Understanding Clinical Features and Histologic Findings in Apthous Ulcers

Clinical Features: Recurrent Aphthous minor occurs somewhat more frequently in women that in men, and the majority of patients report the onset of the disease between the ages of 10 and 30 years.

However, it may commence much earlier in life or not begin until much later. Unfortunately, the disease typically persists with recurring attacks over a period of many years.It is believed that nearly 20% of the general population is affected by this disease at one time or another.

It is interesting that approximately 55% of a large group of professional school students studied by ship and his associates gave a positive history of recurrent Aphthous ulcers.

It is also of interest that a rather remarkable familial tendency for occurrence of the disease has been noted by many workers.The onset of the disease may occur with a variety of manifestations which are not invariably present in all cases.

These include the occurrence of one or more small nodules: generalized edema of the oral cavity, especially the tongue: paresthesia, malaise: low-grade fever: localized lymphadenopathy and vesicle – like lesions containing mucus.

The Number of lesions present in any one patient during a single outbreak may vary from one to more over 100. however, according to Graykowski and his associates, over 90% of patients have six lesions or less during a single outbreak.

They vary in size from 2-3 mm. to over 10mm. in diameter. The most common sites of occurrence are the buccal and lingual sulci, tongue, soft palate, pharynx and gingival, all locations of labile mucosa not bound to predilection of recurrent Intraoral herpes simplex infection.

The ulcer themselves generally with little or no evidence of scarring. Recurrent ophthous major is characterized by the occurrence of large painful ulcers, usually one to ten in number, on the lips, cheeks, tongue, soft palate and fauces.

These ulcers occur at frequent intervals, and many patients with this disease are seldom free from the presence of at least one ulcer. Unlike the typical ulcers of recurrent apthous minor, these lesions may persist for up to 6 weeks and leave a scar upon healing.

Not uncommonly, the ulcers recur in waves over a long period of times, so that eventually the oral mucosa may show a great deal of scarring. Patients with these severe major Aphthae also occasionally show similar lesions of the vagina or penis, rectum and larynx, with associated rheumatoid arthritis or conjunctivitis.

According to the review of the disease by Hjorting-Hansen and siemassen, there is no predilection for occurrence in any particular age group, although females are affected more frequently than males.

An excellent discussion of the disease was published recently by lehner. Recurrent herpetiform ulcers of multiple small, shallow ulcers, often up to 100in number, which may occur as any site oral cavity.

They were first described by Cooke in 1960.Which lehner as well as Brooke and Sapp have expanded our knowledge of this condition. Cooke pointed out the clinical similarities of this disease to the lesions of herpes simplex and that the corresponding histologic changes were not similar, since these lesions resemble the recurrent Aphthous ulcers rather than a viral lesion.

The characteristic clinical features of this uncommon condition know as herpetiform ulceration or recurrent herpetiform ulcers were listed by Brooke and Sapp as Follows:

(1) Numerous, small lesions may be found on any intraoral mucosal surface

(2) Lesions begin as small pinhead –sized erosions that gradually enlarge and coalesce

(3) Lesions are more painful than would be suspected by their sizes

(4) Lesions are present almost continuously for one to three years, with relatively short remissions

(5) The patient receives immediate but temporary relief from symptoms with a 2% tetracycline mouthwash.

While these clinical features are very reminiscent of herpes simplex infection, Brooke and Sapp pointed out that laboratory test show that

(1) The herpes simplex virus cannot be cultured from the lesions or demonstrated by electron microscopy, although Sapp and Brooke have demonstrated non viral intranuclear bodies in adjacent epithelial cells

(2) The Microscopic finding are nearly identical with those described for the recurrent apthous ulcer. Although the exact nature of this disease is unknown, including its etiology and pathogenesis.

It is considered appropriate by most investigators to include it as a variant of recurrent aphthous Stomatitis and await further clarification.

Histologic Features:

The Minor aphthous ulcer of the oral mucous membrane exhibits a fibrinopurulent membrane covering he ulcerated area. Occasional superficial colonies of microorganisms may be present in this membrane.

An intense inflammatory cell infiltration is present in the connective tissue beneath the ulcer, with considerable necrosis of tissue near the surface of the lesion, neutrophils predominating immediately below the ulcer but lymphocytes prevailing adjacent to this. Granulation tissue may be noted near the base of the lesion.

Epithelial proliferation is present at the margins of the lesion, similar to that found in any nonspecific ulcer. Accessory salivary gland tissue, commonly present in areas of Aphthae, will typically exhibit focal periductal and perialveolar fibrosis,ductal ectasia and mild chronic inflammation.

These features may be present in even clinically normal mucosa of the aphthous patient. It has also been found that the apthous ulcer itself, atleast in some cases, begins immediately above the excretory duct of one of these minor glands where there is disruption of this ductal epithelium.

The tissue involvement is generally superficial. Lehner has shown that the historical findings by light microscopy of the sever oral ulcers in recurrent apthous major are identical with those described under the recurrent apthous minor. Electron microscope studies have confirmed this similarity.

Wood and his associates have described characteristic changes in the nuclei of epithelial sells taken by cytologic smear from around recurrent apthous ulcers.

This has been referred to as Anitschkow cells and consists of cells and consists of cells with elongated nuclei containing a linear bar of chromatin extending toward the nuclear membrane.

They are quite abundant in patients with recurrent aphthous Stomatitis but are not pathognomic of disease, since they are also found in patients with sickle cell disease, megaloblastic anemias and iron-deficiency anemias, in children receiving chemotherapy for cancer and even in normal people.

Their ultra structure has been described by Haley and his associates, who found that the nuclear chromatin was made up of pleomorphic masses forming an irregular band along the long axis of the nucleus rather than being randomly dispersed

Treatment: There is no specific treatment for recurrent aphthous ulcers although, over the years, many drugs have been advocated. The results of an excellent comparative clinical trial of a variety of drugs have been reported by Graykowski and his coworkers.

Briefly , it was found that a tetracycline mouthwash (250 mg. per 5 ml).used four times daily for 5 to 7 days, produced a good response in nearly 70 per cent of the patients tested by relieving the pain, reducing the size of the lesions and reducing te healing time.

A steroid ointment, 1.5 percent cortisone acetate, applied locally, and hydrocortisone acetate – antibiotic lozenges also showed some effectiveness but not as great as the tetracycline.Chemical cautery reduced pain but had no other beneficial effects.

No significant improvement was found with the use of antihistaminics, gamma globulin, multiple small pox vaccinations or a Lactobacillus acidophilus-L.bulgaricus preparation, all of which have variously been reported to be effective.

There has also been extensive clinical trial of levamisole, originally developed as an anthelmintic drug against nematodes in both man and animals, which has been fond also to potentiate the immune response in a variety of ways.

The results of a number of these studies in treating recurrent apthous Stomatitis have been reported, some showing a reduction in the duration of symptoms.

Some showing a decrease in the duration of lesions, some showing a diminished frequency of lesions, but others concluding that the drug had magnificent effect on severity or incidence of lesions.

It was concluded in the workshop on Aphthous Stomatitis – behcet’s syndrome, where a number of these reports were presented, that further clinical evaluation of this drug is necessary.

An excellent summary of the many drugs and chemicals which have been used to treat recurrent aphthous Stomatitis over the years has been prepared by antoon and miller. Unfortunately, despite any form of therapy, there is no known cure for the disease.



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