Henoch–Schonlein Purpura

Ig A Vasculitis
Dr. Nisha Singh
Moderator: Dr Sumidha Mittal
 HSP/ IgA vasculitis
• Small vessel vasculitis with IgA-dominant
immune deposits that typically involves the
skin, gut and glomeruli, and is associated with
arthralgia and/or arthritis
European League Against Rheumatism ( EULAR)/Paediatric Rheumatology
International Trials Organisation (PRINTO)/Paediatric Rheumatology
European Society (PRES)
 EPIDEMIOLOGY
• Incidence- 3 to 26.7 per 100, 000
• Age- Few months to late adulthood, More
common in 4-6 years
• M:F=2:1
• The clinical features are often atypical at
extremes of age
• More severe in adults
 PRECIPITATING ORGANISM
• Group A b hemolytic streptococcus-
M.C.
• Hepatitis A and B
• CMV, HIV, Adenovirus,HSV
• Mycoplasma, H.pylori
• Toxacara canis, human parvovirus B19,
Varicella, and scarlet fever
• Vaccinations- MMR, pneumococcal,
influenza, meningococcal and hepatitis
B
 CLINICAL FEATURES
• Many cases follow an upper respiratory tract
infection
 Skin
• Palpable purpura-
– Lower limbs and buttocks.
– Symmetrically distributed
– Extensor dependent surfaces
– May involve the arms, face and ears
– Usually spares the trunk.
• Occur in crops for several months
• May be preceded by urticarial or erythematous, maculo-
papular lesions that usually disappears within 24 hours
• Rash may appear as bullae, necrotic lesions or deep
bruising
• Severe bullous lesions -2%
• Subcutaneous edema over the dorsa of the
hands and feet and around the eyes,
forehead, scalp, and scrotum may occur early
in the disease, particularly in the very young
child.
 Gastrointestinal Involvement
• 50–75% of cases
• GI manifestations may precede purpura by up to 2
weeks in 20% of children
• Colicky abdominal pain- M.C., Periumbilical and/or
epigastric pain
• Vomiting
• GI haemorrhage
– Positive stools for occult blood/overt bleeding
– Due to oedema and haemorrhage of the bowel wall due to
vasculitis
• Gastrointestinal mucosal ulceration and purpura
• Gastritis
• Duodenitis
• Intussusception - rare complication
– Either ileo-ileal, or ileo- colic
• Protein losing enteropathy
• Pancreatitis
• Hydrops of the gall bladder
 Joints
• Arthritis or arthralgia- presenting symptom in
15–25% of cases
• Up to 82% of patients have a degree of joint
involvement during the illness
• Large joints of the lower limbs including
knees, ankles, feet and hips
• Upper limbs may be affected too
 Renal
• In 12–92%
• Develops within four weeks - 75– 80% and
– Within three months - 97–100%
• Haematuria
• Proteinuria
• Nephrotic syndrome/ Nephritis
• Renal impairment
• Hypertension.
 Neurological
• Rare
• Nonspecific headache followed by subtle
encephalopathy with minimal changes in
mental status, such as labile mood, apathy
and hyperactivity
• Seizures
• Subdural haematoma, subarachnoid
haemorrhage, cerebellar haemorrhage,
intraparenchymal bleeding and infarction
 Pulmonary
• Rare
• Diffuse alveolar haemorrhage- M.C.
• Interstitial pneumonia
• Interstitial fibrosis
 Urological
• Orchitis -24%
• Genital swelling may also be due to more
generalised oedema secondary to
hypoalbuminaemia from renal or
gastrointestinal involvement
 PATHOLOGY
• Skin Biopsy - Leucocytoclastic Vasculitis with
perinuclear infiltration of polymorphs and
mononuclear cells.
• IgA is found in most purpuric lesions and can
also be found in non-affected areas
• Renal Biopsy
• The renal lesion of HSP nephritis- indistinguishable
from that of IgA nephropathy
• Focal and segmental proliferative
glomerulonephritis.
• The proliferation of extracapillary cells may result
in crescent formation.
• IF reveals mesangial IgA with IgG, C3 and fibrin.
• It is the non-renal clinical features that
differentiate IgA nephropathy from HSPN.
 INVESTIGATIONS
• No specific test
• Anemia, Leukocytosis, Increased ESR
• Thrombocytosis- Severe disease
• Abdominal USG – to exclude intussception
• IgA is elevated in 50-70%; however there is no
correlation with disease severity.
• C3,C4 maybe low
• Site of infection- blood cultures, swabs, urine C/S
and CXR
• Evidence of recent streptococcal infection-
Raised ASO and anti-DNAse B titres
• Viral investigations (serology and throat swabs)

• Skin Biopsy
• Renal Workup and Biopsy
Skin Biopsy- SHARE GUIDELINES-
European consensus based recommendations
• Skin biopsy should include specific immunofluorescence
staining for IgA
• Leucocytoclastic Vasculitis
• Skin biopsy-
– not required for typical lesions
– for atypical rash (such as extensive lesions or diffusely distributed
lesions) to exclude alternative diagnoses.
– should be of the most recent lesions.
– if taken in the centre of the necrotic lesion, IgA deposition may be
falsely negative due to the presence of proteolytic enzymes
– absence of IgA staining does not exclude the diagnosis of IgAV.
– is also important to exclude other forms of vasculitis such as
ANCA-associated vasculitis, particularly in older children

(SHARE: Single Hub and Access point for paediatric Rheumatology in

Europe)
 Renal Workup - SHARE Guidelines-
European consensus-based recommendations

• Renal involvement should be investigated using eGFR

and urinalysis (haematuria and UP:UC ratio or UA:UC
ratio)
• A paediatric nephrologist should be consulted -
moderate proteinuria and/or impaired GFR
– Moderate proteinuria: UP:UC ratio 100-250 mg/mmol in
an early morning urine sample
– Impaired GFR: <80 ml/min/1.73 m2

• BP and urinalysis- need to be monitored for at least 6-

12 months even if the initial BP and urinalysis are
normal.
 Renal Workup - SHARE Guidelines-
European consensus-based recommendations
• A renal biopsy should be performed if:
– Severe proteinuria (>250 mg/mmol for at least 4
weeks; although shorter duration of severe proteinuria
is also a relative indication) or
– Persistent moderate (100-250 mg/mmol) proteinuria or
– Impaired GFR
– AKI with worsening renal function as part of RPGN
– Patients who are nephrotic (e.g. heavy proteinuria,
hypoalbuminaemia and oedema) or nephritic (e.g.
impaired eGFR, hypertension, haematuria/proteinuria)
at any time point.
 DIFFERENTIAL DIAGNOSIS
In the event of an atypical picture
• Microscopic Polyangitis (MPA), Granulomatous
Polyangitis ( GPA) and Isolated cutaneous
Leucocytclastic vasculitis - ANCA
• SLE - ANA
• Septicemia
• FMF
• ITP
• PSGN -
• Hypersensitivity Vasculitis
 TREATMENT
• Natural history- resolution of all symptoms
except renal disease

• Corticosteroids
• Immunosuppresants : AZT, MMF, CYC,
Ciclosporin
 SHARE Guidelines-Use of analgesia
• Adequate analgesia should be prescribed for
IgAV -associated arthropathy
• NSAIDs are not C/I if renal function is normal
• Adequate analgesia should be prescribed for
IgAV -associated abdominal pain
• Use of NSAID is relatively C/I in the presence
of active gastrointestinal bleeding
 Use of Corticosteroids
• Indications:
• Orchitis, Cerebral Vasculitis, Pulmonary haemorrhage
• Other severe organ- or life-threatening vasculitis
manifestations
• Can be considered: Severe abdominal pain and/or
rectal bleeding
• Dose of prednisolone : 1-2 mg/kg/day
• If CS are indicated, pulsed IV Methylprednisolone (e.g.
10-30 mg/kg with a maximum of 1 g/ day on 3
consecutive days) may be considered for severe cases
• Prophylactic CS treatment to prevent the
development of IgAV-associated nephritis is not
indicated
 IgA V Nephritis

• When starting treatment, paediatric

nephrologist should be consulted.
• ACE inhibitors- to prevent/limit secondary
glomerular injury for patients with
persistent proteinuria
• Mild nephritis:
• Oral prednisolone- 1st line
• AZA, MMF and/or pulsed MP- 2nd-line
treatment following renal biopsy
• Moderate IgAV nephritis:
• Oral prednisolone and/or pulsed MP- 1st
line
• AZA, MMF or IV Cyclophosphamide- 1st or
2nd line
• Cyclosporin or Oral Cyclophosphamide-
not routinely recommended
• Severe IgAV nephritis
• Pulsed MP and/or oral prednisolone with IV
Cyclophosphamide to induce remission
• Lower doses of Corticosteroid + Azathioprine
or Mycophenolate Mofetil as maintenance
treatment
 Gastrointestinal disease
• Recently published prospective study- Prednisolone 1
mg/kg daily for 2 weeks with subsequent weaning over
2 weeks
• Effective in reducing the intensity of abdominal pain
and the duration by a mean of 1.2 days
• Severe GI haemorrhage- High dose
Methylprednisolone
• Occasionally chronic abdominal pain- Methotrexate
• The efficacy of corticosteroids to prevent complications
such as abdominal pain is still debated
 Joint involvement
• Managed with NSAIDs
• Severe cases- Steroids
 Skin involvement
• Rarely requires specific treatment
• Bullous lesions- Respond to steroids
• Dapsone- Steroid sparing agent, particularly
for skin
• Combination of aspirin and colchicine- for
chronic skin and joint disease
• MMF- Recurrent skin, articular, GI symptoms
as well as nephrotic-range proteinuria in
children who failed to respond to systemic
steroid therapy
 PROGNOSIS
• Self-limiting
• 2/3rd of children, HSP runs its entire course within 4 weeks of
onset.
• Younger children have a shorter course and fewer recurrences than
do older patients
• 33% have recurrence -generally within four 4 months of resolution
of the original symptoms-each episode usually being similar but
briefer and milder than the preceding one.
• May occur as late as 2 years after onset
• Patients with renal disease were more likely to have recurrences.
• Fewer than 1% of patients with HSP develop persistent renal
disease
• Fewer than 0.1% develop serious renal disease
• Poor prognosis:
– Nephrotic syndrome
– Renal impairment
– Hypertension
– Decreased Factor XIII at presentation
THANK YOU