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A CASE WITH YEARS IN THE MAKING
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Abstracts: Medically Challenging Cases / Ann Allergy Asthma Immunol 121 (2018) S63−S134
unidentified fungus, which DNA sequencing led to identify as Oxyporus ginkgonis. He was successfully treated with posaconazole. Case 2: A 22-year old with CGD, fever, hilar lymphadenopathy, and multifocal opacities on chest X-ray. Lung biopsy revealed necrotizing granulomatous inflammation with no organisms on Gram stain. DNA sequencing identified Oxyporus latemarginatus. He did not tolerate voriconazole due to side effects, but was transitioned to posaconazole with clinical and radiographic improvement. Discussion: Both cases required an extensive, team-based work up and molecular diagnostics to obtain a final diagnosis of Oxyporus mold infection. To our knowledge, this genus has not been reported as a human pathogen. Two case reports describe Oxyporus infections in dogs2,3. In both cases, the species was Oxyporus corticola; however, they are similar to our CGD patients in that both cases had lymphadenopathy and/or a mass and one case had evidence of immune dysregulation2,3. These two cases underscore the importance of aggressive diagnostic measures and multidisciplinary approaches to obtain tissue diagnosis for patients with CGD.
M252 SPORADIC CASE OF SPLICE SITE BTK MUTATION WITH DELAYED ONSET OF X-LINKED AGAMMAGLOBULINEMIA (XLA) B. Neaves*1, K. Adams2, D. Smith3, 1. JBSA - Lakland, TX; 2. Lackland AFB, TX; 3. Las Vegas, NV Introduction: XLA is a primary immunodeficiency characterized by reduced mature peripheral B cells and hypogammaglobulinemia and is caused by mutations in the BCR signal transduction molecule, Bruton’s tyrosine kinase (Btk). Although most affected males are diagnosed in the first years of childhood, diagnosis may be delayed into adulthood in 30-50% of sporadic cases. Case Description: This 46 year old male was evaluated for recurrent maxillary sinus infections and IgA 1.3mcg/ml, absent HepB sAb conversion after five HepB vaccines, and undetectable IgG A;p.Pro80Pro, a splice-site mutation resulting in an amino acid change of the Btk enzyme plekstrin homology domain, associated with XLA. Discussion: While XLA is typically diagnosed in childhood, individuals with splice-site defects may present with later-life diagnosis because of milder phenotypes.
M253 A CASE WITH YEARS IN THE MAKING L. Vandiver*, C. Kirkpatrick, Denver, CO Introduction: The immune system dysregulation that occurs in some cases of immunodeficiency manifests itself by autoimmunity and malignancy. These complications may be more likely to occur in patients with specific genetic defects that lead to common variable immunodeficiency (CVID). Case Description: A 48-year-old woman with a history of frequent respiratory tract infections and CVID on immunoglobulin replacement has been followed in our immunology clinic for 11 years. In the 18 years since diagnosis of CVID, she has also been diagnosed with type 1 diabetes mellitus, hypothyroidism, rheumatoid arthritis, NonHodgkin’s Lymphoma, and enteropathy. An immunoglobulin G level obtained at the age of 30 revealed an IgG of 672 mg/dL (low). At age 38, she had the following findings: IgG Discussion: CTLA4 plays an active role in self-tolerance, as it is an inhibitory molecule located on T cells to help regulate T cell responses. Mutations in this protein can lead to improper regulation, and therefore, autoimmunity and organ infiltration by T cells. CTLA4 haploinsufficiency has been identified as one of the mutations which may lead to a CVID phenotype.
M254 THE EVALUATION AND MANAGMENT OF DOCK8 DEFICIENCY C. Atkinson*, S. Stutes, Oklahoma City, OK Introduction: We present a case involving a child with a complex medical history who presented with a one-day history of fever, facial swelling, and skin rash. Case Description: Our patient is a 2-year-old male with history of eczema, failure to thrive, chronic lymphadenopathy, developmental delay, and food allergies who presented with a one-day history of fever, facial swelling, and eczema. Physical examination was notable for an ill appearing child with coarse facial features. He had perioral edema, skin lichenification, diffuse eczematous rash, and chronic lymphadenopathy. Labs were notable for leukocytosis and elevated inflammatory markers. Skin and conjunctival cultures were positive for Herpes Simplex Virus. Wound cultures were positive for methicillin-resistant Staphylococcus aureus. He was treated with acyclovir, vancomycin, cefoxitin, and mupirocin ointment. The lab results from hospitalization were obtained. The hyper-IgE panel revealed a homozygous mutation in the DOCK8 gene which is located within one of the regions of homozygosity identified on SNP microarray diagnosing him with DOCK8 deficiency. Discussion: This case demonstrates that DOCK8 deficiency should be included in the differential diagnosis involving children with eczema, failure to thrive, and cutaneous infections. Our patient had coarse facial features, however, this is not a common feature of DOCK8 deficiency. The study, Cutaneous Manifestations of DOCK8 Deficiency Syndrome, evaluated the clinical features of Job Syndrome and DOCK8 deficiency and found that in DOCK8 deficiency, coarse facial features were not present. Our case report shows that the presence of coarse facial features should not necessarily exclude DOCK8 deficiency.
M255 AUTOIMMUNE POLYENDOCRINOPATHY TYPE 1 WITH CVID TREATED WITH MYCOPHENOLATE AND IVIG K. Karpinska-Leydier*1, J. Brooks2, F. Hsu2, 1. Toronto, ON, Canada; 2. New Haven, CT Introduction: Autoimmune Polyendocrine Syndrome (APS) Type 1 is a rare autosomal recessive disorder characterized by candidiasis with the coexistence of at least two glandular autoimmune diseases. It is caused by mutations of the AIRE gene encoding for the transcription factor involved in immune tolerance mechanisms and contributes to autoreactive T lymphocyte negative selection. Candidiasis is the most common initial manifestation, followed by progressive endocrine dysfunction. Management of APS is aimed at symptomatic resolution of the dysfunction, such as systemic antifungals, glucocorticoids, insulin, calcium, vitamin D, and vitamin B12. Immunosuppressant therapies have been utilized with variable results. Case Description: A 41-year-old female, with history of candidiasis, hypoparathyroidism, and premature ovarian failure in the context of APS Type 1, presented with common variable immunodeficiency (CVID). Additional manifestations included Sjogrens syndrome, diffuse vitiligo, autoimmune hepatitis, pernicious anemia, and autoimmune pneumonitis. She was started on intravenous immunoglobulin therapy 15 g monthly and treated with prednisone 40 g daily until she could be tapered off steroids. Her condition worsened after she experienced recurrent pulmonary exacerbations with sputum cultures growing multiple pathogenic organisms. Prednisone was restarted to treat autoimmune pneumonitis. She was transitioned to mycophenolate 1080 mg divided between two doses daily with good symptom control and tapered off prednisone. Discussion: Although immunosuppressive therapy is not routinely used in patients with APS Type 1, the constellation of symptoms,
Abstracts: Medically Challenging Cases / Ann Allergy Asthma Immunol 121 (2018) S63−S134
unidentified fungus, which DNA sequencing led to identify as Oxyporus ginkgonis. He was successfully treated with posaconazole. Case 2: A 22-year old with CGD, fever, hilar lymphadenopathy, and multifocal opacities on chest X-ray. Lung biopsy revealed necrotizing granulomatous inflammation with no organisms on Gram stain. DNA sequencing identified Oxyporus latemarginatus. He did not tolerate voriconazole due to side effects, but was transitioned to posaconazole with clinical and radiographic improvement. Discussion: Both cases required an extensive, team-based work up and molecular diagnostics to obtain a final diagnosis of Oxyporus mold infection. To our knowledge, this genus has not been reported as a human pathogen. Two case reports describe Oxyporus infections in dogs2,3. In both cases, the species was Oxyporus corticola; however, they are similar to our CGD patients in that both cases had lymphadenopathy and/or a mass and one case had evidence of immune dysregulation2,3. These two cases underscore the importance of aggressive diagnostic measures and multidisciplinary approaches to obtain tissue diagnosis for patients with CGD.
M252 SPORADIC CASE OF SPLICE SITE BTK MUTATION WITH DELAYED ONSET OF X-LINKED AGAMMAGLOBULINEMIA (XLA) B. Neaves*1, K. Adams2, D. Smith3, 1. JBSA - Lakland, TX; 2. Lackland AFB, TX; 3. Las Vegas, NV Introduction: XLA is a primary immunodeficiency characterized by reduced mature peripheral B cells and hypogammaglobulinemia and is caused by mutations in the BCR signal transduction molecule, Bruton’s tyrosine kinase (Btk). Although most affected males are diagnosed in the first years of childhood, diagnosis may be delayed into adulthood in 30-50% of sporadic cases. Case Description: This 46 year old male was evaluated for recurrent maxillary sinus infections and IgA 1.3mcg/ml, absent HepB sAb conversion after five HepB vaccines, and undetectable IgG A;p.Pro80Pro, a splice-site mutation resulting in an amino acid change of the Btk enzyme plekstrin homology domain, associated with XLA. Discussion: While XLA is typically diagnosed in childhood, individuals with splice-site defects may present with later-life diagnosis because of milder phenotypes.
M253 A CASE WITH YEARS IN THE MAKING L. Vandiver*, C. Kirkpatrick, Denver, CO Introduction: The immune system dysregulation that occurs in some cases of immunodeficiency manifests itself by autoimmunity and malignancy. These complications may be more likely to occur in patients with specific genetic defects that lead to common variable immunodeficiency (CVID). Case Description: A 48-year-old woman with a history of frequent respiratory tract infections and CVID on immunoglobulin replacement has been followed in our immunology clinic for 11 years. In the 18 years since diagnosis of CVID, she has also been diagnosed with type 1 diabetes mellitus, hypothyroidism, rheumatoid arthritis, NonHodgkin’s Lymphoma, and enteropathy. An immunoglobulin G level obtained at the age of 30 revealed an IgG of 672 mg/dL (low). At age 38, she had the following findings: IgG Discussion: CTLA4 plays an active role in self-tolerance, as it is an inhibitory molecule located on T cells to help regulate T cell responses. Mutations in this protein can lead to improper regulation, and therefore, autoimmunity and organ infiltration by T cells. CTLA4 haploinsufficiency has been identified as one of the mutations which may lead to a CVID phenotype.
M254 THE EVALUATION AND MANAGMENT OF DOCK8 DEFICIENCY C. Atkinson*, S. Stutes, Oklahoma City, OK Introduction: We present a case involving a child with a complex medical history who presented with a one-day history of fever, facial swelling, and skin rash. Case Description: Our patient is a 2-year-old male with history of eczema, failure to thrive, chronic lymphadenopathy, developmental delay, and food allergies who presented with a one-day history of fever, facial swelling, and eczema. Physical examination was notable for an ill appearing child with coarse facial features. He had perioral edema, skin lichenification, diffuse eczematous rash, and chronic lymphadenopathy. Labs were notable for leukocytosis and elevated inflammatory markers. Skin and conjunctival cultures were positive for Herpes Simplex Virus. Wound cultures were positive for methicillin-resistant Staphylococcus aureus. He was treated with acyclovir, vancomycin, cefoxitin, and mupirocin ointment. The lab results from hospitalization were obtained. The hyper-IgE panel revealed a homozygous mutation in the DOCK8 gene which is located within one of the regions of homozygosity identified on SNP microarray diagnosing him with DOCK8 deficiency. Discussion: This case demonstrates that DOCK8 deficiency should be included in the differential diagnosis involving children with eczema, failure to thrive, and cutaneous infections. Our patient had coarse facial features, however, this is not a common feature of DOCK8 deficiency. The study, Cutaneous Manifestations of DOCK8 Deficiency Syndrome, evaluated the clinical features of Job Syndrome and DOCK8 deficiency and found that in DOCK8 deficiency, coarse facial features were not present. Our case report shows that the presence of coarse facial features should not necessarily exclude DOCK8 deficiency.
M255 AUTOIMMUNE POLYENDOCRINOPATHY TYPE 1 WITH CVID TREATED WITH MYCOPHENOLATE AND IVIG K. Karpinska-Leydier*1, J. Brooks2, F. Hsu2, 1. Toronto, ON, Canada; 2. New Haven, CT Introduction: Autoimmune Polyendocrine Syndrome (APS) Type 1 is a rare autosomal recessive disorder characterized by candidiasis with the coexistence of at least two glandular autoimmune diseases. It is caused by mutations of the AIRE gene encoding for the transcription factor involved in immune tolerance mechanisms and contributes to autoreactive T lymphocyte negative selection. Candidiasis is the most common initial manifestation, followed by progressive endocrine dysfunction. Management of APS is aimed at symptomatic resolution of the dysfunction, such as systemic antifungals, glucocorticoids, insulin, calcium, vitamin D, and vitamin B12. Immunosuppressant therapies have been utilized with variable results. Case Description: A 41-year-old female, with history of candidiasis, hypoparathyroidism, and premature ovarian failure in the context of APS Type 1, presented with common variable immunodeficiency (CVID). Additional manifestations included Sjogrens syndrome, diffuse vitiligo, autoimmune hepatitis, pernicious anemia, and autoimmune pneumonitis. She was started on intravenous immunoglobulin therapy 15 g monthly and treated with prednisone 40 g daily until she could be tapered off steroids. Her condition worsened after she experienced recurrent pulmonary exacerbations with sputum cultures growing multiple pathogenic organisms. Prednisone was restarted to treat autoimmune pneumonitis. She was transitioned to mycophenolate 1080 mg divided between two doses daily with good symptom control and tapered off prednisone. Discussion: Although immunosuppressive therapy is not routinely used in patients with APS Type 1, the constellation of symptoms,