Keytruda (Pembrolizumab for Injection) – updated on RxList

<h1>Keytruda (Pembrolizumab for Injection) – updated on RxList</h1>

Keytruda (Pembrolizumab for Injection) – updated on RxList

Included as part of the PRECAUTIONS section. PRECAUTIONS Immune-Mediated Pneumonitis
KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis. Evaluate patients with suspected pneumonitis with radiographic imaging and administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent followed by a taper) for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for moderate (Grade 2) pneumonitis, and permanently discontinue KEYTRUDA for severe (Grade 3), life-threatening (Grade 4), or recurrent moderate (Grade 2) pneumonitis [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS ]. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), Grade 2 (1.3%), Grade 3 (0.9%), Grade 4 (0.3%), and Grade 5 (0.1%) pneumonitis. The median time to onset was 3.3 months (range: 2 days to 19.3 months), and the median duration was 1.5 months (range: 1 day to 17.2+ months). Sixty-three (67%) of the 94 patients received systemic corticosteroids, with 50 of the 63 receiving high-dose corticosteroids for a median duration of 8 days (range: 1 day to 10.1 months) followed by a corticosteroid taper. Pneumonitis occurred more frequently in patients with a history of prior thoracic radiation (6.9%) than in patients who did not receive prior thoracic radiation (2.9%). Pneumonitis led to discontinuation of KEYTRUDA in 36 (1.3%) patients. Pneumonitis resolved in 55 (59%) of the 94 patients. Immune-Mediated Colitis
KEYTRUDA can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent followed by a taper) for Grade 2 or greater colitis. Withhold KEYTRUDA for moderate (Grade 2) or severe (Grade 3) colitis, and permanently discontinue KEYTRUDA for life-threatening (Grade 4) colitis [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS ].
Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), Grade 3 (1.1%), and Grade 4 (<0.1%) colitis. The median time to onset was 3.5 months (range: 10 days to 16.2 months), and the median duration was 1.3 months (range: 1 day to 8.7+ months). Thirty-three (69%) of the 48 patients received systemic corticosteroids, with 27 of the 33 requiring high-dose corticosteroids for a median duration of 7 days (range: 1 day to 5.3 months) followed by a corticosteroid taper. Colitis led to discontinuation of KEYTRUDA in 15 (0.5%) patients. Colitis resolved in 41 (85%) of the 48 patients. Immune-Mediated Hepatitis
KEYTRUDA can cause immune-mediated hepatitis. Monitor patients for changes in liver function. Administer corticosteroids (initial dose of 0.5 to 1 mg/kg/day [for Grade 2 hepatitis] and 1 to 2 mg/kg/day [for Grade 3 or greater hepatitis] prednisone or equivalent followed by a taper) and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS ].
Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), Grade 3 (0.4%), and Grade 4 (<0.1%) hepatitis. The median time to onset was 1.3 months (range: 8 days to 21.4 months), and the median duration was 1.8 months (range: 8 days to 20.9+ months). Thirteen (68%) of the 19 patients received systemic corticosteroids, with 12 of the 13 receiving high-dose corticosteroids for a median duration of 5 days (range: 1 to 26 days) followed by a corticosteroid taper. Hepatitis led to discontinuation of KEYTRUDA in 6 (0.2%) patients. Hepatitis resolved in 15 (79%) of the 19 patients. Immune-Mediated Endocrinopathies Hypophysitis
KEYTRUDA can cause hypophysitis. Monitor for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for moderate (Grade 2) hypophysitis and withhold or discontinue KEYTRUDA for severe (Grade 3) or life-threatening (Grade 4) hypophysitis [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS ].
Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), Grade 3 (0.3%), and Grade 4 (<0.1%) hypophysitis. The median time to onset was 3.7 months (range: 1 day to 11.9 months), and the median duration was 4.7 months (range: 8+ days to 12.7+ months). Sixteen (94%) of the 17 patients received systemic corticosteroids, with 6 of the 16 receiving high-dose corticosteroids. Hypophysitis led to discontinuation of KEYTRUDA in 4 (0.1%) patients. Hypophysitis resolved in 7 (41%) of the 17 patients. Thyroid Disorders
KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism and thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for severe (Grade 3) or life-threatening (Grade 4) hyperthyroidism [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS ].
Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and Grade 3 (0.1%) hyperthyroidism. The median time to onset was 1.4 months (range: 1 day to 21.9 months), and the median duration was 2.1 months (range: 3 days to 15.0+ months). Hyperthyroidism led to discontinuation of KEYTRUDA in 2 (<0.1%) patients. Hyperthyroidism resolved in 71 (74%) of the 96 patients.
Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and Grade 3 (0.1%) hypothyroidism. The median time to onset was 3.5 months (range: 1 day to 18.9 months), and the median duration was not reached (range: 2 days to 27.7+ months). Hypothyroidism led to discontinuation of KEYTRUDA in 1 (<0.1%) patient. Hypothyroidism resolved in 48 (20%) of the 237 patients. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC occurring in 28 (15%) of 192 patients receiving KEYTRUDA, including Grade 3 (0.5%) hypothyroidism. Of these 28 patients, 15 had no prior history of hypothyroidism.
Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. The median time of onset was 1.2 months (range: 0.5 to 3.5 months). Type 1 Diabetes Mellitus
KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients receiving KEYTRUDA. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS ]. Immune-Mediated Nephritis And Renal Dysfunction
KEYTRUDA can cause immune-mediated nephritis. Monitor patients for changes in renal function. Administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent followed by a taper) for Grade 2 or greater nephritis. Withhold KEYTRUDA for moderate (Grade 2), and permanently discontinue KEYTRUDA for severe (Grade 3) or life-threatening (Grade 4) nephritis [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS ].
Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), Grade 3(0.1%), and Grade 4 (<0.1%) nephritis. The median time to onset was 5.1 months (range: 12 days to 12.8 months), and the median duration was 3.3 months (range: 12 days to 8.9+ months). Eight (89%) of the 9 patients received systemic corticosteroids, with 7 of the 8 receiving high-dose corticosteroids for a median duration of 15 days (range: 3 days to 4.0 months) followed by a corticosteroid taper. Nephritis led to discontinuation of KEYTRUDA in 3 (0.1%) patients. Nephritis resolved in 5 (56%) of the 9 patients. Nephritis occurred in 1.7% of 405 patients receiving KEYTRUDA in combination with pemetrexed and platinum in the KEYNOTE-189 study, including Grade 3 (1%) and Grade 4 (0.5%) nephritis. The median time to onset was 3.2 months (range: 16 days to 11.1 months) and the duration ranged from 1.6 to 16.8+ months. Six (86%) of the 7 patients received systemic corticosteroids, with all 6 receiving high-dose corticosteroids for a median duration of 3 days (range: 1 to 17 days) followed by a corticosteroid taper. Nephritis led to discontinuation of KEYTRUDA in 5 (1.2%) patients. Nephritis resolved in 2 (29%) of the 7 patients. Immune-Mediated Skin Adverse Reactions
Immune-mediated rashes, including SJS, TEN (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and exclude other causes. Based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA. [See DOSAGE AND ADMINISTRATION ] Other Immune-Mediated Adverse Reactions
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA. While immune-mediated adverse reactions usually occur during treatment with PD-1/PD-L1 blocking antibodies, they may occur after discontinuation of treatment.
For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the immune-mediated adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS ].
The following clinically significant, immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients treated with KEYTRUDA: arthritis (1.5%), uveitis, myositis, Guillain- Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including cHL, and post-marketing use.
Solid organ transplant rejection has been reported in the post-marketing setting in patients treated with KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment with KEYTRUDA versus the risk of possible organ rejection in these patients. Infusion-Related Reactions
KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 6 (0.2%) of 2799 patients receiving KEYTRUDA. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions, stop infusion and permanently discontinue KEYTRUDA [see DOSAGE AND ADMINISTRATION ]. Complications Of Allogeneic HSCT Allogeneic HSCT After Treatment With KEYTRUDA
Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA on any trial, 6 patients (26%) developed graft-versus-host-disease (GVHD), one of which was fatal, and 2 patients (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, one of which was fatal. Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT. Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immunemediated adverse reactions, and intervene promptly. Allogeneic HSCT Prior To Treatment With KEYTRUDA
In patients with a history of allogeneic HSCT, acute GVHD, including fatal GVHD, has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after treatment with KEYTRUDA. Consider the benefit of treatment with KEYTRUDA versus the risk of possible GVHD in patients with a history of allogeneic HSCT. Increased Mortality In Patients With Multiple Myeloma When KEYTRUDA Is Added To A Thalidomide Analogue And Dexamethasone
In two randomized clinical trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone, a use for which no PD-1 or PD-L1 blocking antibody is indicated, resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PDL1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials. Embryo-Fetal Toxicity
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Animal models link the PD-1/PD-L1 signaling pathway with maintenance of pregnancy through induction of maternal immune tolerance to fetal tissue. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment with KEYTRUDA and for 4 months after the last dose of KEYTRUDA [see Use In Specific Populations ]. Patient Counseling Information Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Inform patients of the risk of immune-mediated adverse reactions that may be severe or fatal, may occur after discontinuation of treatment, and may require corticosteroid treatment and interruption or discontinuation of KEYTRUDA. These reactions may include: Pneumonitis: Advise patients to contact their healthcare provider immediately for new or worsening cough, chest pain, or shortness of breath [see WARNINGS AND PRECAUTIONS ]. Colitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain [see WARNINGS AND PRECAUTIONS ]. Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, or easy bruising or bleeding [see WARNINGS AND PRECAUTIONS ]. Hypophysitis: Advise patients to contact their healthcare provider immediately for persistent or unusual headache, extreme weakness, dizziness or fainting, or vision changes [see WARNINGS AND PRECAUTIONS ]. Hyperthyroidism and Hypothyroidism: Advise patients to contact their healthcare provider immediately for signs or symptoms of hyperthyroidism and hypothyroidism [see WARNINGS AND PRECAUTIONS ]. Type 1 Diabetes Mellitus: Advise patients to contact their healthcare provider immediately for signs or symptoms of type 1 diabetes [see WARNINGS AND PRECAUTIONS ]. Nephritis: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis [see WARNINGS AND PRECAUTIONS ]. Severe skin reactions: Advise patients to contact their healthcare provider immediately for any signs or symptoms of severe skin reactions, SJS or TEN [see WARNINGS AND PRECAUTIONS ]. Other immune-mediated adverse reactions: Advise patients that immune-mediated adverse reactions can occur and may involve any organ system, and to contact their healthcare provider immediately for any new signs or symptoms [see WARNINGS AND PRECAUTIONS ]. Advise patients to contact their healthcare provider immediately for signs or symptoms of infusionrelated reactions [see WARNINGS AND PRECAUTIONS ]. Advise patients of the risk of solid organ transplant rejection and to contact their healthcare provider immediately for signs or symptoms of organ transplant rejection [see WARNINGS AND PRECAUTIONS ]. Advise patients of the risk of post-allogeneic hematopoietic stem cell transplantation complications [see WARNINGS AND PRECAUTIONS ]. Advise patients of the importance of keeping scheduled appointments for blood work or other laboratory tests [see WARNINGS AND PRECAUTIONS ]. Advise females that KEYTRUDA can cause fetal harm. Instruct females of reproductive potential to use highly effective contraception during and for 4 months after the last dose of KEYTRUDA [see WARNINGS AND PRECAUTIONS and Use In Specific Populations ]. Advise nursing mothers not to breastfeed while taking KEYTRUDA and for 4 months after the final dose [see Use In Specific Populations ]. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility
No studies have been performed to test the potential of pembrolizumab for carcinogenicity or genotoxicity.
Fertility studies have not been conducted with pembrolizumab. In 1-month and 6-month repeat-dose toxicology studies in monkeys, there were no notable effects in the male and female reproductive organs; however, most animals in these studies were not sexually mature. Use In Specific Populations Pregnancy Risk Summary
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. In animal models, the PD-1/PD-L1 signaling pathway is important in the maintenance of pregnancy through induction of maternal immune tolerance to fetal tissue [see Data ]. Human IgG4 (immunoglobulins) are known to cross the placenta; therefore, pembrolizumab has the potential to be transmitted from the mother to the developing fetus. There are no available human data informing the risk of embryo-fetal toxicity. Apprise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data
Animal Data
Animal reproduction studies have not been conducted with KEYTRUDA to evaluate its effect on reproduction and fetal development, but an assessment of the effects on reproduction was provided. A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. Blockade of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering KEYTRUDA during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 knockout mice. Based on its mechanism of action, fetal exposure to pembrolizumab may increase the risk of developing immunemediated disorders or of altering the normal immune response. Lactation Risk Summary
It is not known whether KEYTRUDA is excreted in human milk. No studies have been conducted to assess the impact of KEYTRUDA on milk production or its presence in breast milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose. Females And Males Of Reproductive Potential Contraception
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman [see WARNINGS AND PRECAUTIONS and Use In Specific Populations ]. Advise females of reproductive potential to use effective contraception during treatment with KEYTRUDA and for at least 4 months following the final dose. Pediatric Use
There is limited experience with KEYTRUDA in pediatric patients. In a study, 40 pediatric patients (16 children ages 2 years to less than 12 years and 24 adolescents ages 12 years to 18 years) with advanced melanoma, lymphoma, or PD-L1 positive advanced, relapsed, or refractory solid tumors were administered KEYTRUDA 2 mg/kg every 3 weeks. Patients received KEYTRUDA for a median of 3 doses (range: 1-17 doses), with 34 patients (85%) receiving KEYTRUDA for 2 doses or more. The concentrations of pembrolizumab in pediatric patients were comparable to those observed in adult patients at the same dose regimen of 2 mg/kg every 3 weeks.
The safety profile in these pediatric patients was similar to that seen in adults treated with pembrolizumab; toxicities that occurred at a higher rate (≥15% difference) in pediatric patients when compared to adults under 65 years of age were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%) and hyponatremia (18%).
Efficacy for pediatric patients with cHL, PMBCL, MSI-H cancers, or MCC is extrapolated from the results in the respective adult populations [see Clinical Studies ]. Geriatric Use
Of 3991 patients with melanoma, NSCLC, HNSCC, cHL or urothelial carcinoma who were treated with KEYTRUDA in clinical studies, 46% were 65 years and over and 16% were 75 years and over. No overall differences in safety or effectiveness were observed between elderly patients and younger patients. Overdosage & Contraindications

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Drugs for Chronic Illness…Don’t do it!

Drugs for Chronic Illness…Don’t do it!

Drugs for Chronic Illness…Don’t do it! April 18, 2019
Whenever I write about the topic of Western drug dependence, especially as it relates to pharmaceuticals for chronic disease conditions, my heart breaks for all those who are ordained to go through this form of karmic-grace. Those who purchase this ride ticket must enter a diabolical and fraudulent merry-go-round bristling with the worse kind of side effects which further reduce one’s health and well-being.
And many of these pharmaceutical drugs are designed to be taken for life, with no safe exit strategy available.
When I was an acupuncture apprentice in the winter of 1998, we had patients coming in with all kinds of conditions, among them: Aids, cancer, lung disorders, anorexia, pain syndromes & so called auto-immune diseases.
One patient, Liz, a 40 year old female wandered into our acupuncture clinic with a fragile gait, as if walking on rice paper. With a face withered by years of pharmaceutical drug use, her brown eyes were withdrawn and lackluster.
Liz entered the Western Medical System at 18 and was soon diagnosed with the latest fad-label, an auto-immune disease, called Lupus .
Knowing that we have a label, like Lupus, is not helpful when it comes to chronic illness. The label does not identify the underlying physical causative agent, nor does it address the deeper emotional and spiritual dynamics. Labels signify disease processes, syndrome manifestations and symptom complexes. If you research these processes and manifestations, you will find that most have no known cause and no known cure but there are loads of drug treatments. Often the prescribed medications, when researched, only state: “treats Lupus”–insinuating that all your symptoms will resolve once you start taking said drug.
Lupus is a condition with no definitive diagnostic markers. In other words a symptom complex (list of symptoms) that could be caused by many factors, like: virus, bacteria, fungal infections, etc. (The body attacking itself is the current theory with auto-immune diseases, with the over 100 different auto-immune diseases for which Lupus is one).
And yet Western medicine and the pharmaceutical industry claim Lupus is: “a multi-symptom disease, often unpredictable in its activity, requiring expertise from a multi-disciplinary team: rheumatologists, neurologists, cardiologists, and nephrologists.”
This is Pharm-talk absurdity for: Let’s just keep pumping you full of drugs.
The big sell for the pharmaceutical industry, on chronic illness or chronic disease treatments, besides the doctor’s authoritative approval and the patient’s fear, is the lie:
This drug will improve your quality of life or in some cases cure the condition. Why else would we take these drugs with so many known side effects?
Based on my own research, I have found there to be ten major incapacitating agents involved in most physical disease states (including almost every known disease label): Bacterial infections (often hidden), viral strains (some unidentified), Lyme disease, parasites, dental toxins (metals and root canals and cavitation infections), fungal infections, gluten syndrome, environmental exposure to chemicals and food additives.
For over 20 years Liz had been taking steroidal medication in the form of Prednisone for her Lupus, as prescribed by her medical doctor. (The steroid Prednisone is still one of the primary prescribed treatments for Lupus). The idea behind steroidal treatment is to: reduce inflammation, tenderness and pain.
Steroids have been used for many different conditions (and numerous disease labels), such as: allergic disorders, skin conditions, ulcerative colitis, arthritis, lupus, psoriasis, or breathing disorders.
The immediate side-effect of steroidal treatment is immune suppression. Yet, immune suppression is only one of over 20 known side-effects or reactions to Prednisone. Others include:
Headache, dizziness, sleep difficulty, inappropriate happiness, severe mood swings, personality change, slow healing cuts, fragile skin, acne, red blotches under skin, increased body hair growth, extreme tiredness, weak muscles, bulging eyes and this does not include one of the most significant side effects: STROKE.
In a 2019 study of 302,826 people administered steroids, 2708 people suffered a stroke. That is about 1 in 100.
Obviously these side effects far outweigh any benefit derived from the steroids and yet millions of people, for decades and decades, have been willing to undergo this drug treatment in a desperate grasp at symptom improvement.
At our clinic, Liz received light touch therapy to calm her spirit. As my preceptor and I listened, she shared intimate details of her journey and expressed tears of sadness. We treated her with acupuncture and also let her have some alone time for silent reflection. For Liz did not need more diagnostic banter, a disease progression monologue or a new drug therapy. After her treatment an herbal formula, along with lifestyle aids and dietary guidelines were suggested to further improve her overall body balance.
Over a 3-month period Liz’s condition improved gradually. During that time, and under her own initiative while working with her doctor’s approval, she lowered her Prednisone down from 20 mg to 5 mg. Then after another month, anxious to get off the steroids for good, she decided to completely stop against my preceptor’s advice and without her doctor’s knowledge.
A few days later she suffered a moderate stroke and we never saw her again. She had once again been absorbed into the Western medical system.
The adverse medication reaction Liz experienced is quite common. When my father was undergoing cancer treatment, one of the experimental chemo drugs prescribed was called Oxyliplatin, which was somewhat new and used mostly for colon cancer, though my father had gallbladder cancer. One day my father informed me that after taking his first dose of Oxyliplatin, he experienced tunnel vision. After his second dose, he went blind for 10 seconds. At the next appointment with his oncologist, he mentioned his episode of blindness.
“Do you think it has anything to do with the chemo?” he asked her.
“Oh no,” she responded, looking puzzled, and then said, “You should see your general practitioner. Maybe you had a mini stroke or maybe you have pneumonia or a blood infection?”
“Dad, it’s the chemo,” I stated emphatically
I went online and checked on the Oxyliplatin and found a recent study showing that blindness was a known side effect of this particular chemo drug. It showed that of 6,670 people in the trial, 33 went blind. Permanently blind! That does not count any who went temporarily blind or had blind flashes like my father.
Western medicine cannot help us with chronic illness or chronic disease conditions. The strength of Western (allopathic) medicine lies in emergency medical intervention. Western medicine has an abysmal record when it comes to treating chronic illness.
Chemical medicines (pharmaceuticals) like antidepressants have side effects such as “suicidal tendencies.” Coming off these medications, we deal with more repercussions than when we originally took the drug. These pharmaceuticals are in fact a “pseudo-savior” for people in a quick-fix culture unwilling to make necessary lifestyle changes and take responsibility for their own health.
Today 7 out of 10 Americans have a chronic illness, which is defined as an illness of long duration (lasting at least three months) with slow progression that takes away a significant measure of health. Over the last 30 years, there has been a major increase in fatiguing syndromes, from those that are neurological-based, like Alzheimer’s disease, Parkinsons and ALS, to those that involve every major organ and system in the body. So each person will be affected by toxic exposure in a unique way.
We’ve all seen the TV commercials for prescription drugs and medications. They’re on every channel, inside magazines, and on the internet.
Until a decade or two ago, the side effects montage on these pharmaceutical commercials were hidden in small letters at the bottom of the screen. Then, with side effects skyrocketing, the pharmaceutical manufacturers (like their Tobacco Industry relatives) were forced to have the side effects read out loud and listed with oversize type.
Now the list of drug-induced side effects are delivered with soothing music, in a gentle non-threatening voice, while subliminal-like cartoon characters play and dance on the screen, a handsome man or gorgeous lady appears in perfect health, all to camouflage or misdirect attention away from the danger and warning signs. You know the kind: “…Let your doctor know if you experience, chest pain, ear hemorrhage…you might also require emergency medical intervention for brain implosion…it’s not unusual to see collapsed lung, kidney failure or…”
What spurred this blog on was a recent encounter with my client. He was diagnosed with Parkinson’s disease and was dealing with a growing list of symptoms: confusion, hallucination, disorientation, irritability and delusion, not to mention, excessive blinking, bladder issues, (he was having bladder infections without tests being able to locate the assumed bacterial culprit).
Originally I thought most of the signs my client was experiencing related to the Parkinson’s disease progression but in fact they were side effects of one of his prescribed medications for the disease, Sinemet (carbidopa and levodopa tablets). So all of these so called symptoms used to treat muscle stiffness and tremors (the original Parkinson’s symptoms) were side effects!
And once you are on a pharmaceutical like Sinemet, coming off or lowering the medication can increase side effect potential and even lead to death (like many other drugs).
The pharmaceutical merry-go-round is not worth riding. Like this:

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Atopic Dermatitis

<h1>Atopic Dermatitis</h1>

Atopic Dermatitis

Flowers and pollen Are food allergies important in atopic dermatitis?
Allergens are substances from foods, plants, or animals that provoke an overreaction of the immune system and cause inflammation (in this case, the skin). The importance of food allergy in atopic dermatitis is controversial. Although not all researchers agree, most experts think that breastfeeding the infant for at least four months may have a protective effect for the child. New lines of evidence even support exposing young children to normal environmental contaminants such as peanuts. Although such exposures may prevent the development of atopic dermatitis, there is no consensus on how to prevent the development of atopic diseases.
If a food allergy is suspected, it may be helpful to keep a careful diary of everything the patient eats, noting any reactions. Identifying the food allergen may be difficult and require supervision by an allergist if the patient is also being exposed to other allergens. One helpful way to explore the possibility of a food allergy is to eliminate the suspected food and then, if improvement is noticed, reintroduce it into the diet under carefully controlled conditions. A two-week trial is usually sufficient for each food. If the food being tested causes no symptoms after two weeks, a different food can be tested in like manner afterward. Likewise, if the elimination of a food does not result in improvement after two weeks, other foods may be eliminated in turn.
Changing the diet of a person who has atopic dermatitis may not always relieve symptoms. A change may be helpful, however, when a patient’s medical history and specific symptoms strongly suggest a food allergy . It is up to the patient and his or her family and physician to judge whether the dietary restrictions outweigh the impact of the disease itself. Restricted diets often are emotionally and financially difficult for patients and their families to follow. Unless properly monitored, diets with many restrictions can also contribute to nutritional problems in children. What are aeroallergens?
Some allergens are called aeroallergens because they are present in the air. They may also play a role in atopic dermatitis. Common aeroallergens are dust mites, pollens, molds, and dander from animal hair or skin. These aeroallergens, particularly the house dust mite , may worsen the symptoms of atopic dermatitis in some people. Although some researchers think that aeroallergens are an important contributing factor to atopic dermatitis, others believe that they are insignificant.
No reliable test is available that determines whether a specific aeroallergen is an exacerbating factor in any given individual. If the doctor suspects that an aeroallergen is contributing to a patient’s symptoms, the doctor may recommend ways to reduce exposure to the offending agents. For example, the presence of the house dust mite can be limited by encasing mattresses and pillows in special dust-proof covers, frequently washing bedding in hot water, and removing carpeting. However, there is no way to completely rid the environment of aeroallergens. What are home remedies for atopic dermatitis? Share Your Story
Treatment involves a partnership between the doctor and the patient and family members. The doctor will suggest a treatment plan based on the patient’s age, symptoms, and general health. The patient and family members play a large role in the success of the treatment plan by carefully following the doctor’s instructions. Some of the primary components of treatment programs are described below. Most patients can be successfully managed with proper skin care and lifestyle changes and do not require the more intensive treatments discussed.
Skin care : A simple and basic regimen is key. Staying with one recommended soap and one moisturizer is very important. Using multiple soaps, lotions, fragrances, and mixes of products may cause further issues and skin sensitivity.
Healing the skin and keeping it healthy are of primary importance both in preventing further damage and enhancing the patient’s quality of life. Developing and following a daily skin care routine is critical to preventing recurrent episodes of symptoms. The key factor is proper bathing and the application of an emollient to the wet skin without towel drying. Generally, an effective emollient is a reasonably stiff ointment or cream (one that does not move out of an opened inverted jar). People with atopic dermatitis should avoid hot baths and showers. A lukewarm bleach bath with a capful of chlorine bleach (Clorox) helps to cleanse and disinfect the skin. The doctor may recommend limited use of a mild bar soap or non-soap cleanser because soaps can be drying to the skin. Oatmeal baths are often helpful. Red, irritated areas can be treated with 1% hydrocortisone cream (two to three times a day), which can be obtained at most pharmacies and does not require a physician’s prescription.
Once the bathing is finished, apply an emollient immediately without towel drying. This restores the skin’s moisture and inhibits the evaporation of water, increasing the rate of healing, and establishing a barrier against further drying and irritation. Lotions generally are discouraged because they have a high water or alcohol content and evaporate quickly. Creams and ointments work better at healing the skin. Tar preparations can be very helpful in healing very dry, lichenified areas. Whatever preparation is chosen, it should be as free of fragrances and chemicals as possible.
Another key to protecting and restoring the skin is taking steps to avoid repeated skin infections. Although it may not be possible to avoid infections altogether, the effects of an infection may be minimized if they are identified and treated early. Patients and their families should learn to recognize the signs of skin infections, including tiny pustules (pus-filled bumps) on the arms and legs, appearance of oozing areas, or crusty yellow blisters. If symptoms of a skin infection develop, the doctor should be consulted to begin treatment as soon as possible. Treating atopic dermatitis in infants and children Give lukewarm baths. Apply an emollient immediately following the bath. Keep a child’s fingernails filed short. Select soft cotton fabrics when choosing clothing. Consider using antihistamines to reduce scratching at night. Keep the child cool; consider a humidifier. Learn to recognize skin infections and seek treatment promptly. Attempt to distract the child with activities to keep him or her from scratching. What is the treatment for atopic dermatitis?
If the disease does not respond to mild local over-the-counter treatment then a physician is required. With proper treatment, most symptoms can be brought under control within three weeks.
Topical corticosteroid creams and ointments are the most frequently used treatment. Since many of these are quite potent it will be necessary to have frequent physician visits to assure that the treatment is successful.
Tacrolimus ( Protopic ) and pimecrolimus ( Elidel ) are non-steroid topical ointments that contain molecules that inhibit a substance called calcineurin which is important in inflammation. They rather expensive topical medicated creams that are used for the treatment of atopic dermatitis. They are particularly effective in when used on the faces of children since they seem less likely to produce atrophy. These new drugs are referred to as “immune modulators.”
Crisaborole (Eucrisa), a recently approved topical treatment for children and adults with mild to moderate atopic dermatitis (AD) which seems to work by inhibiting a different portion of the inflammatory cascade in skin.
Dupilumab (Duxipent) was recently approved by the FDA for treatment of moderate to severe atopic dermatitis in adults. It is an anti-IL-4 antibody that is given by injection twice a month and shows great promise in the control of severe atopic dermatitis.
A newer class of OTC (over the counter) creams have been recently developed which claim to repair and improve the skin’s barrier function in both children and adults. They include Atopiclair, MimyX, and CeraVe. These creams may be used in combination with topical steroids and other emollients to help repair the overall dryness and broken skin function.
Additional available treatments may help to reduce specific symptoms of the disease. Oral antibiotics to treat staphylococcal skin infections can be helpful in the face of pyoderma. Certain antihistamines that cause drowsiness can reduce nighttime scratching and allow more restful sleep when taken at bedtime. This effect can be particularly helpful for patients whose nighttime scratching aggravates the disease. If viral or fungal infections are present, the doctor may also prescribe medications to treat those infections.
Phototherapy is treatment with light that uses ultraviolet A or B light waves or a combination of both. This treatment can be an effective treatment for mild to moderate dermatitis in older children (over 12 years old) and adults. Photochemotherapy, a combination of ultraviolet light therapy and a drug called psoralen, can also be used in cases that are resistant to phototherapy alone. Possible long-term side effects of this treatment include premature skin aging and skin cancer . If the doctor thinks that phototherapy may be useful in treating the symptoms of atopic dermatitis, he or she will use the minimum exposure necessary and monitor the skin carefully.
When other treatments are not effective, the doctor may prescribe systemic corticosteroids , drugs that are taken by mouth or injected into muscle instead of being applied directly to the skin. An example of a commonly prescribed corticosteroid is prednisone . Typically, these medications are used only in resistant cases and are only given for short periods of time. The side effects of systemic corticosteroids can include skin damage, thinned or weakened bones, high blood pressure , high blood sugar , infections, and cataracts . It can be dangerous to suddenly stop taking corticosteroids, so it is very important that the doctor and patient work together in changing the corticosteroid dose.
In adults, immunosuppressive drugs, such as cyclosporine , are also used to treat severe cases of atopic dermatitis that have failed to respond to any other forms of therapy. Immunosuppressive drugs restrain the overactive immune system by blocking the production of some immune cells and curbing the action of others. The side effects of cyclosporine can include high blood pressure , nausea , vomiting , kidney problems, headaches , tingling or numbness, and a possible increased risk of cancer and infections. There is also a risk of relapse after the drug is discontinued. Because of their toxic side effects, systemic corticosteroids and immunosuppressive drugs are used only in severe cases and then for as short a period of time as possible. Patients requiring systemic corticosteroids or immunosuppressive drugs should be referred to a dermatologist or an allergist specializing in the care of atopic dermatitis to help identify trigger factors and alternative therapies.
In extremely rare cases, when no other treatments have been successful, the patient may have to be hospitalized. A five- to seven-day hospital stay allows intensive skin care treatment and reduces the patient’s exposure to irritants, allergens, and the stresses of day-to-day life. Under these conditions, the symptoms usually clear quickly if environmental factors play a role or if the patient is not able to carry out an adequate skin care program at home. Atopic dermatitis and quality of life
Despite the symptoms caused by atopic dermatitis, it is possible for people with the disorder to maintain a high quality of life. The keys to an improved quality of life are education, awareness, and developing a partnership among the patient, family, and doctor. Good communication is essential for all involved. It is important that the doctor provides understandable information about the disease and its symptoms to the patient and family and demonstrate any treatment measures recommended to ensure that they will be properly carried out.
When a child has atopic dermatitis, the entire family situation may be affected. It is important that families have additional support to help them cope with the stress and frustration associated with the disease. The child may be fussy and difficult and often is unable to keep from scratching and rubbing the skin. Distracting the child and providing as many activities that keep the hands busy are key but require effort and work on the part of the parents or caregivers. Another issue a family may face is the social and emotional stress associated with disfigurement caused by atopic dermatitis. The child may face difficulty in school or other social relationships and may need additional support and encouragement from family members. What is the prognosis of atopic dermatitis?
Although symptoms of atopic dermatitis can be very difficult and uncomfortable, the disease can be successfully managed. People with atopic dermatitis, as well as their families, can lead healthy, normal lives. Long-term management may include treatment with an allergist to control inhalant allergies and a dermatologist to monitor the skin care component.

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Systemic vasculitis: present, future and long future

<h1>Systemic vasculitis: present, future and long future</h1>

Systemic vasculitis: present, future and long future

Posted by Dr Stephen Hall
In this discussion, I will restrict myself to issues of granulomatosis with polyangiitis, eosinophilia with granulomatosis and polyangiitis, polyarteritis nodosa, large-vessel vasculitis (giant cell arteritis) and Takayasu arteritis.
This is probably more than enough to consider where we stand at present, where we might be in five years and where we might be in 20 years.
With respect to the current management of vasculitis, the fundamental treatment modality for all forms of vasculitis remains corticosteroids.
This is a sad reflection of where we are, since corticosteroids have been around since 1949 and first used for systemic vasculitis in the early 1950s. GRANULOMATOSIS WITH POLYANGIITIS
The main changes that have occurred in this disease are to some extent related to nomenclature with the withdrawal of the eponymous name of Wegener’s granulomatosis substantially as a result of historical research by Eric Matteson and his colleagues, and then by consensus of the vasculitis world. The literature has explored a variety of steroid-sparing drugs in an effort to try to minimise toxicity from corticosteroids. It is very clear that the cumulative damage in systemic vasculitis is very similar to that of systemic lupus erythematosus, with part being due to the disease and perhaps an even larger part due to the ravages of our therapies. Methotrexate, azathioprine, mycophenolate and leflunomide have all been employed as steroid-sparing drugs. We have the least experience with leflunomide, but in direct head-to-head studies conducted by Wolfgang Gross, leflunomide in a higher than usual dose of 30mg daily does seem to be more effective than methotrexate.
Having said this, these things are typically studied over a relatively short period of time of one to two years. Given that we are dealing with conditions of extraordinary chronicity with a notorious tendency to relapse, the long-term results really need to be better assessed. In that regard, there is more data supporting the use of azathioprine compared with methotrexate. And there is a total dearth of long-term data looking at leflunomide or mycophenolate.
It was really the introduction of rituximab as an agent for treatment of ANCA-associated vasculitis which changed the complexion of our therapies. In clinical trials, rituximab was found to be as effective as cyclophosphamide and in relapsing disease, probably more effective, according to a post-hoc analysis.
However, it still remains important that everybody involved in the care of patients with systemic vasculitis appreciate that there was no reduction in the toxicity of drugs and in particular, no reduction in the infection risk when comparing cyclophosphamide to rituximab. That suggests that in the setting of systemic vasculitis, as we have already seen in rheumatoid arthritis and systemic lupus erythematosus, the risk of infections very much lies with how much corticosteroid is employed. .
Corticosteroids suffer in the broader general medical community from a degree of “familiarity breeding contempt”, in that people who have used drugs for many years see them as being relatively innocuous, whereas the fact is that corticosteroids are the most potent immunosuppressive agents that we have.
One main goal of therapy has to be to reduce the dose of corticosteroids to as low as possible. There is convincing data from pooled analyses done by Peter Merkel that the continuation of prednisone/prednisolone in doses of 5mg a day is associated with a significant lessening in the risk of relapse. Consequently, there may not be any great argument for taking people off corticosteroids totally and keeping people on a small dose seems to be beneficial.
Clearly for some people, using rituximab is preferable to using cyclophosphamide. In particular, women with childbearing potential, men looking to father children in the future, people who have already received significant amounts of cyclophosphamide and those with relapsing disease all deserve being considered for rituximab. We recognise that there are different forms of GPA and many of these can be managed with much simpler and less toxic remedies.
Low-dose corticosteroids and methotrexate will hold many people who have more limited forms of GPA, particularly those with sinus disease, modest lung disease and unusual conditions such as disease localised to breast. IN FIVE YEARS
One can expect that in five years’ time, the world will have changed. In particular, the multitude of biosimilars available in the market will have reduced the costs of rituximab substantially.
One main advantage of cyclophosphamide remains its minimal cost. Rituximab may well be a drug which is used more frequently in the management of GPA and use may spread to the management of less severe forms of disease in association with lesser doses of corticosteroids once there is a reduction in cost.
The advent of killed herpes zoster vaccines will also mean that the risk of shingles which is a significant source of morbidity in the setting of intensive immunosuppression will become less. However, the vaccine has not proved to be a dramatically effective treatment. There is no denying that it has some effect, but in the setting of rheumatic diseases, the degree of protection confirmed by zoster vaccine is probably no more than 50% straight after vaccination and will wane over the next three to four years.
There is no registration available for repeat administration of Zostavax at this stage.
Less toxic steroids It is possible that studies on newer forms of corticosteroid will also allow the development of corticosteroids of lesser toxicity, though whether this can be achieved within a five-year window is uncertain.
Nevertheless, there are a variety of interesting compounds being analysed, looking to see whether they can maintain corticosteroid effect while at the same time, lessening the degree of steroid toxicity. IN 20 YEARS
The question here will be whether we can predict who will develop rare forms of vasculitis. We already have GWAS studies which have looked at the genetic propensity and there do seem to be some genetics which are significantly associated with the development of GPA.
There is some evolving data suggesting that the gut microbiome might also be of relevance.
There have been reports even as recently as last year’s American College of Rheumatology conference that there are differences in gut microbiota in patients with ANCA-associated vasculitis who have active disease and those in remission.
Whether that means that one can manipulate the gut bacteria to effect a more suppressive state remains to be seen, but the association is tantalisingly suggestive as a treatment option.
However, one would hope that the main intervention which might be possible in the future will relate to vaccination or desensitisation.
There is some seasonal variation in the incidence of GPA. This type of vasculitis looks as if it may begin in the upper airways, then extend to the lung and then become a more systemic disease in many cases, suggesting that perhaps the primary allergen which triggers the process is one which is inhaled.
That lends the possibility of identification of these antigens and then at the first sign of disease, considering desensitisation via nasal spray. It is very clear that that mode of desensitisation is more effective than other forms of desensitisation.
It is tantalising to imagine that at the first sign of somebody having a systemic illness, a widespread battery of tests would be performed on small drops of blood which would then turn up genetic markers equivalent to the ANCA that we use today. On finding this, the clinician could then embark on a nasal desensitisation program which hopefully will then downregulate the immune system’s response to that allergen and then turn off the whole disease process without any further dramatic interventions. EGPA
Eosinophilia with granulomatosis and polyangiitis is another disease which lost its original name (Churg-Strauss vasculitis) in the shuffle which led to Wegener’s granulomatosis no longer being an eponymous immortality for a German pathologist linked to the Nazi movement.
The treatment of EGPA has remained similar to the treatment of GPA, which is to say maintenance corticosteroids, steroid-sparing agents and, in particular, cyclophosphamide. The experience with rituximab has been considerably less than with GPA, but, currently under PBS guidelines, one is allowed to prescribe rituximab for EGPA on the basis of angiitis.
Prognosis for EGPA is determined by its other clinical manifestations. It is considerably rarer than GPA and consequently, my personal experience with this condition is less than it is with GPA. It still carries a significant five-year and 10-year mortality, in part related to the disease manifestations and in part related to complications of therapy. IN FIVE YEARS
IL-5 is critical for development and proliferation of eosinophils. Mepolizumab, an antibody to IL-5 has been found to be helpful in the management of EGPA and other IL-5 agents, including benralizumab and reslizumab, are in the process of being studied. Those results will contribute to determining the direction of therapy in five years’ time. In addition, prospective studies of rituximab in EGPA now being conducted will determine if this agent will continue to be used for this condition.
IL-5-dependent cell proliferation and survival is dependent on Janus kinase-signal transduction, as well as tyrosine kinases including BTK (bruton tyrosine kinase). This would raise the possibility that small molecules such as JAK inhibitors and BTK inhibitors (many of which are already licensed for treating haematological disease) might yet have their hand turned to the management of EGPA.
These would represent potentially dramatically new approaches to the treatment of eosinophilic diseases. Illustration by intern Armando Hasudungan, to help him and others learn. For more, visit https://armandoh.org IN 20 YEARS
There is considerably less data on seasonality in EGPA than there is for other more common forms of vasculitis. EGPA occurs with an incidence of about one tenth that of GPA.
Nevertheless, the nature of the eosinophilia does raise the possibility that there is an allergic aspect to this as well. Therefore, desensitisation could well be a useful approach to therapies in 20 years’ time.
This is a condition where it is very clear that the eosinophil may directly cause damage to the myocardium through toxins in the eosinophilic proteins.
This is similar to what is seen in the hypereosinophilic syndrome.
The development of specific agents capable of blocking the effect of these chemicals would go a long way towards minimising tissue damage. In this situation, as is the case with GPA, tissue damage would have the potential to be modified by regenerative medical approaches which does require very specific stem cells capable of regenerating myocardium or nerve tissue along the lines of the discovery of specific stem cells for skeletal tissues. POLYARTERITIS NODOSA
Polyarteritis nodosa is, with EGPA, the least common of the major systemic vasculitides. Currently, the diagnosis is made on either deep tissue biopsy, angiography or electromyogram depending on the pattern of involvement.
It is important to recognise that cutaneous forms of polyarteritis are highly unlikely to ever evolve into systemic disease and their presence does not mandate the use of aggressive treatments. These are essentially benign local variants of vasculitis and usually do well with low-intensity treatment, such as corticosteroids in moderate doses, coupled with methotrexate.
There are significant differences between polyarteritis and the ANCA-associated vasculitides (AAV), particularly in terms of prognosis.
Polyarteritis has a much lower rate of recurrence than do the other forms of vasculitis and it would be far more typical to be a “one shot” disease while AAV is notorious for its tendency to recur.
There are no immunological markers equivalent to ANCA and thereby the rationale for rituximab is lacking. However, there are case reports of this agent being used in the management of polyarteritis with what seemed to be good results.
There are complexities to the diagnosis of polyarteritis on angiography, particularly related to the increasingly use of CT angiograms as a way of surveying vascular beds.
Unfortunately, the limits of resolution of CT angiograms do not lend themselves to a confident diagnosis of polyarteritis. One has to then perform selective direct injection of vascular beds to try and get down to vessels of 1-2mm diameter, which is typically the target vessel of polyarteritis.
While much attention has been placed on the presence of aneurysms as a form of diagnosis, the irregularity of vessels is probably a more common angiographic manifestation of polyarteritis, and one that needs to be searched for with a good vascular radiologist.
We have little to guide us in terms of treatment. There are no clinical trials of classical polyarteritis and we borrow from the trials of other forms of vasculitis which are rather more common.
Corticosteroids remain the mainstay of treatment and methotrexate or azathioprine are typically used as steroid-sparing agents, though depending on people’s preference, micophenolate mofetil or leflunomide may also be employed.
Cyclophosphamide is used for very aggressive forms of polyarteritis and then those forms which are associated with hepatitis B infection, which is increasingly rare in our community, the use of anti-viral therapies coupled with short-course steroids can lead to total remission of vasculitis with no evidence of recurrence. I would not anticipate any great changes to our treatment options in five years’ time. I do not believe that there will be any clinical trials developed to investigate polyarteritis. Currently there are no such trials registered on clinicaltrials.gov.
At this point, I it is unlikely there will be any change to the way that we make the diagnosis, which is essentially established on either: 1. Tissue biopsy, usually muscle, or 2. Angiography, or 3. Electromyography demonstrating mononeuritis multiplex which in the appropriate context allows for a clinical diagnosis of polyarteritis. GIANT CELL ARTERITIS
The current state of play is that giant cell arteritis (GCA) has expanded its spectrum of involvement in recent years. Having always been considered to be a classical condition of “cranial arteritis” characterised by headaches, visual loss, jaw claudication, scalp tenderness and association with polymyalgia rheumatica, the development of other imaging modalities has allowed the recognition of diseases which are centred more around other large vessels, particularly the aorta and its main branches, most commonly in the supradiaphragmatic aorta.
The probability of having positive temporal artery biopsy in the setting of having a positive imaging of large vessels is only about 50% and there seems no purpose served by pursuing the issue any further once the diagnosis of large vessel vasculitis has been established through imaging.
The approaches to establishing a tissue diagnosis have centred around whether one performs unilateral or bilateral biopsies. My prejudice has always been to perform bilateral biopsies based on studies which are now almost ancient. However, more recent studies presented this year at the ACR have confirmed that the bilateral biopsies dramatically increase the probability of having a positive biopsy and that biopsies should be of 3cm on each artery or longer. This will improve the yield on biopsy by a factor of two.
The treatment for large vessel vasculitis has still centred around corticosteroids.
Significantly, in cases of visual loss, there is absolutely no evidence that any treatment makes any difference in the first two weeks of therapy and it is in that first two weeks after presentation that a person who presents with visual loss in one eye has a 50% chance of developing visual loss in the contralateral eye.
It is very rare to lose vision after the first two weeks of high-dose steroids, virtually irrespective of how well controlled the GCA was.
We are currently in the throes of great enthusiasm for tocilizumab as a treatment for GCA based on the 12-month studies conducted by Roche and a smaller pilot study conducted independently as an investigator-initiated study from Switzerland.
It seems fairly clear that the use of tocilizumab will improve the inflammatory numbers so that ESR and CRP will decline substantially, leaving physician and patient much more comfortable engaging in progressive steroid reduction.
Systemic effects of this disease will also improve markedly with the resolution of fevers and polymyalgic symptoms. However, there is considerable debate as to whether IL-6 inhibition actually makes a lot of difference to the large vessels themselves and there is considerable basic science data to suggest that thid might not be the case.
While there is clinical trial data suggesting that intravenous pulse steroids administered at the beginning of the treatment will allow more effective steroid reduction and a less accumulative dose of steroids over the longer term, there seems to have been very little enthusiasm for adopting this approach in the rheumatology community at large.
The vogue for commencing people on aspirin to prevent occlusive events is now waning and there is a recognition that the data supporting their use occurred not from interventional studies, but rather from observational studies that those people who developed the disease while on aspirin had a lesser risk of visual loss and other occlusive events.
Methotrexate has long been popular as a steroid-sparing agent and pooled analyses suggest that it might be of somewhat effective though it is fair to say that the two largest of the three trials which have been conducted of this treatment have not shown a positive result.
Nevertheless, rheumatologists do feel comfortable with methotrexate as a steroid sparing agent.I suspect that until something else better comes on the market, methotrexate will continue to be our default in terms of steroid-sparing options.
Experience with other treatments such as azathioprine, mycophenolate, leflunomide and cyclophosphamide has been very limited and anecdotal. IN FIVE YEARS
My personal prediction is that IL-6 will have a role as a steroid-sparing agent, but it may well be that JAK inhibition through inhibiting both IL-6, reducing both IL-6 levels and interferon gamma levels may well prove to be more effective. There is one trial of a JAK inhibitor about to be conducted.
There is evidence suggesting that JAK inhibition will reduce interferon gamma levels, which is significant given that interferon gamma is the cytokine most associated with occlusive events in giant cell arteritis.
There have also been preliminary studies looking at abatacept which has yielded some positive results. Ustekinumab, which is an IL-12/23 inhibitor, has also been suggested to be of benefit in giant cell arteritis.
IL-12 is a significant factor promoting the generation of interferon gamma. Levels of IL-12 also correlate positive with IL-6 and it is thought that this agent might have the potential to also affect both the interferon gamma and IL-6 pathways, making it a promising agent for the treatment of giant cell arteritis.
Preliminary data using PET scanning has suggested methotrexate probably has little effect on vasculature in large vessel vasculitis, whereas IL-6 has a moderate effect. It is certain that neither of these agents will render an “inflamed” vessel to a non-inflammatory state as assessed by PET scanning.
It remains to be seen whether other agents that affect interferon gamma will be more effective in that regard and my prediction is that we will find that there will be a role for JAK inhibition.
In five years, the patent for tofacitinib will probably be coming to an end and therefore we have the possibility of having access to relatively inexpensive generic products capable of acting as steroid-sparing agents and modifying giant cell arteritis. IN 20 YEARS
The prediction of what will happen in 20 years is rather more problematic.
Again, one would have to speculate that there are new agents. These new agents could either more specifically target blood vessels or have corticosteroid effect with abrogation of the risk of toxicity, which is the main long-term problem in giant cell arteritis.
There might possibly be novel agents directed at other phenomena.
We do have evidence that the innate immune system is involved in the genesis of temporal arteritis, and there is a strong correlation between patterns of toll-like receptors on different parts of the vasculature and the involvement of those different parts of the vasculature in different forms of large vessel vasculitis.
It is possible that this will give a clue as to what factors might be the triggers for different forms of large vessel vasculitis, and with respect to Takayasu arteritis as well as giant cell arteritis, it may well be that there will be very different triggers which could be addressed in quite different ways.
Once more I suspect that we will find the microbiome has influences on this type of inflammation and manipulation of the microbiome may prove to be very helpful and less toxic than current therapies.
The increased recognition that biological drugs have an effect on the microbiome and the microbiome has an effect on the immune state does lend for the possibility that gut manipulation of bacteria might end up becoming a mainstay of treatment in 20 years time.
Dr Stephen Hall is a private practice rheumatologist with a long interest in vasculitis and a commitment to conducting clinical trials Something to say? Be the First to Comment! Notify of You must be logged in to post a comment. You must be logged in to post a comment. Stay connected with the Medical Republic

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Nivolumab and Ipilimumab in the Treatment of Metastatic Uveal Melanoma: A Single-Center Experience

<h1>Nivolumab and Ipilimumab in the Treatment of Metastatic Uveal Melanoma: A Single-Center Experience</h1>

Nivolumab and Ipilimumab in the Treatment of Metastatic Uveal Melanoma: A Single-Center Experience

Case Reports in Oncological MedicineVolume 2019, Article ID 3560640, 8 pages Case Series Nivolumab and Ipilimumab in the Treatment of Metastatic Uveal Melanoma: A Single-Center Experience Vidhya Karivedu , 1 Ihab Eldessouki , 1 Ahmad Taftaf , 1 Zheng Zhu , 2 Abouelmagd Makramalla , 3 and Nagla Abdel Karim 4
1 Department of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA 2 Department of Biostatistics and Bioinformatics, Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH, USA 3 Division of Vascular and Interventional Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA 4 Department of Internal Medicine, Division of Hematology/Oncology, Medical College of Georgia-Augusta University, Augusta, GA, USA
Correspondence should be addressed to Vidhya Karivedu ;
Received 30 November 2018; Accepted 25 March 2019; Published 17 April 2019
Academic Editor: Jose I. Mayordomo
Copyright © 2019 Vidhya Karivedu et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract
Background . Metastatic uveal melanoma (MUM) is associated with a poor prognosis, with a median overall survival (OS) of 4–15 months. Despite new insights into the genetic and molecular background of MUM, satisfactory systemic treatment approaches are currently lacking. The study results of innovative treatment strategies are urgently needed. Patients and Methods . This was a retrospective case series of 8 patients with MUM managed at the University of Cincinnati between January 2015 and January 2018. The immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1 criteria were used for patient evaluation, and magnetic resonance imaging was used for evaluation at treatment checkpoints. Objective . To assess the clinical outcome of patients with MUM treated with a combination of checkpoint inhibitors. Results . The series included eight patients, six men and two women, with MUM. Their median age at MUM diagnosis was 69 (range, 55–77) years. All patients were treated with ipilimumab and nivolumab combination along with transarterial chemoembolization (TACE), followed by nivolumab maintenance and monthly TACE procedures. The majority of patients had a partial response or stable disease. Two of the patients had partial response, while four others had stable disease. Two other patients experienced disease progression. Conclusion . We report the outcomes of eight patients with MUM treated with the combination of ipilimumab and nivolumab. We report the clinical outcome and toxicity associated with this treatment approach. Further studies are warranted to explore immunotherapy in MUM. These findings support the consideration of immunotherapy in MUM. 1. Introduction
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. It accounts for <5% of all melanoma cases in the United States [ 1 , 2 ]. UM can arise from melanocytes located along the uveal tract, which is the pigmented layer composed of the iris and ciliary body anteriorly and choroid posteriorly. UM is a rare form of melanoma, with an approximate incidence rate of 1,500 new cases diagnosed each year in the US. There is a higher prevalence among Caucasians compared to that in other ethnic groups [ 3 , 4 ]. Despite effective local therapies, there is a high potential for metastases even after a prolonged period of remission [ 4 , 5 ]. While the cumulative five- and ten-year metastatic rates reported by the Collaborative Ocular Melanoma Study (COMS) Group were 25% and 34%, respectively, up to 50% of patients develop metastatic disease [ 6 , 7 ]. The predominant target organ for metastases is the liver (89%). Metastases to the skin, bone, brain, and lungs have also been reported [ 8 ]. According to the TNM staging of metastatic disease in uveal melanoma (MUM), M0 is defined as the absence of distant metastasis, while M1a is a disease with distant metastasis with the largest diameter of 3 cm or less, M1b is metastatic disease with the largest diameter of 3.1 to 8 cm, and M1c is metastatic disease with the largest diameter of 8 cm or more [ 9 , 10 ]. Multiple therapeutic approaches for MUM have been studied but none has shown any impact on the overall survival (OS) [ 11 ]. Recent studies have shown that outcomes of patient with MUM are dismal with median overall survival of 12 months from the time of metastasis diagnosis [ 12 ]. There is no established standard of care for the systemic therapy of patients with MUM as they are usually excluded from large randomized trials; thus, the current treatment paradigm is based on the National Comprehensive Cancer Network (NCCN) guidelines [ 13 ]. Liver-directed therapies such as liver resection in a small subset of patients may induce remission in the setting of single-site metastases potentially prolonging OS, albeit with a high recurrence rate [ 7 , 14 ]. UM is clinically and biologically distinct from cutaneous melanoma. However, the systemic management of MUM is adapted from that of cutaneous melanoma. Major improvements have followed the introduction of BRAF/MEK inhibitors and immunotherapy in metastatic cutaneous melanoma. Unlike cutaneous melanoma, several studies report lack of BRAF kinase mutations, suggesting lack of benefit from BRAF inhibitors in patients with advanced uveal melanoma [ 15 – 17 ]. Oncogenic mutations in G-protein subunits a (GNAQ) and 11 (GNA11) have been described in 80% of uveal melanomas [ 18 ].
Small retrospective studies have reported low response rates to PD-1 inhibitor monotherapy for MUM. The combination of nivolumab and ipilimumab has shown a survival benefit in patients with cutaneous melanoma at the expense of immune-related toxicities and has been approved for the management of metastatic cutaneous melanoma [ 19 – 21 ]. Patients with MUM were excluded from most of the clinical trials; thus, the safety and efficacy of the currently studied combinations remain unclear, especially the ocular toxicity of the combination in patients with MUM [ 22 – 24 ]. Ongoing trials are evaluating the combination of CTLA-4 and PD1 blockade in MUM [ 25 , 26 ].
In this study, we report our experience in treating patients with MUM with the combination of ipilimumab and nivolumab. 2. Case Series 2.1. Case 1
A 68-year-old man was initially diagnosed with right primary choroidal melanoma by histopathology and immunohistochemistry (IHC). He was treated with I-125 plaque brachytherapy in 2013. In April 2016, an abdominal ultrasonography (US) revealed multiple scattered hypodense lesions throughout the liver; the largest lesion was within segment 7 measuring cm (M1b). A US-guided liver biopsy confirmed a recurrence, with a lactic acid dehydrogenase (LDH) level of 220 U/L (110-270 U/L) and alkaline phosphatase (ALP) of 22 (7-52 U/L). In April 2016, the patient started a combination of ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) administered every 3 weeks. After three cycles of treatment, imaging revealed the same number of hypodense lesions; the largest lesion measured cm (Figure 1 ). In July 2016, treatment was stopped due to severe autoimmune colitis as a side effect of the immunotherapy. Later that year, in September 2016, the patient continued nivolumab alone (240 mg every 2 weeks), which was also discontinued in February 2017 due to intolerance. Since then, the patient had received transarterial chemoembolization (TACE) for the hepatic lesions. In June 2017, the patient developed progressive disease, with an LDH of 317 U/L and ALP of 426 U/L. The patient was enrolled to hospice care and the patient expired within a month. Figure 1: (a) Pretreatment scans (MRI). Axial T2 WI (A) and postcontrast (Eovist) Axial T1 WI (B) showing a 7 cm mass in the right liver lobe (arrows) and multiple smaller lesions in both liver lobes. (b) Posttreatment scans (MRI). Axial T2 WI (A) and postcontrast (Eovist) Axial T1 WI (B) show the decrease in size of the largest mass in the right liver lobe (arrows). 2.2. Case 2
A 69-year-old man was referred to an ocular oncologist in 2014 due to visual changes in his left eye. He underwent enucleation in 2014 and histopathology showed T3aN0M0 choroidal melanoma. He underwent systemic staging and did not have metastatic disease at the time. Later in April 2016, surveillance imaging showed multiple pulmonary nodules (M1a), which were diagnosed as metastatic disease by right lung lower lobe wedge resection confirmed by IHC (HMB-45 and MART-1), with an LDH of 191 U/L and ALP of 84 U/L. In July 2016, the patient started nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) administered every 3 weeks. Upon completion of four cycles, the treatment was stopped due to autoimmune colitis as a side effect of immunotherapy. Imaging surveillance in September 2016 showed progressive disease, with an LDH of 231 U/L and ALP of 89 U/L, and the patient started treatment with nab-paclitaxel and he continues to have stable disease with no signs of disease progression for 18 months now. 2.3. Case 3
A 77-year-old man was referred to an ocular oncologist in 2014 for visual changes in his right eye. He was diagnosed with a choroidal melanoma by histopathology and IHC, treated with I-125 plaque brachytherapy. Surveillance imaging in March 2017 showed liver and pulmonary lesions (M1a), with an LDH of 168 U/L and ALP of 54 U/L. A liver nodule biopsy confirmed the presence of MUM. The patient completed selective internal radiation therapy (SIRT) to the liver metastases in March 2017. In March 2017, the patient also started treatment with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) every 3 weeks for a total of four cycles, followed by nivolumab maintenance (240 mg). The patient also underwent TACE simultaneously with immunotherapy every 5–6 weeks starting from May 2017. Nivolumab was stopped in March 2018 due to thrombocytopenia, and the patient continued TACE every eight weeks until September 2018 and later discontinued due to no tumor growth. Repeat imaging in February 2019 showed stable disease. 2.4. Case 4
A 76-year-old woman was referred to an ocular oncologist in 2014 for visual changes in her left eye and was diagnosed with a ciliochoroidal melanoma by histopathology, treated with I-125 plaque brachytherapy. Surveillance imaging in June 2017 showed multiple liver lesions with the largest measuring cm (M1b). A liver biopsy confirmed MUM. The patient started therapy with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) every 3 weeks for four cycles, followed by maintenance nivolumab (240 mg) every two weeks simultaneously with TACE every 4 weeks. In October 2017, imaging showed stable liver lesions. Imaging surveillance in November 2017 showed the progression of the liver lesions, with an LDH of 466 U/L and ALP of 442 U/L. Nivolumab was discontinued in November 2017, and the patient expired in January 2018. 2.5. Case 5
In 2014, a 65-year-old man was referred to an ocular oncologist for a visual change in his left eye and diagnosed with choroidal melanoma by histopathology and IHC, treated with enucleation, T1aN0M0. Surveillance imaging first showed hepatic lesions in January 2016. Active surveillance in August 2016 revealed that his liver lesions had increased in size and number with the largest lesion measuring cm (M1b), with an LDH of 641 U/L and ALP of 111 U/L. Liver biopsy confirmed MUM. The patient started therapy with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) every 2 weeks simultaneously with TACE every 4 weeks in September 2016. A repeated abdominal magnetic resonance imaging (MRI) in November 2016 showed a marked decrease in the size and number of metastatic liver lesions (Figure 2 ). After four cycles of nivolumab/ipilimumab, he started maintenance nivolumab (240 mg every 3 weeks) in January 2017. Repeat imaging showed continued response until August 2018. Imaging in September 2018 showed progression of disease; therapy switched to nab-paclitaxel. The patient currently has stable disease on nab-paclitaxel and TACE q8 weeks as of March 2019. Figure 2: (a) Pretreatment scan (8/22/2016) (MRI). Axial T2 WI (A) and postcontrast (Eovist) Axial T1 WI (B) showing an 11 cm mass in the left liver lobe (arrows) and multiple smaller lesions in both liver lobes. (b) Ongoing treatment (5/2/2018) (MRI). Axial T2 WI (A) and postcontrast (Eovist) Axial T1 WI (B) show the decrease in size of the largest mass in the left liver lobe (arrows) now measuring 4.8 cm with no enhancement. There is a decrease in size and number of the multiple smaller lesions in both liver lobes. 2.6. Case 6
A 63-year-old man was initially referred to an ocular oncologist in February 2016 due to a visual change in his left eye. He was diagnosed with ciliochoroidal melanoma by histopathology, T4bN0M0. He was treated with enucleation of his left eye. In February 2017, surveillance imaging showed liver lesions, with the largest measuring cm in hepatic segment 7 (M1a) and an LDH of 194 U/L, ALP of 94 U/L; biopsy confirmed metastatic melanoma. The patient started treatment with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) in May 2017. After two doses of a combination of ipilimumab and nivolumab, he developed colitis, which was treated with prednisone. Repeated imaging in June 2017 showed a decrease in the size of the metastatic hepatic lesion, from to cm (Figure 3 ). The patient started nivolumab (240 mg every 2 weeks) in August 2017. In October 2017, imaging showed a mixed response, with stable lesions in segment 7 and new hepatic lesions in segment 8, with an LDH of 242 U/L, ALP of 114 U/L. The patient continued nivolumab until disease progression in April 2018, and the patient expired in June 2018. Figure 3: (a) Pretreatment scans (MRI). Axial T2 WI (A, B) and postcontrast (Eovist) Axial T1 WI (C) show multiple metastatic lesions (arrows) in both liver lobes. (b) Posttreatment scans (MRI). Axial T2 WI (A, B) and postcontrast (Eovist) Axial T1 WI (C) show the decrease in size and number of multiple lesions (arrows) in both liver lobes. 2.7. Case 7
A 73-year-old woman was referred to an ocular oncologist in June 2015 for visual changes in her right eye, diagnosed with a primary choroidal melanoma by histopathology. She was treated with I-125 plaque brachytherapy in June 2015. Surveillance imaging showed hepatic lesions in September 2015, with LDH of 194 U/L, ALP of 73 U/L. The largest lesion measured (M1a). A liver biopsy confirmed MUM. She started therapy with nab-paclitaxel and received three cycles simultaneously with TACE for left and right liver lobe metastases. In February 2016, imaging showed disease progression, with LDH of 519 U/L and ALP of 72 U/L. Therefore, the patient started therapy with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). After one cycle, she developed grade IV myalgia and neuropathy requiring hospitalization and immunotherapy was stopped. In May 2016, the patient was initiated on pembrolizumab simultaneously with monthly TACE procedure for liver metastases. However, she was hospitalized for pulmonary edema and autoimmune hepatitis. Imaging repeated in September 2016 showed the progression of the hepatic lesions. She was later enrolled to hospice care and expired in September 2016. 2.8. Case 8
A 55-year-old man was initially diagnosed with primary choroidal melanoma of the left eye in October 2016 by histopathology, treated with I-125 plaque brachytherapy. Surveillance imaging in July 2017 showed numerous liver lesions, the largest measuring up to 1.6 cm (M1a), with an increase in his LDH level to 634 U/L, ALP 65 U/L. A liver biopsy confirmed MUM. He started monthly TACE in August 2017. In September 2017, the patient started therapy with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) every 3 weeks. He finished his fourth cycle in November 2017. In December 2017, an abdominal MRI showed a mixed response, in which several lesions were stable while others had slightly increased in size, with LDH level of 267 U/L and ALP 256 U/L. The patient later continued maintenance therapy with nivolumab (240 mg) every 2 weeks until January 2018. Repeat imaging in February 2018 showed disease progression and the patient expired in April 2018. 3. Discussion
Median OS of MUM patients with M1a disease was 20 months, while M1b disease was 10 months [ 10 ]. The current treatment for MUM is based on the recommendations for metastatic cutaneous melanoma. Local interventions such as chemoembolization further guide therapies for MUM. One chemotherapeutic option, dacarbazine, has shown a limited response in MUM [ 27 ]. Other chemotherapeutic regimens including temozolomide, cisplatin, treosulfan, fotemustine, and various combinations have been investigated in MUM with similar results [ 28 – 30 ].
Several case series and small prospective studies have evaluated immune checkpoint inhibitors in MUM [ 31 – 35 ]. Ipilimumab, an anti-CTLA4 agent, is an immune checkpoint inhibitor that has shown response rates of 5–10% with ipilimumab in patients with MUM, with a median OS time of 6.0–9.7 months [ 35 – 37 ]. Preliminary data from a phase II trial conducted by the Spanish Melanoma Group (GEM), using front line ipilimumab 10 mg/kg IV every 3 weeks for four doses followed by maintenance doses every 12 weeks until disease progression or acceptable toxicity in treatment-naïve MUM patients, showed promising response rates at a median follow-up time of 5.5 months [ 38 ]. However, the Dermatologic Cooperative Oncology Group (DeCOG) conducted an open-label multicenter phase II trial in treatment-naïve or pretreated MUM patients which reported a median progression-free survival (PFS) and OS of only 2.8 and 6.8 months, respectively. Investigators also determined that treatment-naïve patients did not have an improved 1- or 2-year survival compared to previously treated patients [ 39 ].
The anti-PD1 agents nivolumab and pembrolizumab have shown greater efficacy in cutaneous melanoma, with an improved side effect profile compared to that of ipilimumab. However, the activity of PD-1 inhibition in UM is not yet well-described. One case series of 10 patients with MUM treated with pembrolizumab reported one complete response (CR), two partial response (PR), and one patient with stable disease (SD) [ 40 ]. Another large multicenter case series including 56 patients who received anti-PD1 (nivolumab, pembrolizumab) or anti-PDL1 (atezolizumab) agents showed median OS and PFS of 7.6 months and 2.6 months, respectively [ 32 ]. Adverse events should be considered when treating patients with immunotherapy since autoimmune side effects can affect therapy continuation or further management in these patients.
While combination immunotherapy has achieved higher response rates in patients with metastatic cutaneous melanoma compared to those for monotherapy, studies are ongoing to evaluate combination therapy in MUM [ 25 , 26 ]. Afzal et al. reported a case of MUM treated with the combination of nivolumab and ipilimumab for four cycles, followed by maintenance therapy with nivolumab for two cycles in which the patient achieved a durable response and had continued to do well for 22 months since the start of combination therapy. However, subsequent therapy was stopped due to the development of autoimmune hepatitis [ 31 ].
The use of immune checkpoint inhibitors can lead to the development of adverse events and toxicities. The frequencies of immune-related adverse event (iRAE) effects are higher for the combination of PD-1 and CTLA-4 agents compared to the frequencies for any of these therapies alone. Toxicities are common in the GI tract, liver, and skin and the endocrine system. In a phase III trial (CheckMate 067), grade 3 or 4 iRAEs occurred in 55% of the combination group vs. 16% and 27%, respectively, for nivolumab and ipilimumab alone [ 19 ].
Diarrhea and colitis are the most frequent iRAEs after ipilimumab either as monotherapy or in combination with PD1 inhibitors (33.1% and 44.1%, respectively). GI symptoms usually appear 6 weeks after treatment initiation. Treatment-related adverse event of any grade leading to their discontinuation happened in 36.4% and 14.8% in the combination arm and ipilimumab group, respectively, with the most common being diarrhea and colitis. In our study, four out of eight patients experienced autoimmune colitis (50%) with the combination. Adverse events were generally manageable with established guidelines, including the use of steroids for grade 3 or 4 adverse events. The safety profile of ipilimumab and nivolumab combination in our study was similar to that observed in cutaneous melanoma receiving combination.
Our retrospective study assessed patients with MUM treated with immunotherapy combination within a single institute (summarized in Table 1 ). During the study period, no available open and feasible clinical trials were available to this group of patients. After obtaining written informed consent, immunotherapy was administered on a compassionate use basis since no other appropriate medical therapies were available; no other ethical approvals were needed. In our series, patients were treated with the combination of ipilimumab and nivolumab plus TACE followed by maintenance nivolumab along with monthly TACE procedures. The majority of patients had initial PR or SD. Out of the eight patients, two achieved PR, while four others had SD. Two other patients had progression of disease (POD). Median OS (from the date of immunotherapy initiation to the date of death/date of last follow-up) by Kaplan-Meier methodology for the eight patients was 14 months (Figure 4 ). The small size of this study limits further analysis, but we were able to see a response, either in the form of SD or PR. Although SD is not considered a response to the drug, it is considered a disease control endpoint as it delays the time to progression. Patients in our study either had M1a or M1b disease. Five of eight patients had M1a disease, OS of these patients from metastatic disease diagnosis to date of death/date of last follow-up ranged 12, 14, 16, 23, and 24 months. The rest of the patients had M1b disease, OS of these patients ranged 7, 15, and 30 months. While previous studies stated that LDH level, CRP level, eosinophil count, and Eastern Cooperative Oncology Group (ECOG) performance status can be used as prognostic factors for UM [ 41 , 42 ], these data could not be assessed in our study. Table 1: Summary of cases. Figure 4: Median overall survival for the entire cohort. Median overall survival for this cohort was 14.2 months.
TACE depends on the concept of embolization components that can interrupt blood supply to the tumor and thus cause ischemic necrosis and decrease in size. This may lead to controlled growth or even regression of the tumor [ 43 ]. TACE was offered to six of the eight patients included in our study and was well-tolerated. 4. Conclusion
MUM is associated with a poor prognosis with no current standard of care. There is an urgent need for new strategies for patients with MUM as no therapy has succeeded in improving the OS. Given the development of molecular profiling techniques and the availability of additional immunotherapeutic agents, chemotherapeutic agents, and target therapies, dedicated management strategies and guidelines should be feasible. Immunotherapy in MUM remains an area of active exploration. While checkpoint inhibition with anti-PD-1 and anti-CTLA-4 therapy has drastically changed the treatment approach to cutaneous melanoma, its efficacy in MUM is still being evaluated. Our study reported durable responses in MUM patients treated with anti-PD-1/anti-CTLA-4 therapy; thus, this approach may be a viable option for these patients. Patients who receive combination immunotherapy should also be carefully monitored for iRAEs. The major limitations of this study include its retrospective nature as some of the data could not be retrieved. There is an urgent need for specifically approved systemic and local treatment options for patients with MUM. Given the limited activity of the currently approved agents for advanced melanoma in the treatment of MUM, clinical trials should be performed based on our improved understanding of the biology of this disease. Immunotherapy in UM remains an area of active exploration. Conflicts of Interest
The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Authors’ Contributions
NK is the primary oncologist who treated the patients and initiated and edited the manuscript. VK, IE, and AT took care of the patients and wrote the manuscript. AM evaluated the images. All authors have read and approved the final manuscript. Acknowledgments
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Prednisone for Your Dog

<h1>Prednisone for Your Dog</h1>

Prednisone for Your Dog

By Lilly / 04/14/2019
Prednisone for Your Dog
Prednisone for your dog is a synthetic corticosteroid that is often prescribed to treat medical illness in your pup, especially severe allergies. It is used to manage swelling and inflammation in conditions where the immune system has a significant role. It suppresses immune responses that cause certain types of inflammation. Prednisone is a common medication that you may have had prescribed for yourself at one time or another by your own doctor. It is a steroid that is an anti-inflammatory drug and is offered as a treatment to your pet if they are suffering from: Allergies Joint pain caused by arthritis Skin issues such as eczema and dermatitis Lupus Disorders of the central nervous system Liver conditions Inflammatory bowel disease
Why Does My Dog Need Prednisone?
Your dog’s veterinarian may prescribe prednisone to treat various ailments that are present due to a cortisol problem in your pet. Cortisol is an essential adrenal hormone that comes from the adrenal cortex (gland). It is also referred to as the stress hormone which mediates many of the functions related to stress reactions as well as immune responses. They include: Mediating immune responses Nutrient metabolism Maintenance of blood electrolyte levels
Prednisone is a synthetically produced catabolic steroid and a form of synthetic corticosteroid therapy. It closely resembles natural cortisol but is stronger. It is able to mimic cortisol and effectively alter symptoms that are troubling your dog. It is more potent than naturally produced cortisol and supports cortisol function when your pet’s levels are low. Prednisone comes in two forms. One is Prednisone and the other is prednisolone. They both have the same function but just processed by your pet’s body differently. Prednisone is processed by the liver and turned into prednisolone. If a dog has liver issues the veterinarian, then prescribes Prednisolone in place of prednisone to produce the needed synthetic hormone.
When Shouldn’t My Dog Take Prednisone?
As helpful as prednisone can be to your dog, make sure their veterinarian knows about all the medications they might be taking. Prednisone is usually not taken with NSAIDs. It also can react with digoxin, diuretics, insulin, phenobarbital, ketoconazole, and mitotane. Owners must also be very careful if their pup is diabetic or pregnant.
How Does My Dog Take Prednisone?
Prednisone comes in pills, creams or injectables. Your dog’s veterinarian will decide which is more appropriate for your pet that is dependent on the medical condition, the dog’s weight and dosages of a particular form. Dosages are higher for endocrine problems like Lupus or anemia. Smaller doses for something like pain or swelling. Below are some basic guidelines of dosages to give an example of what you might expect for your dog: Addison’s disease, 0.05 to 0.18 mg per pound should be given to dogs until the condition is under control then it will be decreased. To reduce the symptoms of allergies, a dose of 0.25 mg per pound. This may change depending on how your dog reacts and if symptoms are being controlled. It may go up to 1 mg a day. Other conditions amounts are variable and may be dosed differently. A hypoadrenal crisis may need an injection but skin conditions like eczema or itches may be treated with creams.
Prednisone Side Effects in Dogs
Common side effects of prednisone (and most other steroids) include: Increased thirst

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At Vasculitis Conference, Patients Share Hope, Humor & Hardships

<h1>At Vasculitis Conference, Patients Share Hope, Humor & Hardships</h1>

At Vasculitis Conference, Patients Share Hope, Humor & Hardships

/ At Vasculitis Conference, Patients Share Hope, Humor & Hardships At Vasculitis Conference, Patients Share Hope, Humor & Hardships April 15, 2019 Print-Friendly Version / Save PDF SEATTLE— At the first regional vasculitis patient conference ever held in the Pacific Northwest, a panoramic view of Mt. Rainier on a clear January morning set the tone for a day of optimistic talks about recent successes against the various forms of blood vessel inflammation. One attendee at the Jan. 12 conference, sponsored by the Vasculitis Foundation in partnership with the University of Washington’s Division of Rheumatology, noted it was hard to tell patients from caregivers among the 100-plus participants—a definite sign of progress. You Might Also Like Affordable Care Act By The Numbers The succes s of recently approved treatments, such as the monoclonal antibodies rituximab (Rituxan) and mepolizumab (Nucala), and encouraging trial results of drug candidates, such as Avacopan (CCX168), have provided ample reasons for optimism. “The future is bright, I think, for vasculitis in general,” said Gregory C. Gardner, MD, FACP, Gilliland-Henderson Professor in Rheumatology at the University of Washington. Dr. Seo Featured speaker Philip Seo, MD, MHS, associate professor of medicine and director of the Johns Hopkins Vasculitis Center in Baltimore (and physician editor of The Rheumatologist [TR] ), said some newer drugs may even become, “The Tina Feys of vasculitis,” a cheeky reference to the highly successful former cast member of Saturday Night Live . Nevertheless, the humor and sunshine were tempered by more sobering stories of patients struggling to reclaim their lives after lengthy medical odysseys. Throughout the day, audience members shared tales of having to shop around for doctors, not having their symptoms taken seriously, lacking patient advocates, having to navigate a bewildering healthcare system alone, waiting years to receive the correct diagnosis, and even being forced to use spreadsheets to manage their own complex care. Some came to the conference, one of more than 15 now held by the Vasculitis Foundation, to network and find mutual support. Some came to hear specific talks and solicit advice about their symptoms and care. And some came to deliver the message to rheumatologists that far more is needed to help support patients through what can still be an arduous and life-threatening ordeal. Just as attendees learned from the rheumatologists, the doctors received a firsthand look at patients’ main concerns. In Search of Support & Community Kami Schmidt with her daughter, Haley (left), who helped her start the support group. Kami Schmidt, an attendee from Pine City, Minn., believes she’s had microscopic polyangiitis (MPA) for years. She remembers getting pneumonia nearly every fall, like clockwork, and experiencing frequent sinus issues. Her doctors always just knocked the infections back with prednisone—one reason she believes she wasn’t diagnosed sooner. “There does need to be more awareness,” she said in an interview with TR . After nearly dying in 2009, Ms. Schmidt was finally diagnosed via a bronchoscopy and kidney biopsy and treated with intravenous prednisone, cyclophosphamide and plasmapheresis. “I told my doctor, ‘If I live through this, I want to do something to help other people going through this,’” recalled Ms. Schmidt. Even though a team of seven doctors was caring for her at the time, Ms. Schmidt lacked a patient advocate or go-to person to ask her many questions. She decided to launch a support group “so people aren’t alone” and formed the East Central Minnesota Vasculitis Support Group, which regularly attracts more than 30 people to its quarterly meetings. Ms. Schmidt traveled to the conference to report back to her group on the latest studies and treatment options. “I’m happy to see that there’s a lot of research,” she said. She also had high praise for the conference’s emphasis on education, empowerment and networking. “I think it’s great they connect people with vasculitis—people yearn for this. To have all of these people together, it’s amazing,” she said, looking around the room. Sitting at the same table, Rosemary Brechtelsbauer told TR that she came to the conference from a nearby suburb to hear about new drug trials targeting her own rare condition, eosinophilic granulomatosis with polyangiitis (EGPA), as well as other forms of vasculitis. “I like to know everything,” she said. “I want to know what’s going on.” Kami Schmidt (seated at lower left) with the East Central Minnesota Vasculitis Support Group in Minnesota. Ms. Brechtelsbauer’s vasculitis began in 2009 with diffuse urticaria, but it took doctors several years to diagnose it, even though a skin biopsy revealed high eosinophil counts. She developed asthma, and then eosinophilic pneumonia. She tested negative for anti-neutrophil cyto­plasmic antibodies (ANCA) but has since learned that only half of all patients have them. At one point, she said, “I was on 10 different medications just to breathe,” she said. She was getting high-dose prednisone and finally began to improve a bit when doctors put her on omalizumab (Xolair). Even so, she endured five surgeries over five years. In the midst of one of them, she developed a new allergy to the anesthesia that nearly killed her. When she went into cardiac arrest, doctors had to perform CPR for two minutes to resuscitate her. At a June 2015 vasculitis conference in Jacksonville, Fla., she had heard about promising new results from mepolizumab. When the FDA approved the drug in November 2015 to treat adults with eosinophilic asthma, “I was in my doctor’s office the next week, saying, ‘I want this,’” she recalled. “I knew about the Nucala approval before my immunologist.” The combination of omalizumab and mepolizumab has “done wonders” for her EGPA as well, she said, and finally allowed her to taper off prednisone. “I’ve got a great team now,” she said, but she noted that she shopped around and assembled the providers on her own. Nevertheless, Ms. Brechtelsbauer said she feels lucky to be alive. “Right now, I’m doing great,” she said. “Biologics saved my life.” In addition to her wife and caregiver, Cheryl, she said, Facebook groups, national meetings and the Vasculitis Foundation have been strong pillars of support, especially given her ultra-rare disease. “To find your little tribe within that is amazing,” she said. Advances on 3 Fronts Rosemary Brechtelsbauer (left) and her wife, Cheryl (right) enjoying life at a Seattle Seahawks football game with the mascot. In his opening talk, Dr. Seo grouped the emerging vasculitis therapies into three main categories: selective immune cell depletion, cytokine-based strategies and inhibition of immune targeting. Rituximab , in the first category, is a monoclonal anti-CD20 antibody that destroys B cells tagged with the CD-20 cell surface marker. B cell strategies are now standard for the treatment of both MPA and GPA (granulomatosis with polyangiitis). The two forms of ANCA-associated vasculitis attack small blood vessels, mainly in the lungs and kidneys. Rituximab received FDA approval to treat both conditions in 2011, and the drug is now used to treat cryoglobulinemic vasculitis, as well. The second main treatment category, cytokine-based strategies, can “prevent the immune system from ganging up on you,” Dr. Seo said. Because cytokines instigate immune cells, targeting them can prevent a misguided attack. The pro-inflammatory cytokine IL-6, for example, spurs the production of infection- fighting cells and proteins. Mepolizumab works in much the same way by targeting interleukin (IL) 5, which Dr. Seo called “Miracle-Gro for eosinophils.” Weeding out eosinophils can knock back EGPA. Giant cell arteritis (GCA), associated with blindness and stroke, may respond to anti-IL-6 inhibition. Tocilizumab (Actemra) gets rid of IL-6, and a phase 3 clinical trial (GiACTA) concluded that GCA patients on the drug were much less likely to flare as they tapered prednisone use, compared to patients on prednisone and a placebo. 1 In response, the FDA approved tocilizumab for GCA in 2017. Not everyone has benefited: clinical trial data suggest that tocilizumab has been less effective in treating Takayasu’s arteritis, a large vessel vasculitis seen more often in younger women. The third treatment category relies on inhibition of immune targeting, such as blocking or eliminating the antibodies used by the immune system to tag and attack blood vessels. “They can’t hurt you if they can’t find you,” Dr. Seo said. Recent reports from a large multinational study, PEXIVAS, suggest that plasmapheresis, or removing antibodies via plasma exchange, wasn’t effective in significantly reducing mortality or the risk of end-stage renal disease among ANCA-associated vasculitis patients, although the investigators stress the analysis is not yet complete. Dr. Seo noted that researchers have reported more success, at least thus far, in getting rid of other immune tags, such as the protein fragment C5a. The phase 2 CLEAR trial tested a new ANCA-associated vasculitis drug candidate, Avacopan, which Dr. Seo compared with “Teflon for your blood vessels.” By preventing the C5a tag from sticking to them, researchers hypothesized that it could help eliminate the condition. In the CLEAR study, researchers reported that Avacopan plus standard medications did significantly better in getting patients into rapid remission than standard medications alone. Better yet, Dr. Seo said, the drug may work without steroids—a statement that drew appreciative oohs from the audience. Steroids are “what make you cranky and want to throw toasters at people and tell them what you really think about them,” he said, to laughter and vigorous nodding. From an efficacy standpoint, he concluded, Avacopan may yet give rituximab a run for its money. The PEXIVAS study likewise suggested high-dose oral glucocorticoids were no better than low-dose steroids in further improving the outcomes of patients treated with cyclophosphamide or rituximab. In other words, Dr. Seo said, the drugs have opened the possibility, for the first time, of treating vasculitis with much less or even no steroids. That assessment was especially popular with the audience. In response to questions, Dr. Seo cautioned that rituximab carries a small but potentially serious risk for common variable immune deficiency (CVID), a disorder linked to low immunoglobulin levels that can disrupt someone’s ability to produce new antibodies. “It’s not a slam dunk to remain on rituximab forever,” he said. New Clinics & Telling Symptoms For patients with GCA, Ingeborg Sacksen, MD, FACP, clinical associate professor in the Division of Rheumatology at the University of Washington, described another advance in the form of a new fast-track clinic. The vasculitis can inflame the great vessels and dramatically reduce their blood carrying capacity—particularly the temporal and ophthalmic arteries—and cause relentless headaches and sudden, permanent vision loss in one eye, among its many potential symptoms. In fact, Dr. Sacksen said, up to one-third of GCA patients will lose their vision and two-thirds will have distinct warning signs about one week prior to that loss. Quick treatment, then, is critical. “Time is vision,” she emphasized. Modeled after existing clinics in Europe, the university has set up its own fast-track clinic that includes a GCA hotline for physicians and a commitment to see patients within 24 hours for a medical evaluation. Fortunately, ultrasound of the temporal and other arteries can reveal the halo sign, which is highly suggestive of GCA. “There’s nothing else in the world of ultrasound that looks like this,” Dr. Sacksen said. A positive ultrasound triggers immediate treatment with high-dose and sometimes intravenous steroids to prevent blindness. A negative ultrasound can still lead to treatment if doctors detect the presence of other worrisome signs, such as headaches and double vision. Once at-risk patients are treated with steroids, many can be managed with tocilizumab, the “new kid on the block,” she said. Dr. Gardner said the University of Washington’s Division of Rheumatology has also started a once-a-month vasculitis clinic. He confirmed the university is trying to find a vasculitis-trained rheumatologist to head a dedicated vasculitis center and secure the necessary funding. “It’s in the early beginnings, and we’re looking to grow that,” he said. In his talk, Dr. Gardner reviewed the main kinds of lung involvement in vasculitis, including bleeding, inflammation, fibrosis, nodules or cavities and blood vessel enlargement. Diagnosis of bleeding in the lungs or diffuse alveolar hemorrhage (DAH) can be made via a chest X-ray, more sensitive CT scan or bronchoscopy. Coughing up blood, he stressed, is a medical emergency that requires immediate attention. Lung inflammation can present as lung infiltrates or a process that mimics pneumonia. “I’ve seen many patients who have been treated for pneumonia when they actually have lung vasculitis,” Dr. Gardner said. If the supposed pneumonia doesn’t improve, he said, doctors should seriously consider the possibility of vasculitis. Pulmonary scar tissue, he added, is sometimes the first manifestation of vasculitis and may be marked by an increasing cough or shortness of breath. The key, Dr. Gardner emphasized, is to catch the scarring process early and treat it with medications like mycophenolate. “Once the lung has formed scar tissue, we don’t get that back,” he said. A Doctor Becomes a Patient Dr. Rahbar Patients peppered Dr. Gardner with questions about lung symptoms and what they might mean. The topic was revisited over lunch, when attendees heard the story of Habib Rahbar, MD, an associate professor and clinical director of breast imaging at the Seattle Cancer Care Alliance who was diagnosed with vasculitis in 2018. Dr. Rahbar first experienced “the most excruciating pain I’ve ever experienced in my right shoulder” after a snowball fight with his three sons and au pair . Despite his fitness, Dr. Rahbar chalked up the sharp, pulsing pain to old age. Initially, the pain faded in the mornings and reappeared in the evenings. Even as it become harder to bear and was joined by pain in other joints—his toes, knees and elbows—he tried to explain it away. Fortunately, the resident who first saw him didn’t and ordered lab tests to investigate. “Thank goodness she did,” Dr. Rahbar said. An initial blood test revealed an abnormally high eosinophil count and a follow-up showed similarly high ANCA counts. A rheumatology team took over and found groundglass opacity in his lungs, suggestive of inflammation or DAH, and early signs of kidney disease in his urine. “It was a pretty sobering weekend,” he recalled. A bronchoscopy helped finalize the diagnosis: The doctors pulled “cups of blood” from his lungs and confirmed the presence of DAH, he said. He was diagnosed with PR3-ANCA-associated vasculitis. In contrast to the dire prognoses he remembered from medical school, though, his rheumatologist told him he had every reason to be optimistic. “And boy, was he right,” Dr. Rahbar said. After an initial treatment with high-dose steroids, two rounds of rituximab knocked his vasculitis into remission. “The amazing thing is here I am, and nobody would ever guess that I have vasculitis,” he said. For him, he said, rituximab has been a “miracle drug.” Dr. Rahbar said he was sharing his story to let others know that it’s okay to be scared. “It’s also okay to be optimistic,” he added. “We live in a time where the progress that we’re making with this treatment is incredible.” While the audience expressed appreciation for Dr. Rahbar’s story and his sunny outlook, several patients shared a range of frustrations and made clear that not everyone has been as fortunate. One woman told him how she had recently been diagnosed with GPA after experiencing unexplained fatigue as her only major symptom. She has a good doctor, she said. “But it taught me that you really have to pay attention to your body. If we hadn’t pushed on how tired I was, I could have gone into dialysis for kidney issues.” She could have easily ignored it instead of pushing back and saying, “This isn’t right,” she said. Another said she has had to be her own advocate and navigate the system while insiders like Dr. Rahbar have better avenues and access. Multiple people in the crowd nodded in agreement. So how can lay people impress upon doctors the importance of taking their concerns seriously, she asked? A third patient said it had taken six-and-a-half years for her to be properly diagnosed with vasculitis, while a fourth described having to use a spreadsheet to manage her own complicated care after a recent diagnosis of GCA. Dr. Rahbar said he had empathy for those whose diagnosis was unnecessarily delayed and agreed that he had more advantages as a patient and was likely seen faster and diagnosed earlier despite his attempts to ignore his own symptoms. Primary care physicians need to know enough to consider vasculitis as a possibility among their patients, he said. “We need to continue to really emphasize primary care and make sure that some of the smartest doctors who want to be part of primary care go into it.” He urged the audience to ask questions and seek out second opinions if they weren’t satisfied with their doctors’ initial assessments. “Patients know sometimes when their body isn’t quite right,” he said. “We’re not perfect. We’re humans, we make mistakes.” Vaccinations For her talk, Jenna Thomason, MD, MPH, acting instructor in the Division of Rheumatology at the University of Washington, used a work in progress Venn diagram to discuss the preventative medicine responsibilities of vasculitis patients, their medical team and both. To the avid interest of many attendees, she spent most of her time on the complicated topic of vaccinations. Live virus vaccinations are contraindicated in patients on immunosuppressive medications, she reminded the group. For others, “timing really, really matters.” Ideally, patients should be vaccinated before they start steroid or biologic therapy, since multiple medications can impair the immunogenic response and, thus, the vaccine efficacy. Immunosuppressed patients are a particularly high priority for the yearly influenza vaccination that contains inactivated versions of the virus. To overcome many patients’ strong opinions about why they shouldn’t take it, Dr. Thomason said she emphasizes its importance in reducing their risk of being hospitalized or worse. During the 2017–2018 flu season, the CDC estimated that more than 900,000 Americans were hospitalized, and roughly 80,000 died. A 2018 study in New Zealand found that among hospitalized patients who tested positive for influenza, vaccination was associated with a 59% reduction in their odds of being admitted to the ICU. 2 To help prevent pneumococcal infections, patients can now take two vaccines: Pneumovax 23 and Prevnar 13. Doctors often call them pneumonia vaccines, Dr. Thomason said, but she emphasized that they protect against invasive pneumococcal infections, such as meningitis and bacteremia, as well. Because each vaccine causes the other to be less immunogenic, she explained, doctors must wait after the first before delivering the second: at least eight weeks if they start with Prevnar 13 and at least 12 months if they start with Pneumovax 23. Vaccination against shingles is another high priority for vasculitis patients, particularly because patients on immunosuppressive therapies are at higher risk for the painful and potentially serious viral infection. The initial Zostavax option hasn’t been available to all patients since it’s a live virus vaccine; it also has an overall efficacy of about 50% (64% among patients 60 to 69 years old, but protection drops significantly with advancing age). Fortunately, Dr. Thomason said, a new two-dose vaccine, Shingrix, is far more effective and has been approved for all patients who are 50 or older. According to the CDC, “In adults 50 to 69 years old who got two doses, Shingrix was 97% effective in preventing shingles; among adults 70 years and older, Shingrix was 91% effective.” Dr. Thomason said the Shingrix vaccine also protects against postherpetic neuralgia, which can develop after shingles and lead to ongoing, severe pain. A Violin Sendoff Ms. Lint To end the day, Alison Lint, founder of the nonprofit Violin for Vasculitis and a Vasculitis Foundation board member, delivered two heartfelt violin solos and an upbeat message that echoed earlier sentiments about finding and creating community. Diagnosed with GPA when she was 17, Ms. Lint said she’s had the disease for more than half of her life. She continued to relapse until she started taking rituximab in January 2013. “This is my Year 6 of being in remission, which is super awesome,” she said, to a burst of applause from around the room. Once her health stabilized, she founded Violin for Vasculitis and began a 50-state tour to bring her music to vasculitis meetings and organize a young adults group to provide a sense of community. For her second solo of the day, Ms. Lint played part of a melancholy Bach sonata—giving attendees a chance to reflect on new insights and connections while providing a counterweight to the lighter moments. For 90 seconds, only the mournful sounds of a violin and an occasional cough filled the room as afternoon sunshine filtered through the curtains and Mt. Rainier shimmered in the distance. Bryn Nelson, PhD, is a medical journalist based in Seattle. References Stone JH, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis . N Engl J Med . 2017 July 27;377(4):317–328.

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9 Ways Digestive Problems Could Be Totally Screwing With Your Weight

<h1>9 Ways Digestive Problems Could Be Totally Screwing With Your Weight</h1>

9 Ways Digestive Problems Could Be Totally Screwing With Your Weight

9 Ways Digestive Problems Could Be Totally Screwing With Your Weight Locke Hughes From Redbook When everything is flowing smoothly, life is good. And we’re not just talking good hair days or a flawless presentation at work. Your digestive tract counts too. But when it’s out of whack, it could affect – you guessed it – the scale. “Gastrointestinal and digestive issues can definitely have a large effect on the way we eat and how our bodies absorb and digest foods, causing us to gain or lose weight,” says Kenneth Brown , M.D., a board-certified gastroenterologist. “Most digestive problems tend to cause weight loss from poor absorption of food, but there are a few situations in which our intestinal health can contribute to weight gain.” If the number on the scale is changing and you really aren’t sure why, one of these common digestive issues could be the culprit. 1. Acid Reflux Disease Photo credit: Tharakorn – Getty Images More Also known as gastroesophageal reflux disease (GERD), this causes a painful burning sensation, or heartburn, in the lower chest when stomach acid rises back up into your esophagus. And for people who suffer from it, the term “comfort food” takes on a whole new meaning because the act of eating can actually help reduce pain. “Eating provides temporary relief because both the food you’re eating, and the saliva from actually chewing that food, neutralizes acid,” explains Brown. The only problem? Once the food’s been digested, all the symptoms – bloating , nausea, and hiccups that won’t disappear – tend to come back, and they’re usually more aggressive because of rebound acid production. But because people want help, Brown says it’s easy to get sucked into a dangerous cycle of overeating that leads to weight gain. The fix: While plenty of online sources say home remedies like apple cider vinegar or aloe vera can help, Brown says there’s no scientific evidence to support those notions. Instead, he recommends taking an over-the-counter medication, such as Prilosec or Zantac (your doctor can help you choose which is best for you), which don’t have weight gain as a common side effect. And if you still find yourself overeating, try these fixes to help break the cycle. 2. Ulcers Photo credit: ericsphotography – Getty Images More These uncomfortable sores – also known as duodenal ulcers – usually develop in the lining of the stomach or small intestine, and it’s usually because of too much acid production. And just like with GERD, eating food can improve the painful symptoms – including bloat and constant nausea – because it temporarily coats the ulcer with a protective lining and neutralizes the stomach acid, explains Su Sachar , M.D., a board-certified gastroenterologist who specializes in bariatrics, wellness, and optimal health. And, to re-state the obvious, if you’re eating more frequently, those excess calories can lead to weight gain. The fix: To banish ulcers, see your doctor about the best remedy for you, which might involve an acid-blocking medication – aka an anti-acid – like Prilosec or Zantec, says Sachar. And stop taking nonsteroidal anti-inflammatory drugs or NSAID pain relievers like ibuprofen or aspirin, as they could cause internal bleeding and be life-threatening to those with ulcers. Instead, opt for acetaminophen, or Tylenol, when you need help with pain management. 3. Constipation Photo credit: Kittisak Jirasittichai / EyeEm – Getty Images More When you’re stopped up, that weighed-down feeling you get could be weight gain. But there’s good news: your body isn’t actually absorbing more calories, says Brown, so it’s not true weight gain so much as it is extra fecal matter, which is what could be adding a few pounds to the scale. Not to mention that constipation itself doesn’t exactly give us the motivation to hit the gym and crush a workout. Rather, it’s way more likely that you’re feeling sluggish and heavy… and the couch is calling your name. The fix: To stay, err, regular, Brown suggests sticking to a balanced diet of whole foods that have at least 25 to 30 grams of fiber per day, staying well-hydrated (try to drink one to two liters of water per day), and exercise regularly. If something doesn’t seem quite right, look at these signs for what it could mean, and consider talking with your physician. 4. Bacteria Overgrowth Photo credit: lyosha_nazarenko – Getty Images More Bear with us – this one isn’t quite as gross as it sounds. Basically, your bowel contains both good and bad bacteria, and research shows that the good kind plays a crucial role in your overall health by reducing inflammation and keeping your weight in check . The problem occurs when the amount of bacteria increases, or when the type of bacteria gets thrown off-balance. (For optimal health, it’s best to think of it like a seesaw – best when the good and bad is totally balanced.) When that happens, what’s known as small intestinal bacterial overgrowth (SIBO) can occur, and it can cause weight gain in two ways, says Brown. First, the bacteria could produce methane gas, which “slows down the overall function of the small intestine, allowing the intestinal villi – small, finger-like projections in the lining of your intestine – to absorb more calories per bite,” he explains. In other words, the exact opposite of what you want to happen. Second, SIBO can slow down metabolism and affect your insulin and leptin resistance, both of which help regulate hunger and satiety. As a result, you’re likely to crave carbs and probably won’t feel full after eating, even if it’s a fully satisfying meal, says Sachar. The fix: To avoid SIBO, Brown suggests avoiding antibiotics unless absolutely needed (as the name suggests, these medications kill off bacteria, which you only really want if you’re sick to get the seesaw back in balance). If bacteria overgrowth is already happening, though, your doctor may suggest a digestive herbal supplement like Atrantil to help you get back on track. 5. Irritable Bowel Syndrome (IBS) Photo credit: Getty Images More The term IBS gets tossed around a lot these days, as “it’s the most commonly diagnosed GI condition, and it often overlaps with other digestive problems like food sensitivities, a leaky gut, and an imbalance of good and bad bacteria,” says Sachar. And like constipation (a symptom of IBS), it can cause bloat and chronic inflammation, which, once again, could lead to weight gain. The fix: For people who are diagnosed with IBS, it’s about getting to the root of the problem. Your doctor can work with you to build up the good bacteria you need with probiotics, and add digestive enzymes to help break down food so it’s not just sitting around in your gut causing inflammation, explains Sachar. Brown says it could be helpful to try a gluten-free or low gas-producing diet, like FODMAP, as it can help reduce bloating and help get any unnecessary weight gain under control. 6. Crohn’s Disease Photo credit: Brian Evans – Getty Images More While a smaller appetite and excessive weight loss are common symptoms of Crohn’s disease – an incurable chronic inflammatory conditions – the exact opposite can happen as soon as someone gets put on a treatment that involves steroids, which is usually the first step in trying to find a medication that works for you, says Sachar. “Steroids tend to increase your cravings for carbs and cause you to hold on to more water and feel bloated,” says Sachar. Fortunately, it’s usually not too tough to lose the weight once you’re off steroids. That usually happens as soon as a flare-up – or the reappearance of symptoms like diarrhea, constipation, rectal bleeding, and fever – subside and symptoms are better under control. The fix: First of all, your overall health is more important than a few pounds on the scale, so following your doctor’s orders is imperative. But some doctors do shy away from steroid use, like Brown, as he knows the side effects can be less than desirable. Every patient responds differently to medication, though, so talk with your own physician to see what works best for you. 7. Gastroparesis Photo credit: Nerthuz – Getty Images More Often associated with those who have type 1 or type 2 diabetes, gastroparesis – also known as delayed gastric emptying – is a disorder that “slows or stops the movement of food from the stomach to the small intestine,” according to the National Institute of Diabetes and Digestive and Kidney Diseases . Because normal digestion isn’t able to occur, it’s common to feel like you’re gaining weight due to fullness and bloating in the stomach area, but the disorder most commonly leads to weight loss in the end. The fix: According to the American College of Gastroenterology , diet is one of the most important factors in treating gastroparesis. Because fatty and fiber-filled foods take longer to digest, it’s recommended that anyone with the disorder limits or avoids those foods altogether. But since this is a serious condition, it’s best to speak with your doctor to see what the best treatment options are for you. 8. Food Intolerance Photo credit: spukkato – Getty Images More If you’ve noticed your body is easily irritated by certain foods, there’s a good chance you have a food intolerance. Different from a food allergy, which is an immune system response, food intolerance affects the digestive system, making it hard to digest and break down certain foods (the most common being dairy), says the Cleveland Clinic . Those with a food intolerance often experience gas, cramps, and bloating, making it feel like they’re gaining weight. Depending on how severe the food intolerance is, they might also experience diarrhea. The fix: While you might feel super bloated and uncomfortable throughout the day because of your diet, you might not actually be gaining weight. The Cleveland Clinic recommends avoiding or reducing the foods you think are giving you issues, and if you do end up eating something that bothers your stomach, take an antacid. 9. Ulcerative Colitis Photo credit: Monica Schroeder – Getty Images More Although Crohn’s disease can pop up anywhere between the mouth and the anus, UCLA Health says ulcerative colitis stays in the colon, resulting in a constantly inflamed digestive tract that can initially lead to weight loss. Like Crohn’s, though, the treatment for the inflammatory bowel disease – steroids – could make your body gain weight. “An oral steroid like Prednisone can also cause your body fat to redistribute itself, so instead of it being in your stomach or glutes, it could move to the face or neck,” says Sachar. Even though you may notice a difference in your weight during treatment, everything should go back down to normal as soon as you’re able to get off the steroids. The fix: After speaking to your doctor, find a treatment plan that’s right for you and the severity of your ulcerative colitis – one that may or may not involve steroids. While more moderate to severe forms might be treated with steroids, 5-aminosalicylates and immunosuppressant drugs are also options. Whatever you end up using, know your wellbeing is top priority. If that involves gaining a few pounds to better your health, it’s worth it.

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9 Ways Digestive Problems Could Be Totally Screwing With Your Weight

<h1>9 Ways Digestive Problems Could Be Totally Screwing With Your Weight</h1>

9 Ways Digestive Problems Could Be Totally Screwing With Your Weight

From Redbook When everything is flowing smoothly, life is good. And we’re not just talking good hair days or a flawless presentation at work. Your digestive tract counts too. But when it’s out of whack, it could affect – you guessed it – the scale.
“Gastrointestinal and digestive issues can definitely have a large effect on the way we eat and how our bodies absorb and digest foods, causing us to gain or lose weight,” says Kenneth Brown , M.D., a board-certified gastroenterologist. “Most digestive problems tend to cause weight loss from poor absorption of food, but there are a few situations in which our intestinal health can contribute to weight gain.”
If the number on the scale is changing and you really aren’t sure why, one of these common digestive issues could be the culprit.
1. Acid Reflux Disease Photo credit: Tharakorn – Getty Images More Also known as gastroesophageal reflux disease (GERD), this causes a painful burning sensation, or heartburn, in the lower chest when stomach acid rises back up into your esophagus. And for people who suffer from it, the term “comfort food” takes on a whole new meaning because the act of eating can actually help reduce pain. “Eating provides temporary relief because both the food you’re eating, and the saliva from actually chewing that food, neutralizes acid,” explains Brown. The only problem? Once the food’s been digested, all the symptoms – bloating , nausea, and hiccups that won’t disappear – tend to come back, and they’re usually more aggressive because of rebound acid production. But because people want help, Brown says it’s easy to get sucked into a dangerous cycle of overeating that leads to weight gain.
The fix: While plenty of online sources say home remedies like apple cider vinegar or aloe vera can help, Brown says there’s no scientific evidence to support those notions. Instead, he recommends taking an over-the-counter medication, such as Prilosec or Zantac (your doctor can help you choose which is best for you), which don’t have weight gain as a common side effect. And if you still find yourself overeating, try these fixes to help break the cycle.
2. Ulcers Photo credit: ericsphotography – Getty Images More These uncomfortable sores – also known as duodenal ulcers – usually develop in the lining of the stomach or small intestine, and it’s usually because of too much acid production. And just like with GERD, eating food can improve the painful symptoms – including bloat and constant nausea – because it temporarily coats the ulcer with a protective lining and neutralizes the stomach acid, explains Su Sachar , M.D., a board-certified gastroenterologist who specializes in bariatrics, wellness, and optimal health. And, to re-state the obvious, if you’re eating more frequently, those excess calories can lead to weight gain.
The fix: To banish ulcers, see your doctor about the best remedy for you, which might involve an acid-blocking medication – aka an anti-acid – like Prilosec or Zantec, says Sachar. And stop taking nonsteroidal anti-inflammatory drugs or NSAID pain relievers like ibuprofen or aspirin, as they could cause internal bleeding and be life-threatening to those with ulcers. Instead, opt for acetaminophen, or Tylenol, when you need help with pain management.
3. Constipation Photo credit: Kittisak Jirasittichai / EyeEm – Getty Images More When you’re stopped up, that weighed-down feeling you get could be weight gain. But there’s good news: your body isn’t actually absorbing more calories, says Brown, so it’s not true weight gain so much as it is extra fecal matter, which is what could be adding a few pounds to the scale. Not to mention that constipation itself doesn’t exactly give us the motivation to hit the gym and crush a workout. Rather, it’s way more likely that you’re feeling sluggish and heavy… and the couch is calling your name.
The fix: To stay, err, regular, Brown suggests sticking to a balanced diet of whole foods that have at least 25 to 30 grams of fiber per day, staying well-hydrated (try to drink one to two liters of water per day), and exercise regularly. If something doesn’t seem quite right, look at these signs for what it could mean, and consider talking with your physician.
4. Bacteria Overgrowth Photo credit: lyosha_nazarenko – Getty Images More Bear with us – this one isn’t quite as gross as it sounds. Basically, your bowel contains both good and bad bacteria, and research shows that the good kind plays a crucial role in your overall health by reducing inflammation and keeping your weight in check . The problem occurs when the amount of bacteria increases, or when the type of bacteria gets thrown off-balance. (For optimal health, it’s best to think of it like a seesaw – best when the good and bad is totally balanced.) When that happens, what’s known as small intestinal bacterial overgrowth (SIBO) can occur, and it can cause weight gain in two ways, says Brown.
First, the bacteria could produce methane gas, which “slows down the overall function of the small intestine, allowing the intestinal villi – small, finger-like projections in the lining of your intestine – to absorb more calories per bite,” he explains. In other words, the exact opposite of what you want to happen. Second, SIBO can slow down metabolism and affect your insulin and leptin resistance, both of which help regulate hunger and satiety. As a result, you’re likely to crave carbs and probably won’t feel full after eating, even if it’s a fully satisfying meal, says Sachar.
The fix: To avoid SIBO, Brown suggests avoiding antibiotics unless absolutely needed (as the name suggests, these medications kill off bacteria, which you only really want if you’re sick to get the seesaw back in balance). If bacteria overgrowth is already happening, though, your doctor may suggest a digestive herbal supplement like Atrantil to help you get back on track.
5. Irritable Bowel Syndrome (IBS) Photo credit: Getty Images More The term IBS gets tossed around a lot these days, as “it’s the most commonly diagnosed GI condition, and it often overlaps with other digestive problems like food sensitivities, a leaky gut, and an imbalance of good and bad bacteria,” says Sachar. And like constipation (a symptom of IBS), it can cause bloat and chronic inflammation, which, once again, could lead to weight gain.
The fix: For people who are diagnosed with IBS, it’s about getting to the root of the problem. Your doctor can work with you to build up the good bacteria you need with probiotics, and add digestive enzymes to help break down food so it’s not just sitting around in your gut causing inflammation, explains Sachar. Brown says it could be helpful to try a gluten-free or low gas-producing diet, like FODMAP, as it can help reduce bloating and help get any unnecessary weight gain under control.
6. Crohn’s Disease Photo credit: Brian Evans – Getty Images More While a smaller appetite and excessive weight loss are common symptoms of Crohn’s disease – an incurable chronic inflammatory conditions – the exact opposite can happen as soon as someone gets put on a treatment that involves steroids, which is usually the first step in trying to find a medication that works for you, says Sachar.
“Steroids tend to increase your cravings for carbs and cause you to hold on to more water and feel bloated,” says Sachar.
Fortunately, it’s usually not too tough to lose the weight once you’re off steroids. That usually happens as soon as a flare-up – or the reappearance of symptoms like diarrhea, constipation, rectal bleeding, and fever – subside and symptoms are better under control.
The fix: First of all, your overall health is more important than a few pounds on the scale, so following your doctor’s orders is imperative. But some doctors do shy away from steroid use, like Brown, as he knows the side effects can be less than desirable. Every patient responds differently to medication, though, so talk with your own physician to see what works best for you.
7. Gastroparesis Photo credit: Nerthuz – Getty Images More Often associated with those who have type 1 or type 2 diabetes, gastroparesis – also known as delayed gastric emptying – is a disorder that “slows or stops the movement of food from the stomach to the small intestine,” according to the National Institute of Diabetes and Digestive and Kidney Diseases . Because normal digestion isn’t able to occur, it’s common to feel like you’re gaining weight due to fullness and bloating in the stomach area, but the disorder most commonly leads to weight loss in the end.
The fix: According to the American College of Gastroenterology , diet is one of the most important factors in treating gastroparesis. Because fatty and fiber-filled foods take longer to digest, it’s recommended that anyone with the disorder limits or avoids those foods altogether. But since this is a serious condition, it’s best to speak with your doctor to see what the best treatment options are for you.
8. Food Intolerance Photo credit: spukkato – Getty Images More If you’ve noticed your body is easily irritated by certain foods, there’s a good chance you have a food intolerance. Different from a food allergy, which is an immune system response, food intolerance affects the digestive system, making it hard to digest and break down certain foods (the most common being dairy), says the Cleveland Clinic . Those with a food intolerance often experience gas, cramps, and bloating, making it feel like they’re gaining weight. Depending on how severe the food intolerance is, they might also experience diarrhea.
The fix: While you might feel super bloated and uncomfortable throughout the day because of your diet, you might not actually be gaining weight. The Cleveland Clinic recommends avoiding or reducing the foods you think are giving you issues, and if you do end up eating something that bothers your stomach, take an antacid.
9. Ulcerative Colitis Photo credit: Monica Schroeder – Getty Images More Although Crohn’s disease can pop up anywhere between the mouth and the anus, UCLA Health says ulcerative colitis stays in the colon, resulting in a constantly inflamed digestive tract that can initially lead to weight loss. Like Crohn’s, though, the treatment for the inflammatory bowel disease – steroids – could make your body gain weight.
“An oral steroid like Prednisone can also cause your body fat to redistribute itself, so instead of it being in your stomach or glutes, it could move to the face or neck,” says Sachar.
Even though you may notice a difference in your weight during treatment, everything should go back down to normal as soon as you’re able to get off the steroids.
The fix: After speaking to your doctor, find a treatment plan that’s right for you and the severity of your ulcerative colitis – one that may or may not involve steroids. While more moderate to severe forms might be treated with steroids, 5-aminosalicylates and immunosuppressant drugs are also options. Whatever you end up using, know your wellbeing is top priority. If that involves gaining a few pounds to better your health, it’s worth it.
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Suffering From Allergies? Here’s a Quick & Easy Natural Solution

<h1>Suffering From Allergies? Here’s a Quick & Easy Natural Solution</h1>

Suffering From Allergies? Here’s a Quick & Easy Natural Solution

By BlackDoctor.org
Now that the winter is clearing and spring is here, the possibility of allergies and inflammation become more present. BUT there may be a simple and natural way to help alleviate these annoyances, the mushroom.
Mushrooms have so many health benefits in addition to being tasty in our meals and snacks. You may know mushrooms can help with weight loss, but did you know they can also help with seasonal allergies? Yep, you read that right! Eating mushrooms or even adding mushroom powder to your diet can help you beat seasonal allergies, and here’s how.
Natural Stress Reliever To The Rescue: Allergies, like many other health issues, can be brought on by stress. Reishi and Lion’s Maine mushrooms are an excellent choice as an anti-stress herb to ease tension. Many people who take Reishi and Lion’s Maine via mushroom powder or by adding it to their diets on a regular basis notice that they feel much more peaceful than before.
Mushrooms Clear The Liver: Maitake and reishi mushrooms are two of the best liver cleansers. In Eastern medicine, they are commonly used to protect and fortify liver functions. The liver also plays a role in blood sugar management by helping to prevent hypoglycemia. This is important because we are most likely to experience allergic reactions when the blood sugar level falls. It’s been proven that by keeping a balance blood sugar level it’s possible to avoid the onset of seasonal allergies.
Mushrooms Minimize Inflammation: Breathing in allergens irritates the nose and can cause swelling and inflammation. The easiest way to naturally rid the body of inflammation is to eat more foods with anti-inflammatory qualities such as fish, flaxseed, fresh fruit, Black Seed Oil, green tea, garlic, leafy greens, and ginger. In addition, we can use natural products such as reishi and Lion’s Maine to minimize the inflammatory response, as shown in an international scientific study.
Reishi contains steroid-like anti-inflammatory compounds that inhibit inflammation and histamine, the chemical responsible for allergic symptoms such as runny nose, watery eyes, hives, and bronchial constriction. One study found that reishi extracts compared favorably with Prednisone®, a steroidal anti-inflammatory drug with potentially serious side effects. Reishi had few, if any, side effects.
Mushrooms vs Mushroom Powder Benefits: With all the health benefits of mushrooms, you’re probably thinking it doesn’t get any better than this. Well, what if I were to tell you-you’re wrong? Mushroom powder offers similar benefits to raw mushrooms in a much more powerful way. How much more, you ask? Try a 14:1 ratio
Mushroom extract powder is derived from Ancient Chinese Medicinal Techniques. Dating back to 400 A.D. Lions Mane, Reishi, Astragalus, and Shiitake have been shown to improve mood- focus, and lower stress, while Cordyceps and Chaga increase your stamina. These mushrooms are Immunity boosting and cell health supporting. Today hundreds of Scientific Studies have been done on the health and adaptogenic benefits of these mushrooms.
Another win for mushroom powder comes for those who don’t traditionally enjoy mushrooms. Whether it’s the taste or the texture, they’re just not fans of the potent veggie. With mushroom powder, you don’t have to be! You can get all of the benefits of mushrooms without having to eat an actual mushroom. The powder can be added to your morning coffee, smoothies, cooked dishes, and more.
In addition to ALL of this, mushrooms also help strengthen the immune system, in general, to help with fighting off allergies and more. Add mushrooms to your diet or add a powerful mushroom extract powder now before those spring allergies kick in and you’ll be able to thank us later! Featured Videos

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