Journal of Nephrology & Renal Therapy Category: Clinical Type: Case Report
Antineutrophil Cytoplasmic Antibody Pauci-Immune Crescentic Glomerulonephritis and Interstitial Lung Disease in Scleroderma. Case Report and Literature Review
- Leslie Dubin Kerr1*, Anil Mankee2
- 1 Department Of Medicine And Geriatrics, Icahn School Of Medicine At Mount Sinai, Box 1244, One Gustave L. Levy Place, New York, NY 10029, United States
- 2 Associate Clinical Instructor Ii, University Of The West Indies, Jamaica
*Corresponding Author:Leslie Dubin Kerr
Department Of Medicine And Geriatrics, Icahn School Of Medicine At Mount Sinai, Box 1244, One Gustave L. Levy Place, New York, NY 10029, United States
Received Date: Mar 25, 2016 Accepted Date: Apr 29, 2016 Published Date: May 16, 2016
A total of 29 reports with 47 cases were published (Table 1) [4-32]. We included 8 cases with a history of D-penicillamine use. Six cases were excluded: 1 case complicated by renal cell cancer , a case of arthralgia and GERD but without Raynaud’s or skin changes to suggest scleroderma , a report of vasculitis of the foot without renal involvement , and 3 cases where the renal biopsy findings were not typical of PICGN (extensive deposition of IgG, IgA, IgM and C3 on immunofluorescence , renal biopsy describing glomerular sclerosis rather than Glomerulonephritis (GN) , and a renal biopsy with the overall impression of crescentic GN with granular immune deposits ).
An analysis of the literature including our report of 3 cases reveals 80% of patients were female with a mean age of 57 years at onset of glomerulonephritis after a 10-year history of scleroderma. Of the 50 patients, 26 had limited disease, 19 diffuse disease and in 5 cases the description of skin changes did not allow classification. Thirty-five patients were reported to have interstitial lung disease. Seven patients had hemoptysis at time of acute kidney injury and 2 patients after the episode of glomerulonephritis. Blood pressure values were available for 35 patients with a mean systolic of 140 mmHg with 8 patients having a systolic greater than or equal to 160 mmHg. Urinalysis on 45 patients revealed almost all had hematuria and proteinuria. Erythrocyte casts were reported in 6 cases and granular casts in a similar number. Quantification of proteinuria was reported in 28 patients: values ranged from 0.3 to 4.3 g/day, mean 1.4 g/day. Creatinine averaged 3.8 mg/dl from 47 patients at diagnosis of AKI. All patients tested positive for anti-MPO except for 1 positive result for PR3, 1 negative and 2 not tested (92% positive). Of the 41 patients tested for anti-topoisomerase I, 29 were positive resulting in a sensitivity of 71%, similar to the findings by Arad  and Rho .
With regards to treatment, all patients were prescribed steroids with cyclophosphamide except 9 patients not treated with steroids and 12 not treated with cyclophosphamide. There were 12 deaths, 5 from a report by Endo in 1994. Seven patients required long term hemodialysis or renal transplant, 18 patients were left with some renal dysfunction and in 11 patients creatinine returned to normal. Outcomes were not reported in 2 patients.
A recent review in 2012 by Chan and Mok of 19 patients with PICGN in scleroderma revealed similar findings . Their review excluded drug induced cases. Patients were mostly female in the 6th decade of life. While our review demonstrated a slightly higher percentage of patients with limited disease there were equal numbers of limited and diffuse disease in the review by Chan. Eighty-two percent of patients had a blood pressure less than 160 mmHg systolic, similar to our finding, and 10% had nephrotic range proteinuria. Ninety-five percent of patients were MPO-ANCA positive. Roughly 2/3 of patients developed end stage renal disease and the mortality rate was 36%.
Our cases share some features typical of ANCA associated PICGN in scleroderma patients reported in the literature. The prolonged duration of scleroderma symptoms prior to kidney injury is consistent with the report by Arad et al., . Theses authors compared scleroderma renal crisis with ANCA associated PICGN in scleroderma patients; median duration of symptoms in scleroderma renal crisis was 7 months versus a median of 7 years in scleroderma with ANCA renal disease. Generally, there is a female predominance, with onset of kidney injury in the 5th to 6th decade of life. The majority of patients have interstitial lung disease and positive anti-topoisomerase 1. ANCA glomerulonephritis is not exclusive to either limited or diffuse disease. All our cases occurred in patients with diffuse scleroderma but in our literature review limited skin involvement was described in half of the patients.
The prevalence of ANCA antibodies in scleroderma was previously described by Rufatti et al., in 2002 . In a cohort of 115 patients, 5 tested positive for pANCA with 3 demonstrating antibodies to MPO. While the relationship between ANCA antibodies and glomerulonephritis has been established with animal models the evidence of their involvement in pulmonary fibrosis is less clear [42,43]. In 2011 Guilpain published in vitro evidence supporting anti MPO induced increases in reactive oxygen species . Previous work by Servettaz demonstrated increased fibroblast proliferation with sera from patients with scleroderma and interstitial lung disease that contained high amounts of advanced oxidation protein products .
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Citation:Mankee A, Kerr LD (2016) Antineutrophil Cytoplasmic Antibody Pauci-Immune Crescentic Glomerulonephritis and Interstitial Lung Disease in Scleroderma. Case Report and Literature Review. J Nephrol Renal Ther 2: 005.
Copyright: © 2016 Leslie Dubin Kerr, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.