Unveiling Familial Hypercholesterolemia-Review, Cardiovascular Complications, Lipid-Lowering Treatment and Its Efficacy.

Familial hypercholesterolemia (FH) is a genetic disorder primarily transmitted in an autosomal-dominant manner. We distinguish two main forms of FH, which differ in the severity of the disease, namely homozygous familial hypercholesterolemia (HoFH) and heterozygous familial hypercholesterolemia (HeFH). The characteristic feature of this disease is a high concentration of low-density lipoprotein cholesterol (LDL-C) in the blood. However, the level may significantly vary between the two mentioned types of FH, and it is decidedly higher in HoFH. A chronically elevated concentration of LDL-C in the plasma leads to the occurrence of certain abnormalities, such as xanthomas in the tendons and skin, as well as corneal arcus. Nevertheless, a significantly more severe phenomenon is leading to the premature onset of cardiovascular disease (CVD) and its clinical implications, such as cardiac events, stroke or vascular dementia, even at a relatively young age. Due to the danger posed by this medical condition, we have investigated how both non-pharmacological and selected pharmacological treatment impact the course of FH, thereby reducing or postponing the risk of clinical manifestations of CVD. The primary objective of this review is to provide a comprehensive summary of the current understanding of FH, the effectiveness of lipid-lowering therapy in FH and to explain the anatomopathological correlation between FH and premature CVD development, with its complications.

Truxima (rituximab-abbs) for Periocular Xanthogranuloma with Adult-Onset Asthma and Systemic IgG4-Related Disease.

A 58-year-old female with a 3-year history of adult-onset asthma, bilateral blepharoptosis, dry eye, and yellow-orange xanthelasma-like plaques extensively involving both upper eyelids presented with a diagnosis of adult-onset asthma with periocular xanthogranuloma (AAPOX) and systemic IgG4-related disease. Over the next 8 years, she received 10 intralesional triamcinolone injections (40-80 mg) in the right upper eyelid, 7 intralesional triamcinolone injections (30-60 mg) in the left upper eyelid, underwent right anterior orbitotomy twice followed by 4 doses of rituximab (1000 mg intravenous infusion) without regression of the AAPOX. The patient was then treated with 2 monthly doses of Truxima (1000 mg intravenous infusion), a biosimilar to rituximab. At the most recent follow-up, 13 months later, the xanthelasma-like plaques and orbital infiltration had markedly improved. To the best of the authors' knowledge, this is the first report of Truxima being used to treat AAPOX with systemic IgG4-related disease and to generate a sustained clinical response.

IgG4-related ophthalmic disease in association with adult-onset asthma and periocular xanthogranuloma: a case report.

A 54-year-old male presented with a three-year history of bilateral upper eyelid and peri-orbital swelling and adult-onset asthma. Histopathology of a left orbital biopsy showed lymphoid follicles with foamy macrophages and Touton giant cells. Clinical, histological and radiological features were consistent with adult-onset asthma and periocular xanthogranuloma. Treatment with rituximab led to a complete clinical and radiological remission. Nine years later, his condition relapsed with a biopsy of the left orbit and lacrimal gland demonstrating features of IgG4-related disease and adult-onset asthma and periocular xanthogranuloma. Immunohistochemistry showed increased numbers of IgG4+ plasma cells (290 per high power field) and an elevated IgG4+/IgG+ plasma cell ratio of 480%. Involvement by both disorders in the orbit and ocular adnexa of a single patient has not previously been reported in the literature, to the best of our knowledge, and suggests a possible aetiologic or pathophysiologic association.

Differing clinical features between Japanese siblings with cerebrotendinous xanthomatosis with a novel compound heterozygous CYP27A1 mutation: a case report.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal-recessive lipid storage disorder caused by mutations in the CYP27A1 gene encoding the key enzyme in the bile acid synthesis, sterol 27-hydroxylase. Here, we report two Japanese CTX siblings with a novel compound heterozygous CYP27A1 mutation, showing different clinical phenotypes and responses to chenodeoxycholic acid (CDCA) therapy. CASE PRESENTATION: The proband, a 32-year-old man, who had chronic diarrhea, bilateral cataracts, and xanthomas, demonstrated progressive neurological manifestations including ataxia, and spastic paraplegia during a 5-year follow-up period despite normalization of serum cholestanol after initiation of CDCA treatment. He also exhibited cognitive decline although improvement had been observed at the beginning of treatment. Follow-up brain magnetic resonance imaging (MRI) revealed pronounced progressive atrophy in the cerebellum, in addition to expanding hyperintense lesions in the dentate nuclei, posterior limb of the internal capsule, cerebral peduncles, and inferior olives on T2-weighted images. In contrast, the two-year-younger sister of the proband presented with chronic diarrhea, cataracts, xanthomas, and intellectual disability but no other neurological symptoms at the time of diagnosis. CDCA treatment lead to improvement of cognitive function and there were no characteristic CTX-related MRI features during the follow-up period. The siblings shared a paternally inherited c.1420C > T mutation (p.Arg474Trp) and a maternally inherited novel c.1176_1177delGA mutation, predicting p.(Glu392Asp*20). CONCLUSIONS: Our cases suggest that early diagnosis and subsequent initiation of CDCA treatment are crucial before the appearance of characteristic MRI findings and severe neurological manifestations related to CTX. Further studies are required to elucidate mechanisms responsible for the clinical diversity of CTX and prognostic factors for long-term outcomes following initiation of CDCA treatment.

Naturopathic Self-Treatment of an Atypical Fibroxanthoma: Lessons for Dermatologic Surgery.

BACKGROUND: Alternative therapies are favored by some patients. In skin cancer, this may be to try to avoid surgery out of fear for the procedure and its functional or cosmetic consequences. Frequently, use of these therapies is not curative and can cause harm. Our objective is to detail a case where black salve was used as a natural remedy for an atypical fibroxanthoma and resulted in a severe burn. We highlight the challenges of communicating effective treatment options for those who have strong beliefs concerning natural remedies after a cancer diagnosis. CASE REPORT: A 78-year-old man was referred for excision of a small atypical fibroxanthoma of the scalp. He had reservations about conventional treatments, he initially declined surgery. Later, he was found to have a severe burn over the site of the biopsy-proven AFX, extending to 20% of his scalp. He was found to have been applying black salve. Hospital admission and multiple stages of scalp reconstruction with Head and Neck Surgery were required. CONCLUSION: For patients who desire to use alternative medicine, communication is all important. Integrative approaches to use traditional therapy while reconciling patient beliefs in natural medicine can improved oncologic, functional, and psychosocial outcomes. J Drugs Dermatol. 2018;17(6):683-685.

Achilles Tendon Xanthomas: Fat-Water Separation at Baseline and after Treatment.

Purpose To investigate the fat-water content of Achilles tendon xanthomas at baseline and after treatment and to compare this assessment with that of ultrasonography (US) and other magnetic resonance (MR) imaging-based parameters. Materials and Methods Forty-eight Achilles tendons with clinically apparent xanthomas in 24 patients with familial hypercholesterolemia (FH) (six men, 18 women; mean age ± standard deviation, 58 years ± 9) were compared with 20 Achilles tendons in 10 control subjects without FH (two men, eight women; mean age, 62 years ± 7). US imaging measurements (thickness, width, cross-sectional area, echogenicity) and 3.0-T MR imaging measurements (thickness, width, cross-sectional area, volume, and fat-water separation) of the Achilles tendons were obtained at baseline and in patients with FH at 3 and 6 months after treatment with probucol, a cholesterol-lowering agent. Nonparametric tests compared baseline data, whereas repeated-measures analyses assessed treatment change. Results At baseline, all US and MR imaging-based parameters were higher in xanthoma tendons compared with those in control tendons (all P < .05). The mean relative water content per unit volume was 71% higher (42.0% ± 6.7) in xanthoma tendons than in control tendons (24.5% 6 5.8; P < .001). After 6 months of cholesterol-lowering treatment, only MR imaging measurements of tendon volume (P = .007), relative fat (P = .041), and relative water content (P < .001) showed significant changes. As relative tendon fat content decreased with treatment, relative water content increased. Conclusion Most of the enlargement of Achilles tendon xanthomas is due to an increase in water content rather than fat. For depicting treatment change, relative tendon water content was the most sensitive parameter, followed by tendon volume and relative tendon fat content. © RSNA, 2017 Online supplemental material is available for this article.

Treatment of Xanthelasma Palpebrarum With Intralesional Pingyangmycin.

BACKGROUND: Xanthelasma palpebrarum (xanthelasma) is the most common type of cutaneous xanthoma, and many patients tend to seek medical treatments for cosmetic reasons. Many methods treating xanthelasma have been proposed, but none of these options can be regarded as a perfect solution. OBJECTIVE: To study and evaluate the intralesional injection treatment of xanthelasma with pingyangmycin, which has been widely used as a broad-spectrum antitumor antibiotic. MATERIALS AND METHODS: 21 lesions in 12 patients were treated by intralesional pingyangmycin. Photographs were taken before and after each treatment session. Patients were followed up for 7 to 36 months. RESULTS: All patients except one received satisfactory results after up to 2 sessions. Only 1 patient had a local recurrence 1 year after the treatment. No severe complications such as infection, atrophy, ulceration, or scar were noticed. CONCLUSION: Intralesional pingyangmycin is a cheap, effective, and safe treatment for xanthelasma, which has been well accepted by patients.

Adult-Onset Asthma Associated With Simultaneous Conjunctival, Eyelid, and Orbital Xanthogranulomatosis Responsive to Systemic Immunosuppression.

Adult xanthogranulomatous disease involving the ocular or orbital tissues is rare. The authors present a 63-year-old asthmatic woman with progressive left eyelid ptosis and fatigue in whom this diagnosis was clinically suspected on the basis of the characteristic waxy indurated yellow periocular and conjunctival lesions. These findings prompted an incisional biopsy which found evidence of Touton giant cells, necessitating a systemic evaluation which excluded the presence of hematological abnormalities or malignancy. The simultaneous occurrence of conjunctival, eyelid, and orbital xanthogranulomas has not been previously described in adult-onset asthma and periocular xanthogranuloma. The lesions were responsive to long-term systemic immunosuppression.

Adult-onset asthma associated with periocular xanthogranuloma: new diagnostic and therapeutic approaches in a very rare systemic disease.

PURPOSE: To report some novel findings concerning the systemic manifestations and treatment of adult-onset asthma and periocular xanthogranuloma, a rare type of non-Langerhans histiocytosis that can lead to important visual dysfunction. METHODS: A retrospective case series of 2 patients was evaluated for orbital and systemic manifestations using fluorodeoxyglucose positron emission tomography/CT and/or orbital MRI. Histological specimens were reviewed in all patients. Oral prednisone was initiated at 1 mg/kg daily and gradually tapered to a minimum effective dose. Efficacy was assessed on the basis of an objective observation of decreased swelling. RESULTS: One patient displayed original uptake foci involving intrathoracic lymphadenopathies, the trajectory of the paraumbilical vein and perirectal fat. Low-dose prednisone was able to induce a durable response in the authors' patients. CONCLUSIONS: Fluorodeoxyglucose positron emission tomography/CT may be useful for the diagnostic workup and follow-up assessment of patients with adult-onset asthma and periocular xanthogranuloma. Oral corticosteroids can be used successfully as first-line treatment in such patients.

Histiocyte-rich xanthomatous pseudotumor mimicking relapse on positron emission tomography imaging in an adolescent with primary mediastinal diffuse large B-cell lymphoma.

Inflammatory pseudotumors (IPTs) are rare, enigmatic lesions that may develop as a late manifestation of a reparative process. We describe the case of a teenager with primary mediastinal subtype of diffuse large B-cell lymphoma who developed an IPT at the site of the original lymphoma, mimicking relapse of disease on positron emission tomography/computed tomography imaging. This is the first report of IPT in a teenager with mediastinal lymphoma. This case is an important reminder of the limitations of positron emission tomography/computed tomography imaging in patients with lymphoma and stresses the importance of histologic confirmation of suspected treatment failure or relapse.

[Tuberous xanthomas in a pediatric patient: a clue to the early diagnosis of a severe and infrequent disease]. / Xantomas tuberosos en un paciente pediátrico: la clave en el diagnóstico precoz de una patología grave y poco frecuente.

Cutaneous xanthomas reflect lipid deposition on the skin and may be the only early manifestation of a childhoodonset dyslipidemia. Characteristics and distribution of the xanthomas signalize the underlying pathology, tuberous xanthomas being strongly associated with homozygous familial hypercholesterolaemia, an extremely rare condition. Its early detection provides a therapeutic window to prevent accelerated atherosclerosis and mortality. We present the case of a patient who started at two years with tuberous xanthomas, which were the diagnostic clue to identify the underlying homozygous familial hypercholesterolaemia.

Los xantomas cutáneos reflejan el depósito de lípidos en la piel y pueden ser la única manifestación temprana de dislipidemias de inicio en la infancia. Las características y distribución de los xantomas orientan a la patología de base; los xantomas tuberosos tienen una fuerte asociación con la hipercolesterolemia homocigota familiar, una patología muy infrecuente. Su detección temprana otorga una ventana terapéutica para prevenir la ateroesclerosis acelerada y la mortalidad. Se presenta el caso de una paciente que comenzó a los dos años con xantomas tuberosos, que fueron la clave diagnóstica para identificar la hipercolesterolemia homocigota familiar subyacente.