Le Comorbidit nelle immunodeficienze delladulto: quali e quali - PowerPoint PPT Presentation

Le Comorbidità nelle immunodeficienze dell’adulto: quali e quali scelte terapeutiche. Andrea Matucci Immunoallergology Unit AOU Careggi, Florence, Italy andrea.matucci@unifi.it XXXII Congresso della SIAAIC Toscana, Emilia Romagna, S. Marino 11-12 Novembre 2016

The need for a new definition of CVID Secondary Hypogamma Combined immunodeficiency LRBA; NFkB1 ICOS, TACI CRS deficiencies CD19; 20, 21, 81 defects sIgAD PIK3D GOF Agamma CVID Hypogamma of Unkwnon origin Bonilli et al. JACI Pract 2016 (modified)

Infectious manifestations in CVID Cunningan-Rundles; Warnatz K. In: Stiehms – Immuno deficiency (2014)

Phenotypes of CVI and efficacy of IgG replacement “NAIVE” PHENOTYPE OF DISEASE Single system involvement Multiple systems involvement High clinical Low Controllers clinical Controllers High IgG serum Low levels IgG serum levels Low High “CATABOLIC”PHENOTYPE OF IgG; other Matucci A., Vultaggio A., Maggi E 2009

Cunningan-Rundles; Warnatz K. In: Stiehms – Immuno deficiency (2014)

CHRONIC PULMONARY DISEASE Chronic airway disease: Chronic interstitial d.: Bronchiectasis. fibrosis Related to chronic respiratory nfectious No related to chronic respiratory nfectious Extensive bronchiectasis, Interstitial infiltrates, nodular changes

, et al.

J. All. Clin Immunol. 2005; 115:412-7 < Linfociti B = Linfociti B memoria IgM+ memoria IgM+ 1. > Infezioni respiratorie; 1. no Infezioni respiratorie; 2. TC torace positiva 2. TC torace negativa

GRANULOMATOUS DISEASE (10-22% of cases) (Sarcoidosis-like) May co-exist Chronic airways disease: Chronic interstitial dis.: Bronchiectasis. fibrosis

GRASTROINTESTINAL DISEASES (19-32% of cases) Chronic protozoal, bacterial; viral infectious. Villous flattering Inflammatory bowel-like disease Nodular lymphoid Celiac disease («like») hyperplasia Chronic diarrhea; weight loss; steatorrhea; malabsorption; loss of mineral and vitamins Nodular lymphoid Autoimmune enteropaty hyperplasia (jeujunum biopsy) (jeujunum biopsy)

AUTOIMMUNE DISEASES (25% of cases) CYTOPENIAS Vitiligo Trombocytopenic purpura Pernicious anemia Thyroiditis Autoimm. Hemolytic anemia Epatitis Or both (Evans syndrome) Enteropathy Autoimmune neutropenia Alopecia Related clinical manifestations

LYMPHOMA AND OTHER CANCERS (5-15% of cases) POTENTIALLY RISK FACTORS Expansion of mucosa-associated Helicobacter pylori infection lymphoid tissue (MALT/BALT) NON-HODGKIN LYMPHOMA GASTRIC CANCER

Natural history and outcomes of CVID Resnick ES., et al. Blood 2011;119:1650-7

THE Ig EXERT «DIFFERENT» CLINICAL EFFECTS THROUGH «DIFFERENT» MECHANISMS REPLACEMENT IMMUNOREGULATORY STRATEGY EFFECTS AUTOIMMUNE PRIMARY DISEASES IMMUNODEFICIENCY (IDTP; AEA; PM-DM; APS) SECONDARY NEUROLOGICAL IMMUNODEFICIENCY DISORDERS (MMNP; CIDP; others)

Adjust Ig doses in “real time” IDCV n i a t n a m o t y p a r e h t t n e m ” . e … c a . l l a p u e d r i e v s i d o n d i d e h n t a o G t g e I u h q NO chronic lung disease Yes bronchiectasis g i n u u o r s t i . … n e … d r … u b … s … u o “ i t c e f n i l a m i n i 400 mg/Kg/mo 600 mg/Kg/mo m a No serious infectious > Moderate bacterial infections OK, follow up - Increase dosage 150/mg/kg - Reduce interval Tang M. Consensus statement: http/www.aiegg.org

, et al.

Opzioni terapeutiche nei soggetti con rapida cinetica di decadimento delle IgG sieriche post-terapia mg/dl 500 Post-Ig 7 gg 21 gg 28 gg INFUSIONE INFUSIONE S.O.D. Immunoallergologia - Careggi

Cinetica delle IgG sieriche post-terapia # 900mg/dl Ig e.v. Ig s.c. # 100mg/dl Berger M. Clin Immunol 2004; 112: 1-7 Circolo ematico: rapida distribuzione compartimenti extra-vascolari e degradazione “RESERVOIR SOTTOCUTANEO” - Assorbimento plasmatico lineare; - ↓degradazione locale - ↓ n° cellule

et al.

EFFICACIA DELLA TERAPIA SOSTITUTIVA CON Ig + +/- Haemophilus influenzae Streptococcus pneumoniae -------------------------- Staphylococcus aureus Pseudomonas aeruginosa Mycoplasma pneumoniae - +/- Campylobacter Yersinia enteroolitica Giardia lamblia

TREATMENT OF COMORBIDITIES OF CVID Chronic airway disease: Chronic interstitial d.: Granulomatous d.: Bronchiectasis. fibrosis Sarcoidosis-like Higher doses of Ig Systemic steroids Systemic steroids (600mg/kg/month) (?) Immunosuppressors Immunosuppressors Azitromycine (CoA; AZA) (CoA; AZA; Micofen.) Rituximab idroxyclorochine TNF- α inhibitors Inflammatory bowel-like Villous flattering Nodular lymphoid disease Celiac disease («like») hyperplasia 5-aminosalicylic acid No specific treatment Diet without gluten Immunosuppressors (yes for diarrea, etc) (AZA; 6-mercaptopur.) Non-absorbed oral CCS TNF- α inhibitors

TAKE HOME MESSAGE TAKE HOME MESSAGE ERAPIA IMMEDIATA CONTINUO FOLLOW ERAPIA IMMEDIATA CONTINUO FOLLOW N N E E I I C C S S E E N N O O I I Z Z A A G G L L U U V V I I D D I I D D I I M M M M A A R R DIAGNOSI PRECOCE DIAGNOSI PRECOCE

Acknowledgments Dept. BIOMEDICINA Immunoallergology (F. Almerigogna) Immunology and Cellular Therapy (E. Maggi) University of Florence, Italy Alessandra Vultaggio Careggi Hospital Carolina Orsi Oliviero Rossi Battaglini Giulia Carli Francesca Nencini Anna Radice Sara Pratesi Francesca Zanieri