Porphyrias

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Porphyria Cutanea Tarda

Porphyria Cutanea Tarda

Porphyria cutanea tarda (PCT) is the most common porphyria, resulting from decreased hepatic activity of uroporphyrinogen decarboxylase (UROD). It presents with photosensitive cutaneous findings on sun-exposed sites, especially the dorsal hands and forearms, including erosions, scarring, milia, hyperpigmentation, hemorrhagic blisters, hypertrichosis, vesicles, and bullae. Hepatic involvement may lead to hepatomegaly and cirrhosis. Laboratory testing shows plasma fluorescence emission peaks at 620 nm. PCT is multifactorial, with type I being the most common sporadic or acquired form, characterized by defective hepatic UROD enzyme without mutation. Triggers and associations include alcohol abuse, iron overload and hemochromatosis, hepatitis C infection, and HIV/AIDS. The cornerstone of management across porphyrias is rigorous photoprotection with sunblock, protective clothing, avoidance of trauma, and general skin care, along with treatment of triggers and underlying liver disease.

General Concepts

  • Orphans = Porphyrias with cutaneous findings
  • Child applying sunscreen with protective padding = Photoprotection and good skin care in porphyria

Porphyria Cutanea Tarda

  • Tardy orphan = Porphyria cutanea tarda
  • #1 foam finger = Most common porphyria
  • Perforated cardboard box = Decreased hepatic uroporphyrinogen decarboxylase (UROD) activity
  • #1 on shirt = Type I (sporadic/acquired) is the most common form

Skin Findings

  • Eroded gloves = Erosions
  • Tape on gloves = Scarring
  • Bowl of milia-like corn grains = Milia
  • Dark brown hand = Hyperpigmentation
  • Red bubbles on hand = Hemorrhagic blisters
  • Hairy orphan = Hypertrichosis
  • Stone liver = Hepatomegaly and cirrhosis

Laboratory Findings

  • Fluorescing alarm clock at 6:20 AM = Plasma fluorescence emission peaks at 620 nm

Triggers and Associations

  • Drunk orphan = Alcohol abuse
  • Bronze-skinned bodybuilder lifting iron = Iron overload and hemochromatosis
  • Hippo stuffed toy = Hepatitis C
  • First aid kit = AIDS or HIV

PCT: Histology, DIF, and Treatment

PCT – Histology, DIF, and Treatment

Porphyria cutanea tarda (PCT) shows distinctive histopathologic, immunofluorescent, and treatment features. On histology, it is characterized by subepidermal bullae that are cell-poor, festooning of dermal papillae, and caterpillar bodies, which represent eosinophilic basement membrane material within blister cavities and the epidermis. Direct immunofluorescence typically demonstrates linear deposition of immunoglobulins and complement at the basement membrane zone, including IgG, IgM, C3, and fibrinogen, with additional thickened deposits around superficial dermal vessels. Management requires removal of triggers such as alcohol and estrogen, strict photoprotection, and therapies directed at reducing porphyrin accumulation. Phlebotomy remains first-line, while low-dose hydroxychloroquine twice weekly may be used. In cases of iron overload, chelation with deferasirox can be beneficial.

Histology Findings

  • Drawer under oven = Subepidermal bulla
  • Empty drawer = Cell-poor bulla
  • Festooning decorations above oven = Festooning of dermal papillae
  • Pink caterpillars on oven = Caterpillar bodies (pink basement membrane material in blister cavity and epidermis)

Direct Immunofluorescence (DIF)

  • G-shaped snake = Linear IgG deposition
  • Line of M&Ms = Linear IgM deposition
  • Fibrous stick = Fibrinogen deposition
  • 3-shaped snake = C3 deposition
  • Thick red vessel-like hose = Thickened deposits around superficial dermal vessels

Treatment

  • Cook dropping alcohol bottle = Avoid alcohol
  • Crossed-out female estrogen symbol = Avoid estrogen
  • Orphan shielding from light = Aggressive photoprotection
  • Syringe full of blood = Phlebotomy
  • Hydrated Queen with two half-full glasses = Low-dose hydroxychloroquine twice weekly
  • Bronze iron bodybuilder removing socks = Deferasirox for iron removal

Hepatoerythropoetic Porphyria (HEP)

Hepatoerythropoietic Porphyria (HEP)

Hepatoerythropoietic porphyria (HEP) is a rare autosomal recessive porphyria caused by homozygous or compound heterozygous mutations in UROD, resulting in two affected alleles. The disease typically begins in infancy or early childhood and may first present with dark urine in diapers. Clinically, HEP shares many overlapping features with porphyria cutanea tarda (PCT), including vesicles, bullae, scarring, milia, erosions, ulcers, and hypertrichosis, but is often more severe. Progressive disease can result in sclerodermoid changes with skin thickening, tightening, and claw-like contractures. Photosensitivity is profound, and repeated sun exposure can cause disfiguring mutilation. As in PCT, management focuses on rigorous sun avoidance and trauma prevention, with strict photoprotection and protective clothing to limit cutaneous damage.

General Disease Representation

  • Red hippo = Hepatoerythropoietic porphyria (HEP)

Genetic Cause

  • Two perforated cardboard boxes = Homozygous or compound heterozygous mutation in UROD with 2 affected alleles

Age of Onset and Early Presentation

  • Baby hippo = HEP onset in infancy or early childhood
  • Baby hippo swimming in dark yellow/brown puddle = Dark urine in diapers, an early presenting sign

Clinical Overlap with PCT

  • Canvas of PCT graphic = Shared features with porphyria cutanea tarda including scarring, milia, vesicles/bullae, hypertrichosis, erosions, and ulcers

Severity and Additional Findings

  • Sclerodermoid dragon with contracted claws = Sclerodermoid changes with hardening and tightening of the skin
  • Sun lamp melting hippo = Severe photosensitivity leading to mutilation

Management and Prevention

  • Nighttime setting = Need for sun avoidance
  • Hippo applying sunscreen = Use of sunscreen for photoprotection
  • Hippo wearing protective padding = Avoidance of skin trauma

Gunther Disease (Congenital Erythropoietic Porphyria, CEP)

Gunther Disease (Congenital Erythropoietic Porphyria, CEP)

Congenital erythropoietic porphyria, also called Gunther disease, is a rare autosomal recessive disorder caused by a deficiency of uroporphyrinogen III synthase (UROS). The enzyme deficiency leads to accumulation of type I porphyrins, particularly uroporphyrin I and coproporphyrin I, which build up in erythrocytes, plasma, urine, and feces. The disease usually presents in infancy with red urine and pink to violet stained diapers due to porphyrin excretion. Cutaneous features are severe and include photosensitivity leading to mutilating deformities, as well as chronic erosions and scarring. Erythrodontia, characterized by red discoloration of teeth, occurs due to porphyrin deposition, and these teeth fluoresce under a Wood’s lamp. Patients may also develop conjunctivitis, corneal scarring, splenomegaly, and cholelithiasis. The porphyrins are excited by visible light at 400–410 nm (Soret band), which contributes to photosensitivity. Hemolytic anemia is a major systemic feature, resulting from ongoing oxidative damage to erythrocytes. Management centers on photoprotection, symptomatic care, and addressing complications such as anemia and splenomegaly.

Clothes at Excellent Prices (CEP) = CEP

Genetics and Pathogenesis

  • Reese’s chocolate = Autosomal recessive
  • European orphan section = Uroporphyrinogen III synthase (UROS) mutation
  • Clothing for ages 3+ = Number three (UROS III)
  • EUROpean Cop holding one finger = Uroporphyrin I overproduction
  • COP = Coproporphyrin I overproduction

Porphyrin Distribution

  • Red donut = Present in erythrocytes
  • Plasma ball = Present in plasma
  • Fresh cup of yellow lemonade = Present in urine
  • Fresh cup of brown coffee = Present in feces

Cutaneous Features

  • Orphan hunter applying sunscreen = Photosensitivity
  • Mutilated bear skin rug = Mutilating cutaneous deformities
  • Baby peeing red urine = Red urine in infancy
  • Baby’s pink and violet diaper = Pink/violet stained diapers
  • Over 400 sorbet flavors = Specific wavelength 400–410 nm (Soret band)

Other Symptoms

  • Child hunter with red teeth = Erythrodontia (red teeth)
  • Child hunter holding wood lamp = Teeth fluoresce under Woods lamp
  • Red glasses = Conjunctivitis and corneal scarring
  • Large liver and spleen décor = Splenomegaly
  • Lumps of coal = Cholelithiasis
  • Broken red tomatoes = Hemolytic anemia

Gunther’s Disease Treatment

Gunther’s Disease Treatment

In Gunther’s disease, patients develop extreme photosensitivity with blistering hemolytic anemia and mutilating cutaneous damage. Like other porphyrias strict photoprotection is a cornerstone of management to prevent phototoxic injury. Antioxidant therapy with ascorbic acid and alpha tocopherol is used to reduce oxidative damage mediated by porphyrins. Iron chelation with deferoxamine may reduce porphyrin production in transfusion dependent patients. Splenectomy can be considered to reduce hemolysis in selected cases. Severe hematologic disease carries a poor prognosis unless treated definitively with hematopoietic cell transplant which can be curative.

Treatment

  • Dark back room = Strict photoprotection
  • Oranges = Ascorbic acid vitamin C
  • Alpha tacos = Alpha tocopherol
  • Iron bodybuilder removing socks = Iron chelation with deferoxamine
  • Knife cutting spleen = Splenectomy
  • Hunter transplanting plant = Hematopoietic cell transplant

Erythropoietic Protoporphyria

Erythropoietic Protoporphyria

Erythropoietic Protoporphyria is an inherited porphyria caused by reduced activity of ferrochelatase, leading to accumulation of protoporphyrin in erythrocytes, plasma, skin, and liver. It is the most common porphyria in children, with symptom onset typically between ages 1 and 6, although adult onset cases can occur and are often associated with underlying myeloproliferative disorders. Patients develop acute photosensitivity characterized by burning, stinging, and pruritus within 5 to 30 minutes of light exposure, with visible blue light provoking symptoms more strongly than ultraviolet light. Cutaneous findings are usually subtle and include shallow linear pits on the face and papular eruptions over the knuckles rather than blistering. Systemic complications result from excess protoporphyrin and include hemolytic anemia, hypertriglyceridemia, and cholelithiasis due to increased biliary excretion of protoporphyrin.

Disease Identification

  • Red orphan poetry pros = Erythropoietic protoporphyria

Epidemiology and Genetics

  • Kid with #1 foam finger = Most common porphyria in children
  • Poet kid dressed as a pharaoh = Ferrochelatase mutation
  • Group of child poets = Onset between ages 1 to 6
  • Adult poet with dog Milo = Adult onset EPP associated with myeloproliferative disorders

Photosensitivity Features

  • Itchy child on stage = Burning stinging and itching after sun exposure
  • Blue light = Visible blue light triggers symptoms more than UV light

Cutaneous Findings

  • Scratches on kid with number one sign = Shallow linear pits on the face
  • Papular rings on knuckles = Papular eruptions over the knuckles

Systemic Associations

  • Smashed tomatoes = Hemolytic anemia
  • High triglyceride butter = Hypertriglyceridemia
  • Lumps of coal = Cholelithiasis

Erythropoietic Protoporphyria Laboratory Findings and Treatment

Erythropoietic Protoporphyria Laboratory Findings and Treatment

Excess protoporphyrin deposits in the skin and causes immediate painful photosensitivity without blistering. Laboratory evaluation shows elevated free protoporphyrin levels in plasma red blood cells and feces due to hepatobiliary excretion while urine porphyrins remain normal because protoporphyrin is not water soluble. Management centers on strict photoprotection to prevent symptoms. Pharmacologic therapies include oral beta carotene which scavenges free radicals and afamelanotide a melanocortin 1 receptor agonist that increases melanin production resulting in improved light tolerance and reduced pain.

Laboratory Findings

  • Plasma ball, RBC doughnut, brown fecal drink = Increased free protoporphyrin in plasma RBCs and feces
  • No lemonade sign = No free protoporphyrin in urine

Treatment

  • Dark basement = Strict photoprotection
  • Poet eating a carrot = Oral beta carotene
  • Kid with Afro holding melon = Afamelanotide causing increased melanin production better sunlight tolerance and less pain
  • Dark skin = Reminder of increased melanin production

Quiz

Question 1
Porphyria cutanea tarda is due to decreased activity of which enzyme?
A. Ferrochelatase
B. Uroporphyrinogen decarboxylase
C. Uroporphyrinogen III synthase
D. ALA synthase

Question 2
Which is the most common porphyria overall?
A. Erythropoietic protoporphyria
B. Congenital erythropoietic porphyria
C. Porphyria cutanea tarda
D. Hepatoerythropoietic porphyria

Question 3
Which clinical feature is most characteristic of porphyria cutanea tarda?
A. Target lesions
B. Hemorrhagic bullae on dorsal hands
C. Wickham striae
D. Palpable purpura

Question 4
Which laboratory finding is seen in porphyria cutanea tarda?
A. Peak fluorescence at 400 nm
B. Peak fluorescence at 620 nm
C. Elevated urine protoporphyrin only
D. Decreased plasma porphyrins

Question 5
Which is NOT a trigger for porphyria cutanea tarda?
A. Alcohol
B. Iron overload
C. Hepatitis C
D. Low ferritin

Question 6
Which histologic feature is classic for porphyria cutanea tarda?
A. Intraepidermal blister
B. Subepidermal cell-poor blister with festooning
C. Spongiosis
D. Acantholysis

Question 7
Which direct immunofluorescence finding is seen in porphyria cutanea tarda?
A. IgA in dermal papillae
B. Linear IgG, IgM, and C3 at basement membrane
C. Intercellular IgG
D. Perivascular IgE

Question 8
First-line treatment for porphyria cutanea tarda is:
A. Methotrexate
B. Phlebotomy
C. Cyclosporine
D. IVIG

Question 9
Which additional therapy may be used in porphyria cutanea tarda?
A. Hydroxychloroquine
B. Azathioprine
C. Mycophenolate
D. Tacrolimus

Question 10
Hepatoerythropoietic porphyria is caused by:
A. Single UROD mutation
B. Homozygous or compound heterozygous UROD mutations
C. Ferrochelatase mutation
D. UROS mutation

Question 11
Hepatoerythropoietic porphyria typically presents at what age?
A. Late adulthood
B. Adolescence
C. Infancy or early childhood
D. Middle age

Question 12
Which is an early sign of hepatoerythropoietic porphyria?
A. Blue sclera
B. Dark urine in diapers
C. Hearing loss
D. Joint deformity

Question 13
Which feature distinguishes erythropoietic protoporphyria from PCT?
A. Hypertrichosis
B. Blistering
C. Immediate burning without blistering
D. Milia

Question 14
Erythropoietic protoporphyria is caused by deficiency of:
A. UROD
B. UROS
C. Ferrochelatase
D. ALA dehydratase

Question 15
Which light most strongly triggers erythropoietic protoporphyria?
A. UVB
B. UVA
C. Visible blue light
D. Infrared

Question 16
Which lab finding is seen in erythropoietic protoporphyria?
A. Increased urine porphyrins
B. Increased protoporphyrin in RBCs and plasma
C. Decreased fecal porphyrins
D. Normal labs

Question 17
Which systemic complication is associated with erythropoietic protoporphyria?
A. Hypercalcemia
B. Cholelithiasis
C. Nephritis
D. Thyroid storm

Question 18
Congenital erythropoietic porphyria is caused by deficiency of:
A. UROD
B. Ferrochelatase
C. Uroporphyrinogen III synthase
D. ALA synthase

Question 19
Which feature is characteristic of congenital erythropoietic porphyria?
A. Blue sclera
B. Erythrodontia
C. Nail pitting
D. Vesicular eczema

Question 20
Which wavelength excites porphyrins in congenital erythropoietic porphyria?
A. 620 nm
B. 700 nm
C. 400–410 nm
D. 300 nm

Question 21
Which complication is commonly seen in congenital erythropoietic porphyria?
A. Hemolytic anemia
B. Hyperthyroidism
C. Nephrotic syndrome
D. Pancreatitis

Question 22
Which treatment may be curative in severe congenital erythropoietic porphyria?
A. Phlebotomy
B. Hydroxychloroquine
C. Hematopoietic stem cell transplant
D. Beta carotene

Question 23
Which treatment is used to reduce oxidative damage in congenital erythropoietic porphyria?
A. Vitamin C and vitamin E
B. Methotrexate
C. Cyclosporine
D. Rituximab

Question 24
Which porphyria is most common in children?
A. PCT
B. CEP
C. EPP
D. HEP

Question 25
Which treatment improves light tolerance in erythropoietic protoporphyria?
A. Hydroxychloroquine
B. Beta carotene
C. Cyclophosphamide
D. Azathioprine

Question 26
Which medication increases melanin production in erythropoietic protoporphyria?
A. Methotrexate
B. Afamelanotide
C. Rituximab
D. Dapsone

Question 27
Which of the following is NOT a feature of porphyria cutanea tarda?
A. Hypertrichosis
B. Milia
C. Immediate painful photosensitivity without blistering
D. Scarring

Question 28
Which porphyria shows sclerodermoid changes and contractures?
A. PCT
B. HEP
C. EPP
D. AIP

Question 29
Which porphyria presents with red urine and pink diapers in infancy?
A. PCT
B. EPP
C. CEP
D. HEP

Question 30
Which porphyria commonly shows subepidermal blister with caterpillar bodies?
A. CEP
B. PCT
C. EPP
D. AIP

Answers:
1 B. Uroporphyrinogen decarboxylase
2 C. Porphyria cutanea tarda
3 B. Hemorrhagic bullae on dorsal hands
4 B. Peak fluorescence at 620 nm
5 D. Low ferritin
6 B. Subepidermal cell-poor blister with festooning
7 B. Linear IgG, IgM, and C3 at basement membrane
8 B. Phlebotomy
9 A. Hydroxychloroquine
10 B. Homozygous or compound heterozygous UROD mutations
11 C. Infancy or early childhood
12 B. Dark urine in diapers
13 C. Immediate burning without blistering
14 C. Ferrochelatase
15 C. Visible blue light
16 B. Increased protoporphyrin in RBCs and plasma
17 B. Cholelithiasis
18 C. Uroporphyrinogen III synthase
19 B. Erythrodontia
20 C. 400–410 nm
21 A. Hemolytic anemia
22 C. Hematopoietic stem cell transplant
23 A. Vitamin C and vitamin E
24 C. EPP
25 B. Beta carotene
26 B. Afamelanotide
27 C. Immediate painful photosensitivity without blistering
28 B. HEP
29 C. CEP
30 B. PCT