- Email: [email protected]
P200 A case report of disseminated nocardia infection in an adult with moderate lymphopenia
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
Laboratory evaluation was consistent with hemophagocytic lymphohistiocytosis (HLH). The HLH was treated with chemotherapy and immunosuppression, as no suitable haplo-identical stem cell match could be identified. Due to persistence of the severe rash and inability to wean corticosteroids, a rheumatologic evaluation was performed and was consistent with discoid lupus. The patient later contracted recurrent invasive Streptococcus pneumoniae infections (bacteremia and meningitis). An immunologic evaluation revealed absent complement hemolytic activity (CH50) with an undetectable C1q level. Conclusion: Retrospectively, this case suggests that our patient’s initial presentation was MAS secondary to underlying autoimmunity. Evaluation of an underlying classical complement deficiency may be considered in patients with otherwise unexplained HLH/MAS. The need to perform such evaluation certainly exists in the setting of early onset SLE. In addition, prior reports of invasive S. pneumoniae in patients with C1q deficiency exist, but are exceedingly limited. As such infections may be life threatening, Immunologists should be aware of this susceptibility.
P198 ATYPICAL, ATYPICAL HEMOLYTIC UREMIC SYNDROME; REDUCED FACTOR H EXPRESSION WITH NORMAL GENETIC AND ANTIBODY SCREEN L. Prakash Banka*1, L. Scott2, S. Thobani3, M. Li4, S. Xi1, K. Kwong5, 1. Los Angeles, CA; 2. Tarzana, CA; 3. Rancho Palos Verdes, CA; 4. Pasadena, CA; 5. Torrance, CA. Introduction: Unchecked activation of the alternative complement pathway is a common cause of atypical hemolytic uremic syndrome (aHUS). This is most commonly due to a genetic mutation or antibody resulting in reduced expression of the regulatory protein Factor H. We describe a case of aHUS in a trisomy 21 pediatric patient with an abnormal Factor H screen but with absence of genetic mutation for factor H, factor H antibody and exogenous agents. Methods: None Case: A 3-year-old ex-33 week premature male with Trisomy 21 presented with respiratory distress, fever, hypoxia and left lower lobe pneumonia. Laboratory studies revealed anemia, thrombocytopenia and acute kidney injury. The patient was diagnosed with aHUS and on hospital day 4, 10 and 23 received eculizumab (anti-CD5) with overall improvement. He was discharged home on a 6 month course of eculizumab. Infectious workup including isolation of streptococcus pneumoniae and shiga toxin were negative. Complement Factor H was low 33.4 mg/dL (LOW). Genetic testing for ADAMSTS13, C3, CD46, CFH, CFHR4, CFI, LMNA, THBD for deletion/duplication were negative. Factor H Autoantibody: <22 Units/mL negative. Conclusion: To the best of our knowledge this is the first case of aHUS with absence of genetic mutation, Factor H antibody and secondary causes such as infection. Expanded genetic testing or further characterizing the alternative complement pathway in trisomy 21 patients may identify the etiology of reduced Factor H expression. Determining whether there are intrinsic complement/ genetic defects in the alternative complement pathway will have lifelong implications for eculizumab.
P199 ISOLATED MANNOSE-BINDING LECTIN DEFICIENCY PRESENTING AS UNUSUAL INFECTIONS IN AN ADULT D. Patadia, P. Ogbogu*, Columbus, OH. Introduction: Mannose-binding lectin (MBL) is a component of the innate immune system, playing a role in opsonization and
S81
complement activation. Here we describe an adult patient with unusual infections, who was found to have MBL deficiency. Case Presentation: A 38 year old female presented to the immunology clinic for evaluation of recurrent and unusual infections. She had a history of recurrent fevers and apthous ulcers in infancy, which resolved after tonsillectomy at age 2. She remained healthy until age 25, when she had one episode of pneumonia. At age 29, she traveled to Ghana and upon return was diagnosed with latent TB treated with isoniazid, and post-infectious colitis. At age 31, she traveled to Egypt and developed CMV meningitis. At age 35, she presented with Sweet’s syndrome after cleaning out a storage closet. She subsequently was diagnosed with disseminated histoplasmosis, with positive urine antigen and lung biopsy findings. She was treated with 3 months of itraconazole. Immune evaluation, including CBC, lymphocyte subsets, quantitative immunoglobulins, antibody responses to diphtheria, tetanus, and pneumococcus, CH50, and AH50, was unremarkable. Mannose-binding lectin was <5.0 ng/mL, with repeat <0.5 ng/mL. Conclusion: MBL deficiency is thought to be clinically relevant in young children, cystic fibrosis patients, and those who have undergone chemotherapy or transplantation. In adults without other identifiable immunodeficiency, the clinical relevance of MBL deficiency is less clear. This patient demonstrated quite unusual infections such as disseminated histoplasmosis and latent TB, typically associated with defects in cellular immunity, and not previously described in the setting of severe MBL deficiency.
P200 A CASE REPORT OF DISSEMINATED NOCARDIA INFECTION IN AN ADULT WITH MODERATE LYMPHOPENIA A. Dossumbekova*1, T. Patel1, M. Gupta1, R. Goldblum2, S. Sur2, J. Grant2, 1. League City, TX; 2. Galveston, TX. Case Presentation: A 40-year-old male presented with disseminated nocardiosis in acute respiratory failure. He had a 20-year history of granulomatous lesions of the skin, which stabilized without treatment. Six months prior to presentation he developed cavitary lesions of the lungs. Bronchoscopy and biopsy confirmed Nocardia infection. Despite treatment with multiple culturedirected antibiotics, he developed a vertebral abscess, resulting in spinal cord compression and quadraplegia. He had no family history of immunodeficiency. Immune evaluation demonstrated decreased CD4+, CD8+, CD3+, and CD19+ cell counts. Functional studies revealed non-protective pneumococcal, diphtheria and tetanus serum IgG titers. Lymphocyte proliferation was absent to tetanus and low to candida antigens, PHA, ConA, and pokeweed mitogens. NK cell number, complement levels, and NADPH oxidative burst test were normal. HIV PCR test was negative. In collaboration with Dr. Holland at NIH, his serum was examined for autoantibodies to GM-CSF, IFN-y, IL-17A, which were undetectable. Although the defense mechanism against Nocardia is believed to be primarily cell-mediated, these results suggested an additional humoral component of disease, so the patient was treated with IVIG. Discussion: This is an interesting case of disseminated Nocardia associated with moderate lymphopenia. Nocardiosis is a rare opportunistic infection that typically infects patients with cellmediated immunodeficiencies or chronic granulomatous disease. Anticytokine antibodies are an emerging cause of adult-onset immunodeficiency also resulting in increased susceptibility to opportunistic infections. However, in our patient there must be other pathways than GM-CSF autoantibodies and CGD. The patient described here had combined defects in humoral and cellular immunity, presenting in adulthood.
Laboratory evaluation was consistent with hemophagocytic lymphohistiocytosis (HLH). The HLH was treated with chemotherapy and immunosuppression, as no suitable haplo-identical stem cell match could be identified. Due to persistence of the severe rash and inability to wean corticosteroids, a rheumatologic evaluation was performed and was consistent with discoid lupus. The patient later contracted recurrent invasive Streptococcus pneumoniae infections (bacteremia and meningitis). An immunologic evaluation revealed absent complement hemolytic activity (CH50) with an undetectable C1q level. Conclusion: Retrospectively, this case suggests that our patient’s initial presentation was MAS secondary to underlying autoimmunity. Evaluation of an underlying classical complement deficiency may be considered in patients with otherwise unexplained HLH/MAS. The need to perform such evaluation certainly exists in the setting of early onset SLE. In addition, prior reports of invasive S. pneumoniae in patients with C1q deficiency exist, but are exceedingly limited. As such infections may be life threatening, Immunologists should be aware of this susceptibility.
P198 ATYPICAL, ATYPICAL HEMOLYTIC UREMIC SYNDROME; REDUCED FACTOR H EXPRESSION WITH NORMAL GENETIC AND ANTIBODY SCREEN L. Prakash Banka*1, L. Scott2, S. Thobani3, M. Li4, S. Xi1, K. Kwong5, 1. Los Angeles, CA; 2. Tarzana, CA; 3. Rancho Palos Verdes, CA; 4. Pasadena, CA; 5. Torrance, CA. Introduction: Unchecked activation of the alternative complement pathway is a common cause of atypical hemolytic uremic syndrome (aHUS). This is most commonly due to a genetic mutation or antibody resulting in reduced expression of the regulatory protein Factor H. We describe a case of aHUS in a trisomy 21 pediatric patient with an abnormal Factor H screen but with absence of genetic mutation for factor H, factor H antibody and exogenous agents. Methods: None Case: A 3-year-old ex-33 week premature male with Trisomy 21 presented with respiratory distress, fever, hypoxia and left lower lobe pneumonia. Laboratory studies revealed anemia, thrombocytopenia and acute kidney injury. The patient was diagnosed with aHUS and on hospital day 4, 10 and 23 received eculizumab (anti-CD5) with overall improvement. He was discharged home on a 6 month course of eculizumab. Infectious workup including isolation of streptococcus pneumoniae and shiga toxin were negative. Complement Factor H was low 33.4 mg/dL (LOW). Genetic testing for ADAMSTS13, C3, CD46, CFH, CFHR4, CFI, LMNA, THBD for deletion/duplication were negative. Factor H Autoantibody: <22 Units/mL negative. Conclusion: To the best of our knowledge this is the first case of aHUS with absence of genetic mutation, Factor H antibody and secondary causes such as infection. Expanded genetic testing or further characterizing the alternative complement pathway in trisomy 21 patients may identify the etiology of reduced Factor H expression. Determining whether there are intrinsic complement/ genetic defects in the alternative complement pathway will have lifelong implications for eculizumab.
P199 ISOLATED MANNOSE-BINDING LECTIN DEFICIENCY PRESENTING AS UNUSUAL INFECTIONS IN AN ADULT D. Patadia, P. Ogbogu*, Columbus, OH. Introduction: Mannose-binding lectin (MBL) is a component of the innate immune system, playing a role in opsonization and
S81
complement activation. Here we describe an adult patient with unusual infections, who was found to have MBL deficiency. Case Presentation: A 38 year old female presented to the immunology clinic for evaluation of recurrent and unusual infections. She had a history of recurrent fevers and apthous ulcers in infancy, which resolved after tonsillectomy at age 2. She remained healthy until age 25, when she had one episode of pneumonia. At age 29, she traveled to Ghana and upon return was diagnosed with latent TB treated with isoniazid, and post-infectious colitis. At age 31, she traveled to Egypt and developed CMV meningitis. At age 35, she presented with Sweet’s syndrome after cleaning out a storage closet. She subsequently was diagnosed with disseminated histoplasmosis, with positive urine antigen and lung biopsy findings. She was treated with 3 months of itraconazole. Immune evaluation, including CBC, lymphocyte subsets, quantitative immunoglobulins, antibody responses to diphtheria, tetanus, and pneumococcus, CH50, and AH50, was unremarkable. Mannose-binding lectin was <5.0 ng/mL, with repeat <0.5 ng/mL. Conclusion: MBL deficiency is thought to be clinically relevant in young children, cystic fibrosis patients, and those who have undergone chemotherapy or transplantation. In adults without other identifiable immunodeficiency, the clinical relevance of MBL deficiency is less clear. This patient demonstrated quite unusual infections such as disseminated histoplasmosis and latent TB, typically associated with defects in cellular immunity, and not previously described in the setting of severe MBL deficiency.
P200 A CASE REPORT OF DISSEMINATED NOCARDIA INFECTION IN AN ADULT WITH MODERATE LYMPHOPENIA A. Dossumbekova*1, T. Patel1, M. Gupta1, R. Goldblum2, S. Sur2, J. Grant2, 1. League City, TX; 2. Galveston, TX. Case Presentation: A 40-year-old male presented with disseminated nocardiosis in acute respiratory failure. He had a 20-year history of granulomatous lesions of the skin, which stabilized without treatment. Six months prior to presentation he developed cavitary lesions of the lungs. Bronchoscopy and biopsy confirmed Nocardia infection. Despite treatment with multiple culturedirected antibiotics, he developed a vertebral abscess, resulting in spinal cord compression and quadraplegia. He had no family history of immunodeficiency. Immune evaluation demonstrated decreased CD4+, CD8+, CD3+, and CD19+ cell counts. Functional studies revealed non-protective pneumococcal, diphtheria and tetanus serum IgG titers. Lymphocyte proliferation was absent to tetanus and low to candida antigens, PHA, ConA, and pokeweed mitogens. NK cell number, complement levels, and NADPH oxidative burst test were normal. HIV PCR test was negative. In collaboration with Dr. Holland at NIH, his serum was examined for autoantibodies to GM-CSF, IFN-y, IL-17A, which were undetectable. Although the defense mechanism against Nocardia is believed to be primarily cell-mediated, these results suggested an additional humoral component of disease, so the patient was treated with IVIG. Discussion: This is an interesting case of disseminated Nocardia associated with moderate lymphopenia. Nocardiosis is a rare opportunistic infection that typically infects patients with cellmediated immunodeficiencies or chronic granulomatous disease. Anticytokine antibodies are an emerging cause of adult-onset immunodeficiency also resulting in increased susceptibility to opportunistic infections. However, in our patient there must be other pathways than GM-CSF autoantibodies and CGD. The patient described here had combined defects in humoral and cellular immunity, presenting in adulthood.