WEGENER

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WEGENERSGRANULOMATOSIS

• L.Grcevska
• Department of Nephrology
• Faculty of Medicine
• Skopje, R.Macedonia

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Case 1 (typical presentation)

• Male patient, 58 year-old
• Extra-renal clinical features at presentation
• - fever
• - arthralgia
• - weakness
• - cough
• - dyspnea
• - hemoptysis
• Duration of the symptoms prior to admission 2
  weeks

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Case presentation

• Renal symptoms oligoanuria, 4 days prior to
  admission
• Serum urea levels at admission 56 mmol/l
• Serum urea creatinine 939 µmol/l
• Plasma protein level 58g/l
• Hb 101g/l, RBC count 3.200 000, WBC count 11000
• Ultrasound revealed enlarged, edematous kidneys
• Hemodialysis treatment started immediately

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Possibilities

• Acute renal failure associated with infection?
• Acute glomerulonephritis associated with
  infection?
• Rapidly progressive glomerulonephritis?
• Acute tubulo-interstitial nephritis?
• Vasculitis? Which form?
• Other systemic disorders?

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Case presentation

• Chest X-ray examination performed during the
  second day revealed pulmonary granulomata
• ANCA 328
• Anti-DNA negative
• The diagnosis of Wegeners granulomatosis was
  confirmed

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Renal biopsy

• RB was performed during the first week of
  admission and it reveals necrotizing
  glomerulonephritis with crescents.
• 6/12 glomeruli were completely destroyed, the
  other 6 presented partial necrosis. 10/12
  glomeruli presented crescents
• Interstitial granulomata were also present
• IMF was negative

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Case presentation

• We presented a typical case with WG,
  distinguished as a clinical entity by Friedrich
  Wegener in 1936. The first well explained cases
  were described between 1947 and 1958 as an
  illness characterized by symptoms of progressive
  ulceration in the respiratory tract together with
  signs of widespread inflammatory disease,
  histological examination of material from each
  shows disseminated granulomata, most common in
  the respiratory tract and kidneys and wide spread
  vascular lesions similar to polyarteritis nodosa
  

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• It is now clear that WG is a rare disease
  characterized by disseminated granulomatous
  vasculitis which primarily affects upper and
  lower respiratory tract and the kidneys.
• Systemic clinical features (fever, fatigue,
  arthralgia) similar to those present in viral
  infections can also be found
• Antineutrophil cytoplasmic autoantibodies
  directed against various components of the
  neutrophil cytoplasm are now regarded as a
  serological marker for renal-limited necrotizing
  and crescentic glomerulonephritis or associated
  with systemic vasculitis such as WG or other
  vasculitides
• The diagnosis is difficult

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Why?

• The disease is rare, 3 14 per million in
  European countries in 2009
• The epidemiology of WG is largely unknown, and it
  seems that the disease is more frequent in
  northern countries
• The course of the disease may vary, form weeks to
  months
• Various organ involvement may be noted
• - esophageal, colonic, hepatic granulomata
• - pancreatic, thyroid, cardiac, salivary
  glands, ocular, otologic and bone involvement may
  be present
• Affection of the upper and lower respiratory
  tract is more common in the patients from
  northern countries and affection of the
  gastrointestinal tract in ones from southern
  countries

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• Non-renal WG is known in the literature
• Renal involvement in literatures varies from
  lt20 to 80, but invariably increases to 80-94
  during follow-up in the same studies
• So, does the non-renal form exist?

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Our patients with WG

• Number of detected patients 28, biopsied 18
• Male/female ratio 21
• Age 19 68 , 48,61-13,79 (M-SD)
• Extrarenal clinical features prior to admission
  fever, sinusitis, cough, hemoptysis, weight loss,
  arthralgia, otitis, laringeal pain,
  gastrointestinal bleeding, various combinations
  of the symptoms
• Renal symptoms renal failure in all patients
  serum creatinine 265 1704), oligoanuria in
  38,9
• Proteinuria in non-oliguric patients 0,17 5,15
  g/d (only two patients were nephrotic)

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Our experience other cases with WG

• Duration of extra-renal clinical features prior
  to admission one week one year, sometimes with
  relapsing course
• Extra-renal features noted in the other patients
  sinusitis, necrosis of the adipose tissue of
  legs, weight loss, extensive gastrointestinal
  bleeding, granuloma of adipose tissue of legs,
  granulomatous inflammation of skin with necrosis
  (histology), granulomatous inflammation detected
  in biopsies of the gastrointestinal system
  (gastric and colonic granulomata)
• Diffuse proliferative glomerulonephritis with
  crescents on biopsy or necrotizing
  glomerulonephritis

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Treatment of our patient

• Plasmapheresis
• Cyclophosphamide i.v.
• Steroids i.v, continuing orally
• Outcome of the disease
• - diuresis occurred after 3 weeks
• - there was complete recovery of the
  pulmonary involvement
• - renal function improved to serum
  creatinine of 147 µmol/l after 3 months
• - the patient presented slow deterioration
  of the renal function during further 3 years
  (ESRD)

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Case 2 difficult diagnosis

• 36-year old male patient, diagnosed 2009
• 4 years prior to admission relapsing cutaneous
  bullous changes in axillar and inguinal regions,
  TBC excluded
• 6 months prior to admission dysphonia, laringeal
  papilloma was ablated histological diagnosis
  suggested viral etiology
• Two weeks later fever, with relapsing course 5
  months prior to admission
• 4 months prior to admission cough, hemoptysis,
  two in-patient treatments in his town-hospital
• 2 months prior to admission - arthralgia

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Case 2

• Admission at Department of Pulmology on 18th of
  December 2009. Because of development of anuria
  and serum creatinine 450 µmol/l he was
  transferred to our Department
• Diagnosis (Dep.Pulm) Infiltratio pulmonum.
  Status febrilis. Sepsis. Acute renal failure.
  Acne inversa s. Hydradermitis suppurativa
  (dermatologist)
• (Dep.Nephr)Granuloma were detected along GIT
  (gaster, esophagus, colon, cecum)
• Renal biopsy Glomerulonephritis extracapillaris
  proliferativa, 2/10 glomeruli revealed partial
  sclerosis, disruption of Bowmans membrane with
  granulomatous answer was noted in one of the
  glomeruli. Granulomatous infiltration of the
  interstitium was also present.

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Case 2 two years later

• Relapsing otologic and laringeal problems
• There is no pulmonary involvement
• There is no joint and skin involvement
• Granuloma od the esophagus are still present,
  without bleeding
• Serum urea levels 9,7 12 mmol/l, serum
  creatinine 104 113 µmol/l, daily urine out-put
  is normal
• Proteinuria 0,9 1,2 g/daily

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Course of the disease

• The disease in WG runs a rapidly progressive
  course which usually leads to death within a few
  months (sometimes within weeks or days) unless
  treated with immunosuppressive therapy
• The disease is with relapsing course
• Prior to introduction of dialysis, uremia was the
  main cause of death
• Using cyclophosphamide and steroids , 5-year
  survival rate 60-90
• 20-60 of patients with renal involvement at
  start, developed ESRD within 5 years
• Andrassy and co-workers found that 29 developed
  ESRD (short-term follow-up)

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Treatment

• Plasma exchanges
• Steroids
• Cyclophosphamide, azathioprine
• MMF
• Anti-adhesion molecule therapy
• Monoclonal antibody therapy
• Immuno-adsorbtion

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Outcome of the patients diagnosed at Department
of Nephrology

• Death because of respiratory failure (rare) 2
  cases
• Death because of gastrointestinal bleeding (only
  one case)
• Complete remission of pulmonary involvement (most
  frequent)
• Partial remission of pulmonary involvement (only
  one case)
• Relapsing pulmonary disease (rare)- only two
  cases, after 2 and 9 years
• One forth of the patients did not recover renal
  function during the admission
• Complete remission (renalpulmonal) rare (only 3
  cases)
• Persistence of stable renal failure with slow
  progression (most frequent)
• Probability surviving rate after one month
  0,6111, 3 months 0,3889 (Kaplan-Meier)

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Conclusions WG in R.Macedonia

• The disease is rare, we diagnosed only 28 cases
  for the past two decades
• Various organ involvement was noted with
  obligatory pulmonary affection
• Pulmonary involvement is with good prognosis
• Renal involvement reveal crescentic necrotizing
  or diffuse proliferative GN
• Relapsing course of the disease described in the
  literature is rare in R.M.
• Slow deterioration of the renal function is
  dominant renal clinical feature