Multi-System Vasculitis on ICU #LIVES2017

Marlies Ostermann from Guys & St. Thomas’ NHS Trust in London gave an excellent overview of this uncommon but difficult condition.

Firstly, vasculitis is rare and non-specific in its presentation. Unless you work in a specialist centre you might not come across a diagnosis of it (although you might find may more cases you don’t know about…).

Vasculitis involves inflammation of any vessel, arterial or venous and clinical presentation so variable as it depends what organs those vessels are supplying as to what organ dysfunction you get. Classification is completely arbitrary and has changed in recent years as we’ve moved away from Nominals for syndromes.

 

Distribution of vessel size and Vasculitis

 

ALL vasculidities are triggered by something which produces antibody mediated reaction with inflammatory vessel wall and vessel occlusion/necrosis. Type of damage differs with different mediator and particularly important for small vessel diseases, i.e.

 

  • If the antibody is raised and directed the blood vessel wall itself, this is Anti-Glomerular Basement Membrane disease, previously called Goodpasture’s Syndrome.
  • If the antibody is raised by B-cells against systemic cellular components which then cause secondary wall attach, these are usually Anti-Neutrophil Cytoplastic Antibody (ANCA) associated vasculidities.
    • There are different patterns of staining and hence classifications of ANCA depending upon what the antibody is attacking
    • Perinuclear (pANCA) is raised against the antigen myeloperoxidase (MPO) and this causes staining around the nucleus (!)
    • Cytoplasmic (cANCA) is raised against the cytoplasmic (!) antigen PR3. You can see the difference below:

ANCA Staining Patterns

    • pANCA isn’t just raised against MPO though, it can also be raised against lactoferrin or ‘bactericidal permeability inducing protein’ which why pANCA can be positive in sepsis, although it’s usually at a low titre.
      • GPA (Wegner’s) mainly cANCA
      • MPA mainly pANCA
      • Eosinophillic GPA (Churg-Strauss) mainly pANCA
  • You can also form antibodies against drugs like hydrazine, propothyrouracil, D-penicillamine which are similarly deposited in vessel walls and hence can cause a lupus like presentation.
  • If you have some other kind of immune-complex-antigen reaction and those form big complexes, they can occlude the really small blood vessels rather than directly causing wall issues – this is cryoglobulinaemiaIgA vasculitis (Henoch-Schonlein) etc.

 

The chance of it being vasculitis go up with age. Important to remember as well our tests are getting better – the current classification is pretty ANCA heavy, yet as the assays get better it is possible that what we thought of as ‘ANCA-negative’ might not be. Watch this space. The test can also be falsely positive in a number of conditions, particularly autoimmune thyroid disease but also inflammatory bowel disease and viral hepatitis.

We don’t know why some people get lung involvement, others kidney, others rash, etc. However, most do get renal dysfunction hence nephrology’s intimate involvement. Rashes classically petechial and no-blanching, limited to lower limbs

 

Organ Involvement

 

Typical Vasculitis Rash

 

Most people end up on ICU because of their respiratory presentations – this might be respiratory failure which can mimic pulmonary oedema or airway bleeding. HOWEVER, one third of patients with airway bleeding don’t have haemoptysis but you can see blood if CT chest/bronch. Don’t miss important differentials – sepsis (particularly meningococcal), syphyllis and TTP/HUS.

What tests? Most important thing is a degree of suspicion. Do urine dip for blood (non-CSU) and casts, autoab screen, CT chest for bleeding/fibrosis & look for tissue you can get (skin/kidney). Do an echo if is a low pANCA titre and you’re wondering about endocarditis.

Aims of treatment two fold:

  • Remove existing antibodies – plasma exchange
  • Stop making new ones – steroids and chemotherapy

The clear indications for plasma exchange are severe CNS involvement and severe pulmonary haemorrhage. Borderline evidence for indications other than this but that doesn’t mean it might not work.

Classical chemotherapeutic agent was cyclophosphamide – however in recent years there has been a switch towards Rituximab. They both do the same thing, i.e. stop B cell activity but recent trials have shown Rituximab to be non inferior with a better long-term safety profile (marrow/infertility/cancer) hence popularity. No-one is ever going to do a trial of cyclophosphamide or rituximab in critically ill patients so we have to extrapolate. Should be an MDT consensus – they all have major side effects so depends on how bad they are as to how much you want to poison them.

Largest ICU series to date from France – 82 patients from 20 French ICUs over 20 years (!). However, other populations the incidence is much higher so it’s probably that we do not look for it. ICU mortality was only 16% – 70% died of disease and 30% from sepsis underlining why we need to have open mind – they respond to treatment if you do it.

Short answer – not all MIs are atherosclerotic. Not all confusion is ‘delirium.’ Not all AKI is sepsis. We need to get to diagnoses not syndromes.

 

#micdrop