40. Rivaroxaban for treatment of vascular BehÇet's disease

related to a high dose of long duration. Biopsy was rechecked to confirm the diagnosis, but the conclusion remained the same. A therapeutic trial moreofseveraladditionalweekswasplannedbeforeswitchingthemedications. On the fourth follow-up visit, the skin lesions had worsened and began to increase in size over the thighs, breasts and the legs. She received a prolonged course of antibiotics along with daily dressings but all to no avail. Considering refractory disease, azathioprine was discontinued and patient was switched to injectable cyclophosphamide, according to literature for refractory pyoderma gangrenosum. She was given six monthly cycles, during which the patient showed significant improvement. But since the lesions persisted, we added colchicine 0.5 mg twicedaily and gave twomore doses of injectable cyclophosphamide (total 8 doses). The lesions began to heal after second dose but she needed prolonged injectable course to help the disease go in remission. The steroid could be tapered down to 5 mg/day. Currently, our patient is doingwellwithnonewlesions.Shehasbeenkeptonazathioprinemaintenancetherapyalongwithprednisolone5 mg/day. Discussion:Pyoderma gangrenosum is a rare disorder causing multiple non-healing ulcers over the limbs, aggravated by trauma. It is a neutrophilic dermatosis which has been associated mostly with inflammatory bowel disease and haematological malignancies, although most cases remain idiopathic. The association with sarcoidosis is a rare occurence. We did a review of the medical literature and found only four previously reportedcases.Thepathogenesisofpyodermagangrenosumisimmune mediated with predominant neutrophil infiltration. There has been an association with TNF-alpha, IL-8 and I-23 especially the variant associated with immunological diseases. Sarcoidosis is also an immune mediated disease with increased accumulation of CD 4þ T cells at the site of inflammation. The cytokine response in granulomatous inflammation is mediated by IL-2,TNF-alpha and interferon gamma.Skin manifestations are a known complication in sarcoidosis with manifestations like lupus pernio, erythrema nodousum, maculopapular rashes and keloid scars due to underlying inflammation. Pyoderma gangrenosum has not been reported due to the rarity of the cases being diagnosed. Both conditions haveacommondenominatorof increasingskin lesionsafter injury,hence there canbea relation between the two.Ourpatient hada refractorypyoderma gangrenosum, which kept recurring upon tapering steroids. Her lesions hadapredilection forareas of trauma, as the ulcers wouldappear on the sites she got injury with delayed healing. We did a literature search wherecyclophosphamideandTNFBlockershasbeenrecommendedfor refractorypyoderma gangrenosum.She showed adramatic response to cyclophosphamide as after the first dose the wounds started to heal. After three doses of cyclophosphamide, she showed a much better response with larger lesions healing up as well. This case does give us a relationship between sarcoidosis and pyoderma gangrenosum. Unless one has a high index of suspicion, these cases may be overlooked. A chest roentgenogram should be recommended in all patients with idiopathicpyodermagangrenosum. KeyLearningPoints: Thiscasedoes giveusa relationshipbetweensarcoidosis and pyoderma gangrenosum. Unless one has a high index of suspicion, these cases may be overlooked. A chest roentgenogram should be recommended in all patients with idiopathic pyoderma gangrenosum. Disclosure:N.Mendiratta:None.S.Bajad:None.M.Bindroo:None.

area and the thighs. She was already experiencing steroid side effects related to a high dose of long duration. Biopsy was rechecked to confirm the diagnosis, but the conclusion remained the same. A therapeutic trial more of several additional weeks was planned before switching the medications. On the fourth follow-up visit, the skin lesions had worsened and began to increase in size over the thighs, breasts and the legs. She received a prolonged course of antibiotics along with daily dressings but all to no avail. Considering refractory disease, azathioprine was discontinued and patient was switched to injectable cyclophosphamide, according to literature for refractory pyoderma gangrenosum. She was given six monthly cycles, during which the patient showed significant improvement. But since the lesions persisted, we added colchicine 0.5 mg twice daily and gave two more doses of injectable cyclophosphamide (total 8 doses). The lesions began to heal after second dose but she needed prolonged injectable course to help the disease go in remission. The steroid could be tapered down to 5 mg/day. Currently, our patient is doing well with nonewlesions.She hasbeen keptonazathioprinemaintenance therapy along with prednisolone 5 mg/day. Discussion: Pyoderma gangrenosum is a rare disorder causing multiple non-healing ulcers over the limbs, aggravated by trauma. It is a neutrophilic dermatosis which has been associated mostly with inflammatory bowel disease and haematological malignancies, although most cases remain idiopathic. The association with sarcoidosis is a rare occurence. We did a review of the medical literature and found only four previously reported cases .The pathogenesis of pyoderma gangrenosum is immune mediated with predominant neutrophil infiltration. There has been an association with TNF-alpha, IL-8 and I-23 especially the variant associated with immunological diseases. Sarcoidosis is also an immune mediated disease with increased accumulation of CD 4 þ T cells at the site of inflammation. The cytokine response in granulomatous inflammation is mediated by IL-2, TNF-alpha and interferon gamma. Skin manifestations are a known complication in sarcoidosis with manifestations like lupus pernio, erythrema nodousum, maculopapular rashes and keloid scars due to underlying inflammation. Pyoderma gangrenosum has not been reported due to the rarity of the cases being diagnosed. Both conditions have a common denominator of increasing skin lesions after injury, hence there can be a relation between the two. Our patient had a refractory pyoderma gangrenosum, which kept recurring upon tapering steroids. Her lesions had a predilection for areas of trauma, as the ulcers would appear on the sites she got injury with delayed healing. We did a literature search where cyclophosphamide and TNF Blockers has been recommended for refractory pyoderma gangrenosum. She showed a dramatic response to cyclophosphamide as after the first dose the wounds started to heal. After three doses of cyclophosphamide, she showed a much better response with larger lesions healing up as well. This case does give us a relationship between sarcoidosis and pyoderma gangrenosum. Unless one has a high index of suspicion, these cases may be overlooked. A chest roentgenogram should be recommended in all patients with idiopathic pyoderma gangrenosum. Key Learning Points: This case does give us a relationship between sarcoidosis and pyoderma gangrenosum. Unless one has a high index of suspicion, these cases may be overlooked. A chest roentgenogram should be recommended in all patients with idiopathic pyoderma gangrenosum. Disclosure: N.Mendiratta: None. S. Bajad: None. M. Bindroo: None.

SCLEROTIC BONE LESIONS: A DIAGNOSTIC DILEMMA
Premila Kadamban 1 and Nagui Gendi 1 1 Rheumatology, Basildon and Thurrock University Hospital, Basildon, UNITED KINGDOM Introduction:Scleroticbonelesionsarecausedbyavariety of conditions including genetic diseases, metastatic malignancy, lymphoma and Paget's disease. Systemic sarcoidosis is an uncommon cause of sclerotic bone lesions which have been mainly described in middle aged Afro-Caribbean males. Case description: We report a case of a middle-aged Afro-Caribbean builder who presented to the GP in 2013 with a history of weight loss. The initial investigations revealed that his prostate specific antigen (PSA) level was raised and his chest x-ray showed bilateral hilar lymphadenopathy. Further investigations by the urology team revealed that his prostate size was normal in MRI and the prostate biopsy was normal. Hilar lymphadenopathy was further investigated by the respiratory team. The patient had endo-bronchial ultra sound guided trans-bronchial biopsy the histopathology of which showed non-caseating granulomas. At this point patient was referred to the rheumatology team. On review the patient was not symptomatic apart from on and off arthralgia. After a follow-up for six months as the patient remained asymptomatic he was discharged from hospital care. After nearly four years the patient was referred back with a history of sternal chest pain. His ESR and CRP were elevated. A CT chest showed features consistent with stage three pulmonary sarcoidosis but the patient didn't have any respiratory symptoms. In view of the bone pain a bone scan was done which showed multiple sclerotic lesions in the spine and skull. An MRI scan of the spines showed high signal lesions in multiple levels. The CT showed sclerotic bone lesions at multiple vertebrae both in the vertebral bodies and the pedicles. A biopsy of these sclerotic lesions was performed the histology of which did show some giant multi-nucleated Langerhans cells. There was no obvious granuloma. No malignant cells were seen. Therefore systemic sarcoidosis was the presumed cause for the bone lesions and the patient started methotrexate. The patient had a cardiac MRI following this although he didn't have any cardiac symptoms, which revealed features of infiltrative sarcoidosis. He has had good response to methotrexate. He is less symptomatic and his inflammatory markers havecome down to normal range. Discussion:Scleroticbone lesions could be caused bya variety of conditions like systemic mastocytosis, Osteopetrosis, metastatic malignancy (notably breast and prostate), lymphoma and Paget's disease. There are certain radiological features which could distinguish some pathology like systemic mastocytosis and Paget's disease. The rest of the conditions warrant further investigations. The diagnostic dilemma in this patient was between metastatic prostate cancer and sarcoidosis in view of the prior history of high PSA and history of pulmonary sarcoidosis. In this circumstance, bonebiopsy was invaluable inshedding morelightinto thepathology which enabled further treatment. Sarcoid bone lesions are mostly osteolytic and mainly involve the peripheral bones like phalanges. Sclerotic bone lesions are rare; commonly affects the axial skeleton (pelvis, spine, skull, ribs) and the patients are often symptomatic as opposed to the patients with lytic lesions who rarely have any symptoms. Sclerotic bone lesions appear exclusively in middle aged black patients. Sarcoidosis is a multi-system disease with a range of clinical features. Usually involvement of the bone implies multi-system involvement and poor prognosis. In such circumstances pre-emptive screening for cardiac sarcoidosis is useful as the first presentation of cardiac sarcoidosis could be a life threatening arrhythmia. Early diagnosis would be beneficial as early aggressive treatment would lead to better prognosis. Key Learning Points: Bone biopsy is invaluable in diagnosis of sclerotic bone lesions .Presence of skeletal sarcoidosis often implies chronic and more severe multi-system disease which warrants early investigations and aggressive treatment. Disclosure: P.Kadamban:None. N.Gendi: None.

RIVAROXABAN FOR TREATMENT OF VASCULAR BEHÇ ET'S DISEASE
Reem Musa 1 and Loay Al Dhahir 1 1 Internal Medicine, Dr Sulaiman Al Habib Hospital, Riyadh, SAUDI ARABIA Introduction: Treatment of venous thrombosis in Behc¸et's disease (BD) has always been a grey area in medical practice. The authors describe the first treated case of recurrent multiple venous thrombosis (VT) in BD with rivaroxaban in Saudi Arabia. The patient has been successfully treated during the last four years with rivaroxaban without any complications or new VT features. We report this case hoping to start research for new line of management for this condition, which will help other patients for better compliance and efficiency as well as improving the quality of life using novel oral anticoagulants (NOACs). BD (traditionally known as Silk Road disease) is a rare systemic chronic condition with relapsing remitting vasculitis of unknown aetiology. It affects both arteries and veins. Clinical traits include oral and genitalulcers,ocular involvement including anterior and posterior uveitis, and retinal vacuities, which can lead to visual loss if not assessed and treated carefully. The disease mainly manifests as mucocutaneuos disorder but can involve any other systems, multifactorial aetiology has been hypothesised including HLA-B51 and HLA-ERAP-1 genes, but the exact aetiology has not yet been identified. BD has the highest frequency in patients between 20-40 years old, but can also be seen in children and the elderly. Sex distribution is variable but incidence is higher in males in high prevalence areas (Turkish and Middle East populations). The disease is mainly sporadic but can be seen in families. Vascular manifestations are present in up to 40% of the patients with BD with a high rate of recurrence. Refractory thrombosis has been observed to be one of the presenting sign at the time of diagnosis. Although there is no link yet between thrombophilic disorders and BD, patients with this disease have aconsiderable rate of VT and relapse. Case description: A 33 year old male was diagnosed with BD, when presented to our outpatient clinic with the chief complaint of recurrent oral and genital ulcers. The patient was commenced on standard immunosuppressives (azathioprine and colchicine), however during the followup period he developed a deep vein thrombosis (DVT). The decision was made to start oral anticoagulant with vitamin K antagonist agents (VKA); unfortunately, the patient had poor compliance, with erratic INR complicated by bleeding once in addition to multiple presentations to ER and outpatient clinic with recurrent DVT. During one of these episodes, the patient presented with altered visual acuity, and was diagnosed to have left eye retinal vein thrombosis which further deteriorated to complete visual loss. The patient has no family history of BD, other thromboembolic or vasculitic disorders. Unexpectedly, he presented again with DVT despite being on VKA and low molecular weight heparin (LMWH) most likely due to poor compliance, then rivaroxiban was discussed as analternativetreatment. The patient informed aboutthe uncertain use of this medication, side effecst and the fact that there is no evidence of its effectiveness in treating or preventing VT in his disease. Patient commenced on rivaroxaban with satisfying outcome for four years of regular follow-up with no complications or features of vascular thrombosis. The compliance improved as patient felt more comfortable without having repeated INR monitoring. The patient has had an uneventful clinical course after startingrivaroxaban. Discussion: This is the first known case of BD in Saudi Arabia where the frequency of venous thromboembolic events were successfully managed with rivaroxaban over a course of over four years of outpatient follow-up. BD has a high prevalence in the Mediterranean, and considerable prevalence in others. Vascular BD is unique in affecting both arterial and venous systems and is a major cause of morbidity and mortality, despite there being no clear guidelines for the treatment and secondary prevention of VBD. Immunosuppressive agents have demonstrated significant reduction of venous thromboembolic events in BD; however, in clinical practice we often encounter patients with BD who have recurrent VT while on immunosuppressant medications, and oral VKA (warfarin) with the commonest reason cause being sub-therapeutic drug levels due to poor compliance or intolerance. Rivaroxaban has a fixed dose and doesn't require blood monitoring. Moreover, it has limited drugs interactions. It has been proven to be effective, safe and has significant impact in decreasing the recurrence of VT with lower risk of gastrointestinal bleeding and subsequent complications comparing to VKA in situations other than BD. Patients with DVT treated with rivaroxiban have a lower rate of hospitalisation and outpatient visits without increasing the risk of readmission. Rivaroxaban has shown a great result in treatment and secondary prevention in this patient, so this might open a new line of treatment and secondaryprevention of VBD if proven infurtherclinical trials. Key Learning Points: BD is rare but has serious complications, especially vascular issues, if not detected and treated carefully. There are no new guidelines in the treatment of BD. Although immunosuppressive agents proved reduction in vascular complications in BD, we still face patients with venous thrombosis despite being on immunosppressant medications. Rivaroxaban might be a new line in treatment and secondary prevention of vascular BD ifprovenin further clinical trials. Disclosure: R. Musa: None. L.Al Dhahir: None.

LOCALISED AMYLOID: A RARE CAUSE OF STRIDOR
Klara Morsley 1 , Khin Yein 1 , David Collins 1 , Sara Carty 1 , Elizabeth Price 1 , Rosemary Waller 1 , and Azeem Ahmed 1 1 Rheumatology, Great Western Hospital, Swindon, UNITED KINGDOM Introduction: We present a case of a 68 year old female who was admitted with stridor, and subsequently diagnosed with localised subglottic amyloid. The case highlights the importance of keeping an open mind to a wide differentialto ensure that rare causes are not missed. Case description: A 68 year old female patient presented with stridor requiring an emergency tracheostomy. She had a preceding history of two years of a hoarse voice and had recently had a microlaryngoscopy and biopsy of a granuloma on the left vocal cord. Further examinations of the subglottic area revealed oedema with friable areas, and the subglottic biopsy showed amyloid deposition. She was systemically well, with no symptoms elsewhere. She was investigated for causes of secondary amyloid but none found. Her inflammatory markers were normal, ANCA, ANA and anti-CCP were negative with normal serum ACE and complement levels. Serum electrophoresis and bone marrow biopsy were both normal. She was started on a reducing regimen of prednisolone with clinical improvement and successfully extubated. After discharge, she went on to have a SAP scan which showed the amyloid to be localised to the subglottic area, and a subsequent CT-PET showed the biopsy proven amyloid area to be markedly FDG avid with disease extending inferiorly along the trachea Over the next month, she developed increasing shortness of breath on exertion and stridor, requiring up to 40mg prednisolone, and has been referred for consideration of surgical intervention. Discussion: Localised amyloid is a rare disease. In a study at the National Amyloid Centre between 1980 and 2011, 12% of all newly diagnosed patients with amyloid had localised disease with a median age was 59.5 years. 15% of these patients had amyloid localised to the larynx or tonsils. Primary laryngeal amyloidis seen moreoften within the laryngeal ventricle or vocal cords with subglottic involvement being less common. It presents with dysphonia and stridor, and as in our patient, may result in airway compromise. Our patient was initially referred to rheumatology with a possible diagnosis of subglottic granulomatosis with polyangiitis (GPA), which may also be localised to the subglottic area and present with similar symptoms. ANCA may also be negative in patients with limited GPA. Consideration of localised amyloid as an alternative is important and CongoRedstaining onbiopsy will confirm the diagnosis. The prognosis of localised amyloid is generally good, with an estimated five-year overall survival of 90Á6% in the National Amyloid Centre study. Although the literature suggests that steroids are not of benefit in localised laryngeal amyloid, our patient appeared to gain clinical benefit from them. The mainstay of treatment is carbon dioxide laser excision, which may need to be repeated. Key Learning Points: Subglottic stenosis may be an airway threatening problem. Localised amyloid should be included in the differential diagnosis for these patients and Congo Red staining performed on biopsy specimens. All patients with localised amyloid should be carefully evaluated for systemic amyloid,and causes of secondaryamyloid. Introduction: Medication, herbal and dietary supplement induced lupus and liver injuries have been well documented in the literature. We report two cases of skyfruit seed induced autoimmune phenomena and hepatic injury. Swietenia macrophylla seeds, also known as skyfruits or mahogany seeds in Southeast Asia have been used as a remedy for diabetes,hyperlipidemiaandshown tohaveantibioticproperties byitseffect on the innate immune system. Due to its perceived benefits, it is being used as part of traditional medication in Southeast Asia for various ailments. Case description: A 62 year-old Indian male with a history of diabetes mellitus, hypertension, hyperlipidaemia, coronary artery disease and non-alcoholic fatty liver disease presented to the gastroenterology clinic for transaminitis. He had been on stable doses of medications for the above including atorvastatin 10mg ON for the last one year. He presented with polyarthralgia with tenosynovitis and severe restriction of motion of his right shoulder, left wrist and dorsum of right hand at onset with minimal response to a short course of prednisolone. His symptoms improved but were still present until review in the rheumatology clinic six weeks later. Of note he had taken skyfruit seeds six weeks ago. Systemic review was negative for rashes, oral ulcers, sicca symptoms, Raynaud's, hematuria, frothy urine or abdominal pain. He reported a significant unintentional weight loss of 14kg in the preceding 12 months. There was no family history of autoimmune conditions. Physical examination showed synovitis of the right metacarpophalangeal and proximal interphalangeal joints. Full blood count, renal function and thyroid function tests were normal. His liver function test showed transaminitis with alanine transaminase (ALT) of 699 U/L , aspartate aminotransferase (AST) of 645 U/L and gamma-glutamyl transferase (GGT) of 125 U/L. C-reactive protein (CRP) was 75.7 mg/L. Anti-nuclear antibody (ANA) screen was positive; anti-ENA (extractable nuclear antigen) profile and rheumatoid factor were negative. Anti-mitochondrial M2, anti-liver cytosol 1, anti-liver kidney microsomal and anti-soluble liver antibodies were negative. Hepatitis B surface antigen and antibodies against hepatitis A, C and E were nonreactive. He realized that the onset of symptoms -arthritis, weight loss and transminitis correlated with his intake of skyfruit seeds and stopped consuming them. The inflammatory arthritis had completely resolved and CRP and liver enzymes had markedly improved six weeks later. Within a year, his liver function tests had normalised and he had no recurrence of his arthritis.
A 59 year-old Chinese female, previously well, presented with right upper quadrant discomfort for two weeks. Liver function tests were deranged with a total bilirubin 1.51 umol/L, ALT 859 U/L, AST 491 U/L and GGT 98 U/L. Hepatitis B, hepatitis C and human immunodeficiency virus (HIV) antibodies were non-reactive. A CT (Computed tomography scan) of the abdomen and pelvis showed fatty liver, and mesenteric panniculitis with prominent mesenteric nodules. She had noted a 6kg weight loss over six weeks and loss of appetite. Oesophagogastroduodenoscopy and colonoscopy showed chronic atrophic gastritis without dysplasia or malignancy. She had started taking five sky fruit seeds daily for duration of one month prior to presentation. Systemic review was negative for features of connective tissue diseases.Her physical examinationwas normal except for dry skin over hands and feet related to frequent ablutions. Her