Pulmonary/ Renal SyndromesDz

Definition: A number of distinct conditions are characterized by significant pulmonary and renal involvement (Table 35). Typically, they present with hemoptysis related to alveolar hemorrhage and extensive alveolar infiltrates on chest radiograph. Renal involvement in these syndromes is usually a form of proliferative glomerulonephritis and may be asymptomatic at initial presentation. Nephritis often manifests with hematuria, proteinuria, and, in some cases, azotemia. Although the pathogenesis of the various conditions may be quite distinct, their presenting signs and symptoms tend to be similar and do not usually allow differentiation. Nevertheless, optimal treatment of these various diseases may differ; thus, an early specific diagnosis may favorably influence the outcome.

Etiology: See Table 35.

Disease Associations: The presence of symptoms in other organ systems may provide clues to the correct diagnosis. For example, patients with granulomatosis with polyangiitis (GPA) may have nasal airway involvement or sinusitis in addition to the pulmonary and renal signs. Patients with SLE who have severe renal and pulmonary disease often have additional manifestations of lupus in other organ systems. Patient demographics sometimes also provide diagnostic clues. Goodpasture’s syndrome tends to occur in white men in their twenties. SLE affects women 10 times as commonly as men, primarily during their child- bearing years. GPA and cryoglobulinemia tend to affect older persons more commonly than SLE and Goodpasture syndrome. However, males and females of all races and ages can be affected by each of these conditions.

Biopsy: GPA is characterized by granulomatous vasculitis in affected tissues. Goodpasture syndrome is characterized by antibodies to the GBM. Immunofluorescent staining of biopsy specimens from the lungs and kidneys of patients with Goodpasture syndrome reveals a characteristic linear pattern of antibody deposition at the basement membrane. In contrast, diseases such as SLE and cryoglobulinemia are characterized by immune complex formation. Biopsy of affected tissues may reveal a “lumpy-bumpy” pattern of immunofluorescence in these conditions, consistent with immune complex formation.

Histopathology, particularly of renal lesions, may provide important diagnostic clues. For example, cryoglobulinemia may be associated with pathognomonic findings on electron microscopic analysis of renal biopsy specimens. The renal pathologic findings of SLE are not seen commonly in other diseases and, in the correct clinical setting, can provide strong support for diagnosis of SLE.

There is an important caveat to the use of biopsy specimens to provide a diagnosis in patients with pulmonary/renal presentations. Obtaining biopsies, particularly pulmonary biopsies, may be difficult and also dangerous in some cases. For example, in both GPA and Goodpasture syndrome, transbronchial biopsy has a low diagnostic yield and has been associated with uncontrolled bleeding and death. If necessary, open lung biopsy is preferred.

Diagnostic Testing: Laboratory studies are often useful in evaluating patients with pulmonary/renal syndromes. Routine types of laboratory studies may not help to pinpoint the cause, but they can be quite important in defining the severity of end-organ involvement. For example, patients with most of these conditions have a hypoproliferative anemia, consistent with the anemia of chronic disease. In addition, those with significant blood loss from the lungs or kidneys may have a superimposed iron deficiency anemia. Urinalysis will reveal hematuria, pyuria, and proteinuria, and serum creatinine will reflect the extent of renal impairment. These indices are useful not only in establishing renal involvement, but also in following the course of the disease and the response to therapy. Arterial blood gases are important for establishing the severity of pulmonary compromise and the need for specific therapies such as supplemental oxygen. Serum complement protein (C3, C4) levels reflect activation of the complement cascade. They tend to be depressed in conditions characterized by immune complex formation, such as SLE and cryoglobulinemia, and normal or elevated in other conditions.

Specific immunologic laboratory testing can be of great help in defining the etiology underlying a pulmonary/renal syndrome. Anti-GBM antibodies are seen in >95% of patients with Goodpasture syndrome and are rarely seen in other conditions. In the correct clinical setting, the presence of cryoglobulins in the serum offers strong support for this diagnosis. Routine use of an ANA without regard for clinical symptoms or signs may be of little help in establishing the diagnosis of SLE. However, when used in selected patients (e.g., a young woman with a pulmonary/renal syndrome and a malar rash), ANA results have greater predictive value. Other tests, such as anti-DNA and anti-Sm antibodies, are more specific for SLE. Finding ANCA may help establish the diagnosis of a pulmonary/renal syndrome. Finding a C-ANCA or antiproteinase-3 antibody offers strong support for the diagnosis of GPA. P-ANCA antibodies may suggest the presence of other vasculitic conditions associated with pulmonary and renal involvement, including Churg-Strauss syndrome, microscopic polyarteritis, and idiopathic crescentic glomerulonephritis.

Therapy: Treatment generally consists of nonspecific therapies in conjunction with specific immunomodulatory therapies. Interventions such as red cell transfusion, supplemental oxygen, tight control of blood pressure, appropriate therapy with antibiotics, and others may be critical to the patient’s outcome. Immunomodulatory interventions generally include corticosteroids, plasma- pheresis, and cytotoxic drugs such as cyclophosphamide and azathioprine. The choice of agents, dosage, and other variables may differ among the various pulmonary/renal syndromes.

BIBLIOGRAPHY

Jara LJ, Vera-Lastra O, Calleja MC. Pulmonary-renal vasculitic disorders: differential diagnosis and management. Curr Rheumatol Rep 2003;5:107–115. PMID:12628041

Schwarz M, Fontenot AP. Drug-induced diffuse alveolar hemorrhage syndromes and vasculitis. Clin Chest Med 2004;25:133. PMID:15062605