Diagnostic Dilemmas

Background: Excluding immunodeficiency in bronchiectasis can be challenging. Cystic Fibrosis (CF) is one of the causes but usually presents in childhood. Case History and investigations: A 39-year-old nonsmoker had recurrent chest infections for 9 years. Her sputum grew Staphylococci only. She had a normal childhood and no significant family history. HRCT thorax demonstrated right-sided bronchiectasis for which she eventually had a right lobectomy. Serial tests revealed a minor cyclical neutropenia without obvious significance. Bone Marrow, bronchoscopy, alpha-1 antitrypsin, immunoglobulin and neutrophil function tests were normal. Her pneumococcal serotypes were persistently suboptimal despite 3 rounds of vaccination. Repeated sweat tests were equivocal but not diagnostic for CF. CFTR Genes study revealed only a heterozygous 508. Further investigations revealed a disease modifying Thymidine repeat sequence; F508/ND9T/9T suggesting a variant CF genotype. Duodenal ion transport was impaired confirming its functional significance. She also has pancreatic insufficiency. We chose to manage her as an unusual CF variant initially. A trail of immunoglobulin replacement will be offered only if this fails. Diagnostic Dilemma: What constitutes specific pneumococcal antibody deficiency (SPAD)? The phenotype and pathogens were not typical of SPAD. What should guide the decision to start IVIG (or not)? The genes, phenotype and functional tests suggest atypical CF. What are the indications and how hard should we look for CF in someone with late onset bronchiectasis? What would be the consequences of treating the apparent SPAD and ignore CF? How many apparent SPADs have another immunodeficiency either partly or wholly responsible for their phenotype? References: 1. Tabatabaie P, Aghamohammadi A, Mamishi S, et al. Evaluation of humoral immune function in patients with bronchiectasis. Iranian Journal of Allergy Asthma and Immunology. 2008; 7: 69 77. 2. Aghamohammadi A, Moin M, Karimi A, et al. Immunologic evaluation of patients with recurrent ear, nose, and throat infections. American Journal of Otolaryngology. 2008; 29: 385 92. 3. Alachkar H, Taubenheim N, Haeney MR, et al. Memory switched B cell percentage and not serum immunoglobulin concentration is associated with clinical complications in children and adults with specific antibody deficiency and common variable immunodeficiency. Clinical Immunology. 2006; 120: 310 8. 4. Voglis S, Quinn K, Tullis E, et al. Human neutrophil peptides and phagocytic deficiency in bronchiectatic lungs. American Journal of Respiratory and Critical Care Medicine. 2009; 15180: 159 66. 5. Zaibak F, Williamson R. Genetics and Genomics: Providing new Opportunities for the Translation of Basic Research to Clinical Care for Cystic Fibrosis. Expert. Review of Respiratory Medicine 2008; 2: 1 5.