Immunoglobulin A–associated vasculitis (IgAV—formerly called Henoch-Schönlein purpura-HSP) is vasculitis that affects primarily small vessels. It occurs most often in children. Common manifestations include palpable purpura, arthralgias, GI symptoms and signs, and glomerulonephritis. Diagnosis is clinical in children but usually warrants biopsy in adults. Disease is usually self-limited. Corticosteroids can relieve arthralgias and GI symptoms but do not alter the course of the disease. Progressive glomerulonephritis may require high-dose corticosteroids and cyclophosphamide.
IgA-containing immune complexes are deposited in small vessels of the skin and other sites, with consequent activation of complement. Possible inciting antigens include viruses that cause URIs, streptococcal infection, drugs, foods, insect bites, and immunizations. Focal, segmental proliferative glomerulonephritis is typical but mild.
Symptoms and Signs
The disease begins with a sudden palpable purpuric rash typically occurring on the feet, legs, and, occasionally, the trunk and arms. The purpura may start as small areas of urticaria that become palpable and sometimes hemorrhagic and confluent. Crops of new lesions may appear over days to several weeks. Many patients also have fever and polyarthralgia with periarticular tenderness and swelling of the ankles, knees, hips, wrists, and elbows.
GI symptoms are common and include colicky abdominal pain, abdominal tenderness, and melena. Intussusception occasionally develops in children. Stool may test positive for occult blood.
Symptoms usually remit after about 4 wk but often recur at least once after a disease-free interval of several weeks. In most patients, the disorder subsides without serious sequelae; however, some patients develop chronic renal failure.
• Biopsy of skin lesions
IgAV is defined as vasculitis with IgA1-dominant immune deposits, affecting small vessels in the skin and GI tract and frequently causing arthritis. IgAV is also associated with glomerulonephritis indistinguishable from IgA nephropathy.
The diagnosis is suspected in patients, particularly children, with typical skin findings. It is confirmed by biopsy of skin lesions when leukocytoclastic vasculitis with IgA in the vessel walls is identified. Biopsy is unnecessary if clinical diagnosis is clear in children. Urinalysis is done; hematuria, proteinuria, and RBC casts indicate renal involvement.
CBC and renal function tests are done. If renal function is deteriorating, renal biopsy may help define the prognosis. Diffuse glomerular involvement or crescent formation in most glomeruli predicts progressive renal failure.
Primarily corticosteroids and symptomatic measures
If the cause is a drug, it has to be stopped. Otherwise, treatment is primarily symptomatic. Corticosteroids (eg, prednisone 2 mg/kg up to a total of 50 mg po once/day) may help control abdominal pain and are occasionally needed to treat severe joint pain or renal disease. Pulse IV methylprednisolone followed by oral prednisone and cyclophosphamide can be given to attempt to control inflammation when the kidneys are severely affected. However, the effects of corticosteroids on renal manifestations are not clear.
• IgAV is vasculitis that affects primarily small vessels and occurs in children.
• Manifestations can include purpuric rash, arthralgias, fever, abdominal pain, and melena.
• Symptoms usually remit after about 4 wk.
• Diagnose by biopsy.
• Treat symptoms and consider corticosteroids.
A mother brings her 5-year-old boy to the clinic because of a rash on his legs and buttocks that she noticed this morning. He has also been complaining that his "belly hurts," but has had no change in appetite. He had an upper respiratory tract infection and sore throat about 1 week ago. He has not had any fevers, recent weight loss or joint pain, and has not taken any medications. His temperature is 37.0 C (98.6 F). Physical examination shows mild periumbilical tenderness and multiple 3-6 mm raised erythematous lesions on his lower extremities and buttocks. The lesions do not blanch with pressure. His leukocyte count, hemoglobin, platelet count, and coagulation studies are normal. Urinalysis shows 3-5 RBCs per hpf. A rapid strep test is positive. The most likely diagnosis is
A. Henoch-Schönlein purpura
B. Idiopathic thrombocytopenic purpura
C. Kawasaki disease
D. Rocky Mountain spotted fever
E. Wiskott-Aldrich syndrome
The correct answer is A. This patient presents with a classic case of Henoch-Schönlein purpura (HSP). HSP is an Ig-A mediated vasculitis involving the small blood vessels (arterioles and venules) of the skin, GI tract, kidneys, and joints. It is the most common vasculitis affecting children. The mean age is 4-7 years of age with slight male predominance. About 50% of children have a preceding upper respiratory tract infection and about 75% have group A strep recovered from their oropharynx. The classic rash is described as palpable purpura concentrated on the buttocks and lower extremities, but rarely on the trunk. These children can also present with non-migratory arthritis, colicky abdominal pain, microscopic or gross hematuria indicative of nephritis, and males can present with scrotal swelling. These patients must have a normal or elevated platelet count. This is what differentiates HSP from idiopathic thrombocytopenic purpura (ITP) (choice B). ITP also presents with a purpuric rash, but these children have low platelet counts. It is thought that these children develop an autoantibody to the platelet surface after a viral illness.
Kawasaki disease (choice C) is also known as mucocutaneous lymph node syndrome. It is an acute febrile vasculitis, which primarily affects the medium-sized vessels with particular affinity to the coronary arteries. Children must meet certain diagnostic criteria to be given the diagnosis of Kawasaki disease. They include fever for at least 5 days, plus four of the following five criteria: bilateral conjunctival injection; injected pharynx/dry or fissured lips/strawberry tongue; edema/erythema of the hands and feet; non-vesicular truncal rash; and cervical lymphadenopathy. The patient in the vignette does not meet the criteria for Kawasaki disease.
Rocky Mountain spotted fever (choice D) is an infectious disease caused by the bacterium Rickettsia rickettsii. These patients will present with fever, headache, malaise, and the classic rash is maculopapular and begins on the extremities and spreads inward to the trunk and includes the palms and soles. The rash may become purpuric after several days.
Wiskott-Aldrich syndrome (choice E) is an X-linked recessive syndrome characterized by eczema, thrombocytopenia, petechiae, and recurrent infections. This presentation is quite different from the boy in this vignette.
A 7-year-old boy arrives at the emergency room in acute distress. Over the past 3 to 4 days he has become progressively ill with generalized fatigue and mild, mid-abdominal pain that have become steadily worse. On physical examination he has a maculopapular rash on his thighs and feet with some spread of the rash to his buttocks. The rash does not blanch and the some lesions near the ankles look petechial or bruised. His temperature is 39.0 C(102.2 F) and he is drawing his knees to his chest for relief of his stomach pains. He is nauseated and vomited once before coming to the hospital. He has semi-soft dark stool, which is guaiac-positive. The boy has not voided since early morning and cannot provide a urine sample. The doctor determines that he is 10% dehydrated and asks the nurse to start intravenous fluids. Which of the following is the most likely diagnosis?
B. Rocky Mountain spotted fever
C. Nephrotic syndrome
D. Henoch-Schönlein Purpura
D. Henoch- Schönlein Purpura (HSP) is the most likely diagnosis. This boy has abdominal pain with guaiac-positive stools, but also has a prominent rash, mostly on his lower extremities. Other characteristic findings of HSP include hematuria and joint pains. The illness may follow an upper respiratory infection or strep throat. The rash starts out as an urticarial rash and progresses to become petechial and purpuric. There may be a history of migratory joint pain and arthritis. Affected joints include ankles, knees, wrists, and elbows.
If the abdominal pain were described as epigastric with radiation to the back, pancreatitis (choice A) might have been the likely diagnosis.In children, pancreatitis is frequently associated with viral illnesses (e.g., mumps), drugs (e.g., sulfonamides), or underlying systemic disease (e.g., lupus). Although pancreatitis has been reported in association with HSP, it is not the most likely diagnosis.
Rocky Mountain spotted fever (choice B) is one of the most common tick-borne diseases. The typical rash of RMSF appears within a week of the tick bite. It begins on the palms, soles, and extremities and spreads centrally. Severe headache and photophobia are common complaints.
This child did not have the typical findings of nephrotic syndrome (choice C) including: proteinuria, edema, and oliguria. Nephrotic syndrome frequently follows an infectious illness.
In the classic case of appendicitis (choice E) periumbilical pain progresses with localization to the right lower quadrant.Anorexia, nausea, vomiting and changes in bowel movements may all occur. Fever is typically low-grade and rash is not present.
A 6-year-old boy is brought to the office by his mother because of a "red rash" that she noticed today. She says that 3 days ago he had a cough, runny nose, and fever that responded to ibuprofen. In the office, his temperature is 37 C (98.6 F) and he has an erythematous, blanching macular rash on his legs. You diagnose him with a viral exanthem and advise the mother to encourage the child to drink liquids and to use ibuprofen as needed for fever. One week later, the mother brings the child back to the office and reports that the rash has "changed", he has developed colicky abdominal pain several times per day, and he is complaining of left knee pain. In the office, his temperature is 37.2 C (99 F), blood pressure is 100/65 mm Hg, pulse is 100/min, and respiratory rate is 15/min. A physical examination reveals palpable purpura of both lower extremities and a soft, non-tender abdomen. His left knee is painful on flexion, but it is not erythematous or warm, and there does not seem to be an effusion. His gait is normal. The most appropriate study at this time is
C. cultures of blood, urine, and cerebrospinal fluid
The correct answer is D. This patient most likely has Henoch-Schonlein purpura (HSP), a small-vessel vasculitis seen most commonly in children between the ages of 2 and 8. The child's preceding upper respiratory tract infection, low-grade fever, and arthralgias are all common elements of this disease. The typical rash of HSP is an evanescent, erythematous, macular rash on the lower extremities that progresses over the course of days to petechiae and palpable purpura. These change in color from red to purple to brown before eventually fading, normally over the course of weeks. HSP is an IgA-mediated autoimmune vasculitis, which can cause tissue damage as a result of immune complex formation. Deposition of these immune complexes in the kidneys can lead to nephritis, which is the leading cause of permanent sequelae from HSP. End-stage renal disease is an uncommon but possible outcome. It is important to perform frequent urinalyses for early detection of kidney involvement.
The joint manifestations of HSP are commonly arthralgias without arthritis, and can last weeks to months. Residual joint disease is rare, and arthrocentesis (choice A) is not necessary as part of the diagnostic evaluation.
Immune complex deposition in the bowel wall can lead to colicky abdominal pain in the setting of HSP and can result in serious, life-threatening sequelae (e.g., intussusception, perforation). This child's abdomen is benign on examination, and his symptoms should be followed clinically. A colonoscopy (choice B) is not necessary at this time.
While petechiae and purpura can be manifestations of overwhelming infection, often due to N. meningitis, the time course of the disease, the well-appearance of the child, and his stable vital signs argue against an infectious cause of this child's symptoms. Thus, cultures from multiple body sites (choice C) are not warranted at this time.