POLYGLANDULAR

AUTOIMMUNE
SYNDROME
DR BILAL NOOR
POST-GRADUATE RESIDENT
PAEDS-B UNIT, HMC.
CASE STUDY:

• A 12 year old female presented initially with recurrent febrile

episodes, recurrent muco-cutaneous candidiasis and 3 episodes
of fits (tetanic spasms) within last 2 years. Also with history of
poor weight gain.
• Past medical and surgical history was unremarkable
• She was a vaccinated developmentally normal child with no
significant family history of any major illness.
• Patient had a good socioeconomic background
EXAMINATION:

• She was a underweight (5th centile) at tanner stage 2 pale looking

febrile girl with temp of 100.4F
• Hemodynamically stable with R/R=18, P/R=104, BP=100/70
• She was oriented in time and space with GCS 15/15
• Tone. Posture. Reflexes were normal
• Trousseau sign (+)
• Bilateral hands nails showed pitting` dystrophy with oral thrush
• No lymphadnopathy, no Organomegaly
• Rest of the Systemic examination was unremarkable
WORKUP:

• Her full blood count showed mildly raised lymphocytic

count. Hb of 10.1g/dL.
• Liver function, renal functions were normal
• Fits workup revealed normal electrolytes, normal blood
sugar levels but serum total and ionized calcium was low
with low PTH level.
• Dermatology consultation was done for nails dystrophy (dx:
onychomycosis)
• On the basis of findings mentioned above she was labelled as a
case of Polyglandular Autoimmue Syndrome 1
• No other associations of PAS were observed during initial visit
• She was started on oral antifungal plus calcium and vitamin d
supplementation.
• Prognosis and disease course was explained and Regular
followup was advised.
• After an year patient presented again, with complaints of decrease
oral intake and darkening of skin color
• On examination she had hyper pigmented oral mucosa, knuckles and
genitalia.
• BP:100/80 with postural drop
• For PAS associated disorders serum cortisol and serum ACTH level
were sent and results favored Addisons disease

• Polyglandular autoimmune syndrome type 1

• (mucocutaneous candidiasis, hypoparathyroidism and Addisons
disease) whitakers triad
POLYGLANDULAR AUTOIMMUNE
SYNDROMES:
• Wide spectrum of autoimmune disorders
• Loss of tolerance to self antigens
• Subtypes according to :
• Age of presentation
• Patterns of disease combination
• Mode of inheritence

• 4 subtypes.
TYPE 1 PAS:

• Rare
• Infancy-childhood/early adolescence
• Juvenile PAS
• Persistent fungal infection, acquired hypoparathyridism and
Addisons disease
• Female>male
TYPE 2 PAS:

• More common
• 20-60 years
• Female>male
• Familial clustering
• Same clinical manifestation of PAS 1 except there no candidiasis
• Onset of different disease takes decade in between.

• Type 3 is same like type 2 with absence of adrenal failure.

PATHOGENESIS AND GENETICS

• Cell mediated immune process

• PAS 1: mutation in AIRE gene chromosome 21
• Monogenic: Autosomal recessive inheritance
• Defective proteins---autoimmune destruction of target organs

• PAS 2-3:
• Polygenic
• HLA genes, cytotoxic T lymphocyte antigen gene
CLINICAL SPECTRUM:

• Mucocutaneous candidiasis
• Seizures, paresthesia, cramps
• Hyperpigmentation, vomiting, diarrhea
• Hypotension
• Fatigue
• Less common clinical manifestation (associations):
• Primary hypogonadism
• Autoimmune thyroid disease
• Pernicious anemia, Atrophic gastritis, malabsorption
• Enamel hypoplasia, alopecia, vitilligo.
DIAGNOSIS:

• Serological management of organ specific Abs and subsequent

functional testing
• Autoantibodies to:
• Type 1 diabetes: Islet cells,GAD65,insulin
• Graves disease : TSH receptor,
• Hashimoto thyroiditis : TPOT/Tg
• Hypoparathyroidism: Ca sensitive receptor
• Addidons disease: 21-OH, 17-OH
• Pernicious anemia: parietal cells,
• Celiac disease: transglutaminase, gliadin
DIGNOSIS:

• Functional testing:
• TSH, FSH, LH,testosterone estradiol,
• glucose,
• ACTH stimulation test, cortisol,
• serum elecrolytes, calcium, phosphate cbc, FBS, vit b12,
SCREENING:

• 1 in 7 first degree relatives of patients with PAS have

endocrine disorder
• Screening for specific antibodies
TREATMENT:

• Multisystem involvement
• According to cause:
• Dermatology
• Candidias: antifungal- fluconazole > ketoconazole
• Endocrinology
• Hypoparathyroidsim Ca and one alph
• Addisons: hydrocortisone or prednisone + fludocortisone
• Adrenal crisis: levothyroxine without adrenal steroid replacement
increases cortisol turnover
• Type 1DM: insulin
THANK YOU!
Any questions?