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.