V ASCULITIS SYNDROMES Emily B. Martin, MD Rheumatology Board Review April 9, 2008

K AWASAKI S YNDROME Mucocutaneous lymph node syndrome

K AWASAKI DISEASE Diagnostic criteria: Fever for > 5 days plus 4 of the following: Bilateral bulbar conjunctival injection Mucous membrane changes (injected pharynx, cracked lips, strawberry tongue) Extremity changes (edema, erythema, or desquamation of hands or feet) Polymorphous rash Cervical lymphadenopathy (at least one >1.5 cm)

C LINICAL MANIFESTIONS Arthritis and arthralgia Present in 7-25% of patients Involves large or small joints Urethritis Causes sterile pyuria CNS involvement Aseptic meningitis, facial nerve palsy, hearing loss GI symptoms Abdominal pain, diarrhea, vomiting, hepatitis Cardiac involvement Coronary artery aneurysms, myocardial dysfunction

D IFFERENTIAL D IAGNOSIS Viral infections Measles, echovirus, adeno, EBV* Toxin mediated illnesses Scarlet fever, toxic shock* Rickettsial or spirochete infections Rocky mountain spotted fever*, leptospirosis* Drug reactions Stevens-Johnson, serum sickness JRA Mercury hypersensitivity reaction See Mia’s recent case conference

L ABORATORY E VALUATION Markers of systemic inflammation Elevated CRP, ESR, leukocytosis with left shift, reactive thrombocytosis (up to 1 million) Anemia (normocytic, normochromic) Sterile pyuria (urethral origin, don’t do a cath) Transaminase elevation (mild to moderate) CSF findings Mononuclear pleocytosis, hypoglycorrhachia, elevated protein Synovial fluid inflammation Hyponatremia (increased risk for coronary aneurysms)

T REATMENT Mainstay of treatment is IVIG 2 gram/kg over hours. IVIG may need to be repeated in refractory cases. Several studies have shown that IVIG + aspirin decreases the risk of coronary aneurysms compared to aspirin alone. May also decrease risk of depressed myocardial function. High dose aspirin during acute illness then low dose for about 2 months.

F OR THE B OARDS … Know the clinical manifestations of Kawasaki syndrome. Know the differential diagnosis of KD. Know the laboratory abnormalities seen in KD. Recognize the value of high-dose IVIG in treatment of KD.

Q UESTION 1 A 3-year-old girl is brought to your office for re- evaluation of a fever that began 6 days ago. Her mother tells you that her daughter's temperature has been as high as 102.2°F (39°C). Her physical examination was unremarkable when you examined her 3 days ago, but today you note injected sclera; cracked, red lips, a strawberry appearance of her tongue; and a swollen, nontender, cervical node. You tell her mother that you believe this is Kawasaki disease.

Q UESTION 1 Of the following, the MOST appropriate statement to make to the mother is that A. an exercise stress test should be performed as a baseline study B. aspirin therapy will be used until the fever subsides C. cardiac involvement may include abnormalities of the coronary arteries or the myocardium D. echocardiography should be performed to evaluate for the presence of coronary aneurysms E. immediate treatment with intravenous immune globulin will eliminate the chance of coronary involvement

Q UESTION 1 Of the following, the MOST appropriate statement to make to the mother is that A. an exercise stress test should be performed as a baseline study B. aspirin therapy will be used until the fever subsides C. cardiac involvement may include abnormalities of the coronary arteries or the myocardium D. echocardiography should be performed to evaluate for the presence of coronary aneurysms E. immediate treatment with intravenous immune globulin will eliminate the chance of coronary involvement

Q UESTION 1 Of the following, the MOST appropriate statement to make to the mother is that A. an exercise stress test should be performed as a baseline study B. aspirin therapy will be used until the fever subsides C. cardiac involvement may include abnormalities of the coronary arteries or the myocardium D. echocardiography should be performed to evaluate for the presence of coronary aneurysms E. immediate treatment with intravenous immune globulin will eliminate the chance of coronary involvement

H ENOCH -S CHONLEIN P URPURA

Most common systemic vasculitis in children. Immune mediated Deposition of IgA immune complexes. Often a self-limited disease. Occurs more often in fall, winter, and spring. Rare in the summer. About 50% of cases are preceded by URI’s. Streptococcus is often implicated. Vaccines, insect bites, viruses have also been reported as triggers.

C LINICAL P RESENTATION Classic tetrad 1. Palpable purpura (100%) In absence of thrombocytopenia or coagulopathy 2. Arthritis or arthralgia (75%) 3. Abdominal pain (50%) 4. Renal disease (21-50%)

GI SYMPTOMS HSP can cause edema and submucosal hemorrhage of GI tract. May see purpuric lesions on endoscopy. May be the presenting symptom of HSP. Symptoms typically develop within 8 days of the rash. Intussusception is the most common GI complication. Be able to recognize obstruction due to HSP. Know that it is more often ileo-ileal (vs. ileocolic).

R ENAL D ISEASE Occurs in up to 50% of patients. Ranges from hematuria to end-stage renal disease (<1% of patients). Usually presents within four weeks of onset of HSP. Overall prognosis is very good, but there is some long-term risk of progressive renal impairment.

L ABORATORY F INDINGS There is NO definitive diagnostic test. IgA levels may be elevated in 50-70% of patients. Platelet counts and coag studies should be normal. Inflammatory markers may be elevated. Urinalysis Red cells, white cells, casts, proteinuria May not be present until later in the course Remember to continue UA screenings after the acute phase. Negative RF and ANA.

F OR THE B OARDS … Recognize the typical presentation of HSP. Recognize that HSP may present initially with ABDOMINAL PAIN OR JOINT COMPLAINTS. Recognize INTESTINAL OBSTRUCTION secondary to HSP. Know the typical laboratory findings in HSP.

Q UESTION 1 A 3-year-old boy is brought to the office with complaints of intermittent abdominal pain for 2 days. His mother notes that he also had a limp and a faint rash on his legs for 1 day. He has been afebrile and otherwise well except for an upper respiratory tract infection a few weeks ago. On physical examination, he is alert and complains of mild abdominal tenderness on palpation. His left ankle is swollen and tender, and a few 4- to 5-mm nonblanching lesions (Item Q214A) are visible on his thighs bilaterally.

Q UESTION 1 Of the following, the MOST likely diagnosis is A. Henoch-Schonlein purpura B. Immune thrombocytopenic purpura C. Juvenile rheumatoid arthritis D. Parvoviral infection E. Post-streptococcal arthritis

Q UESTION 1 Of the following, the MOST likely diagnosis is A. Henoch-Schonlein purpura B. Immune thrombocytopenic purpura C. Juvenile rheumatoid arthritis D. Parvoviral infection E. Post-streptococcal arthritis

Q UESTION 2 A 3-year-old child presents with a rash, abdominal pain, and joint pain. Physical exam reveals an afebrile patient who has a non-blanching maculopapular rash. The rash is limited to the lower extremities and buttocks. Both knees are swollen and tender.

Q UESTION 2 Of the following, the laboratory finding that is MOST consistent with this disease is: A. Glucosuria B. Hematuria C. Positive rheumatoid factor D. Positive serum antinuclear antibody E. Thrombocytopenia

Q UESTION 2 Of the following, the laboratory finding that is MOST consistent with this disease is: A. Glucosuria B. Hematuria C. Positive rheumatoid factor D. Positive serum antinuclear antibody E. Thrombocytopenia

B EH Ç ET D ISEASE

Very rare systemic vasculitis of unknown etiology. Affects blood vessels of all sizes. Both arteries and veins Clinical manifestations are similar in children and adults. Characterized by recurrent, painful ulcers of the mouth and skin and uveitis.

C LINICAL P RESENTATION Apthous stomatitis Genital ulcerations Uveitis GI symptoms (due to ulcers) Arthritis Lab findings Normal ANA and RF ESR/CRP may be elevated

S CLERODERMA Juvenile systemic sclerosis Localized scleroderma

J UVENILE S YSTEMIC S CLEROSIS Characterized by symmetrical fibrous thickening of skin and various internal organs. Esophagus and GI tract, heart, lungs, kidneys Clinical presentation Skin changes – edema then tightening, thinning, atrophy Raynaud’s – 70% at presentation Arthritis, arthralgia Muscle weakness/pain CREST syndrome Pulmonary fibrosis and pulmonary hypertension are major causes of morbidity in children.

L OCALIZED S CLERODERMA Much more common than systemic and has a much better outcome. Affects a single dermatome. Starts as a linear hypopigmented patch then slowly becomes more fibrotic. Rarely requires treatment, usually self-limited. May cause limb deformities or growth arrest. Lab findings: RF positive in 1/3 of patients +/- ANA

F OR THE B OARDS Recognize the clinical manifestations of scleroderma. Recognize that localized scleroderma is much more common than systemic sclerosis and has a better outcome.

Q UESTION 1 An 11-year-old girl presents with an asymmetric smile of 6-8 months duration. A tight linear band has developed progressively from the vermillion border of the left lower lip and now extends to the lateral aspect of the chin. Results of the remainder of the physical exam are normal. No laboratory studies are obtained.

Q UESTION 1 Of the following, the lesion MOST likely represents A. Granuloma annulare B. Lichen sclerosis et atrophicus C. Localized morphea D. Psoriasis E. Tuberous sclerosis Hint: Localized morphea = linear scleroderma

Q UESTION 1 Of the following, the lesion MOST likely represents A. Granuloma annulare B. Lichen sclerosis et atrophicus C. Localized morphea D. Psoriasis E. Tuberous sclerosis

Q UESTION 2 A 14-year-old girl presents for evaluation of areas of skin thickening, tightness, and discoloration that developed 2 months ago. Physical examination reveals shiny, hypopigmented patches with brown borders on the leg and ankle. The affected skin is immobile, firm, and has a "bound-down" feeling.

Q UESTION 2 Of the following, the MOST likely diagnosis is A. lichen sclerosus et atrophicus B. Linear scleroderma C. Pityriasis alba D. Progressive systemic sclerosis E. Vitiligo

Q UESTION 2 Of the following, the MOST likely diagnosis is A. Lichen sclerosus et atrophicus B. Linear scleroderma C. Pityriasis alba D. Progressive systemic sclerosis E. Vitiligo

O THER QUESTIONS ?