Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology

Abstract

The porphyrias are a group of disorders characterized by defects in the heme biosynthesis pathway. Many present with skin findings including photosensitivity, bullae, hypertrichosis, and scarring. Systemic symptoms may include abdominal pain, neuropsychiatric changes, anemia, and liver disease. With advances in DNA analysis, researchers are discovering the underlying genetic causes of the porphyrias, enabling family members to be tested for genetic mutations. Here we present a comprehensive review of porphyria focusing on those with cutaneous manifestations. In Part I, we have included the epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Treatment and management options will be discussed in Part II. IntroductionThe porphyrias are a group of disorders characterized by defects in heme production, resulting in buildup of toxic heme precursors (Table 1). Cutaneous findings are common and include photosensitivity, painful burning, bullae, and scarring. Diagnosis requires laboratory measurement of heme precursors in plasma, urine, stool, and erythrocytes.Heme is made from glycine and succinyl-coenzyme A in eight steps (Fig. 1). Heme synthesis is ubiquitous throughout the body, but 85% occurs in bone marrow, becoming hemoglobin.1 Porphyrias are classified into two categories based on whether heme precursors build up in the liver (hepatic porphyrias) or bone marrow (erythropoietic porphyrias). Hepatic porphyrias are subdivided into acute and chronic subtypes, and tend to have secondary triggers (e.g., drugs, alcohol, hormone fluctuation, infection, and fasting). Acute hepatic porphyrias present with episodes (acute attacks) of abdominal or neurological symptoms caused by a genetic predisposition with a secondary metabolic trigger. Porphyria cutanea tarda (PCT), the only chronic hepatic porphyria, has a prolonged course of liver damage and photosensitivity. Erythropoietic porphyrias present in childhood with photosensitivity. While the main defect lies in the erythrocytes, the liver may also be involved. Materials and methodsA comprehensive literature search was initially performed using PubMed. Broad searches were performed using the terms "porphyria," "coproporphyria," and "protoporphyria" in the title, and "skin diseases, genetic" in the medical subject heading, but excluding for medical subject heading "acute intermittent." Articles

Porphyria cutanea tarda - A case report

“…[2] Due to abnormalities in the heme biosynthesis pathway leading to the accumulation of porphyrins, which leads to cutaneous lesion predominantly in sun-exposed areas. It has slight male predilection and affects the patient in the fourth or fifth decades; similarly, our reported case was in male and was on the sixth decade.…”

Protoporphyrin IX: the Good, the Bad, and the Ugly

“…Longer exposure can lead to more marked reactions with severe pain, redness, swelling, and even blistering, as well as systemic reactions, and may require several days or more for recovery (Dubrey et al, 2015). Repeated reactions to sunlight can have residual effects, such as waxy thickening of the skin, especially over the knuckles, hands, nose, and cheeks, and mild scarring (Horner et al, 2013). Because sunlight exposure is avoided, EPP and XLP patients are often vitamin D deficient (Wahlin et al, 2011a).…”

Porphyria cutanea tarda: an intriguing genetic disease and marker

“…Evaluation of heme precursors will indicate a specific diagnosis for the exact porphyria which is being suffered by the patient. A urine sample from a patient with PCT will reveal an increased uroporphyrin I to uroporphyrin III ratio . Additional urine findings include an increase in aminolevulinic acid (ALA), with levels of porphobilinogen (PBG) remaining normal .…”