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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2016  |  Volume : 27  |  Issue : 3  |  Page : 602-605
Anti-neutrophil cytoplasmic antibody negative crescentic paucimmune glomerulonephritis in a case of scleroderma with systemic lupus erythematosus overlap


1 Department of Pathology, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Medicine, Armed Forces Medical College, Pune, Maharashtra, India

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Date of Web Publication13-May-2016
 

   Abstract 

Renal Involvement in scleroderma is a known problem and the manifestations are well described. Renal involvement in systemic lupus erythematosus (SLE) is also well known. However, in scleroderma and SLE overlap syndrome, the renal findings may vary being a combination of features of immune complex mediated glomerulonephritis as well as thrombotic microangiopathy. We report a case in which the renal manifestation in such a situation was of a focal necrotising pauci-immune glomerulonephritis with crescents, anti-neutrophil cytoplasmic antibody negative. To the best of our knowledge, such manifestations have not been described before. Renal dysfunction in a normotensive setting in such a case should direct one towards evaluation for other causes and should prompt a kidney biopsy. This would be valuable in delineating the pathological process in the kidney and would help in guiding therapy.

How to cite this article:
Tewari R, Badwal S, Kumar A, Subramaniam S, Nijhawan V S, Srinivas V. Anti-neutrophil cytoplasmic antibody negative crescentic paucimmune glomerulonephritis in a case of scleroderma with systemic lupus erythematosus overlap. Saudi J Kidney Dis Transpl 2016;27:602-5

How to cite this URL:
Tewari R, Badwal S, Kumar A, Subramaniam S, Nijhawan V S, Srinivas V. Anti-neutrophil cytoplasmic antibody negative crescentic paucimmune glomerulonephritis in a case of scleroderma with systemic lupus erythematosus overlap. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2019 Nov 17];27:602-5. Available from: http://www.sjkdt.org/text.asp?2016/27/3/602/182439

   Introduction Top


Renal involvement in scleroderma is a known problem and the manifestations are well des- cribed. They include the presence of a severe thrombotic microangiopathy with glomeruli showing fibrin thrombi, endothelial swelling and fibrinoid necrosis. Associated tubular injury in the form of acute tubular necrosis or tubular atrophy may be present. The clinical manifes-tation is usually as a new onset malignant hypertension with elevated serum creatinine and acute renal failure. Overlap of scleroderma with systemic lupus erythematosus is also known and the renal lesions are well described. We describe such a case of overlap syndrome with differing renal manifestations.


   Case Report Top


A 28-year-old woman, resident of Maharashtra, India, presented with history of Raynaud's phe- nomenon, progressive darkening and tightening of skin (left > right), restricted mouth opening, dysphagia (especially to solids), polyarthral- gia, recurrent oral ulcers and diffuse hair loss from scalp. On clinical examination she had pallor, induration and hyperpigmentation of limbs, sclerodactyly with fixed flexion defor- mities in fingers of left hand, ulcers in buccal mucosa, diffuse alopecia, restricted mouth opening (2 fingers) and chest expansion of 2 cm. Her systemic examination was essentially normal.

Laboratory investigations showed normocytic normochromic anemia. Urine examination showed microscopic hematuria and 24 h uri- nary protein of 400 mg/day. Serum creatinine was 2.9 mg/dL. Liver function tests were within normal range. Immunological work up re- vealed anti-nuclear antibody and anti-double stranded DNA positive, anti-centromere anti- body: 1.56 µ/mL (normal<3.0 µ/mL), SCL-70:

2.53 U/mL (normal<3.00 U/mL), anti Sm antibody: 97.94 IU/L (>15 IU/L positive) and anticardiolipin antibodies (IgG) positive. ELISA for anti-neutrophil cytoplasmic anti- body (ANCA) was negative.

In view of the presence of connective tissue disorder with an active urinary sediment and mild renal dysfunction, a renal biopsy was performed. Biopsy showed focal necrotizing glomerulonephritis with crescents [Figure 1]a and some healed glomerular lesions. A single glomerulus showed presence of glomerulitis with disruption of the bowmans capsule, peri- glomerular inflammation and granuloma for-mation with giant cells [Figure 1]b. There was no glomerular proliferation or capillary wall thickening noted. Tubular interstitial com- partment showed mild degree of tubular atro- phy and interstitial fibrosis. Blood vessels were thickened; however, there were no fea- tures to suggest thrombotic micoangiopathy. There was no vasculitis or arterial fibrinoid necrosis noted. Immunofluorescence studies were negative for IgG, IgA, IgM, C3 and C1q in the glomeruli, tubules and vessels.
Figure 1. (a) Glomerulus showing a cellular crescent and near normal features in the capillary tuft (H and
E, ×40), (b) glomerulus showing glomerulitis (disruption of the Bowmans capsule) with periglomerular
lymphoplasmacytic infiltrate with granuloma formation and giant cells (PAS, ×40)


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Considering the possibility of a coexisting ANCA associated vasculitis, ANCA status was reassessed which was found negative at presentation and also after six months of follow-up.

She was diagnosed as a case of scleroderma with systemic lupus erythematosus (SLE) overlap syndrome with features on biopsy suggestive of focal necrotizing glomerulo- nephritis with crescents (ANCA negative).

She was started on oral prednisolone 40 mg OD, mycophenolate mofetil 500 mg BD, hydroxylchloroquine 200 mg BD. She was stabilised on this treatment and discharged and is on follow-up.


   Discussion Top


Scleroderma and SLE overlap comes under the gamut of mixed connective tissue disease. Renal manifestations in this setting were con- sidered to be rare earlier, but subsequently it was shown that it may occur in 10-26% of adults and 33-50% of children.[1]The glome- rular lesions usually resemble those seen in SLE with a predominance of membranous lesions. The vascular lesions noted are akin to those seen in scleroderma. Clinical renal disease was reported in 16 (64%) of 25 such cases in a study from Japan.[2]Membranous nephropathy was most common (40%), fol- lowed by mesangial proliferative (7%) and membranoproliferative (7%) glomeruloneph- ritis. No obvious glomerular lesion were seen in nine out of the 25 cases. Arterial intimal thickening was a common finding, even in patients without glomerular disease.

Our case showed the presence of focal necro- tizing glomerulonephritis with crescents and healed necrotizing lesions. Any features to suggest an immune complex mediated glome- rulonephritis (as in SLE), or vascular lesions (suggestive of scleroderma renal crisis) were distinctly absent with negative staining on immunofluorescence, thereby confirming a pauci immune etiology. Such manifestations in systemic sclerosis and SLE overlap are rare. An earlier report showed the presence of ANCA positive crescentic glomerulonephritis in scleroderma.[3]A study by Endo et al showed ANCA positivity in six of 100 consecutive Japanese patients with systemic sclerosis.[4]They concluded that ANCA is marker for a subset of systemic sclerosis patients with normotensive renal dysfunction.

ANCA negativity is a known feature in crescentic paucimmune glomerulonephritis and may be seen in up to 10% of cases.[5]In that study, the histological findings in the ANCA negative and the ANCA positive groups were also shown to be comparable. ANCA negative pauci immune necrotizing glomerulonephritis with crescents in a setting of systemic sclerosis and SLE overlap syndrome has never been reported, according to the best of our know- ledge.

Our case also showed the presence of peri- glomerular granulomas, which are a finding in crescentic glomerulonephritis seen in both anti glomerular basement membrane (GBM) di- sease as well as ANCA associated vasculitis. They have been shown to be more specific for myeloperoxidase ANCA associated vasculitis rather than in anti-GBM disease.[6]However, others have also reported the presence of peri- glomerular granulomas in anti-GBM disease without ANCA.[7],[8]These granulomas have never been reported in either scleroderma or SLE or an overlap syndrome. The cells in- volved in this granuloma formation are blood derived monocytes which accumulate as macrophages and which when properly acti- vated are able to produce an arsenal of che- mical mediators with differing properties.[3]

To conclude, renal manifestations in systemic sclerosis and SLE overlap syndrome may be varied. Renal dysfunction in a normotensive setting in such a case should direct one towards evaluation for other causes and should prompt a kidney biopsy. This would be valua-ble in delineating the pathological process in the kidney and would help in guiding therapy.



 
   References Top

1.
Kitridou RC, Akmal M, Turkel SB, Ehresmann GR, Quismorio FP Jr., Massry SG. Renal in- volvement in mixed connective tissue disease: A longitudinal clinicopathologic study. Semin Arthritis Rheum 1986;16:135-45.  Back to cited text no. 1
    
2.
Sawai T, Murakami K, Kurasono Y. Morpho- metric analysis of the kidney lesions in mixed connective tissue disease (MCTD). Tohoku J Exp Med 1994;174:141-54.  Back to cited text no. 2
    
3.
Rastaldi MP, Ferrario F, Crippa A, et al. Glomerular monocyte-macrophage features in ANCA-positive renal vasculitis and cryo- globulinemic nephritis. J Am Soc Nephrol 2000;11:2036-43.  Back to cited text no. 3
    
4.
Endo H, Hosono T, Kondo H. Antineutrophil cytoplasmic autoantibodies in 6 patients with renal failure and systemic sclerosis. J Rheumatol 1994;21:864-70.  Back to cited text no. 4
    
5.
Eisenberger U, Fakhouri F, Vanhille P, et al. ANCA-negative pauci-immune renal vasculitis: Histology and outcome. Nephrol Dial Transplant 2005;20:1392-9.  Back to cited text no. 5
    
6.
Rutgers A, Slot M, van Paassen P, et al. Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase- ANCAs in crescentic glomerulonephritis. Am J Kidney Dis 2005;46:253-62.  Back to cited text no. 6
    
7.
Bajema IM, Hagen EC, Ferrario F, et al. Renal granulomas in systemic vasculitis. EC/BCR Project for ANCA-Assay Standardization. Clin Nephrol 1997;48:16-21.   Back to cited text no. 7
    
8.
Ohashi N, Sugiura T, Isozaki T, Yamamoto T, Hishida A. Anti-glomerular basement membrane antibody-induced glomerulonephritis with periglomerular granulomatous reaction and massive renal eosinophilic infiltration. Am J Kidney Dis 2003;42:E28-35.  Back to cited text no. 8
    

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Correspondence Address:
Rohit Tewari
Department of Pathology, Armed Forces Medical College, Pune - 411 040, Maharashtra
India
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DOI: 10.4103/1319-2442.182439

PMID: 27215259

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