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| Year : 2010 | Volume
: 21
| Issue : 2 | Page : 332-336 |
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| Dilated cardiomyopathy in a patient with antibody-negative Goodpasture's syndrome and pulmonary relapse |
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Yalcin Solak1, Nedim Yilmaz Selcuk1, Ilker Polat2, Huseyin Atalay1, Kultigin Turkmen1
1 Department of Nephrology, Selcuk University, Meram School of Medicine, Meram, Konya, Turkey
2 Department of Internal Medicine, Selcuk University, Meram School of Medicine, Meram, Konya, Turkey
Click here for correspondence address and email
| Date of Web Publication | 9-Mar-2010 |
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 Abstract | | |
The Goodpasture's syndrome, also konwn as anti-GBM disease, is an uncommon disease, responsible for 20% of all cases of rapidly progressive glomerulonephritis. Anti-GBM antibodies are directed against non-collagenous domain (NC-1) of the alpha-3 chain of type IV collagen. When conventional ELISA assays are used, these antibodies can be detected in almost all the patients. Nevertheless, some reports have described antibody-negative relapsing disease. Some aggravating factors, namely, smoking, pulmonary infection and hypervolemia, may expose embedded antigenic target and may be responsible for the relapse. In addition, these antibodynegative relapses also respond to standard treatment, which comprises of plasma exchange, pulse steroids and cyclophosphamide. Herein, we report a patient who presented at the Selcuk University Meram School of Medicine, Meram, Konya, Turkey, with the pulmonary-renal syndrome. He was also found to have idiopathic dilated cardiomyopathy (DCM). To our knowledge, this is the first report describing co-existence of DCM and anti-GBM disease. There is growing evidence showing strong relation of both DCM and anti-GBM disease with HLA. Although not proven, this might have occurred in our patient. In our opinion, volume overload was facilitated by anuria and DCM and led to an antibody-negative pulmonary relapse. The relapse was treated just as the first episode and the patient improved satisfactorily.
How to cite this article:
Solak Y, Selcuk NY, Polat I, Atalay H, Turkmen K. Dilated cardiomyopathy in a patient with antibody-negative Goodpasture's syndrome and pulmonary relapse. Saudi J Kidney Dis Transpl 2010;21:332-6 |
How to cite this URL:
Solak Y, Selcuk NY, Polat I, Atalay H, Turkmen K. Dilated cardiomyopathy in a patient with antibody-negative Goodpasture's syndrome and pulmonary relapse. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2021 Dec 2];21:332-6. Available from: https://www.sjkdt.org/text.asp?2010/21/2/332/60196 |
| Introduction | |  |
The Goodpasture's syndrome, also known as anti-GBM disease, is an uncommon disease, responsible for 20% of all cases of rapidly progressive glomerulonephritis. [1] The anti-GBM antibodies are directed against the non-collagenous domain (NC-1) of the alpha-3 chain of type IV collagen and is responsible for the pulmonary-renal clinical picture. In almost all patients with the anti-GBM disease, circulating anti-GBM antibodies can be detected by ELISA. [2] However, antibody-negative relapses have been described. Herein, we present a young male who had dilated cardiomyopathy (DCM) and anti-GBM disease concomitantly, and developed an antibody-negative pulmonary relapse.
| Case Report | | |
An 18-year-old male patient presented with complaints of shortness of breath, blood-tinged sputum and pretibial edema. He had been hospitalized in another center for 10 days and was referred to our hospital for the pulmonary complaints. He had a flu-like disease 15 days prior to the first hospitalization. Following this, he developed dyspnea and occasional hemoptysis. He had been anuric and on hemodialysis (HD) since the first hospitalization.
At initial evaluation, physical examination revealed a malnourished young man in moderate distress. The blood pressure was 140/80 mmHg, heart rate was 106 beats/min and he was afebrile. Breath sounds were diminished globally and there were crackles at both lung bases. An S-3 gallop was audible and there was a soft 1-2/6 murmur at the mitral region. He had +2 pedal edema.
At admission, results of blood biochemistry and complete blood count studies were as follows: blood urea, 113 mg/dL (N=17-43); serum creatinine, 6.3 mg/dL (0.7-1.2); sodium, 134 mEq/L; potassium, 4.45 mEq/L; calcium, 8.7 mg/dL (N=8.9-10.3); phosphorus, 5.5 mg/dL (N=2.4-4.7); albumin, 2.9 mg/dL; CRP, 47 mg/dL (0-10); total white blood cell (WBC), 9.000/mm 3 ; hemoglobin, 8.9 g/dl and platelet count of 344.000/mm 3 . The INR and aPTT were 1.59 (N=1-1.5) and 115.4 seconds (N=2640 secs), respectively.
Chest X-ray revealed patchy alveolar infiltrates throughout the middle and lower zones of both lungs [Figure 1]. Abdominal ultrasound showed bilateral normal-sized kidneys with increased echogenicity. Thoracic computed tomography (CT) scan showed extensive airspace disease compatible with alveolar hemorrhage [Figure 2].
With initial diagnosis of active pulmonaryrenal syndrome, the patient was admitted to the medical intensive care unit and administered HD with ultrafiltration. After obtaining blood samples for ANCA, anti-GBM antibody and other serologic markers, the patient was administered plasma exchange therapy (PET) with fresh frozen plasma (FFP) (total of 14 sessions) with the possibility that he might have the Goodpasture's syndrome. He was also given three pulses of methylprednisolone (500 mg each) and a single dose of 250 mg of cyclophosphamide, as infusion. A renal biopsy was performed and the result, which showed linear IgG and C3 staining of glomerular capillaries, was consistent with anti- GBM disease.
Anti-GBM antibody, which was studied with ELISA, was found to be positive. Since he had an S-> gallop on auscultation, and was easily becoming volume overloaded despite meticulous fluid restriction and adequate ultraliltration, an echocardiogram was performed. Echocardiography revealed an ejection fraction of 25%, left ventricular wall-motion abnormalities, dilated left atrium and ventricle, and pericardial effusion. Myocardial perfusion scintigraphy with Tc-99 m and MIBI showed normal myocardial perfusion thereby excluding ischemic cardiomyopathy. Cardiac magnetic resonance indicated findings of DC M.
Our study patient had never used alcohol and was not a smoker either. He had no family history of DCM and no hypertension before the current illness. I-le also had no myocarditis, collagen vascular disease or high-output states to account for the development of DCM. We planned to perform an endomyocardial biopsy, which the patient refused. A diagnosis of idiopathic DCM was eventually made.
During the hospitalization, the clinical condition of the patient improved and oral maintenance immunosuppression with prednisolone 0.8 mg/kg body-weight and 25 mpg cyclophosphamide was commenced. Approximately 45 days after completion of the last session of plasmapheresis, the patient developed sudden onset of dyspnea and hemoptysis. Chest X-ray revealed extensive patchy alveolar infiltrates. Anti-GBM antibodies were again negative. Bearing in mind that relapse of pulmonary manifestations of antibody-negative anti-GBM disease was possible, we placed the patient on PET with FFP and administered three-day pulse prednisolone treatment. After 10 sessions of PET, the patient's condition improved and he was discharged on oral prednisolone, amlodipine, trimethoprim-sulpliamethoxaole, erythropoietin and calcitriol.
| Discussion | | |
Anti-GBM disease is defined as the triad of glomerulonephritis, pulmonary hemorrhage, and anti-GBM antibody formation. Despite this triad of clinical findings, patients with anti-GBMdisease may present with a spectrum of conditions ranging from pulmonary hemorrhage with minimal or no renal involvement, to Bill-blown renal failure with limited or no pulmonary involvement. [3]
Anti-GBM disease exemplifies the classic case of pathogenic antibody-mediated disease. The culprit is anti-GBM antibodies, which are directed against non-collagenous domain (NC-1) ol'the alpha-3 chain of type IV collagen. [4] AntiGBM disease has been strongly associated with HLA DR2 which is present in 80% of the cases. [5]
DCM accounts for approximately 25% of all cases of congestive heart failure. [6] Ischemic and hypertensive cardiomyopathies are the leading underlying causes. A number of environmental exposures (mainly alcohol abuse), myocarditis, collagen vascular diseases, high output states, some drugs and heavy metals also cause DCM. There are now abundant gene linkage studies and multiple genes have been identified. [7] Certain specific human leukocyte class-II antigens (particularly DR4) are associated with DCM. The hallmarks of'DCM are enlargement ol'one or both of the ventricles and systolic dysfunction. [8] The most typical symptoms include dyspnea, fatigue and volume gain.
To our knowledge, this is the first report of co-existence of DCM with anti-GBM disease. The importance of DCM being a complication of anti-GBM disease in our patient, is that volume overload made the patient prone to alveolar hemorrhage. Some factors can play a role as a trigger in a patient who already has anti-GBM antibodies. Among them are smoking, pulmonary infection, hypervolemia, hydrocarbons, urinary infection and lithotripsy. [9] Although not convincingly proved, smoking induces damage of the basement membrane with subsequent denudation of certain epitope of the alpha-3 (IV) collagen chain and antibody production. [10] We believe that hypervolemia and pulmonary edema may play a similar role in terms of triggering pulmonary hemorrhage. When we consider the relatively rare relapse rate of anti-GBM disease after effective treatment, preventing pulmonary hemorrhage which is triggered by aforementioned conditions is of particular importance and a delicate fluid regime in oligo-anuric patients who are undergoing HD should be an integral part of treatment. Several serologic studies in recent years, have documented a strong association of antiGBM disease with the MHC class-II gene, HLA DR2. [4] Also, there is mounting, evidence with respect to the relationship between DCM and HLA antigens. Although unable to prove, the co-existence of these two distinct entities in the same patient may be explained by the presence of a HLA gene polymorphism, which is responsible for susceptibility to both diseases.
After having responded to immunosuppressive therapy at first presentation, our patient developed a pulmonary relapse and again, antiGBM antibody was not detected by ELISA. Disease activity usually burns out once the patient develops advanced kidney failure and is started on HD, even without immunosuppressive therapy. [11] Thus, relapses are unusual in patients who are successfully treated or transplanted, despite the presence of the continuous antigenic target. [12]
Our patient's pulmonary relapse occured 45 days after completion of immunsuppressive treatment. Unlike the classical knowledge, he experienced severe alveolar hemorrhage despite presence of advanced renal failure (he had been undergoing HD for approximately four months at that time) and absence of any precipitating, events, except for volume overload. He did not have any detectable anti-GBM antibodies either. There are few reports in the literature about relapse of antibody-negative anti-GBM disease. [13] Precipitating, factors trigger disease activity by exposing pulmonary or renal target antigen and achieve this by increasing anti-GBM antibody titers. However, this was not the case in our patient.
Linear deposition of immunoglobulin along the GBM in the setting of crescentic nephritis confirms the diagnosis. However, renal biopsy is not always feasible when the patients present with catastrophic pulmonary hemorrhage. Rapid diagnosis of anti-GBM disease is increasingly reliant on ELISA techniques to detect circulating, anti-GBM antibodies. False-positive and false-negative results occasionally may occur using this method. [13] Using a highly sensitive method of detecting circulating, antiGBM antibodies with biosensor techniques, Salama AD et al [13] showed that such antibodies can be detected despite negative ELISA and Western blot results. Since we do not have this technique like many other laboratories, we could not show whether our antibody negativity was false negative or not. However, clinicians dealing, with patients with anti-GBM disease should be aware of the possibility of antibody-negative relapses (if studied by ELISA) and should not hesitate to implement PET along with immunosuppression.
| References | | |
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| 10. | Borza DB, Neilson EG, Hudson BG. Pathogenesis of Goodpasture syndrome: A molecular perspective. Semen Nephrol 2003;23: 522-31. |
| 11. | Wilson CB. Dixon FJ. Anti-_glomerular basement membrane antibody-induced eIOI11CrUlonephritis. Kidney II1t 19733:74-89. |
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| 13. | Salama AD, Dougan T. Levy JB. et al. Good-pasture's disease in the absence of circulating anti-glomerutar basement membrane antibodies as detected by standard techniques. Am .1 Kidney Dis 2002;39:1 162-7. |
Correspondence Address:
Yalcin Solak
Department of Nephrology, Selcuk University, Meram School of Medicine, Meram, Konya
Turkey
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PMID: 20228524 
[Figure 1], [Figure 2] |
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