Not t ingham Children’s Hospit al Nottingham University Hospitals NHS Trust

Henoch-Schönlein Purpura (HSP) Title of Guideline (must include the word “Guideline” (not protocol, policy, procedure etc)

Contact Name and Job Title (author)

Directorate & Speciality Date of submission Date on which guideline must be reviewed (this should be one to three years) Explicit definition of patient group to which it applies (e.g. inclusion and exclusion criteria, diagnosis) Abstract

Key Words

Statement of the evidence base of the guideline – has the guideline been peer reviewed by colleagues? Evidence base: (1-5) 1a meta analysis of randomised controlled trials 1b at least one randomised controlled trial 2a at least one well-designed controlled study without randomisation 2b at least one other type of well-designed quasiexperimental study 3 well –designed non-experimental descriptive studies (ie comparative / correlation and case studies) 4 expert committee reports or opinions and / or clinical experiences of respected authorities 5 recommended best practise based on the clinical experience of the guideline developer Consultation Process

Target audience

Guideline for Management of Henoch-Schönlein Purpura and Henoch-Schönlein Purpura Nephritis Dr. Tom Forbes Paediatric Nephrology Registrar Dr. Andrew Lunn Consultant Paediatric Nephrologist Dr Corinne Langstaff Consultant Paediatric Nephrologist Family Health, Renal July 2016 July 2019 All children with a diagnosis of Henoch-Schönlein Purpura (HSP) This guideline describes the diagnosis and management of HSP in the paediatric population, including a pathway for screening for renal involvement. Paediatrics, Children, HenochSchönlein, purpura, HSP, vasculitis, renal, nephritis, abdominal pain, arthritis Use of corticosteroids not indicated to prevent renal involvement in HSP – 1a Use of corticosteroids in severe HSP abdominal pain or arthritis – 1b Screening Pathway for HSP Nephritis –3

Paediatric Nephrology Consultants General Paediatric Consultants Paediatric Clinical Guidelines Group Nottingham Children’s Hospital Staff

This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date.

Dr Andrew Lunn

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Document History Version Number

Date Produced

Author

V1

Jan 2005

V2

Dec 2009

Dr F Hussain

V3

June 2013

v4

June 2016

Dr T Forbes, Dr A Lunn Dr C Langstaff Dr A Lunn

Minor amendments from previous guideline: 1. Clarification of proteinuria criteria for referral to paediatric nephrology – Page 5 and page 9 2. Updated new eGFR reporting – page 12 3. Updated numbering and contents table

Dr Andrew Lunn

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Contents of the Guideline Contents 1.

Patient Pathways ................................................................................................................ 4 Initial Management of Newly Diagnosed HSP ................................................................... 4 General Paediatric Review at 1 Week Following Diagnosis .............................................. 5 HSP Letter for GP if urinalysis/blood pressure normal at 1 week review .......................... 5 General Paediatric Pathway ............................................................................................... 7 Pathway for patients referred back during GP assessment period: ................................... 9

2.

Background ...................................................................................................................... 10

3.

Clinical Features ............................................................................................................... 10

4.

Diagnosis .......................................................................................................................... 11

5.

Investigation ..................................................................................................................... 12

6.

Indications for Admission ................................................................................................. 12

7.

Management..................................................................................................................... 13 7.1. Supportive ................................................................................................................. 13 7.2. Steroids ..................................................................................................................... 13 7.3. Nephrology referral.................................................................................................... 13 7.4. Other Specialist referral............................................................................................. 13

8.

Follow Up.......................................................................................................................... 13

9.

Outcome ........................................................................................................................... 14

10. References ....................................................................................................................... 15 11. Audit Points ...................................................................................................................... 15 Appendix 1: Blood pressure centiles for boys by age and height percentile ........................... 16 Appendix 2: Blood pressure centiles for girls by age and height percentile ............................ 17

Dr Andrew Lunn

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Not t ingham Children’s Hospit al Nottingham University Hospitals NHS Trust

1. Patient Pathways Initial Management of Newly Diagnosed HSP Diagnosis of HSP  Purpura, predominatly lower limbs and buttocks  Abdominal pain (75% cases)  Arthritis / arthralgia (66% cases)  Haematuria / proteinuria  Hypertension Exclude of other causes of purpuric rash (eg. Meningococcal septicaemia, DIC, ALL, TTP, NAI, other vasculitidies)  

Normal urinalysis AND Normotensive

NO

    

 

Any Haematuria or Proteinuria on dipstick AND / OR Hypertension (bp > 95th centile on 3 separate readings)*

 

FBC, Urea, electrolytes, creatinine, albumin Urine protein:creatinine ratio (uPCR)

Any indication for admission?  Hypertension  Oedema  Abnormal blood or urine test results  Severe joint pain  Severe abdo pain  GI haemorrhage  Neurological symptoms  Other acute complications eg.orchitis

Confirm diagnosis with registrar or consultant. Organise general paediatric review within 1 week Counsel re: indications for further medical review Provide urine containers for early morning urine specimen (EMU) Provide infoKID.org.uk web address for information on HSP

YES

Admit under general paediatrics Are any of the following present?  Hypertension  Urine Protein:creatinine ratio (uPCR) >100 mg/mmol creatinine  Macroscopic haematuria  Albumin < 30 g/dl  eGFR < 90ml/min/1.73m2 YES

Refer to Paediatric Nephrology Dr Andrew Lunn



See blood pressure centile charts in Appendices

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General Paediatric Review at 1 Week Following Diagnosis  History and examination  Urine dipstick  Blood pressure measurement

 

Complete GP follow up letter YES  Normal urinalysis and send urgently to GP (a AND template is available on NOTIS)  Normotensive Ensure patient/parents have infoKID.org.uk website address or print out infoKID HUS leaflet NO if parents have no computer access Macroscopic haematuria Urine protein ≥1+ → send urine prot:creat ratio (uPCR) BP >95th centile on three occasions Oedema

YES YES YES YES

NO NO NO NO

If NO to ALL of above   

General Paediatric follow up in one week. Print out GENERAL PAEDIATRIC PATHWAY and file in notes Ensure patient/parents have infoKID.org.uk website address or print out infoKID HUS leaflet if parents have no computer access

If YES to ANY of above      

FBC, PRP, Clotting, ASOT, ANA, dsDNA, ANCA, C3, C4 Renal USS Early morning urine for urine protein: creat ratio (uPCR) Ensure patient/parents have infoKID.org.uk website address or print out infoKID HUS leaflet if parents have no computer access Refer to paediatric nephrology on call consultant – for review within 1 week if above investigations abnormal or uPCR > 200 mg/mmol or uPCR > 100 mg/mmol and rising. General Paediatric follow-up pathway if investigations normal and uPCR does not show significant proteinuria.

Dr Andrew Lunn

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HSP Letter for GP if urinalysis/blood pressure normal at 1 week review Date:_____/_____/_____

Date of Diagnosis:_____/_____/_____

Dear Dr ___________________, RE:

____________________________ has been diagnosed with Henoch-Schönlein Pupura (HSP). The urinalysis was normal and the blood pressure was: ______/______ using a small adult / adult cuff. 95% centile blood pressure for height centile is _____/_____. All children with HSP require follow up screening for the development of HSP nephritis which will develop in up to 50% of patients, usually within the first 6 weeks, but sometimes up to 6 months after the initial episode. We would be grateful if you could perform ongoing clinical review according to the proforma below and refer to the general paediatrician on call (07713097061) if any signs of nephritis develop. Yours sincerely, 2 weeks post diagnosis (date):

Macroscopic or microscopic haematuria YES Urine protein ≥1+ YES th BP >95 centile on three occasions YES Oedema YES If YES to ANY of above refer to general paediatrician on call 07713097061 If No to all of above, review 1 month following diagnosis. 1 month post Macroscopic or microscopic haematuria YES diagnosis (date): Urine protein ≥1+ YES th BP >95 centile on three occasions YES Oedema YES If YES to ANY of above refer to general paediatrician on call 07713097061 If NO to all of above, arrange review for 3 months following diagnosis. 3 months post Macroscopic or microscopic haematuria YES diagnosis (date): Urine protein ≥1+ YES th BP >95 centile on three occasions YES Oedema YES If YES to ANY of above refer to general paediatrician on call 07713097061 If NO to all of above, arrange review for 6 months following diagnosis. 6 months post Macroscopic or microscopic haematuria YES diagnosis (date): Urine protein≥1+ YES BP >95th centile on three occasions YES Oedema YES If YES to ANY of above refer to general paediatrician on call 07713097061 If NO to all of above, no further follow up required Dr Andrew Lunn

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NO NO NO NO

NO NO NO NO

NO NO NO NO

NO NO NO NO

June 2016

Not t ingham Children’s Hospit al Nottingham University Hospitals NHS Trust

General Paediatric Pathway for children with HSP nephritis ie. All patients with microscopic haematuria with no proteinuria at one week post diagnosis Date of diagnosis:

95th centile for bp:

2 weeks post diagnosis (date):

Macroscopic haematuria YES NO Urine protein ≥1+ → send urine prot:creat ratio (uPCR) YES NO uPCR >200 mg/mmol or >100 mg/mmol and increasing BP >95th centile on three occasions YES NO Oedema YES NO If YES to any of above: 1) FBC, PRP, Clotting, ASOT, ANA, dsDNA, ANCA, C3, C4 2) Renal USS 3) Refer to paediatric nephrology – for review within 1 week If NO to all of above, arrange paediatric review for 1 month following diagnosis 1 month post Macroscopic haematuria YES NO diagnosis Urine protein ≥1+ → send urine prot:creat ratio (uPCR) YES NO (date): uPCR >200 mg/mmol or >100 mg/mmol and increasing BP >95th centile on three occasions YES NO Oedema YES NO If YES to any of above: 1) FBC, PRP, Clotting, ASOT, ANA, dsDNA, ANCA, C3, C4 2) Renal USS 3) Refer to paediatric nephrology – for review within 2 weeks If NO to all of above, arrange paediatric review for 2 months following diagnosis 2 months Macroscopic haematuria YES NO post Urine protein ≥1+ → send urine prot:creat ratio (uPCR) YES NO diagnosis uPCR >200 mg/mmol or >100 mg/mmol and increasing (date): BP >95th centile on three occasions YES NO Oedema YES NO If YES to any of above: 1) FBC, PRP, Clotting, ASOT, ANA, dsDNA, ANCA, C3, C4 2) Renal USS 3) Refer to paediatric nephrology – for review within 2 weeks If NO to all of above, arrange paediatric review for 3 months following diagnosis 3 months Macroscopic haematuria YES NO post Urine protein≥1+→ send urine prot:creat ratio (uPCR) YES NO diagnosis uPCR >200 mg/mmol or >100 mg/mmol and increasing (date): BP >95th centile on three occasions YES NO Oedema YES NO If YES to any of above: 1) FBC, PRP, Clotting, ASOT, ANA, dsDNA, ANCA, C3, C4 2) Renal USS 3) Refer to paediatric nephrology – for review within 1 month If NO to all of above, arrange paediatric review for 6 months following diagnosis Dr Andrew Lunn

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6 months post diagnosis (date):

Macroscopic haematuria YES NO Urine protein ≥ 1+ → send urine prot:creat ratio (uPCR) YES NO uPCR >200 mg/mmol or >100 mg/mmol and increasing BP >95th centile on three occasions YES NO Oedema YES NO If YES to any of above: 1) FBC, PRP, Clotting, ASOT, ANA, dsDNA, ANCA, C3, C4 2) Renal USS 3) Refer to paediatric nephrology – for review within 1 month If NO to all of above, arrange paediatric review for 12 months following diagnosis 12 months Macroscopic OR MICROSCOPIC haematuria YES NO post Urine protein ≥1+ → send urine prot:creat ratio (uPCR) YES NO diagnosis uPCR >50 mg/mmol (date): BP >95th centile on three occasions YES NO Oedema YES NO If YES to any of above: Continue to 1) FBC, PRP, Clotting, ASOT, ANA, dsDNA, ANCA, C3, C4 review 6 2) Renal USS monthly 3) Refer to paediatric nephrology – for routine review If NO to all of above for 2 consecutive clinic visits 6 months apart and If urinalysis negative for ≥6 months and Discharge – no further follow up never had a history of proteinuria ≥1+ If urinalysis negative for ≥6 months but history of proteinuria ≥1+

Dr Andrew Lunn

Discharge - arrange lifelong annual GP • review of BP • urine dipstick for proteinuria • All female patients should be counselled about the need to tell their GP and obstetrician about their history of HSP if they become pregnant.

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Pathway for patients referred back during GP assessment period: Macroscopic haematuria Urine protein ≥1+ → send urine prot:creat ratio uPCR >200 mg/mmol or >100 mg/mmol and increasing BP >95th centile on three occasions Oedema

YES NO YES NO YES NO YES NO

If NO to ALL of above (ie. Only microscopic haematuria without significant proteinuria)  General Paediatric follow up o within one week if less than 2 months following diagnosis o within two weeks if more than 2 months following diagnosis.  Print out general paediatric pathway (p6 and 7) and file in notes

If YES to ANY of above  Refer to paediatric nephrology on call consultant  Request Renal USS

Dr Andrew Lunn

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2. Background  

  

HSP is the most common vasculitis of childhood Incidence1  estimated 20.4 per 100,000 children in the UK  more common in Asian (24.0 per 100,000) and caucasian (17.8 per 100,000) children  less common in Afrocarribean children (6.2 per 100,000) Can affect any age but rare in infants and adults  Peak incidence between 4-7 years (70.3 per 100,000) Male to female ratio 1.2-1.8:1.0 More common in winter, autumn and spring than summer2

3. Clinical Features HSP is a small vessel vasculitis that can affect many different organs: Dominant Features  Rash  Abdominal pain ± nausea and vomiting  Arthritis/arthralgia  Nephritis

Uncommon Features  Intussusception  Haematemesis and malaena  Scrotal/testicular swelling  Pancreatitis/gall bladder involvement  Case reports of vasculitis involving lung, brain and heart

3.1. Skin  



Almost 100% children will develop a non-blanching rash, however it may develop late in some children presenting initially with other features. Petechiae, purpura, ecchymoses  Often starts as erythematous maculopapular or urticarial appearance  Extensor surfaces  Often symmetrical  Classically lower limbs and buttocks  Rash on face, trunk, arms in non-ambulant children Sensitivity 90% if localised to lower limbs and buttocks3  Sensitivity drops to 20% if more widespread (see other causes below)

3.2. Joints     

Arthritis or arthralgias, oligo-articular First symptom in 15% of patients Knee (38%) and ankle (85%) most common4 Usually within 1-4 weeks of diagnosis Transient or migratory – often improves within 2-3 days

3.3. Gastrointestinal   

50-75% of patients Precedes rash in 10% of cases4 Common  Nausea and vomiting  Colicky abdominal pain – often improves within 2-3 days  Gastrointestinal bleeding (8%)  Paralytic ileus

Dr Andrew Lunn

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



Uncommon  Intussusception  Pancreatitis  Protein losing enteropathy – hypoalbuminaemia and oedema without proteinuria Rare  Ischaemia and necrosis without intussusception  Gall bladder involvement  Intestinal perforation

3.4. Renal    

20-54% of patients (reports vary based on definition of microscopic haematuria) Isolated hypertension Spectrum of presentation5:  Isolated haematuria (micro or macroscopic) ± proteinuria  Nephritic or nephrotic syndrome A minority of patients will progress to end-stage renal failure (see below)

3.5. Other    

Orchitis (must consider testicular torsion as differential diagnosis) Intracranial (headaches, seizures, encephalopathy) Lung (case reports) Heart (case reports)

4. Diagnosis The diagnosis of HSP is made on clinical grounds. There is no objective laboratory test that will confirm a diagnosis. HSP should remain in the differential diagnosis of any patient presenting with abdominal pain with or without a skin rash. This is one of the reasons why urinalysis in children presenting with non-specific abdominal pain is so important. It is important to consider other causes of non-blanching rash:  Disseminated intravascular coagulation  Meningococcal sepsis  Other sepsis  Other vasculitides  Cutaneous small vessel vasculitis  Granulomatosis with polyangitis (formerly Wegener’s)  Systemic lupus erythematous (SLE)  Microscopic polyarteritis  Polyarteritis nodosa  Causes of thrombocytopaenia  Reduced production: leukaemic, aplastic anaemia  Increased destruction: Idiopathic thrombocytopaenic purpura, haemolytic uraemic syndrome  Hypersplenism

Dr Andrew Lunn

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5. Investigation The role of investigation is to exclude other diagnoses suspected on clinical grounds and to identify patients with renal involvement. All patients should have:  Blood pressure  Dipstick urinalysis If the presentation is classical, the child does not have features requiring admission and the blood pressure and urinalysis are normal, blood tests are not necessary. In patients where there is uncertainty about the diagnosis the following tests should be considered:  Full blood count to exclude thrombocytopenia and autoimmune cytopenias.  Electrolytes, urea and creatinine if:  the urinalysis demonstrates ++ proteinuria or more  hypertension  oliguria  or concerns about dehydration or fluid overload  Coagulation Studies if there are features aside from the rash consistent with sepsis or a bleeding disorder.  Autoantibodies should be discussed with paediatric registrar or consultant on call.  Blood culture if there is concern about sepsis (remember antibiotics should be given within one hour).  Renal tract ultrasound.  Early morning urine protein:creatinine ratio (P:Cr) can be performed to exclude orthostatic proteinuria and quantify pathological proteinuria in a child with a dipstick positive for protein.

6. Indications for Admission 

Any indication of renal involvement  Hypertension  Estimated GFR (eGFR) ,90 ml/min/1.73 m2 as reported with automated reporting system.  If automated reporting not available calculate eGFRwith Schwartz Formula:

eGFR = (height (cm) x K) / serum creatinine (µmol/l) K differs according to the method used to measure creatinine. In Nottingham: K = 36 for males 13 years of age or older K = 30 for all others

    

 Cases with glomerulonephritis, nephrotic syndrome or abnormal eGFR should be discussed with the nephrology registrar or consultant on call. Severe joint pain Severe abdominal pain Gastrointestinal haemorrhage Any neurological symptom Other atypical features should be discussed with the paediatric registrar or consultant on call.

Dr Andrew Lunn

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7. Management 7.1. Supportive  Hydration  Simple analgesia  Paracetamol  NSAIDs – if hypertension or evidence of renal involvement discuss with nephrologist  There is no evidence to suggest that use of NSAIDs for short periods increases the risk of GI bleeding in otherwise well children. 7.2. Steroids  There is no strong evidence supporting the routine use of prednisolone to reduce the long-term renal outcome in children with HSP (Evidence Level 1a).6, 10  In children with severe abdominal or joint pain not responding to simple analgesia, a course of prednisolone 1mg/kg daily for 1-2 weeks may be considered after discussion with treating consultant (Evidence Level 1b).7,8  Surgical review must be considered prior to the use of steroids in HSP abdominal pain. 7.3. Nephrology referral  Nephritic syndrome (haematuria, hypertension, oliguria, abnormal GFR)  Nephrotic syndrome (proteinuria >200 mg/mmol creatinine, hypoalbuminaemia