ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Treatment and prognosis of polyarteritis nodosa

Treatment and prognosis of polyarteritis nodosa
Literature review current through: Jan 2024.
This topic last updated: Aug 09, 2023.

INTRODUCTION — Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that predominantly affects medium-sized muscular arteries and often involves small muscular arteries [1]. The approach to treatment of PAN depends upon the following variables, which require assessment before beginning therapy:

The level of disease severity

The presence of isolated cutaneous PAN or other isolated/single-organ disease

The presence or absence of viral hepatitis

The optimal therapy of PAN remains uncertain, and studies of treatment for PAN have been complicated by the mixture of patients with PAN, microscopic polyangiitis (MPA), and sometimes eosinophilic granulomatosis with polyangiitis (Churg-Strauss) within study cohorts [2-4]. The efficacy of glucocorticoids in the majority of patients with mild disease, and of glucocorticoids plus cyclophosphamide in patients with more severe disease, has been well demonstrated in observational studies in PAN, but there are few randomized trials [2,3,5-9]. The treatment approach in PAN is also derived from indirect evidence of the efficacy of various medications and drug regiments in other forms of necrotizing vasculitis, particularly MPA and granulomatosis with polyangiitis (GPA). Our approach to therapy is generally consistent with guidelines developed by professional organizations, including the American College of Rheumatology (ACR)/Vasculitis Foundation guideline [10,11].

The treatment and prognosis of PAN will be reviewed here. The clinical manifestations, diagnosis, and classification of PAN are presented separately (see "Clinical manifestations and diagnosis of polyarteritis nodosa in adults"). The diagnosis and management of cutaneous-only PAN is also discussed elsewhere. (See "Cutaneous polyarteritis nodosa".)

PRETREATMENT EVALUATION

Baseline evaluation — Prior to treatment for polyarteritis nodosa (PAN), routine evaluation should include the following (see "Clinical manifestations and diagnosis of polyarteritis nodosa in adults"):

Clinical assessment of the extent and severity of organ involvement. The overall goal of the clinical assessment is to determine if the patient has severe or nonsevere disease. PAN may impact multiple organ systems, most commonly the kidneys, nerves, skin, and gastrointestinal tract. Less commonly, PAN can cause digital ischemia.

The specific workup is determined by the patient’s symptoms and findings on examination. (See "Clinical manifestations and diagnosis of polyarteritis nodosa in adults", section on 'Clinical features'.)

Laboratory assessment for active hepatitis B (ie, hepatitis B surface antigen) or hepatitis C (ie, nucleic acid test for hepatitis C virus [HCV] ribonucleic acid [RNA]).

Diagnostic tests, which may include biopsy or angiography of the affected organ. (See "Clinical manifestations and diagnosis of polyarteritis nodosa in adults", section on 'Diagnosis'.)

Minocycline has been suspected of triggering medium-vessel vasculitis and should be stopped [12].

Consideration should also be given to whether the patient’s presentation may either represent another disease process (eg, deficiency of adenosine deaminase 2 [DADA2] or familial Mediterranean fever) or coexist with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. (See "Deficiency of adenosine deaminase 2 (DADA2)" and "Autoinflammatory diseases mediated by NFkB and/or aberrant TNF activity", section on 'Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome' and "Clinical manifestations and diagnosis of familial Mediterranean fever".)

Disease extent and severity — An important factor in determining which medications will be used and the doses employed is disease extent and severity. We use the following definitions [3,4,7,13]:

Severe disease – Patients with severe disease have manifestations that are believed to be organ- or life-threatening (eg, significant kidney disease, mononeuritis multiplex, stroke, myocardial infarction, ischemic bowel). (See 'Treatment of severe PAN' below.)

Nonsevere disease – Patients with nonsevere disease include those without any evidence of severe disease. However, they can have multiple manifestations of PAN, including constitutional symptoms, arthritis, anemia, and skin lesions, or arterial stenoses not causing active ischemia. (See 'Treatment of nonsevere PAN' below.)

PAN confined to the skin is generally treated similarly to nonsevere systemic PAN. (See "Cutaneous polyarteritis nodosa".)

In addition, patients with isolated or single-organ PAN, sometimes identified at the time of an operative procedure, may not require further therapy but should be evaluated for evidence of severe or nonsevere disease manifestations. (See 'Isolated/single-organ PAN' below.)

ASSOCIATED HEPATITIS B OR C INFECTION — Patients with both vasculitis and hepatitis virus infection also benefit from treatment with antivirals and plasma exchange. There are no randomized trials or large case series to guide decision-making in such patients; we base our approach upon the available trials in viral hepatitis and clinical experience.

The treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) and the treatment of kidney disease due to polyarteritis nodosa (PAN) in patients with one of these infections are discussed in detail separately:

(See "Kidney disease associated with hepatitis B virus infection", section on 'Polyarteritis nodosa (PAN)'.)

(See "Overview of the management of chronic hepatitis C virus infection".)

(See "Overview of kidney disease associated with hepatitis C virus infection", section on 'Polyarteritis nodosa'.)

(See "Hepatitis B virus: Overview of management", section on 'Indications for antiviral therapy'.)

Role and timing of antiviral therapy — In patients in whom PAN is associated with HBV or HCV infection, the major focus of therapy is the use of antiviral agents for treatment of the underlying viral disorder.

PAN continues to be associated with HBV in a substantial minority of cases, although this rate is decreasing in countries with comprehensive HBV vaccination programs. (See "Clinical manifestations and diagnosis of polyarteritis nodosa in adults", section on 'Etiology'.)

Far fewer cases of PAN are associated with HCV, which should be differentiated from HCV-associated cryoglobulinemic vasculitis. (See "Overview of the management of chronic hepatitis C virus infection" and "Mixed cryoglobulinemia syndrome: Clinical manifestations and diagnosis".)

The timing of therapy relative to the use of immunosuppressive agents depends upon the severity of the vasculitis:

In patients with nonsevere PAN and evidence of infection with HBV or HCV, we suggest treating initially with antivirals rather than using immunosuppressive medications.

Some patients with moderate to severe disease manifestations of hepatitis virus-associated PAN may benefit from short-term treatment with glucocorticoids until antiviral therapy becomes effective [14].

Role of immunosuppressive therapy — Some patients with PAN associated with viral hepatitis require treatment with the same immunosuppressive regimens employed for patients without viral infections. This group includes:

Patients with severe disease manifestations (eg, ulcerative or gangrenous lesions of the extremities, acute kidney injury, polyneuropathy, central nervous system involvement, mesenteric arteritis, or myocardial ischemia)

Patients with persistent disease manifestations that have had an inadequate response to antiviral therapies

Patients who are intolerant of antiviral therapy

The status of the underlying viral infection should be monitored closely in patients who are treated with immunosuppressive agents. Patients also need to be monitored for treatment-associated toxicities, especially hepatic function (which may be impacted by both the viral infection and the treatment regimen). Clinicians managing the immunosuppressive treatment of patients with hepatitis-associated PAN should work closely with experts in the treatment of viral hepatitis.

Role of plasma exchange — Given the emergence of more effective therapies for HBV, we do not recommend the routine use of plasma exchange for patients with HBV-associated PAN. We reserve plasma exchange for patients with highly severe and progressive disease for whom use of immunosuppressive therapy is contraindicated.

There is controversy as to whether patients with hepatitis-associated PAN benefit from plasma exchange. Plasma exchange, typically administered over two to three weeks, removes circulating immune complexes, which may be beneficial in patients with severe disease manifestations. Although the data supporting the use of plasma exchange are weak, immunosuppression and plasma exchange are part of published treatment protocols for HBV-associated PAN [11,14-22].

A retrospective series treated 80 HBV-associated PAN patients with an antiviral agent (vidarabine, interferon alfa, or lamivudine, depending upon the era), a two-week course of glucocorticoids, and an intensive schedule of plasma exchange [23]. Their clinical course and outcomes were compared with 35 historic controls (before the antiviral era) treated with glucocorticoids with or without cyclophosphamide, with most receiving plasma exchange. The results indicated non-statistically significant clinical benefits:

Remission was attained by 81 percent of all patients; patients who did not achieve remission died within a mean of 178 days. Overall five-year survival was 73 percent.

At a median of 237 months, combination therapy with antivirals, immunosuppression, and plasmapheresis was associated with lower rates of relapse (4 versus 14 percent) and death (30 versus 49 percent), although the difference did not reach statistical significance.

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 and "Cutaneous polyarteritis nodosa", section on 'Follow-up'.)

Isolated/single-organ PAN — Unlike cutaneous PAN, single-organ PAN is usually monophasic and does not relapse. The diagnosis of isolated single-organ PAN is typically made by histological examination of surgical specimens. Treatment beyond surgical excision is usually not necessary [24]. 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.)

TREATMENT OF NONSEVERE PAN — Patients with nonsevere disease, defined as not having organ- or life-threatening manifestations of polyarteritis nodosa (PAN), and without evidence of hepatitis, can be treated initially with glucocorticoids alone. However, because about half of these patients will require an additional agent at some point during their treatment, and given the substantial toxicities of glucocorticoids, we suggest additional immunosuppressive drug beyond glucocorticoids.

The treatment approach in patients with hepatitis B or C infection is discussed above. (See 'Associated hepatitis B or C infection' above.)

Glucocorticoids — In patients with relatively mild disease, initial monotherapy with oral glucocorticoid may be reasonable, with dosing as follows:

Prednisone 1 mg/kg daily (up to a maximum of 60 to 80 mg daily) for two to four weeks

Taper prednisone to 20 mg daily by month 3 to 4

Taper prednisone in 2.5 mg increments every 14 days until glucocorticoids are discontinued

Patients should be monitored closely for evidence of disease relapse, which may require slowing of the prednisone taper or the institution of an additional glucocorticoid-sparing agent. (See 'Other immunosuppressive agents' below.)

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 either azathioprine (2 mg/kg daily) or methotrexate (20 to 25 mg once weekly) for at least one year. (See 'Other immunosuppressive agents' below.)

Rationale - This approach is based upon the potential benefit of glucocorticoids alone seen in retrospective studies [6-8] and in patients with mild PAN and microscopic polyangiitis (MPA) in the nonrandomized initial phase of a randomized trial [2]. As examples:

A retrospective analysis of patients with PAN that was not limited to those with mild disease found that patients treated with glucocorticoids alone, when compared with clinically similar patients who did not receive glucocorticoids, experienced substantially longer median survival (63 versus 3 months) and five-year survival (53 versus 12 percent) [8]. Glucocorticoids have not been compared with treatment with placebo alone in a randomized trial.

In a randomized trial of patients with mild PAN or MPA designed to compare cyclophosphamide and azathioprine in patients who had sustained disease or relapse despite glucocorticoid therapy, 79 percent of patients achieved remission with initial glucocorticoid therapy prior to the randomized trial period [2]; half of these patients had a sustained remission without requiring additional immunosuppression.

Alternatively, some experts advocate longer treatment courses with glucocorticoids, especially if no other immunosuppressive agent is prescribed concurrently, but trials have not been performed to prospectively compare the long-term outcomes of different durations of therapy. Some patients may require a slower taper. Our approach is to steadily taper the dose of glucocorticoids for patients in remission and closely monitor the patient's condition, only resuming or raising the dose of glucocorticoids if there is evidence of recurrent active PAN.

Those who respond to glucocorticoids alone are spared the risk of adverse effects associated with the use of cyclophosphamide or other immunosuppressive drugs. However, treatment with glucocorticoids may be associated with multiple adverse effects that, in many patients, may be more serious that the side effects of other immunosuppressive drugs. The risks of systemic glucocorticoids and prophylaxis for glucocorticoid-induced osteoporosis are discussed in detail separately. (See "Major adverse effects of systemic glucocorticoids" and "Prevention and treatment of glucocorticoid-induced osteoporosis".)

Other immunosuppressive agents

Indications — Patients with mild disease who are resistant to or intolerant of glucocorticoids require additional or alternative treatment. In addition, because about half of patients with mild disease will require an additional agent at some point during their treatment, and given the substantial toxicities of glucocorticoids, we suggest treatment with an additional immunosuppressive drug beyond glucocorticoids for most patients with mild disease.

Methotrexate versus azathioprine — When a decision is made to start an immunosuppressive drug in addition to glucocorticoids for treatment of nonsevere disease, our preference is for either azathioprine (2 mg/kg daily) or methotrexate (20 to 25 mg once weekly) for at least one year.

We base the choice between methotrexate and azathioprine on an evaluation of potential contraindications, and patient and clinician preferences regarding dosing and administration of the drugs. Methotrexate may be faster-acting but should be avoided in patients with kidney disease or hepatitis. We thus prefer azathioprine in patients with kidney disease and in patients with hepatic disease, although these patients should be closely monitored for hepatotoxicity.

There is limited evidence to support this approach to treatment of nonsevere disease. In a small trial of 95 patients with a case mix of PAN, eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss), and MPA compared the addition of azathioprine or placebo to standard daily oral glucocorticoids for patients classified as having nonsevere disease [25]. The trial did not find a benefit of azathioprine in terms of rates of attaining remission, risk of relapse, or cumulative dose of glucocorticoids. However, only a minority, 19 out of 51 (37 percent) had PAN, limiting the interpretation of these results for patients with PAN. The small sample size of patients with PAN precluded disease-specific subset efficacy analysis. More data are needed on the efficacy of azathioprine and methotrexate as "glucocorticoid-sparing" agents for patients with mild PAN to guide therapy.

Other agents

Limited role for cyclophosphamide – There are few randomized trials in patients with PAN that have directly compared the efficacy of azathioprine, methotrexate, cyclophosphamide, and mycophenolate, but we generally avoid the use of cyclophosphamide in patients with nonsevere PAN. One small randomized trial has shown similar benefit but lower toxicity with azathioprine compared with cyclophosphamide in such patients [2]. In our clinical experience as well as in observational studies of PAN, cyclophosphamide appears to have greater toxicity compared with azathioprine or methotrexate; this was observed in trials of patients with other forms of systemic necrotizing vasculitis.

Mycophenolate mofetil – We also prefer to use either methotrexate or azathioprine over mycophenolate (2000 to 3000 mg daily) [26-30]. Mycophenolate has been shown to be less efficacious than azathioprine for maintenance of remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis [30]. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Choice of maintenance therapy'.)

However, this approach is based on clinical experience and limited data from small trials [2,31], as well as from indirect evidence from the use of azathioprine and methotrexate for maintenance of remission in ANCA-associated vasculitis. The role of alternative regimens for the treatment of moderate to severe PAN is not well-established, and there are minimal data to support their use. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Choice of maintenance therapy'.)

TREATMENT OF SEVERE PAN — Patients with disease that is organ- or life-threatening are often treated in two phases: a remission induction phase and a remission maintenance phase.

Remission induction — For patients with severe disease, we suggest initiating treatment with both cyclophosphamide (either oral or intravenous) and high-dose glucocorticoids.

Glucocorticoids — We suggest pulse glucocorticoid therapy along with cyclophosphamide in patients with severe, active polyarteritis nodosa (PAN).

Intravenous methylprednisolone is dosed at 7 to 15 mg/kg to a maximum of 500 to 1000 mg administered intravenously once daily for three days. Afterwards, oral prednisone should be administered at 1 mg/kg daily for two to four weeks and gradually tapered as described above. (See 'Treatment of nonsevere PAN' above.)

In our experience, pulse therapy provides more rapid control of disease. This approach is also supported by other experts, but there are no randomized trials comparing pulse with high-dose oral glucocorticoid therapy in patients with PAN [32].

Cyclophosphamide — We suggest cyclophosphamide along with high-dose glucocorticoids for treatment of severe PAN. Support for the use of cyclophosphamide for remission-induction is indirect and is based upon expert experience and randomized trials using these medications in patients with other forms of necrotizing vasculitis. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy" and "Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Treatment and prognosis".)

Dosing – Oral cyclophosphamide is dosed at 2 mg/kg daily for three to six months until remission is achieved. When intravenous cyclophosphamide is used, we suggest treatment with 15 mg/kg administered at weeks 0, 2, and 4, and then every three weeks [33].

An alternative regimen is intravenous pulse therapy with cyclophosphamide (600 mg/m2) every two weeks for three doses, in addition to the glucocorticoid regimen, then every four weeks for at least four months and until a stable remission has been achieved, but for no greater than six months.

All the recommended doses of cyclophosphamide, both by oral and intravenous routes, must be adjusted for kidney function, for age, and in response to possibly neutropenia or other hematologic toxicities. The use of cyclophosphamide, including monitoring and prevention of adverse effects, and strategies for dose adjustments are discussed in detail separately. (See "General principles of the use of cyclophosphamide in rheumatic diseases".)

Oral versus intravenous administration – In our experience, use of oral versus intravenous cyclophosphamide results in a similar degree of benefit. While the comparative efficacy of treatment with oral and intravenous cyclophosphamide has been studied in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, similar comparisons in patients with PAN have not been performed [33-35].

Theoretically, compared with oral therapy, intravenous therapy may be associated with lower cumulative dose and potentially reduced risk of bone marrow, bladder, ovarian, and testicular toxicity. However, given that current practice for the use of cyclophosphamide in vasculitis is to limit treatment with drug to four to six months, the route of administration is now less of deciding factor since the differences between potential toxicities between oral and intravenous administration are lessened with reduced exposure.

Oral therapy with cyclophosphamide is an alternative preferred by some patients for its convenience and by some experts because of the long experience with this approach in ANCA-associated vasculitis, such as granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). (See "General principles of the use of cyclophosphamide in rheumatic diseases" and "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy".)

Duration of cyclophosphamide treatment – Based upon data in other forms of vasculitis and our experience, we generally avoid courses of cyclophosphamide longer than four months if remission has been achieved by that time.

While one randomized trial of 65 patients with moderate to severe disease (18 patients had PAN; 47 had MPA) reported somewhat better outcomes with 12 versus 6 monthly pulses of cyclophosphamide, only a minority of patients had PAN, and the study did not include a remission-maintenance regimen with an alternative immunosuppressive regimen [36]. Moreover, some toxicities of cyclophosphamide only become apparent several years after treatment (eg, premature ovarian failure or bladder cancer).

Remission maintenance — In patients who have completed a course of therapy with cyclophosphamide, we switch 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 (including cyclophosphamide and the subsequent agent) of 18 months. Patients with relapsing disease may require longer courses of therapy.

We avoid the continued use of cyclophosphamide for remission maintenance due to its toxicity and prefer to use either azathioprine or methotrexate over mycophenolate for this purpose [26-30].

The choice between methotrexate and azathioprine often depends on the potential for treatment-associated adverse events, dosing regimens, and both provider and patient preferences. Methotrexate is likely faster-acting but should be avoided in patients with kidney disease or hepatitis.

In patients with poor tolerance of, or contraindications to, both azathioprine or methotrexate, we use mycophenolate mofetil (2000 to 3000 mg daily).

The highest tolerated dose of a given agent, up to the recommended maximum, should be used for several months before presuming it is insufficient and that another medication is required.

This approach is supported indirectly by randomized trials and experience in patients with ANCA-associated vasculitis, but there are no randomized trials or observational studies that have formally examined this approach or compared azathioprine, cyclophosphamide, methotrexate, and mycophenolate in patients with PAN in this setting [2]. Nonetheless, use of this strategy in patients with PAN has been effective in our experience. The use of this approach in ANCA-associated vasculitis is discussed in detail separately. (See "Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Treatment and prognosis" and "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Maintenance therapy'.)

The monitoring and potential adverse effects of azathioprine, methotrexate, and mycophenolate mofetil are discussed in detail separately. (See "Pharmacology and side effects of azathioprine when used in rheumatic diseases" and "Major side effects of low-dose methotrexate" and "Use of methotrexate in the treatment of rheumatoid arthritis" and "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases" and "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Maintenance therapy'.)

Resistant disease — Infrequently, patients do not respond adequately to glucocorticoids and cyclophosphamide treatment. In patients with severe PAN who have 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 three days), followed by prednisone (1 mg/kg daily taken orally), and switch from cyclophosphamide to a different immunosuppressive agent.

We base the choice of alternative immunosuppressive agent on the patient's history of medication use and comorbidities. We usually prescribe an agent not previously used by the patient from among the following: azathioprine, methotrexate, or mycophenolate. (See 'Other immunosuppressive agents' above.)

Alternate biologic therapies – There has been increasing interest in the use of biologic drugs for the treatment of patients with relapsing or refractory PAN. A multicenter, retrospective case series examined 42 patients with PAN who received anti-tumor necrosis factor (TNF) drugs, rituximab, or tocilizumab after at least one initial course of treatment with glucocorticoids and, usually, another nonbiologic immunosuppressive agent [37]. Complete or partial responses were achieved for 53 percent for patients given anti-TNF drugs, 44 percent for patients given rituximab, and 80 percent for patients given tocilizumab. Almost all patients (95 percent) also received glucocorticoids with the biologic drug.

Although this retrospective series is subject to possible biases in case identification and data collection, these data provide some support to smaller reports which describe treatment of PAN with anti-TNF alpha agents [38], rituximab [39], and tocilizumab [37,40-48]. This report suggests that it is reasonable to consider prescribing an anti-TNF drug or tocilizumab for patients with relapsing/refractory PAN. Although rituximab is also an option for the treatment of patients without hepatitis B virus (HBV) infection, the data from this case series and the long biological impact of rituximab and its effect on response to vaccination make it a less preferred alternative.

Alternate non-biologic therapies – An extremely small number of case reports have been published describing treatment of PAN with leflunomide [49] and tofacitinib [50], but publication bias and other factors make interpretation and application of these results difficult.

Other management considerations

Hypertension — Hypertension can be a major therapeutic issue in patients with PAN. The elevation in blood pressure may be severe and is often mediated by ischemia-induced activation of the renin-angiotensin system [51]. The intrarenal large vessel disease in PAN may, therefore, be the functional equivalent of extrarenal vascular disease in bilateral renal artery stenosis. The management of renovascular hypertension is discussed elsewhere. (See "Treatment of bilateral atherosclerotic renal artery stenosis or stenosis to a solitary functioning kidney", section on 'Medical therapy'.)

Pneumocystis jirovecii prophylaxis — Prophylaxis for Pneumocystis jirovecii infection should be employed in patients being treated for PAN using the regimens associated with such risk in patients with GPA, 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'.)

MONITORING OF DISEASE — Patients with polyarteritis nodosa (PAN; including cutaneous and single-organ 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 disease onset. However, patients with PAN may have relapses of disease that include clinical manifestations of vasculitis not present at diagnosis [52].

Frequency of monitoring – 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.

Components of monitoring – 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 at each visit.

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. (See "Overview of the management of vasculitis in adults", section on 'Monitoring'.)

Role of imaging – 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.

Serial angiograms may be required to differentiate active from inactive disease. 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.

RECURRENT DISEASE — The treatment of recurrent disease depends upon the severity of the flare and whether recurrence occurs on or off immunosuppressive treatment.

Nonsevere relapse – Nonsevere disease relapse may be treated by use of glucocorticoids alone and/or by an increase in dose of immunosuppressive drug, depending upon the patient's treatment at the time of disease exacerbation or recurrence.

Severe relapse – Severe relapse requires reinitiation of remission-induction treatment (see 'Other management considerations' above). If moderate to severe recurrence occurs when the patient is on immunosuppressive treatment, a different immunosuppressive agent should be used. (See 'Resistant disease' above.)

Patients with relapsing disease may benefit from longer courses of therapy. Some patients may also benefit from the addition of low-dose glucocorticoids (eg, prednisone ≤10 mg daily) for maintenance of remission when mild symptoms of PAN recur off glucocorticoids (eg, arthralgias, fatigue, or skin lesions).

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.

Kidney 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 kidney 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 [53] and in approximately 10 percent who undergo dialysis for as long as three to six months [54].

In order to better define prognostic factors in PAN, the French Vasculitis Study Group 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 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 [4,13,55]. The FFS was revised in 2011 based upon additional data and for PAN now only includes four factors associated with increased mortality: age >65 years, cardiac symptoms, gastrointestinal involvement, and kidney insufficiency (plasma creatinine >1.7 mg/dL [150 micromol/L]) [13]. The original FFS 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 [GPA], microscopic polyangiitis [MPA], and eosinophilic granulomatosis with polyangiitis [EGPA; 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].

Kidney transplantation — Few data exist concerning the outcome of patients with PAN and end-stage kidney disease who undergo kidney 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 kidney diseases (eg, glomerulonephritis, interstitial nephritis, toxic nephropathies, and cystic kidney disease) [56]. 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 — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th 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 sophisticated, and more detailed. These articles are written at the 10th to 12th 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

Initial assessment – Prior to initiating pharmacotherapy, patients should undergo a thorough clinical evaluation to determine the extent and severity of polyarteritis nodosa (PAN)-associated organ involvement, which may influence the choice of pharmacotherapy. Patients should also undergo serologic testing for viral hepatitis. If prescribed, minocycline should be stopped, since it can be associated with PAN. (See 'Pretreatment evaluation' above.)

Viral hepatitis-associated disease – In patients with mild PAN and evidence of infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), we suggest initial with antivirals only, rather than also treating initially with immunosuppressive medications (Grade 2C). (See 'Associated hepatitis B or C infection' above.)

Some patients with severe manifestations of hepatitis virus-associated PAN may benefit from short-term treatment with glucocorticoids or plasma exchange until antiviral therapy becomes effective.

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 'Treatment of nonsevere PAN' above and 'Treatment of severe PAN' above.)

Isolated disease – PAN affecting a single organ may be discovered following surgical excision of an involved organ. If the PAN is isolated to the excised tissue, immunosuppressive therapy may not be required, although such patients should be monitored clinically for evidence of disease recurrence or progression. (See 'Isolated/single-organ PAN' above.)

PAN isolated to the skin is discussed elsewhere. (See "Cutaneous polyarteritis nodosa".)

Nonsevere PAN – In patients with nonsevere PAN disease (eg, absence of life- or organ-threatening disease manifestations), we suggest treatment with both glucocorticoids and a steroid-sparing agent rather than glucocorticoids alone (Grade 2C).

Glucocorticoids – In most patients, prednisone is administered orally (1 mg/kg daily to a maximum of 60 to 80 mg daily). 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.

Steroid-sparing agent – We will typically use azathioprine (2 mg/kg daily), methotrexate (20 to 25 mg once weekly) or mycophenolate mofetil (2 to 3 g daily), for a total duration of immunosuppressive therapy of 24 months. (See 'Treatment of nonsevere PAN' above.)

Severe disease – In a patient with severe disease (eg, ulcerative or gangrenous lesions of the extremities, acute kidney injury, polyneuropathy, central nervous system involvement, mesenteric arteritis, or myocardial ischemia), we recommend treatment with both glucocorticoids and cyclophosphamide rather than glucocorticoids alone (Grade 1B). (See 'Treatment of severe PAN' above.)

Glucocorticoids – 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 initiating therapy with oral prednisone. (See 'Glucocorticoids' above.)

Cyclophosphamide – 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 three weeks for at least four months and until a stable remission has been achieved, but for no greater than six months. (See 'Cyclophosphamide' above.)

Remission maintenance – In patients treated with cyclophosphamide, we suggest a maintenance regimen with another immunosuppressive agent, such as azathioprine (2 mg/kg daily) or methotrexate (20 to 25 mg once weekly) (Grade 2C), for a total duration of immunosuppressive therapy of 18 months. (See 'Remission maintenance' above.)

Resistant disease – 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 three days), followed by prednisone (1 mg/kg daily taken orally), and switch from cyclophosphamide to a different immunosuppressive agent. Alternatives in patients unresponsive to or intolerant of azathioprine or methotrexate are mycophenolate mofetil (2000 to 3000 mg daily), tumor necrosis factor (TNF) inhibitors, rituximab, and tocilizumab. (See 'Resistant disease' above.)

Other management considerations – Patients with PAN may develop renovascular hypertension. (See "Treatment of bilateral atherosclerotic renal artery stenosis or stenosis to a solitary functioning kidney", section on 'Medical therapy'.)

Prophylaxis against Pneumocystis jirovecii should also be considered in patients treated with immunosuppressive agents. (See 'Other management considerations' above.)

Disease monitoring – We suggest close follow-up of patients to monitor for disease relapse and for drug toxicities. Disease relapses may include new findings that were not part of the patient’s initial presentation. Angiography is not required unless there are findings suggestive of new disease. (See 'Monitoring of disease' above.)

Recurrent disease – Nonsevere disease recurrence may be treated with glucocorticoids alone and/or an increase in dose of the immunosuppressive drugs.

Severe disease relapse requires reinitiation of the remission induction therapy. Patients with relapsing disease may benefit from the long-term use of low-dose glucocorticoids (See 'Resistant disease' above and 'Remission induction' above.)

Prognosis – Treated PAN is associated with a five-year survival of 80 percent. Older age, kidney failure, and mesenteric and cardiac infarctions are all associated with an increase in mortality.

Most patients will never relapse. Kidney transplantation is associated with worse patient and allograft survival rates compared with patients with other diagnoses (See 'Prognosis' above.)

  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.
  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. 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.
  11. 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.
  12. Kermani TA, Ham EK, Camilleri MJ, Warrington KJ. Polyarteritis nodosa-like vasculitis in association with minocycline use: a single-center case series. Semin Arthritis Rheum 2012; 42:213.
  13. 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.
  14. 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.
  15. Guillevin L, Lhote F, Cohen P, et al. Polyarteritis nodosa related to hepatitis B virus. A prospective study with long-term observation of 41 patients. Medicine (Baltimore) 1995; 74:238.
  16. Guillevin L, Pagnoux C. Indications of plasma exchanges for systemic vasculitides. Ther Apher Dial 2003; 7:155.
  17. Kruger M, Böker KH, Zeidler H, Manns MP. Treatment of hepatitis B-related polyarteritis nodosa with famciclovir and interferon alfa-2b. J Hepatol 1997; 26:935.
  18. Wicki J, Olivieri J, Pizzolato G, et al. Successful treatment of polyarteritis nodosa related to hepatitis B virus with a combination of lamivudine and interferon alpha. Rheumatology (Oxford) 1999; 38:183.
  19. Avşar E, Savaş B, Tözün N, et al. Successful treatment of polyarteritis nodosa related to hepatitis B virus with interferon alpha as first-line therapy. J Hepatol 1998; 28:525.
  20. Simsek H, Telatar H. Successful treatment of hepatitis B virus-associated polyarteritis nodosa by interferon alpha alone. J Clin Gastroenterol 1995; 20:263.
  21. Guillevin L, Lhote F, Sauvaget F, et al. Treatment of polyarteritis nodosa related to hepatitis B virus with interferon-alpha and plasma exchanges. Ann Rheum Dis 1994; 53:334.
  22. Janssen HL, van Zonneveld M, van Nunen AB, et al. Polyarteritis nodosa associated with hepatitis B virus infection. The role of antiviral treatment and mutations in the hepatitis B virus genome. Eur J Gastroenterol Hepatol 2004; 16:801.
  23. Guillevin L, Mahr A, Callard P, et al. Hepatitis B virus-associated polyarteritis nodosa: clinical characteristics, outcome, and impact of treatment in 115 patients. Medicine (Baltimore) 2005; 84:313.
  24. Hernández-Rodríguez J, Hoffman GS. Updating single-organ vasculitis. Curr Opin Rheumatol 2012; 24:38.
  25. Puéchal 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.
  26. 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.
  27. 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.
  28. Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med 2005; 352:351.
  29. Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med 2008; 359:2790.
  30. 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.
  31. Brogan PA, Arch B, Hickey H, et al. Mycophenolate Mofetil Versus Cyclophosphamide for Remission Induction in Childhood Polyarteritis Nodosa: An Open-Label, Randomized, Bayesian Noninferiority Trial. Arthritis Rheumatol 2021; 73:1673.
  32. Guillevin L, Pagnoux C. When should immunosuppressants be prescribed to treat systemic vasculitides? Intern Med 2003; 42:313.
  33. 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.
  34. 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.
  35. 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.
  36. 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.
  37. Hadjadj J, Canzian A, Karadag O, et al. Use of biologics to treat relapsing and/or refractory polyarteritis nodosa: data from a European collaborative study. Rheumatology (Oxford) 2022; 62:341.
  38. Ginsberg S, Rosner I, Slobodin G, et al. Infliximab for the treatment of refractory polyarteritis nodosa. Clin Rheumatol 2019; 38:2825.
  39. Seri Y, Shoda H, Hanata N, et al. A case of refractory polyarteritis nodosa successfully treated with rituximab. Mod Rheumatol 2017; 27:696.
  40. Boistault M, Lopez Corbeto M, Quartier P, et al. A young girl with severe polyarteritis nodosa successfully treated with tocilizumab: a case report. Pediatr Rheumatol Online J 2021; 19:168.
  41. Inoue N, Shimizu M, Mizuta M, Yachie A. Successful treatment of tumor necrosis factor inhibitor-resistant cutaneous polyarteritis nodosa with tocilizumab. Pediatr Int 2020; 62:753.
  42. Watanabe K, Rajderkar DA, Modica RF. A Case of Polyarteritis Nodosa Associated with Vertebral Artery Vasculitis Treated Successfully with Tocilizumab and Cyclophosphamide. Case Rep Pediatr 2016; 2016:7987081.
  43. Krusche M, Ruffer N, Schneider U, et al. Tocilizumab treatment for polyarteritis nodosa. Rheumatology (Oxford) 2020; 59:e63.
  44. Saunier A, Issa N, Vandenhende MA, et al. Treatment of polyarteritis nodosa with tocilizumab: a new therapeutic approach? RMD Open 2017; 3:e000446.
  45. Hočevar A, Lestan B, Šemrl SS, et al. AA amyloidosis in a polyarteritis nodosa patient treated with tocilizumab. Amyloid 2013; 20:275.
  46. Krusche M, Ruffer N, Kötter I. Tocilizumab treatment in refractory polyarteritis nodosa: a case report and review of the literature. Rheumatol Int 2019; 39:337.
  47. Bodoki L, Végh E, Szekanecz Z, Szűcs G. Tocilizumab Treatment in Polyarteritis Nodosa. Isr Med Assoc J 2019; 21:560.
  48. Carrión-Barberà I, Pros A, Salman-Monte TC, et al. Safe and successful treatment of refractory polyarteritis nodosa with tocilizumab in a patient with past hepatitis B virus infection: a case-based review. Clin Rheumatol 2021; 40:2065.
  49. Mustapha N, Barra L, Carette S, et al. Efficacy of leflunomide in the treatment of vasculitis. Clin Exp Rheumatol 2021; 39 Suppl 129:114.
  50. Rimar D, Alpert A, Starosvetsky E, et al. Tofacitinib for polyarteritis nodosa: a tailored therapy. Ann Rheum Dis 2016; 75:2214.
  51. Stockigt JR, Topliss DJ, Hewett MJ. High-renin hypertension in necrotizing vasculitis. N Engl J Med 1979; 300:1218.
  52. 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.
  53. Hind CR, Paraskevakou H, Lockwood CM, et al. Prognosis after immunosuppression of patients with crescentic nephritis requiring dialysis. Lancet 1983; 1:263.
  54. 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.
  55. 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.
  56. 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 23.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟