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Whipple Disease

Updated : March 19, 2024





Background

Tropheryma whippelii is a gram-positive bacterium that causes Whipple illness. This is really a systemic condition that affects the cardiovascular, CNS, vascular systems, and joints in addition to the gastrointestinal tract’s malabsorption. This syndrome was first explained by Dr. George Hoyt Whipple in 1907.

He received the Physiology Nobel Prize as the first American. Dr. Whipple discussed the example of a thirty-six-year-old man who had skin pigmentation, arthralgias, and mesenteric lymphadenopathy in addition to malabsorption.

His report was posted in the Johns Hopkins Hospital Bulletin, and he gave the condition the term “Intestinal Lipodystrophy.” Although he postulated infectious organisms as the cause, the bacteria weren’t properly discovered until 1992. Whipple disease is uncommon, and the literature solely contains case accounts.

Epidemiology

Whipple syndrome is a rare ailment in the world, with the majority of reports coming from Europe and North America. The HLA B27 haplotype is connected to the illness. Around one to three persons out of every million are affected by Whipple illness globally.

The average age at which symptoms first appear is 55. With such a ratio of 4:1, men experience it significantly more frequently than women do. The increasing occurrence in farmers is likely due to the organism’s apparent soil habitation.

Anatomy

Pathophysiology

Although the precise pathophysiology is yet unknown, there is enough data to suggest that host immunity plays a significant role. The majority of people who get T. whippelii are asymptomatic carriers or only have a mild illness, which is followed by the emergence of cellular and humoral defenses.

The immune response to the organism is less in sick people. It mostly comprises type 1 T-cell reaction that is compromised as well as impaired macrophage activation and activity. Shigella flexneri and Streptococcal groups B and G are antigenically similar to Whipple bacillus.

The 2- to 3-fold rise in HLA-B27 antigen frequency across individuals affected suggests that host factors play a significant role in the pathogenesis. The macrophages that can be seen in periodic acid-Schiff consume the creature. Sadly, Whipple disease cannot be diagnosed by looking for periodic acid-Schiff-stained macrophages.

Coccobacillus particles that refract the species may be seen under an electron microscope. The natural villus activity has been disturbed, which results in the observed malabsorption. The microorganism can be discovered in numerous tissues whenever systemic illness develops.

Etiology

1992 saw the description of Tropheryma whipplei. It was given the name Tropheryma whippelii up till 2001 when its name was changed to reflect Dr. George Hoyt Whipple’s correct spelling. It is an acid-fast negative, periodic acid-Schiff positive (PAS), and gram-positive bacillus.

The bacillus core is encased in a plasma membrane, which is encircled by a three-layered cell wall, according to electron microscopy findings. Polysaccharides that PAS positively stain are present inside the inner lining.

The host’s inability to produce a humoral antibody production towards the infection may be explained by the outermost layer, which mimics a plasma membrane and could be of host source.

Genetics

Prognostic Factors

With quick identification and management of Whipple’s illness, the prognosis is typically favorable. Between 2 to 3 weeks of starting the treatment, the patients report feeling significantly better. Patients who are not treated have a dismal prognosis.

Clinical History

Age Group:  

Adults are usually affected with Whipple’s illness, and most occurrences happen in people between the ages of 30 and 60. 

Physical Examination

  • Gastrointestinal Examination: Abdominal tenderness or distension may be present, particularly if there is associated abdominal pain or bloating. 
  • Joint Examination: Joint tenderness, swelling, and limited range of motion may be present, indicating arthritis or arthralgia associated with Whipple’s disease. 
  • Neurological Examination: Cognitive impairment, memory loss, confusion, ataxia, and seizures are only a few examples of the wide range of neurological symptoms. 
  • Skin Examination: Hyperpigmentation, erythema nodosum, and other skin lesions are possible cutaneous signs of Whipple’s illness, albeit they are uncommon. 
  • Ocular Examination: Ocular manifestations of Whipple’s disease are uncommon but may include uveitis, blurry vision, or other visual disturbances. 

Age group

Associated comorbidity

A prevalent aspect of Whipple’s disease is malabsorption syndrome, which results in impairments in the absorption of nutrients because of small intestine injury. 

Whipple’s disease patients may experience joint discomfort and inflammation, which typically affects the larger joints, such the knees. 

The central nervous system may be affected by Whipple’s illness, which can cause symptoms like dementia, memory loss, disorientation, and seizures. 

Associated activity

Acuity of presentation

Many Whipple’s disease cases have a chronic course, meaning that symptoms appear gradually over a period of weeks to months. Non-specific symptoms like exhaustion, weight loss, diarrhea, abdominal pain, and joint pain are possible for patients. Delays in diagnosis may result from these symptoms’ subtlety and potential mimicry of other gastrointestinal conditions. 

A subacute presentation occurs in certain people, in which symptoms increase more quickly over a few weeks to months. This could include systemic symptoms like fever, sweats at night, and malaise, as well as a worsening of the gastrointestinal symptoms. 

Differential Diagnoses

  • Celiac illness: Diarrhea, malabsorption, stomach pain, and weight loss are symptoms of an autoimmune illness of the small intestine that are comparable to those of Whipple’s disease. 
  • Intestinal Lymphoma: Lymphomas involving the gastrointestinal tract can present with symptoms such as abdominal pain, diarrhea, and weight loss, which may overlap with those of Whipple’s disease. 
  • Infectious Gastroenteritis: Various bacterial, viral, and parasitic infections can cause gastrointestinal symptoms resembling those of Whipple’s disease.  
  • Chronic Fatigue Syndrome (CFS): This condition can present with symptoms such as fatigue, malaise, and cognitive difficulties, which may overlap with those seen in Whipple’s disease. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

  • Antibiotic Therapy: The initial phase of treatment typically involves intensive antibiotic therapy to eliminate the bacterium. The preferred regimen is usually a combination of intravenous antibiotics such as ceftriaxone or penicillin G. 
  • Maintenance Phase: After completing the induction phase, patients may transition to long-term oral antibiotic therapy to prevent relapse.  
  • Nutritional Support: Patients with Whipple’s disease may experience malabsorption and nutrient deficiencies. Nutritional supplementation and dietary modifications may be necessary to address deficiencies and support overall health. 
  • Symptomatic Treatment: Depending on the specific symptoms experienced by the patient, symptomatic treatment may be provided to alleviate gastrointestinal symptoms, joint pain, neurological manifestations, and other complications associated with the disease. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Use of non-pharmacological approach for Whipple Disease

  • Dietary Modifications: Avoidance of Trigger Foods: Certain foods may exacerbate gastrointestinal symptoms in individuals with Whipple’s disease. Identifying and avoiding trigger foods such as spicy foods, high-fat foods, dairy products, and gluten-containing grains may help alleviate symptoms. 
  • Hydration: Maintaining proper hydration is important, especially in cases of diarrhea and malabsorption. Drinking plenty of water and avoiding caffeinated and alcoholic beverages can help prevent dehydration. 
  • Stress Management: Stress can exacerbate symptoms in some individuals. Practicing stress reduction techniques such as meditation, deep breathing exercises, yoga, or mindfulness can help promote relaxation and improve overall well-being. 
  • Regular Exercise: Engaging in regular physical activity can have numerous benefits, including improving gastrointestinal motility, boosting mood, and enhancing overall health. 
  • Environmental Hygiene: Avoidance of Potential Infectious Agents: Since Whipple’s disease is caused by a bacterial infection, minimizing exposure to potential infectious agents through good hygiene practices, such as regular handwashing, can help reduce the risk of complications. 

Use of Antibiotics

  • Penicillin G: Penicillin G inhibits bacterial cell wall synthesis, leading to bacterial cell death. 

It is typically administered intravenously during the induction phase of treatment. 

  • Amoxicillin: Amoxicillin, a broad-spectrum penicillin derivative, is commonly used in the treatment of bacterial infections. Amoxicillin inhibits bacterial cell wall synthesis. 
  • Chloramphenicol: Chloramphenicol inhibits bacterial protein synthesis by binding to the bacterial ribosome. 

Use of Intervention with a procedure in treating Whipple Disease

  • Endoscopy with Biopsy: Endoscopy involves the insertion of a flexible tube with a camera into the gastrointestinal tract to visualize the mucosal lining of the esophagus, stomach, and small intestine.  

Biopsy samples can be obtained during endoscopy to examine for characteristic histological features of Whipple’s disease, such as foamy macrophages containing periodic acid-Schiff (PAS)-positive granules within the lamina propria. 

Use of phases in managing Whipple Disease

  • Diagnostic Phase: The diagnostic process begins with the recognition of symptoms suggestive of Whipple’s disease, which may include chronic diarrhea, abdominal pain, weight loss, joint pain, and neurological symptoms. 
  • Maintenance Therapy: Following the induction phase, patients may transition to long-term oral antibiotic therapy, typically with trimethoprim-sulfamethoxazole (TMP-SMX), to prevent relapse.  
  • Monitoring Phase: Patients require regular monitoring and follow-up visits with their healthcare provider to assess treatment response, monitor for complications, and adjust therapy as needed. 
  • Long-Term Management: Long-term management of Whipple’s disease involves ongoing medical care, including continued monitoring, adherence to maintenance antibiotic therapy, and management of any persistent symptoms or complications. 

Medication

Media Gallary

Whipple Disease

Updated : March 19, 2024




Tropheryma whippelii is a gram-positive bacterium that causes Whipple illness. This is really a systemic condition that affects the cardiovascular, CNS, vascular systems, and joints in addition to the gastrointestinal tract’s malabsorption. This syndrome was first explained by Dr. George Hoyt Whipple in 1907.

He received the Physiology Nobel Prize as the first American. Dr. Whipple discussed the example of a thirty-six-year-old man who had skin pigmentation, arthralgias, and mesenteric lymphadenopathy in addition to malabsorption.

His report was posted in the Johns Hopkins Hospital Bulletin, and he gave the condition the term “Intestinal Lipodystrophy.” Although he postulated infectious organisms as the cause, the bacteria weren’t properly discovered until 1992. Whipple disease is uncommon, and the literature solely contains case accounts.

Whipple syndrome is a rare ailment in the world, with the majority of reports coming from Europe and North America. The HLA B27 haplotype is connected to the illness. Around one to three persons out of every million are affected by Whipple illness globally.

The average age at which symptoms first appear is 55. With such a ratio of 4:1, men experience it significantly more frequently than women do. The increasing occurrence in farmers is likely due to the organism’s apparent soil habitation.

Although the precise pathophysiology is yet unknown, there is enough data to suggest that host immunity plays a significant role. The majority of people who get T. whippelii are asymptomatic carriers or only have a mild illness, which is followed by the emergence of cellular and humoral defenses.

The immune response to the organism is less in sick people. It mostly comprises type 1 T-cell reaction that is compromised as well as impaired macrophage activation and activity. Shigella flexneri and Streptococcal groups B and G are antigenically similar to Whipple bacillus.

The 2- to 3-fold rise in HLA-B27 antigen frequency across individuals affected suggests that host factors play a significant role in the pathogenesis. The macrophages that can be seen in periodic acid-Schiff consume the creature. Sadly, Whipple disease cannot be diagnosed by looking for periodic acid-Schiff-stained macrophages.

Coccobacillus particles that refract the species may be seen under an electron microscope. The natural villus activity has been disturbed, which results in the observed malabsorption. The microorganism can be discovered in numerous tissues whenever systemic illness develops.

1992 saw the description of Tropheryma whipplei. It was given the name Tropheryma whippelii up till 2001 when its name was changed to reflect Dr. George Hoyt Whipple’s correct spelling. It is an acid-fast negative, periodic acid-Schiff positive (PAS), and gram-positive bacillus.

The bacillus core is encased in a plasma membrane, which is encircled by a three-layered cell wall, according to electron microscopy findings. Polysaccharides that PAS positively stain are present inside the inner lining.

The host’s inability to produce a humoral antibody production towards the infection may be explained by the outermost layer, which mimics a plasma membrane and could be of host source.

With quick identification and management of Whipple’s illness, the prognosis is typically favorable. Between 2 to 3 weeks of starting the treatment, the patients report feeling significantly better. Patients who are not treated have a dismal prognosis.

Age Group:  

Adults are usually affected with Whipple’s illness, and most occurrences happen in people between the ages of 30 and 60. 

  • Gastrointestinal Examination: Abdominal tenderness or distension may be present, particularly if there is associated abdominal pain or bloating. 
  • Joint Examination: Joint tenderness, swelling, and limited range of motion may be present, indicating arthritis or arthralgia associated with Whipple’s disease. 
  • Neurological Examination: Cognitive impairment, memory loss, confusion, ataxia, and seizures are only a few examples of the wide range of neurological symptoms. 
  • Skin Examination: Hyperpigmentation, erythema nodosum, and other skin lesions are possible cutaneous signs of Whipple’s illness, albeit they are uncommon. 
  • Ocular Examination: Ocular manifestations of Whipple’s disease are uncommon but may include uveitis, blurry vision, or other visual disturbances. 

A prevalent aspect of Whipple’s disease is malabsorption syndrome, which results in impairments in the absorption of nutrients because of small intestine injury. 

Whipple’s disease patients may experience joint discomfort and inflammation, which typically affects the larger joints, such the knees. 

The central nervous system may be affected by Whipple’s illness, which can cause symptoms like dementia, memory loss, disorientation, and seizures. 

Many Whipple’s disease cases have a chronic course, meaning that symptoms appear gradually over a period of weeks to months. Non-specific symptoms like exhaustion, weight loss, diarrhea, abdominal pain, and joint pain are possible for patients. Delays in diagnosis may result from these symptoms’ subtlety and potential mimicry of other gastrointestinal conditions. 

A subacute presentation occurs in certain people, in which symptoms increase more quickly over a few weeks to months. This could include systemic symptoms like fever, sweats at night, and malaise, as well as a worsening of the gastrointestinal symptoms. 

  • Celiac illness: Diarrhea, malabsorption, stomach pain, and weight loss are symptoms of an autoimmune illness of the small intestine that are comparable to those of Whipple’s disease. 
  • Intestinal Lymphoma: Lymphomas involving the gastrointestinal tract can present with symptoms such as abdominal pain, diarrhea, and weight loss, which may overlap with those of Whipple’s disease. 
  • Infectious Gastroenteritis: Various bacterial, viral, and parasitic infections can cause gastrointestinal symptoms resembling those of Whipple’s disease.  
  • Chronic Fatigue Syndrome (CFS): This condition can present with symptoms such as fatigue, malaise, and cognitive difficulties, which may overlap with those seen in Whipple’s disease. 
  • Antibiotic Therapy: The initial phase of treatment typically involves intensive antibiotic therapy to eliminate the bacterium. The preferred regimen is usually a combination of intravenous antibiotics such as ceftriaxone or penicillin G. 
  • Maintenance Phase: After completing the induction phase, patients may transition to long-term oral antibiotic therapy to prevent relapse.  
  • Nutritional Support: Patients with Whipple’s disease may experience malabsorption and nutrient deficiencies. Nutritional supplementation and dietary modifications may be necessary to address deficiencies and support overall health. 
  • Symptomatic Treatment: Depending on the specific symptoms experienced by the patient, symptomatic treatment may be provided to alleviate gastrointestinal symptoms, joint pain, neurological manifestations, and other complications associated with the disease. 

  • Dietary Modifications: Avoidance of Trigger Foods: Certain foods may exacerbate gastrointestinal symptoms in individuals with Whipple’s disease. Identifying and avoiding trigger foods such as spicy foods, high-fat foods, dairy products, and gluten-containing grains may help alleviate symptoms. 
  • Hydration: Maintaining proper hydration is important, especially in cases of diarrhea and malabsorption. Drinking plenty of water and avoiding caffeinated and alcoholic beverages can help prevent dehydration. 
  • Stress Management: Stress can exacerbate symptoms in some individuals. Practicing stress reduction techniques such as meditation, deep breathing exercises, yoga, or mindfulness can help promote relaxation and improve overall well-being. 
  • Regular Exercise: Engaging in regular physical activity can have numerous benefits, including improving gastrointestinal motility, boosting mood, and enhancing overall health. 
  • Environmental Hygiene: Avoidance of Potential Infectious Agents: Since Whipple’s disease is caused by a bacterial infection, minimizing exposure to potential infectious agents through good hygiene practices, such as regular handwashing, can help reduce the risk of complications. 

  • Penicillin G: Penicillin G inhibits bacterial cell wall synthesis, leading to bacterial cell death. 

It is typically administered intravenously during the induction phase of treatment. 

  • Amoxicillin: Amoxicillin, a broad-spectrum penicillin derivative, is commonly used in the treatment of bacterial infections. Amoxicillin inhibits bacterial cell wall synthesis. 
  • Chloramphenicol: Chloramphenicol inhibits bacterial protein synthesis by binding to the bacterial ribosome.