"Renal effects of ACE inhibitors in hypertension".) We suggest the use of angiotensin-converting enzyme (ACE) inhibitors in PAN because they are generally effective in this setting [32]. However, they may worsen renal function due to removal of the effect of angiotensin II on autoregulation and maintenance of the glomerular filtration rate. Switching to other antihypertensive agents (such as calcium channel blockers) may be required if an ACE inhibitor induces a clinically significant elevation (30 percent or greater) in the plasma creatinine concentration. (See "Renal effects of ACE inhibitors in hypertension", section on 'Renovascular hypertension'.) Limited role of plasma exchange Plasma exchange has not been shown to be beneficial for the treatment of PAN that is not associated with HBV infection [25,33,34]; however, it may have a role in the acute management of HBV-associated PAN [13]. The treatment of HBV-associated PAN is discussed separately. (See 'Associated hepatitis B or C infection' above and "Kidney disease associated with hepatitis B virus infection", section on 'Polyarteritis nodosa (PAN)'.) https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 11/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate Pneumocystis jirovecii (PCP) prophylaxis Prophylaxis for Pneumocystis jirovecii (PCP) infection should be employed in patients being treated for PAN using the regimens associated with such risk in patients with granulomatosis with polyangiitis, such as a significant dose of glucocorticoids (eg, 20 mg of prednisone daily for one month or longer) in combination with a second immunosuppressive drug, particularly a cytotoxic agent (eg, cyclophosphamide). (See "Treatment and prevention of Pneumocystis pneumonia in patients without HIV", section on 'Indications'.) ISOLATED AND SINGLE-ORGAN PAN The approach to isolated or single-organ polyarteritis nodosa (PAN) depends upon the affected organ or tissue. Cutaneous PAN is generally treated similarly to mild systemic PAN (see 'Isolated cutaneous PAN' below), while isolated organ involvement, sometimes identified at the time of an operative procedure, may not require further therapy. (See 'Isolated/single-organ PAN' below.) Isolated cutaneous PAN The treatment for isolated cutaneous PAN varies depending on the severity of the cutaneous manifestations and associated symptoms. A detailed discussion on the diagnosis and treatment of cutaneous PAN is presented elsewhere. (See "Cutaneous polyarteritis nodosa".) Patients with isolated cutaneous disease when first seen and initially treated may relapse with disease in other organs, and should be monitored periodically as are other patients with mild disease. (See 'Monitoring of disease' below.) Isolated/single-organ PAN Isolated single-organ PAN, other than isolated cutaneous disease, is usually a monocyclic disease, which typically does not relapse, that is diagnosed by histological examination of surgical specimens. Treatment beyond surgical excision (eg, of isolated PAN of the gallbladder) is usually not necessary [35]. However, we fully evaluate such patients initially and provide regular clinical follow-up (every three months in the first year and every 6 to 12 months thereafter) to determine if additional anatomic areas or other clinical features are present or developing. (See "Clinical manifestations and diagnosis of polyarteritis nodosa in adults" and 'Monitoring of disease' below.) MONITORING OF DISEASE Patients with polyarteritis nodosa (PAN) require regular, long-term follow-up to monitor the disease and drug safety by a clinician familiar with the disease and its treatments. Patients must be monitored for the possibility of disease relapse, particularly in organ systems involved at https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 12/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate disease onset. However, it is important to recognize that patients with PAN may have relapses of disease that include clinical manifestations of vasculitis not present at diagnosis [36]. We generally see patients at least monthly during the initial phase of therapy, until clinically stable, then at least every three months during the first two years of treatment. We continue to follow patients who have been in remission for two years every three to six months. Even after two years of remission, all patients should be followed indefinitely at some reasonable frequency (eg, every 6 to 12 months) since relapses may occur years after initial presentation and attainment of remission, which may be defined for patients with PAN as the absence of any evidence of active disease. In addition to routine physical examinations, including blood pressure testing, a review of systems, and laboratory monitoring for drug toxicities, a serum creatinine and urinalysis should be obtained. New symptoms or findings should be evaluated for their potential to represent recurrent vasculitis, even if such symptoms or findings are different from the original presenting manifestations of disease. Additionally, patients must be followed and treated for the medium- and long-term clinical sequelae of both treatment toxicities and disease-related long-term organ damage. Patients with cutaneous-only PAN or other single-organ presentations of PAN must also be followed regularly for the possible development of disease in new organ systems. In addition to clinical examinations and appropriate follow-up of patient-reported symptoms, periodic testing of serum creatinine and a urinalysis can help monitor for asymptomatic renal disease. Follow-up angiography is not required unless there are signs or symptoms suggestive of new disease, concerns for ischemia that may require intervention, or aneurysms that are at risk for expansion or rupture and may require intervention. Depending on the anatomic location and size of affected arteries, magnetic resonance imaging (MRI) or computed tomographic (CT) angiography may be substituted for catheter-based angiography. The choice of which imaging modality (MR, CT, or catheter-based) to use will depend upon the availability of equipment and expertise at a medical center and may be influenced by an interest in utilizing the same approach used for prior evaluations to allow for direct comparisons. Some complications of PAN can occur when the disease is clinically inactive, since healing of inflamed vessels can lead to progressive narrowing of the vascular lumina and resultant organ ischemia. Such changes should be distinguished from active disease, as they require appropriate supportive care rather than immunosuppression. As an example, a slowly progressive elevation in the serum creatinine concentration occurs in some patients in whom the signs of active vasculitis (such as systemic symptoms and an active urine sediment) have abated. The primary problem in this situation is diminished glomerular flow, not vascular inflammation. Sometimes serial angiograms or a renal biopsy is required to help differentiate active from inactive disease. https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 13/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate RECURRENT DISEASE The treatment of recurrent disease depends upon the severity of the flare and whether recurrence occurs on or off immunosuppressive treatment. Mild disease recurrence may be treated by use of glucocorticoids alone, and/or an increase in dose of immunosuppressive drug, depending upon the patient's treatment at the time of disease exacerbation or recurrence. Moderate to severe relapse requires reinitiation of remission-induction treatment (see 'Initial treatment of moderate and severe PAN' above). If moderate-severe recurrence occurs when the patient is on immunosuppressive treatment, a different immunosuppressive agent should be used. (See 'Resistant disease' above.) PROGNOSIS Morbidity and mortality Untreated polyarteritis nodosa (PAN) is associated with a poor prognosis (13 percent five-year survival) [5,6]. The outcome of PAN has improved in patients receiving treatment; five-year survival is approximately 80 percent [7]. The survival rates for patients with hepatitis B virus (HBV)-associated PAN are lower than for patients with non-HBV- associated disease. In one large cohort, the one- and five-year survival rates were substantially higher among patients diagnosed after 1995 compared with prior to 1995, possibly indicative of more rapid and widespread use of cyclophosphamide for more severe disease [7]. Whether prognosis of HBV-associated PAN has improved with the introduction of newer antiviral treatments is not known. Most deaths in patients with PAN due to active disease occur within 18 months of disease onset [4,7]. Survival is better among those with limited organ involvement. Renal failure and mesenteric, cardiac, or cerebral infarction are the major causes of death. Some of these complications can occur at a time when the disease is clinically inactive, since healing of inflamed vessels can lead to progressive narrowing of the vascular lumina and resultant organ ischemia. Preservation of tissue function is most likely if treatment is instituted early in the course of the disease. Improvement in renal function may be seen even in patients who initially require dialysis. In this setting, sufficient recovery to allow the patient to be maintained off dialysis for one to two years or more occurs in up to 60 percent of cases [37] and in approximately 10 percent who undergo dialysis for as long as three to six months [38]. The French Vasculitis Study Group (FVSG) has established a large, well-characterized longitudinal cohort of patients with PAN and reported a comprehensive series of studies on the natural history and treatment of this disorder [7]. Using regression analytic techniques, this group https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 14/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate derived the "Five-Factor Score" (FFS) in 1996 as a simple prognostic tool for clinicians to use when evaluating patients with various forms of vasculitis, including PAN [4,10,25]. The FFS was revised in 2011 based upon additional data and for PAN now only includes four factors associated with increased mortality: i) age >65 years, ii) cardiac symptoms, iii) gastrointestinal involvement, and iv) renal insufficiency (plasma creatinine >1.7 mg/dL [150 micromol/L]) [10]. The original FFS had included central nervous system disease (dropped from the score in 2011) but did not include age (included in 2011). The FFS has been used to stratify patients in treatment studies; this tool is helpful in both interpreting the data and formulating an approach to treatment of PAN. However, the FFS is based upon mortality and is not designed to predict either relapse or long-term morbidity, both of which are also important outcomes that influence treatment decisions in PAN. Relapse rates Although the proportion of patients with PAN with monocyclic disease courses (ie, a single episode of disease activity without a subsequent relapse) is substantially higher than in many other forms of vasculitis, especially the antineutrophil cytoplasmic antibody (ANCA)- associated diseases (granulomatosis with polyangiitis, microscopic polyangiitis [MPA], and eosinophilic granulomatosis with polyangiitis [Churg-Strauss]), the relapse rate in PAN is still substantial. For example, in a series of 348 patients, the one and five-year relapse rates for patients with non-HBV-associated PAN were at least 9.2 percent and 24 percent, respectively; the relapse rates for HBV-associated PAN were lower [7]. Renal transplantation Few data exist concerning the outcome of patients with PAN and end- stage kidney disease who undergo renal transplantation. Among 112 patients with PAN reported in the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) registry, transplantation was associated with significantly lower patient (77 versus 91 percent) and first cadaveric allograft (60 versus 69 percent) survival rates compared with those diagnosed with other renal diseases (eg, glomerulonephritis, interstitial nephritis, toxic nephropathies, and cystic kidney disease) [39]. Thirteen percent of graft failures were reportedly due to recurrent disease. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vasculitis" and "Society guideline links: Polyarteritis nodosa".) INFORMATION FOR PATIENTS https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 15/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Polyarteritis nodosa (The Basics)") SUMMARY AND RECOMMENDATIONS For patients with polyarteritis nodosa (PAN) with relatively mild disease (constitutional symptoms, arthritis, anemia, but normal renal function and no gastrointestinal, cardiac, or neurologic manifestations), we suggest initial treatment with oral glucocorticoid monotherapy, rather than combining glucocorticoids and another immunosuppressive medication (Grade 2C). We use an initial dose of prednisone of 1 mg/kg per day (maximum 60 to 80 mg daily), typically for approximately four weeks, at which time slow tapering of the glucocorticoids (over approximately six to eight months) can be started if substantial improvement has occurred. We also employ this approach in patients with isolated cutaneous disease. (See 'Mild PAN' above.) In patients with mild disease who are resistant to or intolerant of the dose of glucocorticoids required for disease control, we suggest the addition of azathioprine or methotrexate, rather than adding cyclophosphamide (Grade 2C). Such patients include those who do not respond to glucocorticoids alone, whose glucocorticoid dose cannot be tapered to an acceptable level (eg, prednisone 10 mg/day) without experiencing a relapse of disease, who are at high risk of adverse effects for the expected treatment course with glucocorticoids, or in whom the adverse effects of continued glucocorticoids in the dose being used are unacceptable. The usual doses are azathioprine, 2 mg/kg daily; or methotrexate, 20 to 25 mg once weekly. Mycophenolate mofetil (2000 to 3000 mg daily) is an alternative in patients unable to use azathioprine or methotrexate. (See 'Disease resistant to treatment with glucocorticoids alone' above.) https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 16/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate In patients with moderate to severe disease (eg, any evidence of renal insufficiency, significant proteinuria, gastrointestinal, cardiac, or neurologic involvement), we recommend treatment with both glucocorticoids and cyclophosphamide rather than glucocorticoids alone (Grade 1B). (See 'Initial treatment of moderate and severe PAN' above.) In most patients prednisone is administered orally (1 mg/kg daily to a maximum of 60 to 80 mg daily), but in patients with severe, life-threatening manifestations or worsening mononeuritis multiplex we usually administer intravenous methylprednisolone initially (7 to 15 mg/kg to a maximum of 500 to 1000 mg administered intravenously once daily for three days) prior to the oral prednisone regimen. The initial oral prednisone dose is continued for two to four weeks, until significant improvement is observed. The dose should then be tapered slowly, for an overall course of approximately six to eight months. (See 'Glucocorticoid regimen' above.) Cyclophosphamide may be administered by either intravenous or oral administration. We prefer the use of intravenous pulse therapy with cyclophosphamide 15 mg/kg administered at weeks 0, 2, and 4, and then every 3 weeks for at least 4 months and until a stable remission has been achieved, but for no greater than 6 months. (See 'Moderate and severe PAN' above.) In patients treated with cyclophosphamide, we switch for remission maintenance to another immunosuppressive agent, such as azathioprine (2 mg/kg daily) or methotrexate (20 to 25 mg once weekly), for a total duration of immunosuppressive therapy of 18 months. (See 'Remission-maintenance immunosuppression' above.) In the infrequent patient with moderate to severe PAN who has ongoing severe or worsening disease that is not controlled by treatment with glucocorticoids and cyclophosphamide within two to three months, we treat with pulse glucocorticoids (eg, 1000 mg methylprednisolone administered intravenously daily for 3 days), followed by prednisone (1 mg/kg daily taken orally) and switch from cyclophosphamide to a different immunosuppressive agent, azathioprine (2 mg/kg daily) or methotrexate (20 to 25 mg once weekly). Alternatives in patients unresponsive to or intolerant of these agents are mycophenolate mofetil (2000 to 3000 mg daily) or rituximab. (See 'Resistant disease' above.) In patients with mild PAN and evidence of infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), we suggest treating most patients initially with antivirals only, rather than https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 17/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate also treating initially with immunosuppressive medications (Grade 2C). Some patients with severe manifestations of hepatitis virus-associated PAN may benefit from short-term treatment with glucocorticoids and plasma exchange until antiviral therapy becomes effective. We do not use plasma exchange in patients with idiopathic PAN that is not HBV- related. In patients with persistent manifestations of PAN who are unresponsive to or intolerant of treatment for viral hepatitis alone, we cautiously treat the manifestations of the vasculitis with glucocorticoids and other immunosuppressive medication depending upon the severity of the vasculitis. (See 'Associated hepatitis B or C infection' above.) In patients with hypertension, we suggest treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor antagonist, rather than using another type of antihypertensive (Grade 2B). Such patients should be monitored closely for worsening of renal function. (See 'Hypertension' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65:1. 2. Ribi C, Cohen P, Pagnoux C, et al. Treatment of polyarteritis nodosa and microscopic polyangiitis without poor-prognosis factors: A prospective randomized study of one hundred twenty-four patients. Arthritis Rheum 2010; 62:1186. 3. Gayraud M, Guillevin L, le Toumelin P, et al. Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients. Arthritis Rheum 2001; 44:666. 4. Bourgarit A, Le Toumelin P, Pagnoux C, et al. Deaths occurring during the first year after treatment onset for polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: a retrospective analysis of causes and factors predictive of mortality based on 595 patients. Medicine (Baltimore) 2005; 84:323. 5. Balow JE. Renal vasculitis. Kidney Int 1985; 27:954. 6. Frohnert PP, Sheps SG. Long-term follow-up study of periarteritis nodosa. Am J Med 1967; 43:8. 7. Pagnoux C, Seror R, Henegar C, et al. Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum 2010; 62:616. https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 18/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate 8. Leib ES, Restivo C, Paulus HE. Immunosuppressive and corticosteroid therapy of polyarteritis nodosa. Am J Med 1979; 67:941. 9. Fauci AS, Katz P, Haynes BF, Wolff SM. Cyclophosphamide therapy of severe systemic necrotizing vasculitis. N Engl J Med 1979; 301:235. 10. Guillevin L, Pagnoux C, Seror R, et al. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore) 2011; 90:19. 11. Chung SA, Gorelik M, Langford CA, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Polyarteritis Nodosa. Arthritis Care Res (Hoboken) 2021; 73:1061. 12. Chung SA, Gorelik M, Langford CA, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Polyarteritis Nodosa. Arthritis Rheumatol 2021; 73:1384. 13. Guillevin L, Mahr A, Cohen P, et al. Short-term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus-related polyarteritis nodosa. Arthritis Rheum 2004; 51:482. 14. Pu chal X, Pagnoux C, Baron G, et al. Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors: A Randomized, Controlled Trial. Arthritis Rheumatol 2017; 69:2175. 15. Jayne D, Rasmussen N, Andrassy K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003; 349:36. 16. De Groot K, Rasmussen N, Bacon PA, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005; 52:2461. 17. Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med 2005; 352:351. 18. Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med 2008; 359:2790. 19. Hiemstra TF, Walsh M, Mahr A, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA 2010; 304:2381. https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 19/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate 20. de Groot K, Harper L, Jayne DR, et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med 2009; 150:670. 21. Harper L, Morgan MD, Walsh M, et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis 2012; 71:955. 22. de Groot K, Adu D, Savage CO, EUVAS (European vasculitis study group). The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol Dial Transplant 2001; 16:2018. 23. Guillevin L, Cohen P, Mahr A, et al. Treatment of polyarteritis nodosa and microscopic polyangiitis with poor prognosis factors: a prospective trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in sixty-five patients. Arthritis Rheum 2003; 49:93. 24. Guillevin L, Pagnoux C. When should immunosuppressants be prescribed to treat systemic vasculitides? Intern Med 2003; 42:313. 25. Guillevin L, Lhote F, Gayraud M, et al. Prognostic factors in polyarteritis nodosa and Churg- Strauss syndrome. A prospective study in 342 patients. Medicine (Baltimore) 1996; 75:17. 26. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA- associated vasculitis. N Engl J Med 2010; 363:221. 27. Jones RB, Tervaert JW, Hauser T, et al. Rituximab versus cyclophosphamide in ANCA- associated renal vasculitis. N Engl J Med 2010; 363:211. 28. Matsuo S, Hayashi K, Morimoto E, et al. The Successful Treatment of Refractory Polyarteritis Nodosa Using Infliximab. Intern Med 2017; 56:1435. 29. Krusche M, Ruffer N, K tter I. Tocilizumab treatment in refractory polyarteritis nodosa: a case report and review of the literature. Rheumatol Int 2019; 39:337. 30. Rimar D, Alpert A, Starosvetsky E, et al. Tofacitinib for polyarteritis nodosa: a tailored therapy. Ann Rheum Dis 2016; 75:2214. 31. Stockigt JR, Topliss DJ, Hewett MJ. High-renin hypertension in necrotizing vasculitis. N Engl J Med 1979; 300:1218. 32. Cohen L, Guillevin L, Meyrier A, et al. [Malignant arterial hypertension in periarteritis nodosa. Incidence, clinicobiologic parameters and prognosis based on a series of 165 cases]. Arch Mal Coeur Vaiss 1986; 79:773. 33. Bhimma R, Coovadia HM. Hepatitis B virus-associated nephropathy. Am J Nephrol 2004; 24:198. https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 20/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate 34. Guillevin L, Lhote F, Cohen P, et al. Corticosteroids plus pulse cyclophosphamide and plasma exchanges versus corticosteroids plus pulse cyclophosphamide alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome patients with factors predicting poor prognosis. A prospective, randomized trial in sixty-two patients. Arthritis Rheum 1995; 38:1638. 35. Hern ndez-Rodr guez J, Hoffman GS. Updating single-organ vasculitis. Curr Opin Rheumatol 2012; 24:38. 36. Grayson PC, Cuthbertson D, Carette S, et al. New features of disease after diagnosis in 6 forms of systemic vasculitis. J Rheumatol 2013; 40:1905. 37. Hind CR, Paraskevakou H, Lockwood CM, et al. Prognosis after immunosuppression of patients with crescentic nephritis requiring dialysis. Lancet 1983; 1:263. 38. Nissenson AR, Port FK. Outcome of end-stage renal disease in patients with rare causes of renal failure. III. Systemic/vascular disorders. Q J Med 1990; 74:63. 39. Briggs JD, Jones E. Renal transplantation for uncommon diseases. Scientific Advisory Board of the ERA-EDTA Registry. European Renal Association-European Dialysis and Transplant Association. Nephrol Dial Transplant 1999; 14:570. Topic 8244 Version 21.0 https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 21/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate GRAPHICS Vaccinations for adults with autoimmune inflammatory rheumatic conditions [1-5] Vaccine type Vaccine target Indications Nonlive (inactivated, Pneumococcus All patients who have not previously received a conjugate pneumococcal vaccine*. PCV15 killed, subunit, or recombinant) followed by PPSV23 OR PCV20 Annually for all patients . Seasonal influenza virus Hepatitis A virus At-risk patients who have not been previously vaccinated. All patients 19 to 59 years old and at-risk patients 60 years old (eg, those with occupational or lifestyle risk factors) who have not been previously vaccinated; antibody titers should be checked following completion of vaccine series to ensure response. Hepatitis B virus Meningococcus At-risk patients who have not been previously vaccinated, including those treated with eculizumab and those with impaired splenic function. Haemophilus in uenzae At-risk patients who have not been previously vaccinated, including those with impaired splenic function. Human papillomavirus (HPV) At-risk patients 19 to 26 years old who have not been previously vaccinated. Tetanus, diphtheria, pertussis (Tdap) or tetanus, diphtheria (Td) All patients per guidelines for healthy adults (eg, single dose of Tdap followed by Td booster every 10 years). Recombinant Recommended prior to immunosuppression and for those zoster vaccine (RZV; Shingrix) on immunosuppression. COVID-19 vaccines All patients per guidelines for immunocompromised adults . https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 22/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate Live, attenuated Zoster vaccine, live (ZVL; Zostavax) Can be given prior to immunosuppression and for those on low-dose immunosuppression if RZV is not available. Contraindicated for those receiving moderately to highly immunosuppressive medications. Measles, mumps, rubella Patients who have not been previously vaccinated and/or lack evidence of measles immunity (measles IgG seronegative) or who may have potential for measles exposure (eg, through work or travel) when the vaccine can be given prior to immunosuppression. Contraindicated for immunosuppressed patients. Varicella Patients who have not been previously vaccinated and/or lack evidence of varicella immunity (varicella IgG seronegative) or who may have potential for varicella exposure (eg, through work or family) when the vaccine can be given prior to immunosuppression. Contraindicated for immunosuppressed patients. Yellow fever Patients residing in or traveling to endemic areas prior to immunosuppression. Contraindicated for immunosuppressed patients. As part of our routine initial evaluation of patients with AIIRD, we review each patient's vaccination history and ensure that the above vaccinations have been received when appropriate. For maximal protection, vaccinations should be given prior to the start of immunosuppressive therapy. This increases the likelihood of developing a protective immune response, particularly for rituximab, which substantially impairs the humoral immune response. Vaccinating prior to immunosuppressive therapy also allows for administration of any needed live vaccines, which are generally contraindicated once immunosuppressive therapy has started. For complete information on timing of vaccine administration and vaccine schedules, including revaccination (booster dosing), refer to the UpToDate topic on vaccinations in patients with AIIRD. For more detailed description of at-risk populations, refer to the UpToDate topics regarding each vaccine. PCV20: 20-valent pneumococcal conjugate vaccine; PCV15: 15-valent pneumococcal conjugate vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine; IgG: immunoglobulin G; AIIRD: autoimmune inflammatory rheumatic disease; COVID-19: coronavirus disease 2019. Patients with AIIRD who are planning to receive or are receiving immunosuppressive medications should receive either PCV20 alone or PCV15 followed by PPSV23 at least eight weeks later. Dosing intervals and schedule may vary if either one of these vaccines has been given previously. Please refer to the UpToDate topic on pneumococcal vaccination in adults for more detail. No formulation of the (nonlive) influenza vaccine is preferred over another, although some clinicians prefer to avoid the adjuvant-containing vaccine to avoid any potential risk of worsening autoimmune disease activity. https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 23/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate Patients aged 27 to 45 years may also receive the vaccine based on shared clinical decision-making. Refer to UpToDate topic on HPV vaccination for further details. For vaccine selection and timing of administration, refer to the UpToDate content on COVID-19 vaccines in adults in autoimmune inflammatory rheumatic conditions. Other live attenuated vaccines include the influenza nasal spray, rotavirus, oral typhoid, and some formulations of the Japanese encephalitis vaccine. For most adults, these are not indicated. ZVL is no longer available in the United States. References: 1. Murthy N, Wodi AP, Bernstein H, et al. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older United States, 2022. MMWR Morb Mortal Wkly Rep 2022; 71:229. 2. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid ahritis. Arthritis Rheumatol 2016; 68:1. 3. van Assen S, Agmon-Levin N, Elkayam O, et al. EULAR recommendations for vaccination in adult patients with autoimmune in ammatory rheumatic diseases. Ann Rheum Dis 2011; 70:414. 4. Kobayashi M, Farrar JL, Gierke R, et al. Use of 15-Valent Pneumococcal Conjugate Vaccine and 20-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Updated Recommendations of the Advisory Committee on Immunization Practices United States, 2022. MMWR Morb Mortal Wkly Rep 2022; 71:109. 5. Anderson TC, Masters NB, Guo A, et al. Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged 19 Years: Recommendations of the Advisory Committee on Immunization Practices United States, 2022. MMWR Morb Mortal Wkly Rep 2022; 71:80. Graphic 119665 Version 4.0 https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 24/25 7/7/23, 11:21 AM Treatment and prognosis of polyarteritis nodosa - UpToDate Contributor Disclosures Peter A Merkel, MD, MPH Equity Ownership/Stock Options: Kyverna [Systemic lupus erythematosus]. Grant/Research/Clinical Trial Support: AbbVie [Vasculitis]; AstraZeneca [Vasculitis]; Boehringer Ingelheim [Scleroderma]; Bristol-Myers Squibb [Vasculitis]; ChemoCentryx [Vasculitis]; Electra [Vasculitis]; Genentech/Roche [Vasculitis]; GlaxoSmithKline [Vasculitis]; InflaRx [Vasculitis]; Sanofi [Vasculitis]; Takeda [Vasculitis]. Consultant/Advisory Boards: AbbVie [Vasculitis]; AstraZeneca [Vasculitis]; Boehringer Ingelheim [Scleroderma]; Bristol-Myers Squibb [Vasculitis]; ChemoCentryx [Vasculitis]; CSL Behring [Scleroderma, vasculitis]; Dynacure [Vasculitis]; EMDSerono [Vasculitis]; GlaxoSmithKline [Vasculitis]; InflaRx [Vasculitis]; Janssen [Vasculitis]; Kyverna [Scleroderma, vasculitis]; MiroBio [Vasculitis]; Neutrolis [Vasculitis]; Novartis [Vasculitis]; NS Pharma [Vasculitis]; Otsuka [Vasculitis]; Q32 [Vasculitis]; Regeneron [Vasculitis]; Sparrow [Vasculitis]; Takeda [Vasculitis]. All of the relevant financial relationships listed have been mitigated. Kenneth J Warrington, MD Grant/Research/Clinical Trial Support: Eli Lilly [Giant cell arteritis]; GSK [Giant cell arteritis]; Kiniksa [Giant cell arteritis]. Other Financial Interest: Chemocentryx [Honoraria ANCA-associated vasculitis]. All of the relevant financial relationships listed have been mitigated. Philip Seo, MD, MHS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/treatment-and-prognosis-of-polyarteritis-nodosa/print 25/25