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PRIMARY IMMUNE DISEASE MASQUERADING AS SEVERE ATOPIC DERMATITIS
S104
Abstracts: Medically Challenging Cases / Ann Allergy Asthma Immunol 121 (2018) S63−S134
M259 HYPEREOSINOPHILIC SYNDROME: EXPLORING DIAGNOSTIC DILEMMA V. Devlin*, J. Carlson, New Orleans, LA Introduction: Hypereosinophilic Syndrome (HES) is a group of disorders with peripheral eosinophilia (1500/mm3) and end organ manifestations from eosinophils or inexplicable otherwise. HES’s heterogeneity makes diagnosis and treatment challenging. Case Description: A 53 yo female presented with significant extremity edema with 15-pound weight gain in two months despite oral furosemide. Initial labs revealed an AEC of 2100, albumin of 2.8 g/dL, CRP of 24.7 mg/L., re-check showed AEC of 1500, CRP of 33.1 mg/L, albumin of 3 g/dL two weeks later. Ultrasound of her lower extremities, ESR, CK, coags, UA, BNP, TSH, lipid profile, CK, ESR, HIV, Hepatitis panel, CCP, ANA, SSA, UA, and Urine Protein/Cr were all normal. At our visit Vitamin B12 was 1211 pg/mL. B cell rearrangement, IgE, Tryptase, Strongyloides IgG, TCR, lymphocyte profile, CHIC2, troponins, ECHO, and CT chest/abd/pelvis were normal. Bone marrow biopsy revealed trilineage hematopoietic activity (M/E = 4:1), with increased Eos. The remainder of the molecular oncologic HES workup was negative. Prednisone provided some relief but symptoms continued despite no peripheral eosinophilia. Aldolase of 9.6 U/L points toward involvement of skeletal muscle and a diagnosis of eosinophilic fasciitis. Discussion: HES is a heterogeneous group of illnesses. Care must be taken to clarify the etiology and start treatment. Anti IL-5 therapy or cyclophosphamide may be used as steroid-sparing therapies for HES, cyclophosphamide has shown complete remission. Prednisone is the treatment of choice for eosinophilic fasciitis; other medications are being investigated as possible therapies. Leg swelling as the presenting symptom in hypereosinophilic syndrome
Bilateral marked lower extremity swelling in a patient with HES
M260 PRIMARY IMMUNE DISEASE MASQUERADING AS SEVERE ATOPIC DERMATITIS E. Daniel*, P. Jhaveri, Hershey, PA Introduction: Netherton syndrome is a primary immune disorder that presents with atopy, diffuse ichthyosis, growth retardation, variable immune defects, and elevated IgE levels. The disease is due to a mutation in the SPINK5 gene, which encodes a serine protease
inhibitor, LEKTI, and is inherited in an autosome recessive pattern. We describe a case with features of Netherton syndrome found to have unique mutations in SPINK5 and the filaggrin gene (FLG). Case Description: A 4-year-old male with a history of congenital hydrocephalus with meningocele, ADHD, seasonal rhinitis, reactive airway disease and severe eczema presented for eczema management. He has a limited family history of allergic disease. Physical exam documented his height as <10th percentile and integumentary exam with diffuse erythema, scaling, dyshidrosis, excoriations and shiny patches. He was treated with topical steroids, calcineurin inhibitors and briefly with mycophenolate. Despite treatment, eczema remained uncontrolled and patient developed bacterial superinfections requiring hospitalization for IV antibiotics. Lab studies revealed: IgE 129,031 IU/mL, absolute eosinophil count 3700 cells/uL, low NK cell count 49 cells/ mm3 and decreased NK cell function. Whole exome sequencing highlighted mutations in SPINK5 (heterozygous p.G655D) and FLG (heterozygous S1020X). The patient is currently 15 years old, on dupilumab, and his eczema has greatly improved. He has had no other infections. Discussion: This patient presented with clinical features of Netherton syndrome, abnormal NK cells and a FLG mutation. We believe that this is reflective of a novel heterozygous mutation in the SPINK5 gene combined with the reduced expression of filaggrin.
M261 THINKING CRITICALLY ABOUT PATIENTS WITH CYTOPENIA: WHEN PRIMARY IMMUNE DEFICIENCY (PID) MASQUERADES AS ITP A. Aujnarain*1, C. Roifman2, 1. Mississauga, ON, Canada; 2. Toronto, ON, Canada Introduction: We report a patient who presented with thrombocytopenia and neutropenia, diagnosed with refractory ITP, which was eventually found to be caused by a heterozygous mutation in cytotoxic T lymphocyte antigen-4 (CTLA-4). Case Description: A 12-year-old patient was found to incidentally have thrombocytopenia and neutropenia. She was initially diagnosed with ITP, and her thrombocytopenia became gradually refractory to IVIG and steroids. She developed an inflammatory skin rash diagnosed as dyshidrotic eczema but did not have a significant infectious history. Ultimately, she was referred to immunology for a family history of possible CVID in mother. Her exam was remarkable for patches of eczema and excoriation, as well as healing blisters on her palms and soles. Her laboratory findings demonstrated WBC 5.7 £ 10^9/L hemoglobin 135 g/L, platelet 36 £ 10^9/L, neutrophil 2.8 £ 10^9/L, lymphocytes 1.3 £ 10^9/L, and eosinophils 0.9 £ 10^9/L. Her flow cytometry demonstrated a CD3 count of 817 cell/uL, CD8 322 cell/uL, CD4 393 cell/uL, CD56 31 cell/uL and CD19 488 cell/uL, CD4/ CD8 ratio 1.2. Her serum immunoglobulin levels were IgG 6.3 g/L, IgA 0.6 g/L, and IgM 0.4 g/L. Her T-cell response to mitogen was normal. Her antibody titres were protective to Measles and varicella. Pre and post pneumococcal vaccine titres were 31.8 mg/ml to 88.5 mg/ml respectively. Genetic analysis eventually revealed she had a pathogenic heterozygous mutation in CTLA-4. Discussion: Heterozygous CTLA-4 mutations has been recognized to cause diverse clinical phenotypes and must be considered in patients diagnosed with the more common condition such as thrombocytopenia.
M262 NEWBORN T-CELL RECOMBINATION EXCISION CIRCLE SCREENING REVEALS NON-ARCHETYPAL DIGEORGE PATIENT L. Kohn*, J. Church, Los Angeles, CA Introduction: DiGeorge Syndrome (DGS) is a spectrum of disorders with variable manifestations including congenital heart malformations, immunodeficiency, facial dysmorphism, hypocalcemia, and
Abstracts: Medically Challenging Cases / Ann Allergy Asthma Immunol 121 (2018) S63−S134
M259 HYPEREOSINOPHILIC SYNDROME: EXPLORING DIAGNOSTIC DILEMMA V. Devlin*, J. Carlson, New Orleans, LA Introduction: Hypereosinophilic Syndrome (HES) is a group of disorders with peripheral eosinophilia (1500/mm3) and end organ manifestations from eosinophils or inexplicable otherwise. HES’s heterogeneity makes diagnosis and treatment challenging. Case Description: A 53 yo female presented with significant extremity edema with 15-pound weight gain in two months despite oral furosemide. Initial labs revealed an AEC of 2100, albumin of 2.8 g/dL, CRP of 24.7 mg/L., re-check showed AEC of 1500, CRP of 33.1 mg/L, albumin of 3 g/dL two weeks later. Ultrasound of her lower extremities, ESR, CK, coags, UA, BNP, TSH, lipid profile, CK, ESR, HIV, Hepatitis panel, CCP, ANA, SSA, UA, and Urine Protein/Cr were all normal. At our visit Vitamin B12 was 1211 pg/mL. B cell rearrangement, IgE, Tryptase, Strongyloides IgG, TCR, lymphocyte profile, CHIC2, troponins, ECHO, and CT chest/abd/pelvis were normal. Bone marrow biopsy revealed trilineage hematopoietic activity (M/E = 4:1), with increased Eos. The remainder of the molecular oncologic HES workup was negative. Prednisone provided some relief but symptoms continued despite no peripheral eosinophilia. Aldolase of 9.6 U/L points toward involvement of skeletal muscle and a diagnosis of eosinophilic fasciitis. Discussion: HES is a heterogeneous group of illnesses. Care must be taken to clarify the etiology and start treatment. Anti IL-5 therapy or cyclophosphamide may be used as steroid-sparing therapies for HES, cyclophosphamide has shown complete remission. Prednisone is the treatment of choice for eosinophilic fasciitis; other medications are being investigated as possible therapies. Leg swelling as the presenting symptom in hypereosinophilic syndrome
Bilateral marked lower extremity swelling in a patient with HES
M260 PRIMARY IMMUNE DISEASE MASQUERADING AS SEVERE ATOPIC DERMATITIS E. Daniel*, P. Jhaveri, Hershey, PA Introduction: Netherton syndrome is a primary immune disorder that presents with atopy, diffuse ichthyosis, growth retardation, variable immune defects, and elevated IgE levels. The disease is due to a mutation in the SPINK5 gene, which encodes a serine protease
inhibitor, LEKTI, and is inherited in an autosome recessive pattern. We describe a case with features of Netherton syndrome found to have unique mutations in SPINK5 and the filaggrin gene (FLG). Case Description: A 4-year-old male with a history of congenital hydrocephalus with meningocele, ADHD, seasonal rhinitis, reactive airway disease and severe eczema presented for eczema management. He has a limited family history of allergic disease. Physical exam documented his height as <10th percentile and integumentary exam with diffuse erythema, scaling, dyshidrosis, excoriations and shiny patches. He was treated with topical steroids, calcineurin inhibitors and briefly with mycophenolate. Despite treatment, eczema remained uncontrolled and patient developed bacterial superinfections requiring hospitalization for IV antibiotics. Lab studies revealed: IgE 129,031 IU/mL, absolute eosinophil count 3700 cells/uL, low NK cell count 49 cells/ mm3 and decreased NK cell function. Whole exome sequencing highlighted mutations in SPINK5 (heterozygous p.G655D) and FLG (heterozygous S1020X). The patient is currently 15 years old, on dupilumab, and his eczema has greatly improved. He has had no other infections. Discussion: This patient presented with clinical features of Netherton syndrome, abnormal NK cells and a FLG mutation. We believe that this is reflective of a novel heterozygous mutation in the SPINK5 gene combined with the reduced expression of filaggrin.
M261 THINKING CRITICALLY ABOUT PATIENTS WITH CYTOPENIA: WHEN PRIMARY IMMUNE DEFICIENCY (PID) MASQUERADES AS ITP A. Aujnarain*1, C. Roifman2, 1. Mississauga, ON, Canada; 2. Toronto, ON, Canada Introduction: We report a patient who presented with thrombocytopenia and neutropenia, diagnosed with refractory ITP, which was eventually found to be caused by a heterozygous mutation in cytotoxic T lymphocyte antigen-4 (CTLA-4). Case Description: A 12-year-old patient was found to incidentally have thrombocytopenia and neutropenia. She was initially diagnosed with ITP, and her thrombocytopenia became gradually refractory to IVIG and steroids. She developed an inflammatory skin rash diagnosed as dyshidrotic eczema but did not have a significant infectious history. Ultimately, she was referred to immunology for a family history of possible CVID in mother. Her exam was remarkable for patches of eczema and excoriation, as well as healing blisters on her palms and soles. Her laboratory findings demonstrated WBC 5.7 £ 10^9/L hemoglobin 135 g/L, platelet 36 £ 10^9/L, neutrophil 2.8 £ 10^9/L, lymphocytes 1.3 £ 10^9/L, and eosinophils 0.9 £ 10^9/L. Her flow cytometry demonstrated a CD3 count of 817 cell/uL, CD8 322 cell/uL, CD4 393 cell/uL, CD56 31 cell/uL and CD19 488 cell/uL, CD4/ CD8 ratio 1.2. Her serum immunoglobulin levels were IgG 6.3 g/L, IgA 0.6 g/L, and IgM 0.4 g/L. Her T-cell response to mitogen was normal. Her antibody titres were protective to Measles and varicella. Pre and post pneumococcal vaccine titres were 31.8 mg/ml to 88.5 mg/ml respectively. Genetic analysis eventually revealed she had a pathogenic heterozygous mutation in CTLA-4. Discussion: Heterozygous CTLA-4 mutations has been recognized to cause diverse clinical phenotypes and must be considered in patients diagnosed with the more common condition such as thrombocytopenia.
M262 NEWBORN T-CELL RECOMBINATION EXCISION CIRCLE SCREENING REVEALS NON-ARCHETYPAL DIGEORGE PATIENT L. Kohn*, J. Church, Los Angeles, CA Introduction: DiGeorge Syndrome (DGS) is a spectrum of disorders with variable manifestations including congenital heart malformations, immunodeficiency, facial dysmorphism, hypocalcemia, and