|Year : 2007 | Volume
| Issue : 1 | Page : 29-38
A case of systemic vasculitis
Ashim Das, Vinay Sakhuja, Dheeraj Khurana, Nandita Kakkar, Naveen Kalra, Pradeep Bambery
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Das A, Sakhuja V, Khurana D, Kakkar N, Kalra N, Bambery P. A case of systemic vasculitis. Indian J Nephrol 2007;17:29-38
CPC Editor : Ashim Das, Additional Professor of Histopathology
CPC Chairperson : Vinay Sakhuja, Dean PGI and Professor of Nephrology
Clinical Discussant : Dheeraj Khurana, Assistant Professor of Neurology
Pathology Discussant : Nandita Kakkar, Additional Professor of Histopathology
Radiology Discussant : Naveen Kalra, Assistant Professor of Radiodiagnosis
Commentary : Pradeep Bambery, Professor of Internal Medicine
(This case was discussed on 20 th April, 2005 as a staff clinicopathological exercise at PGIMER, Chandigarh)
Dheeraj Khurana, Assistant Professor of Neurology
A 52-year-old female presented with the chief complaints of fever for 2 months, vomiting for 1 month, reduced urinary output for 1 month, and altered sensorium for 1 week.
She had been asymptomatic 2 months back, when she developed a low-grade fever (98-99°F) with a maximum of 102°F. There were no localizing symptoms. She had been treated elsewhere for typhoid (Widal test was negative) but the fever persisted. Based on chest X-ray findings, she was started on antitubercular drugs in November 2004. There was history of vomiting for the last 1 month, which was nonprojectile and nonbilious. There was no associated diarrhea, hemetemesis, melena, or abdominal pain. There was history of loss of appetite and decreased urinary output (~ 150-300 ml/day) for the last month. There was no history of dysuria or hematuria. The patient was given hemodialysis at another hospital (4 times) and 7 units of blood had also been transfused. Since the last 1 week, the patient had developed altered sensorium, with irrelevant talk and drowsiness; there was no history of seizures, reduced movement of any part of the body, or of neck stiffness. There was history of pain in the small and large joints for 1 week.
She had no history of diabetes, hypertension, or pulmonary tuberculosis in the past. She was postmenopausal and had no history of addictions.
On general physical examination, she was found to be conscious but disoriented to time, place, and person. The pulse was 84 beats/min and regular, blood pressure was 130/70 mm Hg, and the respiratory rate was 20/ min. Pallor and pedal edema were present. Asterixis was noticeable. The cardiovascular system was normal, but chest examination revealed bronchial breathing in the right inter- and infra-scapular regions. The abdomen was soft and there was no visceromegaly. She was disoriented, but was moving all four limbs. The extraocular movements and the pupils were normal, deep tendon reflexes were elicited normally and the plantars were bilaterally flexor.
Dr. Naveen Kalra, Assistant Professor of Radiodiagnosis
Chest X-ray PA view done on 08.11.04 showed consolidation in the right mid-zone. In addition, multiple nodular lesions were seen in the right lower zone [Figure - 1]A and B. A repeat chest X-ray on 04.01.05 showed a decrease in the consolidation in the right mid-zone. However, the left mid-zone and right lower zone showed the appearance of alveolar shadows. The skull X-ray was normal on AP and lateral views. X-ray of the pelvis was normal. The chest X-ray findings could represent infection, including tuberculosis, or pulmonary hemorrhage, Wegener's granulomatosis, or bronchiolo-alveolar carcinoma.
The patient was given a 31/2 h haemodialysis (HD) on 3.1.05. The altered sensorium persisted. She had been on ATT since November 2004. She was now started on parenteral antibiotics. During the hospital stay, the patient was mostly afebrile (~ 37°C) and the urinary output ranged from nil to 150 ml/day. Haemodialysis was repeated on 5.1.05 and 7.1.05. She developed a rash on her palms and soles on 7.1.05. Her sensorium remained blunted, with only intermittent response to commands. She developed purpuric papules (nontender) on the pulp of her fingers and toes. She developed shortness of breath of sudden onset on 8.1.05; the possibility of pulmonary hemorrhage was considered. However, her respiratory distress worsened and she succumbed.
Unit's final diagnosis
Bronchopneumonia: ?tubercular, ?pyogenic; acute renal failure: ?AIN, ?RPGN; and encephalopathy:
| ~ Clinical Discussion|| |
This patient had a fever of 2 months duration with no specific localizing symptoms and an altered sensorium of 1 week duration along with rapidly progressive renal failure. The urinary sediment was active (RBCs 3+, Pus cells +). This would classify the patient as having rapidly progressive glomerulonephritis (RPGN). Since the patient had multisystem involvement, with renal, pulmonary, neurological (altered sensorium), and dermatological (rashes) involvement along with constitutional symptoms like fever, loss of appetite, vomiting, and joint pains, it was possibly due to some immunologically-mediated disease, with RPGN being a secondary glomerulopathy. The possibilities in such a case could be:
I. Collagen vascular diseases
a. Rheumatoid arthritis
b. Systemic lupus erythematosus (SLE)
II. Systemic vasculitides
a. Large-vessel vasculitides
b. Small- to medium-vessel vasculitides
Collagen vascular diseases: Renal involvement is rare in rhematoid arthritis (RA) and the glomerular injury is usually secondary to AA amyloidosis. It is unlikely that she had RA. In systemic lupus erythematosus (SLE), there is a multisystem involvement. Pulmonary involvement is usually in the form of pleural effusions or fleeting infiltrates and intraalveolar haemorrhages, while the renal involvement, which is seen in about 40-80% of patients, may range from isolated urinary sediment abnormalities to chronic renal failure (CRF). Rapidly progressive glomerulonephritis (RPGN) however, is uncommon in SLE. Neurological involvement can be seen in around 60% and takes the form of neuropsychiatric manifestations, with seizures and behavioral disturbances being common. The possibility of SLE appears to be remote in this patient. However, the syndrome of antiphospholipid deserves a mention. Some 12-30% of patients of SLE have antiphospholipid antibodies and 50-70% of patients with these antibodies may have an antiphospholipid antibody syndrome characterized by thrombosis across various arterial and venous beds. Catastrophic antiphospholipid antibody syndrome is a fulminating disease characterized by acute thrombotic microangiopathy with multiple organ involvement: kidneys (78%), lungs (66%), CNS (56%), skin (50%), as well as DIC (25%); it has a mortality rate of 50% and the cause of death is usually multiorgan failure. The precipitating factors are usually infections, surgical procedures, and drugs like oral contraceptives. It is unlikely, however, that this patient had SLE and, therefore, antiphosphlipid antibody syndrome is not a possibility as the cause of her deterioration.
Systemic vasculitides: Among the large-vessel vasculitides, Takayasu's arteritis and giant cell arteritis can be considered here. Glomerular injury is, however, rare in these large-vessel vasculitides and pulmonary involvement is uncommon in these disorders. It is unlikely that this patient had large-vessel vasculitides. Among the small- to medium-vessel vasculitides, polyarteritis nodosa (PAN) causes multisystem involvement. In the kidneys, there is an arteritis without glomerulonephritis, while in the lungs there is involvement of the bronchial artery without involvement of the pulmonary arteries. The urinary sediment is bland and the renal failure is slowly progressive. The neurological involvement is usually in the form of peripheral nerve involvement which manifests as mononeuritis multiplex. About 20-30% patients of PAN may be HBsAg positive. These features make this diagnostic possibility unlikely. The other group of small-vessel vasculitides is the ANCA-associated small-vessel vasculitides which includes Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome (CSS). CSS patients exhibit a predominant lung involvement and the patient clinically presents with asthma. The skin shows purpura and subcutaneous nodules. Peripheral eosinophilia (>80% eosinophils) is a characteristic feature. It is usually associated with p-ANCA positivity is the serum. This patient did not have asthma or eosinophilia and the ANCA status was unknown, renal disease being the dominating feature. Hence, it is unlikely to be a case of the Churg-Strauss syndrome. Microscopic polyangitis is a small-vessel vasculitis with onset at an average age of 50 years. It is characterized by pulmonary involvement in the form of pulmonary haemorrhages; the pulmonary arteries may be involved by the vasculitic process. The renal involvement in microscopic polyangitis may take the form of a RPGN, while the neurological involvement (frequency 14-36%) may be in the form of peripheral nervous system (PNS) involvement (mononeuritis multiplex). Although the features of this case may be consistent with a diagnosis of microscopic polyangiitis, the neurological involvement in microscopic polyangitis is seen more commonly in the form of a mononeuritis multiplex.
Wegener's granulomatosis (WG): This multisystem disorder usually presents at a mean age of around 40 years. Common manifestations are a purulent, bloody nasal discharge due to involvement of the sinuses and the nasopharynx. Renal involvement is fairly common (77%) and it may be the presenting manifestation in 18% patients. RPGN is of common occurrence in WG. Other organs may be involved. Pulmonary involvement (85%) may take the form of asymptomatic infiltrates or may present as nodular cavitary lesions. The skin involvement (46%) may be in the form of papules, vesicles, palpable purpura, ulcers, and subcutaneous nodules. CNS involvement (8%), usually in the form of cranial neuritis, is either due to vasulitis or, more commonly, due to extension of contiguous granulomas. Cerebral vasculitis is not uncommon in WG. WG is associated with c-ANCA, raised ESR, anemia, and leucocytosis. As per the diagnostic criteria (ACR 1990), at least two of the following features, if present, are diagnostic of classical WG: 1) nasal/oral inflammation with purulent, bloody nasal discharge, 2) chest X-ray showing features of infiltrates/nodules/cavities, 3) urinary sediment with microhaematuria (<5 RBCs/HPF) or red cell casts, and 4) granulomatous inflammation in arterial walls. This patient had two of these four features (2 and 3). Another histological and clinical correlate of WG is lymphomatoid granulomatosis, a peripheral T-cell lymphoma that has a predominantly pulmonary involvement which, in fact, may be the presenting manifestation. Renal and skin involvement is also common (40-45%); CNS involvement may occur (20-30%) and may be the presenting manifestation in 20% cases. However, it is not associated with RPGN, making this entity unlikely in our patient.
We should now consider the neurological involvement in our patient; she had altered sensorium and irrelevant talking without localizing neurological signs and the CSF examination showed RBCs (2+) with a high protein of 1.6 gm% and low sugar (12 mg%). This is possibly indicative of an intracranial inflammatory process leading on to an increased production of proteins, possibly globulins, which may suggest a vasculitic process; alternatively, it may simply be a manifestation of a subarachnoid bleed, because although RBCs were present, no WBCs were detected in the CSF. These CSF findings, in light of the other manifestations, can indicate either classical PAN or Wegener's granulomatosis, and are due to an intracranial vasculitis (especially in the latter case) or may occur in association with an aneurysmal rupture.
| ~ Final Diagnosis|| |
Wegnener's granulomatosis with pulmonary involvement, skin rash, RPGN, cerebral vasculitides, and multiple infarcts with ?subarachnoid haemorrage and possibly old, healed tuberculosis.
| ~ Pre-pathology Discussion|| |
One possibility that needs consideration in view of the combination of the involvement of the CNS and the kidneys would be infective endocarditis. The only point against this is the normal cardiovascular examination and ECG findings. Nevertheless we have seen this kind of combination in our CPCs quite often.
K. L. Gupta, Professor of Nephrology
If we look back at the clinical problems of this case, it is quite clear that there is multisystem involvement and that it is a vasculitic process. I would definitely consider Wegener's granulomatosis as a strong possibility and systemic lupus erythematosus would be the second possibility.
Another disease which is often discussed in this hall, and is also a multisystem disease and a secondary cause of vasculitis, is disseminated mucormycosis. This diagnosis would explain the kidney involvement (with the history of oligo-anuria, microhematuria, and normal-sized kidneys) along with bilateral lung shadows. The findings in the CSF, with the presence of RBCs and protein, indicate a meningitic process, so I would not be surprised if we ultimately find a fungal infection in this patient.
Parampreet Singh, Assistant Professor of Neurology
My main thoughts are about the CSF examination. Although no WBCs were seen in the CSF, a value of 12 mg% sugar is very low and it suggests some infection or malignancy. Sometimes, due to a delay in CSF examination, WBCs may not be seen. The underlying process may be a vasculitic process, possibly WG, but somewhere we will most likely find either an infection, such as tuberculosis, or a malignancy or an endocarditis. It is possible that there may be a combination of two of these conditions: an underlying disease with an overlying infection.
Ajay Behl, Assistant Professor of Cardiology
The most striking feature is the high ESR of 170 mm/h. With this high ESR and a normal kidney, along with her anaemia and susceptibility to infection, a diagnosis of multiple myeloma is a strong possibility. The diagnosis of infective endocarditis in the presence of a clinically normal heart is unlikely; although it cannot be totally ruled out.
S. Jain, Professor of Internal Medicine
Another aspect which we are forgetting is that the patient had received 4-5 units of blood transfusion. It means there was a drop in hemoglobin, and in a clinical setting of renal failure and lung shadows, a diagnosis of WG will naturally be number one. With a high ESR of more than 100, there are 6 or 7 possibilities, and these causes include multiple myeloma, infective endocardits, vasculitis, cryoglobulinaemia, etc. If we rule out three at least, we can consider only two in this case, i.e., infective endocarditis and vasculitis.
K. K. Talwar, Director, PGI and Professor of Cardiology
A possibility of infective endocarditis has been raised but the only problem is the clinical protocol. I would like to ask my colleague from radiology about the cardiac size in the X-ray. If we consider the cardiac size in the X-ray, there is significant enlargement of the heart (ignoring the 2 nd film which is probably a portable film), which could be due to WG or infective endocarditis.
Dr. Naveen Kalra
These are all portable X-rays taken with the patient lying down. It will be difficult to comment about the cardiac size. There is apparent cardiomegaly, but I am not sure whether it is real or not.
Dr. Vivek Lal, Assistant Professor of Neurology
We often talk of vasculitic causes when there is multisystem involvement. I feel that it is very unlikely in this case as there is no hypertension or any peripheral nerve involvement. In nine out of ten cases, when a vasculitic process involves the nervous system, the peripheral nervous system is involved before the central nervous system. The central nervous system is involved more commonly than the peripheral nervous system in only one vasculitic process, i.e., in isolated granulomatous angitis of the brain, which is not at all in consideration in this case. A very low CSF sugar would argue against a noninfective process. A CSF sugar of 12 mg% can only occur in infections and hypoglycaemia, which is not in consideration. A CSF protein of 1.6 gm% suggests that the nervous system has got encompassed by some infection somewhere along the line. The primary process began as a vasculitic process but later there was some infection in the brain.
Dr. Yashpal Sharma, Associate Professor of Cardiology
A diagnosis of right-sided endocarditis with embolic infarcts to the pulmonary artery and lungs will be the first possibility but a left-sided endocarditis with paradoxical embolus may also occur.
Prof. V. Sakhuja
Can I now request Dr. Nandita to present the pathology findings?
| ~ Pathology Protocol|| |
Dr. Nandita Kakkar
A complete autopsy was performed on this 52-year-old female. The peritoneal cavity yielded 500 ml of straw-coloured fluid. Post mortem cANCA was 4+.
Both kidneys weighed 240 gms and the external surface and cut surface showed multiple geographic areas of infarcts [Figure - 1]. Renal arteries were within normal limits. Microscopy showed florid necrotizing glomerulonephritis with segmental and diffuse lesions, occasional granulomatous glomerulonephritis, and crescents [Figure - 2],[Figure - 3],[Figure - 4]. Florid acute vasculitis of intralobar, arcuate, interlobular arteries, arterioles, and capillaries was noted [Figure - 5]. Multiple infarcts and dense interstitial inflammation was also seen. Granulomatous vasculitis was occasionally seen [Figure - 6]. Immunohistochemistry for IgG, IgM, IgA, C3, and fibrinogen was negative in the glomeruli indicating the pauci-immune nature of the glomerulonephritis.
The lungs weighed 520 gms. There was focal bronchopneumonia. No lesions of Wegener's granulomatosis, capillaritis, or hemorrhage were noted. The spleen weighed 200 gms. The outer surface and cut sections showed multiple geographic areas of infarction [Figure - 7]. Microscopy revealed vasculitis of small-sized arteries along with multiple infarcts [Figure - 8]. Multiple small ulcers were present diffusely in the colon. Microscopy showed acute vasculitis of the mucosal and submucosal vessels [Figure - 9].
The heart weighed 290 gms. The parietal and visceral pericardium was thickened; the valves and chambers were unremarkable. Microscopy revealed fibrinous pericarditis and acute vasculitis of small arteries in the pericardium and of the left anterior descending artery [Figure - 10]. No infarcts were seen. Right common carotid artery showed intimitis. The abdominal aorta showed florid intimitis [Figure - 11]. Vasculitis of the medium-sized vessels of the mesentery and small-sized vessels of the ovary, liver, bone marrow, and lymph node and of the periadrenal vessels was seen. Subarachnoid hemorrhage was seen at the base of the brain. The left vertebral artery was rudimentary.
In this case, the kidneys showed a cANCA positive pauci-immune necrotizing glomerulonephritis with occasional granulomatous vasculitis. Acute florid vasculitis of intralobar, arcuate, interlobular, arterioles, and capillaries was seen. With this morphology in the kidney, the differential diagnosis is between Wegner's granulomatosis and microscopic polyangiitis. Renal lesions of Wegener's granulomatosis and microscopic polyangitis are indistinguishable and the deciding factor is the involvement of the upper and lower respiratory tract. In this case, there were no lesions of Wegener's granulomatosis in the upper and lower respiratory tract and, hence, I think this case would be best classified under the diagnosis of microscopic polyangitis. In this case, small-sized vessels, medium-sized vessels (coronary artery, inferior mesenteric), and large-sized vessels (abdominal aorta, right common carotid artery) were involved by the vasculitic process. Morphologically this case does not fit into any of the classifications of the vasculitides (i.e., the Chapel Hill or the Lie et al . classification). It is said that some small- and large-vessel vasculitides may involve medium-sized arteries, but large- and medium-sized vessel vasculitides do not involve vessels smaller than arteries. The intimitis seen in the abdominal aorta and right common carotid artery is unique.
Final autopsy diagnosis
- Small-vessel vasculitis, microscopic polyangiitis with pauci-immune necrotizing glomerulonephritis, cANCA 4+
- Small-, medium-, and large-sized vessel vasculitis involving the kidneys, heart, spleen, colon, mesentery, liver, periadrenal vessels, ovaries, bone marrow, lymph nodes, abdominal aorta, and right common carotid artery
- Fibrinous pericarditis
- Focal bronchopneumonia
- Subarachnoid hemorrhage
P. Bambery, Professor of Internal Medicine
One of the most important things one should realize when we are dealing with vasculitis is that the last word in the classification has not been said. Even after James Lie made a classification, there has been another attempt by C. Savage, in which she has further simplified the whole scheme. There is no problem with large-vessel vasculitides, the problem is with ANCA-associated vasculitis. For the average clinicians with their simple diagnostic methods, she has divided small-vessel vasculitis into two groups, with or without granulomatous change. If there is granulomatous change, she calls it Wegener's granulomatosis but if there is no granulomatous change, she labels it microscopic polyangiitis. With that scheme, a clinical diagnosis of Wegener's granulomatosis is inescapable.
I fully endorse the views expressed by Prof. Bambery that if the patient had granulomas, necrotizing vasculitis, and cANCA (4+) positively, the diagnosis is Wegener's granulomatosis. Classically, microscopic polyangitis is pANCA positive but not cANCA. This is a classical case of Wegener's granulomatosis.
The comment that large-vessel vasculitis does not involve the small vessels is debatable. In Takayasu's arteritis, which is a large-vessel vasculitis, the involvement starts from the small vessels which supply the large vessels. In fact, there are distinguishing points based on which one can arrive at a diagnosis. In the case of Takayasu's arteritis, one should not look at the aorta but look for changes in the vasa vasorum, which supplies the aorta.
V. Jha, Additional Professor of Nephrology
Despite the several classification systems which have been devised in the last 50 years, one thing which has remained constant is that if you see granulomas you make a diagnosis of either Wegener's granulomatosis or the Churg-Strauss syndrome, which is characterized by asthma and a predominance of eosinophils. Wegener's granulomatosis is obviously a small-vessel vasculitis, but the large vessels are also involved. If the pathologist is convinced about the granulomatous pathology, the diagnosis must remain Wegener's granulomatosis which is also supported by the finding of cytoplasmic variant of ANCA positivity. In fact, in 90% of cases, Wegener's granulomatosis shows positivity for cANCA.
Dheeraj Gupta, Additional Professor of Pulmonary Medicine
It is wrong to say that the lung is not involved. This patient had definite lung involvement because a 3-month-old X-ray showed cavitary lesions, which is classical for Wegener's granulomatosis. You may not see pathological remnants in the lung at autopsy but this does not mean that the patient did not have lung involvement.
K. S. Chugh, Emeritus Professor of Nephrology
My query is for Nandita. Which kind of large-vessel disease involves only the intima? You have described, primarily, the involvement of the intima but not the media or the adventitia. In fact, most of the large-vessel vasculitis involves the media or the adventitia rather than the intima alone.
In fact, the literature is silent regarding this peculiar involvement of the intima of a large vessel in a small-vessel vasculitic disorder. It may be an early kind of lesion and the whole wall might have got involved with the passage of time.
The granulomatous glomerulonephritis and vasculitis in the kidney is seen in three conditions (Heptinstall's Text book of Renal Pathology)-WG, microscopic polyangiitis, and Churg-Strauss syndrome. There are several studies which have shown that granulomatous glomerulonephritis and vasculitis are seen more often in microscopic polyangiitis than in Wegener's granulomatosis. The renal lesions in WG and microscopic polyangiitis are indistinguishable; it is always the lesions in the upper respiratory tract and lungs that distinguish between the two. Multiple sections were studied but showed nothing to suggest Wegener's granulomatosis. Hence, the diagnosis of microscopic polyangiitis was offered.
You have found subarachnoid hemorrhage. Do you feel that this subarachnoid hemorrhage is due to the vasculitis?
I studied multiple sections from the brain but did not find any evidence of vasculitis. I am not sure about the importance of the rudimentary vertebral artery.
Subarachnoid haemorrhage is one of the very rare complications of WG. The largest series on neurological involvement in WG is from the Mayo Clinic, and they talk about stroke, peripheral nervous system involvement, central nervous system involvement and, very rarely, subarachnoid hemorrhage. The CSF report of low sugar (12 mg%) and high protein seems very odd when the autopsy showed a normal brain.
The low sugar in the CSF does not surprise me. I am aware of situations like rheumatoid arthritis, where low sugar has been reported, particularly in the pleural fluid, and the same is said of CSF also. Of course, I am not sure whether it occurs in WG. There is a defect in the glucose transporter, at least in the pleural fluid, which is well documented. The same mechanism may be responsible in the brain in WG.
K. Joshi, Professor and Chief of Histopathology
Pathologically these two diseases, i.e., the microscopic polyangitits and Wegner's granulomatosis look like one disease with two clinical syndromes. Charles Jennette has mentioned that granulomatous glomerulitis, i.e., destruction of Bowman's capsule, with infiltration of the interstitium in continuity with the glomerulus with giant cells and granulomas, can occur in both these conditions, i.e., WG and microscopic polyangitis. Churg-Strauss described the occurrence of tissue eosinophilia and asthma, which we do not see in this case. Of course soft-tissue eosinophilia can be seen in all these conditions. If there are granulomas which do not originate in the glomeruli, the condition is WG. In this case, we are not sure whether there were a few granulomas that did not originate from glomerulus. Regarding Dr. Jain's comment that there is some overlap in ANCA positivity, I would like to mention that in WG, cANCA is positive in 80% of cases and pANCA in 40%, whereas in microscopic polyangitis, the p-ANCA is positive in 80% of cases but the c-ANCA may be positive in 40% of cases. Hence, these two diseases are actually the same with two clinical syndromes.
The most baffling thing was the widespread intimitis which was almost like an endocarditis of the large blood vessels rather than the heart valves. This has not been seen before. So far as the histology concerned, it is the same as that which I demonstrated a few months ago. We could have found evidence of vasculitis or granulomas; we have taken only minimal sections from the lungs.
| ~ From History to Present-day Knowledge|| |
Prof. Pradeep Bambery
This patient had an extensive multisystem, necrotizing, predominantly small-vessel cANCA positive, granulomatous vasculitis. The question is what do we call it? WG or microscopic polyangiitis (MPA)?
Some will say, what is there in a name? Apparently there may not be much, but…
In the beginning there was only polyarteritis nodosa. A broad term that encompassed all the necrotizing vasculitides that we have discussed today. In the 1930s, first Klinger, and then Wegener, described a clinically and morphologically distinct disorder, characterized by recurrent, unresponsive, sinus and upper airways inflammation for a variable duration which was followed by the development of lung and renal involvement as the predominant features of a rapidly progressive, highly fatal, multisystem disorder. A Norwegian later named it Wegener's granulomatosis, recognizing the seminal contribution of this German pathologist. The first to use to this term in English was Godman and Churg, who also set down the first set of criteria for a diagnosis. The same group, had in the early 1950s defined the asthma, granulomatous inflammation, and eosinophilia-related vasculitis; this condition came to be known as the Churg-Strauss syndrome, again recognizing the pioneering efforts of these stalwarts. Meanwhile, Zeek attempted to classify the vasculitides and used the term 'hypersensitivity vasculitis' that covered these entities. A little earlier, Dawson and colleagues had identified a disorder similar to these, characterized by the lack of aneurysm formation and the other features of classic polyarteritis nodosa. They called it 'microscopic polyarteritis.' Later, the term MPA was adopted.
For a clinician, WG signifies a protean disorder with upper and lower respiratory tract inflammation, multisystem involvement, renal disease leading to renal failure, granulomatous inflammation and necrosis, with extensive necrotizing vasculitis affecting the small vessels at histology. It is a well-recongnized entity. For many decades, no laboratory finding was considered characteristic of this condition. However, with the discovery of ANCA in the 1980s, this void was also filled. Several studies have testified to the cANCA pattern at indirect immunofluorescence as being characteristic of this condition. In contrast, most patients with MPA show the pANCA pattern.
The vasculitides are as much clinical entities as they are pathological ones. A proper understanding of their diverse manifestations can only be reached if one takes into account both, the clinical manifestations and the histological findings. Several attempts at classifying the vasculitides have been made since Zeek's pioneering work in the 1950s. That so many schemes of classifications have emerged in the last 50 years is testimony to both, the unsatisfactory nature of these classifications as well as the remarkable progress in the understanding of these uncommon and often devastating conditions. I personally feel that this is probably because of a brief held by some that many of these entities, which have so much in common, are actually different from each other and need to be surgically compartmentalized. Currently, for a clinician, the term 'ANCA-associated vasculitis' is sufficient to promptly institute the required therapy.
The patient discussed today presented with significant respiratory involvement that led to the introduction of antitubercular drug therapy 2 months before she came to this institution with multisystem involvement, in advanced renal failure, and in extremis . Pulmonary involvement occurs in both WG and MPA. WG starts as a localized granulomatous inflammation and then enters a disseminated vasculitic phase after a variable duration. While lung involvement in WG is often a slowly progressive granulomatous process that mimics tuberculosis, the usual pulmonary presentation of MPA is with pulmonary hemorrhage. Clearly, the patient did not have this problem at the start of her illness. Pulmonary infiltrates mimicking tuberculosis are a common occurrence in WG and have led to delay in diagnosis of several of our patients, with disastrous consequences.
Several recent reviews written after the Chapel Hill conference have highlighted the fact that the salient features in differentiating WG from MPA and Churg-Strauss syndrome (the three main ANCA-associated small-vessel vasculitides) are the presence of asthma, granulomata, and eosinophilia in CSS; granulomatous inflammation alone, without asthma and eosinophilia, in WG; and the absence of asthma, eosinophilia, and granulomatous inflammation in MPA. All these studies have repeatedly emphasized the absence of granulomatous changes in MPA. The clear demonstration of granulomatous changes and the strong c-ANCA positively, in conjunction with the clinical presentation of this patient, make WG the most clinically acceptable diagnosis.
What is there in a name? In reality, quite a lot of history and clinical medicine.
| ~ Acknowledgement|| |
The editor is grateful to Dr. Raje Nijhawan for his help in the preparation of this manuscript.
| ~ References|| |
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11]
[Table - 1]