dermatology in general medicine

1. PORPHYRIA
Presented By-
Anamika Raj Mishra, BDS (3rd Year)
New Horizon Dental College & Research Institute, Bilaspur
Guided By-
Dr. K. D. Prasad
Dr. Kartikay Saxsena
Dr. Kriti Sao

2. Definition:
• A group of metabolic disorders that results due to lack or dysfunction
of enzymes involved in heme-biosynthesis leads to accumulation of
porphyrins & its precursors in the body causing variety of neurologic,
hematologic, dermatologic and oral manifestations.
• In simple words it can be described as a group of disorder arise due to
disruption in heme pathway.

3. Introduction:
• Porphyria occurs mostly due to inborn (congenital) defects of Porphyrin
metabolism.
• Enzyme deficiencies are inherited as autosomal dominant, autosomal
recessive or X-linked traits with exception to Porphyria Cutanea Tarda
(PCT) which is sporadic.
• Group of rare disorders pass through the families.
• Accumulation of Porphyrins & its precursors are excreted through urine
which turns from yellow to reddish dark on exposure to sunlight.
Note: Mostly Porphyrias are autosomal recessive inherited disorder.

4. Facts:
• Porphyria (Greek word porphura, meaning purple.)
• Porphyrins are heterocyclic organic compounds (non-protein portion
of hemoglobin) play vital role in heme-biosynthesis & are normal
body chemicals, generally do not accumulate.
• Porphyrins are essential for the function of hemoglobin- a protein in
RBC that links to porphyrin, binds iron and carries oxygen from lungs
to different body parts.

5. • In the absence of certain enzymes, Porphyrin pathway is blocked
during heme-synthesis and Porphyrin & its precursors start building up
in the body parts.
• The porphyrins that occur in first half of heme synthesis pathways are
water-soluble & excreted through urine.
• Porphyrias are either inherited (autosomal recessive/x-linked) or
acquired (drug intoxication) mainly caused due to mutation in genes
which produce hemoglobin.
• Heme production occurs in : (1) Bone Marrow
(2) Liver

6. Chart showing how absence of different enzymes causing different porphyria
during heme-synthesis along with major symptoms & accumulated products.
ALA-Amino Levulinic Acid
PBG-Porphobilinogen

7. Classification:
• Porphyrias can be classified in three different ways.
(1)On the basis of specific enzyme deficiency.
(2)On the basis of predominant symptoms seen or clinical
manifestations.
(3)On the basis where the excess precursors originate.

8. Classification on basis of Enzyme Deficiency
ENZYMES DISEASES
δ-Aminolevulinate Dehydratase ALAD* Deficiency Porphyria
Porphobilinogen Deaminase Acute Intermittent Porphyria
Uroporphyrinogen III cosynthase Congenital Erythropoietic Porphyria
Uroporphyrinogen Decarboxylase PCT**+ Hepatoerythropoietic Porphyria
Coproporphyrinogen Oxidase Hereditary Co-proporphyria
Protoporphyrinogen Oxidase Variegate Porphyria
Ferrochelatase Erythropoietic Protoporphyria
*Amino Levulinic Acid Dehydratase
**Porphyria Cutanae Tarda

9. Classification on basis of Predominant Symptoms
• Acute Porphyria: Porphyria that causes neurologic, mental &
abdominal or gastric symptoms.
• Cutaneous Porphyria: Porphyria that causes skin problems
when exposed to sunlight.

10. Classification on basis where the excess precursors originates
• Hepatic Porphyria:
(1) Acute Intermittent Porphyria (AIP)
(2) Porphyria Variegate (PV)
(3) Porphyria Cutaneous Tarda (PCT)
(4) Hereditary Coproporphyria (HCP)
• Erythropoietic Porphyria:
(1) Protoporphyria.
(2) Uroporhyria

11. Patient Suffering from Acute Intermittent
Porphyria (AIP)
Patient Suffering from Hereditary
Coproporphyria (HCP)

12. Patient suffering from Variegate Porphyria Patient suffering from Porphyria Cutaneous
Tarda (PCT)

13. Hepatic Type: 1. Acute Intermittent Porphyria
• Most common Porphyria.
• Deficiency of Hepatic PBG-deaminase.
• Affected individuals have 50% reduction in erythrocyte PBG
deaminase activity.
• More common in females than males with latent prior to puberty.
• Increased urinary ALA & PBG.
• Exclusively neuropsychiatric without cutaneous findings.
• Symptoms: Motor neuropathy, Seizures, Confusion, Agitation,
Stupor, Severe Abdominal Pain, Constipation, Diarrhea,
Dehydration, Tachycardia, Hypertension, Hyponatremia.

14. Hepatic Type: 2. Hereditary Coporphyria
• Due to mutation in coproporphyrinogen oxidase (CPOX).
• Attacks in women may occur after ovulation and during last part
of Menstrual Cycle.
• Worst offenders are barbiturates, sulfonamide antibiotics, anti-
seizure drugs, rifampin.
• Symptoms: Severe Abdominal Pain, Pain on sunlight exposed
areas, Motor Neuropathy, Seizures etc.
• Treatment: Water & Sodium Balance, Glucose loading, Hemin
(i.v.).

15. Hepatic Type: 3. Variegate Porphyria
• Deficiency of Protoporphyrinogen Oxidase
• Most common in African People
• Symptoms: Neurovisceral Abnormalities, Combined effects of
skin & acute porphyria are seen.
• Diagnosis: Plasma fluorescence when exposed to UV.
• Treatment: Try to Increase ALA synthetase by heme arginate,
glucose.

16. Hepatic Type: 4. Porphyria Cutaneous Tarda
• Also among most common Porphyria.
• Porphyrin deposition under skin (Cutaneous).
• May be acquired or genetically inherited.
• 60% of PCT patients are male who consume alcohols or smoke &
females on estrogen medications.
• Most patients are above 40yrs with evidence of iron overload.
• Symptoms: Blister on skin when exposed to sunlight,
photosensitivity, redness & swelling of skin, urine darker than
normal, liver damage, increased facial hair growth.
• Treatment: Repeated phlebotomies (removal of blood), low doses
of chloroquine (125mg twice weekly), aim at lowering iron level
in liver.

17. Erythropoietic Porphyria Type 1: Protoporphyria
• Popularly known as Congenital Erythropoietic Porphyria. Also
known as Gunther’s Disease. Arises due to deficiency of
Ferrochelatase enzyme.
• Most common childhood Porphyria. (evident by 2yrs of age)
• Symptoms: Erythema, Skin pain, Burning sensation in sunlight,
Swelling, Scarring-Shallow Circular or Linear.
• Treatment: Repeated phlebotomies (removal of blood), low doses
of chloroquine (125mg twice weekly), aim at lowering iron level
in liver.

18. Patient suffering from Erythropoietic Porphyria

19. Erythropoietic Porphyria Type 2: Uroporphyria
• Due to ‘Fe’ overload. Uroporphyrin overload of skin & bone
marrow leading to hemolysis.
• Deficiency of Uroporphyrinogen III synthetase enzyme.
• Symptoms: Skin Lesions, Teeth Reddish Brown.
• Treatment: Oral Activated Charcoal, Bone Marrow
Transplant, Gene Therapy for bone, Blood transfusion to stop
erythropoiesis in bone marrow.

20. A child suffering from Erythropoietic Uroporphyria

21. ERYTHROBLASTOSIS FATALIS vs. ERYTHROPOEITIC PORPHYRIA
ERYTHROBLASTOSIS – FATALIS ERYTHROPOIETIC – PORPHYRIA
Erythroblastosis fatalis destroys RBC RBC contains special protein known as
‘Hemoglobin’ & in Porphyria, ‘Heme’ is
not made properly during heme-synthesis
Due to destruction of RBC in fetus will
not receive enough oxygen illness or
death occurs.
Due to distorted ‘heme’ group,
hemoglobin of RBC unable to carry
oxygen to different body parts.
Hemolytic effect with antigen system
incompatibilities.
Erythropoietic effect with enzyme
system dysfunction.
High level of Bilirubin, a by-product of
RBC breaksdown & found in blood.
High level of Porphyrin and its
precursors are formed & build up in body
parts. (Eg. Skin etc.)

22. Clinical Features of Porphyria (in general):
• Sex: Both sexes affected equally & transmitted as non-sex-
linked recessive character.
• Urine: First sign is excretion of red urine containing
uroporphyrin which may be noted at birth or first two years
after birth.
• Anemia: Often co-existing with anemia.

23. • Photosensitivity: Deposition of access porphyrins in the skin
lead to photosensitivity. However absent in neonatal period
but may apparent after first few years as soon as skin exposed
to sunlight.
• Vesiculobullous Lesions: Vesicular & Bullous eruptions are
seen on face, back and hand i.e. exposed parts. Vesicle
contains a serous fluid which exhibits red fluorescence.
Ruptured vesicles heals slowly & leaves depressed pigmented
scars.
• Hepatic Porphyria: In this abdominal crisis & psychological
or mental abnormalities observed along with demyelination.

24. (Photosensitivity in Porphyria Patients) (Vesciculobullous Lesions in Porphyria
Patients)

25. Algorithm for Diagnostic Procedure in PORPHYRIA

26. Oral Manifestations:
• Teeth: Porphyrin has an affinity for Calcium Phosphate & due
to this, deposition of porphyrin occurs in dentine. Deciduous
and permanent teeth show red & brownish discolouration
which under ultra violet light exhibits red fluorescence due to
incorporation of porphyrins during development.
• Oral Mucosa: Bullous, erosive lesions of oral mucosa may be
present.
• Cheilitis & Periodontist: There is no atrophic cheilitis &
advanced periodontal disease.

27. A child suffering from Uroporphyria

28. Diagnosis:
• Clinical Diagnosis: Red urine, Photophobia & Oral
Ulcerative lesions will give clue to diagnosis.
• Laboratory Diagnosis: Urine will demonstrate the presence of
5-aminolevulinic acid & porphobilinogen in urine.

29. A Diagnostic Procedure in Porphyria: Urine Analysis
Left figure is urine on the first day while the right figure is the urine after third day,
showing classic change in yellow to purple of a Porphyria patient on exposure to sunlight.

30. Treatment & Management:
• Treatment:
No permanent treatment available. Discolored teeth may be
cosmetically restored with porcelain ventured crown.
• Management:
(1)Venesection: This will reduce hepatic iron overload.
(2)Stoppage of triggering drug: It will reduce the severe
symptoms and intoxication.
(3)I.V. Drugs: Intravenous drugs of heme arginate, fluids,
electrolytes & glucose are given.

31. Long Term Complications:
• Cirrhosis
• Renal Failure
• Neurological Sequelae
• Hepatic Cellular Carcinoma

32. References:
• Shafer’s textbook of Oral Pathology-Shafer, Hine, Levy
• Oral & Maxillofacial Pathology-Neville, Damm, Allen, Bouqot
• Pathologic Basis of Disease- Robbins & Cotran.
• Essential Pathology for Dental Students-Harsh Mohan.
• Wikipedia
• emedicine.medscape.com
• Porphyriafoundation.com
• MSD Manual Professional Edition

33. Fun Fact!! (Do you know, ‘Porphyria’ also known as ‘Vampires Disease’??
Can you guess the reason for this?)
A Vampire Girl Porphyria Three common things