Diagnosis is clinical, based on observation. Biopsy is rarely required.

On X-ray computed tomography (CT), the increased fat component will decrease the density of the liver tissue, making the image less bright. Typically the density of the spleen and liver are roughly equivalent. In steatosis, there is a difference between the density and brightness of the two organs, with the liver appearing darker.

On ultrasound, fat is more echogenic (capable of reflecting sound waves). The combination of liver steatosis being dark on CT and bright on ultrasound is sometimes known as the flip flop sign.

On Magnetic Resonance Imaging, multiecho gradient echo images can be used to determine the percent fat fraction of the liver. The different resonance frequencies between water and fat make this technique very sensitive and accurate. Acquisition of echoes in "in phase" and "out phase" conditions (pertaining to the relative phases of the fat and water proton contingents) enables to obtain a signal proportional to the water and fat contingent, or a signal proportional to the water minus the fat contingent. These signal intensities are then algebraically combined into a percent fat. More recent techniques take into account experimental noise, signal decay and spectroscopic properties of fat. Numerous validation studies have demonstrated excellent correlations between the steatosis level quantified at MRI and the steatosis levels semi-quantitavely and quantitatively determined on liver biopsies (reference methods). Several MRI vendors offer automated calculation of percent fat with acquisition sequences no longer than a single breath hold.

NL is diagnosed by a skin biopsy, demonstrating superficial and deep perivascular and interstitial mixed inflammatory cell infiltrate (including lymphocytes, plasma cells, mononucleated and multinucleated histiocytes, and eosinophils) in the dermis and subcutis, as well as necrotising vasculitis with adjacent necrobiosis and necrosis of adnexal structures. Areas of necrobiosis are often more extensive and less well defined than in granuloma annulare. Presence of lipid in necrobiotic areas may be demonstrated by Sudan stains. Cholesterol clefts, fibrin, and mucin may also be present in areas of necrobiosis. Depending on the severity of the necrobiosis, certain cell types may be more predominant. When a lesion is in its early stages, neutrophils may be present, whereas in later stages of development lymphocytes and histiocytes may be more predominant.

Fat necrosis is a form of necrosis characterized by the action upon fat by digestive enzymes.

In fat necrosis the enzyme lipase releases fatty acids from triglycerides. The fatty acids then complex with calcium to form soaps. These soaps appear as white chalky deposits.

It is usually associated with trauma of the pancreas or acute pancreatitis.

It can also occur in the breast, the salivary glands and neonates after a traumatic delivery.

To classify an individual as TOFI, it is essential to measure their internal fat content. This done by using magnetic resonance Imaging (MRI) or CT scanning. The parameters of the MRI scanner are manipulated to show fat as bright (white) and lean tissue as dark.

Indirect methods such as waist circumference are not suitable as individuals with an identical waist circumference can have vastly different levels of internal fat. The figure clearly shows that despite having an identical waist circumference (in this example all men had a waist of 84 cm), there is considerable variation in the amount of visceral fat (volumes shown on the image in litres) present.

There is no clearly defined cure for necrobiosis. NLD may be treated with PUVA therapy and improved therapeutic control.

Although there are some techniques that can be used to diminish the signs of necrobiosis such as low dose aspirin orally, a steroid cream or injection into the affected area, this process may be effective for only a small percentage of those treated.

Diagnosis is made comprehensively, together with visual observation, body fat assessment, a review of lab panels consisting of A1c, glucose, lipid, and patient history.

Caliper measurements of skinfold thickness is recommended to quantify fat loss as a supportive information. In this measurement, skinfold thickness of less than 10mm for men and 22mm for women at the anterior thigh is suggestive cutoff for the diagnosis of lipodystrophy. Less commonly, biphotonic absorptiometry and magnetic resonance imaging (MRI) can be done for the measurement of body fat.

Other forms of insulin resistance may be assessed for differential diagnosis. Resistance to conventional therapy for hyperglycemia and hypertriglyceridemia serves as an indication for lipodystrophy. Specifically, the diagnosis is strongly considered for those requiring ≥200 units/day of insulin and persistent elevation of ≥250 mg/dl of triglyceride levels.

The use of leptin levels should be carefully approached. While low leptin levels are helpful for making the diagnosis, they are not specific for the lipodystrophy. High leptin levels can help excluding the possible lipodystrophy, but there is no well-established standardized leptin ranges.

Subcutaneous fat necrosis of the newborn (SCFN or SFN) is a rare form of lobular panniculitis occurring in newborns that is usually self-remitting and non-recurring. Proposed causes include perinatal stress, local trauma, hypoxia and hypothermia, though the exact cause is unknown. It has been suggested that the brown fat seen in newborns is more sensitive to hypoxic injury than fat seen in adults, and that such hypoxia, usually in the context of a complicated birth, leads to the fat necrosis. Complications can include hypercalcemia, hyperlipidemia and thrombocytopenia, and can present months after the onset of SCFN symptoms.

Feline hepatic lipidosis shares similar symptoms to other problems, including liver disease, renal failure, feline leukemia, Feline infectious peritonitis and some cancers. Diagnosis requires tests that target the liver to make an accurate diagnosis. Jaundice is highly indicative of the disease. Blood tests and a liver biopsy will confirm the presence of the disease.

The management of lipodermatosclerosis may include treating venous insufficiency with leg elevation and elastic compression stockings; in some difficult cases, the condition may be improved with the additional use of the fibrinolytic agent, stanozol. Fibrinolytic agents use an enzymatic action to help dissolve blood clots.

Stanozol is injected directly into the affected area, Venous Ablation has also been known to help circulation in patients.

Diagnosis of Dercum's disease is done through a physical examination. In order to properly diagnose the patient, the doctor must first exclude all other possible differential diagnosis. The basic criteria for Dercum's disease are patients with chronic pain in the adipose tissue (body fat) and patients who are also obese. Although rare, the diagnosis may not include obesity. Dercum's disease can also be inherited and a family medical history may aid in the diagnosis of this disease. There are no specific laboratory test for this disease. Ultrasound and magnetic resonance imaging can play a role in diagnosis.

Lipedema is commonly misdiagnosed. At this time, only Germany and the Netherlands have standardized ways of diagnosing lipedema. Other countries do not currently have a standardized diagnosis protocol, and therefore the diagnosis is typically made clinically via physical inspection (palpating the adipose tissue).

Some trained clinicians and therapists can feel the physical differences in the adipose tissue, characterized as nodules with "beans in a bag" feeling. When the tissue has excess fluid the nodules are no longer easily palpable. Testing of the major components of the lymphatic system can be done through tools such as lymphoscintigraphy, but lack of noticeable lymphatic impairment does not indicate lipedema is not present, only that the major lymphatics are not (yet) affected.

This is difficult to establish in the general population since the necessary imaging examinations are time consuming and expensive; however, in a recent research study it was estimated that 14% of the men and 12% of the women scanned with a BMI 20–25 kg/m were classified as TOFI.

In regards to the diagnosis of idiopathic sclerosing mesenteritis, a CT scan which creates cross-section pictures of the affected individuals body, can help in the assessment of the condition.

Many conditions mimic or may be mistaken for warfarin necrosis, including pyoderma gangrenosum or necrotizing fasciitis. Warfarin necrosis is also different from another drug eruption associated with warfarin, purple toe syndrome, which usually occurs three to eight weeks after the start of anticoagulation therapy. No report has described this disorder in the immediate postpartum period in patients with protein S deficiency.

Reversion of lipodystrophy does not occur after withdrawal of protease inhibitors.

GHRH analogs such as tesamorelin can be used to treat HIV-associated lipodystrophy.

If a liver biopsy is needed for diagnosis of the condition, the mother should be appropriately stabilized and treated to reduce bleeding related complications. The diagnosis can be made by a frozen-section (as opposed to a specimen in formalin) that is stained with the Oil red O stain, that shows microvesicular steatosis (or small collections of fat within the liver cells). The microvesicular steatosis usually spares zone one of the liver, which is the area closest to the hepatic artery. On the regular trichrome stain, the liver cell cytoplasm shows a foamy appearance due to the prominence of fat. Necrosis is rarely seen. The diagnosis can be enhanced by electron microscopy which can be used to confirm the presence of microvesicular steatosis, and specifically the presence of megamitochondria and paracrystalline inclusions. Liver diseases with similar appearances include Reye's syndrome, drug-induced hepatitis from agents with mitochondrial toxicity, including nucleoside reverse transcriptase inhibitors used to treat HIV, and a rare condition known as Jamaican vomiting sickness which is caused by the eating of the unripened Ackee fruit.

Many drug candidates are in advanced clinical studies as : elafibranor, obeticholic acid.

Lymphedema is usually asymmetrical and can be either acquired (through surgery, trauma or infection damaging the lymphatic system) or congenital (hereditary changes in the lymphatic system). However, symmetrical enlargement of both lower limbs, from waist to ankles (i.e. gynoid fat) is a hallmark of lipedema. As the swelling continues and spreads from lower extremities to other parts of the body, the swelling is likely caused by slower lymphatic flow and changes in the lymphatic vessel structure caused by pressure in the lipedematous limbs. This is known as lipo-lymphedema. Lipo-lymphedema may also develop in combination with chronic venous insufficiency and other vascular disorders.

Lipedema can be underdiagnosed due the difficulty in differentiating it from other edemas and obesity. Trayes 2013 published some tools including tables and a flow chart that can be used to diagnose lipedema and other edemas.

Lipedema / Dercum’s Disease Differentiation

These conditions may co-exist. Dercum’s Disease is characterized by painful lipomas around the body.

Most individuals are asymptomatic and are usually discovered incidentally because of abnormal liver function tests or hepatomegaly noted in unrelated medical conditions. Elevated liver biochemistry is found in 50% of patients with simple steatosis. The serum alanine transaminase level usually is greater than the aspartate transaminase level in the nonalcoholic variant and the opposite in alcoholic FLD (AST:ALT more than 2:1).

Imaging studies are often obtained during the evaluation process. Ultrasonography reveals a "bright" liver with increased echogenicity. Medical imaging can aid in diagnosis of fatty liver; fatty livers have lower density than spleens on computed tomography (CT), and fat appears bright in T1-weighted magnetic resonance images (MRIs). No medical imagery, however, is able to distinguish simple steatosis from advanced NASH. Histological diagnosis by liver biopsy is sought when assessment of severity is indicated.

Common findings are elevated liver enzymes and a liver ultrasound showing steatosis. An ultrasound may also be used to exclude gallstone problems (cholelithiasis). A liver biopsy (tissue examination) is the only test widely accepted as definitively distinguishing NASH from other forms of liver disease and can be used to assess the severity of the inflammation and resultant fibrosis.

Non-invasive diagnostic tests have been developed, such as FibroTest, that estimates liver fibrosis, and SteatoTest, that estimates steatosis, however their use has not been widely adopted. Apoptosis has been indicated as a potential mechanism of hepatocyte injury as caspase-cleaved cytokeratin 18 (M30-Apoptosense ELISA) in serum/plasma is often elevated in patients with NASH and tests based on these parameters have been developed; however, as the role of oncotic necrosis has yet to be examined it is unknown to what degree apoptosis acts as the predominant form of injury.

Other diagnostic tests are available. Relevant blood tests include erythrocyte sedimentation rate, glucose, albumin, and kidney function. Because the liver is important for making proteins used in coagulation some coagulation related studies are often carried out especially the INR (international normalized ratio). In people with fatty liver with associated inflammatory injury (steatohepatitis) blood tests are usually used to rule out viral hepatitis (hepatitis A, B, C and herpes viruses like EBV or CMV), rubella, and autoimmune related diseases. Hypothyroidism is more prevalent in NASH patients which would be detected by determining the TSH.

It has been suggested that in cases involving overweight patients whose blood tests do not improve on losing weight and exercising that a further search of other underlying causes is undertaken. This would also apply to those with fatty liver who are very young or not overweight or insulin-resistant. In addition those whose physical appearance indicates the possibility of a congenital syndrome, have a family history of liver disease, have abnormalities in other organs, and those that present with moderate to advanced fibrosis or cirrhosis.

The first element of treatment is usually to discontinue the offending drug, although there have been reports describing how the eruption evolved little after it had established in spite of continuing the medication. Vitamin K1 can be used to reverse the effects of warfarin, and heparin or its low molecular weight heparin (LMWH) can be used in an attempt to prevent further clotting. None of these suggested therapies have been studied in clinical trials.

Heparin and LMWH act by a different mechanism than warfarin, so these drugs can also be used to prevent clotting during the first few days of warfarin therapy and thus prevent warfarin necrosis (this is called 'bridging').

Based on the assumption that low levels of protein C are involved in the underlying mechanism, common treatments in this setting include fresh frozen plasma or pure activated protein C.

Since the clot-promoting effects of starting administration of 4-hydroxycoumarins are transitory, patients with protein C deficiency or previous warfarin necrosis can still be restarted on these drugs if appropriate measures are taken. These include gradual increase starting from low doses and supplemental administration of protein C (pure or from fresh frozen plasma).

The necrotic skin areas are treated as in other conditions, sometimes healing spontaneously with or without scarring, sometimes going on to require surgical debridement or skin grafting.

Histologically, steatosis is physically apparent as lipid within membrane bound liposomes of parenchymal cells. When this tissue is fixed and stained to be better viewed under a microscope, the lipid is usually dissolved by the solvents used to prepare the sample. As such, samples prepared this way will appear to have empty holes (or vacuoles) within the cells where the lipid has been cleared. Special lipid stains, such as Sudan stains and osmium tetroxide are able to retain and show up lipid droplets, hence more conclusively indicating the presence of lipids. Other intracellular accumulations, such as water or glycogen, can also appear as clear vacuoles, therefore it becomes necessary to use stains to better decide what is accumulating.

Grossly, steatosis causes organ enlargement and lightening in colour. This is due to the high lipid content increasing the organ's volume and becoming visible to the unaided eye. In severe cases, the organ may become vastly enlarged, greasy, and yellow in appearance.

Sclerema neonatorum is a rare and severe skin condition that is characterized by diffuse hardening of the subcutaneous tissue with minimal inflammation. It usually affects premature, ill newborns. Prognosis is poor.

Minimal inflammation helps distinguish sclerema neonaturum from subcutaneous fat necrosis of the newborn.