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• Fast Facts
• First Description
• Who gets Henoch-Schönlein Purpura (the “typical” patients)?
• What causes Henoch-Schönlein Purpura?
• How is Henoch-Schönlein Purpura diagnosed?
• Treatment and Course of Henoch-Schönlein Purpura
• Living with Henoch-Schönlein Purpura

Fast Facts

• HSP is usually self-limited. Therefore, treatment is not indicated in all cases, and full recovery is the rule.
• HSP is more common in children than adults, but has a tendency to be more severe when it occurs in adults.
• In a small minority of cases, HSP can cause severe kidney or bowel disease.

First Description

Dr. William Heberden, a London physician, described the first cases of Henoch-Schönlein purpura (HSP) in 1801. In describing HSP, Heberden wrote of a 5-year old boy who “…was seized with pains and swellings in various parts…He sometimes had pains in his belly with vomiting…and the urine was tinged with blood. Presently, the skin of his leg was all over full of bloody points” (purpura). The young boy suffered all four disease hallmarks of HSP: arthritis, gastrointestinal involvement, kidney inflammation, and purpura. Johann Schönlein (1837) and Edouard Henoch (1874) reported additional cases decades after Heberden. They recognized that the disorder often followed upper respiratory tract infections and was not always self-limited, sometimes progressing to serious kidney involvement.

Who gets Henoch-Schönlein Purpura (the “typical” patient)?

Usually, HSP affects a child shortly after an upper respiratory infection has resolved.

HSP is the most common form of vasculitis in children, with an annual incidence on the order of 140 cases/million persons. The mean age of patients with HSP is 5.9 years.

What causes Henoch-Schönlein Purpura?

In two-thirds of the cases, the disease follows an upper respiratory tract infection, with onset an average of ten days after the start of respiratory symptoms. Despite this association, no single microorganism or environmental exposure has been confirmed as an important cause of HSP.

How is Henoch-Schönlein Purpura Diagnosed?

Purpura not due to a low platelet count, caused by inflammation in blood vessels of the skin, is the hallmark of HSP. The tetrad of purpura, arthritis, kidney inflammation, and abdominal pain is often observed. However, all four elements of this tetrad are not required for diagnosis. The microscopic hallmark of HSP is the deposition of IgA (an antibody found in blood, saliva, tears, etc.) in the walls of involved blood vessels.

More than 90% of cases occur in children. The disease usually resolves within a few weeks. However, adult cases are sometimes more difficult. Skin manifestations are more variable in adults, and sometimes symptoms in adults endure longer [Figure 1, 2].

Figure 1. Pustular lesions. These can occur in HSP, but they are more common with the adult form of HSP.

Figure 2. Vesiculobullous lesions These are also more common with the adult form of HSP.

Adults are more prone to permanent kidney damage. However, patients can take some comfort in knowing that fewer than 5% of patients with HSP develop progressive renal insufficiency.

HSP can be mimicked by other forms of systemic vasculitis that are more often life-threatening. Granulomatosis with polyangiitis and microscopic polyangiitis can also present with purpura, arthritis, and renal inflammation. These disorders both have the potential for serious involvement of other organs (for example, the lungs, eyes, and peripheral nerves) and carry more dire renal prognoses. Therefore, it is very important to distinguish the difference by performing a careful evaluation including bloodwork, urinalysis, chest imaging, and possibly biopsies. HSP may be misdiagnosed as another form of vasculitis – most commonly hypersensitivity vasculitis – because of the frequent failure to perform direct immunofluorescence (DIF) testing on skin biopsy and the consequent failure to detect IgA.

Treatment and Course of Henoch-Schönlein Purpura

NSAIDs may alleviate arthralgias but can aggravate gastrointestinal symptoms, and should be avoided in any patient with renal disease. Dapsone (100 mg/day) may be effective in cases of HSP, perhaps through disrupting the abnormal immune response. Although steroids have not been evaluated rigorously in HSP, they appear to ease joint and gastrointestinal symptoms, in many (but not all) patients. Steroids, however, do not appear to improve the rash; although usually, over weeks to months, the recurrent bouts of purpura usually resolve on their own.

Living With HSP

Supportive care may involve a short course of prednisone or an NSAID, such as naprosyn or ibuprofen, if the kidneys are not involved. Keeping the legs elevated may help prevent purpura during flares of active disease. Additionally, many patients’ purpura will recur after they start to feel better and become more active, inherently increasing their exposures to very minor trauma (e.g. jogging, leg shaving, increasing gravity exposures). Often, the recurring purpura is less prevalent [Figure 3], and additional HSP symptoms are often absent. In many fewer cases, primarily in adults, HSP can progress from hematuria (blood in the urine) to renal insufficiency (decreased kidney function). HSP patients who experience this symptom should be followed more closely, with regular testing of their urine for blood and protein. Recurrences, found in 33% of patients, usually develop within the first few months after resolution of the first bout.

Figure 3. Palpable purpura . Occurring in a more diffuse pattern.

Figure 4. Palpable purpura . Here they are occurring in a very dense pattern with coalescing lesions.

Figure 5. Swelling around the hand and wrist . Although arthralgias are more common in HSP, arthritis can occur as well as periarticular swelling, such as the tenosynovitis shown here.

Figure 6. Swelling around the ankle and foot .

Figure 7. Palpable purpura can appear in many different patterns . This picture shows a denser distribution with a sharp demarcation caused by what is known as Koebner’s Phenomenon (Minor trauma, such as the elastic band in one’s sock, can cause such a pattern). In this case, the “trauma” was caused by the patient’s shaving of her legs, leading to the eruption of purpura in the area of skin where the razor had passed. Sufficient pressure, such as this, causes the rupture of inflamed blood vessels.

Figure 8. CT of abdomen showing bowel edema . This image is of a distended large bowel. The characteristic dips between haustra (bowel sections) are less pronounced because of the swelling / inflammation seen in HSP.

Figure 9. Formally known as DIF (Direct Immunofluorescence) testing. This picture shows immunofluorescence testing of a skin biopsy, IgA positive. Palpable purpura should be biopsied, and two fresh samples should always be sent for testing (an adequate biopsy should be large enough to divide; one for H&E (hematoxylin and eosin) staining, and one for DIF testing.

Figure 10. Arm rash . It is more common to have a purpuric outbreak on the lower extremities. However, an outbreak can occur on the abdomen, chest, or as in the case with this woman, on the upper extremities. Note the hive-like lesions that appear larger than the papules. The rash may also be itchy.

Figure 11. Colonoscopy of HSP-affected bowel . This image shows what the lining of the bowel could look like when it is inflamed and swollen, as in HSP. Looks painful…it is.

What is IVIG/SCIG?

Intravenous immunoglobulin (IVIG) is a therapy consisting of pooled antibodies (immunoglobulin) obtained from healthy donors that is given as an infusion by vein. This same therapy can also be given as a subcutaneous injection (SCIG) rather than an intravenous one.

How does it work?

IVIG and SCIG are often used to treat patients with immunodeficiency syndromes, which are genetic or acquired conditions that lead to low immunoglobulin levels. For these patients, IVIG/SCIG provide the protective effect of antibodies that they otherwise lack.

In treating vasculitis, we sometimes encounter the need for IVIG/SCIG due to the use of Rituximab – a drug that targets B cells. In some patients, the long-term use of rituximab may lead to an acquired deficiency of immunoglobulins. By combining IVIG/SCIG with rituximab, we are able to continue to provide patients with the immunosuppressive benefit of rituximab, while compensating for the increased risk of infection by giving IVIG/SCIG.

How is IVIG/SCIG given?

IVIG is often given as a home infusion. SCIG is given as a subcutaneous injection. These treatments are generally given once per month.

Side effects:

These treatments carry a risk of blood clot, renal injury, and headaches. IVIG constitutes a large fluid challenge, and therefore may not be appropriate for patients with heart or kidney failure.

The term “vasculitis” refers to a group of inflammatory diseases that cause inflammation centered in the wall of blood vessels. This vascular inflammation ultimately leads to damage and dysfunction of the organs that contain the affected vessels. The symptoms of vasculitis depend on the particular blood vessels (and organs) that are involved by the inflammatory process.

As a group, the vasculitis syndromes have the ability to affect nearly every organ in the body. Yet different forms of vasculitis tend to involve blood vessels in specific locations throughout the body. For example, Giant Cell Arteritis typically involves the medium– to large–sized blood vessels supplying the head and neck, but rarely involves the blood vessels of the kidneys. In contrast, Granulomatosis with Polyangiitis (GPA) frequently involves the kidneys, very often the lungs, and almost always the upper respiratory tract, but rarely blood vessels to the brain.

Different types of vasculitis have characteristic (localized) patterns of blood vessel involvement.  However, vasculitis is often a systemic illness. Thus, patients with vasculitis generally feel sick. They often have fevers, weight loss, fatigue, a rapid pulse, and diffuse aches and pains that are difficult to pinpoint. It has been said that vasculitis is a “hurting disease”, because it is so commonly associated with pain of one type or another: pain from a nerve infarction, pain from insufficient blood to the gastrointestinal tract, pain from skin ulcers. In some cases, however, identifying the source and underlying cause of the pain is extremely challenging. Because vasculitis can involve virtually every organ system in the body, it often masquerades as other diseases, and may be a challenging diagnosis to make.

What organ systems may be affected?

It is important to note that not every organ system will be affected in every patient. The pattern of organ involvement (and symptoms) is unique to the individual, as well as the type of vasculitis (category).

Skin

A variety of rashes, the most classic of which is “palpable purpura” –purplish–red spots, usually found on the legs. These spots can usually be felt by the examiner’s fingertips, hence the descriptor “palpable”.

Joints

Symptoms range from full–blown arthritis to aches in the joints without obvious swelling (arthralgias).

Lungs

Cough (particularly coughing up blood), shortness of breath, a pneumonia–like appearance to a patient’s chest X–ray, lung “infiltrates”, and the development of cavities in the lungs are among the manifestations that may occur in forms of vasculitis with lung involvement.

Kidneys

In contrast to many other organs, inflammation in the kidneys does not hurt or cause other symptoms a patient would notice until renal damage is quite advanced. Instead, evidence of vasculitis involving the kidneys is made by obtaining lab tests, and in many cases a kidney biopsy. Glomerulonephritis is the most common type of kidney damage encountered in vasculitis. This syndrome can cause abnormal lab findings in the urine, including the presence of red blood cells (usually invisible to the naked eye), clumps of red blood cells (known as “casts”, also invisible to the naked eye), and abnormal levels of protein in the urine. If renal involvement is not recognized, renal failure can develop, sometimes leading to the need for dialysis or kidney transplant.

Blood

Vasculitis can cause abnormal findings on blood counts. Anemia (low hematocrit or red blood cell count) is a typical finding in patients with active vasculitis. A slightly elevated white blood cell count may also occur. These findings are very non-specific, meaning that they can occur in many other situations and diseases. Elevated inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) are also frequently identified in patients with active vasculitis.

Sinus, Nose & Ears

The sinuses, nose and ears are common sites of involvement by ANCA-associated vasculitis, including GPA, EGPA and MPA. Symptoms can include chronic sinus congestion and “infections” that persist for longer than they should and require repeated courses of antibiotics; bleeding from the nose; perforations (holes) in the nasal septum; hearing loss; inflammatory fluid in the ears requiring drainage; inflammation in the cartilage of the ears or nose.

Eyes

Brain

Nerve

Peripheral nerves are a relatively common site of vasculitis involvement. Damage to the peripheral nerves can cause shooting pains in the arms and legs, numbness, and asymmetrical weakness (i.e., weakness that involves one side of the body more than the other).

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.

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

The name literally means “cold antibody in the blood”, which refers to the chemical properties of the antibodies that cause this disease: cryoglobulins are antibodies that precipitate under cold conditions. Drug use is a prime risk factor for cryoglobulinemia because more than 90% of cases of cryoglobulinemic vasculitis are associated with hepatitis C infections. Hepatitis C is acquired by injection drug use (needle–sharing), tainted blood products, and (probably rarely), sexual transmission. Treatment of the underlying hepatitis may be an effective therapy for this type of vasculitis.

Pictured below is the hand from the same patient at different times. The image on the left is normal and the one on the right shows the patient in the midst of a flare of cryoglobuinemic vasculitis.

Pictured below is an electron micrograph of a kidney biopsy specimen from a patient with cryoglobulinemia.

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

A discussion of Cryoglobulinemia written in medical terms by David Hellmann, M.D. (F.A.C.P.), Co-Director of 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.

Cryoglobulins are immunoglobulins that precipitate in the cold and disolve on rewarming. Three types of cryoglobulins are distinguished based on whether the cryoglboulin is monoclonal and has rheumatoid factor activity. Knowing the type usually allows the physician to predict the clinical features; alternatively knowing the clinical features allows one to deduce the type of cryoglobulin. Type I is a monoclonal antibody that does not have rheumatoid factor activity. Most commonly, type I is associated with lymphoma, Waldenström’s macroglobulinemia, and multiple myeloma. Because type I cryoglobulins do not easily activate complement, patients with type I are asymptomatic until the level of cryoglobulinemia is sufficiently high to cause hyperviscosity syndrome. Both types II and III are rheumatoid factors — antibodies that bind to the Fc fragment of IgG. Therefore, both types are called mixed cryoglobulins. In type II, the rheumatoid factor is monoclonal, whereas in type III it is polyclonal. Type II is associated with lymphoproliferative diseases, and both types can occur in patients with rheumatic diseases and chronic infections. Cryoglobulinemia is said to be essential when there is no identifiable underlying disease. Type II and III cryoglobulinemia frequently presents as vasculitis, most commonly with recurrentlower extremity purpura, glomerulonephritis, and peripheral neuropathy.

It is now evident that most patients diagnosed with type II or type III mixed essential cryoglobulinemia have the disease as an immune response to chronic hepatitis C infection. The role of hepatitis C virus is suggested by finding that the cryoglobulins in these patients are enriched with anti–hepatitis C antibody and hepatitis C RNA. Moreover, antviral therapy can remit the disease in some patients.

Treatment depends on the type of cryoglobulin, underlying disease, and severity of symptoms. Cryoglobulinemia with severe hyperviscosity syndrome requires plasmapheresis and chemotherapy of the underlying malignancy. Some patients with cryoglobulinemia suffer from mild, recurrent crops of lower extremity purpura that require no specific therapy. More extensive vasculitis associated with autoimmune diseases or essential cryoglobulinemia may respond to prednisone, cyclophosphamide, or both. The most effective treatment for cryoglobulinemia associated with hepatitis C has not yet been determined. Brief use of prednisone followed by 6 months of interferon alfa has produced clinical and liver function test improvement, but relapse of liver disease and vasculitis often occurs when interferon alfa is stopped.

• First Description
• Who gets Behcet’s Disease (the “typical” patients)?
• Classic symptoms of Behcet’s Disease
• What causes Behcet’s Disease?
• How is Behcet’s Disease diagnosed?
• Treatment and Course of Behcet’s Disease
• What’s new in Behcet’s Disease?

First Description

In the 1930’s, a Turkish dermatologist, Hulusi Behcet, noted the triad of aphthous oral ulcers, genital lesions, and recurrent eye inflammation, and became the first physician to describe the disease in modern times. Another name for Behcet’s Disease is Behcet’s syndrome.

Who gets Behcet’s Disease (the “typical” patient)?

Behcet’s disease is most common along the “Old Silk Route,” which spans the region from Japan and China in the Far East to the Mediterranean Sea, including countries such as Turkey and Iran. Although the disease is rare in the United States, sporadic cases do occur in patients who would not appear to be at risk because of their ethnic backgrounds (e.g., in Caucasians or African–Americans). The disease is not rare in regions along the Old Silk Route, but the disease’s epidemiology is not well understood. In Japan, Behcet’s disease ranks as a leading cause of blindness. Below is a magnetic resonance image (MRI) study of a Behcet’s patient demonstrating central nervous system involvement (white matter changes in the pons).

Classic symptoms and signs of Behcet’s Disease

Behcet’s disease is virtually unparalleled among the vasculitides in its ability to involve blood vessels of nearly all sizes and types, ranging from small arteries to large ones, and involving veins too. Because of the diversity of blood vessels it affects, manifestations of Behcet’s may occur at many sites throughout the body. However, the disease has a predilection for certain organs and tissues; these are described below.

• Eye
• Mouth
• Skin
• Lungs
• Joints
• Brain
• Genitals
• Gastrointestinal Tract

Eye

• Behcet’s may cause either anterior uveitis (inflammation in the front of the eye) or posterior uveitis (inflammation in the back of the eye), and sometimes causes both at the same time.
• Anterior uveitis results in pain, blurry vision, light sensitivity, tearing, or redness of the eye.
• Posterior uveitis may be more dangerous and vision–threatening because it often causes fewer symptoms while damaging a crucial part of the eye — the retina.

(top of section)

Mouth

• Painful sores in the mouth called “aphthous ulcers”(pictured below). These are very similar in appearance to ulcers that frequently occur in the general population, usually as a result of minor trauma. In Behcet’s, however, the lesions are more numerous, more frequent, and often larger and more painful. Aphthous ulcers can be found on the lips, tongue, and inside of the cheek. Aphthous ulcers may occur singly or in clusters, but occur in virtually all patients with Behcet’s.

Skin

• Pustular skin lesions that resemble acne, but can occur nearly anywhere on the body. This rash is sometimes called “folliculitis”.
• Skin lesions called erythema nodosum: red, tender nodules that usually occur on the legs and ankles but also appear sometimes on the face, neck, or arms. Unlike erythema nodosum associated with other diseases (which heal without scars), the lesions of Behcet’s disease frequently ulcerate.

Lungs

• Aneurysms (outpouchings of blood vessel walls, caused by inflammation) of arteries in the lung, rupture of which may lead to massive lung hemorrhage.

Joints

• Arthritis or “arthralgias” (pain in the joints not accompanied by joint swelling).

Brain

• Central nervous system involvement is one of the most dangerous manifestations of Behcet’s. The disease tends to involve the “white matter” portion of the brain and brainstem, and may lead to headaches, confusion, strokes, personality changes, and (rarely) dementia. Behcet’s may also involve the protective layers around the brain (the meninges), leading to meningitis. Because the meningitis of Behcet’s disease is not associated with any known infection, it is often referred to as “aseptic” meningitis.

Genitals

• Male — painful genital lesions that form on the scrotum, similar to oral lesions, but deeper.
• Female — painful genital ulcers that develop on the vulva.

Gastrointestinal

• Ulcerations may occur anywhere in the gastrointestinal tract from the mouth to the anus. The terminal ileum and cecum are common sites. Involvement of the GI tract by Behcet’s may be difficult to distinguish from inflammatory bowel disease (such as Crohn’s disease).

Blood Vessels

• Clots can occur in veins in any site, most often including veins in the lower extremity (superficial or deep venous thrombosis).
• Inflammation in arteries can occur as well, such as the pulmonary or abdominal arteries, sometimes causing obstruction of the vessel (thrombosis).

What causes Behcet’s Disease?

Behcet’s is one of the few forms of vasculitis in which there is a known genetic predisposition. The presence of the gene HLA–B51 is a risk factor for this disease. However, it must be emphasized that presence of the gene in and of itself is not enough to cause Behcet’s: many people possess the gene, but relatively few develop Behcet’s. Despite the predisposition to Behcet’s conferred by HLA–B51, familial cases are not the rule, constituting only about 5% of cases. Thus, it is believed that other factors (perhaps more than one) play a role. Possibilities include infections and other environmental exposures.

How is Behcet’s Disease Diagnosed?

There is not one specific test to diagnose Behcet’s. Rather the diagnosis is based on the occurrence of symptoms and signs that are compatible with the disease. The presence of certain features that are particularly characteristic (e.g., oral or genital ulcerations), elimination of other possible causes of the patient’s symptoms, and if possible, proof of vasculitis by biopsy of an involved organ would together support a diagnosis of Behcet’s.

A positive pathergy test can be supportive of the diagnosis of Behcet’s but is not diagnostic by itself of the condition. A pathergy test is a simple test in which the forearm is pricked with a small, sterile needle. Occurrence of a small red bump or pustule at the site of needle insertion constitutes a positive test. Please note, that although a positive pathergy test is helpful in the diagnosis of Behcet’s, only a minority of Behcet’s patients demonstrate the pathergy phenomenon (i.e., have positive tests). Patients from the Mediterranean region are more likely to demonstrate pathergy. In addition, other conditions can occasionally result in positive pathergy tests, so the test is not 100% specific.

Pictured below is an example of the pathergy test; 1) taken at the time when the patient was “stuck” with the sterile needle; 2) shows the area immediately after the stick; 3) & 4) show the area one day and two days after the needle stick, respectively.

Treatment and Course of Behcet’s Disease

For disease that is confined to mucocutaneous regions (mouth, genitals, and skin), topical steroids and non–immunosuppressive medications such as colchicine or dapsone may be effective. Apremilast (Otezla) is now FDA-approved for treatment of oral ulcers in Behcet’s. Moderate doses of systemic corticosteroids are also frequently required for disease exacerbations. Some patients require chronic, low doses of prednisone or conventional immunosuppressives such as (azathioprine) to keep the disease under control.

In the event of serious end–organ involvement such as eye or central nervous system disease, both high doses of prednisone and some other form of immunosuppressive treatment are usually necessary. Immunosuppressive agents used in the treatment of Behcet’s include azathioprine, cyclosporine, cyclophosphamide, and TNF-alpha inhibitors (infliximab, adalimumuab). Cyclophosphamide is generally used in life-threatening disease, such as central nervous system involvement. Blood clots can be another manifestation of Behcet’s, and in some scenarios blood thinners may be used in treatment.

 

What is colchicine?

Colchicine is an oral drug used in the treatment of some forms of cutaneous vasculitis. It is a very old medicine that is more frequently encountered in the treatment of gout.

How does colchicine work?

Colchicine seems to work by preventing immune cells from becoming fully activated.

How is colchicine given?

Colchicine is given as an oral pill at a dose of 0.6 mg either once or twice per day.

Side effects:

In contrast to most other vasculitis treatments, colchicine is not an immunosuppressant drug and does not cause any significant risk of infection.

Colchicine can cause gastrointestinal side effects and requires monitoring during its use. Some patients with kidney disease may not be able to safely take colchicine on a long-term basis.