Oral ulceration in HIV infection: Investigation and pathogenesis

Abstract

Oral ulcerations associated with HIV infection include recurrent aphthous ulcers (RAU). Whereas RAU prevalence is not increased, lesion severity is: among a group of HIV+ patients, 66% had the more severe herpetiform or major RAU. This increased severity suggests that HIV disease-related changes in the immune system may exacerbate RAU. In the peripheral blood of healthy subjects with RAU, CD4:CD8 cell ratios may be reversed and the proportion of T cell receptor-gamma delta + cells increased. HIV disease-related immune system changes are characterized by reversed CD4:CD8, lowered CD4 cell counts and an inverse correlation between CD4 cell counts and per cent activated gamma delta lymphocytes. Adhesion molecules and cytokines involved in lymphocyte homing may be important in RAU pathogenesis: ICAM-I and ELAM are strongly expressed, and TNF alpha production is increased in peripheral blood lymphocytes of healthy patients with RAU. In patients with active HIV disease/AIDS, serum TNF alpha levels are increased. Thalidomide, which inhibits TNF alpha production, is effective treatment for RAU. Some RAU patients have vitamin B12 or folate deficiencies, levels of which are commonly low in HIV+/AIDS patients. However, in a case control study of HIV+ patients, vitamin B12- or folate-deficiencies were not found to be significant risk factors for RAU.

Thalidomide for the Treatment of Acquired Immunodeficiency Syndrome–Associated Refractory Oral Ulcers

“…2,3 The finding of numerous macrophages (CD11 + and CD68 + ) in the inflammatory infiltrate and a locally increased expression of adhesion molecules such as endothelial leukocyte adhesion molecule and intercellular adhesion molecule-1 suggest that release of proinflammatory cytokines such as tumor necrosis factor ␣ (TNF-␣) could be implicated in its pathogenesis. 10,11 Human immunodeficiency virus-associated NOS ulceration usually appears in severely immunodepressed patients with less than 0.05 ϫ 10 9 /L (50/µL) CD4 + cells and high TNF-␣ plasma levels. 11,12 In these patients, aphthous ulcers are often painful, disturbing oral intake and leading to malnutrition, progressive debilitation, and poor life expectancy.…”

“…10,11 Human immunodeficiency virus-associated NOS ulceration usually appears in severely immunodepressed patients with less than 0.05 ϫ 10 9 /L (50/µL) CD4 + cells and high TNF-␣ plasma levels. 11,12 In these patients, aphthous ulcers are often painful, disturbing oral intake and leading to malnutrition, progressive debilitation, and poor life expectancy. 2 Although aphthous ulcers can involve any portion of the gastrointestinal tract, 6 the simultaneous appearance of oral and perianal ulcers, such as in our patient, is uncommon.…”

Etiological Factors of Recurrent Aphthous Stomatitis: A Common Perplexity

“…With advancing immune depletion, their aphthous outbreaks are often dominated by larger ulcers that run a more protracted course. 28,29 Attempts to explore the possibility that RAS is fundamentally an antibody-driven disorder have disclosed findings that are at best inconsistent and largely unsupportive. It seems that any previously held conjecture that aphthous ulcers stem from a centrally generated humoral immune mechanism rather than from local cellular immune responses to an antigenically modified oral mucous membrane was predicated on assumptions that have since been discredited.…”

Ulcerative Lesions of the Mouth: An Update for the General Medical Practitioner

“…30 HHV-8 DNA has been detected within such ulcers, although it is unclear whether the virus is causative or merely a passenger. 31 Of note, such ulcers typically resolve with systemic thalidomide (e.g. 200 mg daily), perhaps reflecting an antitumor necrosis factor (TNF)-á effect, which supports a viral etiology.…”