Untitled Document

Pediatric xanthoma

Vinay Varghese Mathai1, Veena Thimmappa2*, Narendra Gangaiah3,
Pavithra Gundappa4

1Junior Resident, 2*Associate Professor, 3Professor and HOD, 4Senior resident
Department of Dermatology,  Sri Siddhartha Medical College & Research Centre, Tumakuru,
Sri Siddhartha Academy of Higher Education, Tumakuru.

Year : 2021 | Volume : 4 | Issue : 1 | Page : 27 | DOI -10.46319/RJMAHS.2021.v04i01.006

Abstract
Xanthomas are cutaneous manifestations of the accumulation of fat in macrophages. They may or may not be associated with systemic derangement of lipids. The derangement could be secondary to a genetic cause like familial hypercholesterolemia. When associated with familial hypercholesterolemia especially the homozygous variant, it needs to be promptly referred due to the difficulty in management and high chances of coronary complications when treatment is delayed. Our case report details a young girl from Tumakuru who developed xanthomatous lesions at around the age of five years and presented to the outpatient department of Dermatology, Sri Siddhartha Medical College.
Key words: Cutaneous xanthoma,  Arcus juvenilis

Introduction
Xanthomas are the cutaneous manifestation of alteration in generalized or localized lipoprotein metabolism, resulting in a morphologic variation as lipids mount up in foam cells in the tissues. [1] Tuberous xanthomas are firm, yellow, indurated papules and nodules seen over the extensor aspect of limbs and buttocks. They are usually associated with hypercholesterolemia and secondary hyperlipidemia with hypothyroidism, monoclonal gammopathy, and biliary disease.[1] Rarely seen in children, they signify a much severe form of hyperlipidemia. Timely detection of these hyperlipo-proteinemias is a fundamental component in averting premature coronary artery disease.[2] The dermatologist's role is in recognizing these lesions and in ensuing prompt referral and treatment.
Case Report
A 6-year-old thin girl from the Tumkur district presented to our outpatient department with a history of yellow plaques on the buttocks, knuckles, and leg for a year. The child was born out of a second degree consanguineous marriage with no family history suggestive of stroke or coronary artery disease. On close cutaneous examination multiple, yellowish brown, non-tender, soft plaques, measuring 0.5 to 1.5 cm in diameter, are distributed on the skin over both the buttocks, intergluteal cleft, left tendoachilles and bilateral second, third and fourth metacarpophalangeal joints (Fig. 1, 2.a. & 2.b.). The surface was smooth. The lesions were not immobile to the structures underneath. The skin over the lesions was normal. The palms and soles were spared. There was no lymphadenopathy or organomegaly. Ophthalmic examination revealed an arcus juvenilis (Figure 3) and suggested a fasting complete lipid profile. Routine blood tests, liver function tests, renal function tests, thyroid profile, chest X-ray, ECG and USG were within normal limits. The fasting serum lipid profile showed significantly elevated total cholesterol and low-density lipoprotein cholesterol. The father and mother also got their fasting serum lipid profiles done, which in turn revealed elevated total cholesterol and low-density lipoprotein cholesterol in both of them. Additional tests like computed tomography (CT) angiography, LDL receptor activity in addition to genetic mutational analysis were not carried out due to monetary restraints. On histopathological examination of the tuberous nodule from the buttocks, foamy macrophages with inflammatory cells suggestive of xanthoma were seen.
Based on the age, clinical history, family history and elevated lipid reports, a final diagnosis of homozygous familial hypercholesterolemia (HoFH) was formulated and medical treatment commenced with statins. A pediatric consultation advocated low fat and high fiber diet. Follow- up after 6 months revealed improvement in the cutaneous lesions and serum fasting lipid levels.
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Fig1: cutaneous xanthoma on left tendoachilles region
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Fig 2a: cutaneous xanthoma on gluteal region
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Fig 2b: cutaneous xanthoma on metacarpophalangeal joints
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Fig 3: Arcus juvenilis
Discussion
Xanthomas come about due to variations in lipid metabolism. From time to time it can be the sole presentation of a grave underlying lipid anomaly. In children, they are generally related to abnormalities of cholesterol metabolism with hypercholesterolemia and high LDL-C.[3] A mutation in the gene coding the receptor for LDL found in chromosome 19 instigates an autosomal dominant genetic disorder called familial hypercholesterolemia.[4] The LDL elimination rate from the plasma is determined by the heterozygous or homozygous state of the individual. One in five hundred people have heterozygous FH, presenting clinically between thirty and sixty years of age. In comparison, homozygous FH befalls very rarely with the prevalence of one in a million individuals.[5, 6] Two abnormal LDL receptor genes are inherited by FH homozygotes, bringing about significantly raised plasma cholesterol levels stretching between 500 and 1200 mg/dl. Triglycerides are either normal or slightly elevated and HDL may be a tad reduced. Clinically pediatric xanthoma is almost exclusively seen in homozygous familial hypercholesterolemia and they are more prone for CVS abnormalities during their second and third decade as their LDL-cholesterol clearance rate is only 33% to normal resulting in very high LDL cholesterol levels.[7]
The challenge that is managing homozygous familial hypercholesterolemia is well known.[8] The standard regimen being dietary control, statins with or without cholesterol absorption inhibitors. Bile acid sequestrants becoming infrequent nowadays. The expert panel of NCEP endorses for children and teenagers that a trial may be given to the pharmacologic treatment of hyperlipidemia if the child is no less than 10 years of age and the acceptable period of dietary control, which is 6 months, has not realized the therapeutic goals. The recommended guidelines further state that in exceptional cases an individual may commence therapy beforehand when there is an extremely excessive level of cholesterol and a family history of premature coronary disease is prevalent.[9] These facts encouraged us to start our patient and family members on atorvastatin (dose dependent on weight) and a fat restricted diet. The patient's condition is yet to be revealed on follow up. In a case series done by Widhalm et al through 9 patients with HoFH confirmed by genetic studies, a good response was seen to combined drug therapy (statins + ezetimibe and/or on colesevelam) on top of LDL apheresis.[10] The advantages of LDL- apheresis being it can be initiated in children as young as 3.5 years and disadvantages include anaphylaxis and cost.[11] Liver transplantation, another option has shown a reduction in total cholesterol and LDL as well as overall improvement in cardiac testing with changes in MRA in a patient with no response to maximal pharmacologic therapy as reported by Palacio et al.[12] Further in the same report they give an account for a 3-year-old Hispanic girl who also got diagnosed with HoFH and didn't respond adequately to maximal pharmacologic therapy or LDL- apheresis but saw adequate relief with LT.
Gaur et al account prognosis of HoFHdepends on elevated levels of LDL cholesterol, LDL- receptor activity and how promptly the disease is identified and is given appropriate management. Untreated HoFH patients seldom survive past the second to fourth decade.[13]
Abbreviations used
CT:      Computed Tomography
FH:      Familial Hypercholesterolemia
HoFH: Homozygous Familial Hypercholesterolemia
NCEP: National Cholesterol Education Program
LDL:    Low Density Lipoprotein
LT:       Liver transplantation
Acknowledgement : Nil
Financial support and sponsorship: Nil
Conflict of interest: Nil
References
1.  Kumar B, Dogra S. Metabolic disorders. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL textbook of dermatology.4th ed. Mumbai: Bhalani Publishing House; 2015. p. 1856­1901.
2.  Maher-Wiese VL, Marmer EL, Grant-Kels JM. Xanthomas and inherited hyperlipoproteinemias in children and adolescents. PediatrDermatol1990;7:166-73.
3.  Jain KS, Kathiravan MK, Somani RS, Shishoo CJ. The biology and chemistry of hyperlipidemia. Bioorg Med Chem. 2007;15:4674-99.
4.  Van Aalst-Cohen ES, Jansen AC, de Jongh S, de SauvageNolting PR, Kastelein JJ. Clinical, diagnostic, and therapeutic aspects of familial hypercholesterolemia. SeminVasc Med. 2004;4:31-41.
5.  Reddy B, Chaudhuri S N. Familial hypercholesterolemia with multiple cutaneous xanthomas. Indian J Dermatol2006;51:204-6
6.  Carlos H. Palacio, Theresa R. Harring, N. Thao T. Nguyen, John A. Goss, Christine A. O'Mahony, "Homozygous Familial Hypercholesterolemia: Case Series and Review of the Literature", Case Reports in Transplantation, vol. 2011, Article ID 154908, 5 pages, 2011. https://doi.org/10.1155/2011/154908
7.  Parihar RK, Razaq M, Saini G. Homozygous familial hypercholesterolemia. Indian J EndocrinolMetab. 2012;16(4):643-645. doi:10.4103/2230-8210.98032
8.  Lavie CJ, Gau GT, Squires RW, Kottke B. Management of lipids in primary and secondary prevention of cardiovascular diseases. Mayo Clin Proc. 1988;63:605-21.
9.  Neal WA. Disorders of lipoprotein metabolism and transport. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson Text book of Pediatrics. 18th ed. Philadelphia: Saunders; 2007. p. 580-93.
10.  Widhalm K, Benke IM, Fritz M, et al. Homozygous familial hypercholesterolemia: Summarized case reports. Atherosclerosis. 2017;257:86-89. doi:10.1016/ j.atherosclerosis. 2017.01.002
11.  Palcoux JB, Atassi-Dumont M, Lefevre P, et al. Low-density lipoprotein apheresis in children with familial hypercholesterolemia: follow-up to 21 years. TherApher Dial. 2008;12(3):195-201. doi: 10.1111/j.1744-9987.2008.00574.x
12.  Palacio CH, Harring TR, Nguyen NTT, Goss JA, O'Mahony CA. Homozygous Familial Hyper cholesterolemia: Case Series and Review of the Literature. Andrews PA, Faenza S, Beiras- Fernandez A, eds. Case Reports in Transplantation. 2012;2011:154908. doi:10.1155/2011/154908
13.  Gaur BK, Maini B, Goel A. Homozygous familial hypercholesterolemia with corneal arcus: A rare case report. Indian J PaediatrDermatol2020;21:150-2


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