Neutrophil Cytoplasmic Antibodies Research Articles

Pulmonary Hemorrhage and Renal Involvement in Benzylthiouracil- Induced Vasculitis

Abstract Introduction: Vasculitis is a rare complication of antithyroid drugs reported with propylthiouracil, carbimazole, methimazole and Benzylthiouracil. Benzylthiouracil –induced Vasculitis are often severe forms with renal or pulmonary involvement, which can be life-threatening if left untreated .We describe the clinical course and medical management of 2 cases of severe vasculitis with alveolar hemorrhage and renal involvement occurred in 2 patients with Graves’ disease treated by Benzylthiouracil . Cases report: A 36 and 33-year-old women with Graves’ disease developed alveolar hemorrhage and acute renal failure after respectively 36 and 144 months of Benzylthiouracil therapy. Kidney biopsy showed pauci-immune crescentic glomerulonephritis in the 2 cases. Anti Neutrophil Cytoplasmic Antibody (ANCA) was positive (P- ANCA in the first patient and c-ANCA in the second patient). The condition of the first patient improved when Benzylthiouracil was withdrawn associated with corticosteroids and immunosuppressive treatment after a follow up of 6 months. However, the second patient died by severe infection after the same treatment. Conclusion: Benzylthiouracil vasculitis is a serious complication but its prognosis is good if diagnosis and treatment are early. However mortality is related to risk of infection.

Familial Non Medullary Thyroid Cancer: Clinic Cases and Review of literature

Abstract Introduction: Vasculitis is a rare complication of antithyroid drugs reported with propylthiouracil, carbimazole, methimazole and Benzylthiouracil. Benzylthiouracil –induced Vasculitis are often severe forms with renal or pulmonary involvement, which can be life-threatening if left untreated. We describe the clinical course and medical management of 2 cases of severe vasculitis with alveolar hemorrhage and renal involvement occurred in 2 patients with Graves’ disease treated by Benzylthiouracil . Cases report: A 36 and 33-year-old women with Graves’ disease developed alveolar hemorrhage and acute renal failure after respectively 36 and 144 months of Benzylthiouracil therapy. Kidney biopsy showed pauci-immune crescentic glomerulonephritis in the 2 cases. Anti Neutrophil Cytoplasmic Antibody (ANCA) was positive (P- ANCA in the first patient and c-ANCA in the second patient). The condition of the first patient improved when Benzylthiouracil was withdrawn associated with corticosteroids and immunosuppressive treatment after a follow up of 6 months. However, the second patient died by severe infection after the same treatment. Conclusion: Benzylthiouracil vasculitis is a serious complication but its prognosis is good if diagnosis and treatment are early. However mortality is related to risk of infection.

Unusual presentation of a case of Sjogren's syndrome with neurological and ocular manifestation

Sjogren's syndrome is an autoimmune disease that commonly presents to the ophthalmologist as a dry eye disease. We report an unusual presentation of a case of Sjogren's syndrome. A 33-year-old man presented with lid swelling, pseudomembraneous conjunctivitis with central corneal epithelial defect and history of limb weakness for past 2 years. There was progressive enlargement of the epithelial defect and conjunctival-scleral necrosis developed during follow-up. Evaluation for underlying connective tissue disorder was positive for SS-B/La antibody and, the rheumatoid factor, anti nuclear antibody, anti neutrophil cytoplasmic antibody titres were negative. Patient was diagnosed as a case of Primary Sjogren's syndrome. Resolution of the conjunctival-scleral necrosis occurred following treatment with combination of cyclosporine and prednisolone. Paramedian tarsorrhaphy was performed to promote healing of the corneal epithelium. The corneal epithelium healed, conjunctival-scleral necrosis resolved completely and the visual acuity improved to 6/36 in the right eye after 3 months of immunosuppressive therapy. The immunosuppressive therapy was discontinued after completion of 6 months of treatment. After 6 months follow-up of stopping immunosuppressive therapy, the ocular and systemic condition is stable.

Delayed subdural hematoma and cerebral venous thrombosis in a patient with spontaneous intracranial hypotension

Spontaneous low cerebrospinal fluid (CSF) pressure syndrome, first described by Schaltenbrand in 1938 [1], is an uncommon but increasingly recognized disease. This syndrome is defined by CSF pressures of 70 mmH2O or less in the lateral position and no history of injuries. Severe complications of this syndrome such as subdural hemorrhage (SDH) and cerebral venous thromboses (CVT) have been rarely reported. In this letter, we discuss a case of this syndrome accompanied by both SDH and CVT. A 34-year-old man presented with diffuse holocranial headache and no history of injuries on 27 September 2007. The pain resolved on recumbency and occurred while sitting and standing, and was relieved in 1 day. The patient again developed orthostatic headache 6 days later which was more severe than the first headache. A computed tomography (CT) scan indicated abnormal superior sagittal sinus (SSS) and straight sinus (Fig. 1a). The patient’s neurological examination showed only neck stiffness. The opening pressure of CSF in the lateral position was 0 mm H2O. Complete blood count (CBC) and hemoglobin electrophoresis were normal. Antiphospholipid, anticardiolipin antibodies, antinuclear antibody, anti-DNA antibodies, and neutrophil cytoplasmic antibodies (ANCA) were negative. There were no laboratory evidence found for protein S and C deficiencies, antithrombin III deficiency and Leiden factor V mutation. Homocystine was also in normal range. Magnetic resonance imaging (MRI) of the brain showed bilateral SDH (Fig. 2a) and diffuse pachymeningeal enhancement on enhanced-gadolinium. T1-weighted images (Fig. 2b). In addition, the results of magnetic resonance venography (MRV) of the brain implied thrombosis in the inferior sagittal sinus (ISS) and straight sinus (Fig. 3a, b). The MR venography 2D-TOF angiographic technique was used. Anticoagulant therapy was considered. When the patient became drowsy 1 week later, an urgent CT scan was obtained, and it showed greater SDH (Fig. 1b). Hematomas were surgically evacuated immediately. After being treated conservatively with analgesics, anticoagulants, hydration, and bed rest, the patient showed an obvious increase in responsiveness, and his headache significantly improved 3 days later. Pain was completely resolved and the neck stiffness disappeared after 3 weeks. At that time, CT and MRV both indicated the recanalization of the cerebral venae (Figs. 1c, 3c, d). The patient was followed regularly for 3 years without incident, and he was able to work and live normally. Because of the absence of any history of trauma or lumbar puncture, spontaneous low CSF pressure syndrome in this patient can be confirmed on the basis of orthostatic headache, low CSF pressure, and diffuse meningeal enhancement observed on MR images. Low CSF pressure, also known as intracranial hypotension (IH), is closely associated with CSF leaks [2]. Although radioisotope cisternography is a valuable technique for localizing any leakages, it may worsen the IH [3], and therefore, we treated him conservatively instead of further examination. In this patient, the occurrence and recovery of IH preceded the SDH and CVT. We believe that there may be a causal relationship between them. It has been reported that 10% of patients with IH had SDH [4]. The dura is relatively fragile and weak because the cell layer bordering the dura lacks collagen fibers. The Y.-T. Mao Q. Dong J.-H. Fu (&) Department of Neurology Huanshan Hospital, Fudan University, Shanghai 200040, China e-mail: neverbad999@yahoo.com.cn

Hydralazine-induced ANCA vasculitis with pulmonary renal syndrome: a rare clinical presentation

Hydralazine is a commonly used drug for treatment of hypertension and is known to cause drug-induced lupus erythematosus. It has rarely been reported to cause anti neutrophil cytoplasmic antibody positive vasculitis, a life-threatening complication. Presentation could be extremely variable delaying diagnosis. Although drug-induced vasculitis has been infrequently associated with rapidly progressing glomerulonephritis, pulmonary involvement presenting as pulmonary renal syndrome is extremely rare. We report a case of hydralazine-induced vasculitis presenting as pulmonary renal syndrome with fatal outcome even after aggressive treatment. Numerous antibodies are associated with hydralazine including anti myeloperoxidase antibody, anti-nuclear antibody, anti-histone antibody, and anti-elastase antibody. Additionally, we also report the presence of anti-phospholipid antibodies specific to anti-cardiolipin, anti-beta2 glycoprotein, and anti-phosphatid that have not been previously reported. We conclude that early diagnosis and prompt discontinuation of the drug is necessary for the treatment of hydralazine-induced anti neutrophil cytoplasmic antibody vasculitis.

188 Hydralazine Induced Anti Neutrophil Cytoplasmic Antibody Vasculitis Presenting as Pulmonary Renal Syndrome

188 Hydralazine Induced Anti Neutrophil Cytoplasmic Antibody Vasculitis Presenting as Pulmonary Renal Syndrome

Churg–Strauss syndrome complicated by central retinal artery occlusion: case report and a review of the literature

A 68-year-old man was admitted with rapid visual loss. Churg-Strauss syndrome (CSS) was diagnosed, based upon the symptoms of asthma, eosinophilia, interstitial pneumonitis, and positive myeloperoxidase-anti neutrophil cytoplasmic antibody (MPO-ANCA). Light reflexes were absent and vision was completely lost in both eyes. Bilateral central retinal artery occlusion (CRAO) was observed by fluorescence angiography. Steroid pulse along with an anticoagulant improved the visual acuity to light perception and hand motion. CSS-associated CRAO should be considered when acute visual loss occurs.

Aseptic meningitis in a patient receiving treatment with anti-tumour necrosis factor alpha

We read with interest the review by Antonio Tristano [1] regarding neurological adverse events associated with antitumour necrosis factor alpha (anti-TNF-a) treatment. We believe that aseptic meningitis is also a potential complication of anti-TNF-a treatment and we report the following case. A 53-year-old plumber presented with 3 weeks of night sweats, fevers and generalised headache. There was no weight loss, recent foreign travel, occupational exposure to sewage or chemicals. He had a single female sexual partner and a recent negative human immunodeficiency virus (HIV) test. He had a pet dog and no further contact with animals or insect bites. His past history included IgA nephropathy (currently quiescent), hypothyroidism and an undifferentiated seronegative inflammatory arthritis. This had involved generalised joint pains but had particularly involved his right ankle and a biopsy had shown synovitis. He was HLA B27 negative. He had been treated with sulphasalazine, which was not tolerated. Despite methotrexate and oral steroids he had continuing right subtalar joint inflammation and adalimumab was added. At presentation his disease was inactive. His medications were levothyroxine, Humira (adalimumab) 40 mg/week since 2008 and oral methotrexate 20 mg/week since 2007 and his arthritis symptoms were well controlled. He was not taking non-steroidal antiinflammatory medication, and took paracetamol (acetaminophen) only for his headache. On admission, examination revealed a pyrexia, \5 splinter haemorrhages, normal heart sounds, chest, abdomen, neurological examination and no meningism, lymphadenopathy or oro-genital ulceration. Investigations showed white cell count 12.7 9 10/L (reference range 3.8–10.6 9 10/L), neutrophil count 9.16 9 10/L (reference range 1.8–6.5 9 10/L), monocyte count 1.12 9 10/L (reference range 0.2–0.8 9 10/L) with C-reactive protein, lactate dehydrogenase and blood film normal. IgA was mildly elevated at 4.11 g/L (reference range 0.8–4.0 g/L). Liver, renal, and thyroid function, plasma viscosity, creatinine kinase, chest X-ray and unenhanced MRI brain/ enhanced MRI spine were normal. Three sets of blood cultures were negative. Urinalysis including Bence-Jones protein and a myeloma screen were negative. Two urine specimens and a sputum specimen were also negative for auramine-phenol stain and tuberculosis (TB) culture after 6 weeks. Complement, extractible nuclear antigens, lupus anticoagulant, anticardiolipin antibody, double stranded DNA and antinuclear antibody were negative. Classical anti neutrophil cytoplasmic antibody (cANCA) was positive (titre 1:320), MPO and PR-3 negative. Cerebrospinal fluid (CSF) was measured serially (see Table 1). Oligoclonal bands were negative. A cytospin with immunophenotyping showed evidence of lymphocyte infiltration, the lymphocyte population consisting of both B and T cells. Cytology revealed reactive lymphocytes. Auramine-phenol stain for TB and TB culture was negative. Cryptococcal antigen and fungal cultures were negative after extended incubation. Herpes simplex virus DNA, enterovirus RNA and CMV (via PCR) were not detected. A CT scan of the thorax/abdomen/pelvis and trans-thoracic echocardiography were normal. HIV and hepatitis A. J. Hamilton (&) N. J. Gutowski Department of Neurology, Royal Devon and Exeter Hospital, Barrack Road, Exeter, Devon EX2 5DW, UK e-mail: alexander.hamilton@nhs.net

ACUTE DISSEMINATED ENCEPHALOMYELITIS FOLLOWING VACCINATION AGAINST HUMAN PAPILLOMA VIRUS

We report a case of severe encephalitis evolving shortly after administration of a new vaccine against human papilloma virus (HPV) recently approved for the prevention of diseases caused by HPV types 6, 11, 16, and 18. ### Case report. A 20-year-old woman developed headache, nausea, vomiting, and diplopia within 28 days of the second immunization with the quadrivalent HPV vaccine Gardasil®. She did not report signs of a preceding infection. On neurologic examination, the patient was without focal deficits. Cranial MRI showed multifocal white matter edema with abnormal patchy or streaky contrast enhancement along deep venular structures. CSF analysis disclosed 80 cells/μL consisting of lymphocytes and 2% eosinophils, increased total protein (0.8 g/L) and immunoglobulin M ratio, no oligoclonal bands (OCB), and normal lactate. Serology and PCR ruled out an infectious etiology with negative testing for Borrelia, Treponema, Listeria, herpes simplex virus 1/2, varicella zoster virus, human herpesvirus 6, HIV, enterovirus, and arbovirus. Laboratory screening revealed elevated antinuclear (1:320; ANA) and antithyroglobulin (445 IU/mL; normal ≤60) antibodies, and increased thyroid-stimulating hormone (5.2 mU/L; normal 0.4–4). ANA subspecificities, neutrophil cytoplasmic, cardiolipin, and aquaporin-4 antibodies, and routine laboratory studies were negative. …

A Case of Simultaneous, Biopsy-Proven, Classic, ANCA-Positive Wegener's Granulomatosis and Anti-GBM Disease, but without Detectible Circulating Anti-GBM Antibodies

Wegener's granulomatosis (WG) is a systemic, necrotizing, granulomatous vasculitis of unknown etiology. Approximately 75% of cases present as classic WG with both pulmonary and renal involvement, while the remaining 25% of patients present with a limited form with either predominantly upper or lower respiratory tract symptoms. Ninety percent of WG patients have circulating anti–neutrophil cytoplasmic antibodies (ANCA), and approximately 10% have both circulating ANCA antibodies and concomitant anti–glomerular basement membrane (anti-GBM) disease on renal biopsy. Virtually all of these patients also have circulating anti-GBM antibodies. While it has been reported that some patients with ANCA vasculitis have circulating anti-GBM antibodies, and patients with anti-GBM disease may have positive ANCA, review of the literature does not demonstrate other cases of biopsy-proven, simultaneous, ANCA-associated vasculitis and anti-GBM disease. We report a case of simultaneous, biopsy-proven, classic, ANCA-positive WG and anti-GBM disease, but without detectible circulating anti-GBM antibodies. We present findings characteristic of both WG and linear IgG deposition along the GBM suggesting concurrent anti-GBM disease, in the absence of detectable circulating anti-GBM antibodies. Possible theories to explain the absence of these antibodies are discussed.

Combined ANCA-associated vasculitis and lupus syndrome following prolonged use of hydralazine: a timely reminder of an old foe

A 55-year-old woman with type II diabetes and resistant hypertension presented to her GP in July 2008 complaining of lethargy, breathlessness, and joint pains. In 2007, based upon a positive antinuclear antibody test (ANA) in the context of pancytopenia, arthralgia, and a persistent malar rash, she had been diagnosed with systemic lupus erythematosis (SLE) by her referring hospital. Her regular medications were perindopril 4 mg daily, amlodipine 5 mg daily, atenolol 100 mg daily, and hydralazine 25 mg twice daily which she had started in 2005. She had remained on hydralazine, despite the diagnosis of SLE, treatment of which was limited to intra-articular corticosteroid injections. In July 2008 she was referred to our renal unit with acute kidney injury (AKI). Upon arrival, examination revealed a malar rash, and a soft systolic murmur. The remainder of the examination was unremarkable. Her blood pressure was 163/81 and she was afebrile. Laboratory investigations confirmed AKI with a serum creatinine of 300 lmol/L, (previously 148 lmol/L in May 2008, and 82 lmol/L in March 2008). Full blood count revealed pancytopenia, and her blood film showed rouleaux formation with occasional spherocytes. ANA remained positive, and she had now developed high titres of serum anti neutrophil cytoplasmic antibodies of the anti-myeloperoxidase subtype (p-ANCA), which were previously negative (See Table 1). Despite immediate cessation of hydralazine and appropriate rehydration, over the following days, her clinical condition deteriorated. A widespread, florid vasculitic rash developed, accompanied by arthralgia, intermittent pyrexia, and a rising serum creatinine. Her symptoms and immunological profile were consistent with hydralazine-induced SLE (although renal involvement in this setting is unusual). However, the presence of serum ANCA and the florid vasculitic rash also made ANCA-associated vasculitis (AAV) a likely diagnosis. Since these two conditions were potentially therapeutically distinct, she underwent renal and skin biopsies, and a bone marrow aspirate and trephine. The renal biopsy confirmed the diagnosis of AAV with pauci-immune crescentic glomerulonephritis, occurring alongside hydralazineinduced lupus syndrome, complicated by autoimmune pancytopenia, the underlying cause of which was attributed to prolonged use of hydralazine. She was treated with three intravenous pulses of methylprednisolone (500 mg) and five sessions of plasma exchange—3 L exchanges with 1.5 L 5% human albumin solution and 1.5 L fresh frozen plasma (FFP). She required three sessions of haemodialysis and, following recovery of her white cell N. Sangala R. W. Lee C. Horsfield D. J. A. Goldsmith (&) Renal and Histopathology Departments, Kings Health Sciences, London 0207-188-5708, UK e-mail: David.goldsmith@gstt.nhs.uk

An Unusual cause of ‘Troponinaemia’ – Answers

The patient was initially commenced on intravenous antibiotics, aspirin, clopidogrel and low molecular weight heparin (LMWH) for a putative diagnosis of community acquired pneumonia complicated by acute coronary syndrome. However, following review of the chest x-ray and careful evaluation of the history, the diagnosis of Wegener’s Granulomatosis (WG) was considered and immunological tests were requested (table 1). Prednisolone 60mg daily was commenced pending the urgent Anti Neutrophil Cytoplasmic Antibody (ANCA) result. A palpable purpuric rash then developed over the dorsal aspects of both feet.

Novel Anti-Glycan Antibodies Related to Inflammatory Bowel Disease Diagnosis and Phenotype

We sought to evaluate whether two novel immunoglobulin A (IgA) cell wall polysaccharide antibodies, anti-laminarin (anti-L) and anti-chitin (anti-C), aid in the diagnosis and phenotype differentiation of Crohn's disease (CD) and ulcerative colitis (UC). A cohort of 818 individuals with inflammatory bowel disease (IBD; 517 CD and 301 UC) from two IBD tertiary referral centers, with median ages of 33 and 39 years, respectively, and disease duration of 8.9 years, were phenotyped using the Montreal classification, and analyzed for seven anti-glycan antibodies (gASCA (anti-Saccharomyces cerevisiae) IgG, gASCA IgA, anti-chitobioside (GlcNAc(beta1,4)GlcNAc(beta)), anti-laminaribioside (Glc(beta1,3)Glb(beta)), anti-mannobioside (Man(alpha1,3)Man(alpha)), anti-L, and anti-C) and perinuclear atypical neutrophil cytoplasmic antibodies (pANCA). In the CD patient population, 73% were positive for >/=1 anti-glycan antibody. All glycan markers were specific for CD (85.4-97.7%) and more prevalent in CD vs. UC (P<0.0015). gASCA IgG and IgA best differentiated CD from UC followed by anti-L (area under the curve 0.818, 0.815, and 0.702, respectively). The addition of anti-L and anti-C to gASCA IgG and pANCA improved discrimination between CD and UC (P<0.001). Adding anti-L to gASCA and pANCA differentiated colonic CD and UC (P=0.02). An increasing number of positive antibodies was associated with early CD onset, penetrating phenotype, perianal disease, and the need for surgery (P<0.001). Anti-L was associated with ileocolonic CD (odds ratio (OR) 2.28, 95% confidence interval (CI) 1.40-3.69; P=0.001), and anti-C with penetrating (OR 2.75, 95% CI 1.50-5.04; P=0.001) and perianal disease (OR 1.95, 95% CI 1.06-3.59; P=0.03). Anti-L and anti-C improve differentiation between CD and UC. Anti-L may also differentiate between isolated colonic CD and UC. Both anti-L and anti-C are independently associated with a more aggressive CD phenotype.

The clinical significance of combined measurement of anti-saccharomyces cerevisia antibody and antiperinuclear neutrophil cytoplasmic antibody in inflammatory bowel disease

Objective To evaluate the clinical significance of combined measurement of antiperinuclear neutrophil cytoplasmic antibody(ANCA)and anti-saccharomyees cerevisia antibody(ASCA)for the diagnosis of inflammatory bowel disease(IBD)patients and difierentiation of Crohn's disease(CD)with ulcerative colitis(UC).Methods A total of 159 patients with IBD(97 UC,62 CD),167 patients with other non-IBD gastrointestinal conditions(NIBDC)and 25 healthy controls(HC)were recruited in our research.ASCA and ANCA were detected by enzyme-linked immunosorbent assay(ELISA)and indirect immunofluorescence assay.respectively.Results The prevalence of ASCA-IsA or IgG in CD group,UC group,NIBDC and HC were43.5%,14.4%,29.3%and 0,respectively.The prevalence of ASCA-IgA or IgG in CD group were higher than those in other groups(X2=16.76 or 4.12,P＜0.01 or＜0.05).The prevalence of ANCA in CD group.UC group,NIBDC and HC were 8.1%,56.7%,4.8%and 0,respectively.The prevalence of AMA in UC group were much higher than those in other groups(X2=38.08 or 90.47,P＜0.01).The sensitivity specificity and positive predictive value(PPV)in ASCA+/ANCA-were 40.3%.93.8% and 80.6%,respectively,and in ANCA+/ASCA-were 48.5%,98.4% and 97.9%,respectively.Condusions ASCA or ANCA testing alone are not sensitive enoulgh for diagnosing CD and UC,but their combination asses are specific for differential diagnosis between CD and UC.Combined testing of ASCA-IgA with IgG can improve the sensitivity in screening CD patients.The ASCA positive pattern in Chinese CD group are correlated with surgery. Key words: Inflammatory bowel disease; Anti-perinuelear neutrophil cytoplasmic antibody; Anti-saceharomyces cerevisia antibody

CMV Pneumonitis in an Immunosuppressed Patient With C-ANCA Positive Glumerulonephritis

Cytomegalovirus (CMV) pneumonitis is an important cause of morbidity and mortality in HIV and post-transplant patients, and is rare in patients with autoimmune diseases treated with immunosppressive therapy. We report the first case of a patient with Cytoplasmic anti neutrophil cytoplasmic antibodies positive glomerulonephritis who developed CMV pneumonitis after treatment with cyclophosphamide and prednisone. The CMV infection developed simultaneously with bacterial respiratory infection. All symptoms resolved rapidly under treatment with gancyclovir and immunoglobulins.

Autoantibodies in patients with Down Syndrome: Early senescence of the immune system or precocious markers for immunological diseases?

Down syndrome (DS) patients present several immunological disturbances, with high rates of infections, malignancies and autoimmune phenomena. The present study aims to evaluate the prevalence of autoantibodies in children and adolescents with DS that are not usually investigated, and to establish possible clinical and laboratory associations. One hundred and fifty Caucasoid DS patients from southern Brazil (93M, 57F; median age 4 years) and 105 healthy children (58M, 47F; median age 8 years) were evaluated for the presence of anti-mitochondrial (AMA), smooth-muscle (SMA), liver-kidney microsomal (LKM), nuclear (ANA), gastric parietal cell (GPC) and neutrophil cytoplasmic (ANCA) antibodies, by indirect immunofluorescence, and rheumatoid factor (RF), by turbidimetry. Forty-three DS patients (28.6%) showed positivity to at least one autoantibody, in comparison with eight of the controls (7.6%; P < 0.001). RF was detected in 28% of the patients and 6.7% of the controls (P < 0.001). ANCA, SMA and ANA were positive in 0.66% of the patients, while AMA, GPC and LKM were negative in all the samples. Currently, none of the RF positive patients has clinical evidence of rheumatic disease. Data from the present study suggest that the high incidence of positive RF observed in DS patients might be related to the senescence of the immune system or could be an earlier marker of rheumatic diseases in these patients.

Selected Summary

Selected Summary

Diffuse Glomerular Crescents and Peritubular Immune Deposits in a Transplant Kidney

CRESCENTIC GLOMERULONEPHRITIS is an uncommon occurrence in renal transplant recipients.1 Most cases are caused by recurrent disease, and de novo disease occurs even less frequently. Differential diagnoses of crescents in the allograft are similar to those in the native kidney, which includes such anti–neutrophil cytoplasmic antibody–associated diseases as Wegener granulomatosis and microscopic polyarteritis,2,3 such immune-complex glomerulonephritides as systemic lupus erythematosus and immunoglobulin A (IgA) nephropathy,4,5 and anti–glomerular basement membrane disease.

Anti-neutrophil Cytoplasmic Antibody in Behçet's Disease

Anti neutrophil cytoplasmic antibody (ANCA) is strongly associated with some vasculitic disorders. Behçet’s disease (BD) is a systemic vasculitis of unknown etiology. In this study, ANCA was found to be positive in 8 out of 66 patients (10.2 %) with BD by combination testing consisting of immunofluorescence and ELISA [one patient showed an atypical pattern by indirect immunofloresence techique, 6 patients were reactive to bacterial-permeability increasing protein (BPI) and one patient was reactive to Cathepsin G in ELISA]. There were no vascular manifestations such as veneous or arterial thrombosis and arterial aneurysms in ANCA-positive patients with BD. The results suggest that ANCA may be found in a minority of BD as those in previous published studies.

Rheumatoid arthritis, Pyrexia of Unknown Origin (PUO) and pancytopenia

A 61-yr-old previously fit lorry driver was referred by his general practitioner in October 1999 to an orthopaedic clinic with a 6-month history of painful hands, shoulders and feet. His general practitioner had treated him with ibuprofen without much improvement. He admitted to a recent history of loss of appetite with loss of two stones (12.7 kg) in weight. His joint pains had been increasing in severity with visible swelling of his fingers and knees. He had no relevant family history. He was an ex-smoker and drank little alcohol. Physical examination revealed a healthy-looking man with signs of synovitis in the symptomatic joints. The orthopaedic surgeon referred him to the rheumatologist (K.C.). The preliminary blood tests showed haemoglobin of 10.4 g/dl with normal haematocrit, leucocyte and platelet counts and normal serum vitamin B12 and red-cell folate levels. His serum ferritin was 468 g/l (normal range 18–400 g/l). He also had transient random hyperglycaemia, which was followed by a normal glucose tolerance test. His rheumatoid factor was elevated at 1:2560. His chest X-ray was normal except for some thickening of the bronchiolar wall. He was seen in the rheumatology clinic 2 months later, in December 1999, with classical symptoms and signs of a symmetrical inflammatory polyarthritis suggestive of rheumatoid disease. His knees were drained and injected with methyl prednisolone and local anaesthetic. He was also given intramuscular methyl prednisolone (120mg) to induce remission of active disease. Investigations revealed haemoglobin 10.3 g/dl, white cell count 6.4 10/l, platelet count 449 l0/l and ESR of 100mm in the first hour. The biochemical screens were all normal, including liver, renal and bone panels. The rheumatoid factor was 2460 IU (normal range 30 IU) and CRP was elevated at 85.1mg/dl (normal range <10mg/dl). The X-rays of his hands and feet showed no obvious erosions. The option of commencing methotrexate as a second-line drug was discussed but he preferred to wait until he returned from a planned Christmas holiday in Spain. Soon after his return from holiday he developed sudden severe cramp-like pains associated with numbness in his legs. He was virtually unable to walk. An MRI scan of his whole spine was done on the advice of the neurosurgeons, and, as the scans were normal, he was referred to the neurologists, who performed a lumbar puncture to exclude acute infective polyneuritis. The neurologists also noted a skin rash on his legs associated with left foot drop (Fig. 1). An autoimmune disease was suspected and the rheumatologist (K.C.) was consulted. On examination he had a vasculitic rash with peripheral neuropathy. There was no lymphadenopathy or organomegaly. Given the recent diagnosis of seropositive rheumatoid arthritis (RA), systemic rheumatoid vasculitis (SRV) seemed to be the most plausible diagnosis. Investigations at this time revealed haemoglobin 9.0 g/dl, white cell count 12.1 10/l and neutrophils 9.6 10/l with normal platelet and lymphocyte count. The ESR was 110mm in the first hour and CRP was 121mg/dl (normal range <5mg/dl). The biochemical, serological and microbiological screens including hepatitis A, B and C were all normal/negative. His anti nuclear antibodies, anti DNA antibodies, extractable nuclear antigens, anti cardiolipin antibodies, anti neutrophil cytoplasmic antibodies and cryoglobulins were all negative. Echocardiogram was normal. A cerebrospinal fluid study showed a mild increase in cerebrospinal fluid protein but no oligoclonal band or albumino-cytological dissociation. Electromyography showed severe sensorimotor polyneuropathy of the axonal type with some denervation changes in the peroneal muscles. A skin biopsy confirmed active necrotizing vasculitis, consistent with SRV (Fig. 2). He was commenced on pulse intravenous methyl prednisolone (500mg) and cyclophosphamide (500mg) with some symptomatic improvement, and was discharged home on a 2-weekly regime.