Females are more often affected than males, with ratio being 3:1.The hallmark characteristics are widespread loss of subcutaneous fat, ectopic fat deposition, leptin deficiency, and severe metabolic abnormalities such as insulin resistance. Subcutaneous fat loss in AGL patients are visible in all parts of the body. AGL mostly affects face and the extremities and may look sunken or swollen in the eyes. However, the degree and location of severity may vary by person. Especially, intra-abdominal fat loss is variable. As subcutaneous fat is lost, affected areas show prominent structures of veins and muscle. Those with panniculitis-associated AGL may present erythematous nodules.Metabolic complications include insulin resistance, high metabolic rate, and uncontrolled lipid levels such as hypertriglyceridemia, low HDL, and high LDL. Patients may develop diabetes mellitus secondary to insulin resistance. Recent case reports revealed that lymphoma is present in some patients but its prevalence is not known at this time. Cause
There is no known cause for this disease; however, three origins of AGL are generally suspected: panniculitis-associated, autoimmune-associated, and idiopathic AGLs. Triggers may include infections that aggravate the panniculitis, or any disease state that can induce autoimmunity. Overlap between panniculitis and autoimmune types also exists. Another theory suggest that AGL is an autoimmune disease itself, as panniculitis can be described as an autoimmune disease, however its triggering factors remains to be unknown. Underlying genetic factor may be associated; however neither confirmed nor rejected. Panniculitis-associated AGL
About 25% of previously reported AGL is associated with panniculitis.
Panniculitis is an inflammatory nodules of the subcutaneous fat, and in this type of AGL, adipose destruction originates locally at the infection or inflammation site and develops into generalized lipodystrophy. Autoimmune-associated AGL
AGL with autoimmune origin is responsible for about 25% of all AGL reports. Those with autoimmune origin stems from other autoimmune diseases, most commonly with juvenile dermatomyositis and autoimmune hepatitis, but also occurs with rheumatoid arthritis, systemic lupus erythematosus, and Sjogren syndrome. Idiopathic AGL
Although idiopathic AGL accounts for about 50% of all AGL, it can vary in its origin and it is unclear how it develops.No known preventive measurement has been reported. Mechanism
The exact pathophysiologic mechanism is mostly unknown; however, each of three main origins, autoimmune, panniculitis, or idiopathic, may have different mechanisms of pathogenesis.Normally, adipose tissues contain adipocytes to store fat for energy during fasting period and release leptin to regulate homeostasis of energy and sensitize insulin. In AGL patients, adipose tissues are insufficient and leads to fat deposition in non-adipose tissues, such as muscle or liver, resulting in hypertriglyceridemia. Continuous elevation in triglyceride levels further contributes to metabolic problems including insulin resistance. As the level of leptin in the body is proportional to the amount of adipose tissue present, AGL patients also have a deficiency of leptin which contributes to excessive eating and worsens the metabolic syndrome.In a few patients with AGL, the presence of antibodies against adipocyte has been identified.