Henoch-Schonlein Purpura

1. 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)
2. 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
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
      8. Parainfluenza
   3. Vaccinations
      1. Typhoid
      2. Measles
      3. Cholera
      4. Yellow Fever
   4. Exposures
      1. Allergens in drugs and foods
      2. Cold exposure
      3. Insect Bites
      4. Nonsteroidal Anti-inflammatory (NSAIDs)
4. 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)
5. 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
6. 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
7. 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
8. Signs: Joint Involvement (70% of cases, especially in children)
   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
9. 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
10. Signs: Miscellaneous
    1. Most common associated findings in adults
       1. Hypertension
       2. Lower extremity edema
11. 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 glomeruloneprhitis (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
12. 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
       4. Hemolytic-Uremic Syndrome
13. 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]
14. 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
       3. RBC Casts may be present
    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
    7. Streptococcus Testing
       1. Rapid Strep Test (Throat Cultures positive in 10-30% of cases)
       2. ASO Titer (increased in 20-50% of cases)
15. Labs: Other
    1. Consider Blood Culture (in differential diagnosis for Purpura)
    2. Fecal Calprotectin
       1. Marker for gastrointestinal involvement
16. 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
17. Imaging
    1. Not routinely indicated
    2. Abdominal Ultrasound
       1. Indicated in suspected Intussusception in children
    3. Abdominal CTAbdomen
       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
18. 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. Nephrology Consultation
       2. Renal biopsy
       3. Children with mild to moderate renal disease
          1. Systemic Corticosteroids are no longer recommended (see below)
       4. Adults and children with moderate to severe disease
          1. High dose Corticosteroids
          2. Immunosuppressants (e.g. Cyclosporine, Mycophenolate, Dapsone, Rituximab)
          3. High dose IV Ig
          4. Plasmapheresis
19. Management: Systemic Corticosteroids
    1. Indications
       1. Children with severe extrarenal, refractory symptoms (e.g. Abdominal Pain, Joint Pain)
       2. Scrotal Swelling
       3. Children with renal involvement
          1. Previously recommended in mild-moderate cases
          2. As of 2013-2015, Corticosteroids (and cyclophosphamide) appear to have no benefit in non-severe disease
             1. Dudley (2013) Arch Dis Child 98(10): 756-63 [PubMed]
             2. Hahn (2015) Cochrane Database Syst Rev (8): CD005128 [PubMed]
    2. Dosing
       1. Prednisone 1-2 mg/kg orally daily for two weeks
20. 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
21. 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
22. 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
23. References
    1. Mace (2021) Crit Dec Emerg Med 35(2): 12-3
    2. Kraft (1998) Am Fam Physician 58(2): 405-408 [PubMed]
    3. Gedalia (2004) Curr Rheumatol Rep 6(3):195-202 [PubMed]
    4. Reamy (2009) Am Fam Physician 80(7): 697-704 [PubMed]
    5. Reamy (2020) Am Fam Physician 102(4): 229-33 [PubMed]
    6. Saulsbury (2007) Lancet 369(9566): 976-8 [PubMed]
    7. Saulsbury (2001) Curr Opin Rheumatol 13(1):35-40 [PubMed]