๐ ็ธฝ็ฎ้ ๏ฝ ๐ ่ฑๆๅๆ๏ผๆฌ็ฏ๏ผ ๏ฝ ๐ ๅฎๆด็ฟป่ญฏ ๏ฝ โญ ็ฒพ่ฏ็ญ่จ
TREATMENT
Therapeutic interventions for lipodystrophy syndromes focus on three aspects: (1) cosmetic concerns; (2) metabolic derangements; and (3) systemic associations. For volume loss due to lipoatrophy, soft tissue fillers and autologous fat transplantation can be helpful, albeit temporarily. Solid synthetic volumetric midfacial implants, constructed using computer-aided design and manufacturing technology, may offer a more durable correction of the defects. A conservative approach can be undertaken when spontaneous improvement may occur as in pressure-induced or traumatic lipoatrophy. For lipohypertrophy, liposuction and lipectomy represent moderately effective treatments. Switching to purified human insulin may improve lipoatrophy at sites of insulin injections, but it may require 1 to 3 years.
The treatment of metabolic abnormalities requires input from dieticians and endocrinologists. Several medications are used to address insulin resistance and glucose control including thiazolidinediones, metformin, sulfonylureas, dipeptidyl peptidase 4 inhibitors (โgliptinsโ), glucagon-like peptide 1 agonists, sodium-glucose cotransporter-2 inhibitors (gliflozins), and insulin. Treatment of hypertriglyceridemia includes diet, fibrates, omega-3 fatty acids, niacin, and statins. For refractory metabolic disease, bariatric surgery can be considered.
Of note, recombinant methionyl human leptin (metreleptin) is FDA-approved for the treatment of congenital or acquired generalized lipodystrophy. Metreleptin binds to hypothalamic leptin receptors, leading to decreased appetite and increased insulin sensitivity. Marked improvements in glycemic control, hyperlipidemia, hepatic steatosis, and diabetic complications such as proteinuria have been reported. Metreleptin is generally well tolerated, with sustained effects as long as neutralizing anti-metreleptin antibodies do not develop. There is also a black box warning regarding risk of lymphoma. It has also been shown to be an effective steroid-sparing therapy for the acquired generalized lipodystrophy that can follow allogeneic hematopoietic stem cell transplantation.
In acquired partial lipodystrophy, longitudinal evaluation will allow identification of associated autoimmune connective tissue diseases (e.g. lupus, dermatomyositis), thyroid disease, or renal disease that requires treatment. Such treatment may halt the progression of the lipodystrophy. If proteinuria, a low serum C3, and C3 nephritic factor (C3NeF) are detected, a renal biopsy to exclude MCGN II may be required. Encouraging results following the use of IVIg have been reported, presumably due to the IVIg containing neutralizing antibodies against C3NeF. When no secondary cause is found, treatment is limited.
Additional potential therapies include volanesorsen, an antisense oligonucleotide that binds to apoC-III mRNA and is EMA-approved for familial chylomicronemia syndrome but not FDA-approved because of the risk of thrombocytopenia. Both evinacumab, a human angiopoietinlike 3 (ANGPTL3) blocking antibody that is currently FDA-approved for homozygous familial hypercholesterolemia, and gemcabene calcium, a dialkyl ether dicarboxylic acid which has orphan drug designation for the same indication, have also shown efficacy in patients with severe hypertriglyceridemia. Setmelanotide, a melanocortin-4 receptor agonist, is FDA-approved for obesity due to deficiencies of proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) and may reduce triglyceride levels.