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Name : Low Wei Quan Group: 88

HenochSchnlein purpura

What is HSP ?-Is called haemorrhagic vasculitis or ANCA negative vasculitis Small vessel vasculitis involving vessels of microcirculation which are venules , capillaries and small arteries and characterised by palpable purpura. - HSP is a systemic disease and it can target any tissue or any organ for example skin , Gastrointestinal Tract ( GI ) , Kidneys , joints , lung and Central nervous system ( CNS).

Incidenceprevalence of HSP peaks in children aged 4-7 years, but the condition is also seen in adultsmale-to-female ratio is 1.5:1.

Etiology Infections:-Mononucleosis-Group A streptococcal Infection(most common)-Hepatitis-Mycoplasmainfection -Campylobacterenteritis-Hepatitis Crelated liver cirrhosis-Subacute bacterial endocarditis- Helicobacter pyloriinfection(specifically noted in China)-Yersiniainfection-Shigellainfection-Salmonellainfection-Brucellosis

Vaccination - Typhoid and paratyphoid A and B-Measles-Yellow fever-CholeraEnvironmental exposure to the following may precede the development of HSP:-Drugs (eg, ampicillin, erythromycin, penicillin, quinidine, quinine, losartan, and cytarabine)-Foods-Horse serum-Cold exposure-Insect bites

Pathogenesis HSP is an acute immunoglobulin A (IgA)mediated disorder.IgA aggregates or IgA complexes with complement deposited in target organs, resulting in activation of inflammatory mediators such as tumor necrotic factor , IL-1, IL-6 prostacyclin, may play a central role in the pathogenesis of HSP vasculitis.A subpopulation of human lymphocytes bears surface Fc and/or C3 receptors (complement receptor lymphocytes), which can bind circulating immune complexes or C3 generated by activation of the alternative complement pathway.

As a result , IgA aggregates or IgA complexes with complement deposited in target organs.

Clinical ManifestationConstitutional symptom : -Fever -anorexia -Headache-arthralgia.

Target organs sign and symptoms-SkinBilateral palpable purpura at the lower extremities and the buttock area . It can be located in anywhere of the body trunk . *The higher the location of the purpura in the body the greater the suspicion of a secondary origin of vasculitis .But if the purpura is not palpable it does not mean that it is not HSP . Skin pigmentation can also be found in HSP. Why? Deposition of hemosiderin in the skin .

*JointLocation : lower extremities . Pain and swelling of the joint but no deformities and non-destructive. *GI tractColicky abdominal pain especially after meal Upper GI will present with melenic stoolLower GI will present with hematochezia Hematemesis massive GI hemorrhage In children , one of the dangerous complication is intussuception as this is a fatal complication that lead to mechanical obstruction and eventually peritonitis. This will require surgical intervention .

*Renal system Glomerulonephritis ( inflammation of glomeruli due to deposition of immune complex ). In one series, acute glomerular lesions, including mesangial hypercellularity, endocapillary proliferation, necrosis, cellular crescents, and leukocyte infiltration,In 80% of patients, renal involvement becomes apparent within the first 4 weeks of illness. Overall, 2-5% of patients progress to end-stage renal failure (ESRD)*Lung- Vasculitis may lead to fatal complication which is pulmonary hemorrhage .*Heart involved myocardium

Investigations: Laboratory investigation :Full blood count : Leukocytosis , normal platelet count , occasionally eosinophilia ,.Serum complement : C3 and C4 will be in normal level . Immunofluorescence test :Ig A will be elevated . ANCA and cryoglobulin can be tested but mostly for differential diagnosis . Urinalysis : proteinuria(< 2 g/day) and hematuria (microscopic) if there is involvement of kidney Skin biopsy , renal biopsy and instrumental investigation (CT and MRI) can be done to check the progression fo the disease.* Diagnosis of HSP is mainly based on clinical signs and symptoms.

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Complication: -Myocardial infarction-Pulmonary hemorrhage-Pleural effusion-Intussusception-GI bleeding-Bowel infarction-Renal failure-Hematuria-Proteinuria-Seizures-CNS bleeding-Mononeuropathies-Recurrence of symptoms, specifically those of renal impairment (rare)

Differential diagnosis -Acute abdomen-Bowel infarction or perforation-Drug reactions-Elevated renal function test results (blood urea nitrogen [BUN]creatinine)-Essential mixed cryoglobulinemia-Global organ involvement-Leukocytoclastic vasculitis-Primary antiphospholipid syndrome-Idiopathic Thrombocytopenic Purpura-IgA Nephropathy-Wegener granulomatosis-Systemic Lupus Erythematosus

Treatment *Induction of remisssion -Induction with 250-750 mg of intravenous (IV) methylprednisolone daily for 3-7 days plus cyclophosphamide 100-200 mg/d administered orally (PO)*Maintanence Maintenance with prednisone 100-200 mg PO every other day plus cyclophosphamide 100-200 mg/d PO 30-75 days*Tapering of prednisone by approximately 25 mg/month (with the cyclophosphamide dose remaining constant)Discontinuance of treatment after at least 6 months by abruptly discontinuing cyclophosphamide and tapering prednisone completely

*Other treatment regimens have included IV or oral steroids with or without any of the following:AzathioprineCyclosporineDipyridamoleHigh-dose IV immunoglobulin G (IVIg)Dapsone ( for skin and joint 100mg /day)mycophenolate mofetil,

Plasmapheresis has been useful in treating rapidly progressive HSPnephritis.If there is massive GI haemorrhage or Pulmonary haemorrhage pulse therapy with glucocorticosteroid should be initiated immediately. If intussusception developed , surgical intervention should be consider.

This is not the end yet

Von Willebrand Disease (vWD)

What is the roles of Von Willebrand factor (vWF)?Facilitates the platelet adhesion to damaged endothelium Acts as the carrier protein for FVIII : C , protecting it from inactivation and clearance

vWD is divided into three major categories: (1) partial quantitative deficiency (type I), (2) qualitative deficiency (type II), and type II is further divided into four variants (IIA, IIB, IIN, IIM),(3) total deficiency (type III). vWD

Pathogenesis Results from either a quantitative or qualitative deficiency of von Willebrand Factor (vWF). This causes defective platelet plug formation Since vWF is a carrier protein for FVIII:C . Patient with vWD laso are deficient in FVIII : CThere are many different mutations in the vWF gene and many different genes types of vWD . Autosomal dominant . Commonest subtype is type 1 (60-80%) usually fairly mild and is often not diagnosed until puberty or adulthood .

Clinical manisfestation -Bruising -Excessive , prolonged bleeding after surgery -Mucosal bleeding such as epistaxis and menorrhagia . In contrast to haemophilia , spontaneous soft tissue bleeding such as large haematomas and haemarthroses are uncommon .

Investigation Coagulation profile : -Prothrombin time (PT)-Activated partial thromboplastin time (aPTT) mildly prolonged -Factor VIII coagulant activity -low level -Ristocetin cofactor (RCoF) activity-Concentration of vWF antigen (vWF:Ag)

Differential diagnosis Factor XFactor XI DeficiencyHemophilia A

Treatment Desmopressin ( DDAVP) and transfusion therapy . Type 1 vWD can usually be treated with DDAVP , which causes secretion of both FVIII and vWF into plasma. DDAVP should be used with caution in children below 1 year of age because it can cause hyponatremia due to water retention and may cause seizures . More severe types of vWD are treat with plasma derived FVIII ( Fresh Frozen Plasma) Cryoprecipitate is no longer used to treat vWD as it has not undergone viral inactivation . IM injection of aspirin and other NSAIDS should be avoided .