Acute intermittent porphyria symptoms during the menstrual cycle.

BACKGROUND: Acute intermittent porphyria (AIP), a life-threatening form of the disease, is accompanied by several pain, mental and physical symptoms. AIMS: In this study, we evaluated the cyclicity of AIP and premenstrual syndrome (PMS) symptoms in 32 women with DNA-diagnosed AIP during their menstrual cycles, in northern Sweden. METHODS: The cyclicity of AIP symptoms and differences in them between the follicular and luteal phases, and the cyclicity of each symptom in each individual woman in different phases of her menstrual cycle were analysed with a prospective daily rating questionnaire. PMS symptoms were also evaluated in the patients on a daily rating scale. RESULTS: Of the 32 women, 30 showed significant cyclicity in at least one AIP or PMS symptom (P < 0.05-0.001). Back pain (10/32) was the most frequent AIP pain symptom and sweet craving (10/15) was the most frequent PMS symptom. Pelvic pain (F = 4.823, P = 0.036), irritability (F = 7.399, P = 0.011), cheerfulness (F = 5.563, P = 0.025), sexual desire (F = 8.298, P = 0.007), friendliness (F = 6.157, P = 0.019), breast tenderness (F = 21.888, P = 0.000) and abdominal swelling (F = 16.982, P = 0.000) showed significant cyclicity. Pelvic pain and abdominal swelling (rs = 0.337, P < 0.001) showed the strongest correlation. The age of women with latent AIP was strongly correlated with abdominal swelling during the luteal phase (rs = 0.493, P < 0.01). CONCLUSION: Our results suggest that the symptoms of AIP patients change during their menstrual cycles.

Screening for hepatocellular carcinoma in acute intermittent porphyria: a 15-year follow-up in northern Sweden.

OBJECTIVES: To evaluate the benefit of screening for hepatocellular carcinoma (HCC) in gene carriers of acute intermittent porphyria (AIP) and estimate the annual incidence of HCC in this group. SUBJECTS: All AIP gene carriers aged ≥55 years from the northernmost county in Sweden, Norrbotten, were invited for screening in this prospective study every 1-1.5 years during the period 1994-2009. We registered all HCC cases amongst AIP gene carriers in the northern region of Sweden (four counties). We compared gene carriers with repeated screening intervals of <2 years (Group A) with controls (Group B; i.e. gene carriers who had never been screened, those screened for the first time or screened at intervals of >2 years, or dropouts). The screening included radiological examination of the liver and relevant laboratory tests. RESULTS: A total of 62 AIP subjects participated in the study, comprising 33% of the total AIP population aged >55 years in the northern region of Sweden. HCC was diagnosed in 22 AIP subjects (12 men and 10 women), mean age 69 (59-82) years. Amongst these subjects, 73% had experienced prior AIP attacks. The incidence rate ratio for HCC was 64 (52 in men and 93 in women). There were no cases of hepatitis B/C or alcohol abuse. Liver cirrhosis was rare. Liver resection could be performed in most subjects in Group A. Fourteen patients died of HCC, one in Group A and 13 in Group B. Compared with those who were not screened regularly, screening was associated with improved 3-year and 5-year survival (P = 0.005 and 0.038). CONCLUSIONS: Screening for HCC in carriers of AIP enables early diagnosis and a choice of potentially curative treatments with improved prognosis. We recommend annual screening using liver imaging for AIP gene carriers >50 years of age.

Patients with ulcerative colitis responding to steroid treatment up-regulate glucocorticoid receptor levels in colorectal mucosa.

BACKGROUND AND AIMS: Glucocorticosteroid treatment (GCS) is effective for attacks of ulcerative colitis (UC). However, 25-30% of patients fails to respond and may be considered steroid resistant. Glucocorticoid receptors (GR) mediate the effects of GCS. Colorectal mucosa levels of GR and NF-κB were analysed before, during and after treatment with GCS-compounds. METHODS: Patients with moderate-severe attacks of ulcerative colitis were included. Patients undergoing colonoscopy with normal finding served as controls. GR and NF-κB levels in colorectal mucosa were analysed by Western Blotting and the DNA-binding activity of NF-κB by EMSA. RESULTS: Twenty-eight patients and seven controls were included. Ten patients were judged clinically steroid resistant. Responders had significantly higher levels of GR in colorectal mucosa after one week of treatment than non-responders (P=0.039) and significantly higher levels of GR were found in responders in remission as compared to before treatment (P=0.013). NF-κB levels did not differ between the groups at first visit. Increasing levels were found only in responders as remission was obtained (P=0.031). EMSA detected 20% lower DNA-binding of NF-κB in responders in remission as compared to first visit (P=0.021). CONCLUSION: GR levels increase in UC-patients responding to GCS-therapy but not in steroid resistant patients and may be the reason for the lack of steroid-efficacy. Increasing NF-κB levels were found in responders attaining remission, possibly reflecting a lower turnover. A decrease in DNA-binding of NF-κB was found in these patients, perhaps because of the increased GR levels counteracting NF-κB activity.

Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones. A population-based study in northern Sweden.

OBJECTIVE: To describe the clinical expression of acute intermittent porphyria (AIP) in women, their use of exogenous sex hormones, and the effects on AIP. DESIGN: A retrospective population-based study. SUBJECTS: All women aged > or =18 years (n = 190) with DNA-diagnosed AIP in northern Sweden. RESULTS: A total of 166 women (87%) participated; 91 (55%) had manifest AIP. Severe attacks were reported by 82%; 39% reported recurrent premenstrual AIP attacks and 22% reported chronic AIP symptoms. Oral hormonal contraceptives had been used by 58% of all these women and by 50 with manifest AIP (57%). Twelve women (24%) associated oral contraceptives as precipitating AIP attacks; in nine cases their first attack. One woman experienced relief from AIP symptoms. On commencing their treatment, 72% of the women with manifest AIP had not yet suffered their first attack. Twenty-two women (25%) aged > or =45 years had used hormonal replacement therapy (HRT) at menopause to remedy climacteric symptoms (the percutaneous route was most frequently used); no AIP attack was precipitated. HRT to remedy vaginal dryness was used by 26 women (28%) aged > or =45 years without triggering an AIP attack. Miscarriages were more frequent in women with manifest AIP (50%) than in the latent group (30%, P = 0.014). CONCLUSIONS: About half of the women with AIP had used oral hormonal contraceptives. As 25% of women with manifest AIP reported attacks associated with such drugs, caution must still be recommended. Menopausal HRT only rarely affected the disorder. Miscarriage was more common amongst women with manifest AIP.

Maternal mortality in Sweden, 1980-1988.

OBJECTIVE: To assess recent maternal mortality in Sweden according to the different definitions of the eighth, ninth, and tenth editions of the International Classification of Diseases (ICD). METHODS: All maternal deaths in Sweden during 1980-1988 were sought in the Medical Birth Registry and in the Registers of Births and Deaths. Hospital records and autopsy reports were requisitioned. RESULTS: According to ICD-9, the maternal mortality ratio in Sweden for 1980-1988 was 7.4 per 100,000 live births. Of the 58 deaths, 36 were direct maternal deaths. Embolism, hemorrhage, preeclampsia, and infection were the predominant causes in the direct cases. Advanced age was the most pronounced risk factor. Suboptimal standard of care was a contributing cause in almost one-third of the direct maternal deaths. Accidental or incidental deaths, including suicide, accidents, and pregnancy-related deaths, added six cases. There were 76 late maternal deaths, occurring 43-365 days postpartum. Malignancy, stroke, and heart disease were the predominant causes. After malignant disease, suicide constituted the leading cause of pregnancy-related deaths within 1 year of delivery. CONCLUSIONS: Regular reviews of maternal mortality are still important in a country with a low rate of maternal deaths. The new classification of maternal deaths allows a better international comparison of mortality risks. Continuous surveillance of maternal deaths and pregnancy-related deaths requires record linkage of birth and death registrations.