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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2016  |  Volume : 27  |  Issue : 4  |  Page : 795-799
Hilar and para-aortic necrotizing lymphadenopathy associated with antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis

1 Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait
2 Department of Radiology, Al-Amiri Hospital, Kuwait City, Kuwait
3 Department of Pathology, Al-Amiri Hospital, Kuwait City, Kuwait

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Date of Web Publication5-Jul-2016


Lymph node involvement as a part of systemic vasculitis is rare. We report a case of women with rapidly progressive renal disease associated with recurrent epigastric pain, weight loss, and massive hilar as well as para-aortic lymphadenopathy. Ultrasound-guided biopsy of her scarred kidneys revealed antineutrophil cytoplasmic antibody-negative crescentic glomerulonephritis and that of lymph nodes showed severe necrotizing vasculitis. Biopsy of the lymph nodes and the failing kidney established the diagnosis of this rare presentation and ruled out lymphoma and tuberculosis. Administration of corticosteroids and cyclophosphamide resulted in a favorable outcome.

How to cite this article:
El-Reshaid K, Varro J, Madda JP. Hilar and para-aortic necrotizing lymphadenopathy associated with antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis. Saudi J Kidney Dis Transpl 2016;27:795-9

How to cite this URL:
El-Reshaid K, Varro J, Madda JP. Hilar and para-aortic necrotizing lymphadenopathy associated with antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2022 Aug 7];27:795-9. Available from: https://www.sjkdt.org/text.asp?2016/27/4/795/185264

   Introduction Top

Pauci-immune (type 3) crescentic glomerulonephritis is a necrotizing and/or crescentic glomerulonephritis with few or no immune deposits by immunofluorescence or electron microscopy. Seventy to 80% are antineutrophil cytoplasmic antibody (ANCA)-positive and have or will develop systemic manifestations of granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis. [1] Patients with ANCA-negative ones are also considered part of this spectrum, and may have similar clinical features, renal biopsy findings, and prognosis. [2] Isolated kidney disease is common, yet most manifest simultaneously or at later stage involvement of upper airway, lung, nervous system, gut, heart, and skin. [3] Hilar lymph node involvement is only rarely reported in patients with severe chest disease associated with Wegner's and Churg-Strauss as well as mesenteric ones in a patient with gut vasculitis. [4],[5],[6] However, massive enlargement of hilar and para-aortic nodes in association with crescentic glomerulonephritis was never described.

   Case Report Top

A 46-year-old Kuwaiti woman was referred for evaluation of severe renal failure with serum creatinine at 720 μmol/L. Four months ago, she has been evaluated by a gastroenterologist for epigastric pain and had endoscopy which showed gastritis and helicobacter infestation. She was treated with amoxicillin, Clarithromycin, and omeprazole. Initially, her serum creatinine was 107 μmol/L then had increased to 130 μmol/L two weeks later. She did not improve with the previous treatment and continue to have periodic abdominal pains. She also admitted having significant weight loss from 85 to 62 kg over the past few months. On her initial physical examination, she did not appear in distress of pain or shortness of breath. She was afebrile, and her blood pressure was 180/110 mm Hg. The rest of her systemic examination was normal. Laboratory investigations showed normal peripheral leukocytic and platelets counts, yet hemoglobin was 85 g/L with erythrocyte sedimentation rate at 120 mm/h. She had normal transferrin saturation%, and Vitamin B 12 levels. Serum urea and creatinine were elevated at 22 mmol/L and 760 μmol/L, respectively. Serum sugar, electrolytes, and liver functions were normal with albumin at 37 g/L. Urine routine and microscopy were normal. Serum complements and protein electrophoresis were normal. ANA, anti-dsDNA, RF, ANCA, hepatitis B surface antigen, and anti-HCV antibodies as well as cryoglobulins were negative. Chest X-ray showed hilar lymphadenopathy. Abdominal and pelvic ultrasound did not show abnormality except for smaller than normal kidneys with increased echogenicity and marked scaring of both kidneys with lobulated appearance as well as significant para-aortic lymphadenopathy. Computed tomography (CT) scan of chest and abdomen confirmed the findings [Figure 1]. Ultrasound-guided biopsy was done from the para-aortic lymph nodes and kidney. The lymph node biopsy showed necrosis with disruption of reticulin on special staining [Figure 2]. The kidney biopsy showed normal tissue alternating with significant linear strips of globally sclerosed and ischemic glomeruli with diffuse yet noncircumferential fibrous crescents and interstitial nephritis [Figure 3]. Immunofluorescent stains were negative. Blood vessels did not show significant hypertensive changes or vasculitis. Since this picture was compatible with systemic vasculitis, she was treated with 1 g intravenous solumedrol for three consecutive days followed by prednisone 60 mg daily which was tapered to 5 mg by the 6 th month. She also had received cyclophosphamide 1 g every month for six consecutive months then is scheduled to receive it every three months for a total period of two years. Ancillary measures included anti-hypertensives, omeprazole, and calcium with one alpha. The abdominal pains disappeared, and her appetite and weight had increased. Her kidney function improved gradually with time and serum creatinine had decreased to 300 μmol/L six months later.
Figure 1: Computed tomography scan of the abdomen showing massive para-aortic lymphadenopathy (arrow).

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Figure 2: Photomicrograph of the lymph node biopsy showing (a) necrosis on H and E stain and (b) disruption of reticulin on reticulin stain (×100).

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Figure 3: Photomicrograph of kidney biopsy showing (a) diffuse linear strips of globally sclerosed and ischemic glomeruli with scattered fibrous crescents and interstitial nephritis (H and E, ×100) and (b) sliver stain showing fibrous crescents (×200).

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   Discussion Top

Rapidly progressive glomerulonephritis is a clinical syndrome characterized by the presence of extensive crescent formation in the affected glomeruli. It manifests by features of glomerular disease in the urine and by progressive loss of renal function over a comparatively short period of time, days, weeks, or months. [7] The severity of the disease is in part related to the degree of crescent formation. Patients with cellular circumferential crescents in more than 80% of the glomeruli tend to present with fulminant renal failure. By comparison, patients with noncircumferential fibrocellular crescents in <50% of the glomeruli, typically follow a more indolent course. [8] Crescent formation appears to represent a nonspecific response to severe injury to the glomerular capillary wall. [9] Rents are induced in the glomerular capillary wall, resulting in the movement of plasma products, including fibrinogen, into Bowman's space with subsequent fibrin formation, the influx of macrophages and T cells, and the release of pro-inflammatory cytokines such as interleukin-1 and tumor necrosis factor-alpha. [10] Thus, crescents may be seen with any form of severe glomerular disease. However, the presence of such crescent with necrotizing lymphadenopathy indicates systemic vasculitis. Systemic vasculitis associated with lymphadenopathy includes systemic lupus erythematosus (SLE), Wegner's granulomatosis, hepatitis, cryoglobulinemia, IgG4-associated vasculitis, Kawasaki disease, and Kikuchi-Fujimoto's disease. [4],[5],[6],[11],[12],[13],[14],[15] SLE is unlikely to be the culprit in our patient with lack of clinical manifestations, serological markers, and immune complex crescentic nephritis (Type 2). There was no upper airway disease or parenchymal lung abnormality to suggest Wegner's or Churg-Straus vasculitis. Moreover, the vascular necrosis of the lymph nodes and glomerular crescents was not associated with granuloma formation. [16] Hepatitis and cryoglobulinemia were not detected on testing. The lymphadenopathy in IgG4-associated vasculitis is usually associated with reactive follicular hyperplasia rather than necrosis. [13] Moreover, our patient had normal levels of gammaglobulins as well as absent staining for IgG-positive plasma cells in lymph nodes. Kawasaki disease is unlikely since it usually manifests as coronary vasculitis in children preceded by the diagnostic criteria established by Tomisaku Kawasaki in 1967. The latter are fever lasting ≥ 5 days, combined with bilateral bulbar conjunctival injection, oral mucous membrane changes, peripheral extremity changes, periungual desquamation, and polymorphous rash. In Kawasaki vasculitis, it is a single cell necrosis associated with vessels containing microthrombi which was not present in our patient. [17] Finally, Kikuchi disease (KF disease) is usually self-limited, and the necrotic areas are associated with histiocytic cell infiltrate. [18] On clinical basis, four diseases may simulate the presentation of our patient, namely, tuberculosis, necrotizing sarcoidosis, hairy cell, and immunoblastic lymphoma. In tuberculosis, the caseation may simulate necrosis. However, it is associated with destruction of reticular framework of lymph nodes associated with nuclear debris. Moreover, the typical granuloma formation associated with Schaumann's, Hamazaki-Wesenberg, and conchoid bodies were not present in our patient. [19] Although sarcoidosis is limited to hilar lymph nodes and is rarely necrotizing, it may be associated with nondigested reticulin, but is usually associated with granuloma formation that includes asteroid, Schaumann's, and Hamazaki-Wesenberg bodies. [20] Finally, hairy cell lymphoma usually presents with generalized lymphadenopathy and was reported once to be associated with polyarteritis nodosa. [21] However, the disease is usually associated with hepatosplenomegaly and pancytopenia which were lacking in our patient. Lymphoma usually presents with generalized lymphadenopathy and moreover the angioimmunoblastic one may present with vasculitis. [22] In our patient, lymphoma was excluded based on the lymph node examination which had shown only necrosis and lacked the histiocytic cell infiltrate as well as the typical lymphomatous changes.

   Conclusion Top

Our case expands the spectrum of clinical manifestations of systemic vasculitis by the finding of massive lymphadenopathy due to vascular necrosis. Biopsy of the affected organs and the lymph node in particular is essential to avoid misdiagnosis of this potentially treatable disease.

Conflict of interest: None declared.

   References Top

Falk RJ, Hogan S, Carey TS, Jennette JC. Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. Ann Intern Med 1990;113:656-63.  Back to cited text no. 1
Chen M, Yu F, Wang SX, Zou WZ, Zhao MH, Wang HY. Antineutrophil cytoplasmic autoantibody-negative pauci-immune crescentic glomerulonephritis. J Am Soc Nephrol 2007;18:599-605.  Back to cited text no. 2
Angangco R, Thiru S, Esnault VL, Short AK, Lockwood CM, Oliveira DB. Does truly 'idiopathic' crescentic glomerulonephritis exist? Nephrol Dial Transplant 1994;9:630-6.  Back to cited text no. 3
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Jeong YG, Kim TH, Lee CM, et al. A case of limited Wegener's granulomatosis with gastroenteritis and mesenteric lymphadenopathy. Korean J Gastroenterol 2010;55:331-5.  Back to cited text no. 6
Couser WG. Rapidly progressive glomerulonephritis: Classification, pathogenetic mechanisms, and therapy. Am J Kidney Dis 1988;11:449-64.  Back to cited text no. 7
Baldwin DS, Neugarten J, Feiner HD, Gluck M, Spinowitz B. The existence of a protracted course in crescentic glomerulonephritis. Kidney Int 1987;31:790-4.  Back to cited text no. 8
Jennette JC. Rapidly progressive crescentic glomerulonephritis. Kidney Int 2003;63:1164-77.  Back to cited text no. 9
Atkins RC, Nikolic-Paterson DJ, Song Q, Lan HY. Modulators of crescentic glomerulonephritis. J Am Soc Nephrol 1996;7:2271-8.  Back to cited text no. 10
Van de Voorde K, De Raeve H, De Block CE, et al. Atypical systemic lupus erythematosus or Castleman's disease. Acta Clin Belg 2004;59:161-4.  Back to cited text no. 11
Charles ED, Dustin LB. Hepatitis C virus-induced cryoglobulinemia. Kidney Int 2009;76:818-24.  Back to cited text no. 12
Wong PC, Fung AT, Gerrie AS, et al. IgG4related disease with hypergammaglobulinemic hyperviscosity and retinopathy. Eur J Haematol 2013;90:250-6.  Back to cited text no. 13
Burns JC, Glodé MP. Kawasaki syndrome. Lancet 2004;364:533-44.  Back to cited text no. 14
Mootsikapun P, Sirijerachai J, Nanagara R. Kikuchi-Fujimoto's disease, histiocytic necrotizing lymphadenitis, mimicking systemic lupus erythematosus. J Med Assoc Thai 2002;85:1037-41.  Back to cited text no. 15
Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994;37:187-92.  Back to cited text no. 16
Katano H, Sato S, Sekizuka T, et al. Pathogenic characterization of a cervical lymph node derived from a patient with Kawasaki disease. Int J Clin Exp Pathol 2012;5:814-23.  Back to cited text no. 17
Seong GM, Kim JH, Lim GC, Kim J. Clinicopathological review of immunohistochemically defined Kikuchi-Fujimoto disease-including some interesting cases. Clin Rheumatol 2012;31:1463-9.  Back to cited text no. 18
Hughes M, Fox H. A histological analysis of granulomatous hepatitis. J Clin Pathol 1972;25:817-20.  Back to cited text no. 19
Chittock DR, Joseph MG, Paterson NA, McFadden RG. Necrotizing sarcoid granulomatosis with pleural involvement. Clinical and radiographic features. Chest 1994;106:672-6.  Back to cited text no. 20
Vankalakunti M, Joshi K, Jain S, Nada R, Radotra BD, Varma S. Polyarteritis nodosa in hairy cell leukaemia: An autopsy report. J Clin Pathol 2007;60:1181-2.  Back to cited text no. 21
Arlet P, Laroche M, Delsol G, Seigneuric G, Duffaut M, Le Tallec Y. Angioimmunoblastic lymphadenopathy with cutaneous leukocyteclastic vasculitis 2 cases. Nouv Presse Med 1982;11:3713-5.  Back to cited text no. 22

Correspondence Address:
Kamel El-Reshaid
Department of Medicine, Faculty of Medicine, Kuwait University, P. O. Box 24923, 13110 Safat, Kuwait City
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.185264

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