Kronik Granülomatöz Hastalık Tanısı Alan Hastaların Klinik Ve İmmünolojik Özelliklerinin Araştırılması

Abstract

Primer immunodeficiencies are a major cause of morbidity and mortality in childhood. Phagocyte system defects are one of the 9 main subgroups of primary immunodeficiencies. This group is associated with defects in number and / or function of phagocytic cells. "Chronic granulomatous disease", one of the phagocytic system defects, is the a primary immunodeficiency caused by dysfunction of the NADPH oxidase complex in neutrophilic granulocytes and monocytes. In our study patients who were followed with chronic granulomatous disease diagnosis at Hacettepe University İhsan Doğramacı Children's Hospital Departmant of Pediatric Immunology between 1984-2017, were included. Demographic, clinical and genetic characteristics of the patients were evaluated in the study. A total of 63 patients were included in the study. 63.5% (n: 40) of the patients had consanguinity history. The mean age of the patients at diagnosis was 82.53 ± 109.96 months and the median was 43 months. The mean duration of follow-up was 73.84 ± 78.81 months and the median follow-up duration was 44 months. The mean diagnostic delay in the study was found to be 38.24 ± 52.29 months and the median was 19.5 months. Patients most frequently come from the Central Anatolian Region (36%) of Turkey. The first most frequent clinical manifestations of patients -with known first clinical findings (74.6%)- were; lung infection (42.6%), followed by lymphadenopathy (19.2%) and skin abscess (14.9%). The distribution of infectious clinical findings were; lung infections (84.1%), skin abscess (68.3%), lymphadenitis (30.2%), liver abscess (17.5%), osteomyelitis (17.5%), otitis media (15,9%) anal-perianal abscess (12,7%). When other clinical findings were examined, 69.8% of the patients had lymphadenopathy, 42.9% had hepatomegaly, 31.7% had splenomegaly, 52.4% had growth retardation, 22.2% had developmental delay, 25.4% had prolonged / refractory fever and 23.8% had chronic diarrhea. The median hemoglobin value at the time of diagnosis was 10,55 g / dl and the median leukocyte level was 10950 / mm3. At the time of diagnosis, ESR median was 27.5 mm / h and CRP median was 3.55 mg / dl. In 60.3% of the patients CGD diagnosis was confirmed by the DHR test. In our study, 23,1% of the cases with known genetic mutation were X-linked (CYBB) and 76,9% were inherited as autosomal recessive. The most frequently detected mutation in our patient group was CYBA gene mutation (35%). Thorax computerized tomography examination was performed in 47.6% (n: 30) of patients; lymphadenopathy (70%), nodule and infiltration (36,7%) were the most common radiological findings. In the study group inflammatory bowel disease was detected in 9.5% of patients with CGD. It was found that 92.1% of patients with CGD used antimicrobial prophylaxis, 92.1% used antibacterial prophylaxis (trimethoprim sulfamethoxazole) and 88.9% used itraconazole prophylaxis. 44.4% (n: 28) of the patients were treated with antituberculosis treatment. Six patients received granulocyte transfusions at least once during their follow-up. 54% of the patients (n: 34) received interferon-gamma therapy. 7.9% of the patients in the study group (n: 5) were found to have undergone hematopoietic stem cell transplantation and one patient died after transplantation. It was determined that 19% (n: 12) of the patients who were followed due to chronic granulomatous disease, died during follow-up. No statistically significant difference was found between the patients' survival and inheritance pattern (X-linked, autosomal recessive).