Case Of Porphyria Research Articles

Familial Case of Porphyria with an Epileptic Seizure in the Moscow Region

Objective a clinical case of a 37-year-old patient with familial acute porphyria is presented (the patient's sister died at the age of 28 during an attack of acute porphyria). Material and methods: we used a qualitative urine test for porphyria with Erdich reagent and quantitative determination of porphyrins (porphobilinogen and delta-aminolevulenic acid on a spectrophotometer “Hitachi 3900”. Results.The attack began with pain in the abdomen and lower back, tachycardia, arterial hypertension during menstruation. After taking ketorol and surgical intervention, tonic-clonic convulsions developed with involuntary release of pink urine. CT of the brain shows signs of ischemic cerebrovascular accident in the parietal region of the right hemisphere. There was a decrease in the level of hemoglobin in the blood and APTT. A urine test for porphyria was positive. Porphobilinogen and delta-aminolevulinic acid in the blood are elevated. After the appointment of glucose at a dose of 300 g of dry matter per day in an oral solution, the condition improved. Conclusion. The presented case demonstrates the difficulties in diagnosing and managing patients with acute porphyria, despite the awareness of the attending physicians about this disease. The patient developed an epileptic seizure and brain damage according to CT, which could be posterior reversible encephalopathy. To improve the efficiency of diagnosis and treatment of porphyria in all laboratories, a simple and cheap qualitative urine test for porphyria with Ehrlich's reagent should be organized and Hitachi 3900 spectrophotometers should be purchased at regional medical centers. Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.

Development and validation of diagnostic algorithms for the laboratory diagnosis of porphyrias.

Porphyrias are rare metabolic disorders of the haem synthesis. They can present with acute neurovisceral attacks, cutaneous symptoms, or a combination of both. As they present with a wide variety of clinical symptoms, diagnosis is often delayed and correct interpretation of porphyria-related tests remains a challenge for many physicians. We developed and validated two algorithms for the laboratory diagnosis of porphyrias based on presenting symptoms. Based on a literature search and clinical/laboratory expertise, we developed algorithms for acute and cutaneous porphyrias. We validated these algorithms using all porphyria related laboratory test requests between January 1st 2000 and September 30th 2020 in UZ Leuven. In addition, we also evaluated our algorithm using samples from the European porphyria network (EPNET) external quality assessment scheme (2010-2021). Sensitivity of the algorithm for acute porphyria was 100.0% [74.9%-100.0%] (13 acute intermittent porphyria (AIP) and 1 variegate porphyria [VP]) with a specificity of 98.5% [91.0%-100.0%] (65 patients). Sensitivity of the algorithm for cutaneous porphyria was 100% [95.1%-100.0%] (7 VP, 59 porphyria cutanea tarda (PCT), 23 erythropoietic protoporphyria (EPP), 2 X-linked erythropoietic protoporphyria [XLEPP]) with a specificity of 93.9% [82.9%-98.5%]. There were no diagnostic samples of other types of porphyria. The algorithms correctly identified 18 of the 19 EPNET porphyria cases. One of the two hereditary coproporphyria cases was missed. The algorithms for acute and cutaneous porphyria showed high sensitivity and specificity and can be used to aid the clinician in correctly interpreting the laboratory findings of porphyria-related tests.

A case of porphyria with hemolytic anemia

A case of porphyria with hemolytic anemia

Healthcare Utilization and Cost Burden of Porphyria in Commercially Insured Adults in the United States.

ObjectivesThe healthcare burden associated with porphyria remains unevaluated despite the associated increased risks of morbidity and mortality. We aimed to assess the healthcare utilization and cost burdens of porphyria in the United States (US) using real-world claims data.MethodsWe performed a case–control analysis of adults in the Truven Health MarketScan® Commercial Claims database (2010–2015). Using propensity scores, 2788 porphyria cases were matched 1:1 to porphyria-free controls with chronic liver disease. Total and service-specific parameters were quantified for the 12 months before porphyria diagnosis versus the 12 months after diagnosis and over the 12 months following a randomly selected date for controls. Wilcoxon signed rank tests and McNemar tests were used to examine incremental differences in burden between cases and controls. Adjusted multivariable generalized linear regression models were used to compare healthcare burdens for cases versus controls.ResultsRelative to the 12 months before porphyria diagnosis, the following 12 months had more claims per patient (35.94 vs 39.67; p < 0.0001) and increased per-patient healthcare costs (US$21,308 vs US$27,270; p < 0.0001). Porphyria cases incurred US$7839 more in total unadjusted costs compared with controls in the 12 months after index date. Compared with controls, cases also had more claims (39.67 vs 34.81), primarily due to inpatient admissions (1.80 vs 0.78) and outpatient visits (21.41 vs 17.98). Cases also had higher healthcare costs for inpatient admissions (US$8882 vs US$4674) and outpatient visits (US$12,378 vs US$9801).ConclusionPorphyria is associated with significant healthcare costs and utilization burdens driven by increased inpatient admissions, outpatient visits, and pharmaceutical claims.Electronic supplementary materialThe online version of this article (10.1007/s41669-020-00229-4) contains supplementary material, which is available to authorized users.

Feasibility of cellular bioenergetics as a biomarker in porphyria patients

Porphyria is a group of metabolic disorders due to altered enzyme activities within the heme biosynthetic pathway. It is a systemic disease with multiple potential contributions to mitochondrial dysfunction and oxidative stress. Recently, it has become possible to measure mitochondrial function from cells isolated from peripheral blood (cellular bioenergetics) using the XF96 analyzer (Seahorse Bioscience). Mitochondrial respiration in these cells is measured with the addition of activators and inhibitors of respiration. The output is measured as the O2 consumption rate (OCR) at basal conditions, ATP linked, proton leak, maximal, reserve capacity, non-mitochondrial, and oxidative burst. We performed cellular bioenergetics on 22 porphyria (12 porphyria cutanea tarda (PCT), seven acute hepatic porphyria (AHP), and three erythropoietic protoporphyria (EPP)) patients and 18 age and gender matched healthy controls. Of porphyria cases, eight were active (2 PCT, 1 EPP, and 5 AHP) and 14 in biochemical remission. The OCR were decreased in patients compared to healthy controls. The bioenergetic profile was significantly lower when measuring proton leak and the non-mitochondrial associated OCR in the eight active porphyria patients when compared to 18 healthy controls. In conclusion, we demonstrate that the bioenergetic profile and mitochondrial activities assessed in porphyria patients and is different than in healthy control individuals. Further, our novel preliminary findings suggest the existence of a mitochondrial dysfunction in porphyria and this may be used as potential non-invasive biomarker for disease activity. This needs to be assessed with a systematic examination in a larger patient cohort. Studies are also suggested to examine mitochondrial metabolism as basis to understand mechanisms of these findings and deriving mitochondrial based therapies for porphyria.

Ultraviolet Absorption Spectral Scan and Fluorescence Emission Spectral Scan Analysis: Potential Tests with Diagnostic Utility in Porphyria

ABSTRACT Introduction Symptoms of porphyria usually overlap with other clinical conditions, thereby leading to misdiagnosis and inappropriate treatment, especially when patient presents with uncommon features. An accurate diagnosis of porphyria can be made only when enzyme defects can be detected, which is costly and not easily available. Classically, Ehrlich's test used to screen porphyria has certain disadvantages too. Hence, we planned this study. Aim To develop comparatively simpler diagnostic tests feasible at tertiary care centers to work up porphyria cases. Materials and methods A suspected case of porphyria was screened using Ehrlich's test. Thereafter, patient's urine and serum samples were analyzed by ultraviolet (UV) absorption spectral scan and fluorescence emission spectral scan using multimode microplate reader and compared against normal controls to validate the results. Results The UV absorption spectral scan revealed a small peak at 410 nm for patient's urine sample, which intensified on acidification. The UV absorption spectral scan for patient's serum also showed absorbance peak at 405 nm vs normal serum. The fluorescence emission spectral scan of urine and serum of patient revealed a sharp emission peak at 626 nm, which was not present in respective samples of control. Fluorescence emission in patient's urine sample was 10.5 times more vs normal urine. Conclusion and clinical significance Novel methods like UV absorption spectral scan and fluorescence emission spectral scan using patient's urine and serum samples can be developed as diagnostic tests considering their practicality and affordability. Further, an algorithm formulated based on clinical features and basic lab tests can also identify the type of porphyria. How to cite this article Nimesh A, Agarwal V, Garg S, Mehndiratta M. Ultraviolet Absorption Spectral Scan and Fluorescence Emission Spectral Scan Analysis: Potential Tests with Diagnostic Utility in Porphyria. Indian J Med Biochem 2017;21(2):136-141.

Intermittently We Get Things Right: A Case of Porphyria After Esophagogastrectomy

Acute porphyrias are rare inherited metabolic disorders of heme production, intermittently presenting with abdominal pain and neurovisceral symptoms. We discuss the case of a 58-year-old African American female with a history of gastroparesis and esophageal adenocarcinoma, who presented with intractable abdominal pain, nausea and vomiting. Her symptoms were initially attributed to her previously established gastrointestinal diagnoses; however, an in-depth workup for gastric, hepatic, biliary and vascular causes was negative. Ultimately, a urine porphyria panel revealed elevated porphyrins and the patient was treated with a high carbohydrate diet and hemin infusion, with subsequent normalization of her urine porphyrins and improvement of her symptoms. Acute Porphyrias are exceedingly rare. However, the occurrence of acute porphyria after gastric surgery has been previously reported and attributed to diminished carbohydrate intake. Similarly, this patient's esophagogastrectomy reduced her caloric carbohydrate intake, perhaps resulting in the accumulation of heme precursors and the onset of a clinical crisis. The patient's dramatic normalization of urine porphyrins following hemin treatment underscores the validity of her diagnosis. Thus, we propose that acute porphyria should be considered in patients with recurrent abdominal pain, nausea and vomiting and a negative work-up for another intra-abdominal pathology. Porphyrias should also be considered in patients with persistent pain after abdominal surgery and those with reduced caloric intake. Early diagnosis of porphyria is key to effective treatment with hemin. Simple spot urine tests for urine porphinobilinogen, although not performed in this case due to low suspicion, can easily rule out the diagnosis, and should be the first step in the workup of such patients.Table 1: Urine porphyria panel results prior to hemin treatment and after hemin treatment. All values were initially elevated and were within normal levels after treatment. Urine ALA remained elevated 10 days after admission.

Acute intermittent porphyria.

Acute intermittent porphyria.

‘Struensée’s memoir on the situation of the King’ (1772): Christian VII of Denmark

Christian VII of Denmark (1749-1808) was insane throughout his long reign. The royal physician, Johann Friedrich Struensée (1737-72), usurped his power. In 1771 the King appointed him Privy Cabinet Minister. Struensée revolutionized the whole administration of the Danish-Norwegian kingdom and had an adulterous relationship with the Queen, Caroline Mathilda, George III's sister. In January 1772 he was arrested, sentenced to death for lese-majesty and executed. During his confinement, he wrote a memoir on the King's condition, which he considered to be caused by, or the effect of, masturbation. In 1906 Christiansen interpreted it as a case of dementia praecox, i.e. schizophrenia. It is now suggested that Christian's insanity, like that of George III (his cousin), might have been due to porphyria - the 'royal malady', possibly inherited through his mother, Princess Louise of England or his father, King Frederik V, who died from an illness which retrospectively resembles a case of porphyria.

Clinical Manifestations and Diagnostic Challenges in Acute Porphyrias

The porphyrias are a group of disorders characterized by an enzyme deficiency in the heme biosynthetic pathway. These can be classified into either erythropoietic or hepatic forms depending on the site of the major enzyme deficiency. The diagnosis of acute porphyrias, however, can be very challenging due to overlapping features amongst the various types. Initial suspicion is based on a myriad of clinical manifestations, which then are confirmed by laboratory testing where available. Genetic testing is now also available for the different types of porphyrias, aiding in the definitive diagnosis. Here, we present a challenging case of porphyria in a patient with end-stage renal disease and present the diagnostic challenges associated with the case and the ways forward.

Porphyrins profile by high performance liquid chromatography/electrospray ionization tandem mass spectrometry for the diagnosis of porphyria

Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway. Most porphyria symptoms are nonspecific and occur intermittently; resulting frequently in missed diagnosis since the disease itself is a rare one. The aim of the study is to establish a new reliable and accurate laboratory method for separation, identification and quantitation of urinary porphyrins by liquid chromatography tandem mass spectrometry (LC/MS/MS) and thereby the diagnosis of different porphyria types for the first time in Egypt. Screening by plasma fluorescence and quantitative determination of urinary porphyrins by high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC/ESI/MS/MS) of 50 clinically suspected patients revealed one case of variegate porphyria and five cases of porphyria cutanea tarda. Plasma fluorescence scanning is a simple procedure that can be used as screening test to detect porphyria patients that require quantitation of urinary porphyrins as a second step. Quantitative determination of urinary porphyrins using HPLC/ESI/MS/MS and ion mapping techniques are applicable for the differential diagnosis of porphyria types, since each type has a characteristic porphyrins excretion profile. Quantitative determination of urinary porphyrins by HPLC/ESI/MS/MS used in this study is a modification for the method Stoev et al. while ion mapping technique is a new technique invented by the research team at the Biochemical Genetics Department.

Porphyria in Switzerland, 15 years experience.

The porphyrias, a group of seven metabolic disorders in the haem biosynthesis, can be classified into acute and non-acute porphyrias. A common symptom of acute porphyrias is severe acute abdominal pain, whereas cutaneous photosensitivity can occur in both acute and non-acute porphyrias. All porphyrias, except for sporadic porphyria cutanea tarda (sPCT), are hereditary disorders caused by mutations in the respective genes. We present porphyria cases documented in our porphyria centre during the past 15 years. Diagnosis was based on clinical symptoms and biochemical analyses. Mutation analysis was performed in patients/families with a confirmed hereditary porphyria. As the porphyria specialist centre of Switzerland, we perform the specialized analyses required for the diagnosis of all types of porphyrias, and give advice to patients, physicians and other laboratories. We therefore estimated that our data cover 80-90% of all diagnosed Swiss cases. A total of 217 patients from 170 families were diagnosed including, 111 acute intermittent porphyria, 45 erythropoietic protoporphyria, 30 variegate porphyria, 21 sPCT, five congenital erythropoietic porphyria, four hereditary coproporphyria and one hepatoerythropoietic porphyria patient. Systematic monitoring of the patients would allow early detection of the potential life-threatening complications such as hepatocellular carcinoma and renal insufficiency in acute porphyrias, and liver failure in EPP. Seventy-five percent of all families underwent genetic testing. Identification of pre-symptomatic mutation carriers so that these individuals and their physicians can be consulted with safety on drug use and other preventive measures, is important in managing acute porphyrias. The unique phenomenon of founder mutations in the Swiss population is also discussed.

The use of C3d and C4d immunohistochemistry on formalin-fixed tissue as a diagnostic adjunct in the assessment of inflammatory skin disease

Direct immunofluorescent (DIF) testing defines an important diagnostic adjunct in the classification of various inflammatory skin conditions; it requires fresh tissue, a laboratory equipped to perform the procedure, and a pathologist skilled in its interpretation. Although advances have been made in the development of antibodies that can be applied to paraffin-embedded tissue, there has been no reported success on the application of paraffin tissue-based immunohistochemistry as a potential substitute for DIF testing on skin biopsy material. We applied C3d and C4d immunohistochemistry on paraffin-embedded, formalin-fixed tissue to define a potential application of these two antibodies as a diagnostic adjunct in the evaluation of various inflammatory skin diseases. A natural language search identified cases submitted for both light microscopic and DIF studies from July 2006 to August 2007. We prospectively included similar cases encountered from August 2007 to March 2008. We correlated the C3d and C4d staining pattern with the DIF and light microscopic findings. All cases of scarring discoid lupus erythematosus (LE) (20/20) and systemic LE (5/5) showed prominent granular C3d along the dermoepidermal junction (DEJ) and a positive lupus band test result in the latter by DIF. All systemic LE cases demonstrated granular DEJ C4d with C3d or C4d in blood vessels (BV). There was a negative lupus band test result without DEJ C3d or C4d in all cases of subacute cutaneous lupus erythematosus (SCLE) (15/15). There were, however, deposits of C4d within epidermal keratinocytes (7/7), corresponding to IgG decoration of keratinocytes by DIF and the presence of anti-Ro antibodies. Dermatomyositis cases showed prominent mural C3d and C4d in BV corresponding to C5b-9 by DIF (12/12) and one case of hydroxyurea-induced dermatomyositis lacked this staining. Although by DIF all dermatomyositis cases had a negative lupus band test result, 25% of cases showed staining for C3d along the DEJ (3/9). Bullous pemphigoid cases demonstrated homogenous DEJ C3d (17/17) whereas C4d was characteristically negative; there was 100% concordance with linear IgG and C3d by DIF. Eighty two percent of pemphigus cases demonstrated prominent intercellular C3d and C4d, roughly mirroring the intercellular pattern for IgG and complement seen by DIF (9/11). Porphyria cases showed homogeneous and granular C3d (11/11) and C4d (7/11), mirroring the vascular immunoglobulin and C5b-9 by DIF. All cases of urticarial (5), leukocytoclastic (6), and lymphocytic (1) vasculitis exhibited prominent mural C3d and C4d in BV, whereas Henoch-Schönlein purpura (10/10) showed primarily mural BV C3d without C4d, with IgA by DIF. Three cases of relapsing polychondritis showed C3d and C4d within chondrocyte nuclei (3/3), in contrast to negative staining in chondrodermatitis nodularis helicis (0/2). Hypersensitivity reactions were negative for C3d and C4d. The small sample size in each category is a limitation. The lack of literature precedent with regard to immunohistochemical assessment of extracellular antigens on paraffin-embedded tissue in skin samples is another limitation of this study. When correlated with the light microscopic and clinical findings, the C3d and C4d assay has significant application in the assessment of select inflammatory skin diseases including vasculopathic conditions, collagen vascular disease, and autoimmune vesiculobullous disorder. It may prompt further DIF testing or, in some instances, may even define a reasonable substitute for DIF and/or add to the morphologic assessment of a biopsy specimen submitted for routine light microscopic assessment primarily in the setting of autoimmune vesiculobullous disease and collagen vascular disease.

Genetic and biochemical characterization of 16 acute intermittent porphyria cases with a high prevalence of the R173W mutation

Acute intermittent porphyria (AIP) is a metabolic disease with a variable prevalence among different countries. In some areas of southern Europe it remains to be fully evaluated. We undertook a genetic and biochemical study of 16 unrelated Spanish AIP patients and relatives. The genetic analyses showed they harboured the following mutations in the porphobilinogen deaminase gene: R173W, G111R, L278P, L238P, R116W, R26C, 340insT, 730delCT, 691del30bp, and IVS14+1g>a. The mutation R173W was found in 6 patients (37.5%), including the only patients of our series with >3 recurrent porphyria attacks. While in clinical remission, all AIP patients exhibited sustained increased excretion of porphyrins and precursors. PBG excretion showed a high between-subject variation and was not related to erythrocyte PBG deaminase activity. The study of family members allowed the identification of 22 asymptomatic AIP carriers. These included 8 persons harbouring the R173W mutation belonging to four different families. Six of these latent AIP subjects showed increased PBG elimination, and in two the urinary levels were >10-fold the normal limit. These results reinforce the hypothesis that the R173W mutation may have a high biochemical and clinical penetrance among AIP patients.

Dual gene defects involving δ‐aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient

Summary A Caucasian male had symptoms of acute porphyria, with increases in urinary delta-aminolaevulinic acid (ALA), porphobilinogen (PBG) and coproporphyrin that were consistent with hereditary coproporphyria (HCP). However, a greater than expected increase in ALA, compared with PBG, and a substantial increase in erythrocyte zinc protoporphyrin, suggested additional ALA dehydratase (ALAD) deficiency. Nucleotide sequence analysis of coproporphyrinogen oxidase (CPO) cDNA of the patient, but not of the parents, revealed a novel nucleotide transition G835-->C, resulting in an amino acid change, G279R. The mutant CPO protein expressed in Escherichia coli was unstable, and produced about 5% of activity compared with the wild-type CPO. Erythrocyte ALAD activity was 32% of normal in the proband. Nucleotide sequence analysis of cloned ALAD cDNAs from the patient revealed a C36-->G base transition (F12L amino acid change). The F12L ALAD mutation, which was found in the mother and a brother, was previously described, and is known to lack any enzyme activity. This patient thus represents the first case of porphyria where both CPO and ALAD deficiencies were demonstrated at the molecular level.

Response of glucose metabolism enzymes in an acute porphyria model: Role of reactive oxygen species

Acute hepatic porphyrias are human metabolic diseases characterized by the accumulation of heme precursors, such as 5-aminolevulinic acid (ALA). The administration of glucose can prevent the symptomatology of these diseases. The aim of this work was to study the relationship between glucose metabolism disturbances and the development of experimental acute hepatic porphyria, as well as the role of reactive oxygen species (ROS) through assays on hepatic key gluconeogenic and glycogenolytic enzymes; phosphoenolpyruvate carboxykinase (PEPCK) and glycogen phosphorylase (GP), respectively. Female Wistar rats were treated with three different doses of the porphyrinogenic drug 2-allyl-2-isopropylacetamide (AIA) and with a single dose of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Thus, rats were divided into the following groups: group L (100 mg AIA + 50 mg DDC/kg body wt.); group M (250 mg AIA + 50 mg DDC/kg body wt.) and group H (500 mg AIA + 50 mg DDC/kg body wt.). The control group (group C) only received vehicles (saline solution and corn oil). Acute hepatic porphyria markers ALA-synthase (ALA-S) and ferrochelatase, heme precursors ALA and porphobilinogen (PBG), and oxidative stress markers superoxide dismutase (SOD) and catalase (CAT) were also measured in hepatic tissue. On the other hand, hepatic cytosolic protein carbonyl content, lipid peroxidation and urinary chemiluminescence were determined as in vivo oxidative damage markers. All these parameters were studied in relation to the different doses of AIA/DDC. Results showed that enzymes were affected in a drug–dose-dependent way. PEPCK activity decreased about 30% in group H with respect to groups C and L, whereas GP activity decreased 53 and 38% in group H when compared to groups C and L, respectively. On the other hand, cytosolic protein carbonyl content increased three-fold in group H with respect to group C. A marked increase in urinary chemiluminescence and a definite increase in lipid peroxidation were also detected. The activity of liver antioxidant enzyme SOD showed an induction of about 235% in group H when compared to group C, whereas CAT activity diminished due to heme depletion caused by both drugs. Based on these results, we can speculate that the alterations observed in glucose metabolism enzymes could be partly related to the damage caused by ROS on their enzymatic protein structures, suggesting that they could be also linked to the beneficial role of glucose administration in acute hepatic porphyria cases.

Porphyrias in Japan: compilation of all cases reported through 2002.

The first case of porphyria on record in Japan was a patient with congenital erythropoietic porphyria (CEP) reported by Sato and Takahashi in 1920. Since then until the end of December 2002, 827 cases of porphyrias have been diagnosed from characteristic clinical and/or laboratory findings (463 males, 358 females, and 6 of unknown sex). Essentially all inherited porphyrias have been found in Japan, with the incidences and clinical symptoms generally being similar to those reported for other countries. The male-female ratio was approximately 1:1 for CEP, whereas it was higher for erythropoietic protoporphyria. In contrast, preponderances of female patients exist with acute hepatic porphyrias, such as acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP), and with undefined acute porphyria. Although porphyria cutanea tarda (PCT) is believed to be increasing recently in women in other countries because of smoking and the use of contraceptives, it is still by far more prominent in males in Japan than in females. The recent increasing contribution of hepatitis C virus infection to PCT in Japan has also been recognized. but there have been no PCT cases in Japan with HFE gene mutations. Familial occurrence and consanguinity were high for CEP, as expected; however, significant consanguinity was also noted in families where CEP, AIP, HCP, VP, or PCT occurred as a single isolated case without a family history of disease. This survey also revealed that as many as 71% of acute hepatic porphyria cases were initially diagnosed as nonporphyria and later revised or corrected to porphyria, indicating the difficulty of diagnosing porphyria in the absence of specific laboratory testing for porphyrins and their precursors in urine, stool, plasma, and erythrocyte samples.

Hereditary coproporphyria and chronic tubulointerstitial nephritis

A 41-year-old woman was admitted to our hospital because of abdominal pain, limb weakness, and red-wine-colored urine. Laboratory data showed renal insufficiency and hyperchloremic metabolic acidosis due to type 4 renal tubular acidosis. Clinical manifestations and investigation of porphyrins in her urine, erythrocytes, and feces established the diagnosis of hereditary coproporphyria (HCP). Renal biopsy revealed chronic tubulointerstitial nephritis. She was treated with corticosteroid, but her renal function showed no improvement. Although rare, renal involvement has been described in several types of porphyrias other than HCP. Previously reported cases of porphyrias with renal histology share the findings of chronic tubulointerstitial nephritis. To our knowledge, this is the first report of a patient with HCP presenting with renal involvement.

Coexistence of lupus erythematosus and porphyria cutanea tarda in fifteen patients

Background: Lupus erythematosus (LE) and porphyria cutanea tarda (PCT) may have similar clinical presentations, and their coexistence presents special problems in diagnosis and management. Objective: The purposes of this study were to describe a patient with discoid LE and PCT and to present a review of 15 patients with coexistent LE (all variants) and PCT. Methods: The medical records of all patients with coexistent LE and PCT seen between 1976 and 1995 were retrospectively reviewed. Results: Of 6179 cases of LE and 676 cases of porphyria (all variants), there were 15 patients, 6 men and 9 women, with coexistent LE and PCT. The mean age at diagnosis of LE was 42.8 years and of PCT was 48 years. Nine patients had discoid LE; five patients had systemic LE, and one patient had subacute cutaneous LE. The initial diagnosis was LE in eight patients, PCT in five patients, and simultaneous LE and PCT in two patients. Precipitating factors for PCT included alcohol in seven patients, iron overload in one patient, and estrogen in one patient. Treatment of LE with hydroxychloroquine 200 mg daily precipitated PCT in two patients. Patients were treated with phlebotomy or low-dose antimalarials for PCT. Patients with systemic LE received systemic glucocorticoid therapy. Patients with discoid LE and subacute cutaneous LE were treated with topical glucocorticoids. Conclusion: The association of LE and PCT poses therapeutic challenges. The preferred treatment for one may exacerbate the other. Use of standard dose antimalarials for LE is inadvisable, and phlebotomy or low-dose antimalarials should be used cautiously in patients with coexistent disease. (J Am Acad Dermatol 1998;38:569-73.)

Dermatoepidemiology. III. ABC principles for a critical review of the literature.

Is the study of disease occurrence in human populations. As a science, epidemiology emphasizes descriptive and analytic observation, clinical trial, behavioral intervention, and the practical utility of diagnostic tests. "Epidemiology" is derived from the Greek epi (among), demos (people), and logos (doctrine). Is the application of epidemiologic principles and methods to problems arising in clinical medicine, dermatology included. For dermatologists, understanding this discipline is as important as mastering other basic sciences, such as immunology, microbiology, and dermatopathology. The recognization of Lyme disease is a classic work of "infectious" disease epidemiology. In 1972, a disease characterized by erythema chronicum migrans and "endemic arthritis" clustered in Lyme, Connecticut. By 1975, an infectious agent was suspected to be the cause of the disease. In 1977, the tick was thought to be the vector; in 1980, the spirochete became the prime suspect and, in 1982, Borrelia burgdorferi was identified as the etiologic agent. The study of hexachlorobenzene exposure, resulting in porphyria turcica, is an example of classic "chronic" disease epidemiology. The illness began in 1955 when sporadic cases of porphyria occurred in eastern Turkey. In 1957, the first case with illness resembling congenital erythropoietic porphyria was described. In subsequent years, over 3000 patients developed "epidemic" porphyria. The cause was due to the ingestion of seed wheat which had been treated with fungicides containing 20% hexachlorobenzene. For research, published elsewhere as Dermatoepidemiology. I., include descriptive observational study, analytic observational study, epidemiologic experimental study and tests for sensitivity, specificity, and positive/negative predictive value. Epidemiologic principles, instead, stress the correct interpretation of data, minimization of bias, and the appreciation of natural variations in collected data.