CLINICAL HISTORY:

Signs and symptoms:  A 38 year-old Caucasian male presented to our office with a one-year history of chronic blisters and non-healing ulcers on both of his upper extremities. His neck and face would incur a pruritic rash with prolong exposure to the sun. His symptoms are worse in the summer. The patient was previously treated with oral prednisone for ten days and an unknown topical cream; neither of which alleviated his symptoms.

Previous Treatment:  Prednisone x 10 days and an unknown prescription topical cream.

Other information:  ROS: He denies any fevers, chills, or general myalgias. All systems are WNL except Skin: He does admit to having chronic blisters and non-healing ulcers on his upper extremities over the past year. PMH: Warts, seasonal allergy. SH: ETOH 4-5 beers/night (12 beers on weekend), tobacco 1ppd, works as an electrician. He had been to several countries outside of the U.S. in the past, while in the military. SxH: Inguinal hernia repair. Meds: None All: NKDA

PHYSICAL EXAM:

On examination, the patient presented with malar hypertrichosis (photo 1). The neck region had areas of sclerodermatous thickenings. The dorsal hands bilaterally revealed multiple ulcerations and erosions (photo 2). On closer examination of his dorsal hands, they were studded with milia.

Photo 1.

Photo 2.

LABORATORY TESTS:

Initial labs: Porphyrins, 24 hour UA: Uroporphyrin 307, Heptacarboxylate porphyrin 249, Corproporphyrin 95; Porphyrins, fecal: Uroporphyrin 34 nmol/g, Protoporphyrin 70 nmol/g, Porphyrin normal; CBC –wnl; LFT’s: ALT 151, AST 123; Hepatitis serology: Hepatitis C AB – Reactive, Hep A IgM – Nonreactive, Hep B CORE-M AB – Nonreactive, Hep B SURF AG – Nonreactive.
Follow-up labs/tests: HIV1-HIV-2 AB Nonreative; Ferritin 659 ng/mL, G6PD 14.1, Hep C RNA Quant PCR 6.2; HFE Molecular Analysis for Hereditary Hemochromatosis Genotype: Exon 4 C282Y Locus – Wild type/ No mutation, Exon 2 H63D Locus – Heterozygous mutation (1 abnl allele), Exon 2S65C Locus – Wild type/ No mutation.

DERMATOHISTOPATHOLOGY:

Two 4 mm punch biopsies were performed. The first biopsy (specimen A) was on the right lateral forearm for hematoxylin-eosin (H&E) staining. The second biopsy (specimen B) was on the right medial forearm for Direct Immunofluorescence (DIF).
Specimen A: The biopsy revealed hyperkeratosis, parakeratosis and a subepidermal blister. A perivascular chronic inflammatory infiltrate admixed with eosinophils was present in the superficial and deep dermis and focally extended into the subcutis. Alcian blue/PAS staining showed thickened basement membranes and around blood vessels in the superficial dermis (Photos 3 & 4).
Specimen B: Direct immunofluorescence showed trace +IgM, C3, and C5b-9 at the dermoepidermal junction in a granular pattern and in blood vessel walls in the superficial dermis. DIF for albumin, IgG, and IgA was negative.

Photo 3. Scanning Power [1]

Photo 4. Medium Power [1]

DIFFERENTIAL DIAGNOSIS:

1.   Polymorphic light eruption
2.   Pseudoporphyria
3.   Epidermolysis bullosa
4.   Porphyria Cutaneous Tarda
5.   Phototoxic and bullous drug eruptions

SCROLL DOWN FOR ANSWER AND DISCUSSION.

CORRECT DIAGNOSIS:

Porphyria Cutaneous Tarda

DISCUSSION:

Porphyria Cutanea Tarda (PCT) is the most common type of porphyria [2, 3]. It is due to a deficiency in the enzyme uroporphyrinogen decarboxylase, leading to a buildup of porphyrins in the liver [4]. Most patients have an acquired form of the disease, but there are patients who possess an autosomal dominant deficiency of the enzyme UPD and a third group of patients with an associated exposure to hepatotoxins.

PCT is considered to be one of the hepatic porphyrias. When the disease becomes active, large amounts of porphyrins build up in the liver. When these increased porphyrins are activated by UV light in the Soret band (400-410 nm) they become unstable and create reactive oxygen species. These free radicals lead to the damage that is clinically seen [5].

PCT can become active when environmental factors such as alcoholism, hepatitis C virus, estrogen use, HIV and iron overload combine to cause the deficiency of uroporphyrinogen decarboxylase in the liver. Additionally, 20% of PCT patients are homozygous for the C282Y mutation that causes Hemochromatosis [5].

Skin lesions of PCT are characterized by bullae formation found on sun-exposed skin. The lesions tend to rupture easily, leaving behind erosions and shallow ulcers on otherwise non-erythematous skin. Lesions tend to heal with scarring, dyspigmentation and milia formation. Patients tend to notice skin fragility with easy bruising and tearing, and hypertrichosis can often be found overlying the cheeks and temples.

The diagnosis is often strongly suggested due to clinical findings alone. A useful office procedure that can be an easy confirmational test is the use of a Wood’s light exam of a random urine specimen, revealing a coral-red fluorescence. Further confirmatory studies would be increased urinary and fecal uroporphyrins, and slightly elevated fecal coproporphyrin and protoporphyrin levels. A skin biopsy would show a subepidermal bullae with dermal papillae arising irregularly from the base of the split in the classic “festooning” pattern.

TREATMENT:

Treatment of acute porphyria should begin first with the removal of all potential precipitating agents, such as alcohol, medications and iron ingestions, and the treatment of underlying HCV infection if it exists. Sun protection in the form of barrier sunscreens and protective clothing is a must. Hydroxychloroquine in low dose (200mg twice weekly) has also been recommended. Phlebotomy however, is the treatment of choice for most patients, which alone or in combination with hydroxychloroquine may provide clinical remission.5 Uroporphyrinogen decarboxylase is inhibited by iron, so the removal of iron stores through phlebotomy may allow recovery of the diminished enzyme activity. For the rare patient who does not respond to the above treatments, desferrioxamine and erythropoietin treatment may offer an alternative treatment.
Our patient was treated with Plaquenil 200mg biweekly and phlebotomy weekly. His symptoms improved significantly after two months of therapy. His hepatitis C was managed with Ribavirin and Pegusus. He was encouraged to get immunization for Hep A & B series due to his Hep C infection. He was counseled to quit drinking alcohol and smoking, and to use sunscreens regularly with SPF >30.

REFERENCES:

1. Bhawan J, Sau P, Byers HR. 2004. Dermatology
Interactive Atlas. 2004, ver 5.
2. Elder GH. Porphyria cutanea tarda. Semin Liver Dis
1998;18:67–75.
3. Bonkovsky HL, Barnard GF. The porphyrias. Curr Treat
Options Gastroenterol 2000;3:487–500.
4. Bonkovsky L, Poh-Fitzpatrick M, Pimstone N, Obando J,
Di Bisceglie A, Tattrie C, et al. Porphyria cutanea
tarda, hepatitis C, and HFE gene mutations in North
America. Hepatology 1998;27:1661–1669.
5. Bolognia JL, Jorizzo LJ, Rapini RP, et al. Bolognia –
Dermatology. 2nd ed. Spain: Elsevier; 2008:49.
6. Mascaro, JM: Phlebotomy in Sporadic Porphyria Cutanea
Tarda. Arch Dermatol,Vol 139, Mar 2003.

Additional Comment:

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