Clinical Approach to ANCA/anti-GBM Abs and Urinary Incontinence (Selby/Miller)

Question 1

What are ANCA-associated vasculitidies (AAV) and what are the two types, and what is the difference between GPA, MPA, and EGPA?

Answer 1

• necrotizing vasculitis of small vessels with few or NO immune deposits
  
  • PR3 (cANCA) - higher relapse rates
  • MPO (pANCA) - higher mortality rates

1. GPA - necrotizing granulomas with NO asthma or eosinophilia (PR3 +)
2. MPA - necrotizing with NO granulomas, asthma, or eosinophilia (MPO +)
3. EGPA - necrotizing granulomas with asthma and eosinophilia (MPO +)

Question 2

Who are ANCA-associated vasculitides seen in commonly and what demographics are more at risk for GPA and MPA?

Answer 2

• usually seen in 5th-7th decades of life in Caucasian and Asian men

GPA - Northern Europe and Australia
MPA - Southern Europe and Asia

Question 3

What are the most common clinical manifestations of AAV, which disease is more commonly associated with ENT symptoms (examples?), and what is Livedo Reticularis?

Answer 3

• commonly Constitutional Symptoms - fever, malaise, anorexia, weight loss, myalgias, migratory arthralgias

ENT more common in GPA pts - nasal crusting, oral/nasal ulcers, SADDLE NOSE DEFORMITY

LR = red-blue, reticulated vascular network present on the legs

Question 4

What are palpable and non-palpable purpura and what pathologies are they more suggestive of?

Answer 4

Palpable - RAISED, non-blanching erythematous lesions
- more common in VASCULITIS

Non-palpable purpura - non-blanching erythematous lesions (simple hemorrhage) on skin
- more common in THROMBOCYTOPENIA

Question 5

How is the diagnosis of ANCA-associated vasculitis made?

What does definitive diagnosis require?

Answer 5

Dx: BIOPSY, ANCA testing, anti-GBM Ab, CBC, CMP, urinalysis, CXR/CT, bronchoscopy

definitive diagnosis is BIOPSY, usually of RENAL or SKIN, less commonly lung

Question 6

What is the Induction Therapy for pts. with AAV?

What is the Maintenance Therapy (2) for pts. with AAV?

What lvls should be checked in pts. prior to starting Azathioprine treatment for AAV?

Answer 6

IT: high-dose glucocorticoids and Rituximab/Cyclophosphamide

MT:

• 1st: azathioprine, mycophenolate, or rituximab
• 2nd: methotrexate

check Thiopurine Methyltransferase (TPMT) lvls prior to starting Azathioprine; pts. could have genetic variation that lead to inc. 6-mercaptopurine (TOXIC METABOLITE)

Question 7

What are the two main organ systems complicated in AAV and how are they affected?

Answer 7

1. LUNGS
   
   • hemoptysis (diffuse alveolar damage)
   • RESPIRATORY FAILURE
2. KIDNEYS
   
   • pauci-immune glomerulonephritis
   • RENAL FAILURE

Question 8

What is anti-GBM disease and who does it commonly affect?

Answer 8

• small vessel vasculitis w/antibodies directed against the glomerular basement membrane (GBM) and alveolar basement membrane (ABM)
• rare but more common in Caucasians in the 2nd (more likely male w/lung and renal involvement) or 6th decade of life (more likely FEMALE w/ONLY renal involvement)

can be associated with ANCA-associated vasculitis

Question 9

What component of the Glomerular Basement Membrane does Anti-GBM Disease and Alport Syndrome affect and in which layer are these components found?

What is the pathogenesis of Anti-GBM disease?

Answer 9

Anti-GBM –> Abs against alpha3 chain
- alpha3 ALSO found in the ABM
Alport –> mutations of alpha5 chain

both chains are found in the LAMINA DENSA of the GBM

Patho: not fully understood; environmental/infection exposes alpha3 to immune system –> Abs directed to NC1 portion of alpha3 bind and cause problems

Question 10

How does Anti-GBM Disease clinically manifest and what are two renal issues it can produce?

Answer 10

• classically presents with SYSTEMIC Symptoms: fever, malaise, weight loss, arthralgias but ONLY for a few weeks

Renal (80-90%): rapidly progressive GN and Nephritic Syndrome (HEMATURIA)

• 40-60% will have concurrent DIFFUSE ALVEOLAR HEMORRHAGE

Question 11

How is Anti-GBM Disease diagnosed and what is commonly seen on renal biopsy?

Answer 11

Dx: Anti-GBM Ab and ANCA testing, RENAL BIOPSY
- dz should be suspected in pts with RPGN and nephritic syndrome

Renal Biopsy: CRESENTIC glomerulonephritis with LINEAR IgG STAINING ALONG THE GBM

• usually > 80% of glomeruli involved
• CXR –> check for diffuse alveolar hemorrhage

Question 12

What does a pathological diagnosis of Anti-GBM Disease require?

Answer 12

• requires demonstration of immunofluorescence of DIFFUSE LINEAR IgG STAINING along the GBMs in the setting of CRESENTIC glomerulonephritis

Question 13

What is the standard treatment for pts with Anti-GBM Disease? (3)

What are the two organ systems that show complications from Anti-GBM Disease?

Answer 13

PLASMAPHRESIS + high-dose glucocorticoids + cyclophosphamide

Complications in:

1. LUNGS
   
   • hemoptysis from diffuse alveolar damage
   • RESPIRATORY FAILURE
2. KIDNEYS
   
   • crescentic, rapidly progressive glomerulonephritis

Question 14

What is the difference between these forms of Urinary Incontinence:

1. Transient UI
2. Chronic UI
3. Functional UI

Answer 14

1. arises suddenly lasting < 6 months; can be reversed
2. 4 subtypes: Stress, Urge, Mixed, and Overflow
3. incontinence in setting of PHYSICAL or COGNITIVE impairment which limits mobility or ability to process information about bladder fullness

Question 15

What is the difference between Stress, Urge, Mixed, and Overflow Incontinence?

Answer 15

S: urine leakage with cough, sneezing, exertion
- most common in WOMEN

U: urine leakage w/sudden compelling desire to void
- both women and men

M: coexistence of stress AND urgency

O: urinary retention from detrusor underactivity or outflow obstruction (5%)
- most common in MEN (prostate enlargement)

Question 16

Urinary Incontinence Risk Factors

What are risk factors specifically seen in women (2) vs men (1)?

Answer 16

Women

• parity (multiple deliveries, especially if vaginal)
• menopause

Men
- benign prostate hypertrophy (BPH)

Question 17

What is Overflow Incontinence and what are 3 main causes of this condition?

Answer 17

OI: when bladder becomes so full and distended that urine leaks out

C: blocked urethra, bladder weakness, enlarged prostate

Question 18

What should you make sure to do if you suspect patient might have Urinary Incontinence?

Answer 18

ASK THEM ABOUT IT!

• patients probably won’t just bring it up, so specifically asking about it is important to helping them treat it

Question 19

How are Functional Assessments, Abdominal Exams, and Urogenital Exams used to help diagnose Urinary Incontinence?

Answer 19

FA: check mental status, mobility, and pts. BMI

AE: look for masses, palpable bladder, CVA tenderness

UE: look for pelvic masses, pelvic floor muscle tone, rectal exam, provocation testing (Cough Stress Test)

Question 20

How are the Q-tip and Provocation Test used to help identify Stress Incontinence?

Answer 20

Q-tip: normal valsalva movement shows bladder movement of < 30 degrees, but pts with Stress UI will show movement of > 30 degrees

PT: pt coughs while either laying supine or standing-up; check for leakage during cough

Question 21

What are two initial Urological Tests that should be performed on pts with Urinary Incontinence?

What test is used to measure completeness of voiding and what are (+) test findings?

What is Pad Testing and what is a positive finding?

Answer 21

1. UA with microscopy
2. Urine Dipstick (check for UTI)
   
   • if UTI present or symptoms –> get urine culture

• use Post-void Residual Volume (PVR) to measure completeness of voiding (use US or in-out cath)
  
  • Normal: < 30-50 mL immediately post-void
  • (+): > 200 mL post-void (abnormal)

PT: worn for 24 hours; > 4g increase in weight of pad is POSITIVE TEST

Question 22

When are Urodynamic Studies used?

Answer 22

• NOT USED AS INITIAL STEP IN UI DIAGNOSIS
• used if incontinence diagnosis is uncertain after initial assessment or if symptoms do not correlate with physical findings
  • invasive procedure

Question 23

What is the DIPPERS mnemonic for Transient UI?

Answer 23

D - delirium
I - infection (acute UTI)
P - pharmaceuticals
P - psychological morbidity
E - excess fluid intake/urine output
R - restricted mobility
S- stool impaction

Question 24

What is the initial treatment for these types of Urinary Incontinence:

1. Stress
2. Urge (3)
3. Overflow

Answer 24

1. conservative management
   
   • pelvic floor muscle strengthening/training
   • Kegel exercises
   • weight loss, stop smoking, good fluid intake
2. antimuscarinics, intravaginal estrogen, mirabegron
3. alpha-adrenergic antagonists

Question 25

Invasive Treatments for Urge UI

What are Neuromodulation and Intravesical Onabotulinumtoxin A used for?

Answer 25

N: direct electrical stimulation to modify bladder sensation/contraction
- both subQ and transcutaneous options

IOA: chemical neuromodulation which acts at detrusor presynaptic NM junction
- repeat every 9-12 months

Question 26

What are 4 major complications of Urinary Incontinence?

Answer 26

1. poor quality of life (MAJOR RISK FACTOR)
2. social isolation, sexual dysfunction, poor marital relationships (associated with above complication)
3. negative effect on psychological burden of family caregivers
4. inc. rates of depression

Question 27

Which UI does not have medical interventions available?

Answer 27

STRESS INCONTINENCE

• used surgery instead (invasive)