Introduction
Goodpasture disease is a rare, rapidly progressive, autoimmune disease affecting the kidneys and lungs, resulting in high mortality and morbidity. It is also known as anti-glomerular basement membrane (anti-GBM) disease, manifesting as vasculitis affecting the glomerular and pulmonary capillaries with GBM deposition of anti-GBM autoantibodies.[1] The typical presentation is of a reno-pulmonary syndrome. Microscopic hematuria is seen in 90%–100% of the patients, with progression to macroscopic hematuria and rapidly progressive renal insufficiency. Alveolar hemorrhage often results in impaired gas exchange and severe pulmonary insufficiency. The presence of circulating anti-GBM antibodies and deposition of antibodies on the GBM, which is usually revealed by immunofluorescence (IF) staining of the renal biopsy specimen, are diagnostic of the condition.[23] Global incidence varies from 0.5–1 case per million per year. Here, we present a case of a 68-year-old female who was initially diagnosed as decompensated chronic liver disease (DCLD) and later developed gross hematuria and alveolar hemorrhage which turned out to be Goodpasture syndrome. Till now, there has been only one case report of Goodpasture syndrome in a patient who had DCLD due to primary billiary cirrhosis (PBC).[4]
Case Report
A 68-year-old woman was admitted to our hospital with a ten-day history of bilateral lower limb swelling extending up to the thighs. There was no previous history suggestive of cardiac, hepatic, or renal disease and she did not have any other comorbidities. There was no prior history of jaundice, chronic liver disease, chronic alcoholism or drug abuse, or multiple blood transfusions. On physical examination, she was drowsy, mildly icteric, and had bilateral pitting pedal edema along with generalized anasarca. She was not dyspneic and was hemodynamically stable on admission. Other systemic examinations were unremarkable. Her blood biochemistry was as given in Table 1. PT/INR was 22/2. Electrocardiogram (ECG), X-ray chest, and echocardiogram were within normal limits, and bilateral lower limb Doppler ruled out deep vein thrombosis (DVT). Ultrasonogram (USG) abdomen revealed shrunken liver with coarse echo structure, ascites, and portal hypertension with splenomegaly. No intra- or extra-hepatic biliary obstruction was noticed. USG kidney showed normal cortical echogenicity. An initial working diagnosis of DCLD with hepatorenal syndrome (HRS) was made. The patient was started on hepatic protective and anti-hyperkalemic regimens with empirical antibiotic for spontaneous bacterial peritonitis (SBP). Over the next three days, she developed progressive oliguria with persistent hyperkalemia and gross hematuria. On the third day, she was shifted to the intensive care unit (ICU) for progressive renal failure and breathlessness.
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Table 1: Biochemistry Parameters
On receiving in ICU, she was drowsy and hemodynamically stable with bilateral extensive crepitations. Arterial blood gas (ABG) displayed hypoxia and metabolic acidosis with hyperkalemia. She was put on mechanical ventilatory support with renal replacement therapy (RRT). Computed tomography (CT) of the chest revealed diffuse ground glass opacities with patchy consolidation involving both lungs with interstitial reticular opacities [Figure 1]. On day two of ICU admission, she developed anemia besides coagulopathy for which blood and blood products support was given. Later, she developed bloody endotracheal secretions following which fiberoptic bronchoscopy was done. Bronchoalveolar lavage (BAL) revealed hemorrhagic fluid with predominant polymorphs and foamy macrophages which were positive for Perl Stain confirming pulmonary hemorrhage. Her anti-nuclear antibodies (ANA) were positive; anti-double stranded DNA (Ds DNA), anti-smooth muscle antibody, anti-mitochondrial antibody (AMA), and anti-neutrophil cytoplasmic antibodies (P-ANCA, C-ANCA) were negative. Complement levels were normal.
Figure 1: CT chest
Because of these clinical manifestations, Goodpasture syndrome was suspected. Anti-GBM antibody was sent, and patient was started on pulse dose of corticosteroids. Renal and liver biopsies were deferred due to coagulopathy. The patient continued to deteriorate and became hemodynamically unstable and succumbed to the disease in 24 hours. Anti-GBM antibodies came positive via immunofluorescence assay which confirmed the diagnosis of Goodpasture syndrome. As patient's relatives were not willing for autopsy, immunofluorescence study on renal specimen could not be done.
Discussion
Goodpasture syndrome was first described by Ernest William Goodpasture in 1919 and was later named after him in 1958.[5] Anti-GBM disease is now a preferred term since it is classified as small vessel vasculitis caused by in situ immune complex formation.[1] The reported incidence in Asian Indians is low.[256] The low incidence could be due to low suspicion index for the disease among clinicians and lack of diagnostic facilities like immunofluorescence. The prognosis is poor with high morbidity and mortality.
Pathogenesis of Goodpasture syndrome is known to be due to the presence of anti-GBM antibodies directed against the NC1 domain of α-3 type IV collagen present in the lungs and kidneys.[7] The diagnosis of Goodpasture syndrome is made through renal or lung biopsy with immunofluorescence staining revealing anti-GBM antibodies. However, a renal or lung biopsy is not always possible in critically ill patients. The presence of circulating anti-glomerular antibodies is diagnostic of the disease. Plasmapheresis in combination with immunosuppressant therapy with cyclophosphamide and prednisone is the treatment of choice. Therapy is effective only when the disease is detected at an early stage.
The uniqueness of the case presented here was the initial presentation of DCLD. This has been reported only once in the past wherein a patient had a history of PBC, anti-GBM antibodies with myeloperoxidase (MPO) and ANCA, with histology suggestive of renopulmonary syndrome. In our patient, no other obvious cause for the liver cirrhosis could be elucidated. Her AMA were negative but liver enzymes were suggestive of PBC. Her workup for autoimmune panel (including c-ANCA, p-ANCA) except for ANA was negative. As we could not do liver biopsy, whether the hepatic involvement in this case was due to PBC or due to a separate entity is not clear. Probably the unusual presentation of DCLD in our case resulted in a delay in diagnosis. Earlier diagnosis could have been crucial in altering the outcome.
Our case study highlights the importance of high index of suspicion for early diagnosis of anti GBM disease, which is very crucial for the therapy to be effective.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's relatives have given their consent for the images and other clinical information to be reported in the journal with the understanding that name and initials of the patient would not be published and due efforts would be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
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Conflicts of interest
There are no conflicts of interest.
References
1. Hellmark T, Segelmark M. Diagnosis and classification of Goodpasture's disease (anti-GBM) J Autoimmun. 2014;48:108–12
2. Prabhakar D, Rathi M, Nada R, Minz RW, Kumar V, Kohli HS, et al Anti-glomerular basement membrane disease: Case series from a tertiary center in North India Indian J Nephrol. 2017;27:108–12
3. Vavilapalli S, Madireddy N, Uppin MS, Kalidindi K, Gudithi S, Taduri G, et al Anti-glomerular basement membrane disease: A clinicomorphological study of 16 cases Indian J Pathol Microbiol. 2020;63:226–9
4. Komatsu T, Utsunomiya K, Oyaizu T. Goodpasture's syndrome associated with primary biliary cirrhosis Intern Med. 1998;37:611–3
5. Li FK, Tse KC, Lam MF, Yip TP, Lui SL, Chan GS, et al Incidence and outcome of antiglomerular basement membrane disease in Chinese Nephrology (Carlton). 2004;9:100–4
6. Dumeer NK, Pragaya AK, Manmadha Rao T, Sundaram C. Goodpasture′s disease: A case report from South India Indian J Crit Care Med. 2006;10:115–6
7. Wieslander J, Bygren P, Heinegård D. Isolation of the specific glomerular basement membrane antigen involved in Goodpasture syndrome Proc Natl Acad Sci U S A. 1984;81:1544–8
