Mad as a Hatter

Deepti Deshpande, MBBS, MPH, FAAPAssistant Professor, Pediatrics and Public Health

University of ArizonaJune 2013

Initial Presentation

20 month old girl admitted with: • Intermittent abdominal pain for 7 weeks. • Diarrhea off and on for 4 weeks.• Increased fussiness and fatigue.• Tactile low grade fevers off and on for 7

weeks. Night sweats. • 5 lbs weight loss. • Brought to the ER because her hands/ toes

were turning cold and purple over past day.

Initial Presentation

• Several PCP, Urgent care and ER visits during this time.

• Diagnosed with a viral illness, constipation, ear infection. Received 1 course of antibiotics. Entire family treated for parasites in Mexico a few weeks prior.

• No sick contacts, No animal exposure.• Travels to Mexico frequently but no other travel.

Initial Thoughts: Differential Diagnoses

• Infectious: infectious gastroenteritis, parasitic illness, pyelonephritis, intra-abdominal abscess, coccidiodomycosis, tuberculosis.

• Non-infectious: nutritional deprivation and deficiencies, inflammatory bowel disease, thyroid disorder, malignancy, other systemic illness.

Additional HistoryOn further directed questioning/ ROS:

• Regression of motor milestones: Over past 7 weeks, stopped running, started walking very slowly and over time stopped walking. Poor balance and falls. Lack of interest in play.

• No suggestion of pain.

• Scalp hair loss and hair pulling for ~ 2 weeks

Physical Exam• Temp 36.8, HR 162, RR 30, BP 122/74, Sats 100% on RA.

– Weight= 9.6 kg (10th percentile), height and head circumference 10-25th percentiles.

• Irritable. Consolable for brief periods. Pulling her hair.

• Cool hands and feet with a dusky bluish-purple color. Centrally well perfused and warm. Distal pulses 2+.

• Abnormal neurological exam: Walks few steps very slowly with some gait instability. Loses balance easily when tries to squat to pick up a toy. Moves all extremities well but unable to stoop and recover. Patellar deep tendon reflexes 2+ but unable to elicit ankle reflexes. Normal tone and strength in the upper body. Fine motor exam appears normal. Tone decreased in the lower extremities. Follows some commands inconsistently. Says a few words.

• Remaining exam within normal limits.

Clinical Presentation in a Nutshell• Neurological: B/L lower extremity weakness and

hypotonia and regression of motor milestones. Gait instability. Inability to elicit ankle reflexes.

• Cardiovascular: Hypertension and Tachycardia.

• Gastrointestinal: Intermittent abdominal pain and diarrhea for several weeks.

• Constitutional: Irritability, weight loss, sweating and dusky hands/ feet. Low grade fever.

Differential Diagnoses

• Guillian Barre syndrome, ADEM, transverse myelitis, encephalitis, intracranial process.

• Endocrine disorders.• Neuroendocrine disorders.• Neuro-degenerative or muscle disorders. • Toxic ingestions.• Genetic disorders.• Metabolic disorders.

Workup• MRI Brain and Spine: Normal.• Lumbar Puncture: Normal CSF cell counts, protein and

glucose. CSF myelin basic protein neg.

• Complete blood count, complete metabolic panel, electrolytes, urinalysis unremarkable. ESR and CK normal.

• Cocci and PPD negative. Celiac disease screen negative. • Blood culture, urine culture, CSF culture, stool studies

negative (occult blood, stool culture, stool ova and parasites negative.

Workup

• Thyroid tests: Initially slightly low TSH with high normal free T4, but normalized on repeat testing.

• Cortisol normal.• Renin and Aldosterone normal.

Imaging:• Abdominal and Chest X-rays normal.• Abdominal/ Renal US normal.• ECHO with mild subjective LVH with age appropriate

measurements.

Workup

• Neuroendocrine workup– Urinary metanephrines, urinary catecholamines,

plasma metanephrines elevated.– Urinary VMA and HVA: Normal– Urinary 5-HIAA: Normal

• This raised concern for Pheochromocytoma:– Abdomen/ Pelvis CT negative– MIBG scan negative

What have we ruled out? Now what?

• GBS, ADEM, intracranial or spine abnormality• Infectious etiologies• Thyroid disorders• Hyperaldosteronism states• Pheochromocytoma, carcinoid tumor,

neuroblastoma

Further Testing revealed…

ELEVATED MERCURY LEVELS

Day5 Day13 Day17 6 months

Blood Mercury ug/L NaN NaN 10 4

Urine Mercury ug/gCR 45.5 54.5 36.4 NaN

5

15

25

35

45

55

45.5

54.5

36.4

10

4

Mercury Levels (Blood and Urine)

Mer

cury

Lev

els (Ref < 35)

(Ref 0-10)

Diagnosis: Mercury Toxicity• Mercury toxicity

– Clinical syndrome suggestive of mercury toxicity. – Elevated urinary and blood mercury levels.– Elevated urinary beta2 microglobulin levels indicate possible

early kidney injury.

• No chelation therapy recommended.– Mercury levels not too high and clinical symptoms not severe

with spontaneous improvement.

• Etiology unclear but suspected due to excessive seafood intake.– Child ate 2-3 servings of shrimp/ tuna almost daily. – No other exposure sources identified on detailed questioning.

Hospital Course

• Admitted to the Pediatric Floor for 23 days.

• Hypertension and Tachycardia: Hypertension controlled using PRN Hydralazine and subsequently started on Propranolol.

• Followed by Nephrology, Endocrinology, Neurology,

Toxicology, Ophthalmology, Cardiology, PT/ OT.

1 3 5 7 9 11 13 15 17 19 21 2370

80

90

100

110

120

130

140135

Mean Systolic Blood Pressure (SBP)

Day of Hospitalization

Mea

n SB

P

95th percentile: 104 mm

1 3 5 7 9 11 13 15 17 19 21 230

20

40

60

80

100

120

140

160

180

Mean Heart Rate

Day of Hospitalization

Mea

n H

eart

Rat

e

Normal Range

Hospital Course

• Lower extremity weakness improved. Walking well prior to discharge. PT ongoing.

• Dusky hands and feet resolved.

• Abdominal pain, diarrhea, sweating resolved. Afebrile during stay.

• Irritability resolved and child more playful and interactive.

Discharge Plan• Recommended avoiding all seafood.

• Propranolol for hypertension.

• Outpatient management– PCP follow up– Nephrology follow up– Toxicology follow up – Repeat mercury levels in 6 months.

Long Term Outcome

• Mercury levels decreased spontaneously without any further seafood exposure.

• Hypertension and tachycardia resolved over the next 2 months. Propranolol stopped. Repeat ECHO normal.

• All systemic, gastrointestinal, cardiovascular and neurological symptoms resolved and back to baseline within about 2-3 months post discharge.

• Meeting age appropriate developmental milestones.

MERCURY POISONING

Forms of Mercury• Elemental or metallic mercury

– Highly volatile- vapors inhaled.– Pulmonary manifestations most severe.– Sources: Thermometers, sphygmomanometers, metallurgy.

• Inorganic salts: Mercurous/ Mercuric salts– Well absorbed through skin, some via GI tract.– Gastrointestinal and Renal manifestations.– Sources: Paints, topical antiseptics, bleaching creams etc.

• Organic: methyl/ ethyl/ phenyl mercury– Almost 100% absorbed via GI tract.– Primarily neurological manifestations.– Sources: Seafood, vaccinations etc.

Mercury Toxicity: Clinical Features

Clinical presentation depends on the type of mercury, route, dose and duration of exposure.

• Acrodynia: Rare idiosyncratic reaction in children. • Neurological: CNS/ Peripheral nerves• Gastrointestinal• Pulmonary• Renal• Skin/ Gingiva/ Eyes

Acrodynia

• Rare idiosyncratic syndrome of mercury toxicity in young children.

• Symptoms may include irritability, erythema of hands and feet, photophobia, hypotonia, painful extremities, hypertension and tachycardia etc.

Mercury Toxicity• Laboratory Diagnosis– Urinary lead levels– Blood lead levels

• Pheochromocytoma like syndrome– Elevated plasma and urine catecholamines and

metanephrines– Inactivates COMT

• Treatment: Chelation used in severe symptomatic children. – DMSA commonly used.

Consider Mercury Toxicity in your differential

Unexplained hypertension with a pheochromocytoma like

presentation, neurological symptoms, developmental

regression, renal, gastrointestinal or skin symptoms.

Mad as a Hatter!

Questions?