To the Editor: Here, we describe a patient with renal amyloid A (AA) amyloidosis that was apparently associated with IgG4-related disease. A 53-year-old man with long-standing malaise and fatigue had a slow-growing mesenteric mass (5 cm in diameter) that had been present 16 years earlier on the basis of a review of previous imaging studies. (The case had been included in a case series of IgG4-related disease.) In July 2015, the patient had received a diagnosis of mesenteric IgG4-related disease with involvement of surrounding lymph nodes, which had fulfilled international consensus criteria (Fig. 1A and 1B). The only blood abnormalities at that time had been the levels of IgG4 (2500 mg per deciliter) and C-reactive protein (8.4 mg per deciliter) and the erythrocyte sedimentation rate (119 mm per hour).
After therapy with prednisone and azathioprine, both the size of the mass and the levels of inflammatory markers decreased rapidly. However, as the prednisone was being tapered, renal impairment with the nephrotic syndrome developed, as indicated by a creatinine level of 1.9 mg per deciliter (168 μmol per liter), an albumin level of 2.2 g per deciliter, and a ratio of urinary albumin (measured in milligrams per liter) to urinary creatinine (measured in grams per liter) of 10.3. Renal AA amyloidosis was diagnosed on kidney biopsy (Fig. 1C and 1D). Retrospectively, the serum amyloid level from July 2015 had been elevated (350 mg per liter). Treatment with intravenous methylprednisolone and rituximab led to slight decreases in the plasma creatinine level (1.7 mg per deciliter [150 μmol per liter]) and in the ratio of urinary protein to creatinine (8.2) and a substantial decrease in the levels of both C-reactive protein (0.1 mg per deciliter) and serum amyloid (4 mg per liter).
IgG4-related disease is associated with previously unexplained clinical conditions that include idiopathic retroperitoneal fibrosis. It is considered to be a fibroinflammatory disease that is responsive to antiinflammatory therapy, which may prevent fibrosis.3 Various long-standing inflammatory conditions such as autoinflammatory and rheumatic disorders may lead to the deposition of AA amyloid. Serum amyloid and C-reactive protein are both acute-phase proteins that are often elevated during inflammation. The formation of serum amyloid can be expected in IgG4-related disease, with elevations in C-reactive protein in approximately 40% of patients, although the incidence and magnitude of elevated serum amyloid levels remain unknown.
In our patient, the disease appeared to have been dormant for at least 16 years, according to the deduced time that the abdominal mass had been present. However, we speculate that the patient’s long-standing inflammatory state probably contributed to the development of amyloidosis. Chronically elevated serum amyloid levels in inflammatory diseases are associated with AA amyloidosis, but how these levels in patients with IgG4-related disease correlate with organ amyloid depositions is unknown.
In conclusion, AA amyloidosis developed in a patient with IgG4-related disease. It is not known whether the treatment of IgG4-related disease not only ameliorates symptoms but also may modulate inflammatory effects that could potentially lead to secondary amyloidosis.

Additional Metadata
Persistent URL dx.doi.org/10.1056/NEJMc1614275, hdl.handle.net/1765/98000
Journal New England Journal of Medicine
Citation
Karim, F, Clahsen-van Groningen, M.C, & van Laar, J.A.M. (2017). AA Amyloidosis and IgG4-Related Disease. New England Journal of Medicine, 376(6), 599–600. doi:10.1056/NEJMc1614275