, David G. I. Scott2 and Chetan Mukhtyar2
(1)
Department of Rheumatology, Ipswich Hospital NHS Trust, Ipswich, UK
(2)
Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK
20.1 Introduction
Peripheral levels of IgG4 were seen to be elevated in patients with cystic fibrosis and atopic dermatitis in the 1970s [1, 2]. Shakib et al. hypothesized that this phenomenon implicated the role of IgG4 in immediate type hypersensitivity disorders. Raised IgG4 levels in the context of a vasculitis syndrome were demonstrated in the 1980s [3, 4]. The term ‘IgG4 related autoimmune disease’ was first proposed by Kamisawa et al. when referring to autoimmune pancreatitis and its related diseases [5]. Retroperitoneal fibrosis in 2002 [6], and subsequently aortitis in 2008 [7] have been recognised to be part of the spectrum of this multi-organ disease.
20.2 Definition and Classification
As a relatively newly described condition, there is no recognised definition or classification criteria. It is accepted that this condition is a result of lymphoplasmacytic infiltration of tissues with IgG4 positive plasma cells resulting in ‘storiform’ fibrosis and obliterative phlebitis.
20.3 Epidemiology
There are no reliable figures for the incidence of this condition due to inconsistency of nomenclature. The majority of literature around this condition has emerged from Japan, and therefore it is thought to be commoner in the Japanese. Various features of IgG4 related disease may have different gender predisposition. Ophthalmopathy appears to have equal gender distribution [8], but non-head and neck manifestations appear to be predominantly in men in the sixth and seventh decades of life [9].
20.4 Aetiology
The aetiology is unknown. There is evidence of immune complex deposition in cases with autoimmune pancreatitis [10]. No autoantigenic target has been isolated. Allergy and hypersensitivity may have a role to play. IgG4 has long been thought to play a role in allergic tolerance [11]. Several HLA and non-HLA genes have been associated with IgG4 related disease [12].
20.5 Clinical Features
IgG4 related disease has been recognised in a large number of sites.
20.5.1 Ocular Disease
Unilateral or bilateral proptosis due to retro-orbital pseudotumour can occur. Lacrimal gland inflammation will cause periorbital swelling and dry eyes.
20.5.2 Salivary Gland Involvement
Unilateral or bilateral salivary gland enlargement with sicca syndrome can be a feature. A proportion of patients who fulfil the classification criteria for Sjogren’s syndrome have been shown to have elevated IgG4 levels [13].
20.5.3 Thyroid Involvement
This can present either as Reidel’s thyroiditis or Hashimoto’s thyroiditis.
20.5.4 Pulmonary Involvement
Cases may present with a chronic cough, haemoptysis, dyspnoea or pleuritic chest pain. Fibrotic lung or pleural disease may occur. The radiological appearances may be discrete nodular or diffuse interstitial. Honeycombing and ground-glass changes can be seen.
20.5.5 Aortic and Periaortic Involvement
20.5.6 Pancreatico-Biliary Involvement
Autoimmune pancreatitis can present with a pancreatic mass or painless jaundice. It may present as diabetes mellitus. Sclerosing cholangitis due to IgG4 related disease may be difficult to differentiate from primary sclerosing cholangitis or cholangiocarcinoma. The cholangiopathy almost never occurs before pancreatic involvement.
20.5.7 Urological Involvement
Tubulointerstitial nephritis may present with renal function or urinary abnormalities. Obstructive uropathy due to retroperitoneal fibrosis may occur. Prostatitis has been described.
20.6 Laboratory Features
20.6.1 Haematology Tests
The full blood count is consistent with acute phase response. The erythrocyte sedimentation rate is usually significantly elevated. Circulating levels of plasmablasts are elevated. This may serve as a biomarker of disease activity.
20.6.2 Serum Biochemistry
Obstructive liver function may be suggestive of pancreatico-biliary involvement. Renal function may be impaired due to tubulo-interstitial nephritis or obstructive uropathy.
20.6.3 Immunology
20.6.4 Urine Analysis
Asymptomatic proteinuria may be a sign of tubulointerstitial nephritis.
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