Polyarteritis Nodosa: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor:
Louis Wolff
,
Alice Horisberger
,
Laura Moi
,
Maria P. Karampetsou
,
Denis Comte

Polyarteritis nodosa (PAN), also known as panarteritis nodosa, represents a form of necrotizing vasculitis that predominantly affects medium-sized vessels, although it is not restricted to them and can also involve smaller vessels. The clinical presentation is heterogeneous and characterized by a significant number of patients exhibiting general symptoms, including asthenia, fever, and unintended weight loss. Although PAN can involve virtually any organ, it preferentially affects the skin, nervous system, and the gastrointestinal tract. Orchitis is a rare but specific manifestation of PAN. The absence of granulomas, glomerulonephritis, and anti-neutrophil cytoplasmic antibodies serves to distinguish PAN from other types of vasculitis. Major complications consist of hemorrhagic and thrombotic events occurring in mesenteric, cardiac, cerebral, and renal systems. Historically, PAN was frequently linked to hepatitis B virus (HBV) infection, but this association has dramatically changed in recent years due to declining HBV prevalence.

  • PAN
  • polyarteritis nodosa
  • panarteritis nodosa
  • monogenic
  • VEXAS
  • DADA2

1. Introduction

PAN was first described in 1866 by Kussmaul and Maier. They reported an “intermittent nodular appearance affecting arteries throughout the body, sparing large vessels (the aorta and its branches), small vessels (arterioles, capillaries, and venules) and pulmonary vessels” [1]. The distinct “pearl necklace” pattern led to the naming of this condition as polyarteritis nodosa. In 1952, pathologist Pearl Zeek laid out the first classification of PAN, distinguishing between hypersensitivity vasculitis, allergic vasculitis, PAN, and temporal arteritis, now, respectively, known as urticarial vasculitis, eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome), PAN, and giant cell arteritis (Horton’s disease) [2]. A pivotal development came in 1982 when autoantibodies directed against neutrophil cytoplasm antigens (ANCA) were identified in eight patients with clinical characteristics of vasculitis, introducing ANCA-associated vasculitis (AAV) as a distinct category of vasculitis separate from PAN [3]. The most recent definition of PAN came from the 2012 Chapel Hill Consensus Conference (CHCC) where the disease was described as “necrotizing arteritis of the medium or small arteries without glomerulonephritis or vasculitis of arterioles, capillaries or venules and without ANCA” [4][5][6]. Over the past two decades, the medical community’s understanding of PAN has significantly evolved. While initially described as either primary vasculitis or Hepatitis B virus (HBV)-related, the current understanding recognizes PAN as a disease often secondary to genetic syndromes and malignant hematologic disorders [7].

2. Epidemiology

The prevalence of PAN varies greatly across different countries, ranging from 2 to 31 per million inhabitants in Europe [8][9]. There are notable north–south and seasonal gradients in the occurrence of the disease. Historically, PAN was frequently linked to HBV infection. With the advent of its vaccine and the enhancement of public health measures in response to the AIDS crisis, the incidence of PAN has seen a significant decline, turning it from one of the most common vasculitis in the 1990s to one of the least common today [8][10]. In addition, the improvement in laboratory techniques for the detection of ANCA in the 1980s led to the reclassification of certain vasculitis that were initially diagnosed as PAN [11]. The challenge in estimating the overall prevalence of PAN arises from a combination of factors, including the absence of serum markers, heterogeneous classification criteria, and a variety of predisposing genetic and environmental factors.

3. Physiopathology

PAN is typically characterized by a segmental, necrotizing, and transmural inflammation, predominantly involving small- to medium-sized arteries, although any arterial size could theoretically be susceptible. The disease most commonly impacts the visceral and muscular arteries, including their branches. In patient biopsies, it is common to observe co-existing lesions of diverse stages of inflammation and scarring within a single sample [12]. Because of the arterial inflammatory process, fibrinoid necrosis may develop, leading to the formation of microaneurysms. Over time, these complications can progress to chronic stages, characterized by fibrous scarring and vascular aneurysms, which can rupture and lead to severe bleeding [13][14]. During the acute phase, the cellular infiltrate, composed of macrophages, T lymphocytes, neutrophils, and eosinophils, is generally observed in the tunica media but can also invade the tunica interna and tunica externa [15]. One distinctive feature of PAN, compared to other vasculitis, is the absence of granulomas. This disease is also characterized by the coexistence of different stages of vascular inflammations at the same time.
The pathophysiology of PAN, not yet fully understood, may vary depending on the disease’s specific etiology. Serum cytokine profile analysis in PAN patients has revealed an elevation in interferon-alpha (IFN-⍺), interleukine-2 (IL-2), tumor necrosis factor-α (TNF⍺), and IL-1-ß compared to healthy individuals and those with granulomatosis with polyangiitis (GPA) [16]. Immunohistochemical studies of muscle and nerve biopsies from patients showed the presence of macrophages (41%) and mostly CD4+ T lymphocytes (41%) [13][17]. Most of these studies, however, primarily focus on PAN associated with HBV.
Viral infections remain a common trigger of PAN and should be excluded in all cases. In PAN associated with HBV, the HBs antigen is responsible for the formation of immune complexes [18][19], as suggested by animal models of hepatitis B antigen-associated PAN, which show an accumulation of immune complexes in blood vessels [20][21]. Hepatitis C virus (HCV) has also been linked to PAN, with HCV-associated PAN tending to present more severe and acute symptoms [22][23]. However, this only concerns 5% of patients with PAN, and the distinction with cryoglobulinemic vasculitis can sometimes be challenging [24]. HIV infection has been associated with PAN, though HIV-associated PAN is generally less aggressive than HBV-associated PAN. The classical manifestation is mononeuritis multiplex and can occur at any stage of HIV infection [25]. Although parvovirus B19 has been associated with PAN, a study using PCR tests found no higher prevalence of this infection in people with PAN compared to those without [26][27][28][29].
More recently, vasculitis has been associated with COVID-19 infection, but to date no cases of PAN have been reported [30][31]. COVID-19 vaccines have been associated with PAN manifestations [32][33][34]. Like other vasculitides, PAN can be induced by the use of certain drugs, such as minocycline [35]. The association between PAN and neoplasia is well established, especially for hematological malignancies, such as hairy T cell leukemia, or, more recently, myelodysplastic syndrome (MDS) [36][37][38][39][40].
More recently, genetic forms of PAN have been described. In the early 2000s, cases of PAN-like vasculitis were described in patients with Familial Mediterranean Fever (FMF) [41][42]. In a nationwide study in Turkey, PAN prevalence in patients with FMF was 0.9% [43]. FMF is caused by mutations in the MEFV gene that encodes for pyrin/marenostrin, which result in unregulated production of IL-1, leading to recurring inflammation, fever, and, sometimes, autoimmune manifestations [44]. Patients with PAN associated with FMF present a higher incidence of perirenal hemorrhages and elevated levels of inflammation [41][42][43][45]. Another condition related to genetic forms of PAN is STING-associated vasculopathy, with onset in infancy (SAVI), which is a type I interferonopathy. This condition is caused by mutations in the TMEM173 gene that induce the inflammation of endothelial cells in children. It often presents PAN-like symptoms in affected children [46]. A monogenic syndrome resulting from a deficiency in Adenosine Deaminase 2 (DAD2) has been described in familial cases of necrotizing vasculitis that resemble PAN [47]. Since 2014, over 60 bi-allelic loss-of-function mutations in the ADA2 gene have been documented [48][49]. Vascular inflammation in DAD2 patients is believed to be caused by an imbalance in macrophages, favoring the M1 type over the M2 type.

4. Clinical Manifestations

Signs and symptoms of PAN result from damage to the vascular walls, potentially affecting all organs. This section provides an overview of organ systems that can be impacted in PAN patients. Unless otherwise stated, the percentages and specifics of the manifestations come from the cohorts shown in Table 1.
Table 1. Characteristics of PAN patients reported in different cohorts (PNP: peripheral neuropathy, CNS: central nervous system, FFS: Five Factor Score, 1996). Results are expressed as percentages.

Characteristics

Pagnoux et al.

(1963 to 2005) [50]

Sönmez et al.

(1990 to 2015) [10]

Rohmer et al.

(2005 to 2019) [50]

Georgin-Lavialle et al. (VEXAS) [51]

Meyts et al. (ADA2) [52]

General symptoms

93.1

  

85

95.7

50

Fever

63.8

53.7

54

64.6

  

Loss of weight

69.5

53.7

50

54.5

  

Myalgia

58.6

46.2

50

    

All cutaneous

49.7

67.2

59

83.6

75

Nodules

17.2

      

14

Purpura

22.1

        

Livedo

16.7

17.9

    

50

Panniculitis

    

7.5

12.9

  

Renal

50.6

47.7

20

9.5

  

Hematuria

15.2

        

Proteinuria

21.6

        

Hypertension

34.8

41.7

    

21

Orchitis

17

14.9

16

  

4

Neurologic

79.0

43.2

59

    

PNP

74.1

    

5.2

9

Mononeuritis

70.7

    

2.6

  

CNS

4.6

      

53

Digestive

37.9

22.3

28

13.8

33

Abdominal pain

35.6

37.3

  

8.6

12

Bleeding

3.4

    

0.9

  

Perforation

4.3

    

0.9

2

Cardiovascular

22.4

  

39

    

Pericarditis

5.5

    

4.3

  

Distal necrosis

6.3

13.5

    

22

Thrombo-embolism

      

35.3

  

Ophthalmic

8.6

  

40.5

  

Retinal vasculitis

4.3

      

Pulmonary

  

2.9

8

49.1

  

Cough

5.7

        

Lung infiltrate

3.4

    

40.5

  

Pleural effusion

3.4

    

9.5

  

Chondritis

      

36.2

  

Arthralgia

48.9

58.2

  

28.4

  

Arthritis

  

17.9

    

5. Treatments

The treatment recommendations for PAN are primarily based on weak empirical evidence and are often drawn from recommendations for other forms of vasculitis, with modifications according to the disease severity. Mild PAN, characterized by non-life- or organ-threatening manifestations like constitutional symptoms, arthritis, or skin lesions, is differentiated from moderate to severe PAN, which involves more severe complications, such as arterial stenosis—particularly those involving the renal arteries and aorta—and ischemic complications that affect the heart, peripheral nervous system, and gastrointestinal system. To aid in risk stratification, the 1996 version of the Five Factor Score (FFS) can be used. This score assigns +1 point for each of the following: proteinuria greater > 1 g/day, serum creatinine > 140 µmol/L, cardiomyopathy, severe gastrointestinal involvement, and CNS involvement [53][54].
Treatment for mild PAN (FFS of 0) may include glucocorticoids (GC) only. The clinical benefit of supplementing glucocorticoids with an immunosuppressive agent is not definitively established, but it could potentially offset the high 40% relapse rate and function as a steroid-sparing strategy. Guidelines, however, show divergence in recommendations. The French protocol typically prescribes glucocorticoids as a standalone treatment, introducing immunosuppressants such as methotrexate or azathioprine only in instances of resistance or intolerance. In contrast, the ACR’s 2021 guidelines advocate for a combined approach from the beginning, recommending the incorporation of azathioprine (administered orally at 2–3 mg/kg/day) or methotrexate (preferably given subcutaneously at 0.3 mg/kg/week) with glucocorticoids. Moderate to severe PAN (FFS > 0) is treated with intravenous (IV) GC in conjunction with an immunosuppressive agent, preferably cyclophosphamide. The start of treatment marks the induction phase, lasting 3 to 6 months, aimed at achieving disease remission, defined by the American College of Rheumatology (ACR) as a complete absence of clinical manifestations, with or without immunosuppressive treatment. Initial treatment strategies recommend starting with at least 1 mg/kg/day of prednisone equivalent, capped at 60 mg/day. In patients with severe manifestations requiring rapid intervention, IV boluses of methylprednisolone are recommended. If remission is incomplete, the duration of cyclophosphamide therapy may be extended, although it is recommended not to exceed a period of 6 months given its potential toxicity [53][54].
Alternative therapies, including rituximab, mycophenolate mofetil, tocilizumab, anti-TNF alpha, JAK inhibitors, IV immunoglobulins, or plasma exchange, have not been well studied and their application is only reserved for certain refractory or relapsed patients [28][55][56][57][58][59][60][61][62][63]. A recent European retrospective study analyzed 42 patients treated for relapsed and/or refractory PAN. Tocilizumab, anti-TNF alpha, and rituximab achieved complete remission in 50%, 40%, and 33% of cases, respectively, with comparable safety profiles. These biotherapies may become first-line treatments in the future, but more data are needed [57]. The induction phase is followed by the maintenance phase, with the objective of preventing relapse. Patients treated with cyclophosphamide with complete remission may be switched to azathioprine or methotrexate for 12 to 18 months [53][54]. In secondary forms of PAN, the therapeutic approach focuses on the underlying etiology. In the context of HBV-associated PAN, antiviral therapy is used as the primary intervention. In severe cases, management with GC and plasma exchange may be considered [64]. When PAN is concomitant with MDS, interventions targeting the MDS are often effective in attenuating the vasculitic manifestations [37]. From this perspective, Mekinian et al. showed that azacytidine successfully treated autoimmune manifestations in 9 out of 11 patients with MDS [65].

This entry is adapted from the peer-reviewed paper 10.3390/ijms242316668

References

  1. Stone, J.H. Vasculitis: A collection of pearls and myths. Rheum. Dis. Clin. N. Am. 2007, 33, 691–739.
  2. Zeek, P.M. Periarteritis nodosa; a critical review. Am. J. Clin. Pathol. 1952, 22, 777–790.
  3. Davies, D.J.; Moran, J.E.; Niall, J.F.; Ryan, G.B. Segmental necrotising glomerulonephritis with antineutrophil antibody: Possible arbovirus aetiology? BMJ 1982, 285, 606.
  4. Karadag, O.; Jayne, D.J. Polyarteritis nodosa revisited: A review of historical approaches, subphenotypes and a research agenda. Clin. Exp. Rheumatol. 2018, 36 (Suppl. 111), 135–142.
  5. Jennette, J.C.; Falk, R.J.; Bacon, P.A.; Basu, N.; Cid, M.C.; Ferrario, F.; Flores-Suarez, L.F.; Gross, W.L.; Guillevin, L.; Hagen, E.C.; et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2012, 65, 1–11.
  6. Guillevin, L.; Mahr, A.; Cohen, P. Les vascularites nécrosantes systémiques: Classification et stratégies actuelles de traitement. Rev. Méd. Interne 2003, 24, 172–182.
  7. Rohmer, J.; Trefond, L.; Nguyen, Y.; Durel, C.A.; Lacout, C.; Maurier, F.; Rouzaud, D.; Cohen, P.; Lazaro, E.; Mekinian, A.; et al. Caractéristiques cliniques et évolution à long-terme des périartérite noueuses systémiques diagnostiquées depuis 2005. Rev. Méd. Interne 2020, 41, A33–A34.
  8. Mahr, A.; Guillevin, L.; Poissonnet, M.; Aymé, S. Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener’s granulomatosis, and Churg-Strauss syndrome in a French urban multiethnic population in 2000: A capture–recapture estimate. Arthritis Care Res. 2004, 51, 92–99.
  9. Lane, S.E.; Watts, R.; Scott, D.G.I. Epidemiology of systemic vasculitis. Curr. Rheumatol. Rep. 2005, 7, 270–275.
  10. Sönmez, H.E.; Armağan, B.; Ayan, G.; Barut, K.; Batu, E.D.; Erden, A.; Ugurlu, S.; Bilginer, Y.; Kasapcopur, O.; Karadag, O.; et al. Polyarteritis nodosa: Lessons from 25 years of experience. Clin. Exp. Rheumatol. 2019, 5, 52–56.
  11. Saadoun, D.; Vautier, M.; Cacoub, P. Medium- and Large-Vessel Vasculitis. Circulation 2021, 143, 267–282.
  12. De Virgilio, A.; Greco, A.; Magliulo, G.; Gallo, A.; Ruoppolo, G.; Conte, M.; Martellucci, S.; de Vincentiis, M. Polyarteritis nodosa: A contemporary overview. Autoimmun. Rev. 2016, 15, 564–570.
  13. Matsumoto, T.; Kobayashi, S.; Ogishima, D.; Aoki, Y.; Sonoue, H.; Abe, H.; Fukumura, Y.; Nobukawa, B.; Kumasaka, T.; Mori, S.; et al. Isolated necrotizing arteritis (localized polyarteritis nodosa): Examination of the histological process and disease entity based on the histological classification of stage and histological differences from polyarteritis nodosa. Cardiovasc. Pathol. 2007, 16, 92–97.
  14. Lie, J.T. Systemic and isolated vasculitis. A rational approach to classification and pathologic diagnosis. Pathol. Annu. 1989, 24 Pt 1, 25–114.
  15. Kallenberg, C.G.; Brouwer, E.; Weening, J.J.; Tervaert, J.W.C. Anti-neutrophil cytoplasmic antibodies: Current diagnostic and pathophysiological potential. Kidney Int. 1994, 46, 1–15.
  16. Grau, G.E.; Roux-Lombard, P.; Gysler, C.; Lambert, C.; Lambert, P.H.; Dayer, J.M.; Guillevin, L. Serum cytokine changes in systemic vasculitis. Immunology 1989, 68, 196–198.
  17. Cid, M.-C.; Grau, J.M.; Casademont, J.; Campo, E.; Coll-Vinent, B.; López-Soto, A.; Ingelmo, M.; Urbano-Márquez, A. Immunohistochemical characterization of inflammatory cells and immunologic activation markers in muscle and nerve biopsy specimens from patients with systemic polyarteritis nodosa. Arthritis Rheum. 1994, 37, 1055–1061.
  18. Guillevin, L.; Ronco, P.; Verroust, P. Circulating immune complexes in systemic necrotizing vasculitis of the polyarteritis nodosa group. Comparison of HBV-related polyarteritis nodosa and Churg Strauss Angiitis. J. Autoimmun. 1990, 3, 789–792.
  19. Prince, A.M.; Trepo, C. Role of immune complexes involving SH antigen in pathogenesis of chronic active hepatitis and polyarteritis nodosa. Lancet 1971, 297, 1309–1312.
  20. Trepo, C.G.; Zuckerman, A.J.; Bird, R.C.; Prince, A.M. The role of circulating hepatitis B antigen/antibody immune complexes in the pathogenesis of vascular and hepatic manifestations in polyarteritis nodosa. J. Clin. Pathol. 1974, 27, 863–868.
  21. Fye, K.H.; Becker, M.J.; Theofilopoulos, A.N.; Moutsopoulos, H.; Feldman, J.-L.; Talal, N. Immune complexes in hepatitis B antigen-associated periarteritis nodosa. Detection by antibody-dependent cell-mediated cytotoxicity and the Raji cell assay. Am. J. Med. 1977, 62, 783–791.
  22. Carson, C.W.; Conn, D.L.; Czaja, A.J.; Wright, T.L.; Brecher, M.E. Frequency and significance of antibodies to hepatitis C virus in polyarteritis nodosa. J. Rheumatol. 1993, 20, 304–309.
  23. Saadoun, D.; Terrier, B.; Semoun, O.; Sene, D.; Maisonobe, T.; Musset, L.; Amoura, Z.; Rigon, M.R.; Cacoub, P. Hepatitis C virus-associated polyarteritis nodosa. Arthritis Care Res. 2010, 63, 427–435.
  24. Cacoub, P.; Maisonobe, T.; Thibault, V.; Gatel, A.; Servan, J.; Musset, L.; Piette, J.C. Systemic vasculitis in patients with hepatitis C. J. Rheumatol. 2001, 28, 109–118.
  25. Patel, N.; Patel, N.; Khan, T.; Patel, N.; Espinoza, L.R. HIV infection and clinical spectrum of associated vasculitides. Curr. Rheumatol. Rep. 2011, 13, 506–512.
  26. Leruez-Ville, M.; Laugé, A.; Morinet, F.; Guillevin, L.; Dény, P. Polyarteritis nodosa and parvovirus B19. Lancet 1994, 344, 263–264.
  27. Gherardi, R.; Belec, L.; Mhiri, C.; Gray, F.; Lescs, M.; Sobel, A.; Guillevin, L.; Wechsler, J. The spectrum of vasculitis in human immunodeficiency virus-infected patients. A clinicopathologic evaluation. Arthritis Rheum. 1993, 36, 1164–1174.
  28. Viguier, M.; Guillevin, L.; Laroche, L. Treatment of parvovirus B19-associated polyarteritis nodosa with intravenous immune globulin. N. Engl. J. Med. 2001, 344, 1481–1482.
  29. Finkel, T.H.; Török, T.J.; Ferguson, P.J.; Durigon, E.L.; Zaki, S.R.; Leung, D.Y.; Harbeck, R.J.; Gelfand, E.W.; Saulsbury, F.T.; Hollister, J.R.; et al. Chronic parvovirus B19 infection and systemic necrotising vasculitis: Opportunistic infection or aetiological agent? Lancet 1994, 343, 1255–1258.
  30. Ramadan, S.M.; Kasfiki, E.V.; Kelly, C.W.; Ali, I. An interesting case of small vessel pathology following coronavirus infection. BMJ Case Rep. 2020, 13, e237407.
  31. Vacchi, C.; Meschiari, M.; Milic, J.; Marietta, M.; Tonelli, R.; Alfano, G.; Volpi, S.; Faltoni, M.; Franceschi, G.; Ciusa, G.; et al. COVID-19-associated vasculitis and thrombotic complications: From pathological findings to multidisciplinary discussion. Rheumatology 2020, 59, e147–e150.
  32. Su, H.-A.; Hsu, H.-T.; Chen, Y.-C. Cutaneous polyarteritis nodosa following ChAdOx1 nCoV-19 vaccination. Int. J. Dermatol. 2022, 61, 630–631.
  33. Ohkubo, Y.; Ohmura, S.-I.; Ishihara, R.; Miyamoto, T. Possible case of polyarteritis nodosa with epididymitis following COVID-19 vaccination: A case report and review of the literature. Mod. Rheumatol. Case Rep. 2022, 7, 172–176.
  34. Ohmura, S.-I.; Ohkubo, Y.; Ishihara, R.; Otsuki, Y.; Miyamoto, T. Medium-vessel Vasculitis Presenting with Myalgia Following COVID-19 Moderna Vaccination. Intern. Med. 2022, 61, 3453–3457.
  35. Kermani, T.A.; Ham, E.K.; Camilleri, M.J.; Warrington, K.J. Polyarteritis nodosa-like vasculitis in association with minocycline use: A single-center case series. Semin. Arthritis Rheum. 2012, 42, 213–221.
  36. Carpenter, M.T.; West, S.G. Polyarteritis nodosa in hairy cell leukemia: Treatment with interferon-alpha. J. Rheumatol. 1994, 21, 1150–1152.
  37. Roupie, A.L.; Guedon, A.; Terrier, B.; Lahuna, C.; Jachiet, V.; Regent, A.; de Boysson, H.; Carrat, F.; Seguier, J.; Terriou, L.; et al. Vasculitis associated with myelodysplastic syndrome and chronic myelomonocytic leukemia: French multicenter case-control study. Semin. Arthritis Rheum. 2020, 50, 879–884.
  38. Veitch, D.; Tsai, T.; Watson, S.; Joshua, F. Paraneoplastic polyarteritis nodosa with cerebral masses: Case report and literature review. Int. J. Rheum. Dis. 2014, 17, 805–809.
  39. Hamidou, M.A.; Boumalassa, A.; Larroche, C.; El Kouri, D.; Blétry, O.; Grolleau, J.-Y. Systemic medium-sized vessel vasculitis associated with chronic myelomonocytic leukemia. Semin. Arthritis Rheum. 2001, 31, 119–126.
  40. Fain, O.; Hamidou, M.; Cacoub, P.; Godeau, B.; Wechsler, B.; ParIès, J.; Stirnemann, J.; Morin, A.-S.; Gatfosse, M.; Hanslik, T.; et al. Vasculitides associated with malignancies: Analysis of sixty patients. Arthritis Rheum. 2007, 57, 1473–1480.
  41. Balbir-Gurman, A.; Nahir, A.M.; Braun-Moscovici, Y. Vasculitis in siblings with familial Mediterranean fever: A report of three cases and review of the literature. Clin. Rheumatol. 2006, 26, 1183–1185.
  42. Ozen, S.; Ben-Chetrit, E.; Bakkaloglu, A.; Gur, H.; Tinaztepe, K.; Calguneri, M.; Turgan, C.; Turkmen, A.; Akpolat, I.; Danaci, M.; et al. Polyarteritis nodosa in patients with Familial Mediterranean Fever (FMF): A concomitant disease or a feature of FMF? Semin. Arthritis Rheum. 2001, 30, 281–287.
  43. Familial Mediterranean fever (FMF) in Turkey: Results of a nationwide multicenter study. Medicine 2005, 84, 1–11.
  44. Ozen, S. The changing face of polyarteritis nodosa and necrotizing vasculitis. Nat. Rev. Rheumatol. 2017, 13, 381–386.
  45. Yalçınkaya, F.; Özçakar, Z.B.; Kasapçopur, O.; Oztürk, A.; Akar, N.; Bakkaloğlu, A.; Arısoy, N.; Ekim, M.; Özen, S. Prevalence of the MEFV gene mutations in childhood polyarteritis nodosa. J. Pediatr. 2007, 151, 675–678.
  46. Liu, Y.; Jesus, A.A.; Marrero, B.; Yang, D.; Ramsey, S.E.; Montealegre Sanchez, G.A.; Tenbrock, K.; Wittkowski, H.; Jones, O.Y.; Kuehn, H.S.; et al. Activated STING in a vascular and pulmonary syndrome. N. Engl. J. Med. 2014, 371, 507–551.
  47. Caratsch, L.; Schnider, C.; Moi, L.; Theodoropoulou, K.; Candotti, F.; Hofer, M. Adenosine deaminase 2 deficiency: A disease with multiple presentations. Rev. Med. Suisse 2022, 18, 669–673.
  48. Navon Elkan, P.; Pierce, S.B.; Segel, R.; Walsh, T.; Barash, J.; Padeh, S.; Zlotogorski, A.; Berkun, Y.; Press, J.J.; Mukamel, M.; et al. Mutant Adenosine Deaminase 2 in a Polyarteritis Nodosa Vasculopathy. N. Engl. J. Med. 2014, 370, 921–931.
  49. Zhou, Q.; Yang, D.; Ombrello, A.K.; Zavialov, A.V.; Toro, C.; Zavialov, A.V.; Stone, D.L.; Chae, J.J.; Rosenzweig, S.D.; Bishop, K.; et al. Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2. N. Engl. J. Med. 2014, 370, 911–920.
  50. Pagnoux, C.; Seror, R.; Henegar, C.; Mahr, A.; Cohen, P.; Le Guern, V.; Bienvenu, B.; Mouthon, L.; Guillevin, L. 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, 616–626.
  51. Georgin-Lavialle, S.; Terrier, B.; Guedon, A.; Heiblig, M.; Comont, T.; Lazaro, E.; Lacombe, V.; Terriou, L.; Ardois, S.; Bouaziz, J.; et al. Further characterization of clinical and laboratory features in VEXAS syndrome: Large-scale analysis of a multicentre case series of 116 French patients. Br. J. Dermatol. 2021, 186, 564–574.
  52. Meyts, I.; Aksentijevich, I. Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment. J. Clin. Immunol. 2018, 38, 569–578.
  53. Chung, S.A.; Gorelik, M.; Langford, C.A.; Maz, M.; Abril, A.; Guyatt, G.; Archer, A.M.; Conn, D.L.; Full, K.A.; Grayson, P.C.; et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Polyarteritis Nodosa. Arthritis Rheumatol. 2021, 73, 1384–1393.
  54. Terrier, B.; Darbon, R.; Durel, C.-A.; Hachulla, E.; Karras, A.; Maillard, H.; Papo, T.; Puechal, X.; Pugnet, G.; Quemeneur, T.; et al. French recommendations for the management of systemic necrotizing vasculitides (polyarteritis nodosa and ANCA-associated vasculitides). Orphanet J. Rare Dis. 2020, 15, 351.
  55. Ribi, C.; Cohen, P.; Pagnoux, C.; Mahr, A.; Arène, J.-P.; Puéchal, X.; Carli, P.; Kyndt, X.; Le Hello, C.; Letellier, P.; 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, 1186–1197.
  56. Samson, M.; Puéchal, X.; Mouthon, L.; Devilliers, H.; Cohen, P.; Bienvenu, B.; Ly, K.H.; Bruet, A.; Gilson, B.; Ruivard, M.; et al. Microscopic polyangiitis and non-HBV polyarteritis nodosa with poor-prognosis factors: 10-year results of the prospective CHUSPAN trial. Clin. Exp. Rheumatol. 2017, 35 (Suppl. 103), 176–184.
  57. Hadjadj, J.; Canzian, A.; Karadag, O.; Contis, A.; Maurier, F.; Sanges, S.; Sartorelli, S.; Denis, L.; de Moreuil, C.; Durel, C.-A.; et al. Use of biologics to treat relapsing and/or refractory polyarteritis nodosa: Data from a European collaborative study. Rheumatology 2022, 62, 341–346.
  58. Guillevin, L.; Fain, O.; Lhote, F.; Jarrousse, B.; Huong, D.L.T.; Bussel, A.; Leon, A. Lack of superiority of steroids plus plasma exchange to steroids alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome. A prospective, randomized trial in 78 patients. Arthritis Rheum. 1992, 35, 208–215.
  59. Machet, L.; Vincent, O.; Machet, M.C.; Barruet, K.; Vaillant, L.; Lorette, G. Cutaneous periarteritis nodosa resistant to combined corticosteroids and immunosuppressive agents. Efficacy of treatment with intravenous immunoglobulins. Ann. Dermatol. Venereol. 1995, 122, 769–772.
  60. Seri, Y.; Shoda, H.; Hanata, N.; Nagafuchi, Y.; Sumitomo, S.; Fujio, K.; Yamamoto, K. A case of refractory polyarteritis nodosa successfully treated with rituximab. Mod. Rheumatol. 2015, 27, 696–698.
  61. Ribeiro, E.; Cressend, T.; Duffau, P.; Grenouillet-Delacre, M.; Rouanet-Larivière, M.; Vital, A.; Longy-Boursier, M.; Mercié, P. Rituximab Efficacy during a Refractory Polyarteritis Nodosa Flare. Case Rep. Med. 2009, 2009, 738293.
  62. Al-Homood, I.A.; Aljahlan, M.A. Successful use of combined corticosteroids and rituximab in a patient with refractory cutaneous polyarteritis nodosa. J. Dermatol. Dermatol. Surg. 2017, 21, 24–26.
  63. Boistault, M.; Corbeto, M.L.; Quartier, P.; Arcobé, L.B.; Durall, A.C.; Aeschlimann, F.A. A young girl with severe polyarteritis nodosa successfully treated with tocilizumab: A case report. Pediatr. Rheumatol. Online J. 2021, 19, 168.
  64. Pașa, V.; Popa, E.; Poroch, M.; Cosmescu, A.; Bacusca, A.I.; Slanina, A.M.; Ceasovschih, A.; Stoica, A.; Petroaie, A.; Ungureanu, M.; et al. The “Viral” Form of Polyarteritis Nodosa (PAN)-A Distinct Entity: A Case Based Review. Medicina 2023, 59, 1162.
  65. Mekinian, A.; Grignano, E.; Braun, T.; Decaux, O.; Liozon, E.; Costedoat-Chalumeau, N.; Kahn, J.-E.; Hamidou, M.; Park, S.; Puéchal, X.; et al. Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: A French multicentre retrospective study. Rheumatology 2015, 55, 291–300.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
Video Production Service
Feedback