Thrombocytopenia, vasculitis, “senile” purpura, and scurvy.
Thrombocytopenia
- ITP
- TTP
- Hereditary: ADAMTS-13 activity assay
Vasculitis
Classified according to histological findings at biopsy; RFTs and LFTs reflect extent of disease; disease activity relates to CRP, ESR, ± Complement C3 and C4
- Systemic necrotising: Antineutrophilic cytoplasmic Ab (ANCA)†
- Polyarteritis nodosa (2-30 cases per million) – systemic necrotising vasculitis of middle-age (peaks 40s-50s) typically affecting medium-sized muscular arteries resulting in secondary tissue ischemia of most commonly the kidneys, skin, joints, muscles, peripheral nerves, and gastrointestinal (GI) tract
- Microangiopathic (non-immune or leucocytoclastic) Haemolysis:[2] Reticulocyte count, bilirubin, LDH, Urinary Hb, Urinary hemosiderin, PT, APTT, Fibrinogen, D-dimer
- Prosthetic cardiac valve
- Metastatic malignancy
- Disseminated intravascular coagulation (DIC)
- Malignant Hypertension
- Pregnancy-induced hypertension (PIH), HELLP syndrome
- Haemolytic Uraemic syndrome – e.g. Shiga-toxin mediated; atypical or complement-mediated
- Renal graft rejection
- Drug-induced: Heparin-induced thrombocytopenia (HITTS); cyclosporin; mitomycin C; quinine; sulfonamides
- Haemangiomas
- March (exercise-induced) Hemoglobinuria
- Microscopic polyangiitis – systemic necrotising pauci-immune vasculitis affecting mainly small vessels that may begin as a pulmonary-renal syndrome with rapidly progressing glomerulonephritis and alveolar haemorrhage
- Granulomatous vasculitis‡ – predominant mononuclear inflammatory cell infiltrate with ongoing cell-mediated hypersensitivity manifest through a cytokine cascade (occasionally confused with sarcoidosis and hypersensitivity pneumonitis/extrinsic allergic alveolitis):
- Granulomatosis with polyangiitis (GPA) orWegener’s granulomatosis – necrotising granulomatous inflammation of small- and medium-sized vessels affecting respiratory tract (ENT, lungs) and kidneys, the latter with crescentic focal necrotising glomerulonephritis
- Lymphomatoid granulomatosis
- Eosinophilic Granulomatosis with Polyangiitis (EGPA) or Churg-Strauss syndrome – lungs – history of allergy with asthma and pulmonary infiltrates often preceding development of systemic symptoms by months or years, dividing the condition into three stages: prodromal (allergic) such as late-onset asthma, eosinophilic, and vasculitic including neurological manifestations of polyneuropathy or mononeuritis multiplex; 40-60% ANCA positive
- Kawasaki’s disease (mucocutaneous lymph node syndrome)
- Drug reaction: frusemide; thiazides; allopurinol
- Connective Tissue Diseases:
- Rheumatoid arthritis: Rheumatoid factor
- SLE: Antinuclear antibody (ANA)
- Henoch-Schönlein purpura
- GMN: Hepatitis B serology, Hepatitis C serology
- Cryoglobulinemia: cryoglobulins
- Large-vessel
- Giant cell (Temporal) arteritis
- Buerger’s disease: thromboangiitis obliterans
- Takayasu’s disease (Aortic Arch Syndrome) – stenosis, occlusion, dilation, or aneurysms, of the aorta, its branches, and pulmonary arteries (more common in younger, Asian, female cohort)
- Erythema nodosum
- Behcet’s syndrome
“Senile” purpura
- Elderly
- Prolonged sun exposure
- Corticosteroid excess
Scurvy
Notes:
* Blistering of the skin seen with porphyria cutanea tarda can be confused with purpura.
† Detection of ANCA may support the diagnosis of granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), or microscopic polyangiitis (sometimes called collectively ANCA-associated vasculitides). ANCA-associated vasculitides are rare, and the ANCA test is not completely specific. Because ANCA-associated vasculitides are rare, and the ANCA test is not completely specific, ANCA testing should be done only when the pre-test probability for ANCA-associated vasculitis is moderately high. A positive ANCA test can occur in infections that can cause a secondary vasculitis, including endocarditis. Other useful laboratory tests include hepatitis B and C serologic testing, serum and urine protein electrophoresis, antinuclear antibody and anti-extractable nuclear antigens panel, testing for the presence of cryoglobulins, and complement levels. Complement levels may be low in viral vasculitis, cryoglobulinemic vasculitis, lymphoproliferative disorders, or vasculitis secondary to other autoimmune diseases. Further testing is determined by clinical findings. Most routine laboratory tests yield results that are nonspecific and must be interpreted in the context of the entire clinical presentation. However, results can often help support the diagnosis, determine the location and degree of organ involvement, or suggest alternative diagnoses. Tests usually include CBC, ESR or C-reactive protein, serum albumin and total protein, AST, and ALT. Often, patients present with elevated ESR or C-reactive protein, anemia due to chronic inflammation, elevated platelets, and low serum albumin. Freshly voided urine must be tested for red blood cells, red blood cell casts, and protein to identify renal involvement. Serum creatinine levels should be checked and monitored. Leukopenia and thrombocytopenia are not typical of primary vasculitis and suggest an alternate diagnosis.
‡ The family of vasculitic granulomatoses comprise Wegener’s granulomatosis, necrotising sarcoidal granulomatosis, Churg-Strauss syndrome, lymphomatoid granulomatosis, polyarteritis nodosa, bronchocentric granulomatosis, giant cell arteritis, and systemic lupus erythematosus. They may occasionally be confused with sarcoidosis and hypersensitivity pneumonitis (extrinsic allergic alveolitis), so a careful clinicopathological synthesis is essential (table 5). Granulomatous vasculitis is a small group of systemic disorders of unknown cause and obscure pathogenesis. It has long been considered that both humoral and cellular immune mechanisms are involved, and a cascade of cytokines may influence their course. The future management may indeed depend upon manipulation of this cytokine network.[1]
References
“Vasculitis.” The Royal College of Pathologists of Australasia (RCPA) Manual. Available at https://www.rcpa.edu.au/Library/Practising-Pathology/RCPA-Manual/Items/Clinical-Problems/V/Vasculitis. Accessed 24 March 2016.
“Microangiopathic haemolysis.” The Royal College of Pathologists of Australasia (RCPA) Manual. Available at https://www.rcpa.edu.au/Library/Practising-Pathology/RCPA-Manual/Items/Clinical-Problems/M/Microangiopathic-haemolysis. Accessed 24 March 2016.
