eMedicine Specialties > Dermatology > Bullous Diseases

Pseudoporphyria

Author: Elizabeth L Tanzi, MD, Co-Director, Laser Surgery, Washington Institute of Dermatologic Laser Surgery
Coauthor(s): Vincent A De Leo, MD, Clinical Professor of Dermatology, Department of Dermatology, College of Physicians and Surgeons of Columbia University; Chairman, Department of Dermatology, Director of Dermatology Residency Training Program, St Luke's-Roosevelt Hospital Center; Chairman, Department of Dermatology, Beth Israel Medical Center
Contributor Information and Disclosures

Updated: Jun 18, 2009

Introduction

Background

Porphyrias are metabolic disorders of heme synthesis. Partial enzymic deficiencies result in excessive accumulation and excretion of 5-aminolevulinic acid, porphobilinogen, and/or porphyrins. Porphyria cutanea tarda (PCT) is the most common of the porphyrias in North America and Europe. First described by Waldenström in 1937, this blistering disorder is caused by a deficiency of uroporphyrinogen decarboxylase, an enzyme in heme biosynthesis.1 Porphyrins accumulate in the liver, are transported in plasma, and are excessively excreted in the urine. Exposure of patients with porphyria cutanea tarda to sunlight results in increased skin fragility, vesicles, bullae, hypertrichosis, hyperpigmentation, sclerodermoid changes, dystrophic calcification, milia, and scarring in a photodistribution. Porphyria cutanea tarda can be inherited or acquired. Treatment options include phlebotomy and antimalarial medications.

Pseudoporphyria describes a bullous photosensitivity that clinically and histologically mimics porphyria cutanea tarda. However, no demonstrable porphyrin abnormalities are present. In 1964, Zelickson was first to describe this type of phototoxic reaction in patients after the use of nalidixic acid.2 The skin lesions were indistinguishable from those observed in patients with porphyria cutanea tarda. Since this initial report, many other drugs have been incriminated in mediating this type of bullous photosensitivity.3 Pseudoporphyria has been reported in patients with chronic renal failure treated with hemodialysis and in those with excessive exposure to ultraviolet A (UV-A) by tanning beds.4,5

Pathophysiology

The precise pathophysiologic mechanism of pseudoporphyria is not fully understood. In 1983, Keane et al developed an animal model for nalidixic acid photosensitivity in CF-1 female mice.6 Animals injected with nalidixic acid and then exposed to ultraviolet radiation for 10 weeks exhibited more severe cutaneous manifestations than mice treated with sodium chloride solution. Light and electron microscopy demonstrated a subepidermal split beneath the basal lamina at the same level as seen in histologic examination of porphyria cutanea tarda and pseudoporphyria. The authors suggested that a photosensitizing drug might behave in a similar fashion to photoactivated endogenous porphyrins and target similar structures in the skin. Several other authors have corroborated these findings.

Other mechanisms have been proposed to explain the role of ultraviolet or visible light radiation in drug-induced pseudoporphyria. An alternative theory is based on the finding that exogenous photosensitizers are deposited along the endothelium of blood vessels of lesional and nonlesional skin. An immune response targeted against antigens is proposed to develop after phototoxic injury to the dermal microvascular endothelium. Dabski and Beutner proposed a multistep mechanism in which exogenous photosensitizers (drugs) damage the vascular endothelium by the release of proteases after sunlight exposure.7 Then, immunoglobulin G (IgG) and immunoreactants bind to the damaged endothelium, causing formation of bullae at the level of the lamina lucida as a secondary or tertiary event.

The pathophysiology of pseudoporphyria associated with hemodialysis has not been fully explained. Aluminum hydroxide has been implicated in hemodialysis-associated pseudoporphyria. Aluminum hydroxide is found in dialysis solution and has been shown to produce a porphyrialike disorder after long-term administration in rats.

Frequency

United States

Pseudoporphyria is not uncommon. Although fewer than 100 cases are documented, pseudoporphyria is most likely underreported in the literature.

Race

Although pseudoporphyria has no predilection toward any one race, it has been shown that fair-skinned children who are highly prone to sunburn are more likely to develop naproxen-induced pseudoporphyria than those children with skin types III or higher. Wallace et al demonstrated that even in the absence of a history of blistering, children with light skin and blue or green eyes are at an increased risk of developing shallow scars on the face while taking naproxen.8

Sex

Pseudoporphyria affects males and females equally.

Age

The ages of patients reported with pseudoporphyria range from 2-81 years.

Clinical

History

  • A careful history is of utmost importance when the diagnosis of pseudoporphyria is being considered. A personal and family history of hepatitis, porphyria, or photosensitivity disorder must be sought.
  • Although a genetic factor has not been considered in pseudoporphyria, one case of monozygotic twins developing pseudoporphyria after excessive UV-A exposure from long-term tanning bed use has been documented.5
  • The patient should be thoroughly questioned regarding any symptoms of connective tissue disorder, which may be the underlying pathology of the photosensitivity. Some reports suggest that a connective-tissue disorder may be a predisposing factor in patients using nonsteroidal anti-inflammatory drugs (NSAIDs) who develop pseudoporphyria.

Physical

  • Pseudoporphyria is clinically characterized by increased skin fragility; erythema; and the appearance of tense bullae and erosions on sun-exposed skin, which are identical to those seen in patients with porphyria cutanea tarda. However, a clinical pearl that may prove helpful in differentiating between pseudoporphyria and porphyria cutanea tarda is that the classic features of hypertrichosis, hyperpigmentation, and sclerodermoid changes found with porphyria cutanea tarda are unusual with pseudoporphyria.
  • A second clinical pattern of pseudoporphyria has a similar presentation to erythropoietic protoporphyria (EPP), an autosomal dominant porphyria resulting from a reduced activity of ferrochelatase.
    • In contrast to porphyria cutanea tarda, erythropoietic protoporphyria usually begins in childhood with a history of photosensitivity, often described as a burning sensation immediately after sunlight exposure.
    • Clinically, erythropoietic protoporphyria is characterized by erythema, edema, shallow scars, and waxy induration of the skin, particularly on the face.
    • Pseudoporphyria that clinically mimics erythropoietic protoporphyria has been described almost exclusively in children taking naproxen for juvenile rheumatoid arthritis.9 Naproxen-induced pseudoporphyria seems to have a dimorphic presentation with the porphyria cutanea tarda–like pattern more often seen in the adult population and the erythropoietic protoporphyria–like pattern more commonly seen in children, although some overlap has been documented.

Causes

  • Pseudoporphyria can be induced by a wide range of medications, excessive UV-A exposure, and hemodialysis.
  • As recognition of pseudoporphyria increases and the number of new medications expands, the list of etiologic agents associated with pseudoporphyria will most likely continue to grow. Agents associated with pseudoporphyria are as follows10 :
    • Propionic acid derivatives (NSAIDs)11,12 - Naproxen,10,13,14,15,16,17,18 diflunisal, ketoprofen, nabumetone,19,20 oxaprozin,21 mefenamic acid,22 rofecoxib23
    • Antibiotics - Nalidixic acid,24,25 tetracycline,26 oxytetracycline,27 ampicillin-sulbactam, cefepime,28  ciprofloxacin29
    • Antifungals - Voriconazole30,31
    • Diuretics - Furosemide,32 chlorthalidone,33 butamide, triamterene/hydrochlorothiazide, torsemide,34 bumetanide35
    • Antiarrhythmics - Amiodarone36
    • Chemotherapy - 5-Fluorouracil,37 imatinib38
    • Immunosuppressants - Cyclosporine
    • Sulfones - Dapsone
    • Vitamins - Brewers' yeast,17 pyridoxine39
    • Vitamin A derivatives - Etretinate,40 isotretinoin41
    • Muscle relaxants - Carisoprodol, aspirin42
    • Nonsteroidal antiandrogens - Flutamide43
    • Other - Hemodialysis,44 excessive UV-A, cola,45 oral contraceptive pills (levonorgestrel and ethinyl estradiol), narrowband UV-B46 phototherapy (rarely)
  • Vitiligo may be associated with pseudoporphyria.47,48 Several reports describe patients with vesicles, bullae, and scarring confined to areas of vitiligo on the dorsa of the hands with sparing of normally pigmented skin while taking medications known to cause pseudoporphyria. It is well established that the clinical findings of pseudoporphyria may be precipitated or exacerbated by sunlight. One author suggests that the presence of melanin in healthy skin may be adequate protection to prevent the development of pseudoporphyria in patients with vitiligo.

More on Pseudoporphyria

Overview: Pseudoporphyria
Differential Diagnoses & Workup: Pseudoporphyria
Treatment & Medication: Pseudoporphyria
Follow-up: Pseudoporphyria
References
[ CLOSE WINDOW ]

References

  1. Waldenström J. Studein uber porphyrie. Acta Med Scand. 1937;82:1.

  2. Zelickson AS. Phototoxic reaction with nalidixic acid. JAMA. Nov 9 1964;190:556-7. [Medline].

  3. Burry JN, Lawrence JR. Phototoxic blisters from high frusemide dosage. Br J Dermatol. May 1976;94(5):495-9. [Medline].

  4. Stenberg A. Pseudoporphyria and sunbeds. Acta Derm Venereol. 1990;70(4):354-6. [Medline].

  5. Wilson CL, Mendelsohn SS. Pseudoporphyria and sunbeds, a coincidence in identical twins?. Br J Dermatol. Aug 1991;125(2):191. [Medline].

  6. Keane JT, Pearson RW, Malkinson FD. Nalidixic acid-induced photosensitivity in mice: a model for pseudoporphyria. J Invest Dermatol. Mar 1984;82(3):210-3. [Medline].

  7. Dabski C, Beutner EH. Studies of laminin and type IV collagen in blisters of porphyria cutanea tarda and drug-induced pseudoporphyria. J Am Acad Dermatol. Jul 1991;25(1 Pt 1):28-32. [Medline].

  8. Wallace CA, Farrow D, Sherry DD. Increased risk of facial scars in children taking nonsteroidal antiinflammatory drugs. J Pediatr. Nov 1994;125(5 Pt 1):819-22. [Medline].

  9. Lang BA, Finlayson LA. Naproxen-induced pseudoporphyria in patients with juvenile rheumatoid arthritis. J Pediatr. Apr 1994;124(4):639-42. [Medline].

  10. Suarez SM, Cohen PR, DeLeo VA. Bullous photosensitivity to naproxen: "pseudoporphyria". Arthritis Rheum. Jun 1990;33(6):903-8. [Medline].

  11. Al-Khenaizan S, Schechter JF, Sasseville D. Pseudoporphyria induced by propionic acid derivatives. J Cutan Med Surg. Jan 1999;3(3):162-6. [Medline].

  12. Taylor BJ, Duffill MB. Pseudoporphyria from nonsteroidal antiinflammatory drugs. N Z Med J. May 27 1987;100(824):322-3. [Medline].

  13. Allen R, Rogers M, Humphrey I. Naproxen induced pseudoporphyria in juvenile chronic arthritis. J Rheumatol. Jun 1991;18(6):893-6. [Medline].

  14. Girschick HJ, Hamm H, Ganser G, Huppertz HI. Naproxen-induced pseudoporphyria: appearance of new skin lesions after discontinuation of treatment. Scand J Rheumatol. 1995;24(2):108-11. [Medline].

  15. Howard AM, Dowling J, Varigos G. Pseudoporphyria due to naproxen. Lancet. Apr 6 1985;1(8432):819-20. [Medline].

  16. Judd LE, Henderson DW, Hill DC. Naproxen-induced pseudoporphyria. A clinical and ultrastructural study. Arch Dermatol. Apr 1986;122(4):451-4. [Medline].

  17. Levy ML, Barron KS, Eichenfield A, Honig PJ. Naproxen-induced pseudoporphyria: a distinctive photodermatitis. J Pediatr. Oct 1990;117(4):660-4. [Medline].

  18. Sterling JC, Pye RJ. Naproxen-induced pseudoporphyria. Br J Rheumatol. Jun 1987;26(3):210-1. [Medline].

  19. Krischer J, Scolari F, Kondo-Oestreicher M, Vollenweider-Roten S, Saurat JH, Pechere M. Pseudoporphyria induced by nabumetone. J Am Acad Dermatol. Mar 1999;40(3):492-3. [Medline].

  20. Magro CM, Crowson AN. Pseudoporphyria associated with Relafen therapy. J Cutan Pathol. Jan 1999;26(1):42-7. [Medline].

  21. Ingrish G, Rietschel RL. Oxaprozin-induced pseudoporphyria. Arch Dermatol. Dec 1996;132(12):1519-20. [Medline].

  22. O'Hagan AH, Irvine AD, Allen GE, Walsh M. Pseudoporphyria induced by mefenamic acid. Br J Dermatol. Dec 1998;139(6):1131-2. [Medline].

  23. Markus R, Reddick ME, Rubenstein MC. Rofecoxib-induced pseudoporphyria. J Am Acad Dermatol. Apr 2004;50(4):647-8. [Medline].

  24. Bilsland D, Douglas WS. Sunbed pseudoporphyria induced by nalidixic acid. Br J Dermatol. Oct 1990;123(4):547. [Medline].

  25. Birkett DA, Garretts M, Stevenson CJ. Phototoxic bullous eruptions due to nalidixic acid. Br J Dermatol. May 1969;81(5):342-4. [Medline].

  26. Epstein JH, Seibert JS. Porphyria-like cutaneous changes induced by tetracycline hydrochloride photosensitization. Arch Dermatol. May 1976;112(5):661-6. [Medline].

  27. Hawk JL. Skin changes resembling hepatic cutaneous porphyria induced by oxytetracycline photosensitization. Clin Exp Dermatol. Sep 1980;5(3):321-5. [Medline].

  28. Phung TL, Pipkin CA, Tahan SR, Chiu DS. Beta-lactam antibiotic-induced pseudoporphyria. J Am Acad Dermatol. Aug 2004;51(2 Suppl):S80-2. [Medline].

  29. Degiovanni CV, Darley CR. Pseudoporphyria occurring during a course of ciprofloxacin. Clin Exp Dermatol. Jan 2008;33(1):109-10. [Medline].

  30. Dolan CK, Hall MA, Blazes DL, Norwood CW. Pseudoporphyria as a result of voriconazole use: a case report. Int J Dermatol. Oct 2004;43(10):768-71. [Medline].

  31. Kwong WT, Hsu S. Pseudoporphyria associated with voriconazole. J Drugs Dermatol. Oct 2007;6(10):1042-4. [Medline].

  32. Breier F, Feldmann R, Pelzl M, Gschnait F. Pseudoporphyria cutanea tarda induced by furosemide in a patient undergoing peritoneal dialysis. Dermatology. 1998;197(3):271-3. [Medline].

  33. Baker EJ, Reed KD, Dixon SL. Chlorthalidone-induced pseudoporphyria: clinical and microscopic findings of a case. J Am Acad Dermatol. Nov 1989;21(5 Pt 1):1026-9. [Medline].

  34. Perez-Bustillo A, Sanchez-Sambucety P, Suarez-Amor O, Rodriiguez-Prieto MA. Torsemide-induced pseudoporphyria. Arch Dermatol. Jun 2008;144(6):812-3. [Medline].

  35. Leitao EA, Person JR. Bumetanide-induced pseudoporphyria. J Am Acad Dermatol. Jul 1990;23(1):129-30. [Medline].

  36. Parodi A, Guarrera M, Rebora A. Amiodarone-induced pseudoporphyria. Photodermatol. Jun 1988;5(3):146-7. [Medline].

  37. Laidman PJ, Gebauer K, Trotter J. 5-Fluorouracil-induced pseudoporphyria. Aust N Z J Med. Aug 1992;22(4):385. [Medline].

  38. Timmer-de Mik L, Kardaun SH, Kramer MH, Hayes DP, Bousema MT. Imatinib-induced pseudoporphyria. Clin Exp Dermatol. Dec 9 2008;[Medline].

  39. Baer RL. Cutaneous skin changes probably due to pyridoxine abuse. J Am Acad Dermatol. Mar 1984;10(3):527-8. [Medline].

  40. McDonagh AJ, Harrington CI. Pseudoporphyria complicating etretinate therapy. Clin Exp Dermatol. Nov 1989;14(6):437-8. [Medline].

  41. Riordan CA, Anstey A, Wojnarowska F. Isotretinoin-associated pseudoporphyria. Clin Exp Dermatol. Jan 1993;18(1):69-71. [Medline].

  42. Hazen PG. Pseudoporphyria in a patient receiving carisoprodol/aspirin therapy. J Am Acad Dermatol. Sep 1994;31(3 Pt 1):500. [Medline].

  43. Borroni G, Brazzelli V, Baldini F, et al. Flutamide-induced pseudoporphyria. Br J Dermatol. Apr 1998;138(4):711-2. [Medline].

  44. Gilchrest B, Rowe JW, Mihm MC Jr. Bullous dermatosis of hemodialysis. Ann Intern Med. Oct 1975;83(4):480-3. [Medline].

  45. Judd L. Pseudoporphyria due to cola. Int J Dermatol. Sep 1991;30(9):674-5. [Medline].

  46. Oh C, Jones B, Solomon R, Egan CA. Pseudoporphyria secondary to narrowband UVB phototherapy for psoriasis. Australas J Dermatol. May 2006;47(2):134-6. [Medline].

  47. Burns DA. Naproxen pseudoporphyria in a patient with vitiligo. Clin Exp Dermatol. Jul 1987;12(4):296-7. [Medline].

  48. Motley RJ. Pseudoporphyria due to dyazide in a patient with vitiligo. BMJ. Jun 2 1990;300(6737):1468. [Medline].

  49. Maynard B, Peters MS. Histologic and immunofluorescence study of cutaneous porphyrias. J Cutan Pathol. Feb 1992;19(1):40-7. [Medline].

  50. Grossman ME, Poh-Fitzpatrick MB. Porphyria cutanea tarda. Diagnosis, management, and differentiation from other hepatic porphyrias. Dermatol Clin. Apr 1986;4(2):297-309. [Medline].

  51. Hrabovsky SL, Elmets CA. Pathogenesis, characteristics, diagnosis and treatment of pseudoporphyria. Curr Opin Dermatol. 1996;3:105-10.

  52. Lim CK, Rideout JM, Peters TJ. Pseudoporphyria associated with consumption of brewers' yeast. Br Med J (Clin Res Ed). Jun 2 1984;288(6431):1640-2. [Medline].

  53. Murphy GM, Wright J, Nicholls DS, et al. Sunbed-induced pseudoporphyria. Br J Dermatol. Apr 1989;120(4):555-62. [Medline].

  54. Poh-Fitzpatrick MB. Porphyria, pseudoporphyria, pseudopseudoporphyria...?. Arch Dermatol. Apr 1986;122(4):403-4. [Medline].

  55. Sharp MT, Horn TD. Pseudoporphyria induced by voriconazole. J Am Acad Dermatol. Aug 2005;53(2):341-5. [Medline].

  56. Silver EA, Silver AH, Silver DS, McCalmont TH. Pseudoporphyria induced by oral contraceptive pills. Arch Dermatol. Feb 2003;139(2):227-8. [Medline].

  57. Sola R, Puig LL, Ballarin JA, Donate T, del Rio G. Pseudoporphyria cutanea tarda associated with cyclosporine therapy. Transplantation. May 1987;43(5):772. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

pseudoporphyria, drug-induced bullous photosensitivity, therapy-induced bullous photosensitivity, PCT, porphyria cutanea tarda

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Elizabeth L Tanzi, MD, Co-Director, Laser Surgery, Washington Institute of Dermatologic Laser Surgery
Elizabeth L Tanzi, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

Coauthor(s)

Vincent A De Leo, MD, Clinical Professor of Dermatology, Department of Dermatology, College of Physicians and Surgeons of Columbia University; Chairman, Department of Dermatology, Director of Dermatology Residency Training Program, St Luke's-Roosevelt Hospital Center; Chairman, Department of Dermatology, Beth Israel Medical Center
Vincent A De Leo, MD is a member of the following medical societies: American Academy of Dermatology, American College of Occupational and Environmental Medicine, American Contact Dermatitis Society, American Dermatological Association, American Medical Association, American Society for Photobiology, Dermatology Foundation, New York Academy of Medicine, New York County Medical Society, Photomedicine Society, Society for Investigative Dermatology, Society of Toxicology, and Women's Dermatologic Society
Disclosure: estee lauder Consulting fee Consulting; laroche posay Consulting fee Consulting; schering plough Consulting fee Consulting; pfizer Consulting fee Consulting; orfagen Grant/research funds study - clinical

Medical Editor

Maureen B Poh-Fitzpatrick, MD, Professor Emerita of Dermatology and Special Lecturer, Columbia University; Professor of Medicine (Dermatology), University of Tennessee
Maureen B Poh-Fitzpatrick, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and New York Academy of Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio
Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

RELATED EMEDICINE ARTICLES
 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.