Case Report. Service of Allergy and Immunology. Fernanda Pinto Mariz
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1 Case Report Service of Allergy and Immunology Fernanda Pinto Mariz
2 v KRSS, DB: 1/2/2007, male, natural from Rio de Janeiro. v 2010 (3 yr. old) referred to our Service to investigate PID. PAST HISTORY v Since 6 months repetitive acute otitis and acute diarrhea. Since 2009, he presented acute otitis every month. vsince 2 years old pneumonia. Total: 4 - Hospitalization: 2 (no severity). v Gestational history and childbirth: normal; normal development. vno vaccine reaction. FAMILY HISTORY v Oldest sister: hypogammaglobulinemia (1yr. 6m); died at the age of eleven. v Father: died of external causes; repetitive pyodermitis during childhood; Mother: healthy; no consanguinity.
3 v BEG, eutrophic. Hepatoesplenomegaly. PHYSICAL EXAMINATION FINDINGS v Normal CBC. LABORATORY TESTS v Liver biochemical tests - normal v Immunoglobulins and lymphocytes profile üiga: 4mg/dl; <P3 üigg: 140 mg/dl; <P3 üigm: 316 mg/dl; >P97 üige: 1 ku/l ütcd4: 839/mm3 ( 24%); P10-50 ütcd8: 2237/mm3 (64%); > P97 ütcd4/tcd8: 0,37; üb cells (CD19): 70/mm3 (2%); < P10 ünk (CD56): 210/mm3 (6%); P10-50 HYPER IgM SYNDROME
4 v 2010: mensal venous infusion of Human Ig and antibiotic prophylaxis was started. OUTCOME v No infections; v keeping hepatoesplenomegaly; v Lymphoadenomegaly v 2010 (3 yr old) lymph node biopsy: no germinative center v No switch memory B cells, increased CD8 efector T cells, decreased naive T cells v 2010 (3 yr old) pneumonia sepsis. No improve with antibiotics. Pancitopenia. Increased levels of ferritin and triglyceride; decreased fibrinogen. Positive EBV (PCR); Bone marrow biopsy Hemophagocitic syndrome. HLH 2004 protocol was started good response. v 2011 (4 yr old) sclerosant colangitis. Cryptosporidiun - negative. High levels of alkaline phosphatase and γ-gt.
5 TO RESUME v Male v Repetitive infections; no severity vhepatoesplenomegaly v Lymphoadenomegaly v Hemophagocitic syndrome v Sclerosant colangitis v Hyper IgM v High levels of CD8 T cells (CD8 efector T cells) v No switch memory B cells v No germinative center v Sister that alread died hypogammaglobulinemia, repetitive infections and severe lung disease
6 EBV+; Hemophagocitic syndrome Low B cells CD40/CD40-L def. Sister: died Sister - Severe lung disease Sclerosant colangitis No switch memory B cells No germinative center AID/UNG def. Repetitive infections High levels of IgM Low levels of IgG, A, E Lymphoadenomegaly Hepatoesplenomegaly EBV+; Hemophagocitic syndrome SAP/XIAP def. Decreased memory B cells Sclerosant colangitis Sister: died
7 RESULTS v CD40 e CD40-L expression: normal (IPPMG/UFRJ) v Functional assay of CD40-L: normal (Otávio Marques; Antônio Condino-Neto) v SAP/XIAP mutations: negative (J. Bosco)
8 OUTCOME v Keeping Ig infusion (400 mg/kg/dose; 28/28) and SMT/TMP prophylaxis. v Significant increase in lymph nodes no criteria for hemophagocitic syndrome nor malignancy. v Significant increase in hepatoesplenomegaly. v Keeping high levels of alkaline phosphatase and γ-gt. High levels of AST and ALT. v High levels trygliceride and LDL. vjaundice. v Low IgG levels (< 200 mg/dl) mensal higher doses were tryed (750 mg/kg/dose). v 2013 (6 yr old): frequent infections; no severity; IgG < 200 mg/dl. No increase in the seric IgG levels with shared doses in a weekly schedule (150 mg/kg/dose) nor 600 mg/kg/dose every two weeks. v 2014 (7 yr old): digital clubbing; polyarthritis corticotherapy.
9 LITERATURE REVISION NEW DIAGNOSIS HYPOTHESIS? v dec/2014: heterozigotic mutation in the gene PIK3CD (exon 24 c.3062g>a, E1021K) Capucine Picard/Alain Fischer APDS? v 2015: treatment with Syrulimos was initiated. v Follow up CMV, EBV, liver function, trygliceride and cholesterol levels. v Fev/2016: Syrolimo 5.6 ng/ml ; Mar/ ng/ml
10 OUTCOME IgG E.V. Syrulimos Feb/Mar 2016 ü TCD3: 89.7% (3079/mm 3 ), >P97 ütcd4: 19.5% (669/mm 3 ), P10-50 ütcd8: 66.4% (2281/mm 3 ), >P97 ütcd4/tcd8: 0.29 üb cells (CD19): 1.4% (47/mm 3 ) <P10 ünk (CD56): 6% (202/mm 3 ), <P10 üiga: undetectable üigg: 556 mg/dl üigm: 2821 mg/dl PERPECTIVES v Therapeutic seric levels of syrolimos (7-15 ng/ml) vanti-tnf-α - arthritis v Sub-cutaneous infusion of gammaglobulin v Transplant liver? BMO (donnor 10x10)
11 ü Alergia/Imunologia ü Pneumologia ü Reumatologia Clemax Sant anna Flávio Sztajnbok Ana Alice Parente Marta Felix Fátima Pombo ü Gastroenterologia ü Nutrologia Hélio Rocha Márcia Angélica Valadares Mariana Aires ü Lab. Multidisciplinar (IPPMG/UFRJ) Elaine Sobral da Costa ü Bárbara Andrade Rezende ü Alain Fischer/Capucine Picard ü Antônio Condino-Neto/ Otávio Marques ü João Bosco Oliveira Filho ü Martin Perez/ Alberto Orfao Tereza Sigaud Ellen de Oliveira Dantas Thiago Sá Patrícia Ferrão
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