bubble_chart Overview

Allergic vasculitis is a relatively common disease characterized histopathologically by leukocytoclastic vasculitis, with both skin injuries and multiple visceral injuries. This condition has many names, but to avoid confusion, Ruiter suggested that it is more appropriate to call it allergic vasculitis, as this name reflects the inflammatory changes in blood vessels caused by allergic reactions. The severity of the disease varies widely—mild cases may only involve skin lesions and heal within weeks, while severe cases can lead to damage in multiple organs and even be life-threatening.

bubble_chart Etiology

The etiology of this disease is relatively diverse and complex. It is generally believed to be primarily caused by drugs and infections. The most common causative drugs include barbiturates, phenothiazines, sulfonamides, penicillin, iodides, aspirin, and foreign proteins. Infections are also a significant factor, such as viruses, streptococci, subcutaneous node bacilli, and leprosy bacilli. Fungi and protozoa are also considered causative agents. Anthelmintics, herbicides, and petroleum products are also associated with this disease. Additionally, intrinsic conditions such as cryoglobulinemia, hyperglobulinemia, systemic lupus erythematosus, and rheumatoid arthritis can also induce this disease.

Most factors are not directly pathogenic; only the M protein of streptococci, subcutaneous node mycobacteria, and hepatitis B surface antigens have been proven to have direct pathogenic significance. These three antigens always appear in the same blood vessels in the same manner alongside their corresponding antibodies. When protein antigens enter the bloodstream, they produce specific antibodies, particularly IgG or IgM. The antigen-antibody complexes form in the bloodstream or interstitial tissues, and these complexes deposit on vascular walls and surrounding tissues, activating complement C3 to produce anaphylatoxins. This triggers mast cells to release histamine, increasing vascular permeability, while simultaneously attracting polymorphonuclear neutrophils to aggregate at the sites of immune complex deposition, causing inflammatory cell infiltration. Immune complexes adhering to the surfaces of platelets and polymorphonuclear neutrophils further bind and reactivate complement, initiating the complement cascade. This leads to the lysis of platelets and polymorphonuclear neutrophils, during which platelets release clotting factors and vasoactive substances, causing fibrin deposition and hemorrhage. Meanwhile, polymorphonuclear neutrophils release collagenase, elastase, and other hydrolytic enzymes, which damage collagen fibers, elastic fibers, the basement membrane, and surrounding tissues. This results in inflammatory cell infiltration of the vascular wall, fibrin deposition, and vascular wall destruction and necrosis, manifesting the various symptoms of vasculitis.

bubble_chart Clinical Manifestations

1. Cutaneous Allergic Vasculitis This disease only affects the skin and mostly occurs in young adults. Common symptoms include lack of strength, joint and muscle pain, and a few cases may present with irregular fever, though some may show none of the above symptoms. Skin lesions can be polymorphic, manifesting as erythema, nodules, purpura, wheals, blood blisters, papules, necrosis, and ulcers. The most common sites are below both knees, particularly the lower legs and dorsum of the feet. Many lesions initially appear as purpuric maculopapules that do not blanch on pressure, caused by inflammatory cell infiltration and exudation in the vessel walls, making these ecchymoses raised and palpable—a hallmark of this disease. Some lesions begin as subcutaneous nodules, ranging from soybean to broad bean or small jujube in size, light red in color, and tender to touch. Others may start as purely purpuric lesions, some resembling erysipelas-like changes, others mimicking morphea-like or erythema multiforme-like alterations. During lesion progression, wheals and papules may accompany. Due to severe inflammatory reactions, blood blisters, necrosis, and ulcers may develop on purpuric macules and papules, and some nodular lesions can ulcerate with pain. Edema is most pronounced at the ankles and dorsum of the feet, worsening in the afternoon and accompanied by soreness and weakness in both lower limbs. Although the lesions vary, almost all cases present with purpura or nodules. Pustules may appear when neutrophils extravasate into surrounding tissues. Lesions can occur anywhere, such as the back, upper limbs, or buttocks, often symmetrically distributed. They may cause pain, itching, or burning sensations, though some are asymptomatic but tender. Healing leaves pigmentation, and ulcers may result in atrophic scars. Acute episodes involve widespread lesions with severe lower leg edema, while chronic cases recur over months or years. Mild cases resolve in 2–4 weeks. Some lesions merge and expand into large patches, commonly on knees, elbows, and hands, resembling erythema elevatum diutinum.

2. Systemic Allergic Vasculitis This disease affects multiple organs and is more severe. Due to involvement of small vessels, particularly post-capillary venules, diffuse exudation and hemorrhagic foci occur within organs. Organ involvement often presents acutely, with symptoms like headache, irregular fever, malaise, lack of strength, and joint or muscle pain. The course varies: a single antigen exposure may resolve in 3–4 weeks, while repeated exposures lead to recurrent episodes lasting months or years. Prognosis depends on the affected organs and disease severity.

67% of patients develop polymorphic skin lesions, often palpable purpura. 75% experience nonspecific fever, and about two-thirds have arthralgia and joint swelling. Mucous membrane involvement may cause epistaxis, hemoptysis, or hematochezia. One-third develop renal involvement with proteinuria or hematuria, and severe renal failure is a leading cause of death. Intestinal involvement manifests as abdominal pain, steatorrhea, hematochezia, or acute cholecystitis. Pancreatitis or diabetes may occur. Chest X-rays show pneumonia, nodular shadows, pleuritis, or effusion. Neurological symptoms include headache, diplopia, delusions, confusion, cerebral thrombosis, paralysis, dysphagia, and sensory/motor dysfunction. Cardiac complications include myocardial infarction, arrhythmias, and pericarditis. Renal cortical ischemia may cause severe hypertension. Common ocular manifestations are episcleritis and retinal hemorrhage. Painful swelling of the epididymis or testes may indicate vasculitis. Renal biopsy and direct immunofluorescence tests are often diagnostic for systemic vasculitis.

bubble_chart Auxiliary Examination

Cutaneous allergic vasculitis generally shows no significant changes. Systemic allergic vasculitis may present with anemia, transient thrombocytopenia, leukocytosis, and eosinophilia in one-third of patients, typically ranging from 0.04 to 0.08, with a few cases reaching 0.56. Urinalysis may reveal proteinuria, red blood cells, and occasionally granular casts. In severe cases, BUN may be elevated. Over half of the patients may exhibit an increased erythrocyte sedimentation rate. Total complement and complement components C₃, C₄ may be decreased. IgG and IgA levels may rise, while IgM decreases, with these changes correlating with disease severity. Liver function abnormalities may also occur. Circulating immune complexes are often positive. Additional relevant laboratory tests include antinuclear antibodies, syphilis serology, anti-streptolysin O, rheumatoid factor, cryoglobulins, and HBsAg. Potential underlying infections, tumors, and connective tissue diseases should also be considered.

Histopathology: The changes depend on disease severity, duration, and sampling timing. Typically, inflammatory cell infiltration is observed around dermal capillaries and small vessels, with abundant neutrophils and nuclear debris (karyorrhexis). Tissue histiocytes and eosinophils are also present, along with fibrin deposition around vessels. On histology, fibrin deposition combined with marked edema gives collagen a blurred appearance, termed fibrinoid degeneration. Vascular endothelial cell swelling may lead to luminal occlusion. Inflammatory cells infiltrate the vessel walls, predominantly neutrophils, causing wall obscurity, along with eosinophils and few mononuclear cells. Fibrin deposition and vascular necrosis are common, as is extravasation of red blood cells. Key histopathological features include perivascular neutrophil infiltration with nuclear debris, erythrocyte extravasation, upper dermal inflammatory cell infiltration, neutrophil invasion of vessel walls, vascular obscurity and necrosis, and perivascular/wall fibrin deposition. Ulcers result from vascular necrosis, often accompanied by hemosiderin deposition. Chronic cases show minimal or no erythrocyte extravasation.

Electron microscopy reveals involvement of postcapillary venules, particularly vessels 8–30 μm in size. Early changes include endothelial swelling, intercellular gaps, active phagocytosis, and basement membrane thickening. Neutrophils initially accumulate in the vascular interstitium. In severe cases, platelets aggregate within the lumen and traverse endothelial cells.

Direct immunofluorescence demonstrates IgA antibodies along the vascular basement membrane, with IgM, IgG, and complement C₃ deposits in the dermis and subcutaneous tissue. Tissue destruction is observed at fixation sites, primarily within areas of fibrinoid necrosis.

bubble_chart Diagnosis

This disease is primarily characterized by the occurrence of erythematous nodules on the lower limbs, which are tender to palpation, and may also be accompanied by skin lesions such as purpura, purpuric papules, wheals, and papulovesicles. The histopathological findings of the skin show inflammatory cell infiltration in the vessel walls, mainly consisting of polymorphonuclear leukocytes and fibrin deposition. There is also infiltration of polymorphonuclear leukocytes around the vessels, accompanied by nuclear dust and extravasation of red blood cells. Based on these features, a definitive diagnosis can be made.

bubble_chart Treatment Measures

Active treatment can be administered based on different causes and symptoms.

1. Due to the patient's lower limb fatigue, weakness, myalgia, arthralgia, and swelling, rest is essential. Severe cases should be bedridden, with the affected limb elevated to reduce the impact of venous pressure on the lesions.

2. Eliminate the disease cause to reduce antigen sources and eradicate infection foci, such as viral or bacterial infections. Discontinue the use of allergenic drugs and the influence of heterologous proteins.

3. For upper respiratory infections, antibiotic treatment can be used: double-effect penicillin 80×104U intramuscular injection, once or twice daily; or erythromycin 0.25g, four times daily, orally; or cephalosporins.

4. To prevent antibody production, reduce immune complex formation, and decrease inflammatory responses, prednisone 20–40mg can be taken orally in divided doses.

5. Colchicine 0.5mg, taken twice daily, may inhibit leukocyte chemotactic factors, inflammation, and stabilize lysosomal enzymes.

6. Indomethacin 25mg, taken three times daily, may inhibit prostaglandin synthesis.

7. Aspirin 0.3g plus dipyridamole 25mg, taken three times daily, can inhibit platelet aggregation.

8. Phenformin 50mg plus ethinyl estradiol 2mg, taken twice daily.

9. Dapsone 50mg, taken twice daily.

10. To improve vascular function, vitamin E 100mg and vitamin C 200mg can be taken three times daily.

11. Chinese medicine and Chinese medicinals should aim to promote blood circulation and remove stasis, clearing heat and removing toxin. Compound Salvia tablets or Fuchun tablets can be used.

bubble_chart Differentiation

(1) Allergic purpura mostly occurs in children and adolescents, with the most common skin lesions being ecchymosis and petechiae on the lower limbs, which may be accompanied by arthralgia. Platelet count is normal, and urinalysis may show proteinuria and hematuria. Occasionally, symptoms of gastrointestinal bleeding may be observed.

(2) Papulonecrotic subcutaneous nodular rash is more common in young women, presenting as scattered, firm papules with central necrosis near limb joints or the buttocks, leaving atrophic scars after healing. The subcutaneous nodule test shows strong positivity, and histopathology reveals the tissue manifestations of subcutaneous nodule disease.

(3) Cutaneous polyarteritis nodosa mainly affects the lower limbs, with subcutaneous nodules distributed along small arteries, accompanied by significant spontaneous pain and tenderness. Histopathological examination shows small arteritis and small artery necrosis.

(4) It should also be differentiated from hyperglobulinemia, acute smallpox-like lichenoid pityriasis, and nodular vasculitis.