Morphology of Purpura

Description
  • <= 4 mm
  • Non-palpable
  • Non-blanchable
Evolution

  1. Main mechanism is hemorrhage: extravasated red blood cells (RBC) + very little inflammation

  2. Clearing of RBC & hemoglobin: predictable resolution w/red/blue/purple → green → yellow/brown → fade

Differential diagnosis

Thrombocytopenia:

  • <10000-20000/mm3
  • ITP; TTP; DIC
  • Rx: chemotherapy, quinine & quinidine
  • Other acquired: bone marrow infiltration, fibrosis or failure

Platelet dysfunction:

  • Congenital / hereditary
  • Acquired: ASA, NSAIDS, renal failure, monoclonal gammopathy (uncommon)
  • Thrombocytosis 2nd to myeloproliferative disorders

Non-platelet causes:

  • ↑ intravascular pressure (Valsalva, vomiting, seizure…)
  • Fixed ↑ pressure (stasis) or intermittent pressure (blood pressure cuff)
  • Trauma (linear)
  • Perifollicular (scurvy)
  • Pigmented purpuras
  • Hypergammaglobulinemic purpura of Waldenström

Description
  • 5-9 cm
  • Non-palpable
  • Non-blanchable
Evolution

  1. Main mechanism is hemorrhage: extravasated red blood cells (RBC) + very little inflammation.

  2. Clearing of RBC & hemoglobin: predictable resolution with red/blue/purple → green → yellow/brown → fade.

Differential diagnosis
  • Hypergammaglobulinemic purpura of Waldenström
  • Infection / inflammation in thrombocytopenic individuals
  • Small vessel vasculitis (occasionally)

Description
  • 1 cm
  • Non-palpable
  • Non-blanchable
Evolution

  1. Main mechanism is hemorrhage: extravasated red blood cells (RBC) + very little inflammation.

  2. Clearing of RBC & hemoglobin: predictable resolution with red/blue/purple → green → yellow/brown → fade.

Differential diagnosis
  • All below categories + minor trauma

Procoagulant defect:

  • Anticoagulant Rx
  • Hepatic failure
  • Vitamin K deficiency
  • DIC (some)

Poor dermal vessel support:

  • Solar/senile purpura
  • Corticosteroids
  • Scurvy
  • Systemic amyloidosis
  • Ehlers-Danlos syndrome

Platelet anomalies:

  • Platelet dysfunction (e.g., Von Willebrand, Rx-induced, metabolic disease)
  • Acquired / congenital thrombocytopenia

Description
  • Round or oval shape
  • Retiform, branching, or stellate
  • +/- Erythema
  • Purpura: Hemorrhage around vessel within dermis (non-blanching)
  • Classic small-vessel vasculitis lesion
Evolution

Microvascular occlusion lesions:

  1. 0-few hours: Minimal ischemia with RBC extravasation and edema, no inflammation. No palpable, increased purpura.
  2. Few-24 hours: Peak occlusion with maximum ischemia and RBC extravasation around dermal vessels. Palpable, maximal purpura, still no erythema.
  3. 24 hours – 3-4 days: Necrosis and wound response (may cause secondary vasculitis). Palpable++, decreased purpura, eschar (if significant necrosis), erythema of wound healing becomes visible. If biopsied late, secondary vasculitis may be seen.

Immune complex-leukocytoclastic vasculitis (LCV) lesions:

  1. 24 hours: Immune complexes in vessels with complement activation and neutrophil (PMN) recruitment. +/- Palpable, +/- erythema, minimal purpura.
  2. 24-48 hours: Destruction of immune complexes by PMN leads to vessel injury, fibrin deposits, and necrosis. Increased palpable, increased erythema, increased purpura.
  3. 2 days: Complete destruction of complexes, decreased complement activation, significantly reduced inflammation. +/- Palpable, +/- erythema, purpura still present.

Age of lesions matters for biopsy:

  • Microocclusion: Best within the first 24 hours to detect occlusion and avoid a late misdiagnosis of vasculitis.
  • Vasculitis: Best at 24-48 hours or older to detect fibrinoid necrosis.
  • DIF for vasculitis: Earliest lesion possible, less than 24 hours.
Differential diagnosis

LCV (Leukocytoclastic vasculitis) 2nd immune complex:

  1. Small vessels only:
  • Idiopathic, infection, or Rx (IgG or IgM)
  • Idiopathic IgA (Henoch-Schönlein purpura – HSP)
  • Hypergammaglobulinemic purpura of Waldenström
  • Urticarial vasculitis
  • Pustular vasculitis (bowel bypass)
  1. Small + medium vessels:
  • Mixed cryoglobulinemia
  • Rheumatic vasculitis (lupus erythematosus – LE, rheumatoid arthritis – RA, Sjögren’s syndrome)

Pauci-immune LCV:

  1. ANCA (Anti-neutrophil cytoplasmic antibody):
  • Granulomatosis with polyangiitis (formerly Wegener’s granulomatosis)
  • Microscopic polyangiitis
  • Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome)
  1. Other:
  • Erythema elevatum diutinum
  • Sweet syndrome (vasculitis unusual)

Non-LCV:

  • Erythema multiforme
  • PLEVA (Pityriasis lichenoides et varioliformis acuta)
  • Pigmented purpuras

Description
  • Peripheral branching (reticular) with 2/3 of the lesion purpuric or necrotic (only 1/3 of the lesion is surrounding erythema).
  • +/- Ulceration, very painful (complete obstruction).
  • Often due to microvascular occlusion (thromboembolic).
Evolution

Microvascular occlusion lesions:

  1. 0-few hours: Minimal ischemia with RBC extravasation and edema, no inflammation. No palpable, increased purpura.
  2. Few-24 hours: Peak occlusion with maximum ischemia and RBC extravasation around dermal vessels. Palpable, maximal purpura, still no erythema.
  3. 24 hours – 3-4 days: Necrosis and wound response (may cause secondary vasculitis). Palpable++, decreased purpura, eschar (if significant necrosis), erythema of wound healing becomes visible. If biopsied late, secondary vasculitis may be seen.

Immune complex-leukocytoclastic vasculitis (LCV) lesions:

  1. 24 hours: Immune complexes in vessels with complement activation and neutrophil (PMN) recruitment. +/- Palpable, +/- erythema, minimal purpura.
  2. 24-48 hours: Destruction of immune complexes by PMN leads to vessel injury, fibrin deposits, and necrosis. Increased palpable, increased erythema, increased purpura.
  3. 2 days: Complete destruction of complexes, decreased complement activation, significantly reduced inflammation. +/- Palpable, +/- erythema, purpura still present.

Age of lesions matters for biopsy:

  • Microocclusion: Best within the first 24 hours to detect occlusion and avoid a late misdiagnosis of vasculitis.
  • Vasculitis: Best at 24-48 hours or older to detect fibrinoid necrosis.
  • DIF for vasculitis: Earliest lesion possible, less than 24 hours.
Differential diagnosis

Occlusion secondary to platelet plug:

  • Heparin-induced thrombocytopenia (HIT)
  • Thrombocytosis (myeloproliferative disorder)
  • Paroxysmal nocturnal hemoglobinuria
  • Thrombotic thrombocytopenic purpura (TTP)

Occlusion secondary to RBC:

  • Sickle cell disease

Vascular coagulopathy:

  • Livedoid vasculopathy
  • Degos disease
  • Sneddon syndrome

Systemic hypercoagulable state:

  • Protein C/S abnormalities
  • Antiphospholipid antibody (lupus anticoagulant)
  • Levamisole-adulterated cocaine

Cold-related agglutination:

  • Cryoglobulinemia
  • Cryofibrinogenemia
  • Cold agglutinins

Occlusion secondary to organisms:

  • Fungi (Mucor, Aspergillus)
  • Ecthyma gangrenosum
  • Disseminated strongyloidiasis
  • Lucio phenomenon (leprosy)
  • Rickettsial infection

Embolization / crystal:

  • Cholesterol embolism
  • Oxalate embolism
  • Marantic endocarditis
  • Atrial myxoma, etc.

Other causes:

  • Calciphylaxis
  • Intravascular B-cell lymphoma
  • Brown recluse spider bite reaction, etc.

Description
  • Peripheral branching (reticular) but only 1/3 of the lesion shows central impending necrosis, while prominent peripheral erythema makes up the majority (>2/3) of the lesion.
  • Often due to vessel wall damage (vasculitis, sepsis, etc.).
Evolution

Microvascular occlusion lesions:

  1. 0-few hours: Minimal ischemia with RBC extravasation and edema, no inflammation. No palpable, increased purpura.
  2. Few-24 hours: Peak occlusion with maximum ischemia and RBC extravasation around dermal vessels. Palpable, maximal purpura, still no erythema.
  3. 24 hours – 3-4 days: Necrosis and wound response (may cause secondary vasculitis). Palpable++, decreased purpura, eschar (if significant necrosis), erythema of wound healing becomes visible. If biopsied late, secondary vasculitis may be seen.

Immune complex-leukocytoclastic vasculitis (LCV) lesions:

  1. 24 hours: Immune complexes in vessels with complement activation and neutrophil (PMN) recruitment. +/- Palpable, +/- erythema, minimal purpura.
  2. 24-48 hours: Destruction of immune complexes by PMN leads to vessel injury, fibrin deposits, and necrosis. Increased palpable, increased erythema, increased purpura.
  3. 2 days: Complete destruction of complexes, decreased complement activation, significantly reduced inflammation. +/- Palpable, +/- erythema, purpura still present.

Age of lesions matters for biopsy:

  • Microocclusion: Best within the first 24 hours to detect occlusion and avoid a late misdiagnosis of vasculitis.
  • Vasculitis: Best at 24-48 hours or older to detect fibrinoid necrosis.
  • DIF for vasculitis: Earliest lesion possible, less than 24 hours.
Differential diagnosis

Vasculitis:

  1. Primary dermal:
  • IgA vasculitis (formerly known as Henoch-Schönlein purpura)
  1. Dermal + subcutaneous vessels:
  • Mixed cryoglobulinemia
  • Rheumatic vasculitis (lupus erythematosus – LE, rheumatoid arthritis – RA)
  • Polyarteritis nodosa
  • Microscopic polyangiitis
  • Granulomatosis with polyangiitis (formerly Wegener’s granulomatosis)
  • Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome)

Dermal vessel inflammation, occlusion, or constriction:

  • Livedoid vasculopathy
  • Septic vasculitis
  • Chilblains
  • Pyoderma gangrenosum