2. HISTORY:
22 years old female had history of left upper molar
tooth extraction 1 week back
was admitted with c/o
1.high grade fever
2.difficulty in opening of mouth
3.b/l purulent ear discharge with difficulty in hearing
4.Oral ulcers with gingivitis
5.difficulty in breathing and gurgling sound while
breathing,
6.associated with cough with expectoration,
7.blood tinged sputum,
8.cheek pain, gum pain.
h/o travel to Chennai… for 2 days
3. Pt was admitted with above complaints to outside
hospital where MRI Brain with sinuses done s/o pan
sinusitis.
Started on broad spectrum antibiotics, but not
responding so shifted to RHC for further
management…
No h/o shortness of breath
No h/o headache and vomitting
4. O/E:General
Febrile-102 F
P- 126/min
BP-126/96 mmHg
SpO2-99% on RA
RR-20/min
Pallor +,No Icterus, Cyanosis, Clubbing, Edema,
Lymphadenopathy
Oral examination s/o oral ulcers with necrotising
gingivitis, with candidiasis over hard palate.
Swelling and excessive lacrimation in right eye,evident
conjunctivitis.
No rash.
Pt had toxic look.
5. On Systemic Examination :
CVS-Tachycardia,s1s2 heard
RS-AEBE,B/l conducted sounds
CNS- concious, oriented, no neck rigidity, no FND
P/A-soft, Non Tender, mild hepatosplenomegaly
Maxillary sinus tenderness was present on palpation of
sinuses
Chest X ray-right lower zone patch
USG abdo-moderate hepatosplenomegaly
6.
7.
8. Day-1
PARAMETER VALUES
WBC 18,900 (86.8% neutrophils)
Hb 10.3
PLATELETS 415
TOTAL BILI 0.4
AST 36
ALT 36
CREAT 0.5
BUN 13
BSL(R) 135 mg/dl
9. Started on Meropenem, Clindamycin, and
Fluconazole.
Blood, Urine, Sputum ,Throat Swab Culture were sent
before starting antibiotics.
KOH mount from throat swab was s/o Budding yeast
cells, with Pseudohyphae.
Tropical Fever workup was negative.
10. ENT evaluation was s/o excessive nasal secretion
with intranasal ulcers and blockage of b/l
Nasolacrimal duct. Multiple Oral Ulcers. with Oral
candidiasis. Tonsils were normal. Ear examination was
s/o serous discharge with intact tympanic membrane.
Audiometry was s/o b/l mild conductive hearing loss.
11. Day 2-
HIV and Hepatitis Markers were negative.
VDRL,TPHA were Non reactive
Serum LDH-393
IL-6-146,hsCRP-17.34
Serum Iron-18.0,
TIBC-124,
% saturation-14
C3 C4 complement levels were low.
12. Workup for Congenital Immunodeficiency Syndrome
was sent-the reports were as follows- Lymphopenia
with Low CD4 counts with Maintained CD4/CD8 ratio
IgG-1652.3
IgA-177
IgM-227
All within normal range.
Vit B12 normal
Vit D3 was low
13.
14. Day 3-
Patient was persistently having high grade fever with
extensive cough and breathlessness.
Had repeated post tussive vomitting.
On Auscultation patient developed expiratory wheeze.
X ray Chest repeated, was s/o increase in patch in rt
lower zone with new patchy consolidation in left upper
lobe.
15.
16.
17. Planned for HRCT chest and Abdomen, pelvis
Suspected more of autoimmune, connective tissue
disease
Autoimmune workup was also done.(ANA Blot test)
S/o Borderline positive antihistone antibodies, rest all
antibodies were negative.
18. Day 4:
HRCT chest and abdomen reports were s/o
Multifocal consolidation with central
breakdown in b/l upper and lower lobes.
Cavitation seen in the consolidation of right UL
and ML .Enlarged b/l hilar necrotic lymph
nodes.Hepatosplenomegaly. Focal
Pyelonephritis.
Clinically and Radiologically we suspected as
Wegener’s Granulomatosis.
We did Antineutrophil antibody work up
C-ANCA Reports came out to be positive.
19. Bronchoscopy was done on Day 4 after HRCT chest
BAL and tissue biopsy was taken
Tissue biopsy from the lung parenchyma was
suggestive of heavy infiltrate of
neutrophils,lymphocytes,areas of necrosis,and some
vessels show fibrinoid necrosis.Features s/o
Vasculitis,most likely Wegeners Granulomatosis.
20. Day 5-
Rheumatology opinion was taken.
Started on IV Methyl Prednisolone pulse Therapy 500
mg BD for 3 days.
Planned for Immunotherapy after covering the
infective phase.
Pt was on higher antibiotics, leukocytosis was
persistent.
Gradually after 4 days of antibiotics fever settled,
leukocyte count became normal.
Patient received first dose of Rituximab Therapy.
21. Patient improved clinically.
Fever settled.
Symptomatically improved and shifted to wards
Discharged on oral steroids.
22.
23. WEGENER’S GRANULOMATOSIS
Multisystem disease of unknown etiology characterized
by
• Granulomatous necrotizing small vessel vasculitis of
the upper & lower respiratory tract &
• Glomerulonephritis.
Also called as Granulomatous Polyangiitis.
24.
25. Epidemiology of Wegener’s Granulomatosis :
Is an uncommon disease
Extremely rare in blacks as compared with whites
M:F ratio is 1:1
Mean Age of Onset is ~40 years, But can present at any
age.
Histopathologic hallmark is necrotising vasculitis of
small veins and arteries along with granuloma
formation. Which could be either intravascular or
extravascular.
28. Treatment:
Induction of remission in GPA is approached as
follows:
Cyclophosphamide with high-dose glucocorticoids
(criterion standard)
Rituximab with high-dose glucocorticoids
Methotrexate (oral or subcutaneous) with high-dose
glucocorticoids, in non–organ-threatening or non–life-
threatening GPA[5]
Plasma exchange may be considered in patients with
rapidly progressive renal disease (serum creatinine
level >5.65mg/dL) in order to preserve renal function.
29. Severe/ generalised WG :
Cyclophosphamide with high dose glucocorticoids is the
drug of choice for 3-6 months
Cyclophosphamide : oral 2mg/kg/day/ intermittent IV –
pulsed therapy 15mg/kg every 2wks of first three pulses.
Prednisolone -1mg/kg/day slowly tapered to not less than
15mg/kg/day within first three months then tapered to
10mg/kg/day over 6-18 months
MESNA- given IV to reduce toxic effects of
cyclophosphamide
Pneumocyctis Jiroveci Prophylaxis with TMP-SMZ
Monitor FBC, Urine,add Vitamin D, Ca supplemetns,
Alendronic acid
Mild/Localised WG :
Methotrexate 20-25mg weekly oral/sc + steroids
30. Maintenance of remission :
Once induction of remission has occurred, treatment for
maintenance of remission should be continued for at least
18 months, often longer
Azathioprine (2 mg/kg/day) is safer than, and as effective
as, cyclophosphamide in maintaining remission
Methotrexate (20-25 mg weekly, oral or subcutaneous) has
been used for the maintenance of remission if the serum
creatinine level is less than 1.5 mg/dL
Leflunomide (20-30 mg/day) is as effective as
methotrexate, but it is associated with more adverse effects
31. Mortality :
According to a meta-analysis, with current
treatments, the 5-year survival rate ranges from 74-
79%.(1) The 1 year mortality rate is still high, around
11% (range, 2.225%), depending on disease severity and
the intensity of treatment(2).
(1) Phillip R, Luqmani R. Mortality in systemic vasculitis: a systematic
review. Clin Exp Rheumatol. September-October 2008;26:S94-S104.
[Medline].
(2) ittle MA, Nightingale P, Verburgh CA, et al. Early mortality in
systemic vasculitis: relative contribution of adverse events and active
vasculitis. Ann Rheum Dis. June 2010;69(6):1036-43. [Medline]
32. Relapse :
Relapse is common in GPA. Typically, up to half of patients
with GPA experience relapse within 5 years. (1) The rate (18-
40% at 24 mo) and time to first relapse (15-29 mo) varies.
Factors associated with relapse include treatment (< 10 g of
cyclophosphamide in the first 6 mo, maintaining a high
dose of prednisone [>20 mg/day] for < 2.75 mo, and goal of
0 dose of glucocorticoids), ANCA status at diagnosis, and
target organ involvement (lung involvement, cardiac
involvement, renal involvement, chronic nasal carriage of S
aureus.(2)
(1) Renaudineau Y, Le Meur Y. Renal involvement in Wegener's
Granulomatosis. Clinic Rev Allerg Immunol. October 2008;35:22-29.
[Medline].
(2) Mukhtyar C, Flossmann O, Hellmich B, et al. Outcomes from studies
of antineutrophil cytoplasm antibody associated vasculitis: a systematic
review by the European League Against Rheumatism systemic vasculitis
task force. Ann Rheum Dis. July 2008;67:1004-1010. [Medline].
