lung vasculitis and alveolar hemorrhage: pathology vasculitis and alveolar... · lung vasculitis...

Lung Vasculitis and Alveolar Hemorrhage:PathologyGregory A. Fishbein, B.A.1 and Michael C. Fishbein, M.D.2

ABSTRACT

Pulmonary vasculitides are a diverse group of limited and systemic disordersassociated with inflammation of pulmonary vessels and parenchyma. These diseases oftenhave distinctive clinical, serological, and histopathological features—extrapulmonary sitesof involvement, circulating autoantibodies, predispositions for small or large vessels, andothers. Some have characteristic inflammatory lesions; others are characterized by theabsence of such lesions. Frequently pathological findings overlap, rendering classification,and diagnosis a challenge.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated small-vessel dis-eases constitute the major pulmonary vasculitides. These include Wegener granulomatosis(WG), Churg Strauss syndrome (CSS), and microscopic polyangiitis (MPA). Lessfrequently, diseases such as polyarteritis nodosa, Takayasu arteritis, Behcet syndrome,and connective tissue diseases may involve pulmonary vessels, but these entities are betterassociated with extrapulmonary disease.

Diffuse alveolar hemorrhage (DAH) is a severe manifestation of pulmonaryvasculitis. DAH is most commonly seen in small-vessel vasculitides, specifically MPA andWG. Other syndromes associated with DAH include Goodpasture syndrome, Henoch-Schonlein purpura, and systemic lupus erythematosus. Less commonly, DAH may besecondary to infection or drugs/toxins. Furthermore, in the absence of discernable systemicdisease, DAH may be idiopathic—referred to as isolated pulmonary capillaritis (IPC) oridiopathic pulmonary hemosiderosis (IPH), depending on the presence of capillaritis.

KEYWORDS: Vasculitis, Wegener granulomatosis, microscopic polyangiitis, Churg-

Strauss syndrome, diffuse alveolar hemorrhage

Literally, vasculitis simply means inflammationof a vessel. However, vasculitis is rarely that simple. Inreality, vasculitides are complex and highly variablesyndromes. The pathology of a vasculitis is frequentlynot limited to vessel inflammation. In some cases,vasculitides exhibit phases during which vessel inflam-mation may not even be present.1,2 Historically, vasculi-

tides have been classified by their histopathology. Inpractice, they are often diagnosed clinically. Moreover,as laboratory tests become more sophisticated, vasculi-tides may be classified serologically. Unfortunately, mostof these clinical, histopathological, and laboratory fea-tures are nonspecific. Therefore, the best attempts atclassification have involved all three. The result is an

1David Geffen School of Medicine at UCLA, Los Angeles, California;2Department of Pathology and Laboratory Medicine, David GeffenSchool of Medicine at UCLA, Los Angeles, California.

Address for correspondence and reprint requests: Michael C.Fishbein, M.D., Department of Pathology and Laboratory Medicine,David Geffen School of Medicine at UCLA, Rm. 13-145H CHS,10833 Le Conte Ave., Los Angeles, CA 90095 (e-mail: [email protected]).

Lung Vasculitis and Alveolar Hemorrhage; Guest Editor, LoıcGuillevin, M.D.

Semin Respir Crit Care Med 2011;32:254–263. Copyright # 2011by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York,NY 10001, USA. Tel: +1(212) 584-4662.DOI: http://dx.doi.org/10.1055/s-0031-1279823.ISSN 1069-3424.

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exceedingly complex schema, fraught with overlap andconfusing nomenclature.3

Vasculitides can be categorized based on severalfeatures:

1. Etiology—primary versus secondary2. Vessel type—arteries, veins, capillaries, lymphatics3. Vessel size—small, medium, large4. Inflammatory features—acute versus chronic, eosino-

philic, granulomatous, necrotic, leukocytoclastic, andso forth

5. Distribution of involvement—systemic versus lim-ited, organs typically affected

6. 6) Laboratory findings—autoantibodies, erythrocytesedimentation rate, peripheral eosinophilia, and soforth

7. Clinical history—rash, asthma, hemoptysis, hematu-ria, myalgia, claudication, and so forth

Each descriptor is not without its shortcomings.The etiology may be uncertain—perhaps idiopathic, butwith risk factors such as family diathesis or history ofviral infection. Commonly, multiple types of vessels areaffected. Multiple sizes of vessels are involved. More-over, our definitions of small, medium, and large arearbitrary (some vasculitides have different opinions ofwhat small means). Inflammatory features can varydepending on the site of involvement. At times, weresort to accommodating atypical histopathology byinventing variants, for example, bronchiolitis obliteransorganizing pneumonia (BOOP)-like variant or eosino-

philic variant. Multiple organs may be involved, andthere are myriad case reports describing unusual sites ofinvolvement. Laboratory findings may only be markersof disease; loose associations are common. Ultimately,the clinical findings of vasculitis may be overwhelminglynonspecific (eg, malaise, myalgia, rash). Furthermore,signs and symptoms at presentation represent only asnapshot of the clinical picture, particularly if the diseaseis chronic or phasic.

Pulmonary vasculitides are as resistant to catego-rization as any vasculitis. The following text is intendedto be descriptive; it is not an attempt at strict classifica-tion. Furthermore, though all pulmonary vasculitis isuncommon, there are numerous rare pulmonary vasculi-tides that will not receive attention. The entities dis-cussed hereafter are enumerated in Table 1.

WEGENER GRANULOMATOSISWegener granulomatosis (WG) is a necrotizing smallvessel vasculitis most commonly affecting the upper andlower respiratory tracts and the kidneys. The pathologistplays an important role in the clinical management ofWG because the diagnosis of this disorder requirespathological confirmation.4

Grossly, the lungs frequently exhibit bilateralnodular masses, roughly 2 to 3 cm in diameter. Thenodules feature irregular borders and areas of centralnecrosis, appearing dark yellow to red. Areas of consol-idations and hemorrhage may be visible, but the sur-rounding parenchyma is often unremarkable. Some

Table 1 Vasculitides That Affect the Lung and Diffuse Alveolar Hemorrhage Syndromes

Vasculitis commonly involving the lung Wegener granulomatosis

Churg-Strauss syndrome

Microscopic polyangiitis

Vasculitis uncommonly involving the lung Polyarteritis nodosa

Takayasu arteritis

Behcet syndrome

Lymphoproliferative disorders

Infection

Foreign body reaction

Drugs/toxin reaction

Diffuse alveolar hemorrhage syndromes Microscopic polyangiitis

Wegener granulomatosis

Goodpasture syndrome

Systemic lupus erythematosus

Henoch-Schonlein purpura

Idiopathic pulmonary

hemosiderosis

Isolated pulmonary capillaritis

Infection

Drugs/toxin reaction

The list above is limited to entities discussed in the text; it is not exhaustive.

LUNG VASCULITIS AND ALVEOLAR HEMORRHAGE: PATHOLOGY/FISHBEIN, FISHBEIN 255

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specimens lack nodules but exhibit features of associatedpathology, such as diffuse alveolar hemorrhage, inter-stitial fibrosis, and lipoid pneumonia.

Microscopically, WG is characterized by threemajor lesions: parenchymal necrosis, vasculitis, andgranulomatous inflammation (Fig. 1). The majority oflung biopsies will demonstrate some mixture of thesethree lesions.5 The most striking of the three is paren-chymal necrosis. Predominant patterns include neutro-

philic microabscesses and geographic necrosis. Necroticareas have characteristic serpentine borders and gran-ular centers. They are often described as blue necrosis,due to the large amounts of basophilic nuclear debris.Peripherally, histiocytes and scattered giant cells sur-round the necrosis in a manner some describe as acartwheel pattern.

WG is a vasculitis of small vessels, under 5 mm indiameter, including arteries, venules, and capillaries.

Figure 1 Wegener granulomatosis with a variety of vascular and parenchymal lesions. (A) Pulmonary capillaritis with alveolar

hemorrhage (hematoxylin and eosin stain [H&E], 40�). (B) Venulitis with fibrinoid necrosis of the vein wall (arrow) (H&E, 200�).

(C) Arteritis with lymphocytic infiltrate and prominent intimal hyperplasia (H&E, 100�). (D) Arteritis with eosinophils present

(H&E, 200�). (E) Granulomatous arteritis with multinucleated giant cell in lumen of artery (H&E, 100�). (F) ‘‘Blue necrosis’’ with

adjacent giant-cell in lung parenchyma (arrow) (H&E, 40�).

256 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 32, NUMBER 3 2011

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Vasculitic areas are typically found adjacent to majorinflammatory lesions. Arteries and veins exhibit cellularchronic inflammatory infiltrate, neutrophils, fibrinoidnecrosis, and poorly formed granulomas. Neutrophiliccapillaritis and diffuse alveolar hemorrhage can bepresent. Cicatricial changes such as intimal proliferationand medial scarring are common.

Extravascular granulomas accompanied bymixed inflammatory cells are characteristic of WG.Lesions composed of lymphocytes, plasma cells, neu-trophils, and eosinophils accompany poorly formedcollections of palisading histiocytes and scattered giantcells. Often the infiltrate surrounds microabscesses.Sarcoid-like non-necrotizing granulomas are presentin rare cases.5

Other minor histological features are frequentlyfound in lung biopsies. These are typically nondiagnosticand are peripheral to major inflammatory lesions. Pa-renchymal tissue demonstrates changes such as intersti-tial fibrosis, lymphoid aggregates, alveolar hemorrhage,and organizing pneumonia. Foamy macrophages arefrequently present, giving the appearance of endogenouslipoid pneumonia. Xanthogranulomatous lesions appearwith prominent cholesterol clefts. Tissue eosinophilsmay be abundant in some cases, and focal areas ofeosinophilic pneumonia may even be seen. This eosino-philic variant of WG closely mimics Churg-Straussdisease but typically is not associated with peripheraleosinophilia.6 Additionally, eosinophilic pleuritis ispresent in roughly half of biopsies. Bronchiolar involve-ment is not uncommon, though the pathology in WG istypically considered angiocentric. Acute and chronicbronchiolitis and bronchiolitis obliterans can be seenalong with prominent organizing pneumonia, represent-ing a cryptogenic organizing pneumonia (COP)-likevariant (i.e., BOOP) of WG.7

CHURG-STRAUSS SYNDROMEChurg-Strauss syndrome (CSS), also called Churg-Strauss angiitis or Churg-Strauss granulomatosis, is adisease characterized by asthmatic bronchitis, peripheraleosinophilia, and vasculitis. These features tend to occurin phases, and the disease usually progresses in the orderlisted earlier.1 Histologically, there are three majorpathological findings: vasculitis, tissue eosinophilia,and granulomatous inflammation (Fig. 2). However,given the phasic nature of the disease course, a singlebiopsy specimen is unlikely to exhibit all three features.1

Therefore, in the context of strong clinical and labora-tory evidence, a diagnosis of CSS can be made even inthe absence of definitive histology.8

The pulmonary histopathological findings mostcharacteristic of CSS are asthmatic bronchitis, eosino-philic pneumonia, extravascular granulomatous inflam-mation, and necrotizing vasculitis of small and medium-

sized arteries and veins. Typical findings of asthmaticbronchitis include eosinophilic inflammation, subepithe-lial basement membrane thickening, submucosal glandhyperplasia, and smooth muscle hypertrophy of airways.Additionally, edema and mucous plugging are common.Eosinophilic pneumonia is quite common, featuring nu-merous intraalveolar eosinophils and mixed degrees oforganizing fibrosis. The granulomas of CSS have a uniqueappearance. Often called allergic granulomas or eosino-philic abscesses, they consist of extravascular collections ofpalisading histiocytes and multinucleated giant cellsaround a central core of necrotic eosinophils. Allergicgranulomas may involve the vessels but are more oftenseen extravascularly. As the granulomas heal, they becomefibrotic and calcified. Vasculitis in CSS chiefly affectssmall and medium-sized arteries and veins, but capillariesmay be involved as well. Fibrinoid necrosis and transmuralchronic inflammation are typical. Numerous eosinophilsare present, along with epithelioid cells, multinucleatedgiant cells, and occasional neutrophils. Alveolar hemor-rhage secondary to eosinophilic capillaritis may occur.1

Extrapulmonary pathology is of notable impor-tance in CSS. A major cause of morbidity and mortalityin CSS is cardiac involvement, affecting nearly half ofpatients.9 Eosinophilic and granulomatous myocarditismay be present, which can manifest as heart failure orconduction disturbance. Interstitial fibrosis may be theonly finding, depending on the chronicity of the disease.The pericardium commonly demonstrates acute fibri-nous pericarditis and pericardial fibrosis.10 Myocardialinfarction due to coronary arteritis may also occur.11

Virtually all organs may be affected, but the morecommon are the gastrointestinal tract,12 skin, and liver.Renal disease is not prominent in CSS but has beenreported to occur in 25% of patients.13

Histologically, CSS may be difficult to distin-guish from other pulmonary diseases in which eosino-phils are a prominent feature. These include theeosinophilic variant of WG,6 parasitic infection, anddrug-induced vasculitis—all may demonstrate markedtissue eosinophilia, vasculitis, and granulomatous in-flammation. Close attention to history and judicioususe of laboratory tests are imperative. Indeed, one mustinterpret ANCA titers with caution because both CSSand WG may present with p-ANCA positivity, c-ANCA positivity, or neither.14 Cavitating lesions, how-ever, are common in WG and rare in CSS. Furthermore,peripheral eosinophilia greater than 5% is unusual forWG.

MICROSCOPIC POLYANGIITISOnce inaptly referred to as microscopic polyarteritis,microscopic polyangiitis (MPA) is a necrotizing vascu-litis of arterioles, venules, and capillaries. Medium-sizedarteries may also be affected. While almost all patients


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have glomerulonephritis, the majority of cases of MPAalso involve the lung, and, like WG, major extrapulmo-nary sites of involvement include the kidney and headand neck.14 Clinically, MPA can present similarly toWG. Histologically, however, MPA differs from WG inthat granulomatous inflammation is not seen. Hence,biopsy is often crucial in distinguishing the two diseases.It should be noted that MPA is the most common causeof pulmonary-renal syndrome.15

The two major pathological features of MPA areneutrophilic capillaritis and pulmonary hemorrhage(Fig. 3). Alveolar hemorrhage is the predominantfeature, with capillaritis present in scattered patchyfoci. Accompanying the hemorrhage are nonspecificchanges such as interstitial thickening, hemosiderosis,and organizing pneumonia. Hyaline membranes maybe present, making MPA difficult to distinguishfrom hemorrhagic diffuse alveolar damage (DAD).

Figure 2 Churg-Strauss syndrome. (A) Eosinophilic arteritis with marked destruction of the arterial wall (hematoxylin and

eosin stain [H&E], 100�). (B) Eosinophilic venulitis (H&E, 200�). (C) Alveolar septal capillaries distended by intraluminal

eosinophils (H&E, 400�). (D) Necrotic eosinophils (eosinophilic abscess) (H&E, 200�). (E) ‘‘Asthmatic bronchitis’’ with

thickening of the subepithelial basement membrane (asterisk), and eosinophilic bronchitis (H&E, 400�). (F) Eosinophilic/

granulomatous myocarditis from a fatal case (H&E, 100�).


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Figure 3 Microscopic polyangiitis. (A) Neutrophilic capillaritis with acute alveolar hemorrhage (hematoxylin and eosin stain

[H&E], 100�). (B) Hemosiderin-laden macrophages (arrow) in a case with chronic hemorrhage (H&E, 200�). (C) Destroyed small

artery with arteritis and luminal thrombosis (T) (H&E, 200�).


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Necrotizing vasculitis may affect medium and smallarteries, venules, and capillaries—in contrast to polyar-teritis nodosa, in which veins and small vessels arespared. Granulomatous inflammation and eosinophilicinfiltrate are absent, distinguishing MPA from otherANCA-associated vasculitides such as WG and CSS.

OTHER PULMONARY VASCULITIDESThe ANCA-associated small vessel diseases account forthe major pulmonary vasculitic disorders. However, adiverse set of other vasculitides are known to affect the

lung. These entities deserve at least brief discussion(Fig. 4).

Polyarteritis Nodosa

Polyarteritis nodosa (PN) is a necrotizing vasculitis ofmedium-sized arteries. Like MPA, PN lacks both gran-ulomatous and eosinophilic inflammation. However, inPN, arterioles, capillaries, and venules are spared.3 PNmore likely affects bronchial arteries than pulmonaryarteries. The fact remains, however, that polyarteritisnodosa rarely affects the lung.16 It is believed that many

Figure 4 Other pulmonary vasculitides. (A) Example of Takayasu disease with giant-cell arteritis (hematoxylin and eosin stain

[H&E], 200�). (B, C) Granulomatous arteritis and venitis in the pulmonary vessels of a patient with sarcoidosis (H&E, 100�). (D,

E) ‘‘Infectious arteritis’’ in a patient with pulmonary mucormycosis with fungal hyphae occluding the arterial lumen (D) and

infiltrating through the arterial media (E) into surrounding tissue. (D) H&E, 200�; (E) methenamine silver stain, 200�.


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previous reports of pulmonary PN would be consideredMPA by current criteria.

Takayasu Arteritis

Takayasu arteritis, also called aortic arch syndrome,young female arteritis, and ‘‘pulseless disease,’’ is a largeartery vasculitis that primarily affects the aorta and itsmajor branches. Pulmonary and bronchial arteries, how-ever, may be involved, and lung involvement has beenlinked to the Bw52/Dw12 haplotype.17 Histologically,Takayasu arteritis appears as chronic inflammation oflarge elastic arteries with scattered giant cells, predom-inantly in the outer two thirds of the vessel wall.Typically, there is marked intimal and adventitial scar-ring. Major complications include stenosis and aneur-ysm, at a ratio of almost 4:1, respectively.18 Fistulaformation is a rare but deadly complication; pulmonaryartery to bronchial artery, and pulmonary artery tocoronary artery fistulas have been reported.19

Behcet Syndrome

Behcet syndrome (pronounced beh ‘chet) is a vasculitisaffecting vessels of virtually all sizes. The disease ischaracterized by the classic triad of oral ulcers, genitalulcers, and uveitis. Other organ systems may beaffected, including the central nervous system, skin,gut, and lung. The major histological finding is anecrotizing lymphocytic vasculitis involving small,medium, and large arteries and veins, and capillaries.The most common pulmonary manifestation is pul-monary artery aneurysms, typically presenting as he-moptysis. The aneurysms may be single or multiple,unilateral or bilateral. Thrombi within the aneurysmsare common.20

Miscellaneous

Vasculitis in the lung may be found in virtually allcollagen-vascular diseases, even those primarily causingsoft tissue injury or those associated with pulmonaryinterstitial or airways disease. In cryoglobulinemia, pul-monary lesions are not uncommon, with small vesselleukocytoclastic vasculitis or medium-sized artery in-volvement.14 In sarcoidosis, classic or necrotizing, gran-ulomatous vasculitis may be seen in systemic andpulmonary arteries.21,22 Even in inflammatory boweldiseases, such as ulcerative colitis, pulmonary vasculitishas been described.23

Furthermore, there are several disorders in whichthe pulmonary vessels are secondarily involved. In lym-phoproliferative disorders affecting the lung, pulmonaryblood vessels may be infiltrated by the lymphoid cells ormay even be necrotic. Certain angioinvasive bacteria andfungi, such as Aspergillus and Phycomycetes, cause vascu-

litis, vascular necrosis, and vascular occlusion with pul-monary infarcts.24 Foreign materials injected byintravenous drug abusers can cause a granulomatousvasculitis. Toxic substances, such as L-tryptophan,25

are associated with eosinophilic vasculitis.

DIFFUSE ALVEOLAR HEMORRHAGEPulmonary hemorrhage is a serious complication of anextensive variety of diseases and drugs. It can be classifiedas acute or chronic, localized or diffuse. When theprocess is diffuse, one can expect a relatively stereotypedhistopathology, independent of the etiology (Fig. 5).Diffuse alveolar hemorrhage (DAH) is commonly im-munologically mediated, often secondary to vasculitis.Indeed, the presence or absence of immune-complexdeposition or capillaritis is an important clue used todistinguish various etiologies of DAH. However, toarrive at a specific diagnosis invariably requires clinical,and often serological, patient information (Table 2).26

Biopsy can assist in identifying the specific causeof DAH. It should be emphasized that the diagnosis ofDAH does not necessitate an open biopsy. Indeed, openbiopsies provide the highest-yield specimens, but trans-bronchial and transthoracic needle core biopsies haveproven sufficient in the majority of cases.27 Upon micro-scopic evaluation, one can anticipate the presence ofextravascular blood. However, when the presence ofintact red cells is the dominant feature, the most likelycause is trauma related to the biopsy procedure.28 Incontrast, hemosiderin-laden macrophages are reliablypresent in DAH. Macrophages may appear as quicklyas within 2 days and may persist for several weeks.29

Additional signs of ‘‘real’’ pulmonary hemorrhage in-clude fibrin deposition, type II pneumocyte hyperplasia,and acute inflammation. Chronic hemorrhage may resultin an organizing pneumonia pattern and vascular en-crustation by hemosiderin—so-called endogenous pneu-moconiosis.30 Of course, with a clinical history ofhemoptysis, one can be more confident that ‘‘real’’pulmonary hemorrhage is present.

Capillaritis is an important feature of DAH, thepresence of which may help narrow the differentialdiagnosis. Histopathologically, capillaritis consists ofvarying degrees of neutrophilic interstitial infiltrationand fibrinoid necrosis. Nuclear debris in the interstitiummay be present, representing leukocytoclasis.31

The presence of immune-complex or antibodydeposits also helps to distinguish the etiology of DAH.However, deposits cannot be easily assessed using ordi-nary light microscopy—immunofluorescence (IF) is clas-sically the technique of choice to identify such deposits.Whereas IF is an invaluable diagnostic technique in renalpathology, it is not routinely performed in the context ofDAH. Nonetheless, DAH manifests in three patternsidentifiable by IF: (1) hemorrhage due to deposition of


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anti–basement membrane antibodies (ABMAs), (2)hemorrhage due to immune-complex deposition, and(3) hemorrhage with little or no deposits. ABMA disease,or Goodpasture syndrome, produces characteristic lineardeposits, whereas diseases of immune-complex deposi-tion, such as systemic lupus erythematosus and Henoch-Schonlein purpura (HSP), appear granular. IdiopathicDAH and diseases associated with ANCA yield nofindings or unimpressive granular deposits and are there-fore referred to as pauci-immune.

Of the pauci-immune DAH syndromes, WG hasthe most characteristic histopathology. Often there is aprofound neutrophilic capillaritis. The presence of micro-abscesses (blue necrosis) and granulomatous inflamma-tion make the diagnosis of WG a slam dunk. More

nonspecific is the histopathology MPA, in which neu-trophilic capillaritis may be prominent, but granuloma-tous inflammation is absent. Extrapulmonary disease ismore common in MPA than in WG, and MPA isstrongly associated with p-ANCA. The histopathologyof DAH in ABMA disease, or Goodpasture syndrome,closely resembles MPA, though capillaritis, if present,tends to be unimpressive. Serology indicating circulatingABMA is highly suggestive but may be absent in ex-tremely rare cases. Furthermore, WG and ABMA diseasemay coexist.32 Diseases of connective tissue also causeDAH—none more commonly than systemic lupus eryth-ematosus (SLE). The pathophysiology of DAH in SLEinvolves immune-complex deposition, therefore produc-ing a granular pattern on IF. Capillaritis is also seen.

Table 2 Characteristics of Diffuse Alveolar Hemorrhage Syndromes

Goodpasture WG MPA SLE HSP IPH IPC

Capillaritis Minimal Abundant Abundant Present Present Absent Present

Immune deposits ABMA None None Immune-complex Immune-complex None None

Immunofluorescence Linear None None Granular Granular None None

Associated serology ABMA ANCA ANCA ANA None None None

ABMA, anti–basement membrane antibody; ANA, antinuclear antibody; ANCA, anti-neutrophilic cytoplasmic antibody; HSP, Henoch-Schonleinpurpura; IPC, isolated pulmonary capillaritis; IPH, idiopathic pulmonary hemosiderosis; MPA, microscopic polyangiitis; SLE, systemic lupuserythematosus; WG, Wegener granulomatosis.

Figure 5 Diffuse alveolar hemorrhage. (A) Pulmonary hemorrhage with neutrophilic capillaritis. Note alveolar septae are

destroyed by the neutrophilic infiltrates (hematoxylin and eosin stain, 400�). (B) Numerous hemosiderin-laden macrophages

indicate true hemorrhage has occurred (Prussian blue stain for iron, 400�). (C) Encrustation of the wall of a vein (V) indicative of

chronic hemorrhage (Prussian blue stain for iron, 100�).


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When extrapulmonary and serological findingsare absent, DAH may be idiopathic or drug related.Idiopathic pulmonary hemosiderosis is a chronic illnessthat tends to affect children more than adults.33 Clin-ically, patients will have recurrent episodes of hemoptysisand are frequently anemic. Histopathological findingsare completely nonspecific—hemosiderin is abundantlypresent and there is no capillaritis. In contrast, isolatedpulmonary capillaritis is a rare form of DAH—histolog-ically, it resembles any of the other DAH syndromesfeaturing capillaritis.

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