s Hopkins Vasculitis Center Wegener's Granulomatosis

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Part 3

s Hopkins Vasculitis Center Wegener's Granulomatosis

Wegener's Granulomatosis

First Description:

The first case was described by Heinz Klinger, a German medical student, in 1931. Several years later a German pathologist, Friedrich Wegener, described 3 additional cases and recognized the disorder as a distinct form of vasculitis.

Other names for Wegener’s Granulomatosis:

Occasionally called Wegener’s arteritis or Wegener’s disease.

Who gets Wegener’s Granulomatosis (the "typical" patient):

Wegener’s Granulomatosis is nearly equally distributed between the sexes, with a slight male predominance. Wegener’s typically occurs in middle age, but is found in people of all ages. Although it is unusual for Wegener’s to occur in childhood, it is not unusual for a Wegener’s patient to be in his/her 70s or even 80s at the time of diagnosis.

Bilateral lung nodules in a 27 year old Indian man with Wegener's granulomatosis.Click image to enlarge.

A CT scan from the same patient whose chest X-ray is depicted in the previous Figure. The view is a cross-section through the patient's lungs. The CT scan not only permits a better appreciation of the lesions' size, it also detects more lesions.Click image to enlarge.

Classic symptoms and signs of Wegener’s Granulomatosis:

Wegener’s can affect virtually any site in the body, but it has a predisposition for certain organs. The classic organs involved in Wegener’s are the upper respiratory tract (sinuses, nose, ears, and trachea [the "windpipe"]), the lungs, and the kidneys. In the table below, we list the organs commonly involved by Wegener's Granulomatosis and the specific disease manifestation(s) in each organ.

Organs and their Manifestations:

Ear

Ear "infections" that are slow to resolve. Recurrent otitis media. Decrease in hearing.

Eye

Inflammation in the white part of the eye, known as the sclera ("scleritis"). Inflammation within the eye, known as "uveitis". Inflammation behind the eye known as an "orbital pseudotumor". An orbital pseudotumor such as those caused by Wegener's Granulomatosis can cause "proptosis", or protrusion of one eye.

A computed tomography (CAT) scan of the eyes in a patient with a retro-orbital mass (a mass behind the eye) in a man with Wegener’s granulomatosis. Masses such as these sometimes cause an abrupt loss of vision through stretching or compression of the optic nerve, which enters the back of the eye.Click image to enlarge.

Nose

Nasal crusting and frequent nosebleeds. Erosion and perforation of the nasal septum. Collapse of the bridge of the nose, resulting in a "saddle-nose deformity".

(Left) "Saddle-nose" deformity, resulting from collapse pf the nasal septum caused by cartilage inflammation. This patient has Wegener's granulomatosis, but an identical lesion may occur in Relapsing Polychondritis. (Right) The same patient after cosmetic surgery.Click image to enlarge.

Sinuses

Chronic sinus inflammation, sometimes leading to a destructive process of tissues around the sinuses.

Trachea

Narrowing of the region just below the vocal cords, (a condition called "subglottic stenosis"), which results in difficulty breathing.

A characteristic respiratory tract complication of Wegener’s granulomatosis: narrowing of the "windpipe" just below the vocal cords. This narrowing, caused by inflammation and scarring, causes difficulty breathing and may, after a subacute progression, necessitate emergency tracheostomy. These two figures illustrate subglottic stenosis before (left) and after (right) laser surgery, performed by an Ear, Nose, & Throat specialist. The surgery provided dramatic improvement in the patient’s breathing. Click image to enlarge.

Lung

A pneumonia-like syndrome, with lung "infiltrates" seen on chest X-ray. Bleeding from the lungs.

Kidney

Inflammation in the kidney, leading to small (or rarely, large) amounts of blood and protein in the urine. This condition is called glomerulonephritis. If not treated aggressively, Wegener’s involvement of the kidneys can lead to kidney failure.

A Langerhans giant cell, containing multiple nuclei, demonstrated in a fine needle aspirate of a renal mass in a patient with Wegener's granulomatosis. Renal masses are an unusual manifestation of this disease.Click image to enlarge.

Skin

Wegener’s can cause many kinds of skin rashes. The most common rash occurs in the form of small purple or red dots on the lower extremities (known as "palpable purpura"). Inadequate blood flow to fingers and toes can lead to Raynaud’s phenomenon (extreme sensitivity of the digits to cold) and even infarctions of the tips of fingers and toes, with the development of gangrene.

Joints

Arthritis, with joint swelling and pain.

Nerves

Peripheral nerve involvement leads to numbness, tingling, shooting pains in the extremities, and sometimes to weakness in a foot, hand, arm, or leg.

Miscellaneous

Wegener’s involvement of nearly all organs has been described, including the meninges (the layers of protective tissue around the brain and spinal cord), the prostate gland, and the genito-urinary tract. In addition to involving specific organs, Wegener’s also commonly results in generalized symptoms of fatigue, low-grade fever, and weight loss.

What causes Wegener’s Granulomatosis?

The cause of Wegener’s Granulomatosis is not known. Compared to disease with obvious genetic predispositions, genetics appear to play a relatively small role in the etiology of Wegener's. It is very unusual for Wegener’s to occur in two people in the same family. (It is possible, however, that less obvious genetic risk factors exist, e.g. genes that might pre-dispose a patient to infection with an etiologic organism). For some time, an infection has been suspected of causing (or at least contributing to) Wegener’s, but no specific infection (bacterial, viral, fungal, or other) has been identified.

How is Wegener’s Granulomatosis diagnosed?

Whenever possible, it is important to confirm the diagnosis of Wegener’s by biopsying an involved organ and finding the pathologic features of this disease under the microscope. Because many diseases may mimic Wegener’s (and vice versa), before starting a treatment regimen it is essential to be as certain of the diagnosis as possible. We discuss some of the specific biopsy procedures used to diagnose Wegener’s in the section of this Webpage entitled "How Do We Diagnose Vasculitis? ".

Because Wegener’s so often involves the upper respiratory tract (sinuses, nose, ears, and trachea ["windpipe"]) and because biopsy of these tissues is a relatively non-invasive procedure, these sites are frequently biopsied in patients suspected of Wegener’s. Unfortunately, the yield of biopsies from these sites is rather low: probably less than 50%. Therefore, sometimes more invasive procedures are required to make the diagnosis.

Lung biopsy (either open or thoracoscopic) is often the best way of diagnosing Wegener’s. The ample amount of tissue obtainable through these procedures usually permits confirmation of the Wegener’s diagnosis. Similarly, although the amount of tissue obtained through a kidney biopsy is usually much smaller, the finding of certain pathologic features in the context of a patient’s overall symptoms, signs, and laboratory tests is frequently diagnostic.

Since 1982, when ANCAs (anti-neutrophil cytoplasmic antibodies) were first described, the role of these antibodies in the diagnosis of Wegener’s has grown. ANCA testing, which involves the performance of a simple blood test, has achieved wide availability during the 1990s. This is both good and bad: use of ANCA tests has led to earlier diagnoses and more rapid institution of appropriate treatment in many cases, but has also resulted in misdiagnosis and incorrect treatment when the tests are not performed or interpreted correctly.

As their name implies, ANCAs are directed against the cytoplasm (the non-nucleus part) of white blood cells. Their precise role in the disease process remains uncertain but is a topic of considerable research interest. ANCAs come in two primary forms: 1) the C-ANCA [C stands for cytoplasmic] and, 2) the P-ANCA [P stands for perinuclear]. C-ANCAs have a particularly strong connection to Wegener’s Granulomatosis (up to 80% of patients - and possibly more of those with active disease - have these antibodies). When C-ANCAs are present in the blood of a patient whose symptoms or signs suggest Wegener’s, the likelihood of the diagnosis increases considerably. In most cases, however, it is still VERY IMPORTANT to biopsy an involved organ to verify the diagnosis.

Treatment and Course of Wegener’s Granulomatosis:

Until the 1970s, Wegener’s granulomatosis was nearly always a fatal condition. The use of prednisone and other steroids helped prolong patients' lives, but most patients eventually succumbed to the disease within a few months or years. The first use of cyclophosphamide in the late 1960s began to change the terrible prognosis of this disease. Using the combination of cyclophosphamide and prednisone, more than 90% of patients with severe disease respond to treatment, and 75% are able to achieve disease remissions. Unfortunately, Wegener’s is a disease in which relapses frequently occur. Approximately half of all patients who achieve disease remissions eventually suffer recurrences ("flares"). Flares of Wegener’s are usually responsive to the same treatment that induced remission, but sometimes intensification of treatment (for example, changing to a more powerful medication) is required.

During the 1990s, physicians have increasingly used the combination of methotrexate and prednisone rather than cyclophosphamide and prednisone for Wegener’s patients who do not have immediately life-threatening disease (particularly disease that does not involve the kidneys severely), because of the frequency of severe side-effects associated with the latter regimen.

Bactrim (or Septra), a combination of two antibiotics (trimethoprim and sulfamethoxazole) may also be helpful in the treatment of Wegener’s, particularly in patients whose disease is limited primarily to the upper respiratory tract. A large, multi-center study demonstrated that Bactrim is useful in preventing flares of Wegener’s in the upper respiratory tract.

What’s new in Wegener’s Granulomatosis:

In the past few years, significant advances have been made in understanding Wegener’s, although many important questions remain. In addition to an improved understanding of how to use the currently available medicines for Wegener’s, it is likely that the next few years will witness the development of new medicines for this disease. Scientific breakthroughs may lead to the design of more specific modulators of the immune system that are of great benefit to patients with Wegener’s.

Currently, physicians at s Hopkins, together with colleagues at the Cleveland Clinic, are conducting an "open-label" trial of etanercept (Enbrel®) in patients with Wegener's granulomatosis. This new treatment, approved by the U.S. Food and Drug Administration for the treatment of rheumatoid arthritis, offers significant promise as a means of obtaining and sustaining disease remissions in this disease. For details about etanercept and other strategies of tumor necrosis factor inhibition in vasculitis, please see...1. Open-label etanercept trial.2. New strategies for the treatment of vasculitis: the anti-TNF approach.

For interested patients, we have provided a more detailed description of Wegener’s Granulomatosis in the link below. The link includes a discussion of Wegener’s Granulomatosis written in medical terms by Hellmann, M.D. (F.A.C.P.), Co-Director of the s Hopkins Vasculitis Center, for the Rheumatology Section of the Medical Knowledge Self-Assessment Program published and copyrighted by the American College of Physicians (Edition 11, 1998). The American College of Physicians has given us permission to make this information available to patients contacting our Website.

Wegener's Granulomatosis (from the Medical Knowledge Self-Assessment Program)