A topic presentation about granulomatosis with polyangiitis. Diagnosis, treatment, patient education and a related clinical trial.

1. Granulomatosis with
polyangiitis
March 4, 2020
PPE 3-4
Presented by: Abdul Rahman Shaaban
Presented to: Dr. Rima Abdul Khalek

2. Introduction
2
● An autoimmune disorder that causes inflammation of
the blood vessels in nose, sinuses, throat, lungs and
kidneys.
● This condition is one of a group of blood vessel disorders
called vasculitis. It slows blood flow to some organs.
● Early diagnosis and treatment of granulomatosis with
polyangiitis might lead to a full recovery. Without
treatment, the condition can be fatal.

3. New Terminology
● Previously known as “Wegener's
granulomatosis”.
● Now called as “Granulomatosis with
Polyangiitis”.
3

4. Risk Factors
● Isn't known. It's not contagious, and
there's no evidence that it's inherited.
● For some time, an infection has been
suspected of causing (or at least
contributing to) Granulomatosis with
Polyangiitis , but no specific infection
(bacterial, viral, fungal, or other) has
been identified.
● Granulomatosis with polyangiitis can
occur at any age. It most often affects
people between the ages of 40 and
65.
4

5. CLASSIFICATION AND DIAGNOSTIC CRITERIA
A. American College of Rheumatology (ACR) 1990 classification criteria.
A. Chapel Hill Consensus Conference criteria (Most Commonly used).
A. European Medicines Agency algorithm.
5

6. American College of
Rheumatology (ACR) 1990
Classification Criteria.
● Nasal or oral inflammation
● Abnormal chest radiograph showing
nodules, fixed infiltrates, or cavities
● Abnormal urinary sediment
(microscopic hematuria)
● Granulomatous inflammation on
biopsy of an artery or perivascular
area
6

7. Chapel Hill Consensus
Conference Criteria.
● Necrotizing granulomatous.
inflammation usually involving the
upper and lower respiratory tract.
● Necrotizing vasculitis affecting
predominantly small to medium
vessels.
● Necrotizing glomerulonephritis is
common.
7

8. European Medicines
Agency Algorithm
● Lower airways: radiograph
evidence of fixed pulmonary
infiltrates, nodules, or
cavitations for more than one
month.
● Upper airways: bloody nasal
discharge and crusting for
more than one month.
● Glomerulonephritis: hematuria
associated with red cell casts. 8

9. Clinical Presentation
Common Clinical Presentation:
Fatigue, fever, weight loss, arthralgias,
rhinosinusitis, cough and dyspnea, urinary
abnormalities.
Ear, nose, and throat:
Nasal crusting, sinusitis, otitis media,
earache, otorrhea, persistent rhinorrhea,
purulent/bloody nasal discharge, oral and/or
nasal ulcers.
9

10. Clinical Presentation
Tracheal and pulmonary disease:
May develop pulmonary fibrosis and pulmonary
arterial hypertension.
Pulmonary parenchyma causing hoarseness, cough,
dyspnea, stridor, wheezing, hemoptysis.
Renal manifestations:
Asymptomatic hematuria.
Rapidly rising serum creatinine with
hematuria, hypertension, and edema.
Variable degree of proteinuria that is usually
subnephrotic.
10

11. Clinical Presentation
Cutaneous manifestations:
Leukocytoclastic angiitis, which causes
purpura involving the lower extremities.
Focal necrosis and ulceration.
Urticaria, livedo reticularis, and nodules.
Neurologic manifestations:
Mononeuritis multiplex, sensory neuropathy,
cranial nerve abnormalities.
External ophthalmoplegia, and hearing loss.
11

12. 12

13. Diagnosis
● If a biopsy of an affected organ is not feasible or
should be delayed, a presumptive diagnosis based
upon clinical findings.
● Urinalysis to determine presence of hematuria.
● Chest radiograph and CT scan should be done in
all patients who have pulmonary symptoms.
● Diagnosis should be confirmed by Biopsy.
13

14. Treatment
Induction:
● Initial Immunosuppressive therapy.
Maintenance:
● Immunosuppressive therapy for a
variable period to prevent relapse.
14

15. 15

16. 16
Treatment
*Cyclophosphamide (intravenous or oral) and rituximab are both effective immunosuppressive agents for the treatment of organ-threatening or life-
threatening ANCA-associated vasculitis. The choice is based upon clinician experience, patient preference, and the toxicities and adverse effects
associated with each drug.
¶Some clinicians treat patients with organ-threatening or life-threatening GPA or MPA by sequentially using both cyclophosphamide (for the first two to
three months) and rituximab (after discontinuation of cyclophosphamide). This induction strategy is controversial.
ΔContraindications to methotrexate include, but are not limited to, heavy alcohol use and chronic liver disease.
◊ The three major indications for plasma exchange in patients with GPA or MPA are as follows:
■ Advanced kidney dysfunction as a result of glomerulonephritis due to GPA or MPA (for example, need for dialysis or a serum creatinine of >4.0
mg/dL [>350 micromol/L]) or rapidly declining kidney function.
■ Positive anti-glomerular basement membrane (anti-GBM) autoantibody.
■ Pulmonary hemorrhage complicated by respiratory compromise or pulmonary hemorrhage that does not respond rapidly to intravenous
glucocorticoids .
§ Some clinicians treat all patients with organ-threatening or life-threatening GPA or MPA with three days of high-dose intravenous pulse
methylprednisolone before initiating oral glucocorticoids, whereas others only give pulse methylprednisolone to patients with necrotizing or crescentic
glomerulonephritis or pulmonary hemorrhage.

17. Cyclophosphamide-Based Regimen
17
Oral cyclophosphamide dosing:
● Given orally in a dose of 1.5 to 2 mg/kg
per day.
Intravenous cyclophosphamide dosing:
● 15 mg/kg every two weeks for three
doses and then every three weeks for
three to six months.
● Other experts treat with 0.5 g/m2 every
two weeks for three to six months.

18. Rituximab-Based Regimen
Use the dose that was used in the RAVE trial,
specifically 375 mg/m2 per week for four
weeks.
Some investigators use an alternative
regimen, administering 1 g of rituximab
initially followed 14 days later by another 1 g
dose.
18

19. Glucocorticoid Dosing
● Pulse methylprednisolone(7 to 15 mg/kg to a maximum dose of 500 to 1000 mg/day for
three days).
● Oral glucocorticoid therapy, either from day 1 or from day 4 if pulse methylprednisolone is
given, typically consists of 1 mg/kg per day (maximum of 60 to 80 mg/day) of oral
prednisone (or its equivalent).
19

20. Respiratory Tract Involvement
A. Nasal ulcers and crusting: Oral antibiotics are frequently required to treat more severe infections
in the upper respiratory tract, an approach may involve direct application of antibiotic ointment just
inside of the nares and/or nasal irrigation with a saline solution.
A. Tracheal or bronchial stenosis: Airway dilation with or without stenting.
20

21. Maintenance Therapy
Once remission is induced, patients are switched to maintenance therapy usually given for 12 to
24 months with other, often less toxic immunosuppressive modalities, usually azathioprine,
rituximab, mycophenolate mofetil (MMF), or methotrexate.
21

22. Resistant Disease
● Presence of active disease that is organ- or life-threatening despite optimal initial
immunosuppressive therapy with glucocorticoids plus either cyclophosphamide or
rituximab for an "adequate" period of time.
● A progressive decline in renal function.
22

23. Treatment of Resistant Disease
● If the disease is resistant to cyclophosphamide, switch to rituximab.
● If the disease is resistant to rituximab,switch to cyclophosphamide.
● If the disease is resistant to both cyclophosphamide and rituximab, switch to
mycophenolate mofetil.
23

24. Alternative Therapy
● Other drugs, such as mycophenolate mofetil, cyclosporine (or other calcineurin inhibitors),
or trimethoprim-sulfamethoxazole, should only be considered in patients who do not
tolerate or have relative contraindications to conventional therapies.
24

25. Case Report
NCBI
25
A report of a case study of a 52-year-old Bangladeshi man
presented with a history of progressively worsening fever,
recurrent cough, and hemoptysis. He developed renal failure
within a month which was successfully treated with high-
dose steroids, cyclophosphamide, and trimethoprim-
sulfamethoxazole (TMP-SMX). Rapidly progressive
glomerulonephritis can be a fulminant manifestation of GPA,
in which case an immediate and aggressive treatment with
pulse steroids, high-dose cyclophosphamide and TMP-SMX
can be lifesaving.

26. Patient
Education
Clinical Recommendations
And Conclusion
26
● Granulomatosis with polyangiitis is a rare autoimmune
disease of unknown etiology that can affect multiple
organ systems.
● Early diagnosis and treatment of granulomatosis with
polyangiitis might lead to a full recovery. Without
treatment, the condition can be fatal.
● Methotrexate toxicity in patients with reduced renal
function, this drug should not be used in patients with
an estimated glomerular filtration rate (eGFR) less than
60.
● Rituximab should generally be avoided in patients who
are positive for hepatitis B surface antigen.
● Azathioprine is the preferred agent for maintenance
therapy in women who want to become pregnant.

27. Related Article to the Topic
Related Article to the topic of interest.
27

28. References
● Up to Date, Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical
manifestations and diagnosis.
● Mayo Clinic, Granulomatosis with polyangiitis Diagnosis and Treatment.
● NCBI, US National Library of Medicine, NAtional Institutes of Health.
28