Lady Windermere Syndrome
Encyclopedia
Mycobacterium avium-intracellulare (MAI) is an atypical mycobacterial infection
which can occur in the later stages of AIDS
. It can also affect people who do not have AIDS and usually first presents as a persistent cough. Additionally, cases in elderly men have increased recently. It is typically treated with a series of 3 antibiotics for a period of at least 6 months.
It is a saprotrophic organism
that is present in soil and water, entry is usually via the GI tract but also can be via the lung
s.
It causes fever
s, diarrhea
, malabsorption
and anorexia
and it can disseminate to the bone marrow
. Therapy for MAI is disappointing as it is typically resistant to standard mycobacterial therapies.
when inhaled or swallowed. Symptoms of MAC diseases are reminiscent of tuberculosis
. They include fever, fatigue, and weight loss. Many patients will have anemia
and neutropenia
if bone marrow is involved. Pulmonary involvement is similar to TB, while diarrhea and abdominal pain are associated with gastrointestinal involvement. MAC should always be considered in a person with HIV
infection presenting with diarrhea. Recently, M. avium has been found to deposit and grow in bathroom shower heads from which it may be easily aerosolized and inhaled.
The various subspecies are prevalent in different areas:
MAC disease is common in immunocompromised
individuals, including senior citizens and those suffering from HIV
or cystic fibrosis
; however, the MAC diseases, particularly Lady Windermere syndrome, do not require that the individual be immunocompromised.
and rifabutin
for 18 to 24 months) reserved for those patients who cannot have surgery.
disease is theorized to represent recent acquisition rather than latent infection reactivating (which is the case in many other opportunistic infection
s in immunocompromised
patients).
The risk of MAC is inversely related to the patient's CD4
count, and increases significantly when the CD4 count decreases below 50 cells/mm³. Other risk factors for acquisition of MAC infection include using an indoor swimming pool
, consumption of raw or partially cooked fish or shellfish, bronchoscopy
and treatment with granulocyte stimulating factor.
Disseminated disease
was previously the common presentation prior to the advent of highly active antiretroviral therapy (HAART). Today, in regions where HAART is the standard of care, localized disease presentation is more likely. This generally includes a focal lymphadenopathy
/lymphadenitis.
AIDS patients are given macrolide antibiotics such as Azithromycin
for prophylactic treatment.
. Bone marrow
culture can often yield an earlier diagnosis, but is usually avoided as an initial diagnostic step because of its invasiveness.
.
Post-infection, treatment involves a combination of antituberculosis antibiotics. These include:
in the lung
s due to Mycobacterium avium complex. It is named after a character in Oscar Wilde
's play Lady Windermere's Fan
.
s.
Immunodeficiency is not a requirement for Mycobacterium avium infection.
Mycobacterium avium Complex (MAC) usually affects patients with abnormal lung
s or bronchi. However, Candace Baker, Jerome Reich and Richard Johnson describe a series of six patients with MAC infection of the right middle lobe or left lingula who did not have any predisposing lung disorders.
The right middle lobe
and left lingula of the lung
s are served by bronchi that are oriented downward when a person is in the upright position. As a result, these areas of the lung may be more dependent upon vigorous voluntary expectoration (cough
) for clearance of bacteria and secretions.
Since the six patients in their retrospective case series were older females, Reich and Johnson and Baker propose that patients without a vigorous cough may develop right middle lobe or left lingular infection with MAC. They propose that this syndrome be named Lady Windermere syndrome, after the character Lady Windermere in Oscar Wilde
's play Lady Windermere's Fan
.
and ethambutol
. Treatment typically lasts at least 12 months.
of the Lady Windermere syndrome suggests that the character Lady Windermere in Oscar Wilde
's Victorian-era play Lady Windermere's Fan
is a good example of the fastidious behavior believed to cause the syndrome. The article states:
Victorian women presumably believed that "Ladies don't spit," and consequently might have been predisposed to develop lung infection.
Shortly after the Lady Windermere syndrome was proposed, a librarian wrote a letter to the editor of Chest challenging the use of Lady Windermere as the eponymous ancestor of the proposed syndrome. In Lady Windermere's Fan
, Lady Windermere is a vivacious young woman, married only 2 years, who never coughs or displays any other signs of illness. While her avoidance of shaking hands might be interpreted as "fastidiousness," two alternative explanations may be just as probable:
The scholars highlight the literary malapropism
, but some in the medical community have adopted the term regardless, and peer-reviewed medical journals still sometimes mention the Lady Windermere syndrome.
In recent years, some have described the eponym as inappropriate, and some have noted that it would have been unlikely that Lady Windermere had the condition to which her name was assigned.
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
which can occur in the later stages of AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
. It can also affect people who do not have AIDS and usually first presents as a persistent cough. Additionally, cases in elderly men have increased recently. It is typically treated with a series of 3 antibiotics for a period of at least 6 months.
It is a saprotrophic organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
that is present in soil and water, entry is usually via the GI tract but also can be via the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s.
It causes fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
s, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, malabsorption
Malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
and anorexia
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
and it can disseminate to the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
. Therapy for MAI is disappointing as it is typically resistant to standard mycobacterial therapies.
Sources and symptoms
MAC bacteria are common in the environment and cause infectionInfection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
when inhaled or swallowed. Symptoms of MAC diseases are reminiscent of tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
. They include fever, fatigue, and weight loss. Many patients will have anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
and neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
if bone marrow is involved. Pulmonary involvement is similar to TB, while diarrhea and abdominal pain are associated with gastrointestinal involvement. MAC should always be considered in a person with HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
infection presenting with diarrhea. Recently, M. avium has been found to deposit and grow in bathroom shower heads from which it may be easily aerosolized and inhaled.
The various subspecies are prevalent in different areas:
- MAA primarily affects birdBirdBirds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s, but has also been found in the group of mammalMammalMammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s known as ruminants, especially deerDeerDeer are the ruminant mammals forming the family Cervidae. Species in the Cervidae family include white-tailed deer, elk, moose, red deer, reindeer, fallow deer, roe deer and chital. Male deer of all species and female reindeer grow and shed new antlers each year...
; - MAP causes paratuberculosis, or Johne's DiseaseJohne's diseaseParatuberculosis or Johne's disease is a contagious, chronic and sometimes fatal infection that primarily affects the small intestine of ruminants. It is caused by the bacterium Mycobacterium avium subspecies paratuberculosis...
;
MAC disease is common in immunocompromised
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
individuals, including senior citizens and those suffering from HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
or cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
; however, the MAC diseases, particularly Lady Windermere syndrome, do not require that the individual be immunocompromised.
Mycobacterium avium infection in children
The M. avium and M. haemophilum infection in children form a distinct clinical entity, not associated with abnormalities of the immune system. M. avium typically causes swelling of the lymph nodes of the neck that is usually unilateral. This node is firm at beginning, but a collarstud abscess is formed eventually which is characteristic blue purple in colour with multiple discharging sinuses. The treatment of choice is surgical excision of the affected lymph nodes, with antibiotic treatment (usually clarithromycinClarithromycin
Clarithromycin is a macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia , skin and skin structure infections...
and rifabutin
Rifabutin
Rifabutin is a bactericidal antibiotic drug primarily used in the treatment of tuberculosis. The drug is a semi-synthetic derivative of rifamycin S. Its effect is based on blocking the DNA-dependent RNA-polymerase of the bacteria. It is effective against Gram-positive and some Gram-negative...
for 18 to 24 months) reserved for those patients who cannot have surgery.
MAC in patients with HIV infection
MAC in patients with HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
disease is theorized to represent recent acquisition rather than latent infection reactivating (which is the case in many other opportunistic infection
Opportunistic infection
An opportunistic infection is an infection caused by pathogens, particularly opportunistic pathogens—those that take advantage of certain situations—such as bacterial, viral, fungal or protozoan infections that usually do not cause disease in a healthy host, one with a healthy immune system...
s in immunocompromised
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
patients).
The risk of MAC is inversely related to the patient's CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
count, and increases significantly when the CD4 count decreases below 50 cells/mm³. Other risk factors for acquisition of MAC infection include using an indoor swimming pool
Swimming pool
A swimming pool, swimming bath, wading pool, or simply a pool, is a container filled with water intended for swimming or water-based recreation. There are many standard sizes; the largest is the Olympic-size swimming pool...
, consumption of raw or partially cooked fish or shellfish, bronchoscopy
Bronchoscopy
Bronchoscopy is a technique of visualizing the inside of the airways for diagnostic and therapeutic purposes. An instrument is inserted into the airways, usually through the nose or mouth, or occasionally through a tracheostomy. This allows the practitioner to examine the patient's airways for...
and treatment with granulocyte stimulating factor.
Disseminated disease
Disseminated disease
Disseminated disease refers to a diffuse disease process, generally either infectious or neoplastic, but sometimes also referring to connective tissue disease....
was previously the common presentation prior to the advent of highly active antiretroviral therapy (HAART). Today, in regions where HAART is the standard of care, localized disease presentation is more likely. This generally includes a focal lymphadenopathy
Lymphadenopathy
Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....
/lymphadenitis.
AIDS patients are given macrolide antibiotics such as Azithromycin
Azithromycin
Azithromycin is an azalide, a subclass of macrolide antibiotics. Azithromycin is one of the world's best-selling antibiotics...
for prophylactic treatment.
Diagnosis
Diagnosis can be achieved through blood cultures, or cultures of other bodily fluids such as sputumSputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....
. Bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
culture can often yield an earlier diagnosis, but is usually avoided as an initial diagnostic step because of its invasiveness.
Treatment
Treat prophylactically with azithromycinAzithromycin
Azithromycin is an azalide, a subclass of macrolide antibiotics. Azithromycin is one of the world's best-selling antibiotics...
.
Post-infection, treatment involves a combination of antituberculosis antibiotics. These include:
- RifampicinRifampicinRifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
- RifabutinRifabutinRifabutin is a bactericidal antibiotic drug primarily used in the treatment of tuberculosis. The drug is a semi-synthetic derivative of rifamycin S. Its effect is based on blocking the DNA-dependent RNA-polymerase of the bacteria. It is effective against Gram-positive and some Gram-negative...
- CiprofloxacinCiprofloxacinCiprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of...
- AmikacinAmikacinAmikacin is an aminoglycoside antibiotic used to treat different types of bacterial infections. Amikacin works by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth.-Administration:Amikacin may be...
- EthambutolEthambutolEthambutol is a bacteriostatic antimycobacterial drug prescribed to treat tuberculosis. It is usually given in combination with other tuberculosis drugs, such as isoniazid, rifampicin and pyrazinamide....
- StreptomycinStreptomycinStreptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin cannot be given...
- ClarithromycinClarithromycinClarithromycin is a macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia , skin and skin structure infections...
- AzithromycinAzithromycinAzithromycin is an azalide, a subclass of macrolide antibiotics. Azithromycin is one of the world's best-selling antibiotics...
Lady Windermere syndrome
"Lady Windermere syndrome" describes infectionInfection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
in the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s due to Mycobacterium avium complex. It is named after a character in Oscar Wilde
Oscar Wilde
Oscar Fingal O'Flahertie Wills Wilde was an Irish writer and poet. After writing in different forms throughout the 1880s, he became one of London's most popular playwrights in the early 1890s...
's play Lady Windermere's Fan
Lady Windermere's Fan
Lady Windermere's Fan, A Play About a Good Woman is a four act comedy by Oscar Wilde, first produced 22 February 1892 at the St James's Theatre in London. The play was first published in 1893...
.
Signs and symptoms
Patients with Lady Windermere syndrome experience chronic cough, shortness of breath, fatigue and other less specific symptomSymptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s.
Pathophysiology
Mycobacterium avium complex is the most commonly found form of non-tuberculous mycobacteria.Immunodeficiency is not a requirement for Mycobacterium avium infection.
Mycobacterium avium Complex (MAC) usually affects patients with abnormal lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s or bronchi. However, Candace Baker, Jerome Reich and Richard Johnson describe a series of six patients with MAC infection of the right middle lobe or left lingula who did not have any predisposing lung disorders.
The right middle lobe
Lobe (anatomy)
In anatomy, a lobe is a clear anatomical division or extension that can be determined without the use of a microscope This is in contrast to a lobule, which is a clear division only visible histologically....
and left lingula of the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s are served by bronchi that are oriented downward when a person is in the upright position. As a result, these areas of the lung may be more dependent upon vigorous voluntary expectoration (cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
) for clearance of bacteria and secretions.
Since the six patients in their retrospective case series were older females, Reich and Johnson and Baker propose that patients without a vigorous cough may develop right middle lobe or left lingular infection with MAC. They propose that this syndrome be named Lady Windermere syndrome, after the character Lady Windermere in Oscar Wilde
Oscar Wilde
Oscar Fingal O'Flahertie Wills Wilde was an Irish writer and poet. After writing in different forms throughout the 1880s, he became one of London's most popular playwrights in the early 1890s...
's play Lady Windermere's Fan
Lady Windermere's Fan
Lady Windermere's Fan, A Play About a Good Woman is a four act comedy by Oscar Wilde, first produced 22 February 1892 at the St James's Theatre in London. The play was first published in 1893...
.
Diagnosis
The diagnosis requires consistent symptoms with two additional signs:- Chest x-rayChest X-rayIn medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
or chest CT scan showing evidence of right middle lobe (or left lingular lobe) lungLungThe lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
infection. - Sputum cultureSputum cultureA sputum culture is a test to detect and identify bacteria or fungi that infect the lungs or breathing passages. Sputum is a thick fluid produced in the lungs and in the adjacent airways. A sample of sputum is placed in a sterile container and sent to the laboratory for testing...
or bronchoalveolar lavageBronchoalveolar lavageBronchoalveolar lavage is a medical procedure in which a bronchoscope is passed through the mouth or nose into the lungs and fluid is squirted into a small part of the lung and then recollected for examination. BAL is typically performed to diagnose lung disease...
culture demonstrating that the infection is caused by Mycobacterium avium complexMycobacterium avium complexMycobacterium avium complex is a group of genetically related bacteria belonging to the genus Mycobacterium. It includes Mycobacterium avium and Mycobacterium intracellulare....
(MAC).
Treatment
Lady Windermere syndrome is usually treated with a three-drug regimen of either clarithromycin or azithromycin, plus rifampicinRifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
and ethambutol
Ethambutol
Ethambutol is a bacteriostatic antimycobacterial drug prescribed to treat tuberculosis. It is usually given in combination with other tuberculosis drugs, such as isoniazid, rifampicin and pyrazinamide....
. Treatment typically lasts at least 12 months.
Literary reference
The original Chest article proposing the existence and pathophysiologyPathophysiology
Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...
of the Lady Windermere syndrome suggests that the character Lady Windermere in Oscar Wilde
Oscar Wilde
Oscar Fingal O'Flahertie Wills Wilde was an Irish writer and poet. After writing in different forms throughout the 1880s, he became one of London's most popular playwrights in the early 1890s...
's Victorian-era play Lady Windermere's Fan
Lady Windermere's Fan
Lady Windermere's Fan, A Play About a Good Woman is a four act comedy by Oscar Wilde, first produced 22 February 1892 at the St James's Theatre in London. The play was first published in 1893...
is a good example of the fastidious behavior believed to cause the syndrome. The article states:
- We offer the term, Lady Windermere's Syndrome, from the Victorian-era play, Lady Windermere's Fan, to convey the fastidious behavior hypothesized: "How do you do, Lord Darlington. No, I can't shake hands with you. My hands are all wet with the roses."
Victorian women presumably believed that "Ladies don't spit," and consequently might have been predisposed to develop lung infection.
Shortly after the Lady Windermere syndrome was proposed, a librarian wrote a letter to the editor of Chest challenging the use of Lady Windermere as the eponymous ancestor of the proposed syndrome. In Lady Windermere's Fan
Lady Windermere's Fan
Lady Windermere's Fan, A Play About a Good Woman is a four act comedy by Oscar Wilde, first produced 22 February 1892 at the St James's Theatre in London. The play was first published in 1893...
, Lady Windermere is a vivacious young woman, married only 2 years, who never coughs or displays any other signs of illness. While her avoidance of shaking hands might be interpreted as "fastidiousness," two alternative explanations may be just as probable:
- 1) Lady Windermere actually is in the midst of arranging flowers and consequently cannot properly greet her guest:
-
- [LADY WINDERMERE is at table R., arranging roses in a blue bowl.]
- 2) Lady Windermere wishes to discourage the flirtatious advances of her would-be suitor Lord Darlington and cites her wet hands as an excuse to keep him from touching her:
-
- LADY WINDERMERE. Lord Darlington, you annoyed me last night at the Foreign Office. I am afraid you are going to annoy me again. . . .
-
- LORD DARLINGTON. [Takes chair and goes across L.C.] I am quite miserable, Lady Windermere. You must tell me what I did. [Sits down at table L.]
-
- LADY WINDERMERE. Well, you kept paying me elaborate compliments the whole evening.]
The scholars highlight the literary malapropism
Malapropism
A malapropism is an act of misusing or the habitual misuse of similar sounding words, especially with humorous results. An example is Yogi Berra's statement: "Texas has a lot of electrical votes," rather than "electoral votes".-Etymology:...
, but some in the medical community have adopted the term regardless, and peer-reviewed medical journals still sometimes mention the Lady Windermere syndrome.
In recent years, some have described the eponym as inappropriate, and some have noted that it would have been unlikely that Lady Windermere had the condition to which her name was assigned.