Tracking the Trickster, Or: The Confounding Tale of IgG4-RD (Chapter III)


Congratulations! In our last installment, despite the odds, you (presumably) reached the correct verdict: The villain responsible for your patient's misery is indeed IgG4-related disease, not one of the many other suspects. Now, what's the sentence?

Congratulations: You've come to grips with the identity of the culprit in Chapter I of this tale, and despite the odds, you managed to confirm in Chapter II that your patient indeed has IgG4-related disease (and not one of the many false suspects).

Now, how should you proceed?

Predictably, the management of this highly complex disorder varies. However, typically corticosteroids are very effective at the outset.23

A common regimen:  40-60 mg daily for 2 weeks
                                 Taper over 3 months
                                 Sometimes, maintenance low-dose prednisone after taper

About 1/3 to 1/2 of patients will flare following steroid treatment.

For those intolerant of corticosteroids or unable to taper without flaring, numerous steroid-sparing agents (azathiprine, mycophenolate mofetil, methotrexate) have been tried, with limited success.

The best alternative appears to be rituximab.24 Typically patients are able to taper steroids rapidly following rituximab therapy.

Rituximab may also be used in place of steroids as induction therapy, especially for those with less severe disease not requiring urgent treatment.

The regimen:   Two 1-gm infusions, 15 days apart                      

Some patients (it is difficult to predict which ones) require re-treatment after about 6 months. 

Serial measurements may be useful to assess disease activity in those cases where serum IgG4 is elevated. However, this is variable and not always reliable.25

Organ-specific interventions such as ureteral or biliary stents may be necessary initially to manage disease. Often these can be removed when medications take effect.


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3. Ebbo M, Daniel L, Pavic M, et al. IgG4-related systemic disease: features and treatment response in a French cohort: results of a multicenter registry. Medicine (Baltimore) (2012) 91:49-56.

4. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med (2001) 344:732-738.

5. Khosroshahi A, Stone JH. IgG4-related systemic disease: the age of discovery. Curr Opin Rheumatol (2011) 23:72-73.

6. Khosroshahi A, Cheryk L, Carruthers M, et al. Spuriously Low Serum IgG4 Concentrations Caused by the Prozone Phenomenon in IgG4-Related Disease. Arthritis Rheum (2013) 66:213-217.

7. Brenner I, Roth S, Puppe B, et al. Primary cutaneous marginal zone lymphomas with plasmacytic differentiation show frequent IgG4 expression. Mod Pathol (2013) 26:1568-1576.

8. Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders. J Clin Pathol (2011) 237-243.

9. Stone JH, Khosroshahi A, Deshpande V, et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum (2012) 64:3061-3067.

10. Kamisawa T, Chari ST, Lerch MM, et al. Recent advances in autoimmune pancreatitis: type 1 and type 2. Gut (2013) 62:1373-1380.

11. Ferry JA, Deshpande V. IgG4-related disease in the head and neck. Semin Diagn Pathol (2012) 29:235-244.

12.  Khosroshahi A, Carruthers MN, Stone JH, et al.Rethinking Ormond's disease: "idiopathic" retroperitoneal fibrosis in the era of IgG4-related disease. Medicine (Baltimore) (2013) 92:82-91.

13. Stone JR. Aortitis, periaortitis, and retroperitoneal fibrosis, as manifestations of IgG4-related systemic disease. Curr Opin Rheumatol (2011) 23:88-94.

14.  Stone JH, Khosroshahi A, Hilgenberg A, et al. IgG4-related systemic disease and lymphoplasmacytic aortitis. Arthritis Rheum (2009) 60:3139-3145.

15. Stone JH, Khosroshahi A, Deshpande V, Stone JR. IgG4-related systemic disease accounts for a significant proportion of thoracic lymphoplasmacytic aortitis cases. Arthritis Care Res (Hoboken) (2010) 62:316-322.

16. Cheuk W, Chan JK. Lymphadenopathy of IgG4-related disease: an underdiagnosed and overdiagnosed entity. Semin Diagn Pathol (2012) 29:226-234.

17. Saeki T, Kawano M. IgG4-related kidney disease. Kidney Int (2013)

18. Bourlon MT, Sanchez-Avila M, Chable-Montero F, Arceo-Olaiz R. IgG4-Related Autoimmune Prostatitis: Is It an Unusual or Underdiagnosed Manifestation of IgG4-Related Disease? Case Rep Urol (2013) 2013:295472.

19. Ebbo M, Schleinitz N. IgG4-related disease (IgG4-RD). Ann Pathol (2012) 32(5 Suppl):S70-71.

20. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol (2012) 25:1181-1192.

21. Sumimoto K, Uchida K, Mitsuyama T, et al. A proposal of a diagnostic algorithm with validation of International Consensus Diagnostic Criteria for autoimmune pancreatitis in a Japanese cohort. Pancreatology (2013) 13:230-237.

22. Khosroshahi A, Stone JH. Treatment approaches to IgG4-related systemic disease. Curr Opin Rheumatol (2011) 23:67-71.

23. Khosroshahi A, Carruthers MN, Deshpande V, et al. Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Medicine (Baltimore) (2012) 91:57-66.

24. Khosroshahi A, Bloch DB, Deshpande V, Stone JH. Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease. Arthritis Rheum (2010) 62:1755-1762.

25. Nirula A, Glaser SM, Kalled SL, Taylor FR. What is IgG4? A review of the biology of a unique immunoglobulin subtype. Curr Opin Rheumatol (2011) 23:119-124.





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