IM BOARD REVIEW A SELF-TEST ON A CME EDUCATIONAL OBJECTIVE: In cases of suspected that present with skin disease, readers will look CREDIT for other sites with potentially life-threatening involvement CLINICAL SACHIN S. GOEL, MD CAROL A. LANGFORD, MD, MHS CASE Department of Cardiovascular Center for Vasculitis Care and Research, Depart- Medicine, Cleveland Clinic ment of Rheumatic and Immunologic Diseases, Cleveland Clinic

A 72-year-old man with a purpuric rash

72-year-old man whose medical his- A tory includes diabetes mellitus, hyper- tension, coronary artery disease, aortic valve replacement, atrial fibrillation, and chronic obstructive pulmonary disease was in his usual state of health until 2 weeks ago, when he de- veloped a purpuric rash on his legs. His physi- cian started him on 40 mg daily for the rash; however, 1 week later he presented to a hospital emergency room when his family found him confused and diaphoretic. In the emergency room, he was found to be hypoglycemic, with a serum glucose level of 40 mg/dL, which was promptly treated. His mental status improved partially. In the hos- pital, the rash worsened and progressed up- FIGURE 1. Diffuse, nonblanching, petechial-purpuric rash wards to his trunk and upper extremities. He with scaling on both legs and extending up to the abdo- was transferred to our institution for further men, flanks, chest, and both arms. workup and management. A review of systems reveals occasional epistaxis in the summer, recent fatigue, cough, Head, eyes, ears, nose, and throat. No and on exertion. His med- pallor or icterus, pupils are equally reactive, ications at the time of transfer include war- nasal mucosa not inflamed or ulcerated, mu- farin (Coumadin), amlodipine (Norvasc), in- cous membranes moist, no sinus tenderness. sulin, ipratropium and albuterol (Combivent) Neck. No jugular venous distention and inhalers, and prednisone 40 mg daily. He has no cervical lymphadenopathy. not undergone surgery recently. Cardiovascular. Tachycardia, irregularly irregular rhythm, prosthetic valve sounds, no ■■Physical examination murmurs, rubs, or gallops. Respiratory. Bibasal crackles (right side He is alert and oriented to person but not to more than the left). No wheezing. time and place. Abdomen. Soft, nontender, nondistend- Vital signs. Oral temperature 101.1°F ed, no palpable organomegaly, bowel sounds (38.4°C), pulse rate 108, blood pressure normal. 108/79 mm/Hg, respiratory rate 22, oxygen Extremities. No , good peripheral pulses. saturation 93% by pulse oximetry on room Skin. Diffuse, nonblanching, petechial- air, weight 94 kg (207 lb). purpuric rash (FIGURE 1) with scaling on both legs and extending up to the abdomen, flanks, doi:10.3949/ccjm.76a.09141 chest, and both arms.

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Neurologic. No focal deficits noted. identified in over 70% of cases. Cutaneous Lymphatic. No enlarged lymph nodes. vasculitis may herald a primary small-vessel Musculoskeletal. Traumatic right second such as Wegener granulo- distal interphalangeal amputation. Otherwise, matosis, , or Henoch- no joint abnormality or restriction of move- Schönlein . It can also be secondary ment. to a spectrum of underlying triggers or diseases Initial laboratory values: that include medications, infections, malig- • White blood cell count 15.78 × 109/L (nor- nancies such as lymphoproliferative­ disorders, mal 4.5–11.0) secondary to hepatitis C • Absolute neutrophil count 13.3 × 109/L viral infection, and connective tissue diseases (4.0–11.0) such as and systemic lu- • Hemoglobin 13.3 g/dL (13.5–17.5) pus erythematosus. • count 133 × 109/L (150–400) Infective endocarditis is associated with • International normalized ratio (INR) 1.8 a secondary form of vasculitis and is a strong • Sodium 136 mmol/L (135–146) possibility in this patient, who has a prosthetic • Potassium 4.6 mmol/L (3.5–5.0) aortic valve, fever, and a high white blood cell • Blood urea nitrogen 31 mg/dL (10–25) count. • Creatinine 1.6 mg/dL (0.70–1.40) Thrombocytopenia should also prompt an • Glucose 62 mg/dL (65–100) assessment for any drugs the patient is taking • Bicarbonate 23 mmol/L (23–32) that affect platelet function. However, throm- • Albumin 2.5 g/dL (3.5–5.0) bocytopenia typically results in nonpalpable • Total protein 4.6 g/dL (6.0–8.4) purpura. • Bilirubin 1.2 mg/dL (0.0–1.5) Idiopathic isolated cutaneous vasculitis, in • Aspartate aminotransferase 41 U/L (7–40) which no underlying cause for the cutaneous • Alanine aminotransferase 74 U/L (5–50) vasculitis can be identified, is the diagnosis in • Alkaline phosphatase 55 U/L (40–150) less than 30% of cases. • C-reactive protein 9.9 mg/dL (0.0–1.0). A vasculitic disease process can involve Given his multiple sites, which may be asymptomatic multiple Other studies on presentation. Identifying these sites is im- Electrocardiography shows atrial fibrilla- portant, not only to establish the diagnosis, medical tion and left ventricular hypertrophy, but no but also to detect potentially life-threatening problems, acute changes. complications early. what might be Computed tomography (CT) of the head Thus, in this patient, urinalysis should be shows no evidence of hemorrhage or infarc- done promptly to check for active sediment causing tion. consisting of red cell casts, which would sug- the new rash? Blood cultures are sent at the time of hos- gest renal involvement (). pital admission. Also, a rising blood pressure and creatinine would point to renal involvement and warrant ■■ which test is next? more aggressive initial therapy. Chest radiography should be done to Which is the most appropriate next step rule out pulmonary infiltrates, septic embo- 1for this patient? li, nodules, or cavities that could represent vasculitic or infectious involvement of the □□ Urinalysis lungs. CT of the chest may be needed to □□ CT of the chest further characterize abnormalities on chest □□ Echocardiography radiography. □□ Skin Echocardiography should certainly be pur- sued as part of the workup for endocarditis, The rash in FIGURE 1 is , which but urinalysis is of the utmost importance in strongly suggests small-vessel cutaneous vas- this patient at this point. culitis, a condition that can occur in a broad More diagnostic information is needed be- range of settings. An underlying cause is fore considering skin biopsy.

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FIGURE 3. Computed tomography of the chest reveals diffuse reticular nodular den- sities associated with ground-glass attenu- FIGURE 2. Chest radiography shows diffuse ation in the areas identified on the chest air-space opacities throughout the right radiograph. lung and in the upper lobe of the left lung.

C lues from the urinalysis any cause, acute viral, eosinophilic, and in- and chest radiography terstitial pneumonias, and Our patient’s sedimentation rate is 24 mm/ pneumonitis. It can also be seen in chronic hour. The urinalysis is strongly positive for disease states such as interstitial lung disease, blood and a moderate amount of protein but bronchoalveolar carcinoma, alveolar pro- negative for leukocyte esterase and nitrite. teinosis, and sarcoidosis. The urine sediment contains numerous casts and 6 to 10 white blood cells ■■ Which test would not help? Palpable per high-power field. purpura Chest radiography (FIGURE 2) shows diffuse Which of the following tests is least likely air-space opacities throughout the right lung 2to help in the diagnostic evaluation at this strongly and in the upper lobe of the left lung. point? suggests Pending return of blood cultures, ceftri- □□ Transthoracic echocardiography small-vessel axone (Rocephin) and azithromycin (Zithro- □□ Transesophageal echocardiography max) are started to treat possible community- □□ Bronchoscopy cutaneous acquired pneumonia. Vancomycin (Vancocin) □□ Cystoscopy vasculitis is empirically added, given the possibility of prosthetic valve endocarditis. Gram stain on In this case, the least likely to help is cystos- blood cultures shows gram-positive cocci. copy. Chest CT (FIGURE 3) reveals diffuse reticu- This patient’s vasculitic-appearing rash, lar nodular densities associated with ground- ground-glass pulmonary infiltrates, and im- glass attenuation in the areas identified on the paired renal function with red cell casts sug- chest radiograph. gest a pulmonary-renal syndrome, and with Ground-glass attenuation implies focal this constellation of features, a systemic vascu- or diffuse opacification of the lung that does litis is very likely. Therefore, the focus of the not obscure the vascular structures, is not as- evaluation should be on any evidence to sup- sociated with air bronchograms, and appears port a diagnosis of vasculitis, as well as other as a “veil” across the lung parenchyma.1 It possible causes. can be seen in acute diseases such as infec- In a patient with diabetes, an artificial heart tion (including pneumonia from atypical valve, and fever, the possibility of infection, bacteria, viruses, acid-fast bacilli, and Pneu- especially endocarditis, remains high. Trans- mocystis jiroveci), pulmonary hemorrhage of thoracic echocardiography is warranted, and if

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it is negative for vegetations, transesophageal tial symptoms of cough, fever, and dyspnea. echocardiography would be a reasonable next Some patients, such as ours, can present with option. severe acute respiratory distress syndrome re- Bronchoscopy is warranted to determine quiring mechanical ventilation. Radiogra- if the infiltrates represent pulmonary hemor- phy most often shows new patchy alveolar rhage, which can be seen in certain types of opacities, and CT may reveal a ground-glass vasculitic and systemic disorders. appearance. On pulmonary function testing, The finding of red cell casts in the urine the Dlco is high, owing to the hemoglobin indicates glomerulonephritis, and therefore within the alveoli. the kidneys are the likely source of the urinary red blood cells, making cystoscopy of no util- ■■ acute glomerulonephritis plus ity in this current, acute setting. pulmonary hemorrhage equals…?

Case continued: His condition worsens Which disease could have manifestations Transthoracic echocardiography reveals a 4consistent with acute glomerulonephritis well-seated mechanical prosthetic aortic and pulmonary hemorrhage? valve, trivial aortic regurgitation, a peak □□ Antiglomerular gradient of 23 mm Hg and a mean gradient disease of 12 mm Hg (normal values for his pros- □□ Wegener granulomatosis thetic valve), and no valvular vegetations. □□ Microscopic polyangiitis Transesophageal echocardiography confirms □□ Systemic erythematosus the absence of vegetations. His oxygen requirement increases, and All of these are possible. analysis of arterial blood gases reveals a pH of The combined presentation of acute

7.37, Pco2 49 mm Hg (normal range 35–45), glomerulonephritis and pulmonary hemor- Po2 102 mm Hg (normal 80–100), and bi- rhage (also called pulmonary-renal syndrome) carbonate 28 mmol/L while breathing 100% is usually seen in antiglomerular basement As many as supplemental oxygen by a nonrebreather face membrane disease () 33% of patients mask. He is taken to the medical intensive and small-vessel systemic vasculitides such care unit for intubation and mechanical ven- as Wegener granulomatosis and microscopic with diffuse tilation. Bronchoscopy performed while he polyangiitis.2,3 It can also be seen in patients alveolar is intubated confirms diffuse alveolar hemor- with systemic lupus erythematosus. hemorrhage rhage. Pulse intravenous methylp­ rednisolone (Solu-Medrol) therapy is started. Antiglomerular basement membrane may not have disease at ■■ diffuse alveolar hemorrhage In antiglomerular basement membrane dis- ease, circulating are directed to- presentation Which of the following is not true about wards an antigen intrinsic to the glomerular 3diffuse alveolar hemorrhage? basement membrane, typically leading to □□ Its onset is usually abrupt or of short acute glomerulonephritis associated with cres- duration cent formation. It may present as acute renal □□ It is always associated with hemoptysis failure in which urinalysis shows □□ Radiography most commonly shows new with sediment characterized by red cell casts. patchy or diffuse alveolar opacities Pulmonary involvement, usually alveolar □□ Pulmonary function testing shows hemorrhage, is present in approximately 60% increased of the lung to 70% of cases. for carbon monoxide (Dlco) The diagnosis requires demonstration of antiglomerular basement membrane antibod- Hemoptysis is absent at presentation in as ies in either the serum or the kidney. Renal many as 33% of patients. biopsy is usually recommended because the The onset of diffuse alveolar hemorrhage accuracy of serum assays is variable. is usually abrupt or of short duration, with ini- A key histologic feature of the renal lesion

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in antiglomerular basement membrane disease Microscopic polyangiitis is crescentic glomerulonephritis in which im- Microscopic polyangiitis is a systemic vasculitis munofluorescence microscopy demonstrates of the capillaries, venules, and arterioles, with the virtually pathognomonic finding of linear little or no deposition. Nearly deposition of along the all patients have renal involvement, and 10% glomerular capillaries. to 30% have lung involvement. In those with The treatment of choice for antiglomerular lung involvement, diffuse alveolar hemorrhage basement membrane disease is is the most common manifestation. and immunosuppression with a combination On histopathologic study, microscopic of glucocorticoids and (Cy- polyangiitis differs from Wegener granulo- toxan). If the disease is high on the differen- matosis in that it does not have granuloma tial diagnosis, empiric plasmapheresis should formation. However, the renal lesion is that be started while waiting for diagnostic studies, of a pauci-immune glomerulonephritis and is because the prognosis of untreated glomerulo- identical to that seen in Wegener granulo- is poor. matosis. From 70% to 85% of patients with microscopic polyangiitis are ANCA-positive, Wegener granulomatosis and most of these have pANCA. Wegener granulomatosis is a systemic vas- The management of active severe micro- culitis of the medium and small arteries, ar- scopic polyangiitis is identical to that of We- terioles, and venules that classically involves gener granulomatosis. the upper and lower respiratory tracts and the kidneys. Patients may present with persistent Systemic lupus erythematosus rhinorrhea and epistaxis, cough with chest ra- Systemic lupus erythematosus is an autoim- diographs showing nodules, fixed infiltrates, or mune disease characterized by tissue-binding cavities, and abnormal urinary sediment with and immune-complex-mediated microscopic with or without red organ damage. It can involve multiple organ cell casts. systems, and the diagnosis is based on char- From 75% to 90% of patients with active acteristic clinical features and . The renal Wegener granulomatosis are positive for anti­ The sensitivity of antinuclear for lu- impairment, neutrophil cytoplasmic antibody (ANCA). pus is close to 100%, which makes it a good In 60% to 80% of cases, ANCA is directed screening tool. Antibodies to dsDNA and red cell casts, against proteinase 3 (PR3), which produces Smith antigen have high specificity for lupus. and a cytoplasmic standing pattern by immuno­ About 75% of patients have renal involve- ground-glass fluorescence (cANCA), while 5% to 20% ment at some point in their disease course. have ANCA directed against myeloper- The different types of renal disease in systemic lung oxidase, which produces a perinuclear stain- lupus are usually differentiated with a renal bi- opacities ing pattern (pANCA). A small number of opsy, with immune-complex-mediated glom- patients with Wegener granulomatosis are erular diseases being the most common. suggest a ANCA-­negative. The most common pulmonary manifesta- pulmonary- The diagnosis is usually confirmed by tis- tion is pleuritis with or without pleural effu- sue biopsy at the site of active disease, which sion. Life-threatening pulmonary manifes- renal syndrome shows necrotizing vasculitis with granuloma- tations include pulmonary hemorrhage and tous inflammation. The renal lesion is typi- interstitial inflammation leading to fibrosis. cally that of a focal, segmental, necrotizing Lupus has great clinical variability and glomerulonephritis that has few to no immune the treatment approach is based on the organ complexes (pauci-immune glomerulonephri- manifestations, disease activity, and severity. tis). The treatment of severe disease involves ■■ Case continued: a combination of cyclophosphamide and glu- ARRIVING AT THE DIAGNOSIS cocorticoids initially to achieve remission fol- lowed by maintenance therapy with metho- We start our patient on cyclophosphamide trexate or (Imuran). 175 mg daily in view of possible Wegener

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granulomatosis. with IgA antibody in the glomeruli. However, Even though purpura is extremely rare in no single antigen has been consistently iden- primary antiglomerular basement membrane tified, so it seems more probable that the de- disease, this patient has life-threatening pul- velopment of IgA deposition in kidneys is a monary hemorrhage, a complication seen in consequence of aberrant IgA immune response over 50% of these patients. Therefore, plas- rather than the antigen itself. mapheresis is started empirically. On the second day of cyclophosphamide ■■ Henoch-Schönlein purpura treatment, tests for ANCA, glomerular base- ment membrane antibody, and antinuclear Henoch-Schönlein purpura is a systemic vas- antibody are reported as negative, and com- culitis with a prominent cutaneous compo- plement levels are normal. Bronchoalveolar nent. It is characterized by the tissue deposi- lavage shows no infection. Follow-up blood tion of IgA-containing immune complexes. cultures are negative. It is predominantly a disease of children but To summarize the findings so far, this patient it can be seen in adults. A UK study found has a purpuric skin rash, active urine sediment the prevalence to be 20 per 100,000 children, with red cell casts indicating glomerulonephri- with the highest prevalence between ages 4 tis, acute renal failure, and severe pulmonary and 7 (70 per 100,000).5 hemorrhage requiring mechanical ventilation. The four cardinal clinical features of Although one set of blood cultures showed Henoch-Schönlein purpura are purpuric rash, gram-positive cocci, no source of infection, par- abdominal pain, arthralgia, and renal involve- ticularly endocarditis, could be identified. ment. Almost all patients have purpuric rash Antiglomerular basement membrane dis- at some point in their disease course. Arthral- ease would still be high on the list of suspect- gia with or without arthritis is typically migra- ed diagnoses, given his diffuse alveolar hem- tory, oligoarticular, and nondeforming, usually orrhage. As mentioned earlier, renal biopsy affecting the large joints of the lower extremi- is imperative to making a diagnosis, because ties; involvement of the upper extremities is Henoch- serologic tests have variable accuracy. And less common. Schönlein making the correct diagnosis has therapeutic Skin biopsy typically shows leukocytoclas- implications. tic vasculitis in postcapillary venules with IgA purpura is Renal biopsy is performed and shows deposition, and these findings are pathogno- usually but not immune-complex mesangiopathic glomeru- monic of Henoch-Schönlein purpura. always lonephritis with positive immunofluorescent Gastrointestinal involvement can range staining in the mesangium for IgA. Only one from mild symptoms such as nausea, vomiting, self-limited glomerulus shows fibrinoid necrosis. abdominal pain, and paralytic ileus to severe Skin biopsy results obtained earlier showed disease such as gastrointestinal hemorrhage, positive direct immunofluorescence for IgA. bowel infarction, bowel perforation, and in- Both renal and skin suggested He- tussusception. noch-Schönlein purpura. Renal involvement is common and is IgA deposition in the kidney and skin has important, as it can in rare cases progress to been associated with liver cirrhosis, celiac dis- end-stage renal disease. The urinalysis usually ease, and infections with agents such as human shows mild proteinuria with active sediment immunodeficiency virus, cytomegalovirus, with red cell casts. Most patients have rela- Haemophilus parainfluenzae, and Staphylococcus tively mild disease, characterized by asymp- aureus. In a Japanese study,4 renal biopsy speci- tomatic hematuria with a normal or slightly mens from 116 patients with IgA nephropathy elevated creatinine. However, severe involve- and from 122 patients with other types of kid- ment may occur, with , ney disease were examined for the presence of S , and acute renal failure. aureus antigen in the glomeruli. Although anti- gen was not detected in non-IgA disease, 68% Different presentation in adults vs children of specimens from patients with IgA nephropa- Adults with Henoch-Schönlein purpura only thy had S aureus cell envelope antigen together rarely present with bowel intussusception,

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whereas some studies have found that adults nous therapy (methylpredniso- are more likely than children to develop sig- lone 250–1,000 mg per day for 3 days), fol- nificant renal involvement, including end- lowed by oral steroids for 3 months.11 stage renal disease.6,7 In anecdotal reports, renal function improved There is a general but not absolute corre- in 19 of 21 children with Henoch-Schönlein lation between the severity of clinical mani- purpura and severe crescentic nephritis.12 Stud- festations and the findings on renal biopsy. A ies have evaluated cyclophosphamide13 and poor prognosis (significant proteinuria, hyper- plasmapheresis,14 but their role remains uncer- tension, renal insufficiency, or end-stage renal tain. Renal transplantation is an option in pa- disease) is associated with crescent formation tients who progress to end-stage renal disease. involving more than 50% of the glomeruli.8 Our current understanding of the long- ■■OUR Case continued term outcome of the renal disease in Henoch- Schönlein purpura is primarily derived from In our patient, plasmapheresis was discon- studies in children. In one study, complete re- tinued. As the pulmonary hemorrhage had covery occurred in 94% of children and 89% developed during treatment with prednisone, of adults.7 A long-term study of 250 adults we decided to continue cyclophosphamide, with Henoch-Schönlein purpura and renal given the life-threatening nature of his dis- involvement of sufficient severity to require ease. His pulmonary status improved and he biopsy reported that, at a median follow up of was extubated. 15 years, 11% had become dialysis-dependent During his initial hospital stay, he was tak- and 13% had severe renal failure (creatinine ing heparin for anticoagulation therapy. How- clearance < 30 mL/min).6 Recurrence is com- ever, given the life-threatening diffuse alveo- mon, occurring in approximately one-third of lar hemorrhage, heparin was stopped during patients, more likely in those with nephritis.8 the course of his stay in the intensive care The diagnosis of Henoch-Schönlein pur- unit. Once he was stable and was transferred pura is typically made on the basis of key out of the intensive care unit, heparin was re- clinical features. In patients such as ours who sumed, and his anticoagulation therapy was Features have an atypical presentation, biopsy of af- bridged to warfarin just before discharge. He of Henoch- fected skin and renal biopsy can be essential was eventually discharged on a tapering dose in the diagnosis. Diffuse alveolar hemorrhage of oral prednisone and cyclophosphamide Schönlein is exceedingly rare in Henoch-Schönlein for 3 months, after which he was switched purpura: 9,10 purpura but can be seen, as in our patient. to azathioprine for maintenance therapy. He rash, In this setting, the findings of IgA deposits was doing well 6 months later, with a serum in skin and renal biopsy specimens, together creatinine level of 1.6 mg/dL, no red cell casts abdominal with the absence of other clinical, serologic, in the urine, and no rash. pain, or histologic features of other more-common potential causes, secured the diagnosis in this ■■TAKE-home point arthralgia, patient. renal Henoch-Schönlein purpura is usually self- In any case of suspected vasculitis that presents limited and requires no specific therapy. Evi- with skin disease, it is essential to look for other involvement dence suggests that glucocorticoids enhance sites with potentially life-threatening involve- the rate of resolution of the arthritis and ab- ment. Henoch-Schönlein purpura is a systemic dominal pain but do not appear to prevent vasculitis with a prominent cutaneous compo- recurrent disease or lessen the likelihood of nent. It is not always benign and can be asso- progression of renal disease.8 Patients with se- ciated with serious complications such as renal vere renal involvement with renal function failure, gastrointestinal events, and, very rarely, impairment may benefit from pulse intrave- diffuse alveolar hemorrhage. ■

■■ REFERENCES 2. Boyce NW, Holdsworth SR. Pulmonary manifestations of the clinical syndrome of acute glomerulonephritis and 1. Collins J, Stern EJ. Ground-glass opacity at CT: the ABCs. lung hemorrhage. Am J Kidney Dis 1986; 8:31–36. AJR Am J Roentgenol 1997; 169:355–367. 3. Gallagher H, Kwan JT, Jayne DR. Pulmonary renal syn-

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drome: a 4-year, single-center experience. Am J Kidney ment in Henoch-Schönlein purpura. Mayo Clin Proc 2004; Dis 2002; 39:42–47. 79:1151–1157. 4. Koyama A, Sharmin S, Sakurai H, et al. Staphylococ- 10. Vats KR, Vats A, Kim Y, Dassenko D, Sinaiko AR. Henoch- cus aureus cell envelope antigen is a new candidate Schönlein purpura and pulmonary hemorrhage: a report for the induction of IgA nephropathy. Kidney Int 2004; and literature review. Pediatr Nephrol 1999; 13:530–534. 66:121–132. 11. Niaudet P, Habib R. Methylprednisolone pulse therapy 5. Gardner-Medwin JM, Dolezalova P, Cummins C, South- in the treatment of severe forms of Schönlein-Henoch wood TR. Incidence of Henoch-Schönlein purpura, Kawa- purpura nephritis. Pediatr Nephrol 1998; 12:238–243. saki disease, and rare vasculitides in children of different 12. Bergstein J, Leiser J, Andreoli SP. Response of crescentic ethnic origins. Lancet 2002; 360:1197–1202. Henoch-Schöenlein purpura nephritis to corticosteroid 6. Pillebout E, Thervet E, Hill G, Alberti C, Vanhille P, Nochy and azathioprine therapy. Clin Nephrol 1998; 49:9–14. D. Henoch-Schönlein purpura in adults: outcome and 13. Tarshish P, Bernstein J, Edelmann CM Jr. Henoch-Schön- prognostic factors. J Am Soc Nephrol 2002; 13:1271–1278. lein purpura nephritis: course of disease and efficacy of 7. Blanco R, Martinez-Taboada VM, Rodriguez-Valverde V, cyclophosphamide. Pediatr Nephrol 2004; 19:51–56. Garcia-Fuentes M, Gonzalez-Gay MA. Henoch-Schönlein 14. Hattori M, Ito K, Konomoto T, Kawaguchi H, Yoshioka T, purpura in adulthood and childhood: two different Khono M. Plasmapheresis as the sole therapy for rapidly expressions of the same syndrome. Arthritis Rheum 1997; progressive Henoch-Schönlein purpura nephritis in chil- 40:859–864. dren. Am J Kidney Dis 1999; 33:427–433. 8. Saulsbury FT. Henoch-Schönlein purpura in children. Report of 100 patients and review of the literature. ADDRESS: Carol A. Langford, MD, MHS, Division of Rheumatic Medicine (Baltimore) 1999; 78:395–409. and Immunologic Diseases, A50, Cleveland Clinic, 9500 Euclid 9. Nadrous HF, Yu AC, Specks U, Ryu JH. Pulmonary involve- Avenue, Cleveland, OH 44195; E-mail [email protected].

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