Oral ulceration in HIV infection: Investigation and pathogenesis

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-γδ⁺ 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 γδ lymphocytes. Adhesion molecules and cytokines involved in lymphocyte homing may be important in RAU pathogenesis: ICAM-I and ELAM are strongly expressed, and TNFα production is increased in peripheral blood lymphocytes of healthy patients with RAU. In patients with active HIV disease/AIDS, serum TNFα levels are increased. Thalidomide, which inhibits TNFα 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.     

Oral lesions of iatrogenic and undefined etiology and neurologic disorders associated with HIV infection.

A review of a miscellaneous group of oral mucosal disorders in the setting of infection with the human immunodeficiency virus is presented. Included is a discussion of oral lesions of iatrogenic and undefined etiology and neurologic disorders. Mechanisms of pathogenesis, including possible common pathways and relationships to underlying immunosuppression, are emphasized.     

Gingival ulceration in HIV infection

Abstract. All cases of HIV-associated gingival ulceration seen at a dedicated dental clinic in a 5-ycar period were reviewed and compared against other patients attending the clinic. 94 (7.1%) of 1308 patients had 146 episodes of gingival ulceration. 89 patients had 140 episodes similar to acute necrotising ulcerative gingivitis (ANUG) and responded well to conventional treatment for ANUG. The cases were compared with 269 controls in logistic regression. Gingival ulceration was associated with oral candidiasis, lower age and lack of AIDS diagnosis possibly due to a protective effect of co-trimoxazole medication. 5 patients with neutropenia had extensive ulceration without the microflora of ANUG. Histopathology, viral and bacterial culture revealed non-specific changes. The ulcers did not respond to the treatment regimen for ANUG but responded to treatment of their neutropenia. Gingival ulceration is not common in HIV infection. Most cases resemble severe ANUG. It is more frequent in younger people, those with oral candidiasis and without AIDS. Co-trimoxazole may be protective. A minority of cases with ulceration and associated neutropenia resembled the non-specific oral ulceration associated with HIV.     

Oral mycoses in HIV infection.

Oral mycoses in human immunodeficiency virus (HIV) infection are becoming increasingly common. Of these, oral candidiasis is by far the most prevalent; fewer than 10 cases of cryptococcosis, histoplasmosis, and geotrichosis have thus far been reported. Oral candidiasis is one of the earliest premonitory signs of HIV infection and may present as erythematous, pseudomembranous, hyperplastic, or papillary variants, or as angular cheilitis. Cumulative data from 23 surveys (incorporating 3387 adults) suggest that in general, oral candidiasis may develop in one third to half of HIV-seropositive persons. Almost equal numbers of cases manifest with either erythematous or pseudomembranous variants. These and related concepts pertaining to oral mycoses in HIV infection are reviewed.     

Oral research and dental treatment in HIV infection.

In June 1991, practicing, research, and academic dentists attended a symposium on oral research and dental treatment in HIV infection at Guy's Hospital in London, England. Oral lesions in HIV infection were classified as strongly associated, probably associated, and possibly associated with HIV infection. A speaker stressed that those strongly associated with HIV infection should be of the most interest to general dental practitioners. Another speaker said that chronic erythematous candidiasis has emerged as an oral infection strongly associated with HIV infection in addition to pseudomembranous candidiasis. A dentist mentioned hairy leukoplakia as a new condition strongly associated with HIV infection. Other HIV associated periodontal disease included gingivitis, necrotizing gingivitis, and periodontitis. A speaker noted that AZT increases longevity of AIDS patients and the drugs dideoxyinosine and dideooxycytidine are being tested. Another dentist spoke about the issue of HIV infected dentists citing the example of the dentist in Florida who infected 5 patients. Other speakers addressed the cases and needs of asymptomatic HIV infected people. A survey of dentists showed that only 33% of dentists would provide dental care to HIV infected people and only 20% would if the patients had AIDS. A dentist addressed the problem of a lack of data on prevention and treatment of oral lesions since their etiology and pathogenesis were unknown. Other presentations focused on research on antibodies and DNA probes in reference to saliva and subgingival flora. The symposium revealed the ran ge and depth of research going on in British schools on oral manifestations of HIV infection.     

Oral manifestations of HIV infection in children.

Human immunodeficiency virus (HIV) infection was first recognized in children in 1983 and has now assumed the proportions of a major public health challenge. This article briefly reviews, on the basis of the literature, the epidemiology, diagnosis, clinical and immunologic characteristics, and prognosis of HIV infection in children. The clinical oral manifestations in children are described on the basis of the literature and the personal observations of HIV-infected pediatric patients.     

Oral ulcerations in HIV infection

Oral ulceration in HIV infection may be due to: (1) mycotic; (2) bacterial, protozoan; (3) and viral infections; (4) oral neoplasia; (5) aphthous ulceration/ulceration not otherwise specified (NOS); or (6) ulceration of iatrogenic origin. Of particular significance are oral ulcerations caused by viruses of the herpes virus group (HSV 1/2, CMV, VZV) and ulcerations of the aphthous type. It was shown recently that coinfection of viral ulcers occurs. The aetiopathogenesis of the aphthous type of ulcerations including the still debated ulceration NOS is not clear. Further basic and clinical research is necessary in order to better understand ulceration particularly in relation to immunoregulation, tissue breakdown and repair.     

Oral EBV and KSHV infection in HIV

The gamma herpesviruses, Kaposi's-sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are tightly associated with the development of AIDS-associated oral disease and malignancy during immune suppression. The objective of this investigation was to characterize oral infection and pathogenesis in healthy and immune-suppressed individuals. To characterize oral EBV and KSHV infection, we examined throat washings and oral epithelial cells from HIV-positive and HIV-negative individuals. Quantitative/real-time polymerase-chain-reaction (PCR) assays, transmission electronmicroscopy, immunostaining, and sequence analysis were used to identify viral infection. Virus was isolated from throat-wash samples and was used to infect epithelial and lymphoid cell lines. We detected EBV and KSHV in the oral cavity in healthy and immune-suppressed individuals. Viral strain analysis of KSHV K1 in multiple clones from the oral cavities of healthy persons and immunosuppressed patients detected several strains previously detected in KS lesions, with minor strain variation within individuals. Immunoelectron microscopy for multiple viral antigens detected consistent expression of viral proteins and oral epithelial specimens. In oral epithelial cells infected with wild-type KSHV in vitro, the K8.1 glycoprotein associated with lytic KSHV infection was detected in both primary and telomerase immortalized oral epithelial cultures by 24 hours post-infection. Virions were detected, subsequent to infection, by scanning electron microscopy. Oral epithelial cells were also infected in vitro with wild-type EBV originating from throat washes. Analysis of these data suggests that, like EBV, KSHV infection is present in the oropharynx of healthy individuals, is transmissible in vitro, and may be transmitted by saliva.     

Oral Geotrichum candidum infection associated with HIV infection. A case report.

Infections with Geotrichum species, although rare, are sometimes seen in immunocompromised hosts. We report a case of oral geotrichosis in a patient seropositive for human immunodeficiency virus who had erythematous mandibular and maxillary gingiva but was otherwise free of any active systemic disease. Geotrichum candidum was shown by both culture and histopathology to be present in the lesion and was deduced to be the causative organism. The patient responded well to several weeks of treatment involving oral topical administration of nystatin vaginal tablets.     

Oral enterobacteriaceae in patients with HIV infection

160 oral swabs of 149 HIV-infected patients and 168 swabs of 166 controls were cultured to detect a possible colonization of the oral cavity with yeasts and Enterobacteriaceae. In 5.0% of the HIV-infected patients and in 4.8% of the controls different species of Enterobacteriaceae were found. Yeasts were always associated with Enterobacteriaceae in the group of HIV-infected patients. Clinically, different oral lesions were seen in the study group. A correlation between the nature of these lesions and the presence of Enterobacteriaceae could not be found. A possible pathogenic role of the Enterobacteriaceae associated with these oral lesions is yet uncertain and remains to be established by further studies.     

Oral aspects of HIV infection in children

Most infants with congenital HIV infection appear normal at birth. Clinical difficulties usually begin as the first year proceeds, and in about half of the children oral manifestations are the first signs. Oral manifestations are commonly found in HIV-positive asymptomatic and pediatric AIDS patients, they are the earliest clinical signs of HIV infection and disease progression in children, and may be used as diagnostic markers, especially in developing countries. Studies have established an accurate association between oral manifestations and progression of HIV disease in children. Since the mouth is easily accessed for clinical examination, the important oral signs should be utilized in the diagnosis and early intervention of AIDS in these vulnerable populations.     

Oral hairy leukoplakia in HIV infection: a diagnostic pitfall.

Twenty-nine human immunodeficiency virus (HIV)-infected patients with white, nonremovable lesions on the lateral border of the tongue, clinically suggestive of oral hairy leukoplakia (HL), were studied. In particular, the value of local antifungal therapy in establishing the diagnosis of HL was investigated. In 15 patients (52%) the lesions could be ultimately attributed to a candidal infection of the tongue. In 10 of the remaining 14 patients, a biopsy was obtained from lesions persisting after local antifungal treatment. In all biopsy specimens, the diagnosis of HL was confirmed by histopathologic examination and the demonstration of Epstein-Barr virus DNA by polymerase chain reaction, Southern blot hybridization, and DNA in situ hybridization. The present data confirm that the diagnosis of HL in HIV-infected patients cannot be reliably made on clinical criteria alone, but requires histopathologic confirmation including the demonstration of Epstein-Barr virus DNA, preferably by DNA in situ hybridization. However, with regard to the differential diagnosis of white, nonremovable lesions on the lateral border of the tongue in HIV-infected patients, the present study suggests that persistence of lesions after local antifungal therapy is highly suggestive of HL.     

Oral manifestations and dental status in paediatric HIV infection

Objective . To describe the incidence and prevalence of oral manifestations of HIV infection in a population of perinatally infected children.
Design . Retrospective and prospective study of a cohort of perinatally HIV-infected children.
Setting. Community hospital and community-based paediatric clinic.
Sample and methods . Forty perinatally HIV-infected children with a median age of 12 months were eligible and selected for the study, which included a medical chart review from birth and prospective follow-up. Each child was examined quarterly for oral manifestations, tooth eruption, and for 27 children, caries and periodontal status.
Results . The incidence of pseudomembranous candidiasis was 43% (95% CI, 27–58%) within 6 months of birth. Oral candidiasis (defined as pseudomembranous or erythematous) was positively associated with low CD4 counts and the occurrence of plaque. Children with low CD4 counts were also found to have fewer teeth than children with high CD4 counts, after adjusting for age.
Conclusions . Oral manifestations are common in paediatric HIV infection and are possible predictors of HIV disease progression. Primary care of HIV-infected children should include periodic oral examinations to monitor their HIV disease progression and to alleviate symptoms associated with oral opportunistic infections.     

Periodontal disease associated with HIV infection.

Patients with severe immunosuppression as a consequence of infection by human immunodeficiency virus (HIV) are at risk for a number of severe periodontal diseases. HIV-associated gingivitis and HIV-associated periodontitis (HIV-P) are seen exclusively in HIV-infected persons. In some cases HIV-P may extend into adjacent soft tissue and bone, resulting in necrotizing stomatitis of periodontal origin. In addition, acute necrotizing ulcerative gingivitis has also been reported to have an increased prevalence in HIV-infected patients. The clinical and microbiologic features of HIV-associated gingivitis and HIV-P suggest that these diseases are early and later stages of the same lesion, that results in severe gingival erythema, extensive soft tissue necrosis, and destruction of alveolar bone. Although acute necrotizing gingivitis and the initial stages of HIV-P share a number of clinical signs current evidence indicates that they are distinct pathologic processes. Treatment of these lesions requires debridement, local antimicrobial therapy, immediate follow-up care, and long-term maintenance. In addition, patients with systemic involvement or extensive and rapidly progressing lesions may require systemic antibiotics appropriate to the organisms that dominate the lesion.     

Oral lesions of HIV infection in developing countries

HIV infection has spread rapidly within developing countries since it was first recognized in the early 1980s. The purpose of this paper is to review the prevalence of oral lesions associated with HIV infection (oral HIV) in the developing world, and to identify additional factors that may complicate the presentation of these lesions. Direct comparison of regional and local prevalence studies within Africa, India and Thailand is speculative because there are few reports available. Furthermore, inherent differences in study design, data collection, standardization and calibration of health workers make any inferences inconclusive. Additional prevalence studies of oral HIV lesions associated with systemic disease or social conditions, such as poverty or malnutrition, are needed. In order to provide a basis for the diagnosis and treatment of HIV-associated oral lesions in the developing world, it is important to recognize any confounding factors that may impact on their presentation and management. Elucidation of these various factors may provide a basis for treatment within the developing and developed world.