Therapeutic management. complicated by invasive aspergillosis.
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1 Therapeutic management in a boy with XL-CGD complicated by invasive aspergillosis. Department of Immunology Children s Memorial Health Institute Warsaw POLAND Maja Klaudel-Dreszler & Magdalena Kurenko-Deptuch
2 Polish Primary Immunodeficiency Registry Currently it includes 1021 patients. 44 of them were given the diagnosis of chronic granulomatous disease. During 26- year- experience, only 11 of our patients afflicted with CGD, developed invasive aspergillosis (IA) despite antifungal prophylaxis.
3 Case report 3 y. o. boy with medical history including recurrent lymphadenitis and pneumonia, otitis media, staphylococcal sepsis, tonsilitis, stomatitis and the suspicion of pulmonary tuberculosis. The diagnosis of CGD based on ESID criteria: - NBT slide test 0% (at the age of 29 mo) - positive for CGD family history
4 The pedigree 6yo pneumonia 7wo pneumonia 3yo meningitis, tumor renis CGD
5 Clinical presentation At the admittance: 6- week- lasting fever dyspnoe + tachycardia cough + vomitting chest pain loss of weight asymmetry of the precordial area generalised lymphadenopathy + hepatomegaly
6 Diagnostics Elevated- CRP, BSR and WBC The diagnosis of IPA was confirmed by: - chest HRCT scan - positive for Aspergillus: bronchoalveolar fluid culture histopathology DNA / PCR serum examination Interestingly- Aspergillus galactomannan ELISA was negative!
7 Chest X- ray before antifungal treatment - bilateral massive pulmonary infiltrates - enlarged lymphnodes in mediastinum
8
9 Therapeutic management monotherapy with Voriconazole antifungal drug- excellently penetrating to either lungs or central nervous system no improvement achieved despite 12- day- treatment
10 Therapeutic management Caspofungin was added. 5- day- treatment: improved general condition a little radiologic regression decreased CRP, BSR, WBC Voriconasole ceasation- due to: acute haematuria + anuria acute renal inssuficiency
11 Therapeutic management During Caspofungin monotherapy clinical (fever, dyspnoe) and radiological worsening was observed. CNS fluid examination- to exclude CNS involvement DNA of Aspergillus fumigatus- detected in CNSF by PCR
12 Therapeutic management general examination of CNSF- negative MRI of brain revealed no pathologic aberrations typical of IA liposomal Ampho B (penetrating through brain/blood barrier) was added. double- drug- treatment conducted for 16 days the recurrence of fever + worsening in HRCT chest scan was observed
13 Therapeutic management Caspofungin was stopped. Liposomal Amphotericin B - in a higher dose up to 7 mg/kg - continued for 76 days - gradual clinical, radiological and laboratory improvement Next the boy was put on oral Voriconasole at the dose of 4 mg/kg b.d.
14 Therapeutic management no important adverse events of Voriconazole only mild and typical problems, like: visual disturbances redish rash (hands + feet) After 3 months the dose of Voriconazole had to be increased (to 7 mg/kg b.d.) due to worsening of laboratory and imaging tests.
15 Therapeutic management 3rd HRCT of thoracic cage performed after 7 mo of Voriconasole treatment It revealed: - treatment resistant 2 masses- precordial area - pulmonary fibrosis - there were neither small nodules nor enlarged lymphnodes
16 Therapeutic management The surgical treatment was performed. Histo- pathological examination confirmed granulomata infiltrated by Aspergillus fumigatus.
17 Therapeutic management Succesful surgery, followed by oral Voriconasole treatment, let us prepare the child to MUD- HSCT. Only after 2nd HSCT procedure the complete donor s chimerism and full reconstitution of granulocytic series was achieved. Immunologic improvement was confirmed by normal either NBT slide test or DHR (respiratory burst).
18 Current flow cytometry analysis of PB CD cells /ml CD3+CD % 3142 CD3+CD % 2666 CD3+CD % 376 CD % 299 CD % 134 CD4+/CD8+ 0.1
19 Normal Respiratory Burst in FC
20 Conclusions Aspergillus sp. infection- an arising and lifethreatening- problem in CGD- patients needs long- term and high- dose antifungal treatment. Voriconasole seems to be the drug of choice in CGD complicated by IA. In patients afflicted with CGD the complete resolution of IA may require HSCT.
21 Thank you for your attention!
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