CIS: Immunodeficiency Case Presentation

1
CIS Immunodeficiency Case Presentation

• Ami Mehra, MD
• September 14, 2008

2

• AG -- is a 5 year old boy with mucocutaneous
  candidiasis, recurrent otitis media, recurrent
  pneumonias, pancreatic insufficiency, lactase
  deficiency and adrenal insufficiency who was
  referred for evaluation of immune deficiency

3

• History of Present Illness
• The patient developed eczema at birth and at age
  10 months presented with recurrent ear
  infections, failure to thrive, frequent episodes
  of diarrhea, and recurrent episodes of thrush
• Thrush was initially responsive to nystatin, and
  later required diflucan
• Following MMR he became febrile, and developed a
  macular rash and thrombocytopenia (plt 30,000)
• At age two, he presented with melena and anemia
  requiring transfusions (unradiated blood) without
  adverse event and was found to have duodenal
  ulcer
• By age three, he had three episodes of pneumonias
  requiring hospitalization, and he was also
  hospitalized for polydipsia, polyuria and
  hyponatremia. He was diagnosed with adrenal
  insufficiency, pancreatic insufficiency and
  lactase deficiency
• Ophthalmological exam vascularized corneal scars

4

• Family History
• Mother is of Finnish descent, and has Hashimotos
  thyroiditis, food allergies to shellfish, eczema,
  and had gestational diabetes
• Fathers is of Hispanic descent and is healthy.
• Older brother, age 7, has eczema, food allergy
  (egg), seasonal allergies, and reactive airway
  disease.
• No history of mucocutaneous candidiasis or
  polyendocrinopathy is known in the family.
• Medications fludrocortisone, and pancrelipase
• Immunizations Age appropriate

5

• Physical Exam
• On initial exam was in the 25-50th percentile for
  weight, and 50-75th percentile for height.
• HEENT exam was notable for low set ears,
  hypertelorism, high arched palate with two
  punctate lesions, tonsils present, lymph nodes
  palpable, lungs clear, heart sounds normal, liver
  edge not palpable, spleen palpable at the costal
  margin, and no rash of the extremities.

6

• Diagnostics Part 1
• CBC normal (lymphocyte 4205/mm3, no
  eosinophilia)
• IgM 106 mg, Total IgG 1478 mg (nl 532-1078), IgG1
  1120 mg (nl 170-650), and IgA 106 mg. 3 months
  later normalized, and have remained in the normal
  range on subsequent checks.
• Chemistry, hepatic function panel, thyroid and
  parathyroid studies were normal.
• No autoantibodies were detected
• Hepatitis A, B, C, EBV, Influenza, CMV, and Lyme
  serologies were negative.

7

• Specific antibodies
• Anti-rubeola antibodies protective titer
• Anti-tetanus toxoid negative (hx of
  immunizations)
• Anti-pneumococcal antibodies were present for 9
  of 12 serotypes. However, on subsequent
  evaluations, antibodies were present to only 4 of
  the 12 serotypes.
• Anti-candida IgG and IgA were present
• Other lab studies
• Stool ova and parasites, and cryptosporidium
  antibodies were negative.
• Sweat test and genetic studies for cystic
  fibrosis were reported normal.

8

• Pathology
• Esophageal biopsy normal mucosa with mild
  increase of intraepithelial lymphocytes
• Duodenal biopsy and gastric biopsy were negative
  for H. pylori.
• KOH of tongue culture was positive for candida
  albicans.
• Diagnostics Part 2
• Delayed type hypersensitivity to candida was
  negative and remained negative on repeat
  challenge.
• PHA, ConA, and PWM normal
• Candida proliferation stimulation index 2.8
  (nl gt5)
• Soluble IL-2 receptor was markedly elevated at
  1948 (nl 223-710 u/ml), serum IL-2 was normal at
  15.3 pg/ml (nl lt31.2 pg/ml Quest labs)
• Immune complex negative

9

• Flow Cytometry
• Normal CD3 71, CD3/CD4 47, CD3/CD8 21,
  CD4/CD45RA 39, CD4/CD45RO 9, CD8/CD57 3,
  CD16/CD56 9, CD19 21, CD3/CD16 9
• Genetic Analysis
• RAG1 and RAG 2 genes were normal.
• Interleukin 7 receptor (IL-7R) revealed an IL-7R
  variant with a 1241 C to T mutation.
• AIRE gene analysis revealed that the patient has
  a heterozygous sequence variant associated with
  Autoimmune Polyglandular syndrome type 1
  (APECED). The nucleotide change was 769 C to T,
  resulting in an amino acid change from Arg to X.

10

• Discussion
• Mucocutaneous candidiasis, recurrent otitis
  media, pneumonia, pancreatic insufficiency,
  lactase deficiency and adrenal insufficiency.
• Antibody titers to candida but anergic to candida
  
• Poor antibody response to Tetanus, yet he is able
  to produce antibodies to Pneumococcal
  vaccination.
• He has high IL-2 receptors levels as seen in
  inflammatory processes.
• He has IL-7R variant that has been described by
  Giliani et al. which has not yet been linked to
  any known immunodeficiencies.
• He is also a carrier of the AIRE gene associated
  with APECED
• Is it likely that this combination resulted in
  this unique phenotype?