Indian Pediatrics 2001; 38: 550-553
Type IIa Hyperlipoproteinemia Manifesting with Different Types of Cutaneous Xanthomas
Xanthomas may only represent a cosmetic abnormality in most patients. However these may signify a serious disorder in some especially in the pediatric age group. We report the clinical and lipid abnormalities in a female child who presented with multiple types of xanthomas, including the rare intertriginous variety and highlight the response to appropriate hypolipedemic drugs and plastic surgery.
A 13-year-old girl, born of a non-consanguineous marriage, presented with asymptomatic nodular lesions which started four years back from the left foot and increased in size and number progressively to involve the hands, feet, buttocks, elbows and palpebral area. There was no history of jaundice, generalized itching, prolonged fever, bone pains, weight loss or anorexia. She also denied any past compaints of chest pain, seizures or transient loss of consciousness. No family member had any such lesions.
On examination, her blood pressure was 160/80 mm of Hg and arcus juvenilis was present in both the eyes. Dermatological examination revealed multiple tendinous xanthomas in the form of discrete, soft, non tender, subcutaneous, nodular swellings of varying sizes over the dorsae of both hands and feet attached to extensor tendons and to achilles tendon (Fig. 1). Soft to firm, skin colored with yellowish tinge to erythematous nodular swelling and plaques of varying size were present over both elbows, knees and buttocks (tuberous xanthomas) (Fig. 2). Intertriginous yellowish plaques with rugose surface were seen in the webs of fingers (Fig. 1). Similar lesions were detected around inner canthus of both eyes (xanthelasma palpebrarum). Rest of the mucocutaneous and systemic examination was normal.
Routine hematological investigations were normal. The lipid profile revealed a serum cholesterol of 640 mg/dl with LDL 575 mg/dl, triglycerides 165 mg/dl, VLDL 32 mg/dl and HDL 32 mg/dl. The electrocardiogram and chest X-ray were within normal limits. X-ray of the hands showed soft tissue swelling with no bony defect and ultrasonography of abdomen revealed no abnormality. Histo-pathology of one of the lesions showed foamy macrophages in the dermis along with Touton’s giant cells. Plasma kept overnight at 4°C was clear. The lipid profile of family members was within normal limits.
A diagnosis of xanthomatosis with Type IIa hyperlipoproteinemia was made and the patient was advised diet control and reduction of fat intake, with total cholesterol of less than 250 mg/day. Medical therapy in the form of oral simvastatin 20 mg per day along with amlodipine 5 mg was started. After four months of therapy, there was a reduction in size of the smaller tuberous lesions by more than half but no change in tendinous and periorbital lesions. The serum cholesterol was 295 mg/dl and LDL was 229 mg/dl. Surgical excision of cosmetically disfiguring tendinous and tuberous lesions was done, with electro-fulguration of xanthelasma palpebrarum.
Fig. 2. Tuberous xanthomas.
Xanthomas may be seen either as a primary disorder or secondary to various acquired systemic diseases like hypo-thyroidism, biliary cirrhosis, diabetes mellitus, nephrotic syndrome, monoclonal gammopathy and intake of drugs like beta blockers, diuretics(1). Classification of primary hyper-lipidemias is based on measurement of fasting lipid fractions. With a raised serum LDL cholesterol, normal triglycerides and after excluding all secondary causes, our patient was diagnosed as Type IIa hyperlipo-proteinemia.
Familial hypercholesterolemia is trans-mitted as an autosomal dominant trait that may occur in one in 500 persons. Individuals have a mutant gene controlling formation of LDL receptor(2). Heterozygotes have a two to three fold increase in plasma beta lipoprotein cholesterol, but symptoms usually develop from the third to sixth decade of life. It is generally believed that the homozygotes have very high cholesterol values and symptoms develop in first few years of life and the same was seen in our patient(2). It may be highlighted here that the homozygous state appears to be due to de novo mutation, as all family members were asymptomatic and had normal lipid profile. Xanthomas are seen in 40-50% patients of Type IIa hyperlipo-proteinemia. Tendinous xanthomas (40-50% cases) and xanthelasma (23%) are most common, with tuberous xanthomas in 10-15% and intertriginous plane xanthomas occurring occasionally(2). Intertriginous xanthomas are thought to be diagnostic of type II hyper-cholesterolemia(3). Our patient had multiple types of xanthomas including tendinous, tuberous, palpebral and the rare plane inter-digital lesions with an onset in first decade of life. These were also present in the cases reported by Kumar et al.; however, in addition they noticed Koebner response(3). In these patients arcus senilis and premature athero-sclerotic cardiovascular disease may be seen, with occurrence of myocardial infarction by the age of 30. Though electrocardiogram was normal, systolic hypertension was present in our patient, who was thus started on 5 mg of amlodipine daily.
To prevent complications of hyper-cholesterolemia like cardiovascular and cere-brovascular accidents which are the usual cause of mortality, it is important to start therapy. The statins have been proven to be effective drugs especially in heterozygous familial hypercholesterolemia(4). They inhibit HMG CoA reductase, the rate limiting enzyme in cholesterol synthesis, thus increasing LDL receptor synthesis. Simvastatin at a dose of 20 mg daily, produces a 30% reduction in serum cholesterol. The lowering of LDL cholesterol can be enhanced by combining a statin with bile acid sequestrants (2 g cholestyramine or colestipol) and diet control(4). With Sim-vastatin our patient had reduction of serum cholesterol by more than half and decrease in size of smaller tuberous xanthomas. It is significant to note that the patient with homozygous disease showed some response to simvastatin, thus indicating partial LDL receptor activity. However, tendinous lesions and xanthelasma showed no response and were excised surgically.
This report highlights the importance of xanthomas as an aid to diagnoses and pre-vention of complications of lipid derangement especially in the pediatric age group.
Contributors: DP reviewed the literature and drafted the paper. CG contributed in clinical documentation and biochemical and histopathological analysis. BSNR drafted the paper and will act as the guarantor for the paper.
Competing interests: None stated.