Journal of Clinical Immunology https://doi.org/10.1007/s10875-018-0485-z ABSTRACTS 2018 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference # Springer Science+Business Media, LLC, part of Springer Nature 2018 Submission ID#401718 30mg/kg daily x3 days, followed by oral prednisolone 2mg/kg/day and anakinra 2mg/kg/day with partial improvement and he was discharged A case of CANDLE syndrome home. He was readmitted 3.5 weeks later due to concerns for macrophage activation syndrome (ferritin 12,362 ng/ml) in the setting of a gastrointestinal Maria M. Pereira, MD1,AmandaBrown,MD2, Tiphanie Vogel, infection and anakinra was increased to 4.5mg/kg/day. However, he contin- MD,PhD3 ued to have persistently elevated inflammatory markers and so the dose was increased again to 7mg/kg/day. Three months after initial presentation, he 1Pediatric Rheumatology Fellow, Baylor College of Medicine / Texas had an upper respiratory and ear infection and became ill with generalized Children's Hospital rash, increased work of breathing, and poor perfusion. Anakinra was con- 2Assistant Professor in Pediatric Rheumatology, Baylor College of sidered a treatment failure at that time. He required several doses of pulse Medicine / Texas Children's Hospital steroids and initiation of tocilizumab 12mg/kg IV every 4weeks with im- 3Assistant Profesor in Rheumatology, Baylor College of Medicine / Texas provement on systemic symptoms. Methotrexate 15mg/m² weekly was Children's Hospital added soon after for persistent arthritis and inability to wean systemic ste- roids. He continued to have abnormal inflammatory indices, including fer- Introduction/Background: Chronic Atypical Neutrophilic Dermatosis ritin (1,586 ng/mL) and IL-18 levels (35,588 pg/mL, normal 89-540). with Lipodystrophy and Elevated Temperature (CANDLE) syndrome is Proband only whole exome sequencing revealed a single heterozygous mu- a rare autoinflammatory disorder that can cause symptoms from infancy. tation in the PSMB4 gene (c.-9G>A), a published pathologic variant. Based Mutations in the genes encoding proteasome subunits (PSMB8, PSMB4, on this finding, the patient was started on tofacitinib 2.5mg orally twice a day PSMA3 and PSMB9) have been identified as the cause of CANDLE with a dramatic response. Laboratory markers of inflammation normalized, syndrome. These mutations lead to malfunction of the proteasome, which and he was able to walk within the first month of treatment. Further genetic results in buildup of cellular waste products. It is hypothesized that dys- testing to detect an additional proteasome subunit variant, as well as func- regulation in the interferon (IFN) signaling pathway in response to this tional testing on a research basis to demonstrate an interferon signature are waste is the driving mechanism of the inflammatory response, and may being pursued. serve as a therapeutic target in these patients. Conclusions: This case highlights the value of early genetic studies in Objectives: To describe a case of suspected CANDLE syndrome success- patients with autoinflammation so that initiation of targeted therapy is fully treated with tofacitinib. not delayed in efforts to achieve control of symptoms and evade future Methods: Retrospective chart review was conducted with respect to di- complications. This case also illustrates the challenges in diagnosing agnosis, treatment and response. monogenic autoinflammatory disorders in young patients that present with Results: A 16-month old Caucasian male was admitted to the hospital for recurrent fevers, generalized rash, arthritis, and systemic inflammation that evaluation of profound anemia. His medical history was significant for mimic systemic juvenile idiopathic arthritis. Our experience contributes to extreme prematurity (born at 22 weeks from premature labor), intraven- the understanding of janus kinase inhibition in type I interferonopathies. tricular hemorrhage grade IV that resulted in hydrocephalus needing ventriculoperitoneal shunting, and developmental delay. He was noted Submission ID#382424 to have a hemoglobin of 6.2 g/dL during a neurosurgical evaluation for routine shunt revision. He developed hemodynamic decompensation and A case of complete STAT1 loss of function required hospital admission for packed red-blood cell transfusion. Review of systems was remarkable for intermittent pruritic macular rash, Jenna Bergerson, MD/MPH1, Aaruni Khanolkar, MBBS, PhD2, daily temperature fluctuations (fever to hypothermia), joint pain/swelling/ Lawrence Jennings, MD/PhD3, William Tse, MD/PhD4,Ramsay stiffness of multiple sites, poor weight gain, irritability, irregular breath- Fuleihan, MD5 ing, abdominal distention, and regression of gross motor milestones (no longer rolling over, sitting without support, or pulling up to stand). 1Staff Clinician, NIH/NIAID/LCIM Workup excluded infections and lymphoproliferative malignancies, and 2Assistant Professor of Pathology, Director of Immunology Lab, he met clinical criteria for systemic juvenile idiopathic arthritis. Department of Pathology, Ann and Robert H. Lurie Children's Hospital His initial laboratory studies showed systemic inflammation (WBC 14x of Chicago and Northwestern University 10^3/uL, Hgb 6.0 g/dL, platelets 558 x10^3/uUL, CRP 14.2 mg/dL, sedi- 3Assistant Professor of Pathology, Director of HLA and Molecular mentation rate 70 mm/h, ferritin 2370 ng/ml). Imaging studies revealed Diagnostics Department of Pathology, Ann and Robert H. Lurie serositis with right-sided pleural and pericardial effusions. He also had myo- Children's Hospital of Chicago and Northwestern University sitis supported by imaging and elevation of muscle enzymes (AST 52 U/L, 4Assistant Professor of Pediatrics (Hematology, Oncology, and Stem Cell aldolase 30.6 U/L). The patient was started on pulse IV methylprednisolone Transplantation) Department of Hematology, Oncology and Stem Cell JClinImmunol Transplantation, Ann and Robert H. Lurie Children's Hospital of Chicago Objectives: To describe a unique case of cutaneous T-cell lymphoma and Northwestern University (CTCL) in a patient with Netherton syndrome. 5Professor of Pedatrics, Jeffrey Modell Diagnostic Center for Primary Methods: A 35-year-old gentleman was evaluated in Allergy/ Immunodeficiencies, Division of Allergy and Immunology, Ann and Immunology clinic for possible immune deficiency syndrome. He de- Robert H. Lurie Children's Hospital of Chicago scribed severe eczema in early childhood, asthma in elementary school, environmental allergy, and hair changes as a child. He also described a Introduction/Background: Complete signal transducer and activator of history of recurrent infections involving the skin and lungs as well as transcription 1 (STAT1) deficiency is a rare autosomal recessive condition gastrointestinal symptoms of soft stools and gas. The patient was diag- that results in complete functional impairment of STAT1-dependent type nosed one year prior to evaluation with CTCL and completed treatment 1 and type 2 interferon responses. Affected patients are predisposed to with bexarotene. His IgE level was 4,347 kU/L (normal less than 214kU/ early and severe mycobacterial and viral infections, and usually succumb L). The patient underwent genetic testing for Hyper-IgE syndromes and to infection in the first two years of life. Attempts at HSCT have been rare, two pathogenic alterations in the SPINK5 gene were identified. Based on and are usually unsuccessful due to either severe infection at the time of genetic testing results and clinical history he was diagnosed with transplantation or profound GVHD in the post-transplant period. Netherton syndrome. Objectives: To characterize the clinical course of a patient with STAT1 Results: Netherton syndrome is a rare autosomal recessive condition loss of function. characterized by congenital ichthyosis, trichorrhexis invaginata (bamboo Methods: A chart review was performed. hair), and atopic diathesis. Hypergammoglobulinemia E, high comple- Results: The patient is a former full-term Caucasian male born to non- ment (C3/C4) and decreased numbers of natural killer cells make these consanguineous parents who presented at 14 months of age with a history patients more susceptible to infections and increase the incidence of an- of two ear infections, RSV infection at 6 months of age requiring hospi- gioedema, allergic rhinitis, and food allergy. There are several papers that talization, as well as vaccine-strain Measles and Varicella infections at 13 describe the development of cutaneous neoplasia in patients with months of age. The diagnosis of VZV was made by positive DFA for VZV inherited ichthyoses, including Netherton syndrome, but after reviewing skin lesions, with viral culture that confirmed Vaccine-strain Varicella. the literature we could find no reported cases of cutaneous T-cell lym- Laboratory testing was notable for eosinophilia. Lymphocyte subsets were phoma (CTCL) described in Netherton patients. normal with the exception of decreased naïve CD8 T cells and increased Conclusions: The present case raises the possibility of an association of activated T cells. Immunoglobulin levels were normal except for an ele- CTCL and Netherton syndrome which may be linked by the presence of vated IgG of 1600 mg/dL. T cell proliferation was normal to candida but alterations in T-cell function. decreased to tetanus; however, tetanus antibody level was adequate. NK cell functional testing was severely decreased to absent. At 18 months of (4) Submission ID#421105 age the patient