OA16 A great imitator of scleroderma

Abstract Introduction/Background Eosinophilic fasciitis is a rare disease of idiopathic aetiology, which can often mimic scleroderma in presentation and has been associated with haematological diseases. We present a case of eosinophilic fasciitis where the diagnosis was delayed due to the attribution of skin manifestations to scleroderma. This case highlights the importance of careful history and examination to recognize these differential diagnoses, prevent delay and improve outcome. Description/Method A 69-year-old gentleman was referred to the Rheumatology clinic with suspected diffuse cutaneous systemic sclerosis. He presented with a 9-month history of skin tightening, pain and swelling affecting his legs, finding it difficult to fully extend at the knees, to drive or walk. His symptoms progressed overtime with skin changes spreading to all four extremities, abdomen and back. He reported weight loss of 12Kg associated with early satiety. He also experienced intermittent numbness of his hands. There were no respiratory symptoms, dysphagia or Raynaud’s phenomenon reported. His medical history includes atrial fibrillation and asbestos exposure. Currently on Apixaban 5mg/daily and Bisoprolol 2.5mg/daily. Physical examination revealed diffuse brown hyperpigmentation, erythema and thickened skin on his upper and lower limbs, abdomen and back, it was difficult to crease the skin and there was ‘peau d’orange’ appearance in his forearms. His face and hands were spared. Phalen's and Tinel’s tests were negative. Prior to clinical review he was investigated for paraneoplastic disease: a CT chest, abdomen and pelvis showed an incidental cyst in the thymus and emphysema with no underlying malignancy. Laboratory tests showed normocytic normochromic anaemia with haemoglobin 112 g/L and eosinophilia 1.5 x 109/L, elevated erythrocyte sedimentation rate 62mm/h, CRP 57mg/L, polyclonal hypergammaglobulinaemia IgA 4.3g/L and IgG 24.85g/L. The myeloma screen were negative. The absence of Raynaud’s, and the distribution of skin changes sparing his face, hands and feet, eosinophilia and raised inflammatory markers, made the diagnosis of eosinophilic fasciitis. Histological analysis of a full thickness skin biopsy confirmed patchy lymphoplasmacytic inflammatory cell infiltrate within the fascia and spilling into subcutis, with eosinophils. Subsequently, he was commenced on prednisolone 40mg/daily reducing regimen and Methotrexate 20mg/weekly, with a good response and regression of the swelling and pain. He is now able to walk without difficulty. Discussion/Results Eosinophilic fasciitis is rare. Symptoms can be similar to those of scleroderma, sometimes considered a variant. The exact aetiology is unknown; however, the literature mentions a potential paraneoplastic, inflammatory, infectious or physical trigger, leading to an abnormal response with accumulation of eosinophils in different tissues. Consequently, this may release transforming growth factor beta to activate fibroblasts, increasing expression of other factors in the connective tissue, resulting in fibrosis. This case highlights that eosinophilic fasciitis present with hardening and thickening of the skin and surrounding tissue similar to that of scleroderma, however, lacks Raynaud’s phenomenon, sclerodactyly. Another striking features from his examination which helped us distinguishing from scleroderma was that his skin changes spare his face, hands and feet. Carpal tunnel syndrome is described in the literature which can progress if untreated. Typical blood tests findings documented in the literature include eosinophilia in 80% of the cases, elevated ESR and C-reactive protein (CRP), polyclonal hypergammaglobulinaemia, are usually present, however, eosinophilia may be transient, therefore normal eosinophil count does not exclude the disease. ANA and Rheumatoid factor can be positive in up to 10 % of the cases. MRI of the extremities to look for thickening of the fascia has been used in other cases, however, it was not required in our case because our Orthopaedics colleagues helped us with performing an urgent full thickness biopsy. Recommended treatment includes high dose steroids and immunosuppressive medication such Methotrexate is most often used for severe or resistant cases. The prognosis is good, however if treatment is delayed patients can develop joint contractures in 85% of patients and skin hardness may persist. In conclusion, careful history and examination is essential in differentiating scleroderma from the scleroderma-mimics especially when there is an atypical distribution, no sclerodactyly and no autoantibodies. Key learning points/Conclusion 1. This case suggest that clinicians should be aware that eosinophilic fasciitis typically spare the hands, feet and face. 2. Eosinophilia may be transient, therefore normal count does not exclude the disease. 3. Recognizing this rare but great imitator of scleroderma set the stage for prompt therapy in either condition and reduce morbidity.

with shortness of breath on exertion, frequent palpitations, nonexertional chest tightness, and fatigue. Description/Method: In 2011, she presented with inflammatory arthritis as well as Raynaud's phenomenon. Her anti-nuclear antibody screen showed a positive anti-SCL-70 and anti-U3RNP. Over the years she developed pulmonary hypertension, renal involvement (proteinuria), dysphagia, cutaneous involvement (sclerodactyly, digital ulcers, telangiectasia) and interstitial lung disease. She was commenced on methotrexate and prednisolone. Her pulmonary hypertension was controlled on macitentan and sildenafil. Her pulse was 112 beats per minute, regular with a blood pressure of 168/85 mmHg. She had a loud P2 and a parasternal heave. She had sparse basal crepitations. She had mild pitting oedema to her knees. Her JVP was not raised. Her weight was 38kg. Her right heart catheterisation in April 2021 reported a mean pulmonary artery pressure of 24mmHg and pulmonary vascular resistance of 255 ARU. A computerized tomography (CT) scan of her chest showed known interstitial lung disease and no pulmonary embolism. Her lung function tests were stable. A cardiovascular magnetic resonance imaging (CMR) guided cardiac catheter in April 2021 showed scleroderma involvement of the heart, with mild pericardial effusion and elevated native myocardial T1 and T2. Left ventricular ejection fraction was normal. The impression was that of scleroderma with myocardia involvement. Her immunosuppression was escalated to cyclophosphamide. A cardiac MRI in September 2021 showed improvements in T1 and T2 mapping parameters. She completed 4 cycles of cyclophosphamide (15mg/kg). However, due to gastrointestinal side effects (nausea and vomiting) and a diagnosis of latent tuberculosis in February 2022, cyclophosphamide was stopped. In March 2022, her repeat CMR showed that the T1 and T2 mapping had slightly increased and presented again with chest pain and palpitations. Following a multidisciplinary team discussion, the patient was treated with rituximab 500mg two weeks apart with 100mg of methylprednisolone as premedication prior to the infusions. Discussion/Results: Although subclinical cardiac involvement in scleroderma is common, only 10 to 30% of patients are symptomatic. Our patients complained of non-exertional chest pain. Macrovascular coronary disease had been excluded; the cause of her chest pain was likely secondary to microvascular dysfunction. In patients with cardiac scleroderma, the mechanism of coronary disease is secondary to myocardial inflammation and repeated microvascular ischaemia. This results in reperfusion defects secondary to necrosis, in turn driving myocardial fibrosis. In the late stages, fibrosis results in left ventricular diastolic dysfunction, a complication related to increased mortality. Supraventricular tachycardia is one of the manifestations in conduction abnormalities in cardiac scleroderma: others include conduction defects and bradyarrhythmias. As with our patient, tachyarrhythmias can be associated with symptoms such as generalised fatigue, shortness of breath, and exercise intolerance. Another complication found on imaging was a small pericardial effusion. This is the most common pericardial disease in scleroderma. For most, pericardial effusions are asymptomatic; however, it can be associated with complications such as tamponade. Whilst cyclophosphamide is a common treatment choice for scleroderma with cardiac involvement, evidence for this is limited to case series due to its rarity. Additionally, it carries significant toxicity: Our case developed significant nausea and vomiting following her third and fourth cyclophosphamide infusions and this was discontinued also in light of her diagnosis of latent TB. Rituximab, the agent to which the patient was subsequently switched, similarly has a growing body of evidence in cardiac scleroderma. Since her rituximab infusions, our case has remained stable and she has noticed an improvement of her clinical symptoms. Key learning points/Conclusion: Cardiac scleroderma is associated with significant reduction in quality of life, morbidity, and mortality. It is often difficult to treat due to sparsity of high-quality evidence (as in other rare conditions) as well as the multiple organ systems and comorbidities involved. This case illustrates the clinical manifestation of cardiac scleroderma and the difficulty in selecting appropriate immunosuppression medication.
has been associated with haematological diseases. We present a case of eosinophilic fasciitis where the diagnosis was delayed due to the attribution of skin manifestations to scleroderma. This case highlights the importance of careful history and examination to recognize these differential diagnoses, prevent delay and improve outcome. Description/Method: A 69-year-old gentleman was referred to the Rheumatology clinic with suspected diffuse cutaneous systemic sclerosis. He presented with a 9-month history of skin tightening, pain and swelling affecting his legs, finding it difficult to fully extend at the knees, to drive or walk. His symptoms progressed overtime with skin changes spreading to all four extremities, abdomen and back. He reported weight loss of 12Kg associated with early satiety. He also experienced intermittent numbness of his hands. There were no respiratory symptoms, dysphagia or Raynaud's phenomenon reported. His medical history includes atrial fibrillation and asbestos exposure. Currently on Apixaban 5mg/daily and Bisoprolol 2.5mg/daily. Physical examination revealed diffuse brown hyperpigmentation, erythema and thickened skin on his upper and lower limbs, abdomen and back, it was difficult to crease the skin and there was 'peau d'orange' appearance in his forearms. His face and hands were spared. Phalen's and Tinel's tests were negative. Prior to clinical review he was investigated for paraneoplastic disease: a CT chest, abdomen and pelvis showed an incidental cyst in the thymus and emphysema with no underlying malignancy. Laboratory tests showed normocytic normochromic anaemia with haemoglobin 112 g/L and eosinophilia 1.5 x 10 9 /L, elevated erythrocyte sedimentation rate 62mm/h, CRP 57mg/L, polyclonal hypergammaglobulinaemia IgA 4.3g/L and IgG 24.85g/L. The myeloma screen were negative. The absence of Raynaud's, and the distribution of skin changes sparing his face, hands and feet, eosinophilia and raised inflammatory markers, made the diagnosis of eosinophilic fasciitis. Histological analysis of a full thickness skin biopsy confirmed patchy lymphoplasmacytic inflammatory cell infiltrate within the fascia and spilling into subcutis, with eosinophils. Subsequently, he was commenced on prednisolone 40mg/daily reducing regimen and Methotrexate 20mg/weekly, with a good response and regression of the swelling and pain. He is now able to walk without difficulty. Discussion/Results: Eosinophilic fasciitis is rare. Symptoms can be similar to those of scleroderma, sometimes considered a variant. The exact aetiology is unknown; however, the literature mentions a potential paraneoplastic, inflammatory, infectious or physical trigger, leading to an abnormal response with accumulation of eosinophils in different tissues. Consequently, this may release transforming growth factor beta to activate fibroblasts, increasing expression of other factors in the connective tissue, resulting in fibrosis. This case highlights that eosinophilic fasciitis present with hardening and thickening of the skin and surrounding tissue similar to that of scleroderma, however, lacks Raynaud's phenomenon, sclerodactyly. Another striking features from his examination which helped us distinguishing from scleroderma was that his skin changes spare his face, hands and feet. Carpal tunnel syndrome is described in the literature which can progress if untreated. Typical blood tests findings documented in the literature include eosinophilia in 80% of the cases, elevated ESR and C-reactive protein (CRP), polyclonal hypergammaglobulinaemia, are usually present, however, eosinophilia may be transient, therefore normal eosinophil count does not exclude the disease. ANA and Rheumatoid factor can be positive in up to 10 % of the cases. MRI of the extremities to look for thickening of the fascia has been used in other cases, however, it was not required in our case because our Orthopaedics colleagues helped us with performing an urgent full thickness biopsy. Recommended treatment includes high dose steroids and immunosuppressive medication such Methotrexate is most often used for severe or resistant cases. The prognosis is good, however if treatment is delayed patients can develop joint contractures in 85% of patients and skin hardness may persist.
In conclusion, careful history and examination is essential in differentiating scleroderma from the scleroderma-mimics especially when there is an atypical distribution, no sclerodactyly and no autoantibodies. Key learning points/Conclusion: 1. This case suggest that clinicians should be aware that eosinophilic fasciitis typically spare the hands, feet and face. 2. Eosinophilia may be transient, therefore normal count does not exclude the disease. 3. Recognizing this rare but great imitator of scleroderma set the stage for prompt therapy in either condition and reduce morbidity.

Kingdom
Introduction/Background: Scleroderma is an autoimmune systemic disease characterised by fibrosis of the skin and vasculopathy mainly affecting the digital arteries. However, it can have variable presentations overlapping with other connective tissue diseases (CTD). It is associated with distinct anti bodies which will determine the clinical phenotype and the prognosis of the disease. Therefore, it is important to ascertain the presence of these antibodies early in the disease. We present a case of limited cutaneous systemic sclerosis (LcSSc) associated with anti PM/Scl antibodies which evolved over time to the characteristic clinical phenotype denoted by the antibodies needing aggressive immunosuppressive treatment. Description/Method: A 60-year-old Caucasian lady was presented to vascular unit with a digital ulcer of the right ring finger following painful bluish discolouration. She had history of cervical cancer, bilateral cervical ribs and was a smoker. Vascular surgeons ruled out large/medium vessel disease and thoracic outlet obstruction. Raynaud syndrome (RS) was diagnosed and started on nifedipine. 3 months later she was admitted with progression of RS involving both hands and painful swelling of the fingers requiring iloprost infusions. Patient was referred to rheumatology team who detected synovitis of the hands and no other features of CTD. She was found to be positive for ANA 1:320-640 titre with a nucleolar pattern. DsDNA and ENA panel were negative. LcSSc was diagnosed.
Over a year she developed gradual onset skin thickening up to the metacarpophalangeal joints, weakness of the proximal muscles of the lower limbs (power 4/5) and symptomatic interstitial lung disease with HRCT findings in keeping with cellular nonspecific interstitial pneumonitis. She was found to be positive for PM/Scl 75 and PM/Scl100 antibodies. Her creatine kinase (CK) was elevated to 2259U/l and MRI confirmed myositis. Treatment decisions were made after liaising with a tertiary care centre. She was started on prednisolone 30 mg daily with good initial response and mycophenolate was introduced while reducing steroids. However, she was unable to stop steroids completely as symptoms worsened requiring frequent dose escalations. Low dose methotrexate was added on but she was intolerant. In the meantime, her myositis and lung disease deteriorated further with involvement of the upper limbs, elevation of CK, new fibrotic changes in the HRCT and deteriorating lung function tests. She was treated with Rituximab with good response in terms of both muscle power and respiratory symptoms. However, after a year, symptoms deteriorated and she is awaiting repeat rituximab. Discussion/Results: The presentation and the progression of the disease of our patient is important to understand especially how scleroderma can evolve over time and how patients' antibody profiles can be used for early identification and management of various phenotypes. Primary RS is unlikely to cause digital ulceration which was the initial presentation of our patient. She also had concomitant cervical ribs complicating the matter and the initial focus was on excluding proximal vascular insufficiency. She was referred to the rheumatology only at the point of worsening RS requiring iloprost infusions. At diagnosis, she only had swollen fingers, synovitis and RS which was initially managed with vasodilators and low dose prednisolone. Over one and half years she developed myositis and ILD in keeping with NSIP pattern emphasizing the importance of close follow up of the patients with scleroderma as the major organ involvement occurs within the first 3 years of diagnosis. Anti PM/Scl 75/100 is a myositis associated antibody that denotes an overlap syndrome characterised by LcSsc, myositis, synovitis, ILD and calcinosis, present in 5% of the patients with Scleroderma. Our patient didn't fulfil EULAR classification criteria for idiopathic inflammatory myositis probably due to the absence of muscle biopsy. Patients with anti PM/Scl 75/100 show a nucleolar pattern on ANA staining as in our patient and usually show better prognosis in terms of ILD. Nevertheless, our patient didn't respond well to first line immunosuppressive medication (steroids and mycophenolate) and needed Rituximab. The first presentation of myositis and ILD were treated with high dose prednisolone (30mg) which was a challenging decision due to high risk of scleroderma renal crisis associated with steroid treatment and it being common within the first 5 years of the diagnosis. Her blood pressure was closely monitored during the treatment. Key learning points/Conclusion: It is important to identify patients with RP secondary to underlying connective tissue disease and refer them early to the rheumatology services for further workup. i10 https://academic.oup.com/rheumap