- Email: [email protected]
Idiopathic Granulomatous Myositis Successfully Treated with IVIG
S210 Abstracts
Toll-Like Receptor 2 as a Functional Receptor to Respiratory Syncytial Virus Y. Inoue, N. Shimojo, T. Arima, Y. Kohno; Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, JAPAN. RATIONALE: Since respiratory syncytial virus (RSV) infection in infancy may well cause for bronchiolitis and development of asthma and innate immunity is suggested to be involved in the recognition of RSV, we investigated the role of TLRs in defense against RSV. METHODS: 1) Human monocytic cell line THP-1 was stimulated by heat-inactivated RSV, mock (Hep2 cell), ultra-purified LPS or synthetic mycoplasmal lipoprotein FSL-1. Blocking analysis was performed by adding TLR4 blocking antibody (HTA125) or TLR2 blocking antibody (TL2.1). The level of IL-12p40 in the culture supernatant was measured by ELISA. 2) Peritoneal macrophage from C57BL/6 or TLR2-KO on BL/6 background mice were stimulated by heat-inactivated RSV, mock, Ultrapurified LPS or FSL-1. The level of IL-6 in the culture supernatant was measured by ELISA. 3) Various amount of soluble CD14 (sCD14) preincubated with RSV, mock, ultra-purified LPS or FSL-1 were used to stimulate THP-1 cells and the level of IL-12p40 in the culture supernatant was measured by ELISA. RESULTS: 1) TLR2 blocking antibody suppressed heat-inactivated RSV induced IL-12p40 production more strongly than TLR4 blocking antibody did. 2) TLR2-KO macrophage was defective in IL-6 production in response to stimulation with heat-inactivated RSV as well as FSL-1. 3) sCD14 enhanced RSV-induced IL-12p40 production as well as LPSinduced IL-12p40 production. On the other hand sCD14 did not affect FSL-1-induced IL-12p40 production. CONCLUSIONS: Our data suggest that TLR2 is a functional receptor for RSV and sCD14 may work as a co-receptor for RSV like TLR4 recognition of LPS. In contrast, FSL-1 recognition by TLR2 does not need sCD14. Funding: Chiba University
809
MONDAY
Idiopathic Granulomatous Myositis Successfully Treated with IVIG J. Y. Patel, D. P. Huston, G. F. Duna; Section of Immunology, Allergy, Rheumatology, Baylor College of Medicine, Houston, TX. RATIONALE: Granulomatous myositis is a rare autoimmune entity generally associated with sarcoidosis. Case reports of idiopathic and sarcoidosis related granulomatous myositis have reported good response to corticosteroids, but for steroid resistant cases, there is no guidance for treatment. We describe a patient with hypercalcemia and steroid resistant granulomatous myositis successfully treated with IVIG. METHODS: A 23 year old white male was treated with doxycycline for a pustular rash days after returning from a trip to New Zealand and Australia. Two days later, he presented with fever, skin rash, and eosinophilia. He was diagnosed with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) and treated with intravenous steroids followed by oral prednisone. Mycophenolate was added because of inability to decrease prednisone below 40mg daily. Four months after presentation, he developed muscle weakness, dysphagia and creatinine kinase level of 1254 U/L. RESULTS: Muscle biopsy showed a florid mixed inflammatory infiltrate with multinucleated giant cells. Infectious, neoplastic, and vasculitic causes were excluded. Treatment with intravenous and oral cyclophosphamide was attempted with some improvement in muscle strength but prednisone could not be decreased without return of symptoms. The patient was switched to IVIG with improvement in symptoms, CPK levels and prednisone requirement.
810
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
CONCLUSIONS: A systemic autoimmune process must be considered as part of the differential diagnosis of DRESS. Granulomatous myositis may present as an acute and profuse inflammatory myositis. Steroid resistant forms of granulomatous myositis may respond well to IVIG. Macrophage Activation Syndrome (MAS) as a Debut of Systemic Lupus Erythematosus (SLE) in a Child. L. M. Kahn Benarroch, G. Sterba, M. Bosque; Hospital de Clinicas Caracas, Caracas, VENEZUELA. The Macrophage Activation Syndrome (MAS) is a rare pediatric condition characterized by enhanced activation of the macrophage and T-cell system, with increased liberation of T-cell cytokines. Clinically it resembles a multiorgan failure syndrome of infectious etiology. MAS a term used to describe a form of secondary hemophagocytic lymphohistiocytosis (HLH) in association with chronic rheumatic diseases of childhood. Here we describe a female patient 11 years old, became acutely ill, persistent fever, malaise, somnolence, and facial rash. Laboratory reported Epstein-Barr (EBV) positive serology, WBC 3.100, urinalysis microhematuria, and protein loss. Two weeks later she presented with purpuric skin rash, unremitting high fever, treated with antibiotics developed facial erytrodermia and edema. Admitted to the ICU: high fever, extensive ecchymotic lesions, lethargy and irritability. She presented with profound depression blood cell lines; low erythrocyte sedimentation rate (ESR), hepatitis with liver dysfunction, hematuria, proteinuria and renal failure. She then developed pancreatitis, abnormalities clotting profile, reduction in fibrinogen, Serum ferritin > 1.500, elevated LDH. Bone marrow study was carried out; haemophagocytosis was confirmed. Positive ANA 4+, antiDNA 4+, P ANCA 4+, anticardiolipin Ab Negative .She developed encephalopathy with confusion, seizures, and lung disease. Methylprednisolone was given, cyclosporin and cyclophosphamide later because of CNS severely compromised. Secondary Hemophagocytic syndromes associated with rheumatic diseases are rarely seen in LES. This patient presented LES with a SAM as an onset.
811
Is Screening with C4 Complement Level Enough to Exclude Hereditary Angioedema? S. Grigoriadou, M. Duddridge; Immunology, University Hospitals of Leicester NHS Trust, Leicester, UNITED KINGDOM. RATIONALE: Hereditary angioedema (HAE) is caused by deficiency of C1 inhibitor. The diagnosis is established by a low C4 complement level, and absent or very low C1 inhibitor level or function. It has been suggested that serum C4 level is a good screening test for the disease and the diagnosis can be excluded if C4 level is normal (1,2). METHODS: The original serology of 35 known HAE patients was reviewed retrospectively. In addition all samples referred for possible C1 inhibitor deficiency over a period of 9 months were analysed for C4 and C1 inhibitor level and function. RESULTS: There were 2 HAE patients with normal C4 levels on first screen: one asymptomatic with a family history of HAE (C4 0.27 g/L, normal range for our laboratory 0.14-0.54 g/L) and another symptomatic without a family history of HAE (C4 0.15 g/L). There were no inconsistencies found on 128 routine samples tested for all 3 parameters i.e. there were no samples with normal C4 level and low C1 inhibitor or function. CONCLUSIONS: The diagnostic efficiency of screening by C4 complement level only for the diagnosis of HAE may be inadequate. It may be necessary to increase the low-end of C4 level that indicates testing for C1 inhibitor level and function. REFERENCES: 1. Sim TC, Grant JA. Hereditary angioedema: its diagnostic and management perspectives. Am J Med 1990;88:656-64. 2. Gompels MM, Lock RJ, Morgan JE et al. A multicentre evaluation of the diagnostic efficiency of serological investigations for C1 inhibitor deficiency. J Clin Pathol 2002;55:145-7.
812
Toll-Like Receptor 2 as a Functional Receptor to Respiratory Syncytial Virus Y. Inoue, N. Shimojo, T. Arima, Y. Kohno; Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, JAPAN. RATIONALE: Since respiratory syncytial virus (RSV) infection in infancy may well cause for bronchiolitis and development of asthma and innate immunity is suggested to be involved in the recognition of RSV, we investigated the role of TLRs in defense against RSV. METHODS: 1) Human monocytic cell line THP-1 was stimulated by heat-inactivated RSV, mock (Hep2 cell), ultra-purified LPS or synthetic mycoplasmal lipoprotein FSL-1. Blocking analysis was performed by adding TLR4 blocking antibody (HTA125) or TLR2 blocking antibody (TL2.1). The level of IL-12p40 in the culture supernatant was measured by ELISA. 2) Peritoneal macrophage from C57BL/6 or TLR2-KO on BL/6 background mice were stimulated by heat-inactivated RSV, mock, Ultrapurified LPS or FSL-1. The level of IL-6 in the culture supernatant was measured by ELISA. 3) Various amount of soluble CD14 (sCD14) preincubated with RSV, mock, ultra-purified LPS or FSL-1 were used to stimulate THP-1 cells and the level of IL-12p40 in the culture supernatant was measured by ELISA. RESULTS: 1) TLR2 blocking antibody suppressed heat-inactivated RSV induced IL-12p40 production more strongly than TLR4 blocking antibody did. 2) TLR2-KO macrophage was defective in IL-6 production in response to stimulation with heat-inactivated RSV as well as FSL-1. 3) sCD14 enhanced RSV-induced IL-12p40 production as well as LPSinduced IL-12p40 production. On the other hand sCD14 did not affect FSL-1-induced IL-12p40 production. CONCLUSIONS: Our data suggest that TLR2 is a functional receptor for RSV and sCD14 may work as a co-receptor for RSV like TLR4 recognition of LPS. In contrast, FSL-1 recognition by TLR2 does not need sCD14. Funding: Chiba University
809
MONDAY
Idiopathic Granulomatous Myositis Successfully Treated with IVIG J. Y. Patel, D. P. Huston, G. F. Duna; Section of Immunology, Allergy, Rheumatology, Baylor College of Medicine, Houston, TX. RATIONALE: Granulomatous myositis is a rare autoimmune entity generally associated with sarcoidosis. Case reports of idiopathic and sarcoidosis related granulomatous myositis have reported good response to corticosteroids, but for steroid resistant cases, there is no guidance for treatment. We describe a patient with hypercalcemia and steroid resistant granulomatous myositis successfully treated with IVIG. METHODS: A 23 year old white male was treated with doxycycline for a pustular rash days after returning from a trip to New Zealand and Australia. Two days later, he presented with fever, skin rash, and eosinophilia. He was diagnosed with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) and treated with intravenous steroids followed by oral prednisone. Mycophenolate was added because of inability to decrease prednisone below 40mg daily. Four months after presentation, he developed muscle weakness, dysphagia and creatinine kinase level of 1254 U/L. RESULTS: Muscle biopsy showed a florid mixed inflammatory infiltrate with multinucleated giant cells. Infectious, neoplastic, and vasculitic causes were excluded. Treatment with intravenous and oral cyclophosphamide was attempted with some improvement in muscle strength but prednisone could not be decreased without return of symptoms. The patient was switched to IVIG with improvement in symptoms, CPK levels and prednisone requirement.
810
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
CONCLUSIONS: A systemic autoimmune process must be considered as part of the differential diagnosis of DRESS. Granulomatous myositis may present as an acute and profuse inflammatory myositis. Steroid resistant forms of granulomatous myositis may respond well to IVIG. Macrophage Activation Syndrome (MAS) as a Debut of Systemic Lupus Erythematosus (SLE) in a Child. L. M. Kahn Benarroch, G. Sterba, M. Bosque; Hospital de Clinicas Caracas, Caracas, VENEZUELA. The Macrophage Activation Syndrome (MAS) is a rare pediatric condition characterized by enhanced activation of the macrophage and T-cell system, with increased liberation of T-cell cytokines. Clinically it resembles a multiorgan failure syndrome of infectious etiology. MAS a term used to describe a form of secondary hemophagocytic lymphohistiocytosis (HLH) in association with chronic rheumatic diseases of childhood. Here we describe a female patient 11 years old, became acutely ill, persistent fever, malaise, somnolence, and facial rash. Laboratory reported Epstein-Barr (EBV) positive serology, WBC 3.100, urinalysis microhematuria, and protein loss. Two weeks later she presented with purpuric skin rash, unremitting high fever, treated with antibiotics developed facial erytrodermia and edema. Admitted to the ICU: high fever, extensive ecchymotic lesions, lethargy and irritability. She presented with profound depression blood cell lines; low erythrocyte sedimentation rate (ESR), hepatitis with liver dysfunction, hematuria, proteinuria and renal failure. She then developed pancreatitis, abnormalities clotting profile, reduction in fibrinogen, Serum ferritin > 1.500, elevated LDH. Bone marrow study was carried out; haemophagocytosis was confirmed. Positive ANA 4+, antiDNA 4+, P ANCA 4+, anticardiolipin Ab Negative .She developed encephalopathy with confusion, seizures, and lung disease. Methylprednisolone was given, cyclosporin and cyclophosphamide later because of CNS severely compromised. Secondary Hemophagocytic syndromes associated with rheumatic diseases are rarely seen in LES. This patient presented LES with a SAM as an onset.
811
Is Screening with C4 Complement Level Enough to Exclude Hereditary Angioedema? S. Grigoriadou, M. Duddridge; Immunology, University Hospitals of Leicester NHS Trust, Leicester, UNITED KINGDOM. RATIONALE: Hereditary angioedema (HAE) is caused by deficiency of C1 inhibitor. The diagnosis is established by a low C4 complement level, and absent or very low C1 inhibitor level or function. It has been suggested that serum C4 level is a good screening test for the disease and the diagnosis can be excluded if C4 level is normal (1,2). METHODS: The original serology of 35 known HAE patients was reviewed retrospectively. In addition all samples referred for possible C1 inhibitor deficiency over a period of 9 months were analysed for C4 and C1 inhibitor level and function. RESULTS: There were 2 HAE patients with normal C4 levels on first screen: one asymptomatic with a family history of HAE (C4 0.27 g/L, normal range for our laboratory 0.14-0.54 g/L) and another symptomatic without a family history of HAE (C4 0.15 g/L). There were no inconsistencies found on 128 routine samples tested for all 3 parameters i.e. there were no samples with normal C4 level and low C1 inhibitor or function. CONCLUSIONS: The diagnostic efficiency of screening by C4 complement level only for the diagnosis of HAE may be inadequate. It may be necessary to increase the low-end of C4 level that indicates testing for C1 inhibitor level and function. REFERENCES: 1. Sim TC, Grant JA. Hereditary angioedema: its diagnostic and management perspectives. Am J Med 1990;88:656-64. 2. Gompels MM, Lock RJ, Morgan JE et al. A multicentre evaluation of the diagnostic efficiency of serological investigations for C1 inhibitor deficiency. J Clin Pathol 2002;55:145-7.
812