HIV immunodeficiency has complicated the differential diagnosis of oral lesions because of the multitude of diverse. signs and symptoms associated with known oral diseases that in the immunocompromised can occur with more severe forms, as well as new oral conditions that are not clearly classified. This complicates management, since optimal treatment depends on an accurate diagnosis. In turn, a successful outcome also depends on knowledge of therapeutic approaches and host factors, which include status of immune competence/staging, other current diseases/conditions being treated, and capability for patient compliance regarding the treatment plan.
All present data indicate that recurrent aphthous ulcerations (RAS) are a reflection of an autoimmune abnormality. In the general population, where occurrence varies between 20% and 40%, there seems to be a genetic influence. In any case, and in all probability, molecules formed on the surface of some epithelial cells attract lymphocytes that in turn lead to the manifestations of RAS. Based on these findings, and in the absence of any other evident causative factors, RAS is classified as an immunologic disorder.
In the HIV patient, RAS attacks can occur for the first time without any previous history; in those who have an RAS history, the lesions can occur more frequently and in more severe forms. The increased severity includes multiple ulcerations and/or larger lesions (major aphthae). The more severe RAS are referred to as aphthous-like, since the diverse appearances can be mistaken for cancers, granulomatous diseases, or a variety of infections. Obviously, this complicates the diagnosis, which in turn often delays the correct therapeutic management through the use of ineffective medications. Therefore, in many cases, the diagnosis is finally reached by ruling out other conditions. Because of the frequently seen unusual appearances, biopsy may be the first diagnostic choice.
Treatment is often mandatory on the degree of pain, which may be almost intolerable and preclude adequate nutritional intake. This can lead to acute weight loss, malaise, depression, and increased susceptibility to infections. The most effective treatment is use of corticosteroids to alter the T-lymphocytes attracted to the site that are critical participants in the immunologic reaction. Adverse side effects should be understood and discussed with patients, and the primary care physicians should concur with the treatment regimen.
Systemic corticosteroids are more predictable and prompt better patient compliance. Our studies have shown that high-dose, short course use usually leads to beneficial results within a week without any clinical or laboratory evidence of aggravating immune incompetence, no matter what the level of CD4 cells might be. Therefore, daily dosages of prednisone vary between 40 and 80 mg. When used less than 10 to 14 days, the dosage is never tapered. Duration of therapy depends on control of signs and symptoms.
As an alternative, topical corticosteroids can be utilized either therapeutically or prophylactically. However, because of the difficulty in maintaining sufficient contact time, the more potent corticosteroids' must be utilized. These would include fluocinonide (0.05%, Lidex) and clobetosol (0.05%, Temovate). They can be mixed with equal parts of Orabase for adherence. Fluocinonide also comes as a 0.05% gel, which some patients prefer. Corticosteroids in the form of mouth rinses are sometimes helpful, for example, elixir of Decadron (dexamethasone, 0.5 mg/5 ml) 1 tablespoon held in the mouth for 1 to 2 minutes, then emptied, about 3 times daily.
Studies have indicated that corticosteroids markedly alter cytokine production of lymphocytes, which in turn diminishes the response and allows epithelial healing and elimination of pain. Sometimes antifungal medications must be used prophylactically because corticosteroids promote conversion of glycogen to glucose, which fosters fungal growth by adding substrate for proliferation.
Other modulators of T-lymphocyte function, such as cyclosporine, thalidomide, and levamisole, are not practical for one or more reasons including cost, inadequate clinical studies, toxicity, hypersensitivity, and availability.
Stemming from the decreased cell-mediated and humoral immunity, acquired allergies are commonly found in advanced HIV immune dysregulation. The reactions can be based on autoimmune reactions or adverse responses to drugs, food, or environmental factors.
The diagnosis is based on history and clinical findings. The lesions may appear similar to erythema multiforme (erythematous, irregular ulcerations covered by pseudomembranes, painful) or to lichen planus (keratotic striations, erythema, ulcerations, bothersome to painful). When allergic-type reactions are suspected, a trial of corticosteroids will help confirm the diagnosis as well as initiate treatment. As stated previously for RAS, systemic corticosteroids are more predictable, but topicals can be used as an alternative. If this approach is used, and in the absence of a satisfactory response, further diagnostic approaches must be used to establish a diagnosis. Biopsy is helpful in confim1ing and/or ruling out various other entities.
Xerostomia, reflecting a complaint of dryness that is usually associated with salivary gland hypofunction, is a not uncommon complaint in HIV-infected patients. This mayor may not be coincidental with salivary gland enlargement. The most common glands involved are the parotids. The major significance is related to the promotion of candidiasis by a xeiostomic environment, which also reflects in all probability a corresponding diminution of antifungal salivary proteins.
The cause of either glandular enlargement and/or salivary hypofunction is not known. However, based on the predisposition to autoimmune disease, lymphocytic infiltration of the salivary glands may suppress the cells that produce saliva, thus rendering a Sjogren's-like syndrome. Alternatively. cytomegalovirus presence and infections are common in HIV patients. Since this virus has a predilection for salivary gland tissue, the xerostomia may be the indirect reflection of a viral infection, with the basic factor being one of immunosuppression.
The diagnosis is established on the basis of clinical findings and ruling out other diseases. Considerations include infection, inflammation. rumor, and lymphoepithelial cysts. Infection can be ruled out by the use of antibiotics and neoplasia utilizing fine needle aspiration biopsy. The most frequent finding is that of benign idiopathic hyperplasia.
There is no definitive or reproducibly effective treatment. Therefore, the approach is symptomatic management. This involves keeping the mouth as moist as possible and maintaining optimal hygiene. The simplest approach is the use of frequent water rinses, antiseptic mouth rinses, and sugarless gum or candy. Physiologic saliva stimulation can be attained by the sialogogues, pilocarpine (Salagen, 5 mg three to four times daily) or bethanechol (Urecholine, 25 to 50 mg three to four times daily).
Many HIV-positive patients produce inappropriate antibodies directed against their own platelets. This thrombocytopenia can lead to easily induced or even spontaneous submucosal bleeding, leading to purpuric discoloration (thrombocytopenia purpura) and hematomas. Therefore, the lowered number of blood platelets can cause some problems with hemostasis and swelling following invasive or traumatic dental procedures.
The first line of treatment is the use of corticosteroids. If this approach is unsuccessful, then splenectomy is considered.
Occasionally HIV patients present with ulcerations that are frequently necrotic, progressive, and painful. In spite of biopsies and cultures, definitive diagnoses remain uncertain. While there might well be associated secondary infection, antibiotics alone are not curative. Since corticosteroids are not helpful, there is no basis to classify such lesions as atypical aphthae. Because these ulcerations usually occur in advanced immunodeficiency, they may simply be due to idiopathic tissue necrosis or even advanced programmed cell death (apoptosis).
Management approaches include ruling out a definitive diagnosis, palliation and general supportive care, empirical trials with medications, consideration of debridement, and follow-up.
Infrequently, other mucosal changes occur that do not fit any established disease classifications. The most practical approach is to rule out known disease entities, treat symptoms (if any) empirically, and follow the patient.
Oral hyperpigmentation (melanotic macules), appearing in a variety of configurations, have been associated with IllY infection. However, the occurrence has not been significantly greater than developing melanotic macules in control groups. The importance remains an enigma. These• depositions of pigment and/or melanin may be responses to various medications or alterations in adrenal steroids.
There have been isolated reports of a variety of oral conditions possibly related to HIV immunodeficiency. But until well-designed and controlled studies are carried out, a definitive association rather than a coincidental relationship remains speculative.