboratory investigationsLaboratory investigations are carried out depending upon the cause suspected. An elaborate list

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of investigations for common causes of palatal ulcer is enlisted in Table 2.

Management

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Management is generally tailored to the cause of palatal ulcer. Analgesics and antibiotics are generally prescribed to all patients, to take care of the pain and secondary infection. In case of

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perforation, management is directed at either sealing the defect or repairing it. Obturators are

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a successful method of managing speech and masticatory problems. Reconstruction is difficult as the ischaemia and necrosis render the tissues more likely to breakdown following surgical

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repair. In case repair is done, local flaps are the best option wherever possible. Distant flaps like forearm flaps may be an option particularly for larger defects.

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Conclusions

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Palatal ulcers are important both due to the difficulty in diagnosis as well as from a therapeutic view point. Though diverse number of causes may lead to palatal ulcers (table 1), the clinical

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presentation is similar. A useful approach is to first classify the ulcers as acute or chronic and look for any associated skin or mucosal lesions(fig1,7,8). Bedside tests may give a useful clue, but biopsy and laboratory investigations are usually required in case of most chronic ulcers. Inspite of all efforts occasionally no cause can be found and thus is still a need for more studies on this vexing clinical problem .

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Table 1: A list of causes of palatal ulcers

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Common

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Acquired

Rare

Aphthous Stomatitis *

Behcet’s syndrome

Infectious

Bacterial Leprosy,tuberculosis, rhinoscleroma, cancrum oris*, acute necotizing ulcerative gingivitis*

Tertiary syphilis, yaws, Paecilomyces sinusitis, tularemia, glanders, Meleny’s ulcer, diphtheria*, typhoid*, granuloma venereum,

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Inflammatory

Fungal Actinomycosis, histoplasmosis, mucormycosis, rhinosporodiosis

Aspergillosis, blastomycosis, sporotrichosis, trichosporonosis, coccidiomycosis, paracoccidiomycosis

Parasitic:- leishmaniasis

Immune- mediated

Viral Herpes simplex*, herpes zoster*, hyperangina*, Lupus erythematosus, Wegener’s granulomatosis, Sweet’s syndrome*, lichen planus, pemphigus and its variants,

Infectious mononucleosis*, HIV Sarcoidosis, Crohn's disease, periarteritis nodosa, Churg Strauss syndrome, mucosal pemphigoid

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Squamous cell carcinoma,

Drug-related

Cocaine, narcotics, methotrexate*, bisphosphonates, erythema multiforme, Stevens Johnson syndrome Maxillectomy*, septoplasty*, intubation*, tooth extraction*, radiation therapy, gastric band tightening, dentures

T cell lymphoma, melanoma, sarcomas Kaposi Sarcoma Mucoepidermoid carcinoma Adenocarcinoma, Anaplastic carcinoma Benign Accessory Salivary Gland Neoplasm Benign Lymphoid Hyperplasia (Follicular Lymphoid Hyperplasia)

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Neoplastic

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Iatrogenic

Idiopathic disease

midline

Others

Factitious, impacted tooth

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Idiopathic

Developmental

destructive

lymphangiomas, Necrotizing sialometaplasia, Necrotizing stomatitis Periapical Abscess

Developmental

Cleft palate Torus Palatinus

Incisive Canal Cyst (Nasopalatine Duct Cyst)

*Indicates the acute causes; HIV: human immunodeficiency virus

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Table 2: List of laboratory investigations for diagnosis of palatal ulceration Investigations

Tubercular ulcer

ESR, Chest x ray,Biopsy,culture

Syphilis

DG,VDRL, TPHA

Herpes simplex

Cytology, ELISA (IgM and Direct

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Suspected cause

fluorescent

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antibody test , Culture

ANA, ds DNA, LE cell test

Wegener’s granulomatosis

ANCA test,biopsy

Pemphigus

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Lupus erythematosis

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immunofluorescence,

Desmoglein ELISA Serum calcium, ACE levels,

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Sarcoidosis

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chest x ray

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ESR: erythrocyte sedimentation rate; DG: dark ground examination; VDRL: venereal disease research laboratory test; TPHA: Treponema pallidum hemagglutination test; HIV: Human immunodeficiency virus; ELISA: enzyme linked immunosorbent assay; ANA: antinuclear antibody; ANCA: antineutrophilic cytoplasmic antibody; ACE: angiotensin converting enzyme

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Figure 1: Site dependent classification of palatal ulcers

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Figure 2: Deep, painful ulcers on the soft palate and faucets of a patient with major aphthous ulcers. The patient responded to a short 7 days course of oral steroids and doxycycline 100g BD for 10 days Figure 3: Deep necrotic ulcer with palatal involvement in a case of Mucormycosis in a diabetic patient Figure 4: Long-standing palatal ulcer in an immunocompetent patient. Trichosporon beigelii was isolated on culture Figure 5: A iatrogenic palatal perforation in a patient with carcinoma of the maxillary region, along with multiple superficial erosions on the buccal mucosa, palate and right half of the face in a segmental distribution (herpes zoster) Figure 6: Hemorrhagic crusting of lips with multiple “typical” target lesions on dorsa of hands in a case of erythema multiforme. Figure 7: A step-wise approach to diagnosis of palatal ulcer depending on the onset ,course and number of ulcers.

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# see Figure 8 *gingival involvement is classic ;** lip crusting is classic ; ***rarely involve the palate ,¶Deep Mycoses: Histoplasmosis ,Blastomycosis ,Mucormycosis, Trichosporonosis

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Figure 8: A schematic approach for diagnosis of chronic long-standing palatal ulcers. (Differentiation between necrotizing sialometaplasia and malignancy is often difficult on histopathology. Idiopathic midline granuloma is usually a diagnosis of exclusion)

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