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CASE REPORT Table of Contents  
Ahead of print publication
A case of microscopic polyangiitis with diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis


 Department of Radiology, Seth GSMC and KEM Hospital, Mumbai, Maharashtra, India

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Date of Submission21-May-2021
Date of Decision10-Aug-2021
Date of Acceptance11-Aug-2021
Date of Web Publication11-Oct-2021
 

  Abstract 


Vasculitis is a rare but important cause of diffuse alveolar hemorrhage (DAH) and should be considered in the differential diagnosis of patients who develop rapidly progressive dyspnea with nonresolving alveolar opacities on thoracic imaging. The coexistence of renal impairment is termed pulmonary-renal syndrome. Microscopic polyangiitis is a nongranulomatous necrotizing systemic vasculitis that affects arterioles and capillaries. We present a case of a 25-year-old female with hemoptysis with bilateral perihilar chest infiltrates and rapidly deteriorating renal function. Positive anti-myeloperoxidase antibodies, presence of significant hemoptysis, parahilar lung infiltrates, and rapidly deteriorating renal function clinched the diagnosis of DAH secondary to small-vessel vasculitis (microscopic polyangiitis). The patient showed significant improvement with hemodialysis, oxygen supplementation, steroids, and cyclophosphamide. Hemoptysis with rapidly deteriorating renal function in a young to middle-aged lady should raise suspicion of underlying vasculitis after ruling out other more common causes.

Keywords: Anti-myeloperoxidase antibodies, diffuse alveolar hemorrhage, microscopic polyangiitis, vasculitis


How to cite this URL:
Reddy G V, Seshadri H. A case of microscopic polyangiitis with diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis. Apollo Med [Epub ahead of print] [cited 2021 Dec 6]. Available from: https://www.apollomedicine.org/preprintarticle.asp?id=327970





  Introduction Top


Microscopic polyangiitis (MPA) is a rare antineutrophil cytoplasmic antibody (ANCA)–associated with necrotizing vasculitis, mainly affecting the pulmonary and renal capillaries. It is characterized by inflammation of the small blood vessels, the absence of granulomas on histopathology, and the presence of circulating ANCAs. It is one of the important causes of pulmonary–renal syndrome. Vasculitis-induced diffuse alveolar hemorrhage (DAH) is an important cause of significant morbidity and mortality and requiring a high degree of clinical and radiological suspicion. We report a female who presented to our hospital with severe DAH with rapidly progressive glomerulonephritis and in whom MPA was subsequently diagnosed.


  Case Report Top


A 25-year-old female presented with bilateral pedal edema for 10 days. She also reported significant weight loss over 3 months. Her history included Plasmodium vivax malaria 3 years ago and an episode of urinary tract infection 1 year ago. On admission, she was afebrile with a temperature of 36.3°C, pulse rate was 70 beats/min, blood pressure 170/100 mmHg, and saturation was 97% on room air. Her conjunctiva was pale. Bilateral pitting pedal edema and periorbital puffiness were noted. Routine laboratory examination showed elevated leukocyte count of 13,500 cells/mm3 (elevated), hemoglobin 9.8 g/dl, erythrocyte sedimentation rate of 70 mm/h (elevated), creatinine of 5.8 mg/dl (elevated), and blood urea nitrogen 90 mg/dl (elevated).

Chest radiography on the day of admission showed no abnormality [Figure 1].
Figure 1: Chest radiograph on the day of admission showed no abnormality

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Ultrasound of the abdomen showed an increase in renal cortical echogenicity with an increased intraparenchymal resistive index of both kidneys suggestive of medical renal disease.

Elevated leukocyte count and elevated levels of procalcitonin (>200 ng/ml) raised the clinical suspicion of sepsis with kidney dysfunction. Urinary analysis showed dysmorphic red blood cells, red cells, and granular casts.

Reduced levels of C3 (52.2 mg/dl) and C4 (9.7 mg/dl) raised the clinical suspicion of lupus nephritis as the cause for kidney dysfunction. Serum MPG blot was positive (44, class ++) – antibodies against myeloperoxidase (MPO) enzyme, i.e. p-ANCA, PR3 antibody (10, class +), and negative for glomerular basement membrane (GBM) antibody. Renal biopsy was advised, however not performed due to the negative consent of the patient.

Over the course of 10 days in the hospital, the patient developed shortness of breath and had two episodes of hemoptysis each 100 ml in quantity with chest radiograph showed bilateral parahilar chest infiltrates [Figure 2]. Her hemoglobin reached a nadir of 5.5 g/dl and creatinine rising to 7 mg/dl. The patient was started on hemodialysis because of rising creatinine and clinical signs of volume overload. High-resolution computed tomography (HRCT) showed parahilar ground-glass opacities, consolidations, bilateral mild pleural effusion [Figure 3]. Over the next 2 days, the patient had another episode of hemoptysis (70 ml) and began to deteriorate with saturation dropping to 90%–92%, requiring noninvasive ventilation.
Figure 2: Chest radiograph on 10th day of admission shows bilateral parahilar lung infiltrates with basal predominance

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Figure 3: HRCT chest-Axial(A & B) shows bilateral dense ground glass and alveolar consolidations with central and parahilar predominance. Coronal reformation (C) shows relative sparing of apices and both costophrenic angles

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On the basis of hemoptysis with progressing pulmonary infiltrates and rapidly progressive glomerulonephritis and positive antibodies against MPO enzyme, diagnosis of DAH with glomerulonephritis secondary to microscopic polyangiitis was considered a working diagnosis.

The patient was started on 1 g of methylprednisolone and 75 mg of cyclophosphamide. Within 2 weeks of starting steroids, immunosuppressants, and supportive measures such as hemodialysis, the patient's condition improved and she was weaned off noninvasive ventilation. Repeat chest radiograph was under normal limits. Repeat HRCT of the chest showed near-complete resolution of pulmonary opacities with new onset of fine reticulations and interspersed ground-glass opacities indicating progression to subacute phase [Figure 4]. The patient was advised regular nephrology and rheumatology follow-up.
Figure 4: Follow up HRCT of chest-Axial(A & B) shows near-complete resolution of pulmonary opacities with new onset of fine reticulations and interspersed ground-glass opacities indicating progression to subacute phase. Coronal reformation (C) shows near complete clearing of bilateral pulmonary infiltrates indicating good treatment response

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  Discussion Top


DAH is an uncommon but life-threatening condition referred to as bleeding into the alveolar space due to injury to alveolar microcirculation. It is linked to several diseases, with causes ranging from coagulopathies to inhaled contaminants to viruses and collagen vascular disorders. The etiology of DAH can be classified as with or without underlying capillaritis. Capillaritis causing DAH can be further characterized into primary and secondary vasculitis. Primary vasculitis includes Wegener's granulomatosis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. Secondary vasculitis includes Behcet's disease, Goodpasture syndrome. DAH without capillaritis is usually nonimmune mediated such as cardiac disorders, pulmonary hemosiderosis, radiation-induced, and toxin inhalation.[1]

Although DAH is rare, its early recognition is extremely crucial in deciding the line of management. Hemoptysis is usually the common presenting symptom; however, it is not seen in all patients with DAH. Anemia in patients with DAH is usually seen in all patients with Goodpasture syndrome but less frequent with other causes of DAH.[1],[2]

DAH is an uncommon condition and is difficult to differentiate from pulmonary edema radiologically. On chest radiograph, DAH usually manifests as confluent consolidations or ground-glass opacities in perihilar and basal predominance with sparing of the costophrenic and apical areas. The opacities are of variable size and show the rapid change in position, size and density with time. With appropriate treatment, there is complete resolution of opacities in 2 weeks leaving behind a reticular pattern secondary to siderophage deposition in the interstitium due to chronic bleeding into the alveoli.[3]

Irrespective of the underlying disease, the findings of DAH are the same on HRCT. In the acute phase of hemorrhage, there are multiple areas of ground-glass opacities which progress to consolidation. In areas of ground-glass opacities, there is apparent prominence of subsegmental airways resulting in “dark bronchus sign.”[4] In the subacute phase, multiple interlobular septal thickening is superimposed on areas of ground-glass opacities resulting in a crazy-paving pattern. These findings take a longer time to resolve as compared to pulmonary edema. There may be incomplete resolution resulting in interstitial fibrosis.

In cases of vasculitis-induced DAH, there are recurrent episodes of alveolar hemorrhages with phases of relapse. During the phase of relapse, HRCT of the chest may show small (1–3 mm) ill-defined centrilobular nodules without any zonal predominance. These nodules represent the interalveolar deposition of pulmonary macrophages.[4]

The radiological findings of DAH are not specific, a similar pattern can be seen in other cases of diffuse alveolar filling patterns caused by fluid (cardiogenic pulmonary edema) or inflammatory exudates (pneumonia). Pulmonary edema presents with similar findings but usually have a dependent gradient of opacities and is associated with cardiomegaly, venous congestion, and pleural effusion. Diffuse pneumonia usually has no dependent gradient. Pulmonary infections are seldom associated with hemoptysis, exceptions being tuberculosis and necrotizing pneumonia. Chest radiograph findings, serum and sputum studies, and clinical history clinches the diagnosis.

The term pulmonary–renal syndrome refers to the combination of DAH and rapidly progressive glomerulonephritis and is characterized by a destructive inflammatory process that involves necrotic pulmonary capillaritis.[5] Microscopic polyangiitis is a nongranulomatous necrotizing systemic vasculitis that affects arterioles and capillaries. It usually presents as pulmonary–renal syndrome.

Glomerulonephritis is invariably present in all cases. Pulmonary symptoms include hemoptysis, breathlessness, and dry cough. Renal disease often leads to progressive decline in renal function with proteinuria and microscopic hematuria and rapidly declining renal function which often leads to the need for initiation of dialysis and associated fluid overload and hypertension. However, in this case, the presentation is often secondary to renal disease, unlike collagen vascular disorders where the presenting complaint is usually hemoptysis. A key differential diagnosis is Goodpasture disease, which was excluded in our patient by a negative anti-GBM antibody test. Serum procalcitonin is a useful marker for the detection of systemic infection in patients with systemic autoimmune disease such as microscopic polyangiitis as in our patient.[6]

The purpose of bronchoscopy with bronchoalveolar lavage is to confirm the presence of intraalveolar blood, exclude the large airways as a source of bleeding, and rule out infection. DAH was reported to be an independent prognostic factor of MPA and the mortality rate of MPA patients with DAH is 8.65 times greater than that of MPA patients without DAH.[7]

Management of DAH includes supportive care in the form of oxygen supplementation, mechanical ventilation, and coagulation correction (to maintain INR <1.5 and platelet count >50,000 cells/μl). European vasculitis study group has classified antibody-associated vasculitides into various subtypes to assign different regimens.[8] Our patient was categorized as severe subtype in view of renal failure and started on induction regimen including cyclophosphamide, steroids, and plasmapheresis, and was put on a maintenance regimen of lower dose steroid. The role of plasma exchange has had conflicting results in the past.[9]


  Conclusion Top


  • Imaging findings of DAH are often nonspecific and often difficult to differentiate from other causes of chest infiltrates like pulmonary edema, but this distinction is critical in arriving at the diagnosis and the underlying etiology
  • Hemoptysis with deteriorating renal function in a young to middle-aged lady should raise suspicion of underlying vasculitis after ruling out other common causes such as infection, toxins, and drugs.
  • Asymptomatic patient with chest infiltrates and chronic severely progressing anemia could suggest chronic asymptomatic DAH.[10]


Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that their name and initial will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wilson CB, Dixon FJ. Anti-glomerular basement membrane antibody-induced glomerulonephritis. Kidney Int 1973;3:74-89.  Back to cited text no. 1
    
2.
Briggs WA, Johnson JP, Teichman S, Yeager HC, Wilson CB. Antiglomerular basement membrane antibody-mediated glomerulonephritis and Goodpasture's syndrome. Medicine (Baltimore) 1979;58:348-61.  Back to cited text no. 2
    
3.
Albelda SM, Gefter WB, Epstein DM, Miller WT. Diffuse pulmonary hemorrhage: A review and classification. Radiology 1985;154:289-97.  Back to cited text no. 3
    
4.
Cheah FK, Sheppard MN, Hansell DM. Computed tomography of diffuse pulmonary haemorrhage with pathological correlation. Clin Radiol 1993;48:89-93.  Back to cited text no. 4
    
5.
Papiris SA, Manali ED, Kalomenidis I, Kapotsis GE, Karakatsani A, Roussos C. Bench-to-bedside review: Pulmonary-renal syndromes – An update for the intensivist. Crit Care 2007;11:213.  Back to cited text no. 5
    
6.
Eberhard OK, Haubitz M, Brunkhorst FM, Kliem V, Koch KM, Brunkhorst R. Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease (systemic lupus erythematosus/systemic antineutrophil cytoplasmic antibody-associated vasculitis) and invasive bacterial infection. Arthritis Rheum 1997;40:1250-6.  Back to cited text no. 6
    
7.
Hogan SL, Nachman PH, Wilkman AS, Jennette JC, Falk RJ. Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol 1996;7:23-32.  Back to cited text no. 7
    
8.
Geetha D, Kallenberg C, Stone JH, Salama AD, Appel GB, Duna G, et al. Current therapy of granulomatosis with polyangiitis and microscopic polyangiitis: The role of rituximab. J Nephrol 2015;28:17-27.  Back to cited text no. 8
    
9.
Klemmer PJ, Chalermskulrat W, Reif MS, Hogan SL, Henke DC, Falk RJ. Plasmapheresis therapy for diffuse alveolar hemorrhage in patients with small-vessel vasculitis. Am J Kidney Dis 2003;42:1149-53.  Back to cited text no. 9
    
10.
Yamato K, Ishii T, Kawamura T. Microscopic polyangiitis in a girl with severe anemia and no respiratory symptoms. Pediatr Int 2012;54:541-3.  Back to cited text no. 10
    

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Correspondence Address:
G Vikram Reddy,
Department of Radiology, Seth GS Medical College and KEM Hospital, Mumbai-400012
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/am.am_42_21



    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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