II. Epidemiology

  1. Incidence
    1. Children: 3 to 26 (mean 14) in 100,000
    2. Adults: 0.8 to 1.8 in 100,000
  2. Age
    1. Children aged 2-11 years represent 75-90% of cases
      1. HSP is the most common acute Vasculitis in children
      2. Peak Incidence at 5 year old
      3. Milder case occur in children under age 2 years
    2. Adults
      1. Affects middle aged adults (32 to 50 years old)
  3. Gender
    1. Occurs more often in boys (2:1)
  4. Timing
    1. Occurs most frequently in spring and winter in children (no seasonality in adults)

III. Pathophysiology

  1. Preceding illness is commonly present
    1. Upper Respiratory Infection precedes HSP in 60-75% cases
    2. Fever, gastrointestinal symptoms and Joint Pain may precede rash by 1-2 weeks
  2. Acute immune complex-mediated, small vessel Leukocytoclastic Vasculitis
    1. Autoantibodies against endothelial cells
    2. IgA immune complexes form and deposit in skin, joints, Kidneys and Gastrointestinal Tract
    3. Results in localized inflammatory reactions with small vessel inflammation and necrosis
  3. Idiopathic inflammatory IgA Hypersensitivity
    1. Petechiae and Purpura
      1. IgA immune complexes deposit in small vessel walls of skin
    2. Gastrointestinal Hemorrhage
      1. IgA immune complexes deposit in small vessel walls of intestinal wall
    3. Crescentic Glomerulonephritis
      1. IgA immune complexes deposit in small vessel walls of renal mesangium

V. Course

  1. Onset over days to weeks (following Upper Respiratory Infection in most cases)
  2. Duration: 4-6 weeks
  3. Symptoms may recurr in up to one third of patients (ultimately resolves within 4 to 6 months)

VI. Symptoms: Classic Triad (beyond rash, triad is not uniformly present)

  1. Palpable Purpura rash on lower extremities (gravity dependent regions)
  2. Abdominal Pain or renal involvement (Nephritis)
  3. Arthritis or Arthralgias

VII. Signs: Rash (100% of cases)

  1. Timing
    1. Rash precedes other signs and symptoms of HSP
    2. First appears as erythematous Papules
    3. Crops of palpable Purpura and Petechiae follow
    4. Purpura may enlarge to Ecchymoses, transition from purple to rust colored, and fade over 10 days
  2. Distribution
    1. Gravity and pressure dependent
    2. Typically appears on extensor surfaces of lower extremities, belt line and buttocks
    3. Can involve face and trunk
  3. Characteristics: Petechiae or palpable Purpura (primary lesion type)
    1. Diameter 1-10 mm Petechiae or Purpura
    2. Non-pruritic, non-blanching hemorrhagic lesions (palpable Purpura and Petechiae)
      1. Initially they may blanch on pressure; later they do not
      2. Lesions may become hemorrhagic or necrotic
    3. Transition from purple to rust-colored and then fade over a 10 day period
  4. Characteristics: Other associated lesions
    1. Urticarial wheels
    2. Erythematous Macules
    3. Erythematous Papules
    4. Target lesions
      1. May appear similar to Erythema Multiforme

VIII. Signs: Abdominal Pain (60-80% of cases, especially in children)

  1. Diffuse, Colicky Abdominal Pain (may mimic Acute Abdomen) typically lasting <24 hours
  2. Abdominal Pain onset typically follows rash
  3. Stools may show occult or gross blood
  4. Hematuria
  5. Vomiting or Hematemesis (rarely severe) in up to 30% of patients
  6. Intussusception occurs in 2-5% of HSP cases

IX. Signs: Joint Involvement (70% of children; 25% of adults)

  1. Arthritis precedes rash in 25% of cases
  2. Transient Arthritis with no permanent deformity or damage
  3. Non-Migratory polyarthritis
    1. Ankles and knees most commonly affected (associated with limp)
    2. Elbows, hands and feet may also be affected
      1. However, frequency decreases with ascending location (knees, more than hips, more than upper extremities)

X. Signs: Renal Disease (25-50% of cases)

  1. General
    1. Most serious complication of HSP
  2. Risk Factors
    1. Age over 10 years old and adults
    2. Persistent Purpura
    3. Gastrointestinal Bleeding
    4. Severe Abdominal Pain
    5. Relapsing episodes
    6. Male gender
  3. Presentation
    1. Develops within 3 months of rash (typically within first month and rarely beyond 6 months)
    2. Hematuria is the most common presenting sign (most commonly asymptomatic Microscopic Hematuria)
    3. Red cell casts and Proteinuria may also be present
    4. Persistent Proteinuria increases risk of progressive Glomerulonephritis
    5. Risk of ESRD in 1% of patients over subsequent months

XI. Signs: Miscellaneous

  1. Most common associated findings in adults
    1. Hypertension
    2. Lower Extremity Edema

XII. Complications (more common in adults)

  1. Most common complications
    1. Gastrointestinal Bleeding
    2. Glomerulonephritis
  2. Cardiopulmonary conditions
    1. Hypertension
    2. Myocardial Infarction
    3. Pulmonary Hemorrhage
    4. Pleural Effusion
  3. Gastrointestinal conditions
    1. Intussusception (mural Hematoma is lead point) in 2-5% of cases
    2. Gastrointestinal Bleeding
    3. Bowel infarction
    4. Pancreatitis
    5. Gallbladder Hydrops
    6. Protein Losing Enteropathy
  4. Neurologic conditions
    1. Headaches
    2. Behavior Changes
    3. Seizures
    4. Mononeuropathy
    5. Intracranial Hemorrhage
  5. Renal disorders (2-20%)
    1. Hematuria
    2. Proteinuria (Nephrotic Syndrome may be present)
    3. Crescentic Glomerulonephritis (HSP Nephritis)
    4. Renal Failure (end-stage renal disease)
      1. Occurs in 1-7% of with NSP Nephritis
  6. Male genitourinary conditions (Testicular Pain in 30% of boys with IgA Vasculitis)
    1. Orchitis
    2. Testicular Torsion

XIV. Diagnosis: EULAR/PReS Criteria

  1. Background
    1. Replaces ACR 1990 criteria
    2. Lab tests are not required to make diagnosis (i.e. Purpura AND Arthralgias or Abdominal Pain)
  2. Major criteria (required)
    1. Purpura or Petechiae affecting the lower extremities
  3. Minor criteria (requires 1 of the following)
    1. Acute Arthritis or Arthralgia involving any joint
    2. Diffuse Acute Abdominal Pain
    3. Biopsy showing Leukocytoclastic Vasculitis or proliferative Glomerulonephritis with IgA deposition
    4. Renal involvement presenting as Proteinuria or Hematuria
  4. Efficacy
    1. Child: 100% Test Sensitivity and 87% Test Specificity
    2. Adult: 99% Test Sensitivity and 86% Test Specificity
  5. References
    1. Ozen (2010) Ann Rheum Dis 69(5): 798-806 [PubMed]

XV. Labs: Initial

  1. First-Line Testing
    1. Urinalysis: Nephritis evaluation (nephrology evaluation if positive)
      1. Most important lab in suspected HSP
      2. Hematuria or Proteinuria in up to 50% of patients
      3. RBC Casts may be present
    2. Streptococcus Testing
      1. Rapid Strep Test (Throat Cultures positive in 10-30% of cases)
      2. ASO Titer (increased in 20-50% of cases)
  2. Second-Line Testing (if Urinalysis positive for Proteinuria)
    1. Renal Function tests (BUN, Creatinine)
      1. Obtain if positive urine for Hematuria or Proteinuria
      2. Elevation may suggest Hypersensitivity Vasculitis
    2. Complete Blood Count (CBC)
      1. Leukocytosis with Eosinophilia
      2. Platelets may be elevated
        1. Low Platelets suggest Thrombocytopenic Purpura
  3. Other labs to consider
    1. Acute phase reactants (e.g. CRP, ESR)
    2. Sedimentation rate (ESR) variably elevated
    3. Coagulation Studies (PTT and INR)
      1. Normal in HSP
        1. Consider in differential diagnosis for Purpura
      2. Stool Guaiac
        1. Occult or gross blood may be present
    4. Blood Culture
      1. Bacteremia in differential diagnosis for Purpura
    5. Fecal Calprotectin
      1. Marker for gastrointestinal involvement

XVI. Labs: Histology

  1. Skin Biopsy (indicated in unclear diagnosis)
    1. Leukocytoclastic Vasculitis with IgA vascular deposits
  2. Renal Biopsy (indicated in progressive Glomerulonephritis)
    1. Proliferative Glomerulonephritis with predominant IgA Deposition
    2. Glomerular crescents
    3. Indistinguishable from IgA Nephropathy

XVII. Imaging

  1. Not routinely indicated
  2. Abdominal Ultrasound
    1. Indicated in suspected Intussusception in Children
  3. Abdominal CT Abdomen
    1. Indicated for concurrent gastrointestinal symptoms suggestive of alternative diagnosis (esp. adults)
  4. Endoscopy
    1. May be indicated in gastrointestinal Hemorrhage
  5. Bronchoscopy
    1. Indicated in Pulmonary Hemorrhage

XVIII. Management: General

  1. Supportive care (Primary strategy)
    1. Hydration
    2. Relative rest
    3. Elevate legs (may reduce Purpura)
  2. Rash
    1. No specific management
  3. Joint Pain
    1. Acetaminophen
    2. NSAIDs (with caution and avoid in renal involvement)
      1. Risk of renal disease
      2. Risk of Gastrointestinal Bleeding
  4. Nephritis (Hematuria or Proteinuria)
    1. Mild to Moderate Disease
      1. Indications for conservative management with no treatment
        1. Hematuria alone
        2. Urine Protein to Creatinine Ratio <0.5
        3. Normotensive
        4. Normal eGFR
      2. Indications for consideration of ACE Inhibitor
        1. Urine Protein to Creatinine Ratio 0.5 to 1.5 persists >2 to 4 weeks
        2. Borderline Hypertension
      3. Corticosteroids are no longer recommended for children with mild to moderate renal involvement
        1. As of 2013-2015, Corticosteroids (and Cyclophosphamide) appear to have no benefit in non-severe disease
        2. Dudley (2013) Arch Dis Child 98(10): 756-63 [PubMed]
        3. Hahn (2015) Cochrane Database Syst Rev (8): CD005128 [PubMed]
    2. Severe Disease
      1. Indications
        1. Urine Protein to Creatinine Ratio
        2. Hypertension
      2. Management
        1. Children with mild to moderate renal disease
          1. Systemic Corticosteroids are no longer recommended (see below)
        2. Adults and children with moderate to severe disease
          1. High dose Corticosteroids
            1. Methylprednisolone IV for decreased eGFR or crescentic Glomerulonephritis
            2. Prednisone for 6 months if significant Proteinuria despite 3 months on ACE Inhibitor
          2. Immunosuppressants (e.g. Cyclosporine, Mycophenolate, Dapsone, Rituximab)
          3. High dose IV Ig
          4. Plasmapheresis
        3. Nephrology Consultation
          1. Consideration for Renal biopsy

XIX. Management: Systemic Corticosteroids

  1. Indications: Symptomatic management
    1. Children with severe extrarenal, refractory symptoms (e.g. Abdominal Pain, Joint Pain)
    2. Scrotal Swelling
  2. Dosing
    1. Prednisone 1 mg/kg (up to 2 mg/kg) orally daily for two weeks

XX. Management: Hospitalization Indications

  1. Severe Dehydration or unable to take oral fluids (e.g. Abdominal Pain, Vomiting)
  2. Intractable pain or Abdominal Pain requiring serial examination and observation
  3. Gastrointestinal Hemorrhage
  4. Inability to ambulate

XXI. Prognosis

  1. Excellent in general
    1. Resolves spontaneously in 94% of children
    2. Resolves spontaneously in 89% of adults
      1. However cases are more severe in adults with worse outcomes than with children
  2. Recurrence
    1. Relapse occurs in up to 30% of children, up to 50% of adults
    2. Relapse may be delayed as long as 10 years after prior episode
    3. Relapse is most common in adults with gastrointestinal symptoms
    4. Calvo-Rio (2016) Medicine 95(28):e4217 [PubMed]
  3. Renal Disease
    1. Up to 50% will have Hematuria or Proteinuria
    2. Longterm renal disease develops in 5% of cases overall
      1. Child: <1% develop End Stage Renal Disease
      2. Adult: Up to 11% develop End Stage Renal Disease
        1. Audemard-Verger (2017) Arthritis Rheumatol 69(9):1862-70 [PubMed]
  4. Predictors of serious nephropathy or ESRD
    1. Early onset of renal findings
      1. Abnormal Urinalysis on the day of HSP diagnosis (children)
      2. Renal involvement occurs within 6 weeks in 91% and 6 months in 97%
        1. Narchi (2005) Arch Dis Child 90(9):916-20 [PubMed]
      3. Low likelihood of chronic renal complications if no renal involvement by 6 months
      4. Nephritis at HSP diagnosis confers longterm Hypertension and urine abnormalities risks
      5. Nephrotic Syndrome at HSP diagnosis (lasting >3 months) confers longterm renal disease risk
    2. Bloody stools
    3. Rash persistence
    4. Renal Biopsy with glomerular crescents
      1. Progresses to ESRD in 100% of cases

XXII. Monitoring

  1. Renal involvement screening
    1. Blood Pressure initially and at each subsequent visit following the HSP diagnosis
    2. Urinalysis in all patients at time of HSP diagnosis and periodic screening over subsequent 6 months
      1. Obtain monthly Urinalysis for 6 months if initial Urinalysis with Hematuria or Proteinuria
    3. If any Urinalysis suggests nephritis (Hematuria and Proteinuria)
      1. Serum Creatinine
      2. Blood Urea Nitrogen
  2. Cancer screening in adults with HSP over age 60 years
    1. Lung Cancer
    2. Renal Cancer
    3. Prostate Cancer

Images: Related links to external sites (from Bing)

Related Studies