PURPURA- Non-palpable
- Primary Cutaneous Ds (Trauma, Solar Purpura, Steroids)
- Systemic Ds
- Coagulation abnormalities (Thrombocytopenia, Abnormal platelet function, Warfarin reaction, clotting factor defects, DIC)
- Vascular Fragility (Scurvy, Amyloidosis, Ehlers-Danlos syndrome)
- Emboli (Fat, cholesterol)
- Palpable(due to vessel wall inflammation)
- Infection (Endocarditis, RMSF, Disseminated Gonoccocemia, Acute Menigococcemia)
- Non-infectious inflammatory i.e Vasculitis (see below in vasculitis)
- References:
VASCULITIS- Classification:
- Large-vessel vasculitis
- Medium-sized-vessel vasculitis (PAN, Kawasaki's Ds)
- PAN
- Some cases are associated with Hep B; most are idiopathic
- Renal and Hepatic Biopsy is contraindicated NEJM 2013
- Kawasaki Disease
 - Small-Vessel vasculitis
- Pauci-immune small-vessel vasculitis (GPA, E-GPA, Microscopic Polyangitis or MPA)
- Diagnosis and management of ANCA associated vasculitis BMJ 2012
- Immune-Complex small-vessel vasculitis
- Drug Induced,
- Cryoglobulinemic (activates classic complement pathway),
- Type 1 Cryo: IgM or Ig G M component; forms cryoprecipitate itself
- Type 2 Cryo: Monoclonal IgM or Ig G M component; has RF activity against polyclonal Ig G (Only to have abnormal light chain, and RF)
- Type 3 Cryo: Polyclonal IgM or Ig G M component; has RF activity against polyclonal Ig G
- Note: RF hence present in type II and III (NOT Type I); B cell clone and abnormal free light chain present in type I and type II (NOT Type III)
- HSP
- Urticarial
- Normocomplementemia
- Hypocomplementemia
- SLE
Case 22-2011: A 79-Year-Old Man with a Rash, Arthritis, and Ocular Erythema (Small Vessel Vasculitis)
Pathophysiology of Vasculitides (Harrisons') 3 main mechanisms - Pauciimmune or ANCA associated : GPA, E-GPA, MPA
- Immune Complex formation or deposition: HSP(IgA), SLE, Hep-B, Hep-C Cryoglubunemic, Serum sickness with cutaneous vasculitis)
- Pathogenic T- Lymbhocytes and granuloma formation: Giant cell, Takayasu, GPA, E-GPA
BEHCET'S DISEASE
Case 7-2015: A 25-Year-Old Man with Oral Ulcers, Rash, and Odynophagia
- Type
- Type I (M spike +, RF -)
- Type II (M spike +, RF +)
- Type III (M spike -, RF +)
Lancet 2012
- 2 main pathogenesis leading to organ damage and clinical manifestations
- Cryoglobulinaemic Vasculitis: Immune-complex mediated activation of classic complement pathway (usually by type II i.e Mixed cryo)
- Hyper-viscosity syndrome, leading to Vascular slugging, mainly by type I Cryo
- Neurological (headache, confusion)
- Ocular (blurry vision, visual loss)
- Rhino-otological (epistaxis, hearing loss)
- Rapidly progressive Renal Failure
- Treatment:
- Urgent
- Needs Plasma Exchange
- IgM and IgG can only activate complement system, hence cryoglobulinemic disorders are either IgG or IgM mediated.
The most common clinical manifestations of cryoglobulinemic vasculitis are cutaneous vasculitis, arthritis, peripheral neuropathy, and glomerulonephritis. Renal disease develops in 10–30% of patients. Life-threatening rapidly progressive glomerulonephritis or vasculitis of the CNS, gastrointestinal tract, or heart occurs infrequently.  Lancet 2012
- Diagnosis:
- Diagnosis highly probable when at least 2 features of clinical, lab, histological findings are present. Panel 1 of Lancet 2012
- Clinical: Skin, Joint, Nerve, Kidney
- Lab: M-spike, Complement, RF, Platelet, ESR
- Histo: Leucocytoclastic Vasculitis, MPGN, Hyaline thrombi in capillaries, endoneural vasculitis, unclassified systemic necrotising vasculitis involving small-medium sized vessels
- Caution:
- Appropriate sample collection and handling is
crucial. Blood should be collected in prewarmed syringes
and tubes, transported, clotted, and centrifuged at
37–40°C, ensuring that the temperature never falls
below 37°C. The serum should then be stored at 4°C for
up to 7 days. Precipitation of type I cryoglobulins usually
occurs within hours. By contrast, mixed cryoglobulins,
particularly type III, can need days to precipitate. Lancet 2012
- References:
Appreciate that all 3 Cryoglobulinemia types (Type I, Type II, Type III) as a cause Immune-Complex-mediated GN with low complement levels as a cause of RPGN
This is an example of cryoglobuminemia as an example of complement mediated disease causing RPGN. Appreciate in B: - There is IgM, Kappa and IgG bands that are prominent. IgM, and Kappa has 2 prominent bands each. Likely 2 clones are involved. IgG on the other hand is polyclonal.
- Because this patient has M-spike (IgM, Kappa), and IgG is also present it is type II (Mixed) Cryoglobunemia.
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