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Acquired Partial Lipodystrophy

Barraquer-Simons Syndrome

Acquired partial lipodystrophy (APL) most likely stems from autoimmune pathophysiological mechanisms and is characterized by the loss of adipose tissue in the upper body - the trunk, the arms, and the abdomen in adolescence and early adulthood. The condition is by far more frequent in females compared to males. Contrary to other types of lipodystrophies, metabolic defects such as diabetes mellitus and hypertriglyceridemia, are rarely encountered. The diagnosis is made through a detailed clinical and immunological workup, whereas treatment principles include dietary changes, physical activity, and use of various drugs if insulin or triglyceride correction is necessary.


Presentation

The clinical presentation of APL starts mainly in early adolescence and adulthood and is distinguished by the loss of adipose tissue that is restricted to the upper part of the body [1] [2]. A cephalocaudal progression of fat loss is observed, initially starting at the face and neck area, followed by the upper extremities, the thorax, and finally the upper abdomen [2] [3] [4] [5]. Interestingly, the gluteal regions, the hips, and the lower extremities (including the feet and soles) are intact and may even accumulate excessive amounts of adipose tissue in later life, which is particularly frequent in female patients [1] [2] [3] [4] [5] [6]. One of the main distinguishing features of APL compared to other forms of lipodystrophy is the relative absence of metabolic derangements, examples being diabetes mellitus (DM), hypertriglyceridemia, and low circulating levels of HDL cholesterol [1] [2] [4]. Studies show that approximately 9% of APL patients suffer from diabetes mellitus and impaired glucose tolerance, the majority being females [1] [2].

Cushingoid
Turkish
  • METHODS: In this nationwide cohort study, we evaluated 21 Turkish patients with APL who were enrolled in a prospective follow-up protocol. Subjects were investigated for metabolic abnormalities. Fat distribution was assessed by whole body MRI.[ncbi.nlm.nih.gov]
Recurrent Bacterial Infection
  • Recurrent bacterial infections, if severe, might be managed with prophylactic antibiotics.[en.wikipedia.org]
Sputum
  • Reports of real-time polymerase chain reaction (PCR) for tuberculosis, sputum for acid-fast bacilli, and antinuclear antibody were negative. Lipid profiles, liver and renal function tests, random blood sugar, and thyroid profile were also normal.[jiaomr.in]
Retinal Pigmentation
  • Retinal pigment alterations, drusen and subretinal neovascularisation were seen without evidence for membranoproliferative glomerulonephritis.[ncbi.nlm.nih.gov]
  • She had marked bilateral drusen and retinal pigment … View Full Text Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service.[pmj.bmj.com]
Loss of Fat of the Upper Body
  • APLD is phenotypically characterised by a loss of fat in the upper body segment, namely, in the face, trunk, and arms. In the lower body segment, the subcutaneous fat depots are spared or even increased.[arthritisresearch.us]
  • With APL, a progressive loss of fat from the upper body that spares the lower body in children under the age of 16 is suggestive of a diagnosis.[rarediseases.org]
Absence of Subcutaneous Fat
  • The physical appearance of patients with familial and acquired PL may be more difficult to discern compared with generalized lipodystrophy (GL) where patients have a stark absence of subcutaneous fat (Figure 1) [ 2 ].[omicsonline.org]
Fear
  • One of the most feared complications of APL is kidney failure, which necessitates a detailed assessment of the renal system when the diagnosis is made. Treatment focuses on dietary changes and implementation of regular physical exercise.[symptoma.com]
Dysmenorrhea
  • Also, it revealed spontaneous miscarriage during her third pregnancy 18 years back and repeated history of gynecological problems such as dysmenorrhea.[jiaomr.in]

Workup

Clinical assessment of patients is the first and perhaps the most important step of the workup for patients in whom lipodystrophy is suspected. A detailed history that covers the onset of symptoms and their progression can provide vital clues, whereas a family history is vital for excluding familial syndromes (Congenital generalized lipodystrophy or Berardinelli-Seip syndrome, and Familial partial lipodystrophy, transferred through autosomal recessive and autosomal dominant patterns of inheritance, respectively) [5] [6]. The physical examination is sufficient to determine the areas that are affected by changes in the amount of adipose tissue, but in order to make a definite diagnosis, follow-up laboratory studies need to be conducted. Key findings in patients with APL are low complement C3 levels and the presence of a polyclonal immunoglobulin C3 nephritic factor [1] [2] [5] [6] [7]. Additional tests that need to be carried out are a full lipid profile, glucose levels, hemoglobin 1Ac, as well as liver transaminases [6]. Because membranoproliferative glomerulonephritis (MPGN) is estimated to occur in about 20% of cases several years after the diagnosis is made, a biopsy of the kidney in the presence of undisclosed proteinuria is beneficial [6]. Systemic lupus erythematosus (SLE) and dermatomyositis have been described as important factors in the pathogenesis of APL [1] [4] [7], suggesting that a thorough immunological workup should be conducted. Although the genetic basis of the disease is not fully understood, genetic testing for lamin B2 (LMB2) genes can be performed, since these mutations have shown to be present [2].

Treatment

Having in mind the fact that acquired partial lipodystrophy is rarely accompanied by metabolic changes, diet and physical activity are the cornerstones of treatment [3]. A balanced intake of macronutrients (the proportion of 50-60% carbohydrates, 20-30% fat, and 10-20% protein has been advised) and a special attention to prevent overfeeding (which can promote hepatic steatosis and diabetes mellitus), coupled with a properly designed program of exercise has proven to be effective in the management of APL [3] [5]. In more detail, simple carbohydrates should be avoided or replaced by complex carbohydrates that are high in fiber, and their consumption must be in combination with either protein or fat [6]. When diabetes mellitus, hypertriglyceridemia, or both are present, pharmacologic therapy is indicated. Either fibrates or statins can be given to reduce circulating triglyceride levels, whereas oral administration of metformin, insulin, sulfonylureas, or thiazolidinediones is recommended for achieving optimal glucose concentrations [3] [5] [6]. Other known therapies include plasmapheresis (used in the setting of very high triglycerides, mainly to prevent pancreatic damage), leptin replacement therapy, and highly concentrated insulin [8] [9] [10] [11].

Prognosis

The prognosis of acquired partial lipodystrophy mainly depends on a timely diagnosis and the extent of kidney damage caused by membranoproliferative glomerulonephritis (MPGN) [1] [4]. Although rare, patients in whom end-stage renal disease developed and required renal transplantation have been documented [4]. For this reason, early recognition must occur.

Etiology

The exact cause of acquired partial lipodystrophy (APL) remains to be elucidated, but an autoimmune origin is most likely. The reason for such claims lies in the fact that the circulating auto-antibody C3 nephritic factor is present in the vast majority of cases and that systemic autoimmune conditions such as SLE and dermatomyositis are present in a small, but a significant portion of individuals [1] [2] [5]. On the other hand, mutations involving the lamin B2 (LMNB2) gene have been confirmed in individuals with APL, but their exact role in the pathogenesis of the disease remains unclear [2]. Interestingly, some studies have observed that fat loss and the development of APL occurred after certain infections, such as measles virus infection, but a clear connection is yet to be made [1] [4].

Epidemiology

Acquired partial lipodystrophy is a rare disorder, as approximately 250 cases described in the literature by the end of the 20th century [4]. A significant predilection toward female gender is confirmed across several reports, with a female-to-male ratio reaching up to 4-8:1 [4] [5] [6]. The onset of symptoms is typically seen in adolescence or adulthood, but some authors reported a median onset of symptoms at 7 years of age [1].

Sex distribution
Age distribution

Pathophysiology

The pathogenesis model of acquired partial lipodystrophy is not completely clear. The term "acquired" denotes a secondary event that produces the characteristic pattern of fat loss, such as infection (measles), SLE, and dermatomyositis, but their association needs solid confirmation [1] [6] [7]. However, the presence of C3 nephritic factor in the majority of patients suggests its evident role as an immune-mediated component of the disorder. It is assumed that lysis of adipocytes that express adipsin (commonly known as factor D, a serine protease enzyme) occurs through the activity of the C3 nephritic factor and that the distribution of fat loss correlates with the level of factor D that is expressed in different parts of the body [7]. Furthermore, LMNB2 gene mutations were confirmed in several cases (although the exact role is not known), suggesting that more research is needed to establish the exact cause of acquired partial dystrophy [2] [7].

Prevention

Because the cause is not yet known, little can be done to prevent the occurrence of acquired partial dystrophy. For this reason, the focus should be shifted to an early diagnosis and prevention of metabolic complications (diabetes mellitus, hepatic steatosis, pancreatitis, etc.) through initiation of proper therapy while being in early stages of the disease [5].

Summary

Lipodystrophies comprise several disorders that cause abnormal adipose tissue loss through different mechanisms [1] [2] [6] [7] [12]. Based on the etiology and distribution of fat loss, they are divided into familial (occurring as a result of genetic mutations) or acquired (developing secondary to other disorders), and into generalized, partial, or localized, respectively [1] [4] [5] [12]. Acquired partial dystrophy (APL), also known as Barraquer-Simons syndrome, is characterized by a loss of adipose tissue that is restricted to the upper part of the body, but the pathogenesis and etiology remain unclear [8] [12]. Genetic (LMNB2 mutations), autoimmune (SLE and dermatomyositis seem to play a role in APL), and infectious (measles) events have been discussed in the model for this disorder, but solid conclusions are yet to be made [1] [2] [4] [5]. APL is rare, females are more frequently affected (female-to-male ratio is 4-8:1) and the clinical presentation starts in early adolescence and adulthood in the majority of patients [4] [5] [6]. A craniocaudal progression of fat loss is the hallmark of APL, starting from the head and neck and ending in the upper abdomen, whereas the lower extremities either exhibit no changes in fat content or paradoxically accumulate increased amounts of adipose tissue after a certain period of time [2] [3]. Disproportionately to other lipodystrophies, APL patients develop metabolic defects in only about 10% of cases, notable examples being diabetes mellitus (DM), hypertriglyceridemia, and low HDL levels [1] [2] [4]. The diagnosis of APL can be made through a detailed clinical examination (supported by a thoroughly obtained patient history) and follow-up laboratory studies. The crucial feature of APL is the presence of a circulating immunoglobulin C3 nephritic factor, which is identified in more than 80% of patients [1] [2] [6]. Its role in the onset of APL is yet to be revealed, but it is assumed to be an important factor for the development of membranous proliferative glomerulonephritis (MPGN), which affects about 20% of individuals and can progress to end-stage renal disease without early treatment [1] [2] [4] [6]. Treatment principles focus on physical exercise and dietary changes that balance the intake of carbohydrates, fats, and proteins, while the use of drugs is indicated in the setting of diabetes and other endocrine changes [3] [5].

Patient Information

Lipodystrophies are a group of several disorders that are characterized by specific patterns of body fat loss and predispose patients to changes to various metabolic defects in the body. They are broadly divided into familial (arising from genetic mutations that are transferred from parents to children) and acquired, and further divided based on the extent of body fat changes (generalized, partial, or localized). Acquired partial dystrophy (APL) is distinguished by the loss of fat on the upper part of the body. First changes are seen on the face and in the neck area, followed by the arms, the trunk, and finally the upper abdomen. The buttocks and legs are usually spared of changes in fat tissue content in the initial stages, but these areas may paradoxically accumulate an excessive amount of fat in later life. These symptoms start in early adolescence or adulthood and females are much more commonly affected than males. Compared to other lipodystrophies, the development of metabolic disorders such as diabetes mellitus, hypertriglyceridemia (increased circulating levels of triglycerides), and low levels of high-density lipoprotein (HDL, known as "good" cholesterol) is not common and affects only 10% of patients. The exact cause of APL remains unknown, but genetic events, infections, and autoimmune disorders have all been included in the model of the disease. The diagnosis of APL can be made through a properly obtained patient history and a detailed physical examination, as they reveal crucial findings and point to the diagnosis early on. Various laboratory studies need to be conducted in order to solidify clinical suspicion. One of the most feared complications of APL is kidney failure, which necessitates a detailed assessment of the renal system when the diagnosis is made. Treatment focuses on dietary changes and implementation of regular physical exercise. Insulin-regulating drugs are used only in the setting of confirmed diabetes, whereas lipid-lowering drugs are also indicated when serum triglyceride levels are high.

References

Article

  1. Misra A, Peethambaram A, Garg A. Clinical features and metabolic and autoimmune derangements in acquired partial lipodystrophy: report of 35 cases and review of the literature. Medicine. 2004;83(1):18-34.
  2. Hegele R, Joy T, Al-Attar S, et al. Thematic review series: adipocyte biology. Lipodystrophies: windows on adipose biology and metabolism. J Lipid Res. 2007;48(7):1433-1444.
  3. Handelsman Y, Oral EA, Bloomgarden ZT, et al. The Clinical Approach to the Detection of Lipodystrophy - An AACE Concensus statement. Endocr Pract. 2013;19(1):107-116.
  4. Oliveira J, Freitas P, Lau E, Carvalho D. Barraquer–Simons syndrome: a rare form of acquired lipodystrophy. BMC Res Notes. 2016;9:175.
  5. Hussain I, Garg A. Lipodystrophy Syndromes. Dermatologic clinics. 2008;26(4):569-ix.
  6. Brown RJ, Araujo-Vilar D, Cheung PT, et al. The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline. J Clin Endocrinol Metab. 2016;101(12):4500-4511.
  7. Fiorenza Christina G, Chou Sharon H, Mantzoros Christos S. Lipodystrophy: pathophysiology and advances in treatment. Nat Rev Endocrinol. 2011;7(3):137–150.
  8. Bolan C, Oral EA, Gorden P, Taylor S, Leitman SF. Intensive, long-term plasma exchange therapy for severe hypertriglyceridemia in acquired generalized lipoatrophy. J Clin Endocrinol Metab. 2002;87:380–384.
  9. Oral EA, Simha V, Ruiz E, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med. 2002;346:570–578.
  10. Javor ED, Cochran EK, Musso C, Young JR, DePaoli AM, Gorden P. Long-term efficacy of leptin replacement in patients with generalized lipodystrophy. Diabetes. 2005;54:1994–2002.
  11. Chan JL, Lutz K, Cochran E, et al. Clinical effects of long-term metreleptin treatment in patients with lipodystrophy. Endocr Pract. 2011;17:922–932.
  12. Garg A. Lipodystrophies. Am J Med. 2000;108(2):143-152.

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Last updated: 2019-07-11 20:10