IgG4 related disease is a rare disease in which cases delayed diagnosis is common. The recent development of diagnostic criteria is helpful for early diagnosis.

1. IgG4 Related Disease:
Case Presentation And
Literature Review
Lanzillotta et al. 2020

2. Why we need to learn and
discuss about IgG4 related
disease?

3. Case summery of Mr. A. Hossain
Photo-taken with permission

4. Case summery
Mr. A Hossain, 30-year-old, has been suffering from recurrent episode of
obstructive jaundice for 2 years. Jaundice was associated with itching but no
history of fever or abdominal pain. No history of ascites. After evaluation,
distal biliary stricture was found on 2019. He underwent ERCP with plastic
biliary stent placement on January 2020 with subsequent resolving of
jaundice. On December 2020, biliary stent was removed. Unfortunately, after
3 months of removing of the stent, his jaundice reappears. This time IgG4
level is done which comes positive (Patient: 330mg/dl, normal value
≤120mg/dl). His IgE level is 1245. CT scan shows pancreato-duodenal groove
pancreatitis(localized) causing biliary obstruction resulting proximal
dilatation. MRCP shows distal biliary stricture.

5. December, 2019
December, 2019
March, 2021
January, 2020
1st episode of jaundice
ERCP with biliary stenting
Biliary stent-removed
Jaundice- reappeared
IgG4-330mg/dl, IgE-
1245
Localized pancreatitis
on CT
Distal biliary stricture
June, 2021
Timeline history

6. IgG4 Related Disease: Literature Review
BMJ 2020;369:m1067 | doi:
10.1136/bmj.m1067

7. IgG4- related disease- Phenotypes
Lanzillotta et al. 2020
31% 24% 24% 22%

8. IgG4- related disease- Diagnosis
Lanzillotta et al. 2020

9. • Serum IgG4: elevate in neoplastic, infectious, and autoimmune
diseases
• Histological examination- mainstay investigation

10. Pathologies associated to serum IgG4 elevation
Cancer Pancreatic adenocarcin, Bile duct
cancer/cholangiocarcinoma,
Intraductal papillary mucinous neoplasm
Autoimmune diseases Systemic lupus erythematosus ,
Antiphospholipid syndrome,
Autoimmune hepatitis, Rheumatoid
arthritis, Systemic sclerosis, Sjögren's
syndrome, Polymyositis/dermatomyositis
ANCA-related vasculitis Churg-Strauss syndrome*, Behcet's
disease, Microscopic polyangiitis
Infections Parasitic infections, Bacterial infections,
Viral infections
Others Multicentric Castleman's disease*,
Eosinophilic disorders (fasciitis,
pneumonia, and hypereosinophilic
syndrome) , Chronic hepatitis, Liver
(doi: 10.1155/2012/602809)

11. All of the above type
Lanzillotta et al. 2020

12. IgG4- related disease- treatment response
Lanzillotta et al. 2020

13. IgG4- related disease- Outcome
Lanzillotta et al. 2020

14. • Rituximab is the most widely used biological agent in IgG4-RD and
allowing early tapering of glucocorticoid therapy.

15. Traditional potential biomarkers of IgG4 related disease
(IgG4-RD)
Lanzillotta et al. 2020

16. Biomarkers for disease activity
Lanzillotta et al. 2020

17. Lanzillotta et al. 2020
Novel potential biomarkers of IgG4 related disease (IgG4-RD)

18. A: abdominal computed tomography scan showing a “sausage-like”
pancreas (*) with a surrounding rim of hypodense
tissue (arrowheads), classic radiological features of autoimmune
pancreatitis.
Lanzillotta et al. 2020

19. Hegade VS et al. Frontline Gastroenterology 2019;10:275–283.

20. Hegade VS et al. Frontline Gastroenterology 2019;10:275–283.

21. D-F: classic histopathological and immunohistochemical features of IgG4-RD in a pancreatic biopsy:
areas of storiform fibrosis (*; (D);, sequential sections shows an IgG4/IgG ratio >40%(E)
Hematoxylin and eosin(D) Immunohistochemistry for IgG4 and IgG (E)
E
Lanzillotta et al. 2020

22. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease (DOI 10.1002/art.41120)

23. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease (DOI 10.1002/art.41120)

24. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease (DOI 10.1002/art.41120)

25. Step 1. Entry criteria Yes† or No
Characteristic* clinical or radiologic
involvement of a typical
organ (e.g., pancreas, salivary glands, bile
ducts, orbits,
kidney, lung, aorta, retroperitoneum,
pachymeninges, or
thyroid gland [Riedel’s thyroiditis]) OR
pathologic evidence
of an inflammatory process accompanied
by a lympho-plasmacytic infiltrate of
uncertain etiology in one of these
same organs
The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease (DOI 10.1002/art.41120)

26. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease (DOI 10.1002/art.41120)

27. QUESTIONS ABOUT MR. HOSSAIN’S
CONDITION
•How many points our
patient get?
Is there anything else that can
we do for
further evaluation?
1. IgG4 2.5 times high- 6points
2. Localized(?) pancreatic involvement+ Biliary
tree involve- 19 points
Total: 25 points (more thant 20
points
meets the criteria)

28. Thank You

29. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease (DOI 10.1002/art.41120)

30. Timeline:
1st episode of jaundice-2019
MRCP(2019)- Biliary stricture
January, 2020- ERCP with stent placement
December, 2020- stent is removed
Reappear jaundice on March-2021

31. • Compared with white patients, Asian patients are at higher risk of
developing IgG4-RD in the head and neck region
• Patients with head and neck involvement also seem to more often have
atopic manifestations
• Patients with Mikulicz’s/systemic disease have more organs involved,
higher values of IgG4-RD responder index (RI), and serum IgE
concentrations.
• Patients with retroperitoneal and head and neck involvement seem more
prone to have a fibrotic outcome than do those with other IgG4-RD
phenotypes, and are thus more challenging to treat

32. • Induction of remission Glucocorticoids Glucocorticoids represent the first line agent for inducing remission in
all patients with active IgG4-
RD.21 Induction of remission should aim to resolve symptoms and biochemical and radiological
abnormalities, and improvement should typically be observed within days to several weeks
• The starting dose of corticosteroids typically consists of 30- 40 mg/day (0.6-1 mg/kg) of prednisone or
steroid equivalent.105 110 One retrospective study and one randomized controlled trial reported no
differences in terms of remission rate between patients with IgG4- RD treated with high dose (0.8-1 mg/kg)
and medium dose (0.5-0.6 mg/kg) corticosteroids
• Immunosuppressive drugs
When predictors of relapse—such as multi-organ
involvement, elevation of serum IgG4 and IgE at
baseline, and peripheral blood eosinophilia—are
present, disease modifying anti-rheumatic drugs
(DMARDs) can be added to first line steroid therapy
to improve the likelihood of obtaining disease
remission. Azathioprine, mycophenolate mofetil,
methotrexate, leflunomide, tacrolimus, ciclospor

33. Available therapeutic strategies for inducing and
maintaining remission of IgG4 related disease
(IgG4-RD)
Lanzillotta et al. 2020

34. Available therapeutic strategies for inducing and
maintaining remission of IgG4 related disease
(IgG4-RD)
Lanzillotta et al. 2020

35. Available therapeutic strategies for inducing and
maintaining remission of IgG4 related disease (IgG4-
RD)
Lanzillotta et al. 2020

36. Established, emerging, and novel potential biological therapies for IgG4 related disease
Lanzillotta et al. 2020

37. Novel diagnostic biomarkers
• Increased ratios of serum IgG4 to total IgG (>10%)
• IgG4:IgG RNA ratio on peripheral blood seemed to accurately
distinguish IgG4 related cholangitis from hepatobiliary malignancies
and inflammatory processes
• Multicolor flow cytometry, next generation sequencing, and gene
expression analyses led to the identification of disease specific B cell
and T cell

38. • FDG-PET: fluorodeoxyglucose- positron emission topography