Letter to the Editor
Immuno complex mediated acute glomerulonephritis in a patient with infectious mononucleosis
Glomerulonefritis aguda por inmunocomplejos en mononucleosis infecciosa
M. Adoración Martín-Gómeza,
, Mercedes Caba Molinab, Gracia Cruz Caparrosc, Encarnación Guerrero Sánchezd, Abelardo Caballero Gonzáleze, Mercedes Gómez Moralesb
Corresponding author
a Unidad de Nefrología, Hospital de Poniente, El Ejido, Spain
b Servicio de Anatomía Patológica, Hospital San Cecilio, Granada, Spain
c Medicina Interna, Hospital de Poniente, El Ejido, Spain
d Sección de Anatomía Patológica, Hospital de Poniente, El Ejido, Spain
e Servicio de Inmunología, Hospital Carlos Haya, Málaga, Spain
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Skin biopsy (B): focal intracellular epidermal spongiosis, mild edema and hepatic extravasation; and; dermal vessels occupied by inflammatory cells (increase: lymphocytes and polymorphonuclear cells with eosinophilic isolates).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">This case is a 44-year-old woman without previous medical history, who presented with fever of 38.7<span class="elsevierStyleHsp" style=""></span>°C of 2 weeks of evolution mainly in the afternoon, without evidence of source of infection, without chills or shaking. She was treated as a flu-like syndrome with NSAIDs and antipyretics. Subsequently, she developed a non-pruriginous generalized cutaneous exanthema, went to the emergency room and the blood tests revealed anemia (11.7<span class="elsevierStyleHsp" style=""></span>μg/dl<span class="elsevierStyleHsp" style=""></span>hb) mild leukopenia with moderate lymphopenia (3640<span class="elsevierStyleHsp" style=""></span>μleuk/μl, 18% lymph), CRP 22 units and a moderate increase high serum transaminase levels. Renal function was normal (serum creatinine 0.73<span class="elsevierStyleHsp" style=""></span>mg/dl), physical exam anodyne except for a temperature of 37.7<span class="elsevierStyleHsp" style=""></span>°C and confluent exanthema including palms/plants that disappear with pressure. Normal chest X-ray. With the diagnosis of exanthematic febrile syndrome with hepatic and hematological alteration, she was admitted for study, and doxycycline was prescribed.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On subsequent days hepatosplenomegaly and pericardial effusion were detected, sedimentation rate was 110 and smears without cell atypias but a 11% of LUC cells were detected. Iron, folic acid, B12, IgA, IgG, C3-4, ANCA, ASLO, normal citrullic peptide. Proteinogram: polyclonal elevation of the gamma globiulins, elevated IgM, FR 300<span class="elsevierStyleHsp" style=""></span>IU/ml cryoglobulins were negative. ANA: 1/80, DNA, negative, ENA negative except 24<span class="elsevierStyleHsp" style=""></span>UI/ml U1-RNP. Serology: negative for HBV, HCV, HIV, Legionella, CMV, parvovirus B19, Leptospira, <span class="elsevierStyleItalic">C. burneti</span>, <span class="elsevierStyleItalic">R. coronii</span>, pneumococcus, negative blood cultures; EBV equivocal IgG/positive IgG.</p><p id="par0025" class="elsevierStylePara elsevierViewall">He remained febrile, the fifth day of admission the fever increased with chills/shivering and respiratory insufficiency; the patient had atelectasis/bibasal condensation with symmetrical pleural effusion (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A) and procalcitonin 4.39<span class="elsevierStyleHsp" style=""></span>μg/ml, and received broad spectrum antibiotic therapy.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Urine showed a proteinuria 1.8<span class="elsevierStyleHsp" style=""></span>g/day, sediment 40<span class="elsevierStyleHsp" style=""></span>H/C (28% dysmorphia), the serum cholesterol was normal, albumin 2.2<span class="elsevierStyleHsp" style=""></span>g/L; Minimal symmetrical pretibial edema, normal blood pressure and normal values of serum creatinine, as well as kidney morphology by ultrasound. He had no signs of systemic disease. Dermal biopsy confirms urticarial process (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). A renal biopsy reported a mesangial proliferative glomerulonephritis with immune deposits mainly IgM/C1q. PCR for EBV in blood was +, but in situ hybridization in the kidney being negative (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). It is diagnosed of infectious mononucleosis (MI) with hematological, pleuropericardic, hepatic and renal involvement with mesangial proliferative glomerulonephritis by immunocomplexes. It evolves favorably, remaining asymptomatic and the PCR for EBV became negative. At the end of the year, remission persists, although anti-U1-RNP+ persists as well as generalized arthralgias treated with usual analgesia that had been present for years. He has not evidence of other autoantibody nor presented any other symptoms of systemic disease.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">In adults the infectious mononucleosis (IM) is presented with atypical symptoms,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> with absence of pharyngotonsillitis, lymphadenopathy and lymphocytosis/lymphocytic atypia. Pleural or pericardial effusions are exceptional that have been described in only isolated cases.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> All this, together with the leucopenia-anemia, serositis and U1-RNP positivity, made us think of the coexistence of infection and autoimmunity.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The prevalence of renal involvement of IM is not well known, it usually goes unnoticed with urinary abnormalities that are asymptomatic (14–17%).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> The published cases are isolated and are mainly tubulointerstitial involvement. There are few cases of various types glomerulopathies, mediated or not by immunocomplexes, which may occur alone or coexisting with interstitial involvement.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The presence of renal failure is estimated to be between 1.6 and 4.8%.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> As for its pathogenesis, several non-exclusive mechanisms have been considered: immune complexes mediated damage or direct toxic-cytopathic damage, the latter being found in interstitial lesions, in which the virus has been isolated and found to be mainly in CD8+ cells. In our case we were unable to find the virus by in situ hybridization and tubulointerstitial damage was minor, so we deduced that the damage was mediated by antibodies/immunocomplexes rather than by direct cytotoxicity. The deposits were mostly IgM/C1q. Andres et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> describe a similar case with IgM/C3 mesangial deposits, this being the same heterologous serum IgM against Paul Bunnell antigen. This is because the humoral immune response to EBV is primarily at the expense of IgM.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Also, activation of the 2 complement pathways has been described in MI.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Hyperstimulation of host immunity by EBV in some cases is unknown, but in vitro and in vivo the natural IgM produced by the polyclonal activation of B lymphocytes during MI has antihistone activity.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Niller et al.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> related different EBV antigens with the activation of autoreactive B lymphocytes in multiple sclerosis, SLE and RA. In this respect, the positivity for U1-RNP is attributed to the virus induced activation of specific immunoglobulin secreting B lymphocytes against that protein, by cross-reactivity with antigens of the EBV itself.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> It is not know why, despite presenting this antibody, it does not develop symptoms although the title presented has never been very high. The patient's HLA was performed and predisposing alleles for autoimmune diseases have not been found.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Regarding treatment, the glomerulopathy resolved in parallel to the mononucleosis. In the literature, some cases received corticosteroids, especially those with tubulointerstitial involvement. That was not our case that only had slight renal clinical and histological involvement (although the mesangial hypercellularity was diffuse in some glomeruli, it was segmental in others and, but in general it was mild). Acyclovir was not given since bibliography reports low efficacy.</p><p id="par0060" class="elsevierStylePara elsevierViewall">We conclude that the frequent atypical presentation of IM in the adult can lead to delay in the diagnosis. The renal involvement is usually tubulointerstitial by cytotoxicity in which the virus can be found, and virus is less frequently observed in glomeruli. Should take into account the pathogenesis by immunocomplexes and complement activation. EBV is considered a “trigger” of self-reactive phenomena that can persist over the time and it may cause an autoimmune disease in cases with a predisposing environment.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Martín-Gómez MA, Caba Molina M, Cruz Caparros G, Guerrero Sánchez E, Caballero González A, Gómez Morales M. Glomerulonefritis aguda por inmunocomplejos en mononucleosis infecciosa. Nefrología. 2017;37:439–441.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 532 "Ancho" => 1500 "Tamanyo" => 165295 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">CT scan (A): atelectasis/bibasal condensation with symmetrical effusion, pericardial effusion. Skin biopsy (B): focal intracellular epidermal spongiosis, mild edema and hepatic extravasation; and; dermal vessels occupied by inflammatory cells (increase: lymphocytes and polymorphonuclear cells with eosinophilic isolates).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1274 "Ancho" => 1700 "Tamanyo" => 385404 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Renal biopsy. PAS 60×: mesangial proliferation (A), prominent podocytes (B, arrow). IF: diffuse and global mesangial IgM (C), C1q mesangial segmental (D). 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 11 | 18 |
| 2024 October | 43 | 43 | 86 |
| 2024 September | 65 | 28 | 93 |
| 2024 August | 81 | 67 | 148 |
| 2024 July | 56 | 34 | 90 |
| 2024 June | 92 | 42 | 134 |
| 2024 May | 55 | 24 | 79 |
| 2024 April | 62 | 42 | 104 |
| 2024 March | 63 | 20 | 83 |
| 2024 February | 38 | 35 | 73 |
| 2024 January | 43 | 24 | 67 |
| 2023 December | 49 | 30 | 79 |
| 2023 November | 58 | 38 | 96 |
| 2023 October | 71 | 43 | 114 |
| 2023 September | 37 | 35 | 72 |
| 2023 August | 41 | 29 | 70 |
| 2023 July | 90 | 20 | 110 |
| 2023 June | 53 | 18 | 71 |
| 2023 May | 58 | 32 | 90 |
| 2023 April | 59 | 12 | 71 |
| 2023 March | 79 | 20 | 99 |
| 2023 February | 84 | 25 | 109 |
| 2023 January | 70 | 18 | 88 |
| 2022 December | 72 | 30 | 102 |
| 2022 November | 63 | 28 | 91 |
| 2022 October | 73 | 34 | 107 |
| 2022 September | 55 | 29 | 84 |
| 2022 August | 52 | 43 | 95 |
| 2022 July | 38 | 46 | 84 |
| 2022 June | 55 | 38 | 93 |
| 2022 May | 42 | 18 | 60 |
| 2022 April | 64 | 35 | 99 |
| 2022 March | 77 | 42 | 119 |
| 2022 February | 93 | 51 | 144 |
| 2022 January | 48 | 27 | 75 |
| 2021 December | 59 | 36 | 95 |
| 2021 November | 54 | 38 | 92 |
| 2021 October | 58 | 39 | 97 |
| 2021 September | 48 | 27 | 75 |
| 2021 August | 57 | 53 | 110 |
| 2021 July | 78 | 33 | 111 |
| 2021 June | 35 | 31 | 66 |
| 2021 May | 43 | 42 | 85 |
| 2021 April | 152 | 35 | 187 |
| 2021 March | 87 | 40 | 127 |
| 2021 February | 57 | 15 | 72 |
| 2021 January | 50 | 23 | 73 |
| 2020 December | 48 | 22 | 70 |
| 2020 November | 56 | 21 | 77 |
| 2020 October | 43 | 26 | 69 |
| 2020 September | 38 | 17 | 55 |
| 2020 August | 59 | 16 | 75 |
| 2020 July | 44 | 13 | 57 |
| 2020 June | 58 | 21 | 79 |
| 2020 May | 50 | 15 | 65 |
| 2020 April | 41 | 17 | 58 |
| 2020 March | 44 | 12 | 56 |
| 2020 February | 59 | 19 | 78 |
| 2020 January | 60 | 31 | 91 |
| 2019 December | 70 | 27 | 97 |
| 2019 November | 74 | 34 | 108 |
| 2019 October | 69 | 21 | 90 |
| 2019 September | 48 | 17 | 65 |
| 2019 August | 61 | 14 | 75 |
| 2019 July | 44 | 24 | 68 |
| 2019 June | 59 | 23 | 82 |
| 2019 May | 45 | 24 | 69 |
| 2019 April | 79 | 25 | 104 |
| 2019 March | 41 | 28 | 69 |
| 2019 February | 37 | 20 | 57 |
| 2019 January | 42 | 18 | 60 |
| 2018 December | 188 | 41 | 229 |
| 2018 November | 369 | 19 | 388 |
| 2018 October | 346 | 13 | 359 |
| 2018 September | 140 | 24 | 164 |
| 2018 August | 61 | 14 | 75 |
| 2018 July | 80 | 11 | 91 |
| 2018 June | 87 | 18 | 105 |
| 2018 May | 103 | 10 | 113 |
| 2018 April | 214 | 14 | 228 |
| 2018 March | 186 | 13 | 199 |
| 2018 February | 263 | 7 | 270 |
| 2018 January | 109 | 10 | 119 |
| 2017 December | 221 | 6 | 227 |
| 2017 November | 75 | 12 | 87 |
| 2017 October | 51 | 9 | 60 |
| 2017 September | 47 | 8 | 55 |
| 2017 August | 49 | 12 | 61 |
| 2017 July | 26 | 7 | 33 |
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