2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of Polyarteritis Nodosa

To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.

[Causes and mechanisms of systemic vasculitides]. / Causes et mécanismes à l'origine des vascularites.

Multiple mechanisms contribute to the pathogenesis of systemic vasculitides: 1. vasculitides resulting from the deposition of circulating immune complexes, comprising polyarteritis nodosa associated with hepatitis B virus infection, cryoglobulinemia associated systemic with vasculitides, mainly the consequence of hepatitis C virus infection, and Schonlein Henoch purpura, which results from the deposition in the mesangium and vessels of IgA forming complexes; 2. vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA), comprising Wegener's granulomatosis associated with anti-proteinase 3 ANCA, and microscopic polyangiitis and Churg-Strauss syndrome, associated with anti-myeloperoxydase ANCA. The pathogenic role of ANCA has been demonstrated in vitro and in vivo in the case of anti-myéloperoxydase antibodies, whereas it has only been demonstrated in vitro in the case of anti-proteinase 3 antibodies; 3. polyarteritis nodosa unrelated to viral infection results from rheologic phenomenon that explain the localisation of vasculitis lesions at the bifurcation of arteries and the presence of microaneurysm.

Cutaneous polyarteritis nodosa in children.

The purpose of this study was to present the clinical courses and histologic findings of 4 children with cutaneous vasculitis characterized by tender cutaneous nodules and fever in the absence of major organ involvement. We conducted a retrospective chart review of 4 patients with cutaneous vasculitis followed up for a mean of 68 months (range, 12-114 months). The patients included 3 boys and 1 girl (ages at onset, 2-10 years). Clinical and laboratory manifestations included tender erythematous cutaneous nodules (n = 4/4), fever 39 degrees C or higher (4/4), nondeforming arthritis (3/4), leukocytosis and elevated erythrocyte sedimentation rate (4/4), positive antinuclear antibodies (1/4), and elevated streptococcal enzymes (3/4). Skin biopsy results showed inflammation of medium-sized cutaneous arteries with a mixed inflammatory cell infiltrate consistent with cutaneous polyarteritis nodosa (4/4). Patients were treated with prednisone with good initial response, but exacerbation occurred once prednisone was tapered. Additional medications given were methotrexate (2/4), dapsone (2/4), colchicine (1/4), and cyclophosphamide (1/4). One patient is in clinical remission after 48 months of disease; the others have continuing disease that requires treatment. Patients with evidence of streptococcal infection received oral penicillin prophylaxis; two of the three patients had recurrent attacks of vasculitis despite penicillin. No patients have developed major organ system involvement after 12 to 114 months of follow-up. Cutaneous polyarteritis nodosa in children is a recognizable entity characterized by painful nodules, fever, absence of major organ involvement, and chronic or recurrent course. Patients should be screened for streptococcal infection and treated with antibiotics when needed.

Prolonged treatment with low-dose intravenous pulse cyclophosphamide may reduce rate of relapse in ANCA-associated vasculitis.

BACKGROUND: Cyclophosphamide has transformed the outcome of ANCA-associated vasculitis, but it is highly toxic. Recent studies have suggested that pulsed intravenous cyclophosphamide (pCyc) is an effective alternative with less complications, but may lead to an increased rate of relapse. However, these studies used relatively short courses of treatment with cyclophosphamide. In this study we used a prolonged course of low-dose intravenous cyclophosphamide for 18-24 months for ANCA-associated vasculitis, evaluated the effectiveness of pCyc and analysed the outcome of a prolonged treatment on the rate of relapse. METHODS: A retrospective analysis of all the patients treated with pCyc from 1995 to 2002 was performed. RESULTS: Thirty-seven patients were followed for an average of 38 months. Thirty-four of 37 patients (91.9%) achieved complete remission at 3 months. Eight (21%) episodes of relapse occurred in 7 patients. The cyclophosphamide was well tolerated with a low rate of infections (18.9%) and 1 death (2.7%) due to sepsis whilst on cyclophosphamide. CONCLUSION: In this study, pCyc was effective in achieving rapid remission and had a low complication rate. If prolonged, this treatment may reduce the rate of relapse.

Synergism between long-acting bromocryptine microcapsules and cyclosporine A in the prevention of various autoimmune diseases in rats.

Pre-treatment of male Sprague-Dawley rats with long-acting bromocryptine microcapsules (CBLA) significantly inhibited the arthritic response to Freund's complete adjuvant and reduced weight loss, thymolysis, splenomegaly and leukocytosis. In the prevention of adjuvant arthritis (AA), the combination of CBLA plus sub-optimal doses of cyclosporine A (CsA) was more efficient than either of the drugs alone. Sub-optimal doses of CsA were 0.1 and 1.0 mg/kg/day s.c. for 5 days. Furthermore, CBLA alone did not decrease the incidence of experimental allergic uveitis (EAU) in the male Lewis rats. Low-dose CsA reduced the incidence of uveitis by 50%, and with the addition of CBLA, 100% of rats were protected. Low-dose CsA was 2 mg/kg/day i.m. for 14 days. Long-term treatment of male Sprague-Dawley rats with CBLA alone reduced the incidence and severity of spontaneous autoimmune periarteritis nodosa (PN) in a dose-dependent manner; CsA was less potent than CBLA, and only additive effects were obtained. Finally, for the prevention of spontaneous autoimmune insulin-dependent diabetes (DM), the administration of CBLA did not improve the effect of a low-dose CsA in male BB rats. Nevertheless, a delay in onset of DM could be achieved. A sequential therapy using CsA plus CBLA clearly showed beneficial effects. The dose of CsA was 10 mg/kg p.o. 6 days/week for 21 weeks. Compared with Sprague-Dawley or Lewis male rats, BB male rats showed only weak prolactin suppression after the same doses of CBLA. It is suggested that the use of CBLA may be particularly beneficial in autoimmune disorders. The effectiveness of the combination therapy CBLA plus CsA, however, was dependent on the model considered. Various factors could play a role: (1) the different ways of administering CsA (s.c. in AA, i.m. in EAU and PN, oral in DM); (2) strain-dependency in the capacity of CBLA to suppress Prl secretion; and (3) at least in the BB rats, the transient increase of CsA bioavailibility which was possibly induced by CBLA.

Prevention of arterial disease in experimental renal hypertension.

1. This study examined the effect of various antihypertensive agents on the development of polyarteritis nodosa lesions along the mesenteric artery system over a 10 week period after renal artery clipping in uninephrectomized rats (lKlC). 2. Of the agents, only hydralazine, enalapril and diltiazem significantly inhibited systolic blood pressure (SBP) rise over the 10 week period (P less than 0.001). 3. All agents except hydralazine reduced the severity of arteritic lesions compared with lKlC rats, but only with enalapril (P less than 0.001), nifedipine (P less than 0.001), diltiazem (P less than 0.005), propranolol (P less than 0.001) and reserpine (P less than 0.05) was this reduction statistically significant. 4. There was a positive correlation between the degree of arteritic change and SBP, but the correlation coefficient was neither high (r = 0.68) nor highly significant (P = 0.03, d.f. = 9). On examining the data, this was due on the one hand to nifedipine, propranolol and reserpine reducing the severity of lesions without significantly inhibiting SBP, and on the other to hydralazine reducing SBP without significantly affecting the extent of arteritic change. 5. These findings suggest that factors other than mere SBP alone are involved in the pathogenesis of these arteritic lesions.