ANCA-associated Kidney disease

Question 1

Clinicopathologic Classification

Answer 1

Granulomatosis with polyangiitis
Eosinophilic Granulomatosis with polyangiitis
Microscopic polyangiitis

Question 2

Pathogenesis

Answer 2

The role of complement in AAV. Priming of neutrophils by inflammatory mediators causes translocation of myeloperoxidase (MPO) and proteinase 3 (PR3) myeloperoxidase to the cell surface, where they can interact with antineutrophil cytoplasmic antibody (ANCA). Binding of ANCA to its target antigen results in neutrophil activation, leading to the release of reactive oxygen species and lytic enzymes that cause tissue damage. In addition, ANCA-induced neutrophil activation releases mediators that activate the alternative complement pathway, thereby leading to C5a generation. C5a is a chemoattractant that recruits and primes additional neutrophils, creating a positive feedback loop that drives disease activity.

Question 3

Manifestations

Answer 3

Nose: Nasal crusting/discharge, nasal ulcers, saddle nose deformity, septal perforation

Paranasal sinuses: Sinusitis

Ear: Otitis media, conductive hearing loss, sensorineural hearing loss, polychondritis

Eye: Scleritis, episcleritis, conjunctivitis, uveitis, retinal vasculitis, retro-orbital pseudotumor

Skin: Purpura, cutaneous ulcers, nodules

Oral mucosa: Oral ulcers

Heart: Pericarditis, myocarditis

Trachea: Tracheal stenosis (typically subglottic)

Lung:Pulmonary nodules/masses, pulmonary hemorrhage, interstitial fibrosis, bronchial stenosis

Kidney: Pauci-immune necrotizing (and often crescentic) glomerulonephritis, interstitial nephritis (almost always associated with glomerulonephritis)

Nervous system: Mononeuritis multiplex, peripheral sensory neuropathy, pachymeningitis, CNS vasculitis

Gastrointestinal system: Mesenteric ischemia, ischemic colitis

Question 4

Drug induced AAV

Answer 4

Hydrazaline, propylthiouracil, methimazole,allopurinol, levamisole-adulterated cocaine

Question 5

Induction of remission
Infektion Prophylaxe
Novel therapy

Answer 5

Cyclophosphamide, rituximab, glucocorticoids
Trimethoprim-sulfamethoxazole ( pneumocystis jiroveci pneunonia)
C5a receptor antagonist AVACOPAN

Question 6

Maintance of remission

Answer 6

Rituximab, azathioprine

Question 7

Side effect Glucocorticoids

Answer 7

Hyperglycemia, weight gain, hypertension, fluid retention, mood disturbances, skin thinning, easy bruising, cataracts, increased intraocular pressure, osteoporosis, myopathy

Question 8

Side effects Cyclophosphamide

Answer 8

Leukopenia, hemorrhagic cystitis; dose-dependent risk of infertility and secondary malignancies

Question 9

Side effects rituximab

Answer 9

Infusion reactions, hypogammaglobulinemia, late-onset neutropenia (LON)

Question 10

Side effects azathioprine

Answer 10

Leukopenia, increase in MCV, nausea/anorexia, pancreatitis, hepatitis, hypersensitivity reaction;
significant interaction with xanthine oxidase inhibitors