| |
Dr. Francis Xavier Dercum first described adiposis dolorosa (AD) in 1888 (1) as a syndrome of painful growths in subcutaneous fat. The fatty growths can occur anywhere in subcutaneous fat from scalp to plantar surface of the foot; are unencapsulated, soft, sometimes occurring as small nodules; and other times are difficult to remove in entirety because of their extensive growth (2). The onset of AD can be rapid or insidious and progressive beginning most often in the third decade (2) with fatigue (3, 4) and pain unresponsive to analgesics (5). Obesity is common in AD with some patients describing rapid weight gain (6). Some cases of AD are familial (5, 7, 8). Pain in AD is difficult to treat (5) and although surgical resection or liposuction improves pain, growths recur in 50% (2). The etiology of AD is unknown, although metabolic or autoimmune components have been proposed (2, 5). Ander's disease may or may not be the same as AD, but at the present, I have not read any of Dr. Ander's work in this area except for brief references in textbooks.
In a survey of 110 individuals with AD, 16.4% had diabetes (2). The percentage of respondents with diabetes by body mass index (BMI) was as follows: 7.6% <25 kg/m2; 4.8% from 25.0-29.9 kg/m2; 7.1% from 30.0-34.9 kg/m2; and 29.2% at ³35 kg/m2. Twenty-nine respondents (26.4%) were diagnosed with the metabolic syndrome or insulin resistance or met NCEP guidelines for metabolic syndrome. The prevalence of diabetes was over twice that of the 2005 US population in AD patients between the ages of 45-64 (9). Comparing rates of diabetes by BMI, the percentage of individuals in our survey with diabetes in the lowest and highest BMI groups was greater than that of published data from NHANES (10). This data suggests that growths in AD might confer insulin resistance even in the absence of obesity. Another suggestion of metabolic derangement in the growths is that 100% of individuals with AD state that they cannot lose weight from fatty growths.
References
1. Dercum FX. A subcutaneous connective-tissue dystrophy of the arms and back, associated with symptoms resembling myxoedema. University Medical Magazine Philadelphia. Vol 1; 1888:140-150.
2. Herbst KL, Asare-Bediako S. Adiposis Dolorosa is More than Painful Fat. The Endocrinologist. Nov/Dec 2007;17(6):326-344. Right click to download a printable PDF.
3. Palmer ED. Dercum's disease: adiposis dolorosa. Am Fam Physician. Nov 1981;24(5):155-157.
4. Harris K, Davies K, Dumont S, Stephenson BM. A pain in the groin. Lancet. Aug 2 1997;350(9074):334.
5. Wortham NC, Tomlinson IP. Dercum's disease. Skinmed. 2005;4(3):157-162; quiz 163-1644.
6. Brorson H, Fagher B. [Dercum's disease. Fatty tissue rheumatism caused by immune defense reaction?]. Lakartidningen. Apr 10 1996;93(15):1430, 1433-1436.
7. Campen R, Mankin H, Louis DN, Hirano M, Maccollin M. Familial occurrence of adiposis dolorosa. J Am Acad Dermatol. Jan 2001;44(1):132-136.
8. Cantu JM, Ruiz-Barquin E, Jimenez M, Castillo L, Macotela-Ruiz E. Autosomal dominant inheritance in adiposis dolorosa (Dercum's disease). Humangenetik. Mar 23 1973;18(1):89-91.
9. National Diabetes Fact Sheet. http://www.cdc.gov/diabetes/pubs/estimates05.htm#prev.
10. Gregg EW, Cadwell BL, Cheng YJ, et al. Trends in the prevalence and ratio of diagnosed to undiagnosed diabetes according to obesity levels in the U.S. Diabetes Care. 2004;27(12):2806-2812.
Neostigmine and Glycine
This section is only for people with AD!
In 1938, two investigators described three obese women with AD who had difficulty performing their activities of daily living secondary to fatigue and asthenia--a feeling of weakness without actual loss of strength (1). All three women were placed on a diet consisting of 70 grams protein, 70 grams of fat and 100 grams carbohydrate or 1500 calories/day (specifics unavailable). All women were prescribed 10 grams glycine (aminoacetic acid) and 15mg neostigmine three times daily (total 45mg) and all three women had decreased pain, ‘nervousness’, asthenia and became more active. Glycine is a chemically simple and abundant conditionally essential amino acid. It combines with many toxic substances and coverts them to harmless forms, which are then excreted.
There are glycine binding sites in the central nervous system (CNS). Specifically, the receptor/channel complex, N-methyl-o-aspartate (NMDA), is widespread within the CNS. The NMDA receptor/channel complex consists of an NMDA sensitive glutamate binding site, an associated calcium channel, a glycine binding site, and multiple modulatory sites. If you antagonize the glycine site (prevent glycine from binding or working at the site), feeding in rats increased (3,1). Glycine may therefore be an appetite suppressant. It may also have other effects in the brain promoting weight loss that we don’t know about at this time. One teaspoon of glycine powder provides 2.8 grams of pure glycine if purchased from many different companies including Life Extension. Glycine powder is inexpensive and easily soluble in juice or water and is not unpleasant tasting. The dose of glycine would be one teaspoon in juice or water three times daily (to reach 10 grams). Glycine may also be anti-inflammatory (2).
Neostigmine is not a drug that I recommend lightly or to everyone. However, it is one of the few drugs that has been tested in women with AD that is not an immunosuppressant (3) and that has resulted in improvement in weight (when combined with glycine) and activity. Neostigmine inhibits the hydrolysis of acetylcholine by competing with acetylcholine for attachment to acetylcholinesterase at sites of cholinergic transmission. It enhances cholinergic action by facilitating the transmission of impulses across neuromuscular junctions. It also has a direct cholinomimetic effect on skeletal muscle and possibly on autonomic ganglion cells and neurons of the central nervous system. Neostigmine undergoes hydrolysis by cholinesterase and is also metabolized by microsomal enzymes in the liver. Protein binding to human serum albumin ranges from 15 to 25 percent. Neostigmine should not be taken without knowledge of your physician because of potential side effects and drug interactions. Neostigmine should be used with caution in patients with epilepsy, bronchial asthma, bradycardia, recent coronary occlusion, vagotonia, hyperthyroidism, cardiac arrhythmias or peptic ulcer. Side effects are generally due to an exaggeration of pharmacological effects of which salivation and fasciculation are the most common. Bowel cramps and diarrhea may also occur. The following additional adverse reactions have been reported following the use of neostigmine.
Allergic: Allergic reactions and anaphylaxis.
Neurologic: Dizziness, convulsions, loss of consciousness, drowsiness, headache, dysarthria, miosis and visual changes.
Cardiovascular: Cardiac arrhythmias (including bradycardia, tachycardia, A-V block and nodal rhythm) and nonspecific EKG changes have been reported, as well as cardiac arrest, syncope and hypotension. These have been predominantly noted following the use of the injectable form of neostigmine.
Respiratory: Increased oral, pharyngeal and bronchial secretions, dyspnea, respiratory depression, respiratory arrest and bronchospasm.
Dermatologic: Rash and urticaria.
Gastrointestinal: Nausea, emesis, flatulence and increased peristalsis.
Genitourinary: Urinary frequency.
Musculoskeletal: Muscle cramps and spasms, arthralgia.
Miscellaneous: Diaphoresis, flushing and weakness.
There also is one report on a woman who improved her AD while on infliximab and methotrexate (3). These drugs suppresst the immune system and TNF-alpha, one of the toxic (bad) cytokines made by inflammatory cells especillay those resideing in adipose tissue (fat). Talk to your doctor about this treatment.
References
1. Wohl, M. G., and Pastor, N. (1938) Adipositas dolorosa (Dercum's disease). . J.A.M.A. 110, 1261-1264
2. Hartog, A., Leenders, I., van der Kraan, P. M., and Garssen, J. (2007) Anti-inflammatory effects of orally ingested lactoferrin and glycine in different zymosan-induced inflammation models: evidence for synergistic activity. Int Immunopharmacol. 7, 1784-1792. Epub 2007 Oct 1788.
3. Singal, A., Janiga, J., Bossenbroek, N., and Lim, H. (2007) Dercum's disease (adiposis dolorosa): a report of improvement with infliximab and methotrexate. J Eur Acad Dermatol Venereol. 21, 717.
|
