An investigation into the causes of intraocular inflammation in HIV-positive and HIV-negative patients in the Western Cape Province, South Africa
Date
2018-03
Authors
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Journal ISSN
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Publisher
Stellenbosch: Stellenbosch University
Abstract
ENGLISH SUMMARY: The causes of intraocular inflammation are divided into 3 large groups namely infectious, non-infectious and idiopathic. This research project set out to establish the prevalence of these 3 large groups and their different subgroups in an effort to determine whether HIV infection plays an important role in how frequently they occur in the Western Cape Province.
Out of a total of 106 participants with uveitis enrolled in this study, 66 cases (62.3%) were HIV- and 40 (37.7%) HIV+ with a median CD4+ cell count of 242 x 106/l. The majority of participants were black (n=52; 49.1%) or of mixed ethnicity (n=49; 46.2%) and 59.6% of blacks were HIV+ versus 16.3% of mixed ethnicity participants. Anatomically, most cases were either anterior uveitis (58.5%) or panuveitis (32.1%) while infectious uveitis (n=70; 66.0%) was more common than non-infectious (n=18; 17.0%) or idiopathic (n=18; 17.0%) uveitis. An infectious cause was found in 80.0% of HIV+ cases versus 57.6% in HIV- cases.
Intraocular tuberculosis (IOTB) was the most common cause of infectious uveitis in this study (n=35; 33.0%) where possible IOTB (n=23; 21.7%) was more common than probable IOTB (n=12; 11.3%). Tuberculin skin testing alone was more sensitive (90.3% vs 85.7%) and had a higher negative predictive value (92.1% vs 81.5%) than QuantiFERON alone and the latter therefore does not warrant the extra expense in our highly endemic setting. Herpetic uveitis formed the second largest group (n=13; 12.2%) with VZV (53.8%) responsible for more cases than CMV (38.5%) and HSV (7.7%). Syphilis was the third most common cause of infectious uveitis (n=11; 10.4%). Using a novel immunoblot approach the study investigated the relationship between ocular and neurosyphilis and demonstrated that these 2 conditions do not always co-exist. HIV infection was present in 31.4% of IOTB cases, 61.5% of herpetic cases and 81.8% of syphilitic cases. Toxoplasma (n=4; 3.8%), Rubella virus and poststreptococcal uveitis (n=3; 2.8% each) as well as HIV-induced uveitis (n=1; 0.9%) were responsible for the remainder of the infectious uveitis cases. EBV was often identified on multiplex PCR (n=11; 10.4%) but no evidence of active intraocular replication or antibody production was found to prove that EBV caused uveitis in these cases. In most cases an alternative treatable cause of uveitis was identified (n=9; 81.8%).
Sarcoidosis and HLA-B27 associated anterior uveitis (n=8; 7.5% each) were the most common causes of non-infectious uveitis. All patients with ocular sarcoid and 75% of patients with HLA-B27 uveitis were HIV-.
The percentage of idiopathic cases in this study was lower than in many similar studies (n=18; 17.0%). This is likely due to the high percentage of cases of possible IOTB diagnosed using a recently proposed classification as many of those cases would have been labelled as idiopathic in other studies. The majority of idiopathic uveitis cases were HIV- (n=12; 66.7%).
This study revealed that infectious uveitis is the commonest form of uveitis in both HIV+ and HIV- patients but that the specific pathogens differ between patients with and without HIV infection.
AFRIKAANSE OPSOMMING: Die oorsake van intraokulêre inflammasie word verdeel in 3 groot groepe naamlik infektief, non-infektief en idiopaties. Die doel van hierdie navorsingsprojek was om die prevalensie van hierdie 3 groepe asook hulle onderskeie subgroepe te bereken om te bepaal of HIV infeksie ‘n belangrike rol speel in hoe dikwels hulle in die Wes-Kaap provinsie voorkom. Uit ‘n totaal van 106 deelnemers aan hierdie studie was 66 gevalle (62.3%) HIV+ and 40 (37.7%) HIV- met ‘n mediane CD4+ seltelling van 242 x 106/l. Die meerderheid deelnemers was swart (n=52; 49.1%) of van gemengde etniese afkoms (n=49; 46.2%) en 59.6% van swart deelnemers was HIV+ teenoor 16.3% van deelnemers van gemengde afkoms. Anatomies was die meeste gevalle anterior uveitis (58.5%) of panuveitis (32.1%) terwyl infektiewe uveitis (n=70; 66.0%) meer algemeen was as non-infektiewe (n=18; 17.0%) of idiopatiese (n=18; 17.0%) uveitis. ‘n Infektiewe oorsaak is gevind in 80.0% van HIV+ gevalle teenoor 57.6% in HIV- gevalle. Intraokulêre tuberkulose (IOTB) was die algemeenste oorsaak van infektiewe uveitis in hierdie studie (n=35; 33.0%) waar moontlike IOTB (n=23; 21.7%) meer algemeen was as waarskynlike IOTB (n=12; 11.3%). ‘n Tuberkulien veltoets alleen was meer sensitief (90.3% vs 85.7%) en het ook ‘n hoër negatiewe voorspellende waarde (92.1% vs 81.5%) gehad as QuantiFERON alleen en laasgenoemde regverdig dus nie die addisionele finansiële uitgawe in hierdie hoogs endemiese gebied nie. Herpetiese uveitis was die tweede grootste groep (n=13; 12.2%) met VZV (53.8%) verantwoordelik vir meer gevalle as CMV (38.5%) en HSV (7.7%). Sifilis was die derde algemeenste oorsaak van infektiewe uveitis (n=11; 10.4%). Met behulp van ‘n nuwe immunoblot benadering is daar ondersoek ingestel na die verwantskap tussen okulêre sifilis en neurosifilis en is bewys dat dié 2 toestande nie altyd saam voorkom nie. HIV infeksie was teenwoordig in 31.4% van IOTB gevalle, 61.5% van herpetiese gevalle en 81.8% van sifilis gevalle. Toksoplasma (n=4; 3.8%), rubella-virus en poststreptokokkale uveitis (n=3; 2.8% elk) asook HIV-geinduseerde uveitis (n=1; 0.9%) was verantwoordelik vir die oorblywende infektiewe uveitis gevalle. EBV was dikwels teenwoordig op multipleks PKR (n=11; 10.4%) maar ons kon geen bewyse vind van aktiewe intraokulêre replikasie of teenliggaam produksie nie wat sou bewys dat EBV uveitis in hierdie gevalle veroorsaak het nie. In meeste gevalle is ‘n alternatiewe behandelbare oorsaak gevind (n=9; 81.8%). Sarkoiedose en HLA-B27 geassosieerde anterior uveitis (n=8; 7.5% elk) was die algemeenste oorsake van non-infektiewe uveitis. Al die pasiënte met okulêre sarkoiedose en 75% van pasiënte met HLA-B27 uveitis was HIV-. Die persentasie idiopatiese gevalle in hierdie studie was laer as in baie soortgelyke studies (n=18; 17.0%). Dit is waarskynlik as gevolg van die hoë persentasie gevalle met moontlike IOTB wat gediagnoseer is met ‘n onlangs gepubliseerde klassifikasie aangesien baie van daardie gevalle in ander studies as idiopaties beskou sou word. Die meerderheid idiopatiese gevalle was HIV- (n=12; 66.7%). Hierdie studie toon dat infektiewe uveitis algemeenste vorm van uveitis is in beide HIV+ en HIV- pasiënte maar dat die spesifieke patogene verskil tussen pasiënte met en sonder HIV infeksie.
AFRIKAANSE OPSOMMING: Die oorsake van intraokulêre inflammasie word verdeel in 3 groot groepe naamlik infektief, non-infektief en idiopaties. Die doel van hierdie navorsingsprojek was om die prevalensie van hierdie 3 groepe asook hulle onderskeie subgroepe te bereken om te bepaal of HIV infeksie ‘n belangrike rol speel in hoe dikwels hulle in die Wes-Kaap provinsie voorkom. Uit ‘n totaal van 106 deelnemers aan hierdie studie was 66 gevalle (62.3%) HIV+ and 40 (37.7%) HIV- met ‘n mediane CD4+ seltelling van 242 x 106/l. Die meerderheid deelnemers was swart (n=52; 49.1%) of van gemengde etniese afkoms (n=49; 46.2%) en 59.6% van swart deelnemers was HIV+ teenoor 16.3% van deelnemers van gemengde afkoms. Anatomies was die meeste gevalle anterior uveitis (58.5%) of panuveitis (32.1%) terwyl infektiewe uveitis (n=70; 66.0%) meer algemeen was as non-infektiewe (n=18; 17.0%) of idiopatiese (n=18; 17.0%) uveitis. ‘n Infektiewe oorsaak is gevind in 80.0% van HIV+ gevalle teenoor 57.6% in HIV- gevalle. Intraokulêre tuberkulose (IOTB) was die algemeenste oorsaak van infektiewe uveitis in hierdie studie (n=35; 33.0%) waar moontlike IOTB (n=23; 21.7%) meer algemeen was as waarskynlike IOTB (n=12; 11.3%). ‘n Tuberkulien veltoets alleen was meer sensitief (90.3% vs 85.7%) en het ook ‘n hoër negatiewe voorspellende waarde (92.1% vs 81.5%) gehad as QuantiFERON alleen en laasgenoemde regverdig dus nie die addisionele finansiële uitgawe in hierdie hoogs endemiese gebied nie. Herpetiese uveitis was die tweede grootste groep (n=13; 12.2%) met VZV (53.8%) verantwoordelik vir meer gevalle as CMV (38.5%) en HSV (7.7%). Sifilis was die derde algemeenste oorsaak van infektiewe uveitis (n=11; 10.4%). Met behulp van ‘n nuwe immunoblot benadering is daar ondersoek ingestel na die verwantskap tussen okulêre sifilis en neurosifilis en is bewys dat dié 2 toestande nie altyd saam voorkom nie. HIV infeksie was teenwoordig in 31.4% van IOTB gevalle, 61.5% van herpetiese gevalle en 81.8% van sifilis gevalle. Toksoplasma (n=4; 3.8%), rubella-virus en poststreptokokkale uveitis (n=3; 2.8% elk) asook HIV-geinduseerde uveitis (n=1; 0.9%) was verantwoordelik vir die oorblywende infektiewe uveitis gevalle. EBV was dikwels teenwoordig op multipleks PKR (n=11; 10.4%) maar ons kon geen bewyse vind van aktiewe intraokulêre replikasie of teenliggaam produksie nie wat sou bewys dat EBV uveitis in hierdie gevalle veroorsaak het nie. In meeste gevalle is ‘n alternatiewe behandelbare oorsaak gevind (n=9; 81.8%). Sarkoiedose en HLA-B27 geassosieerde anterior uveitis (n=8; 7.5% elk) was die algemeenste oorsake van non-infektiewe uveitis. Al die pasiënte met okulêre sarkoiedose en 75% van pasiënte met HLA-B27 uveitis was HIV-. Die persentasie idiopatiese gevalle in hierdie studie was laer as in baie soortgelyke studies (n=18; 17.0%). Dit is waarskynlik as gevolg van die hoë persentasie gevalle met moontlike IOTB wat gediagnoseer is met ‘n onlangs gepubliseerde klassifikasie aangesien baie van daardie gevalle in ander studies as idiopaties beskou sou word. Die meerderheid idiopatiese gevalle was HIV- (n=12; 66.7%). Hierdie studie toon dat infektiewe uveitis algemeenste vorm van uveitis is in beide HIV+ en HIV- pasiënte maar dat die spesifieke patogene verskil tussen pasiënte met en sonder HIV infeksie.
Description
Thesis (PhD (Surgical Sciences. Ophthalmology))--Stellenbosch University, 2018.
Keywords
HIV-positive patients, Intraocular inflammation, Eye -- Inflammation, HIV infections -- Complications, Uveitis, UCTD