Monday, January 27, 2020

Interstitial Cystitis Part I

Interstitial Cystitis: A Comprehensive Overview
Also known as painful bladder syndrome, Interstitial Cystitis (IC) is a chronic disorder causing pain and discomfort for many people, oftentimes impeding normal life.  Though a malady affecting both sexes, females are much more likely to suffer from the condition. Recent studies report an IC incidence rate of 197 diagnoses in women per 100,000 compared to 41 diagnoses in men per 100,000.1 Perhaps the numbers appear at first to be negligible in the grand scheme of things, yet this disease can be life-altering.
As the name implies, IC is an uncomfortable affliction, causing symptoms such as bladder pressure and pain, bladder urgency with little output, painful intercourse, as well as pelvic pain and discomfort. Ranging from mild to severe, the pain can significantly impair everyday activities such as social engagements, exercise, sleep and the ability to perform job duties.2, 3 Further, many people experience flare-ups due to triggering events such as menstruation, stress, exercise and extended periods of sitting.2
Oftentimes difficult to diagnose, doctors frequently attempt to rule out other illnesses with similar symptom profiles such as kidney stones, bladder cancer, sexually transmitted diseases, endometriosis, inflamed prostate, chronic pelvic pain syndrome and infection before looking further into the possibility of an IC diagnosis.2 Frequently, IC symptoms may mirror signs of a chronic urinary tract infection but generally no infection is present in those suffering from this condition.2, 3 If, however, an IC patient does contract a urinary infection, symptoms are oftentimes heightened.3 In addition, most experts agree that due to IC’s wide range of symptoms and intensity of pain and discomfort, that IC may actually be a combination of multiple diseases.2 Further complicating the diagnostic process is the fact that not only are many family physicians lacking in knowledge in regard to IC but there often tend to be multiple comorbidities with it as well.4, 5 These factors oftentimes present symptom-overlap and subsequent misdiagnoses which will be discussed shortly.4, 5
Though IC is predominantly observed and diagnosed during middle age (average age of onset 40 years), both men and women can see the emergence of the disorder between the ages of 20 and 50.6 As mentioned previously, IC is much more common in females than males due to the shorter length of the urethra in women.7 Because of this difference in anatomy, bacteria has an easier method of reaching the bladder and becoming overpopulated, thus causing inflammation.2, 7
IC can be categorized several different ways. Oftentimes it is divided into two phenotypes, non-ulcerative and ulcerative.8 Non-ulcerative IC accounts for approximately 90% of patients with the disorder and is typically identified by the observance of pinpoint hemorrhages in the bladder wall (indicating bladder inflammation is present).8 Ulcerative IC comprises 5-10% of IC patients and is identified when patients present with Hunner’s ulcers (red, bleeding areas) on the bladder wall.8 End stage or severe IC has also been used as a classification of the disorder, referring to patients who have developed very hard bladders as well as low bladder capacity and excruciating pain.8
IC is also sometimes identified as being uncomplicated and complicated in nature.7 Uncomplicated IC is characterized by symptoms contained within the lower urinary tract as well as the absence of risk factors for severe infection or long-term impairment.7 Further, uncomplicated IC is typically easily treatable and eliminated without much difficulty.7  In contrast, complicated IC typically does not respond to antibiotic treatment, may present an increased risk of infection, possible spreading of infection to the kidneys, and inflammation of the renal pelvis (pyelonephritis).7 Particular populations are at greater risk for complicated IC including those with compromised immune systems, kidney problems or who demonstrate anatomical abnormalities in the urinary tract.7
Diagnostic tests for IC include urine samples to test for bacteria, white and red blood cells, proteins and nitrites (can be an indicator of bacteria); ultrasound to examine the kidneys and bladder; and in rare cases, cystoscopy or x-ray (only used when a woman has severe and recurrent symptoms).7 Additional tests that are less common but sometimes performed include bladder and urethra biopsy, bladder stretching and in men, prostate fluid culture.2


 1.  Arora HC, Shoskes DA. The enigma of men with interstitial cystitis/bladder pain syndrome. Translational Andrology and Urology. 2015;4 (6): 668-676.

2. WebMD. Interstitial Cystitis. Available at: Accessibility verified July 6, 2018.
3.     Mayo Clinic. Interstitial Cystitis. Available at: Accessibility verified July 6, 2018.
4.     Clemens JQ, Calhoun EA, Litwin MS, et al. A survey of primary care physician practices in the diagnosis and management of women with interstitial cystitis/ painful bladder syndrome. Urology. 2010; 76(2): 323-328.
5.     American Urological Association. First-ever clinical guidance on interstitial cystitis/bladder pain Syndrome Released: Effective treatment includes valid diagnosis, effective symptom control and focus on quality of life. Available at: Accessibility verified July 6, 2018.
6.     Harvard Health Publishing Harvard Medical School: Trusted Advice for a Healthier Life. Interstitial Cystitis. Available at: Accessibility verified July 6, 2018.
7.     PubMed Health. Cystitis: overview. Available at: Accessibility verified July 6, 2018.

Saturday, January 18, 2020

Diet and Exercise: Implications for Those Suffering From Rheumatoid Arthritis

           Though the prevalence of rheumatoid arthritis (RA) is relatively low at approximately 0.5-1% among most populations, for those suffering from the disease it can be a life-altering reality.1 According to the Centers for Disease Control and Prevention (CDC), RA is an autoimmune disease and manifests itself by causing the immune system to attack healthy cells in error. This, in turn, causes painful swelling and inflammation in the affected regions of the body.2 Typically, RA affects joints in the hands, wrists and knees and can lead to stiffness, tenderness and swelling in the joints, weight loss, fatigue, weakness, and chronic pain.2
Pharmacological Treatment
Treatment options vary, though pharmacologic therapies are often the first line treatment options recommended.3 Nonsteroidal anti-inflammatory drugs, nonbiologic and biologic disease-modifying antirheumatic drugs, immunosuppressants, and corticosteroids are all classes used in medication-based therapies for RA.3 Side effects of these drugs are disturbing at best, including upper respiratory tract infections, headache, diarrhea, inflammation of the mouth and lips, nausea, vomiting, abdominal pain, dizziness, bleeding gums, blurred vision, leukopenia, shaking fingers/hands, muscle spasms, and numbness.4, 5, 6 In addition, biologic agents that are oftentimes used for RA patients have limited long-term safety data, presenting a point of particular concern due to the possibility of enhanced risk of malignancies, more specifically, lymphoma.7 Further, the cost of the newer biologic drugs is quickly escalating, presenting an obstacle for those planning to use such interventions.7 When efficacy is measured across the span of RA-specific drugs, production of positive effects show only low to moderate benefit, pulling into question the risk versus advantage argument.8 In addition, pharmacological treatments carry significant risk and adverse event profiles, oftentimes causing increased drop-out rates in clinical trials.8 A systematic review of multiple RA medications, such as conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib showed efficacy, thus suggesting their usefulness in the treatment of RA.9 However, the review was funded by multiple drug companies including Astra-Zeneca, Lilly, Merck, Glaxo, Sanofi-Aventis, and Pfizer, calling into question the validity of efficacy-reporting.9
With these factors in mind, alternative treatment options appear a warranted area of study in the management and treatment of this disease. Many non-pharmacologic therapies are available, including diet, exercise, physical therapy, and other lifestyle-related treatments.3 For the purposes of this paper, diet and exercise will be explored as non-pharmacologic treatment modalities in RA patients.
Due to the affordability, accessibility and presence of reliable scientific evidence that display benefit, dietary interventions appear to provide a solid alternative to pharmacologic treatments of RA.10 Further, research supports a display of significant benefits from this modality in regard to reducing symptoms such as pain, joint stiffness, swelling, tenderness and associated disability with disease progression.10
In a review of the research, authors deduced that the inclusion of vegetables, spices such as turmeric and ginger and fruits can provide important sources of natural antioxidants as well as anti-inflammatory effects for RA patients.10 Additionally, data suggests that RA patients should employ a reduction in processed and high fat foods as well as avoidance of foods such as oils, butter, sugar and animal products.10 Research performed with patients suffering from a variety of rheumatic diseases studied the effect of antioxidants in the diet when compared to reduction of disease symptoms and overall improvement.11 Outcome measures showed that RA subjects eating a diet consisting of berries, fruits, vegetables, roots, nuts, germinated seeds and sprouts showed a significant benefit in regard to symptoms on subjective and objective measures.11 Similarly, in a study testing the effectiveness of eating an uncooked vegan diet rich in lactobacilli, researchers determined that when compared to the control group, the intervention group experienced subjective relief from RA symptoms.12 Further, when participants returned to eating an omnivorous diet, the RA symptoms were again aggravated.12 Though the intervention group showed somewhat inconsistent results on objective measures, there was an associated decrease in disease activity overall and a prevention of the need for pharmacologic intervention.12 A group of researchers took the diet restriction to a new level by studying 66 patients with active RA and randomizing them to either a gluten-free, vegan diet or a well-balanced, non-vegan diet.13 Participants were studied at three, six, and 12 months and researchers concluded that 40.5% of the gluten-free, vegan group improved while only 4% of the non-vegan group improved.13 Researchers suggested that dietary modification such as the one studied may provide a clinical benefit for RA patients.13 Outcomes of additional studies show a potential for anti-inflammatory effects as well as decreased blood lipids oxidized low-density lipoprotein levels and raised natural atheroprotective antibodies against phosphorylcholine in RA patients who consume a gluten-free, vegan diet.14 Further, in a single-blind dietary intervention study, 24 patients with RA were given a very low-fat (approximately 10% fat), vegan diet and followed for a four-week trial.15 Outcome measures demonstrated that subjects with moderate-to-severe RA experienced a significant reduction in RA symptoms when they ate a very low-fat, vegan diet.15 Additional research points to the beneficial inclusion of probiotics in conjunction with a vegan or vegetarian diet, showing an improvement in symptoms with such combinations.11, 12
The benefit of fasting has also been studied in RA patients when coupled with dietary interventions. A systematic review examined the effect of fasting for at least three months followed by the adoption of a vegetarian diet.16 Results showed that there was a statistically and clinically significant, beneficial, long-term effect on RA patients.16 Due to the fact that the literature review was limited to four applicable studies, concrete conclusions may be premature. However, such convincing data warrants further investigation by way of additional randomized, long-term studies. In a randomized, single-blind, controlled trial, 27 patients with RA were allocated to an intervention group, while 26 RA patients were placed in a control group.17 The intervention group subjects were allocated to a four-week stay at a health farm and were placed on an initial 7-10 day fast.17 Following the fasting period, subjects were put on an individually-adjusted gluten-free, vegan diet for an additional three and a half months, followed by a gradual transition to a lactovegetarian diet for a total trial period of one year.17 The control group was allotted to a four-week stay at a convalescent home, eating an ordinary diet for the entirety of a year.17 Following the initial four week period, study results showed a significant improvement in symptoms for the intervention group such as number of tender and swollen joints, duration of morning stiffness, and an improvement in overall health assessment score.17 Further, the benefits in the intervention group after the completion of one year again showed significant advantages in all measured indices when compared to the control group.17
It appears clearly evident that dietary interventions are beneficial in RA patients and provide a viable and effective method of treatment. Of similar importance is the fact that non-pharmacological interventions such as diet modification do not produce dangerous results or adverse side effects.

Physical Activity
In addition to the clearly beneficial components of dietary intervention, physical activity can also be a significant factor in the management of RA. Research abounds in regard to the overall positive effect of exercise for RA patients.
In a study of 220 patients with RA, subjects were divided into a class exercise group, a home exercise group and a control group.18 Subjects were measured at base line and subsequently at six and 12-week marks.18 Results displayed that in the class exercise group, grip strength, walk time and fatigue greatly improved.18 Further, overall symptoms of pain and depression were all positively affected in the class exercise group.18 Though some improvements were made in the home exercise group, they were not as significant in the class exercise group, despite the similarity of exercises completed, possibly due to the differing levels of intensity.18 Researchers concluded that exercise was a positive influence on RA symptoms.18  A literature review looked at the benefits of exercise for RA patients and also found a positive level of effect.19 Authors deduced that exercise in general showed a clear and proven method of treatment that provided an improvement in overall function for RA patients.19 An additional meta-analysis and literature review of studies looked at the effect of cardiorespiratory aerobic exercise for RA patients in regard to quality of life, function and clinical and radiologic outcomes.20 Collective results showed that cardiorespiratory aerobic exercise proved to be a safe method of treatment, providing improvement in some of the most important outcome measures for RA.20 Another meta-analysis examined the efficacy of resistance exercises in RA patients.21 Following the study of a total of 10 randomized, controlled trials with 547 patients, authors concluded that not only was resistance exercise in RA patients safe, but it also showed improvement in most outcomes and was statistically significant as well as possibly clinically significant for the outcome of RA disability measures.21 Further, subgroup analysis also revealed a trend towards increased efficacy in programs with high-intensity resistance exercise.21 Another literature review showed evidence that physical activity is a significant factor in the common and distressing symptom of fatigue for RA patient.22 The review examined 24 studies with a total of 2,882 participants with RA.22 Authors concluded that physical activity had a positive effect on fatigue in RA patients.22
Not only has exercise been proven as an effective method of treatment for typical RA symptoms, but it has also been shown to have a positive effect on mood for RA patients.18, 23 In a review of the literature, authors concluded that exercise improves depression for RA patients, a common yet not classic symptom of RA.23 Additionally, a systematic review with meta-analysis of 500 articles and 2,449 participants studied the effects of exercise on depressive symptoms in adults with arthritis and rheumatic conditions.24 Authors concluded that depressive symptoms were reduced with the inclusion of exercise.24 Again, though depression is not an RA-specific symptom, it is a common factor experienced in those with this disease and a symptom undeniably worth improving.
Though some of the studies cited in this paper have limitations such as measures of self-reported data, small sample sizes or confounding variables, the preponderance of the evidence clearly shows a positive effect of both dietary intervention and exercise on the symptoms and overall outcome for RA patients. Of similar importance, specific dietary interventions as well as various forms of exercise, like those reviewed in this paper, have not only proven to be safe methods of reducing overall disease markers but have also been shown to be significant factors in symptom management, both without risk of side effects or negative outcomes.  RA patients would clearly benefit from dietary intervention and exercise protocols as first-line treatment options rather than the more commonly prescribed pharmacologic options.

1.     Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Research & Therapy. 2002; 4(3): S265-S272.
2.     Centers for Disease Control and Prevention. Rheumatoid Arthritis. Available at: Accessibility verified March 6, 2018.
3.     Medscape. Rheumatoid arthritis treatment & management. Available at: Accessibility verified March 6, 2018.
4.     RxList. Xeljanz side effect center. Available at: Accessibility verified March 6, 2018.
5.     RxList. Trexall side effect center. Available at: Accessibility verified March 6, 2018.
6.     RxList. Neoral side effect center. Available at: Accessibility verified March 6, 2018.
7.     Nurmohamed MT, Dijkmans BA. Efficacy, tolerability and cost effectiveness of disease-modifying antirheumatic drugs and biologic agents in rheumatoid arthritis. Drugs. 2005; 65(5): 661-94.
8.     Donahue KE, Jonas DE, Hansen RA, et al. Drug therapy for rheumatoid arthritis in adults: an update (internet). Comparative Effectiveness. 2012; 55: 1-159.
9.     Gaujoux-Viala C, Nam J, Ramiro S, et al. Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Annals of the Rheumatic Diseases. 2014; 73(3): 510-515.
10.  Khanna S, Jaiswal KS, Gupta B. Managing rheumatoid arthritis with dietary interventions. Frontiers in Nutrition. 2017; 4(52): 1-16.
11.  Hänninen, Kaartinen K, Rauma AL, et al. Antioxidants in vegan diet and rheumatic disorders. Toxicology. 2000; 155(1-3): 45-53.
12.  Nenonen MT, Helve TA, Rauma AL, Hänninen OO. Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis. British Journal of Rheumatology. 1998; 37(3): 274-281.
13.  Hafström I, Ringertz B, Spångberg A, et al. A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford).2001; 40(10): 1175-1179.
14.  Elkan A-C, Sjöberg B, Kolsrud B, et al. Gluten-free vegan diet induces decreased LDL and oxidized LDL levels and raised atheroprotective natural antibodies against phosphorylcholine in patients with rheumatoid arthritis: a randomized study. Arthritis Research & Therapy. 2008; 10(2): 1-8.
15.  McDougall J, Bruce B, Spiller G, Westerdahl J, McDougall M. Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis. Journal of Alternative and Complimentary Medicine. 2002; 8(1): 71-75.
16.  Müller H, de Toledo FW, Resch KL. Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic review. Scandanavian Journal of Rheumatology. 2001; 30(1): 1-10.
17.  Kjeldsen-Kragh J, Haugen M, Borchgrevink CF, et al. Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet.1991; 338(8772): 899-902.
18.  Neuberger GB, Aaronson LS, Gajewski B, et al. Predictors of exercise and effects of exercise on symptoms, function, aerobic fitness, and disease outcomes of rheumatoid arthritis. Arthritis Rheumatism. 2007; 57(6): 943-952.
19.  Cooney JK, Law R-J, Matschke V, et al. Benefits of exercise in rheumatoid arthritis. Journal of Aging Research. 2011; 2011(681640): 1-14.
20.  Baillet A, Zeboulon N, Gossec L, et al. Efficacy of cardiorespiratory aerobic exercise in rheumatoid arthritis: meta-analysis of randomized controlled trials. Arthritis Care and Research.2010; 62(7): 984-992.
21.  Baillet A, Vaillant M, Guinot M, Juvin R, Gaudin P. Efficacy of resistance exercises in rheumatoid arthritis: meta-analysis of randomized controlled trials. Rheumatology (Oxford). 2012; 51(3): 519-527.
22.  Cramp F, Hewlett S, Almeida C, et al. Non-pharmacological interventions for fatigue in rheumatoid arthritis. Cochrane Database of Systematic Reviews.2013; 23(8): doi: 10.1002/14651858.CD008322.pub2.
23.  Kelley GA, Kelley KS. Exercise reduces depressive symptoms in adults with arthritis: evidential value. World journal of rheumatology. 2016; 6(2): 23-29.
24.  Kelley GA, Kelley KS, Hootman JM. Effects of exercise on depression in adults with arthritis: a systematic review with meta-analysis of randomized controlled trials. Arthritis Research and Therapy.2015; 17(21): 1-22.

Interstitial Cystitis Part II