| The
pulmonary biopsy in the early diagnosis of Wegener's (pathergic)
granulomatosis: a study based on 35 open lung biopsies.Hum
Pathol. 1988 Sep;19(9):1065-71. We
reviewed open lung biopsies from 35 patients with Wegener's (pathergic)
granulomatosis in order to study the histogenesis of the pulmonary
lesions and to identify the early lesions. The process of
pathergic necrosis is fundamental in the production of
extravascular and vascular lesions and was divided into
micronecrotic and macronecrotic types. Micronecrosis, usually with
neutrophils (microabscesses), constitutes the early phase in the
development of the pathognomonic organized palisading granuloma.
The palisading granuloma differs from the compact granuloma of
tuberculoid type, which occurs in infections and sarcoidosis but
not in Wegener's (pathergic) granulomatosis. There is a
progression of disease from micronecrosis to macronecrosis
(widespread necrosis) and then to fibrosis. Macronecrosis
surrounded by palisading histiocytes or diffuse granulomatous
tissue indicates active disease, whereas necrosis surrounded by
fibrous tissue indicates previously active disease. Most cases
have a combination of micronecrosis, and fibrosis. We established
the relative diagnostic value of various histologic features.
Arteritis and phlebitis as classically described in Wegener's
granulomatosis were present in most but not all cases. We believe
that Wegener's granulomatosis primarily affects both vascular and
extravascular collagen and reticulum and that vasculitis
represents a primary necrosis of walls of blood vessels. We
believe that the concept of Wegener's granulomatosis as a
vasculitis is too restrictive and does not include many cases with
only extravascular histologic changes.
Surgical
pathology of the lung in Wegener's granulomatosis. Review of 87
open lung biopsies from 67 patients.Am
J Surg Pathol. 1991 Apr;15(4):315-33.
We report
the pulmonary pathologic features in 87 open lung biopsies from 67
patients with Wegener's granulomatosis (WG) who were treated at a
single institution from 1968 to 1990. At the time of open lung
biopsy, 48 patients (72%) had classical WG with renal involvement;
19 (28%) had limited WG without renal involvement. The pathologic
features were divided into major and minor manifestations. In the
82 specimens demonstrating no infectious organism, the three major
pathologic manifestations of classical WG observed were also
useful diagnostic criteria and included: (a) parenchymal necrosis,
(b) vasculitis, and (c) granulomatous inflammation accompanied by
an inflammatory infiltrate composed of a mixture of neutrophils,
lymphocytes, plasma cells, histiocytes, and eosinophils.
Parenchymal necrosis was found in 84% of biopsy specimens either
as neutrophilic microabscesses (65% of specimens) or as large
(67%) or small (69%) areas of geographic necrosis. Areas of
geographic necrosis were usually surrounded by palisading
histiocytes and giant cells. Additional granulomatous lesions
consisted of microabscesses surrounded by giant cells (69%),
poorly formed granulomas (59%), and scattered giant cells (79%).
Sarcoid-like granulomas were uncommon (4%), and in only one
specimen (1%) appeared within an inflammatory lesion of WG.
Vascular changes were identified in 94% of biopsy specimens.
Vascular inflammation was classified as chronic (37% arterial, 64%
venous), acute (37% arterial, 29% venous), non-necrotizing
granulomatous (22% arterial, 9% venous), and necrotizing
granulomatous (22% arterial, 10% venous). Fibrinoid necrosis was
relatively uncommon (11% arterial, 6% venous). Cicatricial changes
were found in arteries in 41% of biopsy specimens and in veins in
16%. Capillaritis was present in 31% of specimens. Minor
pathologic lesions were commonly observed in biopsy specimens
associated with classical WG lesions, but they were usually
inconspicuous and not useful diagnostic criteria. These included
interstitial fibrosis (26%), alveolar hemorrhage (49%), tissue
eosinophils (100%), organizing intraluminal fibrosis (70%),
endogenous lipoid pneumonia (59%), lymphoid aggregates (37%), and
a variety of bronchial/bronchiolar lesions including acute and
chronic bronchiolitis (51% and 64%), follicular bronchiolitis
(28%), and bronchiolitis obliterans (31%). These minor lesions
were often found at the periphery of typical nodules of WG.
However, in 15 specimens (18%) a minor pathologic feature
represented the dominant or major finding: pulmonary fibrosis (six
specimens, 7%), diffuse pulmonary hemorrhage (six specimens, 7%),
lipoid pneumonia (one specimen, 1%), acute bronchopneumonia (one
specimen, 1%), and chronic bronchiolitis, bronchiolitic obliterans
with organizing pneumonia (BOOP), and bronchocentric
granulomatosis (one specimen, 1%).
Clinical
features and outcome of pediatric Wegener's granulomatosis.
Arthritis Rheum. 2007 May 25;57(5):837-844.
OBJECTIVE:
Wegener's granulomatosis (WG) is a predominantly small-vessel
vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs).
There are few reports describing its clinical features and outcome
in children. We report on the experience at a single tertiary
referral center over 21 years. METHODS: We conducted a
retrospective chart review of all patients diagnosed with WG at
The Hospital for Sick Children between 1984 and 2005. RESULTS:
Twenty-five patients were identified. Median age at diagnosis and
median followup were 14.5 years and 32.7 months, respectively.
Male-to-female ratio was 1:4. Median duration of symptoms before
diagnosis was 2 months. Of 22 patients, 21 were ANCA positive
during their disease course (classic ANCA 78.9%). Constitutional
symptoms were the most common clinical feature at presentation (24
of 25). Glomerulonephritis was present in 22 patients at
presentation. Only 1 of 11 patients who presented with or
developed renal impairment had normalization of serum creatinine.
Upper airway involvement occurred in 21 patients at presentation
and 24 over followup; only 1 had subglottic stenosis. Twenty
patients had initial pulmonary involvement, most commonly nodules
(44%) and pulmonary hemorrhage (44%). Five patients required
ventilation for pulmonary hemorrhage. Four patients (16%) had
venous thrombotic events (VTEs). Treatment included prednisone
(100%), cyclophosphamide (76%), azathioprine (40%), and
methotrexate (32%). CONCLUSION: Pediatric WG typically presents in
adolescence and has a female predominance. Glomerulonephritis and
pulmonary disease are common at diagnosis and frequently present
as a pulmonary-renal syndrome. Loss of renal function is common
and rarely completely reversible. As in adults, children with WG
are at risk of VTEs.
B
lymphocyte differentiation in granulomatous tissues of the lung
and the nasal mucosa in Wegener's granulomatosis : Origin of anti-neutrophil
cytoplasmic antibody formation?
Z
Rheumatol. 2007 May 22;
Wegener's granulomatosis (WG)
starts with granulomatous inflammation of the respiratory tract
before it converts into a potentially organ and life threatening
systemic vasculitis associated with anti-neutrophil cytoplasmic
antibodies (ANCA).The site of formation of the highly specific
ANCA directed against "Wegener's autoantigen" proteinase 3 (PR3)
is still unknown. Previously, we have shown that follicle-like B
lymphocytic infiltrates in the vicinity to PR3 expressing cells in
WG-granulomata. We characterized the immunoglobulin-VH repertoire
in lung and nasal granulomata (paraffin embedded) from four WG
patients. A total of 115 individual VH genes were characterized
and compared to 84 VH genes from the peripheral blood of a healthy
donor. We found an increased frequency of mutations with a bias to
amino acid exchanges within the antigen binding sites (CDR) 1 and
2 in WG tissue. A large number of mutations led to negatively
charged amino acids and may increase affinity to the positively
charged PR3. Furthermore, the occurrence of differently mutated
members of one B cell clone indicates clonal expansion and
intraclonal diversification by an antigen, e.g. PR3. Several WG
tissue derived genes displayed similarities to published sequences
from peripheral PR3 ANCA producing B cells. Thus, granulomata of
the lower and upper respiratory tract contain follicle-like B cell
clusters with a selected VH repertoire infiltrate in WG. WG
granulomata could be the place of autoantigen presentation and
formation of high-affinity ANCA within neoformed ectopic or
tertiary lymphoid-like tissue areas.
A case of
Wegener's granulomatosis presenting as severe acute respiratory
failure.Nihon
Kokyuki Gakkai Zasshi. 2007
Mar;45(3):262-6.
A 19-year-old
man was admitted to another hospital. Pulmonary suppuration was
diagnosed and was treated with antibiotics. However, he developed
acute respiratory failure, which required intubation and ventilation
with 100% oxygen. After treatment with nitric oxide inhalation and
corticosteroid pulse therapy, the patient's condition stabilized and
he gradually regained a satisfactory pulmonary function. He was
discharged about 3 months after admission with a pulmonary function
close to normal. Approximately 1 month later, the patient was admitted
to our hospital because of a 2-week history of fever and chest and
ocular pain. A chest radiograph obtained upon admission showed a
nodule with a cavity in the upper lobe of the right lung. Pulmonary
suppuration was again suspected, and antibiotics were given. The fever
persisted and chest radiograph on hospital day 19 showed marked
extension of the nodules. At that time, the patient complained of
nasal obstruction and hoarseness and his sclera showed intense
congestion, indicating episcleritis. Wegener's granulomatosis was
diagnosed on the basis of the clinical picture, PR3-ANCA titer (63 EU)
and nasal biopsy findings. After treatment with prednisolone and
cyclophosphamide, his condition stabilized, and he recovered
gradually. However, his condition remains poor despite continued
therapy. This is an extremely rare case of Wegener's granulomatosis
presenting as severe acute respiratory failure.
Limited
Wegener's granulomatosis-is it limited?Clin
Rheumatol. 2007 Mar 31;
Complete heart block associated with Wegener's granulomatosis (WG) is
rare especially in the limited form of the disease. We describe a case
of a 43-year-old woman with a limited form of WG who developed a
complete heart block. Prompt treatment with steroids and
cyclophosphamide led to temporary regression of complete heart block.
Further involvement of lung was treated successfully by tumor necrosis
factor-alpha inhibitor infliximab. Cardiac rhythm abnormalities should
always be kept in mind both in diagnosis and follow-up of WG.
Pitfalls
in the diagnosis of Wegener's granulomatosis on fine needle aspiration
cytology.Cytopathology.
2007 Feb;18(1):8-12.
OBJECTIVE: To
review the clinical and pathological findings in six suspected cases
of Wegener's granulomatosis (WG) and highlight the diagnostic
difficulties faced by the cytopathologist. METHODS: Retrospective
review of records of the Cytopathology Department to identify patients
who underwent image-guided transthoracic pulmonary fine needle
aspiration cytology (FNAC) for pulmonary lesions of suspected WG and
those who were subsequently confirmed to have WG. Detailed evaluation
of cytomorphological features was carried out. RESULTS: A total of six
cases were identified in whom the initial procedure to obtain a
pathological diagnosis was transthoracic FNAC. In one case, atypical
squamous cells on cytology initially suggested a diagnosis of squamous
cell carcinoma while in another a diagnosis of WG was made on
cytology; however, a subsequent lung biopsy revealed silicosis.
CONCLUSION: Acute inflammation and necrosis are the most consistent
cytopathological findings in WG. In selected cases FNAC can provide
supportive pathological evidence to establish a diagnosis of WG.
Wegener's
granulomatosis--diagnostic problem.Otolaryngol
Pol. 2006; 60(3):355-62.
Wegener's
granulomatosis there is a small--and middle--vessels vasculitis. The
pathomorphological diagnostic criteria is known as Wegener's triad: 1)
necrotizing granlomatous inflammation of upper and/or lower
respiratory tract, 2) systemic or focal necrotizing vasculitis
involving arteries and vein, and 3) focal segmental necrotizing
crescentic gromerulonephritis. According to the current theory of
pathogenesis of Wegener's granulomatosis, Staphylococcus aureus is
involved. The rise in ANCA level during vascular inflammation is very
important for monitoring disease. The main localization of Wagener's
granulomatosis is in lung, nasal sinusites, nose, kidneys and nasal
pharynx. MATERIAL AND METHODS: The history of 60-years old female
patient who was being treated in Department of Otolaryngology for
chronic bilateral otitis media for many years is presented. During
hospitalization the sinusites, rhinitis and renal failure additionally
were found. The CT sinuses and head, histopatological and ANCA exam in
patient were performed. RESULTS: Based on clinical, physical,
additional exam Wegener's granulomatosis was diagnosed. CONCLUSIONS:
1) Surgical procedure is not indicated method of treatment of
Wegener's granulomatosis, because it can increase the pathologic
process. 2) The prognosis of Wegener's granulomatosis depends mainly
on the ability to diagnose the early disease and the aplication of
adequate treatment.
Wegener
granulomatosis: a case report and update.South
Med J. 2006 Sep;99(9):977-88.
Wegener
granulomatosis (WG) is a systemic disease of unknown etiology
characterized by necrotizing granulomatous inflammation, tissue
necrosis, and variable degrees of vasculitis in small and medium-sized
blood vessels. The classic clinical pattern is a triad involving the
upper airways, lungs and kidneys. Ninety percent of patients present
with symptoms involving the upper and/or lower airways, and 80% will
eventually develop renal disease. WG should be suspected in any
patient with progressive or unresponsive sinus disease,
glomerulonephritis, pulmonary hemorrhage, mononeuritis multiplex or
unexplained multisystem disease. Before the routine use of
glucocorticoids and cyclophosphamide, the one year mortality was 82%.
However in 1973, Fauci and Wolf discovered that daily prednisone and
cyclophosphamide induced complete remission in 75% of patients. The
continued use of prednisone and cyclophosphamide for 1 year past
remission leads to marked improvement in more than 90% of patients;
however, is also associated with serious toxicities. Depending on the
disease severity, current treatments employ induction with short-term
cyclophosphamide followed by less toxic agents such as methotrexate to
maintain disease remission. Although it is a rare disorder, it is
pertinent to internists because it is a multisystem disease that
presents in a variety of ways. We describe a 63-year-old white male
with WG who presented with progressively worsening headaches,
bilateral eye redness, epistaxis, hemoptysis and an unintentional 20
pound weight loss, and review the current treatment recommendations.
Wegener's
granulomatosis is associated with organ-specific antiendothelial cell
antibodies.Kidney
Int. 2004 Sep;66(3):1049-60.
BACKGROUND:
Antiendothelial cell antibodies (AECA), usually detected using human
umbilical vein endothelial cells (HUVEC), are frequently observed in
systemic vasculitis, but their pathogenic role is unclear.
Heterogeneity of endothelial cells necessitates use of clinically
relevant endothelial cells for elucidation of the role of AECA in
systemic vasculitis involving small blood vessels of specific organs.
METHODS: Human endothelial cells were isolated from normal tissue
specimens from the nose, kidney, lung, liver, and umbilical vein.
Using flow cytometry, AECA were detected against both unstimulated and
cytokine-stimulated [tumor necrosis factor-alpha (TNF-alpha) and
interferon-gamma (IFN-gamma)] endothelial cells. Functional capacity
of AECA was determined by complement fixation assay. Sera from
patients with Wegener's granulomatosis (16), limited Wegener's
granulomatosis (8), renal limited disease (4), microscopic
polyangiitis (MPA) (5), rheumatoid arthritis (10), and systemic lupus
erythematosus (SLE) (9), and from healthy controls (20) were analyzed.
RESULTS: Compared with controls (1) Wegener's granulomatosis is
significantly associated with noncytotoxic AECA that selectively bind
surface antigens on unstimulated nasal, kidney, and lung endothelial
cells; (2) binding of Wegener's granulomatosis AECA to kidney and
nasal endothelial cells in particular was lost upon treatment with IFN-gamma
and TNF-alpha; (3) the two cytokines per se were cytotoxic (30%) to
nasal and lung endothelial cells and lysis was further increased (60%)
by addition of systemic vasculitis serum; and (4) Wegener's
granulomatosis serum caused agglutination of cytokine-stimulated nasal
endothelial cells. CONCLUSION: Based on these findings we suggest that
AECA may be one factor involved in the initiation of Wegener's
granulomatosis. Antigen identification and elucidation of the
pathogenic roles of AECA and inflammatory cytokines in systemic
vasculitis using these cells will be particularly important.
Atypical
squamous cells as a diagnostic pitfall in pulmonary Wegener's
granulomatosis. A case report.Acta
Cytol. 2002 May-Jun;46(3):571-6.
BACKGROUND:
Wegener's granulomatosis (WG) is characterized by systemic,
necrotizing, granulomatous inflammation accompanied by vasculitis. It
classically involves the triad of the upper respiratory tract, lungs
and kidneys. Isolated pulmonary lesions of WG may present in some
patients as pulmonary masses, simulating neoplasms. The features of WG
can be suggested by cytologic study. Atypical epithelial cells
associated with WG have previously been reported as a cause of a false
positive diagnosis of bronchoalveolar carcinoma. CASE: In this case
the cytologic findings included atypical squamous cells in a
background of acute, chronic and granulomatous inflammation. In
several respiratory specimens the atypical squamous cells were
incorrectly interpreted as diagnostic of squamous cell carcinoma. The
correct diagnosis of WG was confirmed with open lung biopsy, which
demonstrated necrotizing granulomatous inflammation with geographic
necrosis and associated vasculitis. CONCLUSION: Markedly atypical
squamous cells mimicking squamous cell carcinoma can be found
accompanying the inflammatory process associated with WG and are a
possible diagnostic pitfall. The possibility of WG as well as other
inflammatory processes should always be considered in the differential
diagnosis of squamous cell carcinoma of the lung. This case is the
only reported case of WG in which atypical squamous cells were a
diagnostic pitfall, initially suggesting a diagnosis of squamous cell
carcinoma.
Wegener granulomatosis.
Am J Med Sci. 2001 Jan;321(1):76-82.
Wegener
granulomatosis (WG) is a necrotizing, granulomatous vasculitis that
has a clinical predilection to involve the upper airways, lungs, and
kidneys. Although the first case was reported by Klinger in 1931,
Friedrich Wegener in 1936 characterized the unique clinical and
pathological features of this disease that subsequently came to bear
his name. Vascular inflammation and occlusion leading to tissue
ischemia is a hallmark of WG. Although strong evidence indicates that
such blood vessel damage is immunologically mediated, the mechanisms
that initiate this process are still largely unknown. To date, there
has been no clearly established association with genetic factors,
specific infectious agents, or environmental irritants, although
speculation has remained that these may play a role in triggering the
onset of disease. Until the introduction of therapy with
cyclophosphamide (CYC) and glucocorticoids, WG was uniformly fatal.
Although drug toxicity and disease relapse remain of concern with this
regimen, it has provided us with a successful means of treatment and
the opportunity to better understand this disease through long-term
patient follow-up.
Wegener
granulomatosis in pediatric patients.J
Pediatr. 1985 May;106(5):739-44.
Wegener
granulomatosis is more easily recognized as a distinct clinical
entity than other vasculitides because the initial clinical features
frequently include granulomatous vasculitis of the upper and lower
respiratory tract and glomerulonephritis. Although the disease has
been lethal in the past, prolonged survival and avoidance of
end-stage kidney disease can now be expected when cyclophosphamide
therapy is introduced early in the course. We report four children
with Wegener granulomatosis in whom the initial clinical findings
suggested Henoch-Schonlein purpura. In two of the patients Wegener
granulomatosis was not recognized until after end-stage kidney
disease had developed. The course in these patients emphasizes the
need for attention to even scant evidence of inflammation of the
upper or lower respiratory tract in patients with glomerulonephritis.
Appropriate diagnostic studies may then lead to recognition of
Wegener granulomatosis and the prompt institution of appropriate
treatment.
Wegener granulomatosis in
children and adolescents: clinical presentation and outcome.J
Pediatr. 1993 Jan;122(1):26-31.
We
prospectively studied and compared clinical features, treatment,
course of illness, and long-term morbidity and mortality rates for
Wegener granulomatosis in 23 childhood-onset patients with those of
135 adult-onset patients who were studied concurrently. Treatment
was usually provided with glucocorticoids and cyclophosphamide. The
mean follow-up period was 8.7 years for childhood-onset and 7.6
years for adult-onset Wegener granulomatosis. Most aspects of
Wegener granulomatosis were similar in childhood-onset and
adult-onset patients. Permanent morbidity from disease occurred in
86% of both groups. However, some features were significantly
different. Wegener granulomatosis in childhood-onset patients was
complicated five times more often by subglottic stenosis and twice
as often by nasal deformity. Treatment-related permanent morbidity
occurred in 22% of childhood-onset patients and 45% of adult-onset
patients. After similar periods of cyclophosphamide therapy and
follow-up, cyclophosphamide-related malignancies were less likely
(0% vs 11%) to have developed in childhood-onset patients. Although
89% of patients treated with glucocorticoids and cyclophosphamide
had remission, prolonged delay in achieving remission and relapses
led in both patient groups to freedom from active disease for
approximately 50% of the total patient-years. As a result, morbidity
was substantial and has led to comparative studies of alternative
therapies.
Update on Wegener granulomatosis.Cleve
Clin J Med. 2005 Aug;72(8):689-90, 693-7.
Wegener
granulomatosis classically involves clinical disease of the upper
airways, lungs, and kidneys. Ninety percent of patients present with
symptoms involving the upper or lower airways, or both, and it
should be suspected in any patient with pulmonary hemorrhage,
glomerulonephritis, mononeuritis multiplex, unexplained multisystem
disease, or progressive unresponsive sinus disease. Current
treatments induce remission and allow long-term survival.
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