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Should immunosuppressives be stopped in granulomatosis with polyangiitis (Wegener's granulomatosis) patients undergoing dialysis?
Immunosuppressives are frequently stopped in patients with granulomatosis with polyangiitis (GPA) (Wegener's granulomatosis) who develop end-stage renal disease. This is done because of the high frequency of infections reported among dialysis patients under immunosuppressives and the former impression that GPA patients no longer experience relapses after the development of end-stage renal disease. We present here a 22-year-old male patient with GPA who had gastrointestinal, genitourinary and respiratory system involvement. The patient died because of a gastrointestinal disease activation that occurred after immunosuppressives were stopped at the initiation of dialysis. The decision to stop immunosuppressives while starting dialysis should be made on an individual basis in patients with GPA, and the risks and benefits should be carefully evaluated.
from: Department of Internal Medicine, Cerrahpasa Medical School, University of Istanbul, Turkey.
as reported in: Büyüktas D, Hatemi G, Tascilar K, Fresko I, Yurdakul S. Clin. Exp. Rheumatol.. 2012 Jan-Feb:30(1 Suppl 70):S104-6.
Granulomatosis with polyangiitis presenting as a renal tumor.
Inflammatory tumors of the kidney are uncommon and include primary inflammatory processes and systemic diseases such as sarcoidosis, IgG4 disease, and granulomatosis with polyangiitis (GPA). There are approximately 15 cases of the latter in the literature. Tumors in GPA are well described and have been reported in several organs including breast, orbit, mediastinum, central nervous system, and especially the lung. We report the case of a 48-year-old woman who presented with diffuse frontal headaches. Imaging showed both a cranial/sinus and renal mass. The pathology of the dura and nasal sinus biopsies were unrevealing. A nephrectomy was performed that demonstrated a discrete lesion with extensive necrosis, granulomatous inflammation, and crescentic pauci-immune glomerulonephritis, findings consistent with GPA.
from: Departments of *Pathology †Rheumatology, Harvard Medical School, Beth Israel Deaconess Medical Center ‡Department of Pathology, Harvard Medical School Massachusetts General Hospital, Boston, MA.
as reported in: Ward A, Konya C, Mark EJ, Rosen S. Am. J. Surg. Pathol.. 2014 Oct:38(10):1444-8. doi: 10.1097/PAS.0000000000000294.
See Published Case Report
Refractory pituitary granulomatosis with polyangiitis (Wegener's) treated with rituximab.
Granulomatosis with polyangiitis (GPA), also known as Wegener's granulomatosis, is an autoimmune disease characterized by inflammation of blood vessels most often seen in the upper respiratory tract, lungs, kidneys, and skin. Central nervous system (CNS) involvement of GPA is rare, particularly in the pituitary, and can be difficult to treat. Case report. We present a 30-year-old woman with pituitary and ocular GPA, whose unusually recalcitrant disease led to the development of pan-hypopituitarism and near-total vision loss. After failing multiple systemic immunosuppressants, she was ultimately treated with the novel immunomodulatory agent rituximab together with pulse corticosteroids, which achieved a gratifying response. Pituitary and optic chiasm involvement is a rare complication of GPA. We believe this case illustrates the complexity of management of pituitary GPA and provides insight into the potential utility of the biologic agent rituximab in this disease.
from: Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, CT 06519, USA.
as reported in: Hughes J, Barkhoudarian G, Ciarlini P, Laws ER, Mody E, Inzucchi SE, Woodmansee WW. Endocr Pract. 2013 Jan-Feb:19(1):e1-7. doi: 10.4158/EP12181.CR.
See Published Case Report
Granulomatosis with polyangiitis: recurrence presenting as ependimoplexitis.
A 55-year-old man with granulomatosis with polyangiitis (GPA) developed continuous parietal headache, malaise, nasal crusting and dry cough. Neurological exam revealed only left hand hypoesthesia in 4th and 5th finger. Brain MRI showed enlarged right choroid plexus, hyperintense periventricular white matter, thalami and right side of corpus callosum. The suspected diagnosis was ependimoplexitis due to GPA, the patient received three 500 mg methylprednisolone pulses followed by 1 mg/kg of meprednisone with gradual tapering and was switched to oral cyclophosphamide. He had complete resolution of headache. An MRI following this treatment for relapse revealed only minimal ependimal changes.
from: Section of Rheumatology and Immunology, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina..
as reported in: Pisoni CN, Ibańez S, Guevara M, Castro D, Romero Vidomlansky S. Clin. Exp. Rheumatol.. 2014 May-Jun:32(2 Suppl 82):S70-2.
A typical Wegeners granulomatosis -- but not pauci-immune!
We present a the case of 58-year old man who was admitted to hospital with typical clinical features (bloody nasal discharge, arthralgia, acute kidney injury with a nephritic syndrome) consisting with Wegeners granulomatosis (WG). CT-scan showed pulmonary nodules and antineutrophil cytoplasmatic antibodies (ANCA) were elevated. A kidney biopsy showed a crescentic glomerulonephritis, but not pauci-immune-immune with a histopathological staining of a mesangioproliferative IgA-glomerulonephritis. The patient was put on prednisolone and i.v. cyclophosphamid (CYCLOPS-protocol (1). The anti-proteinase-3 antibody titer decreased and the CT-scan showed decreased activity of Wegener's granulomatosis (BVAS 26 dropped to 2) and the patient`s serum creatinine level was stable. The exact nosological relation of mesangial IgA-nephropathy to WG is still unclear. This case underlines that knowledge of renal histology is essential in the management of patients with renal disease, especially in patients with hematuria and/or proeinuria with positive ANCA.
from: Department of Internal Medicine, Robert-Bosch Hospital, Stuttgart, Germany.
as reported in: Joerg L, Kerstin A, Niko B, Dominik A, Martin K, Latus J, Amann K, Braun N, Alscher MD, Kimmel M. Minerva Urol Nefrol. 2012 Jun:64(2):149-52.
Wegener's granulomatosis - a case report.
Wegener's granulomatosis is an uncommon multi-systemic disease characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tracts and general focal necrotizing vasculitis (commonly known as Wegener's triad). The diagnosis of Wegener's granulomatosis is suggested from the clinical and laboratory findings and from the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA) although the absence of ANCA does not exclude the diagnosis. We described a case of 27-year-old man with pansinusitis, mild azotemia and initial respiratory tract symptoms such as foul smelling nasal discharge and epistaxis. Later he developed fever, poly-arthritis, abdominal pain and haematuria. There were multiple painful oral ulcers and skin showed multiple palpable purpuric rash. C-ANCA was positive. He was treated with IV methyl prednisolone 1gm daily for 3 days followed by oral prednisolone 1mg/kg body weight and oral cyclophosphamide. His condition improved dramatically and on follow up after 3 months he was reasonably well. In this report, we wanted to emphasize that Wegener's granulomatosis, although rare, should be considered in the above clinical scenario and treatment should be initiated as soon as possible.
from: Department of Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
as reported in: Islam MA, Azad AK, Islam MS, Shazzad MN, Haq SA. Mymensingh Med J. 2013 Jan:22(1):196-9.
Pulmonary renal syndrome in a case of Wegener's granulomatosis.
We report a case of a 42-year-old patient who presented with Wegener's granulomatosis complicated by pulmonary renal syndrome, i.e., diffuse alveolar haemorrhage and rapidly progressive crescentic glomerulonephritis. The patient was treated with plasmapheresis and immunosuppressive drugs--intravenous cyclophosphamide and methyl prednisolone. The clinical, haematological and biochemical parameters improved substantially and remission is achieved.
from: Department of Pulmonary Medicine, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India.
as reported in: Kundu S, Misra S, Halder RK, Roychowdhury A. Indian J Chest Dis Allied Sci. 2013 Jan-Mar:55(1):49-52.
Interesting to me to read about cases in India and other places where we don't hear much about GPA. This case was very similar to mine.
Not everything that looks like GPA is GPA!
Culture-negative subacute bacterial endocarditis masquerades as granulomatosis with polyangiitis (Wegener's granulomatosis) involving both the kidney and lung.
Subacute bacterial endocarditis (SBE) occasionally exhibits positive cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) of the anti-proteinase-3 (PR-3) type. Clinically, it mimics ANCA-associated vasculitis, such as Wegener's disease with glomerulonephritis. Lung abscesses are the most common manifestation of lung involvement. We herein report a case of culture-negative SBE strongly c-ANCA/PR3-positive accompanied by pulmonary involvement and glomerulonephritis. In this case, we took biopsies of both the lung and kidney, although renal biopsy is usually preferred over lung biopsy. The lung biopsy showed severe alveolar capillaritis, suggesting vasculitis consistent with polyangiitis. The renal biopsy revealed glomerulonephritis with a membranoproliferative pattern. To our knowledge, this is the first such reported case. A 68-year-old Chinese male patient presented to our hospital with a fever, cough, chest pain, and recurrent peripheral edema. He had a past medical history significant for treated schistosomiasis 20 years previously. Physical examination revealed palpable purpura, mild hypertension, hepatosplenomegaly, and a holosystolic cardiac murmur (Levine 2/6). Echocardiography showed tricuspid valve vegetations with moderate to severe regurgitation. Serum c-ANCA/PR3 and cryoglobulin were strongly positive. Renal biopsy results indicated membranoproliferative glomerulonephritis with several crescents. Chest CT revealed multiple intraparenchymal and subpleural nodules, and lung biopsy showed polyangiitis. The patient's ANCA titers, glomerulonephritis, and pulmonary injury all resolved after antibiotic therapy. SBE may present with positive c-ANCA/PR3, multiple pulmonary nodules, pulmonary polyangiitis, and glomerulonephritis clinically mimicking granulomatosis with polyangiitis (Wegener's granulomatosis).
from: Division of Nephrology, Department of Medicine, The third affiliated hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People's Republic of China.
as reported in: Peng H, Chen WF, Wu C, Chen YR, Peng B, Paudel SD, Lou TQ. BMC Nephrol. 2012:13:174. doi: 10.1186/1471-2369-13-174.
See Published Case Report
Wegener's granulomatosis with pulmonary fungal infection: a case report and brief review.
Wegener's granulomatosis (WG) is an autoimmune, necrotizing granulomatous disease of unknown aetiology that affects small and medium blood vessels, and is usually recurrent. Infection is the most frequent cause of death in patients with WG. A case of WG with pulmonary fungal infection in a 50-year-old man is reported. The patient was hospitalized following a 2-month history of haemoptysis and a 1-month history of intermittent fever. Examination and pathology results confirmed a diagnosis of WG with associated pulmonary fungal infection. The patient's condition was complicated by a septic pneumothorax and sinus formation after lung biopsy, and preexisting diabetes and hypertension, which worsened rapidly due to his critical condition. He was treated with glucocorticoids and cyclophosphamide therapy with the goal of controlling these complications, and had no recurrence within the 4-year follow-up period. This case demonstrated the utility of combined glucocorticoid and cyclophosphamide therapy for the treatment of infection in WG.
from: Department of Respiration, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
as reported in: He Y, Liu J, Gao B. J. Int. Med. Res.. 2012:40(1):383-92.
A case of exorbitism in association with Wegener's granulomatosis with renal involvement.
Wegener's granulomatosis (WG) is a necrotizing granulomatous vasculitis involving the nose, paranasal sinuses, lungs, and kidneys. Ocular involvement can occur in about 50% of cases. There are very few reports of WG with orbital inflammation and exorbitism. We report a case of a female patient who presented with exorbitism related to orbital inflammation secondary to WG, with renal involvement. A 29-year-old woman with a previous history of recurrent pan-sinusitis presented with bilateral exophthalmos and renal failure with rapidly progressive glomerulonephritis. Computed tomography showed extensive bilateral soft tissue in the retro-orbital area. Immunologic tests showed the presence of type-C anti-neutrophil cytoplasmic antibodies and renal biopsy revealed pauci immune crescentic glomerulonephritis. The patient was treated with corticosteroids and pulses of cyclophosphamide followed by azathioprine and trimethoprim-sulfamethoxazole. After a follow-up of 10 months, the renal outcome was favorable with improvement of renal function but there was persistence of exorbitism and loss of visual function. Our case suggests that WG should be considered in the differential diagnosis of persistent bilateral exophthalmos. Prompt recognition of this early manifestation is important for the institution of early treatment.
from: Department of Nephrology, La Rabta Hospital, Tunis, Tunisia.
as reported in: Beji S, Fatma LB, Chebbi A, Rais L, Krid M, Smaoui W, Maiz HB, Zouaghi K, Moussa FB. Saudi J Kidney Dis Transpl. 2012 Mar:23(2):330-3.
Pregnancy in a patient with Wegener's granulomatosis: a case report.
Pregnancy in patients with Wegener's granulamotosis (WG) is rare, and differential diagnosis of WG flare and preeclampsia is difficult. A pregnant 35 year old with WG was referred with diagnosis of severe preeclampsia; caesarean section was performed. Intubation of the patient was difficult due to subglottic stenosis. Because of the clinical symptom, the case was considered preeclampsia, but p-ANCA of the patient was positive. In pregnancies with WG, differential diagnosis of WG flare-ups from preeclampsia should be made from clinical symptoms and laboratory findings. Serum ANCA titers are not useful in the differential diagnosis of WG flare-ups and preeclampsia because it may be positive in preeclampsia. Differential diagnosis of WG flare-up and preeclampsia should be made by clinical features. In the patients with subglottic stenosis, general anesthesia should not be preferred due to the probability of difficult intubation.
from: Department of Obstetrics and Gynecology, Zeynep Kamil Hospital, Istanbul, Turkey.
as reported in: Kayatas S, Asoglu MR, Selcuk S, Sargin MA. Bull NYU Hosp Jt Dis. 2012:70(2):127-9.
Multiple ileal perforations in a patient with Wegener's granulomatosis: a case report and literature review.
Wegener's granulomatosis (WG) is a chronic, multisystemic disease of unknown etiology characterized by necrotizing vasculitis and granulomatous inflammation. WG primarily involves the upper and lower respiratory tract and kidneys, but it may also affect multiple other organs or tissues, including the gastrointestinal system. Gastrointestinal involvement is an extremely rare manifestation of this disease. Moreover, during the course of WG, intestinal perforation is extremely rare in patients with gastrointestinal involvement. To our knowledge, only 13 WG cases with intestinal perforation have been reported in the English language literature as of September 2011. We herein present the case of a 47-year-old male patient with WG who was diagnosed with multiple ileal perforations and ileovesical fistulae. The exact pathogenesis of intestinal perforation in WG is not fully understood. However, early surgical intervention and appropriate management with immunosuppressive therapy can be important to lifesaving measures. A review of 13 cases reported in the English language literature is also discussed, together with the pathogenesis of this serious complication.
from: Department of Surgery, Diyarbakir Education and Research Hospital, 21400, Diyarbakir, Turkey.
as reported in: Akbulut S. J. Gastrointest. Surg.. 2012 Apr:16(4):857-62. doi: 10.1007/s11605-011-1735-z.
See Published Case Report
I had the swollen eyelids and sore eyes recently and thought it might be related to my Wegs. It seems Wegs can mimic or cause almost anything to happen in our bodies.
A 44-year-old man with bilateral eyelid swelling.
Swollen eyelids are commonly ascribed to allergic conjunctivitis, contact dermatitis, eczema, angioedema, or acute sinusitis. The differential diagnosis extends to thyroid eye disease; blepharitis; Sjögren's syndrome; Churg-Strauss vasculitis; Wegener's granulomatosis; Gleich syndrome; orbital and ocular lymphoid hyperplasia or adnexal lymphoma; idiopathic orbital inflammatory disease/idiopathic sclerosing orbital inflammation; rarely, orbital parasitosis; and IgG4-related diseases. The likely diagnosis proceeds from the more to the less common in patients without a history of allergy or infection. Both ocular lymphoid hyperplasia and ocular adnexal lymphoma must be considered in the differential diagnosis of persistent disease, and neither of these entities can be recognized or differentiated from one another clinically or radiologically. Early diagnosis is essential because therapy may consist of frequent follow-up and/or active intervention. Outcomes in patients treated early and appropriately are often favorable.
from: Section of Allergy and Immunology, Department of Medicine, St. Francis Medical Center, Trenton, New Jersey 08629-1986, USA.
as reported in: Ricketti AJ, Cleri DJ, Moser RL, Bilyk JR, Vernaleo JR, Unkle DW. Allergy Asthma Proc. 2012 Mar-Apr:33(2):205-11. doi: 10.2500/aap.2012.33.3523.
A case of ANCA-associated vasculitis presenting with calf claudication.
Wegener's granulomatosis (WG), Churg-Strauss syndrome, and microscopic polyangiitis (MPA) are closely related small vessel vasculitides characterized by anti-neutrophil cytoplasmic antibodies (ANCA). Although there were some reports of MPA presenting with claudication, there are very few reports on WG presenting with claudication of calf muscles. We report an unusual case of ANCA-associated vasculitis in a 75-year-old man who presented with bilateral calf claudication. Comprehensive evaluations, including electromyography, nerve conduction study, lower extremity magnetic resonance imaging, and Doppler scan, did not reveal any other cause of bilateral calf claudication. P-ANCA and anti-myeloperoxidase antibody was positive, but the anti-proteinase 3 antibody was negative. Chest computed tomography scan showed subpleural honeycombing and reticulation, predominantly in both basal lung areas. Biopsy of the calf muscle showed granulomatous vasculitis. Kidney biopsy was also performed which revealed focal necrotizing glomerulonephritis. Our patient does not exhibit typical clinical features for WG, but histopathologic findings of necrotizing granulomatous vasculitis in calf muscle biopsy is highly suggestive of WG.
from: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
as reported in: Kim MY, Bae SY, Lee M, Chung H, Lee J, Ahn JK, Cha HS, Koh EM. Rheumatol. Int.. 2012 Sep:32(9):2909-12. doi: 10.1007/s00296-010-1469-3.
See Published Case Report
Amazing where Wegs might show up?
Vasculitis reminds us that 'Ockham's razor' may still apply in the elderly.
A 76-year-old woman with a history of stage IV chronic kidney disease and hypertension was admitted to the hospital for progressive weakness and acute on chronic kidney injury. She was found to have anaemia requiring transfusion. On the evening of admission, she had worsening respiratory status with subsequent diagnosis of a non-ST-elevation myocardial infarction, pulmonary oedema on chest x-ray presumed to be a result of heart failure, and a possible transfusion reaction. A kidney biopsy performed as part of her ongoing nephrology evaluation revealed granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis). Subsequent bronchoalveolar lavage confirmed diffuse alveolar haemorrhage as the explanation for her anaemia and respiratory decline. She underwent immunosuppressive therapies and initiated dialysis, but subsequently chose hospice care and died 2 months after her diagnosis.
from: Department of Family and Community Medicine, University of Cincinnati/The Christ Hospital, Cincinnati, Ohio, USA.
as reported in: Mount HR. BMJ Case Rep. 2013:2013:. doi: 10.1136/bcr-2013-008685.
See Published Case Report (http://dx.doi.org/10.1136/bcr-2013-008685)
Heart blockage in a patient with cavitary lung lesions.
Cavitary lesions on a chest radiograph can be the manifestations of various diseases. The etiologies include abscess, mycobacterial infections, fungal infections, parasite infection, cavitary tumors, septic pulmonary embolism and vasculitis. While in comparison with the causes that could simultaneously develop a complete heart block, the differential diagnosis is limited. A 43-year-old man presented to the emergency department with a two-week history of dry cough, chest tightness and presyncopal symptoms.A chest radiograph showed patchy opacities in both lower lungs. A computed tomography of the chest revealed cavitary lesions bilaterally. The electrocardiogram showed a complete atrioventricular block. He was later diagnosed with Wegener's granulomatosis that involved nose, lung and heart. Cardiac involvements are not rare in Wegener's granulomatosis, but are not usually clinically apparent. A complete atrioventricular block is a rare but treatable manifestation of cardiac involvement usually indicating early active systemic disease. Patients presenting with cardiac abnormalities and evidence of systemic inflammation should be screened for Wegener's by history, radiographic and laboratory assessment.
from: Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
as reported in: Lin CH, Tsai SH, Chen HC, Chen SJ. Am J Emerg Med. 2012 Oct:30(8):1663.e1-3. doi: 10.1016/j.ajem.2011.09.011.
See Published Case Report
Malignant Wegener's granulomatosis with fibrosing mediastinitis and vena cava superior syndrome.
A 47-year-old man was admitted to hospital for migratory joint pain, fatigue, and cough with bloody sputum and proteinuria with increased serum creatinine level. Diagnosis of Wegener's granulomatosis was established. During follow-up, the vena cava superior syndrome developed. The patient died of respiratory failure after 12 years of follow-up. The autopsy revealed rigid, whitish, 12 mm thick tissue, which embedded and compressed the large vessels upwards from their origin in the heart, thus causing vena cava superior syndrome. This tissue was composed of fibrous material without inflammatory cellulization. We consider this fibrous tissue as a manifestation of fibrosing mediastinitis that may or may not share pathogenesis with Wegener's granulomatosis.
from: Department of Medicine, Charles University 2nd School of Medicine and University Hospital Motol, Prague, Czech Republic.
as reported in: Matousovic K, Martinek V, Spatenka J, Stejskal J, Chadimova M. Ren Fail. 2012:34(2):244-6. doi: 10.3109/0886022X.2011.647208.
See Published Case Report
These studies are a further reminder that our dumb disease is nothing to trifle with...
annekat
04-18-2015, 02:48 AM
Not everything that looks like GPA is GPA!
Culture-negative subacute bacterial endocarditis masquerades as granulomatosis with polyangiitis (Wegener's granulomatosis) involving both the kidney and lung.
That's a lot of articles, drz! Been doing your homework. This one caught my eye because my pulmy originally thought from my chest xray that I might have endocarditis. That's what got me into the hospital overnight for tests and eventually dx'ed with WG. I was a bit miffed because he had asked me if I'd used intravenous drugs, which I haven't, ever. He says that is a cause of endocarditis. And he seemed only marginally to believe me when I said no, I hadn't. Anyway, I thought this was interesting, since I hadn't heard it mentioned since then.
These studies are a further reminder that our dumb disease is nothing to trifle with...
Right on! And weird things can happen from it even if they are even more rare than the disease itself.
whatthewhat
04-18-2015, 05:04 PM
Turkey! Who knew?
whatthewhat
04-18-2015, 05:08 PM
Bey interesting thread! Thanks! And I agree - how interesting to read the locales of the studies.
SMW - Swiss Medical Weekly -*The role of rituximab in the treatment of ANCA-associated vasculitides (AAV) (http://www.smw.ch/content/smw-2015-14103/)
From this great Swiss study on using RTX
Treatment of AAV
Today, standard therapy consists of high-dose glucocorticoids plus intravenous or oral CYC over a period of 3–6 months for induction of remission [19 (http://www.smw.ch/content/smw-2015-14103/#REF19)]. Plasma exchange has also been used to treat cases characterised by alveolar haemorrhage and acute renal insufficiency [20 (http://www.smw.ch/content/smw-2015-14103/#REF20)]. With these treatments, remission rates are between 30–93% in GPA and 75–89% in MPA [19 (http://www.smw.ch/content/smw-2015-14103/#REF19)].
Once remission is achieved, this treatment is usually followed by maintenance therapy, since AAV are chronic diseases with a high risk of relapse. The use of azathioprine or methotrexate has replaced CYC in remission maintenance [21 (http://www.smw.ch/content/smw-2015-14103/#REF21), 22 (http://www.smw.ch/content/smw-2015-14103/#REF22)]. Despite current maintenance treatments, around 50% of responders still relapse within 3–5 years and the 1–year mortality remains at around 12–18% [23 (http://www.smw.ch/content/smw-2015-14103/#REF23)]. Furthermore, around 20% of survivors develop end-stage renal disease, adding to the clinical burden, which already includes increased incidence of cardiovascular disease, infections and malignancies [24 (http://www.smw.ch/content/smw-2015-14103/#REF24)]. The latter two are associated with the use of immune suppressive agents, e.g. CYC and glucocorticoids. Hence, a major focus has been to develop novel therapeutic strategies that reduce toxicity while retaining efficacy.
Conclusions
The approval of RTX not only provides a valuable alternative treatment modality, but encourages us to rethink the way in which we approach AAV. Today, the clinical challenge is shifting; in addition to reducing the disease burden, a key goal is to minimise treatment-related damage. RAVE, RITUXVAS and MAINRITSAN provide us with an important vantage point from which to assess the potential of RTX from a randomised, controlled perspective. Overall, the currently available data suggest (a.) equivalence of RTX to CYC for induction treatment with potential superiority of RTX in relapsing disease (after induction with CYC) and the potential to reduce some of the long term adverse effects of CYC and (b.) possible superiority of repeat RTX compared with azathioprine for maintenance therapy. The main disadvantages of RTX are the considerably higher price and the lack of very long-term data. When balancing the risks and benefits of AAV treatment the following conclusions can be drawn from the discussed evidence to aid in patient-tailored treatment decisions:
1. RTX is equivalent to CYC in inducing remission in severe AAV.
2. RTX could be considered as the preferred regimen in relapsing AAV (at least in RTX-naďve patients).
3. There is limited evidence for the use of RTX as induction regimen in patients with creatinine >354 µmol/l or pulmonary haemorrhage requiring mechanical ventilation at presentation. If RTX is used in these patients, the addition of low dose CYC and/or plasmapheresis should be considered.
4. RTX should be preferred over CYC in premenopausal women whenever possible, because of the potential induction of infertility (dose- and age-dependent in women) [83].
5. The efficacy of RTX in localised and granulomatous disease needs to be further studied.
6. RTX can be used as maintenance therapy as an alternative to azathioprine or MTX. The best treatment regimen will need to be defined as suggested strategies vary widely.
7. Contraception is mandatory in fertile women after RTX treatment owing to the lack of robust information on the effect of RTX on newborns.
Alysia
04-21-2015, 02:50 AM
Multiple ileal perforations in a patient with Wegener's granulomatosis: a case report and literature review.
Wegener's granulomatosis (WG) is a chronic, multisystemic disease of unknown etiology characterized by necrotizing vasculitis and granulomatous inflammation. WG primarily involves the upper and lower respiratory tract and kidneys, but it may also affect multiple other organs or tissues, including the gastrointestinal system. Gastrointestinal involvement is an extremely rare manifestation of this disease. Moreover, during the course of WG, intestinal perforation is extremely rare in patients with gastrointestinal involvement. To our knowledge, only 13 WG cases with intestinal perforation have been reported in the English language literature as of September 2011. We herein present the case of a 47-year-old male patient with WG who was diagnosed with multiple ileal perforations and ileovesical fistulae. The exact pathogenesis of intestinal perforation in WG is not fully understood. However, early surgical intervention and appropriate management with immunosuppressive therapy can be important to lifesaving measures. A review of 13 cases reported in the English language literature is also discussed, together with the pathogenesis of this serious complication.
from: Department of Surgery, Diyarbakir Education and Research Hospital, 21400, Diyarbakir, Turkey.
as reported in: Akbulut S. J. Gastrointest. Surg.. 2012 Apr:16(4):857-62. doi: 10.1007/s11605-011-1735-z.
See Published Case Report
Thank you so much drz for all the links. needs to make this thread a sticky one.
as for this article: colon involvement is not so rare. I have it and I have couple of weggies friends on facebook who have it too.
as for the perforations, I think that this is what killed Dodi's daughter. the docs didn't consider it an option.
actually, just like the saddle nose, wg can make "holes" everywhere. I think that the wg is what made holes in the lungs of my sweet Phil.
also, wg can affect every organ. not so rare. I have a friend with heart involvement.
Alysia
04-21-2015, 02:56 AM
Isr Med Assoc J. (http://www.ncbi.nlm.nih.gov/pubmed/19960854#) 2009 Sep;11(9):566-8.
Refractory Wegener's granulomatosis: effect of rituximab on granulomatous bilateral orbital involvement.Avshovich N (http://www.ncbi.nlm.nih.gov/pubmed/?term=Avshovich%20N%5BAuthor%5D&cauthor=true&cauthor_uid=19960854)1, Boulman N (http://www.ncbi.nlm.nih.gov/pubmed/?term=Boulman%20N%5BAuthor%5D&cauthor=true&cauthor_uid=19960854), Slobodin G (http://www.ncbi.nlm.nih.gov/pubmed/?term=Slobodin%20G%5BAuthor%5D&cauthor=true&cauthor_uid=19960854), Zeina AR (http://www.ncbi.nlm.nih.gov/pubmed/?term=Zeina%20AR%5BAuthor%5D&cauthor=true&cauthor_uid=19960854), Rosner I (http://www.ncbi.nlm.nih.gov/pubmed/?term=Rosner%20I%5BAuthor%5D&cauthor=true&cauthor_uid=19960854), Rozenbaum M (http://www.ncbi.nlm.nih.gov/pubmed/?term=Rozenbaum%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19960854).
author number 4 is my wg doc.
Israel is also on the map
Relapse Common in ANCA Vasculitis
Relapse Common in ANCA Vasculitis | Medpage Today (http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/50545)
Most patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who experienced non-severe relapses after immunosuppressive induction therapy were able to achieve only temporary remission with an increase in glucocorticoid dose, analysis of data from a double-blind study found.
Among 44 patients who had a non-severe relapse during 18 months of follow-up, 80% reached remission after an increase in prednisone dose to a median of 17.5 mg/day (range 2.5 to 80), according to John H. Stone, MD, director of clinical rheumatology at Massachusetts General Hospital in Boston, and colleagues.
However, in only 30% was remission maintained through the 18-month follow-up. The mean time to the second relapse was 9.4 months, and in almost half the relapses were considered severe, the researchers reported online in Arthritis and Rheumatology.
The primary types of ANCA-associated vasculitides are granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. The usual treatment of these conditions consists of induction therapy with cyclophosphamide, rituximab (Rituxan), or methotrexate, but during long-term follow-up more than half of patients relapse.
"Despite reports from some clinical trials that non-severe relapses are three times more common than severe relapses, the clinical course, treatment outcomes, and ultimate implications of such disease relapses remain largely unexamined," Stone and colleagues wrote.
Non-severe relapses are those that "do not pose immediate threats either to major organ function or the patient's life," they noted.
To address this gap, they analyzed data from the published Rituximab in ANCA-Associated Vasculitis trial (RAVE), in which patients with severe disease were treated with cyclophosphamide for 3 to 6 months and then given maintenance therapy with azathioprine through month 18, or were treated with four weekly infusions of rituximab followed by azathioprine or placebo. All patients received prednisone, intended to be tapered and stopped by 6 months.
For inclusion in the trial, patients had to have a Birmingham Vasculitis Activity Score (BVAS) of 3 or one major disease manifestation such as alveolar hemorrhage or serious renal disease. Remission was a BVAS of 0, and non-severe relapse was defined as an increase in BVAS of no more than 3 and no major disease manifestations. Severe relapse was a return to vasculitis activity necessitating cyclophosphamide plus high-dose steroid treatment.
Non-severe relapses were treated with an increase in prednisone dose determined by the investigator for a month, followed by tapering.
During the 18 months of follow-up, 44 patients had non-severe relapses, 41 patients had severe relapses, and 71 remained relapse-free. The average time until first relapse was 7.5 months.
Among patients who had non-severe relapses, 91% had granulomatosis with polyangiitis, 82% had the PR3 subtype of ANCA, and 64% had a history of relapsing disease at baseline.
More than half (55%) of patients with non-severe relapses had all three of those disease features, compared with 30% of those who remained in remission.
The most common manifestations of non-severe relapse were lung, eye, ear, and nose involvement.
The outcome following relapse did not appear to differ depending on whether high- or low-dose prednisone was used. For those who received 20 mg/day or more, 77% once again reached remission and 23% stayed in remission until the study conclusion, while the numbers for those given less than 20 mg/day were 82% and 36%.
A total of 36% of patients given high-dose prednisone had another non-severe relapse, as did 41% of those on the lower dose, while 41% of patients on the high dose had a severe relapse as did 23% of those on the low dose.
"The high rate of second relapses observed in this subgroup of patients suggests a need for a different treatment paradigm than used in the RAVE trial," Stone and colleagues observed.
One possibility could be B-cell depletion with rituximab rather than maintenance with azathioprine. In a recent clinical trial comparing these two agents for maintenance therapy in ANCA-associated vasculitis, more patients receiving rituximab remained in remission at 28 months.
The practice of continuing prednisone for long periods in these patients continues to be controversial.
"Although the follow-up period in this study was likely too short to detect differences in treatment-related adverse events or damage, a recent study of patients with rheumatoid arthritis demonstrated that treatment with prednisone 8 mg/day or higher was associated with an increase in death from any cause in a dose-dependent manner, suggesting that the long-term effects of chronic glucocorticoid use in doses required to maintain stability in granulomatosis with polyangiitis may be substantial," the researchers cautioned.
An ongoing study known as The Assessment of Prednisone In Remission (TAPIR) may help clarify the role of low-dose prednisone in these vasculitides.
A limitation of this study was the lack of standardization of prednisone doses.
The study was funded by the Immune Tolerance Network, the National Institute of Allergy and Infectious Diseases, the Juvenile Diabetes Research Foundation, Genentech, Biogen-Idec, the National Center for Research Resources, and the National Center for Advancing Translational Sciences.
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