Porphyria Cutanea Tarda in a Child Following Multi-Agent Chemotherapy
April 2014 | Volume 13 | Issue 4 | Case Reports | 489 | Copyright © April 2014
Lindsay LaPresto BS,a Hoka Nyanda MD,b Charles F. Knapp MD,b Jennifer Sopkovich MD,b and Christopher G. Nelson MDb
aUniversity of Arizona College of Medicine, Tucson, AZ
bDepartment of Dermatology and Cutaneous Surgery, University of South Florida, Tampa, FL
Porphyria cutanea tarda (PCT) is a blistering skin disorder that occurs most commonly in middle-aged individuals. It is caused by decreased uroporphyrinogen decarboxylase (UROD) activity, which results in elevated levels of uroporphyrinogen. Occurrence remains very rare in children with some sources quoting as few as 50 reports of childhood cases.1 The literature reports occasional cases of PCT onset with various drugs, including barbiturates, estrogens, griseofulvin, rifampicin, sulfonamides, imatinib, methotrexate, tamoxifen, and cyclophosphamide, however its incidence in childhood is uncommon.2-6 We present a case of new-onset PCT in an eight year-old following treatment of pre-B cell acute lymphoblastic leukemia with multi-agent chemotherapy. J Drugs Dermatol.
An eight year-old Hispanic female with a history of pre-B cell acute lymphoblastic leukemia presented to our clinic due to excessive hair on her face and arms for 16 months (Figure 1). Her family believed this started one month after she completed chemotherapy treatments. She had been previously treated with vincristine, 6-mercaptopurine, methotrexate, doxorubicin, PEG asparaginase, cyclophosphamide, thioguanine, and cytarabine. She denied any other symptoms, including abdominal pain. Previous work-up for hypertrichosis revealed normal serum levels of androstenedione, testosterone, and insulin-like growth factor 1. Her past medical history was also significant for asthma for which she was treated with fluticasone (44mcg) inhaler two puffs twice daily, albuterol (2.5 mg/3mL) inhaler 1 unit dose every 6 hours as needed, and montelukast 5 mg by mouth every night.
Physical examination revealed hypertrichosis of the patient’s forehead, upper cheeks, and arms. Also noted were erosions, crusts, scarred papules, and milia on the dorsal surfaces of her hands (Figure 2). An in-office urine sample exhibited fluorescence when viewed using a Wood’s lamp (Figure 3). PCT was suspected based on the constellation of her clinical findings, as well as her urine sample. This suspicion was confirmed by a 24-hour urine sample that showed grossly elevated uroporphyrins (5039.4 mcg/24h) and heptacarboxyporphyrins (1550.2 mcg/24h). In addition, pentacarboxyporphyrin (67.0 mcg/24h) and hexacarboxyporphyrin (7.6 mcg/24h) were elevated. Other potential causes of hypertrichosis were ruled out with normal serum levels of 17-hydroxyprogesterone (17 ng/dl) and DHEA sulfate (<15mcg/dl). There was no known family history of PCT. Baseline labs revealed hemoglobin of 13.7g/dL, hematocrit of 40.7%, platelets of 134,000/u, and elevated ferritin at 1331 ng/mL. We recommended phlebotomy treatment for this patient, with goal hemoglobin between 10-11 g/dL.
PCT results from decreased activity of UROD in the heme biosynthetic pathway, leading to an accumulation of porphyrins, specifically uroporphyrinogen and heptacarboxyporphyrin. The most common clinical findings are skin fragility, bullae, erosions, and milia on the dorsal surface of the hands, feet, or face. These skin changes result from a photosensitivity reaction in which long-wave UV light excites the excess porphyrins in the skin, releasing oxygen radicals and leading to tissue damage.7 Hypertrichosis of the face is also a common finding associated with this disorder.8 PCT usually occurs in adults and is most commonly associated with ethanol use, hepatitis C, or elevated estrogen levels8. There is also a familial form of the disorder caused by a UROD mutation, which is present in about 25% of PCT patients.9 Even with a UROD mutation, symptoms do not manifest until UROD activity is less than 20%, such as when the mutation is combined with one of the known susceptibility factors.10 UROD inhibition is thought to be caused by uroporphomethene, which is created by iron-dependent oxidation.10 There have been oc-