Henoch-Schonlein Purpura
Introduction And Epidemiology
- Immune complex small vessel vasculitis.
- Nomenclature updated to Immunoglobulin A vasculitis.
- Characterized by Immunoglobulin A dominant immune deposits affecting small vessels, including arterioles, capillaries, and venules.
- Represents most common vasculitis in pediatric population.
- Estimated annual incidence ranges from 14 to 20 per 100,000 children.
- Affects males more frequently than females, with ratio of 1.2 to 1.8:1.
- Peak age of onset ranges between 3 and 10 years, with median age of 5 years.
- Distinct seasonal variation observed. Higher frequency during winter and spring.
Etiology And Pathogenesis
- Exact etiology remains elusive.
- Frequently preceded by documented upper respiratory tract infection by 1 to 3 weeks.
- Infectious triggers include
- Group A beta-hemolytic Streptococcus,
- Staphylococcus aureus,
- Mycoplasma,
- adenovirus,
- varicella,
- rubella,
- rubeola,
- Epstein-Barr virus,
- hepatitis viruses, and
- parvovirus B19.
- Environmental triggers include vaccinations (typhoid, measles, cholera) and allergen exposure (drugs, food, cold exposure, insect bites).
- Genetic predisposition linked to specific alleles, including Hla-b34 and Hla-drb1*01 (associated with nephritis risk).
- Immunoglobulin A1 molecule possesses hinge region with glycan chains containing beta-1,3-linked galactose.
- Pathologic state features reduced galactosylation of these O-glycan chains.
- Results in production of abnormally glycosylated, polymeric galactose-deficient Immunoglobulin A1.
- Galactose-deficient molecules recognized by anti-glycan Immunoglobulin A1 or Immunoglobulin G antibodies.
- Forms circulating immune complexes.
- Deposition occurs in walls of small arteries across skin, gastrointestinal tract, joints, and kidneys.
- Alternative or lectin complement pathway activation initiates inflammatory cascade.
- Infiltration of neutrophils and deposition of nuclear fragments leads to leukocytoclastic vasculitis.
- Gravity-dependent deposition explains distinct rash distribution in ambulatory patients.
Clinical Manifestations
- Multisystem disorder. Acute onset frequently associated with non-specific constitutional signs like fever and malaise.
Cutaneous Features
- Present in almost 100% of cases. Often first sign of disease.
- Palpable purpura serves as disease hallmark.
- Lesions evolve from pink macules or urticarial wheals to petechiae, raised purpura, or larger ecchymoses.
- Symmetrical distribution. Predilection for gravity-dependent areas and pressure points, primarily lower extremities and buttocks.
- Subcutaneous edema localizes to dorsum of hands, feet, periorbital area, lips, scalp, and scrotum.
Musculoskeletal Features
- Occurs in up to 75% of children. Joint involvement may precede rash.
- Self-limited, oligoarticular, non-migratory, non-destructive arthritis or arthralgia.
- Predominantly affects large joints, notably knees and ankles.
- Marked by periarticular swelling and tenderness rather than massive joint effusion.
Gastrointestinal Features
- Present in up to 80% of children. Highly disabling.
- Intermittent, colicky, periumbilical abdominal pain.
- Associated with vomiting, diarrhea, paralytic ileus, and melena.
- Severe complications include intussusception (frequently ileoileal), mesenteric ischemia, intestinal perforation, and pancreatitis.
Renal Features
- Manifests in up to 50% of cases. Major driver of long-term morbidity and mortality.
- Presentations range from isolated microscopic hematuria to proteinuria, frank nephritis, nephrotic syndrome, hypertension, and acute or chronic renal failure.
- Progression to end-stage renal disease remains uncommon in pediatric population.
Neurologic Features
- Uncommon. Manifestations driven by hypertension (posterior reversible encephalopathy syndrome) or central nervous system vasculitis.
- Symptoms include headaches, seizures, behavioral changes, depressed consciousness, and peripheral neuropathies.
Diagnostic Criteria
- Diagnosis remains primarily clinical. Endorsed by European League Against Rheumatism, Pediatric Rheumatology International Trials Organization, and Pediatric Rheumatology European Society.
| Criterion Category | Specific Findings |
|---|---|
| Mandatory Criterion | Palpable purpura with lower limb predominance. Absence of coagulopathy or thrombocytopenia. |
| Additional Criteria (Minimum one required) | Diffuse abdominal pain. Acute, diffuse, colicky character. |
| Arthritis or arthralgia. | |
| Biopsy of affected tissue demonstrating predominant Immunoglobulin A deposition. | |
| Renal involvement. Any degree of hematuria or proteinuria. |
Differential Diagnosis
| Disease Category | Alternative Diagnoses |
|---|---|
| Small Vessel Vasculitides | Hypersensitivity vasculitis, hypocomplementemic urticarial vasculitis, cryoglobulinemic vasculitis, microscopic polyangiitis, granulomatosis with polyangiitis. |
| Connective Tissue Diseases | Systemic lupus erythematosus, juvenile dermatomyositis, systemic onset juvenile idiopathic arthritis. |
| Hematologic Disorders | Immune thrombocytopenic purpura, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, disseminated intravascular coagulation. |
| Infections | Septicemia, meningococcemia, acute poststreptococcal glomerulonephritis. |
| Pediatric Mimics | Infantile acute hemorrhagic edema. Affects infants under two years. Tender edema and large ecchymosis on face and extremities. Trunk spared. Normal platelet count. |
Investigations
- Diagnosis primarily clinical. Laboratory tests exclude mimics and assess organ involvement.
- Complete blood count. Mild anemia with leukocytosis. Normal or elevated platelet count excludes immune thrombocytopenic purpura and leukemia.
- Acute phase reactants. Elevated erythrocyte sedimentation rate and C-reactive protein.
- Renal function tests. Elevated blood urea nitrogen and creatinine denote renal impairment. Low serum albumin indicates renal or intestinal protein loss.
- Urinalysis. Crucial for detecting hematuria, proteinuria, and red blood cell casts.
- Stool examination. Occult blood frequently positive.
- Immunologic tests. Normal complement levels. Serum Immunoglobulin A frequently elevated.
- Imaging. Abdominal ultrasound evaluates bowel wall edema and identifies potential intussusception. Plain radiograph demonstrates dilated gut loops.
- Tissue biopsy. Skin or renal biopsy indicated for atypical or severe cases. Demonstrates leukocytoclastic vasculitis with predominant Immunoglobulin A deposition on direct immunofluorescence.
Management
- Multidisciplinary approach required. Focuses on hydration, nutrition, and tailored pharmacotherapy.
| Disease Severity | Clinical Presentation | Management Strategy |
|---|---|---|
| Mild | Isolated rash, mild arthralgia, normal renal parameters. | Supportive care. Rest, adequate hydration. Acetaminophen or nonsteroidal anti-inflammatory drugs for pain relief. |
| Moderate | Disabling abdominal pain, significant arthritis, early renal involvement. | Oral prednisolone (one to two milligrams per kilogram per day) for one to two weeks, followed by taper. Reduces tissue edema, arthritis, and abdominal pain. Decreases intussusception rate. |
| Severe | Nephrotic range proteinuria, progressive renal deterioration, pulmonary hemorrhage, gastrointestinal bleed. | High-dose intravenous methylprednisolone. Adjunct immunosuppressants including azathioprine, cyclophosphamide, cyclosporine, or mycophenolate mofetil. |
| Refractory | End-stage renal disease, rapidly progressive glomerulonephritis. | Intravenous immunoglobulin, plasmapheresis, or renal transplantation. |
Pharmacologic Nuances
- Corticosteroids relieve associated gastrointestinal symptoms and arthralgia.
- Corticosteroids do not prevent onset of nephritis, prevent recurrence of abdominal symptoms, or shorten overall disease duration.
- Persistent proteinuria mandates treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers.
Prognosis And Complications
- Overall prognosis remains excellent. Disease typically runs self-limited course over four weeks.
- Recurrence observed in fifteen to sixty percent of patients, usually within four to six months.
- Subsequent relapses feature milder symptomatology.
- Short-term morbidity driven by severe gastrointestinal involvement, including intussusception and intestinal perforation.
- Long-term prognosis dictated by renal involvement severity.
- Chronic renal disease develops in one to two percent of affected children.
- End-stage renal disease occurs in under five percent of children with nephritis.
- Mandatory serial monitoring of blood pressure and urinalysis for minimum six months post-diagnosis. Crucial for detecting delayed onset nephritis.