c-ANCA Titer Research Articles

Hepatic Artery Aneurysm in Granulomatosis with Polyangiitis

Large vessel involvement and arterial aneurysms are not typically encountered in Granulomatosis with Polyangiitis (GPA), which is a small vessel disease. We report the case of a 70-year-old male presenting with a ruptured hepatic artery aneurysm and elevated Antineutrophil Cytoplasmic Autoantibody, Cytoplasmic (c-ANCA) titer, 9 months after the diagnosis of GPA, while on maintenance therapy with rituximab. The liver aneurysm was successfully treated with coiling and reintroduction of prednisone. Large and medium vessel aneurysms can be seen in the context of GPA, which warrants a low threshold for screening and prompt intervention to prevent life-threatening rupture.

GRANULOMATOSIS WITH POLYANGIITIS MIMICKING ADULT RESPIRATORY DISTRESS SYNDROME WITHOUT PULMONARY HEMORRHAGE

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Granulomatosis with polyangiitis (GPA) is an antineutrophilic cytoplasmic antibody-associated small-vessel vasculitis affecting, but not often limited to, the upper respiratory tract, lungs, and kidneys. Pulmonary involvement varies in clinical presentations and chest imaging findings, making differentiation from pulmonary infections difficult. Granulomatosis with polyangiitis can clinically resemble Adult Respiratory Distress Syndrome (ARDS). This case highlights the challenges encountered in managing an atypical presentation of GPA mimicking ARDS CASE PRESENTATION: We present a case of 45-year-old female with history of chronic sinusitis, recurrent pneumonia and recent diagnosis of granulomatosis with polyangiitis. She presented with progressive shortness of breath, fever, and hypoxia. Initial labs revealed leukocytosis, elevated inflammatory markers and high c-ANCA titers. Her respiratory function worsened after admission and was subsequently intubated. She was diagnosed with severe ARDS due to the presence of bilateral infiltrates, P/F ratio < 100 mmHg, and high PEEP. Her imaging demonstrated pneumatocoeles on the left lower lobe (Figure 1). She received IV broad-spectrum antibiotics, however her respiratory function showed little improvement. She underwent bronchoscopy after intubation and no gross hemorrhage was seen. The bronchial alveolar wash showed elevated WBC levels, no RBCs, no organisms, and cultures were negative. On day 3 post-intubation, she was started on IV cyclophosphamide and high-dose steroids for 6 days, with remarkable improvement of respiratory status noted thereafter. Repeated labs revealed normalization of inflammatory markers and c-ANCA titers. The patient was successfully extubated after 10 days of mechanical ventilation support. DISCUSSION: ARDS comprises an unusual manifestation of this disease flare which can easily go undiagnosed. This case is notable not only for its rarity and benign course after successful treatment with immunosuppressive medications but also for the challenging differential diagnosis. Given the patient’s history of recurrent infections, acute presentation with elevated WBC, inflammatory markers, and fever, distinguishing infectious causes of ARDS from the acute flare of the underlying GPA was a challenge. CONCLUSIONS: Symptom persistence after antibiotic therapy is strongly suggestive of GPA flare even in the absence of pulmonary hemorrhage. Heightened suspicion when treating severe pulmonary failure in patients with GPA can contribute to an earlier diagnosis, better management, and potentially prevent life-threatening pulmonary injury. Reference #1: Tarabishy AB, Schulte M, Papaliodis GN, Hoffman GS. Wegener's granulomatosis: clinical manifestations, differential diagnosis, and management of ocular and systemic disease. Surv Ophthalmol. 2010;55(5):429-44. https://doi.org/10.1016/j.survophthal.2009.12.003. Reference #2: Nasser M, Cottin V. The respiratory system in autoimmune vascular diseases. Respiration. 2018;96(1):12-28. https://doi.org/10.1159/000486899. Reference #3: Reback M, Rahman RA, Donatelli C, Schilz RJ. A Case of Granulomatosis with Polyangiitis Masquerading as Fungal Pneumonia. Am J Resp Crit Care Med. 2018;197:A3057. DISCLOSURES: No relevant relationships by Saif El Naser El Nawaa, source=Web Response No relevant relationships by Mohamed Elmassry, source=Web Response No relevant relationships by Adnanul Karim, source=Web Response No relevant relationships by John Makram, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by Victor Test, source=Web Response

A CASE OF HEMORRHAGE RESCUED BY EXTRACORPOREAL MEMBRANE OXYGENATION

SESSION TITLE: Wednesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a well-known complication of many disease processes including vasculitides. DAH secondary to vasculitis, however rare, is one of the most devastating presentations of vasculidities carrying a substantial mortality. A significant percentage of patients with DAH progress to acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. Venovenous extracorporeal membrane oxygenation (VV ECMO) has been described to improve oxygenation in ARDS while underlying etiologies are addressed. The role of VV ECMO in DAH secondary to vasculitis is unclear. CASE PRESENTATION: A 37-year-old woman presented with severe ARDS. In the preceding two weeks, she experienced polyarthralgias and a lower extremity rash. She presented to the emergency department after developing hemoptysis which necessitated intubation. On presentation to the intensive care unit, she was afebrile and had an oxygen saturation of 95% on an FiO2 of 1. Of note, the patient had non-blanching, palpable, hemorrhagic bullae. Lab-work was notable for a white blood cell count of 13,600, a hemoglobin of 8.4 g/dL, a PaO2/FiO2 (P/F) ratio of 92, and urinalysis with protein and dysmorphic red blood cells. Computed tomography of the chest demonstrated diffuse infiltrates sparing the periphery. She was paralyzed and placed in a prone position for severe ARDS. She was started on pulse-dose steroids and on plasma exchange for suspected DAH. On day three, her P/F ratio was 61 and she was placed on VV ECMO. Bronchoscopy was performed with sequentially bloodier returns on alveolar lavage. Further workup revealed negative bacterial cultures, a positive ANA titer of 1:320, a C-ANCA titer of 1:40, and an elevated PR3 antibody. The patient was diagnosed with granulomatosis with polyangiitis and was started on cyclophosphamide. She was decannulated from ECMO after four days, extubated two days thereafter, and was discharged from the hospital in her premorbid state. DISCUSSION: The causes of DAH are varied but are commonly due to autoimmune phenomena. The current evidence for use of ECMO in DAH is limited to case reports and case series. Before the more widespread deployment of extracorporeal support, the treatment of respiratory failure from DAH was limited to aggressive ventilator management and immunomodulating medications. Despite progress in immunosuppressive therapy, the mortality for DAH remains unacceptably high. The deployment of ECMO may provide enough time with sufficient oxygenation for the causes of DAH to be addressed. CONCLUSIONS: Though there is a dearth of high-quality evidence justifying the use of ECMO in DAH, our case demonstrates that VV ECMO can be used successfully to temporize the hypoxemia in DAH. This measure could provide the time necessary for immunosuppression to take effect and reduce overall mortality from the most devastating consequence of vasculitis. Reference #1: Park M. S. (2013). Diffuse alveolar hemorrhage. Tuberculosis and respiratory diseases, 74(4), 51-62. Reference #2: Guo, Z., Li, X., Jiang, L. Y., & Xu, L. F. (2009). Extracorporeal membrane oxygenation for the management of respiratory failure caused by diffuse alveolar hemorrhage. The journal of extra-corporeal technology, 41(1), 37-40. Reference #3: West S, Arulkumaran N, Ind PW, Pusey CD. (2013). Diffuse Alveolar Haemorrhage in ANCA-associated Vasculitis. Internal Medicine, 52(1):5-13. DISCLOSURES: No relevant relationships by Lisa Daniels, source=Web Response No relevant relationships by Joshua Detelich, source=Web Response No relevant relationships by Maxwell Hockstein, source=Web Response

PULMONARY-RENAL SYNDROME: URINE TROUBLE WHEN YOU DEVELOP ALVEOLAR HEMORRHAGE

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Acute ANCA vasculitis with in-hospital development of alveolar hemorrhage results in significant mortality of up to 24%. Generally, diffuse alveolar hemorrhage has worsening prognostic outcomes in patients age > 60 years, particularly when associated with GFR < 60, tobacco abuse, cardiovascular disease, shock, and mechanical ventilation. Furthermore, ANCA-associated vasculitis has a 90% 2-year mortality if left untreated, which significantly decreases to 74% 5-year mortality in patients receiving prompt corticosteroid therapy. It is important to promptly recognize and treat late onset ANCA vasculitis, especially in patients requiring critical care admission. CASE PRESENTATION: We present an 80-year-old woman with medical history of hypothyroidism, diabetes mellitus type II, and hypertension. She was initially admitted for treatment of Clostridium difficile colitis. Despite clinical improvement of diarrheal illness after treatment with oral vancomycin, she was noted to have worsening acute kidney injury on hospital day 2. On hospital day 4, she had an acute drop in hemoglobin. On day 7, the patient's respiratory status began to decompensate with increasing hypoxia and work of breathing. She was transitioned to an intermediate level of care for high flow nasal cannula, and ultimately was placed on non-invasive positive pressure ventilation for refractory hypoxemia. Computed tomography (CT) imaging was notable for bilateral infiltrates and the patient was treated with broad spectrum antibiotics with concern for pneumonia, though she remained afebrile. She never experienced hemoptysis. On hospital day 10, the patient further declined requiring urgent intubation. Upon intubation, significant bloody secretions were noted. This was further evaluated with bronchoscopy with serial BAL aliquots, which proved to be progressively bloody, consistent with diffuse alveolar hemorrhage. Treatment with pulse dose steroids and plasma exchange was initiated. Serologic workup was consistent with granulomatosis with polyangiitis (GPA) as demonstrated by positive c-ANCA titer 1:640. The patient was started on rituximab, successfully extubated and discharged from intensive care in stable condition on hospital day 22. DISCUSSION: This case is especially interesting considering the new diagnosis of GPA in the inpatient setting following an admission for C. difficile colitis. She had no hemoptysis, no bloody diarrhea, prior diagnosis of CKD, nor other manifestations concerning for GPA. Her presentation was acute and atypical, and her mortality was ameliorated due to urgent intubation and immediate treatment. CONCLUSIONS: By initiating prompt steroid therapy and plasma exchange, this 80-year-old woman with significantly impaired GFR, shock requiring multiple vasopressors, and invasive ventilatory support, defied the expected outcome and significant mortality associated with late-onset granulomatosis with polyangiitis. Reference #1: de Prost N, Parrot A, Picard C, Ancel PY, Mayaud C, Fartoukh M, et al. Diffuse alveolar haemorrhage: Factors associated with in-hospital and long-term mortality. Eur Respir J. 2010;35:1303–11 Reference #2: Biscetti F, Carbonella A, Parisi F, et al. The prognostic significance of the Birmingham Vasculitis Activity Score (BVAS) with systemic vasculitis patients transferred to the intensive care unit (ICU). Medicine (Baltimore). 2016;95(48):e5506 DISCLOSURES: No relevant relationships by Meagan Marshburn, source=Web Response No relevant relationships by Sarah Ellen Stephens, source=Web Response No relevant relationships by Amanda Westbrook, source=Web Response

13. CMV Reactivation in refractory ANCA-associated vasculitis

IntroductionThe anti-neutrophil cytoplasmic antibody (ANCA) - associated vasculitides are a heterogeneous group of rare multisystem disorders characterised by inflammation and necrosis of small and medium blood vessels. Early diagnosis and prompt initiation of immunosuppressive treatment are essential to induce and maintain remission of disease, and thereby prevent severe life- or organ-threatening complications.We present a challenging case of a patient presenting with progressive lung lesions in the context of known ANCA-associated vasculitis (AAV), despite escalating immunosuppressive treatment.Case descriptionA 66-year old-female was diagnosed in 2010 with cANCA (PR3) positive vasculitis with lung involvement. Remission was induced with high dose steroids and cyclophosphamide. Methotrexate was given as maintenance treatment until 2013 when she had a significant renal relapse treated with plasma exchange, steroids and cyclophosphamide. Her maintenance treatment was changed to mycophenolate. She had a further lung relapse in 2014, treated successfully with high dose steroids and rituximab. She was eventually weaned off all treatment in 2017.She was admitted to hospital in 2019 with dry cough, dyspnoea and sinus congestion. She was noted to have several purpuric lesions on her limbs. Her CRP was elevated at 123 with a stable eGFR of 77. ANCA screen was negative. Chest Xray revealed bilateral consolidation. She was initially treated with six pulses of 500mg of IV methylprednisolone and one pulse of rituximab as an inpatient over the course of 2 weeks, with broad spectrum antibiotic cover. Despite this, she continued to deteriorate with a worsening purpuric rash and increasing oxygen requirement. She underwent plasma exchange with little improvement. CT of her chest revealed multiple progressive bilateral cavitating lesions.It was noted that her IgG levels were low (3.72) following rituximab, increasing her risk of infection. An atypical infection screen was performed and she was discovered to have cytomegalovirus (CMV) reactivation with high viral titres of 56889. She underwent bronchoscopic alveolar lavage which was positive for CMV on PCR. CT guided lung biopsy revealed necrotising granulomatous inflammation with occasional CMV positive nuclei.She was given valganciclovir and IV immunoglobulin, and her prednisolone dose was reduced to 10mg. This resulted in her viral load reducing to undetectable levels, her CRP improving to 23 and immunoglobulins normalising. This correlated with a clinical improvement allowing the patient to be discharged home.DiscussionThe patient in this case appeared in the first instance to have another flare of her AAV. However the flare was atypical in that it was not associated with an increase in her cANCA titre and it did not respond quickly to steroids as had been the case on each previous occasion. This prompted a reassessment of her case and investigation into other potential causes for her deterioration.CMV is a persistent herpesvirus which can affect up to 75% of healthy individuals. The primary infection is rarely symptomatic but can be associated with significant morbidity and mortality in immunocompromised patients. Pulmonary CMV disease can mimic pulmonary disease associated with vasculitis. CMV can also directly damage endothelial cells and cause an occlusive vasculitis itself.The patient was immunosuppressed, increasing her risk of acquiring primary CMV infection or developing CMV reactivation. She was given further potent immunosuppression during her admission. Serology is often unreliable in immunosuppressed patients and in this case her CMV IgG was positive with a negative IgM, indicating past CMV infection only. It is important to send samples for viral PCR to detect and diagnose active infection, and allow treatment to be initiated promptly.The lung biopsy was felt to be more in keeping with active AAV, although occasional CMV positive nuclei were present. The patient was therefore managed as having CMV reactivation in the context of active AAV.Treatment of viral infection can pose further challenges when trying to manage coexistent active vasculitis as highlighted in this case. Close monitoring of the patient was required, together with a multidisciplinary approach involving input from colleagues in infectious diseases and immunology, to allow the patient to be managed safely and effectively. Prophylactic antiviral therapy may need to be considered if further immunosuppression is required in future.Key learning pointsCMV reactivation can complicate treatment of ANCA associated vasculitis. Clinicians should have a low threshold to test for CMV in immunocompromised patients with vasculitis, particularly in cases which are atypical or refractory to standard treatment. Viral PCR should be tested, as serology can often be unreliable in immunosuppressed patients.Conflict of interestThe authors declare no conflicts of interest.

AN EXTREMELY RARE CASE OF DIFFUSE ALVEOLAR HEMORRHAGE IN A PATIENT WITH SCLERODERMA AND PREVIOUSLY UNDIAGNOSED GRANULOMATOSIS WITH POLYANGITIS

PURPOSE: To reinforce the sentiment that when DAH is present in the setting of worsening renal function, clinicians should always consider underlying vasculitides such as Granulomatosis with Polyangitis in their differential diagnosis as delay in treatment could lead to life-threatening complications such ARDS and worsening pulmonary renal syndrome. METHODS: Bronchial alveolar lavage was required to confirm the diagnosis of DAH. During bronchoscopy sample aspirated aliquots of fluid revealed persistently bloody returns that worsened with serial sampling. C-ANCA and Proteinase-3 Ab titers were ordered to confirm Granulomatosis with Polyangitis. RESULTS: A 75-year-old male with recent history of abdominal aortic aneurysm status post of AAA s/p endovascular aneurysm repair presents with dyspnea and hemoptysis. He requires intubation and mechanical ventilation. Bronchoscopy findings are consistent with DAH. He transiently improved on pulse steroid regimen, however soon became hemodynamically unstable and required vasopressor support and hemodialysis due to worsening renal function. He was ultimately found to be diagnosed with Granulomatosis with Polyangitis after his C-ANCA was 1:160 and Proteinase-3 Ab was 119.4. He was transferred for plasmapheresis and possible extracorporeal membrane oxygenation. CONCLUSIONS: The patient in this case report had considerable amount of risk factors contributing to his physical deterioration including scleroderma, recent history of pneumonia, recent EVAR, and initiation of clopidogrel therapy. CLINICAL IMPLICATIONS: Prompt diagnosis and treatment are necessary as the mortality rate increases by 60% in patients with granulomatosis with polyangitis in combination with DAH. There is high rate of relapse, with over 50% of patient’s relapsing within first 5 years and 25% relapsing within 2 years.

A Case of Rituximab Use as an Induction and Maintenance of Remission in ANCA-Associated Vasculitis

Antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is a multisystem autoimmune disease affecting mainly microscopic blood vessels due to circulating autoantibodies against neutrophil cytoplasmic antigens. We report a case of a 57-year-old female patient presenting with hemoptysis, sinusitis, and conjunctivitis. Based on lung biopsy, the diagnosis of antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) was established. She was put on rituximab as induction and maintenance therapy. She responded initially to rituximab as induction therapy but failed to respond in the maintenance course of the drug. Rituximab was stopped and mycophenolate mofetil was administered. She responded as laboratory c-ANCA titers turned negative and symptoms subsided. There are no randomized clinical trials addressing rituximab effect in induction and remission at the same time. This case report doubts the efficacy of the use of rituximab therapy for both induction and maintenance of remission at the same time, waiting for the results of the ongoing trials.

Cardiac Tamponade: An Uncommon Presentation of Granulomatosis With Polyangiitis

SESSION TITLE: Pulmonary Manifestations of Systemic Disease Case Report Posters SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 27, 2015 at 01:30 PM - 02:30 PM INTRODUCTION: Cardiac tamponade is a life-threatening condition requiring pericardial drainage to restore hemodynamic balance. We describe a case of tamponade as the presenting manifestation of granulomatosis with polyangiitis (GPA). CASE PRESENTATION: A 58 year-old farmer acutely developed chest pain and dyspnea. He was tachycardic, tachypneic and diaphoretic. He described a productive cough, recurrent sinusitis, malaise, polyarthralgias, night sweats and a 50 pound weight loss. On examination he appeared ill. Jugular venous pulsations were elevated, heart tones were distant and trace pretibial pitting edema was present. Labs demonstrated leukocytosis, anemia, thrombocytosis and normal renal function. Troponin-T was negative. Electrocardiogram revealed sinus tachycardia. Computed tomography ruled out pulmonary embolism but showed a pericardial effusion [image 1] with pericardial enhancement. Irregular nodules were noted in the right lung [image 2], as well as a left pleural effusion and mediastinal lymphadenopathy. Echocardiogram revealed right ventricular and atrial collapse and respirophasic flow reversal in the inferior vena cava, consistent with tamponade. Pericardiocentesis yielded 500 mL of sero-sanguineous fluid. Further studies revealed microscopic hematuria, erythrocyte sedimentation rate of 130 mm/hr, C-reactive protein of 203 mg/L, cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA) titer of 1:256 and markedly elevated proteinase (PR-3). Pericardial cytology and cultures were negative. Treatment for GPA was initiated with prednisone and cyclophosphamide, in addition to colchicine and indomethacin. Four months after diagnosis he is in remission. DISCUSSION: The reported frequency of cardiac involvement with GPA ranges from 6-44% (1); the largest GPA case series found a 10% overall incidence of pericarditis (2). To our knowledge this is the first description of tamponade leading to the diagnosis of GPA, though four cases of tamponade in the setting of established GPA have been previously described. This patient was successfully treated with pericardiocentesis and immunosuppression. CONCLUSIONS: Pericarditis is not uncommon in GPA and can rarely result in tamponade. Reference #1: Grant et al. Wegener's granulomatosis and the heart. Br Heart J. 1994 Jan;71(1):82-6. Reference #2: Hoffman et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992 Mar 15;116(6):488-98. Reference #3: Schiavone et al. Unusual cardiac complications of Wegener's granulomatosis. Chest. 1985 Nov;88(5):745-8. DISCLOSURE: The following authors have nothing to disclose: Erin Sullivan, Rodrigo Cartin-Ceba, Fabien Maldonado No Product/Research Disclosure Information

C1q nephropathy in the setting of granulomatosis with polyangiitis treated with tacrolimus.

C1q nephropathy in the setting of granulomatosis with polyangiitis treated with tacrolimus.

Wegener&amp;rsquo;s granulomatosis mimicking inflammatory bowel disease and presenting with chronic enteritis

Wegener’s granulomatosis, also known as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, is a small vessel vasculitis with primarily pulmonary, renal, and sinus disease manifestations. The prevalence of Wegener’s granulomatosis is three cases per 100,000 patients. Cardiovascular, neurologic, cutaneous, and joint manifestations have been reported in many case reports and case series. Gastrointestinal manifestations are less noted in Wegener’s granulomatosis, although they have been previously reported in the form of intestinal perforation and intestinal ischemia. Additionally, there are characteristic findings of vasculitis that are noted with active Wegener’s granulomatosis of the small bowel. We report a case of an elderly patient who presented with weight loss, diarrhea, and hematochezia. His symptoms were chronic and had lasted for more than 1 year before diagnosis. Inflammatory bowel disease or chronic enteritis due to Salmonella arizonae because of reptile exposure originally were suspected as etiologies of his presentation. The findings of proteinuria, renal failure, and pauci-immune glomerulonephritis on renal biopsy, in conjunction with an elevated c-ANCA titer, confirmed the diagnosis of Wegener’s granulomatosis with associated intestinal vasculitis. This case demonstrates an atypical presentation of chronic duodenitis and jejunitis secondary to Wegener’s granulomatosis, which mimicked inflammatory bowel disease.

Carbimazole-Induced, ANCA-Associated, Crescentic Glomerulonephritis: Case Report and Literature Review

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is a rare complication of antithyroid drug use that was first described with propylthiouracil. We describe an ANCA-associated rapidly progressive glomerulonephritis in a patient treated with carbimazole during 6 months for Graves disease that resulted in end-stage renal disease. A 66-year-old man treated with carbimazole for Graves disease was admitted for macroscopic hematuria and edema of the lower extremities. Laboratory work-up showed elevated serum creatinine (435 μmol/L), mixed hematuria, nephrotic range proteinuria, and a low positive c-ANCA titer with proteinase-3 specificity. Renal biopsy showed necrotizing, crescentic, pauci-immune glomerulonephritis. Carbimazole was discontinued and hemodialysis was initiated as well as high-dose glucocorticoids and pulses of intravenous cyclophosphamide. Despite immunosuppressive treatment, the patient remained dialysis-dependent at 6 months after diagnosis. Graves disease remained in remission after carbimazole withdrawal. ANCA-associated vasculitis manifesting as glomerulonephritis is a potential adverse effect of all antithyroid drugs. Although prognosis is usually good, end-stage renal disease may ensue in rare cases. Physicians should have a high index of suspicion in patients receiving antithyroid drugs who present with symptoms or signs suggestive of progressive renal disease.

Spectrum of clinicoradiological findings in spinal cord infarction: Report of three cases and review of the literature

Spinal cord infarction (SCI) often remains undiagnosed due to infrequent occurrence and lack of established diagnostic procedures. The unique pattern of blood supply explains the heterogeneity of clinical presentation. We present three cases of SCI to highlight the varied spectrum of clinicoradiological findings. The first patient had posterior spinal artery infarction, and spine imaging showed infarction of adjacent vertebral body, which is usually rare. The second patient had anterior spinal artery infarction and the cANCA titers were elevated. The third patient had a pure motor quadriparesis. Initial imaging did not show any cord infarction, but signal changes were noted on serial imaging. Fibrocartilagenous embolism (FCE) seems the most likely etiology in the first and third cases. A high index of clinical suspicion is necessary for prompt diagnosis. Sensitivity of the initial magnetic resonance imaging remains limited, necessitating serial follow-up scans. Infarction of the adjacent vertebral body is a useful confirmatory sign. Fat suppression images can delineate the marrow signal changes better. Elderly patients with vascular risk factors and degenerative discs need to avoid mechanical triggers that predispose to FCE. Younger patients with SCI will need evaluation for cardioembolic source and vasculitis.

A Case of Pulmonary Hemorrhage and Renal Failure

Background: Alveolar hemorrhage can be seen in many vasculitic disorders. However, granulomatosis polyangiitis (formerly Wegener's granulomatosis) uncommonly presents with life threatening alveolar hemorrhage and has only been discussed in a few case reports (1). Case Presentation: A 53 year old Caucasian male presented with hemoptysis and profound anemia. Two weeks prior, he had presented with abdominal pain with normal renal function and numerous pulmonary nodules. During the current admission, the patient was hypoxic with acute renal failure requiring hemodialysis. Urine sediment demonstrated dysmorphic red blood cells. A bronchoscopy revealed diffuse alveolar hemorrhage. The diagnosis of pulmonary-renal syndrome was made and therapeutic plasma exchange was initiated. Laboratory studies were significant for a c-ANCA titer positive at 1:640 FIU and anti-proteinase (PR)-3 antibody titer positive with 78.3 U/ml. Renal biopsy demonstrated necrotizing crescentic glomerulonephritis. A diagnosis of granulomatosis vasculitis was determined. Conclusion: Alveolar hemorrhage is rare to be the presenting symptom of granulomatosis vasculitis where the common presenting features are recurrent sinusitis, epistaxis, chronic otitis media or rhinitis. Physicians should consider granulomatosis vasculitis in the differential diagnosis of pulmonary-renal syndrome presenting with hemoptysis.

Wegener's granulomatosis--an unusual case of colonic haemorrhage

A 45-year-old lady presented to her local hospital with a 7-day history of flu like illness, sore throat, myalgia and bilateral polyarthralgia following a period with rhinitis and epistaxis. She had a vasculitic rash on her arms, legs, scalp and oral mucosa. She was tachypnoeic with low oxygen saturations. She had radiological changes in keeping with pulmonary haemorrhage (Figure 1). She was diagnosed with Wegener’s granulomatosis (WG) with a c-ANCA (antineutrophil cytoplasmic autoantibodies) titre of 1 in 320. She was treated with invasive ventilation, pulsed intravenous (IV) methylprednisolone (500 mg) and plasma exchange. She was further commenced on IV cyclophosphamide (5 mg/kg body weight every 21 days). Figure 1. Chest radiograph: pulmonary haemorrhage. On Day 10 post presentation she began to have significant fresh per rectal bleeding. She underwent multiple transfusions and bidirectional endoscopies. Gastroscopy did not show any abnormal findings, whereas, limited colonoscopy revealed an oedematous and inflamed mucosa with sigmoid and rectal sparing. Colonic biopsies performed at the time showed generalized vasculitis (Figures 2 and 3 …

Chromogranin A — A comparison of serum and plasma results from different ELISA kits

Antineutrophil cytoplasmic antibodies (ANCA) are used as diagnostic markers for systemic vasculitis. However,the specificity and sensitivity of ANCA detection differs from centre to centre due in large part to variations in methodology. We compared 8 commercial ELISA kits and an in-house method (HM) for their specificity and sensitivity in detecting ANCA against proteinase 3 (PR3-ANCA, 7 kits) and meyloperoxidse (MPO-ANCA, 8 kits). Sera from 5 patients with systemic lupus erythematosus (SLE), 28 with Wegener's granulomatosis (WG), 22 with microscopic polyangiitis (MPA), 5 with idiopathic rapidly progressive glomerulonephritis (RPGN), and 5 healthy controls were examined by both the indirect immunofluorescence technique (IFT) and the ELISA kits. Sera from healthy controls and patients with SLE or cANCA-negative WG were shown to be PR3-ANCA negative by all 7 PR3-ANCA kits. In 25 cANCA-positive sera from WG patients, PR3-ANCA positivity ranged from 44% to 84%. An absolute concordance among the 7 kits was noted in 56% of the cANCA-positive samples. The PR3-ANCA levels in 5 of the 7 kits correlated with the cANCA titers in IFT. Sera from the healthy controls and 4 out of the 5 SLE and pANCA-negative patients were found to be MPO-ANCA negative in all 8 MPO-ANCA kits. In 20 pANCA-positive sera, MPO-ANCA positivity ranged from 25% to 75%. Thirty-five percent of MPO-ANCA-positive sera were confirmed by capture ELISA, immunoblot and inhibition assay. The concordance rate was only 30% among pANCA-positive sera in the 8 MPO-ANCA kits. No significant correlation was observed between pANCA titers and MPO-ANCA levels. The HM showed that 65% of cANCA-positive sera were PR3-ANCA positive, and 45% of pANCA-positive sera were MPO-ANCA positive. Our results indicate that the sensitivities and specificities for ANCA detection differ significantly among the commercial kits tested and underline the necessity of establishing uniform international standards for ANCA ELISA procedures in order to permit more reliable interpretation and comparison of data.

A case of cocaine-induced panhypopituitarism with human neutrophil elastase-specific anti-neutrophil cytoplasmic antibodies

To describe a patient with cocaine-induced panhypopituitarism associated with human neutrophil elastase-anti-neutrophil cytoplasmic antibodies (HNE-ANCA). A 41-year-old man presented with extreme fatigue, cold intolerance and anorexia with 20 kg weight loss in the last 6 months. His medical history was unremarkable. He snorted cocaine twice a week during the last 6 years. On examination, we saw a pale and skinny man, with a normal blood pressure. Because of the severity of symptoms central hypothyroidism was suspected and very low values of TSH, free thyroxine and free triiodothyronine were measured. His FSH, LH, ACTH, cortisol, prolactin and testosterone levels were also low. Magnetic resonance imaging and computed tomography scan showed a normal-sized pituitary gland entirely embedded in a dense, oedematous, contrast-enhancing mass, and a total destruction of the nasal septum with the absence of conchae and severely impaired sinus walls. A transnasal biopsy showed an acute necrotising, non-specific and non-granulomatous inflammation. Although cocaine-induced panhypopituitarism was suspected, Wegener's granulomatosis could not be excluded. Serology on ANCA showed a strongly positive C-ANCA titre (320 U/l) with specificity for HNE. A cocaine-induced HNE-ANCA-associated panhypopituitarism was diagnosed. Our patient was advised to quit using cocaine immediately and was initially treated with glucocorticoids and testosterone, followed by thyroxine. This led to a dramatic clinical response with an increase of appetite, weight gain and regained energy. After 2 years, the patient is well and his ANCA titre is no longer positive. We describe the first documented case of cocaine-induced panhypopituitarism associated with HNE-specific ANCA.

Wegener’s granulomatosis effectively treated with rituximab: a case study

Wegener's granulomatosis (WG) is a granulomatous disorder associated with systemic necrotizing vasculitis. Wegener's granulomatosis predominantly involves the upper airways, lung and kidneys. The disease is often associated with cytoplasmic antineutrophil cytoplasmic antibodies (cANCA). B lymphocytes are potential cANCA producers and there is an evident correlation between cANCA titre, severity of the disease and response to treatment. Wegener's granulomatosis usually begins with symptoms limited mostly to the upper and/or lower respiratory tracts and may transform into the generalized phase, characterized by systemic necrotizing vasculitis. If left untreated, it can turn fulminant with poor prognosis. The severe form of the disease is usually treated with a combination of cyclophosphamide and corticosteroids. In refractory cases, rituximab that binds to CD20 expressed on B-cells should be considered. We presented a case of a 38-year-old woman with severe form of WG, refractory to standard therapy. Despite the standard treatment with cyclophosphamide and corticosteroids and the addition of infliximab with methotrexate, progression of the disease was observed. Exacerbation affected mainly the lungs and caused the gradual destruction of pulmonary tissue and development of respiratory insufficiency. Rituximab (500 mg) was given intravenously every week in four infusions, causing a partial remission of WG and the arrest of lung deterioration. The following administration of 500 mg was given every two weeks, which induced the remission of WG and enabled the patient to return to her normal activity and work. Such treatment appeared to be successful and prevented severe pulmonary involvement.

Acro-osteolysis and mononeuritis multiplex as a presenting symptom of systemic angiitis of Wegener's type

Wegener's granulomatosis is a multisystem disorder involving small- and medium-sized vessels, leading to granuloma formation and involvement of upper and lower respiratory tract with or without glomerulonephritis. However, limited forms of angiitis and granulomatosis of the Wegener's type with oligosymptomatic and atypical site involvement are known to occur. We present here a rare case of limited form of angiitis and granulomatosis of Wegener's type who presented sequentially with spontaneous resorption of digits with acro-osteolysis and mononeuritis multiplex over a period of 10 months. His vasculitic workup revealed high proteinase 3 antibodies (c-ANCA) titers and an almost asymptomatic lung involvement, detected on high-resolution computed tomography of chest. The patient was aggressively treated with immunosuppressive therapy, following which he showed good improvement.

Prediction of relapses in PR3-ANCA-associated vasculitis by assessing responses of ANCA titres to treatment

We performed a retrospective evaluation of whether c-ANCA titres (indirect immunofluorescence) and anti-proteinase 3 (PR3)-ANCA levels (ELISA) at diagnosis and following immunosuppressive treatment are predictive of relapse of ANCA-associated vasculitis. Patients diagnosed with PR3-ANCA-associated vasculitis between 1991 and 2002, with at least 2 yr of follow-up, and treated with cyclophosphamide and corticosteroids only (1991-1996) or switched to azathioprine after induction of remission with cyclophosphamide and corticosteroids (1997-2002) were included. ANCA were assessed by immunofluorescence and direct PR3-specific ELISA at diagnosis and 3, 6, 12, 18 and 24 months after diagnosis. Actuarial relapse-free survival was analysed with the log rank test. We studied 87 patients positive for PR3-ANCA: 46 were on cyclophosphamide maintenance therapy and 41 switched to azathioprine. Overall actuarial relapse-free survival was 72% at 2 yr and 34% at 5 yr. Relapse-free survival did not differ between patients on cyclophosphamide maintenance and patients switched to azathioprine maintenance (P = 0.34). Patients who became and stayed negative for c-ANCA (immunofluorescence) or PR3-ANCA (ELISA) until 24 months after diagnosis had a lower risk of relapse (P = 0.01 and P = 0.02, respectively). Positive c-ANCA (immunofluorescence) titres at 3 [relative risk (RR) 2.0; 95% confidence interval (CI) 1.2-3.8], 12 (RR 1.9; 95% CI 1.1-3.3), 18 (RR 2.9; 95% CI 1.3-4.6) and 24 months (RR 2.6; 95% CI 1.2-5.0) were significantly associated with relapse within 5 yr after diagnosis. PR3-ANCA levels >10 U/ml at 18 (RR 2.7, 95% CI 1.1-4.3) and 24 months (RR 4.6; 95% CI 1.2-6.3) were predictive of relapse within 5 yr. In the azathioprine group, a positive c-ANCA titre at the time of switching to azathioprine (RR 2.2; 95% CI 1.0-5.4) was associated with relapse. Positive c-ANCA (immunofluorescence) and PR3-ANCA (ELISA) titres during early follow-up identify patients at increased risk of relapse.

Diffuse granulomatous necrotizing scleritis

A 34-year-old man presented with anterior scleral thinning in the right eye (RE) and a painful nodular scleritis in the left eye (LE). Fundus examination showed a healed vasculitis and an inferior epiretinal neovascular membrane in the LE. Topical and systemic oral steroids and antiviral medication were prescribed. One year later, optic disc hyperaemia and swelling and macular oedema became apparent in the LE. Pulsed intravenous steroids were administered for 1 year, when a nasal septum perforation and vitreous haemorrhage in the LE were diagnosed. The eye was enucleated 3.5 years after the initial complaint. Necrotizing granulomatous tissue replacing the sclera and subconjunctival granulomatous tissue were observed. Six months later, oedema and neovascularization of the right optic disc were observed and cyclophosphamide was started, with regression of the clinical signs. No systemic abnormalities have so far become apparent. Posterior scleritis is most often observed in patients with no signs of associated systemic autoimmune disease. The diagnosis in this case is most probably one of Wegener's granulomatosis (WG). In WG, the diagnosis is based on necrotizing granulomas of the respiratory tract, generalized focal necrotizing vasculitis and focal necrotizing glomerulonephritis. Eye involvement with WG has been reported in up to 58% of cases. Evaluation of the scleritis patient should include a detailed medical history, chest X-rays, blood tests, autoantibody serology and analysis of urinary sediment. Cyclophosphamide is the treatment of choice for patients with ocular manifestations of WG, polyarteritis nodosa or rheumatoid arthritis, either alone or in combination with systemic steroids. Visual loss is expected in 85% of individuals with severe necrotizing posterior scleritis.