Whipple's Disease

Introduction

Whipple's disease is a granulomatous infectious disorder that is uncommon, chronic, multi-systemic, and caused by the bacterium known as Tropheryma whipplei. Traditionally, Whipple's disease is characterised by gastrointestinal symptoms such as nausea, vomiting, diarrhoea, and weight loss; however, this condition can affect a wide variety of organ systems. 

In severe cases, the infection can spread to the central nervous system (CNS). Although neurological symptoms related to Whipple's disease are uncommon, they should still be taken into consideration during the diagnostic process. If the disease is not treated, it can have long-term effects on the nervous system, some of which are irreversible.

About Whipple’s Disease

Signs and Symptoms

For diagnosis of Whipple’s disease, at least one of the systemic symptoms and of the neurological symptoms must be present and not be caused by another known cause.

Systemic Symptoms

• Fever with no known cause
• Symptoms in the intestines (steatorrhea, chronic diarrhoea, abdominal distention, or pain)
• Chronic arthralgias that come and go, or polyarthralgias

Neurological Symptoms

• Vertical gaze palsy of the supranuclear ganglia
• Myoclonus rhythmic
• Dementia accompanied by psychiatric symptoms
• Manifestations of the hypothalamus

The following criteria is essential for definitive Whipple’s disease diagnosis:

• Oculofacial-skeletal myorhythmia or oculomasticatory myorhythmia;
• Positive tissue biopsy in biopsy specimens of involved tissues, with positive PAS staining of foamy macrophages;
• Polymerase chain reaction (PCR) analysis that is positive.

If histological or PCR analysis is performed on CNS tissue (the latter being more rewarding), the patient does not need to exhibit neurological signs. If histological or PCR analysis on CNS tissue is not performed, the patient must also exhibit neurological signs.¹

Risk Factors and Causes

It has been difficult to identify risk factors for Whipple’s disease due to the lack of information on the bacteria that are responsible for causing the disease. According to the most recent reports, it would appear to have a more significant impact on:

• Men in the age range of 40-60 years old
• People who can trace their roots to both Europe and North America
• Outdoor workers who frequently encounter sewage and wastewater, such as farmers and construction workers who work outdoors.

Complications

Hair-like projections are found on the lining of the small intestine called villi, and they play a role in the absorption of nutrients. Whipple’s disease causes damage to the villi, which in turn decreases the body's capacity to absorb nutrients. People who have Whipple’s disease have a higher risk of developing nutritional deficiencies, which can result in symptoms such as exhaustion, weakness, weight loss, and joint pain.

Whipple's disease is characterised by a progression of symptoms that can ultimately result in death. The majority of this can be attributed to incorrect diagnoses, which then lead to treatment delays. There is a high risk that the infection will spread to the CNS, which will result in damage that cannot be reversed.

Diagnosis

• Physical exam

The first step in developing a treatment plan is typically for your physician to perform a physical examination on you. In order to ascertain whether or not this condition is present, they will be on the lookout for any symptoms that may be associated with it. As an illustration, a physician might check for tenderness in the abdomen and a darkening of the skin on parts of the body that are exposed to the sun as possible indications of Whipple’s disease.

• Biopsy

A biopsy of the lining of the small intestine is a common way to get tissue samples that can be used to diagnose Whipple’s disease. Most of the time, this is done with an upper endoscopy. During the procedure, a light and camera are attached to an endoscope that is put into your mouth, throat, stomach, and small intestine. With the scope, the doctor can take tissue samples and look at them.

During the process, several samples of tissue from the small intestine are taken. A doctor looks at this tissue under a microscope in a laboratory. When looking for Tropheryma whipplei bacteria, he or she looks for disease-causing bacteria and sores (lesions). If these samples don't show what's wrong, your doctor may use tissue from a swollen lymph node or do other tests.

PCR is a DNA-based test that can find Tropheryma whipplei bacteria in biopsies or spinal fluid samples. Some medical centres offer this test.

• Blood tests

Your doctor may also give you blood tests, such as a complete blood count. Blood tests can show if you have anaemia, which is a low number of red blood cells, or low levels of albumin, a protein in your blood. Both of these conditions are linked to Whipple’s disease.²

Treatment

Antibiotics

Whipple’s disease is treated with antibiotics, either one at a time or in a combination, to kill the bacteria that are causing the infection.

The goal of antibiotic treatment is to get rid of the bacteria, which can take up to 2 years. Even so, most people feel better within 1-2 weeks at most. After taking antibiotics for the right amount of time, most people who don't have problems with their brains or nervous systems completely recover.

When making their choices, doctors often choose antibiotics that work on both the intestines and the brain (the blood-brain barrier). This is done to get rid of any bacteria that may have gotten into your brain and nervous system.

When you take antibiotics for a long time, your doctor needs to pay close attention. They will watch for signs that your body is becoming resistant to the drugs. If you get sick again while you're being treated, your doctor may change your antibiotics.

Other Pharmacological Interventions

Most of the time, Ceftriaxone or penicillin is given through an IV for the first 2-4 weeks of treating Whipple’s disease. After the first treatment, sulfamethoxazole-trimethoprim (Bactrim, Septra) is usually given by mouth for another 1-2 years. Ceftriaxone and sulfamethoxazole-trimethoprim can cause side effects like allergic reactions, mild diarrhoea, nausea, and vomiting.

Some people have suggested doxycycline (Vibramycin, Doryx, and other brands) and hydroxychloroquine (Plaquenil) as alternatives. You may be required to take them for 1-2 years. 

With doxycycline use, you might feel sick, vomit, or be more sensitive to sunlight. Hydroxychloroquine can make you feel dizzy, sick, cause vomiting or diarrhoea, and give you headaches.¹

Prognosis

Whipple's disease has a higher chance of getting better if it is treated for a long time and found early. If Whipple's disease is left neglected, it is not likely to get better.

The outlook for people with Whipple's disease who have neurological symptoms is less optimistic.

Summary

Whipple's disease is a rare, long-lasting infection that causes symptoms all over the body. Most of the symptoms are in the intestines. It causes a loss of appetite, pain in the joints, diarrhoea, and pain in the abdomen. Although the disease can be fatal, it can be treated. Tell your doctor about any strange signs or the above symptoms. Your doctor can give you some tests to find out what's causing your symptoms.