Case report Fever in a patient with ANCA-associated vasculitis
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1 Case report Fever in a patient with ANCA-associated vasculitis
2 73 years-old white woman PRIOR MEDICAL HISTORY *Hypertension: Enalapril, Furosemide *Dyslipidemia: Pravastatin *Ischemic heart disease: 2008 Angina
3 *ANCA-associated vasculitis (MPO): #Jan/2011: (2 months) asthenia, anorexia, fever of unknown origin (37º-38ºC), arthralgia and myalgia CRP: 12 mg/dl ESR: 110 mm/h -Renal involvement (Proteinuria: 510 mg/24h, 4-10 RBC/f) Focal necrotizing glomerulonephritis with extracapillary proliferation -Neurological involvement: Mononeuritis multiplex -Immunology: p-anca, MPO 222 IU/ml -Microbiology (blood, urine, sputum): negative -CT body: Normal
4
5 Treatment: MYCYC Trial Prednisone (1 mg/kg/day) + Mycophenolate mofetil (1g bid) + Cotrimoxazol 800/160 mg/3 times per week During admission: *Acute coronary syndrome without ST elevation #Coronary angiography: critical lesion of descending artery and stent was placed. Bisoprolol, Aspirin, Clopidogrel *H1N1 Flu: treated with oseltamivir.
6 *ANCA-associated vasculitis (MPO): At 3 months, complete remission was achieved. Clinically without symptoms (only paresthesia) CRP: 1 mg/dl ESR: 28 mm/h -Renal involvement (Proteinuria: 153 mg/24h, 1-3 RBC/f) -Immunology: ANCA MPO 29 IU/ml Treatment: Prednisone (12.5 mg/day + MMF [1 g bid])
7 CURRENT DISEASE: #June/2011: (2 weeks) fever (38ºC), arthralgia and malaise -Physical examination: Alert, oriented. No skin lesions. No signs of arthritis. No lymphadenopathies. Normal breath sounds. Rhythmic heart sounds without murmurs or signs of heart failure. Abdomen: soft, painful deep palpation diffusely. No masses nor organomegaly. Preserved bowel sounds. Neurologic: Normal (paresthesia without changes) Preserved distal pulses. No signs of deep vein thrombosis. Thyroid size and consistency normal.
8 #Blood test: (abnormal results) -PCR 3.6 mg/dl (<1mg/dl). ESR 50 mm/h. -BCC: Leukocytes /l (80% neutrophils), Erythrocytes /l, hemoglobin 92 g/l, MVC 95 fl, Reticulocyte 4.5%. Iron 44 mcg/dl, folic acid and vitamin B12 normal. -Haptoglobin 2.92 g/l, Ferritin 341 ng/dl, Transferrin 2 g/l. -Creatinine 1.1 mg/dl, Liver function test normal. LDH 420 IU/L. Protein 50 g/l, Albumin 31 g/l. -Proteinogram: Increase of a-globulins 1 and 2 fractions (no monoclonality) -Urinalysis: Leucocytes 4-10/field, Erythrocytes 1-3/field. -24-hour Urine Collection: Protein 81 mg/24h. Prot-creat ratio 124 mg/g. -Beta 2 microglobulin 5 mg/l ( mg/l) -ANCA MPO 14.8 IU/l, ANCA PR3 Negative.
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10 In your opinion, this patient had.. 1.Urinary infection, of course 2.Probably, she had a vasculitis flare 3.She had fever as adverse event of MMF 4.Fever secondary to neoplasm (solid or hematological) 5.It doesn't matter! systemic steroids should be immediately increased
11 In addition to diagnostic work-up, what would you do? 1. I m sure that she had an urinary infection and antibiotics should be initiated 2. Vasculitis flare is the most probable option and corticosteroids should be increased 3. Be patient!! Paracetamol and wait for the results of diagnostic work-up
12 Diagnostic work-up and #Microbiology: -Blood Culture x 2: Negative. -Urine Culture: Negative. -Sputum Culture: Negative. #Echocardiogram: Normal. No vegetation. #Abdomino-pelvic CT: Normal. #Colonoscopy: Normal.
13 Evolution After 20 days of admission, the patient persisted with fever but clinically without changes CRP: 2.4 mg/dl ESR: 54 mm/h #Microbiology: -Blood Culture x 4: negative -Urine Culture x 3: negative -Sputum Culture: negative -Serology (EBV, CMV, Coxiella): negative #Gallium bone scan: Normal #Sinuses CT: Partial occupation of ethmoid air cells bilaterally #PET-CT: Normal
14
15 In your opinion, this patient had.. 1. An infection, I suppose 2. I was right!!, she had a vasculitis flare!! 3. A drug fever is a real option 4. Don t forget neoplasm (solid or hematological)!! 5. This patient is the typical case of factitious fever
16 In our opinion The patient had vasculitis activity Treatment: PDN 17.5 mg/day + MMF 3 g/day (MYCYC) Discharged at home.
17 But #Thoracic CT: Multiple pulmonary embolism and. #Doppler: Deep venous thrombosis in both legs Right: Superficial femoral, popliteal, posterior tibial and peroneal veins thrombosis Left: Superficial femoral vein thrombosis
18 Eureka!!!! PE is obviously the cause of the unknown fever 1. Yes, I m sure. ANCA-associated vasculitis are associated with high risk of thrombosis. 2. PE is only an incidental finding. 3. PE does not explain the unknown fever.
19 Evolution LMWH was started and. Gastrointestinal bleeding in the form of rectal bleeding (enterorrhage) Gastrointestinal endoscopy: gastric and duodenal ulcers Fever persisted without clinical and laboratory changes..
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21 Evolution LMWH was started and. Gastrointestinal bleeding in the form of rectal bleeding (enterorrhage) Gastrointestinal endoscopy: gastric and duodenal ulcers Fever persisted without clinical and laboratory changes.. A diagnostic test was performed..
22 #Pathologic study of ulcers: CMV inclusions #Microbiologic study: CMV PCR blood + 16,788 copies/ml Enterocolitis by CMV PE + DVT ANCA-vasculits Treatment: Ganciclovir with improvement of the patient
23 Discussion CMV infection PE + DVT ANCA-vasculitis
24 Discussion CMV infection PE + DVT ANCA-vasculitis
25
26 Incidence rate of venous thrombosis #83% of VTEs occurred within a period of 2 months prior to or following a diagnosis of active AAV Ann Intern Med 2005;142:620-6
27 198 patients: 143 WG, 34 MPA, 21 RLV Median follow-up period since diagnosis of AAV: 6.1 yrs (range: yrs).
28
29 Incidence of AAV-associated VTE during active and inactive disease Healthy population (same age) 0.3 #52% of VTEs occurred within a period of 3 months prior to or following a diagnosis of active AAV Rheumatology 2008;47:530-4
30 #Etiology *Endothelial lesion *Hypercoagulability *Relationship between WG and genetic factors predisposing to thrombotic events?? *CYC and corticosteroids?? Activity phase #Chronic inflammation does not seem to be an independent factor to thrombosis
31 Discussion CMV infection PE + DVT ANCA-vasculitis
32 CMV in patients with AASV is lower than that in transplantation 2.2% of patients Although valganciclovir and surveillance polymerase chain reaction (PCR) is available and used in transplant patients at a high risk of developing CMV, there are no recommendations for their use in patients with autoimmune disease on immunosuppression.
33
34 535 AAV patients ( ) Median duration of follow-up was 5.2 years 133 (25%) deaths were recorded
35 Causes of death within and after the first year of follow-up
36 Discussion CMV infection PE + DVT ANCA-vasculitis
37 Reported in the medical literature almost 100 times Theories: CMV triggers thrombosis by enhancing platelets and leukocytes adhesion to infected endothelial CMV increases the circulatory levels of factor VIII. CMV transiently induces production of anti-phospholipid antibodies Incidence of thrombosis among acute CMV infection hospitalized patients: 6.4% Incidence of acute CMV infection among thrombosis hospitalized patients: %. Most (n=64; 65.9%) reported patients were immunocompetent Mean age of reported patients was years. Female male ratio was 1:1 DVT/PE, splanchnic vein thrombosis and splenic infarction were the most prevalent thromboses associated with acute CMV infection
38 Discussion CMV infection PE + DVT ANCA-vasculitis
39 -Three patients with AAV (1 WG and 2 MPA) and PE-DVT associated with CMV infection. -All three patients were under treatment with CYC and CS (high dose). -CMV Reactivation: 2 cases (flu-like syndrome) 1 case (assymptomatic). -Probable etiology: Endothelium infection lead recruitment of inflammatory cells *Endothelial cells are infected by CMV and endothelium is the main reservoir of CMV during acute infection -Patients with AAV and active CMV infection should be treated with prophylactic anticoagulation.
40 Conclusions *Increased incidence rate of VTE in AAV. *Relationship with activity of AAV. *Etiology unknown. *CMV infection in AAV patients is rare. *There are no recommendations for the use of CMV PCR and prophylactic valganciclovir in patients with autoimmune disease on immunosuppression. *There are no recommendations of prophylactic anticoagulation in AAV patients with CMV infection.
41 Thank you for your attention
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