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 Table of Contents  
Year : 2022  |  Volume : 17  |  Issue : 1  |  Page : 78-81

Familial hypercholesterolemia mimicking juvenile idiopathic arthritis

1 Department of Medicine, Hind Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Pediatrics, Hind Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
3 Department of Pathology, Hind Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Submission23-Jan-2021
Date of Acceptance27-May-2021
Date of Web Publication15-Mar-2022

Correspondence Address:
Dr. Pooja Dhaon
Department of Medicine, Hind Institute of Medical Sciences, Barabanki, Lucknow, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_22_21

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Juvenile idiopathic arthritis (JIA) seen in children is a diagnosis of exclusion, as many systemic and metabolic diseases have similar presentation. Here, we present a case of a 14-year-old female girl who presented with polyarthralgia, fever, and nodules over body. She was diagnosed as JIA initially without any response to treatment. On further assessment, she had xanthelasma on eyelids, and a very high and low-density lipoprotein-cholesterol, a second-degree relative also with similar findings. The histopathology of the nodule was suggestive of xanthoma. Thus, she was diagnosed as familial hypercholesterolemia (FH) and was given statins. Articular manifestations are not very uncommon in patients of FH, and sometimes, they are the presenting symptoms in these patients. There are number of causes of arthritis with subcutaneous nodules in children apart from JIA which have been enumerated. Thus, FH must also be considered as a differential diagnosis in such patients.

Keywords: Familial hypercholesterolemia, juvenile idiopathic arthritis, xanthelasma, xanthoma

How to cite this article:
Dhaon P, Bansal U, Jain D. Familial hypercholesterolemia mimicking juvenile idiopathic arthritis. Indian J Rheumatol 2022;17:78-81

How to cite this URL:
Dhaon P, Bansal U, Jain D. Familial hypercholesterolemia mimicking juvenile idiopathic arthritis. Indian J Rheumatol [serial online] 2022 [cited 2022 Oct 1];17:78-81. Available from:

  Introduction Top

Juvenile idiopathic arthritis (JIA) is the most common chronic childhood arthritis with no definitive diagnostic tool. It is a diagnosis of exclusion and a comprehensive history, including a detailed family history and physical findings help in differentiating various causes of articular disorders in children. Many children are referred to rheumatology clinics with complaints of joint pain and swelling without any signs of inflammation. A spectrum of systemic noninflammatory disorders mimics JIA. It is crucial to diagnose these disorders to provide proper genetic counseling and appropriate treatment to these patients to improve outcomes.[1] This report highlights a patient with familial hypercholesterolemia (FH) who presented with articular complaints and was misdiagnosed as JIA.

  Case Report Top

A 14-year-old female patient was referred from Pediatric Department with complaints of fever on and off, joint pains involving small and large joint, rash on trunks, for the past 6 years. She was diagnosed as JIA by primary care physicians and was on steroids and Disease modifying anti Rheumatic drugs (DMARDs) – methotrexate, sulfasalazine for the past 2 months without any improvement in her symptoms. Thus, she was sent to Rheumatology clinic for further assessment. A detailed history of the patient was taken. The patient had fever daily one spike and was not associated with chills and rigors which responded to oral paracetamol. The patient had severe joint pain involving small and large joints of hand and feet, without early morning stiffness. The patient did not have any features of any connective tissue disease (CTD). There was no history of inflammatory backache, ocular symptoms, bowel involvement or history suggestive of leprosy, rheumatic fever, cardiac symptoms; there was no family history of CTD and arthritis. On examination, tenderness was found in multiple joints though none was swollen. Multiple nodular swelling was found in hands, elbow, and foot [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d,[Figure 1]e. Xanthelasma was present on both eyelids [Figure 1]f. Her father had expired 2 years back due to some unknown causes. History of her mother and other sibling was not available. She was accompanied by her paternal aunt (second-degree relative) who also had the presence of xanthelasma on both eyelids [Figure 1]g. Her laboratory investigations revealed a raised erythrocyte sedimentation rate and positive C-reactive protein [Table 1]. Lipid profile of the patient and her aunt showed a very high total and low-density lipoprotein (LDL) cholesterol levels [Table 2]. Radiographs of both hands and feet showed the presence of multiple dense soft tissue swellings in hands and feet with normal articular margin, normal joint space [Figure 2]a and [Figure 2]b. Subsequently, a biopsy of the foot nodular swelling was taken which showed closely packed lipid laden macrophages suggestive of xanthoma [Figure 3].
Figure 1: (a) Nodular swelling at proximal interphalangeal joints. (b) nodular swelling at metatarsophalangeal joint. (c) nodular swelling at elbow. (d) nodular swelling at Achilles tendon. (e) xanthelasma at eyelids of patient. (f) patient's aunt with xanthelasma at eyelids (g) nodular swelling at Achilles tendon

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Table 1: Laboratory investigations of the patient

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Table 2: Lipid profile of patient and her paternal aunt (second-degree relative)

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Figure 2: (a) Radiographs of both hands posterior-anterior view showing radiolucent opacities at proximal interphalangeal joint marked by arrow. The joint space and articular margins are normal. No erosions are seen. (b) Radiographs of both feel anterior-posterior view showing multiple radiolucent opacities marked by arrows. The joint space and margins are normal. No erosions are seen

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Figure 3: Biopsy of nodule from foot (×10 to ×40 images): showing lipid-laden macrophages

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A final diagnosis of FH was made considering the high levels of LDL cholesterol (LDL-C) and nodular swellings to be tendon xanthoma. The patient and her aunt were advised lifestyle modifications along with statins. The patient's symptoms improved with this treatment.

  Discussion Top

The patient presented with polyarthritis with subcutaneous nodules without any response to DMARDs and steroids. The differential diagnosis to be considered in children with such presentation are in [Table 3].[2],[3],[4],[5]
Table 3: Differential diagnosis of polyarthritis with subcutaneous nodules

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FH is a common inherited condition disorder of cholesterol metabolism characterized by high levels of LDL-C and increased risk of cardiovascular events. The most common mode of inheritance is autosomal dominant caused by defect in gene that codes LDL receptor. A rare autosomal recessive form has also been described.[6]

Diagnosis of FH is based lipid levels, family history, physical findings, and genetic analysis, if available. The most commonly used diagnostic tool is the Dutch Lipid Clinic Network Diagnostic Criteria.[2] It is based on scores and as per these criteria, the patient had elevated cholesterol (entry criteria), presence of tendon xanthoma (6 points), and LDL cholesterol >330 mg/dl (8 points). The total score was 14, and thus, as per these criteria, she was in the category of definite FH. The genetic testing is the gold standard for the diagnosis of FH, but it was not done due to nonavailability. The genetic test also has its own limitations as approximately 1 in 5 patients with a clinical diagnosis of FH have negative test results for all currently known genetic mutations.[7]

Articular manifestations are not so rare and have been described with FH. Sahu et al. reported to cases of FH, with tendinitis and with progressive tendon xanthoma early in life. The patient presented late only when the attacks became severe.[8] The initial articular manifestation of disease in children may be xanthoma of Achilles tendon and before it can be picked clinically, it can be detected by an ultrasound which demonstrates cholesterol infiltration in the Achilles tendon.[9] The largest case series of 73 patients described 29% patients presenting with articular manifestations at some point of time during their lifetime. The observed articular manifestations were classified into four types: Achilles pain (18%),  Achilles tendinitis More Details (11%), oligoarticular arthritis (7%), and polyarticular or rheumatic fever-like arthritis (4%).[10] The exact nature of articular involvement is still not clear and both intra-articular and periarticular involvement have been suggested. Experimental evidence exists in possible role of cholesterol crystals in soft tissues and joint inflammation. There is some evidence regarding the temporal relation with levels of cholesterol and joint inflammation, like in gout attack which relates with serum uric acid level.[11] Furthermore, patients of FH have higher inflammatory, endothelial activation, and oxidative stress.[12] This may be the reason behind raised inflammatory markers in the patient.

Articular manifestations can be the presenting symptoms in many patients and presence of nodules mimicking rheumatoid nodules, make it more likely to be misdiagnosed as a rheumatological disease.[13],[14] A case report published by Schou et al., where the patient was a 10-year-old female, who presented with arthralgia and nodules over body, initially diagnosed as JIA. When she did not respond to treatment, she was evaluated again. The diagnosis of FH was confirmed by high LDL-C, genetic analysis, and biopsy of the nodule suggestive of xanthoma.[15] The present patient was treated as JIA for quite some year before she was finally diagnosed as FH. The clinical implication of FH is grave as it can lead to increase mortality due to premature cardiac events in adults. In children and adolescents, FH can be often asymptomatic.[16] Thus, it is important to diagnose it early and provide correct proper genetic counseling and treatment to patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's legal guardian (as patient is a minor) has given consent for images and patient information to be reported in the journal. Due care has been taken to conceal the identity of the patient.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Sulaiman M. Al-Mayouf. Noninflammatory disorders mimic juvenile idiopathic arthritis. Int J Paediatr Adolesc Med 2018;5:1-4.  Back to cited text no. 1
Feldon M, Sikora K, Huggins JL, Billings SD, Mcmasters R, Brunner HI. Polyarticular arthritis and skin nodulosis in a 14-year-old female. Arthritis Care Res (Hoboken) 2016;68:700-5.  Back to cited text no. 2
Kubota M. Hyperuricemia in children and adolescents: Present knowledge and future directions. J Nutr Metab 2019;2019:3480718.  Back to cited text no. 3
Behera M. Subcutaneous nodules in acute rheumatic fever–An analysis of age old dictums. Indian Heart J 1993;45:463-7.  Back to cited text no. 4
Wakhlu A, Sawlani KK, Himanshu D. Rheumatological manifestations of hansen's disease. Indian J Rheumat 2018;13:14-9.  Back to cited text no. 5
Bouhairie VE, Goldberg AC. Familial hypercholesterolemia. Cardiol Clin 2015;33:169-79.  Back to cited text no. 6
Turgeon RD, Barry AR, Pearson GJ. Familial hypercholesterolemia: Review of diagnosis, screening, and treatment. Can Fam Physician 2016;62:32-7.  Back to cited text no. 7
Sahu P, Mohanan S, Udayshankar C, Sinhasan S, Bhat R. Familial Hypercholesterolemia with Tendinous Xanthomas and Achilles Tendinitis – A Forgotten Dermato-Rheumatologic Association. Serbian Journal of Dermatology and Venereology, 2019:11:25-9.  Back to cited text no. 8
Koivunen-Niemelä T, Viikari J, Niinikoski H, Simell O, Alanen A. Sonography in the detection of achilles tendon xanthomata in children with familial hypercholesterolaemia. Acta Paediatr 1994;83:1178-81.  Back to cited text no. 9
Mathon G, Gagné C, Brun D, Lupien PJ, Moorjani S. Articular manifestations of familial hypercholesterolemia. Ann Rheum Dis 1985;44:599-602.  Back to cited text no. 10
Carroll GJ, Bayliss CE. Treatment of the arthropathy of familial hypercholesterolaemia. Ann Rheum Dis 1983;42:206-9.  Back to cited text no. 11
Rahman T, Hamzan NS, Mokhsin A, Rahmat R, Ibrahim ZO, Razali R, et al. Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study. Lipids Health Dis. 2017;16:81.  Back to cited text no. 12
Li D, You L, Fan S, Tan L. Xanthomatosis in bilateral hands mimicking rheumatoid arthritis: A case report. Medicine (Baltimore) 2017;96:e9399.  Back to cited text no. 13
Ayesh Haj Yousef MH, Shatnawi A, Khdeir M, Alawneh DK. Homozygous familial hypercholesterolaemia in two sisters misdiagnosed as rheumatoid arthritis. BMJ case reports, 2016, bcr2016216097.  Back to cited text no. 14
Schou AJ, Toftedal P, Christensen AE. Familial hypercholesterolemia misinterpreted as juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2011;9(Suppl 1):P228.   Back to cited text no. 15
Lemale J, Tounian P. Familial hypercholesterolemia in children and adolescents. Rev Prat 2019;69:1001-4.  Back to cited text no. 16


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3]


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