Oral medicine case book 64: Some aspects of the pathophysiology of angioedema with special reference to the upper aerodigestive tract.

Angioedema refers to a localized oedematous swelling of subcutaneous or submucosal tissues, caused by dilatation and increased permeability of blood vessels, usually mediated either by histamine or by bradykinin. Deficiency or loss of functional activity of the complement component C1 esterase inhibitor (C1-INH) affects multiple systems, including the kallikrein-kinin, complement, coagulation and fibrinolytic pathways, and in the context of angioedema, the result is increased production and release of bradykinin and other vasoactive substances such as C3a. Owing to impairment of C1-INH, factors Xlla and kallikrein, by a positive feedback mechanism, bring about persistent activation of the kallikrein-kinin pathway with amplification of production of bradykinin, resulting in angioedema. Histamine can cause histaminergic angioedema. As the name implies, this oedema is caused by degranulation of mast cells/basophils as a result of an IgE-dependant allergic reaction to extracts of food, drugs, infectious agents, or to physical stimulation; or as the result of direct degranulation of mast cells/basophils independently of IgE, caused by releasing agents such as opiates, antibiotics or radiocontrast media. As dental, oral and maxillofacial operative procedures may trigger the development of angioederria in susceptible individuals, the dental practitioner should be familiar with its

Oral medicine case book 51: actinic cheilitis in a patient with oculocutaneous albinism.

Patients with oculocutaneous albinism are more prone to sun-induced damage due to the lack of melanin. Actinic cheilitis is a potentially malignant disorder that occurs due to chronic UV-B radiation to the vermillion region of the lip, a region that is already at risk due to its morphology. A case of actinic cheilitis in a patient with oculocutaneous albinism is presented with a literature review.

The relationship between periodontitis and diabetes: a brief review.

It has been reported that a close association exists between inflammatory periodontal diseases and diabetes through which one exerts a reciprocal influence on the other. This two-way relationship is based on the extensively reported assumption that the one condition so modifies the systemic and local environments that the progress of the other is favoured. On the other hand, treating and eliminating inflammatory periodontal diseases results in improved glycaemic control which minimises the microvascular complications of diabetes. This paper provides a brief review in an endeavour to create a better understanding of the interaction between these two relatively common conditions.

The association between periodontitis and systemic health: an overview.

A putative association between periodontitis and several systemic conditions is reflected in the literature. However, the nature of the relationship is not fully understood and at times may be confusing. It is reported that active periodontitis may contribute towards the development of a high systemic disease burden and that oral heath maintenance, following effective periodontal treatment, will improve the quality of life of the patient and reduce the morbidity of these systemic conditions. Evidence has been presented of direct relationships between periodontal disease and cardiovascular disease, with pre-term low-birth-weight infants and with diabetes mellitus, amongst others. Whether these relationships are causal or not, still needs to be established by further investigation. In the endeavour to make sense of this rapidly advancing area of research, a series of papers is planned for publication during the year 2012. These evidence-based, condensed reviews will hopefully provide clarity on the associations and/or possible causal relationships of periodonttis with specific systemic conditions. The present paper introduces and reviews the concept of the inter-relationships between periodontal and systemic health. The importance of a multidisciplinary approach with co-operation between dental and medical professionals, whether general practitioners or specialists, in the management of patients with these diseases is highlighted.

HIV-associated oral lesions as an indicator for HAART failure: a review.

INTRODUCTION: HIV-associated oral lesions have been used as clinical indicators of HIV infection and/or HIV-disease progression. It is well established that there is a significant reduction in the incidence of most HIV-associated oral lesions in patients on HAART compared with the levels seen in HIV-seropositive patients not on HAART. However, the corollary, namely using the presence of HIV-associated oral lesions as indicators of possible HAART failure, has not been sufficiently studied. METHODS: A literature search done in Pubmed, Ovid, Medline and Biomed Central databases identified as suitable for inclusion in this review four reports, which had considered HIV-associated oral lesions as clinical markers of HAART failure. RESULTS: The practicality of relying on the presence of HIV-associated oral lesions in the prediction of HAART failure was evaluated based on existing literature. Although it was suggested as an option in all four papers reviewed, the use of HIV-associated oral lesions as predictors of HAART failure has been recommended by only one of the studies. CONCLUSION: The use of HIV-associated oral lesions as predictors of HAART failure has been suggested. This has not been studied in the South African, or the African setting.

Post-chemotherapeutic resolution of acute myeloid leukaemia-induced gingival enlargement: a case report.

INTRODUCTION: Leukaemia is a neoplastic dsorder characterized by an excessive proliferation of immature white blood cells and their precursors. Patients with this potentially fatal condition may often first present with gingival enlargement. Early diagnosis of the underlying condition and prompt referral for appropriate therapy, may be life-saving. CASE REPORT: A 27-year-old female was referred to the Department of Oral Medicine and Periodontology complaining of a generalised gingival enlargement that was aesthetically displeasing to her. She insisted on immediate surgical removal of the enlarged gingival tissue but, on counseling, agreed to have prior diagnostic tests performed. A full blood count suggested the presence of an underlying acute myeloid leukaemia. The patient was consequently referred to the Oncology Department for further investigation and management. The diagnosis was confirmed and the subsequent chemotherapeutic intervention was strikingly successful, leading to the complete resolution of the gingival enlargement. CONCLUSION: This paper emphasises the importance of a full diagnostic evaluation of all cases of gingival enlargement and immediate referral should a life-threatening condition be identified, such as, in the present case, acute myeloid leukaemia.

Characterising oral lesions in patients who presented with chronic vesiculobullous lesions during a 10-year period.

INTRODUCTION: Vesiculobullous lesions are a subset of lesons with an aetiologic spectrum that ranges from infection to aberrant mmune function. The bulk are chronic immune-mediated or autoimmune diseases in which inappropriate production of antibodies against auto-antigens results in the development of these conditions. METHODS: All departmenta patient records in the ten-year period were reviewed and those indicating a provisional diagnosis of oral chronic immune-mediated lesions were included in the study. Simple descriptive statistics were used. Chronic immune-mediated conditions included were lichen planus, pemphigus vulgaris, benign mucous membrane pemphigoid, including cicatricial pemphigoid, bullous pemphigoid, erythema multiforme and systemic lupus erythematosus. RESULTS: The files of forty-five patients (12 males, 33 females) who had been provisionally diagnosed with immune-mediated oral lesions during a ten-year period, from 2001 to 2010, were identified. Of these, 22 (49%) recorded final diagnoses of chronic immune-mediated conditions. CONCLUSION: This paper characterises the oral lesions of chronic immune-mediated conditions diagnosed in patients attending the oral medicine clinic during a ten-year period.

Diffuse peripheral odontogenic fibroma with concomitant plasma cell gingivitis--a case report and literature review.

Peripheral odontogenic fibroma is a rare odontogenic neoplasm that occurs on the gingiva, and cases of diffuse gingival involvement are most uncommon. An example of such a case compounded by superimposed plasma cell gingivtis is presented together wth a review of the literature.

Oral medicine case book 41--Acanthosis Nigricans.

The Oral Medicine Team at Western Cape have taken a well-earned rest this month, and we are delighted to include a Case Book prepared by a team from Wits. It is likely that the source of the contributions will be varied from time to time. We look forward to the next Case Book, which will again come from Western Cape.

Discoid lupus erythematosus as it relates to cutaneous squamous cell carcinoma and to photosensitivity.

Lupus erythematosus is a chronic inflammatory autoimmune disease with diverse clinical manifestations ranging from an indolent chronic cutaneous form to a severe potentially life-threatening disease, systemic lupus erythematosus. Discoid lupus erythematosus is a subphenotype of chronic cutaneous lupus erythematosus, characterised by scaly disk-shaped plaques which may be localised or widespread, occurring predominantly on sun-exposed skin and which may rarely progress to squamous cell carcinoma. The pathogenesis of discoid LE comprises complex interactions between multiple susceptibility genes involved in immune responses and clearance of apoptotic cells on the one hand, and environmental factors on the other. Herein, we discuss some aspects of the pathogenesis of discoid lupus erythematosus in relation to ultraviolet radiation and malignant transformation.

Bisphosphonate-related osteonecrosis of the jaw.

Bisphosphonates are agents commonly used in the treatment of osteoporosis, and in the management of metastatic bone disease, and of hypercalcaemia of malignancy. Any oral surgical procedure or traumatic event exposing bone to bacterial infection may precipitate osteonecrosis of the jaw in subjects who have been treated with bisphosphonates which suppress bone turnover and inhibit the angiogenesis associated with healing. New guidelines for the treatment of bisphosphonate-related osteonecrosis of the jaw are emerging, but hitherto treatment has been empirically conservative.

HPV-associated oral warts.

Human papillomavirus (HPV) is strictly epitheliotropic, infecting stratified squamous cutaneous and mucosal epithelial cells. Oral HPV infection may be subclinical or putatively associated with benign or malignant oral neoplasms. The benign HPV-associated oral lesions, focal epithelial hyperplasia (Heck disease), oral squamous cell papilloma, oral verruca vulgaris (common wart) and oral condyloma acuminatum, are collectively referred to as oral warts. Oral warts are usually asymptomatic, may be persistent or uncommonly, may regress spontaneously. HPV-associated oral warts have a prevalence of 0.5% in the general population, occur in up to 5% of HIV-seropositive subjects, and in up to 23% of HIV-seropositive subjects on highly active antiretroviral therapy. This paper is a clinico-pathological review of HPV-associated oral warts.

Xeroderma pigmentosum: a case report and review of the literature.

Inherited molecular defects in nucleotide excision repair genes cause the autosomal recessive condition xeroderma pigmentosum. Xeroderma pigmentosum is characterized by photo-hypersensitivity of sun-exposed tissues, and by a several thousand-fold increase in the risk of developing malignant neoplasms of the skin and of the eyes. Mutations in xeroderma pigmentosum genes that regulate nucleotide excision repair, not only predispose persons with xeroderma pigmentosum to multiple malignancies, but also promote premature cutaneous and ocular ageing, and in some cases promote progressive neurodegenerative changes. This paper describes a case of xeroderma pigmentosum with advanced cutaneous squamous cell carcinoma, actinic cheilitis and ocular lesions in a 19-year-old black woman. The extensive ultraviolet radiation-induced skin and eye damage are evidence of neglect of sun-protection and lack of appropriate medical care from childhood.

Facial lymphoedema as an indicator of terminal disease in oral HIV-associated Kaposi sarcoma.

Rapidly progressive facial lymphoedema developing concurrently with, or immediately after rapid enlargment of oral Kaposi sarcoma (KS) in HIV-seropositive highly active antiretroviral treatment (HAART)-naïve subjects, foretokens death. We present here an unusual case of HIV-KS in an 11-year-old HIV-seropositive HAART-naïve boy. Our patient's KS disease had had a fulminant course characterised by rapidly progressing oral HIV-KS, resorption of the mandibular alveolar bone process beneath some of the HIV-KS lesions, and rapidly progressive facial lymphoedema. He died 3 weeks after the onset of facial lymphoedema.

Oral cancer-associated paraneoplastic syndromes.

Paraneoplastic syndromes are cancer-associated endocrinological, haematological, dermatological or neurological disorders, which are directly related neither to the physical effects of the tumour mass, nor to invasion by the primary tumour, nor to metastasis of the tumour; nor are they associated either with the side-effects of anticancer treatment or with any of the complications of cancer. These syndromes are brought about by the ectopic production of biological mediators by the malignant tumour cells, or by immunological responses to the malignancy. Certain cancers are typically associated with specific paraneoplastic disorders. Though uncommonly, oral carcinomata have reportedly been associated with paraneoplastic pemphigus, humoral hypercalcaemia of malignancy, syndrome of inappropriate antidiuretic hormone, and paraneoplastic leukocytosis syndrome.

Chemotherapy- and radiotherapy-induced oral mucositis: pathobiology, epidemiology and management.

Oral mucositis is a debilitating complication of anticancer treatment, characterised by erythematous, atrophic, erosive or ulcerative lesions. Oral mucositis is almost always painful, affects eating, sleeping, and speech and affects the physiological and social well-being of the patient. The pathophysiology of the condition is not well understood. Guidelines to the treatment of oral mucositis are often contradictory so that there is no evidence based standard treatment protocol. Therefore the treatment is empiric. This paper offers a brief review of current knowledge of the pathophysiology and treatment of oral mucositis.

A short account of cancer--specifically in relation to squamous cell carcinoma.

Cancer is the outcome of a complex multifactorial process of cytogenetic and epigenetic changes that affect cell cycle progression, apoptosis, DNA repair mechanisms and cell differentiation. Cancer cells have the capacity to evade the immune system, to invade tissues and to metastasize. Cancer is treated by surgery, chemotherapy and radiotherapy, each as single treatment modalities or more often in combination. Failure of treatment to cure a patient of cancer may be owing to the fact that radiotherapy and chemotherapy can eradicate transit-amplifying cells which are characterized by uncontrolled proliferation and prolonged survival; but cannot eradicate all cancer stem cells that divide slowly, have a relatively unlimited self-renewal capacity and express anti-apoptotic genes; and also owing to the fact that surgery cannot always eliminate occult fields of pre-cancerization.

HPV modulation of host immune responses.

Host immune responses to HPV are generally low-level because the virus, being confined to basal epithelial cells is shielded from the circulating immune cells during initial stages of infection. In this location there is only a limited expression of viral proteins. Other factors contributing to the low level of host immunity are that HPV infection is non-lytic (does not cause death of the infected cell); that a functionally active immune response is generated only at later stages of HPV infection, in post-mitotic suprabasal keratinocytes where all viral genes are expressed; and that only in suprabasal keratinocytes has the HPV DNA been sufficiently amplified to be detected by the host immune-surveillance cells. In addition to the natural low-level immune responses towards HPV, HPV also employs several mechanisms to down-regulate innate and cell-mediated immunity, thus facilitating host immune evasion and persistent infection. The environment, lifestyle, the genetic make-up of the host, and the viral genomic characteristics can also influence the persistence of HPV infection, and consequential diseases. Persistent infection with high-risk HPV is associated with increased risk of developing HPV-mediated premalignancy and malignancy. It is not clear if the natural humoral immune response as opposed to vaccination is effective in eliminating primary HPV infection or in preventing progression of infection; but after initial infection, the host develops HPV-specific T cell immune responses that appear to be capable of clearing established infection, of protecting against progression of early HPV-associated intraepithelial neoplastic lesions to squamous cell carcinoma, and of preventing reinfection.

Focal epithelial hyperplasia (Heck disease) related to highly active antiretroviral therapy in an HIV-seropositive child. A report of a case, and a review of the literature.

Focal epithelial hyperplasia is increasingly frequently observed in rural South African communities. HIV-seropositive subjects have a higher prevalence of oral human papillomavirus (HPV) infections than immunocompetent subjects; and paradoxically, the introduction of highly active antiretroviral therapy for treatment of HIV-seropositive subjects is associated with increased frequency of focal epithelial hyperplasia. We describe a case of focal epithelial hyperplasia in an HIV-seropositive child receiving highly active antiretroviral therapy, who was successfully treated by using diode laser ablation.

HIV-associated Kaposi sarcoma in African children.

HIV-associated Kaposi sarcoma (HIV-KS) is common in African countries where HIV infection is pandemic and anti-retroviral medication is not readily available. Human herpesvirus-8 (HHV-8), which is the essential, but not the sole aetiological factor in KS, is endemic in sub-Saharan Africa and is substantially more prevalent in HIV-seropositive than in HIV-seronegative subjects. In children in sub-Saharan Africa, KS, whether it be HIV-KS or African endemic KS is much more prevalent than any other epidemiological forms of KS. In addition, in sub-Saharan children oral KS is common, and the life-expectancy of HIV-seropositive children with KS is short. Since generalized systemic KS is frequently associated with oral HIV-KS, it is advisable to introduce systemic cytotoxic chemotherapy early in the course of oral HIV-KS. Although the introduction of highly active antiretroviral therapy (HAART) brought about a decline in the incidence of HIV-KS worldwide, HIV-KS remains a significant problem in sub-Saharan Africa where the prevalence of HHV-8 infection is high and access to HAART is limited.