Porphyria cutanea tarda is a rare deficiency of a liver enzyme essential for cellular metabolism. The enzyme deficiency may cause sun exposed skin to blister, ulcerate, turn dark, or bruise. Hair may increase on the forehead, cheeks, or forearms, and the urine may turn pink or brown. It now appears that hepatitis C is the most common trigger of porphyria in people who are predisposed. Topical sunscreens do not prevent the skin lesions. Avoidance of alcohol and removal of iron by repeated phlebotomy (blood removal) or taking medication that binds to iron sometimes helps. Chloroquine (an anti-malaria drug), which removes a toxic by-product of the enzyme deficiency, may help, as well.
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What is your diagnosis?
Diagnosis: Porphyria cutanea tarda
The patient had porphyria cutanea tarda (PCT), a cutaneous disease that results from alteration in the pathway of heme synthesis. Three types of PCT are recognized. Types 1 and 2, which account for the majority of PCT cases, share a deficiency in uroporphyrinogen decarboxylase (UROD), an enzyme present late in the heme synthesis pathway.1 The enzyme deficiency may be acquired (type 1) or inherited (type 2). Clinical penetrance of the genetic variant is low, but evidence suggests that inheritance occurs in an autosomal dominant pattern.
Acquired forms of the disease, which account for more than 80% of cases, are associated with iron overload, such as that seen in hemochromatosis, alcohol abuse, hepatitis C, exogenous estrogen use, and HIV infection.1 Individuals with acquired PCT generally maintain appreciable function of UROD, which is deficient only in hepatocytes. In patients with inherited PCT, both hepatocyes and erythrocytes are affected, and onset of symptoms tends to occur at an earlier age.2
Type 3 PCT-Porphyria cutanea tarda, the rarest form of the disorder, accounts for fewer than 5% of cases.1 It is a poorly understood, familial form of the disease with low hepatic UROD activity, resulting from a yet unknown inherited defect.1
The epidemiology of PCT is complex, with a reported incidence of 1 in 25,000 in the United States but nearly 1 in 5,000 in the Czech Republic.1 Adults are most commonly affected, and though familial forms of the disorder have demonstrated clinical disease as early as infancy, the term "tarda" refers to the well-described, late onset in middle adulthood observed in patients with type 1 PCT.3
Males tend to be affected at higher rates than females.
Skin lesions occur most commonly in sun-exposed areas, such as the dorsum of the hands and the face, likely due to photo-oxidation of porphyrins deposited in the dermis.4 Skin fragility, leading to excessive breakdown, as well as formation of tense, scarring bullae, are the hallmarks of disease. The bullae eventually rupture, leaving behind shallow, atrophic, and pitted scars.4 Sclerodermoid changes are also common in patients with PCT.1,4 Milia may precede or follow development of lesions. Histopathologic examination reveals hypereosinophilia and basement membrane thickening, largely confined to blood vessels in the superficial vascular plexus.5 Immunoglobulin and C5b-9 deposition is marked in PCT.5
A number of other skin disorders can be associated with liver disease. Mixed cryoglobulinemia, another extrahepatic manifestation of hepatitis C, is a systemic vasculitic disease.2 It is most often associated with lower-extremity purpura, arthralgias, and Raynaud syndrome.2 Lichen planus (LP) is an acute or chronic inflammatory disorder of the skin and mucous membranes. On the skin, purple papules are characteristic, while lesions on the mucous membranes appear white.6 Lesions are often found in areas subjected to frequent mechanical stress, such as the wrists, the flexor surfaces of the extremities, and the mouth; the scalp and nails may also be involved.6 LP is also associated with hepatitis.6 Livedoid vasculopathy is a chronic and recurrent cutaneous disease generally confined to the lower extremities. The primary lesion, which is often purpuric in nature, is followed by atrophic, stellate white scars or plaques that are collectively referred to as "atrophie blanche."7 Patients with livedoid vasculopathy often have an underlying hypercoagulable state.7
Sweet's syndrome, known also as acute febrile neutrophilic dermatosis, is characterized by fever, neutrophilia, and tender cutaneous lesions that may present as papules or plaques.8 The disorder is more common in middle-aged women. Sweet's syndrome may be idiopathic or drug-induced and is a possible harbinger of malignancy.8 The lesions of Sweet's syndrome occur most often on the upper extremities.8
Treatment of PCT revolves around discontinuing the offending agent—often alcohol or estrogens—and reducing the degree of siderosis.1 Nearly complete reversal of damage has been reported with abstinence from alcohol. In most patients, plasmapheresis remains the treatment of choice, as well as limiting sun exposure.1 Low-dose chloroquine may be considered for patients in whom plasmapheresis is contraindicated (e.g., those with anemia).1 However, chloroquine has been known to precipitate PCT, and therefore such treatment must be undertaken with absolute caution. It is imperative that practicing clinicians recognize the presence of cutaneous porphyrias, as they are potentially devastating diseases that may be routinely managed. Recognizing the association of PCT with alcohol use and hepatitis is equally important. In fact, all patients presenting with a clinical picture of PCT should be screened for hepatitis C virus, as the incidence of co-infection with the virus has been noted in some regions to approach 90%.3
By the time he presented, our patient had experienced drastic improvement, which we attributed to his cessation of alcohol use, and he was managed with supportive care alone. He did well on discharge but ultimately was lost to further follow-up.
Dr. McGevna is completing her internship at the University of Vermont in Burlington, where she will go on to complete a dermatology residency. Dr. Nelson is a hospitalist at Central Vermont Hospital in Berlin, Vermont, and medical director at a Berlin area nursing home.
References
1. Lambrecht RW, Thapar M, Bonkovsky HL. Genetic aspects of porphyria cutanea tarda. Semin Liver Dis. 2007;27:99-108.
2. Palekar NA, Harrison SA. Extrahepatic manifestations of hepatitis C. South Med J. 2005;98:1019-1023.
3. Sarkany RP. The management of porphyria cutanea tarda. Clin Exp Dermatol. 2001;26:225-232.
4. Lim HW. Pathogenesis of photosensitivity in the cutaneous porphyrias. J Invest Dermatol. 2005;124:xvi-xvii.
5. Vasil KE, Magro CM. Cutaneous vascular deposition of C5b-9 and its role as a diagnostic adjunct in the setting of diabetes mellitus and porphyria cutanea tarda. J Am Acad Dermatol. 2007;56:96-104.
6. Katta R. Lichen planus. Am Fam Physician. 2000;61:3319-3324.
7. Hairston BR, Davis MD, Pittelkow MR, Ahmed I. Livedoid vasculopathy: further evidence for procoagulant pathogenesis. Arch Dermatol. 2006;142:1413-1418.
8. Cohen PR. Sweet's syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34.
All electronic documents accessed May 20, 2010.
http://www.cortlandtforum.com/atrophic-rash-in-a-patient-with-hepatitis-c/article/171640/2/
ALSO SEE Skin Rash During Chronic Hepatitis C Therapy
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Porphyria Cutanea Tarda, Hepatitis C, Uroporphyrinogen Decarboxylase and Mutations of HFE GeneA Case-Control Study
Bernard Cribiera, Christine Chiaverinif, Nassim Dali-Youcefb, Michèle Schmittd, Michèle Grimac, Christine Hirthb, Jean-Philippe Lacourf, Olivier ChosidoweaClinique Dermatologique,bLaboratoire de Biochimie Générale et Spécialisée,cUnité de coordination de la biologie des essais cliniques, Université Louis Pasteur, Faculté de Médecine, Hôpitaux Universitaires de Strasbourg, anddLaboratoire de Diagnostic Génétique, Strasbourg,eUniversité Paris 6 Pierre-et-Marie-Curie et AP-HP, Service de Dermatologie et d’Allergologie, Hôpital Tenon, Paris, andfFaculté de Médicine, Service de Dermatologie, Nice, France
Address of Corresponding Author
Dermatology 2009;218:15-21 (DOI: 10.1159/000173696
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Background:
Hemochromatosis gene (HFE) mutations and the hepatitis C virus (HCV) are known risk factors for porphyria cutanea tarda (PCT), but interactions with erythrocytic uroporphyrinogen decarboxylase (UROD) have seldom been addressed.
Objective:
In order toexamine the links between these factors, we conducted a multicentre prospective case-control study. Methods: PCT patients with (n = 32) or without HCV (n = 28) were matched to HCV+ (n = 32) and HCV– controls (n = 28). HFE mutations (C282Y and H63D) were analyzed by PCR. Results: PCT+/HCV+ patients were younger than PCT+/HCV– patients (46.9 vs. 58.2 years, p <>
Both C282Y and H63D were more frequent in PCT+ patients than in controls, but there was no difference in HFE genotype according to HCV seropositivity. Mean UROD was lower in case of HFE mutations in both PCT patients and controls.
Conclusion:
In French patients, HCV infection is probably the major causal factor of PCT. It is not linked with HFE mutations, although they are significantly associated with PCT. A low erythrocytic UROD might be a predisposing factor. The UROD value was lower in patients with HFE mutations, suggesting a possible interaction between HFE genotype and UROD levels
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