A 72-year-old man with a purpuric rash

ACUTE GLOMERULONEPHRITIS PLUS PULMONARY HEMORRHAGE EQUALS…?

4. Which disease could have manifestations consistent with acute glomerulonephritis and pulmonary hemorrhage?

• Antiglomerular basement membrane disease
• Wegener granulomatosis
• Microscopic polyangiitis
• Systemic lupus erythematosus

All of these are possible.

The combined presentation of acute glomerulonephritis and pulmonary hemorrhage (also called pulmonary-renal syndrome) is usually seen in antiglomerular basement membrane disease (Goodpasture syndrome) and small-vessel systemic vasculitides such as Wegener granulomatosis and microscopic polyangiitis.^2,3 It can also be seen in patients with systemic lupus erythematosus.

Antiglomerular basement membrane disease

In antiglomerular basement membrane disease, circulating antibodies are directed towards an antigen intrinsic to the glomerular basement membrane, typically leading to acute glomerulonephritis associated with crescent formation. It may present as acute renal failure in which urinalysis shows proteinuria with sediment characterized by red cell casts. Pulmonary involvement, usually alveolar hemorrhage, is present in approximately 60% to 70% of cases.

The diagnosis requires demonstration of antiglomerular basement membrane antibodies in either the serum or the kidney. Renal biopsy is usually recommended because the accuracy of serum assays is variable.

A key histologic feature of the renal lesion in antiglomerular basement membrane disease is crescentic glomerulonephritis in which immunofluorescence microscopy demonstrates the virtually pathognomonic finding of linear deposition of immunoglobulin G along the glomerular capillaries.

The treatment of choice for antiglomerular basement membrane disease is plasmapheresis and immunosuppression with a combination of glucocorticoids and cyclophosphamide (Cytoxan). If the disease is high on the differential diagnosis, empiric plasmapheresis should be started while waiting for diagnostic studies, because the prognosis of untreated glomerulonephritis is poor.

Wegener granulomatosis

Wegener granulomatosis is a systemic vasculitis of the medium and small arteries, arterioles, and venules that classically involves the upper and lower respiratory tracts and the kidneys. Patients may present with persistent rhinorrhea and epistaxis, cough with chest radiographs showing nodules, fixed infiltrates, or cavities, and abnormal urinary sediment with microscopic hematuria with or without red cell casts.

From 75% to 90% of patients with active Wegener granulomatosis are positive for antineutrophil cytoplasmic antibody (ANCA). In 60% to 80% of cases, ANCA is directed against proteinase 3 (PR3), which produces a cytoplasmic standing pattern by immunofluorescence (cANCA), while 5% to 20% have ANCA directed against myeloper-oxidase, which produces a perinuclear staining pattern (pANCA). A small number of patients with Wegener granulomatosis are ANCA-negative.

The diagnosis is usually confirmed by tissue biopsy at the site of active disease, which shows necrotizing vasculitis with granulomatous inflammation. The renal lesion is typically that of a focal, segmental, necrotizing glomerulonephritis that has few to no immune complexes (pauci-immune glomerulonephritis).

The treatment of severe disease involves a combination of cyclophosphamide and glucocorticoids initially to achieve remission followed by maintenance therapy with methotrexate or azathioprine (Imuran).

Microscopic polyangiitis

Microscopic polyangiitis is a systemic vasculitis of the capillaries, venules, and arterioles, with little or no immune complex deposition. Nearly all patients have renal involvement, and 10% to 30% have lung involvement. In those with lung involvement, diffuse alveolar hemorrhage is the most common manifestation.

On histopathologic study, microscopic polyangiitis differs from Wegener granulomatosis in that it does not have granuloma formation. However, the renal lesion is that of a pauci-immune glomerulonephritis and is identical to that seen in Wegener granulomatosis. From 70% to 85% of patients with microscopic polyangiitis are ANCA-positive, and most of these have pANCA.

The management of active severe microscopic polyangiitis is identical to that of Wegener granulomatosis.

Systemic lupus erythematosus

Systemic lupus erythematosus is an autoimmune disease characterized by tissue-binding autoantibody and immune-complex-mediated organ damage. It can involve multiple organ systems, and the diagnosis is based on characteristic clinical features and autoantibodies. The sensitivity of antinuclear antibody for lupus is close to 100%, which makes it a good screening tool. Antibodies to dsDNA and Smith antigen have high specificity for lupus.

About 75% of patients have renal involvement at some point in their disease course. The different types of renal disease in systemic lupus are usually differentiated with a renal biopsy, with immune-complex-mediated glomerular diseases being the most common.

The most common pulmonary manifestation is pleuritis with or without pleural effusion. Life-threatening pulmonary manifestations include pulmonary hemorrhage and interstitial inflammation leading to fibrosis.

Lupus has great clinical variability and the treatment approach is based on the organ manifestations, disease activity, and severity.