Management of hemorrhoids

Introduction

Hemorrhoids are common human afflictions known since the dawn of history, defined as the symptomatic enlargement and distal displacement of the normal anal cushions. Essentially, the word “hemorrhoid” is derived from the Greek “haema” = blood, and “rhoos” = flowing, and was originally used by Hippocrates to describe the flow of blood from the veins of the anus.¹MacKay D. Hemorrhoids and varicose veins: a review of treatment options. Altern Med Rev 2001;6(2):126-40.     In effect, hemorrhoids constitute one of the most common arteriovenous disorders, with peak prevalence occurring between the ages of 45 and 65 years; close to 50% of people 50 years or older are affected by hemorrhoids.

Hemorrhoid anatomy

Hemorrhoids are universally classified according to anatomical origin, occurring at two levels relative to the anus. They are either internal, external or a combination of both (Table 1). The classification has practice implications since the level of the hemorrhoid influences the type of treatment.

While external hemorrhoids have an epithelial component and originate below the dentate line, internal hemorrhoids consist of redundant mucus membrane of the anal canal with the origin above the dentate line. The latter are further graded based on the extent to which the tissue descends into the anal canal (Table 2).¹MacKay D. Hemorrhoids and varicose veins: a review of treatment options. Altern Med Rev 2001;6(2):126-40.  ^,2Dennison AR, Whiston RJ, Rooney S, et al. The management of hemorrhoids. Am J Gastroenterol 1989;84:475-481.  

Pathophysiology of hemorrhoids

The pathophysiology of hemorrhoidal development, cause of enlargement and symptoms is debatable; various theories and etiologies have been proposed (Table 3).³Lohsiriwat V. Hemorrhoids: from basic pathophysiology to clinical management. World J Gastroenterol. 2012;18(17):2009-17.     Studies implicate intrinsic weakness of the blood vessel wall, heredity, increased intra-abdominal pressure from many causes, including prolonged forceful Valsalva during defecation or resistance training, obstruction of venous outflow secondary to pregnancy or pelvic masses, and constipated stool in the rectal ampulla are possible contributing factors.¹MacKay D. Hemorrhoids and varicose veins: a review of treatment options. Altern Med Rev 2001;6(2):126-40.  

It appears that the dysregulation of the vascular tone and vascular hyperplasia might play an important role in hemorrhoidal development, and could be a potential target for medical treatment. Indeed, the abnormal dilatation and distortion of the vascular channel, together with destructive changes in the supporting connective tissue within the anal cushion, is a paramount finding of hemorrhoids.³Lohsiriwat V. Hemorrhoids: from basic pathophysiology to clinical management. World J Gastroenterol. 2012;18(17):2009-17.  

As a patient ages and has continual presence of one or more of the above mentioned factors, the integrity of the hemorrhoid “cushions” deteriorates, and the hemorrhoid tissue begins to bulge and descend into the anal canal. Further, when the cushion bulges into the canal, it is exposed to potential trauma and irritation from the passage of the stool.

Clinical presentation

With its characteristic symptomatic presentation (bleeding, protrusion and pain), an estimated third of patients affected by hemorrhoids seek medical attention.⁴Hain JM. Medical treatment of hemorrhoids using flavonoids. Practical gastroenterology, 2011.   In most cases, the common symptom of hemorrhoids is rectal bleeding associated with bowel movement.³Lohsiriwat V. Hemorrhoids: from basic pathophysiology to clinical management. World J Gastroenterol. 2012;18(17):2009-17.  

Patients frequently complain of bleeding with/without defecation, swelling, mild discomfort or irritation. Other symptoms may include soilage or mucous discharge, pruritis, difficulties with hygiene, and a sense of incomplete evacuation.

Internal hemorrhoids, though otherwise painless, produce pain if thrombosed, prolapsed with edema, or strangulated. Likewise, external hemorrhoids result in pain when a thrombosis occurs, and bleed if ulceration occurs from pressure necrosis; essentially, thrombosis in external hemorrhoids results in painful swelling.⁵Halverson A. Hemorrhoids. Clin Colon Rectal Surg. 2007;20(2):77-85.   Skin tags may form from prior acutely edematous or thrombosed external hemorrhoids.

Diagnosis of hemorrhoidal disease

The most important aspect in the diagnosis of hemorrhoidal disease is the exclusion of other, more life threatening conditions. Yet, the definite diagnosis is based on a precise patient history and careful clinical examination, which should include a digital examination and anoscopy in the left lateral position. The perianal area should be inspected for anal skin tags, external hemorrhoid, perianal dermatitis from anal discharge or fecal soiling, fistula-in-ano and anal fissure.³Lohsiriwat V. Hemorrhoids: from basic pathophysiology to clinical management. World J Gastroenterol. 2012;18(17):2009-17.  

Though internal hemorrhoids cannot be palpated, digital examination will detect abnormal anorectal mass, anal stenosis and scar, evaluate anal sphincter tone, and determine the status of prostatic hypertrophy which may be the reason for straining because this aggravates descent of the anal cushions during micturition. Of note, hemorrhoidal size, location, severity of inflammation and bleeding should be noted during anoscopy. Furthermore, intra-rectal retroflexion of the colonoscope or transparent anoscope using flexible endoscope also allow excellent visualization of the anal canal and hemorrhoid, and permit recording pictures.

Management of hemorrhoids

As far as treatment of hemorrhoids is concerned, there is no specific treatment for the hemorrhoids. Whilst there are some symptomatic treatments, such as high fibre diets, bulk laxatives, fecal softeners, oil phenolene injections, topical drug treatments; all these treatments are not able to reach at the root cause of the disease. Furthermore, even though most clinicians advocate adding adequate fluid and fiber intake to appropriately adjust the consistency of the bowel movements, and educate about appropriate defecation hygiene; however, this may prove inadequate with more severe hemorrhoidal disease. Use of topical agents with corticosteroids, anesthetics, astringents, antiseptics, or protectants can provide short relief of symptoms, but has little data to support long term use.⁴Hain JM. Medical treatment of hemorrhoids using flavonoids. Practical gastroenterology, 2011.  

Nevertheless, continued search for better non-surgical therapeutic options led to the introduction of a vasoactive and vasoprotective drug, i.e. calcium dobesilate, considering that hemorrhoids are all after venous swelling, in which formation of a thrombus takes place. However, the drug may not be deemed as completely safe, with side effects of agranulocytosis, gastrointestinal disturbances and drug induced fever being commonly associated with it. In effect, risk of agranulocytosis associated with calcium dobesilate should be considered in relation to poor evidence of its clinical efficacy.⁶Ibáñez L, Ballarín E, Vidal X, et al. Agranulocytosis associated with calcium dobesilate clinical course and risk estimation with the case-control and the case-population approaches. Eur J Clin Pharmacol. 2000;56(9-10):763-7.  

Yet, even as surgical management has its own definite relevance, medical management of hemorrhoidal disease is the ideal initial approach to the vast majority of hemorrhoidal complaints. Today, modern as well as traditional drugs are being increasingly used in all grades of symptomatic hemorrhoids as a part of conservative management or as an adjuvant to invasive outpatient procedures. Also, drug therapy may help in scheduling the definite procedures at a convenient time.⁷Misra MC, Imlitem SU. Drug treatment of haemorrhoids. Drugs. 2005;65(11):1481-91.  

Diosmin – the preferred flavonoid’s role in hemorrhoids

In the etiopathogenesis and physiopathology of hemorrhoids, from the physiopathological viewpoint, particular importance is retained by the vascular factor, which in its turn is influenced by mechanical and sphinceric factors that impair the venous backflow. In effect, in the evidence of a hemorrhoidal crisis, characterized by local edema, pain and bleeding, the use of bioflavonoid drugs is deemed to be the first choice.⁸Diana G, Catanzaro M, Ferrara A, et al. Activity of purified diosmin in the treatment of hemorrhoids. Clin Ter. 2000;151(5):341-4.  

First introduced as a therapeutic agent in 1969, diosmin is a naturally occurring flavonoid glycoside, and is considered to be a vascular-protecting agent with multimodal action – a property justifying

its role in treatment of hemorrhoids, chronic venous insufficiency, lymphedema, and varicose veins. Several large clinical trials have demonstrated diosmin to be effective in treatment of both acute and chronic symptoms of hemorrhoids.⁹Diosmin monograph. Alternative Medicine Review 2004;9(3):308- 311.  

Effectively, the drug has been widely used for more than 30 years worldwide as a phlebotonic and vascular protecting agent with good efficacy and safety profile. Moreover, being a flavonoid, diosmin also exhibits anti-inflammatory, free-radical scavenging, and anti-mutagenic properties (Box 1).

Purified micronised diosmin and its mechanism of action

Purified micronised diosmin is natural in origin. Yet it is synthesized, standardized, micronised and free from impurity such as hesperidin. It can help in reducing grade of hemorrhoids which can prolapse latter and helps in avoiding need for surgery. It can be given pre-surgery and post surgery, with the advantage that it can demarcate the area of operation.

The process of micronisation further enhances the efficacy of diosmin by increasing the bioavailability (Figure 1). Figure 2 shows the multimodal mechanism of action of diosmin.

Rationale for diosmin recommendation: Clinical evidence

Diana et al investigated the use of purified diosmin, given at a dose of two 450 mg tablets bid for the first 7 days, then at 1 tablet bid for up to 2 months, in a group of 66 patients suffering from primitive

hemorrhoids of grade 1-4.⁸Diana G, Catanzaro M, Ferrara A, et al. Activity of purified diosmin in the treatment of hemorrhoids. Clin Ter. 2000;151(5):341-4.     Evidently, the results confirmed diosmin efficacy in decreasing both pain and bleeding: reduction rates of 79% and 67%, respectively, were reached in the first treatment week. In the second week, figures were 98% and 86%, respectively (Figure 3). Diosmin tolerability was excellent, a characteristic that makes the drug very easy to handle by the general practitioner, and also useful to the proctologist in the preparation of the patient to further treatments.

Use of diosmin with other therapies and surgeries

Diosmin may be used in conjunction with sclerotherapy, surgery and/or compression therapy, or as an alternative treatment when surgery is not indicated or is unfeasible.

Diosmin with surgery

Whilst hemorrhoidectomy continues to be an effective modality for the treatment of medically refractory hemorrhoidal disease, the morbidity of surgery in terms of pain and bleeding is still a major consideration. In effect, considering the morbidity of a hemorrhoidectomy, any significant improvement in post-operative pain control and bleeding would be encouraged. Consequently, attempts have been made to decrease the morbidity of an operative hemorrhoidectomy utilizing anti-inflammatory agents; and there has been considerable interest in using bioflavanoid compounds to alleviate the symptoms of pain and/or bleeding after operative hemorrhoidectomies.

Diosmin as initial treatment after Milligan-Morgan open hemorrhoidectomy

A recent observer blinded, randomized trial demonstrated the value of diosmin (flavonidic fraction) in the management of post-hemorrhoidectomic symptoms. Eighty-six consecutive patients with grades III and IV acute mixed hemorrhoids were enrolled in the study that compared post-hemorrhoidectomic symptoms with use of diosmin flavonidic fraction vs. placebo.¹⁰Ma-Mu-Ti-Jiang A et al. How we can improve patients’ comfort after Milligan-Morgan open haemorrhoidectomy. World J Gastroenterol. 2011; 17(11): 1448-1456.     Patients were randomly allocated to receive diosmin flavonidic fraction 500 mg for 1 week (n = 43) or placebo (n = 43). The Milligan-Morgan open hemorrhoidectomy was performed by a standardized diathermy excision method, and pain, bleeding, heaviness, pruritus, wound edema and mucosal discharge were observed after surgery, alongside recording the postoperative symptoms and hospitalization time. The mean age of the diosmin group and controls was 53.2 and 51.3 years, respectively.

In diosmin group, hemorrhoid piles were of the third degree in 33 patients and the fourth degree in 10; and in the control group, 29 were of the third degree and 14 were of the fourth degree. Results showed that there was a statistically significant improvement in pain, heaviness, bleeding, and pruritus from baseline to the 8th week after operation (P < 0.05). Patients in diosmin group experienced significantly less pain at 6 and 12 hours after surgery, and on days 1, 2, 7, 10, and 14 (Figure 4). Also, patients in the experimental group had significantly less defecation pain compared with the placebo group on days 1, 2, 7, 10, 14, and 30 (Figure 5).

Patients taking diosmin had a shorter hospitalization stay after surgery (P < 0.05). Also, there was a significant improvement on the proctoscopic appearance (P < 0.001). Thus, the experience shows that diosmin is effective in alleviating postoperational symptoms of hemorrhoids, and, therefore, should be considered for the initial treatment after hemorrhoid surgery.

Diosmin for hemorrhoids treatment during pregnancy

Pregnancy and the puerperium predispose to symptomatic hemorrhoids as a consequence of hormonal changes and increased intra-abdominal pressure, being the most common ano-rectal disease at these stages – it has been estimated that 25% to 35% of pregnant women are affected by this condition.¹¹Staroselsky A, Nava-Ocampo AA, Vohra S, et al. Hemorrhoids in pregnancy. Can Fam Physician. 2008;54(2):189-190.     Symptoms are usually mild, transient and include intermittent bleeding from the anus and pain. Depending on the degree of pain, quality of life could be affected, varying from mild discomfort to real difficulty in dealing with the activities of everyday life.¹¹Staroselsky A, Nava-Ocampo AA, Vohra S, et al. Hemorrhoids in pregnancy. Can Fam Physician. 2008;54(2):189-190.  ^,12(a) Quijano CE, Abalos E. Conservative management of symptomatic and/or complicated haemorrhoids in pregnancy and the puerperium. Cochrane Database Syst Rev. 2005;(3):CD004077. (b) Quijano CE, et al. Conservative management of symptomatic and/or complicated haemorrhoids in pregnancy and the puerperium. Cochrane Database of Systematic Reviews Issue 2. 2012.  

Particularly during pregnancy, many of the treatment options for hemorrhoids, such as injection, rubber band ligation, and surgery are contraindicated; and treatment here is mainly symptomatic for most patients, and mainly directed to the relief of symptoms using conservative management.¹MacKay D. Hemorrhoids and varicose veins: a review of treatment options. Altern Med Rev 2001;6(2):126-40.  ^,11Staroselsky A, Nava-Ocampo AA, Vohra S, et al. Hemorrhoids in pregnancy. Can Fam Physician. 2008;54(2):189-190.  ^,12(a) Quijano CE, Abalos E. Conservative management of symptomatic and/or complicated haemorrhoids in pregnancy and the puerperium. Cochrane Database Syst Rev. 2005;(3):CD004077. (b) Quijano CE, et al. Conservative management of symptomatic and/or complicated haemorrhoids in pregnancy and the puerperium. Cochrane Database of Systematic Reviews Issue 2. 2012.     In the short term, micronised diosmin is safe, acceptable, and effective in the treatment of hemorrhoids of pregnancy. Treatment was well accepted, and did not affect pregnancy, fetal development, birth weight, infant growth and feeding.¹³Buckshee K, Takkar D, Aggarwal N. Micronized flavonoid therapy in internal hemorrhoids of pregnancy. Int J Gynaecol Obstet. 1997;57(2):145-51.  

Non-excisional office-based procedures

Non-operative office-based approaches include procedures such as sclerotherapy, radiofrequency coagulation and, rubber band ligation (Box 2.).³Lohsiriwat V. Hemorrhoids: from basic pathophysiology to clinical management. World J Gastroenterol. 2012;18(17):2009-17.  

Surgical options

Though most patients with hemorrhoidal disease may be treated conservatively, an operation is indicated when nonoperative approaches have failed or complications have occurred. Along the years several surgical options have been proposed including closed, open and semiclosed hemorrhoidectomy, radiofrequency hemorrhoidectomy (LigaSure), piles’ suture or Farag operation, manual and stapled hemorrhoidopexy (PPH) with or without excision of anal tags, doppler hemorrhoidal artery ligation with or without recto-anal mucopexy, anomucosal flap circumferential hemorrhoidectomy or Whitehead-Rand procedure.¹⁴Arezzo A, Podzemny V, Pescatori M. Surgical management of hemorrhoids. State of the art. Ann Ital Chir. 2011;82(2):163-72.     Indeed, tremendous progress has been made from complex ligation and excision procedures in the past to simpler techniques that allow the patient to return to normal life within a short period. Nevertheless, postoperative pain is invariable, and some procedures may potentially cause appreciable morbidity such as anal stricture and incontinence; and, newer techniques try to improve on the postoperative complications of older ones.¹⁵Agbo SP. Surgical management of hemorrhoids. J Surg Tech Case Rep. 2011 Jul;3(2):68-75.     Yet, dietary manipulation, including fiber supplementation, should always accompany surgical methods.¹⁶Gearhart SL. Symptomatic hemorrhoids. Adv Surg. 2004;38:167-82.  

Conclusion

Hemorrhoidal disease is a common problem that is managed by various physicians, ranging from primary care providers to surgeons. Although they are often asymptomatic, hemorrhoids may cause bleeding, prolapse and, less commonly, pain. Though, various lines of treatment are available, conservative management is essentially the first choice in most cases.

Micronised disomin has well established effect in hemorrhoids; and can be used as the first line treatment alone or in conjunction to other procedures and surgery. The drug has had significant popularity for hemorrhoidal disease and has been used across a heterogeneous population of patients, with a definite scope for treating hemorrhoid patients who benefit due to its no significant side effects or contraindications.

In effect, diosmin should be considered in several clinical situations:

• Symptomatic hemorrhoid patients whom are failing standard interventions or have relative contraindications to office-based procedures (chronic anticoagulants)
• Defer major hemorrhoid surgery if necessary
• An adjunct to decrease post-operative hemorrhoidectomy morbidity.

References

1. MacKay D. Hemorrhoids and varicose veins: a review of treatment options. Altern Med Rev 2001;6(2):126-40.
2. Dennison AR, Whiston RJ, Rooney S, et al. The management of hemorrhoids. Am J Gastroenterol 1989;84:475-481.
3. Lohsiriwat V. Hemorrhoids: from basic pathophysiology to clinical management. World J Gastroenterol. 2012;18(17):2009-17.
4. Hain JM. Medical treatment of hemorrhoids using flavonoids. Practical gastroenterology, 2011.
5. Halverson A. Hemorrhoids. Clin Colon Rectal Surg. 2007;20(2):77-85.
6. Ibáñez L, Ballarín E, Vidal X, et al. Agranulocytosis associated with calcium dobesilate clinical course and risk estimation with the case-control and the case-population approaches. Eur J Clin Pharmacol. 2000;56(9-10):763-7.
7. Misra MC, Imlitem SU. Drug treatment of haemorrhoids. Drugs. 2005;65(11):1481-91.
8. Diana G, Catanzaro M, Ferrara A, et al. Activity of purified diosmin in the treatment of hemorrhoids. Clin Ter. 2000;151(5):341-4.
9. Diosmin monograph. Alternative Medicine Review 2004;9(3):308- 311.
10. Ma-Mu-Ti-Jiang A et al. How we can improve patients’ comfort after Milligan-Morgan open haemorrhoidectomy. World J Gastroenterol. 2011; 17(11): 1448-1456.
11. Staroselsky A, Nava-Ocampo AA, Vohra S, et al. Hemorrhoids in pregnancy. Can Fam Physician. 2008;54(2):189-190.
12. (a) Quijano CE, Abalos E. Conservative management of symptomatic and/or complicated haemorrhoids in pregnancy and the puerperium. Cochrane Database Syst Rev. 2005;(3):CD004077. (b) Quijano CE, et al. Conservative management of symptomatic and/or complicated haemorrhoids in pregnancy and the puerperium. Cochrane Database of Systematic Reviews Issue 2. 2012.
13. Buckshee K, Takkar D, Aggarwal N. Micronized flavonoid therapy in internal hemorrhoids of pregnancy. Int J Gynaecol Obstet. 1997;57(2):145-51.
14. Arezzo A, Podzemny V, Pescatori M. Surgical management of hemorrhoids. State of the art. Ann Ital Chir. 2011;82(2):163-72.
15. Agbo SP. Surgical management of hemorrhoids. J Surg Tech Case Rep. 2011 Jul;3(2):68-75.
16. Gearhart SL. Symptomatic hemorrhoids. Adv Surg. 2004;38:167-82.