Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disorder characterized by generalized degeneration and mineralization of elastic fiber, caused by mutation in the ABCC6 (ATP-binding cassette subfamily C member 6) gene on chromosome 16p13.1.
Pseudoxanthoma elasticum-like lesions have been described in hemoglobinopathies, for example, sickle-cell disease (SCD) and thalassemia, mainly in beta-thalassemia. The clinical presentation, histopathology, ultrastructure and immunochemistry of PXE-like lesions are similar to inherited PXE, but with no ABCC6 mutation.
Our patient was a 44-year-old Thai man who presented with a 6-month history of gradually increasing papules on his neck and shoulders. He had beta-thalassemia/hemoglobin E disease and had regularly received blood transfusion for 25 years. He developed iron overload and had begun iron chelating therapy 3 years prior. No similar skin features were present in his family.
Physical examination revealed multiple discrete and confluent yellowish papules and plaques with “plucked chicken skin” appearance on the neck and shoulders (Fig. 1a). His cardiovascular examination and electrocardiogram were normal. Ophthalmological examination revealed no angioid streak. Skin biopsy showed calcified, distorted and fragmented elastic fibers in the mid-reticular dermis (Fig. 1b), confirmed by Von Kossa staining. Verhoeff-van Gieson elastic stain revealed irregularly clumped elastic fibers, which is characteristic of PXE.
Elastic tissue abnormalities have been reported in patients with hemoglobinopathies. The affected organs are the cardiovascular system, retina and skin, which are composed of numerous elastic fibers. The cardiovascular manifestations include myocardial/intestinal infarction, intermittent claudication and transient ischemic attack, which result from arterial calcification.[3, 4] Moreover, vascular aneurysm leads to gastrointestinal and intracranial hemorrhage.[1, 3] From Aessopos et al.'s case–control study, beta-thalassemia patients demonstrated 55% arterial calcification, 20% PXE-like lesions and 52% angioid streaks. Angioid streaks, characteristic ocular findings caused by disruption of the elastic lamina of Bruch's membrane, showed no symptoms. However, choroidal and retinal vessels destruction caused visual impairment.
The characteristic cutaneous manifestation is yellowish papules resembling “plucked-chicken skin” distributed over neck, axillae, antecubital fossae, popliteal and groin areas. The long-term follow-up study showed that PXE-like lesions were unrelated to severity of anemia, duration of blood transfusion, splenectomy and chelation history.[2, 3] The differences among these two entities are demonstrated in Table 1.
|Mode of inheritance||Autosomal recessive, 90%||Acquired|
|Gene defect/encoding protein||ABCC6/MRP6||None|
|Age of onset||Puberty||Varies; childhood, puberty, adulthood|
|Skin manifestation||“Plucked chicken skin” appearance||Same, 17–20%|
|Angioid streaks||Present, 80%||Present, 10–52%|
|Cardiovascular system||Intermittent claudication, hypertension, early myocardial infarction||Same; arterial calcification 55%|
Oxidative process is the important proposed pathogenetic mechanism of elastic tissue injury. Unbound fractions of hemoglobin and heme in chronic hemolysis have strong oxidative properties. Additionally, toxic hydroxyl radical catalyzed by unbound iron may cause peroxidation of membrane lipids and proteins. This mechanism interferes with elastic metabolism and leads to elastic fiber deterioration.
Hereditary hemochromatosis (HH) is a primary iron overload syndrome but elastic tissue abnormalities have not been found in these patients. Only one case of co-occurrence HH and hereditary PXE was reported in the published work. This may explain by multifactorial causes of PXE-like lesions in hemoglobinopathies besides iron overload, such as oxidative process,  which is absent in HH patients.
The clinical and histopathological findings in our patient diagnosed PXE. However, because of late disease onset and lack of family history, he was diagnosed as having PXE-like lesions in association with thalassemia major.
Unfortunately, no specific treatment for PXE exists. Reducing calcium intake, oral phosphate binder and ethylenediaminetetraacetic acid chelating therapy are still controversial. Patients should be advised to avoid activities and medications that predispose to bleeding. Exercise, weight control, avoidance of smoking, and treatment of hypercholesterolemia and hypertension are essential for preventing cardiovascular complications.
The surveillance of PXE-like lesions in the hemoglobinopathy population is necessary together with annual fundoscopic and cardiovascular examinations to prevent critical complications.