Tag Archives: obesity

Hidradenitis Suppurativa and inflammation –

Hidradenitis Suppurativa (HS)

Hidradenitis suppurativa
Scarring, inflammatory abscess, with small pock marks (SINUS TRACTS) commonly found in Hidradenitis Suppurativa
Hidradenitis suppurativa
Gross ūüôĀ

HS is a chronic inflammatory skin disease associated with the formation of multiple abscesses, nodules, and scars in the apocrine gland-bearing areas. Sites that are affected include inguinofemoral (groin), axillary (arm pit) , perianal, gluteal (buttocks) , and submammary (breast) regions. Approximately 1-4% of the population is affected by this disorder. The apocrine (sweat) glands get occluded by hyperkeratotic (skin material) debris that produce follicles that rupture and cause inflammation.

The course of HS can vary from small pustules to inflammatory nodules, and in some cases become inflammatory, deep abscesses and draining sinus tracts. In other words,  an infected pock marked mess.

This disease is staged in to three categories with Stage 1 being basic abscesses without scarring and Stage 3 being the worst, having destroyed completely an area with multiple abscesses that can be interconnected and have sinus tracts (holes) connected to the skin surface.

For those with this disorder, wearing loose fitting clothes that don’t rub the areas involved, not pinching the lesions, wearing antiperspirants ¬†but not applying perfumes to the area are helpful. Topical anti-bacterial cleansing with Triclosan-containing soaps will decrease bacterial colonization. Don’t scrub the area when washing as that will inflame the lesions more.

Primary treatment includes quitting smoking – which is highly associated with Hidradenitis Suppurativa. If you continue to smoke, don’t expect to get better. Also weight loss is important as 2/3 of those with HS are overweight. The HS may be due to elevated insulin levels, hormonal changes, and dietary problems in these individuals. Avoiding dairy and high glycemic loaded foods can decrease the disease.

Metformin, an anti-diabetic drug can be helpful in decreasing the HS disease burden. This is a result of the insulin-sensitizing effect of Metformin as it is believed that HS results, in part, from elevated insulin levels.

Treatment methods, after the basics listed above, include the use of Resorcinol, a chemical peeling agent, which as a 15% solution and applied twice a day, can improve the HS lesions and decrease pain and inflammation.

Also used are antibiotics, usually Doxycycline and minocycline first line, then Clindamycin if those are not helpful. Clindamycin mixed with Rifampin has been effective in 2/3 of patients with moderate disease.  Some physicians use a combination of Moxifloxacin, Rifampin, and Metronidazole with good success.

Dapsone, an antibiotic with immunomodulatory effect, has had effect in early stage disease.

Intralesional injection of steroids is another option for local treatment as a monthly injection over a period of three months or so. Occasionally surgery must be done or an incision and drainage when a large abscess forms.

Androgens can promote the development of HS. It has been found that drospirenone- (or norgestimate-) containing oral contraceptives with spironolactone ( a blood pressure medication with anti-androgen effects) has been helpful in women.

For patients who don’t want to quit smoking or cannot lose weight and for those who fail other medical therapies, anti-TNF (tumor necrosis factor) agents are effective and have been approved for use in HS. ¬†The injected agent Infliximab was found to have a 50% reduction in severity score with most having improvement in pain and quality of life.¬†Adalimumab was recently FDA approved for HS treatment but has been less effective. Whereas Infliximab is administered by weekly infusions, Adlimumab is given by subcutaneous weekly injections. The problems with the anti- TNF agents include¬†risks for infection, heart failure, demyelinating disease, a lupus-like syndrome, and malignancy.

Oral retinoids such as acitretin and Isotretinoin have shown beneficial effect as well. Acitretin given as  0.6 mg/kg daily for 9 to 12 months showed highly effective in diminishing the disease, an effect that remained after the medicine was stopped, unlike with the biological agents, which have a higher relapse rate after discontinuance. Isotretinoin also has been effective in several studies with lower relapse after discontinuance. Both agents are highly teratogenic.

Systemic prednisone can decrease inflammation when given over 7-10 days at 40 mg a day. Cyclosporine has also been used as well.

Vitamin D3 supplementation at 300-6000 Units daily has been helpful in decreasing HS lesions in some individuals.

 Zinc salts have antiinflammatory and antiandrogenic properties.  Zinc Gluconate at 90 mg daily was very effective (36%) in significantly decreasing the inflammation of low grade HS, with beneficial effect in most who use zinc supplements.

What is interesting about Hidradenitis Suppurativa, is the inflammatory component of the disease. We know that the risk of the disease increases with obesity and cigarette smoking, which are also associated with elevated markers of inflammation themselves. Obesity is associated with elevated inflammatory markers and insulin levels, which appear to play a role in the genesis of HS as well as other diseases (i.e hypertension, fatty liver, diabetes, cancer, etc) In the article listed below, it was recognized that HS and the risk of it’s progression can be estimated by CRP levels, a marker of total body inflammation. ¬†CRP is produced by the liver in response to IL-6, another inflammatory marker. This generalized inflammation affects multiple organ systems.

Correlation of inflammatory serum markers with disease severity in patients with hidradenitis suppurativa (HS)

The above study examined the use of CRP and white blood count (wbc) in estimating the risk of progression and inflammatory content of patients with various stages of HS.

The study found that CRP level and neutrophil counts are effective tools for assessing the extent of disease severity and grade of inflammation in patients with HS above and beyond the association of these inflammatory markers with coincidental comorbidities.   For example, obese patient have elevations in CRP and smokers have higher white blood cell counts, but this study showed that CRP and wbc independently predicted worse disease status in patients with HS. There was a significant correlation between these inflammatory serum markers and disease severity according to HS severity grading scale. The end finding is that CRP is a significant and independent predictor for severe disease activity of Hidradenitis Suppurativa.

What interests me about this disease is it’s associations with comorbidities. Smokers have little hope of remission of HS¬†and HS is associated strongly with obesity. These same disorders are inflammatory in their own right. It is felt that the elevated levels of insulin and insulin resistance in obesity may play a role in worsening of HS. Obesity and the hormonal catastrophe associated with it is also associated with coronary heart disease, hypertension, fatty liver, and a host of other life-limiting diseases. So again, here is a disease process (HS) that is, in part, partially a creature of our own design – bad habits. If we could stop smoking and limit obesity, how much HS would really exist?

Correlation of inflammatory serum markers with disease severity in hidradenitis suppurativa

 

Here is a link to a dermatology page regarding HS:

http://drcamisasblog.com/

 

 

 

 

 

 

Insane Medicine – Liraglutide (Saxenda) for weight loss!!

  • Liraglutide is a glucagon-like 1 peptide that has been available for diabetes management for a few years and now has an added FDA approval for weight loss management!!
  • There are more options for weight management as of now!
    There are more options for weight management as of now!

    obesity-big

  • To date,¬†Phentermine/topiramate ER (Qsymia) is the most effective drug available. Locaserin (Belviq) is another approved drug for weight loss, but it is less effective. ¬†However, it is better tolerated. Other options such as Xenical are helpful, but it prevents absorption of food and can cause excessive bloating and gas in some patients. Contrave (Wellbutrin and Naltrexone) is also effective but has neuropsychiatric effects.
  • Liraglutide is used to treat type 2 diabetes at a dose of 1.8 mg a day. It is injectable. The weight loss form of the drug is a dose of up to 3.0 mg a day injected. The amount of weight loss varies as the dose approaches the upper limit of 3 mg a day.
  • Liraglutide decreases appetite and therefore energy intake, which is how it causes weight loss. It also delays gastric emptying. Used as an adjunct to physical exercise and dieting, it has resulted in up to an 8 kg body weight loss over the 56 week course of treatment [¬†‚ąí8.0¬Ī6.7% (‚ąí8.4¬Ī7.3 kg)].
  • Liraglutide treatment was associated with reductions in cardiometabolic risk factors, including waist circumference, blood pressure, and inflammatory markers. Fasting lipid profiles were also improved as well.¬†The combination of weight loss and improved glycemic control probably contributed to the observed reductions in the prevalence of prediabetes and the delayed onset of type 2 diabetes.
  • Side effects include an increased incidence of gallstones, which commonly increase with weight loss. ¬†Nausea and constipation (or diarrhea) has been reported. Rarely, pancreatitis and kidney failure has occurred. The FDA has required a boxed warning about the risk of thyroid C-cell tumors in the package insert, and in patient’s with a family history of Multiple Endocrine Neoplasia Type 2 or medullary thyroid carcinoma, this treatment is to be avoided.
  • Treatment is started at 0.6 mg injected a day and increased weekly by another 0.6 mg until a total of 3 mg a day is injected. At 16 weeks, if a 4% body weight loss is not achieved, therapy should be stopped. Total cost per month is about $1000.00!
  • For patients who have a BMI>30 (Body mass index) and are not diabetic, or have a BMI>27 with a risk factor, such as hyperlipidemia or diabetes, Saxenda is a consideration for weight loss.
  • Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems

    Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems

Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to methylglyoxal stress

A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management

Liraglutide (Saxenda) for Weight Loss

http://ajpgi.physiology.org/content/302/2/G225

Insane Medicine – Even older people should watch their diet

Successful aging requires continued effort for the best outcome. Do you want to live to one hundred and be bed-bound or live to one hundred and be active? Successfully aging people need to consider healthful behaviors to maintain their independence and health. Conditions that affect people over sixty can be modified and lessened by nutritional strategies:

  1. Cardiovascular disease: High blood pressure, cholesterol/triglycerides, and obesity are modifiable by diet and medication. Weight control allows for better mobility, less pain, and fewer heart attacks. Obesity is associated with sleep apnea, as well, which reduces quality of life because it makes you fatigued in the day time and generally weak.
  2. Cerebrovascular Disease: Such as strokes and dementia are impacted by high blood pressure and diet. First off, quit smoking to decrease your risk of dementia and stroke. Decrease your sodium intake to decrease your blood pressure (1500 mg of sodium a day is about right for an average diet.) Use herbs and spices to flavor your foods. Foods such as cold cuts, cheeses, breads, pizza, pasta dishes, snack foods, and soups have higher levels of sodium, so beware. Consider following the DASH diet: http://www.nhlbi.nih.gov/health/health-topics/topics/dash  and http://health.gov/dietaryguidelines/2015-scientific-report/ 
  3. Diabetes Control: Diabetes affects everything from your eyes to your kidneys. There is a four-fold increased risk of death from heart disease or stroke if you are diabetic. Take your medicines, track your hemoglobin A1C (sugar control measure) and eat ¬†food with a low glycemic index. Eat food with less fat and avoid high-sugar content items, but include more vegetables and whole grains to maintain glucose control. It takes a lot of effort if you are diabetic, so don’t let diabetes take your life one leg at a time!
  4. Cancer: Get your recommended screening examinations. Also, maintain a healthy weight since obese people have higher risks of cancer!
  5. Chronic Kidney Disease: Another disease modifiable by diet control – CKD risk is increased if you have hypertension, diabetes, obesity, or cardiovascular disease. A healthy diet and physical activity will maintain your weight and blood pressure, minimizing aging’s impact on your kidneys!

Suggestions:

  • Eat bright colored vegetables (carrots, brocolli) and deep colored fruits (berries) for phytochemical, healthy support.
  • Chose whole, enriched, fortified grains and cereals, i.e. whole wheat bread.
  • Chose low and non-fat dairy products: Yogurt and low-lactose milk
  • Use herbs and spices to add flavors to meals
  • Lots of fluids: no sodas
  • Exercise

Insane Medicine – New future treatment for obesity –

Insane Medicine: incretins and dpp
Incretins and DPP . GLP-1 stimulates the release of insulin to help lower blood sugar after a meal. It also prevents glucagon release. Glucagon causes the breakdown of glycogen stores in the liver into glucose, thereby raising blood sugar. DPP-4 is an enzyme that inactivates GLP-1.
Action of GLP
Action of GLP – as before, GLp is produced in the stomach in response to food and causes the pancreas to increase insulin production and decreases glucagon expression.
gip and glp actions
Gip and glp actions

Our generally bad diets, high in fat and processed sugar result in obesity and metabolic derangements. As a result of years of insulting foods, the body’s cells reprogram themselves in such a way that even if one exercises and diets well, it¬†remains difficult¬†to lose weight.

Bariatric surgery has been effective in producing significant weight loss and metabolic changes, allowing one to have less appetite, burn more calories, lose fat, and lose weight.

In the diagram above, the body normally responds to a meal by producing GLP-1 and GIP, which act on the pancreas to produce more insulin to lower the blood sugar. GLP-1 also prevents the secretion of glucagon, which is a hormone that causes the production of glucose from fat. In type 2 diabetes, the body does not respond to GLP-1, GIP, or glucagon as it should, so the GLP-1 no longer suppresses appetite or promotes insulin production after a meal. The failure of glucagon to be active in the body results in fat accumulation.  Bariatric surgery has been the only method to boost the effective functioning of GLP-1, GIP, and glucagon.

Researches at the Helmholtz Diabetes Center in Munich, Germany have produces a protein that takes structural pieces of GLP-1, GIP, and glucagon and merges them into a single¬†functional unit.¬† This drug, when injected into rats, increased glucose lowering, fat burning, and weight loss in obese rats through clear metabolic changes. This resulted in test rats to lose up to a third of their body weight! A pill and no surgery…sounds like a great opportunity!

Insane Medicine – Obesity increases your risk of Alzheimer’s disease.

  • Obesity increases your risk of diabetes, hypertension, stroke, and cancer. It also increases your risk of cognitive decline. It has been shown, however, that weight loss can reverse some of the cognitive decline! This was shown in patients with gastric bypass who were found to have improvements in their executive functioning after surgery and weight loss. Executive functioning includes the processes of organizing, planning, an decision-making. Also improved is attention and memory.
  • Also linked to this cognitive decline in obese people is lack of physical activity, poor inflammatory-type diet, and depression.
  • Increased fat causes problems in executive functioning, decreased memory, and ¬†decreased processing speeds, all of which worsen with age as well. The high content of simple sugars and saturated fat cause a disruption in the blood-brain barrier that allow inflammation to occur in the brain, especially from the passage of Interleukin-1, which is secreted by fat and passes through this disrupted brain barrier. The hippocampus is the target that is affected, thereby diminishing memory by disrupting the connections in the brain called synapses. In the lab, lowering the brain’s level of interleukin-1 results in improved cognitive performance.

What to do? Emphasis on healthy choices and then weight loss:

  • Exercise regularly
  • Decrease stress through relaxation, meditation, or other routes.
  • Get plenty of sleep
  • From Harvard's healthy eating plate - one-half the plate is for fruits and vegetables, one-fourth with whole grains, the rest is devoted to fish, beans, nuts, or chicken - all unprocessed.
    From Harvard’s healthy eating plate – one-half the plate is for fruits and vegetables, one-fourth with whole grains, the rest is devoted to fish, beans, nuts, or chicken – all unprocessed.

    healthy-eating-plate-web1000

  • Eat a proper diet, less processed food, for example, use whole wheat bread and avoid processed meats such as hot dogs or salami. Choose low fat dairy products. Avoid additives or flavorings.Chose healthy plant oils such as canola and olive oils. Eat smaller portions of food.
  • Caffeine intake can ¬†be safe in adults up to 400 mg a day and can increase wakefulness, better recall of spatial information, improved attention, faster reaction time, ¬†and decrease feelings of fatigue. ¬†It may also enhance memory and cognition as well. One study linked drinking three to five cups of coffee a day with a 65 % decrease in dementia. Caffeine was noted to decrease the formation of tau protein in the hippocampus of rats. Tau protein deposition is a hallmark of Alzheimer’s disease. ¬†Caffeine enhances the brains’s memory and allows the consolidation of information for the long term.

Insane medicine – Qsymia for weight loss

Insane Medicine - Qsymia for weight loss
Insane Medicine – Qsymia for weight loss
  • Qsymia is a prescribed medication that has phentermine and topiramate in it and¬†acts as a centrally acting appetite suppressant.
  • For this therapy to work, you must add exercise and calorie reduction to the program. It is used generally when you have a BMI (body mass index) of 27 kg/m-sq and a weight-related comorbidity (i.e. diabetes) or if you have ¬†just a BMI of more than 30 kg/m-sq ( anything over 30 is considered obese)
  • The dosage is a 3.75/23 mg tablet (phentermin/topiramate) a day initially, escalating to the maximum dosage of a 15/92 mg tablet a day over several weeks.
  • The combination is safe, and there is no increase in depression rates or arrhythmias or heart valve disease from the phentermine component. However, birth control must be used since phentermine is teratogenic ( it causes cleft lips).
  • There are side effects such as dry mouth and constipation. Some people complain of insomnia. None are bad enough that patients cannot tolerate the medication.
  • At the maximum dose (15/92), the average weight loss was 11% of the initial body weight, ¬†whereas the lower dosages result in an 8% total body weight loss after a year.
  • The other results from this weight loss include blood pressure decreases by 3-5 mm of hg and improvement in diabetes, with hemoglobin AC ( a sugar level) drop of 0.2-0.4%.
  • The medication is taken in the morning starting with the lowest dose (3.75/23) and then escalating to the target dose (7.5/46) in 2 weeks. This can be increased after 12 weeks if there is not a 3% body weight loss.
  • Other medical options for weight loss include Locaserin (Belviq), Orlistat ¬†(Xenical), and plain phentermine.