Porphyria medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Medical Therapy
Acute porphyria
- Carbohydrates and heme
Often, empirical treatment is required if the diagnostic suspicion of a porphyria is high since acute attacks can be fatal. A high-carbohydrate diet is typically recommended; in severe attacks, a glucose 10% infusion is commenced, which may aid in recovery.
Hematin and heme arginate are the drugs of choice in acute porphyria, in the United States and the United Kingdom, respectively. These drugs need to be given very early in an attack to be effective; effectiveness varies amongst individuals. They are not curative drugs but can shorten attacks and reduce the intensity of an attack. Side effects are rare but can be serious. These heme-like substances theoretically inhibit ALA synthase and hence the accumulation of toxic precursors. In the United Kingdom, supplies of this drug are maintained at two national centers. In the United States, one company manufactures Panhematin for infusion. The American Porphyria Foundation has information regarding the quick procurement of the drug.
Any sign of low blood sodium (hyponatremia) or weakness should be treated with the addition of hematin or heme arginate as these are signs of impending syndrome of inappropriate antidiuretic hormone (SIADH) or peripheral nervous system involvement that may be localized or severe progressing to bulbar paresis and respiratory paralysis.
- Precipitating factors
If drugs or hormones have caused the attack, discontinuing the offending substances is essential. Infection is one of the top causes of attacks and requires vigorous treatment.
- Symptom control
Pain is extremely severe, frequently out of proportion to physical signs and almost always requires the use of opiates to reduce it to tolerable levels. Pain should be treated early as medically possible due to its severity. Nausea can be severe; it may respond to phenothiazine drugs but is sometimes intractable. Hot water baths/showers may lessen nausea temporarily, though caution should be used to avoid burns or falls.
- Early identification
Patients with a history of acute porphyria and even genetic carriers are recommended to wear an alert bracelet or other identification at all times in case they develop severe symptoms or in case of accidents where there is a potential for drug exposure: a result of which may be they cannot explain to healthcare professionals about their condition and the fact that some drugs are absolutely contraindicated.
- Neurologic and psychiatric issues
Patients who experience frequent attacks can develop chronic neuropathic pain in extremities as well as chronic pain in the gut. Gut dysmotility, ileus, intussusception, hypoganglionosis, encopresis in children and intestinal pseudo-obstruction have been associated with porphyrias. This is thought to be due to axonal nerve deterioration in affected areas of the nervous system and vagal nerve dysfunction.
In these cases treatment with long-acting opioids may be indicated. Some cases of chronic pain can be difficult to manage and may require treatment using multiple modalities. Opioid dependence may develop.
Depression often accompanies the disease and is best dealt with by treating the offending symptoms and if needed the judicious use of anti-depressants. Some psychotropic drugs are porphyrinogenic, limiting the pharmacotherapeutic scope.
- Seizures
Seizure often accompany this disease. Most seizure medications exacerbate this condition. Treatment can be problematic: barbiturates especially must be avoided. Some benzodiazepines are safe, and, when used in conjunction with newer anti-seizure medications such as gabapentin offer a possible regime for seizure control.
Magnesium sulfate and bromides have also been used in porphyria seizures, however, development of status epilepticus in porphyria may not respond to magnesium alone. The addition of hematin or heme arginate has been used during status epilepticus.
- Underlying liver disease
Some liver diseases may cause porphyria even in the absence of genetic predisposition. These include hemochromatosis and hepatitis C. Treatment of iron overload may be required.
- Hormone treatment
Hormonal fluctuations that contribute to cyclical attacks in women have been treated with oral contraceptives and luteinizing hormones to shut down menstrual cycles. However, oral contraceptives have also triggered photosensitivity and withdrawal of oral contraceptives has triggered attacks. Androgens and fertility hormones have also triggered attacks.
Contraindicated Medications
Porphyria is considered an absolute contraindication to the use of the following medications:
Erythropoietic porphyrias
These are associated with accumulation of porphyrins in erthrocytes and are rare. The rarest is Congenital erythropoetic porphyria (C.E.P) otherwise known as Gunther's disease. Its rarity is partially due to its autosomal recessive mode of inheritance. The signs may present from birth and include severe photosensitivity, brown teeth that fluoresce in ultraviolet light due to deposition of type one porphyrins and later hypertrichosis. Haemolytic anaemia usually develops. Pharmaceutical-grade beta carotene may be used in its treatment.[1]
The pain, burning, swelling and itching that occur in erythropoietic porphyrias generally require avoidance of bright sunlight. Most kinds of sunscreen are not effective, but SPF-rated long-sleeve shirts, hats, bandanas and gloves can help. Chloroquine may be used to increase porphyrin secretion in some EPs. Blood transfusion is occasionally used to suppress innate heme production.
References
- ↑ Martin A Crook.2006. Clinical chemistry and Metabolic Medicine. seventh edition. Hodder Arnold. ISBN 0-340-90616-2