HIV-SGD is AIDS defining in pediatric HIV infection and has increased in the adult HIV population. The term ‘HIV-SGD’ was first coined by Schiødt et al. (1989)
to describe an enlargement of major salivary glands and/or a complaint of xerostomia in the absence of xerogenic agents, medications, and diseases known to cause xerostomia in HIV patients (Schiødt et al., 1989
). In HIV-SGD, quantitative changes occur in the saliva—such as lower secretory rates of sodium, calcium chloride, cystatin, lysozyme, and total anti-oxidant capacity—which affect the homeostasis of the oral cavity and account for significant morbidity during the progression of HIV disease (Lin et al., 2003
). Typically, HIV-SGD presents a unilateral or bilateral diffuse soft swelling resulting in facial disfigurement, and may be associated with pain. Histologically, HIV-SGD is characterized by hyperplastic, intraparotid lymph nodes and/or lymphatic infiltrates within the salivary gland tissue. This lymphocytic infiltrate consists predominantly of CD8 T-cells that are also CD29+, indicative of a memory cell phenotype. Recent histochemical analysis has revealed the location of the infiltrate as periductal with acinar atrophy, ductal dilation, and mild to moderate fibrosis with collagen deposition (McArthur et al., 2003
; Rivera et al., 2003
). HIV-SGD also affects the minor salivary glands, with labial salivary glands demonstrating features of sialadenitis.
HIV-SGD has been universally established as among the most important AIDS-associated oral lesions. Oral lesions are important clinical indicators of HIV/AIDS by suggesting HIV infection in the undiagnosed individual, indicating clinical disease progression, and predicting development of AIDS (Patton and van der Horst, 1999
). Specific common oral lesions are strongly associated with immune suppression, as measured by CD4 cell counts, and are modestly associated with high viral burden, thus serving as potential clinical markers of HIV viremia and the consequent destruction of the immune system with progressive HIV disease. Since the introduction of highly active anti-retroviral therapy (HAART) in the mid-1990s, the prevalence of types of oral cavity infections of HIV-infected patients has changed over time, with hairy leukoplakia (HLP), oral candidiasis (OC), and oral Kaposi’s sarcoma (KS) decreasing and the incidence of HIV-SGD increasing (Patton et al., 2000
; Greenspan and Greenspan, 2002
). For example, in an HIV-infected North Carolina population, HIV-SGD has gone from 1.8% in an early cohort to 5.0% in a late cohort (Patton et al., 2000
This increase in HIV-SGD after the induction of a HAART drug regimen is reminiscent of previously described cases of immune reconstitution disease (IRD). IRD among HIV-infected patients is an adverse consequence of restoration of immune responses during the initial months of anti-retroviral treatment (ART) (Lawn et al., 2005
). Rizos et al. (2003)
described a patient on triple anti-retroviral therapy with excellent immunological and virological responses and parotid gland enlargement that may have reflected immune reconstitution. IRD typically occurs as a result of a pre-existing opportunistic infection or a subclinical infection becoming “unmasked” upon the introduction of HAART treatment, when HIV viral load decreases and CD4 count increases. Therefore, HIV-SGD presenting as an IRD implies that an infectious agent may play a role in its etiology.
In a prospective study, the association of a Sjögren’s-like syndrome (SLS) with the progression of HIV-related disease in a cohort of HIV patients treated with HAART was evaluated (Mastroianni, 2004
). The study identified four cases of SLS in a cohort of 150 HIV-positive patients treated with HAART, whereas none of the HIV-positive patients not treated with HAART fulfilled the diagnostic criteria for SLS. In conclusion, the study suggested that HAART treatment may play an important role in the etiology of SLS, and that SLS may be a new and important complication of long-term HAART regimens (Mastroianni, 2004
). Interestingly, 75% of these patients did not express the autoantibodies typical of SS, and thus probably had HIV-SGD. This study highlights the clinically identical nature of the two diseases and provides further evidence that HIV-SGD increases with HAART therapy. As more people receive HAART therapy, the potential for increasing incidence of HIV-SGD grows.
In developing countries, the incidence of HIV-SGD has been reported to be as high as 48% of HIV-1-infected patients (McArthur et al., 2000
). Parotid gland lesions are generally much larger and more disfiguring in pediatric patients than in adults, and in most children xerostomia is not usually associated with parotid swelling, although in adult patients it is a fairly common complaint. In both adults and children, the lesion often occurs in conjunction with generalized lymphadenopathy. Reasons for the differences between the adult and pediatric manifestations are not yet understood (Leggott, 1992
). In children with HIV infection, it has been shown that the presence of salivary gland enlargement is associated with less rapid progression to death than is found in those with OC or herpes simplex. The time to death averages 5.4 years, compared with 3.4 years in those with OC (Katz et al., 1993
). This may be due to a protective effect of the CD8 T-cells that predominate in the lymphocytic infiltrate in the salivary glands in that condition and are part of diffuse infiltrative lymphocytic syndrome (DILS) (Itescu et al., 1989
). This is perhaps a marker of the ability of the host to respond to viral infection. The HIV-SGD disease process is of particular interest, because in 1-2% of patients, malignant lymphomas have been described in association with these glandular lesions, making this disease a pre-malignant lesion (Ioachim and Ryan, 1988
; DiGiuseppe et al., 1996