18F-Fluorodeoxyglucose positron emission tomography computed tomography detection of single organ vasculitis of the breast: A case report.

RATIONALE: Although single organ vasculitis (SOV) is a rare occurrence and it is difficult to diagnose, its possibility as a cause of fever of unknown origin (FUO) must be considered. Recently, the usefulness of 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG PET/CT) in the diagnosis of unknown fevers due to vasculitis, especially in cases of small and medium-sized vasculitis, has begun to be pointed out. PATIENT CONCERNS: We report the case of an 84-year-old woman with persisting fever for more than 2 weeks. She had no accompanying symptoms, other than fever, and the physical examination, echocardiography, and contrast-enhanced CT did not reveal any diagnostic clue. DIAGNOSES: The FDG PET/CT revealed positive uptakes of FDG in the left breast, with a standardized uptake value (SUV) of 2.9. The biopsy specimen of the left breast lesion revealed rupture of the elastic plate and evidence of fibrinoid necrosis of arteries, leading to the diagnosis of polyarteritis (PAN). Further angiographic examination and additional imaging did not reveal the presence of other lesions. Therefore, the diagnosis was established as a PAN-SOV of the left breast. INTERVENTIONS: This patient has improved with follow-up only. OUTCOMES: There has been no evidence of a relapse of PAN over a 5-year follow-up period. LESSONS: SOV presenting with unspecific local symptoms is difficult to diagnose based on the medical history and clinical examination. Our findings show that early "Combination of PET-CT and biopsy" can be a powerful diagnostic tool in patients with FUO for whom diagnosis of the underlying cause is difficult despite appropriate clinical examination.

Characteristics and Outcomes of Coronary Artery Involvement in Polyarteritis Nodosa.

BACKGROUND: Coronary artery involvement is a severe but uncommon manifestation of polyarteritis nodosa (PAN), so clinicians have little knowledge of it. Our aim was to investigate the clinical characteristics, risk factors and outcomes of patients with PAN complicated with coronary artery lesions. METHODS: Data from 145 patients with PAN who were admitted to Peking Union Medical College Hospital from January 2000 to September 2019 were retrospectively collected. RESULTS: Nineteen patients (13.1%) had coronary artery lesions due to PAN. The age at the onset of PAN was 32.3 ± 11.8 years. There were no significant differences in common risk factors for coronary arterial atherosclerosis between the patients with coronary artery involvement and those without. Affected branches of the coronary arteries were left anterior descending branch (15 patients), right coronary artery (14 patients), and left circumflex branch (9 patients). Eleven of the 19 patients exhibited multivessel lesions. Multivariate logistic regression analysis showed that celiac artery involvement (odds ratio [OR] 3.722, 95% confidence interval [CI] 1.115-12.427; P = 0.033) and new-onset hypertension (OR 6.668, 95% CI 1.936-22.961; P = 0.003) were risk factors for coronary artery involvement in patients with PAN. Stent placement was performed for 2 patients, and in-stent restenosis occurred in 1 of those patients a year later. CONCLUSIONS: PAN with coronary artery involvement exhibits more combined involvement of arteries of other organs and more severe diseases. PAN should be considered when treating young adults with an unknown origin of coronary artery lesions. In addition to systemic immunosuppressive treatment, other measures including antiplatelet and anticoagulation therapy should be initiated; however, determining the optimal time to perform procedures such as intervention or surgery is still challenging.

Clinical characteristics of patients with myalgia as the initial manifestation of small and medium-sized vasculitis: a retrospective study.

Myalgia is a common symptom in small and medium-sized systemic vasculitis, sometimes occurring as the initial or only clinical manifestation of vasculitis. This study investigated the clinical features and diagnostic process in patients presenting with myalgia as the initial symptom of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) or polyarteritis nodosa (PAN). We included 93 patients diagnosed with AAV or PAN by retrospectively reviewing their clinical records at the initial diagnosis. Clinical findings and diagnostic methods were assessed in patients with myalgia. Of 93 patients, myalgia was observed in 21 (22.6%) patients, with diagnostic classifications of microscopic polyangiitis (MPA) in 12 (52.4%), granulomatosis with polyangiitis in 2 (9.5%), eosinophilic granulomatosis with polyangiitis in 2 (9.5%), and PAN in 5 (23.8%). Myalgia was present in the lower extremities of all patients; more than 80% of patients had pain in the calf muscle. In 10 patients with myalgia, including 7 with MPA and 3 with PAN, muscle biopsy was performed because myalgia was the main symptom and no other impaired organs were suitable for biopsy. Consequently, 8 patients had necrotizing vasculitis, leading to MPA or PAN diagnosis, although muscle pathology was not evaluated in patients without myalgia. Muscle magnetic resonance imaging was useful in determining the biopsy site. Myalgia, especially in the lower limbs, may be an initial clinical sign of vasculitis, particularly in MPA or PAN patients. Moreover, the histological evidence of muscular vasculitis can contribute to a definite diagnosis especially in patients presenting with myalgia as an early symptom of AAV or PAN.

Provisional seven-item criteria for the diagnosis of polyarteritis nodosa.

Polyarteritis nodosa (PAN) is a potentially life-threatening systemic vasculitis, which predominantly involves medium arteries. However, it may be difficult to diagnose PAN in its early stage. The aim of our study was to investigate the sensitivity and specificity of the American College of Rheumatology (ACR) and the Japanese Ministry of Health, Labour and Welfare (MHLW) criteria for the diagnosis of PAN in a single-centre retrospective cohort in Japan and to develop simplified criteria with favourable diagnostic performance. All patients with "PAN" or "suspicion of PAN," as indicated on insurance forms, were included. The patient population was classified into PAN and non-PAN groups based on a retrospective chart review. The sensitivity and specificity of the ACR and MHLW criteria were calculated. Items that favourably discriminated the PAN group from the non-PAN group were determined and used as items for our provisional criteria. Thirteen cases of PAN and 24 cases without PAN were included in this study. The sensitivities of the ACR and MHLW criteria were 61.5% (8/13) and 30.8% (4/13), respectively, whereas the specificities were 79.2% (19/24) and 87.5% (21/24), respectively. We developed provisional criteria consisting of seven items, and found that a cut-off of ≥ 4 items had a sensitivity of 92.3% (12/13) and specificity of 91.7% (22/24) (p < 0.000001). The provisional seven-item criteria, developed in our real-world cohort of patients suspected of having PAN, had a high sensitivity and specificity and may be useful in the diagnosis of PAN, although it should be validated in additional patient populations.

Polyarteritis nodosa isolated to muscles-A case series with a review of the literature.

Muscular polyarteritis nodosa where disease is isolated to skeletal muscle is a rare and often poorly recognised clinical entity. Patients typically present with fever and severe muscle pain limiting ability to ambulate without rise in creatine kinase. Often there is a significant delay between presentation and diagnosis, which requires histological confirmation. Musculoskeletal MRI is a sensitive investigation that can lead to timely biopsy and improve diagnostic yield. Early diagnosis of this condition is essential as patients typically respond favourably to corticosteroid treatment. Here we report 4 cases of muscular polyarteritis nodosa and review the reported literature.

Segmental Arterial Mediolysis with Preceding Symptoms Resembling Viral Infection Hampers the Differentiation from Polyarteritis Nodosa.

A middle-aged man presented with a fever, arthralgia, gastrointestinal symptoms, headache, and rash. After two weeks, the patient suddenly complained of severe abdominal pain, and computed tomography revealed aneurysms in the hepatic and splenic arteries, which increased in size progressively. Given the elevated levels of inflammatory markers and orchitis, polyarteritis nodosa (PN) was initially suspected. Catheter embolization for the ruptured hepatic aneurysm and splenectomy for the large splenic ones were performed, and the pathological finding was consistent with segmental arterial mediolysis (SAM). Changes in inflammatory marker levels and aneurysmal size are also informative to differentiate SAM from PN.

Analysis of the Clinical Characteristics and Follow-up Study of Children with Cutaneous Polyarteritis Nodosa.

OBJECTIVE: This study aims to analyze the clinical characteristics, treatment and prognosis of children with cutaneous polyarteritis nodosa (CPAN), in order to improve the understanding of this disease. METHODS: Data of 14 children with CPAN, who were hospitalized in the Beijing Children's Hospital of Capital Medical University from January 2006 to December 2016, were collected. The clinical characteristics of all patients were summarized, the antistreptolysin-O (ASO)-positive and ASO-negative groups were compared, and the follow-up results were analyzed. X2-test, Fisher's exact probability test, t-test and Mann-Whitney test were used for statistical analysis. RESULTS: Among these 14 CPAN patients, nodular rash was the most common manifestation (14/14). The ASO-positive group had more nodules in the lower limbs and the ASO-negative group appeared more in the upper limbs, which were statistically significant (p<0.05). ASOpositive children were more likely to have joint symptoms (P<0.05), and were more prone to elevated white blood cells (P<0.05). Follow-ups were performed on nine patients, and the prognoses were all good. The occurrence of systemic polyarteritis nodosa was not observed. CONCLUSION: The main clinical manifestation of children with CPAN is skin nodules, which rarely affects the internal organs. Streptococcal infection is often the main cause. Anti-infection treatment should be simultaneously considered.

Four distinct clinical phenotypes of vasculitis affecting medium-sized arteries.

Objective: Within the spectrum of polyarteritis nodosa (PAN), cutaneous PAN (cPAN) is further classified into mild cPAN and severe cPAN which presents with ulcers, necrosis, or neuritis. As distinguishing between severe cPAN and systemic PAN can be difficult, this study evaluated the clinical characteristics of patients with necrotizing arteritis of medium-sized arteries. Methods: Forty-one patients diagnosed with necrotizing arteritis of medium-sized arteries between 2008 and 2017 at our institution were enrolled in this study. Clinical background, laboratory findings, treatments, and rates of relapse and death were evaluated. Results: Thirty-six patients were classified as having cPAN (mild, 15; ulcer, nine; neuritis, eight; both, four), and five cases manifested systemic vasculitis. Clinical characteristics of mild cPAN included female predominance (84.6%) and younger age (median 31 years); those of systemic PAN included older age (median 71 years) and higher levels of inflammatory markers. Severe cPAN manifested with intermediate phenotypes. The median doses of prednisolone used to treat mild cPAN, severe cPAN, and systemic PAN were 20.0, 40.0, and 40.0 mg/day, respectively. Immunosuppressants were used in 20.0% of mild cPAN, 90.5% of severe cPAN, and 80.0% of systemic PAN patients. Although the mortality rates were indistinguishable, the relapse rates of severe cPAN (ulcer type) were significantly higher than those of other types (88.9%). Conclusion: The clinical characteristics of mild cPAN, severe cPAN (ulcer type), severe cPAN (neuritis type), and systemic PAN were distinct from each other. In particular, patients with severe cPAN (ulcer type) had higher relapse rates, indicating the importance of combination therapy.

Childhood- versus Adult-Onset Polyarteritis Nodosa Results from the French Vasculitis Study Group Registry.

OBJECTIVE: To investigate differences between childhood (cPAN)- and adult-onset polyarteritis nodosa (aPAN) patients. METHODS: cPAN patients' clinical findings at onset and outcomes were compared to those of aPAN patients from the French Vasculitis Study Group registry matched for year of enrollment and initial systemic versus cutaneous disease. Their information on medications, disease activity and damage were collected. Kaplan-Meier relapse-free survival curves and the log-rank test were used to analyze cPAN versus aPAN differences for predefined outcomes. RESULTS: Twenty-one children with systemic and 13 with cutaneous PAN were compared with 84 systemic- and 27 cutaneous-matched aPAN patients. Median follow-up exceeded 5 years for both groups. At study entry, mononeuritis multiplex was less frequent in systemic cPAN than systemic aPAN (P = 0.04), and purpura and myalgias were less frequent in cutaneous cPAN than cutaneous aPAN (P < 0.03). During follow-up, systemic cPAN relapsed more often than matched systemic aPAN (P < 0.0001), while relapse rates were similar for cutaneous disease (P > 0.05). Mostly minor relapses, predominantly involving the skin, occurred in all 4 groups. At last visit, damage accrual was comparable for cPAN and aPAN patients, but fewer systemic cPAN patients were treatment-free (15% versus 42%; P = 0.03). Two (6%) cPAN and 8 (7%) aPAN patients died. CONCLUSION: Systemic PAN is equally severe in children and adults and carries a higher risk of relapse. The main cutaneous PAN features seem not to be influenced by age at disease onset.

Clinical and Laboratory Markers Associated With Relapse in Cutaneous Polyarteritis Nodosa.

Importance: In cutaneous polyarteritis nodosa (CPAN), less aggressive treatments can be selected, because CPAN is not associated with life-threatening or progressive outcomes. Although patients with a recurrent clinical course may require additional immunosuppressive therapies, no pretreatment factors associated with a worse prognosis in CPAN have been reported. Objective: To identify clinical or laboratory markers associated with relapse of CPAN. Design, Setting, and Participants: This retrospective case series was performed at a dermatology clinic of a tertiary referral center in Okayama, Japan, from October 1, 2001, through April 30, 2017. Of 30 patients identified with CPAN, the 21 with histopathologic evidence of disease were eligible and enrolled in the study. Main Outcomes and Measures: The medical database was examined for sex, age at diagnosis, affected anatomical sites, type and extent of skin lesion, laboratory data, initial therapies, duration of follow-up, and current status. Relapse was defined as the first reoccurrence or new onset of cutaneous disease that required further escalation of treatment with prednisolone at a dosage of greater than 20 mg/d and/or add-on use of immunosuppressant therapy, more than 6 months after initial treatment. The pretreatment factors were statistically evaluated between the groups without and with relapse. Results: The 21 patients included 5 males and 16 females with a median age of 49 years (range, 11-74 years) at diagnosis. The median follow-up was 42 months (range, 8-374 months). Pretreatment cutaneous ulcer was significantly associated with relapse between the 2 groups (0 of 11 in the nonrelapse group vs 4 of 10 in the relapse group; χ21 = 4.67; P < .05). In the laboratory test results, significantly higher mean (SD) values were observed in the relapse group for C-reactive protein level (0.23 [2.00] vs 6.03 [3.10] mg/dL; standard error of the mean [SEM], 3.40 mg/dL; 95% CI, 0.01-10.8 mg/dL; P = .01), absolute neutrophil count (ANC) (3.4 × 103/µL [1.1 × 103/µL] vs 6.0 × 103/µL [3.2 × 103/µL]; SEM, 2.9 × 103/µL; 95% CI, 1.9 × 103/µL to 14.6 × 103/µL; P = .001), neutrophil-to-lymphocyte ratio (1.4 [0.8] vs 2.8 [0.9]; SEM, 1.2; 95% CI, 1.1-4.9; P = .002), and systemic immune-inflammation index (5.1 × 105 [3.9 × 105] vs 11.7 × 105 [7.7 × 105]; SEM, 7.3 × 105; 95% CI, 3.3 × 105 to 31.1 × 105; P = .007). The estimated 2-year cumulative relapse rate was significantly high in the patients with blood ANC of greater than 4.9 × 103/µL compared with 4.9 × 103/µL or less (9 of 10 [90%] vs 2 of 11 [18%]; 95% CI, 6%-72%). Conclusions and Relevance: Pretreatment status of cutaneous ulcer, the serum C-reactive protein level, the blood ANC, the neutrophil-to-lymphocyte ratio, and the systemic immune-inflammation index are associated with a worse prognosis in CPAN.

Mortality in systemic necrotizing vasculitides: A retrospective analysis of the French Vasculitis Study Group registry.

OBJECTIVE: The aim of the study was to describe the evolution of mortality and cause-specific mortality over time in patients with systemic necrotizing vasculitides (SNV), including polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Patients with SNV from the French Vasculitis Study Group registry were divided into 5 groups according to the date of diagnosis: <1980, 1980-1989, 1990-1999, 2000-2010, and ≥ 2010. The causes of death were classified as vasculitis, infection, cardiovascular, malignancy, miscellaneous, or unknown. RESULTS: Among the 2217 patients included (PAN 16.1%, GPA 41.7%, EGPA 22.6%, MPA 19.6%), overall incidence of death was 2.26 per 100 person-years. The overall survival improved during each period considered. The 5-year survival rate increased from 72.2% (95% confidence interval [CI] 59.7-87.2) for patients diagnosed before 1980 to 94.5% (95% CI 90.4-98.8) after 2010 (p < 0.001). Periods of diagnosis, age, and male gender were independently associated with a poor survival with a non-significant difference between vasculitis. The incidence of mortality between the 1980s and after 2010 significantly decreased for vasculitis-related (p = 0.03) and cardiovascular-related deaths (p = 0.04). Incidence of death by infection remained stable between the 1980s and the 2000s but no death by infection occurred after 2010. The incidence of death by malignancy remained stable over time. CONCLUSION: Overall survival of SNV patients has improved since the 1980s with the decrease of vasculitis- and cardiovascular-related deaths, but cancer-related mortality remained stable. These results highlight malignancy as the current target to improve the overall prognosis.

Polyarteritis nodosa revisited: a review of historical approaches, subphenotypes and a research agenda.

Polyarteritis nodosa (PAN) is a rare form of primary systemic vasculitis with heterogeneous presentations, treatments and disease course. Historical approaches to classification and diagnostic terminology are reviewed. Since differentiation of PAN from microscopic polyangiitis (MPA) and other ANCA vasculitides by the Chapel Hill conference statements, and with hepatitis associated PAN defined as a secondary vasculitis, the phenotyping and subclassification of PAN has received little attention. Monogenic disorders similar to PAN have been described (familial Mediterranean fever, Adenosine Deaminase-2 deficiency), and cutaneous PAN and single organ vasculitis, discussed. The overlapping phenotypes between PAN and other primary vasculitic syndromes and subphenotypes within PAN are explored. This work will underpin development of newer treatment regimens and future genetic and related aetiologic studies.

A case report of cutaneous polyarteritis nodosa in siblings.

Cutaneous polyarteritis nodosa (CPAN) is characterized by a necrotizing vasculitis of small and medium-sized arteries in the skin, which can be associated with fever, arthralgia, myalgia, and neuropathy, but, unlike polyarteritis nodosa (PAN), there is no visceral involvement. CPAN is rare in childhood. We report two siblings who developed CPAN during childhood. Interestingly, both had Mediterranean fever gene (MEFV) mutation, i.e. heterozygous E148Q. They also shared HLA-A24, -DR15 alleles. Simultaneous occurrence of MEFV mutation and HLA alleles with CPAN has never been reported in Japan. These cases could provide some hereditary clue for the development of CPAN.

Accelerated atheromatosis and arteriosclerosis in primary systemic vasculitides: current evidence and future perspectives.

PURPOSE OF REVIEW: Primary systemic vasculitides (PSV) encompass a subset of autoimmune diseases, characterized by inflammation of blood vessels. Atheromatosis and arteriosclerosis may be accelerated in several PSV and account for the increased rate of cardiovascular morbidity that some exhibit. We aimed to summarize recent studies reporting on the acceleration of atheromatosis and/or arteriosclerosis in each type of PSV, using state-of-the-art noninvasive vascular biomarkers with clinical value as end points. RECENT FINDINGS: Limited number of PSV patients and methodology limitations reduce the value of many published studies. Accelerated atheromatosis, as measured by the use of carotid ultrasonagraphy (plaques and intimal-medial thickening) and increased arterial stiffening, as measured by the use of applanation tonometry (carotid to femoral pulse wave velocity), are currenly well established in Takayasu arteritis, Kawasaki disease and Behcet's disease. The association of atheromatosis and arteriosclerosis with polyarteritis nodosa and small vessel vasculitides remains less established and studied, so far. SUMMARY: Accelerated atheromatosis and arteriosclerosis or arteriosclerosis are established in some PSV. The potential clinical value of easy-to-measure and clinically useful noninvasive vascular biomarkes prompts the need for large prospective cohorts in order to provide useful future guidance regarding the prognosis and treatment of PSV patients.