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Diffuse alveolar hemorrhage complicating small vessel vasculitis is a

life-threatening emergency and should be considered in the differen-

tial diagnosis of patients who develop rapidly progressive dyspnea with

alveolar opacities on chest imaging. In these patients, the coexistence

of pulmonary and renal involvement suggests a multisystem disease.

We present a case of a man who presented to our hospital with diffuse

alveolar hemorrhage, severe anemia, and rapidly progressive glomeru-

lonephritis.

Microscopic polyangiitis (MPA) is a rare antineu-trophil cytoplasmic antibody (ANCA)–associated necrotizing vasculitis, mainly aff ecting the pul-monary and renal capillaries. One of the so-called

pulmonary-renal syndromes, it is characterized by infl amma-tion of the small blood vessels, the absence of granulomas on histopathology, and the presence of circulating ANCAs. Th e incidence is currently estimated at about 1 in 100,000 per year, with a slight male predominance. Other ANCA-associated vasculitides include granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis), eosinophilic granulo-matosis with polyangiitis (formerly known as Churg-Strauss syndrome), and renal-limited vasculitis (1–7). Because of its severe disease manifestations, diff use alveolar hemorrhage is a cause of signifi cant morbidity and mortality and requires intensive, meticulous, and aggressive care for any chance of a meaningful outcome. Prompt diagnosis is important to permit initiation of therapy that may be both lifesaving and organ sparing. Th is may be challenging because of the nonspecifi c clinical features. We report a man who presented to our hos-pital with severe diff use alveolar hemorrhage and in whom MPA was subsequently diagnosed.

CASE PRESENTATIONA 58-year-old Hispanic man with no signifi cant past medi-

cal history presented to the emergency department of our hos-pital with 5 days of exertional dyspnea and nonproductive cough associated with fever and night sweats. He also reported a 12-pound weight loss over the preceding month. He was not on any medications and was a former cigarette smoker with a 20 pack-year history, having quit 1 month prior to presenta-

From the Department of Medicine, St. Joseph Hospital, Chicago, Illinois.

Corresponding author: Chibuzo Clement Odigwe, MD, Department of Medicine,

St. Joseph Hospital, 2900 North Lake Shore Drive, Chicago, IL 60657 (e-mail:

chibuzo2k2@yahoo.com).

tion. He had the sickle cell trait. On admission he was febrile, with a temperature of 101.7°F, a pulse rate of 106 beats per minute, a respiratory rate of 24 breaths per minute, and a blood pressure of 156/80 mm Hg. His initial oxygen saturation was 97% on room air. His conjunctiva was pale, and his mucous membranes were dry.

His hemoglobin level was 5.4 g/dL and serum creatinine, 7.2 mg/dL (normal range, 0.6–1.3). A chest radiograph showed bilateral pulmonary infi ltrates (Figure 1a). Urinalysis showed large proteinuria and large hematuria. He was transfused with 2 units of packed red blood cells. We excluded the presence of active tuberculosis with a negative Mantoux test and initiated Pneumocystis jiroveci prophylaxis. His HIV test was negative. He rapidly deteriorated, becoming confused and desaturating to 88% oxygen saturation even on 4L nasal cannula supplemental oxygen. A repeat chest radiograph showed worsening of the bilateral infi ltrates compared to his prior fi lm on admission (Figure 1b). He was intubated and transferred to the intensive care unit. His chest radiographic fi ndings progressively wors-ened (Figure 1c).

Further evaluation of his anemia with iron studies revealed a pattern consistent with anemia of chronic disease. Other notable laboratory results were a negative hepatitis panel, tuberculosis QuantiFERON, glomerular basement membrane antibody, anti-dsDNA antibody, and PR3-ANCA, but a positive myelo-peroxidase (MPO-ANCA). Fiber optic bronchoscopy revealed diff use blood oozing from all pulmonary segments, consistent with pulmonary hemorrhage, and a percutaneous kidney biopsy showed Pauci-immune crescentic glomerulonephritis, which is typical for MPA.

Th e patient was treated with 1 g intravenous methylpred-nisolone daily for 3 days and then oral prednisone 60 mg daily, in addition to cyclophosphamide 75 mg twice daily. He was also treated with daily plasmapheresis for 7 days and received atovaquone for pneumocystis prophylaxis. He had some neu-tropenia following cyclophosphamide treatment and was treated

Microscopic polyangiitis causing diffuse alveolar hemorrhage and rapidly progressive glomerulonephritisMohamad Hani Lababidi, MD, Chibuzo Odigwe, MD, Chukwuka Okolo, MD, Ahmed Elhassan, MD, and Nkemakolam Iroegbu, MD, MPH

Proc (Bayl Univ Med Cent) 2015;28(4):469–471

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with subcutaneous fi lgrastim with good response (Figure 1d). Persistent severe anemia and hemorrhage was managed with 5 units of packed red blood cells and 20 units of fresh frozen plasma in total. He recovered signifi cantly, was extubated, was discharged to outpatient nephrology and rheumatology follow-up, and continues to do well.

DISCUSSIONPulmonary hemorrhage is a life-threatening condition that

often develops acutely on a background of a smoldering process. MPA is one of the most common causes of the pulmonary-renal syndrome of alveolar hemorrhage and rapidly progressive glomerulonephritis. It has a variable pulmonary presentation, which ranges from fl eeting focal infi ltrates to massive lung hemorrhage and hemoptysis in the setting of diff use alveolar hemorrhage. Its peak incidence is between the ages of 30 and 50 years and the incidence has been estimated at between 8 to 10 cases per million per year (1–3).

Although MPA is a recognized cause of diff use alveolar hem-orrhage, alveolar hemorrhage is relatively rare as a presenting fea-ture. In a retrospective review of 36 patients, lung involvement was seen in 22% of cases and alveolar hemorrhage in 11% (2–4, 5). Another study by Lane et al found pulmonary involvement in 29% of patients (6). Severe clinical manifestations similar to our index case have also been reported in children (8).

Th e clinical features of MPA present a dilemma in diagnosis on account of their nonspecifi c and varied clinical presenta-tion. Common clinical features that have been reported include acute or chronic cough, dyspnea, fever, weight loss, myalgia, and arthralgia. Mononeuritis multiplex (60% of cases) and cutane-ous vasculitis (>60% cases) have also been reported. Alveolar hemorrhage, in contrast, occurs in only about 20% to 30% of patients, and hemoptysis is sometimes absent due to the ability of the alveoli to absorb a signifi cant amount of blood before it extends to the large airways. In view of the nonspecifi c nature of the chest x-ray fi ndings, computed tomography scanning is

Baylor University Medical Center Proceedings Volume 28, Number 4

Figure 1. The patient’s chest radiographs. (a) On admission, showing bilateral pulmonary infiltrates. (b and c) Between admission and day 2, showing worsening of

the bilateral infiltrates. (d) Improvement after treatment with steroids, immunosuppressant, and plasmapheresis.

a b

c d

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said to be more sensitive in terms of distinguishing pulmonary hemorrhage from other causes of alveolar shadowing. Another test of theoretical interest is the measurement of the carbon monoxide transfer coeffi cient, which may be impractical given the acuity of presentation (1–5).

Indeed, a wide variety of pulmonary manifestations of MPA have been reported, including isolated pulmonary hemorrhage, as against the classic pulmonary renal syndrome, as seen in our patient. Chronic alveolar hemorrhage and nonspecifi c intersti-tial pneumonia with alveolar hemorrhage preceded by hearing loss have also been seen. Pulmonary fi brosis has been reported in association with the pulmonary complications of MPA, al-though the mechanism by which this occurs remains unclear (9). A key diff erential diagnosis is Goodpasture disease, which was excluded in our patient by a negative antiglomerular base-ment membrane antibody test.

Our patient responded to the initial treatment with steroids, immunosuppressant, and plasmapheresis, which is the standard of care (1–8). Th e combination of oral cyclophosphamide and methylprednisolone induces remission in about 80% to 90% of patients with ANCA-associated vasculitis, with about 75% experiencing complete remission and most remissions occurring between 2 and 6 months. However, there are reports of patients who respond poorly to this regimen, for whom the next option would be recombinant factor VII therapy (2, 10). Th ere are case reports of good clinical response, particularly resolution of diff use alveolar hemorrhage, in patients in whom recombinant factor VII treatment was instituted. Rituximab is also an option in place of cyclophosphamide, particularly in young patients desiring fertility preservation, although it has not been studied extensively in patients with serum creatinine >4 mg/dL or in patients who require mechanical ventilation (11, 12).

Adjunctive plasma exchange is also recommended for patients with signifi cant renal dysfunction without concur-rent antiglomerular basement membrane antibody disease or pulmonary hemorrhage in the setting of MPA. Up to seven sessions is recommended over 2 weeks, with 60 mL/kg plasma removal at each session and with albumin or fresh frozen plasma

October 2015

replacement each time depending on the risk of bleeding or the presence of active bleeding (1–5, 7).

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Microscopic polyangiitis causing diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis