Case presentation

หญิงไทย โสด อายุ 59 ปี ภูมิลำเนา สมุทรปราการ CC: ชา และอ่อนแรงแขนขา 5 วัน PI: 1 สัปดาห์ PTA ปวดเมื่อยตามตัว ไม่มีไข้ ไม่มี URI symptom 5 วัน PTA ชาปลายนิ้วเท้าขวาก่อน ไม่มีอ่อนแรง แล้วเริ่มชามือขวา รพ . เอกชน ได้ยามากิน อาการไม่ดีขึ้น 3 วัน PTA ชาปลายนิ้วเท้าซ้าย ขาขวาชามากขึ้นถึงใต้เข่า ไป นอน รพ . เอกชน บอกว่าปลายประสาทอักเสบ กินยาไม่ดีขึ้นเริ่มมี อ่อนแรงแขนซ้ายมากขึ้น ยกไม่ได้ กำมือไม่ได้ ไม่มี อุจจาระปัสสาวะราด ไม่มีกลืนลำบากไม่มีปวดข้อ ไม่มีผื่น หายใจได้ปกติ ขอมา รพ . จุฬา

Past Hx :2 ปี PT ผื่นคันแขนขา รักษา รพ . กินยา ทายาไม่ดีขึ้น 10 ปี PTA เป็นโรคหอบหืด ใช้ยาพ่นขยายหลอดลม และยาตลับสีม่วง เช้า - เย็น ร่วมกับยารับประทาน

Physical examination BT 38 c PR 100/min BP 120/80 mmHg RR 24/min Conscious, not pale, no malar rash, no oral ulcer LN -ve skin : hyperpigmented scar with hemorrhagic crust both forearms and legs lung : clear, equal BS heart: regular, normal s1s2,no murmur abd : soft, not tender, no mass, no hepatosplenomegaly neuro: pupil 3 mm RTL BE, decrease motor tone all extremities

Motor: Rt. Lt. DTR Rt. Lt. deltoid IV IV biceps III+ IV 0 1+ triceps III+ II 0 1+ wrist EX/FLEX IV/II 0/0 0 0 hip E/F IV/III V/IV knee E/F V/III V/III 0 2+ ankle E/F V/I IV/I 0 1+ Sensory: impaired both hand and feet above ankle BBK: plantar flexion Propioception: impaired

Problem list Acute Symmetrical weakness Hx of asthma Hx recurrent pruritus

Acute Symmetrical weakness

Hx of asthma

Hx recurrent pruritus

Laboratory CBC: wbc 21,950 Hct 35 plt 277,000 N 42.5, L 12.3, Mo 3.4, Eo 41.7 normochromic normocytic Rbc UA: sp.gr. 1.015, prot/sugar –ve, Wbc 0-1, Rbc 0-1 FBS 147, BUN 5, Cr 0.39 E lyte Na126, K 3.4, Cl 82, CO2 25, Ca 2 + 9.1 LFT Alb 4.0, Glob 4.0, AST 55, ALT 59, Alk 185 CPK 356 ESR 77

Laboratory ANA <40 Rheumatoid factor 21.9 (<15) P-ANCA- weakly +ve, c-ANCA - negative CRP 114.7 HBsAg- negative Anti-HBs – positive Anti-HCV – negative Anti-HIV - negative

Stool exam: normal Total IgE: 891.7 (<100) CSF: - Rbc 96,000 - Wbc 71 - N 55, L 45 - Prot 121.4, Sugar 53

Stool exam: normal

Total IgE: 891.7 (<100)

CSF:

- Rbc 96,000

- Wbc 71

- N 55, L 45

- Prot 121.4, Sugar 53

There are electrophysiologic evidences of sensori-motor, demyelin and axon, mononeuropathy, distal greater than proximal Electrodiagnosis

There are electrophysiologic evidences of sensori-motor, demyelin and axon, mononeuropathy, distal greater than proximal

Sural nerve biopsy Epineural small vessels are cuffed with lymphocytes. Focal fibrinoid necrosis is demonstrated. Masson trichrome stain reveals loss of myelinated fibers with increase endoneurial connective tissue. Patho Dx: Vasculitic neuropathy

Epineural small vessels are cuffed with lymphocytes.

Focal fibrinoid necrosis is demonstrated.

Masson trichrome stain reveals loss of myelinated fibers with increase endoneurial connective tissue.

Patho Dx: Vasculitic neuropathy

Churg - Strauss Syndrome

introduction Overall in CSS - DDx,Dx - Pathogenesis & clinical - Rx and prognosis CSS & LTRA How about CSS in children ? Quiz

Overall in CSS

- DDx,Dx

- Pathogenesis & clinical

- Rx and prognosis

CSS & LTRA

How about CSS in children ?

Quiz

Clinical manifestration 3 phase - prodomal phase - eosinophillic phase - vasculitic phase Subgroup - ANCA +ve - ANCA -ve

3 phase

- prodomal phase

- eosinophillic phase

- vasculitic phase

Subgroup

- ANCA +ve

- ANCA -ve

Systemic symptom - fever ,wt. loss , arthralgia Organ involvement symptom - respiratory involvement - nervous system involvement - gastrointestinal involvement - cardiac involvement - skin involvement - ranal involvement

Systemic symptom

- fever ,wt. loss , arthralgia

Organ involvement symptom

- respiratory involvement

- nervous system involvement

- gastrointestinal involvement

- cardiac involvement

- skin involvement

- ranal involvement

Respiratory involvement pulmonary involvement - 96-100%, bilateral multifocal consolidation - peripheral infiltration, pulm. nodule - DAH 4% - pleural effusion - AR 75% - sinus problem ,polyp - paradoxical improvement of asthma - persistence of asthma at lease 80% after Rx - rarely ,asthma arise after vasculitis

pulmonary involvement

- 96-100%, bilateral multifocal consolidation

- peripheral infiltration, pulm. nodule

- DAH 4%

- pleural effusion

- AR 75%

- sinus problem ,polyp

- paradoxical improvement of asthma

- persistence of asthma at lease 80% after Rx

- rarely ,asthma arise after vasculitis

Severity of asthma & CSS

FEV1 is lower in CSS and severe asthma compare with mild and moderate asthma. Peripheral blood Eosinophil is higher in asthmatic CSS than asthmatic non CSS patient.

FEV1 is lower in CSS and severe asthma compare with mild and moderate asthma.

Peripheral blood Eosinophil is higher in asthmatic CSS than asthmatic non CSS patient.

Nervous system involvement Peripheral neuropathy 65-75% most common is mononeuritis multiplex ! Cranial nerve involvement Stroke Coma , seizure, psychosis

Peripheral neuropathy 65-75%

most common is

mononeuritis multiplex !

Cranial nerve involvement

Stroke

Coma , seizure, psychosis

Gastrointestinal involvement Most common complaint is abdominal pain Eo. Gastroenteritis Eo. Peritonitis Pancreatitis cholecystitis

Most common complaint is abdominal pain

Eo. Gastroenteritis

Eo. Peritonitis

Pancreatitis

cholecystitis

Cardiac involvement Leading cause of death is CARDIOMYOPATHY Eo. Endomyocarditis Coronary vasculitis Vulvular heart dis. HT pericarditis

Leading cause of death is

CARDIOMYOPATHY

Eo. Endomyocarditis

Coronary vasculitis

Vulvular heart dis.

HT

pericarditis

Cardiac involvement occur in pt. with poor prognosis,ANCA –ve , higher Eosinophil group

Renal involvement Renal failure is rare Microscopic hematuria Proteinuria Renal biopsy mostly focal segmental GN

Renal failure is rare

Microscopic hematuria

Proteinuria

Renal biopsy mostly

focal segmental GN

Renal abnormality 26.7% RPGN 13.8% Abnormal urine12.1% CKD < 1%

Laboratory investigation Eosinophillia Increase ESR CT scan Biopsy ANCA

Eosinophillia

Increase ESR

CT scan

Biopsy

ANCA

cANCA pANCA atypicalANCA atypicalANCA

Karina A.Keogh, Semin Respir Crit Care Med 2006;27:148-157

pathogenesis Unknown Impairment of CD95 ligand mediated apoptosis ? To date that is not true Th2 polarization Clonal CD8+ TCR V β expansion Vascular inflammation from endothelial activation and damage HLA association IL-10 association

Unknown

Impairment of CD95 ligand mediated apoptosis ?

To date that is not true

Th2 polarization

Clonal CD8+ TCR V β expansion

Vascular inflammation from endothelial activation and damage

HLA association

IL-10 association

No different in eosinophillic apoptosis between CSS pt. & healthy control

prognosis Generally good prognosis Long term remission 81-92 % Relapse 26-28% 40% need only steroid monotherapy Poor prognosis in 1.elevate serum Cr (> 1.58mg/dl) 2.proteinuria > 1gm/d 3.GI involvement 4.cardiomyopathy 5.CNS involvement

Generally good prognosis

Long term remission 81-92 %

Relapse 26-28%

40% need only steroid monotherapy

Poor prognosis in

1.elevate serum Cr (> 1.58mg/dl)

2.proteinuria > 1gm/d

3.GI involvement

4.cardiomyopathy

5.CNS involvement

treatment Coricosteroid is standard treatment Depend on prognostic factor Cyclophosphamide Plasma exhange IVIG IFN- α Rituzimab

Coricosteroid is standard treatment

Depend on prognostic factor

Cyclophosphamide

Plasma exhange

IVIG

IFN- α

Rituzimab

Report 2 patients Average age 10.2 yr ( 4-16 yrs) ANCA mostly –ve result Prominent symptom => HT,chorea,seizures, testicular pain Few pathology report Steroid is standard Rx

Report 2 patients

Average age 10.2 yr ( 4-16 yrs)

ANCA mostly –ve result

Prominent symptom => HT,chorea,seizures, testicular pain

Few pathology report

Steroid is standard Rx

LTRA vs CSS

Since 1999-2009 Conflict data Difficult to research design What is hypothesis for LTRA induce CSS ?

Since 1999-2009

Conflict data

Difficult to research design

What is hypothesis for LTRA induce CSS ?

LTRA ICS SABA LABA

Quiz Which of the following is not criteria for Dx CSS in ACR criteria? 1. asthma 2. eosinophillia > 10% 3. systemic vasculitis 4. paranasal sinus abnormality 5. neuropathy

Which of the following is not criteria for Dx CSS in ACR criteria?

1. asthma

2. eosinophillia > 10%

3. systemic vasculitis

4. paranasal sinus abnormality

5. neuropathy

Which HLA may be associated with CSS ? 1. HLA-B27 2. HLA-DRB4 3. HLA-C 4. HLA-DR2 5. HLA-DR3

Which HLA may be associated with CSS ?

1. HLA-B27

2. HLA-DRB4

3. HLA-C

4. HLA-DR2

5. HLA-DR3

All the following are poor prognostic factor for CSS except_______ 1. nephrotic range proteinuria 2. renal failure 3. GI involvement 4. mononeuritis multiplex 5. cardiomyopathy

All the following are poor prognostic factor for CSS except_______

1. nephrotic range proteinuria

2. renal failure

3. GI involvement

4. mononeuritis multiplex

5. cardiomyopathy

Subgroup of CSS is differentiate by ANCA status, which one is not clinical of ANCA +ve patient ? 1. cardiomyopathy 2. small vss. Vasculitis 3. glomerulonephritis 4. pulmonary hemorrhage 5. purpura

Subgroup of CSS is differentiate by ANCA status, which one is not clinical of ANCA +ve patient ?

1. cardiomyopathy

2. small vss. Vasculitis

3. glomerulonephritis

4. pulmonary hemorrhage

5. purpura

Which one of the following is true in childhood CSS ? 1. incidence of CSS is similar between children and adult 2. ANCA +ve 50% of case 3. usually require 2 nd line Rx 4. HT is common problem in childhood CSS 5. pathogenesis of CSS in chlidren differ from adult

Which one of the following is true in childhood CSS ?

1. incidence of CSS is similar between

children and adult

2. ANCA +ve 50% of case

3. usually require 2 nd line Rx

4. HT is common problem in childhood CSS

5. pathogenesis of CSS in chlidren differ

from adult

female 52 yrs Hx asthma 20 yrs on ICS , monteleukast, present with progressive dyspnea on intermittent short course oral steroid PE wheezing and crackle both lung no clubbing CBC wbc 10200 Eo 23 % skin test alternaria , aspergillus +ve ESR 70 IgE 500 CXR bilateral parenchymal infiltration CT chest peripheral airspace subpleural consolidation What is diagnosis ? 1. CSS 2. chronic eosinophillic pneumonia 3. usual interstitial pneumonia 4. ABPA 5. Idiopathic eosinophillic syndrome

female 52 yrs Hx asthma 20 yrs on ICS , monteleukast, present with progressive dyspnea on intermittent short course oral steroid

PE wheezing and crackle both lung no clubbing

CBC wbc 10200 Eo 23 % skin test alternaria , aspergillus +ve

ESR 70 IgE 500 CXR bilateral parenchymal infiltration CT chest peripheral airspace subpleural consolidation What is diagnosis ?

1. CSS

2. chronic eosinophillic pneumonia

3. usual interstitial pneumonia

4. ABPA

5. Idiopathic eosinophillic syndrome

Take home messege Clinical manifestration of CSS Pathogenesis is unknown CSS in children LTRA and CSS association Further research direction

Clinical manifestration of CSS

Pathogenesis is unknown

CSS in children

LTRA and CSS association

Further research direction

THANK YOU FOR YOUR ATTENTION

Differential diagnosis 1.29

1.13