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P196 Hemophagocytic lymphohistiocytosis complicated by posterior reversible encephalopathy syndrome
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
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Hospital Course/Results: Patient was intubated on admission and continues to be intubated. Initial blood culture positive for streptococcus mitis. Endocarditis ruled out with echocardiography. Initial respiratory viral panel positive for rhinovirus, enterovirus, and adenovirus. Patient initially started on vancomycin and piperacillin-tazobactam. Subsequent blood cultures have been negative. Repeat respiratory culture positive for H. influenza and Enterobacter. Antibiotic coverage changed to meropenem with minimal improvement. ANC ranged from 260 to 410 and remained below 500 until IV corticosteroids were started. ANC increased to >2000 within 4 days of starting steroids. Conclusion: Recurrent infections and autoimmunity due to thymic hypoplasia are often seen in 22q11 Deletion syndrome; this is the first reported case of 22q11.2 deletion syndrome presenting with severe congenital neutropenia.
Lab Results Pertinent lab results comprising this patient’s inital workup for severe congenital neutropenia.
P195 MANIFESTATION OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN AN ADOLESCENT WITH A HETEROZYGOUS PRF1 MUTATION K. Grisanti*, D. Patadia, R. Scherzer, Columbus, OH. Background: Hemophagocytic lymphohistiocytosis (HLH) is a lifethreatening condition with defects in cytotoxic granule secretion/ function, causing a dysregulated immune response. HLH is categorized into primary/familial HLH, attributed to a gene defect, and secondary/reactive HLH, triggered by infection, malignancy, or autoimmune disease. Case: 16-year-old male with a one-year history of intermittent joint pain was admitted after one month of worsening polyarthralgia, pharyngitis, fatigue, and cough. On admission he was febrile with a generalized rash. He deteriorated with respiratory failure requiring intubation, and ultimately ECMO. He was diagnosed with pneumonia, and infectious evaluation showed positive EBV serologies, along with positive Adenovirus and Mycoplasma PCRs. Pancytopenia and elevated AST/ALT, ferritin (>15,000 ng/mL) and soluble IL2 receptor (2339 units/mL) levels were found. Bone marrow biopsy was consistent with hemophagocytosis. NK-cell function and perforin expression were decreased. He was diagnosed with both HLH and juvenile idiopathic arthritis (JIA) during admission. Gene analysis revealed a mutation in one allele of the PRF1 gene. He improved on treatment with antibiotics, antivirals, anakinra, corticosteroids, IVIG, and plasmapheresis. Conclusions: This patient had several risk factors for secondary HLH including multiple infections along with newly diagnosed JIA. He also had a heterozygous mutation in PRF1; homozygous
mutations in this gene are implicated in familial HLH2, with decreased or absent perforin expression. This case raises the possibility of overlap between primary and secondary HLH, with genetic predisposition being unmasked by triggers for the disease. As the clinical significance of such gene mutations becomes more apparent, there may be implications for the treatment of these patients.
P196 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS COMPLICATED BY POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME M. Lele*, Brooklyn, NY. Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by uncontrolled activation of cytotoxic T-cells and antigen-presenting cells leading to marked hypercytokinemia. The initial therapy consists of immunosuppressive and chemotherapeutic agents. Neurologic abnormalities are common in HLH due to multiple factors including hypertension, inflammation, and treatment with neurotoxic medications such as cyclosporine. In particular, patients with HLH are at risk of developing posterior reversible encephalopathy syndrome (PRES). The incidence of PRES in HLH is unknown, but case reports of the syndrome have been reported. Case: An 11-year-old girl was diagnosed with HLH after presenting with prolonged fever, thrombocytopenia, anemia, hyperferritinemia, elevated sCD25 levels and hemophagocytosis in the bone marrow. She was started on the HLH-2004 protocol including cyclosporine. Six weeks into therapy she developed upper extremity tremors, headache, and somnolence. MRI showed transcortical white matter signal abnormalities consistent with PRES. Despite aggressive management of her hypertension and discontinuation of cyclosporine, the patient’s neurological status continued to decline and she ultimately died from a fatal intracerebral hemorrhage. Discussion: Patients being treated for HLH are at risk for PRES. This clinico-radiologic entity is characterized by headaches, seizures, altered mental status, and characteristic MRI findings of subcortical white matter edema on T2-weighted and FLAIR images. These findings are often transient and reversible with supportive treatment. However, if not identified early, PRES can be associated with fatal complications such as cerebral hemorrhage and herniation. Patients with HLH, especially while being treated with cyclosporine, require close monitoring of neurologic status to prevent PRES and its complications.
P197 MACROPHAGE ACTIVATION SYNDROME AS THE INITIAL PRESENTATION OF C1Q DEFICIENCY E. Wisner*, S. Kamireddy, P. Prasad, L. Wall, New Orleans, LA. Introduction: In addition to increased susceptibility to sinopulmonary infections, a deficiency in the early classical complement components may predispose to the development of autoimmunity secondary to impaired clearance of immune complexes. We present a patient with previously undiagnosed C1q deficiency whose initial presentation was macrophage activation syndrome (MAS) secondary to new onset systemic lupus erythematosus (SLE). Her case is also unique in that she experienced recurrent invasive Streptococcus pneumoniae infections, not commonly described with classical complement deficiencies. Methods: Retrospective chart review Results: A 17-month-old female presented with a desquamating rash and persistent fever.
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Hospital Course/Results: Patient was intubated on admission and continues to be intubated. Initial blood culture positive for streptococcus mitis. Endocarditis ruled out with echocardiography. Initial respiratory viral panel positive for rhinovirus, enterovirus, and adenovirus. Patient initially started on vancomycin and piperacillin-tazobactam. Subsequent blood cultures have been negative. Repeat respiratory culture positive for H. influenza and Enterobacter. Antibiotic coverage changed to meropenem with minimal improvement. ANC ranged from 260 to 410 and remained below 500 until IV corticosteroids were started. ANC increased to >2000 within 4 days of starting steroids. Conclusion: Recurrent infections and autoimmunity due to thymic hypoplasia are often seen in 22q11 Deletion syndrome; this is the first reported case of 22q11.2 deletion syndrome presenting with severe congenital neutropenia.
Lab Results Pertinent lab results comprising this patient’s inital workup for severe congenital neutropenia.
P195 MANIFESTATION OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN AN ADOLESCENT WITH A HETEROZYGOUS PRF1 MUTATION K. Grisanti*, D. Patadia, R. Scherzer, Columbus, OH. Background: Hemophagocytic lymphohistiocytosis (HLH) is a lifethreatening condition with defects in cytotoxic granule secretion/ function, causing a dysregulated immune response. HLH is categorized into primary/familial HLH, attributed to a gene defect, and secondary/reactive HLH, triggered by infection, malignancy, or autoimmune disease. Case: 16-year-old male with a one-year history of intermittent joint pain was admitted after one month of worsening polyarthralgia, pharyngitis, fatigue, and cough. On admission he was febrile with a generalized rash. He deteriorated with respiratory failure requiring intubation, and ultimately ECMO. He was diagnosed with pneumonia, and infectious evaluation showed positive EBV serologies, along with positive Adenovirus and Mycoplasma PCRs. Pancytopenia and elevated AST/ALT, ferritin (>15,000 ng/mL) and soluble IL2 receptor (2339 units/mL) levels were found. Bone marrow biopsy was consistent with hemophagocytosis. NK-cell function and perforin expression were decreased. He was diagnosed with both HLH and juvenile idiopathic arthritis (JIA) during admission. Gene analysis revealed a mutation in one allele of the PRF1 gene. He improved on treatment with antibiotics, antivirals, anakinra, corticosteroids, IVIG, and plasmapheresis. Conclusions: This patient had several risk factors for secondary HLH including multiple infections along with newly diagnosed JIA. He also had a heterozygous mutation in PRF1; homozygous
mutations in this gene are implicated in familial HLH2, with decreased or absent perforin expression. This case raises the possibility of overlap between primary and secondary HLH, with genetic predisposition being unmasked by triggers for the disease. As the clinical significance of such gene mutations becomes more apparent, there may be implications for the treatment of these patients.
P196 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS COMPLICATED BY POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME M. Lele*, Brooklyn, NY. Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by uncontrolled activation of cytotoxic T-cells and antigen-presenting cells leading to marked hypercytokinemia. The initial therapy consists of immunosuppressive and chemotherapeutic agents. Neurologic abnormalities are common in HLH due to multiple factors including hypertension, inflammation, and treatment with neurotoxic medications such as cyclosporine. In particular, patients with HLH are at risk of developing posterior reversible encephalopathy syndrome (PRES). The incidence of PRES in HLH is unknown, but case reports of the syndrome have been reported. Case: An 11-year-old girl was diagnosed with HLH after presenting with prolonged fever, thrombocytopenia, anemia, hyperferritinemia, elevated sCD25 levels and hemophagocytosis in the bone marrow. She was started on the HLH-2004 protocol including cyclosporine. Six weeks into therapy she developed upper extremity tremors, headache, and somnolence. MRI showed transcortical white matter signal abnormalities consistent with PRES. Despite aggressive management of her hypertension and discontinuation of cyclosporine, the patient’s neurological status continued to decline and she ultimately died from a fatal intracerebral hemorrhage. Discussion: Patients being treated for HLH are at risk for PRES. This clinico-radiologic entity is characterized by headaches, seizures, altered mental status, and characteristic MRI findings of subcortical white matter edema on T2-weighted and FLAIR images. These findings are often transient and reversible with supportive treatment. However, if not identified early, PRES can be associated with fatal complications such as cerebral hemorrhage and herniation. Patients with HLH, especially while being treated with cyclosporine, require close monitoring of neurologic status to prevent PRES and its complications.
P197 MACROPHAGE ACTIVATION SYNDROME AS THE INITIAL PRESENTATION OF C1Q DEFICIENCY E. Wisner*, S. Kamireddy, P. Prasad, L. Wall, New Orleans, LA. Introduction: In addition to increased susceptibility to sinopulmonary infections, a deficiency in the early classical complement components may predispose to the development of autoimmunity secondary to impaired clearance of immune complexes. We present a patient with previously undiagnosed C1q deficiency whose initial presentation was macrophage activation syndrome (MAS) secondary to new onset systemic lupus erythematosus (SLE). Her case is also unique in that she experienced recurrent invasive Streptococcus pneumoniae infections, not commonly described with classical complement deficiencies. Methods: Retrospective chart review Results: A 17-month-old female presented with a desquamating rash and persistent fever.