No abstract

IgG4-RD appears to have a distinctive clinicopathological presentation in the skin, differentiating it from other cutaneous disorders.

IgG4-RD appears to have a distinctive clinicopathological presentation in the skin, differentiating it from other cutaneous disorders.

BackgroundThe adaptor protein Linker for activation of T cell (LAT) is a key signaling hub used by the T cell antigen receptor. Mutant mice expressing loss-of-function mutations affecting LAT and including a mutation in which tyrosine 136 is replaced by a phenylalanine (LatY136F) develop lymphoproliferative disorder involving T helper type 2 effector cells capable of triggering a massive polyclonal B cell activation that leads to hypergammaglobulinemia G1 and E and to non-resolving inflammation and autoimmunity. The purpose of this study was to evaluate whether the phenotypes of LatY136F knock-in mice resemble the immunohistopathological features of immunoglobulin G4-related disease (IgG4-RD).MethodsLatY136F knock-in mice were sacrificed at 4–20 weeks of age, and pancreas, kidney, salivary gland and lung were obtained. All organs were stained with hematoxylin-eosin and with Azan for estimation of collagen in fibrosis, and the severity scores of inflammation and fibrosis were evaluated. Immunostainings were performed to analyze the types of infiltrating cells. In addition, the effects of corticosteroid treatment on the development of tissue lesions and serum levels of IgG1 were assessed.ResultsTissue lesions characterized by inflammatory mononuclear cell infiltration and fibrosis were detected in pancreas, kidney, and salivary gland starting from 6 weeks of age. Immunostainings showed pronounced infiltration of plasma cells, CD4-positive T cells, and macrophages. Infiltrating plasma cells predominantly expressed IgG1. The extent of inflammation in pancreas and salivary glands was markedly reduced by corticosteroid treatment.ConclusionsLatY136F knock-in mice displayed increased production of Th2-type IgG1 (a homologue of human IgG4) and developed multiple organ tissue lesions reminiscent of those seen in patients with IgG4-RD. Moreover, the development of these tissue lesions was highly sensitive to corticosteroid treatment like in IgG4-RD. For these reasons we consider the LatY136F knock-in mouse strain to represent a promising model for human IgG4-RD.

We describe a 60-year-old man with IgG4-related chronic sclerosing dacryoadenitis and sialoadenitis associated with lymphoplasmacytic and eosinophilic infiltration in erythematous nodules. Physical examination revealed left eye extrusion and small itchy nodules on the scalp and neck. The serum IgG level was 1,570 mg/dL, IgG4 463 mg/dL (29.5%), and IgE 4,554 IU/mL. Lacrimal gland biopsy disclosed prominent infiltrates of IgG4-positive plasma cells and scattered eosinophilic infiltrates with fibrosis, consistent with IgG4-related disease. A skin biopsy of a cutaneous nodule demonstrated that the infiltrated plasma cells around arterioles or venules in the deep dermis and subcutaneous fat tissue were strongly positive for IgG4. Although the swollen lacrimal and parotid gland and itchy subcutaneous erythematous nodules improved rapidly with oral prednisolone at a dose of 20 mg per day, the skin, lacrimal, and parotid lesions deteriorated simultaneously during steroid tapering and improved after increasing the dosage. As skin lesions are easy to biopsy, further study of the skin manifestations of IgG4-related disease will be important in further clarifying the clinical spectrum, pathophysiology and response to therapy of this disorder.

Immunoglobulin G4 (IgG4)-related tubulointerstitial nephritis (TIN) is often accompanied by autoimmune pancreatitis (AIP) or chronic sclerosing dacryoadenitis and sialoadenitis. However, IgG4-related TIN without AIP or lacrimal and/or salivary gland lesions has not been well recognized. Here, we report a case of IgG4-related TIN associated with hepatic inflammatory pseudotumor without AIP or lacrimal and/or salivary gland lesions. A 58-year-old Japanese man with epigastralgia underwent contrast-enhanced computed tomography (CT), which revealed multiple low-density lesions in both kidneys and a low density hepatic mass. Laboratory tests showed an extremely high level of serum IgG4. Percutaneous renal and hepatic biopsies showed diffuse infiltration of lymphocytes and IgG4-positive plasma cells with fibrosis in both tissues. Two months after administration of oral prednisolone, both lesions decreased in size on follow-up CT, and the serum creatinine level also improved. No recurrence has been detected for two years with a maintenance dose of prednisolone.

We describe a refractory cutaneous polyarteritis nodosa (CPAN) patient with hepatitis B (HB) carrier status successfully treated with tumor necrosis factor alpha (TNF- blockade, etanercept, and reviewed 5 similar cases. We administered etanercept because of repeated flares despite aggressive therapy.C-reactive protein normalization, prednisolone dose sparing, and absence of any adverse events including HB virus reactivation with nucleotide analogue administration or renal dysfunction have been achieved for 8 months. TNF- blockade should be considered for intractable CPAN.

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