Auto-immunity cases Con Feighery. Auto-immunity Immune mediated damage Absence of infection or other...
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Transcript of Auto-immunity cases Con Feighery. Auto-immunity Immune mediated damage Absence of infection or other...
Auto-immunity cases
Con Feighery
Auto-immunity
• Immune mediated damage• Absence of infection or other cause• Auto-antibodies may be present• Detection of auto-antibodies – help in
diagnosis• Auto-antibodies often NOT cause of damage
Auto-immunity
Characteristic features -• Female preponderance• Auto-antibodies – some are pathogenic• Genetic association – often strongly
associated with MHC class II genes
Case 1 – 35 year old female
• Joint pain, swelling for 6 months, intermittent• Hands and wrists most affected• Sharp pain in chest on breathing, intermittent • No energy x 2 years• Otherwise generally well
Case 1 – 35 year old female
• Examination –• Generally healthy• Some swelling, tenderness of hand, wrist
joints• Pulse rate 90 beats per min• Heart and chest exam normal• Skin rash on face
Case 1 – 35 year old female
Case 3 – 35 year old female
• Test results• Haemoglobin 10g/dl – low• White cell count 3.4 – low• Platelets – 100 – low• Chest x-ray – normal• Rheumatoid factor test (antibody to IgG) -
positive
Case 3 – 35 year old female
• Questions• What do you think is ‘going on’ in this patient?• Do you think she might have arthritis?• What is the cause of her chest pain?• What might be the cause of her lack of
energy?
Case 3 – 35 year old female
• Questions• Do you have any further ideas about what
might be the wrong with this patient?• What additional tests might help decide?
Case 1 – 35 year old female
Answers• Possible diagnoses include “lupus” aka SLE or
rheumatoid arthritis• Autoantibody tests will help • Anti-nuclear antibodies found in SLE• Double stranded DNA antibodies only in SLE• Rheumatoid factor (antibody to IgG) is found
in rheumatoid arthritis, other diseases
Antinuclear antibody test
Antibody to double stranded DNA
Crithidia luciliae – kinetoblast contains dsDNA
Case 3 – 35 year old female
Answers – common features in lupus (SLE) include -
• Low white cell and platelet counts• Skin rash on face “photosensitive” a classic
feature• Chest pain – lung lining inflammation occurs –
“pleurisy”• Energy – due to anaemia, other causes?
Multiple ‘systems’ affected by lupus
SLE
• Classic example of “multi-system” auto-immune disease
• Only 1 or 2 systems involved in many patients• Female:male ratio 9:1• ANA positive – 99%
Case 2 - 14 year old male
Case history • JG, 14 year old male• Intermittent diarrhoea x 3 years • Occasional abdominal pain• Mild abdominal distension• Fatigue, arthralgia
Clinical history (continued)
• Past history – well until 11 years old • Family history – mother has rheumatoid
arthritis; aunt is hypothyroid
Physical examination
Examination –• Thin; weight – 6 stone (38 kg); height – 4 feet, 10
inches (147 cm)• Pre-pubertal• Pale facies; pulse 90/min, regular; chest clear• Abdomen – mild distension, slight tenderness• Joints – no synovitis; skin – no rashes
Early blood test results
• Hgb – 9g/dl; MCV – 75fl• WCC – 11 x 109/l; platelets 500 x 109/l• ESR – 45mm/hr; CRP 80 mg/l – both raised • Albumin 28g/l; GGT 93 IU/l; Alk phos. – 140
IU/l• Urea, creatinine, electrolytes normal
Further blood test results
• Complement levels – C3 – 80 g/l; (normal); C4 – 16 g/l (normal 0.16 – 0.70)
• Immunoglobulins – IgG – 18g/l; IgM – 2g/l; IgA < 0.05 g/l• ANA +, titre 320; Smooth muscle antibody +, titre 80• ANCA +, perinuclear pattern, titre 80• Gliadin antibodies +, 30 units (normal range < 5 units)
Discussion issues
• What additional information would you like to have about the patient’s history?
Discussion issues
• What further physical findings would you look for?
Discussion issues
• What further diagnostic tests should be considered?
Discussion issues
• How would you interpret the above findings?• • What would you include in the differential diagnosis?• • What early investigations are warranted?• • What specific tests would you perform?
Case 2 – further tests
• If this is coeliac disease, test for endomysial antibodies – c. 100% specificity
• Or perform biopsy of small intestine
Endomysial antibody test
> 99% specific for coeliac disease
Coeliac disease
If this is inflammatory bowel disease?
• Examine bowel via endoscope• Small bowel biopsy• Image the bowel via X-ray with barium
Crohn’s - endoscopy
Normal small bowel Crohn’s small bowel with linear ulcers
Crohn’s histology
Classic granulomatous inflammation
Small bowel barium studies
Crohn’s disease -stricture of terminal ileum
Coeliac disease“coin stacking”
Inflammatory bowel disease
Crohn’s disease Ulcerative colitis
Capsule endoscopy – Crohn’s
Outcome in patient JG 1.
• This patient was incorrectly diagnosed with coeliac disease, on the basis of raised gliadin antibodies, a non-specific test for coeliac disease
• He failed to improve on a gluten free diet
Outcome in patient JG 2.
• A barium follow through examination showed narrowing of the terminal ileum
• This was resected and Crohn’s pathology confirmed
• He has had several further resections and now has a short bowel syndrome
Crohn’s disease
• Immune mediated disease• No female preponderance• No specific auto-antibodies• 12 gene loci – GWAS*• No very strong MHC association
* Genome wide association study
Case 3 – 38 year old female
• Just delivered baby boy• Little weight gain during pregnancy• Told she had ‘anxiety’ • Nervous tremor• Family history – sister with coeliac disease
Case 3 – 38 year old female
• Baby healthy but very fast heart rate - 160 beats per min.
• Mum also has fast heart rate – 100 beats per min. and irregular beats
• Brisk reflexes• Staring eye appearance
Case 3 – 38 year old female
Prominent, bulging eyes
Case 3 – 38 year old female
• What diagnosis might you consider?• What tests would you do?
Case 3 – 38 year old female
• Patient has hyper-thyroidism• Caused by antibody vs. TSH receptorDiagnosis• Measure TSH antibody• Measure thyroid hormone levels
Case 3 – 38 year old female
• Cause of rapid heart rate in baby?• Relevance of sister with coeliac disease?
Case 3 – 38 year old female
• Cause of rapid heart rate in baby?Answer• IgG antibody crosses placenta and reacts with
baby’s TSH receptor• Neonatal hyperthyroidism - temporary
Case 3 – 38 year old female
• Relevance of sister with coeliac disease?• Co-association of autoimmune diseases
• Note – many Graves’ disease patients develop hypothyroidism over time
• Hypothyroid patients – develop antibodies to thyroid peroxidase – marker of thyroid inflam
Endocrine auto-immunity
Case 6 – 80 year old female
• Known hypothyroidism• Loss of energy, dysponea on exertion• GP – pale, yellowish pigment• Hg 4g/dl; MCV 115fl• B12 level – very reduced
Case 6 – 80 year old female
• Diagnosis – B12 deficiency• Pernicious anaemia• Auto-immune gastritis• Parietal cell auto-antibodies• Intrinsic factor antibodies**
Case 4 – 25 year old male
• Easy bruising on thighs• Bleeding following shaving• Attended GP – Hgb 10g/dl, iron deficient• Coagulation tests performed – normal• What other information would you request?
Case 4 – skin rash
Case 4 – 25 year old male
Auto-antibody tests• Anti-nuclear antibody +, titre 1250• dsDNA antibodies negative• Is this information useful?• Other test results you should seek?
Case 4 – 25 year old male
• Platelet count – 25 x 109/l• Auto-immune thrombocytopaenia aka “ITP”• Auto-antibodies against platelets• Platelets removed from circulation by spleen• “Idiopathic” TP
• Also found in CVID, HIGM, SLE
Case 4 – 25 year old male
• No good test for platelet antibodies! • Treatment – high dose steroids• High dose IgG infusions• These treatments “interfere” with platelet
antibodies – mechanism uncertain
Case 4 – 25 year old male
• Treatment - • Spleen – antibody coated platelets are
phagocytosed by splenic cells• Splenectomy• Risk of bacterial infection
Case 5 – 17 year old female
• Repeated ear, sinus inflammation• ENT operations with drainage “grommets”
Case 5 – 17 year old female
• Hearing loss in right ear• Acutely unwell in Sept 2008
Case 5 – 17 year old female
• Severe abdominal pain, vomiting• Inflamed joints in hands, wrists• Widespread painful skin rash – black,
blistering areas
Case 5 – 17 year old female
• Possible diagnosis• SLE – negative anti-nuclear antibodies• Vasculitis “blood vessel inflammation”• Wegener’s granulomatosis ?
Case 5 – 17 year old female
• Diagnosis - Wegener’s granulomatosis• Systemic vasculitis• Typically involves ears, sinuses, skin, joints
and other tissues• Highly characteristic auto-antibody• Anti-neutrophil cytoplasmic antibody• Target is enzyme – proteinase 3
Case 5 – 17 year old female
• Highly characteristic auto-antibody – “diagnostic”
• Anti-neutrophil cytoplasmic antibody• Target is enzyme – proteinase 3• Unknown if antibody involved in disease
mechanism
C-ANCA PR3+
Case 5
• Treatment – immunosuppression• Steroids• Cyclophosphamide• Anti-B cell monoclonal antibody – anti-CD20