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Summary The blood flow in 71 Patients and methods Doppler studySixty-seven patients with 71 primary untreated skin melanomas were examined by a 10MHz continuous wave Doppler ultrasound flowmeter before biopsy. The flowmeter was used with a Park's pencil probe of 0.5cm diameter (Park's Inc., USA). The probe was applied over the lesion with ultrasound coupling gel. To avoid any pressure over the lesion the probe was placed 2-3mm away from the tumour, lying embedded in the gel. Dry keratotic lesions were moistened with water before applying the gel. A lesion was called Doppler flow positive if pulsatile audible signals were detected with the probe lying at a tangential plane to the skin surface. In the case of flat macular lesions the probe was put horizontally on the skin surface with its tip being about 4-mm away from the margin of lesion and then pressed gently pointing its tip towards the lesion. If no flow signals were detected at the tangential plane the tumour was called Doppler flow negative. On detection of flow signals, the probe angle was altered to obtain a maximum amplitude (systolic peak) signal on the Angioscan spectrum analyser (Unigon Inc., USA). These signals were then recorded on an audio stereo cassette recorder (AKAI-HX-3; AKAI Electric Company Ltd, Japan Figure 1).

One-hundred children with an acute illness comprising fever and widespread erythematous rash were prospectively studied to determine whether clinical presentations are helpful in defining the causative agent and to identify the most appropriate microbiological specimens. An infectious agent was identified in 65 children; 72% were viruses, 20% were bacteria, 5% were Mycoplasma pneumoniae and in 3% both viruses and bacteria were detected. The most common infectious agents were picornaviruses, an atypical presentation of measles and Group A beta-haemolytic Streptococcus. Different patterns of rash occurred with each of these infections. The clinical presentation of a child with an acute febrile illness and rash was unhelpful in defining the causative agent. Routine management should include a throat swab for bacterial investigation and in selected cases a blood sample for IgM viral titres.

Late-onset erythropoietic protoporphyria (EPP) is a rare complication of myelodysplastic syndrome (MDS) but has not been described in association with a myeloproliferative disorder (MPD). EPP is normally an inherited disorder characterized by photosensitivity that starts in early childhood and results from overproduction of protoporphyrin secondary to ferrochelatase (FECH) deficiency. Severe liver disease occurs in 1% to 2% of patients. Here we report that severe photosensitivity and cholestatic liver disease in a patient with a myeloproliferative disorder was caused by excess protoporphyrin production from a clone of hematopoietic cells in which one FECH allele had been deleted. Our observations suggest that the usual explanation for the association of late-onset EPP with MPD and MDS is acquired somatic mutation of one FECH allele in bone marrow and show for the first time that the consequent overproduction of protoporphyrin may be severe enough to cause acute liver damage. IntroductionErythropoietic protoporphyria (EPP) is an uncommon inherited disorder of heme biosynthesis that results from partial deficiency of ferrochelatase (FECH). It is characterized clinically by childhood onset of lifelong photosensitivity and biochemically by overproduction of protoporphyrin in erythropoietic cells with accumulation of protoporphyrin in erythrocytes, plasma, skin, and liver. 1 Clinical expression of EPP normally requires inheritance of an FECH mutation trans to a lowexpression FECH allele, 2-4 which is present in 13% of the United Kingdom population. 4 In 1% to 2% of patients with EPP, deposition of protoporphyrin in the liver leads to progressive liver failure, usually after at least a decade of photosensitivity. 1,5,6 Late onset of photosensitivity is rare in EPP. 1 Only 10 patients have been reported in whom symptoms started after the age of 40 years, 7-10 7 of whom also had refractory anemia with ring sideroblasts (RARS) or other myelodysplastic syndromes (MDSs). In one patient, EPP was recently shown to be caused by proliferation of a clone of hematopoietic cells in which one allele of the FECH gene had been deleted. 9 Here we describe a patient with a myeloproliferative disorder (MPD) who developed severe photosensitivity and cholestatic liver disease. We postulated that these complications were caused by an acquired somatic mutation of the FECH gene in his hematopoietic cells. Study designA 62-year-old man was diagnosed with polycythemia vera (PV) and hyperuricemia (hemoglobin concentration, 17.5 g/L; hematocrit, 0.513 [51.3%]; leukocyte count, 11.1 ϫ 10 9 /L; platelet count, 191 ϫ 10 9 /L; red cell volume, 34.2 mL/kg [136% of predicted]; plasma volume, 34.4 mL/kg [92.6% of predicted]). Bone marrow examination was consistent with a myeloproliferative disorder (MPD), showing increased cellularity, no excess blasts, no ringed sideroblasts, and normal cytogenetics. He was treated with hydroxyurea, venesections, and allopurinol. Thirty-three months later, an increase in his white cell count (73 ϫ 10 9 /L; 79% neutr...