bubble_chart Overview

Wegener's granulomatosis is characterized by progressive necrotizing granulomas and widespread small vessel vasculitis. It primarily affects organs such as the respiratory tract, kidneys, and skin, leading to corresponding clinical manifestations.

bubble_chart Etiology

It remains unclear. Since most patients initially present with upper respiratory symptoms followed by glomerulonephritis, some believe that slowly released proteins isolated after upper respiratory infections may act as sensitizing agents, triggering an allergic reaction and leading to the disease. Reports indicate that long-term survival has been achieved with treatment using trimethoprim (TMP) and sulfamethoxazole (SMZ), suggesting a link between the disease and microbial infection. Half of the cases test positive for wind-dampness factors, associated with hypergammaglobulinemia and circulating immune complexes, and involve cellular immunity in this autoimmune disorder. Many studies have found that patients with active Wegener's granulomatosis possess anti-leukocyte autoantibodies, anti-SSA, and anti-SSB antibodies. Treatment with immunosuppressants leads to disease remission, during which serum anti-neutrophil cytoplasmic antibodies (ANCA) disappear, only to reappear upon relapse, indicating ANCA's involvement in the disease mechanism. A few cases have ultimately progressed to cervical malignancy with cachexia, raising the question of whether this disease is a response to malignancy, which requires further investigation.

bubble_chart Pathological Changes

The entire body system and organs can be affected, with pathological characteristics including:

1. Both the upper respiratory tract (mainly the nose, paranasal sinuses, nasopharynx, and nasal septum) and the lower respiratory tract (trachea, bronchi, and lungs) may exhibit necrotizing granulomatous sexually transmitted disease changes. The walls of small blood vessels show fibrinoid necrosis, with infiltration of mononuclear cells, epithelioid cells, and multinucleated giant cells throughout the layers. In severe cases, the lesions may invade and destroy bone tissue, and pulmonary lesions may form cavities. Granulomas can also be found in the maxilla, ethmoid bone, orbit, and other areas. Extensive vasculitis-induced infarctions and ulcers can lead to saddle nose deformity, proptosis, and other deformities.

2. Renal lesions manifest as necrotizing glomerulonephritis, with focal or segmental necrosis of glomerular capillaries. The vascular walls show infiltration of neutrophils and eosinophils, with deposits of IgG, IgM, C₃, and C₄. The walls of small blood vessels exhibit fibrinoid changes.

3. Systemic focal necrotizing vasculitis primarily affects small stirred pulse, fine stirred pulse, small veins, capillaries, and surrounding tissues. The vascular walls are infiltrated by polymorphonuclear cells, with fibrinoid degeneration, destruction of the muscular layer and elastic fibers, thrombosis in the lumen, and vascular wall necrosis, leading to the formation of small stirred pulse aneurysms, hemorrhages, and other changes. In addition to the lungs and kidneys, the skin, heart blood vessels, digestive system, nervous system, and other systems may also be involved.

bubble_chart Clinical Manifestations

The condition can occur in both males and females, with a male-to-female ratio of 3:2. Over half of the cases occur between the ages of 30 and 50. Most patients experience fever, weight loss, lack of strength, and symptoms such as arthralgia and myalgia. Typical patients present with the triad of upper respiratory fatigue, pulmonary involvement, and renal disease. Early manifestations often include persistent rhinitis or sinusitis, presenting as nasal discharge, purulent nasal secretions, epistaxis, or even the expulsion of necrotic tissue. The nasal turbinates and septum may appear rough and granular with crusting. In severe cases, nasal septum perforation or destruction of the nasal bones can lead to saddle nose deformity. A minority of cases present with acute airway obstruction. Lower respiratory symptoms vary, including cough and small amounts of hemoptysis, often complicated by secondary bacterial infections. Severe cases may develop massive alveolar hemorrhage, leading to dyspnea or even respiratory failure.

Renal involvement is seen in almost all cases, typically manifesting within six months of onset as proteinuria, hematuria, and casts. Worsening disease is often accompanied by hypertension, which can progress to renal failure. However, the absence of renal disease does not rule out the diagnosis.

Skin and mucous membrane lesions occur in about 60% of cases, presenting as purpura, hemorrhagic vesicles, nodules, infiltrative patches, and ulcers. In one-fourth of cases, these lesions appear early in the disease as necrotic papules and blisters, often symmetrically distributed on the limbs and buttocks. Necrotic pyoderma lesions may sometimes serve as an early sign.

Ocular involvement is seen in 20–60% of cases, likely due to granulomas and vasculitis, and includes keratoconjunctivitis, corneal or scleral ulcers, granulomatous sclerouveitis, optic nerve vasculitis, retinal microvasculitis, and proptosis.

Ear involvement occurs in about one-fourth of cases, often due to granulomatous destruction of the middle ear cavity or mastoid. Nasal ulcers or eustachian tube obstruction can lead to exudative or suppurative otitis media, hearing loss, and vertigo.

Neurological involvement occurs in approximately one-fifth of cases. Vasculitis of the nervous system is the primary cause of symptoms, presenting as polyneuritis or sensorimotor deficits. Granulomas in the nasal or sinus regions may also invade adjacent neural tissues, leading to drooping of the upper eyelid (blepharoptosis) or ocular muscle paralysis. Involvement of the posterior pituitary can result in diabetes insipidus.

Cardiovascular system involvement occurs in about 15% of cases, manifesting as pericarditis, myocarditis, or arrhythmias. Advanced stages may present with hypertension or heart failure.

Gastrointestinal involvement includes ulcers of varying size and depth in the oral or intestinal mucosa, accompanied by abdominal pain, diarrhea, or hematochezia. Rare cases of parotitis, hepatitis, or pancreatitis have been reported. The disease often progresses aggressively with a poor prognosis. It typically begins with upper respiratory symptoms before spreading systemically, most commonly affecting the kidneys within six months. The onset of renal failure is a major cause of death, emphasizing the importance of early and aggressive treatment before renal damage occurs. A minority of patients may present with isolated lung, skin, or gastrointestinal involvement without glomerulonephritis or upper respiratory lesions, classified as limited Wegener's granulomatosis. These cases have a more benign course, though their relationship to classic Wegener's granulomatosis remains unclear.

bubble_chart Auxiliary Examination

1. Leukocytes and eosinophils are often elevated. Patients with chronic renal insufficiency often have microcytic anemia. Elevated erythrocyte sedimentation rate (ESR) is particularly more pronounced when systemic involvement occurs. The presence of protein, red blood cells, and white blood cells in urine tests indicates renal involvement, with renal function consistent with the extent of kidney damage. In some cases, rheumatoid factor is positive, gamma globulin is elevated, circulating immune complexes are increased, blood moistening and tonifying levels are normal or grade I elevated, and anti-SSA, SSB antibodies, as well as anti-smooth muscle antibodies are positive.

In recent years, many studies have reported that the detection of serum anti-neutrophil cytoplasmic antibodies (ANCA) using indirect immunofluorescence with neutrophils as the antigen substrate is a specific antibody for this disease. It presents as bright, coarse granular patterns, with a sensitivity of 70–100% during the active phase and a specificity of 86%, making it a useful marker for diagnosing the disease and monitoring activity.

2. X-ray examination: Chest X-rays show multiple sexually transmitted disease lesions in both lungs. Early stages often present as nonspecific interstitial infiltrates, followed by infiltrative, nodular, or even cavitary sexually transmitted disease lesions, solitary masses, etc., resembling pneumonia, subcutaneous nodes, lung cancer, etc. A few patients may develop atelectasis due to granulomatous obstruction of the airways. Bronchography reveals tracheal or bronchial stenosis. X-rays of the upper respiratory tract show thickening of the sinus mucosa and even destruction of nasal and sinus bones.

3. Pathological examination: Biopsy of upper respiratory tract lesions may reveal vasculitis or necrotizing granulomas. A negative biopsy does not rule out the disease, and repeated examinations can improve the positive rate. Renal biopsies in some cases may show focal, segmental, necrotizing glomerulonephritis, with fibrin deposits often present in active lesions and necrotic areas.

bubble_chart Diagnosis

The diagnostic basis mainly combines clinical and histopathological examinations:

1. Necrotizing granulomas in the upper or lower respiratory tract.

2. Primary focal necrotizing vasculitis in the lungs or skin.

3. Focal necrotizing tubulointerstitial nephritis.

For early diagnosis, attention should be paid to the following conditions, and repeated histopathological examinations should be performed when necessary:

1. Chronic rhinitis and/or sinusitis with mucosal erosion or granulomatous tissue proliferation.

2. Ulceration, necrosis, or granulomas in the mucous membranes of the eyes or oral cavity.

3. Variable nodular shadows or cavities in the lungs.

4. Skin manifestations such as purpura, nodular infiltrative patches, necrosis, or ulcers.

The criteria proposed by the American Bi Disease Association in 1990 can serve as a reference: ① Nasal or oral inflammation (painful or painless oral ulcers, bloody nasal discharge). ② Chest X-ray showing nodules, fixed pulmonary infiltrates, or cavities. ③ Microscopic hematuria (red blood cells >5 per high-power field) or red blood cell casts in urine. ④ Tissue biopsy demonstrating granulomatous inflammation in the arterial wall or around arteries and small vessels. Meeting two or more of the above criteria can diagnose Wegener's granulomatosis, with a sensitivity of 88.2% and specificity of 92%.

bubble_chart Treatment Measures

For localized treatable X-ray therapy, the use of a single corticosteroid or immunosuppressant can be effective. Untreated systemic cases generally have a poor prognosis, with 80% of patients often dying from renal failure within one year. Early diagnosis and early treatment, along with aggressive intervention before renal impairment occurs, significantly improve the prognosis, with 93% of patients achieving complete remission. Currently, the prevailing approach is to initiate combined corticosteroid and immunosuppressant therapy as early as possible. Prednisone is administered at 1 mg/kg daily for 6–10 weeks, with the dose tapered after clinical improvement and maintained for 6–18 months. Immunosuppressants such as cyclophosphamide, azathioprine, or methotrexate may be selected. Cyclophosphamide can serve as a foundational drug for this condition, administered at 2 mg/kg daily, or 4–5 mg/kg (intravenously or orally) in severe cases. After stabilization and remission, treatment should continue for over a year, with gradual dose reduction until discontinuation. Recurrence after discontinuation can still be effectively retreated.

For patients who have already developed renal failure, the therapeutic outcome is generally unsatisfactory. In addition to intensive combination therapy, successful cases have been reported using hemodialysis and kidney transplantation.

Recent reports indicate that treatment with the compound formula sulfamethoxazole yields a 5-year survival rate of 95%. Thus, with aggressive treatment, complete remission of this disease can be anticipated.

bubble_chart Differentiation

The differential diagnoses include polyarteritis nodosa, which primarily involves small and medium-sized arteries segmentally, presenting with inflammatory and necrotic lesions without granulomatous damage. It affects multiple tissues and organs, with diverse clinical manifestations such as subcutaneous nodules, hypertension, abdominal symptoms, and early renal impairment, while the respiratory system is often spared. Lymphomatoid granulomatosis is a systemic angiocentric and angiodestructive necrotizing granulomatosis, typically sparing the upper respiratory tract, with lesions mainly affecting the lungs, skin, nervous system, and renal interstitium. It is characterized by infiltration of lymphocytes, plasma cells, histiocytes, and atypical lymphocytes. Although it may exhibit granulomatous vasculitis, granulomatous damage is often inconspicuous, and the vasculitis does not typically present as leukocytoclastic or fibrinoid necrosis. Midline malignant reticulosis involves destructive lesions of the nose and face, usually sparing the lungs, with pathology dominated by coagulative necrosis and polymorphic cell infiltration, including atypical lymphocytes, without accompanying vasculitis or granulomatous changes. Goodpasture syndrome (pulmonary-renal syndrome) can be distinguished from Wegener's granulomatosis by detecting anti-glomerular basement membrane (GBM) antibodies via immunofluorescence antibody testing of kidney and lung biopsies, as well as circulating anti-GBM antibodies.