Anaphylactoid purpura (also known as IgA vasculitis) is a disease characterized by the deposition of IgA-dominant immune complexes, primarily affecting small blood vessels and capillaries. Clinically, it manifests as non-thrombocytopenic palpable purpura of the skin, abdominal pain, arthritis, and nephritis. It was previously referred to as Henoch-Schönlein syndrome. Laboratory tests lack specificity. The disease is more commonly seen in children and adolescents, with a higher incidence in males than females, and tends to peak during the autumn and winter seasons.
Etiology
The cause remains unclear, and the potential factors are as follows:
- Infections: Beta-hemolytic streptococcal upper respiratory tract infections are the most common, while other potential agents include Helicobacter pylori, Staphylococcus aureus, Mycoplasma pneumoniae, and parainfluenza viruses.
- Drugs and Food: Antibiotics such as clarithromycin, amoxicillin, and cephalosporins; antipyretic analgesics and anti-inflammatory agents such as phenylbutazone and salicylates; and anti-TNF drugs, as well as others like isoniazid and thiazide diuretics. Currently, there is no conclusive evidence linking food allergies to the development of anaphylactoid purpura.
- Genetic Factors: The disease shows a genetic predisposition, primarily involving HLA genes, familial Mediterranean fever genes, and vascular endothelial growth factor genes.
Pathogenesis
The pathogenesis is not fully understood. It primarily involves IgA-mediated humoral immune abnormalities. Various triggering factors, such as infectious agents, may activate T cells in genetically susceptible individuals, leading to functional disturbances. This dysregulation causes polyclonal activation of B cells, resulting in the secretion of IgA, IgG, IgM, IgE, and inflammatory cytokines such as IL-21 and IL-6. These form IgA immune complexes that trigger abnormal immune responses. Among these, the deposition of IgA1 in the walls of small blood vessels plays a key role in initiating autoimmune inflammatory reactions and tissue damage. The deposition of large molecular IgA1-IgG circulating immune complexes in the kidney is the critical mechanism underlying anaphylactoid purpura nephritis.
Clinical Manifestations
Most patients experience prodromal symptoms, such as general malaise, low-grade fever, fatigue, or upper respiratory tract infections, 1–3 weeks before the onset of the characteristic clinical manifestations.
Skin Purpura
This is the most common symptom, presenting as slightly elevated lesions, referred to as "palpable" purpura. The lesions vary in size, are purplish-red in color, and do not fade on pressure. They may merge into patches, form blisters in severe cases, or even develop central necrosis. Typically resolving in 7–14 days, they may appear recurrently in groups. The lesions predominantly involve the distal extremities and buttocks, primarily on the extensor surfaces, and are symmetrically distributed.
Gastrointestinal Symptoms
Symptoms include abdominal pain, emesis, diarrhea, and hematochezia. Abdominal pain is the most common presentation, characterized by paroxysmal colicky pain, often accompanied by tenderness without abdominal muscle rigidity, with rebound tenderness being rare. Complications such as intussusception, intestinal obstruction, intestinal perforation, and hemorrhagic enteritis may occur. Abdominal symptoms often coexist with purpura but can occasionally precede purpura.
Joint Symptoms
These include joint swelling, pain, and functional impairment. Symptoms most commonly affect the knees, ankles, elbows, and wrists, presenting as migratory and recurrent episodes that resolve within days without leaving joint deformities.
Renal Involvement
Manifestations may include hematuria and proteinuria. Approximately 10%–20% of adolescents and adult patients experience progressive renal dysfunction, and a minority may develop chronic nephritis or nephrotic syndrome over months or years.
Other Symptoms
Other less common manifestations include orchitis, headache, and various neurological or psychiatric symptoms, as well as hemoptysis and interstitial pneumonia. Rare cases may present with optic neuritis, Guillain-Barré syndrome, subarachnoid hemorrhage, parotitis, myocarditis, and others.
Laboratory Tests
Blood Routine Examination
White blood cell levels may be normal or elevated, with increased neutrophil counts. Platelet counts are normal or elevated.
Urine Routine Examination
Hematuria, proteinuria, and casts may be present.
Stool Occult Blood Test
Occult blood may test positive.
Platelet Function and Coagulation
Platelet function is normal, with prolonged bleeding time (BT) observed in some patients. Fibrinogen and D-dimer levels may be elevated.
Serological Tests
Serum creatinine and blood urea nitrogen are mostly normal, though elevated levels may occur in acute or rapidly progressive nephritis. Elevated levels of transaminases and cardiac enzymes are occasionally observed. Some patients show increased serum IgA and elevated anti-neutrophil cytoplasmic antibody (IgA ANCA).
Imaging Studies
Imaging plays an important role in the early diagnosis and differential diagnosis of patients with gastrointestinal involvement. CT findings typically demonstrate segmental bowel wall edema, bowel lumen narrowing, mesenteric edema, and mesenteric lymphadenopathy.
Skin Biopsy
Typical changes include leukocytoclastic vasculitis with infiltration of neutrophils and eosinophils around blood vessels. Immunofluorescence may show the deposition of IgA, IgM, C3, and fibrin.
Diagnosis and Differential Diagnosis
Diagnostic Criteria
The 2010 EULAR/PRINTO/PRES criteria (European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society) are as follows: Presence of typical purpura (mandatory); accompanied by at least one of the following:
- Diffuse abdominal pain;
- Histopathology showing leukocytoclastic vasculitis with IgA deposition or membranoproliferative glomerulonephritis with IgA deposition;
- Arthritis/arthralgia;
- Renal involvement (hematuria: red blood cell casts, >5 red blood cells/high-power field; proteinuria: urinary protein >0.3 g/24 h).
Some patients may present only with isolated purpura without other symptoms. In cases of acute onset with typical purpura, a clinical diagnosis can be made after ruling out other diseases. For atypical presentations of purpura, strict adherence to diagnostic criteria is necessary, and a skin biopsy may be required.
Differential Diagnosis
Differential diagnosis should include:
- Secondary hypersensitivity vasculitis;
- Primary immune thrombocytopenia;
- Rheumatoid arthritis;
- Glomerulonephritis;
- Systemic lupus erythematosus;
- Acute surgical abdomen.
Treatment
The disease is typically self-limiting. Isolated purpura generally does not require treatment intervention. Treatment focuses on managing acute symptoms and addressing prognostic factors such as joint pain, abdominal pain, and renal damage.
General Treatment
For gastrointestinal involvement, dietary adjustments are made, including a low-residue, easily digestible diet for mild cases. Severe abdominal pain or emesis may require total parenteral nutrition or bowel rest with enteral nutrient supplementation.
Antimicrobial Treatment
Antimicrobial therapy may be administered for respiratory or gastrointestinal infections during the acute phase.
Medication
Symptomatic Treatment:
- Vitamin C and Rutin: Used to increase vascular resistance and reduce vascular permeability.
- Nonsteroidal Anti-inflammatory Drugs (NSAIDs): For joint symptoms.
- Atropine or Anisodamine: For abdominal pain; antiemetics can be used for severe emesis.
- Angiotensin II Receptor Blockers (ARBs)/Angiotensin-Converting Enzyme Inhibitors (ACEIs): For mild-to-moderate proteinuria.
Glucocorticoids and Immunosuppressants:
- Glucocorticoids: Prednisone at 1–2 mg/(kg·day). Severe cases may require methylprednisolone at 5–10 mg/(kg·day) or dexamethasone at 10–15 mg/day. Treatment duration is generally limited to 30 days. Glucocorticoids are indicated for gastrointestinal symptoms, joint swelling and pain, angioneurotic edema, and severe renal conditions such as rapidly progressive nephritis or nephrotic syndrome.
- Immunosuppressants: Mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus may be used in cases of glucocorticoid resistance or dependence.
- Other Therapies: Intravenous immunoglobulin (IVIG), plasmapheresis, or leukocyte apheresis may also be considered. Large-scale clinical trials are needed to confirm their efficacy.
Prognosis
Short-term prognosis is closely related to gastrointestinal symptoms, whereas long-term prognosis is associated with nephritis. Approximately 2% of patients may progress to end-stage renal disease, which is associated with a poor prognosis.