1 Pediatric Nephrology, 2 Pediatric Gastroenterology, 3 Pediatric Endocrinology, University Pediatric Clinic, 4 Institute for Pathology, Skopje, Macedonia Email: dafk{at}mt.net.mk
Case
A 12-year-old girl was hospitalized in July 2000 for an episode of abdominal pain, vomiting and collapse. Anaemia secondary to acute upper gastrointestinal haemorrhage was diagnosed; however, the reason for the haemorrhage could not be identified. Physical examination revealed normal growth, and hypertension of 180/110 mmHg. Thickened yellowish skin (peau dorange) was noticed in the axilar and inguinal regions and on the abdominal wall (Figure 1). Femoral pulse was palpable. Laboratory tests revealed: haemoglobin 8.1 g/dl, haematocrit 0.20, white blood cell count 11.2 x 109, platelets 230 x 109, erythrocyte sedimentation rate 5/10, and C-reactive protein <4.91 g/l. Urinalysis was within normal limits on several occasions. Serum electrolytes, liver enzymes and kidney function tests were within normal limits. In order to assess the cause of hypertension, the following tests were performed, with normal results: urine catecholamine levels, urine vanilmandelic acid levels, cortisol, adrenocorticotrophic hormone (ACTH), 17 (OH) and progesterone. Aldosterone was 66 µg/24 h, and plasma renin activity (PRA) was 5.18 ng/ml/h (normal 0.984.1). Fundus examination revealed angioid streaks radiating outwards from the peripapillary area bilaterally. Fluorescein angiography was not done (unavailable in our centre). Abdominal ultrasound showed normal liver, spleen, kidneys, pancreas and blood vessels. Suprarenal glands were normal. Doppler studies of aorta, renal arteries, hepatic artery and splenic artery were also normal. Tc99m DMSA scintigraphy, IVP and renal angiography (selective right and left renal arteriography and aortography) were without abnormalities. The electrocardiogram at rest and post-exercise was normal. Echocardiography showed a slight prolapsus of the mitral valve and mild intraventricular septal hypertrophy. There were no signs of aortal coarctation. Renal ultrasonography performed after 6 months showed a characteristic pattern of dotted increased echogenicity at the corticomedullary junction (medullar hyperechogenicity) (Figure 2).
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Question
What is your diagnosis? Is there a link between the skin lesions, gastrointestinal bleeding and hypertension?
Answer to the quiz on the preceding page
The diagnosis is pseudoxanthoma elasticum (PXE). It is an autosomal recessive/dominant inherited defect of the connective tissue, characterized by a degeneration and calcification of elastic fibres in arterial walls, in the lamina elastica of Bruch's membrane of the eye, and in elastic fibres of the middle zone of the reticular dermis [1]. Onset of skin manifestations often occurs during childhood, but early lesions are subtle and may not be recognized clinically before the second decade of life [24]. A characteristic finding is thickened yellowish skin in flexure areas and on the abdomen, often known as plucked chicken skin (Figure 1).
The skin biopsy is considered to be diagnostic for the disease. The dermatological examination in our patient revealed basophilic swollen and degenerated/calcified elastic fibres situated in the middle and deep parts of the reticular dermis, a pathohistological finding consistent with the diagnosis of PXE (Figure 3).
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In the early stages of PXE, superficial erosive lesions may be found in the gastrointestinal tract; however, gastrointestinal bleeding may occur without an identifiable source, as seen in the present patient. In the advanced stages, yellowish papular lesions can be detected on the gastric mucosa [2,3]. The vascular changes associated with PXE are those of stenotic, occlusive disease primarily affecting medium sized peripheral arteries, including renal, splenic, external iliac, femoral and cardiac vessels [2,3]. Patients with PXE are prone to early coronary artery disease and may present with angina and sudden death. Fibrous thickening of the endocardium of the ventricles, atria and atrioventricular valves can be seen. Endocardial calcifications can be determined by echocardiography [5]. Renovascular hypertension has been reported in 25% of patients with PXE, and commonly occurs in adults. There are few reports of hypertension in children [2,3]. The reason for hypertension is increased renin activity as a result of obstruction, due to calcification of renal arteries. Due to calcification of the interlobar and arcuate arteries, a characteristic pattern of dotted increased echogenicity is seen in the corticomedullary junction, by renal ultrasonogoraphy [6]. This increased echogenicity can also be seen in the spleen and pancreas. Our patient did not have vascular obstruction on renal arteriography; however, it is possible that in the early stages of the disease, changes are mild and undetectable by conventional imaging.
High levels of PRA and aldosterone and the characteristic pattern of dotted increased echogenicity at the corticomedullary junction, detected on the subsequent ultrasonography, both indicate a renovascular genesis of hypertension. Because PXE can be an inherited disorder, the family of the patient was evaluated. There was no parental consanguinity, but the father and sister had skin lesions similar to those of the propositus. However, they were not hypertensive and their abdominal ultrasongoraphy was normal. Familial involvement suggests that the disease is inherited as an autsomal dominant disorder in this family. We reported a child with an early presentation of PXE. The appearance of unexplained hypertension, gastrointestinal bleeding or other systemic manifestations in a child who has characteristic skin lesions (thickened yellowish skin) should alert the clinician to the possibility of PXE. A proper diagnosis can explain systemic manifestations, and will help to avoid unnecessary investigations.
Conflict of interest statement. None declared
References