The University of Notre Dame Australia ResearchOnline@ND Medical Papers and Journal Articles School of Medicine 2020 Systemic vasculitides. Part 2: Small vessel diseases Sean M. Conte Peter R. Vale Follow this and additional works at: https://researchonline.nd.edu.au/med_article Part of the Medicine and Health Sciences Commons This article was originally published as: Conte, S. M., & Vale, P. R. (2020). Systemic vasculitides. Part 2: Small vessel diseases. Medicine Today, 21 (5), 21-27. Original article available here: https://medicinetoday.com.au/2020/may/feature-article/systemic-vasculitides-part-2-small-vessel-diseases This article is posted on ResearchOnline@ND at . For more information, please contact [email protected]. This article originally published: - Conte, S. and Vale, P.R. (2020) Systemic vasculitides. Part 2: Small vessel diseases. Medicine Today, 21(5): 21-27. Permission granted by Medicine Today for use on ResearchOnline@ND. © Medicine Today 2020 (http://www.medicinetoday.com.au). PEER REVIEWED FEATURE Systemic vasculitides Part 2: Small vessel diseases SEAN M. CONTE BA, MB BS; PETER R. VALE MB BS, FRACP, FCSANZ, FACC, FACP Small vessel vasculitides often manifest as neurological, renal, pulmonary and dermatological KEY POINTS symptoms. Clinical features of systemic vasculitides • The two main categories of small vessel vasculitis are are often nonspecific; therefore, it is important that antineutrophil cytoplasmic antibody-associated and GPs be aware of the range of symptoms that can immune complex-associated disease, best diagnosed help in the differential diagnosis, treatment and with renal and/or pulmonary biopsy. management of this diverse group of conditions. • Severe renal failure and pulmonary haemorrhage are high-risk features that require urgent management. • Eosinophilic granulomatosis with polyangiitis can be art one of this two-part series on systemic vasculitides associated with severe cardiac disease including heart covered the large, medium and variable vessel vascu- failure, conduction abnormalities and pericarditis. litides. We saw that most primary vasculitides are These complications account for half of the mortality typified by nonspecific systemic manifestations such as associated with this disease. Pfever, weight loss and lethargy but that classic presentations often • Hypocomplementaemic urticarial vasculitis and aid our diagnostic efforts. We also stressed the importance of cryoglobulinaemic vasculitis are commonly associated with underlying systemic conditions including identifying high-mortality and high-morbidity situations such inflammatory rheumatological disease, chronic viral as visual impairment in giant cell arteritis (GCA) and coronary hepatitis and haematological malignancies. These artery aneurysms in Kawasaki disease. should be screened for at the time of diagnosis. Part two will discuss small vessel diseases, a diverse group • Leukocytoclastic vasculitis is the most common of diseases often with neurological, renal, pulmonary and vasculitis encountered in clinical practice, only involves dermatological manifestations, which are summarised in Table 1. the skin and is most commonly associated with We will conclude with a summary outlining a general approach medication use. • Patients receiving long-term corticosteroid or immuno- suppressive therapy require dedicated screening for MedicineToday 2020; 21(5): 21-27 chronic iatrogenic complications such as diabetes mellitus, osteoporosis, hypertension, obesity, Dr Conte is a Medical Registrar and RACP Trainee at St Vincent’s Hospital, opportunistic infections and secondary malignancies. Sydney; and Clinical Associate Lecturer at UNSW, Sydney and the University of Notre Dame Australia, Sydney. Professor Vale is a Professor of Medicine at The University of Notre Dame Australia, Sydney; and a Vascular Physician and Cardiologist at Mater © HEALTH CARE/STOCK.ADOBE.COM Hospital, Sydney, NSW. MedicineToday ❙ MAY 2020, VOLUME 21, NUMBER 5 21 Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2020. SYSTEMIC vasculITIDES PART 2 continued TABLE 1. SUMMARY OF CLINICAL FEATURES AND ASSESSMENT OF SMALL VESICLE DISEASE VASCULITIDES Disease entity Clinical patient features Investigations and diagnosis Management options Granulomatosis with • Sinusitis • Cytoplasmic antineutrophil • Induction: corticosteroids + polyangiitis (GPA) / • Haemoptysis cytoplasmic antibodies: protease cyclophosphamide or rituximab microscopic • Haematuria 3 (granulomatosis with • Maintenance: azathioprine, polyangiitis (MPA) polyangiitis), myeloperoxidase methotrexate, rituximab (GPA) (MPA) Eosinophilic • Asthma, atopy • p-ANCA • Induction: corticosteroids +/− granulomatosis with • Mononeuritis multiplex • Eosinophilia cyclophosphamide polyangiitis • Cardiac conduction • Chest imaging (patchy opacities) • Maintenance: azathioprine, abnormalities • Surgical lung biopsy methotrexate, leflunomide • Anti-interleukin-5 monoclonal antibody Anti-glomerular • Haemoptysis • p-ANCA • Critical/Emergent: intubation, basement membrane • Haematuria • Myeloperoxidase dialysis disease • Acute renal failure • Antibodies against type IV • Initial: plasmapheresis + collagen on ELISA, western blot, corticosteroid + and immunofluorescence of renal cyclophosphamide or pulmonary biopsy • Alternate: rituximab or mycophenolate • Maintenance: low-dose prednisolone +/− second agent IgA-related vasculitis • Asian populations • Renal function • Uncomplicated: NSAIDs, rest, • Palpable purpura on lower • Urine sediment hydration limbs and buttocks • Urine protein • Proteinuria: ACE inhibitor or ARB • Migratory oligoarthralgia • Immunofluorescence of biopsy • Prolonged: low-dose prednisolone • Abdominal pain specimen (IgA) • Severe or marked renal • IgA nephropathy dysfunction: mycophenolate +/− cyclophosphamide Hypocomplementaemic • Constitutional symptoms • Low C3 and C4 • Mild: NSAIDs and antihistamines urticarial vasculitis • Chronic obstructive • Leukocytoclastic vasculitis on • Moderate: prednisolone + pulmonary disease biopsy colchicine, dapsone, • Mild renal dysfunction • Renal function and urinalysis hydroxychloroquine • Migratory polyarthritis • Hepatitis serology • Severe: mycophenolate • Associations: SLE, Sjögren’s • ANCA, antinuclear antibody, disease, drugs, HCV and extractable nuclear antigens, etc. HBV, complement deficiency, • Serum protein electrophoresis haematological malignancies and immunofixation Cryoglobulinaemic • Cutaneous manifestations • Screening for connective tissue • Mild: NSAIDs, rest hydration vasculitis • Arthralgias (hands, knees, diseases (SLE, Sjögren’s) • Proteinuria: ACE inhibitor or ARB ankles) • Screening for haematological • Moderate: low-dose prednisolone • Peripheral neuropathy malignancy (multiple myeloma, • Severe/prolonged: • Glomerulonephritis Waldenström’s) cyclophosphamide +/− • Evaluation of renal function and mycophenolate proteinuria • Renal biopsy Leukocytoclastic • Temporal relationship to new • Absence of evidence of major • Supportive care vasculitis or changed medication visceral involvement • Cessation of offending • Palpable purpura • Exclusion of systemic vasculitis medication • Maculopapular rash or infection • Perivascular neutrophils • Fibrinoid necrosis Abbreviations: ARB = angiotensin-receptor blocker; c-ANCA = cytoplasmic antineutrophil cytoplasmic antibodies; ELISA = enzyme-linked immunosorbent assay; HBV = hepatitis B virus; HCV = hepatitis C virus; IgA = immunoglobin A; p-ANCA = peripheral antineutrophil cytoplasmic antibodies; SLE = systemic lupus erythematosus. 22 MedicineToday ❙ MAY 2020, VOLUME 21, NUMBER 5 Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2020. to investigating and managing systemic 2. in those with pulmonary vasculitides. haemorrhage 3. in the presence of concomitant Classification and clinical anti-glomerular basement features membrane antibodies.3 Antineutrophil cytoplasmic Maintenance therapy is started once antibody-associated vasculitis corticosteroids are tapered, usually after Granulomatosis with polyangiitis and three to six months, and preferred agents microscopic polyangiitis are azathioprine or methotrexate. Rituxi- Granulomatosis with polyangiitis (GPA), mab is an alternative agent for maintenance formerly known as Wegener’s disease, therapy but is not recommended for MPO- Figure 1. CT of the chest in a patient with and microscopic polyangiitis (MPA) most ANCA positive disease.4 granulomatosis with polyangiitis. commonly occur in patients over the age Case courtesy of Radswiki, Radiopaedia.org, rID: 12079. of 65 years and more often in Caucasian Eosinophilic granulomatosis with populations, affecting men and women polyangiitis pulmonary biopsy. Surgical lung biopsy equally. GPA affects the respiratory and Eosinophilic granulomatosis with poly- revealing extravascular granulomas with glomerular epithelia producing haemop- angiitis (EGPA), formerly known as eosinophilic pneumonia is the gold stand- tysis and haematuria, respectively. Ear, Churg-Strauss syndrome, is a multi system ard diagnostic test for EGPA and is superior nose and throat (ENT) manifestations vasculitis of the small and medium-sized in demonstrating typical histopathology such as sinusitis, otitis media, ulcers, vessel with gradual onset in the second or to a transbronchial approach.6 Spirometry polychondritis and subglottic stenosis third decade of life. EGPA is typified by and pulmonary function testing typically are also classically