A 4 year-old male patient was referred to our institution by a dermatologist because of the gradually increasing number of xanthomas on the knees, elbows, and buttocks that first appeared when he was 3 years old. He was born after an uneventful pregnancy and delivery as the second child of apparently non-consanguineous parents. The family history for premature CVD was negative. His early development was normal. Extremely high levels of TC (24.8 mmol/L; 928 mg/dl), LDL-C (21.6 mmol/L; 834 mg/dl), and triglycerides (TGC) (5.0 mmol/L; 443 mg/dl) and low levels of HDL-cholesterol (HDL-C) (0.3 mmol/L; 11.6 mg/dl) were measured at the first exam. Elevated levels of TC and LDL-C were also found in his parents, sister, and daughter (afterward) (). The clinical and biochemical picture suggested the diagnosis of HoFH, which was later confirmed genetically; a previously described homozygous mutation c.1754T>C (p.Ile585Thr) was found in the patient, while both his parents, his sister, and daughter were confirmed to be heterozygotes for the same mutation. Despite treatment with a highly restrictive diet, cholestyramine, statins, and LDL-apheresis (the exact timeline is described in , ), xanthomas extended progressively. At 7 years, increased IMT of the common carotid artery was measured with ultrasound. At 12 years, echocardiographically valvular aortic stenosis and aortic regurgitation were observed. Levels of LDL-C at the time of LDL-apheresis ranged from 2.4 to 11.6 mmol/L (92.8–449 mg/dl) in between treatments. Lp(a) levels ranged from 756 mg/L at the beginning to 135 mg/L after the last treatment. He refused to have apheresis for 3 years, but with psychological support, he continued.\nDue to progressive worsening conditions (valvular aortic stenosis and aortic regurgitation), the patient underwent deceased-donor orthotopic LT when he was 16 years old. There were no intraoperative or postoperative complications. The patient's immunosuppression regimen first consisted of tacrolimus, methylprednisolone, and ursodeoxycholic acid, but the steroid was gradually tapered. Six months after the LT, the patient's xanthomas had regressed, and the TC levels have fallen to 5.2 mmol/L (201 mg/dl). A year and a half after the LT, the TC level was at the lowest value [4.4 mmol/L (170 mg/dl)]. Two years after the LT, an episode of acute rejection developed, which was successfully treated with steroids, and the TC level was measured at 5.1 mmol/L (197 mg/dl).\nEight years after the LT, the patient who was then 24 years old was doing well. The patient had been on maintaining tacrolimus therapy. His cutaneous xanthomas completely resolved. An echocardiogram showed complete regression of aortic stenosis, and his IMT was in the normal range (0.6 mm on both common carotid arteries). His TC and LDL-C levels were 5.4 and 3.9 mmol/L, respectively (209 and 151 mg/dl), and Lp(a) levels were 111 mg/L. His LDL-C levels were lower than the LDL-C levels measured on the same occasion in his parents and sister (). Twelve years after the LT, the PWV velocity was measured with ultrasound, and the values were in the normal range (4.6 ± 0.2 m/s) The RHI was 2.46.\nAfterward, the patient was not responding to the invitations from our clinic for almost 5 years (at that time, he was only seeing his gastroenterologist) and returned for a follow-up visit only in the year 2018, almost 14 years after the LT. The total regression of xanthomas was evident at the last visit. At that point, he was almost 30 years old, employed, and had a child who was scheduled for a later visit at our lipid clinic and was confirmed to be heterozygote for the same mutation. His work was mostly sedentary, and he was not very physically active. In addition, he started smoking. He was still taking tacrolimus, but no antilipemic treatment was prescribed to him after the LT. His TC and LDL-C levels were 7.2 mmol/L (278 mg/dl) and 5.3 mmol/L (205 mg/dl), respectively. In addition, an elevated ApoB level was present (1.48 g/L), while his Lp(a) level was normal (145 mg/L). Furthermore, hsCRP was 2.11 mg/L. His carotid IMT level had increased to 0.90 mm on both carotid arteries (abnormal result for his age) (). He was normotensive (97/67 mmHg), and his BMI was 18 kg/m2. Liver enzyme levels were in the normal range. The HbA1c level was 4.8%, and the fasting insulin level was 4.3 mE/L. The glomerular filtration rate was above 90 ml/min. At the last visit to our lipid clinic, the patient was recommended to start statin treatment (rosuvastatin, 10 mg) and was transitioned to the adult lipid clinic, where his first visit was scheduled in early 2019. At that visit, his TC and LDL-C levels were 7.36 mmol/L (284.6 mg/dl) and 5.9 mmol/L (228.15 mg/dl), respectively.
An 18-year-old woman complained of swelling with morning stiffness in multiple small joints, including the metacarpophalangeal (MCP) and proximal interphalangeal of both hands, and the 1st metatarsophalangeal joint of the left foot, without pain, fever, or signs of Raynaud symptoms. In recent years, the swelling in the joints worsened and joint deformation occurred; in addition, an oval mass appeared on the lateral margin of the right foot. When she was 2 years old, she had multiple nodules on the elbow joint, popliteal fossa, and hip, without any inducements. After surgical resection, the lesion relapsed again symmetrically so that the patient underwent an open excisional biopsy bilaterally on the elbows, first web, heel, and popliteal fossa under general anesthesia in our hospital 3 years ago. After the retraction of the subcutaneous tissue, 4 cm × 4 cm × 4 cm (the largest), solid, soft, sharply defined, yellowish masses were detected. A biopsy specimen showed juvenile xanthogranuloma (Fig. ). Immunohistochemical staining revealed that CD68 (+), CK (−), Ki-67 (+), CD1a (−), S100 (−), and acid fast staining (−).\nHer routine laboratory examination showed that serum cholesterol and low-density lipoprotein cholesterol (LDLC) levels were above normal, and the levels of antistreptolysin O and anticyclic citrullinated peptide antibodies (Anti_ccp) were also higher than the normal range; but the levels of erythrocyte sedimentation rate, antiextractable nuclear antigen, human leukocyte antigen-B27, rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibodies, complement, total protein, C-reactive protein, and blood glucose were normal.\nComputed tomography of the right hand showed that there was only soft tissue swelling on multiple small joints, which revealed hypointensities on T1-weighted images and hyperintensities on T2-weighted images (Figs. and ). In additional, there was an interesting finding of an RA appearance, which was thickened, fusiform, and not uniformly enhanced (Fig. ). Synovial hyperplasia or inflammation of the small joints was also observed.\nRegarding our findings and the clinical progression, the patient underwent an open excisional biopsy and tenolysis of the 3rd MCP joint in her left hand. A biopsy specimen showed several foamy cells in fibrous and fat tumor-like hyperplasia (Fig. ). Further, immunohistochemical staining revealed CD68 (+), S100 (−), MDM-2 (+), HHF (focal+), LCA (+), and Ki-67 (5%+). Finally, it was diagnosed as xanthoma. After 3 months of follow-up, no recurrence or complications were detected regarding a full range of motion remaining of the affected joints.\nIn this case, the patient was an 18-year-old woman with positive Anti_ccp and morning stiffness, which was easily misdiagnosed for RA, especially in the early stage. According to early rheumatoid arthritis (ERA) diagnostic criteria[ (Table ), the patient could be confirmed as ERA. However, RA is defined as a systemic disease of unknown etiology, manifesting as chronic, symmetric, polyarthritis. When there is inflammation, there should be pain. In this case, no joint pain was detected, which did not conform to the typical performance of RA. Taking laboratory examination results into consideration, the levels of total cholesterol and triglycerides were also above normal; it should also be considered that this disease related to whole body metabolic abnormalities or abnormal lipid deposition. It is imperative to evaluate the lesion with the biopsy, because the treatment principle of xanthoma is essentially different from the RA. For the xanthoma, the basic treatment principle is a balanced diet and reducing blood fat, namely, to strengthen health education, adjust the diet structure, restrict calories in food intake, give lipid-decreasing drugs regularly, and detect hematic fat on a regular basis. Moreover, xanthomas on different parts of the body should be treated accordingly. For example, nodular xanthoma on the Achilles tendon can be resected; however, eyelid xanthoma can be treated in steps by using freeze or laser surgery, etc.\nThe patient was treated with 20 mg of atorvastatin daily to reduce blood fat during her hospitalization. Her cholesterol and LDLC levels fell from 16.12 and 13.30 mmol/L to 11.92 and 10.20 mmol/L, respectively. After being discharged, she was switched to 10 mg of rosuvastatin daily. However, during her regular 3-month follow-up, her lipid level effect was poorly controlled—the levels of cholesterol and LDLC were higher.