SESSION TYPE: Miscellaneous Case Report Posters IIPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM

INTRODUCTION:

Lung disease occurs commonly in rheumatoid arthritis (RA) and is associated with significant morbidity and mortality. Recently, Fischer and colleagues demonstrated that anti-cyclic citrullinated peptide (anti-CCP) positive individuals with airways or interstitial lung disease may represent a "pre-articular" RA phenotype.

CASE PRESENTATION:

A 61-year-old Caucasian man, with a 7.5 pack-year smoking history, seasonal allergies, gastroesophageal reflux disease, obstructive sleep apnea, and dyslipidemia presented with pleuritic chest pain and dry cough of five months duration. There was no improvement with two courses of oral antibiotics. There was no evidence of sinusitis, arthralgias, inflammatory arthritis, rash or other symptoms of connective tissue disease. Physical examination was only notable for crackles at the right lung base. His musculoskeletal exam was normal. Cardiopulmonary testing revealed a normal nuclear cardiac stress test, a negative ventilation/perfusion scan and normal pulmonary physiology. Thoracic high-resolution computed tomography (HRCT) images revealed multiple nodules and thick-walled cavities predominantly in the right lung (Figure 1). Latent tuberculosis assessment was negative. Autoimmune serologies demonstrated a high-positive anti-CCP, anti-Ro (SSA) and a weakly positive RF. C-ANCA, P-ANCA, anti-myeloperoxidase, anti-proteinase-3, anti-nuclear and anti-glomerular basement membrane autoantibodies were negative. Surgical lung biopsy revealed necrotizing granulomatous inflammation with geographic necrosis, vasculitis and lymphocytic pleuritis. The patient was started on oral corticosteroids with rapid clinical improvement. Two months after lung biopsy, as corticosteroids were tapered, he developed symmetric inflammatory arthritis involving the small joints of the hands, wrists, and feet with synovitis His arthritis responded to dose escalation of corticosteroids and injectable methotrexate which was initiated and rapidly titrated to 25 mg weekly. Corticosteroids were tapered off over the subsequent 3 months, while synovitis symptoms, pleurisy, and cough remained quiescent. Follow-up HRCT has demonstrated that the pulmonary cavitary nodularity is improving.

DISCUSSION:

In this report we demonstrate that pulmonary vasculitis may be a presenting feature of RA. Although vasculitis is a well recognized extra-articular manifestation of RA, it is usually considered to be associated with long-standing, severe, erosive, nodular, and sero-positive disease. RA-vasculitis may manifest with pyoderma gangrenosum, mononeuritis multiplex, or pulmonary vasculitis. Our findings highlight that severe pulmonary vasculitis may also occur as the first clinical feature of RA.

CONCLUSIONS:

A wide spectrum of lung disease, including pulmonary vasculitis, may be the presenting manifestation of RA.1) Genta M.S, Genta R.M, Gabay C. Systemic Rheumatoid Vasculitis: a review. Semin Arthritis Rheum 2006. 36:88-98DISCLOSURE: The following authors have nothing to disclose: Salvador de la Torre Carazo, Olga Tourin, Daniel Smith, Fischer AryehNo Product/Research Disclosure InformationHospital 12 de Octubre, Madrid, Spain.

Diffuse alveolar hemorrhage (DAH) is a life-threatening and medical emergency that can be caused by numerous disorders and presents with hemoptysis, anemia, and diffuse alveolar infiltrates. Early bronchoscopy with bronchoalveolar lavage is usually required to confirm the diagnosis and rule out infection. Most cases of DAH are caused by capillaritis associated with systemic autoimmune diseases such as anti-neutrophil cytoplasmic antibody-associated vasculitis, anti-glomerular basement membrane disease, and systemic lupus erythematosus, but DAH may also result from coagulation disorders, drugs, inhaled toxins, or transplantation. The diagnosis of DAH relies on clinical suspicion combined with laboratory, radiologic, and pathologic findings. Early recognition is crucial, because prompt diagnosis and treatment is necessary for survival. Corticosteroids and immunosuppressive agents remain the gold standard. In patients with DAH, biopsy of involved sites can help to identify the cause and to direct therapy. This article aims to provide a general review of the causes and clinical presentation of DAH and to recommend a diagnostic approach and a management plan for the most common causes.

Goodpasture's syndrome is a triad of alveolar hemorrhage, Glomerulonephritis and circulating anti Glomerular basement membrane antibodies, 25% of cases test positive for ANCA antibodies, this association is known as Double positive disease. This article describes a rare presentation of this entity and reviews available literature.80 year old female presented with hemoptysis and renal failure, she tested positive for both p ANCA and anti glomerular basement membrane antibodies, and despite aggressive medical treatment, she suffered a frustrating outcome.Double positive disease accounts for 25% of cases of Goodpasture's syndrome, a suggested Pathophysiology of this association is the renal involvement in ANCA Vasculitis leading to the exposure of antigens from the basement membrane and the formation of antibodies. This entity is believed to carry better prognosis when compared to isolated anti glomerular basement membrane disease.

Pulmonary renal syndrome (PRS), denoting the presence of diffuse alveolar hemorrhage and glomerulonephritis as manifestations of systemic autoimmune disease, is very rare in childhood. The coexistence of circulating anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) disease in children affected by this syndrome is exceptional, with unfavorable outcome in five out of seven patients reported to date. We describe a child with PRS associated with both circulating anti-myeloperoxidase (anti-MPO) ANCA and anti-GBM disease on renal biopsy who was successfully treated with immunosuppressive therapy.A 10-year old girl presented with fever, fatigue, malaise, and pallor followed by hemoptysis and severe anemia. Diffuse alveolar hemorrhage was revealed on fiberoptic bronchoscopy. Renal findings consisted of microscopic hematuria, moderate proteinuria, and anti-GBM disease on renal biopsy. ANCA with anti-MPO specificity were present whereas anti-GBM antibodies were on borderline for positivity. Methyl-prednisolone pulses followed by prednisone led to cessation of hemoptysis, marked improvement of lung fuction, and normal finding on chest x-ray within 10 days. An immunosuppressive regimen was then given consisting of prednisone daily for 4 weeks with subsequent taper on alternate day, i.v. cyclophosphamide pulses monthly for 6 doses, followed by mycophenolate mofetil that resulted in normal lung function tests, hemoglobin concentration, and anti-MPO level within four subsequent weeks. During 10-months of follow-up she remained well, her blood pressure and renal function tests were normal, and proteinuria and hematuria gradually resolved.We report a child with an exceptionally rare coexistence of circulating ANCA and anti-GBM disease manifesting as PRS in whom renal disease was not the prominent part of clinical presentation, contrary to other reported pediatric patients. A review of literature on disease with double positive antibodies is also presented. Evaluation of a patient with PRS should include testing for presence of different antibodies. An early diagnosis and rapid institution of aggressive immunosuppressive therapy can induce remission and preserve renal function. Renal prognosis depends on the extent of kidney injury at diagnosis and appropriate treatment.

A 78-year-old man developed rapidly progressive glomerulonephritis (RPGN) in the course of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive UIP that had been found four years previously. When UIP was diagnosed, the MPO-ANCA titer was low and urine was negative for proteinuria and hematuria. On admission, his serum creatinine increased to 16.89 mg/dL and hemoglobin decreased to 5.2 g/dL. Urinalysis revealed that urinary protein excretion was 0.423 g/day and hematuria (30-40/HPF). The MPO-ANCA titer increased to 95.6 U/mL and anti-glomerular basement membrane (GBM) antibody titer elevated to 140 EU. Renal pathology revealed cellular crescents in 10 out of 11 glomeruli excluding two global sclerotic glomeruli. Immunofluorescence showed heavy linear deposits of IgG and C3 along the GBM. Treatments were begun after admission with hemodialysis and intravenous methylprednisolone pulse therapy, oral prednisolone at the dose 30 mg/day. Both MPO-ANCA and anti-GBM antibody were within the normal range after four months. However, the renal function was not restored despite treatment and he died of pulmonary infectious disease after six months from the onset of RPGN. Recently, many cases of RPGN with both MPO-ANCA and anti-GBM antibody have been reported. In this case, persistent UIP-associated MPO-ANCA appeared to have triggered RPGN by anti-GBM antibody.

Classical Goodpasture's (GP) syndrome is a monophasic illness characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis with linear IgG deposition along the glomerular and distal tubular basement membrane and estructive necrotizing diffuse extracapillary crescentic glomerulonephritis. The majority of patients have circulating anti-glomerular basement membrane (GBM) antibodies, detectable with standard anti-GBM ELISA. Concurrence of GP syndrome with proliferative glomerulonephritis has only rarely been described. In this report, for the first time we describe in a 21-year-old woman GP syndrome with 50% crescentic sclerosing glomerulonephritis with linear immunofluorescence characteristic of anti-GBM pathogenesis, combined with mixed membranous and membranoproliferative glomerulonephritis with granular immunofluorescence and subepithelial, mesangial and subendothelial deposits characterizing immune complex pathogenesis. The clinical picture was also unusual for GP syndrome, manifesting a recurrent but non-progressive course, nephrotic syndrome, normal renal function and low values of anti-GBM antibodies, identified only by novel more sensitive techniques.

There are few reports regarding outcomes of anti-glomerular basement membrane (GBM) disease in patients who underwent renal replacement therapy. To help define this we studied all patients with anti-GBM disease who started renal replacement therapy for end-stage renal disease (ESRD) in Australia and New Zealand (ANZDATA Registry) between 1963 and 2010 encompassing 449 individuals (0.8 percent of all ESRD patients). The median survival on dialysis was 5.93 years with death predicted by older age and a history of pulmonary hemorrhage. Thirteen patients recovered renal function, although 10 subsequently experienced renal death after a median period of 1.05 years. Of the 224 patients who received their first renal allograft, the 10-year median patient and renal allograft survival rates were 86% and 63%, respectively. Six patients experienced anti-GBM disease recurrence in their allograft, which led to graft failure in two. Using multivariable Cox regression analysis, patients with anti-GBM disease had comparable survival on dialysis or following renal transplantation (hazard ratios of 0.86 and 1.03, respectively) compared to those with ESRD due to other causes. Also, renal allograft survival (hazard ratio of 1.03) was not altered compared to other diseases requiring a renal transplant. Thus, anti-GBM disease was an uncommon cause of ESRD, and not associated with altered risks of dialysis, transplant or first renal allograft survival. Death on dialysis was predicted by older age and a history of pulmonary hemorrhage.

Diffuse alveolar hemorrhage (DAH) is defined by the presence of red blood cells originating from the lung capillaries or venules within the alveoli. The diagnosis is established on clinical features, radiological pattern, and especially bronchoalveolar lavage. Diffuse alveolar hemorrhage may have many immune or non-immune causes. Immune causes of DAH include vasculitides, connective tissue diseases, especially systemic lupus erythematosus, and antiglomerular basement membrane antibody disease (Goodpasture's syndrome). Treatment is both supportive and causal, often based on high dose corticosteroids and immunosuppressive therapy (especially intravenous cyclophosphamide). Plasma exchanges are performed in antiglomerular basement membrane antibody disease and systemic lupus erythematosus, and are considered in systemic vasculitis. Non-immune causes of DAH mainly include heart diseases, coagulation disorders, infections, drug toxicities and idiopathic DAH. Treatment of non-immune DAH is that of its cause. Whatever the cause, DAH is an emergency requiring prompt assessment and early treatment.

A 66-year-old man with uremia and on hemodialysis was referred to our hospital because of hemoptysis. A chest radiograph showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure accompanied by hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgG along the glomerular basement membrane (GBM). Circulating IgG anti-GBM antibody was not detected. Because the findings of renal biopsy suggested anti-GBM disease, the patient was treated with plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of his pulmonary symptoms and chest radiograph abnormalities. However, sputum culture submitted on admission yielded Mycobacterium tuberculosis 3 weeks later. Therefore, immunosuppressive agents were discontinued and antituberculous agents were administrated. No relapse of pulmonary hemorrhage occurred during the next 1-year period of follow-up, but the patient did not regain renal function and remained on hemodialysis.