Erythropoietic protoporphyria in the U.K.: clinical features and effect on quality of life.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited photodermatosis that causes lifelong painful photosensitivity. Neither its full clinical spectrum nor its impact on quality of life (QoL) has been investigated in a large cohort of patients. OBJECTIVES: To document the clinical features of EPP and its impact on QoL in a high proportion of all patients with EPP resident in the U.K. METHODS: Patients with EPP were identified from U.K. clinical databases and assessed by the same clinical investigator over a 7-month period using a standardized proforma and validated adult (Dermatology Life Quality Index, DLQI) and children's (Children's Dermatology Life Quality Index, CDLQI) QoL questionnaires. RESULTS: Three hundred and eighty-nine living patients with EPP were identified, of whom 223 [114 females, 109 males; median age 34 years (range: 5-87), from 193 families] were investigated. Total erythrocyte porphyrin (TEP) was higher in males (median: 25.3 micromol L1) than females (median: 19.3 micromol L1). The median ages at onset and diagnosis were 1 and 12 years, respectively. Median times for onset of symptoms after sun exposure, onset of signs (oedema, erythema) and resolution of symptoms were 20 min, 6 h and 3 days, respectively. Most patients reported absence of protection by glass (92%), priming (85%), exacerbation by wind (68%), no family history of photosensitivity (56%), no symptoms during winter (56%) and had chronic skin lesions (79%). Symptoms changed little with age but improved during pregnancy in 47% of gravid women. Most patients used protective clothing and a sunscreen; 28% were taking beta-carotene and a further 56% had taken it; 29% were not under regular medical care. Two patients (1%) had liver failure and 8% reported gallstone disease. QoL was markedly impaired, with scores similar to those in severe dermatological disease (mean DLQI score 14.0, n = 176; mean CDLQI score 12.8, n = 44), indicating a large effect on patients' lives. DLQI scores correlated weakly with TEP (rs = 0.228; P = 0.002) and time to onset of symptoms (rs = -0.233; P = 0.002) but not with age at onset. CONCLUSIONS: EPP is a persistent, severely painful, socially disabling disease with a marked impact on QoL. Its diagnosis is often overlooked. None of TEP, age at onset nor time to onset of symptoms is a useful predictor of impaired QoL in individual patients.

Assessment of iron status of Filipino pregnant women.

Plasma ferritin (PF), erythrocyte protoporphyrin (EP) and hemoglobin (Hb) were used to assess the iron status of 158 Filipino pregnant women included as subjects in the third national nutrition survey conducted by the Food and Nutrition Research Institute in 1987. The prevalence of iron depletion was 39.9% based on PF (less than 12 ng/ml). Iron deficient erythropoiesis was present in 36.1% based on EP of greater than 28 micrograms/dl whole blood and 40.5% based on EP/Hb ratio of greater than 2.4. When the criterion of iron deficiency was that both PF and EP were abnormal, the prevalence of deficiency was lower and only 16.4%. Iron deficiency anemia was present in 14.6% based on Hb less than 11 g/dl in addition to abnormal PF and EP. Significantly lower mean values for PF were obtained in women on the 2nd and 3rd trimesters of pregnancy indicating decreasing iron stores and the need for iron therapy to prevent anemia during those periods. The iron status of 38 women who reported taking iron supplements was not significantly different from those who did not take supplements.

Cost effectiveness of lead screening.

Lead-screening programs may reduce childhood disabilities, but at what cost? Through a review of the literature, we performed a cost-effectiveness analysis in which the costs, savings, and health benefits of two lead-screening strategies--employing either a free erythrocyte protoporphyrin assay or blood lead measurement--were compared with each other and with a strategy of no screening in a population of three-year-old children. When the prevalence of lead poisoning among the children screened is 7 per cent or more, we estimate that free erythrocyte protoporphyrin screening averts morbidity and results in net savings: It is both better and cheaper than no screening. At prevalences below 7 per cent, the net positive costs from screening and early treatment must be weighed against the noneconomic benefits of improved quality of life and considered in relation to other investments that could be made to benefit society. At all prevalence rates, free erythrocyte protoporphyrin screening is more cost effective than blood lead screening.

An integrative index of biological effects of lead.

Biological indicators of lead effects on the central nervous system (as measured by performance tests), hematogenous bone marrow (hemoglobin levels) and kidney function (BUN Levels) can be combined in an integrative index (INDEX). This integrative index can be in turn related to indicators of lead exposure and absorption. Such an index was calculated by removing age effects in measures of performance and kidney function and then transforming all the variables to Z (standard) units. Secondary lead smelter workers and a control group were studied. In secondary lead smelter workers this INDEX was found to be significantly correlated with ZPP, blood lead levels, and duration of lead exposure. In this population the magnitude of the correlation coefficients with ZPP levels was much higher than than for blood lead levels. INDEX had a higher correlation with ZPP than with each of its components: performance test scores, hemoglobin, and BUN levels. Although performance test scores, hemoglobin, and BUN levels were shown to discriminate between the control, non-lead-exposed population, and the lead-exposed group, INDEX (and particularly one pair of its components, CNS and hemoglobin levels) achieved the best discrimination between groups. The concept of an integrative index of biological effects of lead may be especially useful in defining populations at high risk for developing chronic, potentially irreversible neurologic and kidney dysfunction, and in assessing the severity of lead effects in individual cases.

Erythrocyte protoporphyrin/heme ratio in the assessment of iron status.

The protoporphyrinemia of iron deficiency is well recognized. Clinically, information on the protoporphyrin/heme molar ratio in whole blood offers certain advantages over protoporphyrin measurement alone. A procedure for determining this ratio is reported. Protoporphyrin is extracted, solubilized, and measured fluorometrically. Heme (as hemin chloride) is precipitated with the blood proteins, the precipitate is dissolved in an alkaline/pyridine solvent, and the resulting bispyridine ferriprotoporphyrin is measured spectrophotometrically. The molar ratio of these two metabolites correlates well with values for plasma ferritin, plasma iron, transferrin saturation, hemoglobin, and hematocrit. In some cases the ratio increases detectably while the other variables, especially hematocrit and hemoglobin, remain normal. Evidently it is a more sensitive index to iron status. For healthy men and women, the mean ratio is 16.0 (SD, 5.3). The mean + 3 SD, or a ratio of 32, is distinctly abnormal, as shown by a confirmatory test. We validated the test by surveying routine blood specimens obtained from several population groups.