The Health of X- linked CGD Carriers in the United Kingdom CGD Society Family Day, Oct 2015
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1 The Health of X- linked CGD Carriers in the United Kingdom CGD Society Family Day, Oct 2015 Dr Alex Battersby Paediatric Registrar, Great North Children s Hospital Newcastle upon Tyne
2 Outline of Presentation Background Why XL- CGD carriers are interesting Outline of aims and methods of study Results Future work
3 Features of CGD CGD Inflammation Infection Autoimmunity
4 Patients XY X chromosome expresses mutated gene
5 XL- CGD Carriers XX One mutated copy, one wild type Only one X chromosome expressed random selection of mutated or wild type 2 populations of cells
6 XL- CGD Carriers Interesting group due to dual population of cells Skin disease reported historically Anecdotally more unwell
7 Literature Review Skin Disease Lupus like rashes Since CGD first described Autoimmunity Infection
8 The UK Registries Originally created in 2000 All patients in the UK and Ireland with CGD Detailed record of symptoms, hospital admissions and causes of death Funded by the CGD Research Trust Updated 2012 Examined IQ and psychological impact Comparisons between conservative and curative treatments
9 Aims of the Study Describe/Evaluate range of symptoms in XL- CGD Carriers prevalence and severity of symptoms psychological symptoms Quality of life Compare symptoms with per cent Neutrophil Oxidative Burst (NOB) reduction Compare symptoms with autoantibodies
10 Methods
11 Recruitment CGD Registry & Society Methods
12 Methods Recruitment CGD Registry & Society Interview Pedigree Medical History
13 Methods Recruitment CGD Registry & Society Interview Pedigree Medical History Medical Records Hospital/GPs
14 Methods Recruitment CGD Registry & Society Interview Pedigree Medical History Questionnaires including Features of SLE Bowel disease Quality of Life (SF36) Fatigue (MFSI- SF) Psychological Health Medical Records Hospital/GPs
15 Methods Recruitment CGD Registry & Society Interview Pedigree Medical History Medical Records Hospital/GPs Questionnaires including Features of SLE Bowel disease Quality of Life (SF36) Fatigue (MFSI- SF) Psychological Health Bloods NOB (DHR) Autoantibody Panel (IF) Serum to store
16 Results: Recruitment CGD Society 4 Postal 16 Birmingham 3 Manchester 3 Royal Free 14 GOS 17 Newcastle Number of Carriers
17 NOB Distribution 11 NUmber of XL- CGD Carriers < >91 % NOB
18 NOB vs Age NOB
19 Infective Inflammat ory Miscellane ous Autoimmu ne
20 Infective Number of XL- CGD Carriers (%) Any Significant Infection 19 (23.5) Fungal 1 (1.2) Pneumonia 4 (4.9) Meningitis 2 (2.5) Recurrent Abscesses 14 (17.3) Sinus 2 (2.5) Lymphadenitis 4 (4.9) Recurrent UTI 6 (7.4)
21 Infection 2 Lower NOB did not seem to correlate with infection EXCEPT Recurrent abscesses significantly more likely with lower NOB BUT more likely to be prescribed prophylactic septrin with lower NOB
22 Inflammatory Skin Gastrointestinal Respiratory
23 Skin Manifestations Photosensitivity common No association with NOB Present throughout the age range Some report improvement with age, others deterioration
24 Number of Carriers (%) Photosensitivity 56 (74%) DLE/Malar Rash 30 (40%) Eczema 11 (14%) Psoriasis 3 (4%) Adult Acne 8 (10%) Erythema Multiforme 2 (3%) Dermatitis 5 (7%) Allergic/Hives 5 (7%) Rosacea 5 (7%) Malignant 1 (1%) Other 12 (16%) Poor Wound Healing 2 (3%)
25 Gastrointestinal Number of Carriers Abdominal Pain Diarrhoea Rectal Bleeding Consfpafon Other GastrointesVnal Symptom
26 Comparison with CGD Patients XL- CGD Carriers CGD Patients [37] Number Abdominal Pain 34% 46 % Diarrhoea 33% 33 % Rectal Bleeding 23% 6 % Constipation 11% 4 %
27 GI Diagnoses Diagnosis Number (%) Inflammatory Bowel Disease 2 (2.5) CGD Colitis 1 (1.2) Irritable Bowel Syndrome 8 (9.8) Other 2 (2.5) None 56 (69)
28 Gastrointestinal Symptoms More likely if index case suffered colitis Symptom Average NOB in Affected Group Average NOB in Unaffected Group P- value Any GI Symptom Abdominal Pain Diarrhoea Rectal Bleeding
29 Respiratory Common site in patients In XL- CGD Carriers: Less commonly reported as symptom 10 Asthma 1 Chronic Bronchitis 1 Pleural Inflammation 3 Cough
30 Autoimmune Features Joint pain and swelling Ulcers Raynaud s Lupus Other
31 Autoimmune Features Affected (%) Joint Symptoms 47 Ulcers 75 Raynaud s 36 Alopecia 4 Miscarriage 11
32 Number of SLE Criterion Met Number of Carriers (%) None 10 (11.6%) 1 11 (12.8%) 2 17 (19.8%) 3 24 (27.9%) (27.9%)
33 Lupus- like Disease Euro- Lupus Cohort [3] CGD Carrier Cohort PR Test p- value Geographical Area Europe United Kingdom Malar Rash 311 (31.1) 26 (40) Photosensitivity 229 (22.9) 47 (71) <0.01 Oral Ulcers 125 (12.5) 49 (75) <0.01 Raynaud s Phenomenon 163 (16.3) 21 (31.8) <0.01 Arthritis 481 (48.1) 41 (61.1) 0.01 Serositis 160 (16.0) 3 (3.8) <0.001 Nephropathy 279 (27.9) 3 (3.8) 1.0 Neurological Involvement 194 (19.4) 3 (3.8) 0.99 Death 68 (6.8) 2 (3) <0.0001
34 Patterns of Symptoms Bowel Sympto ms 34 n= 41 Joint 28 Photose25 Sympto nsivitity 40 ms n=57 n=48
35 Photosensitivity/ Joints Photosensitivity/ Bowel Symptoms Joints/ Bowel Symptoms/ Photosensitivity Joint/Bowel Symptoms Number Affected Average NOB (% normal) Mean Age (years)
36 Autoantibodies (IF) Data Missing 24 AutoanVbody PosiVvity 2+ Posifve 1 Posifve All Negafve Number of XL- CGD Carriers
37 Prescribed Medications Medication Type Warfarin Thyroxine Stafn Quinine OCP Nasal Spray Iron Hydroxychloroquine Bone Protecfon B12 Injecfon Anf- Moflity/Spasmodic Anf- Histamine Anf- Diabefc Anfbiofc (Other) Number of Carriers
38 Fatigue 50% XL- CGD carriers reported excessive fatigue unprompted MFSI and SF- 36 quantified degree Higher MFSI scores in fatigued group
39 Fatigue in XL- CGD Carriers Chronic Psychologic Social Demograph Inflammati al Distress Factors ics on High Caring Female GI Levels of for child Age Sympto Anxiety with ms Evidence chronic Autoimm of illness
40 Chronic Inflammation Associated with physical symptoms Joint pains and GI symptoms Similarities with SLE and IBD Fatigue reported as important symptom in own right IL- 8 Levels Higher in XL- CGD carriers than controls Higher than seen in Sjorgren Higher in fatigued XL- CGD carriers than non- fatigued
41 Psychological Health Bi- directional Association Anxiety Higher fatigue scores in higher anxiety categories Depression Higher fatigue scores in higher categories (not severe)
42 Social Factors Caring for a child with chronic illness Age Number of children Relationship to index case
43 Psychological Health Anxiety predominant feature Anxiety Mean scores higher than norm No difference across relationship category Correlation with bowel symptoms and fatigue Depression Majority normal (HAD <7) Comparable with other groups
44 Anxiety: Comparison to Other Groups No difference with MD Control Group CGD Carriers SLE (High Pain)[5] SLE (Low Pain)[5] SLE Patients [6] CF Parents[7] Number Median Age Mean HAD- A p- value 0.18 <
45 Psychology Summary Anxiety at higher levels than general population Anxiety greater than that seen in parents of other conditions Few receiving treatment (medical or psychological) Depression at comparable rates with other conditions
46 Strengths and Weaknesses Strengths Largest cohort studied to date Recruitment methods Detailed information gathered Weaknesses Investigations of symptomatic not central Not evaluated causation
47 What to do? If you have symptoms, speak to: Your GP The immunologist caring for your family Helen Braggins
48 Summary XL- CGD carriers more symptomatic than previously thought Inflammatory complications more common than infective Anxiety predominant psychological feature Causation uncertain Further work into causation and management needed
49 Acknowledgements Newcastle Andy Gennery Mark Pearce Dawn Barge GOS David Goldblatt Helen Braggins Cathy Cale Royal Free Siobhan Burns Ronnie Chee Sari Workman Manchester Stephen Hughes Birmingham Scott Hackett
50
51
52 The CGD Society 2015 Family Conference 30 October 1 November 2015 With grateful thanks to the Jeffrey Modell Foundation for their grant towards this event
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