ABC | Volume 111, Nº5, November 2018

Case Report Rare Presentation of Dercum’s Disease in a Child with Abnormalities in Lipoprotein Metabolism Maria Cristina de Oliveira Izar, Henrique Andrade Rodrigues da Fonseca, Carolina Nunes França, Valéria Arruda Machado, Carlos Eduardo dos Santos Ferreira, Francisco Antonio Helfenstein Fonseca Escola Paulista de Medicina – Universidade Federal de São Paulo, São Paulo, SP – Brazil Mailing Address: Maria Cristina de Oliveira Izar • Alameda das Dracenas, 290. Postal Code 06539-240, Santana de Parnaíba, SP – Brazil E-mail: mcoizar@cardiol.br , mcoizar@terra.com.br Manuscript received February 17, 2018, revised manuscript April 10, 2018, accepted April 10, 2018 Keywords Adiposis Dolorosa ; Rare Diseases; Inflammation; Lipid Metabolism Disorders; Child; Dyslipidemias. DOI: 10.5935/abc.20180191 Adiposis dolorosa , or Dercum’s disease, is a subcutaneous accumulation of fat in the body accompanied by intense, chronic, and symmetrical pain, often disabling, and usually not responsive to conventional analgesics. It was first described by Dercum, recognized as a separate disease in 1892, 1 and further reported by White in 1899. 2 Termed in the literature Dercum’s disease, Morbus Dercum, lipomatosis dolorosa , adiposalgia, adiposis dolorosa , and adipose tissue rheumatism, this condition is more prevalent in young women, aged 35 to 50 years, and affects preferably those in the post-menopause phase. 1-3 Adiposis dolorosa can also occur in multiple familial lipomatosis, a condition associated with multiple lipomas. 4 Other symptoms and signs include psychiatric (depression, anxiety, sleep disturbances, memory and concentration impairment), cardiovascular (tachycardia), pulmonary (shortness of breath), rheumatological (fatigue, weakness, joint andmuscle aches) and gastrointestinal (bloating, constipation) disorders. 3 Dercum’s disease was described as a general disease of the lymphatic system. In 2014, Rasmussen et al. 5 suggested that this is a lymphovascular disorder with abnormalities in the adipose tissue deposition and lymphatic transport, showing that lipomas appeared to be fed and drained by functional lymphatics. In addition, Huang et al. 6 have reinforced the importance of lymphatic system in cholesterol transport, showing the association with ApoA1, HDL formation, and lymphatic transport to the blood for scavenging by the HDL receptor, or scavenger receptor B1. 6 Although the majority of Dercum’s disease cases occurs sporadically, there are reports suggesting an autosomal dominant inheritance, with variable expression. The prevalence and the pathophysiology are alsounknown, but inflammation, endocrine, adipose tissue, and nervous system dysfunction, trauma, mechanical pressure on the nerves, are possible etiological conditions. 3-4 Considering the abnormal fat deposition, presence of inflammation, and possible metabolic and lipoprotein abnormalities, an increased risk for atherosclerosis should be expected. Albeit the increased fat mass accumulation in Dercum’s disease, it has not been yet reported in association with cardiovascular diseases. 7 Dercum’s disease seems to be rare in children, as the disease usually manifests in adulthood. In the present study, we report the rare case of a child with Dercum’s disease associated with presence of marked dyslipidemia and inflammation. An eight-year-old female child presented with lipomatosis in the backbone, with pain, who became resistant to standard pain-relief medications within one year. Magnetic resonance imaging (MRI) of the backbone revealed the presence of multiple diffuse lipomas (Figure 1), reinforcing the suspicion of Dercum’s disease. 1,2 Many surgical procedures were performed to remove those lipomas, but abnormal fat deposition and pain progressed over time, with impairment of daily activities, requiring combined analgesic medication, including morphine. Lipomas increased in number and size, affecting the backbone, legs, arms, face, neck, and abdominal wall. Fat deposition also included liver steatosis, confirmed by MRI. The patient is currently 13 years-old with sexual maturity range II (by Tanner staging). It is believed that this is a variant presentation of Dercum’s disease, first classified as a localized nodular form that further became generalized and affected a prepubescent girl. This diagnosis was confirmed after ruling out other pathologies with similar clinical presentation, such as those described by Hansson et al. 3 in 2012. There were no reports of lipomatosis in any other family member, including parents and siblings. Laboratory analyses before therapy, to appraise glucose metabolism, lipids and genetic factors revealed hyperinsulinemia (31.8 uU/ml), with normal fasting glucose levels (81 mg/dl) and HbA1c (3.8%), at baseline. Fasting lipid analyses showed low HDL-c (19.3 mg/dl) and Apo A1 (112 mg/dl) concentrations, hypertriglyceridemia (320 mg/dl), hyperbetalipoproteinemia (118 mg/dl), LDL-c in the normal range (108 mg/dl), but with increase in small dense LDL particles (> 40 mg/dl). Her HDL map showed high pre‑beta HDL (29 mg/dl; normal < 17 mg/dl), normal alpha 4 HDL (normal< 5.3 mg/dL), high HDL-3 (33mg/dl; normal < 13.5 mg/dl), low HDL 2 (19.3 mg/dl; normal > 45 mg/dl) and HDL-1 (9.5 mg/dl; normal > 29.3 mg/dl), thus showing the incapacity of larger HDL particles formation, with an excess of smaller, less protective particles. Cholesterol synthesis marker (lathosterol) was below detection level, whereas beta-sitosterol/cholesterol and campesterol/cholesterol ratios were 115 and 149 µmol/mmol of cholesterol (in the normal range). Inflammatory markers, such as high sensitivity-C-reactive protein (13.8 mg/L) and lipoprotein-associated phospholipase A2 (Lp-PLA2, 375ng/ml), were very high. The child did not present signs of thyroid dysfunction. Sexual and intermediary hormones androstenedione (219 ng/mL), 755