Nephrotic syndrome in a patient with renal amyloidosis due to polyangiitis overlap syndrome

Atsushi Komatsuda, Hirotaka Kimura, Yoshikazu Ichikawa, Hiroshi Ohtani, Hideki Wakui and Hirokazu Imai

Third Department of Internal Medicine, Akita University School of Medicine, Akita, Japan

Keywords: polyangiitis overlap syndrome; renal amyloidosis

Introduction

Systemic vasculitides are classified by the size of affected blood vessels [1]. However, some patients have overlapping features of common forms of systemic vasculitis. Leavitt and Fauci proposed the entity of polyangiitis overlap syndrome (POS) [2]. While systemic vasculitis can cause secondary amyloidosis, there are few well-documented case reports of secondary renal amyloidosis in patients with POS. Here we present a patient with nephrotic syndrome due to renal amyloidosis caused by POS.

Case

A 26-year-old woman was admitted to the hospital on 14 February 2000, because of right facial pain and leg oedema. In 1989, she had acute cholecystitis, and cholecystectomy was performed. Histological examination of the gall bladder showed marked lymphoid hyperplasia without vasculitis. In 1995, she was diagnosed with acute idiopathic interstitial pneumonia, and was treated with methyl-prednisolone (m-PSL) pulse therapy (500 mg/day for 3 days) followed by oral PSL therapy (40 mg/day). It improved completely after treatment. In 1998, she suffered from high-grade fever and abdominal pain. As the angiogram showed occlusions of left upper pulmonary artery and a narrowing of rectal artery without aneurysm, she was diagnosed with pulmonary and rectal arteritis (Figure 1Go). She was treated with m-PSL pulse therapy (500 mg/day for 3 days) followed by oral PSL therapy (40 mg/day). These symptoms improved, and the angiogram 3 months after treatment demonstrated the complete resolution of polyarteritis. PSL was tapered to 10 mg, and the level of C-reactive protein (CRP) was less than 0.3 mg/dl. From August 1999, her blood chemistry showed an elevation of CRP. She had right facial pain and bloody rhinorrhoea from November 1999. At this time, proteinuria was observed, and progressed to nephrotic syndrome. She had no history of bronchial asthma and eosinophilia during the course.



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Fig. 1.  (A) Pulmonary angiogram shows complete occlusions of left upper pulmonary artery. (B) Inferior mesenteric artery angiogram shows narrowing of rectal artery.

 
On admission, a physical examination revealed right facial swelling and pitting oedema in both legs. Ophtalmoscopic examination demonstrated bilateral uveitis. The lungs, heart, and the neurologic examination were normal.

CRP was 7.1 mg/dl and serum amyloid A (SAA) 1360 µg/ml (less than 8 µg/ml). The erythrocyte count was 423x104/µl, haemoglobin 10.9 g/dl, haematocrit 35.6%, leukocyte count 12100/µl (neutrophils 70%, monocytes 11%, eosinophils 2%, lymphocytes 17%), and platelet count 55.6x103/µl. The total urinary protein (UP) for 24 h was 5.0 g. The serum total protein (TP) was 6.2 g/dl, albumin 3.0 g/dl, blood urea nitrogen (BUN) 9.0 mg/dl, and creatinine 0.6 mg/dl. Serum immunoglobulins were normal. The rheumatoid factor, ANA, PR-3, MPO-ANCA, and cryoglobulins were negative. Serum complements were within normal limits. Circulating immune complexes were not detected. Soluble interleukin-2 receptor was 109 U/ml (135–483 U/ml). A chest CT scan showed nodules with small satellite lesions in the left upper lobe. Cultures of sputa were negative. A head MRI showed a tumourous lesion with bone destruction in the right maxillary sinus (Figure 2Go).



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Fig. 2.  Magnetic resonance imaging of the head shows a high signal-intensity tumour with bone destruction in the right maxillary sinus on T1 weighted image.

 
A maxillary sinus biopsy showed marked lymphoid hyperplasia without granuloma. A renal biopsy revealed that Congo-red positive homogenous materials were deposited in glomeruli. There was no evidence of necrotizing glomerulonephritis or granuloma. Immunofluorescent studies revealed AA amyloid deposition along the walls of arterioles and mesangial areas. On electron microscopy, many fine amyloid fibrils were observed in mesangial area and the subendothelial space of glomerular capillary walls (Figure 3Go). From these findings, the patient was diagnosed with secondary amyloid nephropathy due to POS.



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Fig. 3.  Electron microscopy displays mesangial and subendothelial deposits of amyloid fibrils (lead citrate and uranyl acetate stain). The bar represents 2 µm. (Inset) High magnification electron microscopy also shows fine fibrillar structures of amyloid deposits. The bar represents 0.5 µm.

 
She was treated with oral PSL (40 mg/day) and cyclophosphamide (100 mg/day) for 4 weeks, and then the drugs were reduced. The total UP for 24 h was less than 1.0 g from December 2000. In May 2001, the serum TP was 5.3 g/dl, albumin 3.4 g/dl, BUN 11.3 mg/dl, creatinine 0.6 mg/dl, and PSL and cyclophosphamide were reduced to 15 and 50 mg/day, respectively.

Discussion

Our patient had experienced various diseases including cholecystitis, interstitial pneumonia, and polyarteritis, and then suffered from sinusitis, pulmonary consolidation, uveitis, and nephrotic syndrome caused by secondary amyloidosis. The clinicopathologic characteristics do not fit into any distinct forms of systemic vasculitis. The clinical manifestations of our patient may mimic those of Wegener's granulomatosis (WG) [3]. However, we could not find necrotizing granulomatous vasculitis on biopsy of the maxillary sinus and kidney or PR-3 ANCA in her serum. We therefore could not diagnose WG. Leavitt and Fauci [2] described POS in several patients with systemic vasculitides which do not fit precisely into any classification, but which have overlapping features of classic polyarteritis nodosa, allergic angiitis, and granulomatosis, WG, Takayasu' arteritis, and the hypersensitivity vasculitis. As our patient had various clinicopathological manifestations, which did not fulfil the criteria for distinct systemic vasculitis, we diagnosed her as POS.

In our patient, a renal biopsy showed AA-type amyloidosis. To our knowledge, there are no case reports of renal amyloidosis due to POS. In 1998, our patient had polyarteritis and was treated with PSL. The level of CRP was reduced to the normal range until July 1999. However, the occurrence of secondary amyloidosis indicates that there was a continued production of the precursors of amyloid proteins called SAA, due to polyarteritis. The discrepancy between the level of CRP and that of SAA had been described in patients with SLE, scleroderma, interstitial pneumonia, and vasculitis [4]. It is therefore important for patients with autoimmune diseases including POS, to measure and monitor SAA during the course of the disease.

Gertz and Kyle [5] analysed the cause of death in patients with secondary amyloidosis, and reported that most of these patients died of renal failure or complications of dialysis. Therefore, effective treatment is necessary for patients with secondary amyloidosis. We reported previously that a patient with rheumatoid arthritis (RA) had nephrotic syndrome caused by secondary renal amyloidosis [6]. This patient reached remission of the nephrotic syndrome approximately 18 months after combined treatment with PSL and methotrexate. Several similar cases are described in the literature. It may take 1–3 years to wash out amyloid depositions from injured glomeruli accompanied by RA, as the production of SAA can be suppressed by decreasing RA activity under effective treatment. We therefore need to treat patients with renal amyloidosis complicated by POS for long periods of time to observe a remission.

Notes

Correspondence and offprint requests to: Atsushi Komatsuda, MD, Third Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita city, Akita 010, Japan. Email: komatsud{at}med.akita\|[hyphen]\|u.ac.jp Back

References

  1. Jennette JC, Falk RJ, Andrassy K et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum1994; 37: 187–192[ISI][Medline]
  2. Leavitt RY, Fauci AS. Polyangiitis overlap syndrome. Classification and prospective clinical experience. Am J Med1986; 81: 79–85[ISI][Medline]
  3. Leavitt RY, Fauci AS, Bloch DA et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum1990; 33: 1101–1107[ISI][Medline]
  4. Sasaki T, Tsukamoto S. Erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A. Nippon Naika Gakkai Zasshi1998; 87: 2390–2395[Medline]
  5. Gertz MA, Kyle RA. Secondary systemic amyloidosis: response and survival in 64 patients. Medicine1991; 70: 246–256[ISI][Medline]
  6. Komatsuda A, Morita K, Ohtani H, Yamaguchi A, Miura AB. Remission of the nephrotic syndrome in a patient with renal amyloidosis due to rheumatoid arthritis treated with prednisolone and methotrexate. Am J Kidney Dis1998; 32: E7[Medline]
Received for publication: 11. 8.01
Revision received 29.11.01.



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