Henoch-Schonlein Purpura

1. Epidemiology
   1. Children and young adults
      1. Most common acute Vasculitis in children
      2. Peak Incidence at 5 year old
      3. Ages 2-11 years represent 75-90% of cases
      4. Milder case occur in children under age 2 years
   2. Occurs more often in boys (2:1)
   3. Incidence: 14 cases per 100,000
   4. Occurs most frequently in spring and fall
2. Pathophysiology
   1. Upper Respiratory Infection precedes in 60-75% cases
   2. Acute immune complex-mediated Leukocytoclastic Vasculitis
   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
3. Associated Conditions (preceding HSP)
   1. Bacterial Infections
      1. Group A Streptococcus (most common - may be responsible for 30% of cases)
      2. Bartonella Henselae
      3. Campylobacter enteritis
      4. Salmonella
      5. Shigella
      6. Methicillin-Resistant Staphylococcus aureus (MRSA)
      7. Mycoplasma
      8. Haemophilus parainfluenza
      9. Helicobacter Pylori
   2. Viral Infections
      1. Adenovirus
      2. Coxsachie Virus
      3. Epstein-Barr Virus (Mononucleosis)
      4. Hepatitis A Virus
      5. Hepatitis BVirus
      6. Parvovirus B19
      7. Varicella Zoster Virus
   3. Vaccinations
      1. Typhoid
      2. Measles
      3. Cholera
      4. Yellow Fever
   4. Environmental exposures
      1. Allergens in drugs and foods
      2. Cold exposure
      3. Insect Bites
4. 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
5. Signs: Rash (100% of cases)
   1. Timing
      1. Rash precedes other signs and symptoms of HSP
      2. First appears as erythematous Papules
      3. Palpable Purpura rash follows
   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. 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
      2. 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
6. Signs: Abdominal Pain (60-80% of cases)
   1. Diffuse, Colicky Abdominal Pain (may mimic Acute Abdomen)
   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
7. Signs: Joint Involvement (70% of cases)
   1. Arthritis precedes rash in 25% of cases
   2. Transient Arthritis with no permanent deformity
   3. Non-Migratory polyarthritis
      1. Ankles and knees most commonly affected
      2. Elbows, hands and feet may also be affected
8. Signs: Renal Disease (25-50% of cases)
   1. General
      1. Most serious complication of HSP
   2. Risk Factors
      1. Age over 10 years
      2. Persistent Purpura
      3. Severe Abdominal Pain
      4. Relapsing episodes
   3. Presentation
      1. Develops within 3 months of rash (typically within first month and rarely beyond 6 months)
      2. Hematuria most common presenting sign (also accompanied by red cell casts and Proteinuria)
9. Complications (more common in adults)
   1. Cardiopulmonary conditions
      1. Myocardial Infarction
      2. Pulmonary Hemorrhage
      3. Pleural Effusion
   2. Gastrointestinal conditions
      1. Intussusception (mural hematoma is lead point) in 5% of cases
      2. Gastrointestinal Bleeding
      3. Bowel infarction
   3. Neurologic conditions
      1. Seizures
      2. Mononeuropathies
   4. Renal disorders: Crescentic glomeruloneprhitis
      1. Renal Failure
      2. Hematuria
      3. Proteinuria
   5. Male genitourinary conditions
      1. Orchitis
      2. Testicular Torsion
10. Differential Diagnosis (based on predominant presenting symptom)
    1. Purpura
       1. Hypersensitivity Vasculitis
          1. Elevated Renal Function tests (BUN, Creatinine)
          2. Global organ involvement
       2. Meningococcal Meningitis or Septicemia
       3. Idiopathic Thrombocytopenic Purpura
       4. Child Abuse
       5. Bacterial Endocarditis
       6. Rheumatic Fever
       7. Rocky Mountain Spotted Fever
       8. Drug Reactions
       9. Polyarteritis Nodosa
       10. Leukemia
       11. Kawasaki Disease
    2. Arthritis
       1. Rheumatoid Arthritis
       2. Systemic Lupus Erythematosus
       3. Granulomatosis with Polyangiitis (previously known as Wegener's Granulomatosis)
    3. Abdominal Pain
       1. Acute Abdomen
       2. Familial Mediterranean Fever
       3. Inflammatory Bowel Disease
11. Diagnosis: International Consensus Conference
    1. Major criteria (required)
       1. Palpable Purpura in the absence of Thrombocytopenia
    2. Minor criteria (requires 1 of the following)
       1. Diffuse Acute Abdominal Pain
       2. Biopsy showing predominant IgA deposition
       3. Arthritis or Arthralgia involving any joint
       4. Renal involvement presenting as Proteinuria or Hematuria
12. Labs: Initial
    1. Complete Blood Count (CBC)
       1. Leukocytosis with Eosinophilia
       2. Platelets may be elevated
          1. Low Platelets suggest Thrombocytopenic Purpura
    2. Sedimentation rate (ESR) variably elevated
    3. Urinalysis: Nephritis evaluation (nephrology evaluation if positive)
       1. Most important lab in suspected HSP
       2. Hematuria or Proteinuria in up to 50% of patients (risk of ESRD in 1% of patients over subsequent months)
    4. Stool Guaiac
       1. Occult or gross blood may be present
    5. Renal Function tests (BUN, Creatinine)
       1. Obtain if positive urine for Hematuria or Proteinuria
       2. Elevation may suggest Hypersensitivity Vasculitis
    6. Coagulation Studies (PTT and INR)
       1. Normal in HSP
       2. Consider in differential diagnosis for Purpura
13. Labs: Other
    1. Consider ASO Titer
    2. Consider Blood Culture (in differential diagnosis for Purpura)
14. Labs: Histology
    1. Skin Biopsy
       1. Leukocytoclastic Vasculitis
    2. Renal Biopsy
       1. Glomerular crescents
       2. Indistinguishable from IgA Nephropathy
15. Imaging
    1. Not routinely indicated
    2. Abdominal Ultrasound or CT Abdomen
       1. Indicated for concurrent gastrointestinal symptoms suggestive of alternative diagnosis
    3. Barium Enema
       1. Indicated if Intussusception is suspected
16. Management
    1. Supportive care (Primary strategy)
       1. Hydration
       2. Relative rest
       3. Elevate legs (may reduce Purpura)
    2. Joint Pain
       1. NSAIDs (with caution)
          1. Risk of renal disease
          2. Risk of Gastrointestinal Bleeding
    3. Nephritis (Hematuria or Proteinuria)
       1. Nephrology Consultation
       2. Renal biopsy
       3. Children with mild to moderate renal disease
          1. Systemic Corticosteroids (see below)
       4. Adults and children with moderate to severe disease
          1. High dose Corticosteroids with immunosuppressants (e.g. Azathioprine, Cyclophosphamide) or
          2. High dose IV Ig
          3. Plasmapheresis
17. Management: Systemic Corticosteroids
    1. Indications
       1. Children with renal involvement
       2. Children with severe extrarenal symptoms (e.g. Abdominal Pain, Joint Pain)
       3. Scrotal swelling
    2. Dosing
       1. Prednisone 1-2 mg/kg orally daily for two weeks
18. Management: Hospitalization indicated
    1. Severe dehydration
    2. Intractable pain or Abdominal Pain requiring serial examination and observation
    3. Gastrointestinal Hemorrhage
19. Course
    1. Onset over days to weeks
    2. Duration: 4-6 weeks
    3. Recurrence in 50% of patients
20. Prognosis
    1. Excellent in general
       1. Resolves spontaneously in 94% of children
       2. Resolves spontaneously in 89% of adults
    2. Renal Disease develops in 5% (<1% develop ESRD)
       1. Although up to 50% will have Hematuria or Proteinuria
    3. Predictors of serious nephropathy or ESRD
       1. Bloody stools
       2. Rash persistence
       3. Nephritis-Nephrotic Signs
          1. Progresses to ESRD within 10 years in 50% of cases
       4. Renal Biopsy with glomerular crescents
          1. Progresses to ESRD in 100% of cases
21. Monitoring: Renal involvement screening
    1. Blood Pressure initially and at each subsequent visit following the HSP diagnosis
    2. If first Urinalysis is normal (or isolated Hematuria)
       1. Monthly Urinalysis for 6 months after HSP diagnosis
    3. If any Urinalysis suggests nephritis (Hematuria and Proteinuria)
       1. Serum Creatinine
       2. Blood Urea Nitrogen
22. References
    1. Kraft (1998) Am Fam Physician 58(2): 405-408 [PubMed]
    2. Gedalia (2004) Curr Rheumatol Rep 6(3):195-202 [PubMed]
    3. Reamy (2009) Am Fam Physician 80(7): 697-704 [PubMed]
    4. Saulsbury (2007) Lancet 369(9566): 976-8 [PubMed]
    5. Saulsbury (2001) Curr Opin Rheumatol 13(1):35-40 [PubMed]