Lipodystrophy

Lipodystrophy can be divided into the following types:{{cite book |author1=James, William D. |author2=Berger, Timothy G. |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6 |display-authors=etal}}{{rp|495–7}}

• Congenital lipodystrophy syndromes
• Congenital generalized lipodystrophy (Berardinelli-Seip syndrome)
• Familial partial lipodystrophy
• Marfanoid–progeroid–lipodystrophy syndrome
• Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome{{cite journal | vauthors = Torrelo A, Patel S, Colmenero I, Gurbindo D, Lendínez F, Hernández A, López-Robledillo JC, Dadban A, Requena L, Paller AS | title = Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome | journal = Journal of the American Academy of Dermatology | volume = 62 | issue = 3 | pages = 489–95 | date = March 2010 | pmid = 20159315 | doi = 10.1016/j.jaad.2009.04.046 }}
• Acquired lipodystrophy syndromes
• Acquired partial lipodystrophy (Barraquer-Simons syndrome)
• Acquired generalized lipodystrophy
• Centrifugal abdominal lipodystrophy (Lipodystrophia centrifugalis abdominalis infantilis)
• Lipoatrophia annularis (Ferreira-Marques lipoatrophia)
• Localized lipodystrophy
• HIV-associated lipodystrophy

Due to an insufficient capacity of subcutaneous tissue to store fat, fat is deposited in non-adipose tissue (lipotoxicity), leading to insulin resistance. Patients may display hypertriglyceridemia, severe fatty liver disease and little or no adipose tissue.{{cite journal | vauthors=Bruder-Nascimento T, Kress TC, Belin de Chantemele EJ | title=Recent advances in understanding lipodystrophy: a focus on lipodystrophy-associated cardiovascular disease and potential effects of leptin therapy on cardiovascular function | journal=F1000Research | volume=8 | pages=F1000 Faculty Rev-1756 | year=2019 | doi = 10.12688/f1000research.20150.1 | pmc = 6798323 | pmid=31656583 | doi-access=free }} Average patient lifespan is approximately 30 years before death, with liver failure being the usual cause of death. In contrast to the high levels seen in non-alcoholic fatty liver disease (NAFLD) associated with obesity, leptin levels are very low in lipodystrophy.

{{Main|Lipohypertrophy}}

Lipodystrophy can appear as a lump or small dent in the skin that forms when a person performs injections repeatedly in the same spot. These types of lipodystrophies are harmless and can be avoided by changing (rotating) the locations of injections. For those with diabetes, using purified insulins and new needles with each injection may also help. (Although, in some cases, rotation of the injection sites may not be enough to prevent lipodystrophy.){{cn|date=May 2024}}

Some of the side-effects of lipodystrophy are the rejection of the injected medication, the slowing down of the absorption of the medication, or trauma which can cause bleeding that, in turn, causes rejection of the medication. In any of these scenarios, the dosage of the medication, such as insulin for diabetics, becomes impossible to gauge correctly and the treatment of the disease for which the medication is administered is impaired, thereby allowing the condition to worsen.{{cn|date=May 2024}}

{{Main|HIV-associated lipodystrophy}}

Lipodystrophy can be a possible side effect of certain antiretroviral drugs. Lipoatrophy is most commonly seen in patients treated with thymidine analogues and other older HIV drug treatments such as the nucleoside reverse transcriptase inhibitors [NRTIs] {{cite journal |vauthors=Carr A, Workman C, Smith DE, Hoy J, Hudson J, Doong N, Martin A, Amin J, Freund J, Law M, Cooper DA |date=July 2002 |title=Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial |journal=JAMA |volume=288 |issue=2 |pages=207–15 |doi=10.1001/jama.288.2.207 |pmid=12095385 |doi-access=free}} like zidovudine (AZT) and stavudine (d4T).{{cite journal |vauthors=John M, McKinnon EJ, James IR, Nolan DA, Herrmann SE, Moore CB, White AJ, Mallal SA |date=May 2003 |title=Randomized, controlled, 48-week study of switching stavudine and/or protease inhibitors to combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected patients |journal=Journal of Acquired Immune Deficiency Syndromes |volume=33 |issue=1 |pages=29–33 |doi=10.1097/00126334-200305010-00005 |pmid=12792352 |s2cid=22845453 |doi-access=free}} Other lipodystrophies manifest as lipid redistribution, with excess, or lack of, fat in various regions of the body. This is often most noticeable in the face. These include, but are not limited to, having sunken cheeks and/or "humps" on the back or back of the neck (also referred to as buffalo hump)[http://www.medicinenet.com/script/main/art.asp?articlekey=19678 Physical and Biochemical Changes in HIV Disease] Eric S. Daar, M.D. MedicineNet, Accessed 22 September 2007 which also exhibits due to excess cortisol (a so-called "stress" hormone).

The diagnosis is a clinical one, usually established by an experienced endocrinologist.Using a skinfold caliper to measure skinfold thickness in various parts of the body or a total body composition scan using Dual-energy X-ray Absorptiometry may also help identify the subtype.{{cite journal | vauthors = Guillín-Amarelle C, Sánchez-Iglesias S, Castro-Pais A, Rodriguez-Cañete L, Ordóñez-Mayán L, Pazos M, González-Méndez B, Rodríguez-García S, Casanueva FF, Fernández-Marmiesse A, Araújo-Vilar D | title = Type 1 familial partial lipodystrophy: understanding the Köbberling syndrome | journal = Endocrine | volume = 54 | issue = 2 | pages = 411–421 | date = November 2016 | pmid = 27473102 | doi = 10.1007/s12020-016-1002-x | s2cid = 19689303 | hdl = 10347/32433 | hdl-access = free }} Dual-energy X-ray Absorptiometry may be useful by providing both regional %fat measurements, and direct visualization of fat distribution by means of a "fat shadow".{{cite journal | vauthors = Meral R, Ryan BJ, Malandrino N, Jalal A, Neidert AH, Muniyappa R, Akıncı B, Horowitz JF, Brown RJ, Oral EA | title = "Fat Shadows" From DXA for the Qualitative Assessment of Lipodystrophy: When a Picture Is Worth a Thousand Numbers | journal = Diabetes Care | volume = 41 | issue = 10 | pages = 2255–2258 | date = October 2018 | pmid = 30237235 | pmc = 6150431 | doi = 10.2337/dc18-0978 }} A genetic confirmation is sometimes possible, depending on the subtype. However, in up to 40% of partial lipodystrophy patients, a causative gene has not been identified.

Leptin replacement therapy with human recombinant leptin metreleptin has been shown to be an effective therapy to alleviate the metabolic complications associated with lipodystrophy, and has been approved by the FDA for the treatment of generalized lipodystrophy syndromes.{{cite journal | vauthors = Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, Wagner AJ, DePaoli AM, Reitman ML, Taylor SI, Gorden P, Garg A | title = Leptin-replacement therapy for lipodystrophy | journal = The New England Journal of Medicine | volume = 346 | issue = 8 | pages = 570–8 | date = February 2002 | pmid = 11856796 | doi = 10.1056/NEJMoa012437 | doi-access = free }} In Europe based on EMA, metreleptin should be used in addition to diet to treat lipodystrophy, where patients have loss of fatty tissue under the skin and build-up of fat elsewhere in the body such as in the liver and muscles. The medicine is used in: adults and children above the age of two years with generalised lipodystrophy (Berardinelli-Seip syndrome and Lawrence syndrome) and in adults and children above the age of 12 years with partial lipodystrophy (including Barraquer-Simons syndrome), when standard treatments have failed.{{Cite web|url=https://www.ema.europa.eu/en/medicines/human/EPAR/myalepta|title=Myalepta {{!}} European Medicines Agency|website=www.ema.europa.eu|date=17 September 2018 |access-date=2019-01-08}}

Volanesorsen is an Apo-CIII inhibitor{{cite journal | vauthors = Gaudet D, Brisson D, Tremblay K, Alexander VJ, Singleton W, Hughes SG, Geary RS, Baker BF, Graham MJ, Crooke RM, Witztum JL | title = Targeting APOC3 in the familial chylomicronemia syndrome | journal = The New England Journal of Medicine | volume = 371 | issue = 23 | pages = 2200–6 | date = December 2014 | pmid = 25470695 | doi = 10.1056/NEJMoa1400284 | doi-access = free }}{{cite journal | vauthors = Gaudet D, Alexander VJ, Baker BF, Brisson D, Tremblay K, Singleton W, Geary RS, Hughes SG, Viney NJ, Graham MJ, Crooke RM, Witztum JL, Brunzell JD, Kastelein JJ | title = Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia | journal = The New England Journal of Medicine | volume = 373 | issue = 5 | pages = 438–47 | date = July 2015 | pmid = 26222559 | doi = 10.1056/NEJMoa1400283 | s2cid = 205096489 | doi-access = free }} that is currently being investigated as a potential therapeutic to reduce levels of hypertriglycerides in Familial Partial Lipodystrophy patients in the BROADEN study.{{Cite news|url=https://clinicaltrials.gov/ct2/show/NCT02527343|title=The BROADEN Study: A Study of Volanesorsen (Formerly ISIS-APOCIIIRx) in Patients With Familial Partial Lipodystrophy - Full Text View - ClinicalTrials.gov|access-date=2018-03-31|language=en}}

Congenital lipodystrophy (due to inherited genetic defect) is estimated to be extremely rare, possibly affecting only one per million persons.{{cite journal | vauthors=Polyzos SA, Perakakis N, Mantzoros CS | title=Fatty liver in lipodystrophy: A review with a focus on therapeutic perspectives of adiponectin and/or leptin replacement| journal=Metabolism: Clinical and Experimental | volume=96| pages=66–82 | year=2019 | doi = 10.1016/j.metabol.2019.05.001 | pmid=31071311 | s2cid=195661123}} Acquired lipodystrophy is much more common, especially affecting persons with HIV infection.

• Keppen–Lubinsky syndrome
• Lipoedema
• Cutis laxa

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{{Medical resources

| DiseasesDB = 30066

| ICD11 = {{ICD11|EF01}}, {{ICD11|LD27.6}}

| ICD10 = {{ICD10|E|88|1|e|70}}

| ICD9 = {{ICD9|272.6}}

| ICDO =

| OMIM =

| MedlinePlus =

| eMedicineSubj = med

| eMedicineTopic = 1307

| eMedicine_mult = {{eMedicine2|med|3523}}

| MeshID = D008060

}}

{{Lipid metabolism disorders}}

{{Disorders of subcutaneous fat}}

Category:Conditions of the subcutaneous fat