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• Who gets Granulomatosis with Polyangiitis (the “typical” patients)?
• Classic symptoms of Granulomatosis with Polyangiitis
• What causes Granulomatosis with Polyangiitis?
• How is Granulomatosis with Polyangiitis diagnosed?
• Treatment and Course of Granulomatosis with Polyangiitis
• What’s new in Granulomatosis with Polyangiitis?
• In medical terms, by David Hellmann, M.D.

Who gets Granulomatosis with Polyangiitis?

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

Pictured below is a chest x–ray showing bilateral lung nodules in a 27 year old Indian man with Granulomatosis with Polyangiitis.

Pictured below is a CT scan from the same patient. 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.

Granulomatosis with Polyangiitis can affect virtually any site in the body, but it has a predisposition for certain organs. The classic organs involved in Granulomatosis with Polyangiitis are the upper respiratory tract (sinuses, nose, ears, and trachea [the “windpipe”]), the lungs, and the kidneys. Listed below are the organs commonly involved in Granulomatosis with Polyangiitis and the specific disease manifestation(s) in each organ.

• Ear
• Eye
• Nose
• Sinuses
• Trachea
• Lungs
• Kidney
• Skin
• Joints
• Nerves
• Miscellaneous

Ear

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

Eye

Inflammation can occur in different parts of the eye. Inflammation in the white part of the eye is known as the sclera (“scleritis”). “Uveitis” is inflammation within the eye. Inflammation behind the eye is known as an “orbital pseudotumor”. An orbital pseudotumor such as those caused by Granulomatosis with Polyangiitis can cause “proptosis”, or protrusion of one eye.

Pictured below is 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 Granulomatosis with Polyangiitis. 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.

Nose

Nasal crusting and frequent nosebleeds can occur. Erosion and perforation of the nasal septum. The bridge of the nose can collapse resulting in a “saddle–nose deformity”. Pictured below is an example of this deformity before and after cosmetic surgery. This resulted from the collapse of the nasal septum caused by cartilage inflammation. This patient has Granulomatosis with Polyangiitis, but an identical lesion may occur in Relapsing Polychondritis.

Sinuses

Chronic sinus inflammation that sometimes leads to a destructive process of tissues around the sinuses.

Trachea

A characteristic respiratory tract complication of Granulomatosis with Polyangiitis: narrowing of the “windpipe” just below the vocal cords, a condition called “subglottic stenosis”. This narrowing, caused by inflammation and scarring, causes difficulty breathing and may, after a subacute progression, necessitate emergency tracheostomy. Pictured below are two figures that show subglottic stenosis before (left) and after (right) surgery, performed by an Ear, Nose, & Throat specialist. The surgery provided dramatic improvement in the patient’s breathing.

Lungs

A pneumonia–like syndrome, with lung “infiltrates“ can be seen on chest x–ray. Bleeding from the lungs can occur.

Kidney

Inflammation can occur 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, Granulomatosis with Polyangiitis’s involvement of the kidneys can lead to kidney failure. Renal masses can occur, but are very unusual in this disease.

The image below is from a urinalysis of a patient with kidney inflammation. When Granulomatosis with Polyangiitis is active, red blood cells will form a clump or “cast” (bracketed in white) within the tubules of inflamed kidneys. These “casts” pass through the renal system and may be viewed under the microscope in a patient’s urine.

Skin

Granulomatosis with Polyangiitis 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 fingers to cold) and even infarctions of the tips of fingers and toes, with the development of gangrene.

Joints

Arthritis can occur, 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

Granulomatosis with Polyangiitis 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, Granulomatosis with Polyangiitis also commonly results in generalized symptoms of fatigue, low–grade fever, and weight loss.

The cause of Granulomatosis with Polyangiitis is not known. Compared to diseases with obvious genetic predispositions, genetics appear to play a relatively small role in the etiology of Granulomatosis with Polyangiitis . It is very unusual for Granulomatosis with Polyangiitis 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) Granulomatosis with Polyangiitis , but no specific infection (bacterial, viral, fungal, or other) has been identified.

How is Granulomatosis with Polyangiitis Diagnosed?

Whenever possible, it is important to confirm the diagnosis of Granulomatosis with Polyangiitis by biopsying an involved organ and finding the pathologic features of this disease under the microscope. Because many diseases may mimic Granulomatosis with Polyangiitis (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 Granulomatosis with Polyangiitis in the section of this Websie entitled What is Vasculitis: Diagnosis?.

Because Granulomatosis with Polyangiitis 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 Granulomatosis with Polyangiitis . 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 Granulomatosis with Polyangiitis . The ample amount of tissue obtainable through these procedures usually permits confirmation of the Granulomatosis with Polyangiitis 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 Granulomatosis with Polyangiitis 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 Granulomatosis with Polyangiitis (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 Granulomatosis with Polyangiitis , 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 Granulomatosis with Polyangiitis

Until the 1970s, Granulomatosis with Polyangiitis 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, Granulomatosis with Polyangiitis is a disease in which relapses frequently occur. Approximately half of all patients who achieve disease remissions eventually suffer recurrences (“flares”). Flares of Granulomatosis with Polyangiitis 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 Granulomatosis with Polyangiitis 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 Granulomatosis with Polyangiitis , 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 Granulomatosis with Polyangiitis in the upper respiratory tract.

What’s New in Granulomatosis with Polyangiitis?

In the past few years, significant advances have been made in understanding Granulomatosis with Polyangiitis , although many important questions remain. In addition to an improved understanding of how to use the currently available medicines for Granulomatosis with Polyangiitis , 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 Granulomatosis with Polyangiitis .

In medical terms, by David Hellmann, M.D.

A discussion of Granulomatosis with Polyangiitis written in medical terms by David Hellmann, M.D. (F.A.C.P.), The Johns 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

Granulomatosis with Polyangiitis is a disease involving granulomatous inflammation, necrosis and vasculitis that most frequently targets the upper respiratory tract, lower respiratory tract, and kidneys. Although Granulomatosis with Polyangiitis can begin at any age, the average age of onset is about 40 years. Other organs frequently affected by Granulomatosis with Polyangiitis granulomatosis include the eye (proptosis and double-vision from retro-orbital pseudotumor, scleritis), skin (ulcers, purpura). or peripheral nerve (mononeuritis multiplex). Granulomatosis with Polyangiitis may be limited to one site for many months or years before disseminating. Systemic symptoms (fever, fatigue, weight loss) are also common. Anemia, mild leukocytosis, and elevated Erythrocyte sedimentation rate (ESR) are nonspecific laboratory findings. Chest radiographs often show infiltrates, nodules, masses, or cavities; only hilar adenopathy is incompatible with the diagnosis of Granulomatosis with Polyangiitis. CT of the chest is more sensitive than chest radiography and can be abnormal when the chest radiograph is negative. Glomerulonephritis causes hematuria, erythrocyte casts, and proteinuria.

A novel group of autoantibodies, ANCAs, helps support the diagnosis of Granulomatosis with Polyangiitis and related forms of vasculitis and gives insight into the pathogenesis of these diseases. ANCAs are directed against enzymes cantained in primary granules of neutrophils and monocytes. Two main types of ANCAs are recognized. The C-ANCAs are directed against serine proteinase 3 and are relatively sensitive and highly specific for Granulomatosis with Polyangiitis. The P-ANCAs are directed against myeloperoxidase and other antigens and are not specific for any single form of vasculitis, but have been seen in some patients with Granulomatosis with Polyangiitis, polyarteritis nodosa, Churg-Strauss vasculitis, and some forms of pauci-immune glomerulonephritis (referred to as microscopic polyarteritis nodosa). Some patients with pulmonary-renal syndromes that may not fit the critieria for Granulomatosis with Polyangiitis are also seropositive for ANCAs. Some patients with inflammatory bowel disease, rheumatoid arthritis, or SLE may have atypical P-ANCA test results, based on the autoantibodies directed against other neutrophil constituents such as lactoferrin.

ANCAs may be not only markers for Granulomatosis with Polyangiitis and related disorders, but they may also be actors in pathogenesis. Studies show that when neutrophils are exposed to cytokines such as tumor necrosis factor, small amounts of serine proteinase and myeloperoxidase, the targets for ANCAs, are expressed on the surface of neutrophils. Adding ANCAs to these cytokine-primed neutrophils causes them to generate oxygen radicals and release enzymes capable of damaging blood vessels.

The diagnosis of Granulomatosis with Polyangiitis is established most securely by biopsy specimens showing the triad of vasculitis, granulomata, and large areas of necrosis (known as geographic necrosis) admixed with acute and chronic inflammatory cells. Only large sections of lung tissue obtained via thoracoscopic or open lung biopsy are likely to show all of the histologic features. However, more easily obtained biopsy specimens of the nose, or sinuses may show several of the changes that are highly suggestive of Granulomatosis with Polyangiitis. Such a biopsy specimen combined with a compatible clinical picture and seropositivity for C-ANCAs should suffice to secure the diagnosis. Seropositivity for C-ANCAs alone is not specific enough to establish the diagnosis of Granulomatosis with Polyangiitis.

Untreated Granulomatosis with Polyangiitis is fatal. Prednisone may slow progression of the disease but by itself is insufficient to arrest the disease. Respiratory tract disease usually progresses slowly, but renal disease can progress rapidly and therefore warrants urgent evaluation and treatment. With the traditional treatment of prednisone (initiated at 1 mg/kg daily for 1 to 2 months. then tapered) and cyclophosphamide (2mg/kg daily for at least 12 months), more than 90% of patients improve and 75% remit. However, 50% of the patients who later remit also relapse, and oral daily cyclophosphamide causes serious toxicity. Short-term toxicity includes cytopenia, infection, and hemorrhagic cystitis. Long-term use of cyclophosphamide in patients with Granulomatosis with Polyangiitis more than doubles the risk of cancer overall, increases the risk of bladder cancer 33-fold and the risk of lymphoma 11-fold. Monthly intravenous cyclophosphamide appears less toxic but also less effective. Weekly, methotrexate appears to be an effective alternative for Granulomatosis with Polyangiitis that is not immediately life-threatening, and it also appears to be beneficial in maintaining remission. The role of trimethoprim-sulfamethoxazole in treating active disease is controversial, with some finding it effective for Granulomatosis with Polyangiitis limited to the respiratory tract, and others not. In patients who have achieved remission, trimethoprim-sulfamethoxazole reduces the relapse rate.

• How do we Diagnose Vasculitis?
• Skin Biopsy
• Kidney Biopsy
• Sural Nerve Biopsy
• Temporal Artery Biopsy
• Lung Biopsy
• Brain Biopsy
• Abdominal Angiogram
• Central Nervous System Angiogram
• Other Useful Tests

How do we diagnose Vasculitis?

Patients with vasculitis learn that making the diagnosis is sometimes quite difficult. Many endure numerous doctors’ visits, tests, and hospitalizations before the pieces of the puzzle are assembled. The diagnosis of vasculitis usually requires a biopsy of an involved organ (skin, kidney, lung, nerve, temporal artery). This allows us to ‘see’ the vasculitis by looking under a microscope to see the inflammatory immune cells in the wall of the blood vessel. Although, making a diagnosis of vasculitis can be quite involved, this is very important for two main reasons:

# ONE:  Vasculitis has many MIMICKERS (other diseases that have similar features but require different treatments). It is important to rule out other causes of vascular inflammation, other than a primary autoimmune condition as the management could be different.

# TWO:  The treatments for vasculitis itself involve substantial risk. No physician should prescribe such treatment without making every effort to secure a firm diagnosis.

Blood tests, X–rays, and other studies may suggest the diagnosis of vasculitis, but often the only way to clinch the diagnosis is to biopsy  involved tissue, examine the tissue under the microscope in consultation with a pathologist (ideally one experienced at examining biopsies in vasculitis), and find the pathologic hallmarks of the disease.

If a patient’s symptoms, physical examination, and diagnostic testing suggest involvement of a particular organ, one of the procedures below may be used to confirm (or exclude) the diagnosis of vasculitis:

1. Skin Biopsy: One of the least invasive ways of making the diagnosis. A minor procedure performed under local anesthesia. The wound is closed with 1–2 stitches that are removed 7–10 days later.

The correct diagnosis of PAN (polyarteritis nodosa) was not confirmed by this biopsy because the biopsy was not deep enough. The biopsy specimen contains only the epidermis and superficial dermis. PAN classically affects medium–sized arteries located in the deep dermis.

In contrast to the biopsy above, the skin biopsy below was deep enough to include the deep dermis as well as some subcutaneous fat.

The white, oval–shaped areas are fat lobules. Just superficial to the subcutaneous fat, within the deep dermis, an inflamed medium–sized vessel is evident.

2. Kidney Biopsy: A kidney biopsy will be performed if there is evidence of kidney involvement by vasculitis (red blood cells or protein in the urine, for example). This procedure is done under local anesthesia while the kidney is visualized by ultrasound. Because of the small but significant risk of bleeding after this procedure, patients are usually monitored in the hospital for 24 hours after the biopsy.

3. Sural Nerve Biopsy: The sural nerve is a sensory nerve over the lateral aspect of the foot. Under local anesthesia in an operating room, a surgeon removes a small piece of the nerve, usually along with a piece of the adjacent muscle (the gastrocnemius). Because the sural nerve does not innervate muscles (remember: it is a sensory nerve, not a motor nerve), the patient does not lose any strength on the side of the foot and lower leg. There maybe, however, some residual numbness on the side of the foot. Patients generally tolerate this numbness well (if the vasculitis has involved the nerve severely enough, some patients already have numbness in that region).

4. Temporal Artery Biopsy: Performed to diagnose Giant Cell Arteritis, also known as Temporal Arteritis, because the temporal artery is often involved. The temporal artery courses up the temples, just in front of the ears. The biopsy, done under local anesthesia, is performed by making a small incision just above the hairline (sometimes shaving a small area of hair is required). The procedure is extremely well–tolerated by patients. Within several weeks, there is usually little or no sign that a biopsy was done. Complications of temporal artery biopsies are extremely rare. Sometimes, to increase the diagnostic yield, both temporal arteries (i.e., the ones on each side of the head) are biopsied.

5. Lung Biopsy : Often the best way to make a diagnosis of vasculitis that involves the lungs, such as granulomatosis with polyangiitis (GPA). A lung biopsy may be performed in one of two ways: 1) open lung biopsy, a sizable surgical procedure; or 2) thoracoscopic lung biopsy, a less invasive but still significant procedure. Even a thoracoscopic biopsy usually requires at least 48 hours in the hospital and the temporary placement of a chest tube to permit the lung to re–expand.

6. Brain Biopsy: Often necessary to confirm the diagnosis of Central Nervous System (CNS) Vasculitis. This is usually performed on the non–dominant side of the patient’s brain (that is, if the patient is right–handed — and therefore “left–brained” — the biopsy is performed on the right side of the brain). Biopsy of the brain’s covering, the meninges, is usually performed at the same time.

7. Angiogram / angiography: Angiography is helpful in the diagnosis of Polyarteritis Nodosa (PAN). Similar to a heart catheterization,  after inserting a catheter into a large artery in the leg and advancing the catheter into the aorta, radiographic dye is injected into blood vessels supplying the gastrointestinal tract. In the proper clinical setting, the detection of aneurysms (small outpouchings of blood vessel walls) is diagnostic of PAN. This gives an accurate picture of the luminal (inside) anatomy of blood vessels.

8. Central nervous system angiogram Frequently part of the “work–up” of CNS vasculitis. The procedure is identical to an abdominal angiogram, except the catheter is advanced all the way up to the large vessels supplying the head and neck (for example, the carotid arteries). On angiography, CNS vasculitis is characterized by “beading” (dilated areas alternating with narrowing of the blood vessels). A strikingly abnormal angiogram may eliminate the need for a brain biopsy.

9. Other Useful Tests: There are many other tests that are helpful in the diagnosis of vasculitis, or in evaluating the activity of the disease:

• Erythrocyte sedimentation rate (ESR)
• C–reactive protein (CRP)
• Urinalysis
• CT Scan
• ANCA tests

Erythrocyte sedimentation rate (ESR):  Also known as the “sed rate”, for short. This is an old but useful test first employed by the ancient Greeks as a test for pregnancy. It is important to note that there are several influences on the ESR such as anemia and hypergammaglobulinemia which may have nothing to do with an inflammatory state.

C–reactive protein (CRP): CRP is a protein produced by the liver in response to inflammation within the body.

Urinalysis: Many forms of vasculitis affect the kidneys. A simple way of determining whether or not the kidneys are involved is to perform a urinalysis. By performing checks for several indicators of inflammation in a patient’s urine, the physician may determine if inflammation is present within the kidneys. These indicators include:

• Protein (“proteinuria”)
• Red blood cells (“hematuria”)
• Clumps of red blood cells (“casts”)

Pictured below is a urine specimen from a patient with Wegener’s granulomatosis and glomerulonephritis (inflammation in the kidneys).

From another Wegener’s granulomatosis patient’s urinalysis, “blebs” (identified by white arrows) protrude from the surface of the red blood cells that have been damaged in transit through the kidney.

CT Scan (a CAT scan, or computed tomography) — A type of radiology test that permits a non-invasive, cross–sectional view of a patient’s anatomy. On the illustration below (a chest CT scan from a patient with GPA), the view is up (looking toward the patient’s head, from his or her feet). The heart is the white, rounded object in the upper center of the picture. The black regions are the patient’s lungs. The large spot in the left lung (corresponding to the patient’s right lung) is a nodule caused by GPA. Other smaller nodules are also evident.

 

MRI / MRA: MRI is another imaging modality that can be useful for diagnosing and following systemic vasculitis; particularly large vessel vasculitis. MRI allows for visualization of the vessel wall. In vasculitis, the vessel wall may be thickened or edematous.

ANCA tests — ANCA is an abbreviation (acronym) for anti–neutrophil cytoplasmic antibodies. These antibodies are found in the blood of patients with several different types of vasculitis, including Wegener’s Granulomatosis, Microscopic Polyangiitis, and the Churg–Strauss Syndrome. ANCAs and their association with vasculitis were recognized in the mid–1980s, and their use has become increasingly widespread since the 1990s. ANCAs are detected by a simple blood test. These antibodies 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 with symptoms or signs suggesting Wegener’s, the likelihood of the diagnosis increases considerably. Because of the long list of other conditions that are sometimes associated with ANCAs, however, in most cases it is still VERY IMPORTANT to biopsy an organ involved by vasculitis to verify the diagnosis.

 

All information contained within the Johns Hopkins Vasculitis Center website is intended for educational purposes only. Visitors are encouraged to consult other sources and confirm the information contained within this site. Consumers should never disregard medical advice or delay in seeking it because of something they may have read on this website.

Vasculitis Center Doctors

Collaborators

Vasculitis can involve virtually any organ system within the body. Hence, our Vasculitis Center maintains close collaborative relationships with experts from other specialties. The Vasculitis Center includes collaborators from several medical disciplines who help provide the highest level of care for our patients. They have extensive experience managing vasculitis within their subspecialty and work closely with the Physicians in the Vasculitis Center to provide comprehensive care for our patients:

Otolaryngology (ENT):

Our ENT team includes specialists in inflammatory sinus disease, sensorineural hearing loss, and chronic middle ear disease. We are pleased to also have a Doctor of Audiology, Dr. Dinkes, who specializes in inflammatory process on our team as well.

• Dr. Jean Kim (sinus disease, middle ear manifestations)
• Dr. Alexander Hiller (upper airway disease)
• Dr. Roni Dinkes (audiology)

Neuro-ophthalmology:

• Dr. Andrew Carey

Endocrinology / Osteoporosis:

• Dr. Han Na Kim

Prednisone is a corticosteroid with potent anti-inflammatory effects. Corticosteroids are a cornerstone of treating most types of vasculitis, and are often used in combination with other immunosuppressive medications. Prednisone works very quickly, and is therefore used (often at high doses) at the time of initial diagnosis to bring vasculitis under control. Then, prednisone is gradually reduced (“tapered”) while another immunosuppressive drug is started for long term treatment. Over time, the “steroid-sparing” immunosuppressive drug is used to control vasculitis, and prednisone is eventually stopped.

Side Effects

Corticosteroids cause a long list of side effects, making it dangerous to use these drugs at significant doses for long term treatment. The side effects of prednisone are related to: 1) the amount of steroid a patient takes in his/her daily dose, and 2) the length of time the patient remains on the medication. We emphasize that not all side effects occur in all patients.

Despite the numerous potential side effects of corticosteroids listed below, their introduction into patient care more than 50 years ago revolutionized the treatment of many diseases, including vasculitis. When used properly, these drugs save lives and avert threats to the function of important organs.

Common Side Effects of Steroids:

• Increased Susceptibility to Infections
• Weight Gain
• Glucose Intolerance
• Hypertension
• Bone Thinning
• Avascular Necrosis of bone
• Easy Bruising
• Abdominal Striae
• Hirsutism
• Acne
• Mood Swings/Insomnia
• Cataracts

Increased Susceptibility to Infections

Patients are at increased risk for many types of infections, from minor fungal infections in the mouth (“thrush”, caused by Candida) to life–threatening infections such as Pneumocystis carinii pneumonia. The higher the steroid dose and the longer the duration of therapy, the greater the risk of infection. The risk is also increased when patients receive combinations of immunosuppressive medications, such as cyclophosphamide (cytoxan) and prednisone. The risk of some infections can be greatly reduced by taking specific types of antibiotics prophylactically (such as Bactrim).

Pictured below is woman under treatment with prednisone and methotrexate for vasculitis and a concurrent neurologic condition (myasthenia gravis) developed painful vesicles in her mouth. The vesicles were confirmed by culture to be caused by reactivation of a Herpes simplex infection, and responded to treatment with acyclovir.

Weight Gain

Weight gain is usually the most dreaded side–effects of steroids, incurred to some degree by nearly all patients who take them. The amount of weight gain varies from individual to individual. In addition to causing weight gain, prednisone leads to a redistribution of body fat to places that are undesirable, particularly the face, back of the neck, and abdomen. Pictured below is an example of redistribution of body fat to the back of the neck. Accumulation of fat in this area is sometimes referred to as a “buffalo hump”.

Another example of this “redistribution” is pictured below. Supraclavical “fat pads” are collections of fat at the base of the neck, just above the collarbones, which are common in patients on steroids. They sometimes cause concern among patients if mistaken for lymph nodes or other causes for worry, but will gradually subside as the prednisone dose is tapered to below 10 milligrams/day.

In addition to this redistribution of fat, many patients undergo loss of muscle strength (muscle atrophy) while taking steroids. Regular physical exercise is key to avoiding this type of deconditioning that often occurs with prednisone treatment.

Glucose Intolerance

High blood sugar, or steroid–induced diabetes. Patients who are “pre-diabetic” can develop diabetes and the need for insulin while taking steroids. This usually resolves when the steroids are decreased or discontinued, but can be worsened by weight gain.

Hypertension

High blood pressure. This usually improves as the corticosteroid dose is reduced.

Bone Thinning (Osteoporosis)

Prednisone may cause thinning of the bones even in people who are not usually at high risk for osteoporosis (for example: males, young people). In people susceptible to osteoporosis, prednisone may accelerate the process of bone loss. Fortunately, in the past few years, excellent treatments and preventive measures have become available for osteoporosis. All patients on prednisone for prolonged periods are candidates for these medicines. Patients should be aware of their daily intake of calcium and Vitamin D while on steroids. Bone density measurement is commonly done using DEXA scans.

Avascular Necrosis of Bone

For reasons that are not known, high dose prednisone (for example, greater than 20 milligrams a day) predisposes some patients to joint damage, most often of the hips. In avascular necrosis (or osteonecrosis, meaning “bone death”) of the hip, the part of the leg bone that inserts into the pelvis dies, resulting in pain with weight–bearing and some loss of joint function. Many patients with avascular necrosis require joint replacements.

Easy Bruising

Prednisone also causes “thin skin”. Patients on moderate to high doses of prednisone often notice that they bruise easily, even with only slight trauma. Pictured below is a patient with giant cell arteritis who suffered a skin laceration after she struck her leg against a chair.

Abdominal Striae

Abdominal striae (“stripes”), as pictured below, frequently occur in patients who take high doses of steroids for long periods of time.

Hirsutism

Hirsutism is excessive growth of body hair. Patients vary in the degree to which this side effect of steroids occurs. Although some patients experience minimal hirsutism, the patient depicted below developed this side effect after taking 10 milligrams of prednisone for a few months.

Acne

High dose prednisone predisposes some patients to acne, especially facial acne, as pictured below. The facial acne developed after several weeks of high steroid doses.

Mood Swings/Insomnia

Many patients find it difficult to fall asleep when taking high doses of steroids. Many also find that they are more irritable or anxious than usual. Steroids sometimes even induce depression or psychosis, which usually improves when the drug is decreased or discontinued.

Cataracts

Long–term steroid use may lead to cataract development in the eyes, which frequently require surgical removal.