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Chapter Contents
Ulcerative Conditions
Recurrent Aphthous Ulcers and Traumatic Ulcers
Most cases of recurrent aphthous ulcers are idiopathic; however, aphthous-like lesions are seen in Behçet disease, Crohn disease (often linear in the sulcus), hematinic deficiencies, some hypersensitivity reactions (such as to food or sodium lauryl sulfate found in toothpaste), cyclic neutropenia, and HIV infection. Complex aphthosis is often used to describe lesions associated with syndromes affecting the skin. Ulcers in children may be part of periodic fever, aphthosis, pharyngitis, and adenopathy (PFAPA) syndrome. Trauma and stress bring on episodes in susceptible individuals. Minor aphthous ulcers do not tend to be biopsied, owing to the typical history and presentation, whereas major ulcers are biopsied to rule out vesiculobullous disease or infections. Chemotherapy-induced ulcerations are much larger and diffuse, resolve predictably over 1 to 2 weeks, and are not aphthous ulcers. New therapies such as mammalian target of rapamycin (mTOR) inhibitors may cause severe aphthous-like ulcers that heal on withdrawal of drug.
Traumatic ulcers are caused by trauma, usually on the buccal mucosa, tongue, and lower lip (that are sites of morsicatio mucosae oris), and are indistinguishable histologically from recurrent aphthous ulcers. They also occur secondarily on lesions that protrude (eg, fibromas and gingival nodules).
Clinical Findings
- •
Idiopathic aphthous ulcers: Onset usually occurs in the second and third decades of life with a 2 : 1 female predilection, and lesions diminish in severity with age. Ulcers are episodic or continuous, single or multiple, and occur almost exclusively on the nonkeratinized mucosa. They are sharply demarcated and painful, with a yellow fibrin membrane with surrounding erythema.
- •
Four clinical types are recognized:
- •
Minor ulcers are the most common, are smaller than 1 cm in size, and last 1 to 2 weeks.
- •
Major ulcers are the least common, are larger than 1 cm in size, last for weeks or months, and often are associated with scarring. This form is often seen in HIV/AIDS.
- •
Herpetiform ulcers are uncommon and number more than 10 ulcers (<1 cm) at each episode.
- •
Severe aphthous ulcers present as continuous minor aphthous ulcerations ( Fig. 7.1A–C ).
FIG 7.1 (A) Recurrent minor aphthous ulcers on the left upper lip mucosa. (B) Recurrent major aphthous ulcer on the left soft palate. (C) Recurrent herpetiform aphthous ulcers on the soft palate. (D) Ulcer caused by mammalian target of rapamycin inhibitor. (E) Traumatic ulcer caused by a broken tooth. (F) Traumatic ulcer on palatal exostosis.
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- •
Aphthous-like ulcers associated with systemic disease may occur on the keratinized mucosa. Those associated with chemotherapy (such as mTOR inhibitors) regress on completion or discontinuation of therapy ( Fig. 7.1D ). Those associated with medications tend to occur in older individuals.
- •
Traumatic ulcers have a history of trauma or identifiable cause of trauma (such as a sharp cusp or broken tooth). They are often seen on protuberant areas, such as fibromas, gingival nodules, or exostoses ( Fig. 7.1E–F ).
- •
New international diagnostic criteria based on a point system have been established for Behçet disease with high sensitivity. Oral aphthous-like ulcers, genital ulcers, and eye lesions are the most important and consistent findings.
Etiopathogenesis and Histopathologic Features
Most cases of recurrent aphthae have a strong family history of recurrent aphthae, and some human leukocyte antigen A haplotypes have been identified. Tumor necrosis factor (TNF)-α plays an important role in etiopathogenesis.
- •
Ulcers consist of a fibrin membrane with enmeshed neutrophils and underlying granulation tissue with acute and chronic inflammatory cells confined to the lamina propria and sometimes involving superficial skeletal muscle fibers. The adjacent epithelium exhibits spongiotic pustules and reactive atypia such as basal cell hyperplasia, nuclear hyperchromasia, and slight pleomorphism. Traumatic ulcers often show adjacent parakeratosis and surface bacterial colonies ( Fig. 7.2 ).
FIG 7.2 (A, B) Aphthous ulcer. (A) Ulcer composed of fibrin with inflammation involving only the superficial lamina propria. (B) The epithelium exhibits spongiosis, hemorrhage, neutrophilic exocytosis, and spongiotic pustules. (C, D) Traumatic ulcer. (C) Fibrin membrane with underlying granulation tissue and acute and chronic inflammation. Note adjacent traumatic parakeratosis with surface bacterial colonization. (D) Acanthosis, many spongiotic pustules, intraepithelial hemorrhage, and reactive epithelial atypia. - •
Healing ulcers or the edge of ulcers demonstrate subepithelial fibrin deposition, spongiotic pustules, reactive epithelial atypia, and often intraepithelial and subepithelial hemorrhage ( Fig. 7.3 ).
FIG 7.3 Edge of an ulcer. (A) Oral mucosa with intact epithelium, traumatic parakeratosis, intraepithelial hemorrhage, subepithelial fibrin deposition, and granulation tissue. (B) Subepithelial fibrin deposition with intraepithelial hemorrhage and reactive epithelial atypia. - •
Spread of inflammation to underlying muscle results in myositis and, if chronic, traumatic ulcerative granuloma with eosinophilia (see later).
Differential Diagnosis
- •
The epithelium adjacent to the ulcer should be evaluated for herpes simplex virus cytopathic effect, and the connective tissue should be searched for cytomegalovirus and fungi in immunocompromised patients.
- •
Neutropenic ulcers have scarce neutrophils ( Fig. 7.4 ).
FIG 7.4 Neutropenic ulcer. (A) Fibrin membrane with underlying granulation tissue. (B) Paucity of neutrophils within fibrin meshwork.
Management and Prognosis
- •
Topical steroid therapy and topical analgesia are effective for minor aphthae, though idiopathic aphthous ulcers are episodic and will recur. Aphthous major and severe and/or continuous aphthous ulcers usually require systemic therapy (see Appendix A ). TNF-α inhibitors are useful for lesions resistant to other systemic therapy.
- •
For systemic conditions presenting with aphthous-like ulcers, careful history taking and work-up are important.
- •
Adenotonsillectomy may be effective in some patients with PFAPA syndrome.
References
Recurrent Aphthous Ulcers and Traumatic Ulcers
Most cases of recurrent aphthous ulcers are idiopathic; however, aphthous-like lesions are seen in Behçet disease, Crohn disease (often linear in the sulcus), hematinic deficiencies, some hypersensitivity reactions (such as to food or sodium lauryl sulfate found in toothpaste), cyclic neutropenia, and HIV infection. Complex aphthosis is often used to describe lesions associated with syndromes affecting the skin. Ulcers in children may be part of periodic fever, aphthosis, pharyngitis, and adenopathy (PFAPA) syndrome. Trauma and stress bring on episodes in susceptible individuals. Minor aphthous ulcers do not tend to be biopsied, owing to the typical history and presentation, whereas major ulcers are biopsied to rule out vesiculobullous disease or infections. Chemotherapy-induced ulcerations are much larger and diffuse, resolve predictably over 1 to 2 weeks, and are not aphthous ulcers. New therapies such as mammalian target of rapamycin (mTOR) inhibitors may cause severe aphthous-like ulcers that heal on withdrawal of drug.
Traumatic ulcers are caused by trauma, usually on the buccal mucosa, tongue, and lower lip (that are sites of morsicatio mucosae oris), and are indistinguishable histologically from recurrent aphthous ulcers. They also occur secondarily on lesions that protrude (eg, fibromas and gingival nodules).
Clinical Findings
- •
Idiopathic aphthous ulcers: Onset usually occurs in the second and third decades of life with a 2 : 1 female predilection, and lesions diminish in severity with age. Ulcers are episodic or continuous, single or multiple, and occur almost exclusively on the nonkeratinized mucosa. They are sharply demarcated and painful, with a yellow fibrin membrane with surrounding erythema.
- •
Four clinical types are recognized:
- •
Minor ulcers are the most common, are smaller than 1 cm in size, and last 1 to 2 weeks.
- •
Major ulcers are the least common, are larger than 1 cm in size, last for weeks or months, and often are associated with scarring. This form is often seen in HIV/AIDS.
- •
Herpetiform ulcers are uncommon and number more than 10 ulcers (<1 cm) at each episode.
- •
Severe aphthous ulcers present as continuous minor aphthous ulcerations ( Fig. 7.1A–C ).
FIG 7.1 (A) Recurrent minor aphthous ulcers on the left upper lip mucosa. (B) Recurrent major aphthous ulcer on the left soft palate. (C) Recurrent herpetiform aphthous ulcers on the soft palate. (D) Ulcer caused by mammalian target of rapamycin inhibitor. (E) Traumatic ulcer caused by a broken tooth. (F) Traumatic ulcer on palatal exostosis.
- •
- •
Aphthous-like ulcers associated with systemic disease may occur on the keratinized mucosa. Those associated with chemotherapy (such as mTOR inhibitors) regress on completion or discontinuation of therapy ( Fig. 7.1D ). Those associated with medications tend to occur in older individuals.
- •
Traumatic ulcers have a history of trauma or identifiable cause of trauma (such as a sharp cusp or broken tooth). They are often seen on protuberant areas, such as fibromas, gingival nodules, or exostoses ( Fig. 7.1E–F ).
- •
New international diagnostic criteria based on a point system have been established for Behçet disease with high sensitivity. Oral aphthous-like ulcers, genital ulcers, and eye lesions are the most important and consistent findings.
Etiopathogenesis and Histopathologic Features
Most cases of recurrent aphthae have a strong family history of recurrent aphthae, and some human leukocyte antigen A haplotypes have been identified. Tumor necrosis factor (TNF)-α plays an important role in etiopathogenesis.
- •
Ulcers consist of a fibrin membrane with enmeshed neutrophils and underlying granulation tissue with acute and chronic inflammatory cells confined to the lamina propria and sometimes involving superficial skeletal muscle fibers. The adjacent epithelium exhibits spongiotic pustules and reactive atypia such as basal cell hyperplasia, nuclear hyperchromasia, and slight pleomorphism. Traumatic ulcers often show adjacent parakeratosis and surface bacterial colonies ( Fig. 7.2 ).
FIG 7.2 (A, B) Aphthous ulcer. (A) Ulcer composed of fibrin with inflammation involving only the superficial lamina propria. (B) The epithelium exhibits spongiosis, hemorrhage, neutrophilic exocytosis, and spongiotic pustules. (C, D) Traumatic ulcer. (C) Fibrin membrane with underlying granulation tissue and acute and chronic inflammation. Note adjacent traumatic parakeratosis with surface bacterial colonization. (D) Acanthosis, many spongiotic pustules, intraepithelial hemorrhage, and reactive epithelial atypia. - •
Healing ulcers or the edge of ulcers demonstrate subepithelial fibrin deposition, spongiotic pustules, reactive epithelial atypia, and often intraepithelial and subepithelial hemorrhage ( Fig. 7.3 ).
FIG 7.3 Edge of an ulcer. (A) Oral mucosa with intact epithelium, traumatic parakeratosis, intraepithelial hemorrhage, subepithelial fibrin deposition, and granulation tissue. (B) Subepithelial fibrin deposition with intraepithelial hemorrhage and reactive epithelial atypia. - •
Spread of inflammation to underlying muscle results in myositis and, if chronic, traumatic ulcerative granuloma with eosinophilia (see later).
Differential Diagnosis
- •
The epithelium adjacent to the ulcer should be evaluated for herpes simplex virus cytopathic effect, and the connective tissue should be searched for cytomegalovirus and fungi in immunocompromised patients.
- •
Neutropenic ulcers have scarce neutrophils ( Fig. 7.4 ).
FIG 7.4 Neutropenic ulcer. (A) Fibrin membrane with underlying granulation tissue. (B) Paucity of neutrophils within fibrin meshwork.
Management and Prognosis
- •
Topical steroid therapy and topical analgesia are effective for minor aphthae, though idiopathic aphthous ulcers are episodic and will recur. Aphthous major and severe and/or continuous aphthous ulcers usually require systemic therapy (see Appendix A ). TNF-α inhibitors are useful for lesions resistant to other systemic therapy.
- •
For systemic conditions presenting with aphthous-like ulcers, careful history taking and work-up are important.
- •
Adenotonsillectomy may be effective in some patients with PFAPA syndrome.
Clinical Findings
- •
Idiopathic aphthous ulcers: Onset usually occurs in the second and third decades of life with a 2 : 1 female predilection, and lesions diminish in severity with age. Ulcers are episodic or continuous, single or multiple, and occur almost exclusively on the nonkeratinized mucosa. They are sharply demarcated and painful, with a yellow fibrin membrane with surrounding erythema.
- •
Four clinical types are recognized:
- •
Minor ulcers are the most common, are smaller than 1 cm in size, and last 1 to 2 weeks.
- •
Major ulcers are the least common, are larger than 1 cm in size, last for weeks or months, and often are associated with scarring. This form is often seen in HIV/AIDS.
- •
Herpetiform ulcers are uncommon and number more than 10 ulcers (<1 cm) at each episode.
- •
Severe aphthous ulcers present as continuous minor aphthous ulcerations ( Fig. 7.1A–C ).
FIG 7.1 (A) Recurrent minor aphthous ulcers on the left upper lip mucosa. (B) Recurrent major aphthous ulcer on the left soft palate. (C) Recurrent herpetiform aphthous ulcers on the soft palate. (D) Ulcer caused by mammalian target of rapamycin inhibitor. (E) Traumatic ulcer caused by a broken tooth. (F) Traumatic ulcer on palatal exostosis.
- •
- •
Aphthous-like ulcers associated with systemic disease may occur on the keratinized mucosa. Those associated with chemotherapy (such as mTOR inhibitors) regress on completion or discontinuation of therapy ( Fig. 7.1D ). Those associated with medications tend to occur in older individuals.
- •
Traumatic ulcers have a history of trauma or identifiable cause of trauma (such as a sharp cusp or broken tooth). They are often seen on protuberant areas, such as fibromas, gingival nodules, or exostoses ( Fig. 7.1E–F ).
- •
New international diagnostic criteria based on a point system have been established for Behçet disease with high sensitivity. Oral aphthous-like ulcers, genital ulcers, and eye lesions are the most important and consistent findings.
Etiopathogenesis and Histopathologic Features
Most cases of recurrent aphthae have a strong family history of recurrent aphthae, and some human leukocyte antigen A haplotypes have been identified. Tumor necrosis factor (TNF)-α plays an important role in etiopathogenesis.
- •
Ulcers consist of a fibrin membrane with enmeshed neutrophils and underlying granulation tissue with acute and chronic inflammatory cells confined to the lamina propria and sometimes involving superficial skeletal muscle fibers. The adjacent epithelium exhibits spongiotic pustules and reactive atypia such as basal cell hyperplasia, nuclear hyperchromasia, and slight pleomorphism. Traumatic ulcers often show adjacent parakeratosis and surface bacterial colonies ( Fig. 7.2 ).
FIG 7.2 (A, B) Aphthous ulcer. (A) Ulcer composed of fibrin with inflammation involving only the superficial lamina propria. (B) The epithelium exhibits spongiosis, hemorrhage, neutrophilic exocytosis, and spongiotic pustules. (C, D) Traumatic ulcer. (C) Fibrin membrane with underlying granulation tissue and acute and chronic inflammation. Note adjacent traumatic parakeratosis with surface bacterial colonization. (D) Acanthosis, many spongiotic pustules, intraepithelial hemorrhage, and reactive epithelial atypia. - •
Healing ulcers or the edge of ulcers demonstrate subepithelial fibrin deposition, spongiotic pustules, reactive epithelial atypia, and often intraepithelial and subepithelial hemorrhage ( Fig. 7.3 ).
FIG 7.3 Edge of an ulcer. (A) Oral mucosa with intact epithelium, traumatic parakeratosis, intraepithelial hemorrhage, subepithelial fibrin deposition, and granulation tissue. (B) Subepithelial fibrin deposition with intraepithelial hemorrhage and reactive epithelial atypia. - •
Spread of inflammation to underlying muscle results in myositis and, if chronic, traumatic ulcerative granuloma with eosinophilia (see later).
Differential Diagnosis
- •
The epithelium adjacent to the ulcer should be evaluated for herpes simplex virus cytopathic effect, and the connective tissue should be searched for cytomegalovirus and fungi in immunocompromised patients.
- •
Neutropenic ulcers have scarce neutrophils ( Fig. 7.4 ).
FIG 7.4 Neutropenic ulcer. (A) Fibrin membrane with underlying granulation tissue. (B) Paucity of neutrophils within fibrin meshwork.
Management and Prognosis
- •
Topical steroid therapy and topical analgesia are effective for minor aphthae, though idiopathic aphthous ulcers are episodic and will recur. Aphthous major and severe and/or continuous aphthous ulcers usually require systemic therapy (see Appendix A ). TNF-α inhibitors are useful for lesions resistant to other systemic therapy.
- •
For systemic conditions presenting with aphthous-like ulcers, careful history taking and work-up are important.
- •
Adenotonsillectomy may be effective in some patients with PFAPA syndrome.
References
Traumatic Ulcerative Granuloma With Stromal Eosinophils, Eosinophilic Ulcer of Tongue
These chronic traumatic ulcers with myositis have bimodal peaks of occurrence.
Clinical Findings
- •
Adult form: This occurs as a sharply punched-out ulcer, often with a white, keratotic rim, commonly on the lateral tongue, present for weeks, with or without pain, and raising the suspicion for malignancy. Any site with underlying muscle may be involved ( Fig. 7.5A–C ). Synchronous bilateral lesions or metachronous lesions may occur.
