Eosinophilic granulomatosis with polyangiitis M30.1

Eosinophilic granulomatosis with polyangiitis, also known as "Churg-Strauss syndrome" is a rare, pANCA+ (in 50-70% of cases), systemic (necrotizing) vasculitis affecting various vessel sizes (small to medium-sized) and associated with intravascular and extravascular granuloma formation, bronchial asthma, and high blood eosinophilia.

Furthermore, there is:

• marked ESR acceleration
• inconstant fever
• inconstant anemia
• volatile pulmonary infiltrates
• cardiac involvement (50%) - eosinophilic granulomatous myocarditis and coronaritis, high eosinophilia, usually ANCA negative,
• mono-polyneuropathy
• Renal involvement in the form of"Rapid Progressive Glomerulonephritis".
• CNS vasculitis
• recurrent thromboembolism
• Skin involvement (40%) - eosinophilic granulomatous dermatitis

Rarely. Incidence: 0.5-1.0/100,000 inhabitants/year.

The pathogenesis is still unknown. As triggers, various. Inhalation allergens are discussed as triggers. Further infections, vaccinations, medication. Repeated cases have been described under Omalizumab, a monoclonal IgE antibody.

trunk, distal extremities, rarely head, no mucous membrane infestation

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) develops in 3 phases:

• Allergic phase with allergic asthma, allergic rhinitis and sinusitis.
• Eosinophilic phase with eosinophilic infiltrates in lungs, heart (skin) and gastrointestinal tract.
• Vasculitic phase with peripheral neuropathy and other organ manifestations.

The skin manifestations are clinically not very characteristic and diagnostically can only be evaluated in the overall view of the clinical symptoms.

They occur in about 40% of Churg-Strauss patients, in about 20% as the first manifestation and appear as cutaneous or subcutaneous, coarse, painful red (hemorrhagic) plaques, nodules or ulcers, following the course of skin vessels (2/3 of cases). However, there can also be exclusively 5.0-10.0 cm large, planar or figured erythema or plaques, which heal under hyperpigmentation (picture as in eosinophilic cellulitis/Wells syndrome).

Corresponding granulomas are found in numerous organs:

• Lung (100%) initially appearing as transient Löffler infiltrates.
• Also spleen, heart, liver, gastrointestinal tract, genitals, muscles, kidney.

Relapsing activities are often associated with fever, arthralgias, or nonspecific skin reactions such as:

• Palpable purpura
• erythema exsudativum multiforme
• fixed drug reaction
• urticaria.

• Inflammation parameters increased (BSG acceleration, CRP)
• Pronounced eosinophilia (up to 80% or 5000/μl)
• IgE i.S. increased
• Positive rheumatoid factor
• Positive ANA
• p-ANCA (in 40-60% of cases)
• Positive circulating immune complexes
• IgG4 frequently increased
• Possibly increased AP .

Necrotizing vasculitis: Picture is largely similar to Wegener's granulomatosis with tissue eosinophilia: Coexistence of leukocytoclastic vasculitis with subcutaneous arterial vasculitis. In addition, extensive extravascular palisade granulomas with central, map-like necrosis zones, many multinucleated giant cells and distinct infiltrates with eosinophilic and neutrophilic leukocytes (Churg-Strauss granulomas).

Criteria of the American College of Rheumatology for the diagnosis of eosinophilic granulomatosis with polyangiits (if at least 4 criteria are present, the diagnosis is likely)

1. bronchial asthma
2. Eosinophilia(>10%) of the blood.
3. Mono- or polyneuropathy
4. Radiologically detectable migrating pulmonary infiltrates
5. Acute or chronic recurrent sinusitis
6. Bioptic detection of extravascular eosinophilia

Eosinophilic granulomatosis with polyangiitis differs clinically from other vasculitides, especially from polyarteritis nodosa (PAN), by the presence of severe (allergic) bronchial asthma (possibly together with allergic rhinitis) in combination with a marked eosinophilia (>10%) of the blood. Furthermore, the following differential diagnosis must be distinguished:

• Wegener's granulomatosis
• Schönlein-Henoch purpura
• Arteritis temporalis
• Takayasu arteritis
• Hypereosinophilia syndrome
• Eosinophilic myalgia syndrome
• eosinophilic pneumonia.

Glucocorticoids in medium doses (1.5-2.0 mg/kg bw prednisone equivalent/day) is often sufficient. Good response in general. Symptom-adapted reduction of steroid medication over a longer period. Maintenance dose: 2.5-7.5 mg prednisolone equivalent/day.

Alternative or complementary: In severe cases a complementary therapy with cyclophosphamide according to the Fauci scheme (see Takayasu arteritis) can be given. This therapy should be continued for at least 6 months to 1 year after full remission.

Alternatively: Mepolizumab. In a randomized, multicenter, double-blind phase III study, mepolizumab was used in eosinophilic granulomatosis with polyangiitis for a period of 52 weeks (dose 300mg s.c. every 4 weeks). Under this therapy, there was a significant reduction in disease activity (reduction in recurrence rate, reduction in glucocorticoid consumption).

Experimental: Positive single observations exist of plasmapheresis treatments.

Untreated, almost always lethal within a few years (cardiac causes); with therapy, often complete remission. 5-year survival rate with optimal therapy >80%.

Most common cause of death cardiac failure, myocardial infarction.

In rare cases, eosinophilic granulomatosis with polyangiitis may occur combined with allergic bronchopulmonary aspergillosis (Ren S 2013).

CS syndrome develops in patients with chronic asthma; insidiously, increasing blood eosinophilia (1,500-5,000/ul), Löffler's infiltrates in the lungs, vasculitic infiltrates in almost all organs.

Clinic, laboratory, histology (American College of Rheumatology criteria -1990-).

The diagnosis is likely if 4 of the following 6 criteria are met:

1. (Difficult to treat) asthma (with transient pulmonary infiltrates).
2. Eosinophilia > 10% in the differential blood count
3. Mononeuropathy or polyneuropathy associated with systemic vasculitis
4. Migratory or transient radiologically detectable pulmonary infiltrates associated with systemic vasculitis
5. Acute or chronic recurrent sinusitis or radiographic changes consistent with chronic sinusitis
6. Bioptic confirmation of vasculitis with evidence of eosinophilia in extravascular tissue.

• The 42-year-old man with long-term bronchial asthma that is difficult to treat and seasonal allergic rhinitis (birch pollen allergy) developed painful red lumps on his chest and hips for about 16 months, which developed into 5.0-10.0 cm red, only moderately painful, bizarrely configured (apparently following the deep vascular plexus of the skin), sharply margined plaques. A recurrent course with moderate shear activity (recurrences with 1-2 new nodules every 4-6 weeks) was characteristic. The healing of the plaques was accompanied by lesional hyperpigmentation.
• Systemic steroid administration (prednisolone between 50 and 20 mg p.o./day) was regularly necessary to treat asthma with dyspnoea. The cutaneous lesions also responded to this with high sensitivity (subsidence under hyperpigmentation, recurrence of skin lesions below a critical threshold of about 5-10 mg/day).
• Laboratory: blood eosinophilia: 35% (absolute: 2085/ul); CRP elevation(7.5 mg/dl); IgE:1000 U/ml, BSG 30/70 mm; rheumatoid factor, ANA, MPO-p-ANCA normative. In a later control, MPO-p-ANCA could be detected with further increasing eosinophilia (30%).
• Histology: Pronounced perivascularly oriented infiltrates of lymphocytes, histiocytes, eosinophilic and neutrophilic granulocytes and nuclear dust. Further signs of leukocytoclastic vasculitis with vasculitis of subcutaneous arteries. Isolated palisade granulomas with central necrobiosis zones.
• Ro.thorax: The radiographically detectable infiltrates of the lung were interpreted as "pneumonia".
• The therapy was carried out in cooperation with pneumologists with internally applied steroids (initial 100 mg prednisolone in decreasing dosage) and supplemented with cyclophosphamide according to the Fauci scheme for 1 year. This included full remission.

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