The cutaneous porphyrias.

The porphyrias are a group of mainly inherited disorders of heme biosynthesis where accumulation of porphyrins and/or porphyrin precursors gives rise to 2 types of clinical presentation: cutaneous photosensitivity and/or acute neurovisceral attacks. The cutaneous porphyrias present with either bullous skin fragility or nonbullous acute photosensitivity. This review discusses the epidemiology, pathogenesis, clinical presentation, laboratory diagnosis, complications, and current approach to porphyria management. Although focusing mainly on their dermatological aspects, the article also covers the management of acute porphyria, which by virtue of its association with variegate porphyria and hereditary coproporphyria, may become the responsibility of the clinical dermatologist.

[Treatment of acute porphyrias. The importance of follow-up of patients and carriers]. / Akut porphyriák kezelése. A betegek és hordozók gondozásának jelentósége.

Acute porphyrias are caused by the inherited decreased activity of the enzymes of the heme biosynthesis pathway. Depending on the affected enzyme there are 4 types of them: acute intermittent porphyria, porphyria variegata, coproporphyria and delta-aminolevulinic acid dehydratase deficient porphyria, listed in order of their frequency. Basically the clinical picture is the same in the four types of acute porphyria. The most frequent complaints and symptoms are: cramping abdominal pain, nausea, vomiting, muscle weakness of the limbs then, in the advanced phase, there is a red-colored urine, hyponatremia, subileus, acute psychosis and Landry-type paralysis. Without proper treatment death is caused by respiratory paralysis or serious arrhythmia. In case of suspicion of acute porphyria it is mandatory to identify the type of the acute porphyria and the actual status of the patient. The later indicates what kind of treatment should be used. In the acute phase the early therapy with heme arginate is the treatment of choice. Since the clinical symptoms are precipitated by endogenous or exogenous inducing factors--most often by drugs-, the drugs negatively affecting the heme biosynthesis should be omitted at once even in the suspicion of acute porphyria. The role of the inducing factors in the manifestation of the clinical symptoms makes possible the prevention. It is possible to avoid the inducing factors and this way to prevent the acute attack if the acute porphyrias are recognized in time and the patients and the carriers are under regular control. The patients receive special identification card and the up-to-date list of safe drugs. They can use only these drugs in any kind of illness. Other drugs should be considered as porphyrinogenic since it is impossible to predict based on their chemical structure if they negatively affect the heme biosynthesis.

The management of porphyria in dental practice.

From time to time a patient may attend your practice with a systemic condition that you may or may not remember from the small print of your undergraduate text books. This paper describes one such systemic condition, porphyria, and its dental management. This paper also describes the use of relative analgesia as an aid to anxiety management in porphyria.

Photodermatoses in the elderly.

Several photodermatoses specifically affect the elderly, and many others continue into old age. Photodermatoses present unique challenges in diagnosis and management when considered in the context of the multiple pathologies and problems of polypharmacy in this age group. This article examines the idiopathic photodermatoses, which include chronic actinic dermatitis, specifically a disease of the middle-aged and elderly. Endogenous (metabolic) and exogenous (drug and chemical) photodermatoses, as well as photo-exacerbated dermatoses, also are discussed.

Prevention of premenstrual exacerbation of hereditary coproporphyria by gonadotropin-releasing hormone analogue.

A 20-year-old Japanese female needed frequent hospitalization due to premenstrual exacerbation of hereditary coproporphyria (HCP). Intranasal buserelin acetate, a gonadotropin-releasing hormone analogue, was given to suppress her menstrual cycles. Her porphyric symptoms subsided dramatically as she became amenorrhoeic. Urinary excretion of porphyrin derivatives fell significantly. She has been free from recurrent attacks, but suffers a minor porphyric attack once in 5 years. However, borderline osteopenia secondary to hypoestrogenism has been noted. Although these analogues are potent in suppressing estrogen-induced porphyric symptoms, due precautions should be taken to avoid bone demineralization in the long-term use.

[Screening program with urinary porphyrins--application to clinical finding in latent porphyrias].

Judging from the incidence of porphyria in Japan, most cases can be diagnosed by measurement of the amount of porphyrin in the urine. Normally, the analysis of porphyrin in urine is performed by high-performance liquid chromatography but this requires about 40 minutes per specimen. However, if one simply measures coproporphyrin I and III only, then one specimen can be measured in about 10 minutes. If screening is performed using this method, those subjects in which high levels of coproporphyrin I and III are detected can undergo further test of urine, blood and feces to detect porphyrin and related materials. Using this screening methods in high school students, 2 cases of congenital porphyria were detected. One case was hereditary coproporphyria and the other was acute intermittent porphyria. If this method is added to screening methods normally used for health checkups, cases of porphyria should be detected with ease.

Experimental latent and acute porphyria in the non-fasted rat; preventive effect of propranolol.

This study demonstrates an experimental model of the biochemical pattern of the 'latent phase' of hepatic porphyria subject to 'acute attack', upon application of prophyrinogenic stimuli. The 'latent phase' was achieved by administering 3,5-diethoxycarbonyl-1, 4-dihydrocollidine [DDC], 70 mg kg-1 day, orally to non-fasted rats. A two- and threefold increase in coproporphyrin in urine and protoporphyrin in faeces, respectively, were observed. An 'acute attack' was induced by phenobarbitone (PB), 100 mg kg-1, administered on the third day of treatment with DDC, followed by administration of 2-allyl-2-isopropylacetamide (AIA), 470 mg kg-1, on the fourth day. A fourfold elevation in urinary porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) and further increase of three- and fourfold in urinary coproporphyrin and faecal protoporphyrin, respectively, was observed. The effect of DDC, AIA and PB on the excretion of PBG and porphyrins was found to be synergistic rather than additive. dl-Propranolol, 700 mg kg-1, given to DDC treated rats 'latent phase' reduced the amount of porphyrins excreted in urine and faeces to those observed in control dimethyl sulphoxide (DMSO) treated rats. It also prevented induction of 'acute attack' caused by the combination of PB and AIA. It is shown that dl-propranolol affects a few parameters in the haem biosynthetic pathway. Its beneficial effect in porphyria is probably the result of increasing the concentration of haem in the free haem pool.

Regulation of cadmium induced porphyria by ascorbic acid in chick embryos.

Sublethal doses of cadmium chloride (2.5, 5.0 and 10.0 mu mole/kg egg weight) were found to significantly alter the first two rate limiting enzymes of heme biosynthesis in chick embryos. Delta-aminolevulinic acid synthase activity was elevated by 2.05 and 2.11 fold with 5.0 and 10.0 mu moles of cadmium treatment respectively. However, this was reduced to 1.25 and 1.3 fold by the simultaneous administration of ascorbic acid. Blood delta-aminolevulinic acid dehydratase (ALA-D) activity was decreased by 48.4 and 55.0 per cent with 5.0 and 10.0 mu moles cadmium treatment respectively; in the presence of ascorbic acid only 18 and 24 per cent inhibition of ALA-D activity was observed. Further 1.39 and 2.08 fold accumulation of delta-aminolevulinic acid and 4.17 and 4.62 fold increase of blood porphyrins was observed in chick embryos treated with 5.0 and 10.0 mu moles cadmium respectively. This elevation of intermediate compounds of heme biosynthesis was effectively checked by the administration of ascorbic acid. Depletion of hepatic heme and free sulfhydryl level by cadmium were countered by the treatment of ascorbic acid. Hence, the present findings suggest the protective role of ascorbic acid against cadmium induced chemical porphyria in chick embryos.

Sunscreen protection against UVB, UVA and blue light: an in vivo and in vitro comparison.

The photoprotection against UVB, UVA and blue light provided by a widely prescribed sunscreen (RoC 15+ A+B) was compared with two new products containing microfine titanium dioxide (Sun E45 lotion SPF 15 and Sun E45 cream SPF 25) [corrected]. Comparisons were made in vivo using photosensitive patients with either chronic actinic dermatitis or erythropoietic protoporphyria, and in vitro using a newly developed spectrophotometric assay. Good agreement was obtained between the in-vivo and in-vitro methods at each waveband. All products showed high protection against UVB radiation, but the products containing microfine titanium dioxide showed significantly higher protection against both UVA and blue light than RoC 15+ A+B. Products containing microfine titanium dioxide are likely to offer superior photoprotection in those patients who are abnormally sensitive to long wavelength ultraviolet radiation than products which are currently available on prescription.

Cimetidine suppresses chemically induced experimental hepatic porphyria.

The ability of cimetidine to reduce the activity of hepatic aminolevulinic acid synthase (ALA-S) was examined in allylisopropyl acetamide (AIA) treated porphyric adult rats. A dose of 20 mg cimetidine/100 gm body weight resulted in a 50% decrease in the AIA-induced hepatic ALA-S activity compared to rats treated with AIA alone. Heme oxygenase activity was decreased 25% compared to rats treated with AIA alone. The effects of AIA and cimetidine on cytochrome P-450 were not additive, suggesting competition for a common site of interaction. The results suggest that cimetidine may prove to be useful in treating porphyria in humans.

A gonadotropin releasing hormone analogue prevents cyclical attacks of porphyria.

Acute intermittent porphyria is a genetic disease in which endogenous hormones affect clinical expression. Premenstrual exacerbations can occur, sometimes often, in women with this disease. Gonadotropin releasing hormone analogues can prevent ovulation by reducing secretion of luteinizing hormone and follicle-stimulating hormone. In six patients with well-documented acute intermittent porphyria and frequent cyclical exacerbations, daily administration of an agonistic gonadotropin releasing hormone analogue, ([ImBzl]-D-His6,Pro9-NET)gonadotropin releasing hormone, intranasally or subcutaneously for as long as 26 months reduced or eliminated premenstrual attacks and caused only minor side effects. Adjustments in dosage or route of administration were sometimes needed. We conclude that endocrine manipulation by treatment with a gonadotropin releasing hormone agonist will prevent neurovisceral attacks of acute intermittent porphyria due to cyclical changes in endogenous hormones and is a safe alternative to exogenous steroids, which may induce attacks of this disease.

LHRH analogue treatment for the prevention of premenstrual attacks of acute porphyria.

We have assessed the value of suppressing ovulation with the luteinizing hormone releasing hormone (LHRH) analogue buserelin in seven patients experiencing crises of acute intermittent porphyria related to the menstrual cycle. Clinical course, plasma oestradiol and progesterone levels, and urinary porphyrin and precursor excretion were monitored over a baseline period of approximately one year, and then for a similar period on buserelin treatment. There was a trend towards clinical improvement on buserelin therapy. The median number of attacks fell from seven during the baseline period to three on treatment (p = 0.06). The response to buserelin varied considerably, with those patients in whom the association between baseline attacks and the menstrual cycle was strongest gaining the most benefit. All patients became amenorrhoeic with suppression of plasma oestradiol and progesterone levels. Urinary delta-aminolaevulinic acid and total porphyrin excretion fluctuated widely both before and during treatment. Our experience indicates that ovulation suppression may be of value in the management of young women in whom recurrent attacks of porphyria are related to the menstrual cycle.

[The screening diagnosis of porphyria cutanea tarda]. / Skriningova diagnostika na porphyria cutanea tarda.

A method is proposed which gives an idea of the type of the absorption spectra of the total porphyrines in the urine without requiring its recording. A single portion of 0,2 ml of urine is mixed with 1,8 ml of IM HCL. The extinctions at 380, 401, 405 and 430 nm are read. The doubled real extinctions (2RE) at 401 and 405 are calculated by the formulae 2RE401--(E380 + E430) and 2E405--(E380 + E430). The extinctions at 380 and 430 outline the "background" of substances which are not porphyrines. When using Spekol 10 the results are multiplied by 1,6 and for Spekol II--they are multiplied by 1,4. 204 patients, 173 of them suffering from porphyria cutanea tarda, were examined by this method and it was established that when the values of 2RE405 exceed 0,060 and are greater than those of 2RE401 uroporphyrine exceeds coproporphyrine and the total porphyrine excretion is above 270 micrograms/l which indicates with great probability an active phase of porphyria cutanea tarda and implies a quantitative determination of the porphyrines.

Porfiria intermitente aguda / Acute intermitted porphyria

La porfiria intermitente aguda es un desorden hereditario caracterizado por la deficiencia del porfobilinógeno deaminasa, enzima necesaria en las biosíntesis del hem. Como resultado una superproducción, acumulación y excreción excesiva de precursores de la porfirina, ác. delta aminolevulínico y porfobilinógeno. Esta enfermedad se caracteriza por exacerbaciones y remisiones. Muchos de los pacientes pasan asintomáticos hasta que uno de los factores precipitantes la activan. Durante el ataque agudo los pacientes experimentan dolores abdominales, naúseas, constipación, dolores musculares y síntomas neurosiquiátricos. El tratamiento se basa en dar una dieta hipercarbohidratada y la administración ev. de hematina. Lo más importante es la prevención de los ataques evitando los factores precipitantes. Esto es importante para el médico clínico, que debe estar en conocimiento de las drogas precipitantes. El paciente debe saber que los ataques agudos de su enfermedad pueden ser evitados. En la casuística presntada predomina el sexo femenino, en una edad que corresponde entre 30 y 40 años. En uno de aparentemente el factor precipitan te fue el embarazo y una sobrecarga hormonal y el último de los casos tenemos como factor precipitantes. Esto es importante para el médico clínico, que debe estaar en conocimiento de las drogas precipitantes. El paciente debe saber que los ataques agudos de su enfermedad pueden ser evitados. En la casuística presentada predomina el sexo femenino, en una edad que ...