A CASE OF LYSOZYME-INDUCED NEPHROPATHY WITH SARCOIDOSIS

Lysozyme-associated nephropathy (LyN) is a rare cause of kidney injury in patients with leukemia, especially chronic myelomonocytic leukemia (CMML). However, only a few cases of LyN have been reported in diseases other than CMML. We herein report a 74-year-old woman with sarcoidosis complicated by lysozyme-induced nephropathy.

The patient was a 74-year-old woman with a history of scleroderma. At age 61, she developed bilateral wrist pain and Raynaud’s phenomenon. The laboratory test was positive for anti-centromere antibodies, leading to a diagnosis of localized scleroderma. Oral steroid therapy was initiated and subsequently tapered and discontinued at age 72.
 At age 72, her chest CT revealed nodular lung lesions, and a transbronchial lung biopsy confirmed sarcoidosis. She also developed uveitis and nodular erythema, consistent with systemic sarcoidosis. At that time, her serum creatinine (Cr) was 0.8 mg/dL.

At 74 years of age, she was asymptomatic but had an elevated serum Cr level of 1.75 mg/dL and was referred to our hospital. Physical examination revealed no edema and other notable findings. Laboratory data showed: blood urea nitrogen 15 mg/dL, Cr 1.38 mg/dL, total protein 7.1 g/dL, and albumin 3.9 g/dL. Urinalysis showed 24-hour urine protein 0.16 g/day, red blood cell <1/high-power field (HPF), white cell 5–9/HPF, and urinary N-acetyl-β-D-glucosaminidase 21.2 U/L. A kidney biopsy was performed to investigate the cause of kidney dysfunction.

Her kidney biopsy demonstrated granulomatous and interstitial nephritis. The granulomas were noncaseating and contained multinucleated giant cells surrounding laminated calcifications (Schaumann bodies), consistent with renal sarcoidosis (Figure a). In addition, electron microscopy revealed numerous membrane-bound vacuoles within proximal tubular cells (Figure b), suggestive of LyN. On light microscopy, proximal tubular epithelial cells contained patchy, round, eosinophilic protein droplets on hematoxylin and eosin staining. These droplets were positive with periodic acid–Schiff staining (Figure c) and were positive with lysozyme (Figure d). Additional blood testing revealed an elevated serum lysozyme level of 24.0 μg/mL (reference range: 5.0–10.2 μ g/mL). Collectively, these findings suggested the diagnosis of LyN.

LyN is typically associated with CMML but has rarely been reported in sarcoidosis.
Lysozyme is a type of enzyme. As it is small in size, it freely passes through the glomerular filtration barrier and is reabsorbed by proximal tubular cells. Excessive amounts of lysozyme can lead to tubular injury and LyN. 

Although CMML is a well-known cause of lysozyme overproduction, elevated lysozyme levels are also seen in sarcoidosis, tuberculosis, and inflammatory bowel disease. A previous report indicated that 76% of LyN cases were associated with CMML, whereas 3% were associated with sarcoidosis, and serum lysozyme levels were elevated in all cases. This case also showed elevated serum lysozyme levels and fulfilled the pathological features of LyN. 

Schaumann bodies can be seen in granulomatous diseases, particularly sarcoidosis. Although only a few reports describe them in renal sarcoidosis, this case presented Schaumann body in the kidney.

This case highlights that renal sarcoidosis may also present with the Schaumann bodies and can develop LyN.