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porphyria cutanea tarda (PCT)

Etiology: 1) acquired or inherited uroporphyrinogen decarboxylase deficiency 2) condition may not be expressed until the individual takes drugs that increase porphyrin synthesis (including estrogens) or drinks large amounts of alcohol, leading to the accumulation of iron in the liver, which further inhibits uroporphyrinogen decarboxylase 3) induced by pharmaceuticals & chemicals a) ethanol b) estrogens c) hexachlorobenzene (a fungicide) d) chlorinated phenols e) iron f) dibenzo-p-dioxin g) high doses of chloroquine 4) predisposing disorders a) diabetes mellitus b) hepatitis C virus, hepatoma c) HIV1 infection, AIDS d) smoking [10] 5) may be expressed in adults without other known medical problems, taking no medications [12] Epidemiology: 1) most common porphyria 2) adults 30-50 years of age, rare in children - presents in adults > 40 years of age 3) women on oral contraceptives 4) males > 60 years of age on estrogen therapy for prostate cancer 5) equal incidence in males & females 6) 1 case/25,000/year Pathology: 1) skin - subepidermal bullae - IgG & other immunoglobulin at dermal-epidermal junction & in & around blood vessels - linear IgG deposits on the basement membrane - thickened capillary walls in dermis due to - multiple replications of vascular basement membrane - deposits of immunoglobulins & fibrin - little or no inflammatory infiltrate - dermal papillae protrude upward into the blister cavity 2) liver - increased iron in hepatocytes & Kupffer cells - frequently fatty liver of alcoholism * histpathology image [8] Genetics: - except for rare familial cases, the disorder is acquired (type 1) - autosomal dominant form associated with mutation in uroporphyrinogen decarboxylase gene (type 2) - associated with defects in HFE Clinical manifestations: 1) skin lesions with photosensitivity are the most obvious clinical manifestations 2) gradual onset of lesions 3) vesicles & tense bullae on normal-appearing skin a) painful erosions from easily traumatized bullae b) atrophic scars at sites of erosions c) distribution: 1] sun-exposed skin 2] dorsal hands & feet, nose 4) fragile skin 5) milia 1-5 mm 6) hypertrichosis a) dark brown or black hair on the temples & cheeks of the face b) in severe disease, the trunk & extremities may be involved 7) scleroderma-like induration a) waxy, yellowish white areas b) sun-exposed areas of face, neck & trunk 8) periorbital purple-red suffusion (heliotrope) 9) diffuse brown hyperpigmentation due to melanin on sun-exposed areas (uncommon) * images [8,9,10] Laboratory: 1) serum chemistries a) hyperglycemia in diabetics (25% if patients with PCT) b) uroporphyrin I: increased c) serum ferritin elevated 2) urine chemistries a) uroporphyrin I: increased b) delta-aminolevulinic acid (ALA): normal c) porphobilinogen: normal 3) feces a) isocoproporphyrin III: increased b) 7-carboxylporphyrin: increased c) protoporphyrin mildly increased in contrast to variegate porphyria in which protoporphyrin is markedly increased 4) examination of urine - urine color (image) [9] - Woods lamp examination of urine* 5) skin biopsy 6) liver biopsy 8) HFE gene mutation * image of Woods lamp examination of urine [8] Differential diagnosis: 1) pseudo-porphyria cutanea tarda (pseudoporphyria) 2) variegate porphyria Management: 1) phlebotomy: top priority [11] a) remove 500 mL of blood weekly or biweekly until the blood hemoglobin drops to 10 g/dL b) remission occurs within 5-12 months after regular phlebotomy 2) twice weekly hydroxychloroquine is a alternative to phlebotomy [7] 3) hydroxychloroquine (low dose) a) if patient is anemic, or other contraindication to phlebotomy b) hydroxychloroquine may exacerbate PCT & cause hepatic failure at higher doses c) combination of phlebotomy (3-4 times) followed by low dose hydroxychloroquine may give best results 4) antiviral treatment of hepatitis C - sofosbuvir-velpatasvir 5) avoid modifiable risk factors (low priority) [11] a) ethanol & smoking* b) stop medications that can induce PCT* c) sun exposure

Interactions

disease interactions

Related

heme synthesis pseudo-porphyria cutanea tarda (PCT) uroporphyrinogen decarboxylase; UPD (UROD)

Specific

hepatoerythropoietic porphyria

General

porphyria vesiculobullous dermatitis

Properties

DEFICIENCY: uroporphyrinogen decarboxylase

Database Correlations

OMIM 176100

References

  1. Textbook of Biochemistry with Clinical Correlations, 3rd ed., TM Devlin (ed), Wiley-Liss, NY 1992 pg 1012
  2. Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 172
  3. Color Atlas and Synopsis of Clinical Dermatology, Common and Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 254-59
  4. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 179
  5. Munoz-Santos C. Familial and sporadic porphyria cutanea tarda: Clinical and biochemical features and risk factors in 152 patients. Medicine 2010 Mar; 89:69. PMID: 20517178
  6. Aarsand AK et al Familial and sporadic porphyria cutanea tarda: characterization and diagnostic strategies. Clin Chem. 2009 Apr;55(4):795-803. Epub 2009 Feb 20. PMID: 19233912
  7. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 19. American College of Physicians, Philadelphia 2012, 2015, 2022.
  8. Poh-Fitzpatrick MB, Elston DM (images) Medscape: Porphyria Cutanea Tarda http://emedicine.medscape.com/article/1103643-overview
  9. DermNet NZ. Porphyria cutanea tarda (images) http://www.dermnetnz.org/systemic/porphyria-cutanea-tarda.html
  10. Patel TS, Mohammed ET. Images in Clinical Medicine Porphyria Cutanea Tarda Associated with Hepatitis C. N Engl J Med 2021; 384:e86. June 10. PMID: 34107183 https://www.nejm.org/doi/full/10.1056/NEJMicm2035140
  11. NEJM Knowledge+ Gastroenterology
  12. Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med. 2017 Aug 31;377(9):862-872. PMID: 28854095 Review. https://www.nejm.org/doi/pdf/10.1056/NEJMra1608634