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A patient, aged 65 years, presented with complaints of blisters on his hands and arms for several weeks. He reported that he thought the blisters were made worse by the sun.
The patient was recently started on metformin for diabetes and naproxen for arthritis. His urine porphyrin levels were normal. A complete exam of the skin and mucous membranes was normal except for blisters on the dorsal hands.
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Also known as pseudoporphyria, pseudo porphyria cutanea tarda mimics porphyria cutanea tarda (PCT) both clinically and histologically. The chief symptom of the condition is photosensitivity with blistering and onycholysis occurring in the exposed areas. Other symptoms of PCT include erosions, crusts, milia, scarring, and skin fragility all being seen in areas exposed to the sun.
Classic sites for these symptoms to develop are the dorsal hands, face, and forearms. In pseudo PCT, patients have normal serum/urine porphyrins and porphyrin synthesis, unlike in true PCT which is caused by derangement in porphyrin metabolism.
The most common cause of pseudo PCT is drug use. NSAIDs, especially naproxen, are often implicated. Certain antibiotics, such as nalidixic acid (a quinolone), also cause pseudo PCT. Chemotherapy agents such as 5-fluorourcil and imatinib have been implicated. Several other drugs including the antiarrhythmic amiodarone and the multi-purpose dapsone have been reported to cause PCT.
The precise pathophysiology of pseudo PCT is still debated. The leading theories center on the offending drugs acting much like the excess porphyrins do in true PCT; that is, these molecules absorb the energy from the ultraviolet light and cause oxidative damage to the surrounding structures.
Patients with chronic kidney disease, especially those on hemodialysis, can be affected. The pathophysiology of why hemodialysis can cause pseudo PCT is not known, but several researchers have suggested that the use of aluminum hydroxide in the dialysis solution may be the causative agent.
Tanning bed use has been reported to cause pseudo PCT as well. The excessive ultraviolet-A light administered during tanning bed use may be the cause.
If true or pseudo PCT is suspected, the clinician should order a plasma porphyrin test. If it is normal, this suggests pseudo PCT. A skin biopsy can differentiate PCT from other diseases, but a biopsy cannot differentiate true PCT from pseudo PCT.
Treatment is centered on discontinuing the causative medication or switching the medication to another drug of the same class. Also, sun avoidance and sun protection should be advised.
True porphyria cutanea tarda
True porphyria cutanea tarda (PCT) is the most common subtype of a type of diseases called the porphyrias. These inherited metabolic disorders are classified by a defect in the body’s synthesis of porphyrins, most notable of which is heme found in hemoglobin. They have varying severities and presentations depending on which step in the pathway for creating the porphyrins is disrupted.
PCT is a non-acute porphyria caused by a defect in the gene coding for the enzyme uroporphyrinogen decarboxylase. The name of PCT is derived from the fact that most of the symptoms are found on the skin (“cutanea”) and that these symptoms develop later in life (“tarda”).
PCT is associated with liver disease. Hepatitis C virus is commonly found, and all patients with PCT should be screen for hepatitis. Alcoholism, hemochromatosis, and other forms of liver damage are also common. Systemic diseases such as diabetes mellitus, systemic lupus erythematosus, and HIV/AIDS have been seen with PCT, and should be considered when a patient with PCT presents.
PCT is divided into two main subtypes. Type 1 is due to a spontaneous mutation and is thus non-familial. This type makes up a majority of the cases of PCT, and the symptoms described above are exacerbated by conditions that increase serum iron. Type 2 is the familial type and shows autosomal dominant inheritance, and the disease usually has an earlier onset of symptoms.
If PCT is suspected based on history and physical, a diagnosis can be confirmed by holding a urine sample in front of a Wood’s lamp and looking for the classic pink or red fluorescence. Urine and plasma porphyrins can also be measured. If the porphyrins are normal, then pseudo-PCT should be expected.
Treatment of PCT involves eliminating high iron states, such as those mentioned above. If further treatment is needed, therapeutic phlebotomy is used.
The treatment for pseudo PCT is stopping the offending agent/drug and sun-avoidance.
In the case presented above, a biopsy was consistent with PCT but the urine porphyrins were negative. This confirms the diagnosis of pseudo PCT. Naproxen is a common offending agent. The naproxen was stopped and the patient’s symptoms resolved.
Jason Preissig, MD, is a graduate of Baylor College of Medicine
Adam Rees, MD, a graduate of the David Geffen School of Medicine at UCLA, practices dermatology in Los Angeles.
References
- William J, Berger T, Elston D. 2011. “Chapter 26 – Errors in Metabolism.” Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunder Elsevier. Print.
- Bolognia J, Jorizzo J, Rapini R. 2008. “Section 8 – Metabolic and Systemic Diseases” Dermatology. St. Louis, MO: Mosby/Elsevier. Print
- Tanzi E, et al. “Pseudoporphyria.” Medscape. WebMD LLC. May 13, 2013. Web. Accessed June 30, 2014. http://emedicine.medscape.com/article/1064345-overview
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