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IgG4 disease

Etiology: associated disorders - hypertrophic pachymeningitis - lymphocytic hypophysitis - Mikulicz syndrome - dacryoadenitis - Kuttner tumor - Riedel thyroiditis - aortitis - autoimmune pancreatitis (recurrent pancreatitis) - retroperitoneal fibrosis (Ormond disease) - tubulointerstitial nephropathy - sclerosing cholangitis Epidemiology: - male/female ratio: 2:1 [14] Pathology: - biopsy (other than lymph node) - dense lymphocytic infiltrate - abundant IgG4 producing plasma cells in tissue - storiform fibrosis - obliterative phlebitis - organ enlargement, fibrosis, dysfunction - mild tissue eosinophilia - increased numbers of IgG4-positive plasma cells - IgG4 antibodies are generally regarded as noninflammatory; there is no evidence that they are directly pathogenic [3] Clinical manifestations: - inflammation & enlargement of - pancreas (autoimmune pancreatitis) thus abdominal pain - lymph nodes (lymphadenopathy) - salivary glands - Mikulicz syndrome - salivary gland inflammation & enlargement, xerostomia - parotid gland enlargement, parotitis - lacrimal gland inflammation (dacryoadenitis) - Kuttner tumor (submandibular glands) - kidney (tubulointerstitial nephropathy) - inflammation of periaortic region (idiopathic aortitis) leading to retroperitoneal fibrosis - retroperitoneal involvement in 20% [6] - dermatitis (rash, skin lesions) - hypertrophic pachymeningitis (headache) - lymphocytic hypophysitis - Riedel thyroiditis [2] - orbital inflammatory mass (orbital pseudotumor) - sclerosing cholangitis - lung & pleural involvement in 15-54% [6] - clinical consequences of hypertrophy & mass effect of organ enlargement, pseudotumor, adenopathy ... - night sweats, weight loss [8] * case report of 36 year old woman presenting with pneumonia [5] * case report of 57 year old woman [8] Laboratory: - IgG4 in serum increased in 70% of cases [2] - positive predictive value = 34% - staining for IgG4 producing plasma cells - serum IgE may be elevated - complete blood count - eosinophilia [2] Special laboratory: - CT-guided biopsy with immunohistochemical staining for plasma cells & immunoglobulins (see Laboratory:) Radiology: - computed tomography - ultrasound Complications: - periaortic mass lesion obstructing ureters Management: - prednisone for autoimmune pancreatitis & sclerosing cholangitis [2] - rituximab [3]

Related

autoimmune pancreatitis; lymphoplasmocytic sclerosing pancreatitis

General

autoimmune disease syndrome

References

  1. Carruthers MN et al. The diagnostic utility of serum IgG4 concentrations in IgG4- related disease. Ann Rheum Dis 2015 Jan; 74:14. PMID: 24651618 http://ard.bmj.com/content/74/1/14 - Fox RI, Fox CM. IgG4 levels and plasmablasts as a marker for IgG4-related disease (IgG4-RD). Ann Rheum Dis 2015 Jan; 74:1. PMID: 25477133 http://ard.bmj.com/content/74/1/1
  2. Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018.
  3. Mahajan VS, Mattoo H, Deshpande V, Pillai SS, Stone JH. IgG4-related disease. Annu Rev Pathol. 2014;9:315-47 PMID: 24111912
  4. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012 Feb 9;366(6):539-51 PMID: 22316447
  5. Khosroshahi A, Digumarthy SR, Gibbons FK, Deshpande V. CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 34-2015. A 36-Year-Old Woman with a Lung Mass, Pleural Effusion, and Hip Pain. N Engl J Med. 2015 Oct 29;373(18):1762-72 PMID: 26510025
  6. Rothaus C A Woman with a Lung Mass. Now@NEJM. October 30th, 2015 http://blogs.nejm.org/now/index.php/a-woman-with-a-lung-mass/2015/10/30/
  7. Saeki T, Kawano M. IgG4-related kidney disease. Kidney Int. 2014 Feb;85(2):251-7. PMID: 24107849
  8. Monach PA, Stone JH, Sharma A, Nazarian RM. Case 6-2017 - A 57-Year-Old Woman with Fatigue, Sweats, Weight Loss, Headache, and Skin Lesions. N Engl J Med 2017; 376:775-786. February 23, 2017 PMID: 2822568 http://www.nejm.org/doi/full/10.1056/NEJMcpc1613461
  9. 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 Mar;92(2):82-91. PMID: 23429355 Free PMC Article
  10. ARUP Consult IgG4-Related Disease - IgG4-RD https://arupconsult.com/content/igg4-related-disease
  11. Zhang P, Cornell LD. IgG4-Related Tubulointerstitial Nephritis. Adv Chronic Kidney Dis. 2017 Mar;24(2):94-100. Review. PMID: 28284385
  12. de la Fuente J, Bird J Coronary Arteritis in IgG4-Related Disease. N Engl J Med 2019; 380:2156. May 30, 2019 PMID: 31141636 https://www.nejm.org/doi/full/10.1056/NEJMicm1809588
  13. NEJM Knowledge+ Complex Medical Care - Khosroshahi A, Wallace ZS, Crowe JL et al International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol. 2015 Jul;67(7):1688-99. PMID: 25809420 Review. - Umehara H, Okazaki K, Kawa S et al Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare (MHLW) Japan. The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD. Mod Rheumatol. 2021 May;31(3):529-533. PMID: 33274670
  14. Jha I, McMahon GA, Perugino CA et al Sex as a predictor of clinical phenotype and determinant of immune response in IgG4-related disease: a retrospective study of patients fulfilling the American College of Rheumatology-European League Against Rheumatism classification criteria. Lancet Rheumatology. 2024 May 30 PMID: 38824935 PMCID: PMC11214762 (available on 2025-07-01) https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(24)00089-4/abstract