Theoni Petropoulou

Chronic Granulomatous Disease: The European Experience

CGD is an immunodeficiency caused by deletions or mutations in genes that encode subunits of the leukocyte NADPH oxidase complex. Normally, assembly of the NADPH oxidase complex in phagosomes of certain phagocytic cells leads to a “respiratory burst”, essential for the clearance of phagocytosed micro-organisms. CGD patients lack this mechanism, which leads to life-threatening infections and granuloma formation. However, a clear picture of the clinical course of CGD is hampered by its low prevalence (∼1∶250,000). Therefore, extensive clinical data from 429 European patients were collected and analyzed. Of these patients 351 were males and 78 were females. X-linked (XL) CGD (gp91phox deficient) accounted for 67% of the cases, autosomal recessive (AR) inheritance for 33%. AR-CGD was diagnosed later in life, and the mean survival time was significantly better in AR patients (49.6 years) than in XL CGD (37.8 years), suggesting a milder disease course in AR patients. The disease manifested itself most frequently in the lungs (66% of patients), skin (53%), lymph nodes (50%), gastrointestinal tract (48%) and liver (32%). The most frequently cultured micro-organisms per episode were Staphylococcus aureus (30%), Aspergillus spp. (26%), and Salmonella spp. (16%). Surprisingly, Pseudomonas spp. (2%) and Burkholderia cepacia (<1%) were found only sporadically. Lesions induced by inoculation with BCG occurred in 8% of the patients. Only 71% of the patients received antibiotic maintenance therapy, and 53% antifungal prophylaxis. 33% were treated with γ-interferon. 24 patients (6%) had received a stem cell transplantation. The most prominent reason of death was pneumonia and pulmonary abscess (18/84 cases), septicemia (16/84) and brain abscess (4/84). These data provide further insight in the clinical course of CGD in Europe and hopefully can help to increase awareness and optimize the treatment of these patients.

Comparison of two antiretroviral triple combinations including the protease inhibitor indinavir in children infected with human immunodeficiency virus

OBJECTIVE The effects of two antiretroviral triple combinations including the protease inhibitor indinavir on the surrogate markers, viral load and CD4 cells were evaluated. METHODS Fifteen patients with high viral load or disease progression under their prior antiretroviral therapy were switched to zidovudine/lamivudine/indinavir (Group A, n = 10) or stavudine/lamivudine/indinavir (Group B, n = 5). Serial determinations of viral load and CD4 cells were performed. RESULTS The median reduction of the viral load was 0.6 log after 3 months and 0.8 log after 6 months in Group A and 2.5 and 2.4 log after 3 and 6 months in Group B, respectively. After 3 and 6 months 3 of 10 patients in Group A and 3 of 5 patients in Group B had viral load reductions below the detection limit of the assay. Patients with an additional switch of nucleoside analogues at start of indinavir therapy (regardless of the specific reverse transcriptase inhibitor used) had significantly better reductions of the viral load than patients without such a switch (median 2.3 log vs. 0.2 log after 6 months, P < 0.05). In Group A the median of the relative increase of CD4 cells was 37% after 3 months and 57% after 6 months (P = 0.002); in Group B the medians of the relative increase of CD4 cells were 145 and 163% (not significant), respectively. Two patients from Group A and 1 from Group B developed renal calculi, which resolved after adequate hydration. One patient was withdrawn because of intractable vomiting attributed to indinavir. CONCLUSION In a small cohort of HIV-infected pediatric patients with extensive prior antiretroviral treatment, triple therapy including indinavir had a sustained effect on the decrease of the viral load and the increase of CD4 cells similar to results obtained in antiretrovirally experienced adults. This effect was significantly better in patients with an additional switch of a nucleoside analogue at start of triple therapy with indinavir than in patients without such a change.

Successful Hematopoietic Stem Cell Transplantation in 2 Children with X-Linked Chronic Granulomatous Disease from Their Unaffected HLA-Identical Siblings Selected Using Preimplantation Genetic Diagnosis Combined with HLA Typing

We report 2 children with X-linked chronic granulomatous disease (X-CGD) who underwent hematopoietic stem cell transplantation (HSCT) using grafts from their siblings selected before implantation to be both unaffected and HLA-matched donors. Preimplantation genetic diagnosis (PGD) along with HLA-typing were performed on preimplantation embryos by single-cell multiplex polymerase chain reaction using informative short tandem repeat markers in the HLA locus together with the gene region containing the mutations. Two singleton pregnancies resulted from the intrauterine transfer of selected embryos; these developed to term, producing 1 healthy female and 1 X-CGD carrier female, which are HLA-identical siblings to the 2 affected children. Combined grafts of umbilical cord blood (UCB) and bone marrow (BM) stem cells were administered to the recipients after myeloablative (MA) conditioning at the ages of 4.5 years and 4 years, respectively. Both patients are well, with complete donor hematopoietic and immunologic reconstitution, at 18 and 13 months posttransplantation, respectively. This report demonstrates that HSCT with HLA-matched sibling donors created by PGD/HLA typing of in vitro fertilized embryos is a realistic therapeutic option and should be presented as such to families with children who require a non-urgent HSCT but lack an HLA-genoidentical donor.

Cases of Tinea capitis due to pale isolates of Trichophyton violaceum (Trichophyton glabrum) in South-East Europe. A challenge to the clinical laboratory

Two recent indigenous cases of tinea capitis in children due to pale isolates of Trichophyton violaceum are reported herein for the first time from South-East Europe (Greece). Pale isolates of Trichophyton violaceum, reported in the past as Trichophyton glabrum, are thus far sporadically reported only from African or Asian countries. The cases reported herein raise the awareness of its existence in the community, assigning special importance to its accurate identification in the clinical laboratory.

Teeth and tongue discoloration after linezolid treatment in children.

We describe 3 children who developed teeth and tongue discoloration while receiving intravenous linezolid for 2 to 3 weeks. Linezolid was coadministered with piperacillin-tazobactam or meropenem. Teeth and tongue discoloration was reversible with dental cleaning after discontinuation of linezolid. We review the published pediatric and adult cases regarding teeth and tongue discoloration after linezolid administration.