RESULTS
Seven of the eight patients were female (87.5%), and one was male (12.5%). The median age was 16 (years) (min: 13.5, max: 17). Only one of the patients was a migrant from Syria (12.5%) and remaining ones were Turkish.
Fever (75%), cough (75%), side pain (37.5%), and swelling at neck (12.5%) were most common complaint of the patients at admission. Four patients had a history of COVID-19 infections. COVID-19 antibody test was positive at six patients. COVID-19 antibody was negative in only a patient and the patient had not been tested for COVID-19 because he had no complaints when his parents with whom they lived in the same house, were COVID-19 positive. The families reported that none of them had any complaint and received any therapy for covid-19 infection. There was no record about their admission to hospital in our national medical database. Patients were diagnosed as Tb at the based on clinical findings, imaging studies, PPD test, pathologic examination of biopsy samples and quantiferon test (Table 1 and Figure 1).
Family screening of all patients was negative, and they had BCG scars. One of the patients had culture positivity (patient 7) and was not resistant to first-line drugs. Only a patient had tuberculosis lenfadenitis as extrapulmonary tuberculosis (patient 6). None of our patients had CD 4 lymphopenia and their HIV tests were also negative.
Two of the patients had chronic disease. One of them diagnosed as primary ciliary dyskinesia in our departmant (patient 8) and second one was following by rheumatology departmant for the diagnosis of juvenile idiopathic rheumatoid arthritis (JİA). P1, admitted to the pediatric infectious disease in patient clinic due to a pleural effusion while receiving TNF-alpha inhibitor for juvenile idiopathic rheumatoid arthritis (JIA). Since TNF-alpha inhibitor treatment was considered responsible for the activation of tuberculosis, we stopped the therapy. The patient had a history of COVID-19 disease which confirmed by PCR. In spite of appropriate antibiotic treatment and discontinuation of TNF alpha inhibitor, the effusion did not regress. Pleural biopsy revealed a necrotizing granulomatous infection (Figure 2). Thus, anti-tuberculosis therapy including isoniazid, rifampicin, pyrazinamide, ethambutol were started. Because of JIA, Tb and extended hospitalization in the patient, immunologic evaluation was performed. His immunological evaluation revealed hypogammaglobulinemia and low memory B cell. Since the patient met the diagnostic criteria for primary immunodeficiency according to ESID, we started IVIG treatment. Almost 6 months after the first COVID19 positive PCR test, the patient admitted to hospital with complaint of fever and cough for the second time and was found to be COVID-19 positive. Then, he hospitalized and treated. Whole exome sequencing which was done for suspicion of common variable immunodeficiency showed an autosomal dominant heterozygous mutation in TNFRSF13B gene (c.204insT ). None of the other patients had an underlying chronic disease.
Immunologic evaluation was done to all 8 patients at the time of diagnosis due to their severe clinical presentation then expected for this age group (Table 2). The results are summarized in Table 2. During the infection, only a patient (patient # 2) had lymphopenia but turn to normal count at the first month of anti Tb treatment. One patient had low serum IgG levels (patient # 1). Two patients had borderline low serum IgG1 levels and one patient had borderline low serum IgM levels [16]. When the peripheral lymphocyte subset was examined, B cells were low in only a patient (patient#2), B cell count could not re-evaluated because the patient did not come to our clinic for follow-up. Natural killer (NK) cells were low in five patients. We could check three of our patients with low NK levels, it returned to normal in patients other than p1 (Table 2).