Diagnosis Of Granulomatosis Research Articles

Utility of Peak Inspiratory Flow in Managing Subglottic Stenosis

To identify the utility of peak inspiratory flow (PIF) in the assessment and management of subglottic stenosis through correlation of clinical presentation with PIF. Case report. Review of the clinical course of a 31-year-old woman with the diagnosis of granulomatosis with polyangiitis. Repeated PIF measurements at clinic visits were obtained over a 30-month follow-up. Twenty-seven PIF measurements were obtained at 31 otolaryngology clinic visits. Correlations were identified between low PIF measurements with the clinical symptom shortness of breath (2.04±0.38 L/s, n=10), clinically recorded stridor at rest (1.64±0.41 L/s, n=3), and urgent operative intervention (1.60±0.23 L/s, n=5). Correlations were identified between high PIF measurement with patient report of normal breathing (3.07±0.35 L/s, n=16) and clinical observation of absence of stridor at rest (2.81±0.32 L/s, n=23). There was a statistically significant difference in the patient's PIF values with patient-documented shortness of breath vs no shortness of breath (P=.001) and clinician-noted stridor vs no stridor (P=.017). Peak inspiratory flow measurements correlate with degree of airway compromise and are helpful to monitor the degree of airway obstruction and document response to treatment.

P278 Extra-corporeal Membrane Oxygenation And Diffuse Alveolar Haemorrhage - A Single Centre Case Series And Analysis Of The Elso Database

Background Diffuse alveolar haemorrhage (DAH) is a potentially fatal complication of the systemic vasculitides and may present directly to the intensivist as a severe acute respiratory distress syndrome (ARDS) with reported mortality of 12- 60%. Whilst a severe respiratory failure (SRF) therapy strategy incorporating extracorporeal membrane oxygenation (ECMO) improves outcomes in ARDS, use of ECMO in DAH is often considered to be relatively contraindicated due to the requirement for systemic anticoagulation. Methods We present a case series of 4 patients with DAH due to underlying ANCA-associated vasculitides managed by a standardised diagnostic pathway and ARDS treatment algorithm in a single, UK SRF centre, since 2012. We analysed the Extracorporeal Life Support Organisation (ELSO) database and report on the current international experience of DAH and ECMO. Results The case series is described in Table 1. Median Lung Injury Score was 3.5. All patients received ECMO (median duration 8 days) and all received immunosuppression. One patient received normal heparin protocol to target APTTr 1.5–2 whilst two patients had 48 h of ECMO with no heparin followed by targeted sub-therapeutic low dose heparin. ICU survival was 100% and six month survival was also 100%. There were no exacerbations of pulmonary haemorrhage, no new events of extra-pulmonary haemorrhage and no clotting complications. ELSO The ELSO database contains 78 patients (adult, 59; paediatric, 19) with pulmonary vasculitides who received ECMO. 43 had a diagnosis of Granulomatosis and Polyangiitis (GPA), whereas the remaining diagnoses included hypersensitivity angiitis, Goodpasture’s syndrome and thrombotic microangiopathy. The median age was 23 yrs (IQR 16–47). The median duration of ECMO was 190hrs (IQR 146–282) and ICU survival was 82%. Twelve patients (15%) were reported to have thrombotic ECMO circuit complications. Conclusion In this case series, ECMO offers an excellent survival rate in SRF due to ANCA-associated DAH. ELSO registry data supports this, suggesting that ECMO should be considered as supportive therapy in DAH with SRF not responsive to conventional therapy.

Różnorodność objawów klinicznych jako przyczyna trudności w prawidłowym rozpoznawaniu ziarniniakowatości z zapaleniem naczyń

Istotą ziarniniakowatości z zapaleniem naczyń (<i>granulomatosis with polyangiitis</i> – GPA) jest występowanie martwiczego ziarniniakowatego zapalenia średnich i małych naczyń krwionośnych. Szczególnie narażone na rozwój choroby są drogi oddechowe oraz nerki.<br /> W pracy przedstawiono przypadek 65-letniej pacjentki, u której rozpoznano GPA. Występowanie niecharakterystycznych objawów klinicznych przyczyniło się do tego, że choroba pozostawała nierozpoznana przez długi czas. Objawem dominującym było oporne na leczenie, długo utrzymujące się owrzodzenie skóry prawego podudzia.<br /> Brak efektu terapeutycznego długotrwałego leczenia owrzodzenia powinien skłonić do poszerzenia diagnostyki i poszukiwania innych przyczyn dolegliwości. Rozwojowi powikłań w GPA zapobiega wdrożenie skutecznego leczenia, co jest możliwe dzięki szybkiemu ustaleniu rozpoznania.

A case of granulomatosis with polyangiitis complicated by cyclophosphamide toxicity and opportunistic infections: choosing between Scylla and Charybdis

BackgroundWe report a case of progressive Granulomatosis with Polyangiitis (Wegener’s Granulomatosis) with life-threatening complications of both the underlying disease and induction immunosuppressive therapy. Here, for the first time, cyclophosphamide toxicity and severe opportunistic infections including pneumocystis jirovecii- pneumonia were found in one case in a close temporal relationship.Case presentationA 34-year-old male patient of Caucasian ethnicity presented with acute renal failure necessitating hemodialysis treatment due to Granulomatosis with Polyangiitis (Wegener’s Granulomatosis). Kidney disease progressed to end-stage renal disease shortly after first diagnosis. After the 2nd bolus of cyclophosphamide shortly, induction immunosuppression (glucocorticoid/cyclophosphamide) was interrupted for repeat infections and resumed 5 years later. By that time, the lungs developed large pulmonary cavernae most likely due to smoldering granuloma indicative for the failed goal of disease remission. Therefore, induction immunosuppression was resumed. Following two monthly boli of cyclophosphamide, the patient developed pericardial effusion and, consecutively, atrioventricular blockade most likely due to cyclophosphamide. After recovery, the patient was discharged without cotrimoxacole. 10 weeks after the last cyclophosphamide bolus and 6 weeks after cessation of cotrimoxacole, the patient was readmitted to the intensive-care unit with Pneumocystis jirovecii pneumonia, and died 6 months later or 74 months after first diagnosis of Granulomatosis with Polyangiitis.ConclusionsThis case illustrates both the need for adequate immunosuppressive therapy to reach disease remission and the limitations thereof in terms of complications including cardiotoxicity of cyclophosphamide and Pneumocystis jirovecii pneumonia. In line with current recommendations, the present case strongly encourages pneumocystis jirovecii- pneumonia chemoprophylaxis for at least 6 months following induction therapy in Granulomatosis with Polyangiitis.

Developing of Granulomatosis with Polyangiitis during Etanercept Therapy

We describe a 67-year-old woman who developed c-ANCA positive vasculitis with involvement in eyes, skin, kidney, peripheral nerves, and upper and lower airway during treatment with etanercept therapy for rheumatoid arthritis. A diagnosis of Granulomatosis with Polyangiitis was done. Thus, anti-TNF therapy may be associated with the development of ANCA positive vasculitis.

Granulomatosis with polyangitis with mononeuritis multiplex-immunosuppressives playing a double-edged sword.

A 52-year-old female was diagnosed with rheumatoid arthritis and was on methotrexate and prednisolone. She developed fever, cough, hemoptysis, and cavitary lesion on chest skiagram. She was put on antitubercular therapy without any improvement, meanwhile she developed painful right foot drop. Clinicoradiology and C-ANCA study confirmed the diagnosis of granulomatosis with polyangitis (GPA). She was started on cyclophosphamide, corticosteroid, and co-trimoxazole. While her treatment was being continued she showed significant improvement of pulmonary manifestations. About 1 year later, there was reappearance of fever, cough, and radiological opacity with oropharyngeal candidiasis. She became very ill with disseminated intravascular coagulation (DIC)-like features. Immunological markers were negative but bronchoalveolar lavage fluid study showed growth of Aspergillus spp. The patient was promptly put on intravenous voriconazole but unfortunately she succumbed to her illness.

Hemorrhagic Acneiform Lesions in a Teenager as the Initial Presentation of Granulomatosis with Polyangiitis

A 19-year-old girl presented with hemorrhagic acneiform lesions on the face for several months that was unresponsive to conventional acne treatment. A biopsy revealed a noninfectious suppurative granulomatous dermatitis with hemorrhage, possibly representing a ruptured folliculitis. A second biopsy revealed chronic granulomatous dermal inflammation and hemorrhage with foreign body giant cells non-infectious by stains. No vasculitis was noted in either biopsy. Later in her course she developed a severe sinusitis and eventually presented with severe fevers, rapid weight loss, sinusitis, and cough. Further workup produced the diagnosis of granulomatosis with polyangiitis (Wegener's granulomatosis). She rapidly improved with intravenous steroids and rituximab. To date, acneiform lesions have only been reported in young adult patients and may represent a clinical manifestation of granulomatosis with polyangiitis unique to this age group, as illustrated in our patient.

Comparison of PR3-specific ANCA assays performance for diagnosis of granulomatosis with polyangiitis (GPA)

Comparison of PR3-specific ANCA assays performance for diagnosis of granulomatosis with polyangiitis (GPA)

Low-dose cyclophosphamide-induced acute hepatotoxicity

Patient: Male, 48Final Diagnosis: Low dose cyclophosphamide-induced acute hepatotoxicitySymptoms: Epigastric painMedication: Withdrawal of cyclophosphamideClinical Procedure: —Specialty: Nephrology • Hepatology • Gastroenterology • ToxicologyObjective:Unexpected drug reactionBackground:Cyclophosphamide is commonly used to treat cancers, systemic vasculitides, and kidney diseases (e.g., lupus nephritis and focal segmental glomerulosclerosis). Acute adverse effects include bone marrow suppression, hemorrhagic cystitis, nausea, vomiting, and hair loss. Hepatotoxicity with high dose cyclophosphamide is well recognized but hepatitis due to low dose cyclophosphamide has rarely been described.Case Report:We report the case of a 48-year-old Chinese man with a rapidly progressive glomerulonephritis secondary to granulomatosis with polyangiitis who developed severe acute hepatic failure within 24 hours of receiving low-dose intravenous cyclophosphamide. The diagnosis of granulomatosis with polyangiitis was supported with a positive c-ANCA serology. The patient was treated with high dose methylprednisolone, plasmapheresis, intermittent hemodialysis, and low-dose intravenous cyclophosphamide.Conclusions:Hepatotoxicity may occur even after low-dose intravenous cyclophosphamide treatment. To the best of our knowledge, this is the first report of severe, non-viral, liver inflammation developing within 24 hours of administration of low-dose intravenous cyclophosphamide (200 mg). Physicians should be aware of this serious adverse reaction and should not repeat the cyclophosphamide dose when there is hepatotoxicity caused by the first dose. Initial and follow-up liver function tests should be monitored in all patients receiving cyclophosphamide treatment.

A case of granulomatosis with polyangiitis (Wegener's granulomatosis) manifested with asymptomatic intracerebral hemorrhage

A 46-year-old man, who had had sinusitis, developed bilateral omalgia, petechiae on his lower extremities and a congested right eye. A blood test detected elevated serum C-reactive protein level. Computed tomography incidentally found an acute lesion of thalamic hemorrhage without neurological symptoms and no specific therapy was given at the time. Thereafter, he developed vertigo, vomiting and pneumonia for which antibiotics were ineffective. He was referred and admitted to our hospital. Further, aural and renal lesions, and presence of serum proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) confirmed his diagnosis of granulomatosis with polyangiitis (Wegener's) (GPA). With corticosteroid and cyclophosphamide therapy, his symptoms disappeared in two months along with faded PR3-ANCA. Afterward he showed neither new cerebral lesion nor symptom. This is a rare case of GPA manifested with asymptomatic intracerebral hemorrhage. It should be noted that GPA could cause various manifestations in central nervous system such as a fatal or an asymptomatic hemorrhagic lesion, which might respond to immunosuppressive therapy.

A Patient Presenting with Bilateral Lung Lesions, Pleural Effusion, and Proteinuria

Diagnosis and management of a systemic vasculitis are among the most demanding challenges in clinical medicine. A patient with a past history of cryptogenic organizing pneumonia presents with new bilateral lung lesions, unilateral pleural effusion, and significant proteinuria. The patient tested p-ANCA and anti-MPO positive but c-ANCA negative. A diagnosis of granulomatosis with polyangiitis GPA was reached after performing both renal and lung biopsies. Step-by-step differential diagnosis and management are discussed.

Granulomatosis with polyangiitis (Wegener’s) presenting as the right ventricular masses: A case report and review of the literature.

Granulomatosis with polyangiitis (Wegener's) is a systemic necrotizing vasculitis. Cardiac involvement in Wegener's has rarely been reported. In this study the echocardiographic findings of granulomatosis with polyangiitis (GPA) in a patient is described. The case was a 45 years old man admitted to the hospital with a 3 months history of persistent fever and sinusitis. Mild left and right ventricular enlargements as well as three small masses in the right ventricular cavity were identified in echocardiography. One mass was attached to the tricuspid valve and the other two masses were attached to the right septum. Pulmonary artery hypertension (45mmHg) was also reported. The masses responded dramatically to plasma exchanges in combination with steroid therapy, followed by oral cyclophosphamid and low-dose steroid therapy. In the kidney biopsy, 8 out of 11 golomeruli contained fibrous crescents along with sclerotic lesions. Spleen has 140 mm diameter with multiple echo-free lesions and coarse parenchyma in abdominal ultrasound. Serum C-ANCA=671, P-ANCA=1.7 (normal= up to 15U/mL). The diagnosis of granulomatosis with polyangiitis (Wegener's) was established. Presence of three small masses in right ventricular cavity and pulmonary artery hypertension in association with the spleen lesions were an uncommon presentation of GPA. GPA should be considered in the differential diagnosis of any nonspecific illnesses with cardiac involvement.

Multiple endocrine abnormalities

In September, 2008, a 48-year-old woman was admitted because of nausea, vomiting, and malaise. She had a history of maxillary sinusitis and otitis media. Physical examination was normal. Laboratory tests showed increased concentrations of infl ammatory markers (CRP 51 mg/L, ESR 90 mm/h), hypernatraemia (150 mmol/L), and hypercalcaemia (2·97 mmol/L, PTH 1·3 pmol/L). Central diabetes insipidus was confi rmed by high plasma osmolality and undetectable ADH. All other hormonal axes were tested and showed hypogonadotropic hypogonadism (LH <0·1 IU/L, FSH 1·2 IU/L), mild hyperprolactinaemia (1·36 U/L), and, surprisingly, primary hyperthyroidism (thyrotropin 0·006 mU/L, free thyroxine 24·2 pmol/L). MRI of her brain showed a diff use enlarged pituitary gland with a swollen stalk.Because chest radiography and CT showed multiple pulmonary infi ltrates, we suspected a granulomatous disease. Tuberculin skin test was negative, ACE concentrations were normal, but antineutrophil cytoplas matic antibodies (ANCA) were positive (c-ANCA 1:128, PR3-ANCA). Fluoro-D-Glucose FDG)- (PET-CT showed increased FDG uptake in the pituitary gland, left nostril, and left lung, and a focal active lesion in the left lobe of the thyroid gland (fi gure). Nasal biopsy showed active, chronic ulcerative infl ammation. Fine-needle aspiration of the thyroid lesion showed infl ammation with giant cells. A diagnosis of granulomatosis with polyangiitis (Wegener’s granulo-matosis) with pulmonary, nasal, pituitary, and probable thyroidal involvement was made. We treated our patient with 1000 mg methylprednisolone intravenously (3 days), followed by oral prednisolone (60 mg, tapering dose), and oral cyclophosphamide (2 mg/kg per day). Central diabetes insipidus was treated with oral desmopressin. There was no clinical need for oestrogen supplemention. Thyroid dysfunction and the hyper-calcaemia resolved soon after initiation of treatment. When last seen in May, 2011, she was in a good clinical condition without relapse.Pituitary insuffi ciency due to hypophysitis as the fi rst presentation of granulomatosis with polyangiitis is rare and therefore not the fi rst diagnosis that came to mind with our patient. The presence of pituitary-stalk thickening is the most striking radiological feature of an infl ammatory process involving the pituitary gland.