AUTHOR AND EDITOR INFORMATION

Section 1 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

INTRODUCTION

Section 2 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

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. Porphyrins accumulate in the liver, are transported in plasma, and are excessively excreted in the urine. Exposure of patients with PCT to sunlight results in increased skin fragility, vesicles, bullae, hypertrichosis, hyperpigmentation, sclerodermoid changes, dystrophic calcification, milia, and scarring in a photodistribution. PCT can be inherited or acquired. Treatment options include phlebotomy and antimalarial medications.

Pseudoporphyria describes a bullous photosensitivity that clinically and histologically mimics PCT. 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. The skin lesions were indistinguishable from those observed in patients with PCT. Since this initial report, many other drugs have been incriminated in mediating this type of bullous photosensitivity. 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.

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. 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 PCT 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. 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.

Sex

Pseudoporphyria affects males and females equally.

Age

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

CLINICAL

Section 3 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

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.
• The patient should be thoroughly questioned regarding any symptoms of connective tissue disorder, which may be the underlying pathology of the photosensitivity. Recent 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 PCT. However, a clinical pearl that may prove helpful in differentiating between pseudoporphyria and PCT is that the classic features of hypertrichosis, hyperpigmentation, and sclerodermoid changes found with PCT 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 PCT, EPP usually begins in childhood with a history of photosensitivity, often described as a burning sensation immediately after sunlight exposure.
  • Clinically, EPP is characterized by erythema, edema, shallow scars, and waxy induration of the skin, particularly on the face.
  • Pseudoporphyria that clinically mimics EPP has been described almost exclusively in children taking naproxen for juvenile rheumatoid arthritis. Naproxen-induced pseudoporphyria seems to have a dimorphic presentation with the PCT-like pattern more often seen in the adult population and the EPP-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 follows (Suarez, 1990):
• • Propionic acid derivatives (NSAIDs) - Naproxen, diflunisal, ketoprofen, nabumetone, oxaprozin, mefenamic acid, rofecoxib
  • Antibiotics - Nalidixic acid, tetracycline, oxytetracycline, ampicillin-sulbactam, cefepime, fluoroquinolones (M Poh, personal communication, June 1999)
  • Antifungals - Voriconazole
  • Diuretics - Furosemide, chlorthalidone, butamide, triamterene/hydrochlorothiazide
  • Antiarrhythmics - Amiodarone
  • Chemotherapy - 5-Fluorouracil
  • Immunosuppressants - Cyclosporine
  • Sulfones - Dapsone
  • Vitamins - Brewers' yeast, pyridoxine
  • Vitamin A derivatives - Etretinate, isotretinoin
  • Muscle relaxants - Carisoprodol, aspirin
  • Nonsteroidal antiandrogens - Flutamide
  • Other - Hemodialysis, excessive UV-A, cola, oral contraceptive pills (levonorgestrel and ethinyl estradiol), narrowband UV-B phototherapy (rarely)
• Vitiligo may be associated with pseudoporphyria. 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.

DIFFERENTIALS

Section 4 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

WORKUP

Section 5 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Lab Studies

• Of critical importance in the diagnosis of pseudoporphyria is the exclusion of true porphyria.
• • The most important test is a serum/plasma porphyrin assay. If this result is negative, the patient does not have a true porphyria.
  • If the serum/plasma porphyrin assay is unavailable, erythrocytes, urine, and stool may be evaluated for abnormal porphyrin levels.
• Other causes of photosensitivity, such as connective tissue disease, must be excluded by obtaining a serum antinuclear antibody titer and more specific studies, such as antibodies to Ro, La, ribonucleoprotein, Smith, and double-stranded DNA.

Procedures

• If the diagnosis of pseudoporphyria is suspected, biopsies for histologic evaluation with hematoxylin and eosin stains and direct immunofluorescence should be performed. Serum samples may also be obtained for indirect immunofluorescence evaluation to aid in the exclusion of bullous pemphigoid.

Histologic Findings

The histologic features of pseudoporphyria are similar to those of PCT with subepidermal bullae and festooning of the dermal papillae. The thickness of the blood vessel wall may prove helpful in differentiating pseudoporphyria from PCT.

In a comparative histologic study from biopsy samples of patients with PCT and pseudoporphyria, Maynard and Peters found thickened blood vessel walls in 11 of 13 patients with PCT. In contrast, similar findings in only 1 of 9 patients with pseudoporphyria were present.

PCT and pseudoporphyria have similar, nonspecific direct immunofluorescence findings of granular deposits of immunoglobulins, mostly IgG, and C3 at the basement membrane zone and in the perivascular region. Although direct immunofluorescence is not a useful tool in distinguishing pseudoporphyria from PCT, it is helpful in the evaluation of other entities in the differential diagnosis of pseudoporphyria, specifically epidermolysis bullosa acquisita. Epidermolysis bullosa acquisita can be ruled out by the lack of intense, linear immunoreactants at the dermal-epidermal junction. Neither PCT nor pseudoporphyria has circulating autoantibodies detected by indirect immunofluorescence study.

TREATMENT

Section 6 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Medical Care

• The primary treatment of pseudoporphyria is to discontinue the offending agent whenever possible.
• Resolution of the clinical findings may take many months, particularly in drug-induced pseudoporphyria.

FOLLOW-UP

Section 7 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Prognosis

• The prognosis is good for pseudoporphyria once the offending agent has been discontinued. However, it may take several months for all the skin lesions to resolve, and some patients are left with permanent scarring.

Patient Education

• Educating patients about the causes of pseudoporphyria is important.
• • Patients should avoid solar and tanning salon radiation.
  • If the condition was drug related, patients should avoid medications in a similar class of drugs (eg, other propionic acid NSAIDs) whenever possible.

REFERENCES

Section 8 of 8

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

• Al-Khenaizan S, Schechter JF, Sasseville D. Pseudoporphyria induced by propionic acid derivatives. J Cutan Med Surg. Jan 1999;3(3):162-6. [Medline].
• Allen R, Rogers M, Humphrey I. Naproxen induced pseudoporphyria in juvenile chronic arthritis. J Rheumatol. Jun 1991;18(6):893-6. [Medline].
• Baer RL. Cutaneous skin changes probably due to pyridoxine abuse. J Am Acad Dermatol. Mar 1984;10(3):527-8. [Medline].
• 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].
• Bilsland D, Douglas WS. Sunbed pseudoporphyria induced by nalidixic acid. Br J Dermatol. Oct 1990;123(4):547. [Medline].
• Birkett DA, Garretts M, Stevenson CJ. Phototoxic bullous eruptions due to nalidixic acid. Br J Dermatol. May 1969;81(5):342-4. [Medline].
• Borroni G, Brazzelli V, Baldini F, et al. Flutamide-induced pseudoporphyria. Br J Dermatol. Apr 1998;138(4):711-2. [Medline].
• 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].
• Burns DA. Naproxen pseudoporphyria in a patient with vitiligo. Clin Exp Dermatol. Jul 1987;12(4):296-7. [Medline].
• Burry JN, Lawrence JR. Phototoxic blisters from high frusemide dosage. Br J Dermatol. May 1976;94(5):495-9. [Medline].
• 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].
• Dolan CK, Hall MA, Blazes DL, Norwood CW. Pseudoporphyria as a result of voriconazole use: a case report. Int J Dermatol. 2004;43:768-71. [Medline].
• Epstein JH, Seibert JS. Porphyria-like cutaneous changes induced by tetracycline hydrochloride photosensitization. Arch Dermatol. May 1976;112(5):661-6. [Medline].
• Gilchrest B, Rowe JW, Mihm MC Jr. Bullous dermatosis of hemodialysis. Ann Intern Med. Oct 1975;83(4):480-3. [Medline].
• Girschick HJ, Hamm H, Ganser G, Huppertz HI. Naproxen-induced pseudoporphyria: appearance of new skin lesions afterdiscontinuation of treatment. Scand J Rheumatol. 1995;24(2):108-11. [Medline].
• 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].
• Hawk JL. Skin changes resembling hepatic cutaneous porphyria induced byoxytetracycline photosensitization. Clin Exp Dermatol. Sep 1980;5(3):321-5. [Medline].
• Hazen PG. Pseudoporphyria in a patient receiving carisoprodol/aspirin therapy. J Am Acad Dermatol. Sep 1994;31(3 Pt 1):500. [Medline].
• Howard AM, Dowling J, Varigos G. Pseudoporphyria due to naproxen. Lancet. Apr 6 1985;1(8432):819-20. [Medline].
• Hrabovsky SL, Elmets CA. Pathogenesis, characteristics, diagnosis and treatment of pseudoporphyria. Curr Opin Dermatol. 1996;3:105-10.
• Ingrish G, Rietschel RL. Oxaprozin-induced pseudoporphyria. Arch Dermatol. Dec 1996;132(12):1519-20. [Medline].
• Judd L. Pseudoporphyria due to cola. Int J Dermatol. Sep 1991;30(9):674-5. [Medline].
• Judd LE, Henderson DW, Hill DC. Naproxen-induced pseudoporphyria. A clinical and ultrastructural study. Arch Dermatol. Apr 1986;122(4):451-4. [Medline].
• 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].
• Krischer J, Scolari F, Kondo-Oestreicher M, et al. Pseudoporphyria induced by nabumetone. J Am Acad Dermatol. Mar 1999;40(3):492-3. [Medline].
• Laidman PJ, Gebauer K, Trotter J. 5-Fluorouracil-induced pseudoporphyria. Aust N Z J Med. Aug 1992;22(4):385. [Medline].
• Lang BA, Finlayson LA. Naproxen-induced pseudoporphyria in patients with juvenile rheumatoidarthritis. J Pediatr. Apr 1994;124(4):639-42. [Medline].
• Leitao EA, Person JR. Bumetanide-induced pseudoporphyria. J Am Acad Dermatol. Jul 1990;23(1):129-30. [Medline].
• Levy ML, Barron KS, Eichenfield A, Honig PJ. Naproxen-induced pseudoporphyria: a distinctive photodermatitis. J Pediatr. Oct 1990;117(4):660-4. [Medline].
• 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].
• Magro CM, Crowson AN. Pseudoporphyria associated with Relafen therapy. J Cutan Pathol. Jan 1999;26(1):42-7. [Medline].
• Markus R, Reddick ME, Rubenstein MC. Rofecoxib-induced pseudoporphyria. J Am Acad Dermatol. 2004;50:647-8. [Medline].
• Maynard B, Peters MS. Histologic and immunofluorescence study of cutaneous porphyrias. J Cutan Pathol. Feb 1992;19(1):40-7. [Medline].
• McDonagh AJ, Harrington CI. Pseudoporphyria complicating etretinate therapy. Clin Exp Dermatol. Nov 1989;14(6):437-8. [Medline].
• Motley RJ. Pseudoporphyria due to dyazide in a patient with vitiligo. BMJ. Jun 2 1990;300(6737):1468. [Medline].
• Murphy GM, Wright J, Nicholls DS, et al. Sunbed-induced pseudoporphyria. Br J Dermatol. Apr 1989;120(4):555-62. [Medline].
• O''Hagan AH, Irvine AD, Allen GE, Walsh M. Pseudoporphyria induced by mefenamic acid. Br J Dermatol. Dec 1998;139(6):1131-2. [Medline].
• 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].
• Parodi A, Guarrera M, Rebora A. Amiodarone-induced pseudoporphyria. Photodermatol. Jun 1988;5(3):146-7. [Medline].
• Phung TL, Pipkin CA, Tahan SR, Chiu DS. Beta-lactam antibiotic-induced pseudoporphyria. J Am Acad Dermatol. 2004;51:S80-2. [Medline].
• Poh-Fitzpatrick MB. Porphyria, pseudoporphyria, pseudopseudoporphyria...?. Arch Dermatol. Apr 1986;122(4):403-4. [Medline].
• Riordan CA, Anstey A, Wojnarowska F. Isotretinoin-associated pseudoporphyria. Clin Exp Dermatol. Jan 1993;18(1):69-71. [Medline].
• Sharp MT, Horn TD. Pseudoporphyria induced by voriconazole. J Am Acad Dermatol. Aug 2005;53(2):341-5. [Medline].
• Silver EA, Silver AH, Silver DS, McCalmont TH. Pseudoporphyria induced by oral contraceptive pills. Arch Dermatol. 2003;139:227-8. [Medline].
• Sola R, Puig LL, Ballarin JA, et al. Pseudoporphyria cutanea tarda associated with cyclosporine therapy. Transplantation. May 1987;43(5):772. [Medline].
• Stenberg A. Pseudoporphyria and sunbeds. Acta Derm Venereol. 1990;70(4):354-6. [Medline].
• Sterling JC, Pye RJ. Naproxen-induced pseudoporphyria. Br J Rheumatol. Jun 1987;26(3):210-1. [Medline].
• Suarez SM, Cohen PR, DeLeo VA. Bullous photosensitivity to naproxen: "pseudoporphyria". Arthritis Rheum. Jun 1990;33(6):903-8. [Medline].
• Taylor BJ, Duffill MB. Pseudoporphyria from nonsteroidal antiinflammatory drugs. N Z Med J. May 27 1987;100(824):322-3. [Medline].
• Waldenström J. Studein uber porphyrie. Acta Med Scand. 1937;82:1.
• 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].
• Wilson CL, Mendelsohn SS. Pseudoporphyria and sunbeds, a coincidence in identical twins?. Br J Dermatol. Aug 1991;125(2):191. [Medline].
• Zelickson AS. Phototoxic reaction with nalidixic acid. JAMA. Nov 9 1964;190:556-7. [Medline].

Article Last Updated: Oct 5, 2006