Wegener's granulomatosis presenting with erosive arthritis

We describe a patient with Wegener's granulomatosis who presented with erosive arthritis. The patient's multisystem disease responded to cyclophosphamide treatment, and the erosions healed. Our findings suggest that Wegener's granulomatosis should be added to the differential diagnosis of diseases associated with erosive arthritis.     

Wegener's granulomatosis in a patient with a rheumatoid arthritis.

A 38-year-old woman with rheumatoid arthritis who developed Wegener's granulomatosis is described. Wegener's granulomatosis appeared with saddle nose, perforation in her nasal septum, and granuloma in the nasal cavity. Laboratory evaluation showed a positive rheumatoid factor and circulating immune complex. Radiographic examination revealed ankylotic changes in both wrist and elbow joints. Bilateral anosmia and other disease manifestations completely responded to treatment with oral cyclophosphamide and prednisolone.     

Wegener's granulomatosis disclosed by clinical symptoms of Horton's disease]

In a series of 60 patients with Wegener's granulomatosis, 2 had initially presented with clinical signs suggestive of temporal arteritis. One of these two patients was a 69-year old woman suffering from inflammatory pain in the shoulders, wrists and knees, myalgias in the lower limbs and intermittent jaw claudication. The other patient was a 60-year old man with febrile polyarthritis predominantly affecting the knees and shoulders, and hyperaesthesia of the scalp. In both cases biopsy of the temporal artery gave negative results. Corticosteroids provided a dramatic improvement, but a relapse corrected the diagnosis. Three similar cases have been reported, but only one had a histological lesion of the temporal artery. Cases of temporal arteritis associated with pulmonary granulomatosis raise the problem of classification with localized Wegener's disease. An initial presentation suggestive of temporal arteritis may hide other systemic diseases, notably rheumatoid arthritis, periarteritis nodosa or Chug and Strauss angitis; Wegener's granulomatosis must be added to this list.     

Granulomatous gastritis in Wegener's disease: differentiation from Crohn's disease supported by a positive test for antineutrophil antibodies.

BACKGROUND: This report concerns the gastric manifestation of Wegener's granulomatosis in a 44 year old white female patient who initially presented with abdominal pain, vomiting, and iridocyclitis. FINDINGS: The clinical findings and the histopathological proof of granulomatous gastritis in the absence of necrotising vasculitis were initially considered to be indicative of a diagnosis of Crohn's disease showing isolated gastric involvement. A five month course of steroids resulted in temporary relief; thereafter the patient developed severe rhinitis with mucosal ulcerations. At this point biopsy of nasal mucosa disclosed the classic histopathological signs of Wegener's granulomatosis. A positive test for antineutrophil cytoplasmic antibodies (ANCAs) with a cytoplasmic pattern (c-ANCA) and antigenic specificity for proteinase 3 (PR-3) were found. The patient is in complete remission one year after diagnosis and treatment with steroids and cyclophosphamide. CONCLUSIONS: Wegener's granulomatosis can also involve the gastrointestinal tract. Granulomatous inflammation of the stomach, although a rare finding and non-specific, should include Wegener's disease in the differential diagnosis. The histological proof of necrotising vasculitis is dependent on the depth of the biopsy and therefore can be easily missed. Differential diagnosis can be clarified by ANCA testing.     

A case of the limited from of Wegener's granulomatosis without c-ANCA]

A 46-year-old woman was admitted to our hospital because of fever, cough and headache in December 2001. Although she had been treated for nasal obstruction and epistaxis by an otorhinolaryngologist in our hospital since 1996, no accurate diagnosis had been made despite repeated biopsies of the nasal mucosa. A chest CT taken in 1999 showed ground-glass opacities in both upper lobes. On admission, chest radiography and CT showed mass shadows without cavitation, corresponding to the lesions causing the ground-glass opacities. In addition, paranasal sinus MRI showed a deformity of the nasal septum accompanied by a space-occupying lesion, suggesting Wegener's granulomatosis. However, the cytoplasmic-antineutrophil cytoplasmic antibody (c-ANCA) test was negative. To achieve a definitive diagnosis, we performed an open lung biopsy. The specimen, obtained from the right upper lobe, showed the typical findings of a Wegener's granulomatosis including necrotizing vasculitis. Oral prednisolone treatment initiated at 20 mg daily, combined with oral cyclophosphamide at 50 mg daily markedly improved not only the clinical symptoms, but also the mass shadows in the left upper lobe. Patients with the limited form of Wegener's granulomatosis are occasionally seronegative and respond well to therapy. However, the natural course and the changes in chest radiographs are not understood well in such cases. In this paper, we report a case of the limited form of Wegener's granulomatosis that progressed slowly over a period of 6 years.     

ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES IN INFLAMMATORY ARTHRITIS--POTENTIAL FOR MISDIAGNOSIS?

Antineutrophil cytoplasmic antibodies (ANCA) are well describedin Wegener's granulomatosis and some forms of vasculitis. Theyhave also been described in patients with arthritis, but thespecificity of these ANCA and their relationship to the presenceof vasculitis, antinuclear antibodies (ANA) and granulocyte-specificANA (GS-ANA), and to disease activity are uncertain. We studied101 patients with forms of inflammatory arthritis and detectedfour cytoplasmic ANCA, eight perinuclear ANCA and 16 atypicalANCA. There was no association between the presence of ANCAand ANA or rheumatoid factor. No anti-PR3 antibodies were foundand no strong anti-myeloperoxidase antibodies were detected.Four GS-ANA were detected and were distinct from ANCA. Therewas no association between rheumatoid arthritis disease activityor disability and ANCA status. ANCA did not predict vasculitisover a 3 yr follow-up. These ANCA appear to be epiphcnomcna.Their importance lies in their potential to mislead physicianstowards a misdiagnosis of vasculitis. KEY WORDS: ANCA, Wegener's granulomatosis, Vasculitis, RA, Myeloperoxidase, Proteinase 3     

Rheumatische Erkrankungen mit Erstmanifestation im mittleren Lebensalter

Rheumatic diseases are manifested in all ages. First manifestations of gout are frequent between the ages of 40-60 years. Furthermore, the incidence of rheumatoid arthritis increases as well as anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides. Recently new treatment options for gout were established but colchicine, which has been used to treat gout for a long time was also further optimized in its use. Remarkable advantages in the treatment of rheumatoid arthritis towards remission have been made by the introduction of biological agents 10 years ago. In granulomatosis with polyangiitis (formerly Wegener's disease) therapeutic optimization has led to a reduction in toxicity and rituximab has proven to be an effective treatment option.     

Bronchocentric granulomatosis in a patient with rheumatoid arthritis

Bronchocentric granulomatosis is an uncommon entity which has no specific clinical, radiological and immunological features. It is usually diagnosed at morphological examination of biopsy or resected lung material. Aetiology of bronchocentric granulomatosis is unclear. A 49–year-old female patient, who was followed up with diagnosis rheumatoid arthritis in our outpatient clinic, presented with right lobe nodular lesion in chest radiography. Right thoracotomy and wedge resection was performed. Pathological examination revealed bronchocentric granulomatosis. Bronchocentric granulomatosis has been rarely reported in rheumatoid arthritis. This case might be a proof that bronchocentric granulomatosis may be one of the respiratory manifestations of rheumatoid arthritis.     

Anti-TNF treatment in secondary amyloidosis

SIR, The efficacy of biological therapies in rheumatoid arthritis(RA) [1, 2], ankylosing spondylitis (AS) [3] and psoriatic arthritis[4] is well known. Other diseases, such as Wegener's granulomatosis[5] and Still's disease [6] are currently being evaluated, butthe hypothetical benefit     

Serum amyloid P component levels are not decreased in patients with systemic lupus erythematosus and do not rise during an acute phase reaction

BACKGROUND: Serum amyloid P component (SAP) and acute phase proteins like C-reactive protein contribute to the clearance of apoptotic cells. This response is diminished in systemic lupus erythematosus (SLE). OBJECTIVES: To analyse SAP concentrations in SLE in relation to disease activity, and investigate whether SAP reacts like an acute phase protein. METHODS: SAP was measured in 40 patients with SLE during active and inactive disease and compared with healthy controls and patients with rheumatoid arthritis and Wegener's granulomatosis. Normal SAP values were determined in 120 healthy controls by ELISA. C reactive protein and serum amyloid A (SAA) were measured in all subjects and their levels related to SAP. SAP was also measured serially in 11 patients with breast cancer treated with recombinant human interleukin-6, and in 16 patients with sepsis. RESULTS: In SLE, SAP was unaltered compared with healthy controls and was not influenced by disease activity, in contrast to C reactive protein and SAA, which increased during active disease. SAP increased in Wegener's granulomatosis but not in rheumatoid arthritis. The rise in C reactive protein and SAA was most pronounced in Wegener's granulomatosis with active disease. SAP did not change significantly during an acute phase response. No correlation was found between SAP and C reactive protein or SAA, but there was a correlation between SAA and C reactive protein (r = 0.4989, p = 0.0492). CONCLUSIONS: Patients with SLE have normal circulating SAP levels. In contrast to C reactive protein or SAA, SAP does not act as an acute phase protein.     

Wegener's granulomatosis in patients with rheumatoid arthritis

OBJECTIVE: To describe 2 cases of coexisting rheumatoid arthritis (RA) and Wegener's granulomatosis (WG), and to summarize the clinical and serological data for all 6 patients reported in the English literature since 1966. METHODS: Medline review over a 35-year period (1966-2002) revealed 4 reported cases of RA associated with WG. Patients were diagnosed based on symptoms, radiographic changes, bronchoalveolar lavage fluid analysis, hematuria, serology, and biopsy. We describe 2 additional cases of WG developing in Caucasian women with RA. These are the first reported patients to possess positive antineutrophil cytoplasmic antibodies (ANCA) and autoantibodies to proteinase 3 (PR3). RESULTS: All 6 cases of coexisting RA and WG were female. The diagnosis of RA preceded WG diagnosis in all cases; mean age at RA onset was 43.7 +/- 15.0 years, duration of RA prior to WG diagnosis 7.9 +/- 9.1 years. Clinical findings included erosive articular disease on radiographs (n = 4; 67%), positive rheumatoid factor (n = 6; 100%), upper respiratory involvement (n = 5; 83%), lower respiratory signs (n = 4; 67%), renal involvement (n = 2; 33%), and positive ANCA (n = 2/3; 67%). Five patients were treated with corticosteroids and cyclophosphamide, with clinical improvement. CONCLUSION: Although rare, WG may develop in patients with preexisting RA and may present with end-organ involvement.     

Lymphomatoid granulomatosis and diffuse alveolar damage associated with methotrexate therapy in a patient with rheumatoid arthritis

We report on a patient of rheumatoid arthritis (RA) who sequentially developed an axillary mass and a fatal interstitial pneumonia during a 2-year course of methotrexate (MTX) therapy. Autopsy revealed a systemic lymph node involvement and the diagnosis of Epstein–Barr virus (EBV)-related lymphoproliferative disease (LPD) with the features of lymphomatoid granulomatosis was made. The lung tissue specimens revealed a typical diffuse alveolar damage (DAD), and small nodules consisting of atypical B lymphocytes showing positive staining for EBV were sparsely recognized only in basal lungs. This is the first report of a RA patient receiving MTX therapy sequentially developing MTX-associated lymphomatoid granulomatosis and DAD.     

Wegener's granulomatosis complicated with intestinal ulceration

We report the case of a 32-year-old man who developed Wegener's granulomatosis complicated with refractory intestinal ulceration. In August 2001, he presented with a high fever, nasal bleeding, and bilateral leg numbness. These symptoms worsened, which prompted him to consult his home doctor on February 18, 2002. In spite of treatment with antibiotics, his symptoms did not improve. Furthermore, abdominal pain and melena occurred as additional symptoms in March 2002. He was admitted to our hospital on April 5, 2002. A deformed nose condition (the so-called saddle nose) was observed at this time. Laboratory data showed a high erythrocyte sedimentation rate (103 mm/h) and a high level of serum C-reactive protein (14.98 mg/dl), and hematuria and proteinuria were also observed. The patient was positive for an antineutrophil cytoplasmic antibody specific for proteinase-3 (PR3-ANCA). A chest computed tomography (CT) scan revealed multiple pulmonary nodules in the lung field. A biopsied-specimen from the nasal mucosa showed necrotizing granulomatosis with giant cells. Together with his symptoms and the laboratory and pathological findings, the patient was diagnosed as having Wegener's granulomatosis. A colon fiberscopy showed multiple ulcerations with bleeding from the terminal ileum to the ascending colon, and nodular lesions at the terminal ileum. We started a combination therapy of prednisolone (60 mg/day) and cylophosphamide (100 mg/day) orally. The patient's gastrointestinal symptoms disappeared and abnormal serological indicators improved. Although Wegener's granulomatosis complicated with refractory intestinal ulceration is rare, this case indicates that the gastrointestinal region is also a target organ of Wegener's granulomatosis.     

A case of Wegener's granulomatosis without PR3-ANCA at relapse]

A 49-year-old man was admitted to our hospital with fever. His chest radiograph showed some nodules in the right upper and lower lung fields. The cytoplasmic-antineutrophil cytoplasmic antibody test was positive, and histopathologic biopsy of a small nasal polyps yielded a diagnosis of Wegener's granulomatosis. He was started on prednisolone and cyclophosphamide. The findings on his chest radiograph and his symptoms improved rapidly, and we stopped these drugs after one year. Two years after cessation of treatment, his chest radiograph showed two nodules with cavities. Relapse of Wegener's granulomatosis was diagnosed. The proteinase 3-antineutrophil cytoplasmic antibody test was negative. He was started on prednisolone and cyclophosphamide, and the findings on his chest radiograph improved rapidly. Chest radiographs are useful for follow-up observation of patients with Wegener's granulomatosis after treatment.     

Eosinophilia in Wegener's granulomatosis

Significant eosinophilia is a prominent feature in Churg-Strauss syndrome but has only rarely been described in Wegener's granulomatosis (WG). We describe two Wegener's granulomatosis patients with > 30% eosinophilia on their initial presentations. Other etiologies that could account for their eosinophilia were excluded. Both patients had pulmonary alveolar hemorrhage, sinusitis, arthritis, high-titer cytoplasmic antineutrophil cytoplasmic antibodies (cANCA), and proteinase-3 antibodies, but no evidence of renal disease. Herein we discuss eosinophilia, the differential diagnosis of pulmonary infiltrates and eosinophilia, the role of cANCA in vasculitis and autoimmune disease, compare Wegener's granulomatosis and Churg-Strauss syndrome, and review possible pathogenic mechanisms.     

Wegener's granulomatosis with papillary adenocarcinoma of the thyroid.

A 59-year-old woman was admitted with scleritis, sinusitis, skin eruptions, nodular lesions of both lung fields in chest X-ray films and renal failure. Skin biopsy and elevation of the titer of anti-neutrophil cytoplasmic antibody confirmed Wegener's granulomatosis. A right nodular goiter was palpated and a diagnosis of thyroid cancer was made based on aspiration cytology. Although combined therapy with cyclophosphamide and corticosteroid was started and the Wegener's granulomatosis improved and disappeared except for the renal lesion, the renal failure worsened and she died. Apparently only 2 cases of Wegener's granulomatosis complicated with carcinoma as in this case have been reported.     

Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide

OBJECTIVE: To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis. METHODS: In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969-95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated. RESULTS: The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis. CONCLUSION: The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis.     

Can sulfasalazine therapy induce or exacerbate Wegener's granulomatosis?

Sulfasalazine (SSZ) can induce serological and clinical autoimmune reactions but the occurrence of SSZ-related Wegener's granulomatosis (WG) has not been reported before. We describe two patients with rheumatoid factor (RF)-positive rheumatoid arthritis (RA) who developed biopsy-proven WG with serious organ involvement during SSZ therapy. The pathogenetic mechanism that explains the relationship between SSZ and the occurrence of a de novo anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis or a flare is discussed. We propose that WG can be a rare complication of SSZ therapy and that this, like other autoimmune adverse events of this drug, is mediated by SSZ-induced apoptosis.     

Wegener's granulomatosis presenting as temporal arteritis

A granulomatous giant cell vasculitis of the temporal artery was observed in a biopsy specimen from a patient with corresponding clinical symptoms. Within weeks, the new onset of pulmonary infiltrates and renal failure prompted biopsy of the patient's kidney. A necrotizing glomerulonephritis, compatible with a diagnosis of Wegener's granulomatosis, was present. Vasculitis of the temporal artery may be a feature of Wegener's granulomatosis.     

Cutaneous nodules recurring in the legs ten years before the diagnosis of Wegener's granulomatosis

INTRODUCTION: Although cutaneous disorders preceding Wegener's granulomatosis are common, they usually are not isolated clinical features. We describe the case of a patient who presented Wegener's granulomatosis-related cutaneous disorders ten years before diagnosis, suggesting a protracted form of the disease. EXEGESIS: At first visit in 1987 a 44-year-old woman presented leg skin nodules since six months. Following biopsy clinical findings showed non-specific inflammation. Due to lung nodular lesions tuberculosis was diagnosed in 1993. Though bacteriology did not confirm diagnosis, treatment was successful. After relapse in 1996, thoracotomy was performed and anatomic pathology findings uncovered Wegener's granulomatosis. The patient's history showed many flares of skin nodules since 1986. This is only in 1997 that cutaneous pathologic findings showed the existence of Wegener's granulomatosis. CONCLUSION: The time to diagnosis after the occurrence of the first clinical signs is usually shorter than that observed. Superficial, protracted forms of the disease have been described. As in the present case, they raise diagnostic issues regarding the lack of specificity of anatomic pathology findings. This also suggests that Wegener's granulomatosis and infections might be related.