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P0437 SARCOIDOSIS OCCURRING DURING ANTI TUMOR NECROSIS FACTOR ALPHA THERAPY, NO RELAPSE AFTER RECHALLENGE
S148
Abstracts from 8th Congress of the European Federation of Internal Medicine / European Journal of Internal Medicine 20S (2009), S1–S283
fell significantly with treatment over the 6 months period. (p<0.001). Mean homocysteine levels did not show significant change (95% CI, P=0.09) but there was a trend towards a fall. Mean body weight and mean systolic/diastolic BP levels did not change significantly. Discussion & conclusion: Significant change in DAS 28, ESR and CRP confirms the powerful anti-inflammatory effect of anti-TNF therapy in RA. But its effect on lipid profile is disappointing in our study. Significant reduction in HDL at 6 months of treatment makes lipid profile more atherogenic, which in theory would lead to increased cardiovascular morbidity and mortality. However it is not clear at this time that this would lead to increased cardiovascular complications in RA in the long term. This could be addressed only by randomized controlled clinical trials over a long period of time. Although there is no significant change in the homocysteine levels in our study we feel that homocysteine could still be an important cardiovascular risk factor in RA patients because its metabolism is altered by RA and its drug treatment (Methotrexate). Further research in this area is definitely required.
P0437 SARCOIDOSIS OCCURRING DURING ANTI TUMOR NECROSIS FACTOR ALPHA THERAPY, NO RELAPSE AFTER RECHALLENGE
Deborah F. Van Der Stoep, Jende Van Zeben, Gert Jan Braunstahl, Vincent Noordhoek Hegt, Jacques M.G.W. Wouters. Sint Franciscus Gasthuis Introduction: The development of sarcoidosis during anti-TNFα is an adverse event that has been reported increasingly. This raises a lot of questions. Since TNFα plays an important role in granuloma formation, anti-TNFα agents are supposed to be effective in the treatment of granulomatous diseases such as Crohn’s disease and sarcoidosis. In the cases described below sarcoidosis occurred during ant-TNFα therapy. After cure/stabilization of the sarcoidosis both patients were re-challenged with the anti-TNFα agent they used originally. Cases The first patient was a 55-year-old woman with a rheumatoid arthritis (RA) for which she uses adalimumab 40mg every two weeks. Under this treatment she develops skin lesions on both knees and dyspnea. A CT scan of the thorax showed an extensive hilar and mediastinal lymfadenopathy. Broncho alveolar lavage (BAL) showed a lymfocytosis with a CD4/CD8 ratio of 2,3. Cultures for routine bacteria’s and TBC (including auramines and PCR) in sputum and BAL fluid were negative. Histological biopsies of the lung and skin lesions showed non-caseeating granulomas. The diagnosis of sarcoidosis was made and treatment with adalumimab was discontinued. The skin lesions as well as the lymfadenopathy and dyspnoea disappeared. Adalimumab was reinitiated and to date, two years later, the patient is still symptom free. The second patient is a 51-year-old woman with rheumatoid arthritis for which she uses etanercept 50mg per week, patient complained of cough, fever, a soar throat and earache, cervical lymfadenopathy and a swollen parotid gland. Methotrexate and etanercept were discontinued. CT thorax showed a hilar lymfadenopathy. BAL showed a lymfocytosis with a CD4/CD8 ratio of 12. A histological lung biopsy shows non-caseeating granulomas. At this stage a diagnosis of sarcoidosis was made. Because of a flare of the RA, prednisone 10mg daily was initiated. Hilar lymfadenopathy stabilized, the cough and parotid gland swelling disappeared. Etanercept was reinitiated and to date (17 months later) the patient is symptom free. Conclusion: This report describes the first two patients who got a rechalenge with their originally anti-TNFα agent after cure/stabilization of the sarcoidosis. The fact that there was no relapse after rechallenge makes a direct causative relation between the granuloma formation and the anti-TNFα therapy unlikely. It could be that the granulomatous disease we have indicated as sarcoidosis, was due to an underlying infection we have not been able to prove.
P0438 SJOGREN’S SYNDROME AND EOSINOPHILIC ESOPHAGITIS – A COINCIDENCE?
Diana Valadares, Ana Sá, Elsa Sousa, Sara Marques, Isabel Almeida, Carlos Vasconcelos. Unidade De Imunologia Clínica, Hospital Santo António Sjogren’s syndrome (SS) is an autoimmune disorder characterized by an increase in B-cell activity and the appearance in the plasma of several antibodies, some organ –specific. Clinically is a chronic inflammatory disorder characterized by diminished exocrine gland (lacrimal and salivary) function and extraglandular involvement, such as lung, skin, heart and gastrointestinal tract. SS occurs in a primary form or associated with systemic diseases (connective tissue disease).
Eosinophilic esophagitis (EoE) is a clinicopathologic entity in which abnormal infiltration of eosinophils into the esophageal mucosa may lead to dysphagia, progressive esophageal stenosis, and food impaction. The pathogenesis of eosinophilic esophagitis is unknown. Eosinophils establish themselves as permanent residents of the gastrointestinal tract early during embryonic development, although they are not normally found in the esophagus. The recruitment of eosinophils is observed in a variety of inflammatory or infectious conditions. The authors report a case of a 40 years old woman with diagnosis of primary SS since 2006 (ocular symptoms, a positive salivary gland scintigraphy, presence of autoantibodies, anti-Ro/SSA and anti-LA/SSB). In July 2008 she developed a clinical picture of progressive solid dysphagia with history of food impaction during three months. No vomiting, abdominal pain or diarrheas were associated. She began Proton Pump Inhibitors (PPI), 40mg 12/12h during one month without any improvement. In the upper endoscopy was documented esophageal dysmotility with proximal strictures and normal macroscopic structures, such as stomach and duodenum. Several biopsies were obtained along the length of the esophagus. Histological findings report a huge esophageal eosinophilic infiltration (≥ 15 eosinophils per high powered) with normal gastric and duodenal mucosal. Serum markers, as peripheral eosinophilia was present (590/uL). Other causes of secondary esophageal eosinophilic infiltration, such as drug exposure, parasitic and fungal infections and gastroesophageal reflux disease were excluded. We treated the patients with systemic corticosteroid, 1 mg/kg per day, divided into twice daily dosing and metoclopramide, 10mg 8/8h. After four weeks of treatment the patients showed remission of clinical and serum findings. In summary, this case is an example of epiphenomenon, two diseases in a single patient or may it be the first manifestation of a SS associated to a scleroderma disease or a gastrointestinal involvement by primary SS?
P0439 CUTANEOUS MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS AND OVERLAP SYNDROME. EXPERIENCE AND RESULTS IN OUR AUTOINMUNE DISEASES CLINIC
Inmaculada Paez, Silvia Quattrino, Ester Ortiz, Carmen Manzano, Begoña Pérez, Francisco Muñoz, Jose Antonio González, Javier Carrasco, Ignacio Martín. Juan Ramón Jiménez Hospital Background: Symptomatic clinical manifestations of the skin and mucous membranes involve in over 80 percent of patients with Systemic Lupus Erythematosus (SLE). The variability of this kind of lesions is very grand. We reviewed the clinical features and treatment of the more frequent disorders. Aims: Evaluation of the clinical features and management of the most common cutaneous lesions in patients with SLE and Overlap Syndrome (OS), who were followed in our Autoimmune Diseases Clinic (ADC) Methods: A descriptive study on patients with SLE and OS was performed. We reviewed the clinical history of 35 patients and described the most relevant disorders. Results: 35 patients were evaluated. Average age was 40 years and 77% were female. The main Clinical Manifestations were: musculoskeletal symptoms in 24 patients, hematologic disorders (9 patients), pulmonary involvement in 5 cases, peripheral neuropathy (2 patients), 1 aseptic meningitis, 2 psychosis and 2 patients with cardiac abnormalities. 7 of them had Antiphospholipid Syndrome (APS) associated and 18 had another autoimmune disease.The clinical course of SLE was characterized by periods of remissions and acute relapse. 4 patients developed severe and life-threatening relapses. On the other hand, the cutaneous manifestations were: 65% had signs of acute SLE (16 patients with butterfly rash and 16 with photosensitivity), 60% developed subacute SLE lesions (18 annular form and 3 psoriasiform lesions) and 11% developed chronic discoid lesions. A variety of other cutaneous lesions were noticed in 19 cases: 7 vascular involvement (livedo reticularis, telangiectasia, Raynaud phenomenon and vasculitis), 3 nonscarring alopecia, 8 oral ulcers, 1 Bullous skin lesions and 1 chronic urthicaria. 80% had cutaneous involvement when they were diagnosed of SLE. We found a case of drug-induced lupus with Leflunomide. About topical therapies, we recommended sun protection and use of sun screens in the most. Glucocorticoids were used in 12 of them and immunosuppressants in 8. 7 patients need systemic glucocorticoids, 23 antimalarials and 11 were treated with immunosuppressive agents. Monoclonal antibodies were reserved for 5 patients with significant organ involvement. A total of 33 patients with SLE developed a mild disease. Topical therapies were useful on 21%. One of our patients died. Conclusions: In our experience, preventive measures should be performed to avoid high sun exposure and we should generally recommend the use of
Abstracts from 8th Congress of the European Federation of Internal Medicine / European Journal of Internal Medicine 20S (2009), S1–S283
fell significantly with treatment over the 6 months period. (p<0.001). Mean homocysteine levels did not show significant change (95% CI, P=0.09) but there was a trend towards a fall. Mean body weight and mean systolic/diastolic BP levels did not change significantly. Discussion & conclusion: Significant change in DAS 28, ESR and CRP confirms the powerful anti-inflammatory effect of anti-TNF therapy in RA. But its effect on lipid profile is disappointing in our study. Significant reduction in HDL at 6 months of treatment makes lipid profile more atherogenic, which in theory would lead to increased cardiovascular morbidity and mortality. However it is not clear at this time that this would lead to increased cardiovascular complications in RA in the long term. This could be addressed only by randomized controlled clinical trials over a long period of time. Although there is no significant change in the homocysteine levels in our study we feel that homocysteine could still be an important cardiovascular risk factor in RA patients because its metabolism is altered by RA and its drug treatment (Methotrexate). Further research in this area is definitely required.
P0437 SARCOIDOSIS OCCURRING DURING ANTI TUMOR NECROSIS FACTOR ALPHA THERAPY, NO RELAPSE AFTER RECHALLENGE
Deborah F. Van Der Stoep, Jende Van Zeben, Gert Jan Braunstahl, Vincent Noordhoek Hegt, Jacques M.G.W. Wouters. Sint Franciscus Gasthuis Introduction: The development of sarcoidosis during anti-TNFα is an adverse event that has been reported increasingly. This raises a lot of questions. Since TNFα plays an important role in granuloma formation, anti-TNFα agents are supposed to be effective in the treatment of granulomatous diseases such as Crohn’s disease and sarcoidosis. In the cases described below sarcoidosis occurred during ant-TNFα therapy. After cure/stabilization of the sarcoidosis both patients were re-challenged with the anti-TNFα agent they used originally. Cases The first patient was a 55-year-old woman with a rheumatoid arthritis (RA) for which she uses adalimumab 40mg every two weeks. Under this treatment she develops skin lesions on both knees and dyspnea. A CT scan of the thorax showed an extensive hilar and mediastinal lymfadenopathy. Broncho alveolar lavage (BAL) showed a lymfocytosis with a CD4/CD8 ratio of 2,3. Cultures for routine bacteria’s and TBC (including auramines and PCR) in sputum and BAL fluid were negative. Histological biopsies of the lung and skin lesions showed non-caseeating granulomas. The diagnosis of sarcoidosis was made and treatment with adalumimab was discontinued. The skin lesions as well as the lymfadenopathy and dyspnoea disappeared. Adalimumab was reinitiated and to date, two years later, the patient is still symptom free. The second patient is a 51-year-old woman with rheumatoid arthritis for which she uses etanercept 50mg per week, patient complained of cough, fever, a soar throat and earache, cervical lymfadenopathy and a swollen parotid gland. Methotrexate and etanercept were discontinued. CT thorax showed a hilar lymfadenopathy. BAL showed a lymfocytosis with a CD4/CD8 ratio of 12. A histological lung biopsy shows non-caseeating granulomas. At this stage a diagnosis of sarcoidosis was made. Because of a flare of the RA, prednisone 10mg daily was initiated. Hilar lymfadenopathy stabilized, the cough and parotid gland swelling disappeared. Etanercept was reinitiated and to date (17 months later) the patient is symptom free. Conclusion: This report describes the first two patients who got a rechalenge with their originally anti-TNFα agent after cure/stabilization of the sarcoidosis. The fact that there was no relapse after rechallenge makes a direct causative relation between the granuloma formation and the anti-TNFα therapy unlikely. It could be that the granulomatous disease we have indicated as sarcoidosis, was due to an underlying infection we have not been able to prove.
P0438 SJOGREN’S SYNDROME AND EOSINOPHILIC ESOPHAGITIS – A COINCIDENCE?
Diana Valadares, Ana Sá, Elsa Sousa, Sara Marques, Isabel Almeida, Carlos Vasconcelos. Unidade De Imunologia Clínica, Hospital Santo António Sjogren’s syndrome (SS) is an autoimmune disorder characterized by an increase in B-cell activity and the appearance in the plasma of several antibodies, some organ –specific. Clinically is a chronic inflammatory disorder characterized by diminished exocrine gland (lacrimal and salivary) function and extraglandular involvement, such as lung, skin, heart and gastrointestinal tract. SS occurs in a primary form or associated with systemic diseases (connective tissue disease).
Eosinophilic esophagitis (EoE) is a clinicopathologic entity in which abnormal infiltration of eosinophils into the esophageal mucosa may lead to dysphagia, progressive esophageal stenosis, and food impaction. The pathogenesis of eosinophilic esophagitis is unknown. Eosinophils establish themselves as permanent residents of the gastrointestinal tract early during embryonic development, although they are not normally found in the esophagus. The recruitment of eosinophils is observed in a variety of inflammatory or infectious conditions. The authors report a case of a 40 years old woman with diagnosis of primary SS since 2006 (ocular symptoms, a positive salivary gland scintigraphy, presence of autoantibodies, anti-Ro/SSA and anti-LA/SSB). In July 2008 she developed a clinical picture of progressive solid dysphagia with history of food impaction during three months. No vomiting, abdominal pain or diarrheas were associated. She began Proton Pump Inhibitors (PPI), 40mg 12/12h during one month without any improvement. In the upper endoscopy was documented esophageal dysmotility with proximal strictures and normal macroscopic structures, such as stomach and duodenum. Several biopsies were obtained along the length of the esophagus. Histological findings report a huge esophageal eosinophilic infiltration (≥ 15 eosinophils per high powered) with normal gastric and duodenal mucosal. Serum markers, as peripheral eosinophilia was present (590/uL). Other causes of secondary esophageal eosinophilic infiltration, such as drug exposure, parasitic and fungal infections and gastroesophageal reflux disease were excluded. We treated the patients with systemic corticosteroid, 1 mg/kg per day, divided into twice daily dosing and metoclopramide, 10mg 8/8h. After four weeks of treatment the patients showed remission of clinical and serum findings. In summary, this case is an example of epiphenomenon, two diseases in a single patient or may it be the first manifestation of a SS associated to a scleroderma disease or a gastrointestinal involvement by primary SS?
P0439 CUTANEOUS MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS AND OVERLAP SYNDROME. EXPERIENCE AND RESULTS IN OUR AUTOINMUNE DISEASES CLINIC
Inmaculada Paez, Silvia Quattrino, Ester Ortiz, Carmen Manzano, Begoña Pérez, Francisco Muñoz, Jose Antonio González, Javier Carrasco, Ignacio Martín. Juan Ramón Jiménez Hospital Background: Symptomatic clinical manifestations of the skin and mucous membranes involve in over 80 percent of patients with Systemic Lupus Erythematosus (SLE). The variability of this kind of lesions is very grand. We reviewed the clinical features and treatment of the more frequent disorders. Aims: Evaluation of the clinical features and management of the most common cutaneous lesions in patients with SLE and Overlap Syndrome (OS), who were followed in our Autoimmune Diseases Clinic (ADC) Methods: A descriptive study on patients with SLE and OS was performed. We reviewed the clinical history of 35 patients and described the most relevant disorders. Results: 35 patients were evaluated. Average age was 40 years and 77% were female. The main Clinical Manifestations were: musculoskeletal symptoms in 24 patients, hematologic disorders (9 patients), pulmonary involvement in 5 cases, peripheral neuropathy (2 patients), 1 aseptic meningitis, 2 psychosis and 2 patients with cardiac abnormalities. 7 of them had Antiphospholipid Syndrome (APS) associated and 18 had another autoimmune disease.The clinical course of SLE was characterized by periods of remissions and acute relapse. 4 patients developed severe and life-threatening relapses. On the other hand, the cutaneous manifestations were: 65% had signs of acute SLE (16 patients with butterfly rash and 16 with photosensitivity), 60% developed subacute SLE lesions (18 annular form and 3 psoriasiform lesions) and 11% developed chronic discoid lesions. A variety of other cutaneous lesions were noticed in 19 cases: 7 vascular involvement (livedo reticularis, telangiectasia, Raynaud phenomenon and vasculitis), 3 nonscarring alopecia, 8 oral ulcers, 1 Bullous skin lesions and 1 chronic urthicaria. 80% had cutaneous involvement when they were diagnosed of SLE. We found a case of drug-induced lupus with Leflunomide. About topical therapies, we recommended sun protection and use of sun screens in the most. Glucocorticoids were used in 12 of them and immunosuppressants in 8. 7 patients need systemic glucocorticoids, 23 antimalarials and 11 were treated with immunosuppressive agents. Monoclonal antibodies were reserved for 5 patients with significant organ involvement. A total of 33 patients with SLE developed a mild disease. Topical therapies were useful on 21%. One of our patients died. Conclusions: In our experience, preventive measures should be performed to avoid high sun exposure and we should generally recommend the use of