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Whipple’s Disease

Whipple's disease is a rare malabsorption syndrome with systemic manifestations (neurologic, cardiac, and musculoskeletal) caused by the bacterium Tropheryma whipplei. Patients often present with weight loss, diarrhea/steatorrhea, and arthralgias, as well as neurologic and cardiac manifestations. Whipple's disease is diagnosed with biopsy after the visualization of periodic acid–Schiff (PAS)-positive foamy macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation in the involved tissues or with PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) for the bacterial DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure. It is managed with antibiotics, namely ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins or penicillin Penicillin Rheumatic Fever G and sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim.

Last updated: Aug 29, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Whipple’s disease is a malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion syndrome with systemic manifestations that is caused by infection with Tropheryma whipplei.

Epidemiology

  • Rare disorder with worldwide distribution
  • Overall incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 1–3 in 1 million individuals 
  • Increased prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in farmers (since T. whipplei is soil-dwelling) and sewage workers
  • Possibly associated with HLA-B27 haplotype
  • Most common in White males (male:female ratio = 8:1)
  • Mean Mean Mean is the sum of all measurements in a data set divided by the number of measurements in that data set. Measures of Central Tendency and Dispersion age at symptom onset: 49 years

Etiology

Causative agent is T. whipplei:

  • Rod-shaped, nonmotile, gram-positive Gram-Positive Penicillins bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus
  • Related to Actinomycetes
  • Acid-fast smear–negative
  • Periodic acid–Schiff (PAS)-positive
  • Enveloped in a trilamellar plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products membrane and covered by a cell wall Cell wall The outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents. Cell Types: Eukaryotic versus Prokaryotic
  • Soil- and sewage-dwelling bacterium
  • Colonizes intestinal tract, lymphoreticular system, and CNS

Host immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome has been implicated in symptomatic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.

Pathophysiology

  • Pathogenesis has not been entirely delineated.
  • Characterized by a general lack of host inflammatory response to T. whipplei
  • Specific immunologic derangements include:
    • Low activity of type 1 Type 1 Spinal Muscular Atrophy T-helper cells and increased type 2 Type 2 Spinal Muscular Atrophy T-helper cells
    • Low CD4:CD8 T-cell ratio
    • Deficient expression of complement receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors type 3 Type 3 Spinal Muscular Atrophy on host mononuclear cells
    • Diminished antigen presentation Antigen presentation The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (apcs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the apc, followed by presentation of fragments on the cell surface. Innate Immunity: Phagocytes and Antigen Presentation by major histocompatibility complex Major histocompatibility complex The genetic region which contains the loci of genes which determine the structure of the serologically defined (sd) and lymphocyte-defined (ld) transplantation antigens, genes which control the structure of the immune response-associated antigens, human; the immune response genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. Innate Immunity: Phagocytes and Antigen Presentation (MHC) class 2 apparatus on intestinal epithelial cells
  • There are no pronounced cytotoxic Cytotoxic Parvovirus B19 effects on host cells, so the organism can accumulate in tissues in large numbers.
  • The organism is ingested and incorporated into tissue macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation.
  • T. whipplei invades a variety of tissues and organs:
    • Intestinal epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology
    • Macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation
    • Capillary and lymphatic endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
    • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
    • Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy
    • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow
    • Synovium
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
  • Infiltration of the lamina propria of the intestines disrupts villous function and causes malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion.
  • Infiltration of other organs causes organ-specific symptoms (e.g., arthralgia Arthralgia Pain in the joint. Rheumatic Fever with synovial infiltration).

Clinical Presentation

Classic Whipple’s disease

  • Arthralgia Arthralgia Pain in the joint. Rheumatic Fever
    • Frequently the first presenting symptom
    • Involves large joints
    • Migratory and nondestructive
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea:
    • Watery or steatorrheic
    • Occult or gross gastrointestinal bleeding Gastrointestinal bleeding Gastrointestinal bleeding (GIB) is a symptom of multiple diseases within the gastrointestinal (GI) tract. Gastrointestinal bleeding is designated as upper or lower based on the etiology’s location to the ligament of Treitz. Depending on the location of the bleeding, the patient may present with hematemesis (vomiting blood), melena (black, tarry stool), or hematochezia (fresh blood in stools). Gastrointestinal Bleeding can also occur.
  • Abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (intermittent, colicky)

Other manifestations

  • Cardiac:
    • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis (valve involvement; most common)
    • Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis, pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis
    • Congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure
  • Neurologic:
    • Confusion
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
    • Delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium
    • Cognitive impairment 
    • Hypersomnia
    • Extrapyramidal symptoms Extrapyramidal Symptoms Ataxia-telangiectasia 
    • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia and clonus Clonus Ehrlichiosis and Anaplasmosis
    • Pathognomonic findings:
  • Systemic:
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
    • Mesenteric or mediastinal lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy (50% of cases)
    • Peripheral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema (due to hypoproteinemia secondary to poor nutrition and protein-losing enteropathy Enteropathy IPEX Syndrome)

Diagnosis

History

  • Middle-aged White males
  • Occupational exposure: farmers, sewage workers
  • Chronic/long-standing diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea with no identifiable cause
  • Abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Arthralgias
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery

Physical exam

  • Nonspecific
  • Emaciated, malnourished appearance, with generalized edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Neurologic/psychiatric findings may be present with nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification involvement.

Laboratory studies

  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types due to chronic disease and iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements, folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12, or vitamin B12 deficiency
  • Mild lymphopenia
  • Hypoalbuminemia Hypoalbuminemia A condition in which albumin level in blood (serum albumin) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (albuminuria). Nephrotic Syndrome in Children with normal globulin levels
  • Prolonged prothrombin Prothrombin A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Hemostasis time 
  • Stool culture to rule out other infectious causes of diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Serologic tests to rule out autoimmune/rheumatic diseases (i.e., rheumatoid factor Rheumatoid factor Antibodies found in adult rheumatoid arthritis patients that are directed against gamma-chain immunoglobulins. Autoimmune Hepatitis, antinuclear antibody)

Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

  • Definitive
  • 1st test is usually upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD), with small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma showing PAS-positive foamy macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation:
    • Mucosa may or may not show gross abnormalities.
    • A false negative False negative An FN test result indicates a person does not have the disease when, in fact, they do. Epidemiological Values of Diagnostic Tests result is common if a patient begins receiving antibiotics before undergoing diagnostic testing.
  • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma of other tissues (cardiac, synovial, cerebrospinal fluid Cerebrospinal Fluid A watery fluid that is continuously produced in the choroid plexus and circulates around the surface of the brain; spinal cord; and in the cerebral ventricles. Ventricular System: Anatomy) should be performed if:
    • The only presenting symptoms are extraintestinal.
    • Intestinal biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is negative, but suspicion remains high.
  • If PAS stain is negative, a diagnosis can be made with the following tests:
    • T. whipplei identification Identification Defense Mechanisms via PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) or 16s rRNA rRNA The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. RNA Types and Structure detection
    • T. whipplei antibody–positive immunohistochemical stain
Lymphangiectasia on endoscopy

Endoscopic view of the jejunal mucosa in Whipple’s disease:
white lesions compatible with diffuse intestinal lymphangiectasia

Image: “ Endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD)” by Department of Internal Medicine, Hospital General Universitario de Alicante, c/ Pintor Baeza, 12, 03010, Alicante, Spain. License: CC BY 4.0

Management and Prognosis

Management

The mainstay of treatment is antibiotics:

  • Because there is a risk of CNS involvement, an antibiotic that can penetrate the blood– brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification barrier is needed.
  • 1st-line regimen:
    • Intravenous ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins or penicillin Penicillin Rheumatic Fever G for 2 weeks (4 weeks for endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis)
    • Oral trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim for 12 months 
  • Alternative regimens for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with penicillin Penicillin Rheumatic Fever and/or sulfa allergies Allergies A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder. Selective IgA Deficiency:
    • Intravenous meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam for 2 or 4 weeks
    • Oral doxycycline + hydroxychloroquine Hydroxychloroquine A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. Immunosuppressants for 12 months

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

  • Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with adequate treatment do very well.
  • Dramatic improvement can be seen within 7–21 days.
  • Neurologic damage can sometimes be irreversible.
  • Complications:
    • Immune reconstitution inflammatory syndrome (IRIS):
      • Can develop within the first few weeks of starting antibiotic regimen
      • High fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and symptoms mimicking relapse Relapse Relapsing Fever
    • Relapse Relapse Relapsing Fever:
      • Failure of clinical response to antibiotics
      • PCR-positive on repeat biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

Differential Diagnosis

  • HIV infection HIV infection Human immunodeficiency virus (HIV), a single-stranded RNA virus belonging to the Retroviridae family, is the etiologic agent of acquired immunodeficiency syndrome (AIDS). The human immunodeficiency virus is a sexually transmitted or blood-borne infection that attacks CD4+ T lymphocyte cells, macrophages, and dendritic cells, leading to eventual immunodeficiency. HIV Infection and AIDS: HIV HIV Anti-HIV Drugs belongs to the family Retroviridae Retroviridae The human immunodeficiency virus (HIV) is a species of Lentivirus, a genus of the family Retroviridae, which causes HIV infections and acquired immunodeficiency syndrome (AIDS). The virus has high genetic variability and is divided into 2 major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). The human immunodeficiency virus is a single-stranded, positive-sense, enveloped RNA virus, which targets and destroys WBCs, leading to frequent opportunistic infections and, eventually, death. Human Immunodeficiency Virus (HIV). Symptoms of the primary infection Primary infection Herpes Simplex Virus 1 and 2 are flu-like, with low grade fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus, and lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy. After decades of latent infection and weakening of host immunity, AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS develops, which is characterized by opportunistic infections Opportunistic infections An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. Autosomal Dominant Hyperimmunoglobulin E Syndrome and cancers. Diagnosis is established by blood PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) testing, and treatment is with antiretroviral drugs.
  • Tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis: infectious disease caused by Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis, acid-fast bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology that can survive in macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, allowing for decades-long, latent, asymptomatic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease: Symptoms include fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, cough, anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, malaise Malaise Tick-borne Encephalitis Virus, and extrapulmonary manifestations, including pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis. The diagnosis is established with a tuberculin Tuberculin A protein extracted from boiled culture of tubercle bacilli (Mycobacterium tuberculosis). It is used in the tuberculin skin test (tuberculin test) for the diagnosis of tuberculosis infection in asymptomatic persons. Type IV Hypersensitivity Reaction skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions test, sputum culture, and lung imaging, and the mainstay of management is antimycobacterial drugs.
  • Connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology disease: Connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology disease comprises a number of conditions: (1) systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus ( SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus), (2) antiphospholipid syndrome Antiphospholipid syndrome Antiphospholipid syndrome (APLS) is an acquired autoimmune disorder characterized by the persistent presence of antiphospholipid antibodies, which create a hypercoagulable state. These antibodies are most commonly discovered during a workup for a thrombotic event or recurrent pregnancy loss, which are the 2 most common clinical manifestations. Antiphospholipid Syndrome, (3) scleroderma Scleroderma Scleroderma (systemic sclerosis) is an autoimmune condition characterized by diffuse collagen deposition and fibrosis. The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Scleroderma, (4) myositis, and (5) Sjögren’s syndrome. These autoimmune diseases Autoimmune diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Selective IgA Deficiency are characterized by autoantibody production and present with symptoms of immune dysfunction. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with dermatologic, arthropathic, and systemic symptoms. Each disease has its own serologic markers and pathogenesis. Treatment frequently includes steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors and immunomodulating drugs.
  • Hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism: a state of excess thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormone synthesis Synthesis Polymerase Chain Reaction (PCR) and secretion Secretion Coagulation Studies: Hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism is most often caused by Graves’ disease Graves’ disease A common form of hyperthyroidism with a diffuse hyperplastic goiter. It is an autoimmune disorder that produces antibodies against the thyroid stimulating hormone receptor. These autoantibodies activate the TSH receptor, thereby stimulating the thyroid gland and hypersecretion of thyroid hormones. These autoantibodies can also affect the eyes (Graves ophthalmopathy) and the skin (Graves dermopathy). Thyrotoxicosis and Hyperthyroidism or a toxic multinodular goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship report palpitations Palpitations Ebstein’s Anomaly, disrupted sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, sweating, and heat Heat Inflammation intolerance. Physical exam shows tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, and tremors of the extremities. Diagnosis is established by measuring blood thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormone levels, and treatment involves antithyroid drugs and beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers).
  • Inflammatory bowel disease (IBD) with arthropathy Arthropathy Osteoarthritis:  
    • Crohn’s disease: a chronic, recurrent condition that causes patchy transmural inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation that can involve any part of the gastrointestinal tract: Crohn’s disease typically presents with intermittent, nonbloody diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and crampy abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. Arthropathy Arthropathy Osteoarthritis is an extraintestinal manifestation for both types of IBD. Diagnosis is confirmed by intestinal biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma, and treatment includes immunosuppressive regimens.
    • Ulcerative colitis Ulcerative colitis Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn’s disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis: an idiopathic Idiopathic Dermatomyositis inflammatory condition that involves the mucosal surface of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy: The rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy is always involved, and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation may extend proximally through the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy. Ulcerative colitis Ulcerative colitis Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn’s disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis typically presents with intermittent, nonbloody diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and crampy abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. Arthropathy Arthropathy Osteoarthritis is an extraintestinal manifestation for both types of IBD. Diagnosis is confirmed by intestinal biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma, and treatment includes immunosuppressive regimens.

References

  1. Antunes C., Singhal M. Whipple Disease. (2020). In: StatPearls. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK441937/
  2. Apstein M. D., Schneider T. (2020). Whipple’s Disease. Retrieved February 21, 2021, from https://www.uptodate.com/contents/whipples-disease
  3. Bally J. F., Méneret A., Roze E., Anderson M., Grabli D., Lang A. E. (2018). Systematic review of movement disorders and oculomotor abnormalities in Whipple’s disease. Mov Disord. 33(11):1700-1711.
  4. Hujoel I. A., Johnson D. H., Lebwohl B., Leffler D., Kupfer S., Wu T. T., Murray J.A., Rubio-Tapia A. (2019). Tropheryma whipplei Infection (Whipple Disease) in the USA. Dig Dis Sci. 64:213-223. 
  5. Dolmans, R. A. V., Boel, C. H. E., Lacle, M. M., Kusters, J. G. (2017). Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections. Clin Microbiol Rev. 30:529-555.

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