Porphyria

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Porphyria

• Presented by
• Dr. Mohammed AL-Ajlan

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Introduction

• The porphyrias are caused by deficiencies of
  enzymes involved in heme biosynthesis which lead
  to blockade of the porphyrin pathway and
  subsequent accumulation of porphyrins and their
  precursors.

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Introduction

• Seven major types of porhyria are now recognized
  .
• They include acute and non-acute
  
  forms.

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Classification of porphyrias
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Introduction

• Cutaneous features are not seen in acute
  intermittent porphyria (AIP) or the very
  rare aminolevulinic acid dehydratase (ALA-D)
  deficient porphyria.
• Erythropoietic protoporphyria and congenital
  erythropoietic porphyria are
  characterized by porphyrins produced mainly in
  the bone marrow. The reminder are
  primarily hepatic porhyrias.

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Introduction

• Excessive concentrations of porhyrins exposed to
  day-light generate free radicals,
  leading to cell membrane damage and cell death.

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Introduction

• The type of cellular damage depends on the
  solubility and tissue distribution of the
  porphyrins. Two main patterns of skin damage are
  seen in the porphyries
• accumulation of water soluble uro- and
  
  coproporphyrins leads to blistering.
• accumulation of the lipophilic protoporphyrins
  leads to burning sensations in the exposed skin.

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PORPHYRIA CUTANEA TARDA
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Epidimiology

• It is the most common porphyria.
• It may be acquired (type I) or
• genetically inherited (typeII).
• 60 of PCT patients are male, most of whom ingest
  excess alcohol.
• Women who develop PCT are often on
  estrogen-containing medications.
• Most patients are 40years, and 66 have
  evidence of iron overload.

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Pathogenesis

• Iron overload leads to reduce activity of the
  uroporphyrinogen decarboxylase enzyme which leads
  to elevated porphyrin levels, in particular
  uroporphyrins.
• Associated disorders
• Alcoholism.
• Hematochromatosis.
• HCV.
• HIV.
• HBV.
• CMV.

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Pathogenesis

• PCT presenting in a young adult should lead to
  consideration of HIV infection , alternatively
  familial PCT could be the explanation.
• familial PCT (typeII) accounts for 10-20 of
  cases. It is inherited as an autosomal dominant
  trait.
• Most PCT is acquired (typeI) and multifactorial
  in origin.

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Investigation
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Pathology

• Subepidermal blister with minimal
  cell-poor dermal inflammatory infiltrate.

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Treatment
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Erythropoietic Protoporphyria
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Epidemiology

• It is the most common childhood
  
  
  porphyria.
• It is usually evident by 2 years of age.

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Pathogenesis

• Protoporphyrin levels are elevated because of
  deficient activity of ferrochelatase enzyme.

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Clinical features, complications and base line
investigation
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Treatment
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Congenital Erythropoietic porphyria ( Gunther's
disease )
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Epidemiology

• It is a very rare autosomal recessive disorder.
• Patients usually present during infancy and
  rarely present in adult life with milder forms.

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Pathogenesis

• It is caused by elevation of both water-soluble
  and lipid-soluble porphyrin levels due to
  deficiency of uroporphyrinogen III synthase
  enzyme.

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Clinical features

• Very severe photosensitivity with phototoxic
  burning and blistering leading to mutilation of
  light exposed parts.
• Erythrodontia.
• Madorosis.
• Scleromalacia perforans.
• Hypersplenism.
• Hemolytic anemia.
• Thrombocytopenia

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Treatment
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Acute cutaneous porphyrias
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INTRODUCTION

• AIP is the most common of the acute porphyries.
  Its true incidence is unknown as it remains
  latent and thus undiagnosed in many peoples.
• VP is less common but , again , latent cases is
  common.
• Hereditary coproporphyria (HC) is very rare , as
  is ALA-D deficient porphyria.
• As disease in many patients carrying gene for
  acute porphyria remains latent, overt disease
  probably occurs in only 10 of abnormal gene
  carriers.

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Pathogenesis

• AIP ? porphobilinogen deaminase deficiency.
• ALA-D deficient porphyria ? ALA dehydratase
  deficiency.
• VP ? protoporphyrinogen oxidase deficiency.
• HC ? coproporphyrinogen oxidase deficiency.

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Pathogenesis

• The exact biochemical basis of acute attacks is
  unknown, and raised ALA levels in plasma are
  insufficient to induce an acute attack.
• Polypeptide levels increase during acute attacks
  and may mediate some of the symptoms.
• other causes include infection, pregnancy,
  excess alcohol consumption and hormonal
  fluctuation.

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Clinical features

• No dermatological signs in AIP or ALA-D deficient
  porphyria , because the porphyrins that
  accumulate are not ring molecules therefore
  photosensitivity does not occur.
• Cutaneous features of VP and HC are identical to
  those seen in PCT.
• Acute porphyria presents usually after puberty,
  less than 10 of patients with overt acute
  porphyria will develop an acute attack.

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Clinical features

• Acute attack features include
• Abdominal pain, nausea, vomiting, constipation,
  diarrhea.
• peripheral neuropathy, Paraesthesia, anxiety,
  seizures, aphonia, muscle and back pain,
  ascending paralysis.
• tachycardia, hypertension.

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Treatment
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Pseudoporphyria
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Pseudoporphyria

• In certain settings patient develop blistering
  and skin fragility identical to PCT with the
  histologic features but with normal urine and
  serum porphyrins.
• Hypertrichosis, dyspigmentation and cutaneous
  sclerosis do not occur.
• This condition called ? pseudoporphyria.

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Pseudoporphyria

• Most commonly due to medications especially
  NSAIDs , usually naproxen .
• other NSAIDs and tetracycline can cause similar
  picture .
• Some patient on hemodyalisis develop
• a similar PCT-like picture.

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Thank you