P22 Paraneoplastic diffuse systemic sclerosis in association with ano-rectal tumour

Abstract Introduction/Background Rheumatic diseases can manifest as a paraneoplastic phenomenon. They can be seen during the course of neoplastic disease, precede the diagnosis, appear simultaneously or occur after the diagnosis of malignancy. Overall, paraneoplastic rheumatic syndromes are rare. It is however important to be aware of this phenomenon as the signs and symptoms of the rheumatic syndrome will usually subside with treatment of the underlying malignant disease. Furthermore, reappearance of symptoms may suggest cancer relapse. Description/Method 51 year old woman with no significant past medical history was referred by her General Practicioner with 6-week history of pain and stiffness in hands, arms and legs. There was also associated 4-week history of change in bowel habit (diarrhoea and faecal incontinence). Clinical examination revealed skin thickening proximal to elbows and knees, sclerodactyly, facial telangiectasia as well as tendon friction rubs in lower limbs. There was also a mass palpable on digital rectal examination. Investigations revealed that the patient had new iron deficiency anaemia and mildly raised carcinoembryonic antigen. Anti-RNA polymerase III antibody returned positive. CT of chest, abdomen and pelvis suggested tumour involving the anus and lower rectum with metastatic lymphadenopathy. Those findings were also confirmed on subsequent MRI pelvis and PET CT. She underwent anal biopsy, examination under anaesthesia and formation of loop colostomy. Histopathology results confirmed poorly differentiated squamous carcinoma. Patient was then reviewed by oncology and discussed at multidisciplinary meeting. She was commenced on palliative chemotherapy (paclitaxel and carboplatin). After the first session she became severely anaemic and developed acute renal failure. She passed away approximately three months after initial referral to rheumatology. Discussion/Results This patient was diagnosed with paraneoplastic diffuse systemic sclerosis in association with ano-rectal tumour. Unfortunately at the time of diagnosis the disease was metastatic therefore the only treatment option available was palliative rather than curative. Paraneoplastic rheumatic syndromes are rare. The signs and symptoms are secondary to the presence of malignancy. They may be induced by the substances that are secreted by the tumour or the immune system’s response to the malignant cells. Usually once patient recovers from the neoplastic disease the rheumatic disease signs/symptoms subside. In our patient’s history there were a number of features which raised the possibility of paraneoplastic aetiology. These included: sudden onset and rapid progression of clinical symptoms, late onset of disease (after 50 years of age), family history of cancer (dad had prostate cancer), new iron deficiency anaemia as well as the presence of anti-RNA polymerase III antibodies. This antibody is linked with cancer-associated systemic sclerosis. Patients who are positive have shorter cancer-scleroderma interval. Anti-RNA polymerase III antibody is unique to scleroderma and is not found in cancer patients without scleroderma. Key learning points/Conclusion The key learning point from this case was not to forget the paraneoplastic aetiology in patients who present with rheumatic syndromes. In particular if the symptoms are of sudden onset or are progressing rapidly/responding poorly to therapy. There is only a small number of cases reported in literature of paraneoplastic systemic sclerosis. Furthermore, the importance of anti-RNA polymerase III antibody testing in scleroderma patients. If positive, it is important to be aware that those patients have >4-fold increased risk of cancer occurring within 2 years of scleroderma onset. It is therefore vital to look for any signs/symptoms during their routine follow-up appointments at rheumatology clinics.

Introduction/Background: Those working in Rheumatology frequently encounter cytopaenia both as adverse effects of many conventional and biological disease modifying drugs and as manifestations of autoimmune diseases. In cases where cytopaenia progresses, other explanations should be sought. Here we present an unusual cause of cytopaenia, seen in a patient with psoriatic arthritis on immunosuppression. Description/Method: An 81-year-old woman with a diagnosis of psoriatic arthritis had been maintained on Infliximab (3mg/kg 8 weekly) and Methotrexate (7.5mg PO weekly) for 12 years. She then developed mild neutropaenia (1.52 x 109/L). Methotrexate was stopped and she continued on Infliximab monotherapy for several months, until ongoing neutropenia resulted in Infliximab being withheld. Sustained mild neutropenia and the development of thrombocytopenia (platelets 95 x 109/ L) prompted a referral to Haematology, who suspected autoimmune neutropenia and advised checking haematinics and monitoring the FBC monthly. The neutropenia improved and Infliximab was restarted. Over 6 months she developed gradually worsening and persistent pancytopenia (neutrophils 1.36 x 109/L, platelets 134 x 109/L, Hb 91 g/L). There was no history of fevers, night sweats, bone pain, headaches, recurrent infections, lumps or bumps, chest symptoms, change in bowel habit or urinary symptoms. Examination revealed no pallor, jaundice, clubbing, peripheral lymphadenopathy or sternal tenderness. The chest was clear and the abdomen soft with no organomegaly. Repeat bloods showed microcytic hypochromic anaemia (Hb 86 g/L, MCV 73 fL, MCH 24.6 pg) with target cells on blood film. Iron was low (iron 5.1 umol/L, transferrin 1.52 g/L). Serum protein electrophoresis showed paraprotein bands with abnormal serum free light chain assay possibly consistent with myeloma, lymphoma or MGUS. Haematology suspected myelodysplasia, potentially secondary to previous long term Methotrexate therapy. A bone marrow biopsy was performed; the unexpected result was Leishmaniasis. Our patient was admitted to hospital and, following microbiology review, was treated with liposomal amphotericin (IV) for Visceral Leishmaniasis as an inpatient. Her Infliximab was suspended and her joints have remained quiescent. Discussion/Results: Leishmania is an intracellular parasitic protozoan that is transmitted to humans by sandfly bites. It is endemic in Africa, America, Central Asia and the Mediterranean. It usually has an incubation period of 3-8 months. Those who are immunosuppressed, for example due to immunotherapy or HIV, are at increased risk of infection. The patient had only ever travelled to Portugal and Gibraltar. One trip to Gibraltar occurred whilst on dual immunosuppression with Infliximab and Methotrexate and prior to the development of neutropenia. She has no recollection of any insect bites.
Visceral leishmaniasis is variable in the severity of symptoms experienced ranging from asymptomatic to a febrile illness with lymphadenopathy, hepatospenomegaly, night sweats, cutaneous pigmentation, appetite loss and weight loss, which can be drastic. Our patient indeed described significant weight loss in the preceding year. This case demonstrated the laboratory abnormalities which are typical of Visceral Leishmaniasis: pancytopenia and hypergammaglobulinaemia. Treatment for visceral Leishmaniasis has classically been with pentavalent antimonials (based on the heavy metal antimony) such as Sodium stibogluconate. Their toxicity profile and growing resistance however has meant amphotericin B is often used first line. This is given intravenously, with the liposomal form preferred as it has lower toxicity. Our patient received 4 mg per kg daily on days 1-5, 10, 17, 24, 31, and 38, following the FDA-approved regimen for immunosuppressed patients. Without treatment Leishmaniasis is usually fatal, with haemmorrhage, infection, cachexia and multiorgan failure as causes of death. Key learning points/Conclusion: Whilst patients with Rheumatological conditions may have cytopaenia due to their disease or its treatment, persistent, progressive or unexplained results should be investigated further. In patients with cytopaenia of unclear aetiology, thorough investigation with Haematology involvement is mandatory. You may find an unexpected diagnosis . . . we did! Introduction/Background: Rheumatic diseases can manifest as a paraneoplastic phenomenon. They can be seen during the course of neoplastic disease, precede the diagnosis, appear simultaneously or occur after the diagnosis of malignancy. Overall, paraneoplastic rheumatic syndromes are rare. It is however important to be aware of this phenomenon as the signs and symptoms of the rheumatic syndrome will usually subside with treatment of the underlying malignant disease. Furthermore, reappearance of symptoms may suggest cancer relapse. Description/Method: 51 year old woman with no significant past medical history was referred by her General Practicioner with 6-week history of pain and stiffness in hands, arms and legs. There was also associated 4-week history of change in bowel habit (diarrhoea and faecal incontinence). Clinical examination revealed skin thickening proximal to elbows and knees, sclerodactyly, facial telangiectasia as well as tendon friction rubs in lower limbs. There was also a mass palpable on digital rectal examination. Investigations revealed that the patient had new iron deficiency anaemia and mildly raised carcinoembryonic antigen. Anti-RNA polymerase III antibody returned positive. CT of chest, abdomen and pelvis suggested tumour involving the anus and lower rectum with metastatic lymphadenopathy. Those findings were also confirmed on subsequent MRI pelvis and PET CT. She underwent anal biopsy, examination under anaesthesia and formation of loop colostomy. Histopathology results confirmed poorly differentiated squamous carcinoma. Patient was then reviewed by oncology and discussed at multidisciplinary meeting. She was commenced on palliative chemotherapy (paclitaxel and carboplatin). After the first session she became severely anaemic and developed acute renal failure. She passed away approximately three months after initial referral to rheumatology. Discussion/Results: This patient was diagnosed with paraneoplastic diffuse systemic sclerosis in association with ano-rectal tumour. Unfortunately at the time of diagnosis the disease was metastatic therefore the only treatment option available was palliative rather than curative. Paraneoplastic rheumatic syndromes are rare. The signs and symptoms are secondary to the presence of malignancy. They may be induced by the substances that are secreted by the tumour or the immune system's response to the malignant cells. Usually once patient recovers from the neoplastic disease the rheumatic disease signs/symptoms subside. In our patient's history there were a number of features which raised the possibility of paraneoplastic aetiology. These included: sudden onset and rapid progression of clinical symptoms, late onset of disease (after 50 years of age), family history of cancer (dad had prostate cancer), new iron deficiency anaemia as well as the presence of anti-RNA polymerase III antibodies. This antibody is linked with cancer-associated systemic sclerosis. Patients who are positive have shorter cancer-scleroderma interval. Anti-RNA polymerase III antibody is unique to scleroderma and is not found in cancer patients without scleroderma. Key learning points/Conclusion: The key learning point from this case was not to forget the paraneoplastic aetiology in patients who present with rheumatic syndromes. In particular if the symptoms are of sudden onset or are progressing rapidly/responding poorly to therapy. There is only a small number of cases reported in literature of paraneoplastic systemic sclerosis. Furthermore, the importance of anti-RNA polymerase III antibody testing in scleroderma patients. If positive, it is important to be aware that those patients have >4-fold increased risk of cancer occurring within 2 years of scleroderma onset. It is therefore vital to look for any signs/symptoms during their routine follow-up appointments at rheumatology clinics.

Manchester, United Kingdom
Introduction/Background: This case explores some classic rheumatology topics -systemic sclerosis and antibodies. It is now well recognised that there are a magnitude of different antibodies, beside the typical anti-Scl-70, anticentromere or anti-RNA polymerase III, that can be associated with systemic sclerosis however in 5-10% of cases all antibody tests are negative, yet the patient still displays characteristic clinical features of the disease. We need to ensure such patients are correctly diagnosed, followed up and managed. Description/Method: This case looks at the uncommon presentation of systemic sclerosis without any positive antibody results. I consulted with a 53-year-old male with a past medical history of hypertension, type 2 diabetes, GORD, hypothyroidism, depression and hyperlipidaemia. He had previously been seen in the rheumatology clinic with costochondritis and Raynaud's phenomenon. At this time, he had antibody tests which were all negative (ANA and ENA). He had nailfold capillaroscopy which showed some concerns with widening of capillaries in areas and some linear haemorrhages. This was felt to not be diagnostic of Systemic sclerosis but advised continued follow up and repeat tests. Unfortunately, he failed to attend a subsequent clinic appointment and was lost to follow up. He was referred back to the Rheumatology department in 2021 with worsening symptoms of Raynaud's. At this time he also described symptoms of reflux and dysphagia. He was suffering from generalised fatigue and pains. On examination he had tightening of the skin on his hands and was prayer sign positive. His antibody tests were repeated, again all coming back negative. We then arranged for repeat nailfold capillaroscopy and thermographic testing. This showed very little rewarming after cold challenge with delay even at 30 degrees. The nailfold capillaroscopy showed generalised widening of the capillaries with occasional distortion and tortuosity. There were multiple linear haemorrhages. This study was reported showing definite abnormality in keeping with a diagnosis of systemic sclerosis. Discussion/Results: This highlights the rare but now well recognised phenomenon of antibody negative systemic sclerosis which makes up around 5-10% of cases. It also shows how nailfold capillaroscopy can be a key tool in diagnosing this, and the features to look out for in order to do so -capillary widening, haemorrhage and loss of architecture. The case demonstrates some of the more common features of antibody negative systemic sclerosis including a higher proportion of male patients and prominent GI features. There are generally less severe vascular features including pulmonary hypertension and telangiectasia, with Raynaud's less often leading to digital ulcers and pitting. In this case we suggested uptitration of his nifedipine to try and help control his Raynaud's symptoms. Given the significant GI features this patient was experiencing we referred him on for further evaluation by the gastroenterology team. I think some aspects of this case were blurred by his comorbidities, especially diabetes, and some of his skin disease and pains were attributed to this. However, with hindsight and seeing how his symptoms progressed, I think we could question if more could have been done earlier in the course of this patient's disease -maybe when the initial abnormal, if not diagnostic, capillaroscopy results were available. Unfortunately, the patient not attending further clinic appointments reduced the opportunities to do this, but this also raised a good question about how we try to ensure patient engagement and deal with patients who don't attend follow up. Key learning points/Conclusion: This was an excellent case for us to be able to learn about systemic sclerosis and the spectrum of disease it encompasses. It was interesting to learn about the different features and presentations of the disease, and how these different phenotypes correlate to certain antibodies classically being present, or as in this case, not present. It also enabled me to consider how we manage complex patients with multiple comorbidities and variable compliance. I feel that this conference would allow us to learn from other complex cases and how to best manage patients with similar issues, including systemic sclerosis, prominent pain issues, and gastrointestinal issues within rheumatology.
Abstract citation ID: rkac067.024 P24 A CASE OF LIMITED CUTANEOUS SYSTEMIC SCLEROSIS TEMIC OSUM

NHS trust, London, United Kingdom
Introduction/Background: Systemic sclerosis is an autoimmune condition characterised by fibrosis of the skin and internal organs. A considerable number of patients with systemic sclerosis may present with symptoms of other connective tissue disorders over time. The onset of overlap syndromes affects management and prognosis. We present a case of a 46-year-old man with limited cutaneous systemic sclerosis who presented with significant proteinuria secondary to lupus nephritis, and non-healing leg ulcers secondary to pyoderma gangrenosum, a condition that is rarely associated with SLE or systemic sclerosis. To our knowledge there are no published reports of SSc-SLE-Pyoderma Gangrenosum Overlap. Description/Method: In 2004, a 28-year-old Black man presented to the rheumatology clinic with a history of Raynaud's phenomenon, digital ulcers, sclerodactyly and widespread telangiectasiae. He was ANA (nucleolar pattern), anti-Ro and anti-Jo1 positive, however he did not have clinical features of Sjogren's syndrome or anti-synthetase syndrome. He was diagnosed with limited cutaneous systemic sclerosis and managed with Nifedipine and Sildenafil. Over the next decade of rheumatology clinic monitoring he did not develop pulmonary hypertension or organ involvement. In 2018, he was admitted to hospital with a pulmonary embolus and had a negative thrombophilia screen and antiphospholipid syndrome screen. Immunology revealed new autoantibodies: anti-Smith, Anti-U1RNP and anti-dsDNA. In 2021, aged 46-years, he was admitted to hospital with a large, painful punched-out ulcer on his left medial malleolus that was rapidly expanding. In addition, he had noticed significant weight loss and breathlessness on minimal exertion. He was hypoalbuminemic (albumin ¼ 30g/l [35-52] ) with proteinuria (urine protein:creatinine ratio 150mg/mmol), however his creatinine and eGFR were normal. Immunology was unchanged. He had hypocomplementenemia. He was ANCA and Cryoglobulin negative. CT chest-abdomen-pelvis showed small pleural effusions but no malignancy or infection. Echocardiogram showed a small pericardial effusion with normal pulmonary artery pressures. Vascular doppler scans showed normal arterial circulation in his lower limbs. Microbiology reported a significant growth of Pseudomonas Aeruginosa from the leg ulcer swab and the skin biopsy showed neutrophilic infiltrates in the dermis, consistent with pyoderma gangrenosum. Renal biopsy was consistent with lupus nephritis class III and V. In-patient management included a course of antibiotics for the Pseudomonas Aeruginosa infection followed by oral Prednisolone and Mycophenolate Mofetil for lupus nephritis. The proteinuria has resolved and the left leg ulcer has reduced in size however he has developed new ulcers on the right leg which are being treated at present. Discussion/Results: Overlap connective tissue disorders are well recognised in rheumatology. This patient initially presented with features of limited cutaneous systemic sclerosis (Raynaud's phenomenon, digital ulcers and sclerodactyly). Limited cutaneous systemic sclerosis is typically associated with anti-centromere antibodies, but it can also be associated with nucleolar staining pattern of ANA or anti-Ro antibodies, which was seen in this patient. On presentation with a pulmonary embolus in 2018, his antibody profile showed anti-dsDNA, anti-Smith, anti-U1RNP, low complements although he had no clinical features suggestive of SLE. When he later presented with a leg ulcer, he had serositis and a raised protein-creatinine ratio, more consistent with SLE. He was normotensive and had a normal creatinine, which would go against a scleroderma renal crisis, and indeed the renal biopsy confirmed lupus nephritis. The incidence of overlap between SLE-SSc has