Attacks Of Acute Intermittent Porphyria Research Articles

Evaluating the Efficacy of a Small Interfering Ribonucleic Acid Molecule, Givosiran, in Treating Acute Intermittent Porphyria: A Systematic Review.

Acute intermittent porphyria (AIP) is a severe multiorgan dysfunction disorder that can be fatal if not treated promptly. The newest treatment modality involving small interfering RNA (siRNA) molecules, givosiran, is administered for AIP. Although it has very beneficial effects in treating attacks of AIP, it comes with an extensive side effect profile that is not fully understood or studied. Hence, this novel drug model treatment's risk-benefit evaluation is still necessary. For relevant medical literature, we explored medical databases such as PubMed/Medline, PubMed Central, Cochrane Library, Internet Archive Scholar, Google Scholar, and Wiley Online Library. The selected papers were screened based on eligibility criteria and filtered through quality appraisal tools, and 13 finalized research papers were included in the study. Of the 13 identified papers, three were clinical trials, and 10 were review articles. The selected papers all discussed the effectiveness and side effects of givosiran in acute and recurrent attacks of AIP. The research papers showed decreased rates of acute attacks of AIP with givosiran and terminating recurrent attacks. But there are certain non-serious side effects, like fatigue and nausea. Also, there are some severe side effects, like pain. There is limited information on renal and liver function impairment using givosiran and the use of givosiran in patients with kidney and liver disease, for which further studies are required.

Biomarkers that predict attacks of acute intermittent porphyria.

Biomarkers that predict attacks of acute intermittent porphyria.

Prophylactic heme arginate therapy in acute intermittent hepatic porphyria: A case report

Introduction. Among the acute hepatic porphyrias, a small percentage of patients, predominantly female, present with recurrent cyclic attacks of acute intermittent porphyria that occur more than three times a year and sometimes at intervals of less than a month. In women, the attacks are typically related to the menstrual cycle, requiring several days of hospitalization and administration of heme arginate. For these patients, prophylactic heme arginate therapy may be the optimal treatment modality. Case report. We presented a 40-year-old female patient who has been suffering from porphyria for seventeen years. The first attack occurred in 2003, presenting with severe neurological symptoms, requiring the use of heme arginate (Normosang?, Orphan Europe), which resulted in a favorable therapeutic response. In 2004 and 2007, gonadorelin analogue goserelin (Zoladex?) was used, but without beneficial effects on the course of the disease. In 2008, a preventive administration of heme arginate was initiated. The patient received heme arginate in the early phase of symptoms, every month in the premenstrual phase of the cycle, which resulted in milder symptoms, full recovery within 24 hours, lower doses of Normosang? (1-2 ampoules), and fewer hospital days (1-2 days) per month. This regimen has significantly improved the patient's quality of life and reduced the risk of potential ad-verse effects. Conclusion. Preventive use of Normosang? is the optimal therapeutic modality in patients with frequent, recurrent severe attacks that are unresponsive to other therapeutic regimens. As a result, patients have a better quality of life due to an effective, short-term, targeted treatment regimen.

Hyponatremia and Isolated Free T4 Elevation in a Patient With Acute Intermittent Porphyria

Background: Porphyrias represent a spectrum of diseases that stem from dysfunction within the heme biosynthetic pathway. Acute intermittent porphyria (AIP) is the most common type of porphyria due to a genetic deficiency of porphobilinogen deaminase which results in a wide range of neurovisceral symptoms. Hyponatremia and abnormalities with thyroid function have been found in AIP but the mechanisms behind these processes are unclear. Clinical Case: A 26-year-old male with a history of chronic, recurrent abdominal pain presented with 10 days of progressively worsening periumbilical abdominal pain and constipation. He describes that preceding the onset of symptoms he had been binging 5-10 standard alcoholic drinks each day for a few days. Initial laboratory workup demonstrated hyponatremia with Na 114 mmol/L (n: 134 – 137 mmol/L), hypochloremia with Cl 76 mmol/L (n: 95 – 108 mmol/L), and hyperbilirubinemia with total bilirubin 2.5 mg/dL (n: 0.2 – 1.3 mg/dL). CT abdomen/pelvis was negative for any concerning pathology. Further studies showed low serum osmolality at 243 mOsm/kg (n: 275 – 295 mOsm/kg), urine Na 62 mmol/L (n > 20mmol/L), and urine osmolality at 394 mOsm/kg (n: 300 – 900 mOsm/kg) consistent with SIADH. The patient was treated with 3% NaCl and free water restriction to 1.2L/day with improvement in Na levels. Further laboratory workup demonstrated normal TSH, but persistently elevated free T4 with maximum free T4 of 2.77 ng/dL (n: 0.80 – 1.70 ng/dL) which downtrended to 1.99 ng/dL by discharge. Thyroid ultrasound was unremarkable. Pituitary evaluation via hormonal workup and MRI brain was negative for any abnormalities. Given the symptomatology and laboratory findings, the patient was evaluated for porphyria. Laboratory evaluation demonstrated severe elevations in urine porphyrins, urine delta aminolevulinic acid (56.8 mg/24h, n < 4.5 mg/24h), and urine porphobilinogen (82.5 mg/g, n < 2.3 mg/g) consistent with AIP. The patient was treated with four days of hematin infusions which resolved his abdominal pain and was discharged in an improved state. Conclusion: AIP is a rare entity brought out by a deficiency in porphobilinogen deaminase, a key enzyme in the heme biosynthesis pathway. Various metabolic disturbances have been described in AIP including hyponatremia and alterations in thyroid function tests suggestive of thyrotoxicosis. Hyponatremia in our patient was likely due to SIADH from neurovisceral pain. Our patient displayed isolated free T4 elevation as well. We hypothesize this developed due to his acute illness causing a greater decrease in D2 deiodinase activity compared to any concomitant increase in D3 deiodinase activity. This was supported by his free T4 level downtrending following treatment of his AIP attack. More research is needed to further elucidate the mechanism behind these derangements in biochemical markers and their impact on patient prognosis.

Liver Transplantation for Acute Intermittent Porphyria.

Recurrent attacks of acute intermittent porphyria (AIP) result in poor quality of life and significant risks of morbidity and mortality. Liver transplantation (LT) offers a cure, but published data on outcomes after LT are limited. We assessed the pretransplant characteristics, complications, and outcomes for patients with AIP who received a transplant. Data were collected retrospectively from the European Liver Transplant Registry and from questionnaires sent to identified transplant and porphyria centers. We studied 38 patients who received transplants in 12 countries from 2002 to 2019. Median age at LT was 37 years (range, 18‐58), and 34 (89%) of the patients were women. A total of 9 patients died during follow‐up, and 2 patients were retransplanted. The 1‐year and 5‐year overall survival rates were 92% and 82%, which are comparable with other metabolic diseases transplanted during the same period. Advanced pretransplant neurological impairment was associated with increased mortality. The 5‐year survival rate was 94% among 19 patients with moderate or no neuropathy at LT and 83% among 10 patients with severe neuropathy (P = 0.04). Pretransplant renal impairment was common. A total of 19 (51%) patients had a GFR < 60 mL/minute. Although few patients improved their renal function after LT, neurological impairments improved, and no worsening of neurological symptoms was recorded. No patient had AIP attacks after LT, except for a patient who received an auxiliary graft. LT is a curative treatment option for patients with recurrent attacks of AIP. Severe neuropathy and impaired renal function are common and increase the risk for poor outcomes. If other treatment options fail, an evaluation for LT should be performed early.

Attack of Acute Intermittent Porphyria in a 34-Year-Old Female Patient after a Lithotrypsy

A 34-old-female patient had acute intermittent porphyria. Rare diseases should be considered in the differential diagnosis, especially in young adults. It is hard to recognize the illness in a district hospital, where access to the specialist laboratory tests is difficult. Although non-specific symptoms and attributing them to prior surgical intervention delayed diagnosis, the maintained diagnostic, careful observation allowed for proper diagnosis of the disease.

Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome: A case report

Acute intermittent porphyria (AIP) is an inborn error caused due to inherited deficiency of porphobilinogen (PBG) deaminase leading to increased levels of aminolevulinic acid and PBG. AIP is rarely associated with posterior reversible encephalopathy syndrome (PRES). This association is important because drugs used in the management of seizures may worsen an attack of AIP. We report the case of a 10-year-old male child with AIP, who presented with encephalopathy and transient blindness of cerebral origin.

An extremely rare combination of acute intermittent porphyria and Turner syndrome.

A very rare case of acute intermittent porphyria (AIP) co-existing Turner syndrome (TS) is reported for the first time. A 32-year-old woman was diagnosed with AIP due to recurrent acute abdominal pain, red urine and pathogenic mutation of Hydroxymethyl synthetase (HMBS) gene. At the same time, TS was confirmed by Karyotype analysis results of 46,X,i(X)(q10), which accompanied by primary amenorrhea, elevated serum concentrations of follicle-stimulating hormone (FSH). Since the first attack of AIP, the patient has been increasingly depressed, and Psychiatry identified major depression. Duloxetine was chosen after careful deliberation, and the patient's mood stabilized. AIP had not recurred after half a year. Since sex hormones are the exacerbating factor of acute attack of AIP, sex hormone replacement therapy for TS was not administered. In conclusion, the conditions of AIP co-existing TS are complicate, and the treatment still needs to be improved by multiple disciplines in the follow-up.

Real-world annualized healthcare utilization and expenditures among insured US patients with acute intermittent porphyria (AIP) treated with hemin

Background and aims: Patients with acute intermittent porphyria (AIP) may suffer from acute non-specific attacks that often result in hospitalizations or emergency room (ER) visits. Prior to the recent approval of givosiran (November 2019), hemin was the only FDA-approved therapy for AIP attacks in the US. Our aim was to estimate the annual healthcare utilization and expenditures for AIP patients treated with hemin using real-world data.Methods: Patients with ≥1 hemin claim and confirmed AIP diagnosis – 1 inpatient claim or 2 outpatient claims ≥30 d apart for AIP (2015–2017) or acute porphyria (prior to 2015) – were identified in MarketScan administrative claims dataset between 2007 and 2017. Continuous enrolment for ≥6 months from confirmed diagnosis was required. A secondary analysis (“active disease population”) limited the sample to adult patients with ≥3 attacks or 10 months of prophylactic use of hemin within a 12-month pre-index period. AIP-related care was defined by hemin use during an attack (daily glucose and/or hemin use) or prophylaxis (non-attack hemin use). Outcomes were annualized and expenditures were inflated to 2017.Results: Across 10 years, patients with a confirmed AIP diagnosis (N = 8,877) and ≥1 hemin claim (N = 164) were restricted by ≥6 months continuous follow-up (N = 139). AIP patients were mostly female (N = 112; 81%), had median age of 40 and 3 years average follow-up. Annualized average total expenditures for AIP-related care were $113,477. Annualized average all-cause (any diagnosis) hospitalizations were statistically significantly lower for patients treated with hemin prophylaxis vs. acute treatment (1.0 vs. 2.1; p < .001). In the secondary analysis (N = 27), annualized average total expenditures for AIP-related care were higher ($187,480).Conclusions: For AIP patients treated with hemin, patients treated for acute attacks may use a greater number of resources compared to patients treated prophylactically.

Systematically Analyzing the Pathogenic Variations for Acute Intermittent Porphyria.

The rare autosomal dominant disorder acute intermittent porphyria (AIP) is caused by the deficient activity of hydroxymethylbilane synthase (HMBS). The symptoms of AIP are acute neurovisceral attacks which are induced by the dysfunction of heme biosynthesis. To better interpret the underlying mechanism of clinical phenotypes, we collected 117 HMBS gene mutations from reported individuals with AIP and evaluated the mutations’ impacts on the corresponding protein structure and function. We found that several mutations with most severe clinical symptoms are located at dipyromethane cofactor (DPM) binding domain of HMBS. Mutations on these residues likely significantly influence the catalytic reaction. To infer new pathogenic mutations, we evaluated the pathogenicity for all the possible missense mutations of HMBS gene with different bioinformatic prediction algorithms, and identified 34 mutations with serious pathogenicity and low allele frequency. In addition, we found that gene PPARA may also play an important role in the mechanisms of AIP attacks. Our analysis about the distribution frequencies of the 23 variations revealed different distribution patterns among eight ethnic populations, which could help to explain the genetic basis that may contribute to population disparities in AIP prevalence. Our systematic analysis provides a better understanding for this disease and helps for the diagnosis and treatment of AIP.

Molecular genetic study of acute intermittent porphyria in Russia: HMBS gene mutation spectrum and problem of penetrance.

Acute intermittent porphyria (AIP) is the most common and severe form of porphyrias. This is a dominant inherited disorder with low penetrance, caused by mutations in gene coding hydroxymethylbilane synthase (HMBS). We present the results of our long-term genetic study of AIP patients and their relatives (N = 153 and 302, respectively). We detected 88 HMBS gene mutations, 24 of which never described before. To identify additional factors conditioning AIP manifestation, we carried out whole exome sequencing on the group of AIP patients (N = 6). Mutation spectra of different patients virtually did not overlap. In 5 out of 6 patients, we found defects in genes regulating nervous system (UNC13A, ALG8, FBXO38, AGRN, DOK7, SCN4A). As usually acute AIP attacks have various neurological symptoms, we proposed a hypothesis of possible contribution of mutations in such genes in AIP manifestation.

Benefits of prophylactic heme therapy in severe acute intermittent porphyria

Acute intermittent porphyria (AIP), an autosomal dominant inborn error of metabolism, is the most common and severe form of the acute porphyrias. Attacks of severe abdominal pain, often with hypertension, tachycardia, are cardinal features of AIP, often requiring hospital admissions. Frequent recurrent attacks of AIP, defined as >3 attacks in one year, during which at least one attack requires intravenous heme therapy, are associated with significant morbidity, lost productivity, and health care burden. We report two patients with such frequent attacks of AIP, who have been managed with prophylactic heme therapy on a weekly basis. We describe results particularly in relation to symptom control, biochemical findings, health care costs, quality of life, and utilization of resources. During 11-month duration of weekly prophylactic heme infusions, we observed a 100% decrease in acute attacks and inpatient admissions in one subject and a 75% decrease in the other. During this time, we also observed a significant decrease in the number of emergency room visits. The decrease in number of acute attacks requiring hospital admission was associated with significantly decreased health care costs and improved quality of life. Reduction of both emergency room visits and hospital admissions decreased the utilization of health care services. Outpatient weekly infusions were also noted to be associated with better reimbursements and reduced overall costs of health care for the subjects. Both our subjects also endorsed better symptom control, quality of life and better understanding of disease. Thus, prophylactic heme therapy, through a multi-disciplinary approach, decreases the incidence of acute attacks, decreases health care costs and leads to better patient satisfaction and quality of life.

Characterization of the hepatic transcriptome following phenobarbital induction in mice with AIP

Acute Intermittent Porphyria (AIP), an autosomal dominant hepatic disorder, results from hydroxymethylbilane synthase (HMBS) mutations that decrease the encoded enzymatic activity, thereby predisposing patients to life-threatening acute neurovisceral attacks. The ~1% penetrance of AIP suggests that other genetic factors modulate the onset and severity of the acute attacks. Here, we characterized the hepatic transcriptomic response to phenobarbital (PB) administration in AIP mice, which mimics the biochemical attacks of AIP. At baseline, the mRNA profiles of 14,138 hepatic genes prior to treatment were remarkably similar between AIP and the congenic wild-type (WT) mice. After PB treatment (~120 mg/kg x 3d), 1347 and 1120 genes in AIP mice and 422 and 404 genes in WT mice were uniquely up- and down-regulated, respectively, at a False Discovery Rate < 0.05. As expected, the ALAS1 expression increased 4.5-fold and 15.9-fold in the WT and AIP mice, respectively. ALA-dehydrogenase also was induced ~1.7-fold in PB-induced AIP mice, but was unchanged in PB-induced WT mice. There was no statistically significant difference in the overall expression of 155 hepatic cytochrome P450 enzymes, although Cyp2c40, Cyp2c68, Cyp2c69, Mgst3 were upregulated only in PB-induced AIP mice (>1.9-fold) and Cyp21a1 was upregulated only in PB-induced WT mice (>9-fold). Notably, the genes differentially expressed in induced AIP mice were enriched in circadian rhythm, mitochondria biogenesis and electron transport, suggesting these pathways were involved in AIP mice responding to PB treatment. These results advance our understanding of the hepatic metabolic changes in PB-induced AIP mice and have implications in the pathogenesis of AIP acute attacks.

Lifestyle factors including diet and biochemical biomarkers in acute intermittent porphyria: Results from a case-control study in northern Norway

BackgroundLifestyle factors, including a low intake of carbohydrates, dieting, alcohol consumption, cigarette smoking and stress are some of the possible triggers of attacks in acute intermittent porphyria (AIP). The influence of lifestyle factors, including energy intake, diet and alcohol consumption on the biochemical disease activity in AIP and biochemical nutritional markers were examined. MethodsA case-control study with 50 AIP cases and 50 controls matched for age, sex and place of residence was performed. Dietary intake was registered using a food diary in 46 matched pairs. Symptoms, alcohol intake, stress and other triggering factors of the last AIP attack were recorded on questionnaires. Porphyrin precursors, liver and kidney function markers, vitamins, diabetogenic hormones and other nutritional biomarkers were analyzed by routine methods. The Wilcoxon matched-pairs signed rank test was used to compare the cases vs. controls. The Spearman's rank correlation coefficient was used on the cases. ResultsIncreasing total energy intake was negatively correlated with the biochemical disease activity. The intake of carbohydrates was lower than recommended, i.e., 40 and 39% of total energy intake in the AIP cases and controls, respectively. The plasma resistin level was significantly higher (p = .03) in the symptomatic than asymptomatic cases. Plasma insulin was lower in those with high porphobilinogen levels. The intake of sugar and candies were higher in the AIP cases with low U-delta aminolevulinic acid (ALA) levels (p = .04). Attacks were triggered by psychological stress (62%), physical strain (38%), food items (24%) and alcohol (32%) in the 34 symptomatic cases. Alcohol was used regularly by 88% of the cases (3.2 g ethanol/day) and 90% of the controls (6.3 g/day), but the intake was significantly lower in symptomatic than in asymptomatic cases (p = .045). ConclusionA high intake of energy, sugar and candies and a higher insulin level were associated with a lower biochemical disease activity. The resistin level was higher in the symptomatic than the asymptomatic cases. AIP patients drink alcohol regularly, but the intake was significantly lower in the symptomatic cases. Trial registrationClinicalTrials.gov Identifier: NCT01617642.

Patient Perspective on Acute Intermittent Porphyria with Frequent Attacks: A Disease with Intermittent and Chronic Manifestations.

ObjectiveAcute intermittent porphyria is a rare metabolic disorder that affects heme synthesis. Patients with acute intermittent porphyria may experience acute debilitating neurovisceral attacks that require frequent hospitalizations and negatively impact quality of life. Although clinical aspects of acute intermittent porphyria attacks have been documented, the experience of patients is not well known, particularly for those more severely affected patients who experience frequent attacks. The aim of the present study was to qualitatively characterize the experience of patients with acute intermittent porphyria who have frequent attacks, as well as the impact of the disease on daily living.MethodsPatients with acute intermittent porphyria who experience frequent attacks were recruited and took part in 2-h qualitative one-on-one interviews with a semi-structured guide. Interviews were anonymized, transcribed, and coded. The inductive coding approach targeted textual data related to acute intermittent porphyria attack symptoms, chronic symptoms, and the impact of the disease. Saturation analysis was conducted to assess whether the research elicited an adequate account of patients’ experiences.ResultsIn total, 19 patients with acute intermittent porphyria were interviewed (mean age 40 years; 79% female). Eighteen patients (95%) experienced both attack and chronic symptoms. Patients described attacks as the onset of unmanageable symptoms that generally lasted 3–5 days requiring hospitalization and/or treatment. Pain, nausea, and vomiting were considered key attack symptoms; pain, nausea, fatigue, and aspects of neuropathy (e.g., tingling and numbness) were considered key chronic symptoms.ConclusionsIn this study population of acute intermittent porphyria with frequent attacks, most patients had symptoms during and between attacks. In these patients, acute intermittent porphyria appears to have acute exacerbations as well as chronic day-to-day manifestations, and is not just intermittent as its name implies. As a result, patients reported limitations in their ability to function across multiple domains of their lives on a regular basis and not just during acute attacks.Electronic supplementary materialThe online version of this article (10.1007/s40271-018-0319-3) contains supplementary material, which is available to authorized users.

Porfirias agudas: enfoque diagnóstico y terapéutico

The acute porphyrias are rare congenital disorders due to alterations in the enzymes of the haem biosynthesis. These enzymopathies can be autosomal dominant in character, such as, acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and autosomal recessive character (ALA dehydratase deficiency porphyria). Porphyrias have traditionally been classified as hepatic or erythropoietic depending on the primary site of overproduction. The clinical importance of these types of diseases in emergency department and intensive care units lies mainly in the so-called acute porphyria attack, mainly the acute attack of acute intermittent porphyria. Acute intermittent porphyria is characterised by a series of signs and symptoms that are not specific to this disease, with acute abdominal pain still being the main symptom of presentation. We should be aware of the precipitating factors of acute attacks due to their high morbidity and mortality. Making a quick and timely diagnosis is of vital importance, using qualitative and quantitative tests such as PBG (Porphobilinogen) and ALA (aminolevulinic acid). The treatment is mainly based on avoid precipitating factors, immediately starting intravenous therapy with derived haematin products (Normosang®, Orphan Europe SARL, Puteaux, France), and in North America as lyophilised haematin (Panhematin®, Ovation Pharmaceuticals Inc., Deerfield, IL, USA), and the management of complications with different drugs approved for their treatment. The prognosis is good if the condition is diagnosed early and treated aggressively.

Treatment of acute intermittent porphyria during pregnancy and posterior reversible encephalopathy syndrome after delivery: A case report.

Acute intermittent porphyria (AIP) is a rare inherited disorder of heme metabolism. It has the ability to trigger posterior reversible encephalopathy syndrome (PRES), a rare acute neurologic condition that is characterized by acute neurological symptoms. Pregnancy may induce AIP attacks. The present report describes the case of a pregnant woman with AIP. The patient was treated with heme-arginate during pregnancy and successfully delivered a healthy baby. Following delivery, the patient presented with PRES and experienced generalized seizures. Treatment including arginine hemoglobin, calcium gluconate and sodium chloride was administered. The symptoms of epilepsy did not recur. Magnetic resonance imaging of the head demonstrated that the bilateral occipital lobe lesions were significantly reduced in size following the treatment. In the present report, it was demonstrated that administration of heme-arginate for AIP during pregnancy is safe. Timely administration of arginine hemoglobin, calcium gluconate and sodium chloride may more efficiently improve the clinical status in AIP patients diagnosed with PRES who experience generalized seizures.

Reversible Posterior Encephalopathy Syndrome in Patient with Acute Intermittent Porphyrin: A Case Report

Acute Intermittent Porphyria (AIP) is a metabolic disease caused by an inherited deficiency of heme biosynthesis. Acute attacks of AIP during pregnancy are very rare. However, it presents the obstetrician with challenging problems. Prompt diagnosis and early detection of the disease are crucial for the appropriate treatment and favorable prognosis. All pregnant patients who complained of unexplained abdominal pain should be considered the diagnosis of acute porphyria. This paper presents a patient with pregnancy complicated by AIP and Posterior Reversible Encephalopathy Syndrome (PRES), who had a good perinatal outcome.

Difficulties of diagnosing acute intermittent porphyria in clinical practice

Acute intermittent porphyria is an inherited metabolic disease with autosomal dominant inheritance pattern. The pathogenesis of the disease includes disturbed function of vegetative regulation. Attacks of acute intermittent porphyria are rare, sometimes are fatal, but in practice they often remain undiagnosed. Significant difficulties are attributed to unspecific clinical manifistations of acute intermittent porphyria. The patients initially visit surgeons with a clinical presentation of acute abdomen. As a result porphyrinogenic diagnostic and remedial procedures are administered including anesthetics and laparoscopy with anesthesia, which worsen the attack and prognosis. Porphyria being an orphan disease and polymorphism of clinical presentation, absence of medications for its treatment in health care facilities in Russian Federation cause challenges for physicians. The article deals with clinical observation of two patients with a diagnosis of acute intermittent porphyria first made in the neurology department. A 53-year old female was brought in to the neurology department by an ambulance in obtundation after a series of generalized tonoclonic spasms with hyperthermia. A 21-year old female was admitted to the surgical department due to intensive epigastric pain, nausea, repeated episodes of vomiting, an episode of diarrhea and significant general fatigue causing impossibility to move. Presented clinical cases reflect a general situation when for a long period of time the patients were wrongfully admitted to different departments, and cover a problem of late and untimely diagnosis of the disease.

Methotrexate and actinomycin D chemotherapy in a patient with porphyria: a case report

BackgroundDespite their broadly recommended use as chemotherapeutic agents, the porphyrogenicity of methotrexate and actinomycin D have not been confirmed. Accordingly, it is not known whether these agents are safe for use in patients with porphyria.Case presentationIn this report, we present a case of an invasive mole with lung metastasis in a 49-year-old Japanese woman who had previously been diagnosed with acute intermittent porphyria at 27 years of age but had no recent history of acute intermittent porphyria attacks. Her serum human chorionic gonadotropin level was elevated 1 month after hysterectomy, and she was referred to our center for chemotherapy. After she received 100 mg of methotrexate, drug eruptions were observed starting on day 3 and grew progressively worse. Erythema and mucosal erosion spread throughout her body, whereupon she was administered prednisolone. In addition, our patient experienced febrile neutropenia and required granulocyte colony- stimulating factor treatment. No changes in our patient’s urinary coproporphyrin or uroporphyrin levels were detected during this entire episode. Methotrexate was replaced by actinomycin D (0.5 mg/body intravenously on days 1–5 every 2 weeks). After five uneventful cycles of actinomycin D, our patient achieved and maintained a normal serum human chorionic gonadotropin level for 3 years.ConclusionsMethotrexate and actinomycin D did not induce acute porphyric attacks in this patient with acute intermittent porphyria; however, severe adverse effects were noted with methotrexate. Although further investigation is required, our data suggest that these agents are nonporphyrinogenic and can therefore be used to treat patients with comorbid porphyria.