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- Y6 Orthopaedics & Rheumatology > Porphyria (incl. acute intermittent and cutanea tarda) > Flashcards

Porphyria (incl. acute intermittent and cutanea tarda) Flashcards

1
Q

Define AIP.

A

Genertic disorder characterised by porphobilinogen deaminase (PBGD) deficiency which causes PBG and ALA to buildup in the haem biosynthesis pathway.

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2
Q

What is the inheritance of AIP?

A

autosomal dominant

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3
Q

How does AIP present?

A

Usually asymptomatic but symptoms may be triggered by certain drugs or alteration of nutritional status

It characteristically presents with abdominal and neuropsychiatric symptoms in 20-40-year-olds. AIP is more common in females (5:1)

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4
Q

What are the clinical features of an acute presentation of AIP?

A

The classical presentation is a combination of abdominal, neurological and psychiatric symptoms:

  • abdominal: abdominal pain, vomiting, constipation
  • neurological: motor neuropathy
  • psychiatric: e.g. depression
  • hypertension and tachycardia common

Other:

  • red or brownish urine - turns this colour when exposed to light as porphobilinogen (colourless) degrades
  • mental symptoms and seizures from SIADH
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5
Q

What are the risk factors for AIP presentation?

A
  • FH
  • Female
  • Drugs - barbiturates, phenytoin, progestins, metoclopramide, sulfonamide antibiotics exacerbate AIP; most are CP450 and ALA inducers
  • Decreased caloric intake
  • High progesterone levels - some get cyclic attacks
  • Smoking - induces haem synthesis and cytochrome P-450 enzym
  • Age >13yo - symptoms rare before puberty
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6
Q

What investigations would you do for AIP?

A
  • Urinary PBG
  • Urinary total porphyrins
  • Serum PBG
  • ALA (delta-aminolevulinic acid)
  • Serum sodium - low, SIADH common

Pathology notes: diagnosed based on…

  • Increased urinary PBG (and ALA) – send urine to lab quickly and keep in the dark otherwise it will turn purple.
    • PBG oxidised –> porphobilin
  • Decreased HMBS activity in erythrocytes
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7
Q

What is the mangement of AIP?

A
  • 1st line: Haem arginate OD for 4days
    • stops synthesis of ALA and PBG by inhibiting ALAS1 enzyme (-ve feedback)
  • 2nd line: glucose - less effective
  • +/- IV fluids
    • correct dehydration, hyponatraemia and electrolyte imbalances

For recurrent attacks haem arginate can be given one or twice weekly as preventative treatment or hormone suppression in females who get cyclic attacks.

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8
Q

What are the complications of AIP?

A
  • Acute attacks - delayed treatment may result in progression of neurological damage and even death. Respiratory depression, SIADH,
  • Hypertension - acutely and long-term
  • CKD - mechanism unclear
  • Hepatocellular carcinoma - increased risk in AIP
  • Neuropathic pain - becomes chronic in a few patients epsecially after many attacks
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9
Q

How common is it to remain asymptomatic in AIP?

A

Approximately 80% of heterozygotes remain asymptomatic and never become unwell.

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10
Q

What kind of diet is recommended in AIP?

A

High carbohydrate diet –> inhibit ALA synthase (low carb intake can provide attack)

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11
Q

What is the prognosis with AIP?

A

Most patients who develop symptoms have only a single attack or a few attacks during their lifetime but a few have recurrent attacks even if avoiding triggers.

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12
Q

Define PCT.

A

A blistering cutaneous condition caused by a substantial deficiency of hepatic uroporphyrinogen decarboxylase, the 5th enzyme in the haem biosynthetic pathway.

Substrates for the deficient enzyme, which are porphyrinogens (reduced porphyrins), accumulate, are oxidised to porphyrins, transported to the skin, and cause photosensitivity.

PCT is usually associated with liver cell damage.

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13
Q

What is deficient in PCT?

A

uroporphyrinogen decarboxylase

It can also be caused by hepatocyte damage e.g. alcohol, hepatitis C, oestrogen

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14
Q

What are the risk factors for PCT?

A
  • Male, middle age, white
  • Alcohol use
  • Smoking
  • Oestrogen use
  • Hepatitis C
  • HIV
  • HFE gene mutation
  • Exposure to halogenated polycyclic aromatic hydrocarbons
  • UROD mutations

NB: Acquired (80%), inherited (20%)

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15
Q

How common is PCT?

A

1 in 25,000

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16
Q

What are the clinical features of PCT?

A
  • classically presents with photosensitive rash with blistering and skin fragility on the face and dorsal aspect of hands (most common feature)
  • hypertrichosis
  • hyperpigmentation
17
Q

What inbvestigations should be done for diagnosis of PCT?

A
  • urine: elevated uroporphyrinogen and pink fluorescence of urine under Wood’s lamp
  • serum iron ferritin level is used to guide therapy
18
Q

What is the management of PCT?

A
  • Avoid precipitants e.g. alcohol, hepatic compromise
  • chloroquine
  • venesection - preferred if iron ferritin is above 600 ng/ml
19
Q

What is the prognosis with PCT?

A

Remission can usually be achieved within 6 months.

20
Q

Where are PCT lesions common?

A

Backs of the hands, and also occur in other sun-exposed areas such as arms, face, ears, and feet

21
Q

What is hypertrichosis?

A

Excess hair growth

22
Q

What are the 3 presentations of porphyrias?

A
  1. Acute neuro-visceral attacks and/or;
  2. Acute or chronic cutaneous symptoms
    • Blistering
    • Non-blistering
23
Q

Porphyrias affect haem synthesis in which parts of the body?

A

Liver cytochrome

Erythroid cells (BM)

24
Q

What is the cause of neurovisceral symptoms in porphyrias?

A

5-ALA build up which is neurotoxic

25
Q

What is the cause of skin lesions in porphyrias?

A
  • Accumulation of porphyrin precursors in the skin
  • These are oxidised and converted by UV light into active porphyrins which are toxic
26
Q

What is the difference between the appearance of porphyrinogens and porphyrins?

A

Porphyrinogens are RAISED in porphyria and COLOURLESS (no double bonds)

27
Q

Which are the acute vs non-acute porphyrias?

A

Acute

  • No skin lesions:
    • Plumboporphyria
    • AIP
  • Skin lesions:
    • Hereditary coproporphyria
    • Variegate porpyria

Non-acute/chronic

  • No skin lesions, only photosensitivity:
    • Erythropoietic protoporphyria
  • Skin lesions:
    • Congenital erythropoietic porphyria
    • PCT
28
Q

How can you differentiate between the different acute porphyrias?

A

DNA analysis offers a definitive diagnosis, but there are several mutations that can cause these conditions

29
Q

What are the most important diagnostic tests for:

  1. Acute porphyrias
  2. Porphyrias with skin features
  3. Photosensitivity porphyrias
A
  1. Urine PBG (excludes attack if normal) +/- enzyme activity +/-urine faecal porphyrins +/- DNA
  2. Urine + faecal porphyrins
  3. Red cell protoporphyrins

- Y6 Orthopaedics & Rheumatology (57 decks)

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