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In the latest Case Record of the Massachusetts General Hospital, a 51-year-old woman presented with a history of recurrent epistaxis and oral ulcers that were transiently responsive to glucocorticoids. Chronic, persistent multifocal ulcers in the oral cavity are seen in the following three broad categories of conditions: infections, immune-mediated disorders, and autoimmune blistering disorders.
The Boston Globe wrote about the Massachusetts Medical Society’s newly appointed executive vice president, Lois Dehls Cornell, who will lead the MMS when Corinne Broderick retires next month.
Oral mucosa shows considerable variation in its normal structure and can be affected by a wide range of conditions.
Specialised mucosa: This includes filiform, fungiform and circumvallate papillae of the dorsal tongue. In order to be able to recognise mucosal abnormality, it is necessary to be familiar with normal anatomical structures that patients may notice and become concerned about. Chronic mechanical, thermal or chemical trauma may induce a keratinising response in buccal mucosa (which is normally non-keratinising) and hyperkeratosis (excessive keratinisation) elsewhere (Fig.
A fibroepithelial polyp is typically a firm sessile or pedunculated polyp that arises most commonly on the labial and buccal mucosa as a result of mechanical trauma from the teeth or dentures (Fig. Histopathologically there is a core of dense fibrous tissue covered by stratified squamous epithelium.
Denture irritation hyperplasia often forms in relation to denture flanges that have become overextended because of alveolar resorption. Connective tissue neoplasms are uncommon in the oral mucosa, but benign tumours including lipoma, neuroma and fibroma may occur and mimic fibrous hyperplasia clinically. On clinical examination, traumatic ulcers typically are painful and surrounded by erythema.
Management is to elicit an accurate history, document the features of the ulcer, eliminate the cause if possible, provide symptomatic treatment and review to ensure that healing takes place. Reurrent aphthous stomatitis (RAS) or recurrent aphthous ulceration is an extremely common disorder of the oral cavity, estimated to affect 20% of the population.
The aetiology of RAS is unknown, though there are strong associations with having a family history of RAS, stress, smoking cessation, anaemia and haematinic deficiency.
It is difficult to prevent ulceration from occurring in susceptible individuals; however, limiting trauma to the oral mucosa by eliminating sharp foods, in particular crisps, from the diet can be of benefit. Oral involvement in herpes simplex (HSV) infection is commonly encountered, especially in children, and is most often due to HHV-1 (Fig. After primary infection, HHV-1 may remain in the trigeminal ganglion and low levels of virus are shed into the axoplasm thereafter. Herpes zoster (HHV-3), the causative agent of chickenpox and shingles (Chapter 14), may involve the oral mucosa.
Human papillomaviruses (low risk types) produce focal proliferative lesions referred to as squamous papillomas (warts).
Initial infection by HIV may be asymptomatic or may cause a febrile illness with diarrhoea.
Kaposi’s sarcoma: This is caused by human herpesvirus 8 (HHV-8), which is endemic in Mediterranean regions.
Hairy leukoplakia: This lesion has been associated with progression from HIV infection to AIDS (acquired immunodeficiency syndrome) as the CD4 T lymphocyte count falls.
July 18, 2012 by mspiro “Thick, sticky mucus layers limit effectiveness of drug delivery to mucosal tissues. Johns Hopkins researchers say they have demonstrated for the first time, in animals, that nanoparticles can slip through mucus to deliver drugs directly to tissue surfaces in need of protection. The researchers used these mucus-penetrating particles, or MPPs, to protect against vaginal herpes infections in mice. Hanes also is a principal investigator with the Johns Hopkins Center of Cancer Nanotechnology Excellence.
The moist mucosal surfaces of the body, like the eyes, lungs, intestines and genital tract, are protected from pathogens and toxins by layers of moist sticky mucus that is constantly secreted and shed, forming our outermost protective barrier. Unfortunately, Ensign noted, mucus barriers also stop helpful drug delivery, especially conventional nanoparticles intended for sustained drug delivery. Ensign explained that conventional nanoparticles actually stick to mucus before releasing their drug payload and are then removed when the mucus is replenished, often within minutes to hours.
Hanes emphasized that the MPPs provided greatly improved protective efficacy while at the same time reducing the effective dose of drug needed 10-fold. Their technology could lead to a once-daily treatment for preventing sexually transmitted diseases, for contraception and for treatment of cervico-vaginal disorders, Ensign said.
Ensign added that MPP technology has the potential to prevent a wide range of mucosal diseases and infections, including chronic obstructive pulmonary disease, lung cancer, and cystic fibrosis,” Ensign said.
Under a licensing agreement between Kala Pharmaceuticals and the Johns Hopkins University, Hanes is entitled to a share of royalties received by the university on sales of products used in the study.
Hanes and the university own Kala Pharmaceuticals stock, which is subject to certain restrictions under university policy. Abnormal Pap smear Results: In the Top 10 List of HIV symptoms for women we keep Abnormal Pap Smear Results in the 1st place.
Severe Vaginal Infections That Recur: In the Top 10 List of HIV symptoms for women we keep Severe Vaginal Infections That Recur in the 2nd place. Frequent Yeast Infections: In the Top 10 List of HIV symptoms for women we keep Frequent Yeast Infections in the 4th place. Abnormal Cervical Changes Including Dysplasia: In the Top 10 List f HIV symptoms for women e keep Abnormal Cervical Changes Including Dysplasia in the 5th place. Genital Ulcers and Warts: In the Top 10 List of HIV symptoms we keep this term in the 6th place.
Mucosal Herpes Infections Which Are Severe: In the Top 10 List of HIV symptoms we keep Mucosal Herpes Infections Which are severe in the 7th place. Examination revealed erosions of the mucous membranes of the tongue, soft palate, and buccal mucosa.
Some important differentiating features include the size and appearance of lesions, involvement of keratinized versus nonkeratinized sites (especially the gingiva), complete healing of lesions between outbreaks, and involvement of skin.
Viruses of the herpesvirus family establish latency and may cause recurrent oral or oropharyngeal ulcers. Patients with a variant of granulomatosis with polyangiitis may present with limited involvement of the upper airways and oral cavity. Patients typically present with bright red, painful denudation on the gingiva (desquamative gingivitis) or with ulcers on the palate.


Lesions begin in the oral cavity in up to 60% of patients, with skin lesions developing months or years later. The identification of oral mucosal abnormalities is important because they can be harmless, minor primary conditions and secondary indications of systemic disease. It forms the buccal and labial mucosa, vestibular, floor of mouth, ventral tongue and soft palate. It is a bilateral, diffuse, whitish translucency of the buccal mucosa found commonly in Black and variably in White people.
11.1 Frictional keratosis in a patient who habitually chewed the buccal mucosa, particularly when stressed.
Elimination of the cause of irritation may reverse the process, resulting in shrinkage or resolution. 11.2 Leaf-like fibrous hyperplasia of the palate caused by chronic irritation from an ill-fitting upper denture. Malignant soft tissue neoplasms are extremely rare but may arise from any connective tissue in the oral cavity. It is also associated with systemic diseases, drug side-effects and with infections (see Section 11.4). The base is covered by fibrinous exudate and at a later stage by granulation tissue and regenerating epithelium (see Fig. Any ulcer that does not heal within 3 weeks should be considered as suspicious and fast-track referred for specialist opinion to exclude carcinoma. RAS is also seen in gastrointestinal disease, particularly Crohn’s disease (which may involve the oral mucosa directly or induce oral ulceration secondary to malabsorption), coeliac disease and other disorders of malabsorption. Because of its association with disease of the gastrointestinal tract, specific enquiry should be made into signs and symptoms of gastrointestinal problems.
Similarly, where trauma from the teeth as a result of parafunctional habits is suspected, the provision of a soft bite guard for night-time wear may help. Treponema pallidum causes syphilis and mucosal lesions include primary chancres, secondary snail track ulcers and tertiary areas of focal necrosis (termed gumma). 11.6 Primary herpetic gingivostomatitis, showing vesicles and erythema of the palatal mucosa and gingivae. Grey blisters, which rapidly break down to form small ulcers, may be present anywhere on the oral mucosa and most frequently involve the gingivae. Local factors, such as exposure of the lip to intense sunlight, and systemic factors, such as depressed general immunity, result in herpes labialis (cold sores) in about 20–30% of individuals.
Shingles tends to affect one or more dermatomes of the trigeminal nerve and is an important cause of facial pain (Chapter 14).
Initial mucosal lesions are flat brown spots, which show haemosiderin deposition and vascular proliferation on biopsy.
It is caused by proliferation of Epstein–Barr virus (HHV-4) in the lateral tongue epithelium and rarely elsewhere in the oral cavity.
Mucus-penetrating particles or MPPs (in red) are able to penetrate mucus, covering the entire surface of the mouse vagina (in blue).
The goal is to create similar MPPs to deliver drugs that protect humans against sexually transmitted diseases or even treat cancer. Results of his team’s experiments are described in the June 13 issue of the journal Science Translational Medicine. In a Johns Hopkins laboratory, researchers developed nanoparticles that do not stick to mucus so they can slip through to reach the cells on the mucosal surface, in this case the surface of the mouse vagina, she added. Abnormal Pap smear results are often one of the first signs of HIV infection notices. The virus causes cell changes in the pelvic area that are picked up by the test.
The HIV virus attacks cervical cells, and can cause abnormal cell changes including cervical dysplasia that can eventually lead to cancer if not detected in time.
One of the top HIV symptoms in women is the appearance of genital ulcers, genital warts, or both. The difference between HIV and AIDS is the ability of your immune system to fight of infections.
These symptoms can include an HIV rash, fever, chills, body aches, nausea, diarrhea, and other common viral infection symptoms. When you are first exposed to the virus your body will make antibodies to fight off HIV infection.
The soft palate and the mucosa of the hard palate are commonly involved because of trauma from swallowing. The situation is further complicated by the multiple causes for many mucosal lesions: for example, ulceration can reflect simple trauma, a habit tic with psychiatric implications, lichen planus, infection, gastrointestinal disease such as Crohn’s disease or a side-effect of a drug. The clinical appearance is considered to be diagnostic and biopsy is not normally indicated. Many fibrous hyperplastic lesions are excised, however, because this is a simple and rapid method of treatment. It is easily excised under local analgesia but will recur unless the source of trauma is corrected. Papillary hyperplasia may be seen in the palatal mucosa covered by a poorly fitting denture. The most frequent cause is mechanical injury from the teeth; such ulcers occur on the buccal mucosa, lateral tongue and lower lip in the occlusal plane. The disorder first manifests in early childhood but more frequently is noticed at around the time of puberty. They persist for a minimum of 4 weeks with one to three ulcers normally being present at a time. Similarly, the possibility of Behcet’s disease leads to enquiry concerning the presence of other signs and symptoms of this disease. In the oral mucosa, rashes of grey vesicles restricted to the distribution of the sensory nerves are seen. Histologically, fronds of keratotic squamous epithelium are supported by delicate fibrovascular stroma. They progress into raised plaques and then nodular purple–red lesions, most often found on the palate, retromolar areas and gingivae. Warty ridged or smooth white plaques are typical: sometimes extended papillary projections are seen. Improved distribution and retention of MPPs led to significantly increased protection in a mouse model for herpes simplex virus infection.


These infections occur because of an organism imbalance and lowered immune system in your body. HIV can lead to severe mucosal herpes infections as your immune system becomes more compromised over time. This discharge can be clear, cloudy, or colored, and may vary in the amount depending on your specific condition.
Recrudescent HSV infections frequently present as herpes labialis and, in immunocompetent patients, as ulcers on the keratinized mucosa of the gingiva, hard palate, and dorsum of the tongue. ANCAs with specificity for serine proteinase 3 (more common) or myeloperoxidase   (less common) are almost always positive. Collapsed bullae and erosions may also occur in other mucosal sites, although they are almost always accompanied by involvement of the gingiva or palate or both.
Recognition of leukoedema is important because it may be mistaken for a clinically significant disorder. All such tissue should be forwarded for histopathological examination to confirm the diagnosis. Ulcers tend to occur in crops of one to five but variable patterns are seen, ranging from occasional single ulcers to over 20 at any one time. Behcet’s disease is a multisystem autoimmune disorder for which RAS is one of the major diagnostic criteria. A full blood count and haematinics (serum vitamin B12, ferritin (an iron-binding protein), folate) should be carried out. Infection is usually accompanied by a febrile illness, and bilateral tender cervical lymphadenopathy is frequently present.
Papillomas on the fingers can be the source of human papillomavirus, particularly for lesions on the lips and circumoral skin.
The lesion is also found in HIV-negative immunosuppressed patients, for example in renal transplant recipients. Scarring is common in ocular pemphigoid but not in oral pemphigoid, and erosive lesions of the larynx, pharynx, and nasal mucosa occur in approximately 35% of cases.
Laryngeal or pharyngeal involvement is present in up to 80% of patients, nasal crusting and erosions are found in up to 60%, and the ears are involved in 20%. Diagnosis is clinical and treatment normally involves eliminating the cause and reviewing to ensure resolution. Where such a drug reaction is suspected, the possibility of changing the medication believed to be responsible should be raised with the patient’s general practitioner, who needs to balance any risks associated with such a change against the benefits to the patient.
The severity of symptoms is greater than in minor RAS, with some patients experiencing a continuous pattern of ulceration.
Where vitamin B12 deficiency is detected, the possibility of pernicious anaemia should be investigated by checking the blood for antibodies to intrinsic factor.
In terms of medication, some relief of symptoms may be obtained by the use of benzydamine mouthwash or spray.
It is important for the dental team to recognise the mucosal lesions of primary and secondary syphilis; while treatment with antibiotic is effective, contact tracing is an important aspect of management. Infection can be spread to the fingers and conjunctiva by direct contact with the oral lesions, and advice should be given to avoid this.
In a small number of individuals, recurrent intraoral HSV infection may occur and lesions most commonly affect the hard palate and attached gingivae. Hairy leukoplakia has been recorded in patients taking a variety of drugs, including steroid inhalers, and HHV-4 may also be a transient mucosal infection in healthy people. Cytotoxic drugs cause oral ulceration through toxicity to the rapidly turning over cell population in the oral epithelium. Low levels of ferritin, in the absence of the an apparent cause such as blood loss from the gastrointestinal or genitourinary tract, are suggestive of coeliac disease and the patient’s blood should be checked for the presence of endomyseal or tissue transglutaminase antibody. Both chlorhexidine and doxycyclin mouthwashes can be of benefit; the latter seems to be of particular value in the treatment of herpetiform ulceration.
Severe recurrent HSV infection may occur in the immunocompromised and further investigation to exclude this possibility should be performed. Direct application of legal and illegal drugs for extended periods to the oral mucosa can produce severe ulceration at the site.
Severe unusual RAS is a recognised manifestation of infection with the human immunodeficiency virus (HIV). Coeliac disease has a prevalence of 0.5–1% in the population and may be diagnosed in children and adults. Topical steroid preparations are widely used (see Section 11.5) and betamethasone mouthwash to be particularly effective, if used on a daily basis, when episodes of ulceration are frequent. Tuberculosis infection is usually secondary to pulmonary lesions and presents as granular ulceration of the posterior palate and dorsal tongue. Rest, maintaining fluid intake, analgesics, chlorhexidine mouthwash to prevent secondary infection of the oral lesions and advice about cross-infection risks should be given.
The high risk HPV types 16 and 18 are an important cause of oropharyngeal carcinoma (see Chapter 12). For severe cases, systemic medication is indicated, for example thalidomide, colchicine or systemic steroids; such agents should only be prescribed by a hospital-based specialist.
Infants under 6 months are at special risk of developing central nervous system infection and contact with infected siblings should be avoided. Chemical causes of traumatic ulceration include placing aspirin in the vestibule, and rinsing with astringent chemicals.
Prescription of systemic aciclovir is only of benefit in the early stages of the infection; a reasonable guide to this is the presence of intact vesicles. Traumatic ulcers are common on the lower lip and may follow mechanical or thermal injury after inferior alveolar nerve block. Diagnosis is usually made on clinical grounds, where doubt exists, serology performed on samples of acute and convalescent (2–3 weeks after onset of symptoms) blood should reveal a significant rise (of the order of four-fold or greater) in IgG antibodies against HSV in the later sample. While correction of haematinic deficiencies can bring about resolution or improvement of the patient’s oral ulceration, this is pointless if the underlying cause of the deficiency is not addressed.



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