An Infant with Rash and Respiratory Failure

1
An Infant with Rash and Respiratory Failure

• Jason Raasch, MD
• Midwest Immunology Clinic
• Childrens Hospitals and Clinics of Minnesota

2
History

• 3 month old girl
• Two weeks of age eczematous peeling dermatitis
  develops poor response to topical emollients,
  desonide, and pimecrolimus
• One month of age GERD dxd, improved with
  ranitidine evolved into frequent emesis over
  last month
• Two weeks prior to presentation subjective
  weight loss, worsening dermatitis and fussiness
  evolved
• Peripheral edema and respiratory distress led to
  evaluation in ED
• No history of fever

3
ED Evaluation

• Physical Exam
• Afebrile RR 60 P130 pOx 97
• Pallor and grunting respirations
• Hepatomegaly
• Rash (extremities and face)
• Peripheral edema
• WBC15K (B2, N40, L54, M3,E 0)
• Hgb9.9 Plt190,000
• Ferritin normal
• Alk phosphatase 30 U/mL (149-369)
• Albumin1.9 g/dL (3.0-4.6)
• Fibrinogen 95 mg/dL (200-400)
• TG620 mg/dL (0-121)
• LDH1039 U/L (208-473)
• Uric acid 2.7 mg/dL (2.1-4.9)

4
Differential Diagnosis of Rash and Suspected
Immunodeficiency

• Omenn syndrome
• Maternal graft versus host in SCID
• Wiskott-Aldrich syndrome
• Hemophagocytic lymphohistiocytosis (HLH)
• Acrodermatitis enteropathica (zinc deficiency)
• Netherton syndrome
• Immune dysregulation, polyendocrinopathy,
  enteropathy, X-linked (IPEX)
• Metabolic disorder?

5
ED Evaluation

• Physical Exam
• Afebrile RR 60 P130 pOx 97
• Pallor and grunting respirations
• Hepatomegaly
• Rash (extremities and face)
• Peripheral edema
• WBC15K (B2, N40, L54, M3,E 0)
• Hgb9.9 Plt190,000
• Ferritin normal
• Alk phosphatase 30 U/mL (149-369)
• Albumin1.9 g/dL (3.0-4.6)
• Fibrinogen 95 mg/dL (200-400)
• TG620 mg/dL (0-121)
• LDH1039 U/L (208-473)
• Uric acid 2.7 mg/dL (2.1-4.9)

6
Hospital Evaluation

• Respiratory status rapidly deteriorated and
  patient was intubated
• Bronchoscopy and lavage demonstrated Pneumocystis
  jiroveci (carinii)
• Bone marrow biopsy, peripheral smear and lumbar
  puncture were unremarkable

7
Immunologic Evaluation

• Quantitative immunoglobulins (IgA, IgM, IgG and
  subclasses, IgE) within reference ranges for age
• Lymphocyte flow cytometry
• CD4CD8 ratio elevated at 3.28
• otherwise normal lymphocyte subset analysis
• a/ß and ?/d T-cell receptor expression
• Lymphocyte proliferation to phytohemagglutinin
  (PHA), pokeweed and concanavalin-A and NK cell
  function normal
• Diagnosis?

8
Patients Diagnosis

• Skin biopsy parakeratosis with epidermal
  spongiosis and pallor suggestive of nutritional
  dermatoses
• Serum zinc 0.35 mcg/mL (0.6 1.1)
• Maternal breast milk zinc 100 mcg/mL
• Diagnosis acrodermatitis enteropathica (AE) zinc
  deficiency (?)

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Acrodermatitis enteropathica Features

• CLINICAL
• Dry, scaly eczematous dermatitis
• Paronychia, hair loss
• Vomiting and diarrhea
• Weight loss
• Photophobia

• IMMUNOLOGIC
• Progressive thymic involution
• Decreased TH1 cytokines
• Lymphopenia
• Defective cytotoxic T cell activity
• Depressed natural killer cell activity

201100
10
Acrodermatitis enteropathica

• PATHOPHYSIOLOGY
• Defective intestinal absorption of zinc
• Autosomal recessive inheritance
• SLC39A4 gene - 8q24.3 transmembrane protein that
  facilitates zinc uptake

• DIAGNOSIS
• Low serum zinc levels and characteristic skin
  biopsy findings
• Analysis of maternal breast milk zinc
• Mutation analysis of SLC39A4 gene?

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Acrodermatitis enteropathica Outcome

• Untreated patients usually die within the first
  years of life
• Severe growth retardation, dermatitis, alopecia,
  secondary bacterial and fungal infections,
  neurologic and behavioral changes
• All are reversible with zinc supplementation
• With treatment, survival is 100

12
Patients Clinical Course

• Rapid clinical improvement after initiation of
  TMP/SMX, solumedrol, FFP and enteral zinc
• All abnormal labs resolved
• Discharged home on oral zinc and TMP/SMX for PCP
  prophylaxis dermatitis improved markedly
• Vomiting resolved serum zinc levels erratic
  dermatitis waxed and waned in accordance to zinc
  levels

13
Patients Clinical Course

• Follow-up immunologic evaluation unremarkable
  TMP/SMX discontinued
• Zinc levels stabilized with ongoing
  supplementation dermatitis in complete remission
• Growth and development are normal at 18 months of
  age continues on zinc

14
Is This Acrodermatitis Enteropathica?

• Supports Diagnosis
• Low serum zinc
• Characteristic histology of rash
• Improvement with zinc supplementation
• Waxing/waning dermatitis correlated with erratic
  zinc levels

• Opposes Diagnosis
• SLC39A4 gene not sequenced

Failed Search
15
Did the Zinc Deficiency Result in Immune
Dysfunction?

• Supports theory
• Human, murine and in vitro data suggest
  importance of zinc in immune function
• Normal immunologic evaluation did not assess
  for T-cell cytotoxicity

• Opposes theory
• Hypoproteinemia
• Normal T-cell numbers
• Normal T-cell proliferation (in vitro)

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Key Points

• Immune deficiency should be considered in any
  child with persistent rash and significant
  illness
• Include acquired causes of immune deficiency in
  differential diagnosis
• Nutritional status plays a vital role in immune
  development and function stay tuned