Immune Conference
By NTUH Ped.R2鄭嘉琪/VS.楊曜旭
/P 江伯倫, 周正成
C.C
Abnormal liver function for 2+ years
Brief Hx
1. Birth history: G1P1, GA: 42wks, NSD, BW:
3780gm, PROM (-), DOIC (-), perinatal insult (-),
neonatal hyperbilirubinemia (-)
2. Vaccination: As scheduled, Hibx3.
3. G & D: BW: 43kg ( 25-50 th percentile)
BH: 144cm ( 3-10 th percentile)
DMS: WNL
4. Maternal history: n.p
5. Previous history: n.p
6. Family history: no contributory
P.I.
• 1993 (4y/o) in高醫hospital
‧Several episodes of GTC
‧Hypocalcemia
Hypoparathyroidism(PTH<8pg/ml)
-Ca. carbonate 5# qd and calcitriol 5# qd
• 1997 (8y/o)
‧Frequent infections (HSV, oral thrush,
submandibular cellulitis); pneumonia r/o
sepsis -> admitted 高醫 hospital
• T-cell immune deficiency was found
P.I.
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2000 ( 11 Y/O) -> Admitted to高醫 hospital
Hypoparathyroidism & hypocalcemia
T3,T4, TSH, ACTH and cortisol: WNL
T cell & B cell number: WNL
T cell & B cell function: WNL
Total T cell:74.2; Active T cell:27.29
Total B cell: 20.42
CD4 36.13; CD8:28.79
P.I.
• 2000 ( 11 Y/O)
• Impaired liver function
GOT/GPT: 97/104; Bil(T/D): 1.53/0.49
‧ Gallstone and medullary nephrocalcinosis
• Anemia:
IDA or chronic dx related
• 2002.4(13y/o) ->小港 hospital
• Abnormal liver function
• Amnonia:195;GOT/GPT:403/411;
Bil(T/D):6.79/5.63;
• ALP:1464; γ-GT:67
Brief hx Summary
13 y/o 7 m/o boy :
(1) GTC-> Hypocalcemia-Hypoparathyroidism since 4
y/o,1993, s/p Ca and Vit D3 supplement
(2) Chronic mucocutaneous candidiasis (oral thrush,
onychomycosis), viral infection
(3) Vitiligo, enamel hypoplasia, nail dystrophy
(4) Anemia, cause to be determined since 8y/o, 1997
(5) Impaired liver function since 11y/o, 2000
(6) Gallstones and nephrocalcinosis since 11y/o, 2000
Our Work Up
Hypocalcemia
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2002.7.2
Ca
P
Mg
Cre
Serum
1.54
9.5
0.73
0.5
Urine
3.59
51.6
4.14
152.2
24hr Ca2+ excretion: 1.75mg/kg/day
24hr CCR: 145.2 cc/min/1.73m2
Urinary Ca/Cr ratio: 0.09
24hr Mg2+excretion: 0.05mmol/kg/day
% TRP: 98.2%
iPTH < 1 pg/ml
D/D of Hypocalcemia
• Parathyroid hormone (PTH) deficiency
• PTH receptor defects
(pseudohypoparathyroidism)
• Ca2+ -sensing receptor activating mutation
• Magnesium deficiency
• Exogenous inorganic phosphate excess
• Vitamin D deficiency
D/D of PTH deficiency
* Aplasia or hypoplasia of parathyroids
& DiGeorge syndrome ; Velocardiofacial syndrome
* Surgery
* Autoimmune parathyroiditis
& Autoimmune Polyendocrinopathy-CandidiasisEctodermal Dystrophy (APECED)(APS type I)
& Wilson disease
* Idiopathic hypoparathyroidism
R/O DiGeorge syndrome
• Parathyroid glands aplasia/ hypoplasia
→ hypoparathyroidism (+)
• Thymus aplasia/ hypoplasia (?)
→ T-cell immunity deficiency (+)
‧Congenital heart disease (atrial and
ventricular septal defects) (-)
‧Anomalies of the great vessels (-)
‧Facial anomalies: (-)
‧Chromosome: normal
Autoimmune Polyendocrinopathy-CandidiasisEctodermal Dystrophy (APECED)(APS type I)
• Chronic mucocutaneous candidiasis
(CMC)
• Hypoparathyroidism
• Addison’s disease
• Other associated disorders
CMC- Immunodeficiency ?
• T.B cell amount( 07/05 ): WNL
IgG, IgA, IgM: WNL
T cell: 82; B cell: 9, NK cell:7; CD8:32,
CD4:44; Native23; Memory:21.
• Mitogen stimulation test (proliferation ):
normal
• Candida delayed skin test: (-)
Induration< 1 cm at 48 hour & 72 hour
• T cell function to candida: decreased
• B-cell function: blood type: O ; Anti-A Titer,
Anti-B Titer: WNL
APECED
Other associated disorders
Endocrine
components
Prevalence Non-endocrine
components
%
Ovarian failure
60
Enamel hypoplasia 77
IDDM
Testicular atrophy
Parietal cell atrophy
18
14
13
Nail dystrophy
T.M calcification
Alopecia
52
33
27
Hypothyroidism
6
Keratopathy
22
Vitiligo
Autoimmune
Hepatitis
Intestinal
malabsorption
13
13
Non- endocrine
Cholelithiasis
rare
Asplenism
rare
Prevalence
%
10
APECED-Other Endocrinopathy
w/u
• Cortisol, ACTH: WNL
• Anti-microsomal Ab, thyroglobulin Ab: (-)
T3, T4, free T4, hs TSH:WNL
• FSH, LH, and testosterone: WNL
• HbA1C, AC sugar: WNL
• Gastric parietal cell Ab (-)
• Anti-parathyroid Ab: (-)
D/D of chronic hepatitis
• Chronic viral hepatitis
HAV, HBV, HCV, EBV, CMV infection
evidence
• Drug induced hepatitis
• Metabolic disorder associated with chronic
liver dx
• Autoimmune hepatitis
elevated liver enzyme, ANA(+), biopsy:
chronic hepatitis, negative viral infection
Chronic Hepatitis w/u
• Liver span: 2fb below RCM
• Anti-HAV; HbsAg, AntiHbs-Ag;AntiHCV(-)
• EBV: no recent infection
• CMV IgM, IgG: (-)
• Ceruloplasmin : WNL
• Elevated liver enzyme
• Autoimmune hepatitis: anti-smooth muscle
Ab(-) and ANA (+)
• Liver echo: increased echogenicity,
gallstone.
Chronic hepatitis
Piece-meal necrosis
Limiting plate disruption
Enlarged portal area
Work up Summary at NTUH
• Definite diagnosis
* Hypoparathyroidism
* Nephrocalcinosis
* Chronic mucocutaneous candidiasis (CMC)
* T cell immunodeficiency
* Ectodermal dystrophy: vitiligo, enamel
hypoplasia, nail dystrophy
* Chronic hepatitis (autoimmune hepatitis)
* Anemia
• Combined hypoparathyroidism,CMC,and chronic
hepatitis in OMIM -> Tentative Dx: APECED
Discussion
Autoimmune Polyendocrinopathy-CandidiasisEctodermal Dystrophy (APECED)(APS type I)
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Chronic mucocutaneous candidiasis (70%, <5 y/o)
Hypoparathyroidism (90%, >3 y/o)
Addison’s disease (90%, > 6 y/o)
Other associated disorders
AIRE(autoimmune regulator) gene mutation
Chronic mucocutaneous candidiasis
Oral thrush, onychomycosis without
disseminated candidiasis (cause ?)
In our patient
• Autoimmune hepatitis: Steroid full dose for
autoimmune process -> f/u liver function and
immune profile at OPD
• CMC: Give topical anti-candida drug
• Hypoparathyroidism: Keep Ca and vit D3,
nutrition education of Ca & P balance for
prevention of nephrocalcinosis progression ->
check level and f/u renal echo per year
• Educate the patient about possible disorders in the
future, like Addison’s disease and adequate mx
OPD f/u
GOT GPT ALP LDH
Ca
P
Am- ANA medication
monia
7/2
89
64
1397
599
1.54 9.5
86
7/15
18
29
1657
553
1.63 4.8
67
7/22
88
89
1738 581
1.38 0.4
8/1
24
29
8/3
30
32
862
8/5
32
35
1073
1:640
nil
1:40- Predonine
Sandimmun
Oral thrush
Predonine, Sandimmun,
Imuran
1.42 6.8
1.01 10.
614
1.38 7.5
Imuran, Predonine