- Eosinophilic Granulomatosis with Polyangiitis, formerly Churg-Strauss Syndrome (EGPA)
- Who gets EGPA (the “typical” patient)?
- Classic symptoms and signs of EGPA
- What causes EGPA?
- How is EGPA Diagnosed?
- Treatment and Course of EGPA
- Shuttles | Transportation Services
- Daytime Bus and Shuttle Service
- What to Do After a Tick Bite : Johns Hopkins Lyme Disease Research Center
- Recognizing the Rash After a Tick Bite
- Requesting and Receiving Care For the Tick Bite
- Diagnosing Lyme Disease:
- Microscopic Polyangiitis
- Who gets Microscopic Polyangiitis? A typical patient
- Classic symptoms of Microscopic Polyangiitis
- Kidney Inflammation
- Constitutional Symptoms
- Skin lesions
- Peripheral nervous system
- Eyes, Muscles, and Joints
- Forms of vasculitis similar to Microscopic Polyangiitis
- What Causes Microscopic Polyangiitis?
- How is Microscopic Polyangiitis diagnosed?
- Treatment and Course of Microscopic Polyangiitis
Eosinophilic Granulomatosis with Polyangiitis, formerly Churg-Strauss Syndrome (EGPA)
Eosinophilic granulomatosis with polyangiitis (EGP), formerly known as the Churg-Strauss Syndrome , is a systemic vasculitis. This disease was first described in 1951 by Dr. Jacob Churg and Dr.
Lotte Strauss as a syndrome consisting of “asthma, eosinophilia [an excessive number of eosinophils in the blood], fever, and accompanying vasculitis of various organ systems”. EGPA shares many of the clinical and pathological features of polyarteritis nodosa (“PAN”, another type of vasculitis) and granulomatosis with polyangiitis (GPA).
However, Drs. Churg and Strauss discovered that the presence of granulomas as well as the abundance of eosinophils distinguished this disease from PAN and GPA.
Who gets EGPA (the “typical” patient)?
The typical patient with EGPA is a middle aged individual with a history of new-onset or newly-worsened asthma. The distribution of the disease among males and females is approximately equal.
Classic symptoms and signs of EGPA
Asthma is one of the cardinal features of EGPA. Asthma symptoms may begin long before the onset of vasculitis – e.g., many years before any other symptoms of EGPA arise, and long before the diagnosis of EGPA is made. Other early symptoms/signs include nasal polyps and allergic rhinitis.
The next phase of the disease is often marked by eosinophilia, the finding of an excessive number of eosinophils in the blood or in tissues. An eosinophil is one subtypes of white blood cell.
Normally, eosinophils comprise 5% or less of the total white blood cell count. In EGPA, the percentage of eosinophils may reach as high as 60%.
In the picture below, the eosinophils are shown by the dark pink stain.
The third phase of the illness is a vasculitis, which involves the skin, lungs, nerves, kidneys, and other organs.
Particular mention should be made of the frequent devastating involvement of the nerves (called mononeuritis multiplex), which produces severe tingling, numbess, shooting pains, and severe muscle wasting/power loss in the hands or feet.
The list below contains the organs commonly involved by EGPA and the specific disease manifestation(s) in each organ.
- Sinusitis, including allergic rhinitis
- Nasal polyps
- Pulmonary infiltrates (only one-third of all patients)
- Bleeding into the lungs (occasionally)
- Diffuse interstitial lung disease (rarely)
- Palpable purpura
- Nodules (above or below the skin), often at sites of pressure, such as the elbows
- Glomerulonephritis (inflammation in the small units of the kidney that filter blood)
- Lesions (vasculitic) are occasionally found in the GI tract
- Granuloma sometimes found in spleen
- Vasculitis lesions in heart, can lead to congestive heart failure or a heart attack
- Peripheral nerve involvement including pain, numbness, or tingling in extremities (neuropathy/mononeuritis multiplex)
What causes EGPA?
The cause of EGPA is unknown but is probably multi-factorial. Genetics may play a small role in the disease, but EGPA is almost never seen in two members of the same family.
Environmental factors such as exposure to industrial solvents may play a role in susceptibility to this disease, but this is largely speculative.
Infections may be the inciting event(s), but to date there is no definitive evidence of this.
How is EGPA Diagnosed?
Among all of the vasculitides, asthma is a distinctive feature of EGPA alone. However, not all patients with asthma have vasculitis – only a tiny minority do, in fact.
It is the specific combination of symptoms and signs, the pattern of organ involvement, and the presence of certain abnormal blood tests (eosinophilia, in particular) that help the doctor make the diagnosis.
In addition to a detailed history and physical examination, blood tests, chest X-rays and other types of imaging studies, nerve conduction tests, and tissue biopsies (e.g., of lung, skin, or nerve) may be performed to help diagnose EGPA.
The following features are consistent with a diagnosis of GPA:
- eosinophilia [>10% on differential WBC count]
- transient pulmonary infiltrates on chest X-rays
- paranasal sinus abnormalities
- biopsy containing a blood vessel with extravascular eosinophils.
Treatment and Course of EGPA
EGPA usually responds to prednisone. Initially, high doses of oral prednisone are used in an attempt to get the disease into remission as quickly as possibly (e.g., using oral prednisone 40-60 mg/day). After the first month or so, this high dose of prednisone is gradually tapered down over the ensuing months.
Other immunosuppressive drugs, such as azathioprine, cellcept, methotrexate, cyclophosphamide, or rituximab may be used in addition to prednisone.
High doses of intravenous steroids (usually methylprednisolone) maybe useful for those patients with severe disease or for those who are unresponsive to the combination of oral prednisone used with other immunosuppressive medications.
Prior to the advent of prednisone, EGPA was often a fatal disease. The majority of patients died from rampant, uncontrolled disease.
With present therapy, constitutional symptoms begin to resolve quite quickly, with gradual improvement in cardiac and renal function, as well as improvement in the pain that results from peripheral nerve involvement.
The course of therapy can last for 1 to 2 years, although the length and type of treatment depend on the severity of disease and the organs involved.
The patient’s response to treatment and the continuation of disease control during lowering of the prednisone dose are the primary determinants of how long therapy is continued. Laboratory monitoring of blood tests is very helpful in gauging the activity of disease. Some of the most useful laboratory tests are the erythrocyte sedimentation rate (ESR) and the eosinophil count.
Shuttles | Transportation Services
Homewood Transportation Services provides several services to faculty, staff and students. These include daytime services which connect the various Johns Hopkins properties across Baltimore, and evening services which provide safe transportation around the Homewood Campus and vicinity.
**Until further notice, all passengers and drivers are required to wear a face covering while on board any JHU vehicles. Effective face coverings include, but are not limited to: masks, bandanas, scarves or any material that fully covers nose and mouth.**
Daytime Bus and Shuttle Service
Using a combination of buses and vans, six routes connect the Homewood Campus with the following Johns Hopkins properties: the Carey Business School, FastForwardU, JHU at Eastern, JHU at Keswick, JHU at Mount Washington, Johns Hopkins Bayview, Johns Hopkins Medical Institute, the Peabody Institute, R. House, and Stieff Silver.
- Homewood – Bayview Express Shuttle: [Map/Schedule] **MODIFIED SCHEDULE EFFECTIVE MARCH 23rd THROUGH MAY 1st; SERVICE WILL BE SUSPENDED THEREAFTER UNTIL FURTHER NOTICE: [Map/Schedule]**
- Homewood – Mt. Washington Express Shuttle: [Map/Schedule] **ON-CALL SERVICE ONLY, EFFECTIVE MARCH 23rd UNTIL FURTHER NOTICE: call (410) 516 4200 weekdays between 8am and 5pm to request pickup**
- Remington Shuttle: [Map/Schedule] **ON-CALL SERVICE ONLY, EFFECTIVE MARCH 23rd UNTIL FURTHER NOTICE: call (410) 516 4200 weekdays between 9am and 5pm to request pickup**
- Carey Business School Shuttle: **NOT OPERATING FOR THE REMAINDER OF THE SPRING 2020 TERM: Summer term dates will be published as soon as available.**
NOTE: for shuttles and buses which originate from the Johns Hopkins Medical Institute aside from the above referenced Homewood-Peabody-JHMI route, please see https://www.hopkinsmedicine.org/security_parking_transportation/transportation/.
Evening Blue Jay Shuttle Service
**EFFECTIVE APRIL 5th UNTIL FURTHER NOTICE: Night Ride will operate from 9am until 9pm.
Vans will be assigned to one traveling party at a time; passengers should BOOK ALL RIDES AS IF FOR ONE PERSON and drivers will allow groups of up to 8 traveling together to board.
Homewood Route and Brody Shuffle service will NOT operate. Normal restrictions on Night Ride pickup requests from Brody Learning Commons and its immediate vicinity are lifted.**
- Blue Jay Shuttle Homewood Route: [Map and Schedule]
- Brody Shuffle: Brody Shuffle departs Brody Learning Commons at 5:40pm, and every 10-20 minutes (at :10, :20, :40, and :50 past each hour) thereafter. Starting at midnight, it departs every 15 minutes (at :00, :15, :30, and :45 past each hour) with the last departure for the evening occurring at 3:30am. Boarding passengers notify the driver of their destination, and the driver will determine an efficient order for drop-offs.
- Night Ride: [Homewood Info] | [Peabody Institute Info] | [Smartphone App] | [Web Interface]
The Blue Jay Shuttle service operates on a combination of request-only Night Ride and ride-anytime fixed-routes in an area proximate to the Homewood campus from 5:30pm to 3:45am nightly, seven days per week, excluding University holidays and other dates as determined by the University.
The service also operates at the Peabody Institute from 6:00pm until 3:45am. Shuttles are equipped with TransLoc, a GPS-based real-time transit information system available online or through a mobile device. To view the Blue Jay Shuttle routes and to track the vans, go to http://jhu.transloc.com on either a computer or a smartphone.
TransLoc’s free app is available at https://transloc.com/app/.
The Homewood route includes marked “flag stops” – safe passenger loading zones – at selected university-owned buildings, off-campus residence halls and commercial/retail locations. Passengers must be at a designated flag stop and use their J-Card to “flag the shuttle” in order to board route vans.
Drivers do not deviate from their fixed route except in the case of emergency, but, may drop off at other safe locations along the route upon request. All Johns Hopkins affiliates with a valid J-card can use the Blue Jay Shuttle. Passengers are expected to carry all personal items, backpacks, grocery bags, etc.
on and off the shuttle in one trip so as not to delay the shuttle.
After 11:30pm the fixed-route service makes its final departure. The Brody Shuffle continues to depart BLC every ten minutes until midnight, then every quarter-hour from midnight until 3:30am.
Passengers notify the driver of their destination and the driver will coordinate drop-offs in an efficient manner. Night Ride continues service until 3:45am.
Use the TransLoc app to request a ride or call (410) 516-8700 to request a Night Ride and the dispatcher will provide passenger(s) with an estimated time of arrival.
Night Ride does not offer pickups from Brody Learning Commons or adjacent locations. Passengers needing rides from these locations should simply board the “Brody Shuffle” service, at one of over 40 departure times between 5:40pm and 3:30am. Visit the Night Ride page for a more complete explanation.
Information Regarding Inclement Weather
In the case of severe weather conditions, bus and shuttle service may be temporarily suspended as circumstances warrant but shall be resumed thereafter as soon as reasonably possible. Our plan for University closures and delayed openings may be found here. Notifications will be kept up to date on http://jhu.transloc.com, http://ts.jhu.edu/, and www..com/jhutransportation.
Additional questions, comments, or concerns may be directed to firstname.lastname@example.org.
What to Do After a Tick Bite : Johns Hopkins Lyme Disease Research Center
Tick attachment time is important. Removing ticks as soon as possible reduces the risk of infection. If you or a loved one is bitten, remove the tick promptly. Here’s how:
- Grasp the tick’s mouthparts against the skin, using pointed tweezers.
- Be patient; the long mouthpart is covered with barbs, so removing it can be difficult and time consuming.
- Pull steadily without twisting until you can ease the tick head straight the skin.
- DO NOT pull back sharply; this may tear the mouthparts from the body of the tick and leave them embedded in the skin.
- If this happens, don’t panic! Embedded mouthparts do not transmit Lyme disease.
- DO NOT squeeze or crush the body of the tick; this may force infected body fluids from the tick into the skin.
- DO NOT apply substances such as petroleum jelly, nail polish, or a lighted match to the tick while it is attached. They may agitate the tick and force more infected fluid into the skin.
- Once you have removed the tick, wash the wound site and your hands with soap and water, and apply rubbing alcohol or antiseptic to the site.
- Observe the bite site over the next two weeks for any signs of an expanding red rash or flu- symptoms.
- Consult with your PCP about sending your tick to a lab to be tested for pathogens.
Recognizing the Rash After a Tick Bite
It is important to understand that a rash is not always present or easily recognizable in early Lyme disease, and this can lead to delayed diagnosis and treatment.
Please refer to our poster of varied Lyme disease rash manifestations as a helpful identification tool.
It is wise to take a picture of the rash with the date for your medical record, since a rash compatible with erythema migrans rash should prompt urgent evaluation and treatment. Lyme disease is most successfully treated in this first stage.
If you have a suspicious rash or your symptoms persist, please seek medical care immediately.
The Lyme disease rash, called erythema migrans, is:
- Round or oval, enlarges in size over days/weeks, & will not fade in a few days
- Usually greater than 2” inches in diameter, often 6-8”
- Usually uniformly red
- Sometimes but not often, a “bull’s eye” rash with a red ring surrounding a clear area and red center
- Minimally tender, minimally itchy (much less itchy than poison ivy), and sometimes warm
- Often confused with spider bites
The incubation period from tick bite to rash is usually 3-10 days but can be 30 days.
The Lyme rash can spread through the bloodstream to other areas of the skin.
Sometimes blisters develop in the center of the rash.
Tick bite reactions are often confused with the rash of Lyme disease.
Tick bite reactions:
- Are small red bumps, less than 1-2” in size
- Appear at the site of the bite, often in the groin, belt area, arm pits, or behind the knee
- Do not expand in size when observed over 24-48 hrs
- May feel warm and tender to the touch
- Can last days, even weeks
Requesting and Receiving Care For the Tick Bite
If you have a tick bite, watch for an expanding red rash or lesion at the site of the tick bite or an unexplained feverish, achy, fatiguing illness within 1 to 4 weeks after the tick bite. If you are concerned about symptoms or a rash, take a picture of the rash and contact your physician.
Diagnosing Lyme Disease:
- Lyme disease is a clinical diagnosis made by a doctor or nurse by examining the patient.
- Acute Lyme disease is not a laboratory diagnosis; a negative Lyme blood test does not exclude Lyme disease in the first few weeks of the illness.
- Many with Lyme disease have a flu- illness and NO rash.
- Fever, aches, and abrupt and severe fatigue can be the main symptoms of acute Lyme.
- Lyme disease is different from a respiratory “cold”.
- A runny nose and prominent cough are NOT symptoms of Lyme disease.
- Blood tests do not accurately diagnose Lyme disease in the first few weeks of infection, so being vigilant about looking for symptoms is a more reliable way to identify an early case of Lyme disease.
The first description of a patient with the illness now known as microscopic polyangiitis (MPA) appeared in the European literature in the 1920s.
The concept of this disease as a condition that is separate from polyarteritis nodosa (PAN) and other forms of vasculitis did not begin to take root in medical thinking, however, until the late 1940s. Even today, some confusing terms for MPA (e.g.
, “microscopic poly arteritis nodosa ” rather than “microscopic poly angiitis ”) persist in the medical literature. Confusion regarding the proper nomenclature of this disease led to references to “microscopic polyarteritis nodosa” and “hypersensitivity vasculitis” for many years.
In 1994, The Chapel Hill Consensus Conference recognized MPA as its own entity, distinguishing it in a classification scheme clearly from PAN, granulomatosis with polyangiitis (GPA, formerly Wegener’s), cutaneous leukocytoclastic angiitis (CLA), and other diseases with which MPA has been confused with through the years.
Much of the explanation for the difficulty in separating MPA from other forms of vasculitis has stemmed from the numerous areas of overlap of MPA with other diseases. MPA, PAN, GPA, and CLA and other disorders all share a variety of features but possess sufficient differences as to justify separate classifications.
Who gets Microscopic Polyangiitis? A typical patient
MPA can affect individuals from all ethnic backgrounds and any age group. In the United States, the typical MPA patient is a middle-aged white male or female, but many exceptions to this exist. The disease may occur in people of all ages, both genders, and all ethnic backgrounds.
Classic symptoms of Microscopic Polyangiitis
Many signs and symptoms are associated with MPA. This disease can affect many of the body’s organ systems including (but not limited to) the kidneys, nervous system (particularly the peripheral nerves, as opposed to the brain or spinal cord), skin, and lungs. In addition, generalized symptoms such as fever and weight loss are very common.
The FIVE most common clinical manifestations of MPA are:
Inflammation in the kidneys, known as glomerulonephritis, causes blood and protein loss through the urine. This process can occur either slowly or very rapidly in the course of the disease. Patients with kidney inflammation may experience fatigue, shortness of breath, and swelling of the legs.
The image below is from a urinalysis of a patient with kidney inflammation. When MPA 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.
Weight loss, fevers, fatigue, and malaise are part of a collection of complaints regarded as “constitutional” symptoms. Constitutional complaints are a common finding in patients with MPA, because the disorder is a systemic disease confining itself generally not to one specific organ system but rather broadly affecting a patient’s “constitution”.
Skin lesions in MPA, as in other forms of vasculitis that involve the skin, can erupt on various areas of the body. The lesions tend to favor the “dependent” areas of the body, specifically the feet, lower legs and, in bed-ridden patients, the buttocks. The skin findings of cutaneous MPA include purplish bumps and spots pictured below (palpable purpura).
These areas range in size from several millimeters in diameter to coalescent lesions that are even larger. Skin findings in MPA may also include small flesh-colored bumps (papules); small-to-medium sized blisters (vesiculobullous lesions); or as small areas of bleeding under the nails that look splinters (pictured below), hence the name splinter hemorrhages.
Peripheral nervous system
Damage to peripheral nerves (i.e., nerves to the hands and feet, arms and legs) results from inflammation of the blood vessels that supply the nerves with nutrients. Inflammation in these blood vessels deprives the nerves of their nutrients, leading to nerve infarction (tissue death).
Multiple nerve involvement that is characteristic of vasculitis is known as “mononeuritis multiplex”. This condition is frequently associated with wrist or foot drop: the inability to extend the hand “backwards” at the wrist or to flex the foot upward toward the head at the ankle joint.
If the condition is caused by nerve deterioration associated with vasculitis, unfortunately, surgery is not a treatment option due to the nerve infarcton (tissue death).
Neurologic symptoms resulting from peripheral nerve damage may also include numbness or tingling in the arm, hand, leg, or foot. Over time, muscle wasting (pictured below) that is secondary to the nerve damage may result from damage caused by vasculitis.
The hand on the left (the patient’s right hand) is normal, displaying normal muscle bulk of the areas between the fingers.
In contrast, the hand on the right (the patient’s left) shows wasting of the muscle in the web space between the thumb and first finger, leading to a hollowed-out, bowl- appearance of that area.
The consequence of this muscle wasting is that the patient is unable to grasp objects between his thumb and fingers (i.e., has a weak pinch) and his hand grip is weak.
Lung involvement can be a dramatic and life-threatening manifestation of MPA.
When lung disease takes the form alveolar hemorrhage – bleeding from the small capillaries that are in contact with the lungs’ microscopic air sacs – the condition may quickly pose a threat to the patient’s respiratory status (and therefore to the patient’s life). Alveolar hemorrhage (pictured below), which is frequently heralded by the coughing up of blood, occurs in approximately 12% of patients with MPA .
Another common lung manifestation of MPA is the development of non-specific inflammatory infiltrates, identifiable on chext x-rays or computed tomography (CT scans) of the lung.
Eyes, Muscles, and Joints
Organs that also merit mention in discussions of MPA include the eyes, muscles, and joints. Intermittent irritation of the eye (resembling “pinkeye”) that is caused by either conjunctivitis or episcleritis may be an early disease manifestation or a sign of a disease flare.
Occasionally other types of inflammation (e.g., uveitis) are also observed in MPA. Muscle or joint pains (known to clinicians as “myalgias” or “arthralgias”, respectively) are common complaints in MPA, generally accompanying the types of constitutional symptoms mentioned above.
Arthritis (inflammation of the joints accompanied by swelling) can also be observed in MPA.
Joint complaints in MPA and related forms of vasculitis tend to migrate from one joint to another – one day involving the left ankle, the next day the right wrist, the third day a shoulder, for example.
Forms of vasculitis similar to Microscopic Polyangiitis
The similarities and differences between MPA, GPA, and PAN are highlighted in the table below.
|BLOOD VESSEL SIZE||Small to Medium||Small to Medium||Medium|
|BLOOD VESSEL TYPE||Arterioles to venules, And sometimes Arteries and veins||Arterioles to venules, And sometimes Arteries and veins||Muscular Arteries|
1 Pulmonary capillaritis in MPA and nodules or cavitary lesions in WG
2MPA can have small blood vessel skin lesions as mentioned above, similar to GPA or medium blood vessel lesions similar to PAN (livedo reticularis, nodules, ulcers, and digital gangrene)
3Stomach pain after meals
4MPA eye complications are typically milder than those of GPA, but serious
ocular problems including necrotizing scleritis can occur
5Constitutional symptoms include weight loss, fevers, joint and muscle aches, and malaise.
What Causes Microscopic Polyangiitis?
The cause of MPA is not known. However, enough is known about a few types of vasculitides that allow us to describe in general terms how MPA affects the body.
MPA is clearly a disorder that is mediated by the immune system; the precise events leading to the immune system dysfunction (hyperactivity), however, remain unclear.
Many elements of the immune system are involved in this process: neutrophils, macrophages, T and B lymphocytes, antibodies, and many, many others.
Because MPA is often associated with anti-neutrophil cytoplasmic antibodies (ANCA), antibodies directed against certain constituents of white blood cells (WBCs), the disease is often termed an “ANCA-associated vasculitis”, or AAV.
ANCA, discovered in 1982, act against certain specific (and naturally occurring) enzymes in the body residing within the neutrophils and the macrophages, all of which are members of the WBC family.
The result of the interactions of ANCA with their target proteins is an increase in the destruction of WBCs at the sites of disease and the release of white blood cell enzymes within blood vessel walls, causing the damage to blood vessels. In MPA, the ANCA are directed generally against to specific proteins: myeloperoxidase (MPO) and proteinase 3 (PR3).
How is Microscopic Polyangiitis diagnosed?
Blood is taken to detect any ANCA levels, if MPA is suspected. In addition, an erythrocyte sedimentation rate (ESR or “sed rate”) and C-reactive protein (CRP) are usually ordered.
Both of these tests are elevated in many different types of inflammation and are not specific to MPA or any particular disease. The ESR and CRP, known as “acute phase reactants”, are often sensitive indicators of the presence of active disease.
In and of themselves, however, elevations in acute phase reactants are not sufficient to justify additional treatment.
A carefully analyzed urine specimen should be obtained at the initial visit (and every follow-up visit!) to maintain vigilance for either the development or the progression of kidney involvement.
A computed tomography (CT) scan of the chest may also be performed to detect the presence of lung involvement. A tissue biopsy may be needed to make the diagnosis of MPA, and is taken from an organ that seems to be involved at the time.
Sometimes an electromyography/nerve conduction (EMG/NCV) study may need to be done to identify a site for biopsy or to detect findings consistent with a mononeuritis multiplex (see classic symptoms section above).
Tissues that might be biopsied are kidney, skin, nerve, muscle, and lung.
Pictured: a biopsy of the gastrocnemius muscle, performed in a 69 year–old man with microscopic polyangiitis. A blood vessel within the muscle shows an intense inflammatory infiltrate with destruction of the blood vessel wall, confirming the diagnosis of vasculitis.
Treatment and Course of Microscopic Polyangiitis
A steroid (usually prednisone) in combination with a cyclophosphamide (CYC) or rituximab is typically the first combination of medications to be prescribed.
After control of the disease – usually around 4 – 6 months of treatment maintenance therapy will be used to keep the disease in remission. This will vary between patients.
Prednisone may be discontinued after approximately 6 months.