Porphyria Cutanea Tarda Associated With Acute Hemorrhagic Pancreatitis.

Porphyria cutanea tarda (PCT) is a condition of dysregulated heme synthesis that leads to accumulation of photosensitizing precursors with resultant fragility and blistering of the skin. It can be hereditary or acquired and has been known to be associated with hepatic C virus, alcohol, HIV, and estrogen. In this article, we report an unusual presentation of PCT associated with acute hemorrhagic pancreatitis in a 57-year-old man. He presented initially to a community hospital with acute onset of epigastric abdominal pain and new-onset ascites. Lipase was elevated. Diagnostic paracentesis was grossly bloody. He was then transferred to our institution for concern for acute hemorrhagic pancreatitis. On arrival, physical examination demonstrated vesicles and bullae with erythematous bases, in different stages of healing seen over the dorsal aspects of both hands with scaling, scarring, and hypopigmentation and hyperpigmentation of the skin. Laboratory evaluation and skin biopsy confirmed the diagnosis of PCT. Search for an underlying etiology failed to reveal typical predisposing factors. This report illustrates that acute hemorrhagic pancreatitis may be an underlying etiology for PCT.

Porphyrias and photosensitivity: pathophysiology for the clinician.

Porphyrias are disorders caused by defects in the biosynthetic pathway of heme. Their manifestations can be divided into three distinct syndromes, each attributable to the accumulation of three distinct classes of molecules. The acute neurovisceral syndrome is caused by the accumulation of the neurotoxic porphyrin precursors, delta aminolevulinic acid, and porphobilinogen; the syndrome of immediate painful photosensitivity is caused by the lipid-soluble protoporphyrin IX and, the syndrome of delayed blistering photosensitivity, caused by the water-soluble porphyrins, uroporphyrin, and coproporphyrin. Porphyrias can manifest with one, or with a combination, of these syndromes, depending on whether one or more types of molecules are being accumulated. Iron plays a significant role in some of these conditions, as evidenced by improvements in both clinical manifestations and laboratory parameters, following iron depletion in porphyria cutanea tarda, or iron administration in some cases of X-linked erythropoietic protoporphyria. While the pathophysiology of a specific type of porphyrias, the protoporphyrias, appears to favor the administration of zinc, results so far have been conflicting, necessitating further studies in order to assess its potential benefit. The pathways involved in each disease, as well as insights into their pathobiological processes are presented, with an emphasis on the development of photosensitivity reactions.

Estudo da imunofluorescência direta, imunomapeamento e microscopia ótica na porfiria cutânea tardia / Study of direct immunofluorescence, immunofluorescence mapping and light microscopy in porphyria cutanea tarda

FUNDAMENTO: Apesar de a porfiria cutânea tardia ser a mais frequente das porfirias, há poucos estudos que abordam sua fisiopatologia cutânea. OBJETIVO: Avaliar as alterações cutâneas na porfiria cutânea tardia utilizando a microscopia ótica e a imunofluorescência direta, antes e depois do tratamento com cloroquina. Realizar o imunomapeamento antigênico da bolha para estudo do seu nível de clivagem. MÉTODOS: Relata-se a microscopia ótica e imunofluorescência direta de 28 pacientes em três fases diferentes: 23 pacientes com porfiria ativa antes do tratamento (Fase A), sete pacientes com remissão clínica durante o tratamento (Fase B) e oito pacientes com remissão bioquímica (Fase C). O imunomapeamento foi realizado em sete pacientes. RESULTADOS: Na porfiria ativa, a imunofluorescência direta demonstrou fluorescência homogênea e intensa no interior e na parede dos vasos e na junção dermoepidérmica. Na remissão clínica (Fase B) e na remissão bioquímica (Fase C), o depósito de imunoglobulinas se manteve, mas o depósito de complemento apresentou diminuição na maioria. O imunomapeamento não demonstrou plano de clivagem fixo. CONCLUSÃO: Não houve correlação entre a resposta clínica e os depósitos de imunoglobulinas. A diminuição do complemento favorece a hipótese de que a ativação da cascata do complemento representa uma via adicional que leva à lesão endotelial.

BACKGROUND: Even though porphyria cutanea tarda is the most frequent type of porphyria, there are few studies about its cutaneous physiopathology. OBJECTIVE: To evaluate skin changes in porphyria cutanea tarda using light microscopy and direct immunofluorescence before and after treatment with chloroquine. To perform antigen immunomapping of bullae to study their level of cleavage. METHODS: Light microscopy and direct immunofluorescence of 28 patients are reported in three different phases: 23 patients with active porphyria before treatment (Phase A), 7 patients with clinical remission during treatment (Phase B), and 8 patients with biochemical remission (Phase C). Immunomapping was performed on 7 patients. RESULTS: In active porphyria, direct immunofluorescence showed homogenous and intense fluorescence on the inside and on the walls of blood vessels as well as in the dermal-epidermal junction. In clinical remission (Phase B) and biochemical remission (Phase C), the deposit of immunoglobulins was maintained, but the deposit of complement was reduced in most cases. Immunomapping revealed no standard cleavage plane. CONCLUSION: No correlation was observed between clinical response and immunoglobulin deposits. The reduction of complement favors the hypothesis that activation of the complement cascade represents an additional pathway that leads to endothelial damage.

Study of direct immunofluorescence, immunofluorescence mapping and light microscopy in porphyria cutanea tarda.

BACKGROUND: Even though porphyria cutanea tarda is the most frequent type of porphyria, there are few studies about its cutaneous physiopathology. OBJECTIVE: To evaluate skin changes in porphyria cutanea tarda using light microscopy and direct immunofluorescence before and after treatment with chloroquine. To perform antigen immunomapping of bullae to study their level of cleavage. METHODS: Light microscopy and direct immunofluorescence of 28 patients are reported in three different phases: 23 patients with active porphyria before treatment (Phase A), 7 patients with clinical remission during treatment (Phase B), and 8 patients with biochemical remission (Phase C). Immunomapping was performed on 7 patients. RESULTS: In active porphyria, direct immunofluorescence showed homogenous and intense fluorescence on the inside and on the walls of blood vessels as well as in the dermal-epidermal junction. In clinical remission (Phase B) and biochemical remission (Phase C), the deposit of immunoglobulins was maintained, but the deposit of complement was reduced in most cases. Immunomapping revealed no standard cleavage plane. CONCLUSION: No correlation was observed between clinical response and immunoglobulin deposits. The reduction of complement favors the hypothesis that activation of the complement cascade represents an additional pathway that leads to endothelial damage.

Severe pruritus after completing pegylated interferon for hepatitis C.

Porphyria cutanea tarda is a disease of disordered accumulation of heme, which is needed for biosynthesis of hepatic cytochromes. It most commonly occurs in a sporadic form among persons infected with hepatitis C virus (HCV); however, HIV infection is also a reported risk factor. Hepatic iron overload appears to play an important role in the pathogenesis of porphyria cutanea tarda. Common cutaneous findings with porphyria cutanea tarda are vesicles or bullae, milia, and hyperpigmentation in sun-exposed areas. We report a case of porphyria cutanea tarda presenting primarily as severe pruritus in an HIV/HCV-coinfected person after completion of therapy for hepatitis C.

Scleroderma-like disorders.

Fibrosing disorders comprise a wide spectrum of heterogeneous diseases characterized by sclerosis of the dermis, subcutis, and sometimes the underlying soft tissues and bone. The hallmark of this group of diseases is skin thickening as in systemic sclerosis with a different distribution pattern and for this reason they have also been referred to as "scleroderma-like" disorders. These diseases may have a different clinical course ranging from a benign disease with a localized cutaneous involvement, to a widespread, systemic, life-threatening disease. Some of them are associated with autoantibodies and/or autoimmune conditions. An accurate recognition of these scleroderma-like diseases is important for the institution of the most appropriate treatment.

[The combination of carbohydrate and porphyrinic exchange disturbances: is it a chance or regularity?].

The subjects of the study were 399 patients with internal diseases and metabolic disturbances. Carbohydrate exchange parameters (fasting level of capillary blood glucose and glucose tolerance test), and porphyrin fractions in urine (uroporphyrin, coproporphyrin), and feces (protoporphyrin, coproporphyrin) were measured. Hepatic type of porphyrinic dysmetabolism was registered in 201 (50.4%) patients. Out of these patients, 38 had disturbances corresponding to the criteria of symptomatic elevation of fecal porphyrin level, 28 had secondary coproporphyrinuria, 40 had latent, and 95 had manifest late cutaneous porphyria. In patients with normal porphyrinic exchange, the frequency of carbohydrate exchange disturbances did not exceed 6%, while in patients with different variants of porphyrinic dysmetabolism it was almost 40%. The results show that patients with hepatic type of porphyrinic dysmetabolism should be considered to have a higher risk of the development of diabetes mellitus and other carbohydrate disorders.

Metabolic diseases and pregnancy.

The skin mirrors the hormonal metabolic and physiologic changes that occur during pregnancy. The metabolic effects are manifested primarily in accentuation of two disorders, porphyria cutanea tarda and acrodermatitis enteropathica. The former may be exacerbated, not only during pregnancy, but also during the post-partum period and with the intake of estrogen-containing birth control pills. Exacerbations of acrodermatitis enteropathica characteristically appear during pregnancy.

The additive effects of hepatitis C infection and end-stage renal disease in porphyria cutanea tarda.

Various factors contribute to the development of porphyria cutanea tarda (PCT). In this case report, we describe a patient with hepatitis C infection and chronic renal failure. The individual mechanisms, which promote cutaneous disease, are discussed. Finally, we propose that each factor may have an additive effect in prolonging the skin lesions of PCT.

Hemochromatosis (HFE) gene mutations and hepatitis C virus infection as risk factors for porphyria cutanea tarda in Hungarian patients.

AIM: It is not clear whether the mutations in hemochromatosis (HFE) gene and hepatitis C virus (HCV) infection act independently in the pathogenesis of porphyria cutanea tarda (PCT). The prevalence of both risk factors varies greatly in different parts of the world. PCT patients from Hungary were evaluated to assess both factors. METHODS: The prevalence of C282Y and H63D mutations in the HFE gene was determined in 50 PCT patients and compared with the reported control frequencies. Furthermore, the presence of HCV infection was determined and related to the patients' HFE gene status. RESULTS: The C282Y mutation was found in 8/50 cases (three homozygotes and five heterozygotes), with an 11% allele frequency (vs. 3.8% control) (P<0.05). Seventeen patients were heterozygous, one was homozygous for the H63D mutation, allele frequency 19%, which did not differ significantly from the reported control prevalence of 12.3%. Twenty-two patients (44%) were HCV-RNA positive; six out of them were heterozygous for H63D mutation, one only for the C282Y mutation and one was compound heterozygous for both mutations. CONCLUSION: HCV infection and HFE C282Y mutation may probably be independent predisposing factors for development of PCT in Hungarian patients.

Long-standing changes in the urinary profile of porphyrin isomers after clinical remission of porphyria cutanea tarda.

Patients with overt porphyria cutanea tarda (PCT) show a distinctive and abnormal urinary profile of porphyrin excretion. It is not known, however, whether clinical remission of the disease produces complete normalization of this profile. We selected 46 patients, previously diagnosed with PCT, who after treatment presented normal levels of total porphyrins in urine (< 35 nmol/mmol creatinine). We analyzed their urine specimens by hplc to identify and quantify the various porphyrins and we compared the urinary porphyrin profiles to those of 40 healthy volunteers. While healthy volunteers gave a pattern dominated by excretion of coproporphyrin III, 80% of the PCT patients in clinical remission showed the characteristic profile of PCT, with decreased coproporphyrin-to-uroporphyrin ratio and/or inversion of the normal coproporphyrin III-to-coproporphyrin I ratio. Detection of uroporphyrin III and heptacarboxyl III intermediates was significantly more common among the patients than the controls (p < 0.05). This study shows that PCT patients demonstrate persistent changes in urinary porphyrin profiles during clinical remission, even when total urinary porphyrin excretion has fallen to the normal range.

Porphyria cutanea tarda with menopausal exacerbation: the possible role of menstruation as natural phlebotomy.

We describe a 48-year-old woman with a 12-year history of porphyria cutanea tarda who showed a remarkable exacerbation of her eruptions accompanied by high serum levels of iron and ferritin at menopause. As iron storage is known to be a triggering factor of porphyria cutanea tarda, the possible role of menstruation as natural phlebotomy to prevent porphyria cutanea tarda exacerbation is discussed.

[Porphyria cutanea tarda and HCV infection]. / Porfiria skórna pózna a zakazenie HCV.

The most common metabolic disorder of hem biosynthesis is porphyria cutanea tarda (PCT). PCT frequently is connected with liver disfunction. We have shown three cases of patients suffering from PCT and HCV infection, treated in Department of Infectious Diseases of Medical University in Wroclaw. There is shown the pathway from the first disorders to the diagnosis and influence of treatment on the course of disease.

[Sporadic porphyria cutanea tarda: a case report in a Moroccan man]. / La porphyrie cutanée tardive, forme sporadique: à propos d'une observation chez un patient marocain.

This report describes a case of sporadic porphyria cutanea tarda involving a 38-year-old Moroccan man. Clinical diagnosis was based on characteristic features, i.e., facial hypertrichosis and bullous lesions lasting four months during the summer of 2000 followed by macular scarring on the dorsal surfaces on the hands. Three well-known precipitating factors were noted, i.e., sun, ethanol and hepatitis C virus infection. Laboratory diagnosis was based on dark red urine and elevated serum and urine uroporphyrin levels. Enhanced uroporphyrin production was due to urodecarboxylase deficiency in the liver. Urodecarboxylase activity in red blood cells and serum ferritin level were normal. The patient is heterozygous for the His63Asp HFE gene mutation associated with hereditary hemochromatosis. The photoprotective effect of melanin in this dark-skinned patient failed to offset uroporphyrin-induced photosensitivity. Avoidance of sun, ethanol and phlebotomy have prevented recurrences.

Porfiria cutánea tarda, con infiltraciones calcáreas / Porphyria cutanea tarda with calcium infiltration

La porfiria cutánea tarda es un desorden del metabolismo del hemo, caracterizado por un aumento de porfirinas y porfinuria, como consecuencia de la disminución en la actividad enzimática uroporfirinógeno decarboxilasa. El signo clínico más importante es la fotosensibilidad cutánea. Este traabajo se realiza a propósito de un caso de porfiria tarda con infiltraciones calcáreas, una revisión de la porfiria cutánea tarda como entidad clínica, considerándose en particular su variante esporádica