eMedicine Specialties > Neurology > Inflammatory and Demyelinating Diseases
Wegener Granulomatosis
Updated: Nov 25, 2008
Introduction
Background
Wegener's granulomatosis (Wegener granulomatosis) is distinguished from other vasculitides by the pattern of organ involvement and by the histologic features of granulomatosis and necrotizing inflammation. Primary involvement occurs in upper and lower respiratory tracts and kidneys (ie, glomerulonephritis). Neurologic involvement, seen primarily as cranial neuropathies and peripheral neuropathies, occurs in about 34% of cases. Other commonly affected organs include skin and salivary glands.
The pathogenesis of Wegener's granulomatosis is unknown; some have proposed that an inhaled allergen and/or infectious agent may provoke the disease in susceptible individuals, because limited evidence indicates a possible association with a history of pulmonary infections. Human leukocyte antigen associations have been sought, but no consistent or convincing evidence of such associations has emerged. Wegener's granulomatosis is referred to as a likely autoimmune disease, given the multiple mechanisms by which the characteristic neutrophil cytoplasmic antibodies found in serum in this disease are capable of mediating immune injury in tissues.
See eMedicine's other articles Wegener Granulomatosis (Rheumatology), Wegener Granulomatosis (Otolaryngology and Facial Plastic Surgery), Wegener Granulomatosis (Dermatology), Wegener Granulomatosis (Pediatrics).
Pathophysiology
The lungs may be affected acutely with alveolitis. Necrotizing granulomatosis develops and initially may appear histologically as microabscesses or geographic (irregularly shaped areas) necrosis, surrounded by palisading histiocytes. Granulomas may be either intravascular or extravascular. Arteritis may involve medium and small vessels, both venous and arterial; pathologic specimens generally show both acute and chronic inflammation. Vascularized scarring may be permanent.The renal lesion of Wegener's granulomatosis is usually a necrotizing glomerulonephritis; however, many types of nephritis may be seen. Granulomatous inflammation may be seen occasionally around glomeruli or may involve small renal arteries. When pathologic specimens are reviewed, lymphomatoid granulomatosis should be kept in mind, since this disorder has overlapping features with Wegener's granulomatosis and this diagnosis also requires lung biopsy in most cases. Lymphomatoid granulomatosis specimens mostly are distinguished by monoclonal atypical lymphocytes, smaller less-destructive granulomas, and less vessel-wall invasion. Subspecialty pathologists often are consulted in these cases.
Although neurologic involvement is fairly common in Wegener's granulomatosis, reports of pathologic specimens are sparse and findings are nonspecific. The few large patient series that are available indicate that about one half of patients manifested neurologic involvement in Wegener's granulomatosis prior to the advent of cyclophosphamide treatment; however, only one fourth exhibited neurologic Wegener's granulomatosis in a more recent study.
Nishino et al presented the definitive work on neurologic involvement of Wegener's granulomatosis.1 This large series remains authoritative due to its size and scope. Of 324 patients reviewed, most were affected by peripheral neuropathy or cranial neuropathies. A pattern of symmetrical polyneuropathy was seen in some patients, but peripheral neuropathy most often manifests as acute mononeuritis multiplex. Cranial nerves II, VI, and VII are affected most commonly, either by direct vasculitic injury, compression, extension of granulomatous disease from adjacent sinuses, or cavernous sinus thrombosis (see Physical for ocular involvement). As with cerebral parenchymal lesions, injury can occur due to direct effects of inflammation, tissue ischemia due to thrombosis of inflamed blood vessels, or compression due granulomatous tissue formation and edema.
The following is a tally of nervous system involvement in a subsample (n = 324) of patients with Wegener's granulomatosis:
- Peripheral neuropathy - 53 patients
- Mononeuritis multiplex - 42 patients
- Cranial neuropathies - 21 patients
- External ophthalmoplegia - 16 patients
- Seizures - 10 patients
- Cerebritis - 5 patients
- Stroke syndrome - 13 patients
Thirty-three percent of patients experienced central or peripheral nervous system involvement in this large series. Cerebral parenchyma may be affected by either cerebritis or stroke syndromes. The most common peripheral nerve injury encountered was peroneal neuropathy, followed by tibial, sural, median, and ulnar neuropathies. Rarely reported neurologic disorders include myopathy, aseptic meningitis, and diabetes insipidus. Wegener's granulomatosis rarely presents as a neurologic illness (9 [3%] of 324 presented as ophthalmoplegia in this series).
A few patients presenting with signs of meningeal inflammation have been reported in whom diffuse dural enhancement was seen on MRI. Similar findings have been reported in cases of neurosarcoidosis. Presentation as cerebritis with edematous masslike lesions and invasive-appearing mass lesions centered around paranasal sinuses are also reported.
Frequency
International
Wegener's granulomatosis appears to be a rare disease with an incidence of approximately 0.4 case per 100,000 population.
Mortality/Morbidity
Permanent residua occur in many patients with Wegener's granulomatosis, but the mortality rate is very low in patients treated with the usual immunosuppressant regimens (precise data concerning mortality rates in neurologic Wegener's granulomatosis are not available).
Race
Wegener's granulomatosis has been observed in persons from all racial groups but is rare in blacks compared with whites.
Sex
A slight male predominance has been reported.
Age
Wegener's granulomatosis can occur in persons of any age; reports indicate onset ranging from individuals as young as 3 months to very elderly persons. The peak incidence is in the fourth and fifth decades of life.
Clinical
History
- The diagnosis of Wegener's granulomatosis is suspected when patients present with chronic sinusitis, nasal ulceration, other upper respiratory tract symptoms, or lower respiratory symptoms of hemoptysis, dyspnea, or cough.
- Symptoms of renal involvement are much less common, although renal involvement is often clinically evident at presentation. Manifestations include proteinuria, hematuria, and renal insufficiency.
- Constitutional symptoms such as fever, weight loss, and anorexia may suggest systemic disease.
- Ocular symptoms are common (referable to involved cranial nerves or orbital structures).
- As indicated in the discussion in Pathophysiology, presentations of neurologic Wegener's granulomatosis are extremely varied, with manifestations in the CNS such as seizures, altered cognition (ie, cerebritis), focal motor and sensory complaints, and stroke syndromes. Presentations may involve chronic, acute, or stepwise deterioration referable to parenchymal or meningeal inflammation and scarring, and this variable tempo of onset also may be seen in the associated peripheral nerve syndromes and cranial neuropathies. A history of headaches and other symptoms related to inflammation of meningeal or parenchymal structures should be sought initially and on follow-up visits.
Physical
- Ocular manifestations of Wegener's granulomatosis include the following:
- Proptosis
- Episcleritis
- Cavernous sinus thrombosis
- Corneoscleral ulcers
- Dacryocystitis
- Uveitis
- Conjunctivitis
- Retinal occlusion/cherry-red spot
- Scleritis
- Afferent pupillary defect, decreased acuity (optic neuritis)
- Ophthalmoplegias (nuclear or supranuclear)
- Other neurologic signs/syndromes
- Delirium (cerebritis)
- Hemiparesis (stroke, cerebritis)
- Other cranial neuropathy (potentially any cranial nerve)
- Seizure (mass lesion)
- Spasticity, hyperreflexia, Babinski sign (ie, upper motor neuron signs)
- Weakness, numbness (neuropathy)
More on Wegener Granulomatosis |
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| Treatment & Medication: Wegener Granulomatosis |
| Follow-up: Wegener Granulomatosis |
| References |
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References
Nishino H, Rubino FA, DeRemee RA, Swanson JW, Parisi JE. Neurological involvement in Wegener's granulomatosis: an analysis of 324 consecutive patients at the Mayo Clinic. Ann Neurol. Jan 1993;33(1):4-9. [Medline].
Bachmeyer C, Cadranel JF, Demontis R. Rituximab is an alternative in a case of contra-indication of cyclophosphamide in Wegener's granulomatosis. Nephrol Dial Transplant. Jun 2005;20(6):1274. [Medline].
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Kerr GS, Fleisher TA, Hallahan CW, Leavitt RY, Fauci AS, Hoffman GS. Limited prognostic value of changes in antineutrophil cytoplasmic antibody titer in patients with Wegener's granulomatosis. Arthritis Rheum. Mar 1993;36(3):365-71. [Medline].
Moore PM. Immune-mediated vasculopathies of the central nervous system. In: Gilchrist J, ed. Prognosis in Neurology. Boston, Mass: Butterworth-Heinemann; 1998.
Scott DG, Watts RA. Classification and epidemiology of systemic vasculitis. Br J Rheumatol. Oct 1994;33(10):897-9. [Medline].
Spranger M, Schwab S, Meinck HM, Tischendorf M, Sis J, Breitbart A, et al. Meningeal involvement in Wegener's granulomatosis confirmed and monitored by positive circulating antineutrophil cytoplasm in cerebrospinal fluid. Neurology. Jan 1997;48(1):263-5. [Medline].
Tervaert JW, Huitema MG, Hené RJ, Sluiter WJ, The TH, van der Hem GK, et al. Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet. Sep 22 1990;336(8717):709-11. [Medline].
Travis WD, Hoffman GS, Leavitt RY, Pass HI, Fauci AS. Surgical pathology of the lung in Wegener's granulomatosis. Review of 87 open lung biopsies from 67 patients. Am J Surg Pathol. Apr 1991;15(4):315-33. [Medline].
Wegener F. [Uber eine eigenartige rhinogene Granulomatose mit besonderer Beteilgung des Arteriensytems und der Nieren]. Beitrage der Pathologischen Anatomie. 1939;102:30-68.
Further Reading
Keywords
Wegener's granulomatosis, granuloma, lymphomatoid granulomatosis, necrotizing inflammation, autoimmune disease, autoantibodies, neutrophil cytoplasmic antibodies, ANCA, c-ANCA, vasculitis, vasculitides, arteritis
