Vasculitis pauciinmune asociada a lupus eritematoso sistémico: a propósito de un caso

Introducción: la poliangeítis microscópica (PAM) hace parte del grupo de vasculitis asociadas a anticuerpos anticitoplasmáticos de neutrófilos (ANCA), cuya presencia de anticuerpos contra mieloperoxidasa (MPO) se observa en la mayoría de los casos (70-95 %), asimismo, el compromiso renal presagia mayores tasas de morbilidad y mortalidad, sin embargo, la coexistencia con lupus eritematoso sistémico (LES) es poco frecuente y con mayor énfasis en la variante de LES del adulto mayor o de inicio tardío. Objetivo: dar a conocer un caso poco común de dos enfermedades autoinmunes, lo cual ha sido reportado como síndrome de superposición y brindar información útil que permita ampliar los diagnósticos diferenciales. Presentación del caso: se presenta el caso de un paciente masculino de 76 años con historia de poliartralgias progresivas en deterioro del estado general, con debut en síndrome confusional agudo, caída de filtrado glomerular, microhematuria y proteinuria casi nefrótica. A la evaluación inicial se encontró anemia y trombocitopenia severa, en perfil inmune ANA 1/320 y complemento consumido, cumpliendo criterios para LES, ANCA reactivo específicamente MPO ANCA (1/320) y sospecha de glomerulonefritis con patrón rápidamente progresivo (GNRP). Dado el contexto clínico, se decidió comenzar con pulsos de metilprednisolona consecutivos, seguidos de prednisolona oral y, como terapia de mantenimiento, se instauró ciclofosfamida. Finalmente, con una biopsia renal se confirmó el diagnóstico de vasculitis sistémica pauciinmune con formación de crescencia celular. La evolución clínica del paciente fue satisfactoria, logrando la estabilización de órganos y la normalización de la función renal, hematopoyética y el estado neurológico. Discusión y conclusión: dado que la presentación clínica de LES es heterogénea, se ha reportado su asociación con vasculitis, las cuales comparten un compromiso común de órganos como articulaciones, piel y riñones. Los hallazgos paraclínicos, como por biopsia, fueron consistentes tanto con PAM como con LES, por lo tanto, se diagnosticó como un caso de superposición. Este caso demuestra el enigma del diagnóstico y la complejidad en el manejo de entidades poco frecuentes, de etiologías inmunológicas superpuestas que ponen en peligro la vida de quien la(s) padece, de no tener un diagnóstico oportuno y un tratamiento temprano.

Introduction: Microscopic polyangiitis (MPA) is part of the group of vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), whose presence of antibodies against myeloperoxidase (MPO) is observed in most cases (70-95 %), likewise, the renal compromise portends higher rates of morbidity and mortality. However, coexistence with Systemic Lupus Erythematosus (SLE) is infrequent, and with greater emphasis on the older adult or late-onset variant of SLE (1). Purpose: Present a rare case of two autoimmune diseases, which has been reported as overlapping syndrome and provide useful information that allows expanding differential diagnoses. Case report: We present the case of a 76-year-old male patient with a history of progressive polyarthralgias in deteriorating general condition, with debut in acute confusional syndrome, drop in glomerular filtration rate, microhematuria and almost nephrotic proteinuria. At the initial evaluation anemia and severe thrombocytopenia were found, in the immune profile ANA 1/320, complement consumed; fulfilling criteria for SLE, ANCAs reactive specifically MPO ANCA (1/320) and suspected Rapidly Progressive Renal Insufficiency (PRRI). Given the clinical context, it was decided to start consecutive pulses of methylprednisolone followed by oral prednisolone, and cyclophosphamide was established as maintenance therapy. Finally, a renal biopsy confirmed the diagnosis of pauci-immune systemic vasculitis with cell crescent formation. These findings were consistent with both SLE and PAM, thus it was diagnosed as a case of overlap. The clinical evolution of the patient was satisfactory, achieving organ stabilization and normalization of renal function, hematopoietic function, and neurological status. Discussion and conclusion: RPGN associated with ANCA present non-nephrotic proteinuria, glomerular filtration rate drop. The most common is anti-glomerular basement membrane (AMBG) antibodies. Serological detection of antineutrophil cytoplasmic antibodies, PR3 and MPO should be available. Microscopic polyangiitis could be determined by renal biopsy, with the presence of cell growth, absence of immune deposits and MPO ANCA positivity. This case is a diagnostic enigma, and the complexity in the management of rare entities, of immunological etiology, superimposed that endanger the life of those who suffer from it, if they do not have a timely diagnosis and early treatment.

Reporte de un caso de glomerulonefritis rápidamente progresiva por anticuerpos antimembrana basal glomerular / Case report of rapidly progressive glomerulonephritis due to anti-glomerular basement membrane antibodies

RESUMEN Una vez más en medicina interna no podemos, aún, prescindir de los métodos invasivos para alcanzar un diagnóstico. Los avances diarios en el hallazgo de nuevas herramientas paraclínicas no permiten reemplazar aquellos métodos de certeza como la anatomía patológica. El caso presentado es una muestra de ello. Se trata de una mujer de 27 años de edad, con antecedente de tiroiditis de Hashimoto que consulta por presentar severo deterioro de la función renal asociado a oligoanuria. Realizamos una revisión del tratamiento de las glomerulonefritis rápidamente progresivas por anticuerpos antimembrana basal glomerular, serológicamente negativas.

ABSTRACT Once again in internal medicine we cannot do a diagnosis without invasive methods. Daily advances in the finding of new paraclinical tools do not allow the replacement of certain methods such as pathological anatomy. The case presented is a sample of this. This is a 27-year-old woman with a history of Hashimoto's thyroiditis who consults for presenting severe impairment of kidney function associated with oligoanuria. We performed a review of the treatment of the rapidly progressive glomerulonephritis for serologically negative anti-GBM antibodies.

Relationship between serum AECA and clinical signatures of ANCA negative pauci-immune deposition type crescentic glomerulonephritis patients / 中国免疫学杂志

Objective:To investigate the expression of anti-endothelial cell antibodies(AECA) in patients serum with anti-neutrophil cytoplasmic antibody( ANCA) negative pauci-immune deposition type crescentic glomerulonephritis and its relationship with clinical signatures. Methods:We selected 94 pauci-immune deposition type crescentic glomerulonephritis patients from 2010 to 2015 treated in our hospital,45 of which with ANCA-negative( observation group) and 49 cases of ANCA-positive patients ( control group) , AECA levels of each groups serum were detected by Western blot test. Results: The average age of the observation group and Bermingham vasculitis activity score(BVAS) respectively (41. 08 +9. 43) years old and (15. 03 +3. 82),significantly lower than the control group (P<0. 05);the observation group had fever,joint pain accounted for 26. 67% and 13. 33%,significantly lower than the control group ( P<0. 05 );the observation group of nephrotic syndrome accounted for 48. 89%, higher than the control group ( P<0. 05);observation group positive rate of serum AECA was 46. 67%,significantly lower than the control group 81. 63% (P<0. 05);the observation group IgG-AECA identified 7 proteins,while the control group had identified 11 proteins,of which the observation group the positive rate of anti 90 kD antibody was 13. 33%( 6/45 ) , significantly lower than the control group 51. 02%( 25/49 ) ( P<0. 05 );observation group of anti 76 kD antibody positive patients had rash ratio of 100%, significantly higher than negative patients ( P<0. 05),anti 200 kD antibody positive the BVAS score of the patients was (18. 02 + 2. 51),which was significantly higher than that of the negative patients ( P < 0. 05 ) . Conclusion: The different level of AECA in ANCA negative pauci-immune crescentic glomerulonephritis patients may be associated with certain clinical manifestations;clinical manifestations differences between the ANCA negative and positive patients may be associated with different expression of the AECA related,the detail need a further study.

A Case of True Renal Lupus Vasculitis Combined with Pauci-immune Glomerulonephritis in a Patient with Systemic Lupus Erythematosus

Renal lupus vasculitis is a rare vascular lesion complicated with systemic lupus erythematosus (SLE). We report an unusual case of true renal lupus vasculitis with antineutrophil cytoplasmic antibodies (ANCA)-negative pauci-immune glomerulonephritis in a patient with SLE. A 32-year-old woman presenting with hematuria and overt proteinuria was admitted to the hospital. She had been diagnosed with SLE at 16 years of age and treated with prednisolone, hydroxychloroquine, and methotraxate. A kidney biopsy revealed 42 glomeruli with ischemic wrinkling, and segmental loop necrosis with fibrin deposition. Prominent inflammatory cell infiltration of interlobular arteries and afferent arterioles with severe necrosis was demonstrated. No electron-dense and immune deposits in the glomeruli were observed by immunofluorescent and electron microscopy; in contrast, those in the renal vascular wall showed a full-house pattern. Antiphospholipid antibodies and ANCA were negative. The patient was treated with monthly intravenous cyclophosphamide pulses and high dose steroid, and showed good response on further follow-up.

Renal histology in pauci-immune rapidly progressive glomerulonephritis: 8-year retrospective study.

Context: The need to perform reporting of renal biopsies of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides in a more uniform manner required relook at our eight-year data. Aims: To document detailed renal histopathology of pauci-immune rapidly progressive glomerulonephritis (RPGN) and also to seek any significant differences in renal histology of C-ANCA-positive, P-ANCA-positive, and ANCA-negative patients. Materials and Methods: A detailed analysis of the histopathologic features of renal biopsies of 48 patients in whom a diagnosis of pauci-immune glomerulonephritis was concluded on renal biopsy and who presented clinically as rapidly progressive renal failure was done. Statistical Analysis Used: One-way ANOVA and Pearson Chi square tests. Results: Compared with ANCA +ve patients, the ANCA -ve patients were much younger (46.85 ± 16.12 years vs 34.28±15.94 years). No significant differences were found between renal lesions of C-ANCA, P-ANCA, and ANCA-negative patients, except for diffuse tubular atrophy which was more severe and more frequently present with P-ANCA positivity (P value=0.013). Conclusions: Pauci-immune RPGN (irrespective of ANCA status) is a relatively rare disorder in patients who are undergoing the renal biopsy at our institute, constituting 2% of all renal biopsies submitted. It is mandatory to have ANCA serology status during reporting of a kidney biopsy showing pauci-immune crescentic or necrotizing glomerulonephritis. Also, if a uniform reporting strategy is followed throughout the country, the studies from this vast country will be comparable.

Crescentic glomerulonephritis: A clinical and histomorphological analysis of 46 cases.

Background: Crescentic glomerulonephritis (CrGN), defined as crescents involving more than 50% of the glomeruli, includes pauci-immune, immune complex-mediated and anti-glomerular basement membrane disease. Objectives: The present study was aimed at evaluating the various clinical, biochemical and histological parameters in CrGN with respect to these categories and clinical outcome. Materials and Methods: Renal biopsies diagnosed as CrGN between Jan 2008 and Feb 2010 were included. Clinical and laboratory parameters were retrieved along with the therapeutic approach and clinical outcome, wherever available. Renal biopsy slides were evaluated for various glomerular, tubulo-interstitial and arteriolar features. Appropriate statistical tests were applied for significance. Results: A total of 46 cases of CrGN were included; majority (71.7%) of cases were pauci-immune (PI) while 28.3% were immune complex-mediated (IC). Among clinical features, gender ratio was significantly different between PI and IC groups (P = 0.006). The various histological parameters, including proportion of cellular crescents, tuft necrosis and Bowman's capsule rupture, were similar in both the groups. Four unusual associations, including idiopathic membranoproliferative glomerulonephritis (MPGN), multibacillary leprosy, acute lymphoblastic leukemia and C1q nephropathy were detected. Adequate follow-up information was available in 21 (46%) of the patients. Of these, 11 (52.4%) were dialysis-dependent at the last follow-up. Adult patients required renal replacement therapy more frequently than pediatric cases (P = 0.05). Presence of arteriolar fibrinoid necrosis also showed association with poor clinical outcome (P = 0.05). Conclusions: Crescentic glomerulonephritis remains one of the main causes of acute renal failure with histological diagnosis. Immunohistologic examination is essential for accurate classification into one of the three categories. This condition should be considered in rare causal associations like leprosy or MPGN with renal failure, to allow for timely performed renal biopsy and appropriate aggressive therapy.

Effects of mycophenolate mofetil on patients with pauci-immune crescentic glomerulonephritis / 中国实用内科杂志

Objective To compare the effect,relapse rate and outcomes between mycophenolate mofetil(MMF)and pulse intravenous cyclophosphamide(CTX)in the induction therapy of pauci-immune crescentic glomerulonephritis(PICGN)in Chinese.Methods A total of 44 patients who had PICGN[16 male,28 female,age(46.8?13.7)y],of whom 25 patients were ANCA positive,were enrolled in this study.All patients had renal involvement with ≥50% crescent formation prior to the study and received either MMF treatment(MMF group,n=22)or intermittent CTX pulse therapy(CTX group,n=22).The patients in both groups also received methylprednisolone(MP)pulse therapy followed by oral prednisone.General conditions,clinicopathological findings,remission rate,relapse rate,and outcomes were compared.All the patients were followed up until June 2005,with an average follow-up of 8～60(Med 27)months in the MMF group,and 6～72(Med 29)months in the CTX group.Results No significant difference was found between MMF group and CTX group in general conditions,base parameters of clinical and pathological findings.The remission rate at the 12th month in MMF and CTX group was 90.9% and 72.7% respectively.The complete remission rate in MMF group(59.1%)was significantly higher than that of the CTX group(27.3%)(P

ANCA-neagtive pauci-immune crescentic glomerulonephritis / 中国实用内科杂志

Objectives To study the clinical and pathological features of patients with ANCA-negative pauci-immune crescentic glomerulonephritis.Methods ANCA was detected and the clinical and pathological features were analyzed in 33 patients with pauci-immune crescentic glomerulonephritis.Results Of the 33 patients with pauci-immune crescentic glomerulonephritis, 15(45%) were ANCA negative, which accounted for 15% of the patients with crescentic glomerulonephritis. Of the 15 patients with negative ANCA,9 had multi-system involvement and 6 were clinically limited to kidney only. Renal biopsies showed small vessel vasculitis in 2 patients. After intensive immunosuppressive therapy, one out of thirteen patients was cured,six achieved clinical remission,while the other 6 became dialysis dependent.Conclusions The clinical and pathological features of the patients with ANCA-negative pauci-immune crescentic glomerulonephritis are similar to those with ANCA-positive,while the ages of these patients are younger and the prognosis poorer.

A Case of P-ANCA Positive Necrotizing Glomerulonephritis with Eosinophilia / 대한류마티스학회지

Antineutrophil cytoplasmic antibodies (ANCAs) are now regarded as a serologic marker for pauci-immune crescentic necrotizing glomerulonephritis either in renal-limited form or in association with systemic vasculitis, such as Wegener? granulomatosis, microscopic polyarteritis, and Churg-Strauss syndrome. Two major ANCA antigens have been indentified: proteinase3, which produces a cytoplasmic staining pattern termed C-ANCA, and myeloperoxidase, which produces a perinuclear pattern termed P-ANCA on ethanol-fixed neutrophils by indirect immunofluorescence. In ANCA- associated diseases, eosinphilia in excess of 1.5X109/L has been proposed to be characteristic of Churg-Strauss syndrome and is rare in other forms of ANCA-associated systemic vasculitis and crescentic necrotizing glomerulonephritis. Recently, there were two cases of P-ANCA positive crescentic necrotizing glomerulonephritis with peripheral blood eosinophilia and extrarenal microscopic vasculitis without asthma or granulomas. We experienced a patient with P-ANCA positive pauci-immune necrotizing glomerulonephritis with few eosinophilic infiltration and eosinophilia. He improved with oral prednisolone along with combination of intravenous cyclophosphamide. So we report this case with the review of literature.