Hemorrhagic Cystitis - An overview

Introduction

Hemorrhagic cystitis is most commonly caused by bacterial infections and neglect may be life-threatening. It has a broad spectrum of possible treatment approaches with a satisfactory prognosis that provide a better standard of living.

What Is Hemorrhagic Cystitis?

It is an inflammatory condition of the urinary bladder caused due to infectious or non-infectious conditions leading to bleeding of the bladder mucosa and hematuria (blood in urine).

What Are the Symptoms to Look Out For?

• The individual may feel a burning sensation while passing urine.

• The individual may have a frequent urge to urinate.

• Unable to control the urge to urinate.

• Nocturia (an urge to pass urine throughout the night).

• The patient may feel a sense of fatigue and may also experience abdominal pain.

What Causes Hemorrhagic Cystitis?

The etiology can be of two types that are infectious and noninfectious.

Infectious Causes:

• Viral: Adenovirus, bk virus, herpes simplex virus, cytomegalovirus.

• Bacterial: E.coli,Proteus mirabilis,Klebsiella.

• Fungal: Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans.

• Parasite: Toxoplasma gondii.

Non-infectious Causes:

Drug-induced:

• Ifosfamide.

• Cyclophosphamide.

• Busulfan.

• Thiotepa.

• Temozolomide.

• 9-nitrocamptothecin.

• Penicillin and its derivatives like methicillin, carbenicillin, ticarcillin, and piperacillin.

• Danazol.

• Tiaprofenic acid.

• Allopurinol.

• Methaqualone.

• Methenamine mandelate.

• Gentian violet.

• Acetic acid.

Chemotherapy medications, such as Cyclophosphamide and Ifosfamide, are commonly used, leading to a high risk of acquiring hemorrhagic cystitis. Busulfan and thiotepa are the lesser common drugs. During the excretion of these drugs, the bladder lining can undergo irritation and, in severe cases, may even lead to ulceration, ultimately leading to hematuria.

Environmental Toxins:

• Aniline dyes.

• Toluidine.

• Chlordimeform.

• Ether.

Systemic Conditions:

• Amyloidosis: Amyloidosis is a condition in which there is the build-up of an abnormal protein (amyloid) that interferes with normal functioning.

• Systemic Lupus Erythematosus: Systemic lupus erythematosus is an autoimmune disease where the immune system attacks its tissues. The organs usually affected are kidneys, blood cells, skin, joints, brain, heart, and lungs.

• Rheumatoid Arthritis: Rheumatoid arthritis is an autoimmune disease that mainly affects the joints, causing inflammation of the joints.

• Crohn's Disease: Inflammatory bowel disease affecting the digestive system leading to pain, discomfort, and diarrhea.

• Boon's Disease.

Radiation therapy for pelvic malignancies.

What Is the Grading of Hemorrhagic Cystitis?

The grading system proposed by Droller et al. is used for hemorrhagic cystitis.

• 0- No symptoms of bladder irritability or hemorrhage.
• 1- Microscopic hematuria.
• 2- Macroscopic hematuria.
• 3- Massive macroscopic hematuria with small clots.
• 4- Massive macroscopic hematuria requiring instrumentation for clot evacuation and/ or causing urinary obstruction.

Who Are the People at Risk?

People undergoing chemotherapy are at high risk, followed by people requiring stem cell and bone marrow transplants.

How Can You Prevent Hemorrhagic Cystitis?

People receiving chemotherapy are usually on high doses of commonly used chemotherapy drugs such as cyclophosphamide and ifosfamide can be recommended for saline diuresis and mesna. Mesna helps to inline the bladder mucosa and helps in the prevention of irritation and bleeding. Mesna can be given orally, intravenously, or subcutaneously. Mesna can have side effects such as diarrhea, pain, and headaches.

What Is the Treatment for Hemorrhagic Cystitis?

Identification of the cause of irritation, elimination of the cause if the cause is drug-induced, the drugs are stopped or tapered down to a lower dose. If it is not possible to stop the drug, it should be substituted with an alternative drug. Toxicity can be reduced by providing hydration to the patient and using forced diuresis. Continuous bladder irrigation is also one of the methods to reduce toxicity. For radiation-induced hemorrhagic cystitis, there is a lack of treatment options. However, ongoing trials suggest that using hyperbaric oxygen therapy may show the desired outcome to a certain extent. The treatment involves the administration of 100 % oxygen at a pressure of 1.4 atm to 3.0 atm at intervals of 60 to 120 minutes. Conjugated estrogens also show an impressive prognosis for radiation-induced hemorrhagic cystitis.

Studies have shown that hyaluronic acid is one of the treatment modalities that can be used.

In cases of viral hemorrhagic cystitis, studies have shown the use of the following drugs :

• Cidofovir.

• Leflunomide.

• Ciprofloxacin.

General treatment modalities include:

• Sodium pentosan polysulfides can help in reducing inflammation.

• Decompressing the bladder is done by inserting a foley catheter and starting saline irrigation.

• Cystoscopy can be used to evaluate the bladder for bleeding and malignancies.

Medical Treatment:

The drugs that can be used are:

• E Aminocaproic Acid: It is given at a maximum dose of 30 g per day, and the loading dose is 5 g. It is given orally, parentally, or intravesically. Side effects involve clot formation.

• 1 % Alum (Aluminum Ammonium Sulfate or Aluminum Potassium Sulfate): It is an astringent given at 250 ml per hour. It helps in the resolution of hematuria. Side effects involve microcytic anemia, osteomalacia, dementia, encephalopathy, metabolic acidosis, and coagulopathy.

• Silver Nitrate (0.5 %-1 %): 10 to 20 minutes. There can be bladder spasms. Side effects involve renal failure.

• Phenol:100 % phenol with 30 ml glycine.

• Prostaglandins :0.8 mg/dL to 1.0 mg/dL.

• Formalin :1 % to 2 % formalin. It helps in fixing the bladder mucosa.

Surgical Modalities:

• Nephrostomy: It is a procedure in which an opening is created between the kidney and the skin to create a diversion in the upper part of the urinary bladder.

• Cystectomy: It is the surgical removal of the entire or portion of the urinary bladder.

• Ileal Loop Diversion: A segment of the small intestine is used to divert the urine from the kidney.

• Ureterosigmoidostomy: Diversion of the ureters to the sigmoid colon.

• Cutaneous Ureterostomy: A procedure in which the surgeon detaches the ureters and brings either one or both towards the abdomen.

• Open Packing of the Bladder: It is a catheterization procedure of the bladder, where one end of the catheter is left open for urine drainage.

• Ligation of Hypogastric Arteries: The hypogastric arteries are ligated to prevent massive bleeding.

Conclusion:

Hemorrhagic cystitis is caused due to anticancer chemotherapy and malignancies. Among the varying causes of hemorrhagic cystitis, the leading causes involve radiation-induced cystitis and the usage of chemotherapy drugs such as cyclophosphamide. It is an inflammatory condition of the urinary bladder caused due to infectious or non-infectious conditions leading to bleeding of the bladder mucosa and hematuria. With the ever-evolving treatment modalities and approaches to treatment planning, the main aim is to improve the quality of patient care and provide a satisfactory prognosis.