Diagnosis and management of ANCA associated vasculitis
BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e26 (Published 16 January 2012) Cite this as: BMJ 2012;344:e26
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Among the small vessel vasculitis which affects vessels like arterioles ,capillaries and venules.The common organ affected are kidney and lungs; the involve anti-neutrophil cytoplasmic antibody (ANCA) as a common pathogenesis .They can be detected by indirect immunofluoroscence and 2 staining pattern are known namely : perinuclear ( P-ANCA) and cytoplasmic ( C-ANCA) .he target organs of PANCA is myeloperoxidase (MPO) and for CANCA is proteinase 3(PR3) .These vasculitis leads to multi-organ involvement. Three major randomised controlled trials namely – CYCAZAREM,WGET,NORAM has been done to see the benefit of disease modifying drugs and induction of remission of approximately 90 % .Anti-B cell therapy ( elimination of B lymphocyte with anti-CD 20 antibody) have shown some benefit. Rituximab has found to have long term disease free remission [1]. This can also be a favourable option in DMARD –refractory case [2].Although leucopenia and infectious complication is a point of concern, but is still well tolerated with ANCA –associated vasculitis.
Reference:
1. Mansfield N, Hamour S, Habib A M, Tarzi R, et al.Prolonged disease free remission following rituximab and low dose cyclophosphamide therapy for renal ANCA associated vasculitis. Nephrology Dialysis and Transplantation, Oct 2011, 26/10 (3280 -6).
2.Szilasi M,Matyus J,File I,Szucs G, Rakoczi E et al.Association of ANCA –associated vasculitis –rheumatoid arthritis overlap syndrome in 4 patients : rituximab may be the right choice ? Autoimmunity, June 2012 45/4 (304-9).
Competing interests: No competing interests
To the Editor,
We read with interest the recent discussion of ANCA vasculitis.(1) We would however like to highlight a particular etiology that was omitted and deserves attention because it raises consequential implications regarding treatment.
Levamisole, an anthelminthic agent with immunomodulatory properties, is reported as an adulterant in the majority of cocaine samples.(2) As was the case when levamisole was used for various conditions in humans, we frequently see cocaine users with neutropenia and cutaneous vasculopathy.(3) In many of these cases, ANCA were specifically detected and in reports of cutaneous vasculopathy related to the use of cocaine adulterated with levamisole, histological studies often revealed a pattern consistent with leukocytoclastic vasculitis with or without thrombotic vasculopathy.(4)
The proper identification of cases related to levamisole-adulterated cocaine is of primary importance as the discontinuation of exposure is usually necessary and sufficient to reverse the pathology. Correct identification of these cases may prevent prolonged unnecessary use of immunosuppressive therapy.(4) It could also allow clinicians to offer the appropriate support for detoxification as the rate of recurrence of complications seems to be high after reexposure to levamisole, suggesting individual susceptibility.
Additionally, we note that cocaine alone is associated with midline destructive lesions where ANCA can also be detected.(4) Thus, we believe that cocaine use should be included in the differential of ANCA and vasculitic syndromes.
Alexandre Larocque MD
Centre Hospitalier de l’Université de Montréal – emergency medicine department
McGill University Health Center – clinical toxicology service
Centre Antipoison du Québec
Robert S. Hoffman MD
Associate Professor of Emergency Medicine and Medicine (Clinical Pharmacology)
New York University School of Medicine
Director, New York City Poison Center
References
1 Berden A, Goceroglu A, Jayne D, Luqmani R, Rasmussen N, Bruijn JA et al. Diagnosis and management of ANCA associated vasculitis. BMJ 2012; 344 :e26
2 Center for Disease Control and Prevention (CDC). Agranulocytosis associated with cocaine use: four states, March 2008 - November 2009. MMWR Morb Mortal Wkly Rep 2009; 58: 1381-5
3 Buchanan JA, Lavonas EJ. Agranulocytosis and other consequences due to use of illicit cocaine contaminated with levamisole. Curr Opin Hematol 2012; 19(1): 27-31
4 Specks U. The growing complexity of the pathology associated with cocaine use. J Clin Rheumatol 2011; 17(4):167-168.
Competing interests: No competing interests
Berden and Co-authors have composed a useful presentation of ANCA-associated vasculitis for the general reader. It is therefore disappointing that ophthalmic involvement, which is both statistically important and potentially devastating, has been virtually excluded from discussion and does not appear on the illustration of affected sites. Ophthalmic involvement in all ANCA-associated vascultis is well-reported, but especially in Wegener's granulomatosis, a substantial minority (up to half in some studies) present with ocular or orbital symptoms, and ultimately at least one half (ref 1) develop significant to substantial ocular pathology including necrotising scleritis or sclerokeratitis, orbitopathy, choroidal and retinal vascular occlusion, most manifestations causing severe pain and all being potentially blinding.
Physicians should be alert to the patient with chronic nasal crusting with bloody discharge, and painful red eyes.
Ref 1. Tarabishy AB, Schulte M, Papaliodis GM, Hoffman GS. Wegener's granulomatosis: clinical manifestations, differential diagnosis, and management of ocular and systemic disease. Surv Ophthalmol 2010;55:429-44
Competing interests: No competing interests
Re: Diagnosis and management of ANCA associated vasculitis
To the Editor,
With great interest we read the clinical review by Berden and co-authors regarding ANCA associated vasculitis.(1) However, we feel that cardiac involvement in this particular disease is underrepresented in this review.
As is known, ANCA associated vasculitis is characterized by necrotizing granulomatous lesions that affect different vessels and organs, most commonly the kidney and lungs. However, cardiac involvement is often underestimated or unrecognised, as such not stated in this manuscript. Its prevalence remains highly variable, ranging from 16% to up to 92%. Nevertheless, relatively larger studies using cardiac MRI report a prevalence of cardiac involvement of up to 62% and 80% in eosinophilic granulomatosis with polyangiitis (EGPA) (Table 1) and granulomatosis with polyangiitis (GPA), respectively.(2,3)
Importantly, recent studies demonstrate that cardiac involvement is an independent predictor of mortality(4,5), and approximately 50% of EGPA and GPA related mortality is caused by cardiac involvement.(4,6) Large trials have demonstrated that long-term immunosuppressive treatment not only improves survival, but may also resolve cardiac abnormalities in these patients.(7)
Therefore, special attention should be made for cardiac involvement, as early detection is crucial since treatment with adjunctive immunosuppressive agents may lead to improved outcome.
Reference:
1. Berden A, Goceroglu A, Jayne D, Luqmani R, et al. Diagnosis and management of ANCA associated vasculitis. BMJ 2012; 344 :e26
2. Dennert RM, van Paassen P, Schalla S, Kuznetzova T, et al. Cardiac involvement in Churg-Strauss syndrome. Arthritis and Rheumatism, Feb 2010 62/2 (627-34).
3. Miszalski-Jamka T, Szczeklik W, Sokolowska B, et al. Standard and feature tracking magnetic resonance evidence of myocardial involvement in Churg-Strauss syndrome and granulomatosis with polyangiitis (Wegener's) in patients with normal electrocardiograms and transthoracic echocardiography. Int J Cardiovasc Imaging. 2012.
4. Guillevin L, Cohen P, Gayraud M, Lhote F, et al. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore), Jan 1999 78/1 (26-37).
5. Mahr A, Katsahian S, Varet H, et al. Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis. Ann Rheum Dis. 2013;72(6):1003-1010.
6. Oliveira GH, Seward JB, Tsang TS, et al. Echocardiographic findings in patients with Wegener granulomatosis. Mayo Clin Proc. 2005;80(11):1435-1440.
7. Brihaye B, Aouba A, Pagnoux C, Vignaux O, et al. Rituximab reversed cardiac involvement of Wegener's granulomatosis: magnetic resonance imaging assessment. Presse Medicale Mar 2008 37/3 (412-5).
Authors:
M.R. Hazebroek MD, R. Dennert MD, PhD, S. Heymans MD, PhD
Maastricht University Medical Center, Department of Cardiology, Maastricht, The Netherlands
P. Van Paassen MD, PhD
Maastricht University Medical Center, Department of Nephrology and Clinical Immunology, Maastricht, The Netherlands
Competing interests: No competing interests